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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

ObjectiveQuantitative values derived from PET brain images are of high interest for neuroscientific applications. Insufficient DT correction (DTC) can lead to a systematic bias of the output parameters obtained by a detailed analysis of the time activity curves (TACs). The DTC method currently used for the Siemens 3T MR BrainPET insert is global, i.e., differences in DT losses between detector blocks are not considered, leading to inaccurate DTC and, consequently, to inaccurate measurements masked by a bias. However, following careful evaluation with phantom measurements, a new block-pairwise DTC method has demonstrated a higher degree of accuracy compared to the global DTC method.ApproachDifferences between the global and the block-pairwise DTC method were studied in this work by applying several radioactive tracers. We evaluated the impact on [11C]ABP688, O-(2-[18F]fluoroethyl)-L-tyrosine (FET), and [15O]H2O TACs.ResultsFor [11C]ABP688, a relevant bias of between -0.0034 and -0.0053 ml/ (cm3 • min) was found in all studied brain regions for the volume of distribution (VT) when using the current global DTC method. For [18F]FET-PET, differences of up to 10% were observed in the tumor-to-brain ratio (TBRmax), these differences depend on the radial distance of the maximum from the PET isocenter. For [15O]H2O, differences between +4% and -7% were observed in the GM region. Average biases of -4.58%, -3.2%, and -1.2% for the regional cerebral blood flow (CBF (K1)), the rate constant k2, and the volume of distribution VT were observed, respectively. Conversely, in the white matter region, average biases of -4.9%, -7.0%, and 3.8% were observed for CBF (K1), k2, and VT, respectively.ConclusionThe bias introduced by the global DTC method leads to an overestimation in the studied quantitative parameters for all applications compared to the block-pairwise method.SignificanceThe observed differences between the two DTC methods are particularly relevant for research applications in neuroscientific studies as they affect the accuracy of quantitative Brain PET images.

Diffusion tensor imaging (DTI) enables the assessment of changes in brain tissue microstructure during maturation and ageing. In general, patterns of cerebral maturation and decline render non-monotonic lifespan trajectories of DTI metrics with age, and, importantly, the rate of microstructural changes is heterochronous for various white matter fibres. Recent studies have demonstrated that diffusion kurtosis imaging (DKI) metrics are more sensitive to microstructural changes during ageing compared to those of DTI. In a previous work, we demonstrated that the Cohen’s d of mean diffusional kurtosis (dMK) represents a useful biomarker for quantifying maturation heterochronicity. However, some inferences on the maturation grades of different fibre types, such as association, projection, and commissural, were of a preliminary nature due to the insufficient number of fibres considered. Hence, the purpose of this follow-up work was to further explore the heterochronicity of microstructural maturation between pre-adolescence and middle adulthood based on DTI and DKI metrics. Using the effect size of the between-group parametric changes and Cohen’s d, we observed that all commissural fibres achieved the highest level of maturity, followed by the majority of projection fibres, while the majority of association fibres were the least matured. We also demonstrated that dMK strongly correlates with the maxima or minima of the lifespan curves of DTI metrics. Furthermore, our results provide substantial evidence for the existence of spatial gradients in the timing of white matter maturation. In conclusion, our data suggest that DKI provides useful biomarkers for the investigation of maturation spatial heterogeneity and heterochronicity.

The cognitive impact of psychological trauma can manifest as a range of post-traumatic stress symptoms that are often attributed to impairments in learning from positive and negative outcomes, aka reinforcement learning. Research on the impact of trauma on reinforcement learning has mainly been inconclusive. This study aimed to circumscribe the impact of psychological trauma on reinforcement learning in the context of neural response in time and frequency domains. Two groups of participants were tested - those who had experienced psychological trauma and a control group who had not - while they performed a probabilistic classification task that dissociates learning from positive and negative feedback during a magnetoencephalography (MEG) examination. While the exposure to trauma did not exhibit any effects on learning accuracy or response time for positive or negative feedback, MEG cortical activity was modulated in response to positive feedback. In particular, the medial and lateral orbitofrontal cortices (mOFC and lOFC) exhibited increased activity, while the insular and supramarginal cortices showed decreased activity during positive feedback presentation. Furthermore, when receiving negative feedback, the trauma group displayed higher activity in the medial portion of the superior frontal cortex. The timing of these activity changes occurred between 160 and 600 ms post feedback presentation. Analysis of the time-frequency domain revealed heightened activity in theta and alpha frequency bands (4–10 Hz) in the lOFC in the trauma group. Moreover, dividing the two groups according to their learning performance, the activity for the non-learner subgroup was found to be lower in lOFC and higher in the supramarginal cortex. These differences were found in the trauma group only. The results highlight the localization and neural dynamics of feedback processing that could be affected by exposure to psychological trauma. This approach and associated findings provide a novel framework for understanding the cognitive correlates of psychological trauma in relation to neural dynamics in the space, time, and frequency domains. Subsequent work will focus on the stratification of cognitive and neural correlates as a function of various symptoms of psychological trauma. Clinically, the study findings and approach open the possibility for neuromodulation interventions that synchronize cognitive and psychological constructs for individualized treatment.

Neural fingerprinting is the identification of individuals in a cohort based on neuroimaging recordings of brain activity. In magneto- and electroencephalography (M/EEG), it is common practice to use second-order statistical measures, such as correlation or connectivity matrices, when neural fingerprinting is performed. These measures or features typically require coupling between signal channels and often ignore the individual temporal dynamics. In this study, we show that, following recent advances in multivariate time series classification, such as the development of the RandOm Convolutional KErnel Transformation (ROCKET) classifier, it is possible to perform classification directly on short time segments from MEG resting-state recordings with remarkably high classification accuracies. In a cohort of 124 subjects, it was possible to assign windows of time series of 1 s in duration to the correct subject with above 99% accuracy. The achieved accuracies are vastly superior to those of previous methods while simultaneously requiring considerably shorter time segments.

Abstract Background For positron emission tomography (PET) ligands, such as [11C]ABP688, to be able to provide more evidence about the glutamatergic hypothesis in schizophrenia (SZ), quantification bias during dynamic PET studies and its propagation into the estimated values of non-displaceable binding potential (BPND) must be addressed. This would enable more accurate quantification during bolus + infusion (BI) neuroreceptor studies and further our understanding of neurological diseases. Previous studies have shown BPND-related biases can often occur due to overestimated cerebellum activity (reference region). This work investigates whether an alternative framing scheme can minimize quantification biases propagated into BPND, whether confounders, such as smoking status, need to be controlled for during the study, and what the consequences for the data interpretation following analysis are. A group of healthy controls (HC) and a group of SZ patients (balanced and unbalanced number of smokers) were investigated with [11C]ABP688 and a BI protocol. Possible differences in BPND quantification as a function of smoking status were tested with constant 5 min (‘Const 5 min’) and constant true counts (‘Const Trues’) framing schemes. In order to find biomarkers for SZ, the differences in smoking effects were compared between groups. The normalized BPND and the balanced number of smokers and non-smokers for both framing schemes were evaluated. Results When applying F-tests to the ‘Const 5 min’ framing scheme, effect sizes (η2p) and brain regions which showed significant effects fluctuated considerably with F = 50.106 ± 54.948 (9.389 to 112.607), P-values 0.005 to

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.

Abstract Despite numerous studies investigating resilience and personality trials, a paucity of information regarding their neurobiological commonalities at the level of the large resting-state networks (rsNWs) remains. Here we address this topic using the advantages of ultra-high-field (UHF) 7T-MRI, characterized by higher signal-to-noise ratio and increased sensitivity. The association between resilience, personality traits and three fMRI measures (fractional amplitude of low-frequency fluctuations (fALFF), degree centrality (DC) and regional homogeneity (ReHo)) determined for three core rsNWs (default mode (DMN), salience (SN), and central executive network (CEN)) were examined in 32 healthy volunteers. The investigation revealed a significant role of SN in both resilience and personality traits and a tight association of the DMN with resilience. DC in CEN emerged as a significant moderator for the correlations of resilience with the personality traits of neuroticism and extraversion. Our results indicate that the common neurobiological basis of resilience and the Big Five personality traits may be reflected at the level of the core rsNWs.

Dysregulated frontostriatal circuitries are viewed as a common target for the treatment of aberrant behaviors in various psychiatric and neurological disorders. Accordingly, experimental neurofeedback paradigms have been applied to modify the frontostriatal circuitry. The human frontostriatal circuitry is topographically and functionally organized into the “limbic,” the “associative,” and the “motor” subsystems underlying a variety of affective, cognitive, and motor functions. We conducted a systematic review of the literature regarding functional magnetic resonance imaging-based neurofeedback studies that targeted brain activations within the frontostriatal circuitry. Seventy-nine published studies were included in our survey. We assessed the efficacy of these studies in terms of imaging findings of neurofeedback intervention as well as behavioral and clinical outcomes. Furthermore, we evaluated whether the neurofeedback targets of the studies could be assigned to the identifiable frontostriatal subsystems. The majority of studies that targeted frontostriatal circuitry functions focused on the anterior cingulate cortex, the dorsolateral prefrontal cortex, and the supplementary motor area. Only a few studies (n = 14) targeted the connectivity of the frontostriatal regions. However, post-hoc analyses of connectivity changes were reported in more cases (n = 32). Neurofeedback has been frequently used to modify brain activations within the frontostriatal circuitry. Given the regulatory mechanisms within the closed loop of the frontostriatal circuitry, the connectivity-based neurofeedback paradigms should be primarily considered for modifications of this system. The anatomical and functional organization of the frontostriatal system needs to be considered in decisions pertaining to the neurofeedback targets.

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 Taylor Aggression Paradigm (TAP) has been widely used to measure reactive aggression following provocation during competitive interactions. Besides being reactive, aggression can be goal-directed (proactive aggression). Our study presents a novel paradigm to investigate proactive aggression during competitive interactions. Sixty-seven healthy participants competed in two modified versions of the TAP against an ostensible opponent while skin conductance responses (SCRs) were recorded. During the proactive TAP (pTAP), only the participant could interfere with the ostensible opponent’s performance by blurring the screen. In the reactive TAP (rTAP), the opponent repeatedly provoked the participant by blurring the screen of the participant, impeding their chance to win. In both versions, the blurriness levels chosen by the participant served as a measure of aggression (unprovoked in the pTAP and provoked in the rTAP). In the pTAP, trial-by-trial mixed model analyses revealed higher aggression with higher self-reported selfishness. SCRs decreased with increasing proactive aggression. An interaction effect between gender and proactive aggression for the SCRs revealed increased SCRs at higher aggression levels in females, but lower SCRs at higher aggression levels in males. In the rTAP, SCRs were not associated with reactive aggression but aggression increased with increasing provocation and especially after losing against the opponent when provoked. While males showed higher aggression levels than females when unprovoked, reactive aggression increased more strongly in females with higher provocation. Mean levels of aggression in both tasks showed a high positive correlation. Our results highlight that, despite being intercorrelated and both motivated by selfishness, proactive and reactive aggression are differentially influenced by gender and physiological arousal. Proactive aggression is related to lower physiological arousal, especially in males, with females showing the opposite association. Reactive aggressive behavior is a result of individual responses to provocation, to which females seem to be more sensitive.

Iterative image reconstruction is widely used in positron emission tomography. However, it is known to contribute to quantitation bias and is particularly pronounced during dynamic studies with 11C-labeled radiotracers where count rates become low towards the end of the acquisition. As the strength of the quantitation bias depends on the counts in the reconstructed frame, it can differ from frame to frame of the acquisition. This is especially relevant in the case of neuro-receptor studies with simultaneous PET/MR when a bolus-infusion protocol is applied to allow the comparison of pre- and post-task effects. Here, count dependent changes in quantitation bias may interfere with task changes. We evaluated the impact of different framing schemes on quantitation bias and its propagation into binding potential (BP) using a phantom decay study with 11C and 3D OP-OSEM. Further, we propose a framing scheme that keeps the true counts per frame constant over the acquisition time as constant framing schemes and conventional increasing framing schemes are unlikely to achieve stable bias values during the acquisition time range. For a constant framing scheme with 5 minutes frames, the BP bias was 7.13±2.01% (10.8% to 3.8%) compared to 5.63±2.85% (7.8% to 4.0%) for conventional increasing framing schemes. Using the proposed constant true counts framing scheme, a stabilization of the BP bias was achieved at 2.56±3.92% (3.5% to 1.7%). The change in BP bias was further studied by evaluating the linear slope during the acquisition time interval. The lowest slope values were observed in the constant true counts framing scheme. The constant true counts framing scheme was effective for BP bias stabilization at relevant activity and time ranges. The mean BP bias under these conditions was 2.56±3.92%, which represents the lower limit for the detection of changes in BP during equilibrium and is especially important in the case of cognitive tasks where the expected changes are low.

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.

The use of hybrid PET/MR imaging facilitates the simultaneous investigation of challenge-related changes in ligand binding to neuroreceptors using PET, while concurrently measuring neuroactivation or blood flow with MRI. Having attained a steady state of the PET radiotracer using a bolus-infusion protocol, it is possible to observe alterations in ligand neuroreceptor binding through changes in distribution volumes. Here, we present an iterative procedure for establishing an administration scheme to obtain steady state [11C]flumazenil concentrations in grey matter in the human brain. In order to achieve a steady state in the shortest possible time, the bolus infusion ratio from a previous examination was adapted to fit the subsequent examination. 17 male volunteers were included in the study. Boli and infusions with different weightings were given to the subjects and were characterised by kbol values from 74 ​min down to 42 ​min. Metabolite analysis was used to ascertain the value of unmetabolised flumazenil in the plasma, and PET imaging was used to assess its binding in the grey matter. The flumazenil time-activity curves (TACs) in the brain were decomposed into activity contributions from pure grey and white matter and analysed for 12 ​vol of interest (VOIs). The curves highlighted a large variability in metabolic rates between the subjects, with kbol ​= ​54.3 ​min being a reliable value to provide flumazenil equilibrium conditions in the majority of the VOIs and cases. The distribution volume of flumazenil in all 12 VOIs was determined.

Psychomotor disturbance has been consistently regarded as an essential feature of depressive disorders. Studying objectively measurable motor behaviors like finger-tapping may help advance the diagnostic methods.Twenty-five patients with major depressive disorder (MDD) and 15 healthy participants underwent functional magnetic resonance imaging (fMRI) measurements while tapping their index fingers. The finger-tapping (FT) task was performed by the right hand (the tapping frequency varied between 1, 2 and 4 Hz) or both hands either in synchrony or alternation (the tapping frequency varied between 1 and 2 Hz). A mixed-model ANOVA was used for between- and within-group comparisons of the task accuracy and fMRI percent signal change in the supplementary motor area (SMA) during 26-second sequences of finger-tapping. Furthermore, using seed-based correlation analyses we compared the connectivity of the SMA between the two samples.At the behavioral level, no significant group differences in FT performance between the patient and control groups was observed. The mean fMRI percent signal change of the SMA was significantly elevated at higher levels of speed in both groups. In the MDD group, an increased connectivity of the left SMA with the bilateral cortical and cerebellar motor- and vision-related regions was found. Most importantly, a decreased connectivity between the SMA and the basal ganglia was found at frequencies of 4 Hz.Our findings support the contention that, in depression, brain connectivity measures during motor performance may reveal deviant neural processes that are potentially relevant to measurable (bio)markers for individual diagnosis and treatment. Keywords: Finger-tapping, Depression, SMA, Seed-based connectivity, Fronto-striatal

Self-relevant functional abnormalities and identity disorders constitute the core psychopathological components in borderline personality disorder (BPD). Evidence suggests that appraising the relevance of environmental information to the self may be altered in BPD. However, only a few studies have examined self-relevance (SR) in BPD, and the neural correlates of SR processing has not yet been investigated in this patient group. The current study sought to evaluate brain activation differences between female patients with BPD and healthy controls during SR processing. A task-based fMRI paradigm was applied to evaluate SR processing in 23 female patients with BPD and 23 matched healthy controls. Participants were presented with a set of short sentences and were instructed to rate the stimuli. The differences in fMRI signals between SR rating (task of interest) and valence rating (control task) were examined. During SR rating, participants showed elevated activations of the cortical midline structures (CMS), known to be involved in the processing of self-related stimuli. Furthermore, we observed an elevated activation of the supplementary motor area (SMA) and the regions belonging to the mirror neuron system (MNS). Using whole-brain, seed-based connectivity analysis on the task-based fMRI data, we studied connectivity of networks anchored to the main CMS regions. We found a discrepancy in the connectivity pattern between patients and controls regarding connectivity of the CMS regions with the basal ganglia-thalamus complex. These observations have two main implications: First, they confirm the involvement of the CMS in SR evaluations of our stimuli and add evidence about the involvement of an extended network including the MNS and the SMA in this task. Second, the functional connectivity profile observed in BPD provides evidence for an altered functional interplay between the CMS and the brain regions involved in salience detection and reward evaluation, including the basal ganglia and the thalamus.

In the past, the eloquent areas could be deliberately localised by the invasive Wada test. The very rare cases of dissociated crossed speech areas were accidentally found based on the clinical symptomatology. Today functional magnetic resonance imaging (fMRI)-based imaging can be employed to non-invasively localise the eloquent areas in brain tumour patients for therapy planning. A 41-year-old, left-handed man with a low-grade glioma in the left frontal operculum extending to the insular cortex, tension headaches, and anomic aphasia over 5 months underwent a pre-operative speech area localisation fMRI measurement, which revealed the evidence of the transhemispheric disposition, where the dominant Wernicke speech area is located on the left and the Broca’s area is strongly lateralised to the right hemisphere. The outcome of the Wada test and the intraoperative cortico-subcortical stimulation mapping were congruent with this finding. After tumour removal, language area function was fully preserved. Upon the occurrence of brain tumours with a risk of impaired speech function, the rare dissociate crossed speech areas disposition may gain a clinically relevant meaning by allowing for more extended tumour removal. Hence, for its identification, diagnostics which take into account both brain hemispheres, such as fMRI, are recommended.

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

Tourette syndrome is a chronic tic disorder characterized by motor and vocal tics. Comorbidities such as attention deficit hyperactivity disorder and obsessive compulsive disorder can be found. The overlap between neuroanatomical regions and neurotransmitter systems in the olfactory system and the pathophysiology of Tourette syndrome let us hypothesize altered olfactory performance in Tourette syndrome. The main objective of this study was to systematically assess olfactory functioning in subjects with Tourette syndrome and to compare it to healthy controls. We assessed 28 adults with Tourette syndrome (age 33.1±9.4 years, disease duration 23.7±9.7 years) and 28 healthy controls (age 32.9±9.0 years) matched in regard to age, sex, education and smoking habits. The "Sniffin Sticks" test battery was applied to assess odor threshold, discrimination, and identification. Additionally, the combined score of the odor threshold test, the odor discrimination test and the odor identification test of the "Sniffin Sticks" test battery was calculated. Although it was not the primary aim of this study, we assessed whether tics and comorbidity could contribute to olfactory alterations in adults with Tourette syndrome. Therefore, clinical scores were used to assess severity of tics and co-morbidity such as attention deficit hyperactivity disorder, obsessive compulsive disorder, anxiety and depression in subjects with Tourette syndrome. Pathology of the nasal cavities was excluded with rhinoendoscopy. Independent sample t-tests were applied to compare performance in olfactory tests. In the case of statistically significant differences (critical p-value: 0.05), multiple linear regression analysis was carried out to explore whether tic severity, social impairment, co-morbidity or medical treatment had an impact on the differences found. Descriptive values are reported as mean ± standard deviation. Tourette syndrome subjects showed lower combined scores (Tourette syndrome subjects 31.9 ± 5.1 versus healthy controls 35.0 ± 3.1; p = 0.007), odor identification scores (Tourette syndrome subjects 12.4 ± 2.0 versus healthy controls 13.7 ± 1.4; p = 0.008) and odor discrimination scores (Tourette syndrome subjects 12.1 ± 2.1 versus healthy controls 13.2 ± 1.6; p = 0.041) in comparison to healthy subjects, while there was no difference in odor threshold (Tourette syndrome subjects 7.3 ± 2.7 versus healthy controls 8.1 ± 2.2; p = 0.22). Seven out of 28 Tourette syndrome subjects (25%) scored in the range of the age- and sex-dependent combined score for hyposmia, while two of 28 healthy controls (7%) had a similar low combined score. None of the participants were found to have functional anosmia. Multiple linear regression analyses suggest that social impairment may a predictor for low combined score and odor identification score in Tourette syndrome subjects (p = 0.003). Compared to healthy controls, altered olfaction in adults with Tourette syndrome was found in this study. Normal odor threshold level but lower scores at tasks involving supra-threshold odor concentrations point towards a central-nervous alteration in the processing of olfactory information in Tourette syndrome.

Trimodal simultaneous acquisition of positron emission tomography (PET), magnetic resonance imaging (MRI), and electroencephalography (EEG) has become feasible due to the development of hybrid PET-MR scanners. To capture the temporal dynamics of neuronal activation on a millisecond-by-millisecond basis, an EEG system is appended to the quantitative high resolution PET-MR imaging modality already established in our institute. One of the major difficulties associated with the development of simultaneous trimodal acquisition is that the components traditionally used in each modality can cause interferences in its counterpart. The mutual interferences of MRI components and PET components on PET and MR images, and the influence of EEG electrodes on functional MRI images have been studied and reported on. Building on this, this study aims to investigate the influence of the EEG cap on the quality and quantification of PET images acquired during simultaneous PET-MR measurements. A preliminary transmission scan study on the ECAT HR+ scanner, using an Iida phantom, showed visible attenuation effect due to the EEG cap. The BrainPET-MR emission images of the Iida phantom with [18F]Fluordeoxyglucose, as well as of human subjects with the EEG cap, did not show significant effects of the EEG cap, even though the applied attenuation correction did not take into account the attenuation of the EEG cap itself.

The role of neurotransmitters in the activity of resting state networks has been gaining attention and has become a field of research with magnetic resonance spectroscopy (MRS) being one of the key techniques. MRS permits the measurement of γ-aminobutyric acid (GABA) and glutamate levels, the central biochemical constituents of the excitation-inhibition balance in vivo. The inhibitory effects of GABA in the brain have been largely investigated in relation to the activity of resting state networks in functional magnetic resonance imaging (fMRI). In this study GABA concentration in the posterior cingulate cortex (PCC) was measured using single voxel spectra acquired with standard point resolved spectroscopy (PRESS) from 20 healthy male volunteers at 3 T. Resting state fMRI was consecutively measured and the values of GABA/Creatine+Phosphocreatine ratio (GABA ratio) were included in a general linear model matrix as a step of dual regression analysis in order to identify voxels whose neuroimaging metrics during rest were related to individual levels of the GABA ratio. Our data show that the connection strength of putamen to the default-mode network during resting state has a negative linear relationship with the GABA ratio measured in the PCC. These findings highlight the role of PCC and GABA in segregation of the motor input, which is an inherent condition that characterises resting state.

Electroencephalography (EEG) frequencies have been linked to specific functions as an "electrophysiological signature" of a function. A combination of oscillatory rhythms has also been described for specific functions, with or without predominance of one specific frequency-band. In a simultaneous fMRI-EEG study at 3 T we studied the relationship between the default mode network (DMN) and the power of EEG frequency bands. As a methodological approach, we applied Multivariate Exploratory Linear Optimized Decomposition into Independent Components (MELODIC) and dual regression analysis for fMRI resting state data. EEG power for the alpha, beta, delta and theta-bands were extracted from the structures forming the DMN in a region-of-interest approach by applying Low Resolution Electromagnetic Tomography (LORETA). A strong link between the spontaneous BOLD response of the left parahippocampal gyrus and the delta-band extracted from the anterior cingulate cortex was found. A positive correlation between the beta-1 frequency power extracted from the posterior cingulate cortex (PCC) and the spontaneous BOLD response of the right supplementary motor cortex was also established. The beta-2 frequency power extracted from the PCC and the precuneus showed a positive correlation with the BOLD response of the right frontal cortex. Our results support the notion of beta-band activity governing the "status quo" in cognitive and motor setup. The highly significant correlation found between the delta power within the DMN and the parahippocampal gyrus is in line with the association of delta frequencies with memory processes. We assumed "ongoing activity" during "resting state" in bringing events from the past to the mind, in which the parahippocampal gyrus is a relevant structure. Our data demonstrate that spontaneous BOLD fluctuations within the DMN are associated with different EEG-bands and strengthen the conclusion that this network is characterized by a specific electrophysiological signature created by combination of different brain rhythms subserving different putative functions.

Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) provides high spatial and temporal resolution. In this study we combined EEG and fMRI to investigate the structures involved in the processing of different sound pressure levels (SPLs).EEG data were recorded simultaneously with fMRI from 16 healthy volunteers using MR compatible devices at 3 T. Tones with different SPLs were delivered to the volunteers and the N1/P2 amplitudes were included as covariates in the fMRI data analysis in order to compare the structures activated with high and low SPLs. Analysis of variance (ANOVA) and ROI analysis were also performed. Additionally, source localisation analysis was performed on the EEG data.The integration of averaged ERP parameters into the fMRI analysis showed an extended map of areas exhibiting covariation with the BOLD signal related to the auditory stimuli. The ANOVA and ROI analyses also revealed additional brain areas other than the primary auditory cortex (PAC) which were active with the auditory stimulation at different SPLs. The source localisation analyses showed additional sources apart from the PAC which were active with the high SPLs.The PAC and the insula play an important role in the processing of different SPLs. In the fMRI analysis, additional activation was found in the anterior cingulate cortex, opercular and orbito-frontal cortices with high SPLs. A strong response of the visual cortex was also found with the high SPLs, suggesting the presence of cross-modal effects.

Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) allow for a non-invasive investigation of cerebral functions with high temporal and spatial resolution. The main challenge of such integration is the removal of the pulse artefact (PA) that affects EEG signals recorded in the magnetic resonance (MR) scanner. Often applied techniques for this purpose are Optimal Basis Set (OBS) and Independent Component Analysis (ICA). The combination of OBS and ICA is increasingly used, since it can potentially improve the correction performed by each technique separately. The present study is focused on the OBS-ICA combination and is aimed at providing the optimal ICA parameters for PA correction in resting-state EEG data, where the information of interest is not specified in latency and amplitude as in, for example, evoked potential. A comparison between two intervals for ICA calculation and four methods for marking artefactual components was performed. The performance of the methods was discussed in terms of their capability to 1) remove the artefact and 2) preserve the information of interest. The analysis included 12 subjects and two resting-state datasets for each of them. The results showed that none of the signal lengths for the ICA calculation was highly preferable to the other. Among the methods for the identification of PA-related components, the one based on the wavelets transform of each component emerged as the best compromise between the effectiveness in removing PA and the conservation of the physiological neuronal content.

Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has shown a number of advantages that make this multimodal technique superior to fMRI alone. The feasibility of recording EEG at ultra-high static magnetic field up to 9.4 T was recently demonstrated and promises to be implemented soon in fMRI studies at ultra high magnetic fields. Recording visual evoked potentials are expected to be amongst the most simple for simultaneous EEG/fMRI at ultra-high magnetic field due to the easy assessment of the visual cortex. Auditory evoked P300 measurements are of interest since it is believed that they represent the earliest stage of cognitive processing. In this study, we investigate the feasibility of recording visual evoked potentials and auditory evoked P300 in a 9.4 T static magnetic field. For this purpose, EEG data were recorded from 26 healthy volunteers inside a 9.4 T MR scanner using a 32-channel MR compatible EEG system. Visual stimulation and auditory oddball paradigm were presented in order to elicit evoked related potentials (ERP). Recordings made outside the scanner were performed using the same stimuli and EEG system for comparison purposes. We were able to retrieve visual P100 and auditory P300 evoked potentials at 9.4 T static magnetic field after correction of the ballistocardiogram artefact using independent component analysis. The latencies of the ERPs recorded at 9.4 T were not different from those recorded at 0 T. The amplitudes of ERPs were higher at 9.4 T when compared to recordings at 0 T. Nevertheless, it seems that the increased amplitudes of the ERPs are due to the effect of the ultra-high field on the EEG recording system rather than alteration in the intrinsic processes that generate the electrophysiological responses.

Cognitive task demands in one sensory modality (T1) can have beneficial effects on a secondary task (T2) in a different modality, due to reduced top-down control needed to inhibit the secondary task, as well as crossmodal spread of attention. This contrasts findings of cognitive load compromising a secondary modality's processing. We manipulated cognitive load within one modality (visual) and studied the consequences of cognitive demands on secondary (auditory) processing. 15 healthy participants underwent a simultaneous EEG-fMRI experiment. Data from 8 participants were obtained outside the scanner for validation purposes. The primary task (T1) was to respond to a visual working memory (WM) task with four conditions, while the secondary task (T2) consisted of an auditory oddball stream, which participants were asked to ignore. The fMRI results revealed fronto-parietal WM network activations in response to T1 task manipulation. This was accompanied by significantly higher reaction times and lower hit rates with increasing task difficulty which confirmed successful manipulation of WM load. Amplitudes of auditory evoked potentials, representing fundamental auditory processing showed a continuous augmentation which demonstrated a systematic relation to cross-modal cognitive load. With increasing WM load, primary auditory cortices were increasingly deactivated while psychophysiological interaction results suggested the emergence of auditory cortices connectivity with visual WM regions. These results suggest differential effects of crossmodal attention on fundamental auditory processing. We suggest a continuous allocation of resources to brain regions processing primary tasks when challenging the central executive under high cognitive load.