Gray Matter Volume Alterations Research Articles

Larger putamen in individuals at risk and with manifest bipolar disorder.

Individuals at risk for bipolar disorder (BD) have a wide range of genetic and non-genetic risk factors, like a positive family history of BD or (sub)threshold affective symptoms. Yet, it is unclear whether these individuals at risk and those diagnosed with BD share similar gray matter brain alterations. In 410 male and female participants aged 17-35 years, we compared gray matter volume (3T MRI) between individuals at risk for BD (as assessed using the EPIbipolar scale; n = 208), patients with a DSM-IV-TR diagnosis of BD (n = 87), and healthy controls (n = 115) using voxel-based morphometry in SPM12/CAT12. We applied conjunction analyses to identify similarities in gray matter volume alterations in individuals at risk and BD patients, relative to healthy controls. We also performed exploratory whole-brain analyses to identify differences in gray matter volume among groups. ComBat was used to harmonize imaging data from seven sites. Both individuals at risk and BD patients showed larger volumes in the right putamen than healthy controls. Furthermore, individuals at risk had smaller volumes in the right inferior occipital gyrus, and BD patients had larger volumes in the left precuneus, compared to healthy controls. These findings were independent of course of illness (number of lifetime manic and depressive episodes, number of hospitalizations), comorbid diagnoses (major depressive disorder, attention-deficit hyperactivity disorder, anxiety disorder, eating disorder), familial risk, current disease severity (global functioning, remission status), and current medication intake. Our findings indicate that alterations in the right putamen might constitute a vulnerability marker for BD.

Grey matter volume reduction in the frontotemporal cortex associated with persistent verbal auditory hallucinations in Chinese patients with chronic schizophrenia: Insights from a 3 T magnetic resonance imaging study

BackgroundPersistent auditory verbal hallucinations (pAVHs) are a fundamental manifestation of schizophrenia (SCZ), yet the exact connection between pAVHs and brain structure remains contentious. This study aims to explore the potential correlation between pAVHs and alterations in grey matter volume (GMV) within specific brain regions among individuals diagnosed with SCZ. Methods76 SCZ patients with pAVHs (pAVH group), 57 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) were investigated using 3 T magnetic resonance imaging. The P3 hallucination item of the Positive and Negative Syndrome Scale was used to assess the severity of pAVHs. Voxel-based morphometry was used to analyze the GMV profile between the three groups. ResultsCompared to the non-AVH and HC groups, the pAVH group exhibited extensive reduction in GMV within the frontotemporal cortex. Conversely, no significant difference in GMV was observed between the non-AVH and HC groups. The severity of pAVHs showed a negative correlation with GMV in several regions, including the right fusiform, right inferior temporal, right medial orbitofrontal, right superior frontal, and right temporal pole (p = 0.0036, Bonferroni correction). Stepwise linear regression analysis revealed that GMV in the right temporal pole (β = −0.29, p = 0.001) and right fusiform (β = −0.21, p = 0.01) were significantly associated with the severity of pAVHs. ConclusionsWidespread reduction in GMV is observed within the frontotemporal cortex, particularly involving the right temporal pole and right fusiform, which potentially contribute to the pathogenesis of pAVHs in individuals with chronic SCZ.

Associations between brain morphology, inflammatory markers and symptoms of fatigue, depression or anxiety in active and remitted Crohn's disease.

Fatigue and psychosocial impairments are highly prevalent in IBD, especially during active disease. Disturbed brain-gut-interactions may contribute to these symptoms. This study examined associations between brain structure, faecal calprotectin and symptoms of fatigue, depression and anxiety in persons with Crohn's Disease (CD) in different disease states. In this prospective observational study, n=109 participants (n=67 persons with CD, n=42 healthy controls) underwent cranial magnetic resonance imaging, 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. Symptoms of fatigue, depression and anxiety were increased in patients with CD compared to controls, with highest scores in active CD. Patients exhibited regionally reduced GMV in cortical and subcortical sensorimotor regions, occipitotemporal and medial frontal areas. Regional GMV differences showed a significant negative association with fatigue, but not with depression or anxiety. Subgroup analyses revealed symptom-GMV-associations for fatigue in remitted, but not in active CD, while fatigue was positively associated with faecal calprotectin in active, but not remitted disease. Our findings support disturbed brain-gut-interactions 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.

Selective disrupted gray matter volume covariance of amygdala subregions in schizophrenia.

Although extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia. To address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV. Our findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure. Our research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.

Molecular mechanisms underlying structural plasticity of electroconvulsive therapy in major depressive disorder.

Although previous studies reported structural changes associated with electroconvulsive therapy (ECT) in major depressive disorder (MDD), the underlying molecular basis of ECT remains largely unknown. Here, we combined two independent structural MRI datasets of MDD patients receiving ECT and transcriptomic gene expression data from Allen Human Brain Atlas to reveal the molecular basis of ECT for MDD. We performed partial least square regression to explore whether/how gray matter volume (GMV) alterations were associated with gene expression level. Functional enrichment analysis was conducted using Metascape to explore ontological pathways of the associated genes. Finally, these genes were further assigned to seven cell types to determine which cell types contribute most to the structural changes in MDD patients after ECT. We found significantly increased GMV in bilateral hippocampus in MDD patients after ECT. Transcriptome-neuroimaging association analyses showed that expression levels of 726 genes were positively correlated with the increased GMV in MDD after ECT. These genes were mainly involved in synaptic signaling, calcium ion binding and cell-cell signaling, and mostly belonged to excitatory and inhibitory neurons. Moreover, we found that the MDD risk genes of CNR1, HTR1A, MAOA, PDE1A, and SST as well as ECT related genes of BDNF, DRD2, APOE, P2RX7, and TBC1D14 showed significantly positive associations with increased GMV. Overall, our findings provide biological and molecular mechanisms underlying structural plasticity induced by ECT in MDD and the identified genes may facilitate future therapy for MDD.

Selective vulnerability of hippocampal sub-regions in patients with subcortical vascular mild cognitive impairment.

Early diagnosis of subcortical vascular mild cognitive impairment (svMCI) is clinically essential because it is the most reversible subtype of all cognitive impairments. Since structural alterations of hippocampal sub-regions have been well studied in neurodegenerative diseases with pathophysiological cognitive impairments, we were eager to determine whether there is a selective vulnerability of hippocampal sub-fields in patients with svMCI. Our study included 34 svMCI patients and 34 normal controls (NCs), with analysis of T1 images and Montreal Cognitive Assessment (MoCA) scores. Gray matter volume (GMV) of hippocampal sub-regions was quantified and compared between the groups, adjusting for age, sex, and education. Additionally, we explored correlations between altered GMV in hippocampal sub-fields and MoCA scores in svMCI patients. Patients with svMCI exhibited selectively reduced GMV in several left hippocampal sub-regions, such as the hippocampal tail, hippocampal fissure, CA1 head, ML-HP head, CA4 head, and CA3 head, as well as decreased GMV in the right hippocampal tail. Specifically, GMV in the left CA3 head was inversely correlated with MoCA scores in svMCI patients. Our findings indicate that the atrophy pattern of patients with svMCI was predominantly located in the left hippocampal sub-regions. The left CA3 might be a crucial area underlying the distinct pathophysiological mechanisms of cognitive impairments with subcortical vascular origins.

The covariant structural and functional neuro-correlates of cognitive impairments in patients with end-stage renal diseases.

Cognitive impairment (CI) is a common complication of end-stage renal disease (ESRD) that is associated with structural and functional changes in the brain. However, whether a joint structural and functional alteration pattern exists that is related to CI in ESRD is unclear. In this study, instead of looking at brain structure and function separately, we aim to investigate the covariant characteristics of both functional and structural aspects. Specifically, we took the fusion analysis approach, namely, multimodal canonical correlation analysis and joint independent component analysis (mCCA+jICA), to jointly study the discriminative features in gray matter volume (GMV) measured by T1-weighted (T1w) MRI, fractional anisotropy (FA) in white matter measured by diffusion MRI, and the amplitude of low-frequency fluctuation (ALFF) measured by blood oxygenation-level-dependent (BOLD) MRI in 78 ESRD patients versus 64 healthy controls (HCs), followed by a mediation effect analysis to explore the relationship between neuroimaging findings, cognitive impairments and uremic toxins. Two joint group-discriminative independent components (ICs) were found to show covariant abnormalities across FA, GMV, and ALFF (all p < 0.05). The most dominant joint IC revealed associative patterns of alterations of GMV (in the precentral gyrus, occipital lobe, temporal lobe, parahippocampal gyrus, and hippocampus), alterations of ALFF (in the precuneus, superior parietal gyrus, and superior occipital gyrus), and of white matter FA (in the corticospinal tract and inferior frontal occipital fasciculus). Another significant IC revealed associative alterations of GMV (in the dorsolateral prefrontal and orbitofrontal cortex) and FA (in the forceps minor). Moreover, the brain changes identified by FA and GMV in the above-mentioned brain regions were found to mediate the negative correlation between serum phosphate and mini-mental state examination (MMSE) scores (all p < 0.05). The mCCA+jICA method was demonstrated to be capable of revealing covariant abnormalities across neuronal features of different types in ESRD patients as contrasted to HCs, and joint brain changes may play an important role in mediating the relationship between serum toxins and CIs in ESRD. Our results show the mCCA+jICA fusion analysis approach may provide new insights into similar neurobiological studies.

Progressive increase of brain gray matter volume in individuals with regular soccer training

The study aimed to investigate alterations in gray matter volume in individuals undergoing regular soccer training, using high-resolution structural data, while also examining the temporal precedence of such structural alterations. Both voxel-based morphometry and source-based morphometry (SBM) methods were employed to analyze volumetric changes in gray matter between the soccer and control groups. Additionally, a causal network of structural covariance (CaSCN) was built using granger causality analysis on brain structural data ordering by training duration. Significant increases in gray matter volume were observed in the cerebellum in the soccer group. Additionally, the results of the SBM analysis revealed significant increases in gray matter volume in the calcarine and thalamus of the soccer group. The analysis of CaSCN demonstrated that the thalamus had a prominent influence on other brain regions in the soccer group, while the calcarine served as a transitional node, and the cerebellum acted as a prominent node that could be easily influenced by other brain regions. In conclusion, our study identified widely affected regions with increased gray matter volume in individuals with regular soccer training. Furthermore, a temporal precedence relationship among these regions was observed.

Two multimodal neuroimaging subtypes of obsessive-compulsive disorder disclosed by semi-supervised machine learning

BackgroundObsessive-compulsive disorder (OCD) is a highly heterogeneous mental condition with a diverse symptom. Existing studies classified OCD on the basis of conventional phenomenology-based taxonomy ignoring the fact that the same subtype identified in accordance with clinical symptom may have different mechanisms and treatment responses. MethodsThis research involved 50 medicine-free patients with OCD and 50 matched healthy controls (HCs). All the participants were subjected to structural and functional magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) and amplitude of low frequency fluctuation (ALFF) were used to evaluate gray matter volume (GMV) and spontaneous neuronal activities at rest respectively. Similarity network fusion (SNF) was utilized to integrate GMVs and spontaneous neuronal activities, and heterogeneity by discriminant analysis was applied to characterise OCD subtypes. ResultsTwo OCD subtypes were identified: Subtype 1 exhibited decreased GMVs (i.e., left inferior temporal gyrus, right supplementary motor area and right lingual gyrus) and increased ALFF value (i.e., right orbitofrontal cortex), whereas subtype 2 exhibited increased GMVs (i.e., left cuneus, right precentral gyrus, left postcentral gyrus and left hippocampus) and decreased ALFF value (i.e., right caudate nucleus). Furthermore, the altered GMVs was negatively correlated with abnormal ALFF values in both subtype 1 and 2. LimitationsThis study requires further validation via a larger, independent dataset and should consider the potential influences of psychotropic medication on OCD patients' brain activities. ConclusionsResults revealed two reproducible subtypes of OCD based on underlying multimodal neuroimaging and provided new perspectives on the classification of OCD.

MRI brain structural and functional networks changes in Parkinson disease with REM sleep behavior disorders.

Rapid eye movement sleep behavior disorder (RBD) is common in individuals with Parkinson's disease (PD). In spite of that, the precise mechanism underlying the pathophysiology of RBD among PD remains unclear. The aim of the present study was to analyze gray matter volumes (GMVs) as well as the changes of functional connectivity (FC) among PD patients with RBD (PD-RBD) by employing a combination of voxel-based morphometry (VBM) and FC methods. A total of 65 PD patients and 21 healthy control (HC) subjects were included in this study. VBM analyses were performed on all subjects. Subsequently, regions with significant different GMVs between PD patients with and without RBD (PD-nRBD) were selected for further analysis of FC. Correlations between altered GMVs and FC values with RBD scores were also investigated. Additionally, receiver operating characteristic (ROC) curves were employed for the evaluation of the predictive value of GMVs and FC in identifying RBD in PD. PD-RBD patients exhibited lower GMVs in the left middle temporal gyrus (MTG) and bilateral cuneus. Furthermore, we observed higher FC between the left MTG and the right postcentral gyrus (PoCG), as well as lower FC between the bilateral cuneus (CUN) and the right middle frontal gyrus (MFG) among PD-RBD patients in contrast with PD-nRBD patients. Moreover, the GMVs of MTG (extending to the right PoCG) was positively correlated with RBD severity [as measured by REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) score]. Conversely, the FC value between the bilateral CUN and the right MTG in PD-RBD patients was negatively correlated with RBDSQ score. This study revealed the presence replace with GMV and FC changes among PD-RBD patients, which were closely linked to the severity of RBD symptoms. Furthermore, the combination of basic clinical characteristics, GMVs and FC values effectively predicted RBD for individuals with PD.

Reduced gray matter volume of the hippocampal tail in melancholic depression: evidence from an MRI study

BackgroundMelancholic depression (MD) is one of the most prevalent and severe subtypes of major depressive disorder (MDD). Previous studies have revealed inconsistent results regarding alterations in grey matter volume (GMV) of the hippocampus and amygdala of MD patients, possibly due to overlooking the complexity of their internal structure. The hippocampus and amygdala consist of multiple and functionally distinct subregions, and these subregions may play different roles in MD. This study aims to investigate the volumetric alterations of each subregion of the hippocampus and amygdala in patients with MD and non-melancholic depression (NMD).MethodsA total of 146 drug-naïve, first-episode MDD patients (72 with MD and 74 with NMD) and 81 gender-, age-, and education-matched healthy controls (HCs) were included in the study. All participants underwent magnetic resonance imaging (MRI) scans. The subregional segmentation of hippocampus and amygdala was performed using the FreeSurfer 6.0 software. The multivariate analysis of covariance (MANCOVA) was used to detect GMV differences of the hippocampal and amygdala subregions between three groups. Partial correlation analysis was conducted to explore the relationship between hippocampus or amygdala subfields and clinical characteristics in the MD group. Age, gender, years of education and intracranial volume (ICV) were included as covariates in both MANCOVA and partial correlation analyses.ResultsPatients with MD exhibited a significantly lower GMV of the right hippocampal tail compared to HCs, which was uncorrelated with clinical characteristics of MD. No significant differences were observed among the three groups in overall and subregional GMV of amygdala.ConclusionsOur findings suggest that specific hippocampal subregions in MD patients are more susceptible to volumetric alterations than the entire hippocampus. The reduced right hippocampal tail may underlie the unique neuropathology of MD. Future longitudinal studies are required to better investigate the associations between reduced right hippocampal tail and the onset and progression of MD.

The Dark and Gloomy Brain: Grey Matter Volume Alterations in Major Depressive Disorder–Fine-Grained Meta-Analyses

Background. While the brain correlates of major depressive disorder (MDD) have been extensively studied, there is no consensus conclusion so far. Various meta-analyses tried to determine the most consistent findings, but the results are often discordant for grey matter volume (GMV) atrophy and hypertrophy. Applying rigorous and stringent inclusion criteria and controlling for confounding factors, such as the presence of anxiety comorbidity, we carried out two novel meta-analyses on the existing literature to unveil MDD signatures. Methods. A systematic literature search was performed up to January 2023. Seventy-three studies on MDD patients reporting GMV abnormalities were included in the first meta-analysis, for a total of 6167 patients and 6237 healthy controls (HC). To test the effects of anxiety comorbidity, we conducted a second meta-analysis, by adding to the original pure MDD sample a new cohort of MDD patients with comorbid anxiety disorders (308 patients and 342 HC). An activation likelihood estimation (ALE) analysis and a coordinate-based mapping approach separate for atrophy and hypertrophy were used to identify common brain structural alterations among patients. Results. The pure MDD sample exhibited atrophy in the left insula, as well as hypertrophy in the bilateral amygdala and parahippocampal gyri. When we added patients with comorbid anxiety to the original sample, bilateral insula atrophy emerged, whereas the hypertrophy results were not replicated. Conclusions. Our findings revealed important structural alterations in pure MDD patients, particularly in the insula and amygdala, which play key roles in sensory input integration and in emotional processing, respectively. Additionally, the amygdala and parahippocampal gyrus hypertrophy may be related to MDD functional overactivation to emotional stimuli, rumination, and overactive self-referential thinking. Conversely, the presence of anxiety comorbidity revealed separate effects which were not seen in the pure MDD sample, underscoring the importance of strict inclusion criteria for investigations of disorder-specific effects.

Right frontal cingulate cortex mediates the effect of prenatal complications on youth internalizing behaviors.

Prenatal and perinatal complications represent well-known risk factors for the future development of psychiatric disorders. Such influence might become manifested during childhood and adolescence, as key periods for brain and behavioral changes. Internalizing and externalizing behaviors in adolescence have been associated with the risk of psychiatric onset later in life. Both brain morphology and behavior seem to be affected by obstetric complications, but a clear link among these three aspects is missing. Here, we aimed at analyzing the association between prenatal and perinatal complications, behavioral issues, and brain volumes in a group of children and adolescents. Eighty-two children and adolescents with emotional-behavioral problems underwent clinical and 3 T brain magnetic resonance imaging (MRI) assessments. The former included information on behavior, through the Child Behavior Checklist/6-18 (CBCL/6-18), and on the occurrence of obstetric complications. The relationships between clinical and gray matter volume (GMV) measures were investigated through multiple generalized linear models and mediation models. We found a mutual link between prenatal complications, GMV alterations in the frontal gyrus, and withdrawn problems. Specifically, complications during pregnancy were associated with higher CBCL/6-18 withdrawn scores and GMV reductions in the right superior frontal gyrus and anterior cingulate cortex. Finally, a mediation effect of these GMV measures on the association between prenatal complications and the withdrawn dimension was identified. Our findings suggest a key role of obstetric complications in affecting brain structure and behavior. For the first time, a mediator role of frontal GMV in the relationship between prenatal complications and internalizing symptoms was suggested. Once replicated on independent cohorts, this evidence will have relevant implications for planning preventive interventions.

White and gray matter alterations in bipolar I and bipolar II disorder subtypes compared with healthy controls - exploring associations with disease course and polygenic risk.

Patients with bipolar disorder (BD) show alterations in both gray matter volume (GMV) and white matter (WM) integrity compared with healthy controls (HC). However, it remains unclear whether the phenotypically distinct BD subtypes (BD-I and BD-II) also exhibit brain structural differences. This study investigated GMV and WM differences between HC, BD-I, and BD-II, along with clinical and genetic associations. N = 73 BD-I, n = 63 BD-II patients and n = 136 matched HC were included. Using voxel-based morphometry and tract-based spatial statistics, main effects of group in GMV and fractional anisotropy (FA) were analyzed. Associations between clinical and genetic features and GMV or FA were calculated using regression models. For FA but not GMV, we found significant differences between groups. BD-I patients showed lower FA compared with BD-II patients (ptfce-FWE = 0.006), primarily in the anterior corpus callosum. Compared with HC, BD-I patients exhibited lower FA in widespread clusters (ptfce-FWE < 0.001), including almost all major projection, association, and commissural fiber tracts. BD-II patients also demonstrated lower FA compared with HC, although less pronounced (ptfce-FWE = 0.049). The results remained unchanged after controlling for clinical and genetic features, for which no independent associations with FA or GMV emerged. Our findings suggest that, at a neurobiological level, BD subtypes may reflect distinct degrees of disease expression, with increasing WM microstructure disruption from BD-II to BD-I. This differential magnitude of microstructural alterations was not clearly linked to clinical and genetic variables. These findings should be considered when discussing the classification of BD subtypes within the spectrum of affective disorders.

Cerebro-cerebellar gray matter abnormalities associated with cognitive impairment in patients with recent-onset and chronic schizophrenia

Although the role of the cerebellum in schizophrenia has gained attention, its contribution to cognitive impairment remains unclear. We aimed to investigate volumetric alterations in the cerebro-cerebellar gray matter (GM) in patients with recent-onset schizophrenia (ROS) and chronic schizophrenia (CS) compared with healthy controls (HCs). Seventy-two ROS, 43 CS, and 127 HC participants were recruited, and high-resolution T1-weighted structural magnetic resonance images of the brain were acquired. We compared cerebellar GM volumes among the groups using voxel-based morphometry and examined the cerebro-cerebellar GM volumetric correlations in participants with schizophrenia. Exploratory correlation analysis investigated the functional relevance of cerebro-cerebellar GM volume alterations to cognitive function in the schizophrenia group. The ROS and CS participants demonstrated smaller cerebellar GM volumes, particularly in Crus I and II, than HCs. Extracted cerebellar GM volumes demonstrated significant positive correlations with the cerebral GM volume in the fronto-temporo-parietal association areas engaged in higher-order association. The exploratory analysis showed that smaller cerebellar GM in the posterior lobe regions was associated with poorer cognitive performance in participants with schizophrenia. Our study suggests that cerebellar pathogenesis is present in the early stages of schizophrenia and interconnected with structural abnormalities in the cerebral cortex. Integrating the cerebellum into the pathogenesis of schizophrenia will help advance our understanding of the disease and identify novel treatment targets concerning dysfunctional cerebro-cerebellar interactions.

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.

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 &lt; 0.05 as significant. Results: SZH and HC groups showed no significant differences in age and gender. However, significant (p &lt; 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 &lt; 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.

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.