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The posterior cingulate cortex (PCC) is a key hub of the default mode network and is known to play an important role in attention. Using ultra-high field 7 Tesla magnetic resonance spectroscopy (MRS) to quantify neurometabolite concentrations, this exploratory study investigated the effect of the concentrations of myo-inositol (Myo-Ins), glutamate (Glu), glutamine (Gln), aspartate or aspartic acid (Asp) and gamma-amino-butyric acid (GABA) in the PCC on attention in forty-six healthy participants. Each participant underwent an MRS scan and cognitive testing, consisting of a trail-making test (TMT A/B) and a test of attentional performance. After a multiple regression analysis and bootstrapping for correction, the findings show that Myo-Ins and Asp significantly influence (p < 0.05) attentional tasks. On one hand, Myo-Ins shows it can improve the completion times of both TMT A and TMT B. On the other hand, an increase in aspartate leads to more mistakes in Go/No-go tasks and shows a trend towards enhancing reaction time in Go/No-go tasks and stability of alertness without signal. No significant (p > 0.05) influence of Glu, Gln and GABA was observed. [ABSTRACT FROM AUTHOR]

Introduction: Vocal and motor tics are characteristic for Tic disorders (TD) and Tourette's syndrome (APA 2022). Because of the pathophysiology of the disorders not being fully understood and the presence of the externally measurable symptoms; great attention has been paid to the cortico-striatal regions of patients with TD. In addition to the alterations in motor symptoms patients can experience a premonitory urge (PU) which can be felt before a tic (Reese et al. Behav. Ther. 2014; 45 177–186). Previous studies found an impact of these urges on sensory perception, attention and social cognition as well as an involvement of the brain regions insula, anterior cingulate cortex (ACC) and the temporoparietal junction (TPJ) (Seeley J. Neurosci. 2019; 39 9878–9882, Kucyi et al. J. Neurophysiol. 2012; 108 3382–3392, Uddin et al. Brain Topogr. 2019; 32 926–942). These findings lead to the idea of altered functional connectivity of the salience network (SN) in patients with TD. Objectives: This study aims to investigate the connectivity changes of the SN in patients with TD. We examined functional resting-state scans of patients with TD and searched for possible correlations between the tic and PU severity and the connectivity of the SN. Methods: 21 Patients (mean age: 30.9 years ± 10.0 [range = 19–57], 6 females) diagnosed with TD, and 20 healthy controls (mean age: 29.7 years ± 8.9 [range = 18–50], 5 females) underwent a resting-state fMRI scan. Functional and anatomical images were conducted on a 3T Siemens Prisma fit MRI scanner. PU and tic severity were measured by the Premonitory Urges for Tics Scale (PUTS) and the Yale Global Tic Severity Scale (YGTSS). The connectivity analysis of the resting-state scans was done using the CONN toolbox v21.a. After pre-processing and de-noising steps, a whole-brain seed-based connectivity analysis was carried out with the seeds being the major cortical nods of the SN. For the correlation analysis a linear regression of the YGTSS score/PUTS score and the brain connectivity of the seed regions was conducted. Results: The PUTS score was 25.3±5.4 (range 10-33) and the YGTSS total tic score was 23.1±7.9 (range 10-38) for the patients. The connectivity analysis revealed a significant difference in connectivity between the groups for the ACC, the right insula and the TPJ. A negative correlation between the YGTSS scores and the connectivity of the left insula and the right superior frontal gyrus (SFG) was shown in the correlation analysis. No significant correlation was found for the PUTS scores in the investigated seed regions. Conclusions: The right SFG mediates motor urgency and inhibitory control. Since we found a negative correlation between the insula and the right SFG regarding to higher YGTSS scores of the patients, our results might shed some light on the pathophysiology regarding lower inhibitory control in patients which experience higher tic severity. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) typically manifests itself in depressed affect, anhedonia, low energy, and additional symptoms. Despite its high global prevalence, its pathophysiology still gives rise to questions. Current research places alterations in functional connectivity among MDD's most promising biomarkers. However, given the heterogeneity of previous findings, the use of higher-resolution imaging techniques, like ultra-high field (UHF) fMRI (≥7 Tesla, 7T), may offer greater specificity in delineating fundamental impairments. In this study, 7T UHF fMRI scans were conducted on 31 MDD patients and 27 age-gender matched healthy controls to exploratorily contrast cerebral resting-state functional connectivity patterns between both groups. The CONN toolbox was used to generate functional network connectivity (FNC) analysis based on the region of interest (ROI)-to-ROI correlations in order to enable the identification of clusters of significantly different connections. Correction for multiple comparisons was implemented at the cluster level using a false discovery rate (FDR). The analysis revealed three significant clusters differentiating MDD patients and healthy controls. In Clusters 1 and 2, MDD patients exhibited between-network hypoconnectivity in basal ganglia-cortical pathways as well as hyperconnectivity in thalamo-cortical pathways, including several individual ROI-to-ROI connections. In Cluster 3, they showed increased occipital interhemispheric within-network connectivity. These findings suggest that alterations in basal ganglia-thalamo-cortical circuits play a substantial role in the pathophysiology of MDD. Furthermore, they indicate potential MDD-related deficits relating to a combination of perception (vision, audition, and somatosensation) as well as more complex functions, especially social-emotional processing, modulation, and regulation. It is anticipated that these findings might further inform more accurate clinical procedures for addressing MDD., (© 2024. The Author(s).)

Aims: Metamizole is quite an old drug with analgesic, antipyretic and spasmolytic properties. Recent findings have shown that it may induce several cytochrome P450 (CYP) enzymes, especially CYP3A4 and CYP2B6. The clinical relevance of these properties is uncertain. We aimed to unravel potential pharmacokinetic interactions between metamizole and the CYP3A4 substrate quetiapine., Methods: Plasma concentrations of quetiapine from a large therapeutic drug monitoring database were analysed. Two groups of 33 patients, either receiving quetiapine as a monotherapy (without CYP modulating comedications) or with concomitantly applied metamizole, were compared addressing a potential impact of metamizole on the metabolism of quetiapine being reflected in differences of plasma concentrations of quetiapine and dose-adjusted plasma concentrations., Results: Patients comedicated with metamizole showed >50% lower plasma concentrations of quetiapine (median 45.2 ng/mL, Q 1  = 15.5; Q 3  = 90.5 vs. 92.0 ng/mL, Q 1  = 52.3; Q 3  = 203.8, P = .003). The dose-adjusted plasma concentrations were 69% lower in the comedication group (P = .001). Subgroup analyses did not suggest a dose dependency of the metamizole effect or an influence of quetiapine formulation (immediate vs. extended release). Finally, the comedication group exhibited a significantly higher proportion of patients whose quetiapine concentrations were below the therapeutic reference range (78.8% in the metamizole group vs. 54.4% in the control group, P = .037) indicating therapeutically insufficient drug concentrations., Conclusion: The combination of metamizole and quetiapine leads to significantly lower drug concentrations of quetiapine, probably via an induction of CYP3A4. Clinicians must consider the risk of adverse drug reactions, especially treatment failure under quetiapine when adding metamizole., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Tic disorders (TD) are characterized by the presence of motor and/or vocal tics. Common neurophysiological frameworks suggest dysregulations of the cortico-striatal-thalamo-cortical (CSTC) brain circuit that controls movement execution. Besides common tics, there are other "non-tic" symptoms that are primarily related to sensory perception, sensorimotor integration, attention, and social cognition. The existence of these symptoms, the sensory tic triggers, and the modifying effect of attention and cognitive control mechanisms on tics may indicate the salience network's (SN) involvement in the neurophysiology of TD. Resting-state functional MRI measurements were performed in 26 participants with TD and 25 healthy controls (HC). The group differences in resting-state functional connectivity patterns were measured based on seed-to-voxel connectivity analyses. Compared to HC, patients with TD exhibited altered connectivity between the core regions of the SN (insula, anterior cingulate cortex, and temporoparietal junction) and sensory, associative, and motor-related cortices. Furthermore, connectivity changes were observed in relation to the severity of tics in the TD group. The SN, particularly the insula, is likely to be an important site of dysregulation in TD. Our results provide evidence for large-scale neural deviations in TD beyond the CSTC pathologies. These findings may be relevant for developing treatment targets., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Orth et al.)

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<0.001) alters functional connectivity in the right and left FP, PCC, and left hippocampus, affirming the pivotal roles of these regions in the brain's resilience network. Moreover, we identified significant moderation effects of social support across various brain regions, each showing unique connectivity patterns. Specifically, the right FP demonstrated a significant interaction effect where high social support levels were linked to increased connectivity with regions involved in socio-cognitive processing, while low social support showed opposite effects. Similar patterns by social support levels were observed in the left FP, with connectivity changes in clusters associated with emotional regulation and cognitive functions. The PCC's connectivity was distinctly influenced by support levels, elucidating its role in emotional and social cognition. Interestingly, the connectivity of the left hippocampus was not significantly impacted by social support levels, indicating a unique pattern within this region. These insights highlight the importance of high social support levels in enhancing the neural foundations of resilience and fostering adaptive neurological responses to environmental challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Khudeish, Ramkiran, Nießen, Akkoc Altinok, Rajkumar, Dammers, Shah, Veselinovic and Neuner.)

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 ( d MK ) 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 d MK 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.

Objective: Quantitative 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., Approach: Differences 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., Results: For [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., Conclusion: The 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., Significance: The 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Issa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Electroencephalography (EEG) microstate analysis seeks to cluster the scalp's electric field into semistable topographical EEG activity maps at different time points. Our study aimed to investigate the features of EEG microstates in subjects with focal epilepsy and psychogenic nonepileptic seizures (PNES)., Methods: We included 62 adult subjects with focal epilepsy or PNES who received video-EEG monitoring at the epilepsy monitoring unit. The subjects (mean age = 42.8 ± 21.2 years) were distributed equally between epilepsy and PNES groups. We extracted microstates from a 4.4 ± 1.0-min, 21-channel resting-state EEG. We excluded subjects with interictal epileptiform discharges during resting-state EEGs. After preprocessing, we derived five main EEG microstates-MS1 to MS5-for the full frequency band (1-30 Hz) and frequency subbands (delta, 1-4 Hz; theta, 4-8 Hz; alpha, 8-12 Hz; beta, 12-30 Hz), using the MATLAB-based EEGLAB toolkit. Statistical features of microstates (duration, occurrence, contribution, global field power [GFP]) were compared between the groups, using logistic regression corrected for age and sex., Results: We detected no differences in microstate parameters in the full frequency band. We found a longer duration (delta: B = -7.680, p = .046; theta: B = -16.200, p = .043) and a higher contribution (delta: B = -7.414, p = .035; theta: B = -7.509, p = .031) of MS4 in lower frequency bands in the epilepsy group. The PNES group showed a higher occurrence of MS5 in the delta subband (B = 3.283, p = .032). In the theta subband, a higher GFP of MS1 was associated with the PNES group (B = 5.674, p = .025), whereas a higher GFP of MS2 was associated with the epilepsy group (B = -6.579, p = .026)., Significance: Microstate features show differences between patients with focal epilepsy and PNES. EEG microstates could be a promising parameter, helping to understand changes in brain dynamics in subjects with epilepsy, and should be explored as a potential biomarker., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)