Peripheral oxytocin levels are linked to hypothalamic gray matter volume in autistic adults: a cross-sectional secondary data analysis.

Oxytocin (OXT) is known to modulate social behavior and cognition and has been discussed as pathophysiological and therapeutic factor for autism spectrum disorder (ASD). An accumulating body of evidence indicates the hypothalamus to be of particular importance with regard to the underlying neurobiology. Here we used a region of interest voxel-based morphometry (VBM) approach to investigate hypothalamic gray matter volume (GMV) in autistic (n = 29, age 36.03 ± 11.0) and non-autistic adults (n = 27, age 30.96 ± 11.2). Peripheral plasma OXT levels and the autism spectrum quotient (AQ) were used for correlation analyses. Results showed no differences in hypothalamic GMV in autistic compared to non-autistic adults but suggested a differential association between hypothalamic GMV and OXT levels, such that a positive association was found for the ASD group. In addition, hypothalamic GMV showed a positive association with autistic traits in the ASD group. Bearing in mind the limitations such as a relatively small sample size, a wide age range and a high rate of psychopharmacological treatment in the ASD sample, these results provide new preliminary evidence for a potentially important role of the HTH in ASD and its relationship to the OXT system, but also point towards the importance of interindividual differences.

Diagnosing autism severity associated with physical fitness and gray matter volume in children with autism spectrum disorder: Explainable machine learning method.

PURPOSE: This study aimed to investigate the relationship between physical fitness, gray matter volume (GMV), and autism severity in children with autism spectrum disorder (ASD). Besides, we sought to diagnose autism severity associated with physical fitness and GMV using machine learning methods. METHODS: Ninety children diagnosed with ASD underwent physical fitness tests, magnetic resonance imaging scans, and autism severity assessments. Diagnosis models were established using extreme gradient boosting (XGB), random forest (RF), support vector machine (SVM), and decision tree (DT) algorithms. Hyperparameters were optimized through the grid search cross-validation method. The shapley additive explanation (SHAP) method was employed to explain the diagnosis results. RESULTS: Our study revealed associations between muscular strength in physical fitness and GMV in specific brain regions (left paracentral lobule, bilateral thalamus, left inferior temporal gyrus, and cerebellar vermis I-II) with autism severity in children with ASD. The accuracy (95 % confidence interval) of the XGB, RF, SVM, and DT models were 77.9 % (77.3, 78.6 %), 72.4 % (71.7, 73.2 %), 71.9 % (71.1, 72.6 %), and 66.9 % (66.2, 67.7 %), respectively. SHAP analysis revealed that muscular strength and thalamic GMV significantly influenced the decision-making process of the XGB model. CONCLUSION: Machine learning methods can effectively diagnose autism severity associated with physical fitness and GMV in children with ASD. In this respect, the XGB model demonstrated excellent performance across various indicators, suggesting its potential for diagnosing autism severity.

The effects of P2 segment of posterior cerebral artery to thalamus blood supply pattern on gait in cerebral small vessel disease: A 7 T MRI based study.

Gait disturbance is a manifestation of cerebral small vessel disease (CSVD). The posterolateral thalamus (PL), whose blood is mainly supplied by the P2 segment of posterior cerebral artery (P2-PCA), plays pivotal roles in gait regulation. We investigated the influence of the distance between P2-PCA and PL on gait with varying CSVD burden. 71 participants were divided into low and high CSVD burden groups. The distance from P2-PCA to PL was measured using 7 T TOF-MRA and categorized into an immediate or distant PCA-to-thalamus pattern. Functional connectivity (FC) and voxel-based morphometry were assessed to evaluate functional and structural alterations. In the low CSVD burden group, immediate PCA-to-thalamus supply strongly correlates with longer step length and higher wave phase time percent, and exhibited enhanced FCs in left supplementary motor area, right precentral cortex (PreCG.R). While in the high CSVD burden group, no association between PCA-to-thalamus pattern and gait was found, and we observed reduced FC in PreCG.R with immediate PCA-to-thalamus pattern. Higher CSVD burden was associated with decreased gray matter density in bilateral thalamus. However, no significant structural thalamic change was observed between the two types of PCA-to-thalamus patterns in all patients. Our study demonstrated patients with immediate PCA-to-thalamus supply exhibited better gait performance in low CSVD burden populations, which also correlated with enhanced FCs in motor-related cortex, indicating the beneficial effects of the immediate PCA-to-thalamus supply pattern. In the higher burden CSVD populations, the effects of PCA-to-thalamus pattern on gait are void, attributable to the CSVD-related thalamic destruction and impairment of thalamus-related FC.

Valproate use associated with frontal and cerebellar gray matter volume reductions: A voxel-based morphometry study.

Recent morphometric magnetic resonance imaging (MRI) studies suggested the possibility that valproate (VPA) use is associated with parieto-occipital cortical thinning in patients with heterogeneous epilepsy syndromes. In this study, we examined the effect of VPA on the brain volume using a large number of homogenous patients with idiopathic generalized epilepsy. Voxel-based morphometry was used to compare regional gray matter (GM) volume between 112 patients currently taking VPA (VPA+ group), 81 patients not currently taking VPA (VPA- group), and 120 healthy subjects (control group). The VPA+ group showed a significant GM volume reduction in the bilateral cerebellum, hippocampus, insula, caudate nucleus, medial frontal cortex/anterior cingulate cortex, primary motor/premotor cortex, medial occipital cortex, and anteromedial thalamus, as compared to the control group. The VPA- group showed a significant GM volume reduction in the anteromedial thalamus and right hippocampus/temporal cortex, as compared to the control group. Compared to the VPA- group, the VPA+ group had a significant GM volume reduction in the bilateral cerebellum, primary motor/premotor cortex, and medial frontal cortex/anterior cingulate cortex. We have provided evidence that VPA use could result in GM volume reductions in the frontal cortex and cerebellum. Our findings should be acknowledged as a potential confounding factor in morphometric MRI studies that include subjects taking VPA.

Mindfulness-based randomized controlled trials led to brain structural changes: an anatomical likelihood meta-analysis.

Mindfulness has become increasingly popular and the practice presents in many different forms. Research has been growing extensively with benefits shown across various outcomes. However, there is a lack of consensus over the efficacy of randomized controlled mindfulness interventions, both traditional and mind-body formats. This study aimed to investigate the structural brain changes in mindfulness-based interventions through a meta-analysis. Scopus, PubMed, Web of Science, and PsycINFO were searched up to April 2023. 11 studies (n = 581) assessing whole-brain voxel-based grey matter or cortical thickness changes after a mindfulness RCT were included. Anatomical likelihood estimation was used to carry out voxel-based meta-analysis with leave-one-out sensitivity analysis and behavioural analysis as follow-ups. One significant cluster (p < 0.001, Z = 4.76, cluster size = 632 mm3) emerged in the right insula and precentral gyrus region (MNI = 48, 10, 4) for structural volume increases in intervention group compared to controls. Behavioural analysis revealed that the cluster was associated with mental processes of attention and somesthesis (pain). Mindfulness interventions have the ability to affect neural plasticity in areas associated with better pain modulation and increased sustained attention. This further cements the long-term benefits and neuropsychological basis of mindfulness-based interventions.

Associations between alcohol use and sex-specific maturation of subcortical gray matter morphometry from adolescence to adulthood: Replication across two longitudinal samples.

Subcortical brain morphometry matures across adolescence and young adulthood, a time when many youth engage in escalating levels of alcohol use. Initial cross-sectional studies have shown alcohol use is associated with altered subcortical morphometry. However, longitudinal evidence of sex-specific neuromaturation and associations with alcohol use remains limited. This project used generalized additive mixed models to examine sex-specific development of subcortical volumes and associations with recent alcohol use, using 7 longitudinal waves (n = 804, 51% female, ages 12-21 at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA). A second, independent, longitudinal dataset, with up to four waves of data (n = 467, 43% female, ages 10-18 at baseline), was used to assess replicability. Significant, replicable non-linear normative volumetric changes with age were evident in the caudate, putamen, thalamus, pallidum, amygdala and hippocampus. Significant, replicable negative associations between subcortical volume and alcohol use were found in the hippocampus in all youth, and the caudate and thalamus in female but not male youth, with significant interactions present in the caudate, thalamus and putamen. Findings suggest a structural vulnerability to alcohol use, or a predisposition to drink alcohol based on brain structure, with female youth potentially showing heightened risk, compared to male youth.

The diamagnetic component map from quantitative susceptibility mapping (QSM) source separation reveals pathological alteration in Alzheimer's disease-driven neurodegeneration.

A sensitive and accurate imaging technique capable of tracking the disease progression of Alzheimer's Disease (AD) driven amnestic dementia would be beneficial. A currently available method for pathology detection in AD with high accuracy is Positron Emission Tomography (PET) imaging, despite certain limitations such as low spatial resolution, off-targeting error, and radiation exposure. Non-invasive MRI scanning with quantitative magnetic susceptibility measurements can be used as a complementary tool. To date, quantitative susceptibility mapping (QSM) has widely been used in tracking deep gray matter iron accumulation in AD. The present work proposes that by compartmentalizing quantitative susceptibility into paramagnetic and diamagnetic components, more holistic information about AD pathogenesis can be acquired. Particularly, diamagnetic component susceptibility (DCS) can be a powerful indicator for tracking protein accumulation in the gray matter (GM), demyelination in the white matter (WM), and relevant changes in the cerebrospinal fluid (CSF). In the current work, voxel-wise group analysis of the WM and the CSF regions show significantly lower |DCS| (the absolute value of DCS) value for amnestic dementia patients compared to healthy controls. Additionally, |DCS| and τ PET standardized uptake value ratio (SUVr) were found to be associated in several GM regions typically affected by τ deposition in AD. Therefore, we propose that the separated diamagnetic susceptibility can be used to track pathological neurodegeneration in different tissue types and regions of the brain. With the initial evidence, we believe the usage of compartmentalized susceptibility demonstrates substantive potential as an MRI-based technique for tracking AD-driven neurodegeneration.

Structural changes in the thalamus and its subregions in regulating different symptoms of posttraumatic stress disorder.

As a key center for sensory information processing and transmission, the thalamus plays a crucial role in the development of posttraumatic stress disorder (PTSD). However, the changes in the thalamus and its role in regulating different PTSD symptoms remain unclear. In this study, fourteen PTSD patients and eighteen healthy controls (HCs) were recruited. All subjects underwent whole-brain T1-weighted three-dimensional Magnetization Prepared Rapid Gradient Echo Imaging scans. Gray matter volume (GMV) in the thalamus and its subregions were estimated using voxel-based morphometry (VBM). Compared to HCs, PTSD patients exhibited significant GMV reduction in the left thalamus and its subregions, including anterior, mediodorsal, ventral-lateral-dorsal (VLD), ventral-anterior, and ventral-lateral-ventral (VLV). Among the significantly reduced thalamic subregions, we found positive correlations between the GMV values of the left VLD and VLV and the re-experiencing symptoms score, arousal symptoms score, and total CAPS score. When using the symptom-related GMV values of left VLV and VLD in combination as a predictor, receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) for binary classification reached 0.813. This study highlights the neurobiological mechanisms of PTSD related to thalamic changes and may provide potential imaging markers for diagnosis and therapy targets.

Multimodal fusion of multiple rest fMRI networks and MRI gray matter via parallel multilink joint ICA reveals highly significant function/structure coupling in Alzheimer's disease.

In this article, we focus on estimating the joint relationship between structural magnetic resonance imaging (sMRI) gray matter (GM), and multiple functional MRI (fMRI) intrinsic connectivity networks (ICNs). To achieve this, we propose a multilink joint independent component analysis (ml-jICA) method using the same core algorithm as jICA. To relax the jICA assumption, we propose another extension called parallel multilink jICA (pml-jICA) that allows for a more balanced weight distribution over ml-jICA/jICA. We assume a shared mixing matrix for both the sMRI and fMRI modalities, while allowing for different mixing matrices linking the sMRI data to the different ICNs. We introduce the model and then apply this approach to study the differences in resting fMRI and sMRI data from patients with Alzheimer's disease (AD) versus controls. The results of the pml-jICA yield significant differences with large effect sizes that include regions in overlapping portions of default mode network, and also hippocampus and thalamus. Importantly, we identify two joint components with partially overlapping regions which show opposite effects for AD versus controls, but were able to be separated due to being linked to distinct functional and structural patterns. This highlights the unique strength of our approach and multimodal fusion approaches generally in revealing potentially biomarkers of brain disorders that would likely be missed by a unimodal approach. These results represent the first work linking multiple fMRI ICNs to GM components within a multimodal data fusion model and challenges the typical view that brain structure is more sensitive to AD than fMRI.

Thalamic asymmetry in Multiple Sclerosis.

BACKGROUND: Multiple Sclerosis (MS) is a chronic neuroinflammatory disease that affects the central nervous system. Asymmetry is one of the finding in brain MRI of these patients, which is related to the debilitating symptoms of the disease. This study aimed to investigate and compare the thalamic asymmetry in MS patients and its relationship with other MRI and clinical findings of these patients. METHODS: This cross-sectional study conducted on 83 patients with relapse-remitting MS (RRMS), 43 patients with secondary progressive MS (SPMS), and 89 healthy controls. The volumes of total intracranial, total gray matter, total white matter, lesions, thalamus, and also the thalamic asymmetry indices were calculated. The 9-hole peg test (9-HPT) and Expanded Disability Status Scale (EDSS) were assessed as clinical findings. RESULTS: We showed that the normalized whole thalamic volume in healthy subjects was higher than MS patients (both RRMS and SPMS). Thalamic asymmetry index (TAI) was significantly different between RRMS patients and SPMS patients (p = 0.011). The absolute value of TAI was significantly lower in healthy subjects than in RRMS (p < 0.001) and SPMS patients (p < 0.001), and SPMS patients had a higher absolute TAI compared to RRMS patients (p = 0.037). CONCLUSIONS: In this cross-sectional study we showed a relationship between normalized whole thalamic volume and MS subtype. Also, we showed that the asymmetric indices of the thalamus can be related to the progression of the disease. Eventually, we showed that thalamic asymmetry can be related to the disease progression and subtype changes in MS.

The role of emotional sensitivity to missed opportunity and grey matter volume of thalamus in risk-taking behaviour.

The ability to make suitable risky decision is necessary for individuals' survival and development. However, individuals vary in risk preference. The current study, adopting a decision task, aimed to explore the emotional sensitivity to missed opportunity and grey matter volume (GMV) of thalamus in high risk-takers by using voxel-based morphology analysis. In the task, eight boxes should be opened successively. Seven boxes contained coins and one box contained the devil to zero coins. Once stopped, collected and missed (missed opportunity) coins were presented. Participants were divided into high- and low risk-takers according to their risk-taking behaviour in the decision task. We found that high risk-takers showed stronger emotional sensitivity to missed opportunity and smaller GMV of thalamus than low risk-takers. In addition, the GMV of thalamus partially mediated the effect of emotional sensitivity to missed opportunity on risk-taking behaviour among all participants. Overall, the current study highlights the role of emotional sensitivity to missed opportunity and the GMV of thalamus in risk-taking behaviour, which helps us understand the possible reason for the variation among individuals in risk preference.

Functional connectivity of sub-cortical brain regions: disparities and similarities.

Sub-cortical grey matter structures, such as the putamen, pallidum, caudate, thalamus, amygdala and hippocampus, play substantial roles in both simple and complex brain functions, including regulation of pleasure and emotions; control of movements; learning; decision-making; language development; and sensory, cognitive, social and other higher-order functions. Most of these regions act as information hubs for the nervous system, relaying and controlling the flow of information to various portions of the brain. To further understand the complex neurophysiological characteristics of sub-cortical areas, the aim of this study was to investigate the functional integrations of six sub-cortical areas to different major functional brain networks. One hundred ninety-eight healthy individuals were examined using resting-state functional MRI. The seeds identified in this study were six sub-cortical deep grey matter regions, namely putamen, pallidum, caudate, thalamus, amygdala and hippocampus. The analysis indicated that the link between the sub-cortical regions and some functional brain networks was similar in some aspects, but there were disparities in the mechanism underlying such a link and in the existence of functional connections between these regions and networks. Despite the substantial functional connectivity linkages between the sub-cortical regions, discrepancies were still noted. On the basis of the connections to the majority of the major brain networks, this study demonstrated the essential functional roles and involvements of the sub-cortical regions. This finding is consistent with an earlier report that revealed a substantial role of the sub-cortical regions in several brain functions.

Abnormal cortical-striatal-thalamic-cortical circuit centered on the thalamus in MDD patients with somatic symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: Somatic symptoms are common comorbidities of major depressive disorder (MDD), and negatively impact the course and severity of the disease. In order to enrich the understanding of the pathological mechanism and clarify the neurobiological basis of somatic symptoms in depression, we attempted to explore the changes of brain structure and function in a large sample between depression with and without somatic symptoms. METHODS: Structure magnetic resonance imaging (MRI) data were collected from 342 patients with somatic symptoms (SD), 208 patients without somatic symptoms (NSD), and 510 healthy controls (HCs) based on the REST-meta-MDD project. We analyzed the whole brain VBM maps of the three groups, and combined with weight degree centrality (DC) index, we investigated whether the brain regions with gray matter volume (GMV) and gray matter density (GMD) abnormalities in MDD patients with somatic symptoms had corresponding brain functional abnormalities. RESULTS: Between depression with and without somatic symptoms, we found that there are extensive GMV and GMD differences involving cortical regions such as the temporal lobe, occipital lobe, and insula, as well as subcortical brain regions such as thalamus and striatum. The comparison results of weight DC signals of GMV and GMD abnormal clusters between the SD and NSD groups were basically consistent with the GMV and GMD abnormal clusters. CONCLUSION: The results indicate that the structure and function of cortical-striatal-thalamic-cortical (CSTC) circuit centered on the thalamus were abnormal in MDD patients with somatic symptoms. This may be the neurobiological basis of somatic symptoms in MDD.

The Fast Gray Matter Acquisition T1 Inversion Recovery Sequence in Deep Brain Stimulation: Introducing the Rubral Wing for Dentato-Rubro-Thalamic Tract Depiction and Tremor Control.

BACKGROUND: The dentato-rubro-thalamic tract (DRT) is currently considered as a potential target in deep brain stimulation (DBS) for various types of tremor. However, tractography depiction can vary depending on the included brain regions. The fast gray matter acquisition T1 inversion recovery (FGATIR) sequence, with excellent delineation of gray and white matter, possibly provides anatomical identification of rubro-thalamic DRT fibers. OBJECTIVE: This study aimed to evaluate the FGATIR sequence by comparison with DRT depiction, electrode localization, and effectiveness of DBS therapy. MATERIALS AND METHODS: In patients with DBS therapy because of medication-refractory tremor, the FGATIR sequence was evaluated for depiction of the thalamus, red nucleus (RN), and rubro-thalamic connections. Deterministic tractography of the DRT, electrode localization, and tremor control were compared. The essential tremor rating scale was used to assess (hand) tremor. Tremor control was considered successful when complete tremor suppression (grade 0) or almost complete suppression (grade 1) was observed. RESULTS: In the postoperative phase, we evaluated 14 patients who underwent DRT-guided DBS: 12 patients with essential tremor, one with tremor-dominant Parkinson disease, and one with multiple sclerosis, representing 24 trajectories. Mean follow-up was 11.3 months (range 6-19 months). The FGATIR sequence provided a clear delineation of a hypointense white matter tract within the hyperintense thalamus. In coronal plane, this tract was most readily recognizable as a "rubral wing," with the round RN as base and lateral triangular convergence. The deterministic DRT depiction was consistently situated within the rubral wing. The number of active contacts located within the DRT (and rubral wing) was 22 (92%), of which 16 (73%) showed successful tremor control. CONCLUSIONS: The FGATIR sequence offers visualization of the rubro-thalamic connections that form the DRT, most readily recognizable as a "rubral wing" in coronal plane. This sequence contributes to tractographic depiction of DRT and provides a direct anatomical DBS target area for tremor control.

Thalamic gray matter volume mediates the association between KIBRA polymorphism and olfactory function among older adults: a population-based study.

The kidney and brain expressed protein (KIBRA) rs17070145 polymorphism is associated with both structure and activation of the olfactory cortex. However, no studies have thus far examined whether KIBRA can be linked with olfactory function and whether brain structure plays any role in the association. We addressed these questions in a population-based cross-sectional study among rural-dwelling older adults. This study included 1087 participants derived from the Multidomain Interventions to Delay Dementia and Disability in Rural China, who underwent the brain MRI scans in August 2018 to October 2020; of these, 1016 took the 16-item Sniffin' Sticks identification test and 634 (62.40%) were defined with olfactory impairment (OI). Data were analyzed using the voxel-based morphometry analysis and general linear, logistic, and structural equation models. The KIBRA rs17070145 C-allele (CC or CT vs. TT genotype) was significantly associated with greater gray matter volume (GMV) mainly in the bilateral orbitofrontal cortex and left thalamus (P < 0.05) and with the multi-adjusted odds ratio of 0.73 (95% confidence interval 0.56-0.95) for OI. The left thalamic GMV could mediate 8.08% of the KIBRA-olfaction association (P < 0.05). These data suggest that the KIBRA rs17070145 C-allele is associated with a reduced likelihood of OI among older adults, partly mediated through left thalamic GMV.

The influence of visual deprivation on the development of the thalamocortical network: Evidence from congenitally blind children and adults.

The thalamus is heavily involved in relaying sensory signals to the cerebral cortex. A relevant issue is how the deprivation of congenital visual sensory information modulates the development of the thalamocortical network. The answer is unclear because previous studies on this topic did not investigate network development, structure-function combinations, and cognition-related behaviors in the same study. To overcome these limitations, we recruited 30 congenitally blind subjects (8 children, 22 adults) and 31 sighted subjects (10 children, 21 adults), and conducted multiple analyses [i.e., gray matter volume (GMV) analysis using the voxel-based morphometry (VBM) method, resting-state functional connectivity (FC), and brain-behavior correlation]. We found that congenital blindness elicited significant changes in the development of GMV in visual and somatosensory thalamic regions. Blindness also resulted in significant changes in the development of FC between somatosensory thalamic regions and visual cortical regions as well as advanced information processing regions. Moreover, the somatosensory thalamic regions and their FCs with visual cortical regions were reorganized to process high-level tactile language information in blind individuals. These findings provide a refined understanding of the neuroanatomical and functional plasticity of the thalamocortical network.

Effects of Mindfulness-Based Interventions on Gray Matter Volume in Patients with Opioid Dependence.

INTRODUCTION: Recently, several mindfulness-based programs showed promising clinical effects in the treatment of psychiatric disorders including substance use disorders. However, very little is known about the effects of mindfulness-based interventions (MBIs) on brain structure in such patients. METHODS: This study aimed to detect changes in gray matter volume (GMV) in opioid-dependent patients receiving MBI during their first month of treatment. Thirty patients were assigned to either 3 weeks of MBI (n = 16) or treatment as usual (TAU, n = 14) and were investigated using structural magnetic resonance imaging before and after treatment. Longitudinal pipeline of the Computational Anatomy Toolbox for SPM (CAT12) was used to detect significant treatment-related changes over time. The identified GMV changes following treatment were related to clinically relevant measures such as impulsivity, distress tolerance, and mindfulness. RESULTS: After treatment, increased mindfulness scores were found in individuals receiving MBI compared to TAU. In the MBI group, there were also significant differences with respect to distress tolerance and impulsivity. Effects on mindfulness, distress tolerance, and impulsivity were also found in the TAU group. Longitudinal within-group analysis revealed increased left anterior insula GMV in individuals receiving MBI. Anterior insula volume increase was associated with decreased impulsivity levels. In the TAU group, significant GMV changes were found in the right lingual gyrus and right entorhinal cortex. DISCUSSION/CONCLUSION: MBI can yield significant clinical effects during early abstinence from opioid dependence. MBI is particularly associated with increased insula GMV, supporting an important role of this region in the context of MBI-induced neural changes.

Altered dynamic functional connectivity of striatal-cortical circuits in Juvenile Myoclonic Epilepsy.

OBJECTIVE: To investigate whether the dynamic functional connectivity (dFC) of striatal-cortical circuits changes in juvenile myoclonic epilepsy (JME). METHODS: The resting-state EEG-fMRI and the sliding-window approach were adopted to explore the dynamic striatal-cortical circuitry in thirty JME patients compared with 30 well-matched health controls (HCs). Six pairs of striatal seeds were selected as regions of interests. The correlation analysis was performed to reveal the relationship between the altered dFC variability and clinical variables in JME group. RESULTS: JME patients exhibited increased dFC variability mainly involved in fronto-striatal and striatal-thalamic networks; decreased dFC variability between striatum subdivisions and default mode network (DMN) regions compared with HCs (p<0.05, GRF corrected). In addition, the hypervariability between left ventral-rostral putamen and left medial superior frontal gyrus was positively (r= 0.493, p=0.008) correlated with the mean frequency score of myoclonic seizures in JME group. CONCLUSION: JME presented altered dFC variability in striatal-cortical circuits. The pattern of altered circuits showed increased variability in fronto-striatal and striatal-thalamic networks and decreased variability in striatal-DMN. These results provide novel information about the dynamic neural striatal-cortical circuitry of JME.

tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel.

BACKGROUND AND OBJECTIVE: Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during anodal tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect. METHODS: Data from five previously conducted MRS studies were combined. The anode was placed over the left primary motor cortex (M1, 3 studies, N = 24) or right temporal cortex (2 studies, N = 32), with the cathode over the contralateral supraorbital ridge. Single voxel spectroscopy was performed in a 2x2x2cm voxel under the anode in all cases. MRS data were acquired before and either during or after 1 mA tDCS using either a sLASER sequence (7T) or a MEGA-PRESS sequence (3T). sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. E-fields were simulated in a finite element model of the head, based on individual structural MR images, using SimNIBS. Separate linear mixed effects models were run for each E-field variable (mean and 95th percentile; magnitude, and components normal and tangential to grey matter surface, within the MRS voxel). The model included effects of time (pre or post tDCS), E-field, grey matter volume in the MRS voxel, and a 3-way interaction between time, E-field and grey matter volume. Additionally, we ran a permutation analysis using PALM to determine whether E-field anywhere in the brain, not just in the MRS voxel, correlated with GABA change. RESULTS: In M1, higher mean E-field magnitude was associated with greater anodal tDCS-induced decreases in GABA (t(24) = 3.24, p = 0.003). Further, the association between mean E-field magnitude and GABA change was moderated by the grey matter volume in the MRS voxel (t(24) = -3.55, p = 0.002). These relationships were consistent across all E-field variables except the mean of the normal component. No significant relationship was found between tDCS-induced GABA decrease and E-field in the temporal voxel. No significant clusters were found in the whole brain analysis. CONCLUSIONS: Our data suggest that the electric field induced by tDCS within the brain is variable, and is significantly related to anodal tDCS-induced decrease in GABA, a key neurophysiological marker of stimulation. These findings strongly support individualised dosing of tDCS, at least in M1. Further studies examining E-fields in relation to other outcome measures, including behaviour, will help determine the optimal E-fields required for any desired effects.

Compensatory thalamocortical functional hyperconnectivity in type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is associated with brain damage and cognitive decline. Despite the fact that the thalamus involves aspects of cognition and is typically affected in T2DM, existing knowledge of subregion-level thalamic damage and its associations with cognitive performance in T2DM patients is limited. The thalamus was subdivided into 8 subregions in each hemisphere. Resting-state functional and structural MRI data were collected to calculate resting-state functional connectivity (rsFC) and gray matter volume (GMV) of each thalamic subregion in 62 T2DM patients and 50 healthy controls. Compared with controls, T2DM patients showed increased rsFC of the medial pre-frontal thalamus, posterior parietal thalamus, and occipital thalamus with multiple cortical regions. Moreover, these thalamic functional hyperconnectivity were associated with better cognitive performance and lower glucose variability in T2DM patients. However, there were no group differences in GMV for any thalamic subregions. These findings suggest a possible neural compensation mechanism whereby selective thalamocortical functional hyperconnectivity facilitated by better glycemic control help to preserve cognitive ability in T2DM patients, which may ultimately inform intervention and prevention of T2DM-related cognitive decline in real-world clinical settings.