Gray Matter Volume Alterations Research Articles

P483 Fatigue and brain morphology in active and remitted Crohn’s Disease

Abstract Background Extraintestinal symptoms like fatigue and psychosocial impairments are highly prevalent in IBD, especially during active phases of the disease. They not only significantly impair patients’ quality of life, but can also alter the disease course. Disturbances of brain-gut-interactions may contribute to these symptoms. The aim of this study was to examine associations between brain structure, inflammatory biomarkers and symptoms of fatigue, depression and anxiety in persons with Crohn’s Disease (CD) in different disease states. Methods We prospectively enrolled n=109 participants (n=67 persons with CD, n=42 healthy controls). All participants underwent cranial magnetic resonance imaging at 3Tesla, provided stool samples for analysis of faecal calprotectin and completed questionnaires to assess symptoms of fatigue, depression and anxiety. We analysed differences in grey matter volume (GMV) between patients and controls and associations between regional GMV alterations, neuropsychiatric symptoms and faecal calprotectin. Results Symptoms of fatigue, depression and anxiety were increased in patients with CD compared to controls, with the highest scores in active CD (Table 1). Patients exhibited regionally reduced GMV in cortical and subcortical sensorimotor regions, occipitotemporal and medial frontal areas. GMV in some of these regions showed a significant negative association with fatigue, but not with depression or anxiety (Fig. 1a). Subgroup analyses revealed symptom-GMV-associations for fatigue in remitted (Fig. 1b), but not in active CD (Fig. 1c), while fatigue was positively associated with fCal in active (Fig. 1c), but not remitted disease (Fig. 1b). Conclusion Our findings support disturbances of brain-gut-interactions in the development extraintestinal symptoms in CD, which may be particularly relevant for fatigue during remitted disease. Reduced GMV in the precentral gyrus and other sensorimotor areas could reflect key contributions to fatigue pathophysiology in CD. A sensorimotor model of fatigue in CD could also pave the way for novel treatment approaches, such as targeted noninvasive brain stimulation. Moreover, differences in gut-brain-disturbances between active and remitted disease with regard to fatigue may indicate the need for differential therapeutic approaches dependent on the disease state.

The network characteristics in schizophrenia with prominent negative symptoms: a multimodal fusion study

Previous studies on putative neural mechanisms of negative symptoms in schizophrenia mainly used single modal imaging data, and seldom utilized schizophrenia patients with prominent negative symptoms (PNS).This study adopted the multimodal fusion method and recruited a homogeneous sample with PNS. We aimed to identify negative symptoms-related structural and functional neural correlates of schizophrenia. Structural magnetic resonance imaging (sMRI) and resting-state functional MRI (rs-fMRI) were performed in 31 schizophrenia patients with PNS and 33 demographically matched healthy controls.Compared to healthy controls, schizophrenia patients with PNS exhibited significantly altered functional activations in the default mode network (DMN) and had structural gray matter volume (GMV) alterations in the cerebello-thalamo-cortical network. Correlational analyses showed that negative symptoms severity was significantly correlated with the cerebello-thalamo-cortical structural network, but not with the DMN network in schizophrenia patients with PNS.Our findings highlight the important role of the cerebello-thalamo-cortical structural network underpinning the neuropathology of negative symptoms in schizophrenia. Future research should recruit a large sample and schizophrenia patients without PNS, and apply adjustments for multiple comparison, to verify our preliminary findings.

Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study

IntroductionRegional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool.Methods15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables.ResultsCompared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges’ g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses.ConclusionEOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

Reduced Gray Matter Volume and Cortical Thickness in Patients With Small-Fiber Neuropathy

Small-fiber neuropathy (SFN) is defined by degeneration or dysfunction of peripheral sensory nerve endings. Central correlates have been identified on the level of gray matter volume (GMV) and cortical thickness (CT) changes. However, across SFN etiologies knowledge about a common structural brain signature is still lacking. Therefore, we recruited 26 SFN patients and 25 age- and sex-matched healthy controls to conduct voxel-based- and surface-based morphometry. Across all patients, we found reduced GMV in widespread frontal regions, left caudate, insula and superior parietal lobule. Surface-based morphometry analysis revealed reduced CT in the right precentral gyrus of SFN patients. In a region-based approach, patients had reduced GMV in the left caudate. Since pathogenic gain-of-function variants in voltage-gated sodium channels (Nav) have been associated with SFN pathophysiology, we explored brain morphological patterns in a homogenous subsample of patients carrying rare heterozygous missense variants. Whole brain- and region-based approaches revealed GMV reductions in the bilateral caudate for Nav variant carriers. Further research is needed to analyze the specific role of Nav variants for structural brain alterations. Together, we conclude that SFN patients have specific GMV and CT alterations, potentially forming potential new central biomarkers for this condition. Our results might help to better understand underlying or compensatory mechanisms of chronic pain perception in the future. PerspectiveThis study reveals structural brain changes in small-fiber neuropathy (SFN) patients, particularly in frontal regions, caudate, insula, and parietal lobule. Notably, individuals with SFN and specific Nav variants exhibit bilateral caudate abnormalities. These findings may serve as potential central biomarkers for SFN and provide insights into chronic pain perception mechanisms.

Comparative Study of Cerebral Volumetric Variations in Patients with Schizophrenia with their Unaffected First-degree Relatives, using Magnetic Resonance Imaging Technique, a Case-control Study

Background and purpose: Schizophrenia (SZH) is a chronic mental disorder affecting the individuals` thoughts, perceptions, emotions, and behaviors. People with SZH may experience a wide range of positive, negative, and cognitive symptoms. Since there are no laboratory assays for definite SZH diagnosis, the authors aimed to identify the cerebral volumetric variations in SZH patients with the most prevalent positive symptoms as a diagnostic tool. This study selected 15 SZH patients displaying the most prevalent positive symptoms based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Assessment tools included the Mini-Mental State Examination (MMSE) for cognitive impairment, the Positive and Negative Syndrome Scale (PANSS) for symptom evaluation, and the Wechsler Intelligence Scale (WIS) for intelligence assessment. Additionally, 15 Healthy Controls (HC) without cerebral pathologies were recruited. T1w MRI images underwent analysis using Freesurfer software. Data analysis employed Mann-Whitney U and χ² tests, considering p < 0.05 as significant. Results: SZH and HC groups showed no significant differences in age and gender. However, significant (p < 0.05) alterations in Gray Matter (GM) volume were observed in SZH patients compared to HC. In the right hemisphere, several regions exhibited volume reduction, including the Fusiform sulcus, Rostral middle frontal gyrus, isthmus cingulate, Frontal pole, Middle temporal gyrus, Lateral occipital gyrus, and Inferior Parietal gyrus. Notably, the Precentral sulcus and Postcentral gyrus demonstrated volume acceleration. Similarly, in the left hemisphere, various regions showed volume reduction while the Paracentral gyrus indicated volume acceleration, all significant (p < 0.05). Conclusion: SZH patients display significant volumetric brain changes, indicating potential for future diagnostic procedures in SZH.

Source-based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1-weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source-based morphometry (SBM) pipeline (SS-Detect) to generate structural brain patterns (SBPs) that capture co-varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV-SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel-based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism.

Altered Brain Structure in Hemifacial Spasm Patients: A Multimodal Brain Structure Study.

Hemifacial spasm (HFS) is a clinical neurosurgical disease, which brain structural alterations caused by HFS remain a topic of debate. We evaluated changes in brain microstructure associated with HFS and observed their relevance to clinical characteristics. We enrolled 72 participants. T1-weighted structural and diffusion tensor images were collected from all participants using 3.0T magnetic resonance equipment. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to identify changes in gray matter volume (GMV) and disruptions in white matter (WM) integrity. The severity of the spasms was graded using the Cohn scale. VBM analysis revealed that the GMV was significantly reduced in the left Thalamus and increased GMV in the right Cerebellum IV-V of the HFS group. TBSS analysis showed that FA in the left superior longitudinal fasciculus (SLF) of the HFS group was significantly increased. GMV in the thalamus showed a negative correlation with disease duration and Cohn grade, while FA in the left SLF had a positive correlation with both the disease duration and Cohn grade. We identified regions with altered GMV in HFS patients. Additionally, we determined that FA in the left SLF might serve as a significant neural indicator of HFS.

Structural Neuroimaging and Molecular Signatures of Drug‐Naive Depression With Melancholic Features

Objectives: Melancholic depression (MD) is a common subtype of major depressive disorder (MDD). It is difficult to treat because its neurobiological basis is poorly understood. Therefore, to investigate whether MD patients have any structural changes in gray matter (GM) and the molecular foundation of these changes, we combined voxel‐based morphometry (VBM) analysis with neurotransmitter system‐derived mapping from public data.Methods: 137 drug‐naive MDD patients and 75 healthy controls (HCs) were recruited for structural magnetic resonance imaging. The imaging results were analyzed using VBM analysis. MDD patients were then divided into MD and nonmelancholic depression (NMD) subgroups according to their scores on the Montgomery–Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale. Next, we analyzed the spatial correlation between the changes in the gray matter volume (GMV) maps and the neurotransmitter receptor/transporter protein density maps provided by the JuSpace toolbox.Results: Compared to HCs, patients with MD had significant GMV reduction in the bilateral hippocampus, bilateral thalamus, right amygdala, and right posterior cingulate cortex (PCC)/precuneus. Compared to patients with NMD, MD patients had significant GMV reduction in the bilateral PCC/precuneus and lateral occipital cortex. Moreover, compared to HCs, changes in GMV introduced by MD were spatially associated with the serotonin transporter, cannabinoid receptor, and μ‐opioid receptor. Compared to NMD patients, changes in GMV introduced by MD were spatially associated with the vesicular acetylcholine transporter.Conclusion: The present study discovered abnormal GMV alterations in patients with subtypes of depression. We also found a series of neurotransmitter receptors that may be associated with the alterations. The findings of the current study may provide a more comprehensive understanding of the molecular mechanisms underlying the structural abnormalities in subtypes of depression and potentially offer new insights into developing new therapeutic strategies.

Progressive brain structural abnormality in cerebral small vessel disease assessed with MR imaging by using causal network analysis

AimsCerebral small vessel disease (CSVD) is a complex condition characterized by a combination of microcirculation disorders and neurodegenerative processes, CSVD is associated with structural abnormalities in multiple brain regions. However, the progressive pattern of structural changes remains unknown. MethodsIn order to detail the progressive structural changes in CSVD patients according to the degree of cognitive impairment, we recruited 121 CSVD patients and 104 healthy controls (HCs). Voxel-based morphometry was employed to measure the gray matter volume (GMV) of each participant. According to the VICCCS-2 diagnostic criteria, patients were initially divided into three stage groups, then we investigated the GMV changes in each stage and their causal relationships using causal structure covariance network (CaSCN) analysis. ResultsOverall, patients with CSVD presented stage-specific GMV alterations compared with HCs. With the worsening of cognitive impairment, the decrease in gray matter volume starts from the right hippocampus and gradually spreads to the cortical-subcortical brain regions. Importantly, the right hippocampus in CSVD patients plays a driving role in the directional network and forms both positive and negative causal effect networks with cortical-subcortical brain regions. ConclusionsThis study reveals the significance of the right hippocampus as an early pathological area in CSVD patients and its causal impact on brain GMV changes with disease progression, shedding light on structural brain damage hierarchy and compensatory mechanisms.

Shared and Distinct Neurobiological Bases of Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: A Comparative Meta-Analysis of Structural Abnormalities

Pediatric bipolar disorder (PBD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur and share dysfunctions in affective and cognitive domains. As the neural substrates underlying their overlapping and dissociable symptomatology have not been well delineated, a meta-analysis of whole-brain voxel-based morphometry studies in PBD and ADHD was conducted. A systematic literature search was performed in PubMed, Web of Science, and Embase. The seed-based d mapping toolbox was used to identify altered clusters of PBD or ADHD and obtain their conjunctive and comparative abnormalities. Suprathreshold patterns were subjected to large-scale network analysis to identify affected brain networks. The search revealed 10 PBD studies (268 patients) and 32 ADHD studies (1,333 patients). Decreased gray matter volumes in the right insula and anterior cingulate cortex relative to typically developing individuals were conjunctive in PBD and ADHD. Reduced volumes in the right inferior frontal gyrus, left orbitofrontal cortex, and hippocampus were more substantial in PBD, while decreased volumes in the left precentral gyrus, left inferior frontal gyrus, and right superior frontal gyrus were more pronounced in ADHD. Neurodevelopmental effects modulated patterns of the left hippocampus in PBD and those of the left inferior frontal gyrus in ADHD. These findings suggest that PBD and ADHD are characterized by both common and distinct patterns of gray matter volume alterations. Their overlapping abnormalities may represent a transdiagnostic problem of attention and emotion regulation shared by PBD and ADHD, whereas the disorder-differentiating substrates may contribute to the relative differences in cognitive and affective features that define the 2 disorders. Pediatric bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur, with overlapping changes in emotional and cognitive functioning. This meta-analysis summarizes findings from 10 articles on BD and 32 articles on ADHD to identify similarities and differences in brain structure between youth with BD and youth with ADHD. The authors found that both disorders share decreased gray matter volumes in the right insula and anterior cingulate cortex, which play important roles in emotion processing and attention, respectively. Youth with BD had decreased gray matter volume in the right inferior frontal gyrus, left orbitofrontal gyrus, and left hippocampus, while youth with ADHD had decreased volumes in the left precentral gyrus, left inferior frontal gyrus, and right superior frontal gyrus. Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder in Children/Adolescents: An Overlapping Meta-analysis; https://osf.io; trg4m.

Healthy Dietary Intake Reduces Longitudinal Brain Iron Accumulation in Older Adults

AbstractBackgroundBrain iron, which tends to accumulate with normal aging, negatively affects cognitive performance. However, the impact of brain iron on cognition appears modifiable. In a recent study from our group [1], we demonstrated that those older adults with high dietary intake of antioxidants, iron chelating nutrients and polyunsaturated fatty acids (Factor 2 in [1]), tended to have lower brain iron and better working memory performance than expected for their age. Here, we extend our previous work by evaluating associations between baseline consumption of Factor 2 nutrients and longitudinal brain iron accumulation, evaluated three years after baseline.MethodsForty‐three, cognitively normal, older adults (26 women, age range 63‐88 years) underwent MRI‐based structural brain imaging and quantitative susceptibility mapping for assessment of brain iron concentration at two time points: baseline (T1) and three years after baseline (T2). Additionally, at T1, nutritional‐intake was assessed via a validated questionnaire. Nutrients were grouped into nutrition factors based on previous literature and factor analysis. Factor 2, comprised vitamin E, lysine, DHA omega‐3 and LA omega‐6, representing antioxidants, iron chelating nutrients and polyunsaturated fatty acids.ResultsVoxelwise, whole‐brain, linear mixed‐effects models (qFDR < 0.05), controlling for longitudinal gray matter volume alterations, age, gender and education, revealed brain iron accumulation within several subcortical and cortical brain regions. Importantly, a significant time point by nutrition interaction was also observed. Specifically, those participants who consumed higher amounts of Factor 2 nutrients at baseline exhibited lower longitudinal brain iron accumulation within the left middle frontal gyrus, left superior parietal lobule, left insular cortex, right inferior temporal cortex, and bilateral hippocampus. Time point by nutrition interactions were not observed for other nutrition factors discussed in [1], such as those comprised of nutrients found in fruits and vegetables, or in green tea.ConclusionOur results indicate that dietary patterns rich in oxidative stress‐reducing antioxidants, iron chelating nutrients and polyunsaturated fatty acids may slow down age‐related, brain iron accumulation in older adults.

Gray matter volume abnormalities in vascular cognitive impairment and their association with gene expression profiles

BackgroundIt has been revealed that brain gray matter volume (GMV) abnormalities are present in patients with vascular cognitive impairment (VCI). However, the GMV alterations that have been uncovered are highly inconsistent, and their correlation with gene expression profiles is still largely unknown. PurposeTo establish a correlation between VCI-related GMV alterations and gene expression patterns and uncover potential genetic profiles underlying GMV abnormalities in VCI. Materials and methodsHere, a quantitative meta-analysis that compared voxel-based GMV between VCI patients and healthy controls (HCs) was carried out on 11 datasets (10 from previous studies and 1 newly collected), comprising 385 VCI individuals and 334 ​HCs, to investigate GMV alterations in VCI patients. Partial least squares regression analysis was then conducted to investigate the relationship between the GMV alterations in VCI and gene expression profiles obtained from Allen Human Brain Atlas database. ResultsCompared with healthy controls, patients with VCI showed consistent decreased GMV which predominantly included the right insula, right Rolandic operculum, right putamen, right superior temporal gyrus, left medial superior frontal gyrus, and right median cingulate and paracingulate gyri. Meta-regression analysis revealed that decreased GMV in left medial superior frontal gyrus was negatively correlated with Mini-Mental State Examination score in VCI. Furthermore, 2835 genes were identified whose expression patterns were correlated with VCI-related GMV changes, and these genes were enriched in distinct biological processes, brain cell types and lifespan windows across brain regions. ConclusionTogether, these findings could provide the potential neurobiological underpinnings and the genetic substrates underlying GMV abnormalities of VCI.

Preliminary investigation of the interactive role of physiological arousal and insomnia complaints in gray matter volume alterations in chronic widespread pain.

Brain regions involved in insomnia and chronic pain are overlapping and diffuse. The interactive role of physiological arousal in associations between insomnia symptoms and neural regions is unknown. This preliminary study examined whether arousal interacted with sleep in associations with gray matter volume of frontal (dorsolateral prefrontal cortex, anterior cingulate cortex) and temporal (right/left hippocampus) regions in adults with chronic widespread pain and insomnia complaints. Forty-seven adults with chronic widespread pain and insomnia (mean age = 46.00, standard deviation = 13.88, 89% women) completed 14 daily diaries measuring sleep onset latency (SOL), wake time after sleep onset, and total sleep time (TST), as well as Holter monitor assessments of heart rate variability (measuring physiological arousal), and magnetic resonance imaging. Multiple regressions examined whether average SOL, wake time after sleep onset, or TST were independently or interactively (with arousal/heart rate variability) associated with dorsolateral prefrontal cortex, anterior cingulate cortex, and left/right hippocampus gray matter volumes. Shorter TST was associated with lower right hippocampus volume. TST also interacted with arousal in its association with right hippocampal volume, Specifically, shorter TST was associated with lower volume at highest and average arousal levels. SOL interacted with arousal in its association with anterior cingulate cortex volume, such that, among individuals with lowest arousal, longer SOL was associated with lower volume. Preliminary findings highlight the interactive roles of physiological arousal and insomnia symptoms in associations with neural structure in chronic widespread pain and insomnia. Individuals with the highest physiological arousal may be particularly vulnerable to the impact of shorter TST on hippocampal volume loss. Reducing SOL may only impact anterior cingulate cortex volume in those with lower physiological arousal. Curtis AF, Nair N, Hayse B, etal. Preliminary investigation of the interactive role of physiological arousal and insomnia complaints in gray matter volume alterations in chronic widespread pain. J Clin Sleep Med. 2024;20(2):293-302.

Gray matter volume abnormalities in obsessive-compulsive disorder correlate with molecular and transcriptional profiles

Neuroimaging studies have consistently established altered brain structure in obsessive-compulsive disorder (OCD). However, the molecular and genetic mechanisms underlying structural brain abnormalities remain unclear. In this study, we aimed to investigate altered gray matter volume and its underlying molecular and genetic mechanisms in patients with OCD. Gray matter morphological abnormalities measured with voxel based morphometry analysis were identified in patients with OCD in comparison to sex- and age-matched healthy controls (HCs). Spatial correlations between gray matter morphological abnormalities and neurotransmitter maps were calculated to identify neurotransmitters relating to structural abnormalities. Structural abnormalities related genes were identified by conducting transcriptome-neuroimaging spatial correlations. Compared with HCs, patients with OCD demonstrated significant morphological abnormalities in distributed brain areas, including gray matter atrophy in the anterior cingulate and increased gray matter volume in the thalamus, caudate and precentral and postcentral gyrus. The morphological abnormalities were significantly associated with dopamine synthesis capacity and expression profiles of 1110 genes enriched for trans-synaptic signaling, regulation of membrane potential, modulation of chemical synaptic transmission, brain development, synapse organization and regulation of neurotransmitter levels. These results elucidate the molecular and transcriptional basis of altered gray matter morphology and build linking between molecular, transcriptional and neuroimaging information facilitating an integrative understanding of OCD.

Assessment of functional and structural brain abnormalities with resting-state functional MRI in patients with vestibular neuronitis.

Vestibular neuritis (VN) is a disorder manifesting as acute, isolated, spontaneous vertigo. There are few comprehensive studies on the changes in related functional and structural brain regions. To evaluate alterations in spontaneous neural activity, functional connectivity (FC), and gray matter volume (GMV) in patients with VN. A total of 24 patients with VN and 22 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI) and three-dimensional T1-weighted anatomical imaging. We calculated the amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) to discern local brain abnormalities. The most abnormal brain region was selected as the region of interest (ROI) for FC analysis based on ALFF and ReHo values after Bonferroni correction. Voxel-based morphometry (VBM) was used to assess differences in GMV. Patients with VN, compared to healthy controls, showed increased ALFF (P < 0.001), ReHo values (P = 0.002, <0.001), and DC (P = 0.013) in the left lingual gyrus and right postcentral gyrus. FC analysis demonstrated enhanced connectivity between the left lingual gyrus and the left superior frontal gyrus, and decreased connectivity with the right insula gyrus, right and left supramarginal gyrus (P = 0.012, 0.004, <0.001, 0.014). In addition, GMV was reduced in the bilateral caudate (P = 0.022, 0.014). Patients with VN exhibit abnormal spontaneous neural activity and changes in ALFF, ReHo, DC, GMV, and FC. Understanding these functional and structural brain abnormalities may elucidate the underlying mechanisms of VN.

Causal associations between sleep traits and brain structure: a bidirectional Mendelian randomization study

BackgroundEmerging evidence suggests bidirectional causal relationships between sleep disturbance and psychiatric disorders, but the underlying mechanisms remain unclear. Understanding the bidirectional causality between sleep traits and brain imaging-derived phenotypes (IDPs) will help elucidate the mechanisms. Although previous studies have identified a range of structural differences in the brains of individuals with sleep disorders, it is still uncertain whether grey matter (GM) volume alterations precede or rather follow from the development of sleep disorders.ResultsAfter Bonferroni correction, the forward MR analysis showed that insomnia complaint remained positively associated with the surface area (SA) of medial orbitofrontal cortex (β, 0.26; 95% CI, 0.15–0.37; P = 5.27 × 10–6). In the inverse MR analysis, higher global cortical SA predisposed individuals less prone to suffering insomnia complaint (OR, 0.89; 95%CI, 0.85–0.94; P = 1.51 × 10–5) and short sleep (≤ 6 h; OR, 0.98; 95%CI, 0.97–0.99; P = 1.51 × 10–5), while higher SA in posterior cingulate cortex resulted in a vulnerability to shorter sleep durations (β, − 0.09; 95%CI, − 0.13 to − 0.05; P = 1.21 × 10–5).ConclusionsSleep habits not only result from but also contribute to alterations in brain structure, which may shed light on the possible mechanisms linking sleep behaviours with neuropsychiatric disorders, and offer new strategies for prevention and intervention in psychiatric disorders and sleep disturbance.

Network-Based Spreading of Gray Matter Changes Across Different Stages of Psychosis

Psychotic illness is associated with anatomically distributed gray matter reductions that can worsen with illness progression, but the mechanisms underlying the specific spatial patterning of these changes is unknown. To test the hypothesis that brain network architecture constrains cross-sectional and longitudinal gray matter alterations across different stages of psychotic illness and to identify whether certain brain regions act as putative epicenters from which volume loss spreads. This case-control study included 534 individuals from 4 cohorts, spanning early and late stages of psychotic illness. Early-stage cohorts included patients with antipsychotic-naive first-episode psychosis (n = 59) and a group of patients receiving medications within 3 years of psychosis onset (n = 121). Late-stage cohorts comprised 2 independent samples of people with established schizophrenia (n = 136). Each patient group had a corresponding matched control group (n = 218). A sample of healthy adults (n = 356) was used to derive representative structural and functional brain networks for modeling of network-based spreading processes. Longitudinal illness-related and antipsychotic-related gray matter changes over 3 and 12 months were examined using a triple-blind randomized placebo-control magnetic resonance imaging study of the antipsychotic-naive patients. All data were collected between April 29, 2008, and January 15, 2020, and analyses were performed between March 1, 2021, and January 14, 2023. Coordinated deformation models were used to estimate the extent of gray matter volume (GMV) change in each of 332 parcellated areas by the volume changes observed in areas to which they were structurally or functionally coupled. To identify putative epicenters of volume loss, a network diffusion model was used to simulate the spread of pathology from different seed regions. Correlations between estimated and empirical spatial patterns of GMV alterations were used to quantify model performance. Of 534 included individuals, 354 (66.3%) were men, and the mean (SD) age was 28.4 (7.4) years. In both early and late stages of illness, spatial patterns of cross-sectional volume differences between patients and controls were more accurately estimated by coordinated deformation models constrained by structural, rather than functional, network architecture (r range, >0.46 to <0.57; P < .01). The same model also robustly estimated longitudinal volume changes related to illness (r ≥ 0.52; P < .001) and antipsychotic exposure (r ≥ 0.50; P < .004). Network diffusion modeling consistently identified, across all 4 data sets, the anterior hippocampus as a putative epicenter of pathological spread in psychosis. Epicenters of longitudinal GMV loss were apparent in posterior cortex early in the illness and shifted to the prefrontal cortex with illness progression. These findings highlight a central role for white matter fibers as conduits for the spread of pathology across different stages of psychotic illness, mirroring findings reported in neurodegenerative conditions. The structural connectome thus represents a fundamental constraint on brain changes in psychosis, regardless of whether these changes are caused by illness or medication. Moreover, the anterior hippocampus represents a putative epicenter of early brain pathology from which dysfunction may spread to affect connected areas.

Functional Alterations of the Basal Ganglia Are Associated with Voluntary Activation of the Core Stabilizing Muscles in Patients with Chronic Low Back Pain: A Cross-Sectional Study.

Deficits in voluntary activation of the core stabilizing muscles are consistently observed in patients with chronic low back pain (CLBP); however, the underlying neural mechanism remains unclear. This cross-sectional study aimed at testing the hypothesis that the impaired voluntary activation of core stabilizing muscles is associated with structural and functional alterations in the basal ganglia, thalamus, and cortex in patients with CLBP. We obtained structural and resting-state functional magnetic resonance imaging (rs-fMRI) data from 53 patients with CLBP and 67 healthy controls and estimated the alterations in grey matter volume (GMV) and functional and effective connectivity (EC) of regions with altered GMV via whole brain analysis. The voluntary activation of the multifidus (MF) and transversus abdominis (TrA) was evaluated by ultrasound imaging in these patients. Compared with the HCs, they displayed a significant decrease in GMV in the bilateral thalamus and caudate nucleus, a significant increase in GMV in the left middle frontal gyrus, and increased resting-state functional connectivity between the right caudate nucleus and the bilateral precuneus (voxel-level p < 0.005, Gaussian random field-corrected p < 0.05). The patients also showed increased EC from the right caudate nucleus to the bilateral precuneus, which was significantly correlated with voluntary activation of the bilateral MF and TrA (all p < 0.050). Grey matter alterations may be confined to regions responsible for perception, motor control, and emotion regulation in patients with CLBP. The interrupted EC from the basal ganglia to the default mode network might be involved in the impairment of voluntary activation of the core stabilizing muscles.

Gray Matter Changes Following Mild COVID-19: An MR Morphometric Study in Healthy Young People.

Although COVID-19 is primarily an acute respiratory infection, 5%-40% of patients develop late and prolonged symptoms with frequent neurological complaints, known as long COVID syndrome. The presentation of the disease suggests that COVID infection may cause functional and/or morphological central nervous system alterations, but studies published in the literature report contradictory findings. To investigate the chronic effects of COVID-19 on cerebral grey matter in a group of young patients without comorbidities, with mild course of COVID infection and no medical complaints at the time of examination. Prospective. Thirty-eight young (age = 26.6 ± 5.0 years; male/female = 14/24), adult participants who recovered from mild COVID infection without a history of clinical long COVID and 37 healthy control subjects (age = 25.9 ± 2.8 years; male/female = 14/23). Three Tesla, 3D T1-weighted magnetization-prepared rapid gradient-echo, 2D T2-weighted turbo spin-echo. MRI-based morphometry and volumetry along with neuropsychological testing and self-assessed questionnaire. Fisher's exact test, Mann-Whitney U-test, and multiple linear regression analyses were used to assess differences between COVID and healthy control groups. P < 0.05 was used as cutoff for significance. In the COVID group, significantly lower bilateral mean cortical thickness (left/right-hemisphere: 2.51 ± 0.06 mm vs. 2.56 ± 0.07 mm, η2 p = 0.102/2.50 ± 0.06 mm vs. 2.54 ± 0.07 mm, η2 p = 0.101), lower subcortical gray matter (57881 ± 3998 mm3 vs. 60470 ± 5211 mm3, η2 p = 0.100) and lower right olfactory bulb volume (52.28 ± 13.55 mm3 vs. 60.98 ± 15.8 mm3, η2 p = 0.078) were found. In patients with moderate to severe anosmia, cortical thickness was significantly lower bilaterally, as compared to patients without olfactory function loss (left/right-hemisphere: 2.50 ± 0.06 mm vs. 2.56 ± 0.05 mm, η2 = 0.173/2.49 ± 0.06 mm vs. 2.55 ± 0.05 mm, η2 = 0.189). Using further exploratory analysis, significantly reduced cortical thickness was detected locally in the right lateral orbitofrontal cortex in the COVID group (2.53 ± 0.10 mm vs. 2.60 ± 0.09 mm, η2 p = 0.112). Even without any subjective or objective neurological complaints at the time of the MR scan, subjects in the COVID group showed gray matter alterations in cortical thickness and subcortical gray matter volume. 2 TECHNICAL EFFICACY: Stage 3.

Unraveling neurotransmitter changes in de novo GBA-related and idiopathic Parkinson's disease

BackgroundPresently, neurotransmitter deficits in GBA-related Parkinson's disease (GBA-PD) and relationships with cognitive impairment are poorly understood. A better understanding of neurotransmitter impairments in GBA-PD — particularly in the newly diagnosed drug-naïve phase — may support developing targeted intervention strategies. We aimed to investigate patterns of neurotransmitter deficits in GBA-PD and idiopathic PD (iPD) and cognitive performance correlations. MethodsWe recruited 189 newly diagnosed PD patients for GBA sequencing. Voxel-wise gray matter volume (GMV) was evaluated in a subgroup of 17 GBA-PD, 100 iPD, and 32 age- and sex-matched healthy controls (HCs). The JuSpace toolbox covering various neurotransmitter maps helped assess whether the spatial patterns of GMV alterations in GBA-PD or iPD patients (relative to HCs) were associated with specific neurotransmitter systems. ResultsGBA-PD patients indicated widespread GM atrophy in the fronto-temporal-occipital region compared with HCs. GMV atrophy was spatially correlated in GBA-PD and iPD with serotonergic, dopaminergic, and acetylcholinergic pathway distributions (p < 0.05, false discovery rate corrected). Executive function and language in cognitive domains were also associated with the strength of GMV colocalization of serotonergic, dopaminergic, and acetylcholinergic circuits. ConclusionsRegional GM atrophy related to specific neurotransmitter deficits in de novo GBA-PD and iPD patients could provide new insights into pathophysiological processes, facilitating potential therapeutic targets to support PD management.