Corrigendum: Diagnosis for autism spectrum disorder children using T1-based gray matter and arterial spin labeling-based cerebral blood flow network metrics.

[This corrects the article DOI: 10.3389/fnins.2024.1356241.].

Combining Quantitative Susceptibility Mapping With the Gray Matter Volume to Predict Neurological Deficits in Patients With Small Artery Occlusion.

BACKGROUND: Currently, there is still a lack of valuable neuroimaging markers to assess the clinical severity of stroke patients with small artery occlusion (SAO). Quantitative susceptibility mapping (QSM) is a quantitative processing method for neuroradiological diagnostics. Gray matter (GM) volume changes in stroke patients are also proved to be associated with neurological deficits. This study aims to explore the predictive value of QSM and GM volume in neurological deficits of patients with SAO. METHODS: As neurological deficits, the National Institutes of Health Stroke Scale (NIHSS) was used. Sixty-six SAO participants within 24 h of first onset were enrolled and divided into mild and moderate groups based on NIHSS. QSM values of infarct area and GM volume were calculated from magnetic resonance imaging (MRI) data. Two-sample t-tests were used to compare differences in QSM value and GM volume between the two groups, and the diagnostic efficacy of the combination of QSM value and GM volume was evaluated. RESULTS: The results revealed both the QSM value and GM volume within the infarct area of the moderate group were lower compared to the mild group. Moderate group exhibited lower GM volume in some specific gyrus compared with mild group in the case of voxel-wise GM volume on whole-brain voxel level. The support vector machine (SVM) classifier's analysis showed a high power for the combination of QSM value, GM volume within the infarct area, and voxel-wise GM volume. CONCLUSION: Our research first reported the combination of QSM value, GM volume within the infarct area, and voxel-wise GM volume could be used to predict neurological impairment of patients with SAO, which provides new insights for further understanding the SAO stroke.

Progressive brain structural abnormality in cerebral small vessel disease assessed with MR imaging by using causal network analysis.

AIMS: Cerebral small vessel disease (CSVD) is a complex condition characterized by a combination of microcirculation disorders and neurodegenerative processes, CSVD is associated with structural abnormalities in multiple brain regions. However, the progressive pattern of structural changes remains unknown. METHODS: In order to detail the progressive structural changes in CSVD patients according to the degree of cognitive impairment, we recruited 121 CSVD patients and 104 healthy controls (HCs). Voxel-based morphometry was employed to measure the gray matter volume (GMV) of each participant. According to the VICCCS-2 diagnostic criteria, patients were initially divided into three stage groups, then we investigated the GMV changes in each stage and their causal relationships using causal structure covariance network (CaSCN) analysis. RESULTS: Overall, patients with CSVD presented stage-specific GMV alterations compared with HCs. With the worsening of cognitive impairment, the decrease in gray matter volume starts from the right hippocampus and gradually spreads to the cortical-subcortical brain regions. Importantly, the right hippocampus in CSVD patients plays a driving role in the directional network and forms both positive and negative causal effect networks with cortical-subcortical brain regions. CONCLUSIONS: This study reveals the significance of the right hippocampus as an early pathological area in CSVD patients and its causal impact on brain GMV changes with disease progression, shedding light on structural brain damage hierarchy and compensatory mechanisms.

Expanded gray matter atrophy with severity stages of adult comorbid insomnia and sleep apnea.

OBJECTIVE: To investigate gray matter volume (GMV) changes in patients with comorbid insomnia and sleep apnea (COMISA) of differing severity and relationships between GMV alterations and clinical measures. METHODS: Thirty-four COMISA patients and 24 healthy controls (HC) were recruited. All patients underwent structural MRI and completed measures related to respiration, sleep, mood, and cognition. COMISA patients were further divided into a mild and moderate COMISA (MC) and a severe COMISA (SC) group. Changes in GMV of COMISA patients were investigated via VBM. The voxel-wise differences in GMV were compared between HC group and COMISA group. Analysis of covariance (ANCOVA) was performed on individual GMV maps in MC, SC, and HC groups to further investigate effects of different stages of COMISA severity on GMV. Partial correlation analysis was then performed to analyze relationships between altered GMV and clinical measures. RESULTS: GMV atrophy was mainly located in the temporal lobes and fusiform gyrus in COMISA group. The post-hoc analysis of the ANCOVA revealed temporal lobes and fusiform gyrus atrophy in MC and SC groups compared to HC and the temporal lobe atrophy was expanded in SC group based on cluster size. Moreover, the SC group showed GMV atrophy of the right amygdala compared to both MC and HC groups. Partial correlation analysis revealed positive relationships between the GMV and mood-and cognitive-related measures and negative correlation between GMV and respiration measure. CONCLUSIONS: Our findings showed GMV atrophy expansion from temporal lobe to limbic system (right amygdala) as severity stages increase in COMISA patients. These findings contribute to our understanding of neurobiological mechanisms underlying different stages of severity in COMISA patients.

Autism is associated with in vivo changes in gray matter neurite architecture.

Postmortem investigations in autism have identified anomalies in neural cytoarchitecture across limbic, cerebellar, and neocortical networks. These anomalies include narrow cell mini-columns and variable neuron density. However, difficulty obtaining sufficient post-mortem samples has often prevented investigations from converging on reproducible measures. Recent advances in processing magnetic resonance diffusion weighted images (DWI) make in vivo characterization of neuronal cytoarchitecture a potential alternative to post-mortem studies. Using extensive DWI data from the Adolescent Brain Cognitive Developmentsm (ABCD®) study 142 individuals with an autism diagnosis were compared with 8971 controls using a restriction spectrum imaging (RSI) framework that characterized total neurite density (TND), its component restricted normalized directional diffusion (RND), and restricted normalized isotropic diffusion (RNI). A significant decrease in TND was observed in autism in the right cerebellar cortex (ß = -0.005, SE =0.0015, p = 0.0267), with significant decreases in RNI and significant increases in RND found diffusely throughout posterior and anterior aspects of the brain, respectively. Furthermore, these regions remained significant in post-hoc analysis when the autism sample was compared against a subset of 1404 individuals with other psychiatric conditions (pulled from the original 8971). These findings highlight the importance of characterizing neuron cytoarchitecture in autism and the significance of their incorporation as physiological covariates in future studies.

Immune-mediated impairment of tonic immobility defensive behavior in an experimental model of colonic inflammation.

Ulcerative colitis has been associated with psychological distress and an aberrant immune response. The immunomodulatory role of systemic cytokines produced during experimental intestinal inflammation in tonic immobility (TI) defensive behavior remains unknown. The present study characterized the TI defensive behavior of guinea pigs subjected to colitis induction at the acute stage and after recovery from intestinal mucosa injury. Moreover, we investigated whether inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-8, IL-10, and prostaglandins) act on the mesencephalic nucleus, periaqueductal gray matter (PAG). Colitis was induced in guinea pigs by intrarectal administration of acetic acid. The TI defensive behavior, histology, cytokine production, and expression of c-FOS, IBA-1, and cyclooxygenase (COX)-2 in PAG were evaluated. Colitis reduced the duration of TI episodes from the first day, persisting throughout the 7-day experimental period. Neuronal c-FOS immunoreactivity was augmented in both columns of the PAG (ventrolateral (vlPAG) and dorsal), but there were no changes in IBA-1 expression. Dexamethasone, infliximab, and parecoxib treatments increased the duration of TI episodes, suggesting a modulatory role of peripheral inflammatory mediators in this behavior. Immunoneutralization of TNF-α, IL-1ß, and IL-8 in the vlPAG reversed all effects produced by colitis. In contrast, IL-10 neutralization further reduced the duration of TI episodes. Our results reveal that peripherally produced inflammatory mediators during colitis may modulate neuronal functioning in mesencephalic structures such as vlPAG.

Behavioral and brain morphological changes before and after hemispherotomy.

Hemispherotomy is an effective surgery for treating refractory epilepsy from diffuse unihemispheric lesions. To date, postsurgery neuroplastic changes supporting behavioral recovery after left or right hemispherotomy remain unclear. In the present study, we systematically investigated changes in gray matter volume (GMV) before and after surgery and further analyzed their relationships with behavioral scores in two large groups of pediatric patients with left and right hemispherotomy (29 left and 28 right). To control for the dramatic developmental effect during this stage, age-adjusted GMV within unaffected brain regions was derived voxel by voxel using a normative modeling approach with an age-matched reference cohort of 2115 healthy children. Widespread GMV increases in the contralateral cerebrum and ipsilateral cerebellum and GMV decreases in the contralateral cerebellum were consistently observed in both patient groups, but only the left hemispherotomy patients showed GMV decreases in the contralateral cingulate gyrus. Intriguingly, the GMV decrease in the contralateral cerebellum was significantly correlated with improvement in behavioral scores in the right but not the left hemispherotomy patients. Importantly, the preoperative voxelwise GMV features can be used to significantly predict postoperative behavioral scores in both patient groups. These findings indicate an important role of the contralateral cerebellum in the behavioral recovery following right hemispherotomy and highlight the predictive potential of preoperative imaging features in postoperative behavioral performance.

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.

Meta-analysis of structural and functional brain abnormalities in early-onset schizophrenia.

Background: Previous studies based on resting-state functional magnetic resonance imaging(rs-fMRI) and voxel-based morphometry (VBM) have demonstrated significant abnormalities in brain structure and resting-state functional brain activity in patients with early-onset schizophrenia (EOS), compared with healthy controls (HCs), and these alterations were closely related to the pathogenesis of EOS. However, previous studies suffer from the limitations of small sample sizes and high heterogeneity of results. Therefore, the present study aimed to effectively integrate previous studies to identify common and specific brain functional and structural abnormalities in patients with EOS. Methods: The PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases were systematically searched to identify publications on abnormalities in resting-state regional functional brain activity and gray matter volume (GMV) in patients with EOS. Then, we utilized the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software to conduct a whole-brain voxel meta-analysis of VBM and rs-fMRI studies, respectively, and followed by multimodal overlapping on this basis to comprehensively identify brain structural and functional abnormalities in patients with EOS. Results: A total of 27 original studies (28 datasets) were included in the present meta-analysis, including 12 studies (13 datasets) related to resting-state functional brain activity (496 EOS patients, 395 HCs) and 15 studies (15 datasets) related to GMV (458 EOS patients, 531 HCs). Overall, in the functional meta-analysis, patients with EOS showed significantly increased resting-state functional brain activity in the left middle frontal gyrus (extending to the triangular part of the left inferior frontal gyrus) and the right caudate nucleus. On the other hand, in the structural meta-analysis, patients with EOS showed significantly decreased GMV in the right superior temporal gyrus (extending to the right rolandic operculum), the right middle temporal gyrus, and the temporal pole (superior temporal gyrus). Conclusion: This meta-analysis revealed that some regions in the EOS exhibited significant structural or functional abnormalities, such as the temporal gyri, prefrontal cortex, and striatum. These findings may help deepen our understanding of the underlying pathophysiological mechanisms of EOS and provide potential biomarkers for the diagnosis or treatment of EOS.

How to detect affect recognition alterations in amyotrophic lateral sclerosis.

OBJECTIVE: To define the clinical usability of an affect recognition (AR) battery-the Comprehensive Affect Testing System (CATS)-in an Italian sample of patients with amyotrophic lateral sclerosis (ALS). METHODS: 96 ALS patients and 116 healthy controls underwent a neuropsychological assessment including the AR subtests of the abbreviated version of the CATS (CATS-A). CATS-A AR subtests and their global score (CATS-A AR Quotient, ARQ) were assessed for their factorial, convergent, and divergent validity. The diagnostic accuracy of each CATS-A AR measure in discriminating ALS patients with cognitive impairment from cognitively normal controls and patients was tested via receiver-operating characteristics analyses. Optimal cut-offs were identified for CATS-A AR measures yielding an acceptable AUC value (≥ .70). The ability of CATS-A ARQ to discriminate between different ALS cognitive phenotypes was also tested. Gray-matter (GM) volumes of controls, ALS with normal (ALS-nARQ), and impaired ARQ score (ALS-iARQ) were compared using ANCOVA models. RESULTS: CATS-A AR subtests and ARQ proved to have moderate-to-strong convergent and divergent validity. Almost all considered CATS-A measures reached acceptable accuracy and diagnostic power (AUC range = .79-.83). ARQ showed to be the best diagnostic measure (sensitivity = .80; specificity = .75) and discriminated between different ALS cognitive phenotypes. Compared to ALS-nARQ, ALS-iARQ patients showed reduced GM volumes in the right anterior cingulate, right middle frontal, left inferior temporal, and superior occipital regions. CONCLUSIONS: The AR subtests of the CATS-A, and in particular the CATS-A ARQ, are sound measures of AR in ALS. AR deficits may be a valid marker of frontotemporal involvement in these patients.

Multimodal magnetic resonance longitudinal study on the deep gray matter in multiple sclerosis patients with teriflunomide.

Disease-modifying therapies (DMTs) are used in an increasing number of patients with multiple sclerosis (MS). However, whether DMTs have intrinsic effects on deep gray matter (DGM) microstructure and atrophy is still poorly understood. In this study, we described the quantitative susceptibility values (QSV) and diffusion kurtosis imaging (DKI) metrics of DGM in relapsing-remitting MS (RRMS) patients and their association with cognitive deficits. We recruited 62 patients with RRMS receiving DMTs and 30 patients with RRMS not receiving DMTs underwent MRI on a 3T scanner. Fractional anisotropy (FA), kurtosis fractional anisotropy (KFA), mean diffusivity (MD), mean kurtosis (MK), QSV and volumes of bilateral caudate nucleus (CAU), amygdala (AMYG), putamen (PUT), hippocampus (Hipp), globus pallidus (GP) and thalamus (THA) were measured. Correlation analysis was performed between those image indexes with longitudinal significant changes and clinical neurological scores, including Expanded Disability Status Scale (EDSS), Digit Span Testand (DST), Symbol Digit Modalities Test (SDMT), Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Significant longitudinal increases in FA, KFA and MK values were found in both groups in bilateral CAU, AMYG, PUT, Hipp, GP and THA (all p < 0.005). MD values of the right of CAU in the two groups were significant longitudinal increase (p = 0.009, p = 0.047); MD values of the right of GP (p = 0.042), the left of THA (p = 0.003), the right of THA (p = 0.001) in treated MS were significant longitudinal decrease; There were no significant longitudinal changes between treated and untreated groups in normalized deep gray matter volume. For QSV, longitudinal increase in the right of PUT (p = 0.022) in the treated MS group and in the left of Hipp (p = 0.045) in the untreated MS group. The QSV and DKI measures were highly correlated with cognitive and disability tests. The treated RRMS patients showed different longitudinal changes of MD value and QSV with untreated in several DGM regions, and these differences were correlated with cognitive and microstructural integrity.

Hypoperfusion of periaqueductal gray as an imaging biomarker in chronic migraine beyond diagnosis: A 3D pseudocontinuous arterial spin labeling MR imaging.

BACKGROUND: The periaqueductal gray (PAG) is at the center of a powerful descending antinociceptive neuronal network, and is a key node in the descending pain regulatory system of pain. However, less is known about the altered perfusion of PAG in chronic migraine (CM). AIM: To measure the perfusion of PAG matter, an important structure in pain modulation, in CM with magnetic resonance (MR) perfusion without contrast administration. METHODS: Three-dimensional pseudocontinuous arterial spin labeling (3D-PCASL) and brain structure imaging were performed in 13 patients with CM and 15 normal subjects. The inverse deformation field generated by brain structure image segmentation was applied to the midbrain PAG template to generate individualized PAG. Then the perfusion value of the PAG area of the midbrain was extracted based on the individual PAG mask. RESULTS: Cerebral blood flow (CBF) value of PAG in CM patients (47.98 ± 8.38 mL/100 mg min) was significantly lower than that of the control group (59.87 ± 14.24 mL/100 mg min). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve was 0.77 (95% confidence interval [CI], 0.60, 0.94), and the cutoff value for the diagnosis of CM was 54.83 mL/100 mg min with a sensitivity 84.60% and a specificity 60%. CONCLUSION: Imaging evidence of the impaired pain conduction pathway in CM may be related with the decreased perfusion in the PAG, which could be considered as an imaging biomarker for the diagnosis and therapy evaluation.

Brain structural changes underlying clinical symptom improvement following fast-acting treatments in treatment resistant depression.

BACKGROUND: Electroconvulsive therapy (ECT), ketamine infusion (KI), and total sleep deprivation (TSD) are effective and fast in treating patients with treatment-resistant depression (TRD). However, it remains unclear whether the three treatments have the same effect on clinical symptom improvement and have common brain structural mechanisms. METHODS: The current study included 127 TRD patients and 37 healthy controls, which were obtained from the Perturbation of the Treatment Resistant Depression Connectome Project. We aimed to investigate the shared and distinct brain structural changes underlying clinical symptom improvement among ECT, KI, and TSD treatments. RESULTS: All of the three treatments significantly reduced the depressive symptoms in TRD patients, but they differently affected other clinical measurements. Neuroimaging results also revealed that all of ECT, KI, and TSD treatments significantly increased gray matter volume of left caudate after treatment in TRD patients. However, the gray matter volume of other brain regions including hippocampus, parahippocampus, amygdala, insula, fusiform gyrus, several occipital and temporal areas was increased only after ECT treatment. Still, the baseline or the change of gray matter volume did not correlate with the depressive symptom improvement for all of the three treatments. LIMITATIONS: A higher sample size would be required to further validate our findings. CONCLUSIONS: The results observed in the current study suggested that the ECT, KI, and TSD treatments differently affected clinical measurements and brain structures in TRD patients, though all of them were effective in depressive symptom improvement, which might facilitate the development of personalized treatment protocol for this disease.

Identification of high-functioning autism spectrum disorders based on gray-white matter functional network connectivity.

In the field of autism spectrum disorder (ASD), research on functional connectivity between gray matter and white matter remains under-researched. To address this gap, this study innovatively introduced a nested cross-validation method that integrates gray-white matter functional connectivity with an F-Score algorithm. This method calculates the correlation based on signals extracted from functional magnetic resonance imaging data using gray matter and white matter brain region templates. After applying the method to a New York University Langone Medical Center dataset consisting of 55 individuals with high-functioning ASD and 52 healthy subjects, we achieved a classification accuracy of 72.94%. This study found abnormal functional connectivity, primarily involving the left anterior prefrontal cortex and right superior corona radiata, left retrosplenial cortex and left superior corona radiata, as well as the left ventral anterior cingulate cortex and body of corpus callosum. Besides, we discovered that these abnormal connections are closely related to social impairment and restrictive and repetitive behaviors in ASD. In conclusion, this study provides a gray-white matter functional connectivity perspective for the diagnosis and understanding of ASD.

The Role of 3' Regulatory Region Flanking Kinectin 1 Gene in Schizophrenia.

Objective: Schizophrenia is often associated with volumetric reductions in cortices and expansions in basal ganglia, particularly the putamen. Recent genome-wide association studies have highlighted the significance of variants in the 3' regulatory region adjacent to the kinectin 1 gene (KTN1) in regulating gray matter volume (GMV) of the putamen. This study aimed to comprehensively investigate the involvement of this region in schizophrenia. Methods: We analyzed 1136 single-nucleotide polymorphisms (SNPs) covering the entire 3' regulatory region in 4 independent dbGaP samples (4604 schizophrenia patients vs. 4884 healthy subjects) and 3 independent Psychiatric Genomics Consortium samples (107 240 cases vs. 210 203 controls) to identify consistent associations. Additionally, we examined the regulatory effects of schizophrenia-associated alleles on KTN1 mRNA expression in 16 brain areas among 348 subjects, as well as GMVs of 7 subcortical nuclei in 38 258 subjects, and surface areas (SA) and thickness (TH) of the entire cortex and 34 cortical areas in 36 936 subjects. Results: The major alleles (f > 0.5) of 25 variants increased (ß > 0) the risk of schizophrenia across 2 to 5 independent samples (8.4 × 10-4 ≤ P ≤ .049). These schizophrenia-associated alleles significantly elevated (ß > 0) GMVs of basal ganglia, including the putamen (6.0 × 10-11 ≤ P ≤ 1.1 × 10-4), caudate (8.7 × 10-4 ≤ P ≤ 9.4 × 10-3), pallidum (P = 6.0 × 10-4), and nucleus accumbens (P = 2.7 × 10-5). Moreover, they potentially augmented (ß > 0) the SA of posterior cingulate and insular cortices, as well as the TH of frontal (pars triangularis and medial orbitofrontal), parietal (superior, precuneus, and inferior), and temporal (transverse) cortices, but potentially reduced (ß < 0) the SA of the whole, frontal (medial orbitofrontal), and temporal (pole, superior, middle, and entorhinal) cortices, as well as the TH of rostral middle frontal and superior frontal cortices (8.9 × 10-4 ≤ P ≤ .050). Conclusion: Our findings identify significant and functionally relevant risk alleles in the 3' regulatory region adjacent to KTN1, implicating their crucial roles in the development of schizophrenia.

Synergistic associations of CD33 variants and hypertension with brain and cognitive aging among dementia-free older adults: A population-based study.

INTRODUCTION: CD33 rs3865444 and hypertension (HTN) are related to cognitive impairment, individually. However, little is known about their combined effects on cognitive function in older adults. METHODS: This population-based study included 4368 dementia-free participants (age ≥65 years) in the Multimodal Interventions to Delay Dementia and Disability in Rural China (MIND-China), with data available in 1044 persons for gray matter volume and 85 persons for cerebral blood flow (CBF). We used general linear regression and mediation models to examine the associations of rs3865444 and HTN with cognition, brain atrophy, and CBF. RESULTS: Among rs3865444 CC carriers, HTN and late-life HTN were significantly associated with impaired cognition. Midlife and late-life HTN were correlated with brain atrophy. CD33 rs3865444 CC moderated the mediation effect of gray matter volume on the association between HTN and global cognition. HTN was correlated with low CBF in rs3865444 CC carriers. DISCUSSION: There are synergistic associations of CD33 rs3865444 and HTN with brain and cognitive aging in dementia-free older adults.

Decoding MRI-informed brain age using mutual information.

OBJECTIVE: We aimed to develop a standardized method to investigate the relationship between estimated brain age and regional morphometric features, meeting the criteria for simplicity, generalization, and intuitive interpretability. METHODS: We utilized T1-weighted magnetic resonance imaging (MRI) data from the Cambridge Centre for Ageing and Neuroscience project (N = 609) and employed a support vector regression method to train a brain age model. The pre-trained brain age model was applied to the dataset of the brain development project (N = 547). Kraskov (KSG) estimator was used to compute the mutual information (MI) value between brain age and regional morphometric features, including gray matter volume (GMV), white matter volume (WMV), cerebrospinal fluid (CSF) volume, and cortical thickness (CT). RESULTS: Among four types of brain features, GMV had the highest MI value (8.71), peaking in the pre-central gyrus (0.69). CSF volume was ranked second (7.76), with the highest MI value in the cingulate (0.87). CT was ranked third (6.22), with the highest MI value in superior temporal gyrus (0.53). WMV had the lowest MI value (4.59), with the insula showing the highest MI value (0.53). For brain parenchyma, the volume of the superior frontal gyrus exhibited the highest MI value (0.80). CONCLUSION: This is the first demonstration that MI value between estimated brain age and morphometric features may serve as a benchmark for assessing the regional contributions to estimated brain age. Our findings highlighted that both GMV and CSF are the key features that determined the estimated brain age, which may add value to existing computational models of brain age. CRITICAL RELEVANCE STATEMENT: Mutual information (MI) analysis reveals gray matter volume (GMV) and cerebrospinal fluid (CSF) volume as pivotal in computing individuals' brain age. KEY POINTS: Mutual information (MI) interprets estimated brain age with morphometric features. Gray matter volume in the pre-central gyrus has the highest MI value for estimated brain age. Cerebrospinal fluid volume in the cingulate has the highest MI value. Regarding brain parenchymal volume, the superior frontal gyrus has the highest MI value. The value of mutual information underscores the key brain regions related to brain age.

Correlations of brain structure with the social behavior of 15q11-13 duplication mice, an animal model of autism.

Duplication of chromosome 15q11-13 has been reported to be one of the most frequent cytogenetic copy number variations in autism spectrum disorder (ASD), and a mouse model of paternal 15q11-13 duplication was generated, termed 15q dup mice. While previous studies have replicated some of the behavioral and brain structural phenotypes of ASD separately, the relationship between brain structure and behavior has rarely been examined. In this study, we performed behavioral experiments related to anxiety and social behaviors and magnetic resonance imaging (MRI) using the same set of 15q dup and wild-type mice. 15q dup mice showed increased anxiety and a tendency toward alterations in social behaviors, as reported previously, as well as variability in terms of sociability. MRI analysis revealed that a lower sociability index was correlated with a smaller gray matter volume in the right medial entorhinal cortex. These results may help to understand how variability in behavioral phenotypes of ASD arises even in individuals with the same genetic background and to determine the individual differences in neurodevelopmental trajectory correlated with specific brain structures that underlie these phenotypes.

Disrupted single-subject gray matter networks are associated with cognitive decline and cortical atrophy in Alzheimer's disease.

Background: Research has shown disrupted structural network measures related to cognitive decline and future cortical atrophy during the progression of Alzheimer's disease (AD). However, evidence regarding the individual variability of gray matter network measures and the associations with concurrent cognitive decline and cortical atrophy related to AD is still sparse. Objective: To investigate whether alterations in single-subject gray matter networks are related to concurrent cognitive decline and cortical gray matter atrophy during AD progression. Methods: We analyzed structural MRI data from 185 cognitively normal (CN), 150 mild cognitive impairment (MCI), and 153 AD participants, and calculated the global network metrics of gray matter networks for each participant. We examined the alterations of single-subject gray matter networks in patients with MCI and AD, and investigated the associations of network metrics with concurrent cognitive decline and cortical gray matter atrophy. Results: The small-world properties including gamma, lambda, and sigma had lower values in the MCI and AD groups than the CN group. AD patients had reduced degree, clustering coefficient, and path length than the CN and MCI groups. We observed significant associations of cognitive ability with degree in the CN group, with gamma and sigma in the MCI group, and with degree, connectivity density, clustering coefficient, and path length in the AD group. There were significant correlation patterns between sigma values and cortical gray matter volume in the CN, MCI, and AD groups. Conclusion: These findings suggest the individual variability of gray matter network metrics may be valuable to track concurrent cognitive decline and cortical atrophy during AD progression. This may contribute to a better understanding of cognitive decline and brain morphological alterations related to AD.

Cortical lobar volume reductions associated with homocysteine-related subcortical brain atrophy and poorer cognition in healthy aging.

Homocysteine (Hcy) is a cardiovascular risk factor implicated in cognitive impairment and cerebrovascular disease but has also been associated with Alzheimer's disease. In 160 healthy older adults (mean age = 69.66 ± 9.95 years), we sought to investigate the association of cortical brain volume with white matter hyperintensity (WMH) burden and a previously identified Hcy-related multivariate network pattern showing reductions in subcortical gray matter (SGM) volumes of hippocampus and nucleus accumbens with relative preservation of basal ganglia. We additionally evaluated the potential role of these brain imaging markers as a series of mediators in a vascular brain pathway leading to age-related cognitive dysfunction in healthy aging. We found reductions in parietal lobar gray matter associated with the Hcy-SGM pattern, which was further associated with WMH burden. Mediation analyses revealed that slowed processing speed related to aging, but not executive functioning or memory, was mediated sequentially through increased WMH lesion volume, greater Hcy-SGM pattern expression, and then smaller parietal lobe volume. Together, these findings suggest that volume reductions in parietal gray matter associated with a pattern of Hcy-related SGM volume differences may be indicative of slowed processing speed in cognitive aging, potentially linking cardiovascular risk to an important aspect of cognitive dysfunction in healthy aging.