Dynamic changes in brain structure-function correspondence in typical and atypical upper limb motor recovery after stroke.

Background After a central nervous system lesion, the ability to control muscle activation and relaxation in specific joint ranges may be impaired. The underlying mechanism of this sensorimotor impairment is related to a decreased ability to regulate the tonic stretch reflex threshold (TSRT) through descending and peripheral control processes. In dynamics, the reflex threshold and its velocity-sensitivity (μ) describe how movement in specific upper limb (UL) joint ranges is impaired after stroke. Objective To examine the relationships between measures of elbow flexor impairment using TSRT and μ, and clinical scores of spasticity and motor function. We hypothesized that TSRT and μ would be related to clinical spasticity and motor impairment scores in patients with acute and chronic stroke. Methods TSRT, μ, and clinical data of the resistance to passive movement (Modified Ashworth Scale) and UL motor function (Fugl-Meyer Assessment [FMA]) were collected from 120 patients. Relationships between variables were determined using simple correlations and multiple regression analysis. Results TSRT and μ explained 72.0% of the variance in the FMA of the Upper Extremity [FMA-UE] describing only in-synergy and out-of-synergy movements and reflex function. TSRT explained 68.7% of the variance in the total score of the FMA-UE. Conclusions This study shows for the first time, a significant relationship between deficits in TSRT regulation and μ with UL motor impairment after stroke. TSRT and μ may be valuable clinical biomarkers of sensorimotor impairment for monitoring spontaneous or treatment-induced motor recovery.

Analyzing structural and functional brain changes related to an integrative cognitive remediation program for schizophrenia: A randomized controlled trial.

Event Abstract Back to Event Functional brain changes underlying irritability in premanifest Huntington’s disease Jan Van Den Stock1*, François-Laurent De Winter1, Rawaha Ahmad2, Stefan Sunaert2, Koen Van Laere2, Wim Vandenberghe3 and Mathieu Vandenbulcke1 1 KU Leuven, Division of Psychiatry, Department of Neurosciences, Belgium 2 KU Leuven, Department of Imaging and Pathology, Belgium 3 KU Leuven, Department of Neurosciences, Belgium The clinical phenotype of Huntington’s disease consists of motor, cognitive and psychiatric symptoms, of which irritability is an important manifestation. Our aim was to identify the functional and structural brain changes that underlie irritability in premanifest Huntington’s disease. Twenty premanifest Huntington’s disease carriers and 20 gene-negative controls from Huntington’s disease families took part in the study. Although the 5 year probability of disease onset was only 11 percent, the premanifest Huntington’s disease group showed striatal atrophy and increased clinical irritability ratings. Functional MRI was performed during a mood induction experiment by means of recollection of emotional (angry, sad, happy) and neutral autobiographical episodes. While there were no significant group differences in the subjective intensity of the emotional experience, the premanifest Huntington’s disease group showed increased anger-selective activation in a distributed network, including the pulvinar, cingulate cortex and somatosensory association cortex, compared to gene-negative controls. Pulvinar activation during anger experience correlated negatively with putaminal grey matter volume and positively with irritability ratings in the premanifest Huntington’s disease group. In addition, the premanifest Huntington’s disease group showed a decrease in anger-selective activation in the amygdala, which correlated with putaminal and caudate grey matter volume. In conclusion, compared to gene-negative controls, anger experience in premanifest Huntington’s disease is associated with activity changes in a distributed set of regions known to be involved in emotion regulation. Increased activity is related to behavioral and volumetric measures, providing insight in the pathophysiology of early neuropsychiatric symptoms in premanifest Huntington’s disease. References Van den Stock, J., De Winter, F. L., Ahmad, R., Sunaert, S., Van Laere, K., Vandenberghe, W., & Vandenbulcke, M. (2015). Functional brain changes underlying irritability in premanifest Huntington's disease. Hum Brain Mapp. doi: 10.1002/hbm.22799 Keywords: Pulvinar, Gyrus Cinguli, Amygdala, Emotions, Affective Symptoms, Aggression Conference: 11th National Congress of the Belgian Society for Neuroscience, Mons, Belgium, 22 May - 22 May, 2015. Presentation Type: Oral or Poster presentation Topic: Neuroscience Citation: Van Den Stock J, De Winter F, Ahmad R, Sunaert S, Van Laere K, Vandenberghe W and Vandenbulcke M (2015). Functional brain changes underlying irritability in premanifest Huntington’s disease. Front. Neurosci. Conference Abstract: 11th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/conf.fnins.2015.89.00054 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 29 Apr 2015; Published Online: 05 May 2015. * Correspondence: Dr. Jan Van Den Stock, KU Leuven, Division of Psychiatry, Department of Neurosciences, Leuven, Belgium, jan.vandenstock@med.kuleuven.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jan Van Den Stock François-Laurent De Winter Rawaha Ahmad Stefan Sunaert Koen Van Laere Wim Vandenberghe Mathieu Vandenbulcke Google Jan Van Den Stock François-Laurent De Winter Rawaha Ahmad Stefan Sunaert Koen Van Laere Wim Vandenberghe Mathieu Vandenbulcke Google Scholar Jan Van Den Stock François-Laurent De Winter Rawaha Ahmad Stefan Sunaert Koen Van Laere Wim Vandenberghe Mathieu Vandenbulcke PubMed Jan Van Den Stock François-Laurent De Winter Rawaha Ahmad Stefan Sunaert Koen Van Laere Wim Vandenberghe Mathieu Vandenbulcke Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

INTRODUCTION:Various chronic pain conditions go along with functional and structural brain changes. This study aimed to investigate functional and structural brain changes by magnetic resonance imaging (MRI) in inflammatory bowel disease (IBD) patients with chronic abdominal pain.METHODS:Sixty-four subjects were included in the final analysis (32 IBD patients with chronic abdominal pain; 32 age-matched and sex-matched controls). All patients suffered from chronic abdominal pain, defined as a score of ≥3/10 on the visual analog scale for at least 3 months in the past 6 months. Besides structural MRI, resting state functional MRI was used to compare functional connectivity of 10 networks between groups.RESULTS:Patients with IBD showed no structural brain alterations but a significantly increased resting state functional connectivity of the secondary somatosensory cortex within the salience network.DISCUSSION:Because the secondary somatosensory cortex saves sensory stimuli and compares novel information with latter experiences, these functions may be maladaptive in IBD patients with abdominal pain.

COVID-19 Infection and Risk for Neuropsychiatric Symptoms

During the past decades brain structure and function have been studied intensively in schizophrenic patients. Schizophrenic patients have been reported to have smaller total brain volume and sulcal and ventricular enlargement compared with healthy controls. Functionally, lower metabolism or rCBF in prefrontal cortex, especially during frontal activation tests, has been the most reproducible finding. These structural and functional brain changes have been studied relative to specific schizophrenic symptoms. There seems to be a tendency that structural brain changes are related to more negative or less positive symptoms. The findings concerning functional brain changes are more complex, pointing to a lower total metabolism in autistic patients, while patients with many positive symptoms and/or thought disorder may have a relatively higher rCBF/metabolism in some cortical brain areas.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis with a characteristic neuropsychiatric syndrome and severe and prolonged clinical courses. In contrast, standard clinical magnetic resonance imaging (MRI) remains normal in the majority of patients. Here, we investigated structural and functional brain changes in a cohort of patients with anti-NMDAR encephalitis. Twenty-four patients with established diagnosis of anti-NMDAR encephalitis and age- and gender-matched controls underwent neuropsychological testing and multimodal MRI, including T1w/T2w structural imaging, analysis of resting state functional connectivity, analysis of white matter using diffusion tensor imaging, and analysis of gray matter using voxel-based morphometry. Patients showed significantly reduced functional connectivity of the left and right hippocampus with the anterior default mode network. Connectivity of both hippocampi predicted memory performance in patients. Diffusion tensor imaging revealed extensive white matter changes, which were most prominent in the cingulum and which correlated with disease severity. In contrast, no differences in T1w/T2w structural imaging and gray matter morphology were observed between patients and controls. Anti-NMDAR encephalitis is associated with characteristic alterations of functional connectivity and widespread changes of white matter integrity despite normal findings in routine clinical MRI. These results may help to explain the clinicoradiological paradox in anti-NMDAR encephalitis and advance the pathophysiological understanding of the disease. Correlation of imaging abnormalities with disease symptoms and severity suggests that these changes play an important role in the symptomatology of anti-NMDAR encephalitis.

Coronavirus disease 2019 (COVID-19) has been associated with brain functional, structural, and cognitive changes that persist months after infection. Most studies of the neurologic outcomes related to COVID-19 focus on severe infection and aging populations. Here, we investigated the neural activities underlying COVID-19 related outcomes in a case-control study of mildly infected youth enrolled in a longitudinal study in Lombardy, Italy, a global hotspot of COVID-19. All participants (13 cases, 27 controls, mean age 24 years) completed resting-state functional (fMRI), structural MRI, cognitive assessments (CANTAB spatial working memory) at baseline (pre-COVID) and follow-up (post-COVID). Using graph theory eigenvector centrality (EC) and data-driven statistical methods, we examined differences in ECdelta (i.e., the difference in EC values pre- and post-COVID-19) and Volumetricdelta (i.e., the difference in cortical volume of cortical and subcortical areas pre- and post-COVID) between COVID-19 cases and controls. We found that ECdelta significantly between COVID-19 and healthy participants in five brain regions; right intracalcarine cortex, right lingual gyrus, left hippocampus, left amygdala, left frontal orbital cortex. The left hippocampus showed a significant decrease in Volumetricdelta between groups (p = 0.041). The reduced ECdelta in the left amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory. Our results show persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition. These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19.

Longitudinal observations of upper limb motor recovery after stroke have suggested that certain subgroups may exhibit distinct recovery patterns. Here we sought to examine whether the predictive ability for post-stroke upper limb motor outcomes could be enhanced by applying conventional stratification strategies. For 60 individuals who suffered the first stroke, upper limb motor impairment was assessed with the upper extremity Fugl-Meyer assessment (UE-FMA) at 2 weeks as a baseline and then 3 months post-stroke. Brain structural damage at baseline was assessed by MRI data-derived markers ranging from traditional lesion size to the lesion load and to the disconnectome. Linear regression models for predicting upper limb motor outcomes (UE-FMA score at 3 months post-stroke) based on baseline upper limb motor impairment (UE-FMA score at 2 weeks post-stroke), brain structural damage, and their combinations were generated, and those with the best predictive performance were determined for individual subgroups stratified according to initial impairment (severe and non-severe), lesion location (cortical and non-cortical), and neurophysiological status (motor evoked potential-positive and motor evoked potential-negative). The best predictions were made by baseline upper limb motor impairment alone for subgroups with less functional impairment (non-severe) or less structural involvement (non-cortical), but by the combination of baseline upper limb motor impairment and brain structural damage for the other subgroups. The predictive models tailored for subgroups determined according to initial impairment and neurophysiological status yielded a smaller overall error than that for the whole group in upper limb motor outcome predictions. The predictive ability for upper limb motor outcomes could be enhanced beyond the one-size-fits-all model for all individuals with stroke by applying specific stratification strategies, with stratification according to initial impairment being the most promising. We expect that predictive models tailored for individual subgroups could lead closer to the personalized prognosis of upper limb motor outcomes after stroke.

Phenocopy frontotemporal dementia (phFTD) shares core characteristics with behavioral variant frontotemporal dementia (bvFTD), yet without associated cognitive deficits and brain abnormalities on conventional magnetic resonance imaging (MRI), and without progression. Using advanced MRI techniques, we previously observed subtle structural and functional brain changes in phFTD similar to bvFTD. The aim of the current study was to follow these as well as cognition in phFTD over time, by means of a descriptive case series. Cognition, gray matter (GM) volume and white matter (WM) microstructure, and perfusion of 6 phFTD patients were qualitatively compared longitudinally (3-years follow-up), and cross-sectionally with baseline data from 9 bvFTD patients and 17 controls. For functional brain changes, arterial spin labeling (ASL) was performed to assess GM perfusion. For structural brain changes, diffusion tensor imaging was performed to assess WM microstructure and T1w imaging to assess GM volume. MRI acquisition was performed at 3T (General Electric, US). Clinical profiles of phFTD cases at follow-up are described. At follow-up phFTD patients showed clinical symptomatology similar to bvFTD, but had a relatively stable clinical profile. Longitudinal qualitative comparisons in phFTD showed some deterioration of language and memory function, a stable pattern of structural brain abnormalities and increased perfusion over time. Additionally, both baseline and follow-up cognitive scores and structural values in phFTD were generally in between those of controls and bvFTD. Although a descriptive case series does not allow for strong conclusions, these observations in a unique longitudinal phFTD patient cohort are suggestive of the notion that phFTD and bvFTD may belong to the same disease spectrum. They may also provide a basis for further longitudinal studies in phFTD, specifically exploring the structural vs. functional brain changes. Such studies are essential for improved insight, accurate diagnosis, and appropriate treatment of phFTD.

IntroductionThis study aimed to develop an automated approach for assessing upper limb (UL) motor impairment severity in stroke patients using a deep learning framework applied to resting-state functional magnetic resonance imaging (rs-fMRI).MethodsDynamic functional connectivity (dFC) was computed with the ipsilesional primary motor cortex (M1) as a seed and extracted from rs-fMRI data of 69 stroke patients. These dFC features were used to train a three-dimensional convolutional neural network (3D-CNN) for automatic classification of UL motor impairment severity. Patients were divided into two groups according to UL Fugl-Meyer Assessment (UL-FMA) scores: mild-to-moderate impairment (UL-FMA > 20; n = 29, maximum = 66) and severe impairment (0 ≤ UL-FMA ≤ 20; n = 40). UL-FMA scores served as labels for supervised learning.ResultsThe model achieved a balanced accuracy of 99.8% ± 0.2%, with a specificity of 99.9% ± 0.2% and a sensitivity of 99.7% ± 0.3%. Several brain regions—including the angular gyrus, medial orbitofrontal cortex, dorsolateral superior frontal gyrus, superior parietal lobule, supplementary motor area, thalamus, cerebellum, and middle temporal gyrus—were linked to UL motor impairment severity.DiscussionThese findings demonstrate that a 3D deep learning framework based on dFC features from rs-fMRI enables highly accurate and objective classification of UL motor impairment in stroke patients. This approach may provide a valuable alternative to manual UL-FMA scoring, particularly in clinical settings with limited access to experienced evaluators.

Wilson disease (WD) can manifest with hepatic or neuropsychiatric symptoms. Our understanding of the in vivo brain changes in WD, particularly in the hepatic phenotype, is limited. Thirty subjects with WD and 30 age- and gender-matched controls participated. WD group underwent neuropsychiatric assessment. Unified WD Rating Scale neurological exam scores were used to determine neurological (WDN, score > 0) and hepatic-only (WDH, score 0) subgroups. All subjects underwent 3 Tesla anatomical and resting-state functional MRI. Diffusion tensor imaging (DTI) and susceptibility-weighted imaging (SWI) were performed only in the WD group. Volumetric, DTI, and functional connectivity analyses were performed to determine between-group differences. WDN and WDH groups were matched in demographic and psychiatric profiles. The entire WD group compared to controls showed significant thinning in the bilateral superior frontal cortex. The WDN group compared to control and WDH groups showed prominent structural brain changes including significant striatal and thalamic atrophy, more subcortical hypointense lesions on SWI, and diminished white matter integrity in the bilateral anterior corona radiata and corpus callosum. However, the WDH group also showed significant white matter volume loss compared to controls. The functional connectivity between the frontostriatal nodes was significantly reduced in the WDN group, whereas that of the hippocampus was significantly increased in the WDH group compared to controls. In summary, structural and functional brain changes were present even in neurologically non-manifesting WD patients in this cross-sectional study. Longitudinal brain MRI scans may be useful as biomarkers for prognostication and optimization of treatment strategies in WD.

Post-stroke upper limb (UL) motor improvement is associated with adaptive neuroplasticity and motor learning. Both intervention-related (including provision of intensive, variable, and task-specific practice) and individual-specific factors (including the presence of genetic polymorphisms) influence improvement. In individuals with stroke, most commonly, polymorphisms are found in Brain Derived Neurotrophic Factor (BDNF), Apolipoprotein (APOE) and Catechol-O-Methyltransferase (COMT). These involve a replacement of cystine by arginine (APOEε4) or valines by 1 or 2 methionines (BDNF:val66met, met66met; COMT:val158met; met158met). However, the implications of these polymorphisms on post-stroke UL motor improvement specifically have not yet been elucidated. Examine the influence of genetic polymorphism on post-stroke UL motor improvement. Systematic Review and Meta-Analysis. We conducted a systematic search of the literature published in English language. The modified Downs and Black checklist helped assess study quality. We compared change in UL motor impairment and activity scores between individuals with and without the polymorphisms. Meta-analyses helped assess change in motor impairment (Fugl Meyer Assessment) scores based upon a minimum of 2 studies/time point. Effect sizes (ES) were quantified based upon the Rehabilitation Treatment Specification System as follows: small (0.08-0.18), medium (0.19 -0.40) and large (≥0.41). We retrieved 10 (4 good and 6 fair quality) studies. Compared to those with BDNF val66met and met66met polymorphism, meta-analyses revealed lower motor impairment (large ES) in those without the polymorphism at intervention completion (0.5, 95% CI: 0.11-0.88) and at retention (0.58, 95% CI:0.06-1.11). The presence of CoMT val158met or met158met polymorphism had similar results, with lower impairment (large ES ≥1.5) and higher activity scores (large ES ranging from 0.5-0.76) in those without the polymorphism. Presence of APOEε4 form did not influence UL motor improvement. Polymorphisms with the presence of 1 or 2 met alleles in BDNF and COMT negatively influence UL motor improvement. https://osf.io/wk9cf/.

Autism spectrum disorder (ASD) is a developmental disorder involving regional changes and local neural disturbances. However, few studies have investigated the dysfunctional phenomenon across different age stages. This study explores the structural and functional brain changes across different developmental stages in individuals with ASD, focusing on childhood (6-12 years), adolescence (12-18 years), and adulthood (18 + years). Using a comprehensive set of neuroimaging metrics, including modulated and non-modulated voxel-based morphometry (VBM), regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional ALFF (fALFF), we identified significant stage-specific alterations in both VBM and functional measurements. Our results reveal that ASD is associated with progressive and stage-specific abnormalities in brain structure and function, with distinct patterns emerging at each developmental stage. Specifically, we observed significant modulated VBM reductions in the precuneus, lentiform nucleus, and inferior parietal lobule, accompanied by increases in the midbrain and sub-gyral regions. Moreover, we observed unmodulated VBM increment in regions including lentiform nucleus and thalamus. Functionally, ReHo analyses demonstrated disrupted local synchronization in the medial frontal gyrus, while ALFF and fALFF metrics highlighted altered spontaneous brain activity in the sub-gyral and sub-lobar. Finally, correlation analyses revealed that stage-specific findings are closely linked to clinical social- and behavior-related scores, with VBM in the inferior parietal lobule and putamen as well as ReHo in supplemental motor area being significantly associated with restrictive repetitive behaviors in childhood. These findings underscore the importance of considering age-specific brain changes when studying ASD and suggest that targeted interventions may be necessary at different developmental stages.

To characterize individuals with stroke who responded or did not respond to upper limb motor treatment by analyzing muscle synergy patterns (similarity, merging, and fractionation). This study is a secondary analysis of a multicenter randomized controlled trial. Inpatients of 2 specialized neurorehabilitation hospitals. We enrolled individuals (N=62) with a unilateral first-event ischemic or hemorrhagic stroke and severe-to-mild upper limb motor impairment (Fugl-Meyer Assessment-Upper Extremity score of 5-61, of 66). We excluded people with untreated seizure, severe cognitive, or verbal comprehension impairment. After randomization, individuals were allocated to conventional, virtual reality, or robot-assisted treatment groups (20 sessions, 1 h/d, 5 d/wk, 4wk). A blinded assessor performed assessments both before and after the intervention. Surface electromyography recordings from 16 muscles during reaching tasks were collected pre- and post-treatment. We extracted muscle synergy patterns (similarity, merging, and fractionation) of the stroke-affected and unaffected upper limb of each subject. Overall, individuals improved upper limb motor function (Fugl-Meyer Assessment-Upper Extremity change score=7.14±7.46; P<.001). We identified 34 responders to treatment showing clinically significant improvement (over the Minimal Clinically Important Difference of 5 points on the Fugl-Meyer Assessment-Upper Extremity). The responders showed decreased merging of synergies (P=.016) as compared with the non-responders (P=.025), who conversely showed improved similarity of synergies (P=.006). In individuals with stroke undergoing upper limb motor rehabilitation, changes in the synergy merging pattern may serve as a potential marker to distinguish responders from non-responders.