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[Display omitted] • Social behavior is altered by nanoplastic (NPx) administration. • NPx-induced alteration of social behavior is partly dependent on neurodevelopment. • NPx administration affects the neural circuit where the dopamine system innervates. • NPx-induced alteration of neural activity depends on neurodevelopment. • Therefore, NPx induces different effects at different developmental stages. Exposure to environmental microplastics has been demonstrated to impact health. However, its effect on development remains unclear. This study investigated whether consumption of nanoplastics (NPx) during development affects social and cognitive functions in rodents. In this study, we utilized male Institute of Cancer Research mice; they were divided into five subgroups based on the duration of NPx administration. NPx (100 nm) was orally administered via gavage for 6 days from gestational day (GTD) 7, representing the mid-gestation period, and for 5–6 days from GTD13 to birth, representing the late-gestation period; the male offspring were used for experiments. NPx was orally administered for 15 days starting at postnatal day (PND) 21 as the juvenile, PND38 as the adolescent, and PND56 as adulthood. On PND77, offspring were assessed for locomotion, social behavior, and nest-building tests. We observed that NPx administration altered dopamine system responses in GTD13 and PND56 groups. Social behavior was similarly affected by NPx treatment, with GTD13 and PND56 groups displaying decreased familiarity. Additionally, NPx treatment enhanced local field potentials in the prefrontal cortex, nucleus accumbens, and amygdala of GTD7 group and in the striatum of GTD13 group, while amphetamine treatment induced changes of local field potentials compared to saline treatment in the prefrontal cortex and the ventral tegmental area of CTR, GTD7, PND21, and PND56 groups. Taken together, these results showed that NPx treatment induced changes in social behavior partly depending on developmental stage, and these changes are associated with neural circuits innervated by the dopamine system. [ABSTRACT FROM AUTHOR]

Calcium imaging, especially two-photon imaging, has become essential in neuroscience for studying neuronal and astrocytic activity under in vivo and in vitro conditions. Current advances in the development of calcium sensors as well as imaging hardware enable high-frequency measurements of calcium signals in hundreds of cells simultaneously. The analysis of these large datasets requires special tools and usually a certain level of programming experience. Despite advancements in calcium imaging analysis software development, significant gaps remain, particularly for data acquired at a high sampling rate that would allow for the spectral analysis of calcium signals. The FluoAnalysis MATLAB toolbox addresses these gaps by offering a comprehensive solution for analyzing simultaneously measured calcium imaging and electrophysiological data. It features both GUI-based and command-line approaches, emphasizing frequency domain analysis to reveal network-level oscillatory signals linked to single-cell activity. In addition, the toolbox puts special emphasis on differentiating between astrocytes and neurons, revealing the interactions between the network activity of the two major cell types of the brain. It facilitates a streamlined workflow for data loading, ROI identification, cell classification, fluorescence intensity calculation, spectral analysis, and report generation, supporting both manual and automated high-throughput analysis. This versatile platform enables the comprehensive analysis of large imaging datasets. In conclusion, the FluoAnalysis MATLAB toolbox provides a robust and versatile platform for the integrated analysis of calcium imaging and electrophysiological data, supporting diverse neuroscience research applications. [ABSTRACT FROM AUTHOR]

The aging population suffers from memory impairments. Slow-wave activity (SWA) is composed of slow (0.5–1 Hz) and delta (1–4 Hz) oscillations, which play important roles in long-term memory and working memory function respectively. SWA disruptions might lead to memory disturbances often experienced by older adults. We conducted behavioral tests in young and older C57BL/6 J mice. SWA was monitored using wide-field imaging with voltage sensors. Cell-specific calcium imaging was used to monitor the activity of excitatory and inhibitory neurons in these mice. Older mice exhibited impairments in working memory but not memory consolidation. Voltage-sensor imaging revealed aberrant synchronization of neuronal activity in older mice. Notably, we found older mice exhibited no significant alterations in slow oscillations, whereas there was a significant increase in delta power compared to young mice. Calcium imaging revealed hypoactivity in inhibitory neurons of older mice. Combined, these results suggest that neural activity disruptions might correlate with aberrant memory performance in older mice. • Slow wave activity disruptions lead to memory disturbances in older adults. • Older mice show impairments in working memory, but not memory consolidation. • Older mice showed abnormal synchronization of neuronal activity across the cortex. • Older mice exhibited aberrant activity of inhibitory neurons within the circuit. • The neural activity disruptions may be related to memory impairments in Older mice. [ABSTRACT FROM AUTHOR]

Aims: The mechanism underlying the reversible unconsciousness induced by general anesthetics (GA) remains unclear. Recent studies revealed the critical roles of myelin and oligodendrocytes (OLs) in higher functions of the brain. However, it is unknown whether myelin actively participates in the regulation of GA. The aim of this study is to investigate the roles and possible mechanisms of myelin in the regulation of consciousness alterations induced by isoflurane anesthesia. Methods: First, demyelination models for the entire brain and specific neural nuclei were established to investigate the potential role of myelination in the regulation of GA, as well as its possible regional specificity. c‐Fos staining was then performed on the demyelinated nuclei to verify the impact of myelin loss on neuronal activity. Finally, the activity of neurons during isoflurane anesthesia in demyelinated mice was recorded by optical fiber photometric calcium signal. The related behavioral indicators and EEG were recorded and analyzed. Results: A prolonged emergence time was observed from isoflurane anesthesia in demyelinated mice, which suggested the involvement of myelin in regulating GA. The demyelination in distinct nuclei by LPC further clarified the region‐specific roles of isoflurane anesthesia regulation by myelin. The effect of demyelination on isoflurane anesthesia in the certain nucleus was consistent with that in neurons towards isoflurane anesthesia. Finally, we found that the mechanism of myelin in the modulation of isoflurane anesthesia is possibly through the regulation of neuronal activity. Conclusions: In brief, myelin in the distinct neural nucleus plays an essential role in regulating the process of isoflurane anesthesia. The possible mechanism of myelin in the regulation of isoflurane anesthesia is neuronal activity modification by myelin integrity during GA. Our findings enhanced the comprehension of myelin function, and offered a fresh perspective for investigating the neural mechanisms of GA. [ABSTRACT FROM AUTHOR]

Advances in neuroimaging technology, like functional near-infrared spectroscopy (fNIRS), support the evaluation of task-dependent brain activity during functional tasks, like balance, in healthy and clinical populations. To date, there have been no studies examining how interventions, like yoga, impact task-dependent brain activity in adults with chronic acquired brain injury (ABI). This pilot study compared eight weeks of group yoga (active) to group exercise (control) on balance and task-dependent neural activity outcomes. Twenty-three participants were randomized to yoga (n = 13) or exercise groups (n = 10). Neuroimaging and balance performance data were collected simultaneously using a force plate and mobile fNIRS device before and after interventions. Linear mixed-effects models were used to evaluate the effect of time, time x group interactions, and simple (i.e., within-group) effects. Regardless of group, all participants had significant balance improvements after the interventions. Additionally, regardless of group, there were significant changes in task-dependent neural activity, as well as distinct changes in neural activity within each group. In summary, using advances in sensor technology, we were able to demonstrate preliminary evidence of intervention-induced changes in balance and neural activity in adults with ABI. These preliminary results may provide an important foundation for future neurorehabilitation studies that leverage neuroimaging methods, like fNIRS. [ABSTRACT FROM AUTHOR]

Aims: The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ‐associated behavioral phenotype, which is associated with dysregulated dopamine system function induced by hippocampal hyperactivity. However, the neural mechanism of hippocampus underlying hyperlocomotion remains largely unclear. Methods: Mouse pups were injected with N‐methyl‐D‐aspartate receptor antagonist (MK‐801) or vehicle twice daily on postnatal days (PND) 7–11. In the adulthood phase, one cohort of mice underwent electrode implantation in field CA1 of the hippocampus for the recording local field potentials and spike activity. A separate cohort of mice underwent surgery to allow for calcium imaging of the hippocampus while monitoring the locomotion. Lastly, the effects of atypical antipsychotic (aripiprazole, ARI) were evaluated on hippocampal neural activity. Results: We found that the hippocampal theta oscillations were enhanced in MK‐801‐treated mice, but the correlation coefficient between the hippocampal spiking activity and theta oscillation was reduced. Consistently, although the rate and amplitude of calcium transients of hippocampal neurons were increased, their synchrony and correlation to locomotion speed were disrupted. ARI ameliorated perturbations produced by the postnatal MK‐801 treatment. Conclusions: These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ. [ABSTRACT FROM AUTHOR]

Background. Stress, a phenomenon which has turned into an epidemic, is a major health concern because it affects the general population, having a strong negative impact on the psychoemotional, physical and social health. Aims. The aim of this research was to investigate the impact of Health&Wellness Coaching (HWC) intervention on stress levels, as evidenced by physical/mental/psychological changes, and to identify non-invasive ways of early detection of high stress levels, which may play an essential role in the prophylaxis of chronic diseases often associated with stress. Methods. The HWC intervention was carried out on 24 subjects, and consisted in 8 online sessions for each of them. The sessions were mixed training and coaching sessions, held once every two weeks, and lasted for approximately 60 min/session. In the training sessions, useful medical information related to stress was provided (info training), while in the coaching sessions subjects were guided and empowered to reduce their stress levels. Results. The results showed an optimization of physical/mental/psychological parameters, with a simultaneous decrease in perceived stress levels, and a favorable impact on the subjects’ quality of life, as evidenced by psychometric measurements (DASS_21R, Decisional Capacity and QOLI) and mental/brain measurements using fNIRS technology (Functional Near- Infrared Spectroscopy, with the Mendi device). Conclusion. The present research confirms that HWC is an effective intervention in reducing the level of perceived stress and we believe that it can be a promising alternative for the prophylaxis of chronic diseases, and that DASS-21R could be a useful tool for the detection of a high degree of psycho/emotional/mental impairment, which can negatively influence the level of stress in the body, i.e. QOLI can detect the most affected areas of satisfaction with life. [ABSTRACT FROM AUTHOR]

It has been more than a century since Pío del Río‐Hortega first characterized microglia in histological stains of brain tissue. Since then, significant advances have been made in understanding the role of these resident central nervous system (CNS) macrophages. In particular, it is now known that microglia can sense neural activity and modulate neuronal circuits accordingly. We review the mechanisms by which microglia detect changes in neural activity to then modulate synapse numbers in the developing and mature CNS. This includes responses to both spontaneous and experience‐driven neural activity. We further discuss activity‐dependent mechanisms by which microglia regulate synaptic function and neural circuit excitability. Together, our discussion provides a comprehensive review of the activity‐dependent functions of microglia within neural circuits in the healthy CNS, and highlights exciting new open questions related to understanding more fully microglia as key components and regulators of neural circuits. [ABSTRACT FROM AUTHOR]

Simple Summary: This study delves into the turning behavior of pigeons by examining the neural mechanisms of their midbrain motor nucleus. Correlating brain oscillations with turning behavior, we identified the distinct roles of oscillatory patterns in different frequency bands during active and passive turning behavior. Specifically, 80 Hz stimulation induced higher-frequency oscillation patterns. These findings unveil the intricate relationship between neural oscillations and pigeon turning, highlighting the significance of specific frequency bands. This study enhances our understanding of avian brain–behavior connections, offering valuable insights for further research on avian locomotion neural processes and serving as a reference for future studies on neuromodulation techniques in flying animal robots. Flexible turning behavior endows Homing Pigeons (Columba livia domestica) with high adaptability and intelligence in long-distance flight, foraging, hazard avoidance, and social interactions. The present study recorded the activity pattern of their local field potential (LFP) oscillations and explored the relationship between different bands of oscillations and turning behaviors in the formatio reticularis medialis mesencephali (FRM). The results showed that the C (13–60 Hz) and D (61–130 Hz) bands derived from FRM nuclei oscillated significantly in active turning, while the D and E (131–200 Hz) bands oscillated significantly in passive turning. Additionally, compared with lower-frequency stimulation (40 Hz and 60 Hz), 80 Hz stimulation can effectively activate the turning function of FRM nuclei. Electrical stimulation elicited stronger oscillations of neural activity, which strengthened the pigeons' turning locomotion willingness, showing an enhanced neural activation effect. These findings suggest that different band oscillations play different roles in the turning behavior; in particular, higher-frequency oscillations (D and E bands) enhance the turning behavior. These findings will help us decode the complex relationship between bird brains and behaviors and are expected to facilitate the development of neuromodulation techniques for animal robotics. [ABSTRACT FROM AUTHOR]

Background: Mechanisms underlying cognitive dysfunction following traumatic brain injury (TBI) partially due to abnormal amyloid processor protein (APP) cleavage and neural hyperactivity. Binding of the extension domain of APP (ExD17) to the GABAbR1 receptor results in reduced neural activity, which might play a role in the mechanisms of cognitive dysfunction caused by TBI. Methods: Stretch‐induced injury was utilized to establish a cell injury model in HT22 cells. The TBI model was created by striking the exposed brain tissue with a free‐falling weight. Topical or intraperitoneal administration of ExD17 was performed. Cell viability was assessed through a cell counting kit‐8 assay, while intracellular Ca2+ was measured using Fluo‐4. Western blotting was used to investigate the expression of APP amyloidogenic cleavage proteins, GABAbR1, phospholipase C (PLC), PLCB3, and synaptic proteins. ELISA was performed to analyze the levels of Aβ42. Seizures were assessed using electroencephalography (EEG). Behaviors were evaluated through the novel object recognition test, open field test, elevated plus maze test, and nest‐building test. Results: ExD17 improved cell viability and reduced intracellular calcium in the cell injury model. The treatment also suppressed the increased expression of APP amyloidogenic cleavage proteins and Aβ42 in both cell injury and TBI models. ExD17 treatment reversed the abnormal expression of GABAbR1, GRIA2, p‐PLCG1/PLCG1 ratio, and p‐PLCB3/PLCB3 ratio. In addition, ExD17 treatment reduced neural activity, seizure events, and their duration in TBI. Intraperitoneal injection of ExD17 improved behavioral outcomes in the TBI mouse model. Conclusions: ExD17 treatment results in a reduction of amyloidogenic APP cleavage and neuroexcitotoxicity, ultimately leading to an improvement in the behavioral deficits observed in TBI mice. [ABSTRACT FROM AUTHOR]

Current trends in neurobiological research focus on analyzing complex interactions within brain structures. To conduct relevant experiments, it is often essential to employ animals with unhampered mobility and utilize electrophysiological equipment capable of wirelessly transmitting data. In prior research, we introduced an open-source wireless electrophysiology system to surmount these challenges. Nonetheless, this prototype exhibited several limitations, such as a hefty weight for the wireless module, redundant system components, a diminished sampling rate, and limited battery longevity. In this study, we unveil an enhanced version of the open-source wireless electrophysiology system, tailored for in vivo monitoring of neural activity in rodent brains. This new system has been successfully tested in real-time recordings of in vivo neural activity. Consequently, our development offers researchers a cost-effective and proficient tool for studying complex brain functions. [ABSTRACT FROM AUTHOR]

Background: Bulimia nervosa (BN) is an eating disorder characterized by recurrent binge eating and compensatory behaviors. The thalamus plays a crucial role in the neural circuitry related to eating behavior and needs to be further explored in BN. Methods: In this study, 49 BN patients and 44 healthy controls (HCs) were recruited. We applied the fractional amplitude of low-frequency fluctuation to investigate regional brain activity in the thalamus and functional connectivity (FC) to examine the synchronization of activity between thalamic subregions and other brain regions in both groups. All results underwent false discovery rate (p < 0.05, FDR correction) correction. Pearson correlation analysis was performed to assess the relationship between the patients' abnormal clinical performance and the thalamic alterations (p < 0.05, FDR correction). Results: We found no significant differences in neural activity between BN patients and HCs in the sixteen thalamic subregions. However, compared to the HCs, the individuals with BN showed decreased FC between the thalamic subregions and several regions, including the bilateral prefrontal cortex, right inferior parietal lobule, right supplementary motor area, right insula, cingulate gyrus and vermis. Additionally, BN patients showed increased FC between the thalamic subregions and visual association regions, primary sensorimotor cortex, and left cerebellum. These altered FC patterns in the thalamus were found to be correlated with clinical variables (the frequency of binge eating/purging per week and external eating behavior scale scores) in the BN group. All results have passed FDR correction. Conclusions: Our study provides evidence that there is disrupted FC between thalamic subregions and other brain regions in BN patients during resting state. These regions are primarily located within the frontoparietal network, default mode network, somatosensory, and visual network. These findings elucidate the neural activity characteristics underlying BN and suggest that thalamic subregions have potential as targets for future neuromodulation interventions. Plain English summary: The high recurrence rate of bulimia nervosa (BN) poses a clinical challenge, and thus, it is crucial to improve the characterization and identification of brain functional abnormalities as direct targets for novel therapies. To investigate the neural circuitry associated with BN, the thalamus is a critical node since it serves as a higher-order relay point in the cortico-thalamo-cortical information pathway. Our findings reveal that altered functional connectivity (FC) between thalamic nuclei and other brain regions is evident throughout the whole brain, particularly within the frontoparietal network, default mode network, somatosensory, and visual network. These changes in FC are significantly associated with disordered eating behavior and the severity of illness in BN patients. Therefore, these findings help identify the neural mechanisms underlying disordered eating behavior and BN severity and suggest potential targets for future neuromodulation interventions. [ABSTRACT FROM AUTHOR]

Magnetoencephalography (MEG) could explore and resolve brain signals with realistic temporal resolution to investigate the underlying electrophysiology of major depressive disorder (MDD) and the treatment efficacy. Here, we explore whether neuro-electrophysiological features of MDD at baseline can be used as a neural marker to predict their early antidepressant response. Sixty-six medication-free patients with MDD and 48 healthy controls were enrolled and underwent resting-state MEG scans. Hamilton depression rating scale (HAMD-17) was assessed at both baseline and after two-week pharmacotherapy. We measured local and large-scale resting-state oscillatory dysfunctions with a data-driven model, the Fitting Oscillations & One-Over F algorithm. Then, we quantified band-limited regional power and functional connectivity between brain regions. After two-week follow-up, 52 patients completed the re-interviews. Thirty-one patients showed early response (ER) to pharmacotherapy and 21 patients did not. Treatment response was defined as at least 50 % reduction of severity reflected by HAMD-17. We observed decreased regional periodic power in patients with MDD comparing to controls. However, patients with ER exhibited that functional couplings across brain regions in both alpha and beta band were increased and significantly correlated with severity of depressive symptoms after treatment. Receiver operating characteristic curves (ROC) further confirmed the predictive ability of baseline large-scale functional connectivity for early antidepressant efficacy (AUC = 0.9969). Relatively small sample size and not a double-blind design. The current study demonstrated the electrophysiological dysfunctions of local neural oscillatory related with depression and highlighted the identification ability of large-scale couplings biomarkers in early antidepressant response prediction. • Depressed patients with early antidepressant response (ER) showed decreased regional periodic power comparing to controls. • Depressed patients with ER showed increased alpha and beta functional couplings across brain regions than those without ER. • ROCs confirmed predictive ability of baseline large-scale functional connectivity for early antidepressant efficacy. [ABSTRACT FROM AUTHOR]

Background: Sensory over-responsivity (SOR) is an impairing sensory processing challenge in autism spectrum disorder (ASD) which shows heterogenous developmental trajectories and appears to improve into adulthood in some but not all autistic individuals. However, the neural mechanisms underlying interindividual differences in these trajectories are currently unknown. Methods: Here, we used functional magnetic resonance imaging (fMRI) to investigate the association between age and neural activity linearly and nonlinearly in response to mildly aversive sensory stimulation as well as how SOR severity moderates this association. Participants included 52 ASD (14F) and 41 (13F) typically developing (TD) youth, aged 8.6–18.0 years. Results: We found that in pre-teens, ASD children showed widespread activation differences in sensorimotor, frontal and cerebellar regions compared to TD children, while there were fewer differences between ASD and TD teens. In TD youth, older age was associated with less activation in the prefrontal cortex. In contrast, in ASD youth, older age was associated with more engagement of sensory integration and emotion regulation regions. In particular, orbitofrontal and medial prefrontal cortices showed a nonlinear relationship with age in ASD, with an especially steep increase in sensory-evoked neural activity during the mid-to-late teen years. There was also an interaction between age and SOR severity in ASD youth such that these age-related trends were more apparent in youth with higher SOR. Limitations: The cross-sectional design limits causal interpretations of the data. Future longitudinal studies will be instrumental in determining how prefrontal engagement and SOR co-develop across adolescence. Conclusions: Our results suggest that enhanced recruitment of prefrontal regions may underlie age-related decreases in SOR for a subgroup of ASD youth. [ABSTRACT FROM AUTHOR]

In clinical populations, the movement of cerebrospinal fluid (CSF) during sleep is a growing area of research with potential mechanistic connections in both neurodegenerative (e.g., Alzheimer's Disease) and neurodevelopmental disorders. However, we know relatively little about the processes that influence CSF movement. To inform clinical intervention targets this study assesses the coupling between (a) real-time CSF movement, (b) neuronal-driven movement, and (c) non-neuronal systemic physiology driven movement. This study included eight young, healthy volunteers, with concurrently acquired neurofluid dynamics using functional Magnetic Resonance Imaging (MRI), neural activity using Electroencephalography (EEG), and non-neuronal systemic physiology with peripheral functional Near-Infrared Spectroscopy (fNIRS). Neuronal and non-neuronal drivers were assessed temporally; wherein, EEG measured slow wave activity that preceded CSF movement was considered neuronally driven. Similarly, slow wave oscillations (assessed via fNIRS) that coupled with CSF movement were considered non-neuronal systemic physiology driven. Our results document neural contributions to CSF movement were only present during light NREM sleep but low-frequency non-neuronal oscillations were strongly coupled with CSF movement in all assessed states – awake, NREM-1, NREM-2. The clinical/research implications of these findings are two-fold. First, neuronal-driven oscillations contribute to CSF movement outside of deep sleep (NREM-3); therefore, interventions aimed at increasing CSF movement may yield meaningful increases with the promotion of NREM sleep more generally – a focus on NREM S3 may not be needed. Second, non-neuronal systemic oscillations contribute across wake and sleep stages; therefore, interventions may increase CSF movement by manipulating systemic physiology. • Coupling between cerebral hemodynamics and CSF movement in the low-frequency range is independent of the wake/sleep states in young healthy adults. • EEG slow wave activity was observed shortly before cerebral blood volume changes in both cranial and caudal directions, exclusively during NREM sleep. • Non-neuronal systemic physiology continue to contribute significantly towards low-frequency neurofluid oscillations during NREM sleep similar to resting wakefulness. • These results inform the development of therapeutics aimed at improving CSF circulation with precise targets (neuronal or systemic physiological mechanisms) based on wake/sleep state. [ABSTRACT FROM AUTHOR]

Patients who have undergone surgery in early life may be at elevated risk for suffering neuropathic pain in later life. The risk factors for this susceptibility are not fully understood. Here, we used a mouse chronic pain model to test the hypothesis that early exposure to the general anesthetic (GA) Isoflurane causes cellular and molecular alterations in dorsal spinal cord (DSC) and dorsal root ganglion (DRG) that produces a predisposition to neuropathic pain via an upregulation of the mammalian target of the rapamycin (mTOR) signaling pathway. Mice were exposed to isoflurane at postnatal day 7 (P7) and underwent spared nerve injury at P28 which causes chronic pain. Selected groups were treated with rapamycin, an mTOR inhibitor, for eight weeks. Behavioral tests showed that early isoflurane exposure enhanced susceptibility to chronic pain, and rapamycin treatment improved outcomes. Immunohistochemistry, Western blotting, and q-PCR indicated that isoflurane upregulated mTOR expression and neural activity in DSC and DRG. Accompanying upregulation of mTOR and rapamycin-reversible changes in chronic pain-associated markers, including N-cadherin, cAMP response element-binding protein (CREB), purinergic P2Y12 receptor, glial fibrillary acidic protein (GFAP) in DSC; and connexin 43, phospho-extracellular signal-regulated kinase (p-ERK), GFAP, Iba1 in DRG, were observed. We concluded that early GA exposure, at least with isoflurane, alters the development of pain circuits such that mice are subsequently more vulnerable to chronic neuropathic pain states. [ABSTRACT FROM AUTHOR]

Zero is a magic number. It represents emptiness, nothing -- and yet it is considered one of the greatest cultural achievements of mankind. For a brain that has evolved to process sensory stimuli ('something'), conceiving of empty sets ('nothing') as a meaningful category demands high-level abstraction. Recent studies of cognitive neuroscience now provide an insight into how an abstract concept like zero can emerge. In both behavioral and neural processing, the emergence of zero passes through four stages. In the first stage, the absence of a stimulus, 'nothing', corresponds to a (mental/neural) resting state lacking a specific signature. In the second stage, the absence of stimulus is grasped as a meaningful behavioral category, but is still devoid of quantitative relevance. In the third stage, 'nothing' acquires a quantitative meaning and is represented as an empty set at the low end of a numerical continuum or number line. Finally, the empty-set representation is extended to become the number zero, thus becoming part of a combinatorial number of the symbols system used for calculation and mathematics. The concept of zero shows how our minds and brains originally evolved to represent stimuli and detach from empirical properties to achieve the ultimate in abstract thinking. Because of this, the story of zero tells us a great deal about the mind, leaving empirical grounds behind and raising it to new intellectual heights. [ABSTRACT FROM AUTHOR]

Time and space are fundamental elements that permeate the fabric of nature, and their significance in relation to neural activity and consciousness remains a compelling yet unexplored area of research. The Temporospatial Theory of Consciousness (TTC) provides a framework that links time, space, neural activity, and consciousness, shedding light on the intricate relationships among these dimensions. In this review, I revisit the fundamental concepts and mechanisms proposed by the TTC, with a particular focus on the central concept of temporospatial nestedness. I propose an extension of temporospatial nestedness by incorporating the nested relationship between the temporal circuit and functional geometry of the brain. To further unravel the complexities of temporospatial nestedness, future research directions should emphasize the characterization of functional geometry and the temporal circuit across multiple spatial and temporal scales. Investigating the links between these scales will yield a more comprehensive understanding of how spatial organization and temporal dynamics contribute to conscious states. This integrative approach holds the potential to uncover novel insights into the neural basis of consciousness and reshape our understanding of the world–brain dynamic. [ABSTRACT FROM AUTHOR]

Background: In the field of neuroscience, neural modules and circuits that control biological functions have been found throughout entire neural networks. Correlations in neural activity can be used to identify such neural modules. Recent technological advances enable us to measure whole-brain neural activity with single-cell resolution in several species including C a e n o r h a b d i t i s e l e g a n s . Because current neural activity data in C. elegans contain many missing data points, it is necessary to merge results from as many animals as possible to obtain more reliable functional modules. Results: In this work, we developed a new time-series clustering method, WormTensor, to identify functional modules using whole-brain activity data from C. elegans. WormTensor uses a distance measure, modified shape-based distance to account for the lags and the mutual inhibition of cell–cell interactions and applies the tensor decomposition algorithm multi-view clustering based on matrix integration using the higher orthogonal iteration of tensors (HOOI) algorithm (MC-MI-HOOI), which can estimate both the weight to account for the reliability of data from each animal and the clusters that are common across animals. Conclusion: We applied the method to 24 individual C. elegans and successfully found some known functional modules. Compared with a widely used consensus clustering method to aggregate multiple clustering results, WormTensor showed higher silhouette coefficients. Our simulation also showed that WormTensor is robust to contamination from noisy data. WormTensor is freely available as an R/CRAN package https://cran.r-project.org/web/packages/WormTensor. [ABSTRACT FROM AUTHOR]

Purpose: This is an observational, non-invasive study which measures the VEPs of twelve individuals, at baseline, and under the effect of six monochromatic filters used in visual therapy, to understand their effect on neural activity to propose successful treatments. Methods: Monochromatic filters were chosen to represent the visible light spectrum, going from red to violet color, 440.5–731 nm, and light transmittance from 19 to 89.17%. Two of the participants presented accommodative esotropia. The impact of each filter, differences, and similarities among them, were analyzed using non-parametric statistics. Results: There was an increase on the N75 and P100 latency of both eyes and a decrease was on the VEP amplitude. The neurasthenic (violet), omega (blue), and mu (green) filter had the biggest effects on the neural activity. Changes may primarily be attributable to transmittance (%) for blue-violet colors, wavelength (nm) for yellow-red colors, and a combination of both for the green color. No significant VEPs differences were seen in accommodative strabismic patients, which reflects the good integrity and functionality of their visual pathway. Conclusions: Monochromatic filters, influenced the axonal activation and the number of fibers that get connected after stimulating the visual pathway, as well as the time needed for the stimulus to reach the visual cortex and thalamus. Consequently, modulations to the neural activity could be due to the visual and non-visual pathway. Considering the different types of strabismus and amblyopia, and their cortical-visual adaptations, the effect of these wavelengths should be explored in other categories of visual dysfunctions, to understand the neurophysiology underlying the changes on neural activity. [ABSTRACT FROM AUTHOR]

The neural correlates of most cognitive functions in fish are unknown. This project aimed to identify brain regions involved in visual learning in the cichlid fish Pseudotropheus zebra. The expression of the protein pS6 was measured in 19 brain areas and compared between groups of individuals subjected to four different behavioral contexts (control, avoidance, trained, and novelty groups). Control group individuals were sacrificed with minimal interactions. Fish in the avoidance group were chased with a net for an hour, after which they were sacrificed. Individuals in the trained group received daily training sessions to associate a visual object with a food reward. They were sacrificed the day they reached learning criterion. Fish in the novelty group were habituated to one set of visual stimuli, then faced a change in stimulus type (novelty stimulus) before they were sacrificed. Fish in the three treatment groups showed the largest activation of pS6 in the inferior lobes and the tectum opticum compared to the control group. The avoidance group showed additional activation in the preoptic area, several telencephalic regions, the torus semicircularis, and the reticular formation. The trained group that received a food reward, showed additional activation of the torus lateralis, a tertiary gustatory center. The only area that showed strong activation in all three treatment groups was the nucleus diffusus situated within the inferior lobe. The inferior lobe receives prominent visual input from the tectum via the nucleus glomerulosus but so far, nothing is known about the functional details of this pathway. Our study showed for the first time that the inferior lobes play an important role in visual learning and object recognition. [ABSTRACT FROM AUTHOR]

Vagus nerve stimulation (VNS) is used to treat drug‐resistant epilepsy and depression, with additional applications under investigation. The noradrenergic center locus coeruleus (LC) is vital for VNS effects; however, the impact of varying stimulation parameters on LC activation is poorly understood. This study characterized LC activation across VNS parameters. Extracellular activity was recorded in rats' left LC while 11 VNS paradigms, utilizing variable frequencies and bursting characteristics, were pseudorandomly delivered to the left cervical vagus for five cycles. Neurons' change from baseline firing rate and timing response profiles were assessed. The proportion of neurons categorized as responders over 5 VNS cycles doubled in comparison to the first VNS cycle (p < 0.001) for all VNS paradigms, demonstrating an amplification effect. The percentage of positively consistent/positive responders increased for standard VNS paradigms with frequencies ≥10 Hz and for bursting paradigms with shorter interburst intervals and more pulses per burst. The synchrony between pairs of LC neurons increased during bursting VNS but not standard paradigms. Also, the probability of evoking a direct response during bursting VNS was higher with longer interburst intervals and a higher number of pulses per burst. Standard paradigms between 10–30 Hz best positively activates LC with consistency to VNS while the best bursting paradigm to increase activity was 300 Hz, seven pulses per burst separated by 1 s. Bursting VNS was effective in increasing synchrony between pairs of neurons, suggesting a common network recruitment originating from vagal afferents. These results indicate differential activation of LC neurons depending on the VNS parameters delivered. [ABSTRACT FROM AUTHOR]

Magnetic resonance provides exquisite anatomical images and functional MRI monitors physiological activity by recording blood oxygenation. This review attempts to answer the following question: Can MRI be used as a sensor to directly record neural behavior? It considers MRI sensing of electrical activity in the heart and in peripheral nerves before turning to the central topic: recording of brain activity. The primary hypothesis is that bioelectric current produced by a nerve or muscle creates a magnetic field that influences the magnetic resonance signal, although other mechanisms for detection are also considered. Recent studies have provided evidence that using MRI to sense neural activity is possible under ideal conditions. Whether it can be used routinely to provide functional information about brain processes in people remains an open question. The review concludes with a survey of artificial intelligence techniques that have been applied to functional MRI and may be appropriate for MRI sensing of neural activity. [ABSTRACT FROM AUTHOR]

Parvalbumin‐positive neurons (PVs) are the main class of inhibitory neurons in the mammalian central nervous system. By examining diurnal changes in synaptic and neuronal activity of PVs in the supragranular layer of the mouse primary visual cortex (V1), we found that both PV input and output are modulated in a time‐ and sleep‐dependent manner throughout the 24‐h day. We first show that PV‐evoked inhibition is stronger by the end of the light cycle (ZT12) relative to the end of the dark cycle (ZT0), which is in line with the lower inhibitory input of PV neurons at ZT12 than at ZT0. Interestingly, PV inhibitory and excitatory synaptic transmission slowly oscillate in opposite directions during the light/dark cycle. Although excitatory synapses are predominantly regulated by experience, inhibitory synapses are regulated by sleep, via acetylcholine activating M1 receptors. Consistent with synaptic regulation of PVs, we further show in vivo that spontaneous PV activity displays daily rhythm mainly determined by visual experience, which negatively correlates with the activity cycle of surrounding pyramidal neurons and the dorsal lateral geniculate nucleus‐evoked responses in V1. These findings underscore the physiological significance of PV's daily modulation. Synopsis: Unveiling the modulatory mechanism of cortical parvalbumin‐positive neurons (PVs) in the mature mammalian brain is critical for understanding how cognitive function is regulated in normal and diseased brains. Here the behavior of PVs in area V1 of the mouse visual cortex is investigated ex vivo and in vivo and a circadian output is identified. The excitatory and inhibitory synaptic transmissions of PV neurons bidirectionally oscillate in opposite directions during the 24‐h day.Experience and sleep dominate the daily regulation of the excitatory and inhibitory synapses onto PV neurons, respectively.ACh mediates the daily regulation of PV inhibitory synaptic transmission via targeting the presynaptic M1Rs.In line with synaptic modulation of PVs, evoked PV output ex vivo and spontaneous PV activity in vivo are both altered at different times of the day.Functional oscillation of PVs negatively correlates with the spontaneous activity of surrounding pyramidal neurons and dorsal lateral geniculate nucleus‐evoked responses in area V1 of the mouse visual cortex. [ABSTRACT FROM AUTHOR]

How spontaneous brain neural activities emerge from the underlying anatomical architecture, characterized by structural connectivity (SC), has puzzled researchers for a long time. Over the past decades, much effort has been directed toward the graph modeling of SC, in which the brain SC is generally considered as relatively invariant. However, the graph representation of SC is unable to directly describe the connections between anatomically unconnected brain regions and fail to model the negative functional correlations. Here, we extend the static graph model to a spatiotemporal varying hypergraph Laplacian diffusion (STV-HGLD) model to describe the propagation of the spontaneous neural activity in human brain by incorporating the Laplacian of the hypergraph representation of the structural connectome (${h}$ SC) into the regular wave equation. Theoretical solution shows that the dynamic functional couplings between brain regions fluctuate in the form of an exponential wave regulated by the spatiotemporal varying Laplacian of ${h}$ SC. Empirical study suggests that the cortical wave might give rise to resonance with SC during the self-organizing interplay between excitation and inhibition among brain regions, which orchestrates the cortical waves propagating with harmonics emanating from the ${h}$ SC while being bound by the natural frequencies of SC. Besides, the average statistical dependencies between brain regions, normally defined as the functional connectivity (FC), arises just at the moment before the cortical wave reaches the steady state after the wave spreads across all the brain regions. Comprehensive tests on four extensively studied empirical brain connectome datasets with different resolutions confirm our theory and findings. [ABSTRACT FROM AUTHOR]

The cerebellum is the largest sensorimotor structure in the brain. A fundamental organizational feature of its cortex is its division into a series of rostrocaudally elongated zones. These are defined by their inputs from specific parts of the inferior olive and Purkinje cell output to specific cerebellar and vestibular nuclei. However, little is known about how patterns of neuronal activity in zones, and their microcircuit subdivisions, microzones, are related to behaviour in awake animals. In the present study, we investigated the organization of microzones within the C3 zone and their activity during a skilled forelimb reaching task in cats. Neurons in different microzones of the C3 zone, functionally determined by receptive field characteristics, differed in their patterns of activity during movement. Groups of Purkinje cells belonging to different receptive field classes, and therefore belonging to different microzones, were found to collectively encode different aspects of the reach controlled by the C3 zone. Our results support the hypothesis that the cerebellar C3 zone is organized and operates within a microzonal frame of reference, with a specific relationship between the sensory input to each microzone and its motor output. Key points: A defining feature of cerebellar organization is its division into a series of zones and smaller subunits termed microzones.Much of how zones and microzones are organized has been determined in anaesthetized preparations, and little is known about their function in awake animals.We recorded from neurons in the forelimb part of the C3 zone 'in action' by recording from single cerebellar cortical neurons located in different microzones defined by their peripheral receptive field properties during a forelimb reach–retrieval task in cats.Neurons from individual microzones had characteristic patterns of activity during movement, indicating that function is organized in relation to microcomplexes. [ABSTRACT FROM AUTHOR]

• fMRI assessed neural correlates of understanding expected and unexpected actions. • Mirror neuron system brain regions responded to expected actions. • The mirror neuron system and mentalizing system function in concert for unexpected actions. • Functional coupling of both networks and other brain regions occurs only during unexpected actions. • Action expectancy is an important factor affecting action representation. Action understanding involves two distinct processing levels that engage separate neural mechanisms: perception of concrete kinematic information and recognition of abstract action intentions. The mirror neuron system and the mentalizing system have both been linked to concrete action and abstract information processing, but their specific roles remain debatable. Here, we conducted a functional magnetic resonance imaging study with 26 participants who passively observed expected and unexpected actions. We performed whole-brain activation, region of interest, and effective connectivity analyses to investigate the neural correlates of these actions. Whole-brain activation analyses revealed that expected actions were associated with increased activation in the left medial superior frontal gyrus, while unexpected actions were linked to heightened activity in the left supramarginal gyrus, left superior parietal lobule, right inferior temporal gyrus, and left middle frontal gyrus. Region of interest analyses demonstrated that the left ventral premotor cortex exhibited greater activation during the observation of expected actions compared to unexpected actions, while the left inferior frontal gyrus, left superior parietal lobule, and left precuneus showed stronger activation during the observation of unexpected actions. Effective connectivity was observed between the left ventral premotor cortex and the left angular gyrus, left intraparietal sulcus, left dorsal premotor cortex, and left ventromedial prefrontal cortex with the middle frontal gyrus when observing unexpected, but not expected, actions. These findings suggest that expected actions are primarily processed by the mirror neuron system, whereas unexpected actions engage both the mirror neuron system and the mentalizing system, with these systems playing complementary roles in the understanding of unexpected actions. [ABSTRACT FROM AUTHOR]

Establishing the biological basis of cognition and its disorders will require high precision spatiotemporal measurements of neural activity. Recently developed genetically encoded voltage indicators (GEVIs) report both spiking and subthreshold activity of identified neurons. However, maximally capitalizing on the potential of GEVIs will require imaging at millisecond time scales, which remains challenging with standard camera systems. Here, application of single photon avalanche diode (SPAD) sensors is reported to image neural activity at kilohertz frame rates. SPADs are electronic devices that when activated by a single photon cause an avalanche of electrons and a large electric current. An array of SPAD sensors is used to image individual neurons expressing the GEVI Voltron‐JF525‐HTL. It is shown that subthreshold and spiking activity can be resolved with shot noise limited signals at frame rates of up to 10 kHz. SPAD imaging is able to reveal millisecond scale synchronization of neural activity in an ex vivo seizure model. SPAD sensors may have widespread applications for investigation of millisecond timescale neural dynamics. [ABSTRACT FROM AUTHOR]

The brain’s connectome provides the scaffold for canonical neural computations. However, a comparison of connectivity studies in the mouse primary visual cortex (V1) reveals that the average number and strength of connections between specific neuron types can vary. Can variability in V1 connectivity measurements coexist with canonical neural computations? We developed a theory-driven approach to deduce V1 network connectivity from visual responses in mouse V1 and visual thalamus (dLGN). Our method revealed that the same recorded visual responses were captured by multiple connectivity configurations. Remarkably, the magnitude and selectivity of connectivity weights followed a specific order acrossmost of the inferred connectivity configurations. We argue that this order stems fromthe specific shapes of the recorded contrast response functions and contrast invariance of orientation tuning. Remarkably, despite variability across connectivity studies, connectivity weights computed from individual published connectivity reports followed the order we identified with our method, suggesting that the relations between the weights, rather than theirmagnitudes, represent a connectivity motif supporting canonical V1 computations. [ABSTRACT FROM AUTHOR]

Depression is a debilitating mood disorder with highly heterogeneous pathogenesis. The limbic system is well-linked to depression. As an important node in the limbic system, the lateral septum (LS) can modulate multiple affective and motivational behaviors. However, the role of LS in depression remains unclear. By using c-Fos expression mapping, we first screened and showed activation of the LS in various depression-related behavioral tests, including the forced swim test (FST), tail suspension test (TST), and sucrose preference test. In the LS, more than 10% of the activated neurons were somatostatin-expressing (SST) neurons. We next developed a microendoscopic calcium imaging method in freely moving mice and revealed that LSSST neural activity increased during mobility in the TST but not open field test. We hypothesize that LSSST neuronal activity is linked to stress and depression. In two mouse models of depression, repeated lipopolysaccharide (LPS) injection and chronic restraint stress (CRS), we showed that LS neuronal activation was suppressed. To examine whether the re-activation of LSSST neurons can be therapeutically beneficial, we optogenetically activated LSSST neurons and produced antidepressant-like effects in LPS-injected mice by increasing TST motility. Moreover, chemogenetic activation of LSSST neurons increased FST struggling in the CRS-exposed mice. Together, these results provide the first evidence of a role for LSSST neurons in regulating depressive-like behaviors in mice and identify them as a potential therapeutic target for neuromodulation-based intervention in depression. [ABSTRACT FROM AUTHOR]

A brain-computer interface (BCI) is a system that translates brain activity into commands to operate technology. A common design for an electroencephalogram (EEG) BCI relies on the classification of the P300 event-related potential (ERP), which is a response elicited by the rare occurrence of target stimuli among common nontarget stimuli. Few existing ERP classifiers directly explore the underlying mechanism of the neural activity. To this end, we perform a novel Bayesian analysis of the probability distribution of multi-channel real EEG signals under the P300 ERP-BCI design. We aim to identify relevant spatial temporal differences of the neural activity, which provides statistical evidence of P300 ERP responses and helps design individually efficient and accurate BCIs. As one key finding of our single participant analysis, there is a 90% posterior probability that the target ERPs of the channels around visual cortex reach their negative peaks around 200 milliseconds poststimulus. Our analysis identifies five important channels (PO7, PO8, Oz, P4, Cz) for the BCI speller leading to a 100% prediction accuracy. From the analyses of nine other participants, we consistently select the identified five channels, and the selection frequencies are robust to small variations of bandpass filters and kernel hyper parameters. for this article are available online. [ABSTRACT FROM AUTHOR]

Balance and walking are fundamental to support common daily activities. Relatively accurate characterizations of normal and impaired gait features were attained at the kinematic and muscular levels. Conversely, the neural processes underlying gait dynamics still need to be elucidated. To shed light on gait‐related modulations of neural activity, we collected high‐density electroencephalography (hdEEG) signals and ankle acceleration data in young healthy participants during treadmill walking. We used the ankle acceleration data to segment each gait cycle in four phases: initial double support, right leg swing, final double support, left leg swing. Then, we processed hdEEG signals to extract neural oscillations in alpha, beta, and gamma bands, and examined event‐related desynchronization/synchronization (ERD/ERS) across gait phases. Our results showed that ERD/ERS modulations for alpha, beta, and gamma bands were strongest in the primary sensorimotor cortex (M1), but were also found in premotor cortex, thalamus and cerebellum. We observed a modulation of neural oscillations across gait phases in M1 and cerebellum, and an interaction between frequency band and gait phase in premotor cortex and thalamus. Furthermore, an ERD/ERS lateralization effect was present in M1 for the alpha and beta bands, and in the cerebellum for the beta and gamma bands. Overall, our findings demonstrate that an electrophysiological source imaging approach based on hdEEG can be used to investigate dynamic neural processes of gait control. Future work on the development of mobile hdEEG‐based brain–body imaging platforms may enable overground walking investigations, with potential applications in the study of gait disorders. [ABSTRACT FROM AUTHOR]

Purpose: Alzheimer's disease (AD) and mild cognitive impairment (MCI) are characterized by both aberrant regional neural activity and disrupted inter-regional functional connectivity (FC). However, the effect of AD/MCI on the coupling between regional neural activity (measured by regional fluorodeoxyglucose imaging (rFDG)) and inter-regional FC (measured by resting-state functional magnetic resonance imaging (rs-fMRI)) is poorly understood. Methods: We scanned 19 patients with MCI, 33 patients with AD, and 26 healthy individuals by simultaneous FDG-PET/rs-fMRI and assessed rFDG and inter-regional FC metrics (i.e., clustering coefficient and degree centrality). Next, we examined the potential moderating effect of disease status (MCI or AD) on the link between rFDG and inter-regional FC metrics using hierarchical moderated multiple regression analysis. We also tested this effect by considering interaction between disease status and inter-regional FC metrics, as well as interaction between disease status and rFDG. Results: Our findings revealed that both rFDG and inter-regional FC metrics were disrupted in MCI and AD. Moreover, AD altered the relationship between rFDG and inter-regional FC metrics. In particular, we found that AD moderated the effect of inter-regional FC metrics of the caudate, parahippocampal gyrus, angular gyrus, supramarginal gyrus, frontal pole, inferior temporal gyrus, middle frontal, lateral occipital, supramarginal gyrus, precuneus, and thalamus on predicting their rFDG. On the other hand, AD moderated the effect of rFDG of the parietal operculum on predicting its inter-regional FC metric. Conclusion: Our findings demonstrated that AD decoupled the link between regional neural activity and functional segregation and global connectivity across particular brain regions. [ABSTRACT FROM AUTHOR]

Fish use a variety of sensory systems when foraging. Salmonids are generally considered visual feeders. However, some species feed on zooplanktons under dark conditions, suggesting they also detect prey using nonvisual cues. Under experimental conditions, hatchery‐reared rainbow trout (Oncorhynchus mykiss) have been shown to use olfaction when searching for food pellets, but olfactory foraging has not been documented in wild salmonids. In the present study, to examine their behavioural response and neural activity in the olfactory nervous system using c‐fos expression as a neural molecular marker, immature wild‐caught lacustrine sockeye salmon (Oncorhynchus nerka) in a flow‐through aquarium were exposed to zooplanktons (Daphnia spp.) extract including zooplanktons odorant and to dimethyl sulfide. The salmon exposed to zooplanktons odour increased their total swimming distance and time, numbers of turns and ascents, and c‐fos expression in the olfactory bulb, suggesting that they can detect zooplanktons extract to locate prey in the laboratory experiments. However, no response was seen in those exposed to dimethyl sulfide. The results of this study suggest that prey odour may serve as a chemosensory cue for wild immature salmonids. [ABSTRACT FROM AUTHOR]

Anodal transcranial direct current stimulation (a-tDCS) aims to hone motor skills and improve the quality of life. However, the non-repeatability of experimental results and the inconsistency of research conclusions have become a common phenomenon, which may be due to the imprecision of the experimental protocol, great variability of the participant characteristics within the group, and the irregularities of quantitative indicators. The aim of this study systematically summarised and analysed the effect of a-tDCS on lower extremity sensorimotor control under different experimental conditions. This narrative review was performed following the PRISMA guidelines until June 2022 in Web of Science, PubMed, Science Direct, Google Scholar, and Scopus. The findings of the present study demonstrated that a-tDCS can effectively improve the capabilities of lower extremity sensorimotor control, particularly in gait speed and time-on-task. Thus, a-tDCS can be used as an effective ergogenic technology to facilitate physical performance. In-depth and rigorous experimental protocol with larger sample sizes and combining brain imaging technology to explore the mechanism have a profound impact on the development of tDCS. [ABSTRACT FROM AUTHOR]

Monitoring neural activity and associating neural dynamics with the anatomical connectome are required to understand how the brain works. Neural dynamics are measured by electrophysiology and optical imaging. Since the discovery of the two-photon excitation phenomenon, significant progress has been made in deep imaging for capturing neural activity from numerous neurons in vivo. The development of two-photon microscopy is aimed to image neural activity from a large and deep region with high spatial (x , y , and z) and temporal (t) resolutions at a high signal-to-noise ratio. Imaging deep regions along the optical axis (z -axis) is particularly challenging because heterogeneous biological tissues scatter and absorb light. Recent advances in the light focus modulation technology at high speeds in three dimensions (x , y , and z) have allowed multiplane two-photon imaging. z -Focus control by varifocal optical systems, such as ferroelectric liquid lenses, gradient refractive index lenses, and adaptive optical element systems, and multiplexing by time- and wavelength-division strategies have allowed to rapidly observe specimens at different focal depths. Herein, we overview the recent advances in multiplane functional imaging systems that enable four-dimensional (x , y , z , and t) analysis of neural dynamics, with a special emphasis on z -scanning mechanisms and multiplexing strategies. • Multiplane two-photon imaging allows 4D (x , y , z , and t) analysis of neural dynamics. • Multiplane imaging is achieved using fast z -focus scanning and/or multiplexing techniques. • Fast varifocal optical system without moving objective is used in z -focus scanning. • Multiplexing via time- or wavelength-division allows signal separation and acquisition. [ABSTRACT FROM AUTHOR]

Microelectrode arrays (MEAs) are pivotal brain-machine interface devices that facilitate in situ and real-time detection of neurophysiological signals and neurotransmitter data within the brain. These capabilities are essential for understanding neural system functions, treating brain disorders, and developing advanced brain-machine interfaces. To enhance the performance of MEAs, this study developed a crosslinked hydrogel coating of calcium alginate (CA) and chitosan (CS) loaded with the anti-inflammatory drug dexamethasone sodium phosphate (DSP). By modifying the MEAs with this hydrogel and various conductive nanomaterials, including platinum nanoparticles (PtNPs) and poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS), the electrical properties and biocompatibility of the electrodes were optimized. The hydrogel coating matches the mechanical properties of brain tissue more effectively and, by actively releasing anti-inflammatory drugs, significantly reduces post-implantation tissue inflammation, extends the electrodes' lifespan, and enhances the quality of neural activity detection. Additionally, this modification ensures high sensitivity and specificity in the detection of dopamine (DA), displaying high-quality dual-mode neural activity during in vivo testing and revealing significant functional differences between neuron types under various physiological states (anesthetized and awake). Overall, this study showcases the significant application value of bioactive hydrogels as excellent nanobiointerfaces and drug delivery carriers for long-term neural monitoring. This approach has the potential to enhance the functionality and acceptance of brain-machine interface devices in medical practice and has profound implications for future neuroscience research and the development of strategies for treating neurological diseases. [ABSTRACT FROM AUTHOR]

Simply withholding a response while viewing an appetizing food, over the course of many presentations (i.e., during food go/no-go training) can modify individuals' food preferences—which could, in turn, promote healthier eating behaviors. However, the neural mechanisms underlying this food go/no-go training-induced change in food preferences are still relatively unclear. We addressed this issue in the present functional magnetic resonance imaging (fMRI) study. To this end, we administered a novel passive viewing task before and after food go/no-go training to 91 participants in the scanner. Participants' food preferences were measured with a binary food choice task. At the behavioral level, we found the expected training effect on food preferences: Participants preferred go over no-go foods following training. At the neural level, we found that changes in food preferences were associated with training-related go vs. no-go differences in activity and functional connectivity, such as less activity in the anterior cingulate cortex and superior frontal gyrus but greater functional connectivity between the superior frontal gyrus and middle occipital gyrus. Critically, Dynamic causal modeling showed that this preference change effect was largely driven by top-down influence from the superior frontal gyrus to the middle occipital gyrus. Together, these findings suggest a neural mechanism of the food go/no-go training effect—namely, that the food-viewing-related interplay between prefrontal regions and visual regions might be related to the food preference change following food go/no-go training. • Changes in food preferences induced by the food go/no-go training are linked to decreased activity in both the anterior cingulate cortex and the superior frontal gyrus. • Increased functional connectivity between the superior frontal gyrus and the middle occipital gyrus is associated with the changes in preferences resulting from the training. • The directional influence from the superior frontal gyrus to the middle occipital gyrus plays a crucial role in the preference changes induced by the training. [ABSTRACT FROM AUTHOR]

Learning and decision-making are greatly influenced by context. When navigating a complex social world, individuals must quickly ascertain where to gain important resources and which group members are useful sources of such information. Such dynamic behavioural processes require neural mechanisms that are flexible across contexts. Here we examine how the social context influences the learning response during a cue discrimination task and the neural activity patterns that underlie acquisition of this novel information. Using the cichlid fish, Astatotilapia burtoni, we show that learning of the task is faster in social groups than in a non-social context. We quantify the neural activity patterns by examining the expression of Fos, an immediate-early gene, across brain regions known to play a role in social behaviour and learning (such as the putative teleost homologues of the mammalian hippocampus, basolateral amygdala and medial amygdala/BNST complex). We find that neural activity patterns differ between social and non-social contexts. Taken together, our results suggest that while the same brain regions may be involved in the learning of a cue association, the activity in each region reflects an individual's social context. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex (TSC) is caused by mutations in Tsc1 or Tsc2, whose gene products inhibit the small G-protein Rheb1. Rheb1 activates mTORC1, which may cause refractory epilepsy, intellectual disability, and autism. The mTORC1 inhibitors have been used for TSC patients with intractable epilepsy. However, its effectiveness for cognitive symptoms remains unclear. We found a new signaling pathway for synapse formation through Rheb1 activation, but not mTORC1. Here, we show that treatment with the farnesyltransferase inhibitor lonafarnib increased unfarnesylated (inactive) Rheb1 levels and restored synaptic abnormalities in cultured Tsc2+/- neurons, whereas rapamycin did not enhance spine synapse formation. Lonafarnib treatment also restored the plasticityrelated Arc (activity-regulated cytoskeleton-associated protein) expression in cultured Tsc2+/- neurons. Lonafarnib action was partly dependent on the Rheb1 reduction with syntenin. Oral administration of lonafarnib increased unfarnesylated protein levels without affecting mTORC1 and MAP (mitogen-activated protein (MAP)) kinase signaling, and restored dendritic spine morphology in the hippocampi of male Tsc2+/- mice. In addition, lonafarnib treatment ameliorated contextual memory impairments and restored memory-related Arc expression in male Tsc2+/- mice in vivo. Heterozygous Rheb1 knockout in male Tsc2+/- mice reproduced the results observed with pharmacological treatment. These results suggest that the Rheb1 activation may be responsible for synaptic abnormalities and memory impairments in Tsc2+/- mice, and its inhibition by lonafarnib could provide insight into potential treatment options for TSC-associated neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

This article is part of a Festschrift commemorating the 50th anniversary of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Established in 1970, first as part of the National Institute of Mental Health and later as an independent institute of the National Institutes of Health, NIAAA today is the world’s largest funding agency for alcohol research. In addition to its own intramural research program, NIAAA supports the entire spectrum of innovative basic, translational, and clinical research to advance the diagnosis, prevention, and treatment of alcohol use disorder and alcohol-related problems. To celebrate the anniversary, NIAAA hosted a 2-day symposium, “Alcohol Across the Lifespan: 50 Years of Evidence Based Diagnosis, Prevention, and Treatment Research,” devoted to key topics within the field of alcohol research. This article is based on Dr. Sinha’s presentation at the event. NIAAA Director George F. Koob, Ph.D., serves as editor of the Festschrift. [ABSTRACT FROM AUTHOR]

Objective: Our goal was to analyze the electrophysiological response to direct electrical stimulation (DES) systematically applied at a wide range of parameters and anatomical sites, with particular focus on neural activities associated with memory and cognition. Methods: We used a large set of intracranial EEG (iEEG) recordings with DES from 45 subjects with electrodes implanted both subdurally on the cortical surface and subcortically into the brain parenchyma. Subjects were stimulated in blocks of alternating frequency and amplitude parameters during quiet wakefulness. Results: Stimulating at different frequencies and amplitudes of electric current revealed a persistent pattern of response in the slow and the fast neural activities. In particular, amplification of the theta (4–7 Hz) and attenuation of the gamma (29–52 Hz) power-in-band was observed with increasing the stimulation parameters. This opposite effect on the low and high frequency bands was found across a network of selected local and distal sites proportionally to the proximity and magnitude of the electric current. Power increase in the theta and decrease in the gamma band was driven by the total electric charge delivered with either increasing the frequency or amplitude of the stimulation current. This inverse effect on the theta and gamma activities was consistently observed in response to different stimulation frequencies and amplitudes. Conclusion: Our results suggest a uniform DES effect of amplifying theta and suppressing gamma neural activities in the human brain. Significance: These findings reveal the utility of simple power-in-band features for understanding and optimizing the effects of electrical stimulation on brain functions. [ABSTRACT FROM AUTHOR]

Sleep disorders, increasingly prevalent in the general population, induce impairment in daytime functioning and other clinical problems. As changes in cortical excitability have been reported as potential pathophysiological mechanisms underlying sleep disorders, multiple studies have explored clinical effects of modulating cortical excitability through non-invasive brain stimulation in treating sleep disorders. In this study, we critically reviewed clinical studies using non-invasive brain stimulation, particularly transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), for treatment of sleep disorders. Previous studies have reported inconsistent therapeutic effects of TMS and tDCS for various kinds of sleep disorders. Specifically, low-frequency repetitive TMS (rTMS) and cathodal tDCS, both of which exert an inhibitory effect on cortical excitability, have shown inconsistent therapeutic effects for insomnia. On the other hand, high-frequency rTMS and anodal tDCS, both of which facilitate cortical excitability, have improved the symptoms of hypersomnia. In studies of restless legs syndrome, high-frequency rTMS and anodal tDCS induced inconsistent therapeutic effects. Single TMS and rTMS have shown differential therapeutic effects for obstructive sleep apnea. These inconsistent findings indicate that the distinctive characteristics of each non-invasive brain stimulation method and specific pathophysiological mechanisms underlying particular sleep disorders should be considered in an integrated manner for treatment of various sleep disorders. Future studies are needed to provide optimized TMS and tDCS protocols for each sleep disorder, considering distinctive effects of non-invasive brain stimulation and pathophysiology of each sleep disorder. [ABSTRACT FROM AUTHOR]

This work presents a novel method of exploring human brain-visual representations, with a view towards replicating these processes in machines. The core idea is to learn plausible computational and biological representations by correlating human neural activity and natural images. Thus, we first propose a model, EEG-ChannelNet, to learn a brain manifold for EEG classification. After verifying that visual information can be extracted from EEG data, we introduce a multimodal approach that uses deep image and EEG encoders, trained in a siamese configuration, for learning a joint manifold that maximizes a compatibility measure between visual features and brain representations. We then carry out image classification and saliency detection on the learned manifold. Performance analyses show that our approach satisfactorily decodes visual information from neural signals. This, in turn, can be used to effectively supervise the training of deep learning models, as demonstrated by the high performance of image classification and saliency detection on out-of-training classes. The obtained results show that the learned brain-visual features lead to improved performance and simultaneously bring deep models more in line with cognitive neuroscience work related to visual perception and attention. [ABSTRACT FROM AUTHOR]

• Melamine impairs mPFC-dependent working memory. • Melamine reduces the level of AMPA receptor mGluR2/3 subunit in the mPFC. • Melamine depresses the neural activity during delay period of working memory test. • mGluR2/3 agonists can effectively mitigate the neural and cognitive dysfunction. Recent studies have reported that melamine can accumulate in several regions of the brain including the medial prefrontal cortex (mPFC). Although melamine accumulation in the hippocampus has been verified to induce cognitive impairments, whether it can cause mPFC-dependent working memory deficits is still unknown. After chronic treatment with melamine (150 (Mel(150)) or 300 (Mel(300)) mg/kg), rats were tested during both delay nonmatching-to-sample spatial and odor discrimination tasks. Levels of AMPA receptor subunits in the mPFC were detected using western blotting. To further explore the mechanism at the cellular level, prefrontal activity was recorded during the odor discrimination. The working memory of Mel(150) rats was found to be significantly impaired in a 3-minute delay odor discrimination task (control: n = 6, Mel(150): n = 6; P < 0.05). Compared with the control group (n = 6), rats in the 300 mg/kg Mel(300)-treated group (n = 8) displayed working memory deficits in 60-second delay Y-maze task (P < 0.05), 1-minute and 3-minute delay odor discrimination tasks (both P < 0.05). The levels of AMPA receptor mGluR2/3 subunit were significantly decreased in rats of the Mel(150) (n = 7) and Mel(300) (n = 7) groups (both P < 0.05). Exposure to 150 (n = 7) or 300 mg/kg (n = 7) melamine resulted in significant inhibition of the regular-spiking neuron activity during the delay period of the memory test (both P < 0.05). Intraperitoneal (n = 7) and intra-mPFC (n = 6) infusions of GluR2/3 agonists, effectively enhanced the neural correlate (both P < 0.05) while rescuing cognitive deficits in Mel(300)-treated rats (both P < 0.05). Collectively, these findings suggested that melamine could induce prefrontal dysfunction and cause cognitive impairments. [ABSTRACT FROM AUTHOR]

• A holographic two-photon microscope was developed for dual-plane imaging. • A spatial light modulator generated an additional focal plane. • A temporal multiplexing strategy allowed fast imaging of two different focal planes. • 4-D imaging was achieved at cellular resolution and physiological timescales. • 4-D imaging and analysis will facilitate studies linking structure and function. Spatiotemporal patterns of neural activity generate brain functions, such as perception, memory, and behavior. Four-dimensional (4-D: x , y , z , t) analyses of such neural activity will facilitate understanding of brain functions. However, conventional two-photon microscope systems observe single-plane brain tissue alone at a time with cellular resolution. It faces a trade-off between the spatial resolution in the x -, y -, and z -axes and the temporal resolution by a limited point-by-point scan speed. To overcome this trade-off in 4-D imaging, we developed a holographic two-photon microscope for dual-plane imaging. A spatial light modulator (SLM) provided an additional focal plane at a different depth. Temporal multiplexing of split lasers with an optical chopper allowed fast imaging of two different focal planes. We simultaneously recorded the activities of neurons on layers 2/3 and 5 of the cerebral cortex in awake mice in vivo. The present study demonstrated the proof-of-concept of dual-plane two-photon imaging of neural circuits by using the temporally multiplexed SLM-based microscope. The temporally multiplexed holographic microscope, combined with in vivo labeling with genetically encoded probes, enabled 4-D imaging and analysis of neural activities at cellular resolution and physiological timescales. Large-scale 4-D imaging and analysis will facilitate studies of not only the nervous system but also of various biological systems. [ABSTRACT FROM AUTHOR]

Assessment of neural activity in the specific brain area is critical for understanding the circuit mechanisms underlying altered brain function and behaviors. A number of immediate early genes (IEGs) that are rapidly transcribed in neuronal cells in response to synaptic activity have been used as markers for neuronal activity. However, protein detection of IEGs requires translation, and the amount of newly synthesized gene product is usually insufficient to detect using western blotting, limiting their utility in western blot analysis of brain tissues for comparison of basal activity between control and genetically modified animals. Here, we show that the phosphorylation status of eukaryotic elongation factor-2 (eEF2) rapidly changes in response to synaptic and neural activities. Intraperitoneal injections of the GABA A receptor (GABAAR) antagonist picrotoxin and the glycine receptor antagonist brucine rapidly dephosphorylated eEF2. Conversely, potentiation of GABAARs or inhibition of AMPA receptors (AMPARs) induced rapid phosphorylation of eEF2 in both the hippocampus and forebrain of mice. Chemogenetic suppression of hippocampal principal neuron activity promoted eEF2 phosphorylation. Novel context exploration and acute restraint stress rapidly modified the phosphorylation status of hippocampal eEF2. Furthermore, the hippocampal eEF2 phosphorylation levels under basal conditions were reduced in mice exhibiting epilepsy and abnormally enhanced excitability in CA3 pyramidal neurons. Collectively, the results indicated that eEF2 phosphorylation status is sensitive to neural activity and the ratio of phosphorylated eEF2 to total eEF2 could be a molecular signature for estimating neural activity in a specific brain area. [ABSTRACT FROM AUTHOR]

• Olfactory receptors determine temporal patterns of spontaneous neural activity. • Different patterns of neural activity induce expression of different sets of gene. • Firing pattern-dependent gene expression regulate glomerular map formation. The development of precise neural circuits is initially directed by genetic programming and subsequently refined by neural activity. In the mouse olfactory system, axons from various olfactory sensory neurons expressing the same olfactory receptor converge onto a few spatially invariant glomeruli, generating the olfactory glomerular map in the olfactory bulbs. Using the glomerular map formation as a model, this review summarizes the current understanding of mechanisms underlying topographic map development in the mouse olfactory system and highlights how neural activity instructs the map refinement process. [ABSTRACT FROM AUTHOR]

• We review the current literature on modulators and determinants of social decisions. • Social decisions are influenced by external factors such as others' trustworthiness. • They are also influenced by internal psychological determinants and neuromodulators. • The neural mechanisms underlying social decisions are discussed. Social decision making is a highly complex process that involves diverse cognitive mechanisms, and it is driven by the precise processing of information from both the environment and from the internal state. On the one hand, successful social decisions require close monitoring of others' behavior, in order to track their intentions; this can guide not only decisions involving other people, but also one's own choices and preferences. On the other hand, internal states such as own reward or changes in hormonal and neurotransmitter states shape social decisions and their underlying neural function. Here, we review the current literature on modulators and determinants of human social decisions. [ABSTRACT FROM AUTHOR]

Graphene microelectrode arrays (MEAs) have emerged as a viable neurointerfacing tool for their combined benefits in mechanical, electrical, and optical properties. To evaluate their promise for high-resolution neurointerfacing applications, here we presented a 28-μm pitched, poly (3, 4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)-coated graphene MEA that can achieve one order higher spatial resolution than previous graphene MEAs in both neurostimulation and optogenetic electrophysiology. The electroplated PEDOT:PSS layer improved the impedance and the charge-injection capacity of the graphene electrodes by 40–60 times (sub-100 kΩ, >1.31 mC/cm2 and maintained low light-induced artifacts among them (sub-3 μV). As a result, our MEA was able to stimulate neuronal ensemble with single electrodes and record optogenetically evoked neural spikes with high signal-to-noise ratios. These results shed light on the possible use of PEDOT:PSS-coated graphene MEAs toward high-resolution interrogation of neural activity. [ABSTRACT FROM AUTHOR]