ORCID Profile
0000-0001-5756-3195
Current Organisation
KU Leuven
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Publisher: Springer Science and Business Media LLC
Date: 04-2021
DOI: 10.1038/S41398-021-01314-W
Abstract: Psychomotor dysfunction (PMD) is a core element and key contributor to disability in late life depression (LLD), which responds well to electroconvulsive therapy (ECT). The neurobiology of PMD and its response to ECT are not well understood. We hypothesized that PMD in LLD is associated with lower striatal volume, and that striatal volume increase following ECT explains PMD improvement. We analyzed data from a two-center prospective cohort study of 110 LLD subjects ( years) receiving ECT. Brain MRI and assessment of mood, cognition, and PMD was performed 1 week before, 1 week after, and 6 months after ECT. Volumetry of the caudate nucleus, putamen, globus pallidus, and nucleus accumbens was derived from automatically segmented brain MRIs using Freesurfer®. Linear multiple regression analyses were used to study associations between basal ganglia volume and PMD. Brain MRI was available for 66 patients 1 week post ECT and in 22 patients also six months post ECT. Baseline PMD was associated with a smaller left caudate nucleus. One week after ECT, PMD improved and volume increases were detected bilaterally in the caudate nucleus and putamen, and in the right nucleus accumbens. Improved PMD after ECT did not relate to the significant volume increases in these structures, but was predicted by a nonsignificant volume change in the right globus pallidus. No volume differences were detected 6 months after ECT, compared to baseline. Although PMD is related to lower striatal volume in LLD, ECT-induced increase of striatal volume does not explain PMD improvement.
Publisher: Springer Science and Business Media LLC
Date: 28-01-2021
DOI: 10.1186/S12888-021-03063-Y
Abstract: Major depressive disorders rank in the top ten causes of ill health in all but four countries worldwide and are the leading cause of years lived with disability in Europe (WHO). Recent research suggests that neurodegenerative pathology may contribute to the development of late-life depression (LLD) in a sub-group of patients and represent a target for prevention and early diagnosis. In parallel, electroconvulsive therapy (ECT), which is the most effective treatment for severe LLD, has been associated with significant brain structural changes. In both LLD and ECT hippoc al volume change plays a central role however, the neurobiological mechanism underlying it and its relevance for clinical outcomes remain unresolved. This is a monocentric, clinical cohort study with a cross-sectional arm evaluating PET-MR imaging and behavioural measures in 64 patients with LLD compared to 64 healthy controls, and a longitudinal arm evaluating the same imaging and behavioural measures after 10 ECT sessions in 20 patients receiving ECT as part of their normal clinical management. Triple tracer PET-MRI data will be used to measure: hippoc al volume (high resolution MRI), synaptic density using [ 11 C]UCB-J, which targets the Synaptic Vesicle Glycoprotein 2A receptor, tau pathology using [ 18 F]MK-6240, and cerebral amyloid using [ 18 F]-Flutemetamol, which targets beta-amyloid neuritic plaques in the brain. Additional MRI measures and ultrasound will assess cerebral vascular structure and brain connectivity. Formal clinical and neuropsychological assessments will be conducted alongside experience s ling and physiological monitoring to assess mood, stress, cognition and psychomotor function. The main aim of the study is to identify the origin and consequences of hippoc al volume differences in LLD by investigating how biomarkers of pathological ageing contribute to medial temporal lobe pathology. Studying how synaptic density, tau, amyloid and vascular pathology relate to neuropsychological, psychomotor function, stress and ECT, will increase our pathophysiological understanding of the in vivo molecular, structural and functional alterations occurring in depression and what effect this has on clinical outcome. It may also lead to improvements in the differential diagnosis of depression and dementia yielding earlier, more optimal, cost-effective clinical management. Finally, it will improve our understanding of the neurobiological mechanism of ECT. ClinicalTrials.gov Identifier: NCT03849417 , 21/2/2019.
Publisher: Frontiers Media SA
Date: 2014
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.NEUBIOREV.2019.08.017
Abstract: Due to their ability to capture attention, emotional stimuli tend to benefit from enhanced perceptual processing, which can be helpful when such stimuli are task-relevant but hindering when they are task-irrelevant. Altered emotion-attention interactions have been associated with symptoms of affective disturbances, and emerging research focuses on improving emotion-attention interactions to prevent or treat affective disorders. In line with the Human Affectome Project's emphasis on linguistic components, we also analyzed the language used to describe attention-related aspects of emotion, and highlighted terms related to domains such as conscious awareness, motivational effects of attention, social attention, and emotion regulation. These terms were discussed within a broader review of available evidence regarding the neural correlates of (1) Emotion-Attention Interactions in Perception, (2) Emotion-Attention Interactions in Learning and Memory, (3) In idual Differences in Emotion-Attention Interactions, and (4) Training and Interventions to Optimize Emotion-Attention Interactions. This comprehensive approach enabled an integrative overview of the current knowledge regarding the mechanisms of emotion-attention interactions at multiple levels of analysis, and identification of emerging directions for future investigations.
Publisher: Oxford University Press (OUP)
Date: 04-03-2020
Abstract: The behavioural variant of frontotemporal dementia (bvFTD) is a frequent cause of early-onset dementia. The diagnosis of bvFTD remains challenging because of the limited accuracy of neuroimaging in the early disease stages and the absence of molecular biomarkers, and therefore relies predominantly on clinical assessment. BvFTD shows significant symptomatic overlap with non-degenerative primary psychiatric disorders including major depressive disorder, bipolar disorder, schizophrenia, obsessive-compulsive disorder, autism spectrum disorders and even personality disorders. To date, ∼50% of patients with bvFTD receive a prior psychiatric diagnosis, and average diagnostic delay is up to 5–6 years from symptom onset. It is also not uncommon for patients with primary psychiatric disorders to be wrongly diagnosed with bvFTD. The Neuropsychiatric International Consortium for Frontotemporal Dementia was recently established to determine the current best clinical practice and set up an international collaboration to share a common dataset for future research. The goal of the present paper was to review the existing literature on the diagnosis of bvFTD and its differential diagnosis with primary psychiatric disorders to provide consensus recommendations on the clinical assessment. A systematic literature search with a narrative review was performed to determine all bvFTD-related diagnostic evidence for the following topics: bvFTD history taking, psychiatric assessment, clinical scales, physical and neurological examination, bedside cognitive tests, neuropsychological assessment, social cognition, structural neuroimaging, functional neuroimaging, CSF and genetic testing. For each topic, responsible team members proposed a set of minimal requirements, optimal clinical recommendations, and tools requiring further research or those that should be developed. Recommendations were listed if they reached a ≥ 85% expert consensus based on an online survey among all consortium participants. New recommendations include performing at least one formal social cognition test in the standard neuropsychological battery for bvFTD. We emphasize the importance of 3D-T1 brain MRI with a standardized review protocol including validated visual atrophy rating scales, and to consider volumetric analyses if available. We clarify the role of 18F-fluorodeoxyglucose PET for the exclusion of bvFTD when normal, whereas non-specific regional metabolism abnormalities should not be over-interpreted in the case of a psychiatric differential diagnosis. We highlight the potential role of serum or CSF neurofilament light chain to differentiate bvFTD from primary psychiatric disorders. Finally, based on the increasing literature and clinical experience, the consortium determined that screening for C9orf72 mutation should be performed in all possible robable bvFTD cases or suspected cases with strong psychiatric features.
Publisher: American Academy of Sleep Medicine (AASM)
Date: 18-08-2023
DOI: 10.5664/JCSM.10778
Publisher: Elsevier BV
Date: 06-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-09-2020
Publisher: Springer Science and Business Media LLC
Date: 10-06-2021
DOI: 10.1038/S42003-021-02235-6
Abstract: Repetition suppression (RS) reflects a neural attenuation during repeated stimulation. We used fMRI and the subsequent memory paradigm to test the predictive coding hypothesis for RS during visual memory processing by investigating the interaction between RS and differences due to memory in category-selective cortex (FFA, pSTS, PPA, and RSC). Fifty-six participants encoded face and house stimuli twice, followed by an immediate and delayed (48 h) recognition memory assessment. Linear Mixed Model analyses with repetition, subsequent recognition performance, and their interaction as fixed effects revealed that absolute RS during encoding interacts with probability of future remembrance in face-selective cortex. This effect was not observed for relative RS, i.e. when controlled for adapter-response. The findings also reveal an association between adapter response and RS, both for short and long term (48h) intervals, after controlling for the mathematical dependence between both measures. These combined findings are challenging for predictive coding models of visual memory and are more compatible with adapter-related and familiarity accounts.
Publisher: Oxford University Press (OUP)
Date: 31-01-2020
Publisher: Elsevier BV
Date: 05-2018
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.CORTEX.2014.11.009
Abstract: Mental imagery is a powerful mechanism that may facilitate visual perception as well as compensate for it. The role of V1 in mental imagery is still a matter of debate. Our goal here was to investigate whether visual imagery was still possible in case of bilateral V1 destruction behaviorally evidenced by total clinical blindness and if so, whether it might boost residual visual perception. In a factorial fMRI design, faces, scenes or scrambled images were presented while a rare patient with cortical blindness over the whole visual field due to bilateral V1-lesions (TN) was instructed to imagine either an angry person or a neutral object (tree). The results show that visual imagery of a person activates frontal, parietal and occipital brain regions similar to control subjects and hence suggest that V1 is not necessary for visual imagery. In addition, the combination of visual stimulation and visual imagery of socio-emotional stimuli triggers activation in superior parietal lobule (SPL) and ventromedial (vmPFC) and dorsolateral prefrontal cortex (DLPFC). Finally, activation during residual vision, visual imagery and their interaction overlapped in the SPL, arguing for a central role of feeling in V1-independent vision and imagery.
Publisher: American Psychiatric Association Publishing
Date: 03-2017
DOI: 10.1176/APPI.AJP.2016.16030319
Abstract: Hippoc al volume is commonly decreased in late-life depression. According to the depression-as-late-life-neuropsychiatric-disorder model, lower hippoc al volume in late-life depression is associated with neurodegenerative changes. The purpose of this prospective study was to examine whether lower hippoc al volume in late-life depression is associated with Alzheimer's disease pathology. Of 108 subjects who participated, complete, good-quality data sets were available for 100: 48 currently depressed older adults and 52 age- and gender-matched healthy comparison subjects who underwent structural MRI, [ A significant difference was observed in mean normalized total hippoc al volume between patients and comparison subjects, but there were no group differences in cortical amyloid uptake or proportion of amyloid-positive subjects. The difference in hippoc al volume remained significant after the amyloid-positive subjects were excluded. There was no association between hippoc al volume and amyloid uptake in either patients or comparison subjects. Lower hippoc al volume was not related to amyloid pathology in this s le of patients with late-life depression. These data counter the common belief that changes in hippoc al volume in late-life depression are due to prodromal Alzheimer's disease.
Publisher: Cold Spring Harbor Laboratory
Date: 09-02-2021
DOI: 10.1101/2021.02.08.21251205
Abstract: MRI derived hippoc al volume (HV) and amyloid PET may be useful clinical biomarkers for differentiating between geriatric depression and Alzheimer’s Disease (AD). Here we investigated the incremental value of HV and 18F-flutemetmol PET in tandem and sequentially to improve discrimination in unclassified participants. Two approaches were compared in 41 participants with geriatric depression and 27 participants with probable AD: (1) amyloid and HV combined in one model and (2) HV first and then amyloid. Both HV(χ 2 (1) = 6.46: p= 0.011) and amyloid (χ 2 (1) =11.03: p=0.0009) were significant diagnostic predictors of depression (sensitivity: 95%, specificity: 89%). (2) 51% of participants were correctly classified according to clinical diagnosis based on HV alone, increasing to 87% when adding amyloid data (sensitivity: 94%, specificity: 78%). Hippoc al volume may be a useful gatekeeper for identifying depressed in iduals at risk for AD who would benefit from additional amyloid biomarkers when available.
Publisher: Elsevier BV
Date: 12-2008
Publisher: Springer Science and Business Media LLC
Date: 20-08-2019
DOI: 10.1038/S41398-019-0530-6
Abstract: Several studies have shown that electroconvulsive therapy (ECT) results in increased hippoc al volume. It is likely that a multitude of mechanisms including neurogenesis, gliogenesis, synaptogenesis, angiogenesis, and vasculogenesis contribute to this volume increase. Neurotrophins, like vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) seem to play a crucial mediating role in several of these mechanisms. We hypothesized that two regulatory SNPs in the VEGF and BDNF gene influence the changes in hippoc al volume following ECT. We combined genotyping and brain MRI assessment in a s le of older adults suffering from major depressive disorder to test this hypothesis. Our results show an effect of rs699947 (in the promotor region of VEGF ) on hippoc al volume changes following ECT. However, we did not find a clear effect of rs6265 (in BDNF ). To the best of our knowledge, this is the first study investigating possible genetic mechanisms involved in hippoc al volume change during ECT treatment.
Publisher: Cambridge University Press (CUP)
Date: 14-08-2023
DOI: 10.1017/S0033291723002258
Abstract: Very-late-onset schizophrenia-like psychosis (VLOSLP) is associated with significant burden. Its clinical importance is increasing as the global population of older adults rises, yet owing to limited research in this population, the neurobiological underpinnings of VLOSP remain insufficiently clarified. Here we address this knowledge gap using novel morphometry techniques to investigate grey matter volume (GMV) differences between VLOSLP and healthy older adults, and their correlations with neuropsychological scores. In this cross-sectional study, we investigated whole-brain GMV differences between 35 in iduals with VLOSLP (mean age 76.7, 26 female) and 36 healthy controls (mean age 75.7, 27 female) using whole-brain voxel-based morphometry (VBM) and supplementary source-based morphometry (SBM) on high resolution 3D T1-weighted MRI images. Additionally, we investigated relationships between GMV differences and cognitive function assessed with an extensive neuropsychological battery. VBM showed lower GMV in the thalamus, left inferior frontal gyrus and left insula in patients with VLOSLP compared to healthy controls. SBM revealed lower thalamo-temporal GMV in patients with VLOSLP. Processing speed, selective attention, mental flexibility, working memory, verbal memory, semantic fluency and confrontation naming were impaired in patients with VLOSLP. Correlations between thalamic volumes and memory function were significant within the group of in iduals with VLOSLP, whereas no significant associations remained in the healthy controls. Lower GMV in the thalamus and fronto-temporal regions may be part of the underlying neurobiology of VLOSLP, with lower thalamic GMV contributing to memory impairment in the disorder.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JAD.2019.03.055
Abstract: Gray matter volume decrease, white matter vascular pathology and amyloid accumulation are age-related brain changes that have been related to the pathogenesis of late life depression (LLD). Furthermore, lower hippoc al volume and more white matter hyperintensities (WMH) may contribute to poor response to electroconvulsive therapy (ECT) in severely depressed older adults. We hypothesized that the accumulation of age-related brain changes negatively affects outcome following ECT in LLD. 34 elderly patients with severe LLD were treated twice weekly with ECT until remission. All had both 3T structural magnetic resonance imaging (MRI) and β-amyloid positron emission tomography (PET) imaging using 18F-flutemetamol at baseline. MADRS and MMSE were obtained weekly which included 1 week prior to ECT (T0), after the sixth ECT (T1), and one week (T2) after the last ECT as well as at four weeks (T3) and 6 months (T4) after the last ECT. We conducted a multiple logistic regression analysis and a survival analysis with neuroimaging measures as predictors, and response, remission and relapse as outcome variable. We did not find any association between baseline hippoc al volume, white matter hyperintensity volume and total amyloid load and response or remission at 1 and 4 weeks post ECT, nor with relapse at week 4. The present exploratory study was conducted at a single center academic hospital, the s le size was small, the focus was on hippoc al volume and the predictive effect of structural and molecular changes associated with aging were used. Our study shows no evidence of relationship between response to ECT and age-related structural or molecular brain changes, implying that ECT can be applied effectively in depressed patients irrespective of accumulating age-related brain changes.
Publisher: Elsevier BV
Date: 04-2015
Publisher: Elsevier BV
Date: 10-2020
Publisher: BMJ
Date: 28-09-2021
Publisher: Springer Science and Business Media LLC
Date: 05-08-2021
DOI: 10.1038/S41598-021-95206-0
Abstract: Late-life depression (LLD) is associated with a risk of developing Alzheimer’s disease (AD). However, the role of AD-pathophysiology in LLD, and its association with clinical symptoms and cognitive function are elusive. In this study, one hundred subjects underwent amyloid positron emission tomography (PET) imaging with [ 18 F]-flutemetamol and structural MRI: 48 severely depressed elderly subjects (age 74.1 ± 7.5 years, 33 female) and 52 age-/gender-matched healthy controls (72.4 ± 6.4 years, 37 female). The Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test (RAVLT) were used to assess the severity of depressive symptoms and episodic memory function respectively. Amyloid deposition was quantified using the standardized uptake value ratio. Whole-brain voxel-wise comparisons of amyloid deposition and gray matter volume (GMV) between LLD and controls were performed. Multivariate analysis of covariance was conducted to investigate the association of regional differences in amyloid deposition and GMV with clinical factors, including GDS and RAVLT. As a result, there were no significant group differences in amyloid deposition. In contrast, LLD showed significant lower GMV in the left temporal and parietal region. GMV reduction in the left temporal region was associated with episodic memory dysfunction, but not with depression severity. Regional GMV reduction was not associated with amyloid deposition. LLD is associated with lower GMV in regions that overlap with AD-pathophysiology, and which are associated with episodic memory function. The lack of corresponding associations with amyloid suggests that lower GMV driven by non-amyloid pathology may play a central role in the neurobiology of LLD presenting as a psychiatric disorder. Trial registration : European Union Drug Regulating Authorities Clinical Trials identifier: EudraCT 2009-018064-95.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Springer International Publishing
Date: 2017
Publisher: Springer Science and Business Media LLC
Date: 09-12-2022
DOI: 10.1038/S42003-022-04324-6
Abstract: Affective experience colours everyday perception and cognition, yet its fundamental and neurobiological basis is poorly understood. The current debate essentially centers around the communalities and specificities across in iduals, events, and emotional categories like anger, sadness, and happiness. Using fMRI during the experience of these emotions, we critically compare the two dominant conflicting theories on human affect. Basic emotion theory posits emotions as discrete universal entities generated by dedicated emotion category-specific neural circuits, while psychological construction theory claims emotional events as unique, idiosyncratic, and constructed by psychological primitives like core affect and conceptualization, which underlie each emotional event and operate in a predictive framework. Based on the findings of 8 a priori-defined model-specific prediction tests on the neural response litudes and patterns, we conclude that the neurobiological basis of affect is primarily characterized by idiosyncratic mechanisms and a common neural basis shared across emotion categories, consistent with psychological construction theory. The findings provide further insight into the organizational principles of the neural basis of affect and brain function in general. Future studies in clinical populations with affective symptoms may reveal the corresponding underlying neural changes from a psychological construction perspective.
Publisher: Elsevier BV
Date: 2019
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.PSCYCHRESNS.2022.111443
Abstract: Amyloid positron emission tomography (PET) and hippoc al volume derived from magnetic resonance imaging may be useful clinical biomarkers for differentiating between geriatric depression and Alzheimer's disease (AD). Here we investigated the incremental value of using hippoc al volume and 18F-flutemetmol amyloid PET measures in tandem and sequentially to improve discrimination in unclassified participants. Two approaches were compared in 41 participants with geriatric depression and 27 participants with probable AD: (1) amyloid and hippoc al volume combined in one model and (2) classification based on hippoc al volume first and then subsequent stratification using standardized uptake value ratio (SUVR)-determined amyloid positivity. Hippoc al volume and amyloid SUVR were significant diagnostic predictors of depression (sensitivity: 95%, specificity: 89%). 51% of participants were correctly classified according to clinical diagnosis based on hippoc al volume alone, increasing to 87% when adding amyloid data (sensitivity: 94%, specificity: 78%). Our results suggest that hippoc al volume may be a useful gatekeeper for identifying depressed in iduals at risk for AD who would benefit from additional amyloid biomarkers when available.
Publisher: Cold Spring Harbor Laboratory
Date: 10-02-2021
DOI: 10.1101/2021.02.08.21250568
Abstract: Late-life depression (LLD) is associated with a risk of developing Alzheimer’s disease (AD). However, the role of AD-pathophysiology in LLD, and its association with clinical symptoms and cognitive function are elusive. In this study, one hundred subjects underwent amyloid positron emission tomography (PET) imaging with [ 18 F]-flutemetamol and structural MRI: 48 severely depressed elderly subjects (age 74.1±7.5 years, 33 female) and 52 age-/gender-matched healthy controls (72.4±6.4 years, 37 female). The Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test (RAVLT) were used to assess the severity of depressive symptoms and episodic memory function respectively. Amyloid deposition was quantified using the standardized uptake value ratio. Whole-brain voxel-wise comparisons of amyloid deposition and gray matter volume (GMV) between LLD and controls were performed. Multivariate analysis of covariance was conducted to investigate the association of regional differences in amyloid deposition and GMV with clinical factors, including GDS and RAVLT. As a result, there were no significant group differences in amyloid deposition. In contrast, LLD showed significant lower GMV in the left temporal and parietal region. GMV reduction in the left temporal region was associated with episodic memory dysfunction, but not with depression severity. Regional GMV reduction was not associated with amyloid deposition. LLD is associated with lower GMV in regions that overlap with AD-pathophysiology, and which are associated with episodic memory function. The lack of corresponding associations with amyloid suggests that lower GM driven by non-amyloid pathology may play a central role in the neurobiology of LLD presenting as a psychiatric disorder.
Publisher: Wiley
Date: 13-08-2023
DOI: 10.1002/MDS.29570
Abstract: To investigate whether mild motor signs (MMS) in old age correlate with synaptic density in the brain. Normal aging is associated with a decline in movement quality and quantity, commonly termed “mild parkinsonian signs” or more recently MMS. Whether MMS stem from global brain aging or pathology within motor circuits remains unresolved. The synaptic vesicle glycoprotein 2A positron emission tomography (PET) ligand 11 C‐UCB‐J allows the investigation of brain‐motor associations at the synaptic level in vivo. Fifty‐eight healthy older adults (≥50 years) were included from two monocentric control cohorts. Brain magnetic resonance imaging and 11 C‐UCB‐J PET data were available in 54 participants. 11 C‐UCB‐J PET binding was quantified by standardized uptake value ratio (SUVR) values in grey matter (GM) volumes of interest (VOIs): caudate, putamen, globus pallidus, substantia nigra, thalamus, cerebellum, and the frontal, parietal, temporal, and occipital cortex. Multiple linear regression analyses were performed with Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) part III score measuring MMS as the dependent variable and mean SUVR values in each VOI as the independent variable with age, Fazekas score (white matter lesion [WML] load), VOI and cohort as covariates. Participants (68 ± 7.5 years 52% female) had an average MDS‐UPDRS part III score of 3.3 ± 2.8. The MDS‐UPDRS part III score was inversely associated with synaptic density, independently of WML load or GM volume, in the caudate, substantia nigra, thalamus, cerebellum, and parietal, occipital, temporal cortex. Cohen's f 2 showed moderate effect sizes for subcortical (range, 0.30–0.35), cortical (0.28–0.35) and cerebellar VOIs (0.31). MMS in healthy aging are associated with lower synaptic density throughout the brain. © 2023 International Parkinson and Movement Disorder Society.
No related grants have been discovered for Jan Van den Stock.