Voxel-based Morphometry Analysis Research Articles

Alterations of the resting-state brain network connectivity and gray matter volume in patients with fibromyalgia in comparison to ankylosing spondylitis

Fibromyalgia (FM) and ankylosing spondylitis (AS) are both rheumatic diseases characterized by significant musculoskeletal pain. In this study, we investigated the differences of the resting-state network (RSN) connectivity and gray matter volume (GMV) between FM, AS and healthy controls (HCs). We recruited 38 FM patients, 82 AS patients and 61 HCs in this study. All the participants underwent resting-state functional MRI (rs-fMRI) scans in a GE 3.0T MR system. Independent component analysis (ICA) was conducted on the rs-fMRI data, and group differences of the rsFC between different resting-state networks were calculated using dual regression. We also conducted voxel-based morphometry (VBM) analysis to investigate the differences of the GMV in FM, AS and HCs. The rsFC between the dorsal default mode network (DDMN) and the body of left caudate nucleus was significantly decreased in FM patients in comparison to AS patients (87 voxels, p = 0.025). VBM analysis showed that the GMV of the left posterior lobe of cerebellum was significantly increased in FM patients compared with AS patients (88 voxels, p = 0.036). Neither ICA nor VBM analysis revealed significant differences of RSN connectivity or GMV between FM patients and HCs. The altered rsFC between DMN and the caudate nucleus suggested an aberrant cortico-striato-thalamo-cortical circuit in FM patients, indicating aberrant reward processing, with potential association with mood, motivation and cognitive functions. The increased GMV in the left posterior lobe of cerebellum indicated the participation of cerebellum in the abnormal pain processing in FM patients.

“High empathic response but low interest”: Machiavellianism and its neurostructural basis relate to perceived risk of social exclusion and workplace deviance

The manipulative, exploitative, and indifferent behavior of individuals with high scores on the trait of Machiavellianism attracts research interest in their cognitive and affective emphathic skills; however, the findings are contradictory. We explored the neurostructural substrates of Machiavellianism using voxel-based morphometry analysis with a large sample of 202 full-time employees. Consistent with our expectation, the association of Machiavellianism and its neurostructural basis with the perceived risk of social exclusion were supported whereas that with workplace deviance were not fully supported; the results only showed a significant relationship between Machiavellianism and organizational deviance at the trait level. Our results together provide novel insights into Machiavellianism by highlighting the perspective of “High empathic response but low interest”; namely, individuals with high Machiavellianism possess affective empathic capacity, but they do not care about others.

Frontal neurodegeneration associated with Frontal Assessment Battery in early Alzheimer's disease

BackgroundThe Frontal Assessment Battery (FAB) is widely used to assess executive dysfunction in patients with amnestic mild cognitive impairments due to Alzheimer's disease (aMCI-AD), but its neurobiological meaning is unclear. To elucidate this, we examined the relationship between the FAB score and three key imaging biomarkers: gray matter volume, amyloid-beta (Aβ) deposition, and glucose metabolism. MethodsTwenty Aβ- and tau-positive aMCI-AD patients and age-matched controls underwent structural magnetic resonance imaging and positron emission tomography with [11C]PiB and [18F]FDG. Voxel-based morphometry and statistical parametric mapping analyses were performed to elucidate the relationships between FAB scores and regional gray matter volume, [11C]PiB uptake for Aβ deposition, and [18F]FDG uptake for glucose metabolism. ResultsFAB scores were significantly lower in aMCI-AD than in controls (p < 0.001). In aMCI-AD, FAB was significantly correlated with right inferior frontal gray matter volume and right medial and left middle frontal glucose metabolism (family-wise error p < 0.05). However, there was no correlation between Aβ deposition and FAB (family-wise error p < 0.05). ConclusionsThe decreased FAB score is linked more with frontal-lobe neurodegeneration than with Aβ pathology in aMCI-AD. The FAB could be an early marker for neurodegeneration related to frontal-lobe executive dysfunction.

Neurobiological correlates of reactive aggression in young adults with internet gaming disorder

BackgroundPrevious research has found a significant positive correlation between internet gaming disorder (IGD) and reactive aggression (RA), with excessive use of online games increasing aggression in subjects. However, the neural mechanisms underlying increased RA in IGD are unclear. This study explores the neurobiological underpinnings of reactive aggression in young adults with IGD. MethodThis case-control study included 84 young adults, comprised of 23 subjects with IGD, 24 at-risk participants, and 37 healthy controls. Employing T1-weighted magnetic resonance imaging (MRI), voxel-based morphometry (VBM) analysis was conducted to evaluate the gray matter volume (GMV) changes among groups, and the partial correlations between GMV alterations and RA score were investigated. Finally, mediation analyses were conducted to examine whether GMV alterations could modulate the relationship between IGD degree and RA score. ResultsCompared with controls, the IGD group showed significantly increased GMV in the middle frontal gyrus (MFG), parahippocampal gyrus and significantly decreased GMV in the right median cingulate and paracingulate gyri (DCG), while the at-risk group showed significantly increased GMV in the left MFG. In addition, the RA score showed a significant negative correlation (r=-0.301, p=0.006) with the mean GMV of the right DCG. Furthermore, the mean GMV of the right DCG significantly mediated the correlation between degrees of IGD and RA score, and the effect size for this mediation effect was 22.8 %. ConclusionOur findings provide potential early risk biomarkers for IGD and enhance our understanding of the neurobiological mechanisms linking RA to IGD, thus facilitating several potential avenues for therapeutic intervention.

Functional connectivity in procrastination and emotion regulation

Procrastination, an irrational delay of intended action, leads to numerous adverse effects in many life domains, such as low academic performance, poor mental health, and financial distress. Previous studies have revealed a substantial negative correlation between emotional regulation and procrastination. However, the neural basis for the association between emotion regulation and procrastination remains unclear. Therefore, we employed the voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) methods to explore the neural substrates underlying how emotion regulation is responsible for procrastination (N = 243). In line with our hypothesis, the results showed a significant negative correlation between emotion regulation ability and procrastination. Additionally, the VBM analysis showed that emotion regulation ability was positively correlated with gray matter (GM) volumes in the right dorsal-lateral prefrontal cortex (dlPFC). The mediation analysis revealed that emotion regulation ability mediated the relationship between the GM volumes of the right dlPFC and procrastination. Furthermore, the RSFC results indicated that right dlPFC-left insula functional connectivity was positively associated with emotion regulation ability. Emotion regulation ability further mediated the relationship between the right dlPFC-left insula functional connectivity and procrastination. The current findings suggest that the neural pathway related to cognitive control over aversive emotion may be responsible for the close relationship between emotion regulation and procrastination, which provides a novel perspective for explaining the tight association between emotion regulation and procrastination.

Middle frontal gyrus volume moderates the relationship between interleukin-1β and antidepressant response in major depressive disorder.

Inflammation is a leading biological risk factor contributing to unfavorable outcomes of major depressive disorder (MDD). Both inflammation and depression are associated with similar alterations in brain structure, indicating that brain structural alterations could serve as a mediating factor in the adverse influence of inflammation on clinical outcomes in MDD. Nonetheless, longitudinal research has yet to confirm this hypothesis. Therefore, this study aimed at elucidating the relationships between peripheral inflammatory cytokines, gray matter volume (GMV) alterations, and antidepressant response in MDD. We studied 104 MDD patients treated with selective serotonin reuptake inhibitors and 85 healthy controls (HCs). Antidepressant response was assessed after 8-week antidepressant treatment by changes in 17-item Hamilton Depression Rating Scale (HAMD-17) scores. The GMV alterations were investigated using a voxel-based morphometry analysis. Inflammatory cytokines were measured using flow cytometry. Partial correlations were used to explore the relationships between inflammatory cytokines, GMV alterations, and antidepressant response. Compared to HCs, MDD patients showed reduced GMVs primarily in the frontal-limbic area, right insula, and right superior temporal gyrus. Furthermore, the alterations in GMVs, particularly in the right middle frontal gyrus and the left anterior cingulate gyrus, were associated with ΔHAMD-17 and inflammatory cytokines. Additionally, GMV alterations in the right middle frontal gyrus mediated the negative relationship between interleukin -1β and ΔHAMD-17. This study contributes to understanding the effect of inflammation on the brain and their relationships with antidepressant response, offering a potential explanation for the connection between inflammatory status and treatment efficacy.

Abnormal Granger causal connectivity based on altered gray matter volume and associated neurotransmitters of adolescents with internet gaming disorder revealed by a multimodal neuroimaging study

Although prior studies have revealed alterations in gray matter volume (GMV) among individuals with internet gaming disorder (IGD). The brain's multifaceted functions hinge crucially on the intricate connections and communication among distinct regions. However, the intricate interaction of information between brain regions with altered GMV and other regions, and how they synchronize with various neurotransmitter systems, remains enigmatic. Therefore, we aimed to integrate structural, functional and molecular data to explore the GMV-based Granger causal connectivity abnormalities and their correlated neurotransmitter systems in IGD adolescents. Voxel-based morphometry (VBM) analysis was firstly performed to investigate GMV differences between 37 IGD adolescents and 35 matched controls. Brain regions with altered GMV were selected as seeds for further Granger causality analysis (GCA). Two-sample t tests were performed using the SPM12 toolkit to compare the GMV and Granger causal connectivity between IGD and control groups (GRF corrected, Pvoxel<0.005, Pcluster<0.05). Then, GMV-based Granger causal connectivity was spatially correlated with PET- and SPECT-derived maps covering multifarious neurotransmitter systems. Multiple comparison correction was performed using false discovery rate (FDR). Compared with controls, IGD adolescents showed higher GMV in the caudate nucleus and lingual gyrus. For the GCA, IGD adolescents showed higher Granger causal connectivity from insula, putamen, supplementary motor area (SMA) and middle cingulum cortex (MCC) to the caudate nucleus, and lower Granger causal connectivity from superior/inferior parietal gyrus (SPG/IPG) and middle occipital gyrus (MOG) to the lingual gyrus. Besides, GMV-based Granger causal connectivity of IGD adolescents were associated with the dopaminergic, serotonergic, GABAergic and noradrenaline systems. This study revealed that the caudate nucleus and lingual gyrus may be the key sites of neuroanatomical changes in IGD adolescents, and whole-brain Granger causal connectivity abnormalities based on altered GMV involved large brain networks including reward, cognitive control, and visual attention networks, and these abnormalities are associated with a variety of neurotransmitter systems, which may be associated with higher reward sensitivity, cognitive control, and attention control dysfunction.

Increased cerebellar vermis volume following repetitive transcranial magnetic stimulation in drug-resistant epilepsy: a voxel-based morphometry study.

Voxel-based morphometry (VBM) was applied to explore structural changes induced by repetitive transcranial magnetic stimulation (rTMS) and the relationship with clinical outcomes. Moreover, the relationship between each segmented regional gray matter (GM) volume was investigated to identify circuits involved in the rTMS treatment process in patients with drug-resistant epilepsy (DRE). Nineteen patients with DRE were finally included in the analysis. A session of rTMS was applied for 5 consecutive days. Participants received either 1,000 or 3,000 pulses, at a frequency of 0.5 Hz and the intensity was set at 90% of the individual's resting motor threshold. VBM analysis was performed to explore regional GM volume changes 2 months after rTMS application. The regional volume change was correlated with seizure reduction rate. Relationships between changes in GM volume in each anatomically parcellated region were analyzed using a fully-automated segmentation pipeline. Compared to the baseline, seizure frequency was reduced, and quality of life was improved after rTMS treatment. Regional volume was increased in the cerebellar vermis 2 months after rTMS application. The increased cerebellar vermis volume correlated with the reduced seizure frequency. Regional volume changes in the cerebellar vermis were correlated with changes in the subcortical and cortical GM regions including the thalamus, caudate, and frontal cortex. These results indicate that rTMS treatment effectively reduced seizure frequency in patients with DRE. Increased volume in the cerebellar vermis and activations of the cerebello-thalamo-cortical circuit may be a crucial mechanism underlying the effectiveness of rTMS application in patients with DRE.

Delineating the neural substrates of autobiographical memory impairment in Huntington's disease.

Emerging evidence suggests that autobiographical memory (ABM) is altered in Huntington's disease (HD). While these impairments are typically attributed to frontostriatal dysfunction, the neural substrates of ABM impairment in HD remain unexplored. To this end, we assessed ABM in 30 participants with genetically confirmed HD (18 premanifest, 12 manifest) and 24 age-matched healthy controls. Participants completed the Autobiographical Interview to assess free and probed ABM recall and underwent structural brain imaging. Whole-brain voxel-based morphometry (VBM) was used to explore voxel-wise associations between ABM performance and grey matter intensity (False Discovery Rate corrected at q= 0.05). Relative to controls, HD participants displayed significantly less detailed ABM retrieval across free and probed recall conditions, irrespective of disease stage. Recall performance did not differ significantly between manifest and premanifest HD groups. VBM analyses indicated that poorer ABM performance was associated with atrophy of a distributed cortico-subcortical network. Key regions implicated irrespective of ABM condition included the bilateral occipital cortex, left precuneus, right parahippocampal gyrus and right caudate nucleus. In addition, probed ABM recall was associated with the superior and inferior frontal gyri, frontal pole, right hippocampus, nucleus accumbens, paracingulate gyrus and cerebellum. Overall, our findings indicate that ABM impairments in HD reflect the progressive degeneration of a distributed cortico-subcortical brain network comprising medial temporal, frontal, striatal and posterior parietal cortices. Our findings advance our understanding of the neurocognitive profile of HD, providing an important foundation for future interventions to support memory function in this population.

Graph theory network analysis reveals widespread white matter damage in brains of patients with classic ALS.

Objective: Amyotrophic lateral sclerosis (ALS) exhibits several different presentations and clinical phenotypes. Of these, classic ALS (ALS-Cl), which is the most common phenotype, presents with relatively equal amounts of upper motor neuron and lower motor neuron signs. Magnetic resonance imaging (MRI) provides a noninvasive way to assess central nervous system damage in these patients. To our knowledge no study is available where exploratory whole brain grey matter (GM) and white matter (WM) network analysis is performed considering only the ALS-Cl subgroup of ALS patients. Methods: GM voxel-based morphometry analysis and WM network analysis using graph theory was performed in the MRI dataset of 14 neurologic controls and 25 ALS-Cl patients. Results and Conclusions: No significant GM differences were observed between ALS-Cl and neurologic controls. WM network revealed significant (p < 0.05) reduction and increase in degree measure in several extramotor brain regions of ALS-Cl patients. Both global and local graph metrics revealed significant abnormal values in ALS-Cl patients when compared to neurologic controls. Significant WM changes in ALS-Cl patients with no significant GM changes suggest that neurodegeneration may onset as an "axonopathy" in this ALS subtype.

History of Peripartum Depression Moderates the Association Between Estradiol Polygenic Risk Scores and Basal Ganglia Volumes in Major Depressive Disorder

BackgroundThe neurobiological differences between women who have experienced a peripartum episode and those who have only had episodes outside of this period are not well understood. MethodsSixty parous female patients with major depressive disorder who had either a positive (n = 30) or negative (n = 34) history of peripartum depression (PPD) underwent magnetic resonance imaging acquisition to obtain structural brain images. An independent 2-sample t test comparing patients with and without a history of PPD was performed using voxel-based morphometry analysis. Additionally, polygenic risk scores for estradiol were calculated, and a moderation analysis was conducted between 3 estradiol polygenic risk scores and PPD history status on extracted cluster volumes using IBM SPSS PROCESS macro. ResultsThe voxel-based morphometry analysis identified larger gray matter volumes in bilateral clusters encompassing the putamen, pallidum, caudate, and thalamus in patients with a PPD history than in patients without a history. The moderation analysis identified a significant interaction effect between 2 estradiol polygenic risk scores and PPD history on gray matter cluster volumes, with a positive effect in women with PPD and a negative effect in women with no history of PPD. ConclusionsOur findings demonstrate that women who have experienced a peripartum episode are neurobiologically distinct from women who have no history of PPD in a cluster within the basal ganglia, an area important for motivation, decision making, and emotional processing. Furthermore, we show that the genetic load for estradiol has a differing effect in this area based on PPD status, which supports the claim that PPD is associated with sensitivity to sex steroid hormones.

Structural neuroanatomy of human facial behaviors.

The human face plays a central role in emotions and social communication. The emotional and somatic motor networks generate facial behaviors, but whether facial behaviors have representations in the structural anatomy of the human brain is unknown. We coded 16 facial behaviors in 55 healthy older adults who viewed five videos that elicited emotions and examined whether individual differences in facial behavior were related to regional variation in gray matter volume. Voxel-based morphometry analyses revealed that greater emotional facial behavior during the disgust trial (i.e. greater brow furrowing and eye tightening as well as nose wrinkling and upper lip raising) and the amusement trial (i.e. greater smiling and eye tightening) was associated with larger gray matter volume in midcingulate cortex, supplementary motor area, and precentral gyrus, areas spanning both the emotional and somatic motor networks. When measured across trials, however, these facial behaviors (and others) only related to gray matter volume in the precentral gyrus, a somatic motor network hub. These findings suggest that the emotional and somatic motor networks store structural representations of facial behavior and that the midcingulate cortex is critical for generating the predictable movements in the face that arise during emotions.

Immunomodulatory treatment may change functional and structural brain imaging in severe mental disorders

Neuroinflammation has been implicated in the pathophysiology of schizophrenia and obsessive-compulsive disorder (OCD) and deviations in brain structure and connectivity are seen in these disorders. Here, we explore the effects of a potent immunomodulatory treatment on neuroimaging. In a pilot study of rituximab treatment in schizophrenia and OCD, a subgroup (n = 13) underwent structural and functional magnetic resonance imaging before and 5 months after treatment, to study longitudinal changes in resting-state functional connectivity (rsFC) and voxel-based morphometry (VBM).A hypothesis-free exploratory whole-brain analysis was performed twice to assess changes in rsFC, using anterior cingulate cortex, anterior insula, posterior insula and nucleus accumbens as seed regions. There were significant interactions (diagnosis x time) in connectivity between right posterior insula and two clusters encompassing basal ganglia and anterior frontal pole, and between left anterior insula and a cluster in basal ganglia, where connectivity decreased in OCD and increased in schizophrenia. The increase of connectivity after rituximab, between left anterior insula and parts of cerebellum and lingual gyrus and between left posterior insula and parts of cerebellum, correlated with improved global psychosocial functioning according to the Personal and Social Performance Scale, especially in schizophrenia. VBM analysis identified two clusters with increased grey matter volumes (GMV) after rituximab, one in right insula overlapping one of the seed regions with significant rsFC changes. This pilot study implies that rituximab may influence both brain structure and connectivity and that GMV changes and rsFC changes are regionally associated.

Anatomo-functional changes in neural substrates of cognitive memory in developmental amnesia: Insights from automated and manual Magnetic Resonance Imaging examinations.

Despite bilateral hippocampal damage dating to the perinatal or early childhood period and severely impaired episodic memory, patients with developmental amnesia continue to exhibit well-developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypothesize about the neural substrate that supports their remarkable capacity for encoding and retrieval of semantic memory. In particular, we need to assess whether the residual hippocampal tissue is involved in this preservation, or whether the surrounding cortical areas reorganize to rescue aspects of these critical cognitive memory processes after early injury. We used voxel-based morphometry (VBM) analysis, automatic (FreeSurfer) and manual segmentation to characterize structural changes in the brain of an exceptionally large cohort of 23 patients with developmental amnesia in comparison with 32 control subjects. Both the VBM and the FreeSurfer analyses revealed severe structural alterations in the hippocampus and thalamus of patients with developmental amnesia. Milder damage was found in the amygdala, caudate, and parahippocampal gyrus. Manual segmentation demonstrated differences in the degree of atrophy of the hippocampal subregions in patients. The level of atrophy in CA-DG subregions and subicular complex was more than 40%, while the atrophy of the uncus was moderate (-24%). Anatomo-functional correlations were observed between the volumes of residual hippocampal subregions in patients and selective aspects of their cognitive performance, viz, intelligence, working memory, and verbal and visuospatial recall. Our findings suggest that in patients with developmental amnesia, cognitive processing is compromised as a function of the extent of atrophy in hippocampal subregions. More severe hippocampal damage may be more likely to promote structural and/or functional reorganization in areas connected to the hippocampus. In this hypothesis, different levels of hippocampal function may be rescued following this variable reorganization. Our findings document not only the extent, but also the limits of circuit reorganization occurring in the young brain after early bilateral hippocampal damage.

Neural basis of false recognition in Alzheimer's disease and dementia with lewy bodies.

In Alzheimer's disease (AD), reports on the association between false recognition and brain structure have been inconsistent. In dementia with Lewy bodies (DLB), no such association has been reported. This study aimed to identify brain regions associated with false recognition in AD and DLB by analyzing regional gray matter volume (rGMV). We included 184 patients with AD and 60 patients with DLB. The number of false recognitions was assessed using the Alzheimer's Disease Assessment Scale' word recognition task. Brain regions associated with the number of false recognitions were examined by voxel-based morphometry analysis. The number of false recognitions significantly negatively correlated with rGMV in the bilateral hippocampus, left parahippocampal gyrus, bilateral amygdala, and bilateral entorhinal cortex in patients with AD (p < 0.05, family-wise error [FEW] corrected) and in the bilateral hippocampus, left parahippocampal gyrus, right inferior frontal gyrus, right middle frontal gyrus, right basal forebrain, right insula, left medial and lateral orbital gyri, and left fusiform in those with DLB (p < 0.05, FWE corrected). Bilateral hippocampus and left parahippocampal gyrus were associated with false recognition in both diseases. However, we found there were regions where the association between false recognition and rGMV differed from disease to disease.

Structural brain characteristics of epilepsy patients with comorbid migraine without aura

Migraine is a common bi-directional comorbidity of epilepsy, indicating potential complex interactions between the two conditions. However, no previous studies have used brain morphology analysis to assess possible interactions between epilepsy and migraine. Voxel-based morphometry (VBM), surface-based morphometry (SBM), and structural covariance networks (SCNs) can be used to detect morphological changes with high accuracy. We recruited 30 individuals with epilepsy and comorbid migraine without aura (EM), along with 20 healthy controls (HC) and 30 epilepsy controls (EC) without migraine. We used VBM, SBM, and SCN analysis to compare differences in gray matter volume, cortical thickness, and global level and local level graph theory indexes between the EM, EC, and HC groups to investigate structural brain changes in the EM patients. VBM analysis showed that the EM group had gray matter atrophy in the right temporal pole compared with the HC group (p < 0.001, false discovery rate correction [FDR]). Furthermore, the headache duration in the EM group was negatively correlated with the gray matter volume of the right temporal pole (p < 0.05). SBM analysis showed cortical atrophy in the left insula, left posterior cingulate gyrus, left postcentral gyrus, left middle temporal gyrus, and left fusiform gyrus in the EM compared with the HC group (p < 0.001, family wise error correction). We found a positive correlation between headache frequency and the cortical thickness of the left middle temporal gyrus (p < 0.05). SCN analysis revealed no differences in global parameters between the three groups. The area under the curve (AUC) of the nodal betweenness centrality in the right postcentral gyrus was lower in the EM group compared with the HC group (p < 0.001, FDR correction), and the AUC of the nodal degree in the right fusiform gyrus was lower in the EM group compared with the EC group (p < 0.001, FDR correction). We found clear differences in brain structure in the EM patients compared with the HC group. Accordingly, migraine episodes may influence brain structure in epilepsy patients. Conversely, abnormal brain structure may be an important factor in the development of epilepsy with comorbid migraine without aura. Further studies are needed to investigate the role of brain structure in individuals with epilepsy and comorbid migraine without aura.

Involvement of the basal forebrain and hippocampus in memory deficits in Parkinson's disease

IntroductionMagnetic resonance imaging (MRI)-determined atrophy of the nucleus basalis of Meynert (Ch4) predicts cognitive decline in Parkinson's disease (PD). However, interactions with other brain regions causing the decline remain unclear. This study aimed to describe how MRI-determined Ch4 atrophy leads to cognitive decline in patients with PD. MethodsWe evaluated 137 patients with PD and 39 healthy controls using neuropsychological examinations, MRI, and 123I-ioflupane single-photon emission computed tomography. First, we explored brain areas with regional gray matter loss correlated with Ch4 volume reduction using voxel-based morphometry (VBM). We then assessed the correlation between Ch4 volume reduction and cognitive impairments in PD using partial correlation coefficients (rpar). Finally, we examined whether the regional gray matter loss mediated the association between Ch4 volume reduction and cognitive impairments using mediation analysis. ResultsOur PD cohort was “advanced-stage enriched.” VBM analyses revealed that Ch4 volume loss was correlated with volume reduction in the medial temporal lobe in PD (P < 0.05, family-wise error corrected, >29 voxels). Ch4 volume reduction was significantly correlated with verbal memory deficits in PD when adjusted for age, sex, total brain volume, and 123I-ioflupane uptake in the caudate (rpar = 0.28, P < 0.001). The mediation analysis revealed that the hippocampus mediated the effects of Ch4 volumes on verbal memory (average causal mediation effect = 0.013, 95 % CI = 0.006–0.020, P < 0.001). ConclusionParticularly in advanced-stage PD, Ch4 atrophy was associated with medial temporal lobe atrophy, which played an intermediary role in the relationship between Ch4 atrophy and verbal memory impairments.

Differences in Grey Matter Concentrations and Functional Connectivity between Young Carriers and Non-Carriers of the APOE ε4 Genotype.

Background: The pathophysiology of Alzheimer's disease (AD) may begin developing years or even decades prior to the manifestation of its first symptoms. The APOE ε4 genotype is a prominent genetic risk for AD that has been found to be associated with brain changes across the lifespan since early adulthood. Thus, studying brain changes that may occur in young adults with an APOE ε4 status is highly relevant. Objective: Examine potential differences in grey matter (GM) and functional connectivity (FC) in brains of cognitively healthy young APOE ε4 carriers and non-carriers, denoted here as ε4(+) and ε4(-), respectively. Methods: Three Tesla magnetic resonance imaging (MRI) brain scans were acquired from cognitively healthy young participants aged approximately 20 years (n = 151). Voxel-based morphometry (VBM) analysis was employed to identify potential structural differences in GM between ε4(+) and ε4(-). In a subsequent seed-based connectivity (SBC) analysis, brain regions that structurally differed in the VBM analysis were considered as seeds and correlated with all the remaining voxels across the brains to then measure the differences in FC between groups. Results: The VBM analysis suggested that ε4(+) (n = 28) had greater GM densities relative to ε4(-) (n = 123) in the left hippocampus and the left posterior insula (puncorr < 0.001). However, the effect did not survive the correction for multiple comparisons, suggesting minimal structural differences in this age range. In contrast, the SBC analysis indicated that ε4(+) exhibited significantly decreased FC between the left hippocampus and areas of the left middle temporal gyrus (n = 27) compared to ε4(-) (n = 102). These results remained significant after multiple comparisons (pFDR < 0.05). Lastly, no statistically significant differences in FC between groups were observed for the left insular seed (pFDR > 0.05). Discussion: These results suggest early structural and functional brain changes associated with the APOE ε4 genotype on young adults. Yet, they must be cautiously interpreted and contrasted with both older adults with genetic risk for AD and patients diagnosed with AD.

Progressive gray matter atrophy in parkinsonian variant of multiple system atrophy assessed by using causal structural covariance network.

Multiple system atrophy (MSA), a rare neurodegenerative disease, is usually accompanied by brain morphological alterations. However, the causal relationships between progressive gray matter atrophy in MSA parkinsonian (MSA-P) subtype remain unknown. In total, thirty-five MSA-P patients and thirty-five healthy controls (HC) underwent three-dimensional high-resolution T1-weighted structural imaging and voxel-based morphometry analysis. The causal structural covariance network (CaSCN) of gray matter was assessed to explore the causal relationships in MSA-P. With greater illness duration, the reduction of gray matter was originated from right cerebellum and progressed to bilateral cerebellum, fusiform gyrus, insula, putamen, caudate nucleus, frontal lobe, right angular gyrus, right precuneus, left middle occipital lobe and left inferior temporal lobe, then expanded to midbrain, bilateral para-hippocampus, thalamus, temporal lobe, inferior parietal lobule (IPL), precentral gyrus, postcentral gyrus and middle cingulate cortex. The right cerebellum was revealed to be the core node of the directional network and projected positive causal effects to bilateral cerebellum, caudate nucleus and left IPL. MSA-P patients showed progression of gray matter atrophy over time, with the right cerebellum probably as a primary hub. Furthermore, the early structural vulnerability of cerebellum in MSA-P may play a pivotal role in the modulation of motor and non-motor circuits at the structural level.

Structural covariance network activity in the medial prefrontal cortex is modulated by childhood abuse in adolescents with depression

Aberrant structural covariance (SC) in the medial prefrontal cortex (mPFC) is believed to play a crucial role in adolescent-onset major depressive disorder (AO-MDD). However, the effect of childhood abuse (CA) on SC in AO-MDD patients is still unknown. Here, we measured anomalous SC in the mPFC of AO-MDD patients and assessed the potential modulation of this feature by CA. We acquired T1-weighted structural images of AO-MDD patients (n = 93) and healthy controls (HCs, n = 81). Using voxel-based morphometry analysis, we calculated gray matter volumes for each subject. Subsequently, we classified abnormal SC in the mPFC into three subtypes according to overall CA. Compared with HCs, AO-MDD patients showed alterations in the structural covariance network of the mPFC, which is a central region in the default mode network (DMN). We also found an anterior-posterior dissociation in the structural covariance connectivity of the DMN. A history of CA modulated bilateral mPFC SC. These changes were primarily focused on the SC between the mPFC and the limbic system, indicating a gap in the rate of neural maturation between these regions. In summary, the DMN and frontal-limbic system, which are involved in emotional processing, appear to play a significant role in the development of AO-MDD. These findings highlight the crucial effects of CA on neurophysiological alterations in individuals with AO-MDD.