
Developmental stuttering is a neurodevelopmental speech disorder characterized by speech disfluency and variable persistence into adolescence. While white matter and functional connectivity abnormalities have been widely reported, the topological organization of gray matter (GM) networks in affected children remains unclear. This study investigated GM morphological network alterations in children with persistent developmental stuttering (CWS) and examined their relationships with stuttering severity. Thirty-three CWS and thirty age- and sex-matched healthy controls underwent T1-weighted MRI. Individual GM morphological networks were constructed using Kullback–Leibler divergence of voxel-based morphometry data across 90 brain regions. Graph-theoretical analyses quantified global and local topological properties, and network-based statistics (NBS) were used to identify alterations in morphological connectivity. Both groups exhibited small-world topology; however, CWS showed significantly higher clustering coefficient(Cp), local efficiency (Eloc), and modularity (Q) (P < 0.05), indicating a hyper-segregated GM organization. NBS revealed reduced morphological connectivity within a subnetwork encompassing the default mode, sensorimotor, basal ganglia–thalamic, and visual regions. Greater network segregation (Cp, Eloc, Q) was positively correlated with stuttering severity, whereas reduced subnetwork connectivity was negatively correlated with stuttering severity (FDR-corrected P < 0.05). These findings suggest that children with persistent stuttering exhibit excessive local specialization and decreased interregional integration, reflecting a network-level imbalance that may underlie the persistence and severity of stuttering. Altered GM network topology may represent a potential neurostructural biomarker for early identification and targeted intervention.
To investigate alterations in the amplitude of low-frequency fluctuations (ALFF) in herpes simplex encephalitis (HSE) patients using resting-state functional magnetic resonance imaging (rs-fMRI) and evaluate their associations with anxiety symptoms. In this single-center cohort study, 45 HSE patients and 46 healthy controls (HC) were recruited from the First Affiliated Hospital of Zhejiang University School of Medicine, China. HSE was confirmed by clinical features and positive herpes simplex virus (HSV) DNA in cerebrospinal fluid via polymerase chain reaction. Participants underwent rs-fMRI scans within one week of ICU admission. ALFF was calculated using REST software; group differences were assessed with voxel-wise two-sample t-tests (covariates: age, sex, education, framewise displacement; whole-brain voxel-wise FDR-corrected P < 0.05) and validated nonparametrically. Associations between ALFF and anxiety (Hamilton Anxiety Rating Scale, HAMA) were examined via general linear models, controlling for age, sex, hypertension, and education, with Spearman’s correlations for robustness. Compared to HC, HSE patients exhibited increased ALFF in the left precuneus and right putamen, alongside decreased ALFF in the right angular gyrus and right caudate nucleus (whole-brain voxel-wise FDR-corrected P < 0.05). These changes correlated significantly with HAMA scores: positive associations in hyperactive regions (left precuneus: β = 0.558, 95
Although resting-state fMRI is a promising alternative to task-fMRI in presurgical mapping, protocols to simultaneously assess language lateralization and sensorimotor networks within a single acquisition remain limited. To evaluate the feasibility of using connectivity analysis derived from a language fMRI task to assess language lateralization and extract the sensorimotor network in presurgical patients with space-occupying lesions. In a retrospective study, 40 presurgical patients underwent a verb generation task (VGT) and a hand motor task (HMT). Single-subject spatially-constrained ICA (scICA) was performed on VGT scans to extract sensorimotor components. Sensitivity, specificity and Dice coefficient between scICA-derived scans and HMT activation maps were calculated. The effects of different variables were analyzed using ANOVA. Forty patients (mean age, 40.50 ± 13.99; 21 men) were included. Sensorimotor components could be extracted in all patients within the predefined constrained scICA framework. Using HMT activation as comparative reference, mean ipsilesional voxelwise sensitivity, specificity and Dice coefficient of scICA-derived maps were 78
The cingulate cortex (CC) and cingulum bundle (CB) are key structures involved in pain processing. Thus, we explored the correlations between cortical morphometry of the CC, white matter integrity of the CB, and pain-related assessments in lung cancer patients with cancer pain (CP+). Structural and diffusion spectrum imaging, along with emotion and pain-related assessments, were collected from 45 CP+ patients, 47 lung cancer patients without pain (CP−), and 35 healthy controls (HC). Cortical morphometry and tract-based automatic analysis evaluated the CC and CB. One-way ANOVA revealed significant group differences in sulcal depth (SD) within the CC, as well as in fractional anisotropy (FA) and radial diffusivity (RD) within the CB. Post-hoc tests indicated that the CP+ group had greater SD than the CP− group, and smaller FA as well as greater RD than both the CP − and HC groups. In the CP+ group, RD of the CB was positively correlated with SD of the CC, and the anxiety score was positively correlated with RD of the CB and SD of the CC. In the HC group, the anxiety score was negatively correlated with SD of the CC. This study revealed distinct patterns of structural alterations across the three groups. Differences in both CB and CC structures were observed in CP+ relative to CP − and HC groups, were interrelated, and were associated with anxiety. These findings highlight the significant contribution of CC and CB in cancer pain processing, while also serving as potential biomarkers for negative emotion.
We aimed to investigate the topology alterations of white matter functional networks (WMFNs) associated with varying white matter hyperintensities (WMH) burden, and assess the relationship between topological changes of WMFNs and cognitive function in the individuals with moderate to severe WMH (m/sWMH). Fifty-four cognitively unimpaired individuals were enrolled and stratified into two groups: 26 with m/sWMH and 28 with mild WMH (mWMH). We used graph theory analysis to investigate the global and nodal topological alteration between two groups and to examine the association between WMFNs topological alterations and cognition. The results demonstrated that, compared to the mWMH group, the m/sWMH group exhibited alterations of global and nodal properties, including decreased clustering coefficient (Cp) and shortest path length (Lp), decreased nodal clustering coefficient (Ncp), increased nodal efficiency (Ne), as well as mixed increases and decreases in nodal degree centrality (Dc) and betweenness centrality (Bc). These alterations mainly occurred in the body of corpus callosum, left sagittal stratum (SS) (including the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus, ILF and IFOF), the anterior limb of the internal capsule, cingulate gyrus, and inferior longitudinal fasciculus. The Pearson correlation analysis revealed that nodal properties (Ncp and Dc) in SS (including ILF and IFOF) were associated with cognitive scores in the m/sWMH group. Increased WMH burden may lead to the disintegration of WMFNs topology, which was closely associated with cognitive dysfunction (global cognitive function, attention and processing speed). The SS may be a biomarker for cognitive impairment in individuals with m/sWMH.
Cognitive decline during aging affects daily life in older adults and is associated with altered functional connectivity (FC) between brain networks. However, the dynamic functional network connectivity (dFNC) alterations among brain networks in healthy older adults in response to natural stimuli are unclear. The present study included functional magnetic resonance imaging data of 217 healthy subjects from the Cambridge Centre for Aging and Neuroscience in the movie-watching state to analyze brain networks' dFNC and investigate the relationship between dynamic temporal metrics and cognition. Seven brain networks were obtained using independent component analysis. Four dFNC states were obtained in young and older groups, and connectivity between the salience network and the cerebellum decreased in state 3 in older adults compared to young adults. Older adults spent less time in the strong FC state 2, which was significantly associated with cognition, suggesting that integration across brain networks contributes to the execution of cognitive tasks. In conclusion, using a naturalistic viewing paradigm, this study provides novel evidence that healthy aging is associated with altered spatiotemporal dynamics of large-scale brain networks. Specifically, we identified reduced connectivity between the salience network and cerebellum in older adults and found that the diminished persistence of a key dFNC state (State 2) directly correlates with cognitive performance. These findings offer new insights into the neural mechanisms of cognitive aging by highlighting the critical role of dynamic inter-network integration.
The aim of this study was to examine the temporal sequence of the appearance of vestibular symptoms and migraine, as well as whether they coexist or not, while assessing their influence on cerebral functional activity. The present investigation is a cross-sectional study. This study included 69 participants from the outpatient headache unit at our hospital who were divided into six groups: 33 patients with vestibular migraine (VM) (12 the onset of migraine was earlier than vertigo, 10 the onset of vertigo was earlier than migraine, 11 vertigo was accompanied with migraine), 9 patients with benign recurrent vertigo (BRV), 14 patients with migraine without aura (MoA), and 13 healthy controls. We compared the differences in spontaneous cerebral functional activity between groups, and used the bilateral thalamus as a seed point to analyze its functional connectivity with the whole brain. The relationship between changed cerebral functional activity and clinical features was compared. We have observed variations in the spontaneous functional activity of the right middle and inferior frontal gyrus among individuals in each group, as well as discrepancies in the functional connectivity of the right superior frontal gyrus with the bilateral thalamus. The severity of vertigo disability exhibits a negative correlation with the functional activity in the right inferior frontal gyrus, while the duration of vertigo demonstrates a positive correlation with the functional activity in the right inferior frontal gyrus. Furthermore, the severity of migraine disability displays a negative correlation with the functional connectivity between the bilateral thalamus and the right superior frontal gyrus. In patients with VM, the temporal relationship between vestibular symptoms and migraine did not have any impact on cerebral functional activity. The functional activity of the right middle and inferior frontal gyrus may be influenced by vestibular stimulation, while headache stimulation could potentially modify the functional connectivity between the bilateral thalamus and the right superior frontal gyrus. These findings suggest that VM may be considered as a distinct disease entity.
Growth-associated protein 43 (GAP-43), a synaptic protein involved in neuronal plasticity, has emerged as a potential biomarker for Alzheimer’s disease (AD) and mild cognitive impairment (MCI), with elevated levels linked to synaptic dysfunction. This dysfunction, in turn, has been associated with reduced cerebral glucose metabolism, which further exacerbates cognitive decline and accelerates disease progression. However, the link between CSF GAP-43 and cerebral glucose metabolism, measured by FDG-PET, remains less understood. This study aimed to investigate the relationship between CSF GAP-43 levels, cerebral glucose metabolism, and cognitive performance across different stages of cognitive impairment, specifically in individuals with AD (n = 83), MCI (n = 370), and cognitively normal (CN; n = 215). Cognitive function was assessed using the ADAS-Cog 13 scale, CSF GAP-43 levels were measured via ELISA, and cerebral glucose metabolism was analyzed with FDG-PET. The results showed that CSF GAP-43 levels were significantly elevated in the AD group compared to the CN and MCI groups (p < 0.001). In the MCI group, there was a modest but statistically significant negative association between CSF GAP-43 levels and cerebral glucose metabolism (β = -0.126, FDR p = 0.003), whereas this association was not significant in the CN (β = -0.031, FDR p = 0.612) or AD groups (β = 0.157, FDR p = 0.584). Mediation analysis, adjusted for age, sex, education, and APOE ε4 carrier status, showed that FDG-PET cerebral glucose metabolism partly and statistically mediated the association between CSF GAP-43 and cognitive performance only in the MCI group (β = 0.047, FDR-adjusted p = 0.009). These findings indicate that higher CSF GAP-43 was associated with lower cerebral glucose metabolism, which in turn was associated with worse cognitive performance in MCI. However, because of limitations, cross-sectional design, and modest magnitude of the effects, these results should be interpreted as statistical associations rather than evidence that CSF GAP-43 impairs glucose metabolism or cognition.
Cerebral blood flow (CBF) is lower in males than females in cortical gray matter, but these sex effects are unknown in the hippocampus. Potential interactions between sex and cognitive status on CBF, which may contribute to the greater risk for females to develop mild cognitive impairment (MCI), are also understudied. Moreover, these effects may vary when regional CBF is normalized relative to individual differences in reference region CBF (residual rCBF) compared to more common difference scores (traditional rCBF). The current study examined effects of sex, cognitive status, and their interaction on residual and traditional rCBF in the cortical lobes and hippocampus in 111 cognitively unimpaired older adults (CU; 61.3%) and 49 older adults diagnosed with MCI (46.9% female) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with T1-weighted and perfusion-weighted magnetic resonance imaging data. As expected, rCBF was significantly lower in males than females in the occipital lobe, p = 0.010, but was unexpectedly significantly higher in males than females in the hippocampus, p < 0.001, with the sex effect being larger for traditional rCBF in the occipital lobe and residual rCBF in the hippocampus, ps < 0.024. Cognitive status significantly interacted with rCBF metric and region, ps < 0.014, but yielded no significant between group difference for any metric in any region, ps > 0.06. There were no significant interactions between sex and cognitive status, ps > 0.10. Taken together, these findings indicate that effects of sex on rCBF are region specific, independent of cognitive status, and vary with rCBF normalization method in non-demented older adults.
The serotonin transporter gene-linked polymorphic region (5-HTTLPR) has been linked to psychiatric disorders. This meta-analysis aimed to investigate the association between the 5-HTTLPR polymorphism and the availability of the serotonin transporter (SERT) or serotonin 1 A receptor (5-HT1AR), measured by positron emission tomography (PET) or single-photon emission computed tomography (SPECT). A systematic search was conducted to identify studies comparing SERT or 5-HT1AR availability by 5-HTTLPR genotype using PET or SPECT scans in healthy subjects. The standardized mean difference in SERT or 5-HT1AR availability between LL and S-carrier genotypes was calculated for each study in both frequentist and Bayesian meta-analyses. Eleven studies met the inclusion criteria. Pooled analysis showed no differences in SERT availability in the striatum, frontal lobe, brainstem, or thalamus between LL and S carriers of 5-HTTLPR. Similarly, no significant difference was observed in 5-HT1AR availability in the raphe nuclei between two genotypes. Bayesian meta-analysis confirmed that the standardized mean difference in SERT availability between LL and S carriers overlapped substantially with zero. In conclusion, the 5-HTTLPR polymorphism does not appear to affect the availability of SERT or 5-HT1AR in healthy individuals. This suggests that the relationship between 5-HTTLPR polymorphisms and psychiatric disorders is complex and that this polymorphism alone may not fully explain susceptibility.
Identifying biomarkers for serious mental illnesses (SMI) has significant implications for early intervention and prevention. The current study uses machine learning to build a model of risk prediction and transition based on multi-modal neuroimaging, clinical, and behavioral data from youth at transdiagnostic risk. Participants aged 12–25 were recruited at two sites in Canada, and followed for 4 years. Symptom severity was measured using the Scale of Psychosis-Risk Symptoms (SOPS) and K10 Distress Scale, and a range of cognitive and behavioral measures were collected, as well as magnetic resonance imaging (MRI) data. Participants were assigned to one of 5 groups: healthy controls (HC; n = 42), familial risk (stage 0; n = 40), mild symptoms (stage 1a; n = 48), attenuated syndromes (stage 1b; n = 82), or discrete disorder (transition; n = 31). Constrained spherical deconvolution was used to generate whole brain tractography maps from diffusion MRI, which were then used to calculate connectivity matrices for graph theory analysis. Graph theory was also used to analyze correlations of functional MRI signal between pairs of brain regions. All measures were evaluated in a model to predict transition between groups. Random Forest analysis identified diffusion MRI-derived nodal metrics of betweenness centrality in the angular gyrus, inferior temporal gyrus, amygdala and calcarine fissure as potential features which can discriminate between the groups. Additionally, SOPS and K10 Distress Scales were useful behavioral predictors of transdiagnostic risk. Our findings show that combining neuroimaging with clinical characteristics may result in a promising predictive model for transdiagnostic risk and transition to SMI.
This study investigated the associations of modifiable lifestyle factors with incident dementia, dementia subtypes, and structural brain changes, examined whether these associations differed across KDIGO-defined kidney function risk categories. We analyzed 304,369 participants from the UK Biobank. Kidney function was classified using the KDIGO risk framework, with participants grouped into low- and increased-risk categories. A composite lifestyle score, derived from the American Heart Association Life's Essential 8 framework, was constructed based on eight modifiable components: diet quality, physical activity, smoking status, sleep duration, body mass index, blood lipid, blood glucose, and blood pressure. Outcomes included incident dementia and total and regional brain volumes. Among participants at increased KDIGO-defined risk, those in the intermediate and highest tertiles of the lifestyle score had a lower risk of dementia compared with those in the lowest tertile (hazard ratios, 0.826 [95% CI, 0.689-0.990] and 0.749 [95% CI, 0.585-0.958], respectively). Associations differed by dementia subtype: higher lifestyle scores were consistently associated with a lower risk of vascular dementia, whereas no overall association was observed with Alzheimer's disease. Higher lifestyle scores were also associated with larger total grey matter volume and greater volumes of subcortical structures, including caudate, pallidum, putamen, and thalamus, as well as lower volumes of total, deep, and periventricular white matter hyperintensities. Similar associations were observed in the low-risk group. A healthier lifestyle was associated with a lower risk of dementia, particularly vascular dementia, and with more favorable structural brain characteristics, with similar associations across KDIGO risk groups.
Post-stroke cognitive impairment (PSCI) significantly impacts patients’ quality of life following a stroke. Its effects on white matter functional networks remain unclear. This study used resting-state functional MRI to examine alterations in white matter functional connectivity and spontaneous activity in this condition. Resting-state functional MRI data were acquired from PSCI (n = 21), non-PSCI (PSNCI, n = 16), and healthy subjects (HSs, n = 29). A clustering analysis was employed to identify white matter functional networks. Functional connectivity and the amplitude of low-frequency fluctuation within these networks were compared across groups. Correlation analyses assessed their relationships with neuropsychological scores. Sixteen stable white matter networks were identified. Both patient groups showed reduced functional connectivity between the inferior longitudinal fasciculus and anterior cingulum compared to HSs. PSCI patients also exhibited decreased functional connectivity between the anterior and posterior cingulum compared to HSs. Furthermore, the amplitude of low-frequency fluctuation in the posterior cingulum was lower in PSCI group than in PSNCI group. These altered metrics showed correlations with neuropsychological performance across multiple cognitive domains. This study identified alterations in functional connectivity and spontaneous activity within specific WM networks in PSCI, which were associated with cognitive performance. These findings suggest that white matter functional abnormalities may be involved in the neural mechanisms underlying PSCI and could inform future research on early identification.
Acceptance and Commitment Therapy (ACT) has demonstrated effectiveness in treating Major Depressive Disorder (MDD); however, its underlying neural mechanisms remain poorly understood. Therefore, this study aims to investigate neural changes following an 8-week, group-based ACT intervention using task-based functional magnetic resonance imaging (fMRI) in patients diagnosed with MDD. Forty-two patients (21 in the ACT group and 21 in a waitlist control group) underwent fMRI scans before and after the intervention, using stimuli designed to evoke cognitive fusion alongside psychological assessments. The ACT group exhibited significant improvements in depressive symptoms and ACT-related psychological processes. fMRI analyses revealed increased posttreatment activation in brain regions central to emotion regulation, particularly the medial prefrontal cortex (mPFC) and anterior cingulate cortex. These neural changes were associated with improvements in depressive symptoms and reductions in cognitive fusion and experiential avoidance. Additionally, enhanced functional connectivity between the mPFC and posterior cingulate cortex/precuneus was observed, which was negatively correlated with rumination. These findings suggest that midline brain structures may serve as critical neural substrates for reducing ruminative thinking and enhancing cognitive defusion and acceptance, offering insights into the neurobiological mechanisms through which ACT exerts its antidepressant effects.
Although the associations between cerebrovascular dysfunctions and Alzheimer's disease are increasingly appreciated, the relationship of cerebral blood flow and white matter hyperintensities with tau and amyloid-β pathology remains unclear, particularly in the longitudinal context. This study investigated cross-sectional and longitudinal associations of cerebral blood flow and white matter hyperintensities with tau and amyloid-β pathology using multimodal imaging and blood biomarkers in 179 participants from the ADNI3 cohort. Participants underwent structural (T1-weighted, T2-weighted FLAIR) and arterial spin labelling perfusion MRI, tau and amyloid-β PET, and plasma assay tests for amyloid-β 42, amyloid-β 40, and phosphorylated tau-217. Tau from PET was negatively associated with cerebral blood flow both cross-sectionally and longitudinally in the posterior brain, independent of amyloid-β quantified from PET. Higher white matter hyperintensities volumes were associated with higher levels of tau and amyloid-β at baseline, but the associations were significantly attenuated after further adjusting for amyloid-β and tau, respectively. Plasma amyloid-β 42/40 ratio was negatively associated with white matter hyperintensity volumes both cross-sectionally and longitudinally. In conclusion, tau pathology showed spatially specific associations with cerebral hypoperfusion, independent of amyloid-β, particularly in posterior regions. The attenuation of associations of white matter hyperintensities with amyloid-β and tau after adjustment may reflect shared disease-related variance rather than distinct independent effects.
Midlife in females typically involves a significant neuroendocrine transition that may have effects on brain connectivity that are relevant to both normal and pathological aging. One potential contributing factor to the individual differences in cognition and risk for pathological aging is the brain's response to decreased levels of estradiol. We assessed the relationship between estradiol level and task-modulated effective connectivity between brain regions during an episodic memory task in females during midlife. We utilized data from the Human Connectome Project - Aging 2.0 release. One hundred and fifty female participants between 40 and 55 years of age were included in our analysis of the relationship between estradiol and connectivity. Pre-, peri-, and postmenopausal participants were included to capture a range of estradiol levels present during midlife. We assessed connectivity during the fMRI FaceName task utilizing Conn Toolbox on a connection level as a pairwise comparison between regions. Five connections associated with estradiol were significant during the recall portion of the FaceName task at a p<.05 FDR corrected level after controlling for age. Significant connections among the superior frontal gyrus left and brain stem and the middle temporal gyrus anterior division right and superior temporal gyrus posterior division right were identified. Negative associations between these regions were also present. There was no significant relationship between estradiol and FaceName task performance. Our results indicated that task-modulated effective connectivity was related to estradiol level during midlife in females between brain regions known to be important for memory functioning during the recall portion of an episodic memory task. These findings may have long term implications for memory function in females during the aging process due to the low levels of estradiol present post-menopause.
Sports/exercise engagement across the lifetime has been proposed to contribute to cognitive reserve and promote healthy brain aging. Few studies have examined whether past sports experiences are associated with current cognitive and social functions and resting-state brain activity in lifespan. The present study aimed to address that gap. Ninety healthy participants aged 20–83 years were categorized into four groups based on their self-reported sports experience: single sports (N = 25), team sports (N = 11), combined single and team sports (N = 20), and no experience (N = 34). We assessed cognitive function, social adaptation, and quality of life. Resting-state functional magnetic resonance imaging data were analyzed using amplitude of low-frequency fluctuations and seed-based functional connectivity to investigate local spontaneous activity and network-level integration. Participants with sports experience demonstrated enhanced performance in several cognitive tasks and higher social adaptation scores than those without experience. Neuroimaging analyses revealed increased amplitude of low-frequency fluctuations in the right middle frontal gyrus in the team-sport group. Furthermore, exploratory functional connectivity analysis showed reduced coupling between the right middle frontal gyrus and posterior sensory-visual regions, including the postcentral gyrus, lateral occipital cortex, and occipital fusiform gyrus. These findings suggest that lifetime sports engagement may be associated with differences in cognitive and psychosocial functioning, together with a tentative pattern of resting-state brain variation. Although the observed connectivity pattern may be broadly consistent with accounts of functional specialization or neural efficiency, the principal ALFF finding did not survive correction for multiple comparisons. Accordingly, the neuroimaging results should be regarded as preliminary and hypothesis-generating rather than confirmatory, while still providing a concrete basis for future hypothesis-driven investigation.
Identifying brain phenotypes influencing social participation may help understand social deficits in psychiatric disorders. Previous research shows methodological inconsistencies, lacking consensus on which brain regions are crucial. Data-driven variable selection may overcome this, facilitating unbiased replication and discovery of social brain regions. We compare data-driven selection to literature-identification of brain regions in explaining social participation variation. In 37,576 UK Biobank participants (mean age 65 ± 8, 53
Identifying individuals with mild cognitive impairment (MCI) who are at risk of progressing to Alzheimer's disease (AD) is crucial for early interventions and understanding disease mechanisms. While previous studies using resting-state fMRI (functional magnetic resonance imaging) have identified various neural markers in MCI, there is limited research on alterations in interhemispheric functional interactions. Fifty-three MCI patients and 68 age-, gender-, and education-matched healthy controls were included in the study. Structural cranial MRI and resting-state fMRI data were collected. We investigated voxel-mirrored homotopic connectivity (VMHC) alterations in patients with mild cognitive impairment (MCI) using resting-state fMRI. Functional connectivity was then calculated using the regions with abnormal VMHC as seed points. Correlation analyses were performed to examine the relationship between altered functional connectivity and Core Neuropsychological Test (CNT) scores. Compared to controls, MCI patients exhibited increased VMHC in the bilateral postcentral gyrus. Functional connectivity was enhanced between the bilateral postcentral gyrus and the left cerebellar Crus I, as well as the right inferior temporal gyrus. In contrast, decreased connectivity was observed with the left Gyrus rectus and right supplementary motor area. Correlation analysis revealed a significant negative relationship between VMHC values and CNT scores, as well as with verbal analogy and Chinese word matching scores. MCI patients not only show disrupted interhemispheric VMHC but also demonstrate significant associations with core neuropsychological impairments. These findings provide insights into cognitive changes in MCI and highlight potential biomarkers for early Alzheimer's disease detection.