ORCID Profile
0000-0003-0011-4158
Current Organisations
KU Leuven
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Universitair Psychiatrisch Centrum KU Leuven
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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: Cambridge University Press (CUP)
Date: 26-11-2013
DOI: 10.1017/S0033291713002845
Abstract: White matter (WM) abnormalities are proposed as potential endophenotypic markers of bipolar disorder (BD). In a diffusion tensor imaging (DTI) voxel-based analysis (VBA) study of families multiply affected with BD, we previously reported that widespread abnormalities of fractional anisotropy (FA) are associated with both BD and genetic liability for illness. In the present study, we further investigated the endophenotypic potential of WM abnormalities by applying DTI tractography to specifically investigate tracts implicated in the pathophysiology of BD. Diffusion magnetic resonance imaging (MRI) data were acquired from 19 patients with BD type I from multiply affected families, 21 of their unaffected first-degree relatives and 18 healthy volunteers. DTI tractography was used to identify the cingulum, uncinate fasciculus (UF), arcuate portion of the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), corpus callosum, and the anterior limb of the internal capsule (ALIC). Regression analyses were conducted to investigate the effect of participant group and genetic liability on FA and radial diffusivity (RD) in each tract. We detected a significant effect of group on both FA and RD in the cingulum, SLF, callosal splenium and ILF driven by reduced FA and increased RD in patients compared to controls and relatives. Increasing genetic liability was associated with decreased FA and increased RD in the UF, and decreased FA in the SLF, among patients. WM microstructural abnormalities in limbic, temporal and callosal pathways represent microstructural abnormalities associated with BD whereas alterations in the SLF and UF may represent potential markers of endophenotypic risk.
Publisher: Elsevier BV
Date: 04-2012
Publisher: S. Karger AG
Date: 08-05-2020
DOI: 10.1159/000507556
Publisher: Elsevier BV
Date: 2017
Publisher: Elsevier BV
Date: 11-2020
Publisher: Springer Science and Business Media LLC
Date: 08-01-2014
Publisher: American Academy of Sleep Medicine (AASM)
Date: 18-08-2023
DOI: 10.5664/JCSM.10778
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: Cold Spring Harbor Laboratory
Date: 02-10-2020
DOI: 10.1101/2020.09.30.20204701
Abstract: Brain atlases and templates are at the heart of neuroimaging analyses, for which they facilitate multimodal registration, enable group comparisons and provide anatomical reference. However, as atlas-based approaches rely on correspondence mapping between images they perform poorly in the presence of structural pathology. Whilst several strategies exist to overcome this problem, their performance is often dependent on the type, size and homogeneity of any lesions present. We therefore propose a new solution, referred to as Virtual Brain Grafting (VBG), which is a fully-automated, open-source workflow to reliably parcellate MR images in the presence of a broad spectrum of focal brain pathologies, including large, bilateral, intra- and extra-axial, heterogeneous lesions with and without mass effect. The core of the VBG approach is the generation of a lesion-free T1-weighted input image which enables further image processing operations that would otherwise fail. Here we validated our solution based on Freesurfer recon-all parcellation in a group of 10 patients with heterogeneous gliomatous lesions, and a realistic synthetic cohort of glioma patients (n=100) derived from healthy control data and patient data. We demonstrate that VBG outperforms a non-VBG approach assessed qualitatively by expert neuroradiologists and Mann-Whitney U tests to compare corresponding parcellations (real patients U(6,6) = 33, z = 2.738, P .010, synthetic patients U(48,48) = 2076, z = 7.336, P .001). Results were also quantitatively evaluated by comparing mean dice scores from the synthetic patients using one-way ANOVA (unilateral VBG = 0.894, bilateral VBG = 0.903, and non-VBG = 0.617, P .001). Additionally, we used linear regression to show the influence of lesion volume, lesion overlap with, and distance from the Freesurfer volumes of interest, on labelling accuracy. VBG may benefit the neuroimaging community by enabling automated state-of-the-art MRI analyses in clinical populations, for ex le by providing input data for automated solutions for fiber tractography or resting-state fMRI analyses that could also be used in the clinic. To fully maximize its availability, VBG is provided as open software under a Mozilla 2.0 license ( github.com/KUL-Radneuron/KUL_VBG ). (A) shows T1 images from two patients with gliomatous lesions. VBG is a lesion replacement/filling workflow with one approach for unilateral lesions (uVBG) and another for bilateral lesions (bVBG). (B) shows the recon-all approach selected, (C) & (D) show the output, tissue segmentations (C) and whole brain parcellations (D). If VBG is not used (non-VBG) recon-all may finish with some errors in the parcellations (left) or fail to generate a parcellation entirely (right). However, using either VBG method allows recon-all to complete where it had previously failed and also improves parcellation quality.
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: Elsevier BV
Date: 11-2021
Publisher: Elsevier BV
Date: 04-2023
Publisher: American Society of Clinical Oncology (ASCO)
Date: 07-2014
Abstract: To examine whether cognitive complaints after treatment for breast cancer are associated with detectable changes in brain activity during multitasking. Eighteen patients who were scheduled to receive chemotherapy performed a functional magnetic resonance imaging multitasking task in the scanner before the start of treatment (t1) and 4 to 6 months after finishing treatment (t2). Sixteen patients who were not scheduled to receive chemotherapy and 17 matched healthy controls performed the same task at matched intervals. Task difficulty level was adjusted in idually to match performance across participants. Statistical Parametric Mapping 8 (SPM8) software was used for within-group, between-group, and group-by-time interaction image analyses. Voxel-based paired t tests revealed significantly decreased activation (P .05) from t1 to t2 at matched performance in the multitasking network of chemotherapy-treated patients, whereas no changes were noted in either of the control groups. At baseline, there were no differences between the groups. Furthermore, in contrast to controls, the chemotherapy-treated patients reported a significant increase in cognitive complaints (P .05) at t2. Significant (P .05) correlations were found between these increases and decreases in multitasking-related brain activation. Moreover, a significant group-by-time interaction (P .05) was found whereby chemotherapy-treated patients showed decreased activation and healthy controls did not. These results suggest that changes in brain activity may underlie chemotherapy-induced cognitive complaints. The observed changes might be related to chemotherapy-induced damage to the brain or reduced connectivity between brain regions rather than to changes in effort or changes in functional strategy. To the best of our knowledge, this is the first longitudinal study providing evidence for a relationship between longitudinal changes in cognitive complaints and changes in brain activation after chemotherapy.
Publisher: Elsevier BV
Date: 02-2020
Publisher: Elsevier BV
Date: 05-2017
Publisher: CMA Joule Inc.
Date: 03-2016
DOI: 10.1503/JPN.140322
Abstract: The evidence on the mechanisms of action of electroconvulsive therapy (ECT) has grown over the past decades. Recent studies show an ECT-related increase in hippoc al, amygdala and subgenual cortex volume. We examined grey matter volume changes following ECT using voxel-based morphometry (VBM) whole brain analysis in patients with severe late life depression (LLD). Elderly patients with unipolar depression were treated twice weekly with right unilateral ECT until remission on the Montgomery-Åsberg Depression Rating Scale (MADRS) was achieved. Cognition (Mini Mental State Examination) and psychomotor changes (CORE Assessment) were monitored at baseline and 1 week after the last session of ECT. We performed 3 T structural MRI at both time points. We used the VBM8 toolbox in SPM8 to study grey matter volume changes. Paired t tests were used to compare pre- and post-ECT grey matter volume (voxel-level family-wise error threshold p < 0.05) and to assess clinical response. Twenty-eight patients (mean age 71.9 ± 7.8 yr, 8 men) participated in our study. Patients received a mean of 11.2 ± 4 sessions of ECT. The remission rate was 78.6%. Cognition, psychomotor agitation and psychomotor retardation improved significantly (p < 0.001). Right-hemispheric grey matter volume was increased in the caudate nucleus, medial temporal lobe (including hippoc us and amygdala), insula and posterior superior temporal regions but did not correlate with MADRS score. Grey matter volume increase in the caudate nucleus region correlated significantly with total CORE Assessment score (r = 0.63 p < 0.001). Not all participants were medication-free. Electroconvulsive therapy in patients with LLD is associated with significant grey matter volume increase, which is most pronounced ipsilateral to the stimulation side.
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: 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: 09-2013
DOI: 10.1016/J.PSCYCHRESNS.2013.03.001
Abstract: The cavum septum pellucidum (CSP) is a fluid-filled cavity in the thin midline structure of the septum pellucidum. The CSP has been linked to several neurodevelopmental disorders, but it also occurs as a result of head injury. The aims were to assess the presence and characterization of the CSP in youth with traumatic brain injury (TBI), to assess whether injury severity or IQ measures were related to CSP size, and to examine brain morphometry changes associated with the CSP size. Ninety-eight survivors of TBI and 34 control children underwent magnetic resonance imaging (MRI). Numerous methods were used to define the presence and characterization of the CSP including length, classification of abnormally large CSP, rating of the CSP, and volume. There was no difference in presence of CSP between TBI patients and controls however, there was larger and more severely graded CSP in the patient group. Size of the CSP correlated positively with injury severity, and regions that correlated most significantly with CSP size were the right entorhinal cortex and bilateral hippoc us. Characterizing the CSP and related brain changes may provide important information concerning disturbances seen after a TBI.
Publisher: Cold Spring Harbor Laboratory
Date: 03-02-2021
DOI: 10.1101/2021.02.01.21250951
Abstract: White matter pathology is thought to contribute to the pathogenesis of bipolar disorder (BD). However, most studies of white matter in BD have used the simple diffusion tensor imaging (DTI) model, which has several limitations. DTI studies have reported heterogenous results, leading to a lack of consensus about the extent and location of white matter alterations. Here, we applied two advanced diffusion magnetic resonance imaging (MRI) techniques to investigate white matter microstructure in BD. Twenty-five patients with BD and 24 controls comparable for age and sex were included in the study. Whole-brain voxel-based analysis (VBA) and a network-based connectivity approach using constrained spherical deconvolution (CSD)-tractography were used to assess group differences in diffusion kurtosis imaging (DKI) and DTI metrics. VBA showed lower mean kurtosis in the corona radiata and posterior association fibers in BD following threshold-free cluster enhancement. Regional differences in connectivity were indicated by lower mean kurtosis and kurtosis anisotropy in streamlines traversing the temporal and occipital lobes, and lower mean axial kurtosis in the right cerebellar, thalamo-subcortical pathways in BD. Significant differences were not seen in the DTI metrics following FDR- correction. Differences between BD and controls were observed in DKI metrics in multiple brain regions, indicating altered connectivity across cortical, subcortical and cerebellar areas. DKI was more sensitive than DTI at detecting these differences, suggesting that DKI is useful for investigating white matter in BD.
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: Springer Science and Business Media LLC
Date: 09-02-2016
DOI: 10.1038/MP.2015.227
Publisher: Public Library of Science (PLoS)
Date: 17-01-2019
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: 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: 19-01-2017
DOI: 10.1007/S11682-016-9665-8
Abstract: In a previous longitudinal diffusion tensor imaging (DTI) study, we observed cerebral white matter (WM) alterations (reduced fractional anisotropy (FA)) related to decreased cognitive performance 3-5 months after chemotherapy-treatment (t2) when compared to baseline (t1) (Deprez et al. in Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 30(3), 274-281. doi:10.1200/JCO.2011.36.8571, 2012). The current study investigates the evolution and the nature of these previously observed microstructural changes. Twenty-five young women with early-stage breast cancer who received chemotherapy treatment (C+), 14 who did not receive chemotherapy (C-) and 15 healthy controls (HC) previously studied, underwent reassessment 3-4 years after treatment (t3). We assessed (1) longitudinal changes of cognitive performance and FA and (2) cross-sectional group differences in myelin-water-imaging and multishell diffusion MRI metrics at t3. MRI metrics were assessed on a voxel-by-voxel basis and in regions-of-interest (ROI) in which previous WM injury was detected. Longitudinal results: Mixed-effects modeling revealed significant group-time interactions for verbal memory and processing speed (p < 0.05) reflecting regained performance in the C+ group at t3. Furthermore, in chemotherapy-treated patients, FA returned to baseline levels at t3 in all ROIs (p < 0.002), whereas no FA changes were seen in controls. Additionally, FA increase from t2 to t3 correlated with time since treatment in two of the four regions (r = 0.40, p < 0.05). Cross-sectional results: Advanced diffusion MRI and myelin-water imaging metrics in the ROIs did not differ between groups. Similarly, no whole-brain voxelwise differences were detected. Initial WM alterations and reduced cognitive performance following chemotherapy-treatment were found to recover in a group of young breast cancer survivors three to four years after treatment.
Publisher: SAGE Publications
Date: 10-02-2020
Abstract: Apathy symptoms are defined as a lack of interest and motivation. Patients with late-life depression (LLD) also suffer from lack of interest and motivation and previous studies have linked apathy to vascular white matter hyperintensities (WMH) of the brain in depressed and nondepressed patients. The aim of this study was to investigate the relationship between apathy symptoms, depressive symptoms, and WMH in LLD. We hypothesize that late-onset depression (LOD first episode of depression after 55 years of age) is associated with WMH and apathy symptoms. Apathy scores were collected for 87 inpatients diagnosed with LLD. Eighty patients underwent brain magnetic resonance imaging. Associations between depressive and apathy symptoms and WMH were analyzed using linear regression. All 3 subdomains of the 10-item Montgomery–Åsberg Depression Rating Scale correlated significantly with the apathy scale score (all P .05). In the total s le, apathy nor depressive symptoms were related to specific WMH. In LOD only, periventricular WMH were associated with depression severity (β = 5.21, P = .04), while WMH in the left infratentorial region were associated with apathy symptoms (β coefficient = 5.89, P = .03). Apathy and depressive symptoms are highly overlapping in the current cohort of older patients with severe LLD, leading to the hypothesis that apathy symptoms are part of depressive symptoms in the symptom profile of older patients with severe LLD. Neither apathy nor depressive symptoms were related to WMH, suggesting that radiological markers of cerebrovascular disease, such as WMH, may not be useful in predicting these symptoms in severe LLD.
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 10-2014
Publisher: Cold Spring Harbor Laboratory
Date: 22-04-2021
DOI: 10.1101/2021.04.19.21255633
Abstract: Electroconvulsive therapy (ECT) applies electric currents to the brain to induce seizures for therapeutic purposes. ECT increases gray matter (GM) volume, predominantly in the medial temporal lobe (MTL). The contribution of induced seizures to this volume change remains unclear. T1-weighted structural MRI was acquired from thirty patients with late-life depression (mean age 72.5±7.9 years, 19 female), before and one week after one course of right unilateral ECT. Whole brain voxel-/deformation-/surface-based morphometry analyses were conducted to identify tissue-specific (GM, white matter: WM), and cerebrospinal fluid (CSF) and cerebral morphometry changes following ECT. Whole-brain voxel-wise electric field (EF) strength was estimated to investigate the association of EF distribution and regional brain volume change. The association between percentage volume change in the right MTL and ECT-related parameters (seizure duration, EF, and number of ECT sessions) was investigated using multiple regression. ECT induced widespread GM volume expansion with corresponding contraction in adjacent CSF compartments, and limited WM change. The regional EF was strongly correlated with the distance from the electrodes, but not with regional volume change. The largest volume expansion was identified in the right MTL, and this was correlated with the total seizure duration. Right unilateral ECT induces widespread, bilateral regional volume expansion and contraction, with the largest change in the right MTL. This dynamic volume change cannot be explained by the effect of electrical stimulation alone and is related to the cumulative effect of ECT-induced seizures.
Publisher: Cold Spring Harbor Laboratory
Date: 14-10-2021
DOI: 10.1101/2021.10.13.464139
Abstract: Virtual dissection of white matter (WM) using diffusion MRI tractography is confounded by its poor reproducibility. Despite the increased adoption of advanced reconstruction models, early region-of-interest driven protocols based on diffusion tensor imaging (DTI) remain the dominant reference for virtual dissection protocols. Here we bridge this gap by providing a comprehensive description of typical WM anatomy reconstructed using a reproducible automated subject-specific parcellation-based approach based on probabilistic constrained-spherical deconvolution (CSD) tractography. We complement this with a WM template in MNI space comprising 68 bundles, including all associated anatomical tract selection labels and associated automated workflows. Additionally, we demonstrate bundle inter- and intra-subject variability using 40 (20 test-retest) datasets from the human connectome project (HCP) and 5 sessions with varying b-values and number of b-shells from the single-subject Multiple Acquisitions for Standardization of Structural Imaging Validation and Evaluation (MASSIVE) dataset. The most reliably reconstructed bundles were the whole pyramidal tracts, primary corticospinal tracts, whole superior longitudinal fasciculi, frontal, parietal and occipital segments of the corpus callosum and middle cerebellar peduncles. More variability was found in less dense bundles, e.g., the first segment of the superior longitudinal fasciculus, fornix, dentato-rubro-thalamic tract (DRTT), and premotor pyramidal tract. Using the DRTT as an ex le, we show that this variability can be reduced by using a higher number of seeding attempts. Overall inter-session similarity was high for HCP test-retest data (median weighted-dice = 0.963, stdev = 0.201 and IQR = 0.099). Compared to the HCP-template bundles there was a high level of agreement for the HCP test-retest data (median weighted-dice = 0.747, stdev = 0.220 and IQR = 0.277) and for the MASSIVE data (median weighted-dice = 0.767, stdev = 0.255 and IQR = 0.338). In summary, this WM atlas provides an overview of the capabilities and limitations of automated subject-specific probabilistic CSD tractography for mapping white matter fasciculi in healthy adults. It will be most useful in applications requiring a highly reproducible parcellation-based dissection protocol, as well as being an educational resource for applied neuroimaging and clinical professionals. (Top) shows the FWT pipeline for both CSTs, AF, and motor CC bundles. (Left to right) show the required input structural parcellation maps and a priori atlases for FWT and the resulting virtual dissection include/exclude VOIs. FWT provides two approaches to virtual dissection: (1) is a bundle-specific approach where streamlines are only seeded for the bundle of interest, (2) is a whole brain tractography followed by streamlines segmentation, (top right) shows output tractograms. (Middle) Group-averaged T1 and fODF images are generated from the HCP test-retest data, and FWT is applied to generate the HCP-atlas using the bundle-specific approach (1*). FWT’s whole brain tracking and segmentation approach (2*) was applied to the HCP and MASSIVE dataset (right and left) and conducted model-based, and pair-wise similarity analyses and generated voxel-wise cumulative maps per bundle. FWT= Fun With Tracts, FS= FreeSurfer, MSBP= MultiScaleBrainParcellator, PD25= NIST Parkinson’s histological, JHU= John’s Hopkins university, Juelich= Juelich university histological atlas, AC/PC= anterior commissure osterior commissure) UKBB= UK Biobank, SUIT (spatially unbiased cerebellar atlas template), dMRI= diffusion magnetic resonance imaging, CSD= constrained spherical deconvolution, fODF= fiber orientation distribution function, CST= corticospinal tract, AF= arcuate fasciculus, CC= corpus callosum, HCP= human connectome project, MASSIVE= Multiple acquisitions for standardization of structural imaging validation and evaluation.
Publisher: Informa UK Limited
Date: 2009
DOI: 10.1080/09540260902962081
Abstract: There is an increasing body of literature fuelled by advances in high-resolution structural MRI acquisition and image processing techniques which implicates subtle neuroanatomical abnormalities in the aetiopathogenesis of bipolar disorder. This account reviews the main findings from structural neuroimaging research into regional brain abnormalities, the impact of genetic liability and mood stabilizing medication on brain structure in bipolar disorder, and the overlapping structural deviations found in the allied disorders of schizophrenia and depression. The manifold challenges extant within neuroimaging research are highlighted with accompanying recommendations for future studies. The most consistent findings include preservation of total cerebral volume with regional grey and white matter structural changes in prefrontal, midline and anterior limbic networks, non-contingent ventriculomegaly and increased rates of white matter hyperintensities, with more pronounced deficits in juveniles suffering from the illness. There is increasing evidence that medication has observable effects on brain structure, whereby lithium status is associated with volumetric increase in the medial temporal lobe and anterior cingulate gyrus. However, research continues to be confounded by the use of highly heterogeneous methodology and clinical populations, in studies employing small scale, low-powered, cross-sectional designs. Future work should investigate larger, clinically homogenous groups of patients and unaffected relatives, combining both categorical and dimensional approaches to illness classification in cross-sectional and longitudinal designs in order to elucidate trait versus state mechanisms, genetic effects and medication/illness progression effects over time.
Publisher: Elsevier BV
Date: 05-2018
Publisher: Royal College of Psychiatrists
Date: 06-2022
DOI: 10.1192/J.EURPSY.2022.429
Abstract: Bipolar disorder has been repeatedly associated with abnormalities of white matter. However, DTI is intrinsically limited and the precise cellular mechanisms that underlie these alterations remains unknown. Our aim was to investigate microscopical characteristics of white matter using MRI in patients with bipolar and healthy controls. 77 patients and 71 controls from 3 sites had a T1 structural MRI, a multi-shell HARDI MRI and at one site with a T1-weighted VFA-SPGR acquisition, and a T2 MSME acquisition. The volume fraction and the orientation dispersion was extracted using NODDI from DW images in each site. Myelin Water Fraction was extracted in 33 patients and 36 controls to probe myelin characteristics. White matter bundles were reconstructed using deterministic tractography. Statistical analyses were performed after harmonization by the ComBat algorithm and controlled for age, gender and handedness. We found significant lower axonal density in patients along the short fibers of the left cingulum, the left anterior arcuate and the left inferior fronto-occipital fasciculus. We found lower mean MWF in patients along the short fibers of the right cingulum, the left inferior fronto-occipital fasciculus, the left anterior arcuate and the splenium of the corpus callosum. We found higher mean orientation dispersion in patients only along the left uncinate fasciculus. We report alterations of limbic and inter-hemispheric white matter tracts in patients with bipolar disorder reflecting axonal loss, demyelination and architecture alterations. These results contribute to better capture the plurality of the mechanisms involved in bipolar disorder that cannot be deciphered with classical diffusion MRI. No significant relationships.
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: 2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-06-2020
DOI: 10.1212/WNL.0000000000009818
Abstract: To investigate in vivo whether synaptic loss and neurofibrillary tangle load spatially overlap and correlate with clinical symptoms in patients with amnestic mild cognitive impairment (aMCI). In this cross-sectional study, 10 patients with aMCI and 10 healthy controls underwent triple PET-MRI with 11 C-UCB-J (synaptic vesicle protein 2A), 18 F-MK-6240 (tau deposition), and 11 C-Pittsburgh compound B (β-amyloid) and neuropsychological assessment. Gray matter atrophy was assessed by voxel-based morphometry with T1-weighted MRIs. Voxel-wise and volume-of-interest analyses were conducted on PET data. The interrelationship of synaptic density and tau deposition was investigated. We also investigated correlations of 18 F-MK-6240 and 11 C-UCB-J binding with cognitive performance. Compared to controls, patients with aMCI showed a decreased 11 C-UCB-J binding mainly in substructures of the medial temporal lobe (MTL 48%–51%, p cluster = 0.02). Increased 18 F-MK6240 binding in the same region was observed (42%–44%, p cluster = 0.0003), spreading to association cortices. In the MTL, higher 18 F-MK-6240 binding inversely related to lower 11 C-UCB-J binding ( p = 0.02, r = −0.76). Decreased performance on cognitive tests was associated with both increased 18 F-MK-6240 and decreased 11 C-UCB-J binding in the hippoc us ( p 0.01, r 0.7), although in a multivariate analysis only 18 F-MK-6240 binding was significantly related to cognitive performance. Patients with aMCI have high tau deposition and synaptic density loss mainly in key regions known to be involved in early cognitive impairment, indicating that these are interrelated in the MTL, while tau binding had already spread toward association cortices. Longitudinal data are needed to provide further insight into the temporal aspects of this relationship.
Publisher: Springer New York
Date: 2016
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.NEUROIMAGE.2010.12.005
Abstract: Diffusion tensor imaging (DTI) is increasingly being used to study white matter (WM) degeneration in patients with psychiatric and neurological disorders. In order to compare diffusion measures across subjects in an automated way, voxel-based analysis (VBA) methods were introduced. In VBA, all DTI data are transformed to a template, after which the diffusion measures of control subjects and patients are compared quantitatively in each voxel. Although VBA has many advantages compared to other post-processing approaches, such as region of interest analysis or tractography, VBA results need to be interpreted cautiously, since it has been demonstrated that they depend on the different parameter settings that are applied in the VBA processing pipeline. In this paper, we examine the effect of the template selection on the VBA results of DTI data. We hypothesized that the choice of template to which all data are transformed would also affect the VBA results. To this end, simulated DTI data sets as well as DTI data from control subjects and multiple sclerosis patients were aligned to (i) a population-specific DTI template, (ii) a subject-based DTI atlas in MNI space, and (iii) the ICBM-81 DTI atlas. Our results suggest that the highest sensitivity and specificity to detect WM abnormalities in a VBA setting was achieved using the population-specific DTI atlas, presumably due to the better spatial image alignment to this template.
Publisher: Springer New York
Date: 2016
Publisher: Elsevier BV
Date: 05-2020
DOI: 10.1016/J.BRS.2020.02.020
Abstract: Electroconvulsive therapy (ECT) is the most effective treatment option for major depressive disorder, so understanding whether its clinical effect relates to structural brain changes is vital for current and future antidepressant research. To determine whether clinical response to ECT is related to structural volumetric changes in the brain as measured by structural magnetic resonance imaging (MRI) and, if so, which regions are related to this clinical effect. We also determine whether a similar model can be used to identify regions associated with electrode placement (unilateral versus bilateral ECT). Longitudinal MRI and clinical data (Hamilton Depression Rating Scale) was collected from 10 sites as part of the Global ECT-MRI research collaboration (GEMRIC). From 192 subjects, relative changes in 80 (sub)cortical areas were used as potential features for classifying treatment response. We used recursive feature elimination to extract relevant features, which were subsequently used to train a linear classifier. As a validation, the same was done for electrode placement. We report accuracy as well as the structural coefficients of regions included in the discriminative spatial patterns obtained. A pattern of structural changes in cortical midline, striatal and lateral prefrontal areas discriminates responders from non-responders (75% accuracy, p < 0.001) while left-sided mediotemporal changes discriminate unilateral from bilateral electrode placement (81% accuracy, p < 0.001). The identification of a multivariate discriminative pattern shows that structural change is relevant for clinical response to ECT, but this pattern does not include mediotemporal regions that have been the focus of electroconvulsive therapy research so far.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 2014
Publisher: Frontiers Media SA
Date: 2014
Publisher: Springer New York
Date: 2016
Publisher: BMJ
Date: 28-09-2021
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: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.PSCYCHRESNS.2015.08.004
Abstract: Disrupted structural connectivity is associated with psychiatric illnesses including bipolar disorder (BP). Here we use structural brain network analysis to investigate connectivity abnormalities in multiply affected BP type I families, to assess the utility of dysconnectivity as a biomarker and its endophenotypic potential. Magnetic resonance diffusion images for 19 BP type I patients in remission, 21 of their first degree unaffected relatives, and 18 unrelated healthy controls underwent tractography. With the automated anatomical labelling atlas being used to define nodes, a connectivity matrix was generated for each subject. Network metrics were extracted with the Brain Connectivity Toolbox and then analysed for group differences, accounting for potential confounding effects of age, gender and familial association. Whole brain analysis revealed no differences between groups. Analysis of specific mainly frontal regions, previously implicated as potentially endophenotypic by functional magnetic resonance imaging analysis of the same cohort, revealed a significant effect of group in the right medial superior frontal gyrus and left middle frontal gyrus driven by reduced organisation in patients compared with controls. The organisation of whole brain networks of those affected with BP I does not differ from their unaffected relatives or healthy controls. In discreet frontal regions, however, anatomical connectivity is disrupted in patients but not in their unaffected relatives.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JAD.2017.06.063
Abstract: Differences in corpus callosum (CC) morphology and microstructure have been implicated in late-life depression and may distinguish between late and early-onset forms of the illness. However, a multimodal approach using complementary imaging techniques is required to disentangle microstructural alterations from macrostructural partial volume effects. 107 older adults were assessed: 55 currently-depressed patients without dementia and 52 controls without cognitive impairment. We investigated group differences and clinical associations in 7 sub-regions of the mid-sagittal corpus callosum using T1 anatomical data, white matter hyperintensity (WMH) quantification and two different diffusion MRI (dMRI) models (multi-tissue constrained spherical deconvolution, yielding apparent fibre density, AFD and diffusion tensor imaging, yielding fractional anisotropy, FA and radial diffusivity, RD). Callosal AFD was lower in patients compared to controls. There were no group differences in CC thickness, surface area, FA, RD, nor whole brain or WMH volume. Late-onset of depression was associated with lower FA, higher RD and lower AFD. There were no associations between any imaging measures and psychotic features or depression severity as assessed by the geriatric depression scale. WMH volume was associated with lower FA and AFD, and higher RD in patients. Patients were predominantly treatment-resistant. Measurements were limited to the mid-sagittal CC. dMRI analysis was performed on a smaller cohort, n=77. AFD was derived from low b-value data. Callosal structure is largely preserved in LLD. WMH burden may impact on CC microstructure in late-onset depression suggesting vascular pathology has additional deleterious effects in these patients.
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.BIOPSYCH.2012.09.023
Abstract: White matter microstructural changes detected using diffusion tensor imaging have been reported in bipolar disorder. However, findings are heterogeneous, which may be related to the use of analysis techniques that cannot adequately model crossing fibers in the brain. We therefore sought to identify altered diffusion anisotropy and diffusivity changes using an improved high angular resolution fiber-tracking technique. Diffusion magnetic resonance imaging data was obtained from 35 prospectively confirmed euthymic bipolar disorder type 1 patients (age 22-59) and 43 control subjects (age 22-59) drawn from a s le of 120 age- and gender-matched demographically similar case-control pairs. Tractography using a constrained spherical deconvolution approach to account for crossing fibers was implemented. Changes in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity between patient and control groups in sub isions of the corpus callosum, cingulum, and fornix were measured as indicators of trait differences in white matter microstructural organization in bipolar disorder. Patients had significantly reduced fractional anisotropy and increased mean diffusivity and radial diffusivity in all isions of the corpus callosum, left fornix, and subgenual cingulum compared with control subjects. Axial diffusivity was increased in the fornix bilaterally and right dorsal-anterior cingulum. By using an improved fiber-tracking method in a clinically homogeneous population, we were able to localize trait diffusivity changes to specific sub isions of limbic fiber pathways, including the fornix. Our findings extend previous reports of altered limbic system microstructural disorganization as a trait feature of bipolar disorder.
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.BIOPSYCH.2019.07.010
Abstract: Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response. Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites. Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean ± SD of 1.04 ± 1.03% (Cohen's d = 1.01, p < .001) and the subcortical gray matter volume increased by 1.47 ± 1.05% (d = 1.40, p < .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearman's rank correlation ρ = -.44, p < .001), while total white matter volume remained unchanged (d = -0.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome. The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response.
Publisher: Cold Spring Harbor Laboratory
Date: 19-10-2023
Publisher: Elsevier BV
Date: 04-2010
Publisher: Cambridge University Press (CUP)
Date: 03-2015
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.PSCYCHRESNS.2016.10.002
Abstract: Avolition is a core feature of schizophrenia and may arise from altered brain connectivity. Here we used diffusion kurtosis imaging (DKI) to investigate the association between white matter (WM) microstructure and volitional motor activity. Multi-shell diffusion MRI and 24-h actigraphy data were obtained from 20 right-handed patients with schizophrenia and 16 right-handed age and gender matched healthy controls. We examined correlations between fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), and motor activity level, as well as group differences in these measures. In the patient group, increasing motor activity level was positively correlated with MK in the inferior, medial and superior longitudinal fasciculus, the corpus callosum, the posterior fronto-occipital fasciculus and the posterior cingulum. This association was not found in control subjects or in DTI measures. These results show that a lack of volitional motor activity in schizophrenia is associated with potentially altered WM microstructure in posterior brain regions associated with cognitive function and motivation. This could reflect both illness related dysconnectivity which through altered cognition, manifests as reduced volitional motor activity, and/or the effects of reduced physical activity on brain WM.
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.NEUROBIOLAGING.2015.02.029
Abstract: Age-related microstructural differences have been detected using diffusion tensor imaging (DTI). Although DTI is sensitive to the effects of aging, it is not specific to any underlying biological mechanism, including demyelination. Combining multiexponential T2 relaxation (MET2) and multishell diffusion MRI (dMRI) techniques may elucidate such processes. Multishell dMRI and MET2 data were acquired from 59 healthy participants aged 17-70 years. Whole-brain and regional age-associated correlations of measures related to multiple dMRI models (DTI, diffusion kurtosis imaging [DKI], neurite orientation dispersion and density imaging [NODDI]) and myelin-sensitive MET2 metrics were assessed. DTI and NODDI revealed widespread increases in isotropic diffusivity with increasing age. In frontal white matter, fractional anisotropy linearly decreased with age, paralleled by increased "neurite" dispersion and no difference in myelin water fraction. DKI measures and neurite density correlated well with myelin water fraction and intracellular and extracellular water fraction. DTI estimates remain among the most sensitive markers for age-related alterations in white matter. NODDI, DKI, and MET2 indicate that the initial decrease in frontal fractional anisotropy may be due to increased axonal dispersion rather than demyelination.
Publisher: Research Square Platform LLC
Date: 06-2023
DOI: 10.21203/RS.3.RS-2925196/V1
Abstract: Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated in iduals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this common causal network (CCN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis (Principal Component Analysis, PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CCN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CCN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes. This evidence further supports that treatment interventions converge on a CCN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.
Publisher: eLife Sciences Publications, Ltd
Date: 23-10-2019
DOI: 10.7554/ELIFE.49115
Abstract: Recent longitudinal neuroimaging studies in patients with electroconvulsive therapy (ECT) suggest local effects of electric stimulation (lateralized) occur in tandem with global seizure activity (generalized). We used electric field (EF) modeling in 151 ECT treated patients with depression to determine the regional relationships between EF, unbiased longitudinal volume change, and antidepressant response across 85 brain regions. The majority of regional volumes increased significantly, and volumetric changes correlated with regional electric field (t = 3.77, df = 83, r = 0.38, p=0.0003). After controlling for nuisance variables (age, treatment number, and study site), we identified two regions (left amygdala and left hippoc us) with a strong relationship between EF and volume change (FDR corrected p .01). However, neither structural volume changes nor electric field was associated with antidepressant response. In summary, we showed that high electrical fields are strongly associated with robust volume changes in a dose-dependent fashion.
Publisher: Springer New York
Date: 2016
Publisher: Elsevier BV
Date: 10-2018
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.CRITREVONC.2016.05.001
Abstract: Neurocognitive sequelae are known to be induced by cranial radiotherapy and central-nervous-system-directed chemotherapy in childhood Acute Lymphoblastic Leukemia (ALL) and brain tumor patients. However, less evidence exists for solid non-CNS-tumor patients. To get a better understanding of the potential neurotoxic mechanisms of non-CNS-directed chemotherapy during childhood, we performed a comprehensive literature review of this topic. Here, we provide an overview of preclinical and clinical studies investigating neurotoxicity associated with chemotherapy in the treatment of pediatric solid non-CNS tumors. Research to date suggests that chemotherapy has deleterious biological and psychological effects, with animal studies demonstrating histological evidence for neurotoxic effects of specific agents and human studies demonstrating acute neurotoxicity. Although the existing literature suggests potential neurotoxicity throughout neurodevelopment, research into the long-term neurocognitive sequelae in survivors of non-CNS cancers remains limited. Therefore, we stress the critical need for neurodevelopmental focused research in children who are treated for solid non-CNS tumors, since they are at risk for potential neurocognitive impairment.
Publisher: Elsevier BV
Date: 03-2014
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.RIDD.2019.103569
Abstract: Diffusion magnetic resonance imaging (dMRI) is able to detect, localize and quantify subtle brain white matter abnormalities that may not be visible on conventional structural MRI. Over the past years, a growing number of studies have applied dMRI to investigate structure-function relationships in children with cerebral palsy (CP). To provide an overview of the recent literature on dMRI and motor function in children with CP. A systematic literature search was conducted in PubMed, Embase, Cochrane Central Register of Controlled trials, Cinahl and Web of Science from 2012 onwards. In total, 577 children with CP in 19 studies were included. Sixteen studies only included unilateral CP, while none included dyskinetic CP. Most studies focused on specific regions/tracts of interest (n = 17) versus two studies that investigated the whole brain. In unilateral and bilateral CP, white matter abnormalities were widespread including non-motor areas. In unilateral CP, consistent relationships were found between white matter integrity of the corticospinal tract and somatosensory pathways (e.g. thalamocortical projections, medial lemniscus) with upper limb sensorimotor function. The role of commissural and associative tracts remains poorly investigated. Also results describing structure-function relationships in bilateral CP are scarce (n = 3). This review underlines the importance of both the motor and somatosensory tracts for upper limb sensorimotor function in unilateral CP. However, the exact contribution of each tract requires further exploration. In addition, research on the relevance of non-motor pathways is warranted, as well as studies including other types of CP.
Publisher: CMA Joule Inc.
Date: 07-2021
DOI: 10.1503/JPN.200176
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.NEUROIMAGE.2013.12.047
Abstract: Ever since the introduction of the concept of fiber tractography, methods to generate better and more plausible tractograms have become available. Many modern methods can handle complex fiber architecture and take on a probabilistic approach to account for different sources of uncertainty. The resulting tractogram from any such method typically represents a finite random s le from a complex distribution of possible tracks. Generating a higher amount of tracks allows for a more accurate depiction of the underlying distribution. The recently proposed method of track-density imaging (TDI) allows to capture the spatial distribution of a tractogram. In this work, we propose an extension of TDI towards the 5D spatio-angular domain, which we name track orientation density imaging (TODI). The proposed method aims to capture the full track orientation distribution (TOD). Just as the TDI map, the TOD is amenable to spatial super-resolution (or even sub-resolution), but in addition also to angular super-resolution. Through experiments on in vivo human subject data, an in silico numerical phantom and a challenging tractography phantom, we found that the TOD presents an increased amount of regional spatio-angular consistency, as compared to the fiber orientation distribution (FOD) from constrained spherical deconvolution (CSD). Furthermore, we explain how the litude of the TOD of a short-tracks distribution (i.e. where the track length is limited) can be interpreted as a measure of track-like local support (TLS). This in turn motivated us to explore the idea of TOD-based fiber tractography. In such a setting, the short-tracks TOD is able to guide a track along directions that are more likely to correspond to continuous structure over a longer distance. This powerful concept is shown to greatly robustify targeted as well as whole-brain tractography. We conclude that the TOD is a versatile tool that can be cast in many different roles and scenarios in the expanding domain of fiber tractography based methods and their applications.
Publisher: Elsevier BV
Date: 2017
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: 07-2021
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2013.07.024
Abstract: Insight into the neural architecture of multitasking is crucial when investigating the pathophysiology of multitasking deficits in clinical populations. Presently, little is known about how the brain combines dual-tasking with a concurrent short-term memory task, despite the relevance of this mental operation in daily life and the frequency of complaints related to this process, in disease. In this study we aimed to examine how the brain responds when a memory task is added to dual-tasking. Thirty-three right-handed healthy volunteers (20 females, mean age 39.9 ± 5.8) were examined with functional brain imaging (fMRI). The paradigm consisted of two cross-modal single tasks (a visual and auditory temporal same-different task with short delay), a dual-task combining both single tasks simultaneously and a multi-task condition, combining the dual-task with an additional short-term memory task (temporal same-different visual task with long delay). Dual-tasking compared to both in idual visual and auditory single tasks activated a predominantly right-sided fronto-parietal network and the cerebellum. When adding the additional short-term memory task, a larger and more bilateral frontoparietal network was recruited. We found enhanced activity during multitasking in components of the network that were already involved in dual-tasking, suggesting increased working memory demands, as well as recruitment of multitask-specific components including areas that are likely to be involved in online holding of visual stimuli in short-term memory such as occipito-temporal cortex. These results confirm concurrent neural processing of a visual short-term memory task during dual-tasking and provide evidence for an effective fMRI multitasking paradigm.
Publisher: Elsevier BV
Date: 2014
Publisher: Elsevier BV
Date: 04-2014
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.JAGP.2016.09.005
Abstract: The clinical profile of late-life depression (LLD) is frequently associated with cognitive impairment, aging-related brain changes, and somatic comorbidity. This two-site naturalistic longitudinal study aimed to explore differences in clinical and brain characteristics and response to electroconvulsive therapy (ECT) in early- (EOD) versus late-onset (LOD) late-life depression (respectively onset <55 and ≥55 years). Between January 2011 and December 2013, 110 patients aged 55 years and older with ECT-treated unipolar depression were included in The Mood Disorders in Elderly treated with ECT study. Clinical profile and somatic health were assessed. Magnetic resonance imaging (MRI) scans were performed before the first ECT and visually rated. Response rate was 78.2% and similar between the two sites but significantly higher in LOD compared with EOD (86.9 versus 67.3%). Clinical, somatic, and brain characteristics were not different between EOD and LOD. Response to ECT was associated with late age at onset and presence of psychotic symptoms and not with structural MRI characteristics. In EOD only, the odds for a higher response were associated with a shorter index episode. The clinical profile, somatic comorbidities, and brain characteristics in LLD were similar in EOD and LOD. Nevertheless, patients with LOD showed a superior response to ECT compared with patients with EOD. Our results indicate that ECT is very effective in LLD, even in vascular burdened patients.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Springer New York
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 08-06-2016
DOI: 10.1038/NPP.2016.86
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.SCHRES.2014.09.037
Abstract: Diffusion tensor imaging (DTI) studies suggest abnormalities in the white matter microstructure of the fornix in schizophrenia patients. Research evaluating schizophrenia patient and relatives also suggests that the white matter microstructure of the fornix is heritable. However, previous studies have been hindered by limited DTI methodology. Therefore, the goal of this study was to assess whether fornix abnormalities were related to the genetic liability for schizophrenia using the novel methodological approach of assessing multiple metrics of along-tract measurements, in addition to whole-tract means. Twenty-five schizophrenia patients, 24 adult non-psychotic first-degree biological relatives, and 27 community controls underwent neuroimaging. No group differences were found for any of the DTI metrics using the classical whole-tract measures of the fornix. Along-tract analysis detected local increases in fractional anisotropy (FA) in the right fimbria of the fornix for relatives compared to patients and controls corrected for false discovery rate. No significant associations were found between symptoms, global functioning, or IQ and whole-tract FA means in schizophrenia patients or relatives. Increased FA in non-psychotic relatives could represent a compensatory mechanism to guard against psychosis or an abnormality associated with the genetic liability for the disorder. These findings underscore the importance of obtaining along-tract measurements, in addition to whole-tract measurements to fully understand white matter abnormalities in schizophrenia.
Publisher: Springer New York
Date: 2016
Publisher: Springer New York
Date: 2016
Publisher: Cambridge University Press (CUP)
Date: 13-02-2017
DOI: 10.1017/S0033291717000058
Abstract: Although repeatedly associated with white matter microstructural alterations, bipolar disorder (BD) has been relatively unexplored using complex network analysis. This method combines structural and diffusion magnetic resonance imaging (MRI) to model the brain as a network and evaluate its topological properties. A group of highly interconnected high-density structures, termed the ‘rich-club’, represents an important network for integration of brain functioning. This study aimed to assess structural and rich-club connectivity properties in BD through graph theory analyses. We obtained structural and diffusion MRI scans from 42 euthymic patients with BD type I and 43 age- and gender-matched healthy volunteers. Weighted fractional anisotropy connections mapped between cortical and subcortical structures defined the neuroanatomical networks. Next, we examined between-group differences in features of graph properties and sub-networks. Patients exhibited significantly reduced clustering coefficient and global efficiency, compared with controls globally and regionally in frontal and occipital regions. Additionally, patients displayed weaker sub-network connectivity in distributed regions. Rich-club analysis revealed subtly reduced density in patients, which did not withstand multiple comparison correction. However, hub identification in most participants indicated differentially affected rich-club membership in the BD group, with two hubs absent when compared with controls, namely the superior frontal gyrus and thalamus. This graph theory analysis presents a thorough investigation of topological features of connectivity in euthymic BD. Abnormalities of global and local measures and network components provide further neuroanatomically specific evidence for distributed dysconnectivity as a trait feature of BD.
Publisher: Springer New York
Date: 2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-09-2020
Publisher: Wiley
Date: 12-07-2018
DOI: 10.1111/ACPS.12942
Abstract: There is ongoing concern about the possible negative impact of ECT on neurocognitive functioning in older patients. In this study, we aimed to characterize the long-term cognitive effects of ECT in patients with late-life depression, using an extensive neuropsychological battery. A total of 110 patients aged 55 years and older with unipolar depression, referred for ECT were included. The neuropsychological test battery was assessed prior to ECT and 6 months after the last ECT session. There were no statistically significant group-level changes from baseline to 6 months post-ECT in any of the neuropsychological measurements. In idual differences in cognitive performance were detected using the Reliable Change Index. Patients with late-life depression do not show deleterious cognitive effects 6 months following an ECT index course, although there are considerable differences at an in idual level. Clinicians should not hesitate to prescribe ECT in older patients, as most of these patients will tolerate the treatment course and a small group will even experience a cognitive enhancement. However, clinicians should be aware that a small group of patients can experience cognitive side-effects. Further study is needed to predict which patients have a higher risk of developing cognitive side-effects.
Publisher: Cold Spring Harbor Laboratory
Date: 20-06-2023
DOI: 10.1101/2023.06.13.23290806
Abstract: Accurate presurgical brain mapping enables preoperative risk assessment and intraoperative guidance. This work investigated whether constrained spherical deconvolution (CSD) methods were more accurate than diffusion tensor imaging (DTI)-based methods for presurgical white matter mapping using intraoperative direct electrical stimulation (DES) as the ground truth. Five different tractography methods were compared (3 DTI-based and 2 CSD-based) in 22 preoperative neurosurgical patients. The corticospinal tract (CST, N=20) and arcuate fasciculus (AF, N=7) bundles were reconstructed, then minimum distances between tractograms and DES coordinates were compared between tractography methods. Receiver-operating characteristic (ROC) curves were used for both bundles. For the CST, binary agreement, linear modeling, and posthoc testing were used to compare tractography methods while correcting for relative lesion and bundle volumes. Distance measures between 154 positive (functional response, pDES) and negative (no response, nDES) coordinates, and 134 tractograms resulted in 860 data points. Higher agreement was found between pDES coordinates and CSD-based compared to DTI-based tractograms. ROC curves showed overall higher sensitivity at shorter distance cutoffs for CSD (8.5 mm) compared to DTI (14.5 mm). CSD-based CST tractograms showed significantly higher agreement with pDES, which was confirmed by linear modeling and posthoc tests (PFWE 0.05). CSD-based CST tractograms were more accurate than DTI-based ones when validated using DES-based assessment of motor and sensory function. This demonstrates the potential benefits of structural mapping using CSD in clinical practice. CSD-based tractograms of the CST are more sensitive than DTI-based tractograms when validated against sensory-motor DES mapping. This also demonstrated the feasibility of fully-automated CSD-based tractography for presurgical planning of the CST. Presurgical white matter mapping using probabilistic CSD tractography is more accurate and sensitive than manual DTI FACT or automated probabilistic DTI tractography. This study included 22 patients with DES data, which was used as the ground truth. Distance in mm between tractograms and DES data resulted in 860 datapoints, 685 of which belonged to the CST and were used for linear modeling, DTI = diffusion tensor imaging, CSD = constrained spherical deconvolution, TCK = tractogram/tractography, FWE = family-wise error rate, AUC = area under the curve
Publisher: Cambridge University Press (CUP)
Date: 27-01-2020
DOI: 10.1017/S0033291719004112
Abstract: Lithium (Li) is the gold standard treatment for bipolar disorder (BD). However, its mechanisms of action remain unknown but include neurotrophic effects. We here investigated the influence of Li on cortical and local grey matter (GM) volumes in a large international s le of patients with BD and healthy controls (HC). We analyzed high-resolution T1-weighted structural magnetic resonance imaging scans of 271 patients with BD type I (120 undergoing Li) and 316 HC. Cortical and local GM volumes were compared using voxel-wise approaches with voxel-based morphometry and SIENAX using FSL. We used multiple linear regression models to test the influence of Li on cortical and local GM volumes, taking into account potential confounding factors such as a history of alcohol misuse. Patients taking Li had greater cortical GM volume than patients without. Patients undergoing Li had greater regional GM volumes in the right middle frontal gyrus, the right anterior cingulate gyrus, and the left fusiform gyrus in comparison with patients not taking Li. Our results in a large multicentric s le support the hypothesis that Li could exert neurotrophic and neuroprotective effects limiting pathological GM atrophy in key brain regions associated with BD.
Publisher: CMA Joule Inc.
Date: 09-2015
DOI: 10.1503/JPN.140262
Abstract: Previous studies have reported MRI abnormalities of the corpus callosum (CC) in patients with bipolar disorder (BD), although only a few studies have directly compared callosal areas in psychotic versus nonpsychotic patients with this disorder. We sought to compare regional callosal areas in a large international multicentre s le of patients with BD and healthy controls. We analyzed anatomic T1 MRI data of patients with BD-I and healthy controls recruited from 4 sites (France, Germany, Ireland and the United States). We obtained the mid-sagittal areas of 7 CC subregions using an automatic CC delineation. Differences in regional callosal areas between patients and controls were compared using linear mixed models (adjusting for age, sex, handedness, brain volume, history of alcohol abuse/dependence, lithium or antipsychotic medication status, symptomatic status and site) and multiple comparisons correction. We also compared regional areas of the CC between patients with BD with and without a history of psychotic features. We included 172 patients and 146 controls in our study. Patients with BD had smaller adjusted mid-sagittal CC areas than controls along the posterior body, the isthmus and the splenium of the CC. Patients with a positive history of psychotic features had greater adjusted area of the rostral CC region than those without a history of psychotic features. We found small to medium effect sizes, and there was no calibration technique among the sites. Our results suggest that BD with psychosis is associated with a different pattern of interhemispheric connectivity than BD without psychosis and could be considered a relevant neuroimaging subtype of BD.
Publisher: Springer Science and Business Media LLC
Date: 07-06-2012
DOI: 10.1007/S00406-012-0333-8
Abstract: The neurobiological correlates of impaired insight in psychotic illness remain uncertain and may be confounded by factors such as illness progression and medication use. Our study consisted of two separate experiments. In the first experiment, we examined the association between measures of insight and regional brain volume in thirty-two patients with first-episode psychosis. In the second experiment, we looked at similar associations in thirty in iduals with chronic schizophrenia. Detailed measures of symptom awareness and symptom attribution were obtained using the Scale to assess Unawareness of Mental Disorder. MRI scans were acquired and analysed using Statistical Non-Parametric Mapping for voxel-based analyses of grey matter maps. Regression models were used to assess the relationship between insight and grey matter volume in both the first-episode psychosis and the chronic schizophrenia experiments whilst controlling for potential confounds. In first-episode psychosis patients, symptom misattribution was associated with increased grey matter in the right and left caudate, right thalamus, left insula, putamen and cerebellum. In the chronic schizophrenia study, there were no significant associations between regional grey matter volume and measures of insight. These findings suggest that neuroplastic changes within subcortical and frontotemporal regions are associated with impaired insight in in iduals during their first episode of psychosis.
Publisher: Elsevier BV
Date: 12-2019
Publisher: Elsevier BV
Date: 12-2014
Publisher: Springer Science and Business Media LLC
Date: 25-09-2015
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.PSCYCHRESNS.2015.05.012
Abstract: Previous structural magnetic resonance imaging (S-MRI) studies of bipolar disorder have reported variable morphological changes in subcortical brain structures and ventricles. This study aimed to establish trait-related subcortical volumetric and shape abnormalities in a large, homogeneous s le of prospectively confirmed euthymic bipolar I disorder (BD-I) patients (n=60), compared with healthy volunteers (n=60). Participants were in idually matched for age and gender. Volume and shape metrics were derived from manually segmented S-MR images for the hippoc us, amygdala, caudate nucleus, and lateral ventricles. Group differences were analysed, controlling for age, gender and intracranial volume. BD-I patients displayed significantly smaller left hippoc al volumes and significantly larger left lateral ventricle volumes compared with controls. Shape analysis revealed an area of contraction in the anterior head and medial border of the left hippoc us, as well as expansion in the right hippoc al tail medially, in patients compared with controls. There were no significant associations between volume or shape variation and lithium status or duration of use. A reduction in the head of the left hippoc us in BD-I patients is interesting, given this region's link to verbal memory. Shape analysis of lateral ventricular changes in patients indicated that these are not regionally specific.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.PSCYCHRESNS.2019.07.006
Abstract: Accumulating evidence suggests that late-life depression is associated with reduced hippoc al volume and that cortisol might be related to this volumetric reduction. We explored whether cortisol awaking response (CAR), which is the increase in cortisol after awakening, was associated with volumetric changes in the medial temporal lobe (MTL) after electroconvulsive therapy (ECT) in 41 patients (age ≥ 55) treated for major depressive disorder (MDD) with ECT. Cortisol was measured before the start of the ECT treatment and was related to MTL volumes derived from structural T1-weighted images. The study assessed associations between CAR and pre-treatment MTL volumes, and CAR and ECT-induced MTL volumetric changes. There were no significant correlations found between CAR, operationalized as Area Under the Curve with respect to ground (AUCg) and Area Under the Curve with respect to increase (AUCi), and pre-treatment MTL volumes. Neither was there an association between AUCg or AUCi and the ECT-induced changes in MTL volumes after correction for multiple comparisons. Finally, neither AUCg or AUCi were able to predict ECT-induced volumetric changes in the MTL. Hence, we conclude that CAR is unrelated to pre-treatment hippoc us and amygdala volumes, and to the volumetric changes in the aforementioned areas following ECT.
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: 11-2021
DOI: 10.1016/J.PSCYCHRESNS.2021.111341
Abstract: White matter pathology likely contributes to the pathogenesis of bipolar disorder (BD). Most studies of white matter in BD have used diffusion tensor imaging (DTI), but the advent of more advanced multi-shell diffusion MRI imaging offers the possibility to investigate other aspects of white matter microstructure. Diffusion kurtosis imaging (DKI) extends the DTI model and provides additional measures related to diffusion restriction. Here, we investigated white matter in BD by applying whole-brain voxel-based analysis (VBA) and a network-based connectivity approach using constrained spherical deconvolution tractography to assess differences in DKI and DTI metrics between BD (n = 25) and controls (n = 24). The VBA showed lower mean kurtosis in the corona radiata and posterior association fibers in BD. Regional differences in connectivity were indicated by lower mean kurtosis and kurtosis anisotropy in streamlines traversing the temporal and occipital lobes, and lower mean axial kurtosis in the right cerebellar, thalamo-subcortical pathways in BD. Significant differences were not seen in DTI metrics following FDR-correction. The DKI findings indicate altered connectivity across cortical, subcortical and cerebellar areas in BD. DKI is sensitive to different microstructural properties and is a useful complementary technique to DTI to more fully investigate white matter in BD.
Publisher: Elsevier BV
Date: 10-2017
Publisher: Wiley
Date: 06-09-2019
DOI: 10.1111/ACPS.13086
Abstract: Electroconvulsive therapy (ECT)-induced hippoc al volume change (HVC) has been repeatedly described in recent years. The similar time course of HVC and ECT-related cognitive effects suggest a relation, that is to date, understudied. This study investigates whether HVC following ECT predicts the change in memory performance six months after the end of the ECT treatment. Hippoc al volume (HV) was measured via high-resolution 3D T1-weighted images in 88 patients with late-life depression, within 1 week before and after ECT. Memory performance was assessed before and six months after ECT. Multiple linear regression was used to examine whether change in memory performance could be predicted based on ECT-induced changes in HV. Larger right absolute HVC predicts less pronounced improvement on the VAT (visual memory) in the whole s le. For the 8-Word Test (verbal memory), Category Fluency Test (semantic memory), and MMSE, the effect is only present in patients who switched from right unilateral to bitemporal stimulation after six ECT sessions. Absolute HVC in the left hemisphere was not significantly related to cognitive change. A larger absolute change in right HV during ECT is associated with less improvement in memory performance up to 6 months post-ECT.
Publisher: Wiley
Date: 29-04-2013
DOI: 10.1111/BDI.12073
Abstract: A broad range of subtle and markedly heterogenous neuroanatomical abnormalities of grey matter and white matter have been reported in bipolar disorder. Euthymic bipolar disorder patients represent a clinically homogenous group in which to identify trait-based biomarkers of bipolar disorder. In this study, we sought to clarify the nature and extent of neuroanatomical differences in a large, clinically homogeneous group of euthymic bipolar disorder patients. Structural magnetic resonance imaging (sMRI) was obtained for 60 patients with prospectively confirmed euthymic bipolar I disorder and 60 in idually age- and gender-matched healthy volunteers. High angular resolution diffusion tensor imaging (DTI) scans were obtained for a subset of this s le comprising 35 patients and 43 controls. Voxel-based analysis of both sMRI and DTI data sets was performed. Bipolar disorder patients displayed global reductions in white matter volume and fractional anisotropy reductions in the corpus callosum, posterior cingulum, and prefrontal white matter compared with controls. There were corresponding increases in radial diffusivity in the callosal splenium in patients compared with controls. No significant group differences were detected in grey matter. In patients, lithium was associated with a bilateral increase in grey matter volume in the temporal lobes, but not with any DTI parameter. Euthymic bipolar I disorder is characterized by both diffuse global white matter deficits and potential regional disorganization in interhemispheric and longitudinal tracts, while grey matter appears to be preserved.
Publisher: Springer Science and Business Media LLC
Date: 22-10-2013
DOI: 10.1038/NPP.2013.294
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.NEUROIMAGE.2022.119029
Abstract: Virtual dissection of white matter (WM) using diffusion MRI tractography is confounded by its poor reproducibility. Despite the increased adoption of advanced reconstruction models, early region-of-interest driven protocols based on diffusion tensor imaging (DTI) remain the dominant reference for virtual dissection protocols. Here we bridge this gap by providing a comprehensive description of typical WM anatomy reconstructed using a reproducible automated subject-specific parcellation-based approach based on probabilistic constrained-spherical deconvolution (CSD) tractography. We complement this with a WM template in MNI space comprising 68 bundles, including all associated anatomical tract selection labels and associated automated workflows. Additionally, we demonstrate bundle inter- and intra-subject variability using 40 (20 test-retest) datasets from the human connectome project (HCP) and 5 sessions with varying b-values and number of b-shells from the single-subject Multiple Acquisitions for Standardization of Structural Imaging Validation and Evaluation (MASSIVE) dataset. The most reliably reconstructed bundles were the whole pyramidal tracts, primary corticospinal tracts, whole superior longitudinal fasciculi, frontal, parietal and occipital segments of the corpus callosum and middle cerebellar peduncles. More variability was found in less dense bundles, e.g., the fornix, dentato-rubro-thalamic tract (DRTT), and premotor pyramidal tract. Using the DRTT as an ex le, we show that this variability can be reduced by using a higher number of seeding attempts. Overall inter-session similarity was high for HCP test-retest data (median weighted-dice = 0.963, stdev = 0.201 and IQR = 0.099). Compared to the HCP-template bundles there was a high level of agreement for the HCP test-retest data (median weighted-dice = 0.747, stdev = 0.220 and IQR = 0.277) and for the MASSIVE data (median weighted-dice = 0.767, stdev = 0.255 and IQR = 0.338). In summary, this WM atlas provides an overview of the capabilities and limitations of automated subject-specific probabilistic CSD tractography for mapping white matter fasciculi in healthy adults. It will be most useful in applications requiring a reproducible parcellation-based dissection protocol, and as an educational resource for applied neuroimaging and clinical professionals.
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.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Louise Emsell.