Gray Matter Structures Research Articles

Macroscopic brain gray matter staining: historical protocol overview and neuroanatomy learning applications in second-year medical students.

Macroscopic staining in anatomical samples of the central nervous system is a technique that has been used for decades to achieve better differentiation of multiple gray matter structures, such as the cortex, basal ganglia, and cerebellar nuclei. Staining methods are based on using the different components of the brain, mainly the lipids present in the white matter. These techniques have been progressively forgotten while computer renderings are increasing; however, as a primary exposure to surgical anatomy, stained brain specimens are considered a helpful tool. We aim to summarize different staining techniques, their principles, and their current applications for neuroanatomy learning purposes. In total, four gray matter staining protocol descriptions (Mulligan's, Roberts's, Alston's, and Prussian Blue) were performed, as well as Likert scale surveys of second-year medical students about their perceptions of the stained sections. The results showed that the different macroscopic stains for brain tissue are based on lipid and reactant interactions, intending to increase the white matter (WM) and gray matter (GM) contrast. The search also showed that most staining protocols would take 2 days to develop. Efficient preservation options include submerging the sections in formaldehyde solutions, formaldehyde-free solutions, ethanol, or applying plastination techniques. Based on the student's perspective, the stained slices seem to be a valuable alternative to facilitate the study and identification of the basal ganglia and their relationships with the white matter (from 51.2 to 72% based on the Likert scale) compared with the non-stained sections. In conclusion, macroscopic staining of brain tissue continues to be a valuable tool for comprehensively studying the brain. Further research is needed to determine the efficacy of stained specimens as teaching tools.

Quantitative susceptibility mapping from basal ganglia and related structures: correlation with disease severity in progressive supranuclear palsy.

We examined whether mean magnetic susceptibility values from deep gray matter structures in patients with progressive supranuclear palsy (PSP) differed from those in patients with Parkinson's disease (PD) and healthy volunteers, and correlated with the PSP rating scale. Head of caudate nucleus, putamen, globus pallidus, substantia nigra and red nucleus were the regions of interest. Mean susceptibility values from these regions in PSP patients were estimated using quantitative susceptibility mapping. Correlations with clinical severity of disease as measured by the PSP rating scale were examined. The mean susceptibility values were also compared with those from healthy volunteers and age- and disease duration-matched patients with PD. Data from 26 healthy volunteers, 26 patients with PD and 27 patients with PSP, were analysed. Patients with PSP had higher mean susceptibility values from all regions of interest when compared to both the other groups. The PSP rating scale scores correlated strongly with mean susceptibility values from the red nucleus and moderately with those from the putamen and substantia nigra. The scores did not correlate with mean susceptibility values from the caudate nucleus or globus pallidus. In patients with PD, the motor deficits correlated moderately with mean susceptibility values from substantia nigra. In patients with PSP, mean susceptibility values indicating the severity of mineralization of basal ganglia and related structures correlate with disease severity, the correlation of red nucleus being the strongest. Further studies are warranted to explore whether mean susceptibility values could serve as biomarkers for PSP.

Reduced neurite density index in the prefrontal cortex of adults with autism assessed using neurite orientation dispersion and density imaging.

Core symptoms of autism-spectrum disorder (ASD) have been associated with prefrontal cortex abnormalities. However, the mechanisms behind the observation remain incomplete, partially due to the challenges of modeling complex gray matter (GM) structures. This study aimed to identify GM microstructural alterations in adults with ASD using neurite orientation dispersion and density imaging (NODDI) and voxel-wise GM-based spatial statistics (GBSS) to reduce the partial volume effects from the white matter and cerebrospinal fluid. A total of 48 right-handed participants were included, of which 22 had ASD (17 men; mean age, 34.42 ± 8.27 years) and 26 were typically developing (TD) individuals (14 men; mean age, 32.57 ± 9.62 years). The metrics of NODDI (neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISOVF]) were compared between groups using GBSS. Diffusion tensor imaging (DTI) metrics and surface-based cortical thickness were also compared. The associations between magnetic resonance imaging-based measures and ASD-related scores, including ASD-spectrum quotient, empathizing quotient, and systemizing quotient were also assessed in the region of interest (ROI) analysis. After controlling for age, sex, and intracranial volume, GBSS demonstrated significantly lower NDI in the ASD group than in the TD group in the left prefrontal cortex (caudal middle frontal, lateral orbitofrontal, pars orbitalis, pars triangularis, rostral middle frontal, and superior frontal region). In the ROI analysis of individuals with ASD, a significantly positive correlation was observed between the NDI in the left rostral middle frontal, superior frontal, and left frontal pole and empathizing quotient score. No significant between-group differences were observed in all DTI metrics, other NODDI (i.e., ODI and ISOVF) metrics, and cortical thickness. GBSS analysis was used to demonstrate the ability of NODDI metrics to detect GM microstructural alterations in adults with ASD, while no changes were detected using DTI and cortical thickness evaluation. Specifically, we observed a reduced neurite density index in the left prefrontal cortices associated with reduced empathic abilities.

Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET

Multimodal imaging techniques have furthered our understanding of how different aspects of Alzheimer's disease (AD) pathology relate to one another. Diffusion tensor imaging (DTI) measures such as mean diffusivity (MD) may be a surrogate measure of the changes in gray matter structure associated with AD. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has been used to quantify synaptic loss, which is the major pathological correlate of cognitive impairment in AD. In this study, we investigated the relationship between gray matter microstructure and synaptic density. DTI was used to measure MD and [11C]UCB-J PET to measure synaptic density in 33 amyloid-positive participants with AD and 17 amyloid-negative cognitively normal (CN) participants aged 50-83. Univariate regression analyses were used to assess the association between synaptic density and MD in both the AD and CN groups. Hippocampal MD was inversely associated with hippocampal synaptic density in participants with AD (r=-0.55, p <0.001, df=31) but not CN (r=0.13, p=0.62, df=15). Exploratory analyses across other regions known to be affected in AD suggested widespread inverse associations between synaptic density and MD in the AD group. In the setting of AD, an increase in gray matter MD is inversely associated with synaptic density. These co-occurring changes may suggest a link between synaptic loss and gray matter microstructural changes in AD. Imaging studies of gray matter microstructure and synaptic density may allow important insights into AD-related neuropathology.

Assessments of variability in cortical and subcortical measurements and within-network connectivity of the brain using test-retest data.

The evaluation and diagnosis of structural changes in brain caused by disease or treatment over time has become one of the important applications of medical imaging methods, in particular MRI, and it is growing. It is critical to evaluate the reliability of the changes in measurements observed in an individual patient for any clinical decision-making. In this paper, we calculated the repeatability coefficient (RC) as a measure of uncertainty for MRI measurements of subcortical volumes and cortical thickness, and within-network connectivity using test-retest data of 20 healthy subjects. We also evaluated changes in 13 patients who received 20 sessions of transcranial magnetic stimulation as a treatment. The most reliable measure seems to be in the thickness of the left occipital with RC% of 3.5 and the least reliable measure is the brain connectivity within visual network using Yeo's atlas with RC% of 29.4. The most sensitive measure to the percentage of true changes in treated patients is the connectivity within subcortical network of AAL with 76.9%.Clinical Relevance- The results of this study can be useful for evaluating changes in the gray matter structures or functional connectivity of the brain due to a neurological disease such as Alzheimer's or Parkinson's. Also, the obtained results can be used to evaluate the changes caused by any intervention or treatment that may have any positive or negative effect on the brain.

Corticocerebellar White Matter Integrity Is Related to Naming Outcome in Post-Stroke Aphasia.

Studies have shown that the integrity of white matter tracts connecting different regions in the left cerebral hemisphere is important for aphasia recovery after stroke. However, the impact of the underlying structural connection between the cortex and the cerebellum in post-stroke aphasia is poorly understood. We studied the microstructural integrity of the cerebellum and the corticocerebellar connections and their role in picture naming. Fifty-six patients with left cerebral infarcts (sparing the cerebellum) underwent diffusion tensor imaging (DTI) and Boston Naming Test. We compared the fractional anisotropy (FA) and mean diffusivity (MD) values of the right and the left cerebellum (lobular gray and white matter structures) and cerebellocortical connections. Recursive feature elimination and Spearman correlation analyses were performed to evaluate the relationship between naming performance and the corticocerebellar connections. We found that the right, relative to left, cerebellar structures and their connections with the left cerebrum showed lower FA and higher MD values, both reflecting lower microstructural integrity. This trend was not observed in the healthy controls. Higher MD values of the right major cerebellar outflow tract were associated with poorer picture naming performance. Our study provides the first DTI data demonstrating the critical importance of ascending and descending corticocerebellar connections for naming outcomes after stroke.

Association of Circumscribed Subcortical Gray and White Matter Lesions With Apraxic Deficits in Patients With Left Hemisphere Stroke.

Apraxia is commonly attributed to left hemisphere (LH) lesions of the cortical fronto-temporo-parietal praxis networks or white matter lesions causing disconnections between cortical nodes. By contrast, the contribution of lesions to the subcortical gray matter, that is, basal ganglia or thalamus, to apraxic deficits remains controversial. Here, we investigate whether damage to these subcortical gray matter structures (i.e., caudate nucleus, putamen, globus pallidus, and thalamus) or the adjacent white matter tracts was associated with apraxic deficits. We identified patients with distinct subcortical lesions with and without apraxia from a large retrospective sample of subacute LH ischemic stroke patients (n = 194). To test which subcortical structures (caudate nucleus, putamen, globus pallidus, thalamus, and adjacent white matter tracts), when lesioned, contributed to apraxic deficits, we statistically compared the proportion of lesioned voxels within subcortical gray and white matter structures between the apraxic and nonapraxic patients. Of the 194 stroke patients screened, 39 (median age = 65 years, range 30-82 years; median time poststroke at the apraxia assessment = 7 days, range 1-44 days) had lesions confined to subcortical regions (gray and white matter). Eleven patients showed apraxic deficits when imitating gestures or pantomiming object use. Region-wise statistical lesion comparison (controlled for lesion size) revealed a more significant proportion of damage ('lesion load') in the caudate nucleus in apraxic stroke patients (mean difference = 6.9%, 95% CI 0.4-13.3, p = 0.038, η p 2 = 0.11). By contrast, apraxic patients had lower lesion load in the globus pallidus (mean difference = 9.9%, 95% CI 0.1-19.8, p = 0.048, η p 2 = 0.10), whereas the lesion load in other subcortical structures (putamen, thalamus, and adjacent white matter tracts) did not differ significantly between the apraxic and nonapraxic patients. These findings provide new insights into the subcortical anatomy of apraxia after LH stroke, suggesting a specific contribution of caudate nucleus lesions to apraxic deficits.

Adenosine A2A receptor availability in cerebral gray and white matter of patients with Parkinson's disease

ObjectiveAtrophic changes in cerebral gray matter of patients with PD have been reported extensively. There is evidence suggesting an association between cortical gyrification changes and white matter abnormalities. Adenosine A2A receptors have been shown to be upregulated in cerebral white matter and on reactive astrocytes in preclinical models of neurodegenerative diseases. We, therefore, sought to investigate in vivo changes in A2A receptor availability in cerebral gray and white matter of PD patients and its association with gray matter atrophy. MethodsEighteen patients with PD without dyskinesia and seven healthy controls were enrolled for this study. Brain MRI and dynamic PET scan was acquired with [11C]TMSX radioligand which binds selectively to A2A receptors. FreeSurfer software was used to segment cerebral gray and white matter structures. The resulting masks were used to calculate region specific volumes and to derive distribution volume ratios (DVRs), after co-registration with PET images, for the quantification of specific [11C]TMSX binding. ResultsWe showed an increase in A2A receptor availability in frontal (P < 0.001) and parietal (P < 0.001) white matter and a decrease in occipital (P = 0.02) gray matter of PD patients as compared to healthy controls. A decrease in gray matter volume ratios was observed in frontal (P < 0.01), parietal (P < 0.001), temporal (P < 0.01) and occipital (P < 0.01) ROIs in patients with PD versus healthy controls. ConclusionsOur results suggest a role of A2A receptor-based signaling in the neurodegenerative changes seen in the cerebral gray and white matter of patients with PD.

Spatiotemporal profile of atrophy in the first year following moderate-severe traumatic brain injury.

Traumatic brain injury (TBI) triggers progressive neurodegeneration resulting in brain atrophy that continues months-to-years following injury. However, a comprehensive characterization of the spatial and temporal evolution of TBI-related brain atrophy remains incomplete. Utilizing a sensitive and unbiased morphometry analysis pipeline optimized for detecting longitudinal changes, we analyzed a sample consisting of 37 individuals with moderate-severe TBI who had primarily high-velocity and high-impact injury mechanisms. They were scanned up to three times during the first year after injury (3 months, 6 months, and 12 months post-injury) and compared with 33 demographically matched controls who were scanned once. Individuals with TBI already showed cortical thinning in frontal and temporal regions and reduced volume in the bilateral thalami at 3 months post-injury. Longitudinally, only a subset of cortical regions in the parietal and occipital lobes showed continued atrophy from 3 to 12 months post-injury. Additionally, cortical white matter volume and nearly all deep gray matter structures exhibited progressive atrophy over this period. Finally, we found that disproportionate atrophy of cortex along sulci relative to gyri, an emerging morphometric marker of chronic TBI, was present as early as 3 month post-injury. In parallel, neurocognitive functioning largely recovered during this period despite this pervasive atrophy. Our findings demonstrate msTBI results in characteristic progressive neurodegeneration patterns that are divergent across regions and scale with the severity of injury. Future clinical research using atrophy during the first year of TBI as a biomarker of neurodegeneration should consider the spatiotemporal profile of atrophy described in this study.

How does the brain age in individuals with multiple sclerosis? A systematic review.

Multiple Sclerosis (MS) is a complex neurological disorder that involves demyelination, lesions and atrophy in both white and gray matter. Such changes in the central nervous system are diagnostic in MS and has a strong relationship with both physical and cognitive symptoms. As a result, magnetic resonance imaging (MRI) scans as a metric of brain atrophy have emerged as an important outcome measure in MS studies. Recently, research has begun to focus on the contribution of aging to the structural changes in the brain associated with MS; prompting questions about whether there is an amplifying effect of aging superimposed on MS-related brain atrophy. To examine current evidence of how the brain ages in individuals with MS, a systematic review of the literature was performed. Specific questions were focused on how aging affects gray and white matter structure, whether patterns of brain atrophy differ in younger and older cohorts and if there are structural differences in the brain as a function of sex in aging people with MS. This review considered studies that used MRI to examine the effects of aging in adults with MS. Twenty-one studies met eligibility criteria. Findings across these studies revealed that gray matter atrophy was more pronounced in older adults with MS, particularly in subcortical regions such as the thalamus; that the rates of atrophy were similar but varied by region for younger and older cohorts; and that males may experience more brain atrophy than females. Further studies that use multimodal MRI acquisition methods are needed to capture changes in both males and females over time, particularly in middle to older adulthood.

Immunohistochemical characteristics of the gray matter of the human spinal cord in the late prenatal period

The study is dedicated to the relevant problem of studying the patterns of age-related (prenatal) restructuring in the brain and spinal cord and provides opportunities for predicting and correcting the occurrence of congenital defects. The aim of the research was to establish the nature of immunohistochemical marker expression in the gray matter structures of the human spinal cord during the late prenatal period. The material for the study consisted of spinal cord preparations from 27 human fetuses at gestational age 35-40 weeks. The following methods were used during the research: anatomical, general histological, special histological, immunohistochemical, morphometric, and statistical analysis of the obtained data. It was found that at 35-36 weeks of the gestational period, the proliferation of neural stem cells (NSCs) occurs more intensively in the ventral neuroepithelium of spinal cord segments compared to the dorsal neuroepithelium. In the ventral neuroepithelium, there are 5-6 mitotic or post-mitotic NSCs, while in the dorsal part, there are only 2-3 cells. In fetuses at 39-40 weeks, the proliferative activity of neural stem cells in the dorsal neuroepithelium is higher in cervical and lumbar segments, where Ki-67 expression is detected in 6 % of cells (reactive in 7-8 cells), and in thoracic and sacral segments, it is 4 % (reactive in 3-4 cells). In contrast to the dorsal neuroepithelium, in the ventral part of the neuroepithelium of the segments, the proliferative activity of neural stem cells is slightly less intense. In cervical and lumbar segments, Ki-67 expression occurred in 4 % of cells (reactive in 3-4 cells), and in thoracic and sacral segments, it was 2 % (reactive in 1-2 cells). At 35-36 weeks of gestation, high vimentin expression was observed around the neuroepithelium, at the base of the posterior horns, and along the posterior median septum. Vimentin expression in the mantle layer was relatively weak and persisted along blood vessels and in the area of spinal cord root formation. Before birth, relatively weak vimentin expression was detected in the remnants of radial glia surrounding the neuroepithelial layer. Vimentin expression was absent in the neuroepithelium proper, but focal vimentin expression was observed around blood vessels. The absence of vimentin expression in the neuroepithelium indicates the disappearance of radial cells. At 35-40 weeks of the gestational period, relatively strong synaptophysin expression was observed in the mantle layer of spinal cord segments, indicating the intensity of neuronal connectivity establishment and myelination of nerve fibers. These processes continue after birth. Synaptophysin expression was absent in the neuroepithelium proper.

Impact of social isolation on grey matter structure and cognitive functions: A population-based longitudinal neuroimaging study.

Social isolation has been suggested to increase the risk to develop cognitive decline. However, our knowledge on causality and neurobiological underpinnings is still limited. In this preregistered analysis, we tested the impact of social isolation on central features of brain and cognitive ageing using a longitudinal population-based magnetic resonance imaging (MRI) study. We assayed 1992 cognitively healthy participants (50-82years old, 921women) at baseline and 1409 participants after~6y follow-up. We found baseline social isolation and change in social isolation to be associated with smaller volumes of the hippocampus and clusters of reduced cortical thickness. Furthermore, poorer cognitive functions (memory, processing speed, executive functions) were linked to greater social isolation, too. Combining advanced neuroimaging outcomes with prevalent lifestyle characteristics from a well-characterized population of middle- to older aged adults, we provide evidence that social isolation contributes to human brain atrophy and cognitive decline. Within-subject effects of social isolation were similar to between-subject effects, indicating an opportunity to reduce dementia risk by promoting social networks. European Union, European Regional Development Fund, Free State of Saxony, LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, German Research Foundation.

Imaging the Human Brain on Oral Contraceptives

Oral contraceptives (OCs) are the most popular form of birth control in the United States and in European countries. However, little is known about the extent OCs affect the brain’s function and morphology, although it is known that endogenous sex hormones shape the brain across the life span. Here, we reviewed studies that investigated structural gray and white matter in women using OCs in comparison to naturally cycling women. We focused on neuroimaging methods used to quantify structural gray and white matter changes: structural (sMRI) and diffusion MRI (dMRI). Relatively few imaging studies have been performed to answer the question of the effect of OCs on brain architecture. Studies have reported morphometric abnormalities in whole brain, cortical, and subcortical gray and white matter with no consistent pattern. Rather, findings in gray and white matter seem to be dependent on whether women using OCs and naturally cycling women were split into groups (active/inactive intake phase vs. follicular/luteal phase). There is a lack of sMRI and dMRI studies in this field of research. However, current studies demonstrate that it is important to compare women according to the follicular and luteal phase, as well as the active and inactive intake phase of OCs. Future studies with standardized protocols and larger sample sizes will allow an in-depth characterization of the effect of OCs on the brain. Furthermore, longitudinal studies comparing naturally cycling women to women using OCs over time and at different life stages are of particular importance.

A multicentre study on grey matter morphometric biomarkers for classifying early schizophrenia and parkinson’s disease psychosis

Psychotic symptoms occur in a majority of schizophrenia patients and in ~50% of all Parkinson’s disease (PD) patients. Altered grey matter (GM) structure within several brain areas and networks may contribute to their pathogenesis. Little is known, however, about transdiagnostic similarities when psychotic symptoms occur in different disorders, such as in schizophrenia and PD. The present study investigated a large, multicenter sample containing 722 participants: 146 patients with first episode psychosis, FEP; 106 individuals in at-risk mental state for developing psychosis, ARMS; 145 healthy controls matching FEP and ARMS, Con-Psy; 92 PD patients with psychotic symptoms, PDP; 145 PD patients without psychotic symptoms, PDN; 88 healthy controls matching PDN and PDP, Con-PD. We applied source-based morphometry in association with receiver operating curves (ROC) analyses to identify common GM structural covariance networks (SCN) and investigated their accuracy in identifying the different patient groups. We assessed group-specific homogeneity and variability across the different networks and potential associations with clinical symptoms. SCN-extracted GM values differed significantly between FEP and Con-Psy, PDP and Con-PD, PDN and Con-PD, as well as PDN and PDP, indicating significant overall grey matter reductions in PD and early schizophrenia. ROC analyses showed that SCN-based classification algorithms allow good classification (AUC ~0.80) of FEP and Con-Psy, and fair performance (AUC ~0.72) when differentiating PDP from Con-PD. Importantly, the best performance was found in partly the same networks, including the thalamus. Alterations within selected SCNs may be related to the presence of psychotic symptoms in both early schizophrenia and PD psychosis, indicating some commonality of underlying mechanisms. Furthermore, results provide evidence that GM volume within specific SCNs may serve as a biomarker for identifying FEP and PDP.

Deviation From Normative Whole Brain and Deep Gray Matter Growth in Children With MOGAD, MS, and Monophasic Seronegative Demyelination.

Pediatric-acquired demyelination of the CNS associated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG; MOG antibody-associated disease [MOGAD]) occurs as a monophasic or relapsing disease and with variable but often extensive T2 lesions in the brain. The impact of MOGAD on brain growth during maturation is unknown. We quantified the effect of pediatric MOGAD on brain growth trajectories and compared this with the growth trajectories of age-matched and sex-matched healthy children and children with multiple sclerosis (MS, a chronic relapsing disease known to lead to failure of normal brain growth and to loss of brain volume) and monophasic seronegative demyelination. We included children enrolled at incident attack in the prospective longitudinal Canadian Pediatric Demyelinating Disease Study who were recruited at the 3 largest enrollment sites, underwent research brain MRI scans, and were tested for serum MOG-IgG. Children seropositive for MOG-IgG were diagnosed with MOGAD. MS was diagnosed per the 2017 McDonald criteria. Monophasic seronegative demyelination was confirmed in children with no clinical or MRI evidence of recurrent demyelination and negative results for MOG-IgG and aquaporin-4-IgG. Whole and regional brain volumes were computed through symmetric nonlinear registration to templates. We computed age-normalized and sex-normalized z scores for brain volume using a normative dataset of 813 brain MRI scans obtained from typically developing children and used mixed-effect models to assess potential deviation from brain growth trajectories. We assessed brain volumes of 46 children with MOGAD, 26 with MS, and 51 with monophasic seronegative demyelinating syndrome. Children with MOGAD exhibited delayed (p < 0.001) age-expected and sex-expected growth of thalamus, caudate, and globus pallidus, normalized for the whole brain volume. Divergence from expected growth was particularly pronounced in the first year postonset and was detected even in children with monophasic MOGAD. Thalamic volume abnormalities were less pronounced in children with MOGAD compared with those in children with MS. The onset of MOGAD during childhood adversely affects the expected trajectory of growth of deep gray matter structures, with accelerated changes in the months after an acute attack. Further studies are required to better determine the relative impact of monophasic vs relapsing MOGAD and whether relapsing MOGAD with attacks isolated to the optic nerves or spinal cord affects brain volume over time.

Binge drinking is associated with higher cortisol and lower hippocampal and prefrontal gray matter volume: Prospective association with future alcohol intake

BackgroundCortisol is a significant driver of the biological stress response that is potently activated by acute alcohol intake and increased with binge drinking. Binge drinking is associated with negative social and health consequences and risk of developing alcohol use disorder (AUD). Both cortisol levels and AUD are also associated with changes in hippocampal and prefrontal regions. However, no previous research has assessed structural gray matter volume (GMV) and cortisol concurrently to examine BD effects on hippocampal and prefrontal GMV and cortisol, and their prospective relationship to future alcohol intake. MethodsIndividuals who reported binge drinking (BD: N = 55) and demographically matched non-binge moderate drinkers (MD: N = 58) were enrolled and scanned using high-resolution structural MRI. Whole brain voxel-based morphometry was used to quantify regional GMV. In a second phase, 65% of the sample volunteered to participate in prospective daily assessment of alcohol intake for 30 days post-scanning. ResultsRelative to MD, BD showed significantly higher cortisol and smaller GMV in regions including hippocampus, dorsal lateral prefrontal cortex (dlPFC), prefrontal and supplementary motor, primary sensory and posterior parietal cortex (FWE, p < 0.05). GMV in bilateral dlPFC and motor cortices were negatively associated with cortisol levels, and smaller GMV in multiple PFC regions was associated with more subsequent drinking days in BD. ConclusionThese findings indicate neuroendocrine and structural dysregulation associated with BD relative to MD. Notably, BD-associated lower GMV regions were those involved in stress, memory and cognitive control, with lower GMV in cognitive control and motor regions also predicting higher levels of future alcohol intake in BD.

Structural magnetic resonance imaging in Parkinson disease with freezing of gait: A systematic review of literature.

This review aims to the existing structural neuroimaging literature in Parkinson disease presenting with freezing of gait. The summary of this article provides an opportunity for a better understanding of the structural findings of freezing of gait in Parkinson disease based on MRI. This systematic review of literature follows the procedures as described by the guideline of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Initial searches yielded 545 documents. After exclusions, 11 articles were included into our study. Current findings of structural MRI on freezing of gait in Parkinson disease are associated with structural damage between sensorimotor-related cortical grey matter structures and thalamus, but not cerebellum and smaller systems, as well as extensive injuries on white matter connecting between those structures. Current findings of structural MRI on freezing of gait in Parkinson disease are associated with structural damage between sensorimotor-related cortical grey matter structures and thalamus, but not cerebellum and smaller systems, as well as extensive injuries on white matter connecting between those structures.

Is it all in the baseline? Trajectories of chair stand performance over 4 years and their association with grey matter structure in older adults.

Understanding individual variability in response to physical activity is key to developing more effective and personalised interventions for healthy ageing. Here, we aimed to unpack individual differences by using longitudinal data from a randomised-controlled trial of a 12-month muscle strengthening intervention in older adults. Physical function of the lower extremities was collected from 247 participants (66.3 ± 2.5 years) at four time-points. At baseline and at year 4, participants underwent 3 T MRI brain scans. K-means longitudinal clustering was used to identify patterns of change in chair stand performance over 4 years, and voxel-based morphometry was applied to map structural grey matter volume at baseline and year 4. Results identified three groups showing trajectories of poor (33.6%), mid (40.1%), and high (26.3%) performance. Baseline physical function, sex, and depressive symptoms significantly differed between trajectory groups. High performers showed greater grey matter volume in the motor cerebellum compared to the poor performers. After accounting for baseline chair stand performance, participants were re-assigned to one of four trajectory-based groups: moderate improvers (38.9%), maintainers (38.5%), improvers (13%), and decliners (9.7%). Clusters of significant grey matter differences were observed between improvers and decliners in the right supplementary motor area. Trajectory-based group assignments were unrelated to the intervention arms of the study. In conclusion, patterns of change in chair stand performance were associated with greater grey matter volumes in cerebellar and cortical motor regions. Our findings emphasise that how you start matters, as baseline chair stand performance was associated with cerebellar volume 4 years later.

Neurodegenerative disease after hematopoietic stem cell transplantation in metachromatic leukodystrophy.

Metachromatic leukodystrophy is a lysosomal storage disease caused by deficient arylsulfatase A. It is characterized by progressive demyelination and thus mainly affects the white matter. Hematopoietic stem cell transplantation may stabilize and improve white matter damage, yet some patients deteriorate despite successfully treated leukodystrophy. We hypothesized that post-treatment decline in metachromatic leukodystrophy might be caused by gray matter pathology. Three metachromatic leukodystrophy patients treated with hematopoietic stem cell transplantation with a progressive clinical course despite stable white matter pathology were clinically and radiologically analyzed. Longitudinal volumetric MRI was used to quantify atrophy. We also examined histopathology in three other patients deceased after treatment and compared them with six untreated patients. The three clinically progressive patients developed cognitive and motor deterioration after transplantation, despite stable mild white matter abnormalities on MRI. Volumetric MRI identified cerebral and thalamus atrophy in these patients, and cerebellar atrophy in two. Histopathology showed that in brain tissue of transplanted patients, arylsulfatase A expressing macrophages were clearly present in the white matter, but absent in the cortex. Arylsulfatase A expression within patient thalamic neurons was lower than in controls, the same was found in transplanted patients. Neurological deterioration may occur after hematopoietic stem cell transplantation in metachromatic leukodystrophy despite successfully treated leukodystrophy. MRI shows gray matter atrophy, and histological data demonstrate absence of donor cells in gray matter structures. These findings point to a clinically relevant gray matter component of metachromatic leukodystrophy, which does not seem sufficiently affected by transplantation.

Brain morphometric changes in fibromyalgia and the impact of psychometric and clinical factors: a volumetric and diffusion-tensor imaging study

BackgroundPrevious studies have repeatedly found distinct brain morphometric changes in patients with fibromyalgia (FM), mainly affecting gray and white matter abnormalities in areas related to sensory and affective pain processing. However, few studies have thus far linked different types of structural changes and not much is known about behavioral and clinical determinants that might influence the emergence and progression of such changes.MethodsWe used voxel-based morphometry (VBM) and diffusion-tensor imaging (DTI) to detect regional patterns of (micro)structural gray (GM) and white matter (WM) alterations in 23 patients with FM compared to 21 healthy controls (HC), while considering the influence of demographic, psychometric, and clinical variables (age, symptom severity, pain duration, heat pain threshold, depression scores).ResultsVBM and DTI revealed striking patterns of brain morphometric changes in FM patients. Bilateral middle temporal gyrus (MTG), parahippocampal gyrus, left dorsal anterior cingulate cortex (dACC), right putamen, right caudate nucleus, and left dorsolateral prefrontal cortex (DLPFC) showed significantly decreased GM volumes. In contrast, increased GM volume was observed in bilateral cerebellum and left thalamus. Beyond that, patients displayed microstructural changes of WM connectivity within the medial lemniscus, corpus callosum, and tracts surrounding and connecting the thalamus. Sensory-discriminative aspects of pain (pain severity, pain thresholds) primarily showed negative correlations with GM within bilateral putamen, pallidum, right midcingulate cortex (MCC), and multiple thalamic substructures, whereas the chronicity of pain was negatively correlated with GM volumes within right insular cortex and left rolandic operculum. Affective-motivational aspects of pain (depressive mood, general activity) were related to GM and FA values within bilateral putamen and thalamus.ConclusionsOur results suggest a variety of distinct structural brain changes in FM, particularly affecting areas involved in pain and emotion processing such as the thalamus, putamen, and insula.