Voxel-based Morphometry Analysis Research Articles

Changes of cerebral structure and perfusion in subtypes of systemic sclerosis: a brain magnetic resonance imaging study.

The characteristics of brain impairment in different subtypes of systemic sclerosis (SSc) (dcSSc, diffuse cutaneous SSc; lcSSc, limited cutaneous SSc) remain unclear. This study aimed to characterize cerebral structure and perfusion changes in different subtype of SSc patients using magnetic resonance (MR) imaging. Seventy SSc patients (46.0 ± 11.7 years, 62 females) and 30 healthy volunteers (44.8 ± 13.7 years, 24 females) were recruited and underwent brain MR imaging and Montreal Cognitive Assessment (MoCA) test. Gray matter (GM) volumes were measured using voxel-based morphometry analysis on T1-weighted images. Voxel-based and regional cerebral blood flow (CBF) was calculated on arterial spin labelling images. The cerebral structural and perfusion measurements by MR imaging were compared among dcSSc, lcSSc and healthy subjects using one-way ANOVA. The correlations between clinical characteristics and MR imaging measurements were also analyzed. The dcSSc patients exhibited a significant reduction in GM volume in the para-hippocampal region (cluster p < 0.01, FWE corrected) compared with healthy volunteers. Whereas, SSc patients, particularly lcSSc patients, showed elevated CBF in cerebellum, insula, cerebral cortex, and subcortical structures (regional analyses: all p < 0.05; voxel-based analyses: cluster p < 0.01, FWE corrected). Furthermore, clinical characteristics of modified Rodnan skin score (mRSS) (r value ranged from -0.29 to -0.45), MoCA scores (r = 0.40) and antinuclear antibody (ANA) positivity (r=-0.33) were significantly associated with CBF in some regions (all p < 0.05). The manifestations of brain involvement vary among different subtypes of SSc. In addition, severe skin sclerosis may indicate higher risk of brain involvement in SSc patients.

Impact of Sleeve Gastrectomy on Brain Structural Integrity.

Potential brain structural differences in people with obesity (PwO) who achieve over or less than 50% excess weight loss (EWL) after sleeve gastrectomy (SG) are currently unknown. We compared measures of gray matter volume (GMV) and white matter (WM) microstructural integrity of PwO who achieved over or less than 50% EWL after SG with a group of controls with obesity (CwO) without a past history of metabolic bariatric surgery. Sixty-two PwO underwent 1.5T MRI scanning: 24 who achieved more than 50% of EWL after SG ("group a"), 18 who achieved less than 50% EWL after SG ("group b"), and 20 CwO ("group c"). Voxel-based morphometry and tract-based spatial Statistics analyses were performed to investigate GMV and WM differences among groups. Multiple regression analyses were performed to investigate relationships between structural and psychological measures. Group a demonstrated significantly lower GMV loss and higher WM microstructural integrity with respect to group b and c in some cortical regions and several WM tracts. Positive correlations were observed in group a between WM integrity and several psychological measures; the lower the WM integrity, the higher the mental distress, emotional dysregulation, and binge eating behavior. The present results gain a new understanding of the neural mechanisms of outcome in patients who undergo SG. We found limited GMV changes and extensive WM microstructural differences between PwO who achieved over or less than 50% EWL after SG, which may be due to higher vulnerability of WM to the metabolic dysfunction present in PwO.

MRI Signature of α-Synuclein Pathology in Asymptomatic Stages and a Memory Clinic Population

The lack of an in vivo measure for α-synuclein (α-syn) pathology until recently has limited thorough characterization of its brain atrophy pattern, especially during early disease stages. To assess the association of state-of-the-art cerebrospinal fluid (CSF) seed amplification assays (SAA) α-syn positivity (SAA α-syn+) with magnetic resonance imaging (MRI) structural measures, across the continuum from clinically unimpaired (CU) to cognitively impaired (CI) individuals, in 3 independent cohorts, and separately in CU and CI individuals, the latter reflecting a memory clinic population. Cross-sectional data were used from the Swedish BioFINDER-2 study (inclusion, 2017-2023) as the discovery cohort and the Swedish BioFINDER-1 study (inclusion, 2007-2015) and Alzheimer's Disease Neuroimaging Initiative (ADNI; inclusion 2005-2022) as replication cohorts. All cohorts are from multicenter studies, but the BioFINDER cohorts used 1 MRI scanner. CU and CI individuals fulfilling inclusion criteria and without missing data points in relevant metrics were included in the study. All analyses were performed from 2023 to 2024. Presence of α-syn pathology, estimated by baseline CSF SAA α-syn. The primary outcomes were cross-sectional structural MRI measures either through voxel-based morphometry (VBM) or regions of interest (ROI) including an automated pipeline for cholinergic basal forebrain nuclei CH4/4p (nucleus basalis of Meynert [NBM]) and CH1/2/3. Secondary outcomes were domain-specific cross-sectional cognitive measures. Analyses were adjusted for CSF biomarkers of Alzheimer pathology. A total of 2961 participants were included in this study: 1388 (mean [SD] age, 71 [10] years; 702 female [51%]) from the BioFINDER-2 study, 752 (mean [SD] age, 72 [6] years; 406 female [54%]) from the BioFINDER-1 study, and 821 (mean [SD] age, 75 [8] years; 449 male [55%]) from ADNI. In the BioFINDER-2 study, VBM analyses in the whole cohort revealed a specific association between SAA α-syn+ and the cholinergic NBM, even when adjusting for Alzheimer copathology. ROI-based analyses in the BioFINDER-2 study focused on regions involved in the cholinergic system and confirmed that SAA α-syn+ was indeed independently associated with smaller NBM (β = -0.271; 95% CI, -0.399 to -0.142; P <.001) and CH1/2/3 volumes (β = -0.227; 95% CI, -0.377 to -0.076; P =.02). SAA α-syn+ was also independently associated with smaller NBM volumes in the separate CU (β = -0.360; 95% CI, -0.603 to -0.117; P =.03) and CI (β = -0.251; 95% CI, -0.408 to -0.095; P =.02) groups. Overall, the association between SAA α-syn+ and NBM volume was replicated in the BioFINDER-1 study and ADNI cohort. In CI individuals, NBM volumes partially mediated the association of SAA α-syn+ with attention/executive impairments in all cohorts (BioFINDER-2, β = -0.017; proportion-mediated effect, 7%; P =.04; BioFINDER-1, β = -0.096; proportion-mediated effect, 19%; P =.04; ADNI, β = -0.061; proportion-mediated effect, 20%; P =.007). In this cohort study, SAA α-syn+ was consistently associated with NBM atrophy already during asymptomatic stages. Further, in memory clinic CI populations, SAA α-syn+ was associated with NBM atrophy, which partially mediated α-syn-induced attention/executive impairment.

Subjective well-being can be predicted by caudate volume and promotion focus.

It is well-known that the caudate nucleus is associated with motivational behaviors and subjective well-being. However, no longitudinal studies have examined the relationship between brain structure, behavioral orientations, and subjective well-being. This study analyzes data from our previous longitudinal study to examine whether future subjective well-being can be predicted by the volume of the caudate nucleus. We also examined whether behavioral orientation, based on the regulatory focus theory showing two orientations-promotion and prevention focus-was related to the volume of the caudate nucleus. Voxel-based morphometry analysis indicated that the left caudate volume was positively associated with rating scores for future subjective well-being and promotion orientation. Further, mediation analysis indicated that promotion orientation significantly mediated the relationship between future subjective well-being and left caudate volume. The findings indicate that future subjective well-being can be predicted by the volume of the left caudate nucleus, and that this relationship is mediated by promotion focus orientation.

Milk Fat Globule-EGF Factor 8 (MFGE8) Mitigates Cognitive Impairment in Rats with Sepsis-Associated Encephalopathy: An fMRI Study.

Sepsis-associated encephalopathy (SAE) impairs hippocampal microglial efferocytosis, causing cognitive deficits. Previous research found that milk fat globule epidermal growth factor 8 protein (MFGE8) stimulates efferocytosis, reducing hippocampal inflammation in SAE rats. In this study, we explore MFGE8's role in alleviating cognitive impairment and its impact on neural activity using functional magnetic resonance imaging (fMRI). Sixty male Sprague Dawley rats were divided into four groups: Sham, cecal ligation and puncture (CLP), CLP+MFGE8, and CLP+MFGE8+CGT (Cilengitide). After CLP, CLP+MFGE8 rats received intracerebroventricular MFGE8 (3.3 µg), while CLP+MFGE8+CGT rats received intraperitoneal Cilengitide (10 mg/kg). We assessed cognitive function with the Morris water maze and open field test over five days. Eight days post-surgery, rats underwent T2-weighted magnetic resonance imaging (MRI) and resting state (rs)-fMRI scans. Brain tissues were collected for western blot, hematoxylin-eosin (HE) staining, and immunofluorescence. Statistical analysis employed one-way analysis of variance (ANOVA) followed by Tukey's post-test for multiple comparisons. MFGE8 improved neurobehavioral performance in open field task (OFT) and morris water maze (MWM) tests. fMRI indicated a significant reduction in abnormal neural activity in the right hippocampal CA1, CA3, and dentate gyrus of SAE rats following MFGE8 treatment. Voxel-based morphometry (VBM) analysis revealed decreased high-signal areas in the hippocampus, along with reduced hippocampal volume due to alleviated neural edema. Western blot analysis demonstrated that MFGE8 enhanced ras-related C3 botulinum toxin substrate 1 (Rac1) and microtubule-associated protein 1A/1B-light chain 3 (LC3) expression in the rat hippocampus, while CGT reduced these protein levels. Behavioral experiments and fMRI results confirmed that CGT reversed the cognitive effects of MFGE8 by inhibiting microglial αVβ3/αVβ5 integrin receptors. Our findings show that MFGE8 reduced amplitude of low-frequency fluctuations (ALFF) values in the right hippocampal CA1, CA3, and the dentate gyrus, mitigating abnormal neural activity and decreasing hippocampal volume. This led to an improvement in cognitive dysfunction in SAE rats. These results suggest that MFGE8 enhances microglial efferocytosis by activating αVβ3 and αVβ5 integrin receptors on microglial surfaces, ultimately improving cognitive function in SAE rats.

Association of sarcopenia with regional brain atrophy and white matter lesions in a general older population: the Hisayama Study.

Sarcopenia has been reported to be associated with cognitive decline and the risk of dementia. However, few studies have addressed the association between sarcopenia and brain morphological changes in the general population. A total of 1373 community-dwelling participants aged ≥ 65years underwent brain MRI. Sarcopenia was defined based on the Asian Working Group for Sarcopenia's criteria. The pattern of regional gray matter volume loss associated with sarcopenia were assessed using a voxel-based morphometry (VBM) analysis. Regional brain volumes, intracranial volumes (ICV), and white matter lesions volumes (WMLV) were also measured using FreeSurfer. An analysis of covariance was used to examine the associations of sarcopenia with regional brain volumes in proportion to ICV. Of the participants, 112 had sarcopenia. The participants with sarcopenia had significantly lower total brain volume/ICV and total gray matter volume/ICV and higher WMLV/ICV than those without sarcopenia after adjusting for confounders. In VBM, sarcopenia was associated with lower gray matter volume in the frontal lobe, insula, cingulate gyrus, hippocampus, amygdala, and basal ganglia. Using FreeSurfer, we confirmed that the participants with sarcopenia had significantly lower frontal, insular, cingulate, and hippocampal volumes than those without sarcopenia. The current study showed that participants with sarcopenia had significantly lower volume in the frontal lobe, insula, cingulate, and hippocampus and higher WMLV than participants without sarcopenia. As these brain regions are likely to play an important role in cognitive function, these changes may suggest a shared underlying mechanism for the progression of sarcopenia and cognitive decline.

Brain functional gradient and structure features in adolescent and adult autism spectrum disorders.

Understanding how function and structure are organized and their coupling with clinical traits in individuals with autism spectrum disorder (ASD) is a primary goal in network neuroscience research for ASD. Atypical brain functional networks and structures in individuals with ASD have been reported, but whether these associations show heterogeneous hierarchy modeling in adolescents and adults with ASD remains to be clarified. In this study, 176 adolescent and 74 adult participants with ASD without medication or comorbidities and sex, age matched healthy controls (HCs) from 19 research groups from the openly shared Autism Brain Imaging Data Exchange II database were included. To investigate the relationship between the functional gradient, structural changes, and clinical symptoms of brain networks in adolescents and adults with ASD, functional gradient and voxel-based morphometry (VBM) analyses based on 1000 parcels defined by Schaefer mapped to Yeo's seven-network atlas were performed. Pearson's correlation was calculated between the gradient scores, gray volume and density, and clinical traits. The subsystem-level analysis showed that the second gradient scores of the default mode networks and frontoparietal network in patients with ASD were relatively compressed compared to adolescent HCs. Adult patients with ASD showed an overall compression gradient of 1 in the ventral attention networks. In addition, the gray density and volumes of the subnetworks showed no significant differences between the ASD and HC groups at the adolescent stage. However, adults with ASD showed decreased gray density in the limbic network. Moreover, numerous functional gradient parameters, but not VBM parameters, in adolescents with ASD were considerably correlated with clinical traits in contrast to those in adults with ASD. Our findings proved that the atypical changes in adolescent ASD mainly involve the brain functional network, while in adult ASD, the changes are more related to brain structure, including gray density and volume. These changes in functional gradients or structures are markedly correlated with clinical traits in patients with ASD. Our study provides a novel understanding of the pathophysiology of the structure-function hierarchy in ASD.

Causal Roles of Ventral and Dorsal Neural Systems for Automatic and Control Self-Reference Processing: A Function Lesion Mapping Study.

Background: Humans perceive and interpret the world through the lens of self-reference processes, typically facilitating enhanced performance for the task at hand. However, this research has predominantly emphasized the automatic facet of self-reference processing, overlooking how it interacts with control processes affecting everyday situations. Methods: We investigated this relationship between automatic and control self-reference processing in neuropsychological patients performing self-face perception tasks and the Birmingham frontal task measuring executive functions. Results: Principal component analysis across tasks revealed two components: one loaded on familiarity/orientation judgments reflecting automatic self-reference processing, and the other linked to the cross task and executive function indicating control processing requirements. Voxel-based morphometry and track-wise lesion-mapping analyses showed that impairments in automatic self-reference were associated with reduced grey matter in the ventromedial prefrontal cortex and right inferior temporal gyrus, and white matter damage in the right inferior fronto-occipital fasciculus. Deficits in executive control were linked to reduced grey matter in the bilateral inferior parietal lobule and left anterior insula, and white matter disconnections in the left superior longitudinal fasciculus and arcuate fasciculus. Conclusions: The causal evidence suggests that automatic and control facets of self-reference processes are subserved by distinct yet integrated ventral prefrontal-temporal and dorsal frontal-parietal networks, respectively.

The functional connectivity between right insula and anterior cingulate cortex underlying the association between future self-continuity and delay discounting.

Delay discounting refers to the tendency of individuals to devalue future rewards as the delay in their receipt increases over time. Previous studies have indicated that future self-continuity correlates with delay discounting rates. However, the neural basis underlying the relationship between future self-continuity and delay discounting is not clear. To address this question, we used voxel-based morphometry and resting-state functional connectivity analyses to investigate the neural basis underlying the association between future self-continuity and delay discounting. Behavioral result showed that future self-continuity was positively associated with delay discounting. Voxel-based morphometry analysis result indicated that gray matter volume in the right dorsal anterior insula was positively correlated with future self-continuity. Resting-state functional connectivity analysis found that functional connectivity between the right dorsal anterior insula and anterior cingulate cortex was positively associated with future self-continuity. Mediation analysis showed that the right dorsal anterior insula-right anterior cingulate cortex functional connectivity partially mediated the relationship between future self-continuity and delay discounting. These results suggested that right dorsal anterior insula-right anterior cingulate cortex functional connectivity could be the neural basis underlying the association between future self-continuity and delay discounting. In summary, the study provided novel insights into how future self-continuity affected delay discounting and offers new explanations from a neural perspective.

Gray matter volume alterations in de novo Parkinson's disease: A mediational role in the interplay between sleep quality and anxiety.

Parkinson's disease (PD) is increasingly recognized for its non-motor symptoms, among which emotional disturbances and sleep disorders frequently co-occur. The commonality of neuroanatomical underpinnings for these symptoms is not fully understood. This study is intended to investigate the differences in gray matter volume (GMV) between PD patients with anxiety (A-PD) and those without anxiety (NA-PD). Additionally, it seeks to uncover the interplay between GMV variations and the manifestations of anxiety and sleep quality. A total of 37 A-PD patients, 43 NA-PD patients, and 36 healthy controls (HCs) were recruited, all of whom underwent voxel-based morphometry (VBM) analysis. Group differences in GMV were assessed using analysis of covariance (ANCOVA). Partial correlation between GMV, anxiety symptom, and sleep quality were analyzed. Mediation analysis explored the mediating role of the volume of GMV-distinct brain regions on the relationship between sleep quality and anxiety within the PD patient cohort. A-PD patients showed significantly lower GMV in the fusiform gyrus (FG) and right inferior temporal gyrus (ITG) compared to HCs and NA-PD patients. GMV in these regions correlated negatively with Hamilton Anxiety Rating Scale (HAMA) scores (right ITG: r = -0.690, p < 0.001; left FG: r = -0.509, p < 0.001; right FG: r = -0.576, p < 0.001) and positively with sleep quality in PD patients (right ITG: r = 0.592, p < 0.001; left FG: r = 0.356, p = 0.001; right FG: r = 0.470, p < 0.001). Mediation analysis revealed that GMV in the FG and right ITG mediated the relationship between sleep quality and anxiety symptoms, with substantial effect sizes accounted for by the right ITG (25.74%) and FG (left: 11.90%, right: 15.59%). This study has shed further light on the relationship between sleep disturbances and anxiety symptoms in PD patients. Given the pivotal roles of the FG and the ITG in facial recognition and the recognition of emotion-related facial expressions, our findings indicate that compromised sleep quality, under the pathological conditions of PD, may exacerbate the reduction in GMV within these regions, impairing the recognition of emotional facial expressions and thereby intensifying anxiety symptoms.

Exploring brain asymmetry in early-stage Parkinson's disease through functional and structural MRI.

This study explores the correlation between asymmetrical brain functional activity, gray matter asymmetry, and the severity of early-stage Parkinson's disease (PD). Ninety-three early-stage PD patients (ePD, H-Y stages 1-2.5) were recruited, divided into 47 mild (ePD-mild, H-Y stages 1-1.5) and 46 moderate (ePD-moderate, H-Y stages 2-2.5) cases, alongside 43 matched healthy controls (HCs). The study employed the Hoehn and Yahr (H-Y) staging system for disease severity assessment and utilized voxel-mirrored homotopic connectivity (VMHC) for analyzing brain functional activity asymmetry. Asymmetry voxel-based morphometry analysis (VBM) was applied to evaluate gray matter asymmetry. The study found that, relative to HCs, both PD subgroups demonstrated reduced VMHC values in regions including the amygdala, putamen, inferior and middle temporal gyrus, and cerebellum Crus I. The ePD-moderate group also showed decreased VMHC in additional regions such as the postcentral gyrus, lingual gyrus, and superior frontal gyrus, with notably lower VMHC in the superior frontal gyrus compared to the ePD-mild group. A negative correlation was observed between the mean VMHC values in the superior frontal gyrus and H-Y stages, UPDRS, and UPDRS-III scores. No significant asymmetry in gray matter was detected. Asymmetrical brain functional activity is a significant characteristic of PD, which exacerbates as the disease severity increases, resembling the dissemination of Lewy bodies across the PD neurological framework. VMHC emerges as a potent tool for characterizing disease severity in early-stage PD.

Brain alterations in individuals with exercise dependence: A multimodal neuroimaging investigation.

Exercise dependence (ED) is characterised by behavioural and psychological symptoms that resemble those of substance use disorders. However, it remains inconclusive whether ED is accompanied by similar brain alterations as seen in substance use disorders. Therefore, we investigated brain alterations in individuals with ED and inactive control participants. In this cross-sectional neuroimaging investigation, 29 individuals with ED as assessed with the Exercise Dependence Scale (EDS) and 28 inactive control participants (max one hour exercising per week) underwent structural and functional resting-state magnetic resonance imaging (MRI). Group differences were explored using voxel-based morphometry and functional connectivity analyses. Analyses were restricted to the striatum, amygdala, and inferior frontal gyrus (IFG). Exploratory analyses tested whether relationshipsbetween brain structure and function were differently related to EDS subscales among groups. No structural differences were found between the two groups. However, right IFG and bilateral putamen volumes were differently related to the EDS subscales "time" and "tolerance", respectively, between the two groups. Resting-state functional connectivity was increased from right IFG to right superior parietal lobule in individuals with ED compared to inactive control participants. Furthermore, functional connectivity of the angular gyrus to the left IFG and bilateral caudate showed divergent relationships to the EDS subscale "tolerance" among groups. The findings suggest that ED may be accompanied by alterations in cognition-related brain structures, but also functional changes that may drive compulsive habitual behaviour. Further prospective studies are needed to disentangle beneficial and detrimental brain effects of ED.

Greater physical fitness ( ) in healthy older adults associated with increased integrity of the locus coeruleus-noradrenergic system.

Physical activity (PA) is a key component for brain health and Reserve, and it is among the main dementia protective factors. However, the neurobiological mechanisms underpinning Reserve are not fully understood. In this regard, a noradrenergic (NA) theory of cognitive reserve (Robertson, 2013) has proposed that the upregulation of NA system might be a key factor for building reserve and resilience to neurodegeneration because of the neuroprotective role of NA across the brain. PA elicits an enhanced catecholamine response, in particular for NA. By increasing physical commitment, a greater amount of NA is synthetised in response to higher oxygen demand. More physically trained individuals show greater capabilities to carry oxygen resulting in greater - a measure of oxygen uptake and physical fitness (PF). We hypothesized that greater would be related to greater Locus Coeruleus (LC) MRI signal intensity. In a sample of 41 healthy subjects, we performed Voxel-Based Morphometry analyses, then repeated for the other neuromodulators as a control procedure (Serotonin, Dopamine and Acetylcholine). As hypothesized, greater related to greater LC signal intensity, and weaker associations emerged for the other neuromodulators. This newly established link between and LC-NA system offers further understanding of the neurobiology underpinning Reserve in relationship to PA. While this study supports Robertson's theory proposing the upregulation of the NA system as a possible key factor building Reserve, it also provides ground for increasing LC-NA system resilience to neurodegeneration via enhancement.

Assessment of Gray Matter Microstructural Alterations in Alzheimer's Disease by Free Water Imaging.

Cortical neurodegenerative processes may precede the emergence of disease symptoms in patients with Alzheimer's disease (AD) by many years. No study has evaluated the free water of patients with AD using gray matter-based spatial statistics. The aim of this study was to explore cortical microstructural changes within the gray matter in AD by using free water imaging with gray matter-based spatial statistics. Seventy-one participants underwent multi-shell diffusion magnetic resonance imaging, 11C-Pittsburgh compound B positron emission tomography, and neuropsychological evaluations. The patients were divided into two groups: healthy controls (n = 40) and the AD spectrum group (n = 31). Differences between the groups were analyzed using voxel-based morphometry, diffusion tensor imaging, and free water imaging with gray matter-based spatial statistics. Voxel-based morphometry analysis revealed gray matter volume loss in the hippocampus of patients with AD spectrum compared to that in controls. Furthermore, patients with AD spectrum exhibited significantly greater free water, mean diffusivity, and radial diffusivity in the limbic areas, precuneus, frontal lobe, temporal lobe, right putamen, and cerebellum than did the healthy controls. Overall, the effect sizes of free water were greater than those of mean diffusivity and radial diffusivity, and the larger effect sizes of free water were thought to be strongly correlated with AD pathology. This study demonstrates the utility of applying voxel-based morphometry, gray matter-based spatial statistics, free water imaging and diffusion tensor imaging to assess AD pathology and detect changes in gray matter.

Neuroanatomical Signature of the Transition from Normal Cognition to MCI in Parkinson's Disease.

The progression of Parkinson's disease (PD) is often accompanied by cognitive decline. We had previously developed a brain age estimation program utilizing structural MRI data of 949 healthy individuals from publicly available sources. Structural MRI data of 244 PD patients who were cognitively normal at baseline was acquired from the Parkinson Progression Markers Initiative (PPMI). 192 of these showed stable normal cognitive function from baseline out to 5 years (PD-SNC), and the remaining 52 had unstable normal cognition and developed mild cognitive impairment within 5 years (PD-UNC). 105 healthy controls were also included in the analysis as a reference. First, we examined if there were any baseline differences in regional brain structure between PD-UNC and PD-SNC cohorts utilizing the three most widely used atrophy estimation pipelines, i.e., voxel-based morphometry (VBM), deformation-based morphometry and cortical thickness analyses. We then investigated if accelerated brain age estimation with our multivariate regressive machine learning algorithm was different across these groups (HC, PD-SNC, and PD-UNC). As per the VBM analysis, PD-UNC patients demonstrated a noticeable increase in GM volume in the posterior and anterior lobes of the cerebellum, sub-lobar, extra-nuclear, thalamus, and pulvinar regions when compared to PD-SNC at baseline. PD-UNC patients were observed to have significantly older brain age compared to both PD-SNC patients (p=0.009) and healthy controls (p<0.009). The increase in GM volume in the PD-UNC group could potentially indicate an inflammatory or neuronal hypertrophy response, which could serve as a biomarker for future cognitive decline among this population.

Multimodal imaging analyses in neuromyelitis optica spectrum disorder with or without visual disturbance

Background and purposeNeuromyelitis optica spectrum disorder is a demyelinating and inflammatory affliction that often leads to visual disturbance. Various imaging techniques, including free-water imaging, have been used to determine neuroinflammation and degeneration. Therefore, this study aimed at determining multimodal imaging differences between patients with neuromyelitis optica spectrum disorder, especially those with visual disturbance, and healthy controls. Materials and methodsEighty-five neuromyelitis optica spectrum disorder patients and 89 age- and sex-matched healthy controls underwent 3-T magnetic resonance imaging (MRI). We analyzed adjusted brain-predicted age difference, voxel-based morphometry, and free-water–corrected diffusion tensor imaging (DTI) by tract-based spatial statistics in each patient group (MRI-positive/negative neuromyelitis optica spectrum disorder patients with or without a history of visual disturbance) compared with the healthy control group. ResultsMRI-positive neuromyelitis optica spectrum disorder patients exhibited reduced volumes of the bilateral thalamus. Tract-based spatial statistics showed diffuse white matter abnormalities in all DTI metrics in MRI-positive neuromyelitis optica spectrum disorder patients with a history of visual disturbance. In MRI-negative neuromyelitis optica spectrum disorder patients with a history of visual disturbance, voxel-based morphometry showed volume reduction of bilateral thalami and optic radiations, and tract-based spatial statistics revealed significantly lower free-water–corrected fractional anisotropy and higher mean diffusivity in the posterior dominant distributions, including the optic nerve radiation. ConclusionFree-water–corrected DTI and voxel-based morphometry analyses may reflect symptoms of visual disturbance in neuromyelitis optica spectrum disorder.

Gray Matter Atrophy in a 6-OHDA-induced Model of Parkinson’s Disease

IntroductionMagnetic resonance imaging (MRI) based brain morphometric changes in unilateral 6-hydroxydopamine (6-OHDA) induced Parkinson’s disease (PD) model can be elucidated using voxel-based morphometry (VBM), study of alterations in gray matter volume and Machine Learning (ML) based analyses. MethodsWe investigated gray matter atrophy in 6-OHDA induced PD model as compared to sham control using statistical and ML based analysis. VBM and atlas-based volumetric analysis was carried out at regional level. Support vector machine (SVM)-based algorithms wherein features (volume) extracted from (a) each of the 150 brain regions (b) statistically significant features (only) and (c) volumes of each cluster identified after application of VBM (VBM_Vol) were used for training the decision model. The lesion of the 6-OHDA model was validated by estimating the net contralateral rotational behaviour by the injection of apomorphine drug and motor impairment was assessed by rotarod and open field test. Results and discussionIn PD, gray matter volume (GMV) atrophy was noted in bilateral cortical and subcortical brain regions, especially in the internal capsule, substantia nigra, midbrain, primary motor cortex and basal ganglia-thalamocortical circuits in comparison with sham control. Behavioural results revealed an impairment in motor performance. SVM analysis showed 100% classification accuracy, sensitivity and specificity at both 3 and 7 weeks using VBM_Vol. ConclusionUnilateral 6-OHDA induced GMV changes in both hemispheres at 7th week may be associated with progression of the disease in the PD model. SVM based approaches provide an increased classification accuracy to elucidate GMV atrophy.

Hoffmann's sign in cervical spondylotic myelopathy patients: pathological insights from neuroimaging.

Hoffmann's sign testing is a commonly used physical examination in clinical practice for patients with cervical spondylotic myelopathy (CSM). However, the pathophysiological mechanisms underlying its occurrence and development have not been thoroughly investigated. Therefore, the present study aimed to explore whether a positive Hoffmann's sign (PHS) in CSM patients is associated with spinal cord and brain remodeling and to identify potential neuroimaging biomarkers with diagnostic value. Seventy-six patients with CSM and 40 sex- and age-matched healthy controls (HCs) underwent multimodal MRI. Based on the results of the Hoffmann's sign examination, patients were divided into two groups: those with a PHS (n = 38) and those with a negative Hoffmann's sign (NHS; n = 38). Quantification of spinal cord and brain structural and functional parameters of the participants was performed using various methods, including functional connectivity analysis, voxel-based morphometry, and atlas-based analysis based on functional MRI and structural MRI data. Furthermore, this study conducted a correlation analysis between neuroimaging metrics and neurological function and utilized a support vector machine (SVM) algorithm for the classification of PHS and NHS. In comparison with the NHS and HC groups, PHS patients exhibited significant reductions in the cross-sectional area and fractional anisotropy (FA) of the lateral corticospinal tract (CST), reticulospinal tract (RST), and fasciculus cuneatus, concomitant with bilateral reductions in the volume of the lateral pallidum. The functional connectivity analysis indicated a reduction in functional connectivity between the left lateral pallidum and the right angular gyrus in the PHS group. The correlation analysis indicated a significant positive association between the CST and RST FA and the volume of the left lateral pallidum in PHS patients. Furthermore, all three variables exhibited a positive correlation with the patients' motor function. Finally, using multimodal neuroimaging metrics in conjunction with the SVM algorithm, PHS and NHS were classified with an accuracy rate of 85.53%. This research revealed a correlation between structural damage to the pallidum and RST and the presence of Hoffmann's sign as well as the motor function in patients with CSM. Features based on neuroimaging indicators have the potential to serve as biomarkers for assessing the extent of neuronal damage in CSM patients.

Structural brain changes associated with cocaine use and digital cognitive behavioral therapy in cocaine use disorder treatment

BackgroundFew studies have investigated changes in brain structure and function associated with recovery from cocaine use disorder (CUD), and fewer still have identified brain changes associated with specific CUD treatments, which could inform treatment development and optimization. MethodsIn this longitudinal study, T1-weighted magnetic resonance imaging scans were acquired from 41 methadone-maintained individuals with CUD (15 women) at the beginning of and after 12 weeks of outpatient treatment. As part of a larger randomized controlled trial, these participants were randomly assigned to receive (or not) computer-based training for cognitive behavioral therapy (CBT4CBT), and galantamine (or placebo). ResultsIrrespective of treatment condition, whole-brain voxel-based morphometry analyses revealed a significant decrease in right caudate body, bilateral cerebellum, and right middle temporal gyrus gray matter volume (GMV) at post-treatment relative to the start of treatment. Subsequent region of interest analyses found that greater reductions in right caudate and bilateral cerebellar GMV were associated with higher relative and absolute levels of cocaine use during treatment, respectively. Participants who completed more CBT4CBT modules had a greater reduction in right middle temporal gyrus GMV. ConclusionsThese results extend previous findings regarding changes in caudate and cerebellar GMV as a function of cocaine use and provide the first evidence of a change in brain structure as a function of engagement in digital CBT for addiction. These data suggest a novel potential mechanism underlying how CBT4CBT and CBT more broadly may exert therapeutic effects on substance-use-related behaviors through brain regions implicated in semantic knowledge.

The neuroanatomical correlates of daily habitual tendencies and mediating effect on the association between daily habitual tendencies and symptoms of behavioral addictions

Habitual behaviors significantly shape our daily actions. Furthermore, habit formation is proposed as a key mechanism contributing to the development and maintenance of addiction. However, the neural substrates underlying daily habitual tendencies and their contribution to behavioral addiction symptoms in everyday life remain poorly understood. To explore these questions, we conducted a comprehensive analysis of data from 219 individuals who underwent neuroimaging (structural MRI) assessments alongside evaluations of their daily habitual tendencies and symptoms of Internet Gaming Disorder (IGD) and Problematic Smartphone Use (PSU). Using voxel-based morphometry, meta-analytic decoding, and mediation analysis, we found that daily habitual tendencies were positively correlated with larger gray matter volumes in the ventromedial prefrontal cortex (vmPFC), precuneus, superior frontal gyrus (SFG), inferior temporal gyrus (ITG), and supplementary motor area (SMA). Notably, the midline regions, including the vmPFC and precuneus, play a crucial role in value-based computation, emotional regulation, social cognition, and self-referential thinking. Individual variations in gray matter volumes within these regions served as mediators, influencing the bidirectional relationship between daily habitual tendencies and IGD symptoms. However, vmPFC variations were specifically found to mediate the pathway from PSU to daily habitual tendencies. Our findings suggest that the morphological architecture of the vmPFC and precuneus is associated with habitual tendencies in daily life and may mediate the development of addictive behaviors. This study contributes to a more nuanced understanding of the neuroanatomical basis of daily habitual tendencies and their role in addictive behaviors.