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With age, adolescents increasingly demonstrate the ability to forgo immediate, smaller rewards in favor of larger delayed rewards, indicating reduced delay discounting. Adolescence is also a time of social reorientation, where decisions not only involve weighing immediate against future outcomes, but also consequences for self versus those for others. In this functional Magnetic Resonance Imaging study, we examined the neural correlates of immediate and delayed reward choices where the delayed outcomes could benefit self, friends, or unknown others. A total of 196 adolescent twins aged 14-17 completed a social delay discounting task, with fMRI data acquired from 174 participants. Out of these, 156 adolescents had valid fMRI data, and 138 adolescents had observations in every condition. Adolescents more often chose the immediate reward when it was larger, and when the delay was longer. Area-under-the-curve (AUC) comparisons revealed that behavior differed across delay-beneficiaries, with AUC being highest for the self, followed by friends, and lowest for unknown others. This suggests that adolescents are more willing to wait for rewards for self. Neuroimaging analyses showed increased activity in the midline areas medial prefrontal cortex (MPFC) and precuneus, as well as bilateral temporal parietal junction (TPJ) when considering delayed reward for unknown others and friends compared to self. A whole-brain interaction with choice showed that the bilateral insula and right dorsolateral prefrontal cortex (DLPFC) were more active for delayed choices for unknown others and for immediate choices for friends and self. This underscores that the neuro-cognitive processing of how delays reduce the value of rewards depends on closeness of the beneficiary., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Accumulating evidence points to imbalanced dopamine (DA) signaling and circulating levels in the pathophysiology of major depressive disorder (MDD). However, the use of conventional MRI scanners and acquisition techniques has prevented a thorough examination of DA neural pathways in MDD. We uniquely employed ultra-high field diffusion MRI at 7.0 Tesla to map the white matter architecture and integrity of several DA pathways in MDD patients. Fifty-three MDD patients and 12 healthy controls (HCs) were enrolled in the final analysis. Images were acquired using a 7.0 Tesla MRI scanner. FreeSurfer was used to segment components of DA pathways, and MRtrix was used to perform preprocessing and tractography of mesolimbic, mesocortical, nigrostriatal, and unconventional DA pathways. Bayesian analyses assessed the impact of MDD and clinical features on DA tracts. MDD was associated with perturbed white matter microstructural properties of the nigrostriatal pathway, while several MDD features (severity of depression/age of onset/insomnia) related to connectivity changes within mesocortical, nigrostriatal, and unconventional pathways. MDD is associated with microstructural differences in the nigrostriatal pathway. The findings provide insight into the structural architecture and integrity of several DA pathways in MDD, and implicate their involvement in the clinical manifestation of MDD., Competing Interests: Declaration of competing interest Matthan Caan is a shareholder of Nico-lab International Ltd. Guido van Wingen has received research support from Philips for unrelated work. The other authors declare that they have no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: Alterations in sleep timing can lead to disturbances in glycaemic control, although the evidence is inconsistent. Therefore, this systematic review summarizes results from human intervention studies of altered sleep timing on glycaemic outcomes., Materials and Methods: As part of a broader search on the effect of altering timing of sleep, physical activity and dietary intake, Medline and Embase were searched from inception to February 2023, and subsequent reference searches were done. With the help of a machine learning-aided program 'ASReview', we selected any type of intervention study in the general adult population, which acutely delayed sleep by ≥2 h for at least one night, while the total time in bed was the same between early and late sleep. Quality assessment was done using the quality assessment tool for quantitative studies., Results: In total, 14 studies (159 adults with normal or increased weight) were identified. Methodological quality was high (n = 4), moderate (n = 7) or low (n = 3). Acute delays of sleep onset showed unfavourable effects in 10 out of 27 measured glycaemic outcomes (one-six studies reported on each outcome) with outcomes mostly measured in the postprandial period, compared to (early) nighttime sleep., Conclusions: Acutely delaying sleep timing might have unfavourable effects on glycaemic outcomes, compared to (early) nighttime sleep. Future research does however need better controlled trials, also measuring and controlling sleep quantity, sleep quality, physical activity and dietary intake, with longer follow-up periods, consistent outcomes and designs and more diverse populations to provide targeted advice regarding the optimal timing for sleep., Protocol Registration: This review is part of a larger search 'The effect of altering timing of physical activity, sleep and energy intake on glycaemia and Type 2 Diabetes risk in humans', of which the protocol was registered in the PROSPERO database on 27 November 2021 under number: CRD42021287828., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: The locus coeruleus (LC) noradrenergic system may provide a potential new target for pharmacological insomnia treatment, particularly in patients suffering from elevated distress. The selective α2 noradrenergic agonist dexmedetomidine attenuates LC activity in sub-anesthetic doses, yet no adequate non-parental delivery systems of dexmedetomidine are currently available. To examine the feasibility of oro-mucosal dexmedetomidine administration, we developed two distinct - one sublingual and one buccal - oro-mucosal, fast-disintegrating dexmedetomidine formulas tailored for self-administration. Here we established their pharmacokinetic and pharmacodynamic (PK-PD) profiles., Methods: In a pilot study (sublingual formulation; n=8 good sleepers) and a main study (buccal formulation; n=17 poor sleepers), each following a randomized, double-blind, placebo-controlled, cross-over design, we investigated sub-anesthetic doses (20 & 40 µg) of the two formulas. We complemented the PK assessments with all-night polysomnography, nocturnal cortisol and melatonin measurements, assessments of cardiovascular functions during and after sleep, cortisol awakening response, and post-awakening examination of subjective state and vigilance., Results: Particularly buccal dexmedetomidine was rapidly absorbed and exhibited excellent dose-proportionality with minimal between-subject variation in exposure. In poor sleepers, 40 µg of buccal dexmedetomidine shortened the sleep latency by 11.5 min, increased the time spent in non-rapid-eye-movement (NREM) sleep by 37.2 min, and elevated NREM sleep electroencephalographic slow wave energy (0.75-4.0 Hz) in the first half of the night by roughly 23 %. REM sleep latency was dose-dependently prolonged (20 µg: 55.0 min; 40 µg: 115.3 min). Nocturnal cortisol, melatonin and heart rate, and morning cortisol were not significantly affected by dexmedetomidine, nor did post-awakening orthostatic regulation, subjective sleepiness and mood, and psychomotor vigilance differ among the conditions., Conclusions: The favorable PK-PD profile of oro-mucosal dexmedetomidine delivery warrants further dose-finding and clinical studies, to establish the exact roles of α2 receptor agonism in pharmacological sleep enhancement and as possible novel mechanism to alleviate stress-related insomnia., Competing Interests: CONFLICT OF INTEREST STATEMENT: Dr. Rafael Wespi, Dr. Dario A. Dornbierer, and Dr. Hans-Peter Landolt are listed as inventors on a pending patent on “Dexmedetomidine for the treatment of sleep disorders” (UniTectra Fall-Nr. UZ-231534a) that is assigned to University of Zurich, Zurich, Switzerland. Dr. Dario A. Dornbierer declares that he co-founded Reconnect Labs, an academic spin-off company of the University of Zurich, focused on the development of dexmedetomidine-based products for the treatment of sleep disorders. Dr. Hans-Peter Landolt has received consultation fees from Heel Biologische Heilmittel GmbH., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Anesthesiologists.)

The noradrenergic locus coeruleus (LC) regulates arousal levels during wakefulness, but its role in sleep remains unclear. Here, we show in mice that fluctuating LC neuronal activity partitions non-rapid-eye-movement sleep (NREMS) into two brain-autonomic states that govern the NREMS-REMS cycle over ~50-s periods; high LC activity induces a subcortical-autonomic arousal state that facilitates cortical microarousals, whereas low LC activity is required for NREMS-to-REMS transitions. This functional alternation regulates the duration of the NREMS-REMS cycle by setting permissive windows for REMS entries during undisturbed sleep while limiting these entries to maximally one per ~50-s period during REMS restriction. A stimulus-enriched, stress-promoting wakefulness was associated with longer and shorter levels of high and low LC activity, respectively, during subsequent NREMS, resulting in more microarousal-induced NREMS fragmentation and delayed REMS onset. We conclude that LC activity fluctuations are gatekeepers of the NREMS-REMS cycle and that this role is influenced by adverse wake experiences., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The first, introductory part of this paper presents an overview of the long quest for a universal map of the human cortex, useful as a standard reference for all remaining studies on this brain part. It is pointed out that such a map does still not exist, but that systematic comparison of some recently produced 3D maps may well be conducive toward this important goal. Hence, the second part of this article is devoted to a detailed comparison of two of such maps, the multimodal MRI-based parcellation of Glasser et al. (Nature 536:171-178, 2016) and the myeloarchitectonic parcellation presented by Nieuwenhuys and Broere (Brain Struct Funct 228:1549-1559, 2023), with the specific aim to detect areal concordances between these two maps. In the search for these concordances, the following three criteria were used: (1) the relative or topological position of the various areas, (2) the relation of the areas to particular invariant sulci, and (3) the overall myelin content of the areas. In total 61 concordances were detected, most of which were located in the frontal and parietal lobes. These concordances were recorded in standard views of the two maps compared (Figs. 5, 6, 7, 8), as well as in Table 1. We consider these findings as a first step towards the creation of a unified, consensus (canonical) parcellation of the human neocortex., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Many children suffer from neurodevelopmental aberrations that have long-term effects. To understand the consequences of pathological processes during particular periods in neurodevelopment, one has to understand the differences in the developmental timelines of brain regions. The cerebellum is one of the first brain structures to differentiate during development but one of the last to achieve maturity. This relatively long period of development underscores its vulnerability to detrimental environmental exposures throughout gestation. Moreover, as postnatal functionality of the cerebellum is multifaceted, enveloping sensorimotor, cognitive, and emotional domains, prenatal disruptions in cerebellar development can result in a large variety of neurological and mental health disorders. Here, we review major intrauterine insults that affect cerebellar development in both humans and rodents, ranging from abuse of toxic chemical agents, such as alcohol, nicotine, cannabis, and opioids, to stress, malnutrition, and infections. Understanding these pathological mechanisms in the context of the different stages of cerebellar development in humans and rodents can help us to identify critical and vulnerable periods and thereby prevent the risk of associated prenatal and early postnatal damage that can lead to lifelong neurological and cognitive disabilities. The aim of the review is to raise awareness and to provide information for obstetricians and other healthcare professionals to eventually design strategies for preventing or rescuing related neurodevelopmental disorders.

The visual system needs to identify perceptually relevant borders to segment complex natural scenes. The primary visual cortex (V1) is thought to extract local borders, and higher visual areas are thought to identify the perceptually relevant borders between objects and the background. To test this conjecture, we used natural images that had been annotated by human observers who marked the perceptually relevant borders. We assessed the effect of perceptual relevance on V1 responses using human neuroimaging, macaque electrophysiology, and computational modeling. We report that perceptually relevant borders elicit stronger responses in the early visual cortex than irrelevant ones, even if simple features, such as contrast and the energy of oriented filters, are matched. Moreover, V1 neurons discriminate perceptually relevant borders surprisingly fast, during the early feedforward-driven activity at a latency of ~50 ms, indicating that they are tuned to the features that characterize them. We also revealed a delayed, contextual effect that enhances the V1 responses that are elicited by perceptually relevant borders at a longer latency. Our results reveal multiple mechanisms that allow V1 neurons to infer the layout of objects in natural images., Competing Interests: Competing interests statement:The authors declare no competing interest.

Previous studies demonstrated the existence of hand and tool areas in lateral and ventral occipitotemporal cortex (OTC), as well as an overlap between them. We reinvestigated this organization using 7T fMRI, benefiting from a higher signal-to-noise ratio than 3T. This enabled us to include a wider array of categories to achieve a more holistic perspective, and to omit certain spatial preprocessing steps. Despite these improvements, univariate analysis confirmed the existence of hand-tool overlap across OTC, which is striking given the omission of the spatial preprocessing steps that can influence overlap. There was significantly more overlap between hands and tools, compared to other overlap types in the left hemisphere of OTC. The overlap was also larger in the left lateral OTC as compared to the right lateral OTC. We found in all hand areas a differentiation between tools and other types of objects, although they still responded more to bodies than to tools. Regarding the tool areas, we observed a differentiation between hands and other categories such as faces and non-tool objects. Left hemisphere tool areas also differentiated between hands and bodies. When excluding the overlapping voxels from the hand and tool areas, they still showed a significant response to tools or hands (compared to objects or faces) respectively. Multi-voxel pattern analysis indicated that neural representations in the hand areas showed greater similarity between hands and tools than between hands and other objects. In the tool areas, the neural representations between tools and hands and between tools and other type of objects were all equally similar. To summarize, capitalizing on the benefits of 7T fMRI, we further substantiate the evidence in favor of hand-tool overlap in several regions of occipitotemporal cortex., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pillet 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.)

Background: The thalamus serves as a central relay station within the brain, and thalamic connectional anomalies are increasingly thought to be present in major depressive disorder (MDD). However, the use of conventional MRI scanners and acquisition techniques has prevented a thorough examination of the thalamus and its subnuclear connectional profile. We combined ultra-high field diffusion MRI acquired at 7.0 Tesla to map the white matter connectivity of thalamic subnuclei., Methods: Fifty-three MDD patients and 12 healthy controls (HCs) were involved in the final analysis. FreeSurfer was used to segment the thalamic subnuclei, and MRtrix was used to perform the preprocessing and tractography. Fractional anisotropy, axial diffusivity, mean diffusivity, radial diffusivity, and streamline count of thalamic subnuclear tracts were measured as proxies of white matter microstructure. Bayesian multilevel model was used to assess group differences in white matter metrics for each thalamic subnuclear tract and the association between these white matter metrics and clinical features in MDD., Results: Evidence was found for reduced whiter matter metrics of the tracts spanning from all thalamic subnuclei among MDD versus HC participants. Moreover, evidence was found that white matter in various thalamic subnuclear tracts is related to medication status, age of onset and recurrence in MDD., Conclusions: Structural connectivity was generally reduced in thalamic subnuclei in MDD participants. Several clinical characteristics are related to perturbed subnuclear thalamic connectivity with cortical and subcortical circuits that govern sensory processing, emotional function, and goal-directed behavior., Competing Interests: Declaration of competing interest Matthan Caan is a shareholder of Nico-lab International Ltd. Guido van Wingen has received research support from Philips for unrelated work. The other authors declare that they have no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The rise of large, publicly shared functional magnetic resonance imaging (fMRI) data sets in human neuroscience has focused on acquiring either a few hours of data on many individuals ('wide' fMRI) or many hours of data on a few individuals ('deep' fMRI). In this opinion article, we highlight an emerging approach within deep fMRI, which we refer to as 'intensive' fMRI: one that strives for extensive sampling of cognitive phenomena to support computational modeling and detailed investigation of brain function at the single voxel level. We discuss the fundamental principles, trade-offs, and practical considerations of intensive fMRI. We also emphasize that intensive fMRI does not simply mean collecting more data: it requires careful design of experiments to enable a rich hypothesis space, optimizing data quality, and strategically curating public resources to maximize community impact., Competing Interests: Declaration of interests The authors declare no competing interests in relation to this work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hyperarousal is a key symptom of anxiety, stress-related disorders, and insomnia. However, it has been conceptualized in many different ways, ranging from various physiological markers (e.g. cortisol levels, high-frequency EEG activity) to personality traits, or state assessments of subjective anxiety and tension. This approach resulted in partly inconsistent evidence, complicating unified interpretations. Crucially, no previous studies addressed the likely variability of hyperarousal within and across days, nor the relationship of such variability in hyperarousal with the night-by-night variability in sleep quality characteristic of insomnia. Here, we present a novel data-driven approach to understanding dynamics of state hyperarousal in insomnia. Using ecological momentary assessment, we tracked fluctuations in a wide range of emotions across 9 days in 169 people with insomnia disorders and 38 controls without sleep problems. Exploratory factor analysis identified a hyperarousal factor, comprised of items describing tension and distress. People with insomnia scored significantly higher on this factor than controls at all timepoints. In both groups, the hyperarousal factor score peaked in the morning and waned throughout the day, pointing to a potential contributing role of sleep or other circadian processes. Importantly, the overnight increase in hyperarousal was stronger in people with in insomnia than in controls. Subsequent adaptive LASSO regression analysis revealed a stronger overnight increase in hyperarousal across nights of worse subjective sleep quality. These findings demonstrate the relationship between subjective sleep quality and overnight modulations of hyperarousal. Disorders in which hyperarousal is a predominant complaint might therefore benefit from interventions focused on improving sleep quality., Competing Interests: Declaration of competing interest Financial disclosure: None. Non-financial disclosure: None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: ADHD is highly comorbid with Delayed Sleep Phase Syndrome (DSPS). Both are associated with obesity and diabetes, which can be caused by long-term dysregulations of appetite and glucose metabolism. This study explores hormones involved in these processes and the effects of chronotherapeutic interventions in a small sample of adults with ADHD and DSPS. Methods: Exploratory, secondary analysis of data from the PhASE study, a three-armed randomized clinical trial, are presented, including 37 adults (18-53 years) with ADHD and DSPS receiving three weeks of 0.5 mg/day (1) placebo, (2) melatonin, or (3) melatonin plus 30 minutes of bright light therapy (BLT). Leptin (appetite-suppressing), ghrelin (appetite-stimulating), insulin, insulin-like growth factor-1 (IGF-1), and glucose were measured from blood collected at 08:00 hours. Salivary cortisol was collected during the first 30 minutes after awakening and self-reported appetite was assessed. Results: Baseline leptin and IGF-1 levels were higher than reference ranges, and ghrelin and cortisol levels were lower, while insulin and glucose were normal. Melatonin treatment decreased leptin and insulin. Other outcomes remained unchanged and melatonin + BLT had no effects. Conclusion: Due to the small sample size and exploratory nature of the study, results should be interpreted with caution. Overall, these results show no strong indications for dysregulation of appetite and glucose metabolism to suggest high risk of obesity and diabetes in this small sample of adults with ADHD and DSPS. However, baseline appetite was suppressed, likely because measurements took place in the early morning which could be considered the biological night for this study population. Melatonin treatment seemed to cause subtle changes in appetite-regulating hormones suggesting increased appetite. Chronotherapeutic treatment may affect appetite-regulating hormones by advancing the biological rhythm and/or altering eating behaviors, but this remains to be investigated in larger samples using detailed food diaries., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Obesity represents a major public health emergency worldwide, and its etiology is shaped by a complex interplay of environmental and genetic factors. Over the last decade, polygenic risk scores (PRS) have emerged as a promising tool to quantify an individual's genetic risk of obesity. The field of PRS in obesity genetics is rapidly evolving, shedding new lights on obesity mechanisms and holding promise for contributing to personalized prevention and treatment. Challenges persist in terms of its clinical integration, including the need for further validation in large-scale prospective cohorts, ethical considerations, and implications for health disparities. In this review, we provide a comprehensive overview of PRS for studying the genetics of obesity, spanning from methodological nuances to clinical applications and challenges. We summarize the latest developments in the generation and refinement of PRS for obesity, including advances in methodologies for aggregating genome-wide association study data and improving PRS predictive accuracy, and discuss limitations that need to be overcome to fully realize its potential benefits of PRS in both medicine and public health., (© 2024 The Author(s). Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Purpose: T2-weighted DANTE-SPACE (Delay Alternating with Nutation for Tailored Excitation - Sampling Perfection with Application optimized Contrasts using different flip angle Evolution) sequences facilitate non-invasive intracranial vessel wall imaging at 7T through simultaneous suppression of blood and CSF. However, the achieved vessel wall delineation depends closely on the selected sequence parameters, and little information is available about the performance of the sequence using more widely available 3T MRI. Therefore, in this paper a comprehensive DANTE-SPACE simulation framework is used for the optimization and quantitative comparison of T2-weighted DANTE-SPACE at both 7T and 3T., Methods: Simulations are used to propose optimized sequence parameters at both 3T and 7T. At 7T, an additional protocol which uses a parallel transmission (pTx) shim during the DANTE preparation for improved suppression of inflowing blood is also proposed. Data at both field strengths using optimized and literature protocols are acquired and quantitatively compared in six healthy volunteers., Results: At 7T, more vessel wall signal can be retained while still achieving sufficient CSF suppression by using fewer DANTE pulses than described in previous implementations. The use of a pTx shim during DANTE at 7T provides a modest further improvement to the inner vessel wall delineation. At 3T, aggressive DANTE preparation is required to achieve CSF suppression, resulting in reduced vessel wall signal. As a result, the achievable vessel wall definition at 3T is around half that of 7T., Conclusion: Simulation-based optimization of DANTE parameters facilitates improved T2-weighted DANTE-SPACE contrasts at 7T. The improved vessel definition of T2-weighted DANTE-SPACE at 7T makes DANTE preparation more suitable for T2-weighted VWI at 7T than at 3T., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Functional neuroimaging studies suggest that a large-scale brain network transforms others' pain into its vicarious representation in the observer, potentially modulating helping behavior. However, the neuromolecular basis of individual differences in vicarious pain and helping is poorly understood. We investigated the role of the endogenous μ-opioid receptor (MOR) system in altruistic costly helping. MOR density was measured using [ 11 C]carfentanil. In a separate fMRI experiment, participants could donate money to reduce a confederate's pain from electric shocks. Participants were generally willing to help, and brain activity was observed in amygdala, anterior insula, anterior cingulate cortex (ACC), striatum, primary motor cortex, primary somatosensory cortex and thalamus when witnessing others' pain. Haemodynamic responses were negatively associated with MOR availability in emotion circuits. However, MOR availability positively associated with the ACC and hippocampus during helping. These findings suggest that the endogenous MOR system modulates altruism in the human brain., (© 2024. The Author(s).)

Reliable predictors for electroconvulsive therapy (ECT) effectiveness would allow a more precise and personalized approach for the treatment of major depressive disorder (MDD). Prediction models were created using a priori selected clinical variables based on previous meta-analyses. Multivariable linear regression analysis was used, applying backwards selection to determine predictor variables while allowing non-linear relations, to develop a prediction model for depression outcome post-ECT (and logistic regression for remission and response as secondary outcome measures). Internal validation and internal-external cross-validation were used to examine overfitting and generalizability of the model's predictive performance. In total, 1892 adult patients with MDD were included from 22 clinical and research cohorts of the twelve sites within the Dutch ECT Consortium. The final primary prediction model showed several factors that significantly predicted a lower depression score post-ECT: higher age, shorter duration of the current depressive episode, severe MDD with psychotic features, lower level of previous antidepressant resistance in the current episode, higher pre-ECT global cognitive functioning, absence of a comorbid personality disorder, and a lower level of failed psychotherapy in the current episode. The optimism-adjusted R² of the final model was 19%. This prediction model based on readily available clinical information can reduce uncertainty of ECT outcomes and hereby inform clinical decision-making, as prompt referral for ECT may be particularly beneficial for individuals with the above-mentioned characteristics. However, despite including a large number of pretreatment factors, a large proportion of the variance in depression outcome post-ECT remained unpredictable., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Cortical feedback connections are extremely numerous but the logic of connectivity between higher and lower areas remains poorly understood. Feedback from higher visual areas to primary visual cortex (V1) has been shown to enhance responses on perceptual figures compared to backgrounds, an effect known as figure-background modulation (FBM). A likely source of this feedback are border-ownership (BO) selective cells in mid-tier visual areas (e.g. V4) which represent the location of figures. We examined the connectivity between V4 cells and V1 cells using noise-correlations and micro-stimulation to estimate connectivity strength. We show that connectivity is consistent with a model in which BO-tuned V4 cells send positive feedback in the direction of their preferred figure and negative feedback in the opposite direction. This connectivity scheme can recreate patterns of FBM observed in previous studies. These results provide insights into the cortical connectivity underlying figure-background perception and establish a link between FBM and BO-tuning., (© 2024. The Author(s).)

Disorders of Arousal (DOA) are non-rapid eye movement (NREM) parasomnias traditionally regarded as unconscious states. However, recent research challenges this assumption. This narrative review aims to explore the presence and qualitative features of conscious experiences in patients with DOA during their episodes. The literature indicates a higher recall of conscious experiences during DOA episodes than previously believed, estimated at about 50-60 % in adults (immediately post-episode). Data on children are limited but suggest a lower recall rate (<30 % when interviewed retrospectively). Patient reports range from brief scenic fragments to elaborate scenarios with plot development, often fraught with negative emotions and misfortunes and with considerable correspondence between subjective experiences and observed behaviors. In many of the described cases, patients appear to enact their dreams, entering a hallucinatory state where internally generated images overlay external percepts. The potential implications for clinical management, research endeavors, and legal considerations regarding nocturnal violence, along with existing limitations and controversial points, are discussed., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Memory reprocessing during sleep is a well-established phenomenon in numerous studies. However, it is unclear whether the intensity of memory reprocessing is consistently maintained throughout the night or exhibits dynamic changes. This study investigates the temporal dynamics of negative emotional memory reprocessing during sleep, with a specific focus on slow oscillation (SO)-spindle coupling and its role in memory reprocessing. In the first experiment (N = 40, mean age = 22.5 years), we detected the negative emotional memory reprocessing strength in each sleep cycle, we found that the 2nd sleep cycle after negative emotional memory learning constitute the most sensitive window for memory reprocessing, furthermore, SO-spindle coupling signals in this window plays a role in stabilizing negative emotional memory. To verify the role of SO-spindle coupling in negative emotional memory reprocessing, we utilized transcranial alternating current stimulation (tACS) to disrupt SO-spindle coupling during the 2 nd sleep cycle (N = 21, mean age = 19.3 years). Notably, the outcomes of the tACS intervention demonstrated a significant reduction in the recognition of negative emotional memories. These findings offer new insights into the mechanisms that regulate emotional memory consolidation during sleep and may have implications for addressing psychiatric disorders associated with pathological emotional memory., (© 2024. The Author(s).)

Navigating around the world, we must adaptively allocate attention to our surroundings based on anticipated future stimuli and events. This allocation of spatial attention boosts visuocortical representations at attended locations and locally enhances perception. Indeed, spatial attention has often been analogized to a "spotlight" shining on the item of relevance. Although the neural underpinnings of the locus of this attentional spotlight have been relatively well studied, less is known about the size of the spotlight: to what extent can the attentional field be broadened and narrowed in accordance with behavioral demands? In this study, we developed a paradigm for dynamically estimating the locus and spread of covert spatial attention, inferred from visuocortical activity using fMRI in humans. We measured BOLD activity in response to an annulus while participants (4 female, 4 male) used covert visual attention to determine whether more numbers or letters were present in a cued region of the annulus. Importantly, the width of the cued area was systematically varied, calling for different sizes of the attentional spotlight. The deployment of attention was associated with an increase in BOLD activity in corresponding retinotopic regions of visual areas V1-V3. By modeling the visuocortical attentional modulation, we could reliably recover the cued location, as well as a broadening of the attentional enhancement with wider attentional cues. This modeling approach offers a useful window into the dynamics of attention and spatial uncertainty., Competing Interests: The authors declare no competing financial interests.

Dreaming, a common yet mysterious cognitive phenomenon, is an involuntary process experienced by individuals during sleep. Although the fascination with dreams dates back to ancient times and gained therapeutic significance through psychoanalysis in the early twentieth century, its scientific investigation only gained momentum with the discovery of rapid eye movement (REM) sleep in the 1950s. This review synthesises current research on the neurobiological and psychological aspects of dreaming, including factors influencing dream recall and content, neurophysiological correlates, and experimental models, and discusses the implications for clinical practice., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Regulating cardiolipin to maintain mitochondrial homeostasis is a promising strategy for addressing Parkinson's disease (PD). Through a comprehensive screening and validation process involving multiple models, ginsenoside Rg3 (Rg3) as a compound capable of enhancing cardiolipin levels is identified. This augmentation in cardiolipin levels fosters mitochondrial homeostasis by bolstering mitochondrial unfolded protein response, promoting mitophagy, and enhancing mitochondrial oxidative phosphorylation. Consequently, this cascade enhances the survival of tyrosine hydroxylase positive (TH + ) dopaminergic neurons, leading to an amelioration in motor performance within PD mouse models. Using limited proteolysis-small-molecule mapping combined with molecular docking analysis, it has confirmed Growth Factor Receptor-Bound Protein 2 (GRB2) as a molecular target for Rg3. Furthermore, these investigations reveal that Rg3 facilitates the interaction between GRB2 and TRKA (Neurotrophic Tyrosine Kinase, Receptor, Type 1), thus promotes EVI1 (Ecotropic Virus Integration Site 1 Protein Homolog) phosphorylation by ERK, subsequently increases CRLS1 (Cardiolipin Synthase 1) gene expression and boosts cardiolipin synthesis. The absence of GRB2 or CRLS1 significantly attenuates the beneficial effects of Rg3 on PD symptoms. Finally, Tenofovir Disoproxil Fumarate (TDF) that also promotes the binding between GRB2 and TRKA is further identified. The identified compounds, Rg3 and TDF, exhibit promising potential for the prevention of PD by bolstering cardiolipin expression and reinstating mitochondrial homeostasis., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Microglia, a vital homeostasis-keeper of the central nervous system, perform critical functions such as synaptic pruning, clearance of cellular debris, and participation in neuroinflammatory processes. Recent research has shown that microglia exhibit strong circadian rhythms that not only actively regulate their own immune activity, but also affect neuronal function. Disruptions of the circadian clock have been linked to a higher risk of developing a variety of diseases. In this article we will provide an overview of how lifestyle factors impact microglial function, with a focus on disruptions caused by irregular sleep-wake patterns, reduced physical activity, and eating at the wrong time-of-day. We will also discuss the potential connection between these lifestyle factors, disrupted circadian rhythms, and the role of microglia in keeping brain health. This article is part of the Special Issue on "Microglia"., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Epilepsy, characterized as a network disorder, involves widely distributed areas following seizure propagation from a limited onset zone. Accurate delineation of the epileptogenic zone (EZ) is crucial for successful surgery in drug-resistant focal epilepsy. While visual analysis of scalp electroencephalogram (EEG) primarily elucidates seizure spreading patterns, we employed brain connectivity techniques and graph theory principles during the pre-ictal to ictal transition to define the epileptogenic network., Method: Cortical sources were reconstructed from 40-channel scalp EEG in five patients during pre-surgical evaluation for focal drug-resistant epilepsy. Temporal Granger connectivity was estimated ten seconds before seizure and at seizure onset. Results have been analyzed using some centrality indices taken from Graph theory (Outdegree, Hubness). A new lateralization index is proposed by taking into account the sum of the most relevant hubness values across left and right regions of interest., Results: In three patients with positive surgical outcomes, analysis of the most relevant Hubness regions closely aligned with clinical hypotheses, demonstrating consistency in EZ lateralization and location. In one patient, the method provides unreliable results due to the abundant movement artifacts preceding the seizure. In a fifth patient with poor surgical outcome, the proposed method suggests a wider epileptic network compared with the clinically suspected EZ, providing intriguing new indications beyond those obtained with traditional electro-clinical analysis., Conclusions: The proposed method could serve as an additional tool during pre-surgical non-invasive evaluation, complementing data obtained from EEG visual inspection. It represents a first step toward a more sophisticated analysis of seizure onset based on connectivity imbalances, electrical propagation, and graph theory principles., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

During discourse comprehension, every new word adds to an evolving representation of meaning that accumulates over consecutive sentences and constrains the next words. To minimize repetition and utterance length, languages use pronouns, like the word "she," to refer to nouns and phrases that were previously introduced. It has been suggested that language comprehension requires that pronouns activate the same neuronal representations as the nouns themselves. We recorded from individual neurons in the human hippocampus during a reading task. Cells that were selective to a particular noun were later reactivated by pronouns that refer to the cells' preferred noun. These results imply that concept cells contribute to a rapid and dynamic semantic memory network that is recruited during language comprehension.

The molecular and cellular organization of the primate cerebellum remains poorly characterized. We obtained single-cell spatial transcriptomic atlases of macaque, marmoset, and mouse cerebella and identified primate-specific cell subtypes, including Purkinje cells and molecular-layer interneurons, that show different expression of the glutamate ionotropic receptor Delta type subunit 2 ( GRID2 ) gene. Distinct gene expression profiles were found in anterior, posterior, and vestibular regions in all species, whereas region-selective gene expression was predominantly observed in the granular layer of primates and in the Purkinje layer of mice. Gene expression gradients in the cerebellar cortex matched well with functional connectivity gradients revealed with awake functional magnetic resonance imaging, with more lobule-specific differences between primates and mice than between two primate species. These comprehensive atlases and comparative analyses provide the basis for understanding cerebellar evolution and function.

Human primary visual cortex (V1) responds more strongly, or resonates, when exposed to ∼10, ∼15-20, and ∼40-50 Hz rhythmic flickering light. Full-field flicker also evokes the perception of hallucinatory geometric patterns, which mathematical models explain as standing-wave formations emerging from periodic forcing at resonant frequencies of the simulated neural network. However, empirical evidence for such flicker-induced standing waves in the visual cortex was missing. We recorded cortical responses to flicker in awake mice using high-spatial-resolution widefield imaging in combination with high-temporal-resolution glutamate-sensing fluorescent reporter (iGluSnFR). The temporal frequency tuning curves in the mouse V1 were similar to those observed in humans, showing a banded structure with multiple resonance peaks (8, 15, and 33 Hz). Spatially, all flicker frequencies evoked responses in V1 corresponding to retinotopic stimulus location, but some evoked additional peaks. These flicker-induced cortical patterns displayed standing-wave characteristics and matched linear wave equation solutions in an area restricted to the visual cortex. Taken together, the interaction of periodic traveling waves with cortical area boundaries leads to spatiotemporal activity patterns that may affect perception., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Empathy determines our emotional and social lives. Research has recognized the role of the right temporoparietal junction (rTPJ) in social cognition; however, there is less direct causal evidence for its involvement in empathic responses to pain, which is typically attributed to simulation mechanisms. Given the rTPJ's role in processing false beliefs and contextual information during social scenarios, we hypothesized that empathic responses to another person's pain depend on the rTPJ if participants are given information about people's intentions, engaging mentalizing mechanisms alongside simulative ones. Participants viewed videos of an actress freely showing or suppressing pain caused by an electric shock while receiving 6 Hz repetitive transcranial magnetic stimulation (rTMS) over the rTPJ or sham vertex stimulation. Active rTMS had no significant effect on participants' ratings depending on the pain expression, although participants rated the actress's pain as lower during rTPJ perturbation. In contrast, rTMS accelerated response times for providing ratings during pain suppression. We also found that participants perceived the actress's pain as more intense when they knew she would suppress it rather than show it. These results suggest an involvement of the rTPJ in attributing pain to others and provide new insights into people's behavior in judging others' pain when it is concealed., (© The Author(s) 2024. Published by Oxford University Press.)

Circadian disruption is an important factor driving the current-day high prevalence of obesity and type-2 diabetes. While the impact of incorrect timing of caloric intake on circadian disruption is widely acknowlegded, the contribution of incorrect timing of physical activity remains relatively understudied. Here, we modeled the incorrect timing of physical activity in nightshift workers in male Wistar rats, by restricting running wheel access to the innate inactive (light) phase (LR). Controls included no wheel access (NR); access only during the innate active (dark) period (DR); or unrestricted ( ad libitum ) access (ALR). LR did not shift the phase of the muscle or liver clock, but dampened the muscle clock amplitude. As our previous study demonstrated that light-phase restricted feeding did shift the liver clock, but made the muscle clock arrhythmic, we next combined the time restriction of wheel and food access to either the light phase (LRLF) or dark phase (DRDF). LRLF produced a ∼12 h shift in the majority of clock gene rhythms in both skeletal muscle and liver. On the other hand, DRDF was most effective in reducing body weight and the accumulation of fat mass. Therefore, in order to shift the muscle clock in male Wistar rats, synergy between the timing of feeding and physical activity is necessary. These findings may contribute to further improve the design of lifestyle strategies that try to limit metabolic misalignment caused by circadian disruption., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ayano Shiba reports financial support was provided by Bioclock Consortium. Paul de Goede reports financial support was provided by ZonMW. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Feeding, like many other biological functions, displays a daily rhythm. This daily rhythmicity is controlled by the circadian timing system of which the central master clock is located in the hypothalamic suprachiasmatic nucleus (SCN). Other brain areas and tissues throughout the body also display rhythmic functions and contain the molecular clock mechanism known as peripheral oscillators. To generate the daily feeding rhythm, the SCN signals to different hypothalamic areas with the lateral hypothalamus, paraventricular nucleus and arcuate nucleus being the most prominent. With respect to the rewarding aspects of feeding behavior, the dopaminergic system is also under circadian influence. However the SCN projects only indirectly to the different reward regions, such as the ventral tegmental area where dopamine neurons are located. In addition, high palatable, high caloric diets have the potential to disturb the normal daily rhythms of physiology and have been shown to alter for example meal patterns. Around a meal several hormones and peptides are released that are also under circadian influence. For example, the release of postprandial insulin and glucagon-like peptide following a meal depend on the time of the day. Finally, we review the effect of deletion of different clock genes on feeding behavior. The most prominent effect on feeding behavior has been observed in Clock mutants, whereas deletion of Bmal1 and Per1/2 only disrupts the day-night rhythm, but not overall intake. Data presented here focus on the rodent literature as only limited data are available on the mechanisms underlying daily rhythms in human eating behavior., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Traditionally, the neural basis of social perception has been studied by showing participants brief examples of the actions or emotions of others presented in randomized order to prevent participants from anticipating what others do and feel. This approach is optimal to isolate the importance of information flow from lower to higher cortical areas. The degree to which feedback connections and Bayesian hierarchical predictive coding contribute to how mammals process more complex social stimuli has been less explored, and will be the focus of this review. We illustrate paradigms that start to capture how participants predict the actions and emotions of others under more ecological conditions, and discuss the brain activity measurement methods suitable to reveal the importance of feedback connections in these predictions. Together, these efforts draw a richer picture of social cognition in which predictive coding and feedback connections play significant roles. We further discuss how the notion of predicting coding is influencing how we think of autism spectrum disorder., Competing Interests: Declaration of Interest None, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The generation of new neurons at the hippocampal neurogenic niche, known as adult hippocampal neurogenesis (AHN), and its impairment, have been implicated in Alzheimer's disease (AD). MicroRNA-132 (miR-132), the most consistently downregulated microRNA (miRNA) in AD, was recently identified as a potent regulator of AHN, exerting multilayered proneurogenic effects in adult neural stem cells (NSCs) and their progeny. Supplementing miR-132 in AD mouse brain restores AHN and relevant memory deficits, yet the exact mechanisms involved are still unknown. Here, we identify NACC2 as a novel miR-132 target implicated in both AHN and AD. miR-132 deficiency in mouse hippocampus induces Nacc2 expression and inflammatory signaling in adult NSCs. We show that miR-132-dependent regulation of NACC2 is involved in the initial stages of human NSC differentiation towards astrocytes and neurons. Later, NACC2 function in astrocytic maturation becomes uncoupled from miR-132. We demonstrate that NACC2 is present in reactive astrocytes surrounding amyloid plaques in mouse and human AD hippocampus, and that there is an anticorrelation between miR-132 and NACC2 levels in AD and upon induction of inflammation. Unraveling the molecular mechanisms by which miR-132 regulates neurogenesis and cellular reactivity in AD, will provide valuable insights towards its possible application as a therapeutic target., (© 2024. The Author(s).)

Numerals, that is, semantic expressions of numbers, enable us to have an exact representation of the amount of things. Visual processing of numerals plays an indispensable role in the recognition and interpretation of numbers. Here, we investigate how visual information from numerals is processed to achieve semantic understanding. We first found that partial occlusion of some digital numerals introduces bistable interpretations. Next, by using the visual adaptation method, we investigated the origin of this bistability in human participants. We showed that adaptation to digital and normal Arabic numerals, as well as homologous shapes, but not Chinese numerals, biases the interpretation of a partially occluded digital numeral. We suggest that this bistable interpretation is driven by intermediate shape processing stages of vision, that is, by features more complex than local visual orientations, but more basic than the abstract concepts of numerals.

B cells of people with multiple sclerosis (MS) are more responsive to IFN-γ, corresponding to their brain-homing potential. We studied how a coding single nucleotide polymorphism (SNP) in IFNGR2 (rs9808753) co-operates with Epstein-Barr virus (EBV) infection as MS risk factors to affect the IFN-γ signaling pathway in human B cells. In both cell lines and primary cells, EBV infection positively associated with IFN-γ receptor expression and STAT1 phosphorylation. The IFNGR2 risk SNP selectively promoted downstream signaling via STAT1, particularly in transitional B cells. Altogether, EBV and the IFNGR2 risk SNP independently amplify IFN-γ signaling, potentially driving B cells to enter the MS brain., Competing Interests: Declaration of competing interest Marvin M. van Luijn received research support from EMD Serono, Merck, Novartis, GSK and Idorsia Pharmaceutical Ltd. Joost Smolders received lecture and/or consultancy fees from Biogen, Merck, Novartis, Sanofi-Genzyme and Roche. The remaining authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The growing field of nanoscale neural stimulators offers a potential alternative to larger scale electrodes for brain stimulation. Nanoelectrodes made of magnetoelectric nanoparticles (MENPs) can provide an alternative to invasive electrodes for brain stimulation via magnetic-to-electric signal transduction. However, the magnetoelectric effect is a complex phenomenon and challenging to probe experimentally. Consequently, quantifying the stimulation voltage provided by MENPs is difficult, hindering precise regulation and control of neural stimulation and limiting their practical implementation as wireless nanoelectrodes. The work herein develops an approach to determine the stimulation voltage for MENPs in a finite element analysis (FEA) model. This model is informed by atomistic material properties from ab initio Density Functional Theory (DFT) calculations and supplemented by experimentally obtainable nanoscale parameters. This process overcomes the need for experimentally inaccessible characteristics for magnetoelectricity, and offers insights into the effect of the more manageable variables, such as the driving magnetic field. The model's voltage is compared to in vivo experimental data to assess its validity. With this, a predictable and controllable stimulation is simulated by MENPs, computationally substantiating their spatial selectivity. This work proposes a generalizable and accessible method for evaluating the stimulation capability of magnetoelectric nanostructures, facilitating their realization as wireless neural stimulators in the future., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Morphological changes in the hippocampal, thalamic, and amygdala subfields have been suggested to form part of the pathophysiology of major depressive disorder (MDD). However, the use of conventional MRI scanners and acquisition techniques has prevented in-depth examinations at the subfield level, precluding a fine-grained understanding of these subfields and their involvement in MDD pathophysiology. We uniquely employed ultra-high field MRI at 7.0 Tesla to map hippocampal, thalamic, and amygdala subfields in MDD. Fifty-six MDD patients and 14 healthy controls (HCs) were enrolled in the final analysis. FreeSurfer protocols were used to segment hippocampal, thalamic, and amygdala subfields. Bayesian analysis was then implemented to assess differences between groups and relations with clinical features. While no effect was found for MDD diagnosis (i.e., case-control comparison), clinical characteristics of MDD patients were associated with subfield volumes of the hippocampus, thalamus, and amygdala. Specifically, the severity of depressive symptoms, insomnia, and childhood trauma in MDD patients related to lower thalamic subfield volumes. In addition, MDD patients with typical MDD versus those with atypical MDD showed lower hippocampal, thalamic, and amygdala subfield volumes. MDD patients with recurrent MDD versus those with first-episode MDD also showed lower thalamic subfield volumes. These findings allow uniquely fine-grained insights into hippocampal, thalamic, and amygdala subfield morphology in MDD, linking some of them to the clinical manifestation of MDD., (© 2024. The Author(s).)

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

Background: In adults, cortisol levels show a pronounced 24-hour rhythm with a peak in the early morning. It is unknown at what age this early-morning peak in cortisol emerges during infancy, hampering the establishment of optimal dosing regimens for hydrocortisone replacement therapy in infants with an inborn form of adrenal insufficiency. Therefore, we aimed to characterize daily variation in salivary cortisol concentration across the first year of life., Methods: We conducted a systematic review followed by an individual participant data meta-analysis of studies reporting on spontaneous (i.e., not stress induced) salivary cortisol concentrations in healthy infants aged 0-1 year. A one-stage approach using linear mixed-effects modelling was used to determine the interaction between age and time of day on cortisol concentrations., Findings: Through the systematic review, 54 eligible publications were identified, reporting on 29,177 cortisol observations. Individual participant data were obtained from 15 study cohorts, combining 17,079 cortisol measurements from 1,904 infants. The morning/evening cortisol ratio increased significantly from 1.7 (95% CI: 1.3-2.1) at birth to 3.7 (95% CI: 3.0-4.5) at 6-9 months (p < 0.0001). Cosinor analysis using all available data revealed the gradual emergence of a 24-hour rhythm during infancy., Interpretation: The early-morning peak in cortisol secretion gradually emerges from birth onwards to form a stable morning/evening ratio from age 6-9 months. This might have implications for hydrocortisone replacement therapy in infants with an inborn form of adrenal insufficiency., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Non-invasive perfusion imaging by Arterial spin labeling (ASL) can be advantageous at Ultra-high field (UHF) MRI, since the image SNR and the T1 relaxation time both increase with the static field. However, ASL implementation, especially at 7T, is not trivial. Especially for ASL, UHF MRI comes with many challenges, mainly due to B1+ inhomogeneities. This study aimed to investigate the effects of different transmit coil configurations on perfusion-weighted imaging at 7T using a flow-sensitive alternating inversion recovery (FAIR) technique with time-resolved frequency offset corrected inversion (TR-FOCI) pulses for labeling and background suppression. We conducted a performance comparison between a parallel transmit (pTx) system equipped with 32 receive (Rx) and 8 transmit (Tx) channels and a standard setup with 32Rx and 2Tx channels. Our findings demonstrate that the pTx system, characterized by a more homogeneous B1 transmit field, resulted in a significantly higher contrast-to-noise ratio, temporal signal-to-noise ratio, and lower coefficient of variance (CoV) than the standard 2Tx setup. Additionally, both setups demonstrated comparable capabilities for functional mapping of the hand region in the motor cortex, achieving reliable results within a short acquisition time of approximately 5 minutes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Oliveira 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.)

The striatum, the main input nucleus of the basal ganglia, receives topographically organized input from the cortex and gives rise to the direct and indirect output pathways, which have antagonistic effects on basal ganglia output directed to the cortex. We optogenetically stimulated the direct and indirect pathways in a visual and a working memory task in mice that responded by licking. Unilateral direct pathway stimulation increased the probability of lick responses toward the contralateral, non-stimulated side and increased cortical activity globally. In contrast, indirect pathway stimulation increased the probability of responses toward the stimulated side and decreased activity in the stimulated hemisphere. Moreover, direct pathway stimulation enhanced the neural representation of a contralateral visual stimulus during the delay of the working memory task, whereas indirect pathway stimulation had the opposite effect. Our results demonstrate how these two pathways influence perceptual decisions and working memory and modify activity in the dorsal cortex., Competing Interests: The authors declare no competing interests. Affiliations to other research institutions that authors may have at the time of publication are not relevant for the work in this manuscript, nor do they form a conflict of interest., (© 2024 The Author(s).)

Crosstalk between peripheral metabolic organs and the central nervous system is essential for body weight control. At the base of the hypothalamus, β-tanycytes surround the portal capillaries and function as gatekeepers to facilitate transfer of substances from the circulation into the cerebrospinal fluid and vice versa. Here, we investigated the role of the neuroplasticity gene doublecortin-like (DCL), highly expressed by β-tanycytes, in body weight control and whole-body energy metabolism. We demonstrated that DCL-knockdown through a doxycycline-inducible shRNA expression system prevents body weight gain by reducing adiposity in mice. DCL-knockdown slightly increased whole-body energy expenditure possibly as a result of elevated circulating thyroid hormones. In white adipose tissue (WAT) triglyceride uptake was increased while the average adipocyte cell size was reduced. At histological level we observed clear signs of browning, and thus increased thermogenesis in WAT. We found no indications for stimulated thermogenesis in brown adipose tissue (BAT). Altogether, we demonstrate an important, though subtle, role of tanycytic DCL in body weight control through regulation of energy expenditure, and specifically WAT browning. Elucidating mechanisms underlying the role of DCL in regulating brain-peripheral crosstalk further might identify new treatment targets for obesity., (© 2024. The Author(s).)

Precisely tracking time over second-long timescales is important for accurate anticipation and consequential actions, yet the neurobiological underpinnings remain unknown. In this issue of Neuron, Garcia-Garcia and colleagues 1 show that computations in the cerebellum resulting from interactions between the mossy fiber and climbing fiber pathways contribute to long-interval learning during operant conditioning., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To describe phenotypic, genotypic, and histopathological features of inherited retinal dystrophies associated with the CRX gene (CRX-RDs)., Design: Retrospective multicenter cohort study including histopathology., Subjects: Thirty-nine patients from 31 families with pathogenic variants in the CRX gene., Methods: Clinical data of 152 visits were collected from medical records. The median follow-up time was 9.1 years (interquartile range (IQR), 3.3-15.3 years; range, 0.0-48.8 years). Histopathologic examination of the eye of a 17-year-old patient with advanced early-onset CRX-RD was performed., Main Outcome Measures: Visual acuity, retinal imaging, electroretinography, genotype-phenotype correlation, and histopathological examination were evaluated., Results: The age at onset ranged from birth to the eighth decade of life. Median visual acuity was 1.00 logarithm of the minimum angle of resolution (logMAR) (IQR, 0.69-1.48 logMAR; range, 0.06-3.00 logMAR) at a mean age of 52.0 ± 19.9 years (range, 4.6-81.9 years). Sufficient imaging was available for 36 out of 39 patients (92.3%), and all showed degeneration of at least the macula. Of these 36 patients, 22 (61.1%) had only macular dystrophy. Another 10 patients (27.8%) had additional degeneration beyond the vascular arcades, and 4 patients (11.1%) panretinal degeneration. Two patients (5.1%) had Leber congenital amaurosis. In total, 21 different disease-associated heterozygous CRX variants were identified (10 frameshift, 7 missense, 2 deletion, 1 nonsense, 1 deletion-insertion variants). Missense variants in the CRX homeodomain and 2 variants deleting all functional domains, thus causing haploinsufficiency, generally tended to cause milder late-onset phenotypes. Histopathologic examination of the eye of a 17-year-old patient with advanced early-onset retinal dystrophy due to a heterozygous deletion of exons 3 and 4 of the CRX gene revealed loss of laminar integrity and widespread photoreceptor degeneration especially in the central retina, with extensive loss of photoreceptor nuclei and outer segments., Conclusions: This study illustrates the large clinical and genetic heterogenic spectrum of CRX-RDs, ranging from Leber congenital amaurosis to mild late-onset maculopathy resembling occult macular dystrophy. Haploinsufficiency and missense variants tended to be associated with milder phenotypes. Patients showed degeneration predominantly affecting the central retina on imaging. The histopathological findings also mirror these clinical findings and features similar to previously reported animal models of CRX-RDs., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. All rights reserved.)

Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an α 2 -adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABA A receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS., (© 2024. The Author(s).)

While standard polysomnography has revealed the importance of the sleeping brain in health and disease, more specific insight into the relevant brain circuits requires high-density electroencephalography (EEG). However, identifying and handling sleep EEG artifacts becomes increasingly challenging with higher channel counts and/or volume of recordings. Whereas manual cleaning is time-consuming, subjective, and often yields data loss (e.g., complete removal of channels or epochs), automated approaches suitable and practical for overnight sleep EEG remain limited, especially when control over detection and repair behavior is desired. Here, we introduce a flexible approach for automated cleaning of multichannel sleep recordings, as part of the free Matlab-based toolbox SleepTrip. Key functionality includes 1) channel-wise detection of various artifact types encountered in sleep EEG, 2) channel- and time-resolved marking of data segments for repair through interpolation, and 3) visualization options to review and monitor performance. Functionality for Independent Component Analysis is also included. Extensive customization options allow tailoring cleaning behavior to data properties and analysis goals. By enabling computationally efficient and flexible automated data cleaning, this tool helps to facilitate fundamental and clinical sleep EEG research., 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., (Copyright © 2024 Cox, Weber and Van Someren.)

Control of microglia activity through CD200-CD200R and CD47-SIRPα interactions has been implicated in brain homeostasis. Here, we assessed CD200, CD47, CD200R and SIRPα expression with qPCR and immunohistochemistry in multiple sclerosis (MS) normal-appearing cortical grey matter (NAGM), normal-appearing white matter (NAWM), cortical grey matter (GM) lesions and perilesional GM, and compared this to control GM and white matter (WM), to investigate possible altered control of microglia in MS. In MS NAGM, CD200 expression is lower compared with control GM, specifically in cortical layers 1 and 2, and CD200 expression in NAGM negatively correlates with the cortical lesion rate. Interestingly, NAGM and NAWM CD200 expression is positively correlated, and NAGM CD200 expression negatively correlates with the proportion of active and mixed WM lesions. In GM lesions, CD200 and CD47 expressions are lower compared with NAGM and perilesional GM. CD200R expression is lower in MS NAGM, whereas SIRPα was increased in and around GM lesions. Taken together, our data indicate that CD200 and CD47 play a role in GM MS lesion formation and progression, respectively, and that targeting CD200 pathways may offer therapeutic avenues to mitigate MS pathology in both WM and GM., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Hand visibility affects motor control, perception, and attention, as visual information is integrated into an internal model of somatomotor control. Spontaneous brain activity, i.e., at rest, in the absence of an active task, is correlated among somatomotor regions that are jointly activated during motor tasks. Recent studies suggest that spontaneous activity patterns not only replay task activation patterns but also maintain a model of the body's and environment's statistical regularities (priors), which may be used to predict upcoming behavior. Here, we test whether spontaneous activity in the human somatomotor cortex as measured using fMRI is modulated by visual stimuli that display hands vs. non-hand stimuli and by the use/action they represent. A multivariate pattern analysis was performed to examine the similarity between spontaneous activity patterns and task-evoked patterns to the presentation of natural hands, robot hands, gloves, or control stimuli (food). In the left somatomotor cortex, we observed a stronger (multivoxel) spatial correlation between resting state activity and natural hand picture patterns compared to other stimuli. No task-rest similarity was found in the visual cortex. Spontaneous activity patterns in somatomotor brain regions code for the visual representation of human hands and their use., (© 2024. The Author(s).)