Gray Matter Volume Alterations Research Articles

The interaction between first-episode drug-naïve schizophrenia and age based on gray matter volume and its molecular analysis: a multimodal magnetic resonance imaging study.

Schizophrenia is a neurodevelopmental disorder characterized by progressive and widespread gray matter (GM) atrophy. Studies have shown that normal brain development has an impact on schizophrenia-induced GM alterations. However, the neuropathology and underlying molecular mechanisms of interaction between age and schizophrenia are unclear. This study enrolled 66/84 first-episode drug-naïve patients with early-onset/adult-onset schizophrenia ((EOS)/(AOS)) and matched normal controls (NC) (46 adolescents/73 adults), undergoing T1-weighted high-resolution magnetic resonance imaging. Gray matter volume (GMV) in four groups was detected using 2-way analyses of variance with diagnosis and age as factors. Then, factors-related volume maps and neurotransmitter maps were spatially correlated using JuSpace to determine the relationship to molecular structure. Compared to AOS, EOS and adult NC had larger GMV in right middle frontal gyrus. Compared to adolescent NC, EOS and adult NC had smaller GMV in right lingual gyrus, right fusiform gyrus, and right cerebellum_6. Disease-induced GMV reductions were mainly distributed in frontal, parietal, thalamus, visual, motor cortex, and medial temporal lobe structures. Age-induced GMV alterations were mainly distributed in visual and motor cortex. The changed GMV induced by schizophrenia, age, and their interaction was related to dopaminergic and serotonergic receptors. Age is also related to glutamate receptors, and schizophrenia is also associated with GABAaergic and noradrenergic receptors. Our results revealed the multimodal neural mechanism of interaction between disease and age. We emphasized age-related GM abnormalities of ventral stream of visual perceptual pathways and high-level cognitive brain in EOS, which may be affected by imbalance of excitatory and inhibitory neurotransmitters.

Unravelling neurotransmitters impairment in primary progressive aphasias.

Primary progressive aphasias (PPAs) are a group of neurodegenerative diseases mainly characterized by language impairment, and with variably presence of dysexecutive syndrome, behavioural disturbances and parkinsonism. Detailed knowledge of neurotransmitters impairment and its association with clinical features hold the potential to develop new tailored therapeutic approaches. In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of magnetic resonance imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission. We included 103 PPA patients and 80 age-matched healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in PPA patients (relative to HC) are correlated with specific neurotransmitter systems. As compared to HC, voxel-based brain changes in PPA were significantly associated with spatial distribution of serotonin, dopamine, and glutamatergic pathways (p< .05, False Discovery Rate corrected-corrected). Disease severity was negatively correlated with the strength of GMV colocalization of D1 receptors (p= .035) and serotonin transporter (p= .020). Moreover, we observed a significant negative correlation between positive behavioural symptoms, as measured with Frontal Behavioural Inventory, and GMV colocalization of D1 receptors (p= .007) and serotonin transporter (p< .001). This pilot study suggests that JuSpace is a helpful tool to indirectly assess neurotransmitter deficits in neurodegenerative dementias and may provide novel insight into disease mechanisms and associated clinical features.

Gray matter volume reduction in orbitofrontal cortex correlated with plasma glial cell line-derived neurotrophic factor (GDNF) levels within major depressive disorder

BackgroundMajor depressive disorder (MDD) is a severe mental disorder characterized by reduced gray matter volume (GMV). To date, the pathogenesis of MDD remains unclear, but neurotrophic factors play an essential role in the pathophysiological alterations of MDD during disease development. In particular, plasma glial cell line-derived neurotrophic factor (GDNF) has been suggested as a potential biomarker that may be associated with disease activity and neurological progression in MDD. Our study investigated whether plasma GDNF levels in MDD patients and healthy controls (HCs) are correlated with GMV alterations. MethodsWe studied 54 MDD patients and 48 HCs. The effect of different diagnoses on whole-brain GMV was investigated using ANOVA (Analysis of Variance). The threshold of significance was p < 0.05, and Gaussian random-field (GRF) correction for error was used. All analyses were controlled for covariates such as ethnicity, handedness, age, and gender that could affect GMV. ResultCompared with the HC group, the GMV in the MDD group was significantly reduced in the right inferior orbitofrontal cortex (OFC), and plasma GDNF levels were significantly higher in the MDD group than in the HC group. In the right inferior OFC, the GDNF levels were positively correlated with GMV reduction in the MDD group, whereas in the HC group, a negative correlation was observed between GDNF levels and GMV reduction. ConclusionAlthough increased production of GDNF in MDD may help repair neural damage in brain regions associated with brain disease, its repairing effects may be interfered with and hindered by underlying neuroinflammatory processes.

Detangling the Structural Neural Correlates Associated with Resting versus Dynamic Phantom Limb Pain Intensity Using a Voxel-based Morphometry Analysis.

The management of phantom limb pain (PLP) is still challenging due to a partial understanding of its neurophysiological mechanisms. Structural neuroimaging features are potential biomarkers. However, only a few studies assessed their correlations with clinical severity and treatment response. This study aims to explore the association between brain gray matter volume (GMV) with phantom limb manifestations severity and PLP improvement after neuromodulatory treatments (transcranial direct current stimulation and mirror therapy). Voxel-based morphometry analyses and functional decoding using a reverse inference term-based meta-analytic approach were used. We included 24 lower limb traumatic amputees with moderate to severe PLP. We found that alterations of cortical GMV were correlated with PLP severity but not with other clinical manifestations. Less PLP severity was associated with larger brain clusters GMV in the non-affected prefrontal, insula (non-affected mid-anterior region), and bilateral thalamus. However, only the insula cluster survived adjustments. Moreover, the reverse inference meta-analytic approach revealed that the found insula cluster is highly functionally connected to the contralateral insula and premotor cortices, and the decoded psychological processes related to this cluster were "rating," "sustained attention," "impulsivity, " and "suffering." Moreover, we found that responders to neuromodulatory treatment have higher GMV in somatosensory areas (total volume of S1 and S2) in the affected hemisphere at baseline, compared to non-responders, even after adjustments.

The relationship between Central Nervous System morphometry changes and key symptoms in Crohn’s disease

Alterations in grey matter volume (GMV) and cortical thickness (CT) in Crohn’s disease (CD) patients has been previously documented. However, the findings are inconsistent, and not a true representation of CD burden, as only CD patients in remission have been studied thus far. We investigate alterations in brain morphometry in patients with active CD and those in remission, and study relationships between brain structure and key symptoms of fatigue, abdominal pain, and extraintestinal manifestations (EIM). Magnetic Resonance Imaging brain scans were collected in 89 participants; 34 CD participants with active disease, 13 CD participants in remission and 42 healthy controls (HCs); Voxel based morphometry (VBM) assessed GMV and white matter volume (WMV), and surface-based analysis assessed cortical thickness (CT). We show a significant reduction in global cerebrospinal fluid (CSF) volume in CD participants compared with HCs, as well as, a reduction in regional GMV, WMV and CT in the left precentral gyrus (motor cortex), and an increase in GMV in the frontal brain regions in CD compared with HCs. Atrophy of the supplementary motor area (SMA) was associated with greater fatigue in CD. We also show alterations in brain structure in multiple regions in CD associated with abdominal pain and extraintestinal inflammations (EIMs). These brain structural alterations likely reflect neuroplasticity to a chronic systemic inflammatory response, abdominal pain, EIMs and fatigue. These findings will aid our understanding of the cross-linking between chronic inflammation, brain structural changes and key unexplained CD symptomatology like fatigue.

Specific Brain Gray Matter Volume Changes in Pediatric Complete Spinal Cord Injury without Fracture or Dislocation Using Voxel-Based Morphometry Analysis: Preliminary Results.

This study aims to investigate the brain gray matter volume (GMV) alterations of pediatric complete thoracolumbar spinal cord injury (SCI) without fracture or dislocation (SCIWOFD) using voxel-based morphometry (VBM) analysis and assess the sensitive neuroimaging biomarkers that may be surrogate targets to enhance brain plasticity. A total of 52 pediatric subjects (age range, 6-12 years), including 25 pediatric SCIWOFD patients and 27 typically developing (TD) children were recruited. An independent two-sample t test was performed to assess between-group differences of brain GMV. Partial correlation analyses were performed to explore the correlations between GMV values and The International Standards for Neurological Classification of Spinal Cord Injury scores, age at the time of injury, time after initial SCI. Receiver operating characteristic analysis was performed to compute the sensitivity and specificity of the imaging biomarkers for pediatric SCIWOFD diagnosis. As for the results, pediatric SCIWOFD patients showed significantly decreased GMV of bilateral cerebellum lobule VIII, right middle occipital gyrus and putamen (PUT), left pallidum (PAL) and thalamus, and increased GMV of vermis III, right cerebellum lobule VI, and supramarginal gyrus. In addition, GMV of left PAL and right PUT were negatively correlated with the pinprick/light touch sensory scores in pediatric SCIWOFD patients. Finally, when using the GMV values of left PAL and right PUT in combination as the predictor, area under the curve reached the highest-0.93. These findings provided evidence that the brain undergoes GMV changes after pediatric SCIWOFD, which may suggest important targets for functional remodeling after SCI in children and provide valuable information for the development of novel and effective rehabilitation therapies in the future.

Integrative brain structural and molecular analyses of interaction between tobacco use disorder and overweight among male adults.

Tobacco smoking and overweight lead to adverse health effects, which remain an important public health problem worldwide. Researches indicate overlapping pathophysiology may contribute to tobacco use disorder (TUD) and overweight, but the neurobiological interaction mechanism between the two factors is still unclear. This study used a mixed sample design, including the following four groups: (i) overweight long-term smokers (n=24, age=31.80 ± 5.70, cigarettes/day=20.50 ± 7.89); (ii) normal weight smokers (n=28, age=31.29 ± 5.56, cigarettes/day=16.11 ± 8.35); (iii) overweight nonsmokers (n=19, age=33.05 ± 5.60), and (iv) normal weight nonsmokers (n=28, age=31.68 ± 6.57), a total of 99 male subjects. All subjects underwent T1-weighted high-resolution MRI. We used voxel-based morphometry to compare gray matter volume (GMV) among the four groups. Then, JuSpace toolbox was used for cross-modal correlations of MRI-based modalities with nuclear imaging derived estimates, to examine specific neurotransmitter system changes underlying the two factors. Our results illustrate a significant antagonistic interaction between TUD and weight status in left dorsolateral prefrontal cortex (DLPFC), and a quadratic effect of BMI on DLPFC GMV. For main effect of TUD, long-term smokers were associated with greater GMV in bilateral OFC compared with nonsmokers irrespective of weight status, and such alteration is negatively associated with pack-year and FTND scores. Furthermore, we also found GMV changes related to TUD and overweight are associated with μ-opioid receptor system and TUD-related GMV alterations are associated with noradrenaline transporter maps. This study sheds light on novel multimodal neuromechanistic about the relationship between TUD and overweight, which possibly provides hints into future treatment for the special population of comorbid TUD and overweight.

Baseline global brain structural and functional alterations at the time of symptom onset can predict subsequent cognitive deterioration in drug-naïve first-episode schizophrenia patients: Evidence from a follow-up study.

Alterations in the global brain gray matter volume (gGMV) and global functional connectivity density (gFCD) play a pivotal role in the cognitive impairment and further deterioration in schizophrenia. This study aimed to assess the correlation between alterations in the gGMV and gFCD at baseline (ΔgGMV and ΔgFCD), and the subsequent alterations of cognitive function in schizophrenia patients after 2-year antipsychotic treatment. Global-brain magnetic resonance imaging scans were acquired from 877 drug-naïve, first-episode schizophrenia patients at baseline and after two years of antipsychotic treatment with adequate dosage and duration, and 200 healthy controls. According to ΔgGMV at baseline, schizophrenia patients were divided into mild, moderate, and severe alteration groups. The MATRICS consensus cognitive battery and Global Deficit Score (GDS) were used to assess cognitive impairment. We found that ΔgGMV and ΔgFCD at baseline were significantly correlated with the severity of the cognitive deterioration (ΔGDS). The correlation coefficient indicated a significant positive correlation between baseline ΔgFCD and subsequent cognitive deterioration, with a relatively stronger relation in the mild alteration group (r = 0.31). In addition, there was a significant positive correlation between baseline ΔgGMV and subsequent cognitive deterioration, with a stronger relation in the moderate and severe alteration groups (r = 0.303; r = 0.302, respectively). Our results showed that ΔgGMV and ΔgFCD are correlated with the severity of cognitive deterioration after completion of a 2-year antipsychotic treatment in schizophrenia patients. These findings suggest that baseline alterations in gGMV and gFCD hold potential for predicting subsequent cognitive decline in schizophrenia.

Gray matter reduction in bilateral insula mediating adverse psychiatric effects of body mass index in schizophrenia

BackgroundBoth schizophrenia (SZ) and overweight/obesity (OWB) have shown some structural alterations in similar brain regions. As higher body mass index (BMI) often contributes to worse psychiatric outcomes in SZ, this study was designed to examine the effects of OWB on gray matter volume (GMV) in patients with SZ.MethodsTwo hundred fifty subjects were included and stratified into four groups (n = 69, SZ patients with OWB, SZ-OWB; n = 74, SZ patients with normal weight, SZ-NW; n = 54, healthy controls with OWB, HC-OWB; and n = 53, HC with NW, HC-NW). All participants were scanned using high-resolution T1-weighted sequence. The whole-brain voxel-based morphometry was applied to examine the GMV alterations, and a 2 × 2 full factorial analysis of variance was performed to identify the main effects of diagnosis (SZ vs HC), BMI (NW vs OWB) factors, and their interactions. Further, the post hoc analysis was conducted to compare the pairwise differences in GMV alterations.ResultsThe main effects of diagnosis were located in right hippocampus, bilateral insula, rectus, median cingulate/paracingulate gyri and thalamus (SZ < HC); while the main effects of BMI were displayed in right amygdala, left hippocampus, bilateral insula, left lingual gyrus, and right superior temporal gyrus (OWB < NW). There were no significant diagnosis-by-BMI interaction effects in the present study, but the results showed that both SZ and OWB were additively associated with lower GMV in bilateral insula. Moreover, mediation analyses revealed the indirect effect of BMI on negative symptom via GMV reduction in bilateral insula.ConclusionThis study further supports that higher BMI is associated with lower GMV, which may increase the risk of unfavourable disease courses in SZ.

Convergent molecular and structural neuroimaging signatures of first-episode depression

BackgroundConvergent studies have demonstrated morphological abnormalities in various brain regions in depression patients. However, the molecular underpinnings of the structural impairments remain largely unknown, despite a pressing need for treatment targets and mechanisms. Here, we investigated the gray matter volume (GMV) alteration in patients with depression and its underlying molecular architecture. MethodsWe recruited 195 first-episode, treatment-naïve depression patients and 78 gender-, age-, and education level-matched healthy controls (HCs) who underwent high-resolution T1-weighted magnetic resonance scans. Voxel-based morphometry (VBM) was adopted to calculate the GMV differences between two groups. Then we analyzed the spatial correlation between depression-induced alteration in GMV and density maps of 10 receptors/transporters deriving from prior molecular imaging in healthy people. ResultsCompared to HCs, the depression group had significantly increased GMV in the left ventral portions of the ventral medial prefrontal cortex, parahippocampal gyrus, amygdala, the right superior parietal lobule and precuneus while decreased GMV in the bilateral hippocampus extending to the thalamus and cerebellum. The GMV alteration introduced by depression was spatially correlated with serotonin receptors (5-HT1a, 5-HT1b, and 5-HT2a), dopamine receptors (D1 and D2) and GABAergic receptor (GABAa) densities. LimitationsThe conclusions drawn in this study were obtained from a single dataset. ConclusionsThis study reveals abnormal GMV alteration and provides a series of neurotransmitters receptors possibly related to GMV alteration in depression, which facilitates an integrative understanding of the molecular mechanism underlying the structural abnormalities in depression and may provide clues to new treatment strategies.

A comparative study of gray matter volumetric alterations in adults with attention deficit hyperactivity disorder and bipolar disorder type I

BackgroundAttention deficit hyperactivity disorder (ADHD) and bipolar disorder type I (BD-Ι) share great overlapping symptoms and are highly comorbid. We aimed to compare and obtain the common and distinct gray matter volume (GMV) patterns in adult patients. MethodWe searched four databases to include whole-brain voxel-based morphometry studies and compared the GMV patterns between ADHD and healthy controls (HCs), between BD-I and HCs, and between ADHD and BD-I using anisotropic effect-size signed differential mapping software. ResultsWe included 677 ADHD and 452 BD-Ι patients. Compared with HCs, ADHD patients showed smaller GMV in the anterior cingulate cortex (ACC) and supramarginal gyrus but a larger caudate nucleus. Compared with HCs, BD-Ι patients showed smaller GMV in the orbitofrontal cortex, parahippocampal gyrus, and amygdala. No common GMV alterations were found, whereas ADHD showed the smaller ACC and larger amygdala relative to BD-Ι. Subgroup analyses revealed the larger insula in manic patients, which was positively associated with the Young Mania Rating Scale. The decreased median cingulate cortex (MCC) was positively associated with the ages in ADHD, whereas the MCC was negatively associated with the ages in BD-Ι. LimitationsAll included data were cross-sectional; Potential effects of medication and disease course were not analyzed due to the limited data. ConclusionsADHD showed altered GMV in the frontal-striatal frontal-parietal circuits, and BD-Ι showed altered GMV in the prefrontal-amygdala circuit. These findings could contribute to a better understanding of the neuropathology of the two disorders.

Pathological fear, anxiety and negative affect exhibit distinct neurostructural signatures: evidence from psychiatric neuroimaging meta-analysis

Internalizing disorders encompass anxiety, fear and depressive disorders, which exhibit overlap at both conceptual and symptom levels. Given that a neurobiological evaluation is lacking, we conducted a Seed-based D-Mapping comparative meta-analysis including coordinates as well as original statistical maps to determine common and disorder-specific gray matter volume alterations in generalized anxiety disorder (GAD), fear-related anxiety disorders (FAD, i.e., social anxiety disorder, specific phobias, panic disorder) and major depressive disorder (MDD). Results showed that GAD exhibited disorder-specific altered volumes relative to FAD including decreased volumes in left insula and lateral/medial prefrontal cortex as well as increased right putamen volume. Both GAD and MDD showed decreased prefrontal volumes compared to controls and FAD. While FAD showed less robust alterations in lingual gyrus compared to controls, this group presented intact frontal integrity. No shared structural abnormalities were found. Our study is the first to provide meta-analytic evidence for distinct neuroanatomical abnormalities underlying the pathophysiology of anxiety-, fear-related and depressive disorders. These findings may have implications for determining promising target regions for disorder-specific neuromodulation interventions (e.g. transcranial magnetic stimulation or neurofeedback).

Brain structural and functional changes during menstrual migraine: Relationships with pain.

ObjectivesMenstrual migraine (MM) is a special type of migraine associated with the ovarian cycle, which imposes a marked burden on female patients. However, the pathogenesis of MM is not completely understood. We investigated gray matter volume (GMV) and functional connectivity (FC) alterations in patients with MM to explore whether there are changes in resting-state FC (rsFC) in brain regions with structural GMV abnormalities and investigated their relevance to pain and concomitant symptoms.MethodsSeventy-five patients with MM and 54 female healthy controls underwent functional magnetic resonance imaging and examination. The patients completed a patient’s headache diary, which included the frequency of migraine attacks, a visual analog scale for pain, a self-rating anxiety scale, and a self-rating depression scale. We used voxel-based morphometry (VBM) to examine the GMV differences between the MM and healthy control groups. The identified brain areas were selected as seeds to assess functional changes in the MM group. Correlation analysis between the altered VBM/rsFC and clinical outcomes was performed.ResultsCompared with healthy controls, patients with MM showed decreased GMV in the right anterior cingulum cortex (ACC) and increased GMV in the right superior parietal cortex. Pearson’s correlation analysis illustrated that only GMV in the right ACC was associated with visual analogue scale pain scores in the MM group. RsFC with the ACC as the seed showed that patients with MM exhibited increased FC between the ACC and the left inferior temporal gyrus, bilateral angular gyrus, and right precuneus. Correlation analysis showed that the change in FC between the right ACC and the right precuneus was positively correlated with headache frequency, and the change in FC between the right ACC and the right angular gyrus was positively correlated with the depression score.ConclusionOur results suggested that the ACC may be an important biomarker in MM, and its structural and functional impairments are significantly associated with the severity of pain and pain-related impairment of emotion in patients with MM. These findings demonstrated that headache-associated structural and functional abnormalities in the ACC may can provide integrative evidence on the physiological mechanisms of MM.

Aberrant gray matter volume and functional connectivity in Parkinson's disease with minor hallucination.

BackgroundMinor hallucination (MH) is the most common psychotic symptom in Parkinson’s disease (PD); it can develop into well-structured visual hallucination (VH), suggesting that MH may be a staccato form of well-structured VH. However, it remains unclear whether the pathogenesis is the same. Therefore, the aim of this study was to investigate the altered gray matter volume (GMV) and functional connectivity (FC) of MH in PD to further understand the complex mechanisms.Materials and methodsWe included 67 PD patients who attended the outpatient clinic of Nanjing Medical University Affiliated Brain Hospital and recruited 31 healthy controls (HC). Demographic data and clinical characteristics of all subjects were recorded, and cranial structural magnetic resonance imaging (MRI) and resting-state functional MRI data were acquired. Patients were classified into the PD with MH (PD-MH) group and PD without hallucinations or delusions (PD-NH) group. Voxel-based morphometry was used to analyze the differences in GMV in the structural pattern. Seed-based FC was used to analyze the functional pattern. Gaussian random field correction was used, with voxel level P < 0.001 and cluster level P < 0.05 representing statistically significant differences. Finally, the correlation between FC values and scores on the clinical characteristics assessment scale was analyzed.ResultsIn the GMV analysis, compared to the PD-NH group, the PD-MH group had reduced GMV in the medial superior frontal gyrus (SFGmed). In the FC analysis, the FC between the SFGmed and the left middle occipital gyrus and right calcarine sulcus decreased in the PD-MH group compared with the PD-NH group, while the FC between SFGmed and the left middle temporal gyrus increased. Correlation analysis revealed that the FC values of the SFGmed and right calcarine sulcus were correlated with the assessment scores for anxiety and sleep symptoms. The FC values of the SFGmed and left middle occipital gyrus were correlated with assessment scores for rapid eye movement disorder.ConclusionThe aberrant structure and function of the default mode network and visual processing areas seems to facilitate the generation of MH in PD, as the alteration was previously found in well-structured VH, suggesting that the two hallucinations have similar pathophysiological mechanisms.

Combined fractional anisotropy and subcortical volumetric deficits in patients with mild-to-moderate depression: Evidence from the treatment of antidepressant traditional Chinese medicine

Numerous neuroimaging studies have demonstrated that diverse brain structural plasticity could occur in a human brain during a depressive episode. However, there is a lack of knowledge regarding the underlying mechanisms of mild-to-moderate depression (MMD), especially the changes of brain structural characteristics after treatment with the Shuganjieyu capsule (SG), a kind of traditional Chinese medicine that has been recommended for the specialized treatment of MMD. In this study, we investigated the structural brain plasticity in MMD that have been undergoing 8 weeks of SG treatment compared with age- and sex-matched healthy controls (HCs) and assessed the relationship between these brain structural alternations and clinical symptoms in MMD. At the baseline, we found that: (1) fractional anisotropy (FA) values in patients with MMD were found to be significantly increased in the regions of anterior limb of internal capsule (ALIC) [MNI coordinates: Peak (x/y/z) = 102, 126, 77; MMD FApeak (Mean ± SD) = 0.621 ± 0.043; HCs FApeak (Mean ± SD) = 0.524 ± 0.052; MMD > HCs, t = 9.625, p < 0.001] and posterior limb of internal capsule (PLIC) [MNI coordinates: Peak (x/y/z) = 109, 117, 87; MMD FApeak (Mean ± SD) = 0.694 ± 0.042; HCs FApeak (Mean ± SD) = 0.581 ± 0.041; MMD > HCs, t = 12.90, p < 0.001], and FA values were significantly positively correlated with HAMD scores in patients with MMD. (2) Patients with MMD showed smaller gray matter volume (GMV) of the dorsolateral prefrontal cortex (DLPFC), frontal cortex, occipital cortex, and precuneus, and the GMV of DLPFC was negatively correlated with HAMD scores. After SG treatment, we found that (1) the HAMD scores decreased; (2) FA values were significantly decreased in the regions of the ALIC and PLIC compared to those at baseline and TBSS revealed no significant differences in FA values between patients with MMD and HCs. (3) The structural characteristics of DLPFC in patients with MMD obtained at the 8th week were improved, e.g., no significant differences in GMV of DLPFC between the two groups. Taken together, our results provided neuroimaging evidence suggesting that SG is an effective treatment for patients with MMD. Moreover, alterations of GMV after 8 weeks of SG treatment indicated a potential modulation mechanism in brain structural plasticity within the DLPFC in patients with MMD.

Gray Matter Abnormalities in Patients with Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis of Voxel-Based Morphometry Studies.

Current findings on brain structural alterations in complex regional pain syndrome (CRPS) are heterogenous and controversial. This study aimed to perform a systematic review and meta-analysis to explore the significant gray matter volume (GMV) abnormalities between patients with CRPS and healthy controls (HCs). A systematic search of the PubMed, Web of Science, and MEDLINE databases was performed, updated through 27 January 2022. A total of five studies (93 CRPS patients and 106 HCs) were included. Peak coordinates and effect sizes were extracted and meta-analyzed by anisotropic effect size–signed differential mapping (AES-SDM). Heterogeneity, sensitivity, and publication bias of the main results were checked by the Q test, jackknife analysis, and the Egger test, respectively. Meta-regression analysis was performed to explore the potential impact of risk factors on GMV alterations in patients with CRPS. The main analysis exhibited that patients with CRPS had increased GMV in the left medial superior frontal gyrus (SFGmedial.L), left striatum, and an undefined area (2, 0, −8) that may be in hypothalamus, as well as decreased GMV in the corpus callosum (CC) (extending to right supplementary motor area (SMA.R), right median cingulate/paracingulate gyri (MCC.R)), and an undefined area (extending to the right caudate nucleus (CAU.R), and right thalamus (THA.R)). Meta-regression analysis showed a negative relationship between increased GMV in the SFGmedial.L and disease duration, and the percentage of female patients with CRPS. Brain structure abnormalities in the sensorimotor regions (e.g., SFGmedial.L, SMA.R, CAU.R, MCC.R, and THA.R) may be susceptible in patients with CRPS. Additionally, sex differences and disease duration may have a negative effect on the increased GMV in SFGmedial.L.

Associations of cognitive impairment in patients with schizophrenia with genetic features and with schizophrenia-related structural and functional brain changes.

Cognitive impairment is highly prevalent in patients with major psychiatric disorders (MPDs), including schizophrenia (SCZ), bipolar disorder, major depressive disorder, in whom it can be highly disruptive to community functioning and worsen prognosis. Previously, genetic factors and cognitive impairments in MPD patients have been examined mostly in isolated circuits rather than in the whole brain. In the present study, genetic, neuroimaging, and psychometric approaches were combined to investigate the relationship among genetic factors, alterations throughout the brain, and cognitive impairments in a large cohort of patients diagnosed with SCZ, with a reference healthy control (HC) group. Single nucleotide polymorphisms (SNPs) in SCZ-risk genes were found to be strongly related to cognitive impairments as well as to gray matter volume (GMV) and functional connectivity (FC) alterations in the SCZ group. Annotating 136 high-ranking SNPs revealed 65 affected genes (including PPP1R16B, GBBR2, PDE4B, CANCNA1C, SLC12AB, SATB2, MAG12, and SATB2). Only one, a PDE4B SNP (rs1006737), correlated with GMV (r = 0:19 p = 0.015) and FC (r = 0.21, p = 0.0074) in SCZ patients. GMV and FC alterations correlated with one another broadly across brain regions. Moreover, the present data demonstrate three-way SNP-FC-GMV associations in patients with SCZ, thus providing clues regarding potential genetic bases of cognition impairments in SCZ. SNP-FC-GMV relationships correlated with visual learning and reasoning dimensions of cognition. These data provide evidence that SCZ-related cognitive impairments may reflect genetically underlain whole-brain structural and functional alterations.

Associations between aerobic fitness, negative symptoms, cognitive deficits and brain structure in schizophrenia—a cross-sectional study

Negative symptoms and cognitive deficits are common in individuals with schizophrenia, greatly affect their outcome, and have been associated with alterations in cerebral gray and white matter volume (GMV, WMV). In the last decade, aerobic endurance training has emerged as a promising intervention to alleviate these symptoms and improved aerobic fitness has been suggested as a key moderator variable. In the present study, we investigated, whether aerobic fitness is associated with fewer cognitive deficits and negative symptoms and with GMVs and WMVs in individuals with schizophrenia in a cross-sectional design. In the largest study to date on the implications of fitness in individuals with schizophrenia, 111 participants at two centers underwent assessments of negative symptoms, cognitive functioning, and aerobic fitness and 69 underwent additional structural magnetic resonance imaging. Multilevel Bayesian partial correlations were computed to quantify relationships between the variables of interest. The main finding was a positive association of aerobic fitness with right hippocampal GMV and WMVs in parahippocampal and several cerebellar regions. We found limited evidence for an association of aerobic fitness with cognitive functioning and negative symptoms. In summary, our results strengthen the notion that aerobic fitness and hippocampal plasticity are interrelated which holds implications for the design of exercise interventions in individuals with schizophrenia.

Differences in gut microbiota correlate with symptoms and regional brain volumes in patients with late-life depression.

Depression is associated with gut dysbiosis that disrupts a gut-brain bidirectional axis. Gray matter volume changes in cortical and subcortical structures, including prefrontal regions and the hippocampus, have also been noted in depressive disorders. However, the link between gut microbiota and brain structures in depressed patients remains elusive. Neuropsychiatric measures, stool samples, and structural brain images were collected from 36 patients with late-life depression (LLD) and 17 healthy controls. 16S ribosomal RNA (rRNA) gene sequencing was used to profile stool microbial communities for quantitation of microbial composition, abundance, and diversity. T1-weighted brain images were assessed with voxel-based morphometry to detect alterations in gray matter volume between groups. Correlation analysis was performed to identify the possible association between depressive symptoms, brain structures and gut microbiota. We found a significant difference in the gut microbial composition between patients with late-life depression (LLD) and healthy controls. The genera Enterobacter and Burkholderia were positively correlated with depressive symptoms and negatively correlated with brain structural signatures in regions associated with memory, somatosensory integration, and emotional processing/cognition/regulation. Our study purports the microbiota-gut-brain axis as a potential mechanism mediating the symptomatology of LLD patients, which may facilitate the development of therapeutic strategies targeting gut microbes in the treatment of elderly depressed patients.

Causal Structural Covariance Network Suggesting Structural Alterations Progression in Type 2 Diabetes Patients.

Background and PurposeAccording to reports, type 2 diabetes (T2D) is a progressive disease. However, no known research has examined the progressive brain structural changes associated with T2D. The purpose of this study was to determine whether T2D patients exhibit progressive brain structural alterations and, if so, how the alterations progress.Materials and MethodsStructural magnetic resonance imaging scans were collected for 81 T2D patients and 48 sex-and age-matched healthy controls (HCs). Voxel-based morphometry (VBM) and causal structural covariance network (CaSCN) analyses were applied to investigate gray matter volume (GMV) alterations and the likely chronological processes underlying them in T2D. Two sample t-tests were performed to compare group differences, and the differences were corrected using Gaussian random field (GRF) correction (voxel-level p < 0.001, cluster-level p < 0.01).ResultsOur findings demonstrated that GMV alterations progressed in T2D patients as disease duration increased. In the early stages of the disease, the right temporal pole of T2D patients had GMV atrophy. As the diseases duration prolonged, the limbic system, cerebellum, subcortical structures, parietal cortex, frontal cortex, and occipital cortex progressively exhibited GMV alterations. The patients also exhibited a GMV alterations sequence exerting from the right temporal pole to the limbic-cerebellum-striatal-cortical network areas.ConclusionOur results indicate that the progressive GMV alterations of T2D patients manifested a limbic-cerebellum-striatal-cortical sequence. These findings may contribute to a better understanding of the progression and an improvement of current diagnosis and intervention strategies for T2D.