ORCID Profile
0000-0002-4950-8169
Current Organisations
Turku University Hospital
,
University of Turku
,
Terveystalo Ltd
,
University of Sydney
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Psychology | Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology) | Neurocognitive Patterns and Neural Networks | Decision Making | Developmental Psychology and Ageing
Expanding Knowledge in Psychology and Cognitive Sciences | Expanding Knowledge in the Biological Sciences |
Publisher: Elsevier BV
Date: 02-2014
Publisher: Society for Neuroscience
Date: 22-06-2022
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.NEUROIMAGE.2016.03.032
Abstract: Clinical differentiation between Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD) is challenging due to overlapping clinical features at presentation. Whilst diagnostic criteria for both disorders incorporate evidence of frontal and temporal cortical atrophy, understanding of the progression of atrophy in these disorders is limited. This study aimed to elucidate common and disease-specific progressive changes in cortical and subcortical brain structures in AD and bvFTD. Forty-one AD, 37 bvFTD and 33 healthy controls underwent baseline MRI and of these longitudinal follow-up was obtained for 20AD and 20 bvFTD (1 to 4years). A total of 87 AD and 70 bvFTD consecutive scans were included in the study. The trajectories of progression in cortical and subcortical structures were identified with FreeSurfer and linear mixed effect modelling. The results uncovered cortical and subcortical disease-specific trajectories of neurodegeneration in AD and bvFTD. Specifically, direct comparisons between patient groups revealed that over time AD showed greater cortical atrophy in the inferior parietal and posterior cingulate cortex than bvFTD. Conversely, bvFTD patients showed greater atrophy in the striatum than AD over time. These results indicate that atrophy in the posterior cingulate and the striatum erges with disease progression in these dementia syndromes and may represent a potential diagnostic biomarker for tracking rates of progression of AD and bvFTD. These findings may help inform future drug trials by identifying appropriate outcome measures to quantify drug efficacy and their ability to modulate disease progression over time.
Publisher: Society for Neuroscience
Date: 08-06-2016
Publisher: Elsevier BV
Date: 09-2020
Publisher: Wiley
Date: 14-10-2022
DOI: 10.1002/WCS.1630
Abstract: Autobiographical memory represents a defining feature of human cognition, enabling us to vividly re‐experience salient events from the personal past. By mentally traversing different temporal contexts, humans can maintain an enduring sense of who we are as in iduals, as well as envisaging our future goals and behaviors. The relative ease with which we engage in these endeavors, however, belies the remarkable complexity of the autobiographical memory system. Dementia syndromes offer compelling insights into the cognitive neuroarchitecture of autobiographical memory in the face of progressive neural insult to large‐scale brain networks. Importantly, the atrophy profiles of many neurodegenerative disorders follow coordinated and predictable trajectories, affecting key regions implicated in episodic and semantic memory. A wealth of evidence suggests that autobiographical memory disruption is a transdiagnostic feature of dementia, yet this impairment takes many forms and arises due to differential neurocognitive disturbances. This review aims to provide a comprehensive overview of the literature on autobiographical memory in typical and atypical presentations of Alzheimer's disease, as well as younger‐onset dementia syndromes such as frontotemporal dementia and primary progressive aphasia. I will demonstrate how the systematic study of autobiographical memory across dementia syndromes can constrain and inform our fundamental understanding of memory function and, in turn, stimulate new directions in how we conceptualize and assess these cognitive capacities. Consideration will further be given to clinical implications of autobiographical memory dysfunction with a view to developing targeted interventions to better support the person living with dementia. This article is categorized under: Psychology Memory Neuroscience Clinical Neuroscience Psychology Brain Function and Dysfunction
Publisher: Cambridge University Press (CUP)
Date: 27-06-2014
DOI: 10.1017/S1041610214001136
Abstract: Autobiographical memory (ABM), personal semantic memory (PSM), and autonoetic consciousness are affected in in iduals with mild cognitive impairment (MCI) but their relationship with Alzheimer's disease (AD) biomarkers are unclear. Forty-five participants (healthy controls (HC) = 31, MCI = 14) completed the Episodic ABM Interview and a battery of memory tests. Thirty-one (HC = 22, MCI = 9) underwent β-amyloid positron emission tomography (PET) and magnetic resonance (MR) imaging. Fourteen participants (HC = 9, MCI = 5) underwent one imaging modality. Unlike PSM, ABM differentiated between diagnostic categories but did not relate to AD biomarkers. Personal semantic memory was related to neocortical β-amyloid burden after adjusting for age and apolipoprotein E ( APOE ) ɛ 4. Autonoetic consciousness was not associated with AD biomarkers, and was not impaired in MCI. Autobiographical memory was impaired in MCI participants but was not related to neocortical amyloid burden, suggesting that personal memory systems are impacted by differing disease mechanisms, rather than being uniformly underpinned by β-amyloid. Episodic and semantic ABM impairment represent an important AD prodrome.
Publisher: SAGE Publications
Date: 10-10-2018
Abstract: Despite consistent activation on tasks of episodic memory, the precise contribution of the left angular gyrus (AG) to mnemonic functions remains vigorously debated. Mounting evidence suggests that AG activity scales with subjective ratings of vividness and confidence in recollection, with further evidence pointing to its involvement during construction of detailed and coherent future simulations. Lesion studies, however, indicate that damage to the AG does not render patients amnesic on standard source and associative memory paradigms. To reconcile these findings, we present the Contextual Integration Model as a unifying framework that couches the mnemonic role of the AG in terms of multimodal integration and representation of contextual information across temporal contexts. Irrespective of whether one is remembering the past or constructing future or hypothetical scenarios, the Contextual Integration Model holds that the core elements of an event (i.e., the who, what, when, where) are bound within the medial temporal lobes while the multimodal details, which give rise to perceptually rich recollection, are integrated and represented in the AG. Building on previous work, the Contextual Integration Model therefore provides a comprehensive exposition of the mnemonic and constructive functions of the AG across temporal contexts, offering a novel test-bed for future work.
Publisher: MDPI AG
Date: 12-08-2021
Abstract: Impaired verbal ‘phonological’ short-term memory is considered a cardinal feature of the logopenic variant of primary progressive aphasia (lv-PPA) and is assumed to underpin most of the language deficits in this syndrome. Clinically, examination of verbal short-term memory in in iduals presenting with PPA is common practice and serves two objectives: (i) to help understand the possible mechanisms underlying the patient’s language profile and (ii) to help differentiate lv-PPA from other PPA variants or from other dementia syndromes. Distinction between lv-PPA and the non-fluent variant of PPA (nfv-PPA), however, can be especially challenging due to overlapping language profiles and comparable psychometric performances on verbal short-term memory tests. Here, we present case vignettes of the three PPA variants (lv-PPA, nfv-PPA, and the semantic variant (sv-PPA)) and typical Alzheimer’s disease (AD). These vignettes provide a detailed description of the short-term and working memory profiles typically found in these patients and highlight how speech output and language comprehension deficits across the PPA variants differentially interfere with verbal memory performance. We demonstrate that a combination of verbal short-term and working memory measures provides crucial information regarding the cognitive mechanisms underlying language disturbances in PPA. In addition, we propose that analogous visuospatial span tasks are essential for the assessment of PPA as they measure memory capacity without language contamination.
Publisher: Proceedings of the National Academy of Sciences
Date: 04-02-2019
Abstract: Humans spend much of their waking life engaged in mind wandering. Underlying brain systems supporting this complex ability have been established in healthy in iduals, yet it remains unclear how mind wandering is altered in neuropsychiatric populations. We reveal changes in the thought profiles elicited during periods of low cognitive demand in dementia, resulting in reduced mind wandering and an increased propensity toward stimulus-bound thought. These altered thought profiles were associated with structural and functional brain changes in the hippoc us, default, and frontoparietal networks, key regions implicated in internal mentation in healthy in iduals. Our findings provide a unique clinical validation of current theoretical models of mind wandering and reveal a dimension of cognitive dysfunction that has received scant attention in dementia.
Publisher: MDPI AG
Date: 12-2021
Abstract: Mounting evidence suggests that, in parallel with well-defined changes in language, primary progressive aphasia (PPA) syndromes display co-occurring social cognitive impairments. Here, we explored multidimensional profiles of carer-rated social communication using the La Trobe Communication Questionnaire (LCQ) in 11 semantic dementia (SD), 12 logopenic progressive aphasia (LPA) and 9 progressive non-fluent aphasia (PNFA) cases and contrasted their performance with 19 Alzheimer’s disease (AD) cases, 26 behavioural variant frontotemporal dementia (bvFTD) cases and 31 healthy older controls. Relative to the controls, the majority of patient groups displayed significant overall social communication difficulties, with common and unique profiles of impairment evident on the LCQ subscales. Correlation analyses revealed a differential impact of social communication disturbances on functional outcomes in patient and carer well-being, most pronounced for SD and bvFTD. Finally, voxel-based morphometry analyses based on a structural brain MRI pointed to the degradation of a distributed brain network in mediating social communication dysfunction in dementia. Our findings suggest that social communication difficulties are an important feature of PPA, with significant implications for patient function and carer well-being. The origins of these changes are likely to be multifactorial, reflecting the breakdown of fronto-thalamic brain circuits specialised in the integration of complex information.
Publisher: Oxford University Press (OUP)
Date: 12-02-2014
DOI: 10.1093/BRAIN/AWU003
Abstract: Semantic dementia is a progressive neurodegenerative disorder characterized by the amodal and profound loss of semantic knowledge attributable to the degeneration of the left anterior temporal lobe. Although traditionally conceptualized as a language disorder, patients with semantic dementia display significant alterations in behaviour and socioemotional functioning. Recent evidence points to an impaired capacity for theory of mind in predominantly left-lateralized cases of semantic dementia however, it remains unclear to what extent semantic impairments contribute to these deficits. Further the neuroanatomical signature of such disturbance remains unknown. Here, we sought to determine the neural correlates of theory of mind performance in patients with left predominant semantic dementia (n=11), in contrast with disease-matched cases with behavioural-variant frontotemporal dementia (n=10) and Alzheimer's disease (n=10), and healthy older in iduals (n=14) as control participants. Participants completed a simple cartoons task, in which they were required to describe physical and theory of mind scenarios. Irrespective of subscale, patients with semantic dementia exhibited marked impairments relative to control subjects however, only theory of mind deficits persisted when we covaried for semantic comprehension. Voxel-based morphometry analyses revealed that atrophy in right anterior temporal lobe structures, including the right temporal fusiform cortex, right inferior temporal gyrus, bilateral temporal poles and amygdalae, correlated significantly with theory of mind impairments in the semantic dementia group. Our results point to the marked disruption of cognitive functions beyond the language domain in semantic dementia, not exclusively attributable to semantic processing impairments. The significant involvement of right anterior temporal structures suggests that with disease evolution, the encroachment of pathology into the contralateral hemisphere heralds the onset of social cognitive deficits in this syndrome.
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 06-2017
Publisher: Wiley
Date: 24-04-2018
DOI: 10.1111/JNP.12160
Abstract: Autobiographical memory (ABM) is typically held to comprise episodic and semantic elements, with the vast majority of studies to date focusing on profiles of episodic details in health and disease. In this context, 'non-episodic' elements are often considered to reflect semantic processing or are discounted from analyses entirely. Mounting evidence suggests that rather than reflecting one unitary entity, semantic autobiographical information may contain discrete subcomponents, which vary in their relative degree of semantic or episodic content. This study aimed to (1) review the existing literature to formally characterize the variability in analysis of 'non-episodic' content (i.e., external details) on the Autobiographical Interview and (2) use these findings to create a theoretically grounded framework for coding external details. Our review exposed discrepancies in the reporting and interpretation of external details across studies, reinforcing the need for a new, consistent approach. We validated our new external details scoring protocol (the 'NExt' taxonomy) in patients with Alzheimer's disease (n = 18) and semantic dementia (n = 13), and 20 healthy older Control participants and compared profiles of the NExt subcategories across groups and time periods. Our results revealed increased sensitivity of the NExt taxonomy in discriminating between ABM profiles of patient groups, when compared to traditionally used internal and external detail metrics. Further, remote and recent autobiographical memories displayed distinct compositions of the NExt detail types. This study is the first to provide a fine-grained and comprehensive taxonomy to parse external details into intuitive subcategories and to validate this protocol in neurodegenerative disorders.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.CORTEX.2016.07.003
Abstract: Logopenic progressive aphasia (lv-PPA) is a form of primary progressive aphasia and is predominantly associated with Alzheimer's disease (AD) pathology. The neuropsychological profiles of lv-PPA and typical clinical AD are, however, distinct. In particular, these two syndromes differ on attention span measures, where auditory attention span is more impaired in lv-PPA than in AD and visuospatial span appears more impaired in AD than in lv-PPA. The neural basis of these span profiles, however, remains unclear. Sixteen lv-PPA and 21 AD matched patients, and 15 education-matched healthy controls were recruited. All participants were assessed by a neurologist and completed a neuropsychological assessment that included the Wechsler Memory Scale-III Digit and Spatial Span tasks, and underwent a high-resolution structural brain MRI to conduct cortical thickness analyses. Patient groups were impaired on all span tasks compared to Controls. In addition, performance on Digit Span Forward (DSF) was significantly lower in the lv-PPA than the AD group, while Spatial Span Forward (SSF) was significantly lower in the AD than the lv-PPA group. No differences were found between patient groups on the Digit or Spatial Span Backward tasks. Neuroimaging analyses revealed that reduced DSF performance correlated to thinning of the left superior temporal gyrus in the lv-PPA group, whereas reduced SSF performance was related to bilateral precentral sulcus and parieto-occipital thinning in the AD group. Analyses of the backward span tasks revealed that reduced Spatial Span Backward (SSB) performance in the lv-PPA group related to cortical thinning of the left superior parietal lobule. This study demonstrates that while lv-PPA and AD commonly share the same underlying neuropathology, their span profiles are distinct and are mediated by ergent patterns of cortical degeneration.
Publisher: Oxford University Press (OUP)
Date: 04-07-2022
DOI: 10.1093/BRAINCOMMS/FCAC161
Abstract: The Addenbrooke’s Cognitive Examination III is a brief cognitive screening tool that is widely used for the detection and monitoring of dementia. Recent findings suggest that the three variants of primary progressive aphasia can be distinguished based on their distinct profiles on the five subdomain scores of this test. Here, we investigated the utility of the Addenbrooke’s Cognitive Examination III to differentiate the primary progressive aphasia variants based on their item-by-item performance profiles on this test. From these results, we created an interactive primary progressive aphasia Addenbrooke’s Cognitive Examination III calculator which predicts the variant based on a patient’s unique item-by-item profile. Twenty-eight logopenic variant, 25 non-fluent variant and 37 semantic variant primary progressive aphasia patients and 104 healthy controls completed the Addenbrooke’s Cognitive Examination III at first clinical presentation. Multinomial regression analyses were conducted to establish performance profiles among groups, and R Shiny from RStudio was used to create the interactive Addenbrooke’s Cognitive Examination III diagnostic calculator. To verify its accuracy, probability values of the regression model were derived based on a 5-fold cross-validation of cases. The calculator’s accuracy was then verified in an independent s le of 17 logopenic, 19 non-fluent and 13 semantic variant primary progressive aphasia patients and 68 Alzheimer’s disease patients who had completed the Addenbrooke’s Cognitive Examination III (or an older version of this test: Revised) and had in vivo amyloid-PET imaging and/or brain autopsy pathological confirmation. Cross-validation of cases in the calculator model revealed different rates of sensitivity in classifying variants: semantic = 100%, non-fluent = 80.6% and logopenic = 79.9% healthy controls were distinguished from primary progressive aphasia patients with 100% sensitivity. Verification of in vivo amyloid and/or autopsy-confirmed patients showed that the calculator correctly classified 10/13 (77%) semantic variant, 3/19 (16%) non-fluent variant and 4/17 (24%) logopenic variant patients. Importantly, for patients who were not classified, diagnostic probability values mostly pointed toward the correct clinical diagnosis. Furthermore, misclassified diagnoses of the primary progressive aphasia cohort were rare (1/49 2%). Although 22 of the 68 Alzheimer’s disease patients (32%) were misclassified with primary progressive aphasia, 19/22 were misclassified with the logopenic variant (i.e. falling within the same neuropathological entity). The Addenbrooke’s Cognitive Examination III primary progressive aphasia diagnostic calculator demonstrates sound accuracy in differentiating the variants based on an item-by-item Addenbrooke’s Cognitive Examination III profile. This calculator represents a new frontier in using data-driven approaches to differentiate the primary progressive aphasia variants.
Publisher: Informa UK Limited
Date: 19-08-2019
DOI: 10.1080/09658211.2019.1654519
Abstract: Autobiographical memory is widely posited to serve self, social and directive functions. Recent evidence suggests marked autobiographical memory impairments in Huntington's disease (HD), however, no study to date has determined how the perceived functions of autobiographical reminiscence may be altered in HD. The current study aimed to assess the self-reported frequency and function of autobiographical reminiscence in HD. We assessed autobiographical reminiscence in late premanifest (
Publisher: MDPI AG
Date: 12-11-2021
Abstract: The capacity for subjective time in humans encompasses the perception of time’s unfolding from moment to moment, as well as the ability to traverse larger temporal expanses of past- and future-oriented thought via mental time travel. Disruption in time perception can result in maladaptive outcomes—from the innocuous lapse in timing that leads to a burnt piece of toast, to the grievous miscalculation that produces a traffic accident—while disruption to mental time travel can impact core functions from planning appointments to making long-term decisions. Mounting evidence suggests that disturbances to both time perception and mental time travel are prominent in dementia syndromes. Given that such disruptions can have severe consequences for independent functioning in everyday life, here we aim to provide a comprehensive exposition of subjective timing dysfunction in dementia, with a view to informing the management of such disturbances. We consider the neurocognitive mechanisms underpinning changes to both time perception and mental time travel across different dementia disorders. Moreover, we explicate the functional implications of altered subjective timing by reference to two key and representative adaptive capacities: prospective memory and intertemporal decision-making. Overall, our review sheds light on the transdiagnostic implications of subjective timing disturbances in dementia and highlights the high variability in performance across clinical syndromes and functional domains.
Publisher: Elsevier BV
Date: 03-2016
Publisher: Wiley
Date: 27-05-2015
DOI: 10.1111/BJC.12090
Abstract: Prospection, or future thinking, refers to the ability to mentally simulate plausible events at a future point in time and draws heavily upon the capacity to retrieve autobiographical details from the past. This review examines the extent to which prospection is compromised in neurodegenerative disorders with a view to identifying (1) underlying mechanisms of future thinking disruption and (2) the impact of future thinking deficits on everyday adaptive functioning. PubMed and MEDLINE were searched for peer-reviewed articles published or in press up to 14 October 2014. The key criterion for inclusion was that the primary outcome measure concerned the envisaging of episodic events at a future time point. Search terms of 'future thinking', 'prospection', and 'future simulation' were used in combination with the following terms: 'dementia', 'Mild Cognitive Impairment', 'Alzheimer's disease', 'semantic dementia', 'frontotemporal dementia', 'Parkinson's disease', 'Motor Neuron disease', 'Vascular dementia', and 'Dementia with Lewy bodies' (e.g., 'future thinking' AND 'Alzheimer's disease'). Searches were limited to articles published in English. A total of nine unique papers were identified in which prospection was the main outcome measure in dementia. Collectively, these studies reveal marked impairments in the ability to simulate personally relevant events at a future time point in dementia syndromes. Future research investigating the real-world implications of prospection deficits in dementia is crucial to elucidate the interplay between future-oriented thought and everyday adaptive functions such as prospective memory, decision-making, and maintaining a coherent sense of self over time.
Publisher: Frontiers Media SA
Date: 20-11-2018
Publisher: Elsevier BV
Date: 2013
Publisher: Frontiers Media SA
Date: 24-06-2014
Publisher: Wiley
Date: 25-11-2013
DOI: 10.1002/HBM.22420
Publisher: Cambridge University Press (CUP)
Date: 2019
DOI: 10.1017/S0140525X19001894
Abstract: The syndrome of semantic dementia represents the “other side of the coin” to Alzheimer's disease, offering convergent evidence to help refine Bastin et al.’s integrative memory model. By considering the integrative memory model through the lens of semantic dementia, we propose a number of important extensions to the framework, to help clarify the complex neurocognitive mechanisms underlying recollection and familiarity.
Publisher: Center for Open Science
Date: 21-01-2019
Abstract: Memory and the self have long been considered intertwined, leading to the common assumption that without memory, there can be no self. This line of reasoning has led to the common misconception that a loss of memory in dementia necessarily results in a diminished sense of self. Here, we challenge this assumption by considering discrete facets of the self, and their relative profiles of loss and sparing, across three neurodegenerative disorders: Alzheimer’s disease, semantic dementia, and frontotemporal dementia. By exploring canonical expressions of the self across past, present, and future contexts in dementia, relative to healthy ageing, we reconcile previous accounts of loss of self in dementia, and propose a new framework for understanding and managing everyday functioning and behaviour. Notably, our approach highlights the multifaceted and dynamic nature in which the self is likely to change in healthy and pathological ageing, with important ramifications for development of person-centred care. Collectively, we aim to promote a cohesive sense of self in dementia across past, present, and future contexts, by demonstrating how, ultimately, ‘All is not lost’.
Publisher: SAGE Publications
Date: 14-07-2013
Abstract: The effects of empathy loss in frontotemporal dementia (FTD) and Alzheimer disease (AD) on carer symptomatology were investigated. Carers of patients with 2 clinical subtypes of FTD (behavioral-variant FTD [bvFTD] = 18 semantic dementia [SD] = 14) and AD (n = 18) completed the Interpersonal Reactivity Index (IRI), a standardized questionnaire of empathy as well as a measure of perceived burden (Zarit Burden Interview) and the quality of the marital relationship (Intimate Bond Measure). Patient ratings were also obtained on the IRI. Loss of empathy was most striking in the bvFTD group with a marked discrepancy observed between carer and patient ratings for change in emotional warmth and the ability to take the perspective of others. Empathy loss in bvFTD was associated with a loss of a caring marital relationship. Empathic deficits in SD were milder by comparison to bvFTD and correlated with disease severity and increased perceived carer burden. The behavioral pattern observed in AD differed from the FTD syndromes deficits were observed only for measures of personal distress with carers reporting that patients were less able to handle emotionally evocative situations. Results highlight that changes in aspects of empathy differ across dementia syndromes and are associated with differing carer and clinical variables. These findings might be explained by the progression of atrophy in regions that are known to be critical for empathy and social behavior and has implications for the delivery and planning of services in dementia.
Publisher: Oxford University Press (OUP)
Date: 22-05-2012
DOI: 10.1093/BRAIN/AWS119
Abstract: Semantic dementia is a progressive neurodegenerative condition characterized by the profound and amodal loss of semantic memory in the context of relatively preserved episodic memory. In contrast, patients with Alzheimer's disease typically display impairments in episodic memory, but with semantic deficits of a much lesser magnitude than in semantic dementia. Our understanding of episodic memory retrieval in these cohorts has greatly increased over the last decade, however, we know relatively little regarding the ability of these patients to imagine and describe possible future events, and whether episodic future thinking is mediated by ergent neural substrates contingent on dementia subtype. Here, we explored episodic future thinking in patients with semantic dementia (n=11) and Alzheimer's disease (n=11), in comparison with healthy control participants (n=10). Participants completed a battery of tests designed to probe episodic and semantic thinking across past and future conditions, as well as standardized tests of episodic and semantic memory. Further, all participants underwent magnetic resonance imaging. Despite their relatively intact episodic retrieval for recent past events, the semantic dementia cohort showed significant impairments for episodic future thinking. In contrast, the group with Alzheimer's disease showed parallel deficits across past and future episodic conditions. Voxel-based morphometry analyses confirmed that atrophy in the left inferior temporal gyrus and bilateral temporal poles, regions strongly implicated in semantic memory, correlated significantly with deficits in episodic future thinking in semantic dementia. Conversely, episodic future thinking performance in Alzheimer's disease correlated with atrophy in regions associated with episodic memory, namely the posterior cingulate, parahippoc al gyrus and frontal pole. These distinct neuroanatomical substrates contingent on dementia group were further qualified by correlational analyses that confirmed the relation between semantic memory deficits and episodic future thinking in semantic dementia, in contrast with the role of episodic memory deficits and episodic future thinking in Alzheimer's disease. Our findings demonstrate that semantic knowledge is critical for the construction of novel future events, providing the necessary scaffolding into which episodic details can be integrated. Further research is necessary to elucidate the precise contribution of semantic memory to future thinking, and to explore how deficits in self-projection manifest on behavioural and social levels in different dementia subtypes.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2017.08.016
Abstract: Social relevance has an enhancing effect on learning and subsequent memory retrieval. The ability to learn from and remember social interactions may impact on susceptibility to financial exploitation, which is elevated in in iduals with dementia. The current study aimed to investigate learning and memory of social interactions, the relationship between performance and financial vulnerability and the neural substrates underpinning performance in 14 Alzheimer's disease (AD) and 20 behavioural-variant frontotemporal dementia (bvFTD) patients and 20 age-matched healthy controls. On a "trust game" task, participants invested virtual money with counterparts who acted either in a trustworthy or untrustworthy manner over repeated interactions. A non-social "lottery" condition was also included. Participants' learning of trust/distrust responses and subsequent memory for the counterparts and nature of the interactions was assessed. Carer-rated profiles of financial vulnerability were also collected. Relative to controls, both patient groups showed attenuated learning of trust/distrust responses, and lower overall memory for social interactions. Despite poor learning performance, both AD and bvFTD patients showed better memory of social compared to non-social interactions. Importantly, better memory for social interactions was associated with lower financial vulnerability in AD, but not bvFTD. Learning and memory of social interactions was associated with medial temporal and temporoparietal atrophy in AD, whereas a wider network of frontostriatal, insular, fusiform and medial temporal regions was implicated in bvFTD. Our findings suggest that although social relevance influences memory to an extent in both AD and bvFTD, this is associated with vulnerability to financial exploitation in AD only, and is underpinned by changes to different neural substrates. Theoretically, these findings provide novel insights into potential mechanisms that give rise to vulnerability in people with dementia, and open avenues for possible interventions.
Publisher: Wiley
Date: 12-02-2019
DOI: 10.1111/JNP.12152
Abstract: In healthy adults, the ability to prioritize learning of highly valued information is supported by executive functions and enhances subsequent memory retrieval for this information. In Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD), marked deficits are evident in learning and memory, presenting in the context of executive dysfunction. It is unclear whether these patients show a typical memory bias for higher valued stimuli. We administered a value-directed word-list learning task to AD (n = 10) and bvFTD (n = 21) patients and age-matched healthy controls (n = 22). Each word was assigned a low, medium or high point value, and participants were instructed to maximize the number of points earned across three learning trials. Participants' memory for the words was assessed on a delayed recall trial, followed by a recognition test for the words and corresponding point values. Relative to controls, both patient groups showed poorer overall learning, delayed recall and recognition. Despite these impairments, patients with AD preferentially recalled high-value words on learning trials and showed significant value-directed enhancement of recognition memory for the words and points. Conversely, bvFTD patients did not prioritize recall of high-value words during learning trials, and this reduced selectivity was related to inhibitory dysfunction. Nonetheless, bvFTD patients showed value-directed enhancement of recognition memory for the point values, suggesting a mismatch between memory of high-value information and the ability to apply this in a motivationally salient context. Our findings demonstrate that value-directed enhancement of memory may persist to some degree in patients with dementia, despite pronounced deficits in learning and memory.
Publisher: eLife Sciences Publications, Ltd
Date: 10-09-2019
DOI: 10.7554/ELIFE.50890
Abstract: An fMRI experiment reveals distinct brain regions that respond in a graded manner as humans process distance information across increasing spatial scales.
Publisher: Cambridge University Press (CUP)
Date: 18-10-2016
DOI: 10.1017/S1355617716000837
Abstract: Objectives: With comparable baseline performance on executive functions (EF) and memory between Alzheimer’s disease (AD) and behavioral-variant frontotemporal dementia (bvFTD), it is currently unclear if both diseases can be distinguished longitudinally on these measures reliably. Methods: A total of 111 participants (33 AD, 31 bvFTD, and 47 controls) were followed-up annually over a 4-year period and tested on measures of EF, memory, and orientation. Linear mixed-effect models were constructed using disease severity as a nuisance variable to examine profiles of neuropsychological performance decline. Results: At baseline, overlap in terms of cognitive impairment between bvFTD and AD on multiple EF, memory, and orientation measures was present. Longitudinally, only disinhibition (Hayling total errors) appeared sensitive to discriminating AD from bvFTD however, only after the first annual follow-up. Subgroup analyses on smaller s les revealed comparable profiles on EF tasks at baseline and over time between bvFTD and AD who presented with impaired EF at presentation, and on memory and orientation tasks between AD and bvFTD who presented with severe amnesia. Conclusions: Our results replicate previous findings showing only moderate discriminability between AD and bvFTD at clinical presentation on EF and memory measures. More importantly, we also show that longitudinal trajectories strongly overlap for both dementias on these measures. Disinhibition emerged as the sole measure that in the long run was significantly more impaired in bvFTD. Future studies should use tests designed to target cortical regions that are specifically impaired in bvFTD, such as the ventromedial prefrontal cortex, to improve the accurate discrimination of these diseases. ( JINS , 2017, 23 , 34–43)
Publisher: Wiley
Date: 14-05-2013
DOI: 10.1002/HBM.22263
Publisher: Center for Open Science
Date: 22-09-2020
Abstract: Co-operative social behaviour in humans hinges upon our unique ability to make appropriate moral decisions in accordance with our ethical values. The complexity of the neurocognitive mechanisms underlying moral reasoning is revealed when this capacity breaks down. Patients with the behavioural variant of frontotemporal dementia (bvFTD) display striking moral transgressions in the context of atrophy to frontotemporal regions supporting affective and social conceptual processing. Developmental studies have highlighted the importance of social knowledge to moral decision making in children, yet the role of social knowledge in relation to moral reasoning impairments in neurodegeneration has largely been overlooked. Here, we sought to examine the role of affective and social conceptual processes in personal moral reasoning in bvFTD, and their relationship to the integrity and structural connectivity of frontotemporal brain regions. Personal moral reasoning across varying degrees of conflict was assessed in 26 bvFTD patients and compared with demographically matched Alzheimer’s disease (AD) patients (n = 14), and healthy older adults (n = 22). Following each moral decision, we directly probed participants’ subjective emotional experience as an index of their affective response, while social norm knowledge was assessed via an independent task. While groups did not differ significantly in terms of their moral decisions, bvFTD patients reported feeling better about their decisions than healthy Controls. In other words, although bvFTD patients could adjudicate between different courses of action in the moral scenarios, their affective responses to these decisions were highly irregular. This blunted emotional reaction was exclusive to the personal high-conflict condition, with 61.5% of bvFTD patients reporting feeling ‘extremely good’ about their decisions, and was correlated with reduced knowledge of socially acceptable behaviour. Voxel-based morphometry analyses revealed a distributed network of frontal, subcortical, and lateral temporal grey matter regions involved in the attenuated affective response to moral conflict in bvFTD. Crucially, diffusion-tensor imaging implicated the uncinate fasciculus as the pathway by which social conceptual knowledge may influence emotional reactions to personal high-conflict moral dilemmas in bvFTD. Our findings suggest that altered moral behaviour in bvFTD reflects the dynamic interplay between degraded social conceptual knowledge and blunted affective responsiveness, attributable to atrophy of, and impaired information transfer between, frontal and temporal cortices. Delineating the mechanisms of impaired morality in bvFTD provides crucial clinical information for understanding and treating this challenging symptom, which may help pave the way for targeted behavioural interventions.
Publisher: Society for Neuroscience
Date: 07-01-2015
Publisher: BMJ
Date: 12-05-2016
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2017.03.014
Abstract: Compromised autobiographical memory (ABM) retrieval is well established in dementia, attributable to degeneration of a core memory brain network. It remains unclear, however, how the progressive spread of atrophy with advancing disease severity impacts ABM retrieval across life epochs. To this end, we conducted a longitudinal study of recent and remote ABM in Alzheimer's disease (AD, n =11), and a frontotemporal lobar degeneration group (FTD, n =13) comprising 7 behavioral variant FTD and 6 semantic dementia patients, in comparison with 23 healthy older Controls. Patients were re-assessed approximately one year following their initial visit and underwent repeat testing and brain imaging. Linear mixed modeling neuroimaging analyses explored disease-specific cortical changes driving ABM alterations over time. AD patients showed comparable ABM profiles across assessment periods however, follow-up performance correlated strongly with lateral temporal lobe integrity. In contrast, recent ABMs were disproportionately disrupted at follow-up relative to baseline in the FTD group, attributable to cortical thinning in posterior brain regions, including the right posterior cingulate cortex. Our findings offer new insights regarding the potential time-specific role of discrete cortical regions in ABM retrieval and the differential fate of formerly evocative memories with advancing disease severity in dementia syndromes.
Publisher: Oxford University Press (OUP)
Date: 2021
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.CORTEX.2018.03.019
Abstract: Apathy is the most prevalent and disabling non-cognitive symptom of dementia and affects 90% of patients across the disease course. Despite its pervasiveness, how apathy manifests across dementia syndromes and the neurobiological mechanisms driving these symptoms are poorly understood. Here, we applied the multidimensional ABC model of apathy, which recognizes Affective, Behavioural and Cognitive apathy, in Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD). One hundred and twenty-two patients (53 AD 69 bvFTD) were included. Informants completed the Neuropsychiatric Inventory (NPI), Cambridge Behavioral Inventory and Disability and Dementia scale to quantify Affective, Behavioural and Cognitive apathy. All patients underwent structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) was employed to identify brain regions correlated with increased Affective, Behavioural and Cognitive apathy. On the NPI, 60% of AD and 84% of bvFTD patients had some degree of apathy, but bvFTD had more severe and more frequent symptoms than AD. Importantly, bvFTD patients had higher affective and cognitive apathy whereas AD had higher cognitive apathy only. Neuroimaging analyses revealed that affective apathy was associated with the ventral prefrontal cortex behavioural apathy with the basal ganglia and cognitive apathy with the dorsomedial prefrontal cortex. Finally, affective and behavioural apathy significantly predicted carer burden. Our results support the notion that apathy is multidimensional and manifests differently across dementia syndromes. Thus, novel interventions which target these ergent mechanisms will be necessary to improve motivation and goal-directed behaviour in people with dementia.
Publisher: Oxford University Press (OUP)
Date: 13-03-2012
Abstract: Episodic memory has recently been shown to be impaired in the behavioral variant of frontotemporal dementia (bvFTD) when so-called non-progressive cases are excluded. Such non-progressive cases present with the behavioral features of bvFTD, but show no evidence of cognitive decline over time. To date, evidence regarding episodic memory performance in bvFTD subgroups on more stringent tasks is lacking. We investigated temporal and spatial source memory in progressive (n = 7) versus non-progressive (n = 12) bvFTD. BvFTD cases were retrospectively classified based on general cognitive decline on the Addenbrooke's Cognitive Examination Revised, and the presence of atrophy on structural neuroimaging, over 3 years following diagnosis. Progressors showed impaired temporal and spatial source retrieval. Non-progressors displayed temporal source deficits only. These differential source memory profiles point to the variability of episodic memory performance in bvFTD, and underscore the importance of differential diagnosis of bvFTD subgroups using longitudinal and neuroimaging data.
Publisher: Elsevier BV
Date: 07-2018
Publisher: Public Library of Science (PLoS)
Date: 14-11-2014
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.CORTEX.2013.03.002
Abstract: Remembering the past and imagining the future are complex endeavours proposed to rely on a core neurobiological brain system. In the behavioural variant of frontotemporal dementia (bvFTD), regional patterns of brain atrophy affect medial prefrontal and temporal cortices of this core network. While autobiographical memory impairments have been documented in bvFTD, it remains unknown whether the ability to imagine future events is also compromised. Here, we investigated episodic future thinking in 10 bvFTD patients and contrasted their performance with Alzheimer's disease (AD, n = 10) and healthy matched Control (n = 10) participants. Participants were asked to remember 3 events from the previous year and to envisage 3 possible events that could occur in the next year. Both patient groups showed equivalent episodic detail performance for the retrieval of past events and the simulation of possible future episodes. Patients with bvFTD, however, showed additional impairments for the generation of external (non-episodic) details irrespective of condition. Voxel-based morphometry analyses revealed ergent neural correlates of episodic past and future thinking performance specific to each patient group. Atrophy in the posterior cingulate cortex was implicated in the disruption of past and future thinking in AD. In contrast, in bvFTD, disruption of past retrieval correlated with atrophy in medial prefrontal regions, whereas future thinking deficits were associated with atrophy of frontopolar, medial temporal regions including the right hippoc us, and lateral temporal and occipital cortices. Our results point to the involvement of multiple brain regions in facilitating retrieval of past, and simulation of future, events. Damage to any of these key regions thus adversely affects the ability to engage in personally relevant mental time travel.
Publisher: Oxford University Press (OUP)
Date: 12-04-2021
Abstract: Much of human behaviour is motivated by the drive to experience pleasure. The capacity to envisage pleasurable outcomes and to engage in goal-directed behaviour to secure these outcomes depends upon the integrity of frontostriatal circuits in the brain. Anhedonia refers to the diminished ability to experience, and to pursue, pleasurable outcomes, and represents a prominent motivational disturbance in neuropsychiatric disorders. Despite increasing evidence of motivational disturbances in frontotemporal dementia (FTD), no study to date has explored the hedonic experience in these syndromes. Here, we present the first study to document the prevalence and neural correlates of anhedonia in FTD in comparison with Alzheimer’s disease, and its potential overlap with related motivational symptoms including apathy and depression. A total of 172 participants were recruited, including 87 FTD, 34 Alzheimer’s disease, and 51 healthy older control participants. Within the FTD group, 55 cases were diagnosed with clinically probable behavioural variant FTD, 24 presented with semantic dementia, and eight cases had progressive non-fluent aphasia (PNFA). Premorbid and current anhedonia was measured using the Snaith-Hamilton Pleasure Scale, while apathy was assessed using the Dimensional Apathy Scale, and depression was indexed via the Depression, Anxiety and Stress Scale. Whole-brain voxel-based morphometry analysis was used to examine associations between grey matter atrophy and levels of anhedonia, apathy, and depression in patients. Relative to controls, behavioural variant FTD and semantic dementia, but not PNFA or Alzheimer’s disease, patients showed clinically significant anhedonia, representing a clear departure from pre-morbid levels. Voxel-based morphometry analyses revealed that anhedonia was associated with atrophy in an extended frontostriatal network including orbitofrontal and medial prefrontal, paracingulate and insular cortices, as well as the putamen. Although correlated on the behavioural level, the neural correlates of anhedonia were largely dissociable from that of apathy, with only a small region of overlap detected in the right orbitofrontal cortices whilst no overlapping regions were found between anhedonia and depression. This is the first study, to our knowledge, to demonstrate profound anhedonia in FTD syndromes, reflecting atrophy of predominantly frontostriatal brain regions specialized for hedonic tone. Our findings point to the importance of considering anhedonia as a primary presenting feature of behavioural variant FTD and semantic dementia, with distinct neural drivers to that of apathy or depression. Future studies will be essential to address the impact of anhedonia on everyday activities, and to inform the development of targeted interventions to improve quality of life in patients and their families.
Publisher: Cambridge University Press (CUP)
Date: 2018
DOI: 10.1017/S0140525X17001364
Abstract: Theoretical accounts placing episodic memory as central to constructive and communicative functions neglect the role of semantic memory. We argue that the decontextualized nature of semantic schemas largely supersedes the computational bottleneck and error-prone nature of episodic memory. Rather, neuroimaging and neuropsychological evidence of episodic-semantic interactions suggest that an integrative framework more accurately captures the mechanisms underpinning social communication.
Publisher: Oxford University Press
Date: 05-04-2018
DOI: 10.1093/OXFORDHB/9780190464745.013.6
Abstract: The capacity to engage in spontaneous self-generated thought is fundamental to the human experience, yet surprisingly little is known regarding the neurocognitive mechanisms that support this complex ability. Dementia syndromes offer a unique opportunity to study how the breakdown of large-scale functional brain networks impacts spontaneous cognition. Indeed, many of the characteristic cognitive changes in dementia reflect the breakdown of foundational processes essential for discrete aspects of self-generated thought. This chapter discusses how disease-specific alterations in memory-based/construction and mentalizing processes likely disrupt specific aspects of spontaneous, self-generated thought. In doing so, it provides a comprehensive overview of the neurocognitive architecture of spontaneous cognition, paying specific attention to how this sophisticated endeavor is compromised in dementia.
Publisher: American Medical Association (AMA)
Date: 03-2016
DOI: 10.1001/JAMANEUROL.2015.4478
Abstract: Abnormal eating behaviors are common in patients with frontotemporal dementia (FTD), yet their exact prevalence, severity, and underlying biological mechanisms are not understood. To define the severity of abnormal eating behavior and sucrose preference and their neural correlates in patients with behavioral variant FTD (bvFTD) and semantic dementia. Forty-nine patients with dementia (19 with bvFTD, 15 with semantic dementia, and 15 with Alzheimer disease) were recruited, and their eating behavior was compared with that of 25 healthy controls. The study was conducted from November 1, 2013, through May 31, 2015, and data analyzed from June 1 to August 31, 2015. Patients participated in an ad libitum breakfast test meal, and their total caloric intake and food preferences were measured. Changes in eating behavior were also measured using the Appetite and Eating Habits Questionnaire (APEHQ) and the Cambridge Behavioral Inventory (CBI). Sucrose preference was tested by measuring liking ratings of 3 desserts of varying sucrose content (A: 26%, B: 39%, C: 60%). Voxel-based morphometry analysis of whole-brain 3-T high-resolution brain magnetic resonance imaging was used to determine the gray matter density changes across groups and their relations to eating behaviors. Mean (SD) ages of patients in all 4 groups ranged from 62 (8.3) to 66 (8.4) years. At the ad libitum breakfast test meal, all patients with bvFTD had increased total caloric intake (mean, 1344 calories) compared with the Alzheimer disease (mean, 710 calories), semantic dementia (mean, 573 calories), and control groups (mean, 603 calories) (P < .001). Patients with bvFTD and semantic dementia had a strong sucrose preference compared with the other groups. Increased caloric intake correlated with atrophy in discrete neural networks that differed between patients with bvFTD and semantic dementia but included the cingulate cortices, thalami, and cerebellum in patients with bvFTD, with the addition of the orbitofrontal cortices and nucleus accumbens in patients with semantic dementia. A distributed network of neural correlates was associated with sucrose preference in patients with FTD. Marked hyperphagia is restricted to bvFTD, present in all patients with this diagnosis, and supports its diagnostic value. Differing neural networks control eating behavior in patients with bvFTD and semantic dementia and are likely responsible for the differences seen, with a similar network controlling sucrose preference. These networks share structures that control cognitive-reward, autonomic, neuroendocrine, and visual modulation of eating behavior. Delineating the neural networks involved in mediating these changes in eating behavior may enable treatment of these features in patients with complex medical needs and aid in our understanding of structures that control eating behavior in patients with FTD and healthy in iduals.
Publisher: Cambridge University Press (CUP)
Date: 08-01-2013
DOI: 10.1017/S1355617712001269
Abstract: Logopenic progressive aphasia (LPA) is a form of primary progressive aphasia (PPA) characterized by hesitant speech with marked impairment in naming and repetition. LPA is associated with brain atrophy in the left temporal and inferior parietal cortices and is predominantly associated with Alzheimer's disease (AD) pathology. In contrast to LPA, “typical” AD is commonly associated with episodic memory disturbance and bilateral medial temporal lobe atrophy. Recent evidence suggests verbal short-term memory is more impaired than visuospatial short-term memory in LPA. This study investigated verbal and visuospatial short-term memory in 12 LPA and 12 AD patients matched for disease severity, and in 12 age- and education-matched healthy controls. Overall, both patient groups showed significantly reduced verbal and visuospatial spans compared with controls. In addition, LPA patients performed significantly worse than AD patients on both forward and backward conditions of the Digit Span task. In contrast, no difference was present between patient groups on either version of the Spatial Span task. Importantly, LPA patients showed better visuospatial than verbal span whereas AD patients and controls did not differ across modality. This study demonstrates the specificity of the short-term memory disturbance in LPA, which arises from a breakdown of the phonological system. ( JINS , 2012, 19 , 1–7)
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2019.02.017
Abstract: Autobiographical memory dysfunction is a pervasive feature of neurodegenerative disorders, but less is known about the integrity of autobiographical memory in Huntington's disease (HD). Deficits in anterograde verbal episodic memory on traditional neuropsychological tests have been detected in HD, however, whether personally-relevant autobiographical retrieval is also affected is unknown. We examined autobiographical memory performance in 26 participants genetically confirmed to have HD who were in the peri-manifest stage of the disease (including 12 in the late premanifest stage and 14 who were early diagnosed), and 24 matched controls using the Autobiographical Interview (AI), a semi-structured interview assessing retrieval of autobiographical details from discrete epochs across the lifetime. Relative to controls, people with HD exhibited global episodic autobiographical memory impairments, regardless of recency or remoteness of the memory being retrieved. While specific cues bolstered the retrieval of episodic (internal) details in HD participants, their performance remained significantly below that of controls. Moreover, following probing, people with HD retrieved more extraneous (external) details not directly related to the autobiographical event they originally retrieved, including semantic details, repetitions, and metacognitive statements. Our results reveal marked autobiographical memory dysfunction in HD, not directly attributable to strategic retrieval deficits, and suggest that autobiographical memory impairment may represent an overlooked feature of the cognitive phenotype of HD.
Publisher: FapUNIFESP (SciELO)
Date: 03-2013
DOI: 10.1590/S1980-57642013DN70100014
Abstract: ABSTRACT Objective: Semantic dementia, a subtype of frontotemporal lobar degeneration, is characterised by cross-modal loss of conceptual knowledge attributable to progressive degeneration of the left anterior temporal lobe. Much less is known regarding the clinical presentation of SD patients with predominantly right-lateralised atrophy. Recent reports emphasise marked socioemotional and behavioural disturbances in such cases. Given the importance of the right anterior temporal lobes in social cognition, we hypothesised that socioemotional functioning would be disproportionately affected in right versus left-lateralised SD cases. Methods: We assessed well-characterised cases of predominantly right (n=10) and left (n=12) SD and 20 matched healthy controls on tests of emotion processing and interpersonal functioning. Results: Right SD cases showed disproportionate difficulties in the recognition of positive and negative facial emotions, specifically happiness and anger, compared with left SD cases. Deficits in anger recognition persisted in right SD despite covarying for facial and semantic processing. On a contextually rich task of emotion recognition using multimodal videos, no subgroup differences were evident. Finally, empathic concern was rated as significantly lower by caregivers of right versus left SD cases. Overall, the extent of socioemotional disturbance was associated with the degree of behavioural changes in SD. Conclusion: Our results reveal considerable overlap in the extent to which socioemotional processes are disrupted in left and right-lateralised cases of SD. Notably, however, right SD cases show disproportionate deficits for recognition of facial emotions and the capacity for empathic concern, supporting a specialised role for the right anterior temporal lobes in mediating these cognitive functions.
Publisher: Frontiers Media SA
Date: 20-07-2016
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2015.12.005
Abstract: Episodic memory impairment represents one of the hallmark clinical features of patients with Alzheimer's disease (AD) attributable to the degeneration of medial temporal and parietal regions of the brain. In contrast, a somewhat paradoxical profile of relatively intact episodic memory, particularly for non-verbal material, is observed in semantic dementia (SD), despite marked atrophy of the hippoc us. This retrospective study investigated the neural substrates of episodic memory retrieval in 20 patients with a diagnosis of SD and 21 disease-matched cases of AD and compared their performance to that of 35 age- and education-matched healthy older Controls. Participants completed the Rey Complex Figure and the memory subscale of the Addenbrooke's Cognitive Examination-Revised as indices of visual and verbal episodic recall, respectively. Relative to Controls, AD patients showed compromised memory performance on both visual and verbal memory tasks. In contrast, memory deficits in SD were modality-specific occurring exclusively on the verbal task. Controlling for semantic processing ameliorated these deficits in SD, while memory impairments persisted in AD. Voxel-based morphometry analyses revealed significant overlap in the neural correlates of verbal episodic memory in AD and SD with predominantly anteromedial regions, including the bilateral hippoc us, strongly implicated. Controlling for semantic processing negated this effect in SD, however, a distributed network of frontal, medial temporal, and parietal regions was implicated in AD. Our study corroborates the view that episodic memory deficits in SD arise very largely as a consequence of the conceptual loading of traditional tasks. We propose that the functional integrity of frontal and parietal regions enables new learning to occur in SD in the face of significant hippoc al and anteromedial temporal lobe pathology, underscoring the inherent complexity of the episodic memory circuitry.
Publisher: Center for Open Science
Date: 22-09-2020
Abstract: Traditional analyses of autobiographical construction have tended to focus on the ‘internal’ or episodic details of the narrative. Contemporary studies employing fine-grained scoring measures, however, reveal the ‘external’ component of autobiographical narratives to contain important information relevant to the in idual’s life story. Here, we used the recently developed NExt scoring protocol to explore profiles of external details generated by patients with Alzheimer’s disease (AD) (n = 11) and semantic dementia (SD) (n = 13) on a future thinking task. Voxel-based morphometry analyses of structural MRI were used to determine the neural correlates of external detail profiles in each patient group. Overall, distinct NExt profiles were observed across past and future temporal contexts in AD and SD groups, which involved elevations in external details, in the context of reduced internal details, relative to healthy Controls. Specifically, AD patients provided significantly more General Semantic details compared with Controls during past retrieval, whereas Specific Episode external details were elevated during future simulation. These increased external details within future narratives related to grey matter integrity in medial and lateral frontal regions in AD. By contrast, SD patients displayed an elevation of Specific Episode, Extended Episode, and General Semantic details exclusively during future simulation relative to Controls, which related to integrity of medial and lateral parietal regions. Our findings suggest that the compensatory external details generated during future simulation comprise an array of episodic and semantic details that vary in terms of specificity and self-relevance. Moreover, these profiles appear to be differentially affected depending on the locus of underlying neuropathology in dementia. Adopting a fine-grained approach to external details provides important information regarding the interplay between episodic and semantic content during future stimulation and highlights the differential vulnerability and preservation of distinct components of the constructed narrative in clinical disorders.
Publisher: American Medical Association (AMA)
Date: 12-2014
DOI: 10.1001/JAMANEUROL.2014.1931
Abstract: Presence of eating abnormalities is one of the core criteria for the diagnosis of behavioral variant frontotemporal dementia (bvFTD), yet their occurrence in other subtypes of frontotemporal dementia (FTD) and effect on metabolic health is not known. To define and quantify patterns of eating behavior and energy, sugar, carbohydrate, protein, and fat intake, as well as indices of metabolic health in patients with bvFTD and semantic dementia (SD) compared with patients with Alzheimer disease (AD) and healthy control participants. Prospective case-controlled study involving patient and caregiver completion of surveys. Seventy-five participants with dementia (21 with bvFTD, 26 with SD, and 28 with AD) and 18 age- and education-matched healthy controls were recruited from FRONTIER, the FTD research clinic at Neuroscience Research Australia in Sydney. Caregivers of patients with FTD and AD completed validated questionnaires on appetite, eating behaviors, energy consumption, and dietary macronutrient composition. All participants completed surveys on hunger and satiety. Body mass index and weight measurements were prospectively collected. The bvFTD group had significant abnormalities in the domains of appetite (U = 111.0, z = 2.7, P = .007), eating habits (U = 69.5, z = 3.8, P = .001), food preferences (U = 57.0, z = 4.1, P = .001), swallowing (U = 109.0, z = 3.0, P = .003), and other oral behaviors (U = 141.0, z = 2.6, P = .009) compared with the AD group. The bvFTD and SD groups tended to have increased energy consumption. Compared with controls, the bvFTD group had significantly increased carbohydrate intake (251 vs 170 g/d P = .05) and the SD group had significantly increased sugar intake (114 vs 76 g/d P = .049). No significant differences in total fat or protein intake between the groups were found. Despite similar energy intake, the SD group had lower hunger and satiety scores compared with the bvFTD group. In contrast, hunger and satiety scores did not differ between the bvFTD group and controls. The abnormal eating behavior was found in the 2 groups (bvFTD and SD) with the highest body mass index (F = 4.2, P = .008) and waist circumference (F = 6.4, P = .001). Abnormal eating behaviors are prominent in patients with bvFTD and those with SD and are not limited to increased appetite. The observed higher intake of sugar and carbohydrates was found in patients with the FTD subtypes and those with higher body mass index and waist circumference and was not explained simply by increased hunger or lower satiety.
Publisher: Frontiers Media SA
Date: 24-05-2016
Publisher: Springer Science and Business Media LLC
Date: 14-02-2012
Abstract: Converging evidence suggests that when in iduals are left to think to themselves, a so-called default network of the brain is engaged, allowing the in idual to daydream, reflect on their past, imagine possible future scenarios, and consider the viewpoints of others. These flexible self-relevant mental explorations enable the anticipation and evaluation of events before they occur, and are essential for successful social interactions. Such self-projective efforts are particularly vulnerable to disruption in frontotemporal dementia (FTD), a neurodegenerative disorder involving damage to the frontal and temporal lobes of the brain. In this Review, we explore how the progressive degeneration of the neural networks in two subtypes of FTD-the behavioral variant and semantic dementia-affects key structures of the default network and putative self-projective functions. We examine the available evidence from studies of autobiographical memory, episodic future thinking, theory of mind, moral reasoning, and economic decision-making in these neurodegenerative diseases. Finally, we propose that the mapping of default-network functions onto discrete subsystems of the default network may need revision in light of neuropsychological and clinical evidence from studies in patients with FTD.
Publisher: Springer Science and Business Media LLC
Date: 16-08-2022
DOI: 10.3758/S13421-021-01222-W
Abstract: While traditional analyses of autobiographical construction tend to focus on the 'internal' or episodic details of the narrative, contemporary studies employing fine-grained scoring measures reveal the 'external' component to contain important information relevant to the in idual's life story. Here, we used the recently developed NExt scoring protocol to explore profiles of external details generated by patients with Alzheimer's disease (AD) (n = 11) and semantic dementia (SD) (n = 13) on a future thinking task. Overall, distinct NExt profiles were observed for future events in AD and SD. Specifically, AD patients provided significantly more Specific Episode external details compared with Controls. Using voxel-based morphometry, these increased external details within future narratives related to grey matter intensity in medial and lateral frontal regions in AD. By contrast, SD patients displayed an elevation of Specific Episode, Extended Episode, and General Semantic details during future simulation relative to Controls, which related to grey matter intensity of medial and lateral parietal regions. Our findings suggest that the compensatory external details generated during future simulation comprise an array of episodic and semantic details that vary in terms of specificity and self-relevance, which may be differentially affected depending on the locus of underlying neuropathology in dementia. Adopting a fine-grained approach to external details helps to characterise the interplay between episodic and semantic content during future stimulation and suggests potentially differential vulnerability and preservation of distinct components of the constructed narrative in clinical disorders.
Publisher: Oxford University Press (OUP)
Date: 09-07-2013
DOI: 10.1093/BRAIN/AWT185
Abstract: The enhancing effect of emotion on subsequent memory retrieval is well established. Patients with frontotemporal dementia show profound emotion processing difficulties, yet the extent to which such deficits attenuate emotional enhancement of memory remains unknown. Here, we studied the intersection between emotion and memory using a visual forced-choice recognition test for negative and neutral stimuli in 34 patients with frontotemporal dementia compared with 10 patients with Alzheimer's disease and 15 control subjects. Control subjects and patients with Alzheimer's disease recognized more emotional than neutral items, as demonstrated by a significant interaction between emotion and memory for true recognition. This emotional enhancement effect was notably absent in the frontotemporal dementia cohort, with comparable recognition performance regardless of emotional content. Voxel-based morphometry analyses revealed distinct neural substrates for overall memory versus emotional memory performance. Overall memory performance correlated with the hippoc us, precuneus and posterior cingulate, regions crucial for successful episodic memory performance. Emotional enhancement of memory, by contrast, was associated exclusively with the integrity of the right orbitofrontal and subcallosal cortex. Our findings demonstrate differential disruption of emotional enhancement of memory in neurodegenerative disorders, and point toward the potentially pivotal role of the orbitofrontal cortex in supporting the successful retrieval of emotionally charged negative stimuli.
Publisher: Informa UK Limited
Date: 04-05-2021
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.NEUROBIOLAGING.2021.09.004
Abstract: Although characterized primarily as a language disorder, mounting evidence indicates episodic amnesia in Logopenic Progressive Aphasia (LPA). Whether such memory disturbances extend to information encoded pre-disease onset remains unclear. To address this question, we examined autobiographical memory in 10 LPA patients, contrasted with 18 typical amnestic Alzheimer's disease and 16 healthy Control participants. A validated assessment, the Autobiographical Interview, was employed to explore autobiographical memory performance across the lifespan under free and probed recall conditions. Relative to Controls, LPA patients showed global impairments across all time periods for free recall, scoring at the same level as disease-matched cases of Alzheimer's disease. Importantly, these retrieval deficits persisted in LPA, even when structured probing was provided, and could not be explained by overall level of language disruption or amount of information generated during autobiographical narration. Autobiographical memory impairments in LPA related to gray matter intensity decrease in predominantly posterior parietal brain regions implicated in memory retrieval. Together, our results suggest that episodic memory disturbances may be an under-appreciated clinical feature of LPA.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.BANDC.2014.11.001
Abstract: Self-generated cognition, or mind wandering, refers to the quintessentially human tendency to withdraw from the immediate external environment and engage in internally driven mentation. This thought activity is suggested to be underpinned by a distributed set of regions in the brain, referred to as the default network. To date, experimental assessment of mind wandering has typically taken place during performance of a concurrent attention-demanding task. The attentional demands of concurrent tasks can influence the emergence of mind wandering, and their application to clinical disorders with reduced cognitive resources is limited. Furthermore, few paradigms have investigated the phenomenological content of mind wandering episodes. Here, we present data from a novel thought s ling task that measures both the frequency and qualitative content of mind wandering, in the absence of a concurrent task to reduce cognitive demand. The task was validated in a non-pathological cohort of 31 older controls and resting-state functional connectivity analyses in a subset of participants (n=18) was conducted to explore the neural bases of mind wandering. Overall, instances of mind wandering were found to occur in 37% of experimental trials. Resting state functional connectivity analyses confirmed that mind wandering frequency was associated with regional patterns of both increased and decreased default network connectivity, namely in the temporal lobe, posterior cingulate cortex and dorsal medial prefrontal cortex. Our findings demonstrate that the novel task provides a context of low cognitive demand, which is conducive to mind wandering. Furthermore, performance on the task is associated with specific patterns of functional connectivity in the default network. Together, this new paradigm offers an important avenue to investigate the frequency and content of mind wandering in the context of low cognitive demands, and has significant potential to be applied in clinical conditions with reduced cognitive resources.
Publisher: Wiley
Date: 18-02-2016
DOI: 10.1111/BJC.12107
Abstract: Imagining future events, which contain episodic and non-episodic details, has been found to (1) engage the temporal lobes bilaterally and (2) be impaired in patients with bilateral temporal lobe pathology. Here, we examined whether unilateral temporal lobe dysfunction also impairs the ability to generate future events. Prospective cross-sectional. Twenty patients with a history of unilateral temporal lobe epilepsy [TLE 10 left (LTLE) and 10 right (RTLE)] and 20 normal control (NC) subjects comparable on age, sex and education completed the Adapted Autobiographical Interview, which required recall of past and generation of future events and distinguished episodic (internal) from non-episodic (external) details. Participants also completed a battery of neuropsychological tests. Patients with unilateral TLE were significantly impaired in provision of internal details for past and future events, but not in the generation of external details. Examination of detail subcategories revealed that patients with LTLE did exhibit a significant deficit relative to patients with RTLE (and NC) with respect to the generation of perceptual details for both past and future events. Moreover, patients with LTLE generated significantly fewer place details for future events (relative to NC only). The overall number of internal details recalled by patients with LTLE was related to semantic fluency. Our study provides the first evidence that unilateral temporal lobe dysfunction is associated with not only impaired recall of past, but also the generation of future episodic details. Clinically, deficits in future thinking may reduce motivation and decision-making, and as such adversely impact behavioural regulation and socialization. Patients with temporal lobe epilepsy generate less details when asked to describe past and potential future events, particularly with regard to details involving specific events, places and perceptions. These same patients are aware of their difficulties in this realm, but judge their past memories as similar in vividness and even more personally significant than the memories generated by control participants. The deficits in generation of future episodic details were particularly pronounced in patients with left temporal lobe epilepsy. Verbal semantic fluency was correlated with the ability to generate future scenarios.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-09-2015
Publisher: Oxford University Press (OUP)
Date: 07-01-2021
Abstract: Cooperative social behaviour in humans hinges upon our unique ability to make appropriate moral decisions in accordance with our ethical values. The complexity of the neurocognitive mechanisms underlying moral reasoning is revealed when this capacity breaks down. Patients with the behavioural variant of frontotemporal dementia (bvFTD) display striking moral transgressions in the context of atrophy to frontotemporal regions supporting affective and social conceptual processing. Developmental studies have highlighted the importance of social knowledge to moral decision making in children, yet the role of social knowledge in relation to moral reasoning impairments in neurodegeneration has largely been overlooked. Here, we sought to examine the role of affective and social conceptual processes in personal moral reasoning in bvFTD, and their relationship to the integrity and structural connectivity of frontotemporal brain regions. Personal moral reasoning across varying degrees of conflict was assessed in 26 bvFTD patients and compared with demographically matched Alzheimer’s disease patients (n = 14), and healthy older adults (n = 22). Following each moral decision, we directly probed participants’ subjective emotional experience as an index of their affective response, while social norm knowledge was assessed via an independent task. While groups did not differ significantly in terms of their moral decisions, bvFTD patients reported feeling ‘better’ about their decisions than healthy control subjects. In other words, although bvFTD patients could adjudicate between different courses of action in the moral scenarios, their affective responses to these decisions were highly irregular. This blunted emotional reaction was exclusive to the personal high-conflict condition, with 61.5% of bvFTD patients reporting feeling ‘extremely good’ about their decisions, and was correlated with reduced knowledge of socially acceptable behaviour. Voxel-based morphometry analyses revealed a distributed network of frontal, subcortical, and lateral temporal grey matter regions involved in the attenuated affective response to moral conflict in bvFTD. Crucially, diffusion-tensor imaging implicated the uncinate fasciculus as the pathway by which social conceptual knowledge may influence emotional reactions to personal high-conflict moral dilemmas in bvFTD. Our findings suggest that altered moral behaviour in bvFTD reflects the dynamic interplay between degraded social conceptual knowledge and blunted affective responsiveness, attributable to atrophy of, and impaired information transfer between, frontal and temporal cortices. Delineating the mechanisms of impaired morality in bvFTD provides crucial clinical information for understanding and treating this challenging symptom, which may help pave the way for targeted behavioural interventions.
Publisher: Center for Open Science
Date: 23-09-2021
Abstract: Intertemporal decision-making has long been assumed to measure self-control, with prominent theories treating choices of smaller, sooner rewards as failed attempts to override immediate temptation. If this view is correct, people should be more confident in their intertemporal decisions when they “successfully” delay gratification than when they do not. In two pre- registered experiments with built-in replication, adult participants (n=117) made monetary intertemporal choices and rated their confidence in having made the right decisions. Contrary to assumptions of the self-control account, confidence was not higher when participants chose delayed rewards. Rather, participants were more confident in their decisions when possible rewards were further apart in time-discounted subjective value, closer to the present, and larger in magnitude. Demonstrating metacognitive insight, participants were more confident in decisions that better aligned with their independent valuation of possible rewards. Decisions made with less confidence were more prone to changes-of-mind and more susceptible to a patience-enhancing manipulation. Together, our results establish that confidence in intertemporal choice tracks uncertainty in estimating and comparing the value of possible rewards – just as it does in decisions unrelated to self-control. Our findings challenge self- control views and instead cast intertemporal choice as a form of value-based decision-making about future possibilities.
Publisher: Springer Science and Business Media LLC
Date: 12-2010
Publisher: Cambridge University Press (CUP)
Date: 09-2018
DOI: 10.1017/S1355617718000541
Abstract: Objectives: The Addenbrooke’s Cognitive Examination (ACE) is a common cognitive screening test for dementia. Here, we examined the relationship between the most recent version (ACE-III) and its predecessor (ACE-R), determined ACE-III cutoff scores for the detection of dementia, and explored its relationship with functional ability. Methods: Study 1 included 199 dementia patients and 52 healthy controls who completed the ACE-III and ACE-R. ACE-III total and domain scores were regressed on their corresponding ACE-R values to obtain conversion formulae. Study 2 included 331 mixed dementia patients and 87 controls to establish the optimal ACE-III cutoff scores for the detection of dementia using receiver operator curve analysis. Study 3 included 194 dementia patients and their carers to investigate the relationship between ACE-III total score and functional ability. Results: Study 1: ACE-III and ACE-R scores differed by ≤1 point overall, the magnitude varying according to dementia type. Study 2: a new lower bound cutoff ACE-III score of 84/100 to detect dementia was identified (compared with 82 for the ACE-R). The upper bound cutoff score of 88/100 was retained. Study 3: ACE-III scores were significantly related to functional ability on the Clinical Dementia Rating Scale across all dementia syndromes, except for semantic dementia. Conclusions: This study represents one of the largest and most clinically erse investigations of the ACE-III. Our results demonstrate that the ACE-III is an acceptable alternative to the ACE-R. In addition, ACE-III performance has broader clinical implications in that it relates to carer reports of functional impairment in most common dementias. ( JINS , 2018, 24 , 854–863)
Publisher: Elsevier BV
Date: 2018
Publisher: MDPI AG
Date: 06-09-2022
Abstract: Balanced time perspective refers to the ability to flexibly switch between different temporal foci in an adaptive manner according to the current context. Functional connectivity within the default mode network (DMN) has been suggested to support balanced time perspective. The coupling between the DMN and fronto-parietal network (FPN) may drive many important expressions of internally directed cognition. However, it remains unclear whether balanced time perspective is supported by the interaction between the FPN and DMN. To examine these issues, we recruited 91 participants (52 males with mean age of 19.6, and 39 females with mean age of 20.0) to undergo resting-state brain imaging scan and to complete a questionnaire measuring balanced time perspective. Seed-based voxel-wise functional connectivity analyses implicated midline DMN regions including the anterior medial prefrontal cortex (amPFC) and posterior cingulate cortex (PCC) along with the anterior cingulate cortex (ACC), precuneus, and cerebellum in supporting a balanced time perspective. More importantly, functional connectivity between the right amPFC and right dorsal lateral prefrontal cortex (DLPFC) in the FPN was found to associate with balanced time perspective. Our findings suggest the importance of coordinated brain activity in supporting a balanced time perspective.
Publisher: S. Karger AG
Date: 2006
DOI: 10.1159/000093487
Abstract: The enhancing effect of music on autobiographical memory recall in mild Alzheimer’s disease in iduals (n = 10 Mini-Mental State Examination score /30) and healthy elderly matched in iduals (n = 10 Mini-Mental State Examination score 25–30) was investigated. Using a repeated-measures design, each participant was seen on two occasions: once in music condition (Vivaldi’s ‘Spring’ movement from ‘The Four Seasons’) and once in silence condition, with order counterbalanced. Considerable improvement was found for Alzheimer in iduals’ recall on the Autobiographical Memory Interview in the music condition, with an interaction for condition by group (p 0.005). There were no differences in terms of overall arousal using galvanic skin response recordings or attentional errors during the Sustained Attention to Response Task. A significant reduction in state anxiety was found on the State Trait Anxiety Inventory in the music condition (p 0.001), suggesting anxiety reduction as a potential mechanism underlying the enhancing effect of music on autobiographical memory recall.
Publisher: Wiley
Date: 23-12-2022
DOI: 10.1111/EJN.15557
Abstract: Primary progressive aphasia (PPA) is a neurodegenerative clinical syndrome characterised by a progressive decline in speech and language functions. Deficits in behaviour, mood and functional capacity are reported in PPA but are less well understood. This study examined the PPA variants' profiles on these domains at initial presentation and over time and evaluated their relations to overall cognitive ability. Behaviour, mood and functional capacity were measured annually (over ~6 years) in 145 in iduals diagnosed with PPA (41 logopenic [lv‐PPA], 44 non‐fluent [nfv‐PPA] and 60 semantic variants [sv‐PPA]) using the Cambridge Behavioural Inventory‐Revised (CBI‐R) carer questionnaire. Overall cognition was assessed annually with the Addenbrooke's Cognitive Examination‐III. Distinct profiles were observed across PPA syndromes. Notably, sv‐PPA carers reported greater behavioural, eating and motivational disturbances than the other PPA variants throughout the disease course. Reported memory problems were also greater in sv‐PPA and lv‐PPA than in nfv‐PPA across all time points. These disturbances occurred in the context of the sv‐PPA group demonstrating a slower rate of cognitive decline than the lv‐PPA group and a parallel rate to that found in the nfv‐PPA group. Associations between overall cognition and the CBI‐R domains were trivial at baseline assessment however, distinct profiles emerged when mapping each syndrome's overall cognitive decline with their behavioural, mood and functional trajectories. Our findings demonstrate that the evolving behaviour, mood and functional capacity profiles of the PPA variants are distinct and extend beyond the primary disorder of language. These findings have important implications for clinical management and caregiver education in PPA.
Publisher: Wiley
Date: 06-08-2021
DOI: 10.1111/ENE.15035
Abstract: Differentiating the primary progressive aphasia (PPA) variants in clinical settings remains complex and challenging, especially for the logopenic (lv‐PPA) and non‐fluent variants (nfv‐PPA). Recent studies suggest that visuospatial memory is more compromised in lv‐PPA than in nfv‐PPA and is relatively spared in the semantic variant (sv‐PPA). Accordingly, assessment of visuospatial memory performance may assist in the differential diagnosis of PPA variants. Here, we investigated the utility of a novel computerised visuospatial working memory test—the Box Task—to differentiate the three PPA variants and typical Alzheimer’s disease (AD). Eighteen lv‐PPA, 14 nfv‐PPA, 23 sv‐PPA, 33 AD patients, and 32 healthy controls matched for age and education were recruited. All participants completed the computerised Box Task and WMS‐III Spatial Span as measures of visuospatial working memory. The lv‐PPA group made significantly more Box Task between‐search errors than nfv‐PPA, sv‐PPA and control groups. The AD group, however, displayed the greatest impairments on this measure relative to the PPA variants. Logistic regression analyses in lv‐PPA and nfv‐PPA demonstrated that the combination of Box Task between‐search error variables (i.e., 4‐ and 6‐box levels) could correctly classify 72% of lv‐PPA patients and nearly 79% of nfv‐PPA patients. Area under the receiver operator characteristics curve (AUC) analyses revealed the Box Task was more sensitive than Spatial Span at differentiating lv‐PPA from nfv‐PPA. Our findings suggest that a simple, computerised measure of visuospatial working memory—the Box Task—shows potential diagnostic utility in differentiating lv‐PPA from the other PPA variants.
Publisher: Cold Spring Harbor Laboratory
Date: 17-06-2019
Abstract: Converging evidence suggests a critical role for the parietal cortices in episodic memory retrieval. Here, we examined episodic memory performance in Corticobasal Syndrome (CBS), a rare neurodegenerative disorder presenting with early parietal atrophy in the context of variable medial temporal lobe damage. Forty-four CBS patients were contrasted with 29 typical Alzheimer's disease (AD), 29 healthy Controls, and 20 progressive supranuclear palsy patients presenting with brainstem atrophy as a disease control group. Participants completed standardized assessments of verbal episodic memory (learning, delayed recall, and recognition), and underwent structural and diffusion-weighted MRI. Selective delayed recall deficits were evident in the CBS group relative to Controls, at an intermediate level to the stark amnesia displayed by AD, and Control-level performance noted in progressive supranuclear palsy. Considerable variability within the CBS group on delayed recall performance led to the identification of memory-spared ( N = 19) and memory-impaired ( N = 25) subgroups. Whereas CBS-Spared showed no significant memory deficits, the CBS-Impaired subgroup were indistinguishable from typical AD across all episodic memory measures. Whole-brain voxel-based morphometry analyses implicated fronto-parietal and medial temporal regions in delayed recall performance in both the CBS-Impaired and AD groups. Furthermore, diffusion tensor imaging analyses revealed correlations between delayed recall performance and altered structural connectivity between fronto-parietal and frontotemporal regions in the CBS-Impaired group. Our findings underscore the importance of a distributed brain network including frontal, medial temporal, and parietal brain regions in supporting the capacity for successful episodic memory retrieval.
Publisher: Oxford University Press (OUP)
Date: 20-07-2022
Abstract: The logopenic variant of primary progressive aphasia is characterized by early deficits in language production and phonological short-term memory, attributed to left-lateralized temporoparietal, inferior parietal and posterior temporal neurodegeneration. Despite patients primarily complaining of language difficulties, emerging evidence points to performance deficits in non-linguistic domains. Temporoparietal cortex, and functional brain networks anchored to this region, are implicated as putative neural substrates of non-linguistic cognitive deficits in logopenic variant primary progressive aphasia, suggesting that degeneration of a shared set of brain regions may result in co-occurring linguistic and non-linguistic dysfunction early in the disease course. Here, we provide a Review aimed at broadening the understanding of logopenic variant primary progressive aphasia beyond the lens of an exclusive language disorder. By considering behavioural and neuroimaging research on non-linguistic dysfunction in logopenic variant primary progressive aphasia, we propose that a significant portion of multidimensional cognitive features can be explained by degeneration of temporal/inferior parietal cortices and connected regions. Drawing on insights from normative cognitive neuroscience, we propose that these regions underpin a combination of domain-general and domain-selective cognitive processes, whose disruption results in multifaceted cognitive deficits including aphasia. This account explains the common emergence of linguistic and non-linguistic cognitive difficulties in logopenic variant primary progressive aphasia, and predicts phenotypic ersification associated with progression of pathology in posterior neocortex.
Publisher: MDPI AG
Date: 24-12-2021
Abstract: Scene construction refers to the process by which humans generate richly detailed and spatially cohesive scenes in the mind’s eye. The cognitive processes that underwrite this capacity remain unclear, particularly when the envisaged scene calls for the integration of various types of contextual information. Here, we explored social and non-social forms of scene construction in Alzheimer’s disease (AD n = 11) and the behavioural variant of frontotemporal dementia (bvFTD n = 15) relative to healthy older control participants (n = 16) using a novel adaptation of the scene construction task. Participants mentally constructed detailed scenes in response to scene–object cues that varied in terms of their sociality (social non-social) and congruence (congruent incongruent). A significant group × sociality × congruence interaction was found whereby performance on the incongruent social scene condition was significantly disrupted in both patient groups relative to controls. Moreover, bvFTD patients produced significantly less contextual detail in social relative to non-social incongruent scenes. Construction of social and non-social incongruent scenes in the patient groups combined was significantly associated with independent measures of semantic processing and visuospatial memory. Our findings demonstrate the influence of schema-incongruency on scene construction performance and reinforce the importance of episodic–semantic interactions during novel event construction.
Publisher: Springer Science and Business Media LLC
Date: 23-12-2019
DOI: 10.1007/S00415-019-09679-1
Abstract: Apathy is one of the most prevalent and disabling non-cognitive symptoms of dementia. This loss of motivation and pervasive decline in goal-directed behaviour represents a core diagnostic feature of behavioural-variant frontotemporal dementia (bvFTD) and is also common in Alzheimer's disease (AD). However, despite growing recognition of a multidimensional model, apathy has typically been examined as a unitary symptom. Here, we employed a cross-sectional design to characterise the multidimensional nature of apathy across syndromes and disease course. 92 participants (44 bvFTD, 20 AD, 28 controls) completed the Dimensional Apathy Scale (DAS) to quantify emotional, executive, and initiation apathy. Patients were ided into early and late stages based on time since symptom onset. All participants underwent structural MRI and voxel-based morphometry was used to identify neural correlates of apathy dimensions. In the early stage of the disease ( 5 years since onset), executive apathy was greater in AD than bvFTD, although apathy was elevated across all dimensions compared to controls. Notably, apathy was observed in the absence of self-reported depression in 46.2% of patients, with no patients classified as depressed only. Neuroimaging analyses revealed both common and ergent prefrontal and subcortical neural correlates associated with apathy dimensions. Our results reveal differing profiles of apathy across the disease course, in AD and bvFTD, with distinct brain regions mediating these dimensions. These findings will inform the development of appropriate treatment targets to ameliorate the impact of apathy in dementia.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.NEUROSCIENCE.2017.10.049
Abstract: Human lesion studies represent the cornerstone of modern day neuropsychology and provide an important adjunct to functional neuroimaging methods. The study of human lesion groups with damage to distinct regions of the brain permits the identification of underlying mechanisms and structures not only associated with, but essential for, complex cognitive processes. Here, we consider a recent review by McCormick et al., 2018 in which the power of the lesion model approach is elegantly presented with respect to a host of sophisticated cognitive endeavors, including autobiographical memory, future thinking, spatial navigation, and decision-making. By comparing profiles of loss and sparing in hippoc al (HC) and ventromedial prefrontal cortex (vmPFC) lesion groups, the authors provide new insights into the underlying neuroarchitecture of these erse cognitive functions. Building on this framework, we consider how vmPFC and HC degeneration, in the context of large-scale network dysfunction in dementia, impacts discrete facets of memory and social cognition. Notably, we find remarkable concordance between the available evidence in dementia and that of the HC and vmPFC lesion literature. We further assess the role of the prefrontal cortex in modulating aspects of spatial navigation and discuss the role of schema-related processing in the service of memory more broadly. Far from being obsolete, we contend that human lesion work occupies a crucial position in cognitive neuroscience and offers an array of exciting areas for future study within this field.
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.CORTEX.2015.08.004
Abstract: Episodic memory dysfunction represents one of the most prominent and characteristic clinical features of patients with Alzheimer's disease (AD), attributable to the degeneration of medial temporal and posterior parietal regions of the brain. Recent studies have demonstrated marked impairments in the ability to envisage personally relevant events in the future in AD. It remains unclear, however, whether AD patients can imagine fictitious scenes free from temporal constraints, a process that is proposed to rely fundamentally upon the integrity of the hippoc us. The objective of the present study was to investigate the capacity for atemporal scene construction, and its associated neural substrates, in AD. Fourteen AD patients were tested on the scene construction task and their performance was contrasted with 14 age- and education-matched healthy older Control participants. Scene construction performance was strikingly compromised in the AD group, with significant impairments evident for provision of contextual details, spatial coherence, and the overall richness of the imagined experience. Voxel-based morphometry analyses based on structural MRI revealed significant associations between scene construction capacity and atrophy in posterior parietal and lateral temporal brain structures in AD. In contrast, scene construction performance in Controls was related to integrity of frontal, parietal, and medial temporal structures, including the parahippoc al gyrus and posterior hippoc us. The posterior cingulate cortex (PCC) emerged as the common region implicated for scene construction performance across participant groups. Our study highlights the importance of regions specialised for spatial and contextual processing for the construction of atemporal scenes. Damage to these regions in AD compromises the ability to construct novel scenes, leading to the recapitulation of content from previously experienced events.
Publisher: Oxford University Press (OUP)
Date: 2020
DOI: 10.1093/BRAINCOMMS/FCAA194
Abstract: Mounting evidence suggests an association between cerebellar atrophy and cognitive impairment in the main frontotemporal dementia syndromes. In contrast, whether cerebellar atrophy is present in the motor syndromes associated with frontotemporal lobar degeneration (corticobasal syndrome and progressive supranuclear palsy) and the extent of its contribution to their cognitive profile remain poorly understood. The current study aimed to comprehensively chart profiles of cognitive impairment in relation to cerebellar atrophy in 49 dementia patients (corticobasal syndrome = 33 progressive supranuclear palsy = 16) compared to 33 age-, sex- and education-matched healthy controls. Relative to controls, corticobasal syndrome and progressive supranuclear palsy patients demonstrated characteristic cognitive impairment, spanning the majority of cognitive domains including attention and processing speed, language, working memory, and executive function with relative preservation of verbal and nonverbal memory. Voxel-based morphometry analysis revealed largely overlapping patterns of cerebellar atrophy in corticobasal syndrome and progressive supranuclear palsy relative to controls, primarily involving bilateral Crus II extending into adjacent lobules VIIb and VIIIa. After controlling for overall cerebral atrophy and disease duration, exploratory voxel-wise general linear model analysis revealed distinct cerebellar subregions differentially implicated across cognitive domains in each patient group. In corticobasal syndrome, reduction in grey matter intensity in the left Crus I was significantly correlated with executive dysfunction. In progressive supranuclear palsy, integrity of the vermis and adjacent right lobules I–IV was significantly associated with language performance. These results are consistent with the well-established role of Crus I in executive functions and provide further supporting evidence for vermal involvement in cognitive processing. The current study presents the first detailed exploration of the role of cerebellar atrophy in cognitive deficits in corticobasal syndrome and progressive supranuclear palsy, offering insights into the cerebellum’s contribution to cognitive processing even in neurodegenerative syndromes characterized by motor impairment.
Publisher: MDPI AG
Date: 03-2022
Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of the same disease spectrum. While thalamic–cerebellar degeneration has been observed in C9orf72 expansion carriers, the exact subregions involved across the clinical phenotypes of the ALS–FTD spectrum remain unclear. Using MRIs from 58 bvFTD, 41 ALS–FTD and 52 ALS patients compared to 57 controls, we aimed to delineate thalamic and cerebellar subregional changes across the ALS–FTD spectrum and to contrast these profiles between cases with and without C9orf72 expansions. Thalamic involvement was evident across all ALS–FTD clinical phenotypes, with the laterodorsal nucleus commonly affected across all groups (values below the 2.5th control percentile). The mediodorsal nucleus was disproportionately affected in bvFTD and ALS–FTD but not in ALS. Cerebellar changes were only observed in bvFTD and ALS–FTD predominantly in the superior–posterior region. Comparison of genetic versus sporadic cases revealed significantly lower volumes exclusively in the pulvinar in C9orf72 expansion carriers compared to non-carriers, irrespective of clinical syndrome. Overall, bvFTD showed significant correlations between thalamic subregions, level of cognitive dysfunction and severity of behavioural symptoms. Notably, strong associations were evident between mediodorsal nucleus atrophy and severity of behavioural changes in C9orf72-bvFTD (r = −0.9, p 0.0005). Our findings reveal distinct thalamic and cerebellar atrophy profiles across the ALS–FTD spectrum, with differential impacts on behaviour and cognition, and point to a unique contribution of C9orf72 expansions in the clinical profiles of these patients.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.NEUBIOREV.2017.01.004
Abstract: Frontotemporal dementia (FTD) is the second most common cause of young onset dementia. It is increasingly recognized that there is a clinical continuum between FTD and amyotrophic lateral sclerosis (ALS). At a clinical, pathological and genetic level there is much heterogeneity in FTD, meaning that our understanding of this condition, pathophysiology and development of treatments has been limited. A number of mouse models focusing predominantly on recapitulating neuropathological and molecular changes of disease have been developed, with most transgenic lines expressing a single specific protein or genetic mutation. Together with the species-typical presentation of functional deficits, this makes the direct translation of results from these models to humans difficult. However, understanding the phenotypical presentations in mice and how they relate to clinical symptomology in humans is essential for advancing translation. Here we review current mouse models in FTD and compare their phenotype to the clinical presentation in patients.
Publisher: Wiley
Date: 27-05-2016
DOI: 10.1111/JNP.12073
Abstract: Compromised retrieval of autobiographical memory (ABM) is well established in neurodegenerative disorders. The recounting of autobiographical events is inextricably linked to linguistic knowledge, yet no study to date has investigated whether tense use during autobiographical narration is disrupted in dementia syndromes. This study investigated the incidence of correct past tense use during ABM narration in patients with Alzheimer's disease (AD, n = 10) and semantic dementia (SD, n = 10) in comparison with healthy older Controls (n = 10). Autobiographical narratives were analysed for episodic content (internal/external) and classified according to tense use (past resent). Across both patient groups, use of the past tense was significantly compromised relative to Controls, with increased levels of off-target present tense verbs observed. Voxel-based morphometry analyses based on structural MRI revealed differential associations between past tense use and regions of grey matter intensity in the brain. Bilateral temporal cortices were implicated in the SD group, whereas frontal, lateral, and medial temporal regions including the right hippoc us emerged in AD. This preliminary study provides the first demonstration of the disruption of specific linguistic constructs during autobiographical narration in AD and SD. Future studies are warranted to clarify at what point in the disease trajectory such deficits in tense use emerge, and whether these deficits are a product or contributing factor in memory disruption in these syndromes.
Publisher: Wiley
Date: 07-2018
DOI: 10.1002/ANA.25271
Abstract: Increasing evidence suggests that cerebellar damage impacts on cognitive functions. Frontotemporal dementias (FTDs) are neurodegenerative brain conditions, primarily affecting the frontal and/or temporal lobe. Three main phenotypes are recognized, each with a distinct clinical and cognitive profile: behavioral-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). The severity of cerebellar changes and their relation to cognition in FTD, however, remain unclear. This study aimed to establish cerebellar gray matter changes on magnetic resonance imaging (MRI) and their relation to profiles of cognitive deficits in FTD subtypes. Ninety-six FTD patients (45 bvFTD, 28 SD, and 23 PNFA), meeting current clinical diagnostic criteria, and 35 age-, sex-, and education-matched controls underwent brain MRI and cognitive assessment. Cerebral and cerebellar gray matter integrity were investigated using voxel-based morphometry. Compared with controls, widespread bilateral cerebellar changes were observed in all FTD subtypes, with the greatest atrophy present in bvFTD. Significant associations were found between cerebellar integrity and cognitive performance in attention and working memory in bvFTD, visuospatial function in SD, and language-motor function in PNFA. Bilateral atrophy of crus and lobule VI were most commonly associated with cognitive deficits, irrespective of FTD phenotype. This study is the first to identify distinct patterns of cerebellar atrophy across FTD syndromes, which in turn relate to discrete cognitive dysfunctions, after accounting for the effect of cerebral atrophy. These findings extend our understanding of the cerebellum and point to its involvement across an array of processes beyond the domain of motor function. Ann Neurol 2018 :98-109.
Publisher: American Psychological Association (APA)
Date: 11-2016
DOI: 10.1037/NEU0000291
Abstract: The loss of autobiographical memories (ABM) is a pervasive feature of neurodegenerative diseases. Studies to date have not investigated ABM retrieval in amyotrophic lateral sclerosis (ALS), a multisystem disorder that may be associated with cognitive dysfunction and dementia. The integrity of autobiographical memory was evaluated in 22 ALS patients compared with 28 age-matched controls using the Autobiographical Interview (AI), a semistructured interview assessing autobiographical events from discrete time periods across the life span. ABM retrieval was preserved in ALS and remained rich in detail for personal events in recent (last 12-months) and remote (teenage years) time epochs. ABM retrieval was positively correlated with months since ALS symptom onset, with a greater number of contextual details being recalled as ALS progressed. A shift in how ABMs were perceived in ALS patients became apparent, with more recurrent reflection of recent life, which was also weighted with greater personal importance. The preservation of ABM in ALS has clinical implications for the use of life review as a therapeutic tool in a multidisciplinary care setting. (PsycINFO Database Record
Publisher: BMJ
Date: 15-12-2015
Abstract: Right-lateralised semantic dementia (right SD) and behavioural-variant frontotemporal dementia (bvFTD) appear clinically similar, despite different patterns of underlying brain changes. This study aimed to elucidate distinguishing clinical and cognitive features in right SD versus bvFTD, emphasising emotion processing and its associated neural correlates. 12 patients with right SD and 19 patients with bvFTD were recruited. Clinical features were documented. All patients were assessed on standardised neuropsychological tests and a facial emotion processing battery. Performance was compared to 20 age-matched and education-matched controls. Grey matter intensity was related to emotion processing performance using whole-brain voxel-based morphometry analysis. Patients with right SD exhibited disproportionate language dysfunction, prosopagnosia and a suggestion of increased obsessive personality/behavioural changes versus patients with bvFTD. In contrast, patients with bvFTD demonstrated pronounced deficits in attention/working memory, increased apathy and greater executive dysfunction, compared to patients with right SD. Decreased empathy, disinhibition and diet changes were common to both dementia subtypes. Emotion processing deficits were present in both FTD syndromes but were associated with ergent patterns of brain atrophy. In right SD, emotion processing dysfunction was associated with predominantly right medial and lateral temporal integrity, compared to mainly left temporal, inferior frontal and orbitofrontal and right frontal gyrus integrity in bvFTD. This study demonstrates comparable deficits in facial emotion processing in right SD and bvFTD, in keeping with their similar clinical profiles. These deficits are attributable to ergent neural substrates in each patient group, namely, right lateralised regions in right SD, versus predominantly left lateralised regions in bvFTD.
Publisher: Springer Science and Business Media LLC
Date: 06-10-2019
DOI: 10.1007/S00426-018-1102-8
Abstract: An intriguing aspect of human cognition is the unique capacity to mentally retreat from our immediate surroundings to consider perspectives distinct from the here and now. Despite increasing interest in this phenomenon, relatively little is known regarding age-related changes in off-task, self-generated thought (often referred to as "mind-wandering"), particularly under conditions of low cognitive demand. While a number of studies have investigated the temporal orientation of mind-wandering with increasing age, findings have been largely inconsistent. Here, we explored the frequency, temporal focus, and self-referential/social content of spontaneous task-unrelated, perceptually decoupled thought in 30 young and 33 healthy older adults using the Shape Expectations task, a validated experimental paradigm in which discrete facets of inner mentation are quantified along a conceptual continuum using open-ended report. Participants also completed the daydreaming subscale of the Imaginal Process Inventory (IPI) as a trait measure of mind-wandering propensity. Significant group differences emerged on the Shape Expectations task, with reduced instances of mind-wandering in the context of elevated task-related thoughts relative to younger adults. In terms of temporal focus, a preponderance of present/atemporal off-task thoughts was evident irrespective of group however, significantly higher levels of future-oriented thoughts were provided by younger adults, contrasting with significantly higher instances of retrospection in the older group. In addition, older adults displayed significantly fewer incidences of self-referential cognition relative to their younger counterparts. Our findings indicate a distinct attenuation of off-task, self-generated thought processes with increasing age, with evidence for a shift in temporal focus and self-referential quality, during periods of low cognitive demand.
Publisher: Frontiers Media SA
Date: 2013
Neurocognitive mechanisms of theory of mind impairment in neurodegeneration: a transdiagnostic approach
Publisher: Informa UK Limited
Date: 02-2019
DOI: 10.2147/NDT.S158996
Publisher: Center for Open Science
Date: 28-09-2020
Abstract: While traditional analyses of autobiographical construction tend to focus on the ‘internal’ or episodic details of the narrative, contemporary studies employing fine-grained scoring measures reveal the ‘external’ component to contain important information relevant to the in idual’s life story. Here, we used the recently developed NExt scoring protocol to explore profiles of external details generated by patients with Alzheimer’s disease (AD) (n = 11) and semantic dementia (SD) (n = 13) on a future thinking task. Overall, distinct NExt profiles were observed for future events in AD and SD. Specifically, AD patients provided significantly more Specific Episode external details compared with Controls. Using voxel-based morphometry, these increased external details within future narratives related to grey matter intensity in medial and lateral frontal regions in AD. By contrast, SD patients displayed an elevation of Specific Episode, Extended Episode, and General Semantic details during future simulation relative to Controls, which related to grey matter intensity of medial and lateral parietal regions. Our findings suggest that the compensatory external details generated during future simulation comprise an array of episodic and semantic details that vary in terms of specificity and self-relevance, which may be differentially affected depending on the locus of underlying neuropathology in dementia. Adopting a fine-grained approach to external details helps to characterise the interplay between episodic and semantic content during future stimulation and suggests potentially differential vulnerability and preservation of distinct components of the constructed narrative in clinical disorders.
Publisher: Oxford University Press (OUP)
Date: 29-12-2022
DOI: 10.1093/BRAINCOMMS/FCAC344
Abstract: Two common clinical variants of frontotemporal dementia are the behavioural variant frontotemporal dementia, presenting with behavioural and personality changes attributable to prefrontal atrophy, and semantic dementia, displaying early semantic dysfunction primarily due to anterior temporal degeneration. Despite representing independent diagnostic entities, mounting evidence indicates overlapping cognitive–behavioural profiles in these syndromes, particularly with disease progression. Why such overlap occurs remains unclear. Understanding the nature of this overlap, however, is essential to improve early diagnosis, characterization and management of those affected. Here, we explored common cognitive–behavioural and neural mechanisms contributing to heterogeneous frontotemporal dementia presentations, irrespective of clinical diagnosis. This transdiagnostic approach allowed us to ascertain whether symptoms not currently considered core to these two syndromes are present in a significant proportion of cases and to explore the neural basis of clinical heterogeneity. Sixty-two frontotemporal dementia patients (31 behavioural variant frontotemporal dementia and 31 semantic dementia) underwent comprehensive neuropsychological, behavioural and structural neuroimaging assessments. Orthogonally rotated principal component analysis of neuropsychological and behavioural data uncovered eight statistically independent factors explaining the majority of cognitive–behavioural performance variation in behavioural variant frontotemporal dementia and semantic dementia. These factors included Behavioural changes, Semantic dysfunction, General Cognition, Executive function, Initiation, Disinhibition, Visuospatial function and Affective changes. Marked in idual-level overlap between behavioural variant frontotemporal dementia and semantic dementia was evident on the Behavioural changes, General Cognition, Initiation, Disinhibition and Affective changes factors. Compared to behavioural variant frontotemporal dementia, semantic dementia patients displayed disproportionate impairment on the Semantic dysfunction factor, whereas greater impairment on Executive and Visuospatial function factors was noted in behavioural variant frontotemporal dementia. Both patient groups showed comparable magnitude of atrophy to frontal regions, whereas severe temporal lobe atrophy was characteristic of semantic dementia. Whole-brain voxel-based morphometry correlations with emergent factors revealed associations between fronto-insular and striatal grey matter changes with Behavioural, Executive and Initiation factor performance, bilateral temporal atrophy with Semantic dysfunction factor scores, parietal-subcortical regions with General Cognitive performance and ventral temporal atrophy associated with Visuospatial factor scores. Together, these findings indicate that cognitive–behavioural overlap (i) occurs systematically in frontotemporal dementia (ii) varies in a graded manner between in iduals and (iii) is associated with degeneration of different neural systems. Our findings suggest that phenotypic heterogeneity in frontotemporal dementia syndromes can be captured along continuous, multidimensional spectra of cognitive–behavioural changes. This has implications for the diagnosis of both syndromes amidst overlapping features as well as the design of symptomatic treatments applicable to multiple syndromes.
Publisher: Wiley
Date: 17-03-2017
DOI: 10.1002/HIPO.22722
Abstract: The medial temporal lobes (MTLs) are widely held to support a range of constructive endeavors including remembering the past, envisaging the future, and imagining hypothetical scenarios. While right MTL structures have been ascribed a prominent role in the construction of spatial contexts, lesion evidence to directly test this hypothesis is lacking. To this end, we assessed scene construction performance in two cases, GC and DF, who presented with left- and right-lateralized presentations of semantic dementia, respectively. GC displayed characteristic semantic processing difficulties in the context of marked left anterior and medial temporal lobe atrophy. Despite significant volume loss across the entire length of the left hippoc us, GC was capable of generating richly detailed, spatially coherent scenes, most likely reflecting the preservation of his right anterior MTL. In contrast, DF's cognitive profile was one of dense prosopagnosia, with subjectively reported gaps in autobiographical memory and wayfinding difficulties. Formal testing on the scene construction task revealed striking deficits, with DF producing impoverished descriptions of spatially fragmented scenes. We attribute DF's inability to construct spatially contiguous scenes to the degeneration of right-sided MTL structures, most prominently the right anterior hippoc us (19% volume loss) and right parahippoc al cortex (23% volume loss). Our findings complement the extant fMRI literature to suggest a fundamental role for right medial temporal regions in the construction of rich detailed spatial arrays.
Publisher: Oxford University Press (OUP)
Date: 10-2021
DOI: 10.1093/BRAINCOMMS/FCAB257
Abstract: The disease syndromes of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) display considerable clinical, genetic and pathological overlap, yet mounting evidence indicates substantial differences in progression and survival. To date, there has been limited examination of how profiles of brain atrophy might differ between clinical phenotypes. Here, we address this longstanding gap in the literature by assessing cortical and subcortical grey and white matter volumes on structural MRI in a large cohort of 209 participants. Cognitive and behavioural changes were assessed using the Addenbrooke’s Cognitive Examination and the Cambridge Behavioural Inventory. Relative to 58 controls, behavioural variant FTD (n = 58) and ALS–FTD (n = 41) patients displayed extensive atrophy of frontoinsular, cingulate, temporal and motor cortices, with marked subcortical atrophy targeting the hippoc us, amygdala, thalamus and striatum, with atrophy further extended to the brainstem, pons and cerebellum in the latter group. At the other end of the spectrum, pure-ALS patients (n = 52) displayed considerable frontoparietal atrophy, including right insular and motor cortices and pons and brainstem regions. Subcortical regions included the bilateral pallidum and putamen, but to a lesser degree than in the ALS–FTD and behavioural variant FTD groups. Across the spectrum the most affected region in all three groups was the insula, and specifically the anterior part (76–90% lower than controls). Direct comparison of the patient groups revealed disproportionate temporal atrophy and widespread subcortical involvement in ALS–FTD relative to pure-ALS. In contrast, pure-ALS displayed significantly greater parietal atrophy. Both behavioural variant FTD and ALS–FTD were characterized by volume decrease in the frontal lobes relative to pure-ALS. The motor cortex and insula emerged as differentiating structures between clinical syndromes, with bilateral motor cortex atrophy more pronounced in ALS–FTD compared with pure-ALS, and greater left motor cortex and insula atrophy relative to behavioural variant FTD. Taking a transdiagnostic approach, we found significant associations between abnormal behaviour and volume loss in a predominantly frontoinsular network involving the amygdala, striatum and thalamus. Our findings demonstrate the presence of distinct atrophy profiles across the ALS–FTD spectrum, with key structures including the motor cortex and insula. Notably, our results point to subcortical involvement in the origin of behavioural disturbances, potentially accounting for the marked phenotypic variability typically observed across the spectrum.
Publisher: Elsevier BV
Date: 2017
Publisher: Elsevier BV
Date: 04-2020
Publisher: Oxford University Press (OUP)
Date: 26-10-2015
DOI: 10.1093/BRAIN/AWV315
Abstract: Adherence to social norms is compromised in a variety of neuropsychiatric conditions. Functional neuroimaging studies have investigated social norm compliance in healthy in iduals, leading to the identification of a network of fronto-subcortical regions that underpins this ability. However, there is a lack of corroborative evidence from human lesion models investigating the structural anatomy of norm compliance across this fronto-subcortical network. To address this, we developed a neuroeconomic task to investigate social norm compliance in a neurodegenerative lesion model: behavioural variant frontotemporal dementia, a condition characterized by gross social dysfunction. The task assessed norm compliance across three behaviours that are well-studied in the neuroeconomics literature: fairness, prosocial and punishing behaviours. We administered our novel version of the Ultimatum Game in 22 patients with behavioural variant frontotemporal dementia and 22 age-matched controls, to assess how decision-making behaviour was modulated in response to (i) fairness of monetary offers and (ii) social context of monetary offers designed to produce either prosocial or punishing behaviours. Voxel-based morphometry was used to characterize patterns of grey matter atrophy associated with task performance. Acceptance rates between patients and controls were equivalent when only fairness was manipulated. However, patients were impaired in modulating their decisions in response to social contextual information. Patients' performance in the punishment condition was consistent with a reduced tendency to engage in punishment this was associated with decreased grey matter volume in the anterior cingulate, orbitofrontal cortex, left dorsolateral prefrontal cortex and right inferior frontal gyrus. In the prosocial condition, patients' performance suggested a reduced expression of prosocial behaviour, associated with decreased grey matter in the anterior insula, lateral orbitofrontal cortex, anterior cingulate and dorsal striatum. Acceptance rates in the Ultimatum Game were also significantly related to impairments in the everyday expression of empathic concern. In conclusion, we demonstrate that compliance to basic social norms (fairness) can be maintained in behavioural variant frontotemporal dementia however, more complex normative behaviours (prosociality, punishment) that require integration of social contextual information are disrupted in association with atrophy in key fronto-striatal regions. These results suggest that the integration of social contextual information to guide normative behaviour is uniquely impaired in behavioural variant frontotemporal dementia, and may explain other common features of the condition including gullibility and impaired empathy. Our findings also converge with previous functional neuroimaging investigations in healthy in iduals and provide the first description of the structural anatomy of social norm compliance in a neurodegenerative lesion model.
Publisher: Center for Open Science
Date: 09-08-2021
Abstract: The behavioural variant of frontotemporal dementia (bvFTD) is characterised by pronounced alterations in social functioning, including the understanding of others’ thoughts and feelings via theory of mind. The emergence of such impairments in other social disorders such as autism and schizophrenia is suggested to reflect an inability to imagine the other person’s visual perspective of the world. To our knowledge, this hypothesis is yet to be explored in bvFTD. Here, we sought to examine the capacity for different forms of perspective taking, including visual perspective taking and theory of mind in bvFTD, and to establish their inter-relationships and underlying neural correlates. Fifteen bvFTD patients and 15 healthy Controls completed a comprehensive battery of perspective taking measures, comprising Level 1 (‘what’) and Level 2 (‘how’) visual perspective taking tasks, a cartoon task capturing theory of mind, and a questionnaire assessing perspective taking in daily life. Compared with Controls, bvFTD patients displayed significant impairments across all perspective taking measures. These perspective taking impairments, however, were not correlated with one another in bvFTD. Moreover, controlling for visual perspective taking performance did not ameliorate the deficits in theory of mind or real-world perspective taking. Region-of-interest voxel-based morphometry analyses suggested distinct neural correlates for visual perspective taking (inferior frontal gyrus) versus theory of mind (medial prefrontal cortex, precuneus), which appeared to partially overlap with those implicated in real-world perspective taking (inferior frontal gyrus, precuneus, temporoparietal junction). Despite pervasive impairments in all aspects of perspective taking in bvFTD, our findings suggest that these deficits may reflect distinct underlying processes. Future studies manipulating discrete aspects of the tasks will help to clarify the neurocognitive mechanisms of, and relationships between different forms of perspective taking in bvFTD, along with their real-world implications.
Publisher: MDPI AG
Date: 28-07-2021
Abstract: Semantic dementia (SD) is a younger-onset neurodegenerative disease characterised by progressive deterioration of the semantic knowledge base in the context of predominantly left-lateralised anterior temporal lobe (ATL) atrophy. Mounting evidence indicates the emergence of florid socioemotional changes in SD as atrophy encroaches into right temporal regions. How lateralisation of temporal lobe pathology impacts the hedonic experience in SD remains largely unknown yet has important implications for understanding socioemotional and functional impairments in this syndrome. Here, we explored how lateralisation of temporal lobe atrophy impacts anhedonia severity on the Snaith–Hamilton Pleasure Scale in 28 SD patients presenting with variable right- (SD-R) and left-predominant (SD-L) profiles of temporal lobe atrophy compared to that of 30 participants with Alzheimer’s disease and 30 healthy older Control participants. Relative to Controls, SD-R but not SD-L or Alzheimer’s patients showed clinically significant anhedonia, representing a clear departure from premorbid levels. Overall, anhedonia was more strongly associated with functional impairment on the Frontotemporal Dementia Functional Rating Scale and motivational changes on the Cambridge Behavioural Inventory in SD than in Alzheimer’s disease patients. Voxel-based morphometry analyses revealed that anhedonia severity correlated with reduced grey matter intensity in a restricted set of regions centred on right orbitofrontal and temporopolar cortices, bilateral posterior temporal cortices, as well as the anterior cingulate gyrus and parahippoc al gyrus, bilaterally. Finally, regression and mediation analysis indicated a unique role for right temporal lobe structures in modulating anhedonia in SD. Our findings suggest that degeneration of predominantly right-hemisphere structures deleteriously impacts the capacity to experience pleasure in SD. These findings offer important insights into hemispheric lateralisation of motivational disturbances in dementia and suggest that anhedonia may emerge at different timescales in the SD disease trajectory depending on the integrity of the right hemisphere.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.CORTEX.2018.06.016
Abstract: Posterior Cortical Atrophy (PCA) is a rare neurodegenerative syndrome characterised by profound visuoperceptual processing disturbances, attributable to focal parieto-occipital cortical atrophy. Despite relative sparing of the medial temporal lobes, converging evidence reveals significant autobiographical memory impairments in this syndrome, underscoring the crucial role of visual imagery for episodic memory processes. The contribution of visual imagery to complex constructive endeavours, however, remains unclear. Here, we investigated the capacity for atemporal scene construction in 5 well-characterised cases of PCA and contrasted their performance with 10 typical amnestic Alzheimer's Disease (AD) and 10 healthy older Control participants. Behavioural data were analysed using case-Control statistics comparing each PCA patient's scene construction scores to the mean scores of AD and Control groups. In keeping with their clinical phenotype, PCA patients demonstrated significant visuoperceptual and episodic memory impairments on standard neuropsychological tasks. Scene construction performance was grossly impaired in PCA, at a level comparable to that observed in the AD group, manifesting in impoverished and spatially fragmented scenes. Structural neuroimaging confirmed prominent grey matter intensity decrease predominantly in posterior cortical regions in PCA, in the absence of frank hippoc al atrophy. Using an a priori motivated region-of-interest approach across all participants, scene construction performance was found to correlate with grey matter intensity in the left angular gyrus, right precuneus, and right hippoc us. This study is the first to reveal compromised scene construction capacity in PCA, extending our understanding of the cognitive profile of this rare syndrome and pointing towards the fundamental contribution of visual imagery to atemporal forms of imagination.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Cambridge University Press (CUP)
Date: 19-03-2010
DOI: 10.1017/S1355617710000172
Abstract: Autonoetic consciousness refers to the ability to mentally transport oneself back in subjective time to relive elements of, or all, of a past event, and is compromised in the early stages of Alzheimer’s disease (AD). Here, we investigate autobiographical memory (ABM) and the recollective experience in amnestic mild cognitive impairment (aMCI). aMCI participants exhibited significant deficits compared with healthy elderly controls for both personal semantic and event detail components of ABM. These decrements were evident across all life epochs for episodic recall. Recall of an event that occurred 1 week previously, was tested in the same spatiotemporal context, and provided the greatest group dissociation, with elderly controls benefitting from a context-dependent memory effect. This reinstantiation of context did not ameliorate the anterograde deficits in the aMCI cohort, nor did it facilitate the mental reliving of these memories for either participant group. Whereas reliving judgments were comparable in both groups, aMCI participants exhibited a compromised capacity to generate vivid, self-referential visual imagery and to re-experience the original emotion of events. These contextual and experiential deficits extended beyond recently encountered events into remote epochs, and suggest a greater level of ABM impairment in aMCI than previously assumed. ( JINS , 2010, 16 , 546–555.)
Publisher: Springer Science and Business Media LLC
Date: 04-08-2011
Publisher: Wiley
Date: 06-11-2018
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2012.09.012
Abstract: Semantic dementia (SD) is a progressive neurodegenerative disorder characterised by the amodal loss of semantic knowledge in the context of relatively preserved recent episodic memory. Recent studies have demonstrated that despite relatively intact episodic memory the capacity for future simulation in SD is profoundly impaired, resulting in an asymmetric profile where past retrieval is significantly better than future simulation (referred to as a past>future effect). Here, we sought to identify the origins of this asymmetric profile by conducting a fine-grained analysis of the contextual details provided during past retrieval and future simulation in SD. Participants with SD (n=14), Alzheimer's disease (n=11), and healthy controls (n=14) had previously completed an experimental past-future interview in which they generated three past events from the previous year, and three future events in the next year, and provided subjective qualitative ratings of vividness, emotional valence, emotional intensity, task difficulty, and personal significance for each event described. Our results confirmed the striking impairment for future simulation in SD, despite a relative preservation of past episodic retrieval. Examination of the contextual details provided for past memories and future simulations revealed significant impairments irrespective of contextual detail type for future simulations in SD, and demonstrated that the future thinking deficit in this cohort was driven by a marked decline in the provision of internal (episodic) event details. In contrast with this past>future effect for internal event details, SD patients displayed a future>past effect for external (non-episodic) event details. Analyses of the qualitative ratings provided for past and future events indicated that SD patients' phenomenological experience did not differ between temporal conditions. Our findings underscore the fact that successful extraction of episodic elements from the past is not sufficient for the generation of novel future simulations in SD. The notable disconnect between objective task performance and patients' subjective experience during future simulation likely reflects the tendency of SD patients to recast entire past events into the future condition. Accordingly, the familiarity of the recapitulated details results in similar ratings of vividness and emotionality across temporal conditions, despite marked differences in the richness of contextual details as the patient moves from the past to the future.
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2011.05.017
Abstract: Episodic autobiographical memory (ABM) comprises recollection for events that are grounded within a specific spatiotemporal context, and usually accompanied by perceptual and emotional information. The neural substrates mediating ABM retrieval are those harbouring significant pathology in semantic dementia (SD) and behavioural-variant frontotemporal dementia (bvFTD), the most common subtypes of FTD. Relatively little is known, however, regarding the differential patterns of contextual details during episodic ABM retrieval across these dementia syndromes. This study investigated episodic ABM retrieval under free and probed recall conditions from 4 time periods with the aim to identify disease-specific profiles of episodic ABM contextual details. Episodic ABM was measured in 25 SD and 15 bvFTD patients and their performance contrasted to that of 17 Alzheimer's disease (AD) patients and 19 age-matched controls. Critically, SD patients showed relatively preserved recent ABM in comparison with remote epochs. In contrast, bvFTD and AD patients showed a reduced capacity to recall specific and contextually rich ABMs across all life epochs, in both free and probed recall conditions. Analyses of the recent period (last 12 months) provided evidence for different profiles of contextual episodic details recalled in dementia syndromes. Following probing, SD patients' recall deficits emanated exclusively from compromised Emotion/Thoughts and Spatiotemporal details. In contrast, bvFTD patients were significantly impaired across all categories of contextual details whereas AD patients showed deficits for Event and Emotion/Thoughts details only. As the largest study of ABM in FTD to date, these findings emphasise the differential impairment of recent ABM contextual details contingent on the underlying disease pathology. In addition, these results point towards the importance of investigating the constituent elements of emotion processing and strategic retrieval processes as potential variables mediating recent episodic ABM retrieval.
Publisher: Oxford University Press (OUP)
Date: 03-2023
DOI: 10.1093/BRAINCOMMS/FCAD045
Abstract: This scientific commentary refers to ‘The architecture of abnormal reward behaviour in dementia: multimodal hedonic phenotypes and brain substrate’, by Chokesuwattanaskul et al. (0.1093/braincomms/fcad027).
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.CORTEX.2010.01.002
Abstract: The capacity to mentally travel back in time and relive past events via autonoetic consciousness has been shown to be compromised even in the early stages of Alzheimer's disease (AD). To further understand the unravelling of the recollective experience in pathological ageing, we investigated autobiographical memory (ABM) using the Episodic Autobiographical Memory Interview (EAMI) in thirty middle-aged and thirty healthy elderly controls, and twenty patients with mild AD. Of key interest was the recall of contextual details and the behavioural markers predictive of autonoetic reliving. AD patients exhibited significant difficulties in recalling contextual details across all life epochs on the EAMI manifesting in a negative temporal gradient from the Early Adulthood epoch onwards. Overall there was a low incidence of autonoetic consciousness during ABM recall across all participant groups and life epochs when compared with previous studies. AD patients showed a compromised capacity to mentally relive past memories (AD<healthy elderly<middle-aged controls), across all life epochs on the EAMI. AD patients tended to recall past events as semanticised accounts ested of rich sensory-perceptual imagery. The impoverished capacity to generate egocentric or self-referential imagery resulted in the production of fragmented and depersonalised accounts of formerly evocative events and likely stems from medial temporal and frontal pathology exhibited from early stages of the disease.
Publisher: Public Library of Science (PLoS)
Date: 21-06-2013
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.CORTEX.2015.03.016
Abstract: Spatial disorientation is a prominent feature of early Alzheimer's disease (AD) attributed to degeneration of medial temporal and parietal brain regions, including the retrosplenial cortex (RSC). By contrast, frontotemporal dementia (FTD) syndromes show generally intact spatial orientation at presentation. However, currently no clinical tasks are routinely administered to objectively assess spatial orientation in these neurodegenerative conditions. In this study we investigated spatial orientation in 58 dementia patients and 23 healthy controls using a novel virtual supermarket task as well as voxel-based morphometry (VBM). We compared performance on this task with visual and verbal memory function, which has traditionally been used to discriminate between AD and FTD. Participants viewed a series of videos from a first person perspective travelling through a virtual supermarket and were required to maintain orientation to a starting location. Analyses revealed significantly impaired spatial orientation in AD, compared to FTD patient groups. Spatial orientation performance was found to discriminate AD and FTD patient groups to a very high degree at presentation. More importantly, integrity of the RSC was identified as a key neural correlate of orientation performance. These findings confirm the notion that i) it is feasible to assess spatial orientation objectively via our novel Supermarket task ii) impaired orientation is a prominent feature that can be applied clinically to discriminate between AD and FTD and iii) the RSC emerges as a critical biomarker to assess spatial orientation deficits in these neurodegenerative conditions.
Publisher: Cambridge University Press (CUP)
Date: 25-10-2017
Abstract: Empathy involves being able to understand and respond to others’ emotional experiences. Whilst deficits in empathy have been observed in frontotemporal dementia, the extent to which empathy is disrupted in dementia syndromes with predominant language impairment remains unclear. The current study investigated cognitive and affective empathy in the two non-fluent primary progressive aphasia syndromes: progressive non-fluent aphasia (PNFA) and logopenic progressive aphasia (LPA). Informants of 23 PNFA and 16 LPA patients completed the Interpersonal Reactivity Index (IRI), regarding patients’ capacity for empathy pre- and post-disease onset. Twenty-four healthy control participants completed the self-rated IRI for comparison of post-disease empathy capabilities. Within-group analyses revealed reduced cognitive empathy and increased personal distress in both patient groups. In addition, lowered affective empathy was reported in PNFA, with a similar trend observed in LPA. Interestingly, reduced affective empathy was associated with greater carer burden in LPA. Between-group analyses revealed reduced cognitive empathy in both patient groups relative to controls. The current study is the first to document empathy changes in PNFA and LPA, offering insight into the social cognitive deficits experienced in these syndromes. Future neuroimaging studies are needed to identify the underlying neural correlates and mechanisms driving empathy deficits in PNFA and LPA.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2015.03.020
Abstract: The ability to perceive, learn and recognise faces is a complex ability, which is key to successful social interactions. This ability is proposed to be coordinated by neural regions in the occipital and temporal lobes, specialised for face perception and memory. While previous studies have suggested that memory for faces is compromised in some dementia syndromes, it remains unclear whether this simply reflects more generalised memory deficits. Here, we examined basic face perception (Identity-Matching), face recognition (Cambridge Face Memory Task) and object recognition (Cambridge Car Memory Task) in 11 semantic dementia (SD) patients (8 left-lateralised, 3 right-lateralised) and 13 behavioural-variant frontotemporal dementia (bvFTD) patients, compared with 11 controls. On the Identity-Matching task, bvFTD were impaired compared to controls, with a similar trend observed in the SD group. Importantly, both bvFTD and SD also demonstrated impaired face recognition. In contrast, only bvFTD showed impaired object recognition, with SD performing within normal limits on this task. Voxel-based morphometry analyses revealed that Identity-Matching and face recognition were associated with partly dissociable regions including the fusiform cortex and anterior temporal lobe. Object-memory was associated with thalamic integrity in the bvFTD group only. These results reveal that face perception and face memory deficits are common in bvFTD and SD, and have been previously underestimated. These deficits are due to neurodegeneration of key regions within the 'core' and 'extended' face processing system, providing convergent evidence of the neural regions supporting face perception. From a clinical perspective, impaired ability to recognise faces is common in bvFTD and SD and therefore strategies to improve face perception and memory may be beneficial for these patients.
Start Date: 02-2017
End Date: 09-2021
Amount: $688,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 02-2021
End Date: 02-2024
Amount: $273,850.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2013
End Date: 06-2016
Amount: $375,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2018
End Date: 12-2020
Amount: $358,912.00
Funder: Australian Research Council
View Funded ActivityStart Date: 05-2022
End Date: 04-2025
Amount: $508,250.00
Funder: Australian Research Council
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