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Recent resilience research has increasingly emphasized the importance of focusing on investigating the protective factors in mentally healthy populations, complementing the traditional focus on psychopathology. Social support has emerged as a crucial element within the complex interplay of individual and socio-environmental factors that shape resilience. However, the neural underpinnings of the relationship between social support and resilience, particularly in healthy subjects, remain largely unexplored. With advances in neuroimaging techniques, such as ultra-high field MRI at 7T and beyond, researchers can more effectively investigate the neural mechanisms underlying these factors. Thus, our study employed ultra-high field rs-fMRI to explore how social support moderates the relationship between psychological resilience and functional connectivity in a healthy cohort. We hypothesized that enhanced social support would amplify resilience-associated connectivity within neural circuits essential for emotional regulation, cognitive processing, and adaptive problem-solving, signifying a synergistic interaction where strong social networks bolster the neural underpinnings of resilience. (n = 30). Through seed-based functional connectivity analyses and interaction analysis, we aimed to uncover the neural correlates at the interplay of social support and resilience. Our findings indicate that perceived social support significantly (p

Abstract Currently, the metabotropic glutamate receptor 5 (mGluR5) is the subject of several lines of research in the context of neurology and is of high interest as a target for positron-emission tomography (PET). Here, we assessed the feasibility of using [11C]ABP688, a specific antagonist radiotracer for an allosteric site on the mGluR5, to evaluate changes in glutamatergic neurotransmission through a mismatch-negativity (MMN) task as a part of a simultaneous and synchronized multimodal PET/MR-EEG study. We analyzed the effect of MMN by comparing the changes in nondisplaceable binding potential (BPND) prior to (baseline) and during the task in 17 healthy subjects by applying a bolus/infusion protocol. Anatomical and functional regions were analyzed. A small change in BPND was observed in anatomical regions (posterior cingulate cortex and thalamus) and in a functional network (precuneus) after the start of the task. The effect size was quantified using Kendall’s W value and was 0.3. The motor cortex was used as a control region for the task and did not show any significant BPND changes. There was a significant ΔBPND between acquisition conditions. On average, the reductions in binding across the regions were - 8.6 ± 3.2% in anatomical and - 6.4 ± 0.5% in the functional network (p ≤ 0.001). Correlations between ΔBPND and EEG latency for both anatomical (p = 0.008) and functional (p = 0.022) regions were found. Exploratory analyses suggest that the MMN task played a role in the glutamatergic neurotransmission, and mGluR5 may be indirectly modulated by these changes.

Abstract Given the huge symptom diversity and complexity of mental disorders, an individual approach is the most promising avenue for clinical transfer and the establishment of personalized psychiatry. However, due to technical limitations, knowledge about the neurobiological basis of mental illnesses has, to date, mainly been based on findings resulting from evaluations of average data from certain diagnostic groups. We postulate that this could change substantially through the use of the emerging ultra-high-field MRI (UHF-MRI) technology. The main advantages of UHF-MRI include high signal-to-noise ratio, resulting in higher spatial resolution and contrast and enabling individual examinations of single subjects. Thus, we used this technology to assess changes in the properties of resting-state networks over the course of therapy in a naturalistic study of two depressed patients. Significant changes in several network property measures were found in regions corresponding to prior knowledge from group-level studies. Moreover, relevant parameters were already significantly divergent in both patients at baseline. In summary, we demonstrate the feasibility of UHF-MRI for capturing individual neurobiological correlates of mental diseases. These could serve as a tool for therapy monitoring and pave the way for a truly individualized and predictive clinical approach in psychiatric care.

Tourette syndrome (TS) is characterized by multiple motor and vocal tics, and high-comorbidity rates with other neuropsychiatric disorders. Obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), major depressive disorder (MDD), and anxiety disorders (AXDs) are among the most prevalent TS comorbidities. To date, studies on TS brain structure and function have been limited in size with efforts mostly fragmented. This leads to low-statistical power, discordant results due to differences in approaches, and hinders the ability to stratify patients according to clinical parameters and investigate comorbidity patterns. Here, we present the scientific premise, perspectives, and key goals that have motivated the establishment of the Enhancing Neuroimaging Genetics through Meta-Analysis for TS (ENIGMA-TS) working group. The ENIGMA-TS working group is an international collaborative effort bringing together a large network of investigators who aim to understand brain structure and function in TS and dissect the underlying neurobiology that leads to observed comorbidity patterns and clinical heterogeneity. Previously collected TS neuroimaging data will be analyzed jointly and integrated with TS genomic data, as well as equivalently large and already existing studies of highly comorbid OCD, ADHD, ASD, MDD, and AXD. Our work highlights the power of collaborative efforts and transdiagnostic approaches, and points to the existence of different TS subtypes. ENIGMA-TS will offer large-scale, high-powered studies that will lead to important insights toward understanding brain structure and function and genetic effects in TS and related disorders, and the identification of biomarkers that could help inform improved clinical practice.

Abstract The symbiosis of neuronal activities and glucose energy metabolism is reflected in the generation of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) signals. However, their association with the balance between neuronal excitation and inhibition (E/I-B), which is closely related to the activities of glutamate and γ-aminobutyric acid (GABA) and the receptor availability (RA) of GABAA and mGluR5, remains unexplored. This research investigates these associations during the resting state (RS) condition using simultaneously recorded PET/MR/EEG (trimodal) data. The trimodal data were acquired from three studies using different radio-tracers such as, [11C]ABP688 (ABP) (N = 9), [11C]Flumazenil (FMZ) (N = 10) and 2-[18F]fluoro-2-deoxy-d-glucose (FDG) (N = 10) targeted to study the mGluR5, GABAA receptors and glucose metabolism respectively. Glucose metabolism and neuroreceptor binding availability (non-displaceable binding potential (BPND)) of GABAA and mGluR5 were found to be significantly higher and closely linked within core resting-state networks (RSNs). The neuronal generators of EEG microstates and the fMRI measures were most tightly associated with the BPND of GABAA relative to mGluR5 BPND and the glucose metabolism, emphasising a predominance of inhibitory processes within in the core RSNs at rest. Changes in the neuroreceptors leading to an altered coupling with glucose metabolism may render the RSNs vulnerable to psychiatric conditions. The paradigm employed here will likely help identify the precise neurobiological mechanisms behind these alterations in fMRI functional connectivity and EEG oscillations, potentially benefitting individualised healthcare treatment measures.

Introduction: The insular cortex is part of a network of highly connected cerebral “rich club” - regions and has been implicated in the pathophysiology of various psychiatric and neurological disorders, of which major depressive disease is one of the most prevalent. “Rich club” vulnerability can be a contributing factor in disease development. High-resolution structural subfield analysis of insular volume in combination with cortical thickness measurements and psychological testing might elucidate the way in which the insula is changed in depression. Material and methods: High-resolution structural images of the brain were acquired using a 7T-MRI scanner. The mean grey matter volume and cortical thickness within the insular subfields were analysed using voxel-based morphometry (VBM) and surface analysis techniques respectively. Insular subfields were defined according to the Brainnetome Atlas for VBM - and the Destrieux-Atlas for cortical thickness - analysis. Thirty-three patients with confirmed major depressive disease, as well as thirty-one healthy controls matched for age and gender, were measured. The severity of depression in MDD patients was measured via a BDI-II score and objective clinical assessment (AMDP). Intergroup statistical analysis was performed using ANCOVA. An intragroup multivariate regression analysis of patient psychological test results was calculated. Corrections for multiple comparisons was performed using FDR. Results: Significant differences between groups were observed in the left granular dorsal insula according to VBM-analysis. AMDP-scores positively correlated with cortical thickness in the right superior segment of the circular insular sulcus. Conclusions: The combination of differences in grey matter volume between healthy controls and patients with a positive correlation of cortical thickness with disease severity underscores the insula’s role in the pathogeneses of MDD. The connectivity hub insular cortex seems vulnerable to disruption in context of affective disease.

The default mode network (DMN), the salience network (SN), and the central executive network (CEN) are considered as the core resting-state brain networks (RSN) due to their involvement in a wide range of cognitive tasks. Despite the large body of knowledge related to their regional spontaneous activity (RSA) and functional connectivity (FC) of these networks, less is known about the dynamics of the task-associated modulation on these parameters and the task-induced interaction between these three networks. We have investigated the effects of the visual-oddball paradigm on three fMRI measures (amplitude of low-frequency fluctuations for RSA, regional homogeneity for local FC, and degree centrality for global FC) in these three core RSN. A rest-task-rest paradigm was used and the RSNs were identified using independent component analysis (ICA) on the resting-state data. The observed patterns of change differed noticeably between the networks and were tightly associated with the task-related brain activity and the distinct involvement of the networks in the performance of the single subtasks. Furthermore, the inter-network analysis showed an increased synchronization of CEN with the DMN and the SN immediately after the task, but not between the DMN and SN. Higher pre-task inter-network synchronization between the DMN and the CEN was associated with shorter reaction times and thus better performance. Our results provide some additional insights into the dynamics within and between the triple RSN. Further investigations are required in order to understand better their functional importance and interplay.

Tourette Syndrome (TS) is a neuropsychiatric disorder characterized by the presence of motor and vocal tics. Major pathophysiological theories posit a dysfunction of the cortico-striato-thalamo-cortical circuits as being a representative hallmark of the disease. Recent evidence suggests a more widespread dysfunction of brain networks in TS including the cerebellum and going even beyond classic motor pathways.In order to characterize brain network dysfunction in TS, in this study we investigated functional and effective-like connectivity as well as topological changes of basal ganglia-thalamo-cortical and cortico-cerebellar brain networks. We collected resting-state fMRI data from 28 TS patients (age: 32 ± 11 years) and 28 age-matched, healthy controls (age: 31 ± 9 years). Region of interest based (ROI-ROI) bivariate correlation and ROI-ROI bivariate regression were employed as measures of functional and effective-like connectivity, respectively. Graph theoretical measures of centrality (degree, cost, betweenness centrality), functional segregation (clustering coefficient, local efficiency) and functional integration (average path length, global efficiency) were used to assess topological brain network changes.In this study, TS patients exhibited increased basal ganglia-cortical and thalamo-cortical connectivity, reduced cortico-cerebellar connectivity, and an increase in parallel communication through the basal ganglia, thalamus and cerebellum (increased global efficiency). Additionally, we observed a reduction in serial information transfer (reduction in average path length) within the default mode and the salience network.In summary, our findings show that TS is characterized by increased connectivity and functional integration of multiple basal ganglia-thalamo-cortical circuits, suggesting a predominance of excitatory neurotransmission and a lack of brain maturation. Moreover, topological changes of cortico-cerebellar and brain networks involved in interoception may be underestimated neural correlates of tics and the crucial premonitory urge feeling. Keywords: Tourette's syndrome, Connectivity, Basal ganglia, Cerebellum, Brain network topology