Specific Substantial Dysconnectivity in Schizophrenia: A Transdiagnostic Multimodal Meta-analysis of Resting-State Functional and Structural Magnetic Resonance Imaging Studies

S230. Convergence of Specifically Altered Intrinsic Brain Connectivity and Aberrant Brain Volume in Schizophrenia Transdiagnostic Multimodal Meta-Analysis of Resting-State Functional and Structural MRI

Differentiating between bipolar and unipolar depression in functional and structural MRI studies

ObjectiveWe aimed to investigate changes in whole-brain gray matter volumes (GMVs) before and after electroconvulsive therapy (ECT) in adolescents with major depressive disorder (MDD) and suicidal ideation (SI).MethodsThirty adolescents with MDD and SI were observed, and structural magnetic resonance imaging (sMRI) was performed at baseline and after ECT for each patient. But Twenty-five healthy controls (HCs) were scanned only at baseline. The voxel-based morphometry (VBM) techniques were used to examine GMVs.ResultsCompared with HCs, MDDs at baseline showed decreased GMVs in the left middle temporal gyrus, right superior temporal gyrus, right middle temporal gyrus, left precuneus, right precuneus, and left superior frontal gyrus. After ECT, MDDs showed increased GMVs in the right superior frontal gyrus and right superior temporal gyrus. Pearson’s correlation found that Beck Scale for Suicide Ideation (BSSI) scores at baseline were negatively correlated with GMVs in the left superior frontal gyrus and HAMD and BSSI scores after ECT were negatively correlated with GMVs in the right superior temporal gyrus.ConclusionFrontal–temporal–precuneus structure changes may be a potential cause of depressive and suicidal symptoms in adolescents. ECT may improve depressive and suicidal symptoms in adolescents by regulating brain structures to compensate original defects.

Neuroimaging studies have consistently identified brain activation in the motor area and the cerebellum during chewing. In this study, we further investigated the structural and functional brain signature associated with masticatory performance, which is a widely used index for evaluating overall masticatory function in the elderly. Twenty-five healthy elderly participants underwent oral examinations, masticatory performance tests, and behavioral assessments, including the Cognitive Abilities Screening Instrument and the short-form Geriatric Depression Scale. Masticatory performance was assessed with the validated colorimetric method, using color-changeable chewing gum. T1-weighted structural magnetic resonance imaging (MRI) and resting-state function MRI were performed. We analyzed alterations in gray matter volume (GMV) using voxel-based morphometry and resting-state functional connectivity (rsFC) between brain regions using the seed-based method. The structural and functional MRI analyses revealed the following findings: (1) the GMV change in the premotor cortex was positively correlated with masticatory performance. (2) The rsFC between the cerebellum and the premotor cortex was positively correlated with masticatory performance. (3) The GMV changes in the dorsolateral prefrontal cortex (DLPFC), as well as the rsFC between the cerebellum and the DLPFC, were positively correlated with masticatory performance. The findings showed that in the premotor cortex, a reduction of GMV and rsFC would reflect declined masticatory performance. The positive correlation between DLPFC connectivity and masticatory performance implies that masticatory ability is associated with cognitive function in the elderly. Our findings highlighted the role of the central nervous system in masticatory performance and increased our understanding of the structural and functional brain signature underlying individual variations in masticatory performance in the elderly.

ObjectivesBrain structural and functional abnormalities have been separately reported in patients with classic trigeminal neuralgia (CTN). However, whether and how the functional deficits are related to the structural alterations remains unclear. This study aims to investigate the anatomical and functional deficits in patients with CTN and explore their association.MethodsA total of 34 patients with CTN and 29 healthy controls (HCs) with age- and gender-matched were recruited. All subjects underwent structural and resting-state functional magnetic resonance imaging (fMRI) scanning and neuropsychological assessments. Voxel-based morphometry (VBM) was applied to characterize the alterations of gray matter volume (GMV). The amplitude of low-frequency fluctuation (ALFF) method was used to evaluate regional intrinsic spontaneous neural activity. Further correlation analyses were performed between the structural and functional changes and neuropsychological assessments.ResultsCompared to the HCs, significantly reduced GMV was revealed in the right hippocampus, right fusiform gyrus (FFG), and temporal-parietal regions (the left superior/middle temporal gyrus, left operculo-insular gyrus, left inferior parietal lobule, and right inferior temporal gyrus) in patients with CTN. Increased functional activity measured by zALFF was observed mainly in the limbic system (the bilateral hippocampus and bilateral parahippocampal gyrus), bilateral FFG, basal ganglia system (the bilateral putamen, bilateral caudate, and right pallidum), left thalamus, left cerebellum, midbrain, and pons. Moreover, the right hippocampus and FFG were the overlapped regions with both functional and anatomical deficits. Furthermore, GMV in the right hippocampus was negatively correlated with pain intensity, anxiety, and depression. GMV in the right FFG was negatively correlated with illness duration. The zALFF value in the right FFG was positively correlated with anxiety.ConclusionOur results revealed concurrent structural and functional changes in patients with CTN, indicating that the CTN is a brain disorder with structural and functional abnormalities. Moreover, the overlapping structural and functional changes in the right hippocampus and FFG suggested that anatomical and functional changes might alter dependently in patients with CTN. These findings highlight the vital role of hippocampus and FFG in the pathophysiology of CTN.

Reductions in body weight and insulin resistance are not associated with changes in grey matter volume or cortical thickness during the PREVIEW study

Functional Connectivity of the Striatum in Schizophrenia and Psychotic Bipolar Disorder

Objective To investigate the changes of brain gray matter volume (GMV) and brain activity in patients with long-term methamphetamine (MA) abstinence compared with healthy controls. Methods This study included 44 abstinent MA patients and 40 demographically equivalent healthy controls. Structural magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) were obtained on Siemens 3.0 T MR. Differences in GMV between abstinent MA group and control group were assessed using voxel-based morphometry (VBM) method. Within each region showed significant differences between two groups, the value of the fractional amplitude of low frequency fluctuation (fALFF) was calculated using the rs-fMRI data. Differences of fALFF between groups were also evaluated. Furthermore, partial correlation coefficients adjusted for age, years of education, smoking and drinking were calculated in the abstinent MA group to assess associations between the mean GMV and fALFF values in significant clusters and variables of MA use and abstinence. Results Compared with controls, abstinent MA group showed increased GMV in the right cerebellum crus and decreased GMV in the right calcarine. While fALFF values within bilateral cerebellum crus in abstinent MA patients were significantly increased. Moreover, GMV of the left cerebellar crus was positively correlated with the withdrawal time among abstinent MA patients. Conclusions Both structural and functional abnormalities were found in abstinent MA patients even after long-term abstinence. The positive correlation between GMV of left cerebellum crus and abstinent duration suggested that prolonged abstinence may be beneficial to brain recovery. The fALFF of the right calcarine was increased even with decreased GVM in the abstinent MA group. It indicates that the brain activity of this area is increased, which may imply that drug cue-induced craving is significant among methamphetamine patients even after long-term abstinence. Key words: Methamphetamine; Magnetic resonance imaging; Voxel-based morphometry; Fractional amplitude of low frequency fluctuation

Meta-analyses and mega-analyses of structural magnetic resonance imaging (sMRI) and diffusion MRI (dMRI) studies in thousands of people with schizophrenia have shown reduced brain volumes and structural connectivity relative to healthy controls, some of which consistently correlate with the severity of symptoms and cognitive impairment. Post-mortem studies point to a pathophysiology of reduced neuronal size and dendritic arborisation, which is multifactorial. Magnetic resonance spectroscopy (MRS) reductions in N-acetyl-aspartate in some regions and reduced glucose uptake in the pre-frontal cortex (PFC) on positron emission tomography (PET) both suggest impaired cerebral mitochondrial metabolism. MRS studies also suggest glutamatergic abnormalities, which other studies suggest may be the primary neurochemistry of schizophrenia, while fluorodopa PET shows increased dopamine turnover in the striatum as the likely cause of psychotic symptoms. Single-photon emission computed tomography (SPECT) and PET measured blood flow are both reduced in the PFC, compounded by age, chronicity and antipsychotic medication. The functional imaging literature, including functional magnetic resonance imaging (fMRI), consistently points to the superior temporal gyrus (STG) and connected regions as the areas underpinning auditory hallucinations. Resting state fMRI is delivering consistent findings of dysconnectivity in schizophrenia, and studies of learning and reward are linking physiology, pharmacology and phenomenology. Necessarily, this is a very technical review. Box 7.1 presents a lay summary of the chapter. Overall, the vast neuroimaging literature in schizophrenia can be summarised as showing premorbid structural and functional changes that probably become more pronounced, especially in prefrontal and temporal lobes (reflecting reduced top-down cognitive control and input from the regularities of experience respectively), as people develop psychosis, driven by increased dopamine synthesis and turnover, with some likely progression in general and in those with a poor outcome. None of these findings has, however, been shown to be specific to schizophrenia, and there are generally similar but lesser changes in bipolar disorder. Progress in scientific understanding and evaluating clinical applications will require clear hypotheses, adequately powered studies, standardised methods and reporting.

A longitudinal investigation of structural brain changes during second language learning

To explore cross-sectional and longitudinal gray matter (GM) volume changes in patients with migraine and their association with patients' clinical characteristics and disease activity. Brain T2-weighted and 3-dimensional T1-weighted scans were acquired from 73 episodic migraineurs and 46 age- and sex-matched nonmigraine controls at baseline. Twenty-four migraineurs and 25 controls agreed to be reexamined after a mean follow-up of 4 years. Using a general linear model and SPM12, a whole-brain analysis was performed to assess GM volume modifications. At baseline, compared to controls, patients with migraine showed lower cerebellar GM volume and higher volume of regions of the frontotemporal lobes. At follow-up, migraineurs were significantly older than controls. Over the follow-up, migraineurs developed an increased volume of frontotemporoparietal regions, which was more prominent in patients with a higher baseline disease activity: long disease duration and high attack frequency. Migraineurs also developed decreased GM volume of visual areas, which was related to higher pain severity. Patients with an increased attack frequency at follow-up experienced both increased and decreased volume of nociceptive regions. In migraineurs, reduced GM volume of extrastriate visual areas during the follow-up was significantly correlated to baseline disease activity: shorter disease duration and lower attack frequency. In this cohort, the migraine brain changes dynamically over time, and different pathophysiologic mechanisms can occur in response to patients' disease severity. The interaction between predisposing brain traits and experience-dependent responses might vary across different nociceptive and visual areas, thus leading to distinct patterns of longitudinal GM volume changes.

This study aimed to explore gray matter volume (GMV) changes in patients undergoing hemodialysis and assess the clinical risk factors associated with GMV changes and the relationship between GMV changes and neuropsychologic test results. Eighty-eight hemodialysis patients and 76 healthy controls (HCs) were recruited in this study. Fifty patients underwent follow-up examinations (follow-up duration: 1.75 ± 0.55 years), including magnetic resonance imaging, blood biochemical, and neuropsychologic testing. Changes in GMV between the patients and HCs were assessed. Longitudinal GMV changes were also explored in the patients. The clinical risk factors associated with longitudinal GMV changes and the correlations between longitudinal GMV changes and neuropsychologic test results were analyzed in the patients. Patients undergoing hemodialysis had diffusely decreased GMV compared with HCs (with age, sex, and total intracranial volume [TIV] as covariates, P<0.001, voxel-wise threshold false discovery rate [FDR] corrected). Compared with patients at baseline, regional decreased GMV were found in patients at follow-up (with age and TIV as covariates, P<0.05, voxel-wise threshold FDR corrected). Increased serum urea concentrations, parathyroid hormone levels, and hemodialysis duration were independent risk factors for decreased GMV in patients undergoing hemodialysis (all P<0.05, FDR corrected). Patients undergoing hemodialysis had lower mini-mental state examination (MMSE) (27[26, 29]) and Montreal cognitive assessment (MoCA) (22[19.5, 24.0]) scores than those of the HCs (30[29, 30] and 28[26.9, 29]) (all P<0.05). The MMSE scores of the patients at follow-up (26[25, 28.5]) were lower than those of patients at baseline (28[25, 29.5]) (P=0.02). The decreased left caudate volumes were positively correlated with reduced MMSE scores in hemodialysis patients (rs=0.437, P=0.033). Patients undergoing hemodialysis had noticeable GM atrophy over time, related to cognitive impairments.

Neurodegenerative changes are key manifestations of Wilson disease (WD), causing neurological symptoms including parkinsonism, tremors, and dystonia. However, the neuroimaging correlates of specific neurological manifestations (especially dystonia) in WD remain poorly characterized. 37 WD patients and 37 healthy controls (HC) were recruited. All subjects underwent structural magnetic resonance scanning, muscle biomechanical measurements, and the Unified Wilson Disease Rating Scale for Neurology (UWDRS-N) assessment. Neurodegenerative changes, identified as gray matter volume (GV) changes, were analyzed via voxel-based morphometry (VBM) in WD compared to HC. Clinical symptoms were linked to GV changes in WD patients' brains. Compared with HC, WD patients had GV loss in the bilateral caudate nucleus, putamen, cerebellum (Crus1), left amygdala, right posterior insular lobe, and right parahippocampal gyrus and increased GV in the bilateral anterior insular lobes. In cortical areas, UWDRS-N significantly negatively correlated with GV in the bilateral posterior insula lobes, part of temporal lobe, optic cortex, frontal lobe, and cingulate cortex, while positively correlated with that in bilateral anterior insular lobes and putamen. Moreover, the GV from the left parahippocampal gyrus, bilateral hippocampus, and bilateral caudate nucleus showed a strong positive correlation with the F value of the right gastrocnemius medial head. In WD patients with neurological symptoms, obvious abnormal GV values in the cortico-striatal-thalamo-cortical (CSTC) circuit were noted. These GV changes were linked to UWDRS-N and correlated with muscle tension. The study mapped UWDRS-N and muscle biomechanics in GV-impaired areas, suggesting altered GV (especially in basal ganglia) as a key imaging sign of WD severity. This indicates that the CSTC circuit could act as a biomarker for WD neurological symptoms and affect WD dystonia mechanisms. Additionally, it shows that muscle-related biological parameters can assess WD dystonia severity and neurological damage. clinicaltrials.gov, identifier NCT05305872.

EPA-1579 - Classifying schizophrenia using joint multivariate pattern recognition analysis of brain function and structure

White matter microstructural abnormalities and gray matter volume alterations in obsessive-compulsive disorder: A coordinate-based meta-analysis