We investigated dynamic changes in nicotinamide adenine dinucleotide (NAD+) metabolism in the human occipital lobe using ultra-high field 31P functional magnetic resonance spectroscopy (fMRS) at 7 T. Twenty-five healthy volunteers (mean age 24 ± 4 years, 10 females) performed a visual task alternating between fixation and flashing checkerboard stimuli. 31P MRS spectra were acquired from a visual cortex voxel functionally localized by prior functional magnetic resonance imaging (fMRI). Linear mixed-effects modeling revealed a significant reduction in NAD+ concentrations during the first stimulation block, while no significant change was observed during the second block. No significant changes were observed for other high-energy phosphate metabolites (ATP, phosphocreatine, and inorganic phosphate), indicating specificity in the NAD+ response. Exploratory analyses, dividing the blocks in two halves, suggested further reductions in NAD+ and tNAD in the second halves of both stimulation blocks, though these trends were not statistically significant. Our findings demonstrate the feasibility of using fMRS at 7 T to detect stimulus-induced dynamics in cerebral NAD+ metabolism in vivo, providing insights into the interplay between glycolysis and oxidative phosphorylation during neural activation.

Many studies have demonstrated that the basolateral complex of the amygdala (BLA) can facilitate offline consolidation processes in the hippocampus. However, an open question is how online neuronal oscillations in these regions dynamically couple at the moment of encoding to enable an episodic prioritization for important ecologically relevant stimuli. In the current study, local field potentials (LFPs) were recorded in the BLA and hippocampus (ventral CA1) of female rats as they spontaneously explored many novel and repeated plant-based odors and rat urine odors, which convey ecologically relevant information about conspecifics. Rats' estrous cycle was tracked and used to estimate sexual receptivity. Moments of exploring urine odors, particularly from male donors, were associated with different neural activity in the BLA and hippocampus versus plant-based odors, activity that also depended on the novelty of the odors as well as the rats' sexual receptivity. Specifically, prominent slow-gamma (20-50 Hz) oscillations during odor exploration showed a BLA-to-hippocampus directionality and were associated with odor novelty, odor category (male urine vs female urine vs plant-based odors), and better subsequent memory. Spiking-associated (150-200 Hz) activity in the LFPs was also influenced by odor novelty and odor category and was significantly higher in both the BLA and hippocampus on days for which the rats were sexually receptive. Thus, stimulus novelty and ecological relevance combined with the rats' emotional state to shape the neural correlates of prioritized encoding. The results are discussed in terms of endogenous mechanisms of memory enhancement for important to-be-remembered stimuli.

While reinforcement learning algorithms have made significant progress in solving multi-armed bandit problems, they often lack biological plausibility in architecture and dynamics. Here, we propose a bio-inspired neural model based on interacting populations of rate neurons, drawing inspiration from the orbitofrontal cortex and anterior cingulate cortex. Our model reports robust performance across various stochastic bandit problems, matching the effectiveness of standard algorithms such as Thompson Sampling and UCB. Notably, the model exhibits adaptive behavior: employing greedy strategies in low-uncertainty situations while increasing exploratory behavior as uncertainty rises. Through evolutionary optimization, the model's hyperparameters converged to values that align with the principles of synaptic mechanisms, particularly in terms of synapse-dependent neural activity and learning rate adaptation. These findings suggest that biologically-inspired computational architectures can achieve competitive performance while providing insights into neural mechanisms of decision-making under uncertainty.

Brain oxygen levels fluctuate with changes in neural activity and systemic physiology, yet it remains unclear whether oxygen responses to salient stimuli are structure-specific or reflect generalized brain activation. Using oxygen sensors coupled with high-speed amperometry in freely moving rats, we compared oxygen dynamics in three structures with markedly different neuronal firing properties: nucleus accumbens, medial thalamus, and substantia nigra pars reticulata, along with simultaneous measurements in the subcutaneous space. Natural arousing stimuli produced rapid oxygen increases in all brain sites coupled with robust subcutaneous oxygen decreases, though there are minor differences in magnitude. In contrast, intravenous fentanyl (30 µg/kg) induced uniform hypoxic responses in all brain sites, consisting of a rapid and strong decrease followed by a weaker post-hypoxic rebound, with low between-site variability. These findings show that physiological oxygen increases during arousal are largely generalized and likely dominated by systemic mechanisms such as peripheral vasoconstriction, cerebral vasodilation, and global increases in cerebral blood flow, whereas fentanyl-induced hypoxia reflects purely systemic effect induced by respiratory depression. Overall, these results indicate that brain oxygen dynamics are shaped predominantly by systemic physiology rather than local neuronal firing properties, highlighting important constraints on interpreting oxygen-based signals as markers of neuronal activity.

This study examines how two facial attributes of robots—the facial width-to-height ratio (fWHR) and eye shape—influence users’ judgments of trustworthiness, and how these features are processed at the neural level. To achieve this goal, we conducted a within-subject Electroencephalogram (EEG) experiment using a 2 (fWHR: low/high) × 3 (eye shape: round/rectangular/obround) full factorial design. EEG signals were analyzed using event-related potentials (ERPs). Results reveal that eye shape significantly influences trustworthiness, with round and obround eyes rated higher than rectangular ones. High fWHR robots with round or obround eyes elicited more negative N1 and N170 amplitudes, while round eyes reduced P3 amplitudes compared to other shapes. These findings not only clarify the neural mechanisms underlying the evaluation of robotic facial cues but also provide practical insights for designing socially trustworthy robots.

Alterations of brain activity in noise-exposed rats after transcutaneous auricular vagus nerve stimulation evaluated via fMRI.

Intensive exercise and high-altitude exposure can disrupt neural activity and impair cognitive functioning. Previous research suggests that ketone ester (KE) ingestion may counteract cognitive impairments, however, its impact on neural activity during exercise and hypoxia remains unclear. Therefore, we investigated the impact of KE on electroencephalography (EEG) patterns and cognition during hypoxia and exercise. Twelve healthy males completed three randomized crossover sessions: i) normoxia + placebo, ii) hypoxia + placebo, and iii) hypoxia + KE. Each session included normoxic endurance (ET120') and high-intensity interval training (HIIT80'), followed by a 16-h period including sleep in either normoxia or hypoxia. The next day, participants performed a normoxic 30-min all-out time-trial (TT30'). EEG was recorded during rest and exercise, while cerebral tissue oxygenation index (cTOI) and cognitive performance were evaluated during rest. At rest, KE attenuated hypoxia-induced increases in alpha and beta power and cTOI declines. Nonetheless, cognitive performance remained unaffected. Brain activity rose throughout ET120' and normalized during recovery, while HIIT80' elicited a fluctuating neural response but normalized during recovery. Following TT30', theta, alpha, and gamma power remained elevated during recovery. Altogether, these data, obtained in healthy males, show the potential of KE to stabilize resting-state EEG patterns in hypoxia. Moreover, they shed light on how EEG patterns vary with exercise intensity, with sustained post-exercise increases in theta, alpha, and gamma power following high-intensity efforts. These findings suggest that KE can help to preserve neural stability under hypoxia and highlight EEG's potential for monitoring fatigue and tailoring training or recovery strategies.

Interpretable EEG biomarkers for neurological disease models in mice using bag-of-waves classifiers.

Tinnitus, characterized by phantom sound perception, exhibits heterogeneous pathophysiology influenced by hearing status. This study investigated dynamic neural activity patterns in 82 participants: 29 healthy controls (HC), 21 tinnitus patients with normal hearing (G1), and 32 tinnitus patients with hearing impairment (G2). Using resting-state fMRI, we computed dynamic amplitude of low-frequency fluctuation (d-ALFF) and dynamic regional homogeneity (d-ReHo) through sliding-window analyses, measuring temporal variability via coefficient of variation. One-way ANOVAs (covarying age/sex) revealed six d-ALFF clusters showing group differences (voxel p < 0.01, cluster p < 0.05 GRF-corrected). Post-hoc analyses demonstrated that G1 exhibited significantly increased d-ALFF variability versus HC and G2 in cerebellar, fusiform, and occipital regions. Conversely, both patient groups showed reduced d-ALFF variability in frontal clusters versus HC. Negative correlations emerged in G2 between fusiform d-ALFF and tinnitus distress/anxiety, while G1 showed positive correlations between temporal d-ALFF and depression. d-ReHo analysis identified reduced variability in the right anterior cingulate in both patient groups versus HC. These findings highlight distinct neural dynamics: tinnitus with normal hearing involves hypervariability in sensory processing regions, while hearing-impaired tinnitus shows distinct clinical correlations. Reduced activity variability in the superior and middle frontal gyri and reduced temporal synchrony in the anterior cingulate suggest a common tinnitus mechanism irrespective of hearing status.

Indigenous high-altitude populations maintain relatively normal brain function despite chronic hypoxia, yet the underlying neurophysiological mechanisms and the potential role of gut-brain interaction remain unclear. This study combined 16S rRNA gut microbiota profiling in 211 high-altitude indigenous populations at 2, 3, and 4 km altitudes with resting-state and task-based electroencephalography recordings in 135 of them. Residents at 4 km showed enhanced delta (1-4 Hz) power across most brain regions along with increased frontal-occipital functional connectivity (FC) during resting state. During a cognitive oddball task, the 4 km group exhibited elevated P3 amplitude in response to oddball stimuli, together with larger parietal delta power. In parallel, the 4 km group displayed higher species richness and an elevated abundance of short-chain fatty acid-producing genera such as Roseburia, Blautia, and Coprococcus. Furthermore, the abundance of Blautia was positively associated with resting-state FC, a relationship that may further influence anxiety and sleep quality. Our findings demonstrate a coordinated gut-brain interaction adaptation to high altitude, highlighting the homeostatic role of microbial pathways.IMPORTANCEIndigenous high-altitude populations maintain normal cognitive function under chronic hypoxia, a process potentially involving the gut microbiota. Our study added evidence that the neural activity patterns and gut microbiota structure may work in coordination to assist the host in adapting to extreme environments.

Anorexia nervosa (AN) and bulimia nervosa (BN) are two primary subtypes of eating disorders (ED), often presenting with overlapping clinical features that complicate diagnosis. Despite shared symptoms, the underlying neural mechanisms of two subtypes remain incompletely understood. Delineating both shared and unique neural alterations may support biomarker discovery and inform targeted interventions. We recruited 28 patients with AN, 26 with BN, and 31 matched healthy controls (HC), aged from 14 to 40 years old. Resting-state functional magnetic resonance image (Rs-fMRI) data were acquired to investigate alterations in spontaneous brain activity. Four voxel-wise metrics were analyzed: amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC). Symptom severity was assessed using the Eating Disorder Examination-Questionnaire (EDEQ), which includes four subscales: Eating concern (EDEQ_E), Shape concern (EDEQ_S), Weight concern (EDEQ_W), and Restraint (EDEQ_R). Pearson correlation analysis was used to examine associations between altered imaging metrics and clinical variables. Both AN and BN exhibited convergent alterations, including reduced activity in the bilateral middle frontal gyrus (MFG), insular cortex (INS), superior temporal gyrus (STG), and left parahippocampal gyrus (PHG), alongside increased activity in the bilateral striatum, middle occipital gyrus (MOG), and cerebellum. Disorder-specific alterations in AN included increased activity in the right striatum and right precuneus, increased DC in the right superior frontal gyrus (SFG), and decreased fALFF and DC in the left calcarine. In contrast, patients with BN exhibited elevated fALFF in the right precentral gyrus (PCG_R) and increased DC in the right calcarine. Correlation analyses revealed negative association between the ReHo value of the MOG_L and EDEQ, and positive associations between the DC value of the PCG_R and EDEQ and EDEQ_E in patients with BN. Our findings revealed both shared and diagnosis-specific alterations in intrinsic brain activity within the cortico- striatal-limbic circuit, underscoring its role in the pathophysiology of ED.

Large field-of-view (FOV) two-photon microscopy enables simultaneous recording across multiple brain regions, but larger FOVs lengthen raster scans and limit temporal resolution. A modular, open-source solution that increases imaging speed and adds fluorescence-lifetime capability on standard systems would broaden access to mesoscale neural measurements. We aimed to develop and validate an open-source, modular field-programmable gate array (FPGA)-based acquisition platform and a circular delay-path (CDP) module that together enable multiarea, multidepth mesoscale two-photon imaging and large-FOV two-photon fluorescence lifetime imaging (2p-FLIM) using an 80MHz laser. We built an FPGA system that digitizes photomultiplier signals at and integrated it with a CDP module for a Diesel2p mesoscope. The CDP temporally multiplexes excitation for four focal planes; the FPGA demultiplexes and reconstructs images. Lifetime imaging was implemented on the same platform. The system enabled simultaneous recording of neurons across the bilateral dorsal cortex at up to four depths and demonstrated large-FOV 2p-FLIM. All hardware and software are open-source and compatible with existing two-photon microscopes. This modular, open-source FPGA + CDP system increases throughput of large-FOV two-photon imaging and adds lifetime contrast without specialized lasers, facilitating multiscale in vivo studies and broad biomedical applications.

Recent advancements in cognitive impairment research have led to significant progress. Electroencephalography (EEG)-based cognitive state identification can detect early cognitive decline in the elderly, providing a critical window for intervention. As cognitive function worsens, neural activity patterns in the brain also change. Functional connectivity between brain regions, a key indicator of synchronized neural activity, is widely used to reveal brain network characteristics under different cognitive states. In this study, we introduce a novel framework, PowerSyncNet, based on functional connectivity to identify cognitive states. PowerSyncNet mainly consists of three modules. The Channel-Pair Feature Sequences Builder extracts features that characterize functional connectivity across different frequency bands. The Encoder4Band module captures temporal-frequency representations that reflect cognitive states and combines cross-band information to improve feature clarity. The Classifier then determines the corresponding cognitive states. We tested PowerSyncNet on the publicly available Chung-Ang University Hospital EEG (CAUEEG) dataset and our own collected Emotion and Cognition EEG (ECED) dataset. Results show that PowerSyncNet has superior cognitive identification capabilities compared with existing deep learning frameworks, facilitating early assessment and timely intervention for patients with cognitive impairment.

Although there are several evidence-based treatments for post-traumatic stress disorder (PTSD), up to half of patients do not experience significant symptom relief. Executive functioning (EF) impairment is believed to impede PTSD recovery and diminish treatment response, but is not directly targeted by traditional treatments. Cognitive training for EF has emerged as a promising treatment alternative for PTSD, but may only benefit certain patients. The present study aimed to identify, validate, and characterize the subgroup of patients with PTSD who respond to an EF training program. Veterans with PTSD (N = 79) completed neuropsychological tests and a working memory task during functional magnetic resonance imaging scanning, followed by 16 sessions of an EF training program (working memory training [WMT]). Growth mixture modeling identified subgroups based on session-by-session working memory changes. Mixed-effects models then evaluated differences in spatial working memory and PTSD symptom improvement among these subgroups. Finally, the subgroups were compared on baseline neuropsychological performance and neural activity. Three subgroups were extracted, with one subgroup (labeled low-WM/steep improvement subgroup) exhibiting steeper working memory improvement across training and greater spatial working memory and PTSD symptom improvement following training. The low-WM/steep improvement subgroup was uniquely characterized by a combination of lower EF task performance and lower working memory-related neural activity at baseline. WMT may be a promising alternative PTSD treatment for Veterans with EF impairments. Patients likely to benefit from WMT could be identified using a combination of neuropsychological and neuroimaging assessments, but further research is needed to confirm these indicators.

While genetically encoded Ca2+ indicators are valuable for visualizing neural activity, their speed and sensitivity have had limited performance when compared to chemical dyes and electrophysiology, particularly at synaptic compartments. We addressed these limitations by engineering a suite of next-generation GCaMP8-based indicators, targeted to presynaptic boutons, active zones, and postsynaptic compartments at the Drosophila neuromuscular junction. We first validated these sensors to be superior to previous versions and synthetic dyes. Next, we developed a Python-based analysis program, CaFire, which enables the automated quantification of evoked and spontaneous Ca²+ signals. Using CaFire, we show a ratiometric presynaptic GCaMP8m sensor accurately captures physiologically relevant presynaptic Ca2+ changes with superior sensitivity and similar kinetics compared to chemical dyes. Moreover, we test the ability of an active zone-targeted, ratiometric GCaMP8m sensor to report differences in Ca²+ between release sites. Finally, a newly engineered postsynaptic GCaMP8m, positioned near glutamate receptors, detects quantal events with temporal and signal resolution comparable to electrophysiological recordings. These next-generation indicators and analytical methods demonstrate that GCaMP8 sensors, targeted to synaptic compartments, can now achieve the speed and sensitivity necessary to resolve Ca2+ dynamics at levels previously only attainable with chemical dyes or electrophysiology.

Despite decades of research, the underlying mechanism of auditory verbal hallucinations (AVH), a core symptom of schizophrenia, remain unclear. Previous studies have tried to capture the neural activity during AVH episodes, whereas trait features of AVH have been less investigated. To address this gap, we employed functional Near-Infrared Spectroscopy (fNIRS) to investigate the neuroimaging patterns in healthy controls (HCs), patients with schizophrenia with a history of AVH (AVHh+) and those without a history of AVH history (AVHh-). We hypothesized that significant differences of functional connectivity (FC) changes would be observed in AVHh+. We recruited 23 AVHh+, 16 AVHh-, and 17 matched HCs. Participants underwent an 8-minute resting-state fNIRS scanning. Data processing and analysis were conducted by the NirSpark software (HuiChuang, China) package and R Studio. Compared to the AVHh-, the AVHh+ showed significantly lower FC between the Broca's area and the left supplementary motor area (SMA). The hypoconnectivity of Broca-left SMA circuit might serve as a trait-like marker of vulnerability to AVH.

Abstract The integration of sensory information in humans may be confined to a time window of 2–3 seconds. In language, this time window constrains the grouping of words into multi-word chunks, required for comprehension. Chunk boundaries are known to elicit a characteristic event-related brain potential, the Closure Positive Shift (CPS). The likelihood of a CPS increases with the duration of the chunk. In the frequency-domain, boundaries have been associated with neural oscillations in the delta band (&amp;lt;4 Hz). Here, we assessed whether the pace for chunking might be imposed by electrophysiological processing cycles of the brain with phase-locking of such activity underlying the CPS. We recorded participants’ magnetoencephalogram while they listened to globally ambiguous sentences allowing for two alternative ways of chunking. Chunking was not externally imposed, but the temporal limits of integration windows influenced chunk termination. Phase-locking of narrow-band low-frequency neural activity (i.e., &amp;lt;4 Hz) at the boundaries of multi-word chunks increased with sentence duration, and covaried with event-related fields. Behavioral data further indicate subtle interindividual differences in the duration of the integration time window. Source localization revealed neural generators in bilateral posterior temporal and right anterior regions. The brain appears to project duration-limited integration windows onto the incoming auditory speech signal, thus structuring language comprehension in time.

Non-invasive modulation of brain activity and behavior by transcranial radio frequency stimulation.

Corticomuscular coherence and its non-invasive modulation in stroke applications: a narrative review.

During the shooting-preparation phase, shooters frequently encounter multiple interfering factors, such as task load, social evaluation, and complex environments. These factors can induce intricate changes in neural activity, leading to variations in shooting performance. This study aims to investigate the neural mechanisms underlying brain activity during the shooting preparation phase in high-risk tasks (e.g., Hostage-Rescue Condition) and high-precision tasks (e.g., Long-Range Condition). Electroencephalographic (EEG) signals, the shooting performance metrics, and the self-report measures were collected from 30 shooters who completed shooting tasks under three conditions: Hostage-Rescue Condition, Long-Range Condition, and Close-Range Condition. EEG signals were subjected to sensor-level spectral analysis, source-level spectral analysis, functional connectivity analysis, and graph-theoretic analysis. Compared with Close-Range Condition, shooters exhibited the following characteristics during Hostage-Rescue Condition and Long-Range Condition: (1) perceived pressure increased significantly; however, shooting score and aiming time improved significantly only in the Hostage-Rescue Condition; (2) significant differences were observed across multiple frequency bands and brain regions. Sensor-level spectral analysis revealed the greatest number of significant differences in beta-band event-related desynchronization/synchronization across conditions. Source-space analysis indicated that the theta band exhibited the highest number of significant differences across conditions; (3) functional connectivity between the frontal lobe and other lobes weakened significantly, whereas intra-lobar connectivity strengthened significantly. In addition, small-worldness increased, but the clustering coefficient and global efficiency decreased significantly. Under Hostage-Rescue Condition and Long-Range Condition, shooters perceived greater pressure, yet the shooting score improved only under Hostage-Rescue Condition. Intra-lobar functional connectivity strengthened, whereas connectivity between the frontal lobe and other lobes was suppressed. Nodal clustering coefficients increased in vision-related regions but decreased in semantically related regions. These changes indicate that, when confronting Hostage-rescue and Long-Range Conditions, the brain achieves adaptive regulation by redistributing neural resources to optimize information-processing efficiency.