ORCID Profile
0000-0002-9244-2900
Current Organisation
University of Melbourne
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Pain | Biological psychology | Psychology | Sensory processes perception and performance | Cognitive neuroscience | Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology) | Sensory Processes, Perception and Performance | Linguistic Processes (incl. Speech Production and Comprehension) |
Learner and Learning Processes | Expanding Knowledge in Psychology and Cognitive Sciences | Expanding Knowledge in Language, Communication and Culture
Publisher: Cold Spring Harbor Laboratory
Date: 05-11-2020
DOI: 10.1101/2020.11.04.366856
Abstract: Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Subcortical regions play critical roles in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behavior at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioral data in 828 in iduals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behavior to non-lesioned subcortical volumes (Bonferroni-corrected, p .004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behavior was associated with a smaller ipsilesional thalamic volume in both early (n=179 d =0.68) and subacute (n=274, d =0.46) stroke. In chronic stroke (n=404), worse sensorimotor behavior was associated with smaller ipsilesional putamen ( d =0.52) and nucleus accumbens ( d =0.39) volumes, and a larger ipsilesional lateral ventricle ( d =-0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment n=256) was associated with smaller ipsilesional putamen ( d =0.72) and larger lateral ventricle ( d =-0.41) volumes, while several measures of activity limitations (n=116) showed no significant relationships. In the full cohort across all time (n=828), sensorimotor behavior was associated with the volumes of the ipsilesional nucleus accumbens ( d =0.23), putamen ( d =0.33), thalamus ( d =0.33), and lateral ventricle ( d =-0.23). We demonstrate significant relationships between post-stroke sensorimotor behavior and reduced volumes of subcortical gray matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings may provide additional targets for improving post-stroke sensorimotor outcomes.
Publisher: Cold Spring Harbor Laboratory
Date: 29-04-2022
DOI: 10.1101/2022.04.27.489791
Abstract: Sensorimotor performance after stroke is strongly related to focal injury measures such as corticospinal tract lesion load. However, the role of global brain health is less clear. Here, we examined the impact of brain age, a measure of neurobiological aging derived from whole brain structural neuroimaging, on sensorimotor outcomes. We hypothesized that stroke lesion damage would result in older brain age, which would in turn be associated with poorer sensorimotor outcomes. We also expected that brain age would mediate the impact of lesion damage on sensorimotor outcomes and that these relationships would be driven by post-stroke secondary atrophy (e.g., strongest in the ipsilesional hemisphere in chronic stroke). We further hypothesized that structural brain resilience, which we define in the context of stroke as the brain’s ability to maintain its global integrity despite focal lesion damage, would differentiate people with better versus worse outcomes. We analyzed cross-sectional high-resolution brain MRI and outcomes data from 963 people with stroke from 38 cohorts worldwide using robust linear mixed-effects regressions to examine the relationship between sensorimotor behavior, lesion damage, and brain age. We used a mediation analysis to examine whether brain age mediates the impact of lesion damage on stroke outcomes and if associations are driven by ipsilesional measures in chronic (≥180 days) stroke. We assessed the impact of brain resilience on sensorimotor outcome using logistic regression with propensity score matching on lesion damage. Stroke lesion damage was associated with older brain age, which in turn was associated with poorer sensorimotor outcomes. Brain age mediated the impact of corticospinal tract lesion load on sensorimotor outcomes most strongly in the ipsilesional hemisphere in chronic stroke. Greater brain resilience, as indexed by younger brain age, explained why people have better versus worse sensorimotor outcomes when lesion damage was fixed. We present novel evidence that global brain health is associated with superior post-stroke sensorimotor outcomes and modifies the impact of focal damage. This relationship appears to be due to post-stroke secondary degeneration. Brain resilience provides insight into why some people have better outcomes after stroke, despite similar amounts of focal injury. Inclusion of imaging-based assessments of global brain health may improve prediction of post-stroke sensorimotor outcomes compared to focal injury measures alone. This investigation is important because it introduces the potential to apply novel therapeutic interventions to prevent or slow brain aging from other fields (e.g., Alzheimer’s disease) to stroke.
Publisher: Springer Science and Business Media LLC
Date: 17-11-2015
DOI: 10.1038/TP.2015.174
Abstract: Subthreshold depression (StD) is a prevalent condition associated with social morbidity and increased service utilization, as well as a high risk of developing into a major depressive disorder (MDD). The lack of well-defined diagnostic criteria for StD has limited research on this disorder, with very few brain-imaging studies examining the neurobiology of StD. Yet, identifying the neural pathology of StD has the potential to elucidate risk factors and prognostic markers for major depression and is crucial for developing tailored treatments for patients at mild stages of depression. We investigated resting-state functional connectivity (rs-FC) of the cognitive control network (CCN), known to be dysregulated in MDD, using the bilateral dorsolateral prefrontal cortex (DLPFC) as a seed, focusing on two cohorts of StD subjects (young and middle aged) as well as matched controls. Irrespective of age, we found a significant rs-FC decrease in the CCN of the StD subjects, compared with matched controls, particularly between the DLPFC and the brain regions associated with the representation of self and other mental states (temporo-parietal junction (TPJ) and precuneus), as well as salience detection and orienting (insula). The functional connectivity between the DLPFC and the left TPJ was also associated with depressive symptom scores measured by the Center for Epidemiologic Studies Depression Scale. This finding may shed light on the neural pathology of StD, leading to better understanding of mild stages of depression, its diagnosis and the development of new treatments.
Publisher: Elsevier BV
Date: 2019
Publisher: Wiley
Date: 07-2017
Publisher: Acoustical Society of America (ASA)
Date: 10-2010
DOI: 10.1121/1.3508334
Abstract: A wealth of behavioral research suggests that infants become increasingly specialized in their native dialect/language in infancy. In contrast, few studies document how this early specialization is reflected in neural activation, most of which have compared familiar and unfamiliar languages, and none focused on different dialects. This study aimed to fill that gap, focusing on cerebral activation in temporal areas, as measured with near infrared spectroscopy. Audiovisual infant-directed speech was recorded from talkers of either Parisian or Quebecois French. These videos were presented to 5-month-old Parisian infants in blocks within which videos from two talkers alternated in one of two ways. In pure blocks, both talkers were either Parisian (pure-familiar) or Quebecois (pure-unfamiliar). In mixed blocks, the two talkers had different dialects. A robust and mostly bilateral activation was found for both mixed and pure blocks. Follow-up comparisons revealed a stronger activation for mixed blocks than for pure ones, and a trend for more activation in response to the unfamiliar dialect than to the familiar one. These findings are congruent with behavioral studies showing early sensitivity to dialects and extend the brain imaging literature on early neural attunement to the language as spoken in the infant’s environment.
Publisher: The Royal Society
Date: 12-07-2023
Abstract: Humans and other animals value information that reduces uncertainty or leads to pleasurable anticipation, even if it cannot be used to gain tangible rewards or change outcomes. In exchange, they are willing to incur significant costs, sacrifice rewards or invest effort. We investigated whether human participants were also willing to endure pain—a highly salient and aversive cost—to obtain such information. Forty participants performed a computer-based task. On each trial, they observed a coin flip, with each side associated with different monetary rewards of varying magnitude. Participants could choose to endure a painful stimulus (low, moderate or high pain) to learn the outcome of the coin flip immediately. Importantly, regardless of their choice, winnings were always earned, rendering this information non-instrumental. Results showed that agents were willing to endure pain in exchange for information, with a lower likelihood of doing so as pain levels increased. Both higher average rewards and a larger variance between the two possible rewards independently increased the willingness to accept pain. Our results show that the intrinsic value of escaping uncertainty through non-instrumental information is sufficient to offset pain experiences, suggesting a shared mechanism through which these can be directly compared.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2020
DOI: 10.1161/STROKEAHA.120.030256
Abstract: Brain atrophy can be regarded as an end-organ effect of cumulative cardiovascular risk factors. Accelerated brain atrophy is described following ischemic stroke, but it is not known whether atrophy rates vary over the poststroke period. Examining rates of brain atrophy allows the identification of potential therapeutic windows for interventions to prevent poststroke brain atrophy. We charted total and regional brain volume and cortical thickness trajectories, comparing atrophy rates over 2 time periods in the first year after ischemic stroke: within 3 months (early period) and between 3 and 12 months (later period). Patients with first-ever or recurrent ischemic stroke were recruited from 3 Melbourne hospitals at 1 of 2 poststroke time points: within 6 weeks (baseline) or 3 months. Whole-brain 3T magnetic resonance imaging was performed at 3 time points: baseline, 3 months, and 12 months. Eighty-six stroke participants completed testing at baseline 125 at 3 months (76 baseline follow-up plus 49 delayed recruitment) and 113 participants at 12 months. Their data were compared with 40 healthy control participants with identical testing. We examined 5 brain measures: hippoc al volume, thalamic volume, total brain and hemispheric brain volume, and cortical thickness. We tested whether brain atrophy rates differed between time points and groups. A linear mixed-effect model was used to compare brain structural changes, including age, sex, years of education, a composite cerebrovascular risk factor score, and total intracranial volume as covariates. Atrophy rates were greater in stroke than control participants. Ipsilesional hemispheric, hippoc al, and thalamic atrophy rates were 2 to 4 times greater in the early versus later period. Regional atrophy rates vary over the first year after stroke. Rapid brain volume loss in the first 3 months after stroke may represent a potential window for intervention. URL: www.clinicaltrials.gov . Unique identifier: NCT02205424.
Publisher: Cold Spring Harbor Laboratory
Date: 30-10-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2018
Publisher: Springer Science and Business Media LLC
Date: 08-12-2017
DOI: 10.1038/S41398-017-0038-X
Abstract: Around one-third of people develop depression following ischaemic stroke, yet the underlying mechanisms are poorly understood. Post-stroke depression has been linked to frontal infarcts, mainly lesions in the left dorsolateral prefrontal cortex (DLPFC). But depression is a network disorder that cannot be fully characterised through lesion-symptom mapping. Researchers of depression in non-stroke populations have successfully tapped into the cognitive control network (CCN) using the bilateral DLPFC as a seed, and found that CCN resting-state connectivity is reduced in even mildly depressed subjects, compared to healthy controls. Hence, we aimed to investigate the association between post-stroke depressive features and the CCN resting-state connectivity in a stroke population. We analysed DLPFC resting-state connectivity in 64 stroke participants, 20 of whom showed depressive features assessed with the Patient Health Questionnaire (PHQ-9) at 3 months after stroke. We directly compared groups showing symptoms of depression with those who did not, and performed a regression with PHQ-9 scores in all participants, controlling for age, gender, lesion volume and stroke severity. Post-stroke depression was associated with lower connectivity between the left DLPFC and the right supramarginal gyrus (SMG) in both group and regression analyses. Neither the seed nor the results overlapped with stroke lesions. These findings confirm an important role of the left DLPFC in post-stroke depression, but now show that large-scale network disruptions following stroke associated with depressive features occur without lesions in the DLPFC.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2015
Publisher: Wiley
Date: 12-12-2020
DOI: 10.1002/EJP.1510
Publisher: Elsevier BV
Date: 11-2019
Publisher: Elsevier BV
Date: 2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2020
DOI: 10.1161/STROKEAHA.119.028143
Abstract: We examined if ischemic stroke is associated with white matter degeneration predominantly confined to the ipsi-lesional tracts or with widespread bilateral axonal loss independent of lesion laterality. We applied a novel fixel-based analysis, sensitive to fiber tract–specific differences within a voxel, to assess axonal loss in stroke (N=104, 32 women) compared to control participants (N=40, 15 women) across the whole brain. We studied microstructural differences in fiber density and macrostructural (morphological) changes in fiber cross-section. In participants with stroke, we observed significantly lower fiber density and cross-section in areas adjacent, or connected, to the lesions (eg, ipsi-lesional corticospinal tract). In addition, the changes extended beyond directly connected tracts, independent of the lesion laterality (eg, corpus callosum, bilateral inferior fronto-occipital fasciculus, right superior longitudinal fasciculus). We conclude that ischemic stroke is associated with extensive neurodegeneration that significantly affects white matter integrity across the whole brain. These findings expand our understanding of the mechanisms of brain volume loss and delayed cognitive decline in stroke.
Publisher: Springer Science and Business Media LLC
Date: 08-07-2021
Publisher: Wiley
Date: 2021
DOI: 10.1002/DAD2.12195
Abstract: Hippoc al subfield volumes are more closely associated with cognitive impairment than whole hippoc al volume in many diseases. Both memory and whole hippoc al volume decline after stroke. Understanding the subfields’ temporal evolution could reveal valuable information about post‐stroke memory. We s led 120 participants (38 control, 82 stroke), with cognitive testing and 3T‐MRI available at 3 months and 3 years, from the Cognition and Neocortical Volume after Stroke (CANVAS) study. Verbal memory was assessed using the Hopkins Verbal Learning Test‐Revised. Subfields were delineated using FreeSurfer. We used partial Pearson's correlation to assess the associations between subfield volumes and verbal memory scores, adjusting for years of education, sex, and stroke side. The left cornu ammonis areas 2/3 and hippoc al tail volumes were significantly associated with verbal memory 3‐month post‐stroke. At 3 years, the associations became stronger and involved more subfields. Hippoc al subfield volumes may be a useful biomarker for post‐stroke cognitive impairment.
Publisher: Elsevier BV
Date: 2019
Publisher: Wiley
Date: 13-03-2014
DOI: 10.1111/DESC.12160
Abstract: The present study investigated the neural correlates of infant discrimination of very similar linguistic varieties (Quebecois and Parisian French) using functional Near InfraRed Spectroscopy. In line with previous behavioral and electrophysiological data, there was no evidence that 3-month-olds discriminated the two regional accents, whereas 5-month-olds did, with the locus of discrimination in left anterior perisylvian regions. These neuroimaging results suggest that a developing language network relying crucially on left perisylvian cortices sustains infants' discrimination of similar linguistic varieties within this early period of infancy.
Publisher: Frontiers Media SA
Date: 10-12-2019
Publisher: Elsevier BV
Date: 10-2023
Publisher: SAGE Publications
Date: 05-10-2021
DOI: 10.1177/17474930211048323
Abstract: Fatigue is associated with poor functional outcomes and increased mortality following stroke. Survivors identify fatigue as one of their key unmet needs. Despite the growing body of research into post-stroke fatigue, the specific neural mechanisms remain largely unknown. This observational study aimed to identify resting state brain activity markers of post-stroke fatigue. Sixty-three stroke survivors (22 women age 30–89 years mean 67.5 ± 13.4 years) from the Cognition And Neocortical Volume After Stroke study, a cohort study examining cognition, mood, and brain volume in stroke survivors following ischemic stroke, underwent brain imaging three months post-stroke, including a 7-minute resting state functional magnetic resonance imaging. We calculated the fractional litude of low-frequency fluctuations, which is measured at the whole-brain level and can detect altered spontaneous neural activity of specific regions. Forty-five participants reported experiencing post-stroke fatigue as measured by an item on the Patient Health Questionnaire-9. Fatigued compared to non-fatigued participants demonstrated significantly lower resting-state activity in the calcarine cortex ( p 0.001, cluster-corrected p FDR = 0.009, k = 63) and lingual gyrus ( p 0.001, cluster-corrected p FDR = 0.025, k = 42) and significantly higher activity in the medial prefrontal cortex ( p 0.001, cluster-corrected p FDR = 0.03, k = 45). Post-stroke fatigue is associated with posterior hypoactivity and prefrontal hyperactivity reflecting dysfunction within large-scale brain systems such as fronto-striatal-thalamic and frontal-occipital networks. These systems in turn might reflect a relationship between post-stroke fatigue and abnormalities in executive and visual functioning. This whole-brain resting-state study provides new targets for further investigation of post-stroke fatigue beyond the lesion approach.
Publisher: Elsevier BV
Date: 2017
Publisher: Springer International Publishing
Date: 2017
DOI: 10.1007/978-3-319-57193-5_18
Abstract: This chapter is intended as a primer to the most widely used neuroimaging methods available in the prediction, diagnosis and monitoring of the neurodegenerative diseases. We describe the imaging methods that allow us to examine brain structure, function and pathology and investigate neurodegenerative mechanisms in vivo. We describe methods to interrogate brain structure with magnetic resonance imaging (MRI), and brain function with molecular imaging, functional MRI and electro- and magneto-encephalography. We highlight the major neuroimaging advances, including brain stimulation and connectomics, which have brought new insights into a wide range of neurodegenerative diseases and describe some of the challenges in imaging clinical populations. Finally, we discuss the future of neuroimaging in neurodegenerative disease and its potential for generating predictive, diagnostic and prognostic biomarkers.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.NEUROBIOLAGING.2017.07.011
Abstract: Disruptions to functional connectivity in subsystems of the default mode network are evident in Alzheimer's disease (AD). Functional connectivity estimates correlations in the time course of low-frequency activity. Much less is known about other potential perturbations to this activity, such as changes in the litude of oscillations and how this relates to cognition. We examined the litude of low-frequency fluctuations in 44 AD patients and 128 cognitively normal participants and related this to episodic memory, the core deficit in AD. We show higher litudes of low-frequency oscillations in AD patients. Rather than being compensatory, this appears to be maladaptive, with greater litude in the ventral default mode subnetwork associated with poorer episodic memory. Perturbations to default mode subnetworks in AD are evident in the litude of low-frequency oscillations in the resting brain. These disruptions are associated with episodic memory demonstrating their behavioral and clinical relevance in AD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-05-2022
Abstract: Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippoc us is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper‐limb sensorimotor impairment. We investigated associations between non‐lesioned hippoc al volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippoc al volumes would be associated with greater sensorimotor impairment. Cross‐sectional T1‐weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta‐Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA‐UE (Fugl‐Meyer Assessment of Upper Extremity). Robust mixed‐effects linear models were used to test associations between poststroke sensorimotor impairment and hippoc al volumes (ipsilesional and contralesional separately Bonferroni‐corrected, P .025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippoc al volume. Greater sensorimotor impairment was significantly associated with ipsilesional ( P =0.005 β=0.16) but not contralesional ( P =0.96 β=0.003) hippoc al volume, independent of lesion volume and other covariates ( P =0.001 β=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional ( P =0.008 β=−0.26) and contralesional ( P =0.006 β=−0.27) hippoc al volumes compared with men. Hippoc al volume was associated with lesion size ( P .001 β=−0.21) and extent of sensorimotor damage ( P =0.003 β=−0.15). The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippoc al volume that are not caused by lesion size and may be stronger in women.
Publisher: Wiley
Date: 12-05-2017
DOI: 10.1002/EJP.1024
Publisher: Cold Spring Harbor Laboratory
Date: 17-03-2021
DOI: 10.1101/2021.03.17.21253777
Abstract: Fatigue is associated with poor functional outcomes and increased mortality following stroke. Survivors identify fatigue as one of their key unmet needs. Despite the growing body of research into post-stroke fatigue, the specific neural mechanisms remain largely unknown. This observational study included 63 stroke survivors (22 women age 30-89 years mean 67.5±13.4 years) from the Cognition And Neocortical Volume After Stroke (CANVAS) study, a cohort study examining cognition, mood, and brain volume in stroke survivors following ischaemic stroke. Participants underwent brain imaging 3 months post-stroke, including a 7-minute resting state fMRI echoplanar sequence. We calculated the fractional litude of low-frequency fluctuations, a measure of resting state brain activity at the whole-brain level. Forty-five participants reported experiencing post-stroke fatigue as measured by an item on the Patient Health Questionnaire-9. A generalised linear regression model analysis with age, sex, and stroke severity covariates was conducted to compare resting state brain activity in the 0.01-0.08 Hz range, as well as its subcomponents - slow-5 (0.01-0.027 Hz), and slow-4 (0.027-0.073 Hz) frequency bands between fatigued and non-fatigued participants. We found no significant associations between post-stroke fatigue and ischaemic stroke lesion location or stroke volume. However, in the overall 0.01-0.08 Hz band, participants with post-stroke fatigue demonstrated significantly lower resting-state activity in the calcarine cortex (p .001, cluster-corrected p FDR =0.009, k=63) and lingual gyrus (p .001, cluster-corrected p FDR =0.025, k=42) and significantly higher activity in the medial prefrontal cortex (p .001, cluster-corrected p FDR =0.03, k=45), attributed to slow-4 and slow-5 oscillations, respectively. Post-stroke fatigue is associated with posterior hypoactivity and prefrontal hyperactivity, reflecting dysfunction within large-scale brain systems such as fronto-striatal-thalamic and frontal-occipital networks. These systems in turn might reflect a relationship between post-stroke fatigue and abnormalities in executive and visual functioning. This first whole-brain resting-state study provides new targets for further investigation of post-stroke fatigue beyond the lesion approach.
Publisher: Cold Spring Harbor Laboratory
Date: 05-08-2021
DOI: 10.1101/2021.08.03.21261461
Abstract: Stroke survivors are at high risk of dementia, associated with increasing age and vascular burden and with pre-existing cognitive impairment, older age. Brain atrophy patterns are recognised as signatures of neurodegenerative conditions, but the natural history of brain atrophy after stroke remains poorly described. We sought to determine whether stroke survivors who were cognitively normal at time of stroke had greater total brain (TBV) and hippoc al volume (HV) loss over 3 years than controls. We examined whether stroke survivors who were cognitively impaired (CI) at 3 months following their stroke had greater brain volume loss than cognitively normal (CN) stroke participants. Cognition And Neocortical Volume After Stroke (CANVAS) study is a multi-centre cohort study of first-ever or recurrent adult ischaemic stroke participants compared to age- and sex-matched community controls. Participants were followed with MRI and cognitive assessments over 3 years and were free of a history of cognitive impairment or decline at inclusion. Our primary outcome measure was TBV change between 3 months and 3 years secondary outcomes were TBV and HV change comparing CI and CN participants. We investigated associations between group status and brain volume change using a baseline-volume adjusted linear regression model with robust standard error. Ninety-three stroke (26 women, 66.7±12 years) and 39 control participants (15 women, 68.7±7 years) were available at 3 years. TBV loss in stroke patients was greater than controls: stroke mean (M)=20.3cm 3 ±SD14.8cm 3 controls M=14.2cm 3 ±SD13.2cm 3 (adjusted mean difference 7.88 95%CI [2.84,12.91] p-value=0.002). TBV decline was greater in those stroke participants who were cognitively impaired (M=30.7cm 3 SD=14.2cm 3 ) at 3 months (M=19.6cm 3 SD=13.8cm 3 ) (adjusted mean difference 10.42 95%CI [3.04,17.80], p-value=0.006). No statistically significant differences in HV change were observed. Ischaemic stroke survivors exhibit greater neurodegeneration compared to stroke-free controls. Brain atrophy is greater in stroke participants who were cognitively impaired people early after their stroke. Early cognitive impairment may predict greater subsequent atrophy, reflecting the combined impacts of stroke and vascular brain burden. Atrophy rates could serve as a useful biomarker for trials testing interventions to reduce post-stroke cognitive impairment.
Publisher: Oxford University Press (OUP)
Date: 28-03-2020
Abstract: Sleep–wake disruption is a key modifiable risk factor and sequela of stroke. The pathogenesis of poststroke sleep dysfunction is unclear. It is not known whether poststroke sleep pathology is due to focal infarction to sleep–wake hubs or to accelerated poststroke neurodegeneration in subcortical structures after stroke. We characterize the first prospective poststroke regional brain volumetric and whole-brain, fiber-specific, white matter markers of objectively measured sleep–wake dysfunction. We hypothesized that excessively long sleep (& h) duration and poor sleep efficiency (& %) measured using the SenseWear Armband 3-months poststroke (n = 112) would be associated with reduced regional brain volumes of a priori-selected sleep–wake regions of interest when compared to healthy controls with optimal sleep characteristics (n = 35). We utilized a novel technique known as a whole-brain fixel-based analysis to investigate the fiber-specific white matter differences in participants with long sleep duration. Stroke participants with long sleep (n = 24) duration exhibited reduced regional volumes of the ipsilesional thalamus and contralesional amygdala when compared with controls. Poor sleep efficiency after stroke (n = 29) was associated with reduced ipsilesional thalamus, contralesional hippoc us, and contralesional amygdala volumes. Whole-brain fixel-based analyses revealed widespread macrostructural degeneration to the corticopontocerebellar tract in stroke participants with long sleep duration, with fiber reductions of up to 40%. Neurodegeneration to subcortical structures, which appear to be vulnerable to accelerated brain volume loss after stroke, may drive sleep–wake deficiencies poststroke, independent of lesion characteristics and confounding comorbidities. We discuss these findings in the context of the clinicopathological implications of sleep-related neurodegeneration and attempt to corroborate previous mechanistic-neuroanatomical findings.
Publisher: Elsevier BV
Date: 2015
Publisher: Frontiers Media SA
Date: 16-02-2016
Publisher: Elsevier BV
Date: 05-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-04-2023
DOI: 10.1212/WNL.0000000000207065
Abstract: Cerebral white matter health can be estimated by MRI-derived indices of microstructure. White matter dysfunction is increasingly recognized as a contributor to neurodegenerative disorders affecting cognition and to functional outcomes after stroke. Reduced indices of white matter microstructure have been demonstrated cross-sectionally in stroke survivors compared with stroke-free participants, but longitudinal changes in the structure of white matter after stroke remain largely unexplored. We aimed to characterize white matter micro- and macrostructure over 3 years after stroke and study associations with white matter metrics and cognitive functions. Patients with first-ever or recurrent ischemic stroke of any etiology in any vascular territory were compared with stroke-free age- and sex-matched controls. Those diagnosed with hemorrhagic stroke, TIA, venous infarction, or significant medical comorbidities, psychiatric and neurodegenerative disorders, substance abuse, or history of dementia were excluded. Diffusion-weighted MRI data at 3, 12, and 36 months were analyzed using a longitudinal fixel-based analysis, sensitive to fiber tract–specific differences within a voxel. It was used to examine whole-brain white matter degeneration in stroke compared with control participants. We studied microstructural differences in fiber density and macrostructural changes in fiber-bundle cross-section, in relation to cognitive performance. Analyses were performed controlling for age, intracranial volume, and education (family-wise error–corrected p 0.05, nonparametric testing over 5,000 permutations). We included 71 participants with stroke (age 66 ± 12 years, 22 women) and 36 controls (age 69 ± 5 years, 13 women). We observed extensive white matter structural degeneration across the whole brain, particularly affecting the thalamic, cerebellar, striatal, and superior longitudinal tracts and corpus callosum. Importantly, follow-up regression analyses in 72 predefined tracts showed that the decline in fiber density and cross-section from 3 months to 3 years was associated with worse cognitive performance at 3 years after stroke, especially affecting visuospatial processing, processing speed, language, and recognition memory. We conclude that white matter neurodegeneration in ipsi- and contralesional thalamic, striatal, and cerebellar tracts continues to be greater in stroke survivors compared with stroke-free controls. White matter degeneration persists even years after stroke and is associated with poststroke cognitive impairment. ClinicalTrails.gov NCT02205424.
Publisher: Center for Open Science
Date: 08-04-2022
Abstract: Diffusion-weighted imaging has produced useful biomarkers of verbal fluency post-stroke but acquiring diffusion data is not always clinically feasible. Further, it has been demonstrated that subcortical regions may contribute to verbal fluency, though the predominant focus in the literature has been on cortical contributions to verbal fluency. Finally, the majority of recovery-oriented research on language in stroke has been cross-sectional, which does not allow for actual modelling of language change over time. Focusing on the contribution of subcortical and white matter structures to language recovery of in iduals with ischaemic stroke, our present study, therefore, used the information of white matter disconnection and volumetric measurements obtained directly from non-diffusion-weighted anatomical images (T1, T2 and FLAIR), which are routinely acquired in clinical settings, to understand verbal fluency performance over time. We derived neuropsychological and anatomical neuroimaging data of in iduals at 3- and 12-months post-stroke from the Cognition And Neocortical Volume After Stroke study, a longitudinal study of ischaemic stroke survivors and healthy stroke-free in iduals. Cortical volumetric and thickness measurements were derived from FreeSurfer. White matter disconnection was quantified by two metrics based on BCBToolkit: Disconnection severity – the proportion of lesioned voxel volume to the total volume of a tract, and disconnection probability – the probability of the overlap between a subject’s lesion and a tract. Using the linear mixed multiple regression method based on 5-fold cross-validation, we correlated the semantic and phonemic fluency scores of participants with longitudinal measurements of subcortical grey matter volume and 22 literature-driven bilateral white matter tracts of interests, while controlling for demographic variables (age, sex, handedness and education), total brain volume, lesion volume, and cortical thickness at both time points.Our results showed that the right subcortical grey matter volume was positively associated with phonemic fluency (p & 0.05) from 3 months to 12 months post-stroke and the model predictions improved with cross-validation. The disconnection probability of the left superior longitudinal fasciculus II and the left posterior arcuate fasciculus was negatively correlated to semantic fluency (p & 0.05) from 3 months to 12 months post-stroke, but this model did not generalize well following cross-validation.We conclude that subcortical grey matter volume is strongly related to phonemic fluency recovery after stroke, and that the association of white matter disruptions with semantic fluency recovery are strongly influenced by the specific lesion features of the stroke patients within the present study.
Publisher: Elsevier BV
Date: 2016
Publisher: Oxford University Press (OUP)
Date: 10-2021
DOI: 10.1093/BRAINCOMMS/FCAB254
Abstract: Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioural data in 828 in iduals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P & 0.004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behaviour was associated with a smaller ipsilesional thalamic volume in both early (n = 179 d = 0.68) and subacute (n = 274, d = 0.46) stroke. In chronic stroke (n = 404), worse sensorimotor behaviour was associated with smaller ipsilesional putamen (d = 0.52) and nucleus accumbens (d = 0.39) volumes, and a larger ipsilesional lateral ventricle (d = −0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment n = 256) was associated with smaller ipsilesional putamen (d = 0.72) and larger lateral ventricle (d = −0.41) volumes, while several measures of activity limitations (n = 116) showed no significant relationships. In the full cohort across all time (n = 828), sensorimotor behaviour was associated with the volumes of the ipsilesional nucleus accumbens (d = 0.23), putamen (d = 0.33), thalamus (d = 0.33) and lateral ventricle (d = −0.23). We demonstrate significant relationships between post-stroke sensorimotor behaviour and reduced volumes of deep grey matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings provide additional insight into how different cortico-thalamo-striatal circuits support post-stroke sensorimotor outcomes.
Publisher: Center for Open Science
Date: 20-11-2020
Abstract: Diffusion MRI has provided the neuroimaging community with a powerful tool to acquire in-vivo data sensitive to microstructural features of white matter, up to 3 orders of magnitude smaller than typical voxel sizes. The key to extracting such valuable information lies in complex modelling techniques, which form the link between the rich diffusion MRI data and various metrics related to the microstructural organisation. Over time, increasingly advanced techniques have been developed, up to the point where some diffusion MRI models can now provide access to properties specific to in idual fibre populations in each voxel in the presence of multiple "crossing" fibre pathways. While highly valuable, such fibre-specific information poses unique challenges for typical image processing pipelines and statistical analysis. In this work, we review the "fixel-based analysis" (FBA) framework that implements bespoke solutions to this end, and has recently seen a stark increase in adoption for studies of both typical (healthy) populations as well as a wide range of clinical populations. We describe the main concepts related to fixel-based analyses, as well as the methods and specific steps involved in a state-of-the-art FBA pipeline, with a focus on providing researchers with practical advice on how to interpret results. We also include an overview of the scope of current fixel-based analysis studies (until August 2020), categorised across a broad range of neuroscientific domains, listing key design choices and summarising their main results and conclusions. Finally, we critically discuss several aspects and challenges involved with the fixel-based analysis framework, and outline some directions and future opportunities.
Publisher: Elsevier BV
Date: 09-2020
Publisher: SAGE Publications
Date: 28-08-2015
Publisher: Cold Spring Harbor Laboratory
Date: 28-10-2021
DOI: 10.1101/2021.10.26.465924
Abstract: Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippoc us is involved in sensorimotor behavior but has not been widely studied within the context of post-stroke upper limb sensorimotor impairment. The hippoc us is vulnerable to secondary degeneration after stroke, and damage to this region could further weaken sensorimotor circuits, leading to greater chronic sensorimotor impairment. The purpose of this study was to investigate the cross-sectional association between non-lesioned hippoc al volume and upper limb sensorimotor impairment in people with chronic stroke. We hypothesized that smaller ipsilesional hippoc al volumes would be associated with worse upper-limb sensorimotor impairment. Cross-sectional T1-weighted brain MRIs were pooled from 357 participants at the chronic stage after stroke ( days post-stroke) compiled from 18 research cohorts worldwide in the ENIGMA Stroke Recovery Working Group (age: median = 61 years, interquartile range = 18, range = 23-93 135 women and 222 men). Sensorimotor impairment was estimated from the Fugl-Meyer Assessment of Upper Extremity scores. Robust mixed-effects linear models were used to test associations between post-stroke sensorimotor impairment and hippoc al volumes (ipsilesional and contralesional separately Bonferroni-corrected, p - value 0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. We also performed an exploratory analysis to test whether sex differences influence the relationship between sensorimotor impairment and hippoc al volume. Upper limb sensorimotor impairment was positively associated with ipsilesional ( p = 0.005 d = 0.33) but not contralesional ( p = 0.96 d = 0.01) hippoc al volume, such that impairment was worse for participants with smaller ipsilesional hippoc al volume. This association remained significant independent of lesion volume or other covariates ( p = 0.001 d = 0.36). Evidence indicates an interaction between sensorimotor impairment and sex for both ipsilesional ( p = 0.008 d = −0.29) and contralesional ( p = 0.006 d = −0.30) hippoc al volumes, whereby women showed progressively worsening sensorimotor impairment with smaller hippoc al volumes compared to men. The present study has identified a novel association between chronic post-stroke sensorimotor impairment and ipsilesional, but not contralesional, hippoc al volume. This finding was not due to lesion size and may be stronger in women. We also provide supporting evidence that smaller hippoc al volume post-stroke is likely a consequence of ipsilesional damage, which could provide a link between vascular disease and other disorders, such as dementia.
Publisher: Wiley
Date: 27-11-2021
DOI: 10.1002/JMRI.28009
Abstract: The structural integrity of hippoc al subfields has been investigated in many neurological disorders and was shown to be better associated with cognitive performance than whole hippoc us. In stroke, hippoc al atrophy is linked to cognitive impairment, but it is unknown whether the hippoc al subfields atrophy differently. To evaluate longitudinal hippoc al subfield atrophy in first year poststroke, in comparison with atrophy in healthy in iduals. Cohort. A total of 92 ischemic stroke (age: 67 ± 12 years, 63 men) and 39 healthy participants (age: 69 ± 7 years, 24 men). A3 T/T1‐MPRAGE, T2‐SPACE, and T2‐FLAIR. FreeSurfer (6.0) was used to delineate 12 hippoc al subfields. Whole hippoc al volume was computed as sum of subfield volumes excluding hippoc al fissure volume. Separate assessments were completed for contralesional and ipsilesional hippoc i. A mixed‐effect regression model was used to compare subfield volumes cross‐sectionally between healthy and stroke groups and longitudinally between 3‐month and 12‐month timepoints. False discovery rate at 0.05 significance level was used to correct for multiple comparisons. Also, a receiver operating characteristic (ROC) curve analysis was performed to assess differentiation between healthy and stroke participants based on subfield volumes. There were no volume differences between groups at 3 months, but there was a significant difference ( P = 0.027) in whole hippoc al volume reduction over time between control and stroke ipsilesionally. Thus, the ipsilesional whole hippoc al volume in stroke became significantly smaller ( P = 0.035) at 12 months. The hippoc al tail was the highest single‐region contributor (22.7%) to ipsilesional hippoc al atrophy (1.19%) over 9 months. The cornu ammonis areas (CA1) subfield volume reduction was minimal in controls and stroke contralesionally but significant ipsilesionally ( P = 0.007). CA1 volume significantly outperformed whole hippoc al volume ( P 0.01) in discriminating between stroke participants and healthy controls in ROC curve analysis. Greater stroke‐induced effects were observed in the ipsilesional hippoc us anteriorly in CA1 and posteriorly in the hippoc al tail. Atrophy of CA1 and hippoc al tail may provide a better link to cognitive impairment than whole hippoc al atrophy. 2 3
Publisher: Oxford University Press (OUP)
Date: 03-2022
DOI: 10.1093/BRAINCOMMS/FCAC061
Abstract: Dynamic whole-brain changes occur following stroke, and not just in association with recovery. We tested the hypothesis that the presence of a specific behavioural deficit after stroke would be associated with structural decline (atrophy) in the brain regions supporting the affected function, by examining language deficits post-stroke. We quantified whole-brain structural volume changes longitudinally (3–12 months) in stroke participants with (N = 32) and without aphasia (N = 59) as assessed by the Token Test at 3 months post-stroke, compared with a healthy control group (N = 29). While no significant difference in language decline rates (change in Token Test scores from 3 to 12 months) was observed between groups and some participants in the aphasic group improved their scores, stroke participants with aphasia symptoms at 3 months showed significant atrophy (& %, P = 0.0001) of the left inferior frontal gyrus not observed in either healthy control or non-aphasic groups over the 3–12 months period. We found significant group differences in the inferior frontal gyrus volume, accounting for age, sex, stroke severity at baseline, education and total intracranial volume (Bonferroni-corrected P = 0.0003). In a subset of participants (aphasic N = 14, non-aphasic N = 36, and healthy control N = 25) with available diffusion-weighted imaging data, we found significant atrophy in the corpus callosum and the left superior longitudinal fasciculus in the aphasic compared with the healthy control group. Language deficits at 3 months post-stroke are associated with accelerated structural decline specific to the left inferior frontal gyrus, highlighting that known functional brain reorganization underlying behavioural improvement may occur in parallel with atrophy of brain regions supporting the language function.
Publisher: Frontiers Media SA
Date: 2013
Publisher: Elsevier BV
Date: 07-2021
Publisher: Springer Science and Business Media LLC
Date: 07-02-2017
DOI: 10.1038/SREP41581
Abstract: Cognitive impairment is one of the most common problem saffecting older adults. In this study, we investigated whether Tai Chi Chuan and Baduanjin practice can modulate mental control functionand the resting state functional connectivity (rsFC) of the cognitive control network in older adults. Participants in the two exercise groups practiced either Tai Chi Chuan or Baduanjin for 12 weeks, and those in the control group received basic health education. Memory tests and fMRI scans were conducted at baseline and at the end of the study. Seed-based (bilateral dorsolateral prefrontal cortex, DLPFC) rsFC analysis was performed. We found that compared to the controls, 1) both Tai Chi Chuan and Baduanjin groups demonstrated significant improvements in mental control function 2) the Tai Chi Chuan group showed a significant decrease in rsFC between the DLPFC and the left superior frontal gyrus (SFG) and anterior cingulate cortex and 3) the Baduanjin group showed a significant decrease in rsFC between the DLPFC and the left putamen and insula. Mental control improvement was negatively associated with rsFC DLPFC-putamen changes across all subjects. These findings demonstrate the potential of Tai Chi Chuan and Baduanjin exercises in preventing cognitive decline.
Publisher: Springer Science and Business Media LLC
Date: 17-10-2022
DOI: 10.1007/S00429-022-02579-7
Abstract: Poor performance on verbal fluency tasks is associated with an increased risk of post-stroke cognitive impairment. Grey matter regions supporting verbal fluency have been identified via lesion–symptom mapping, but the links between verbal fluency and white matter structure remain less well described. We examined white matter correlates of semantic (Category Fluency Animals) and phonemic or lexical fluency (COWAT FAS) after stroke, accounting for stroke severity measured with the National Institutes of health Stroke Scale (NIHSS), age, sex, and level of education. White matter fibre density and cross-section measures were automatically extracted from 72 tracts, using MRtrix and TractSeg software in 72 ischaemic stroke survivors assessed 3 months after their event. We conducted regression analyses separately for phonemic and semantic fluency for each tract. Worse semantic fluency was associated with lower fibre density in several tracts, including the arcuate fasciculus, superior longitudinal fasciculus, inferior occipito-frontal fasciculus, inferior longitudinal fasciculus, optic radiation, striato-occipital, thalamo-occipital tracts, and inferior cerebellar peduncle. Our stroke s le was heterogenous with largely non-overlapping and predominantly right-lateralised lesions (lesion distribution: left N = 27, right N = 43, bilateral N = 2), dissimilar to previous studies of verbal fluency. Yet, the tracts we identified as correlates of semantic fluency were all left-lateralised. No associations between phonemic fluency performance and fibre density metrics in any of the white matter tracts we extracted survived correction for multiple comparisons, possibly due to the limitations in the selection of tracts and s le characteristics. We conclude that when accounting for the effects of stroke severity, sex, age, and education, semantic fluency is associated with white matter microstructure in the left arcuate fasciculus, superior longitudinal fasciculus, and several occipital tracts, possibly reflecting the disconnection in the sagittal stratum. Our results obtained with fixel-based analysis, complement previous findings obtained with lesions–symptom mapping and neurodegenerative approaches.
Publisher: Springer Science and Business Media LLC
Date: 20-11-2013
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2013.12.002
Abstract: A new perspective on cognition views cortical cell assemblies linking together knowledge about actions and perceptions not only as the vehicles of integrated action and perception processing but, furthermore, as a brain basis for a wide range of higher cortical functions, including attention, meaning and concepts, sequences, goals and intentions, and even communicative social interaction. This article explains mechanisms relevant to mechanistic action perception theory, points to concrete neuronal circuits in brains along with artificial neuronal network simulations, and summarizes recent brain imaging and other experimental data documenting the role of action perception circuits in cognition, language and communication.
Publisher: Elsevier BV
Date: 2023
Publisher: Springer Science and Business Media LLC
Date: 14-06-2018
DOI: 10.1007/S00429-018-1695-0
Abstract: The multilingual brain implements mechanisms that serve to select the appropriate language as a function of the communicative environment. Engaging these mechanisms on a regular basis appears to have consequences for brain structure and function. Studies have implicated the caudate nuclei as important nodes in polyglot language control processes, and have also shown structural differences in the caudate nuclei in bilingual compared to monolingual populations. However, the majority of published work has focused on the categorical differences between monolingual and bilingual in iduals, and little is known about whether these findings extend to multilingual in iduals, who have even greater language control demands. In the present paper, we present an analysis of the volume and morphology of the caudate nuclei, putamen, pallidum and thalami in 75 multilingual in iduals who speak three or more languages. Volumetric analyses revealed a significant relationship between multilingual experience and right caudate volume, as well as a marginally significant relationship with left caudate volume. Vertex-wise analyses revealed a significant enlargement of dorsal and anterior portions of the left caudate nucleus, known to have connectivity with executive brain regions, as a function of multilingual expertise. These results suggest that multilingual expertise might exercise a continuous impact on brain structure, and that as additional languages beyond a second are acquired, the additional demands for linguistic and cognitive control result in modifications to brain structures associated with language management processes.
Publisher: Elsevier BV
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 18-11-2015
DOI: 10.1038/SREP16809
Abstract: Our experience with the world is shaped not only directly through personal exposure but also indirectly through observing others and learning from their experiences. Using a conditioning paradigm, we investigated how directly and observationally learned information can affect pain perception, both consciously and non-consciously. Differences between direct and observed cues were manifest in higher pain ratings and larger skin conductance responses to directly experienced cues. However, the pain modulation effects produced by conditioning were of comparable magnitude for direct and observational learning. These results suggest that social observation can induce positive and negative pain modulation. Importantly, the fact that cues learned by observation and activated non-consciously still produced a robust conditioning effect that withstood extinction highlights the role of indirect exposure in placebo and nocebo effects.
Publisher: Springer Science and Business Media LLC
Date: 11-05-2022
DOI: 10.1038/S41398-022-01949-3
Abstract: The relationship between pain and depression is thought to be bidirectional and the underlying neurobiology ‘shared’ between the two conditions. However, these claims are often based on qualitative comparisons of brain regions implicated in pain or depression, while focused quantitative studies of the neurobiology of pain-depression comorbidity are lacking. Particularly, the direction of comorbidity, i.e., pain with depression vs. depression with pain, is rarely addressed. In this systematic review (PROSPERO registration CRD42020219876), we aimed to delineate brain correlates associated with primary pain with concomitant depression, primary depression with concurrent pain, and equal pain and depression comorbidity, using activation likelihood estimation (ALE) meta-analysis. Neuroimaging studies published in English until the 28th of September 2021 were evaluated using PRISMA guidelines. A total of 70 studies were included, of which 26 reported stereotactic coordinates and were analysed with ALE. All studies were assessed for quality by two authors, using the National Institute of Health Quality Assessment Tool. Our results revealed paucity of studies that directly investigated the neurobiology of pain-depression comorbidity. The ALE analysis indicated that pain with concomitant depression was associated with the right amygdala, while depression with concomitant pain was related primarily to the left dorsolateral prefrontal cortex (DLPFC). We provide evidence that pain and depression have a cumulative negative effect on a specific set of brain regions, distinct for primary diagnosis of depression vs. pain.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-05-2023
DOI: 10.1212/WNL.0000000000207219
Abstract: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes. We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage. We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (β = 0.21 95% CI 0.04–0.38, p = 0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (β = −0.28 95% CI −0.41 to −0.15, p 0.001) and across multiple domains of function (β = −0.14 95% CI −0.22 to −0.06, p 0.001). Brain age mediated 15% of the impact of lesion damage on sensorimotor performance (95% CI 3%–58%, p = 0.01). Greater brain resilience explained why people have better outcomes, given matched lesion damage (odds ratio 1.04, 95% CI 1.01–1.08, p = 0.004). We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets.
Publisher: SAGE Publications
Date: 17-05-2019
Abstract: Cerebrospinal fluid circulation is crucial for the functioning of the brain. Aging and brain pathologies such as Alzheimer’s disease have been associated with a change in the morphology of the ventricles and the choroid plexus. Despite the evidence from animal models that the cerebrospinal fluid system plays an important role in neuroinflammation and the restoration of the brain after ischemic brain injury, little is known about changes to the choroid plexus after stroke in humans. Our goal was to characterize structural choroid plexus changes poststroke. We used an automatic segmentation tool to estimate the volumes of choroid plexus and lateral ventricles in stroke and control participants at three time points (at baseline, 3 and 12 months) over the first year after stroke. We assessed group differences cross-sectionally at each time point and longitudinally. For stroke participants, we specifically differentiated between ipsi- and contra-lesional volumes. Statistical analyses were conducted for each region separately and included covariates such as age, sex, total intracranial volume, and years of education. We observed significantly larger choroid plexus volumes in stroke participants compared to controls in both cross-sectional and longitudinal analyses. Choroid plexus volumes did not exhibit any change over the first year after stroke, with no difference between ipsi- and contra-lesional volumes. This was in contrast to the volume of lateral ventricles that we found to enlarge over time in all participants, with more accelerated expansion in stroke survivors ipsi-lesionally. Our results suggest that chronic stages of stroke are characterized by larger choroid plexus volumes, but the enlargement likely takes place prior to or very early after the stroke incident.
Publisher: Elsevier BV
Date: 2017
Location: Australia
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2018
End Date: 2020
Funder: Australian Research Council
View Funded ActivityStart Date: 07-2023
End Date: 06-2027
Amount: $988,306.00
Funder: Australian Research Council
View Funded ActivityStart Date: 08-2018
End Date: 11-2022
Amount: $366,403.00
Funder: Australian Research Council
View Funded Activity