Frontiers in Integrative Neuroscience

Background and Objectives In ADHD, a heterogeneous neurodevelopmental condition, behavioral and motor manifestations may reflect multiple inefficient or perturbed inhibitory systems. To evaluate Transcranial Magnetic Stimulation (TMS) evoked cortical silent period (CSP) duration, an indicator of GABA(B) receptor-mediated inhibition in motor cortex, as a potential biomarker of Attention-Deficit/Hyperactivity Disorder (ADHD) in children. Method We retrospectively analyzed TMS data, obtained using both round and figure-of-8 coils, from three cross-sectional studies conducted in 8- to 12-year-old children with ADHD (n=79; 10.7 +/- 1.5 years old) and age-and-sex-matched typically developing controls (n=96; 10.5 +/- 1.4 years old). Results Median CSP was 32% shorter in ADHD (p=0.02). Regression analysis demonstrated a relationship between shorter CSP and both lower active motor thresholds (p < 0.0001) and more severe hyperactivity symptom rating (p = 0.026). Test-retest CSP measures in 83 children showed moderate reliability (intraclass correlation 0.77 [ADHD], 0.75 [controls]). Conclusion TMS-evoked CSP may be a useful biomarker in future investigations of ADHD subtypes, domains of impaired function, or treatment outcomes.

BackgroundAutism Spectrum Disorder (ASD) is marked by pronounced biological heterogeneity, yet most neurochemical studies have relied on single-analyte comparisons that cannot capture coordinated variation across neurotransmitter systems. Whether ASD blood neurotransmitter profiles reflect discrete subtypes, a continuous landscape, or something in between remains unresolved. MethodsWe applied NeuroCLAD, a structured multivariate analytical framework, to peripheral blood neurotransmitter profiles from 261 children with ASD (mean age 6.98 {+/-} 3.13 years; 78.5% male). The pipeline incorporated z-score normalisation, natural cubic spline residualisation for age and sex, principal component analysis, k-means clustering, consensus stability assessment, Gaussian mixture modelling, Cohens d enrichment analysis, and clinical symptom mapping. Cross-compartment consistency was explored using urine neurotransmitter profiles from the same cohort. ResultsTwelve reproducible biochemical cluster patterns were identified, each characterised by distinct pathway-level fingerprints spanning trace amines, monoamines, catecholamine turnover, histamine signalling, and excitatory-inhibitory amino acid balance. Cluster stability was confirmed across 200 bootstrap iterations. Gaussian mixture modelling showed that most individuals were assigned with high confidence, while a subset occupied transitional positions between clusters, consistent with stable biochemical modes embedded within a continuous landscape. Descriptive behavioral mapping revealed graded symptom tendencies across biochemical modes, particularly for aggressiveness, self-injurious behaviour, and picky eating. LimitationsThe findings are based on peripheral blood measurements, which indirectly reflect central neurochemical activity. The study is cross-sectional, lacks a neurotypical comparison group, and behavioural associations are exploratory given cluster sizes. External replication in an independent cohort has not yet been performed. ConclusionsBlood neurotransmitter biology in ASD is neither uniform nor discretely partitioned, but organised into reproducible biochemical modes within a continuous multivariate landscape. These findings support a dimensional view of ASD neurochemistry and provide a foundation for pathway-informed, individualised approaches to biological characterisation.

Adeno-associated viral (AAV) vectors are foundational tools for dissecting brain structure-function relationships, but AAV serotype tropism varies across brain regions and species, requiring empirical validation to inform experimental design. This need is especially important in non-model organisms, where molecular neuroscience tools remain underdeveloped and access to research subjects is often limited. The Arctic ground squirrel (AGS, Urocitellus parryii) is a valuable model for studying extreme physiology, including metabolic suppression during hibernation and resistance to cerebral ischemia/reperfusion, yet no studies have evaluated AAV performance in the AGS brain. Here, we investigated the ability of AAV serotypes 1, 8, 9, and DJ to transduce the AGS hypothalamus using the human synapsin (hSyn) promoter and directly compared cellular transduction rates in a region implicated in thermoregulation and hibernation. To maximize data collection from a limited experimental population, we used a within-animal, contralateral stereotaxic injection design. Recombinant AAV vectors expressing enhanced green fluorescent protein or mCherry were delivered bilaterally, and reporter expression was analyzed four weeks later. All tested serotypes produced clear and reproducible reporter expression, establishing AAV as a viable molecular tool in the AGS hypothalamus. AAV1 produced significantly greater cellular transduction rates than AAV-DJ (17.2% {+/-} 3.5% vs 8.4% {+/-} 2.9%, paired t-test, p = 0.032). AAV8 and AAV9 showed transduction rates of 22.8% {+/-} 0.6% and 20.1% {+/-} 1.5%, respectively; however, with only two biological replicates per serotype, formal statistical comparison was not performed. These findings provide the first direct characterization of AAV-mediated gene delivery in the AGS brain and establish a foundation for future molecular interrogation of hypothalamic circuits in this extreme mammalian hibernator.

Background and Purpose: Ambient air pollution is an established risk factor for incident stroke, but whether post-discharge pollutant exposure influences stroke recurrence remains unknown. We investigated the association between post-discharge exposure to six ambient air pollutants and stroke recurrence in patients with acute ischemic stroke. Methods: We analyzed data from 27,346 patients in the CRCS-K-NIH nationwide multicenter registry of acute ischemic stroke patients (2014-2021) with confirmed ischemic stroke, residential address data, and matched air quality records. The primary exposure was the 3-month post-discharge average concentration of PM10, PM2.5, NO2, SO2, CO, and O2, assessed at the district level using inverse-distance weighted interpolation. The primary outcome was stroke recurrence from 3 to 15 months post-discharge. Cause-specific Cox proportional hazards models accounting for the multilevel data structure were used, with all-cause mortality as a competing risk. Restricted cubic splines assessed nonlinear dose-response relationships. Results: During follow-up (median 364.8 days), 765 patients experienced stroke recurrence and 471 died. Among the six pollutants, only SO2 showed a statistically significant association with recurrence (P for overall association in the restricted cubic spline analysis = 0.024). A potential threshold was identified at approximately 8.2 ppb, above which recurrence risk increased progressively (P for non-linearity = 0.095). The association was numerically stronger among older adults ([&ge;]75 years; P for interaction = 0.051) and women (P for interaction = 0.062). The highest SO2 concentrations were observed in harbor cities (Incheon, Ulsan, Busan), consistent with maritime shipping emissions. No significant associations were observed for the other five pollutants. Conclusions: Elevated post-discharge SO? exposure is associated with increased stroke recurrence risk, particularly in harbor regions and among older adults and women. These findings support incorporating ambient air quality monitoring into secondary stroke prevention strategies.

Common terns (Sterna hirundo) are regionally threatened migratory seabirds that form large breeding colonies during the North American summer months. They are highly vocal and serve as important bioindicators of aquatic ecosystems. Historically, acoustic studies on colonial seabirds have proven difficult due to the dense aggregations of individuals and high rate of call overlap. However, as passive acoustic monitoring (PAM) becomes increasingly common for studying seabird colonies, quantitative descriptions of species vocalizations are needed to accurately interpret behavioral information from colony soundscapes and support automated analysis of large acoustic datasets. This study aims to quantify the vocal repertoire of adult common terns. We deployed AudioMoths to collect acoustic data at a tern colony on Seavey Island, New Hampshire, USA from across the breeding season. Using RavenPro, unique call types were identified through visual and aural inspection of the acoustic data in the spectrogram. For each call, we then extracted measurements of peak frequency (Hz), bandwidth 90% (Hz), syllable duration 90% (s), and total bout duration (s) to quantify the characteristics of each call type. Statistical analyses for acoustic parameters by call type were performed using Kruskal-Wallis tests, followed by post-hoc Dunn tests. Our results demonstrate that each call type is significantly different from another by at least one parameter, with the exception of the kek and kip/tjuk calls. These findings present the first quantitative analysis of common tern vocalizations for North America. By defining temporal and spectral characteristics for multiple call types, this work helps translate colony soundscape into biologically meaningful information about tern behavior and colony dynamics. These descriptions also provide key parameters for developing automated tools to detect and classify vocalizations in dense, noisy colonies. Integrating quantified vocal characteristics with PAM offers a promising approach for monitoring colony activity and behavior while minimizing disturbance relative to traditional methods.

BackgroundIntegrating multimodal data into medical artificial intelligence (AI) tools and evaluating whether they outperform human experts remains a critical challenge. Epilepsy surgery offers a unique paradigm for this evaluation, as it provides an expert-independent measure (Engel score) of post-surgical outcome. Currently, evaluation for epilepsy surgery relies on the visual interpretation and human synthesis of multimodal data. While clinical evaluations are individualized and account for complex anatomical variability, integrating these diverse, high-dimensional modalities to generate a probability of surgical success remains challenging. Here, we leverage this objective outcome score to investigate the feasibility of a data-driven, phenotype-based model against the current clinical gold standard. MethodsThe evaluation was performed on an epilepsy-type controlled cohort of 57 patients from six tertiary epilepsy surgery centers who underwent resective/ablative surgery in the mesiotemporal lobe. Multimodal data, namely, patient demographics, semiology, invasive electrophysiology monitoring, and neuroimaging, were utilized. We first estimated how human experts perceive surgery success. Subsequently, we developed a data-driven model integrating these modalities to predict surgery outcomes. The model performance was compared to the current clinical gold standard (three independent human experts) and published outcome calculators. Finally, modality-level phenotypes were derived based on the models predictions. ResultsPredictions by human experts correlated poorly with post-surgical outcomes, and published outcome calculators did not perform better than the experts (DeLongs p = 0.367). Our model incorporating multimodal data achieved an area under the receiver operating characteristic curve (AUROC) of 0.801. It performed statistically better than the best human expert (DeLongs p = 0.043) and achieved a higher AUROC than the best published surgical outcome calculator (0.801 vs. 0.694). ConclusionsWe demonstrated the proof-of-concept that data-driven multimodal phenotypes can inform personalized surgery planning in epilepsy. Furthermore, we provide a framework for integrating multimodal data and benchmarking medical AI performance against human experts.

The dentate gyrus (DG) is thought to play a key role in the formation of dissociable memory representations for similar contexts. Neurons in the DG receive highly processed spatial and nonspatial sensory information from the medial and lateral entorhinal cortices, respectively. Changes in spatially tuned firing patterns of DG place cells occur after spatial changes to an environment, but the degree to which DG place cells respond to ethologically relevant nonspatial stimuli is largely unknown. Spatial and nonspatial information is thought to be transmitted to the DG during discrete local field potential events called dentate spikes. Here, we tested the extent to which different spatial and nonspatial stimuli modulate place cell firing patterns and dentate spike dynamics. We performed extracellular recordings of DG place cells and local field potentials in rats of both sexes exploring a familiar spatial environment, in which social stimuli and nonsocial odors of varying ethological relevance were presented, and a novel spatial environment. As expected, DG place cells exhibited different firing patterns between familiar and novel environments. Significant changes in firing were not observed, however, with any of the nonspatial stimuli. Surprisingly, the occurrence of dentate spikes associated with lateral entorhinal cortex input increased during exploration of ethologically relevant stimuli, and this increase was greater for social stimuli. Altogether, these results suggest that the DG preferentially responds to social stimuli at the network level, providing novel insights into how spatial and nonspatial information is processed in the DG. Significance StatementThe dentate gyrus (DG) encodes spatial and nonspatial sensory information. Here, we investigated how place cells in the DG respond to changes in spatial and nonspatial cues in familiar and novel environments in rats. We found that DG place cell firing patterns significantly changed in a novel spatial environment but did not significantly change when nonspatial stimuli were presented in a familiar environment. Conversely, discrete dentate spike events reflecting presumed nonspatial inputs from the lateral entorhinal cortex increased during investigation of ethologically relevant nonspatial stimuli. These findings suggest novel mechanisms of nonspatial information processing in the DG.

IntroductionTo leverage high-frequency oscillations (HFOs) as a biomarker with significant potential, this study compared a large set of detectors on a unified dataset, aiming to evaluate their clinical applicability under realistic conditions. MethodsEleven automatic detectors were applied to a retrospective dataset of intracranial and scalp EEGs from 27 consecutive pediatric patients. Inter-detector agreement was assessed using Spearmans Rho, and the area under the curve (AUC) for seizure onset zone (SOZ) prediction served as a consistent reference standard to enable reliable comparisons across recording modalities. Analyses were conducted separately for HFO and Spike-HFO detections. ResultsThe average age of our cohort was 12.4 years (SD 4.0; range 5-18). AUC values in scalp EEG ranged from 0.61 to 0.67 for HFOs and from 0.53 to 0.63 for Spike-HFO. AUC values in intracranial EEG ranged from 0.48 to 0.66 for HFOs and 0.54 to 0.69 in Spike-HFO. Although only three of the 11 detectors were specifically developed or adapted for scalp EEG, the detectors generally achieved higher AUC values and stronger agreement in scalp EEG ConclusionsWe present the first study comparing intracranial and scalp detectors by testing them beyond the modalities for which they were originally designed. Although the clinical utility of detections was comparable across EEG modalities, it remained lower than reported in original studies assessing the diagnostic value of HFOs. Caution is warranted when applying a publicly available detector to a new dataset, and detector robustness remains a critical issue. Key points- A comprehensive head-to-head comparison of 11 detectors demonstrated significant variability in detector agreement and clinical utility - Clinical utility was not necessarily linked to the EEG recording type the detector was originally designed for - Despite widely accepted use of automatic detections, detector robustness remains a critical issue

Ethylene oxide is a widely used industrial chemical,yet evidence linking its exposure to Parkinsons disease remains limited.Using data from participants in the United States,we examined whether exposure to ethylene oxide is associated with Parkinson's disease.This cross-sectional study included 8,430 adults from the National Health and Nutrition Examination Survey (NHANES) collected between 2013 and 2020.Information on demographic characteristics,socioeconomic factors,lifestyle behaviors,body mass index,sedentary time and major chronic conditions was analyzed. Levels of hemoglobin ethylene oxide adducts,a biomarker of ethylene oxide exposure, were evaluated in relation to Parkinsons disease using statistical modeling approaches.After accounting for potential confounding factors,higher levels of ethylene oxide exposure were associated with an increased likelihood of Parkinson's disease.The association followed a positive and linear pattern.These findings provide new population-based evidence suggesting that ethylene oxide may be linked to Parkinsons disease and highlight the need for further studies to confirm causality and to better understand the biological mechanisms involved.

ImportanceImplantable sub-scalp EEG systems with a small number of channels have emerged as promising solutions for long-term seizure monitoring in patients with epilepsy. How seizure detection performance varies by montage configuration is unknown. ObjectiveTo quantify how automated seizure detection performance differs between full and reduced montages, and how these differences vary by epilepsy characteristics. DesignRetrospective cross-sectional study. SettingSingle-center at the Hospital of the University of Pennsylvania Epilepsy Monitoring Unit (EMU). ParticipantsEEG data from 2281 consecutive EMU admissions between January 2017 and December 2024 were screened. Admissions with at least one annotated seizure and one interictal clip [&ge;]20 minutes from any seizure were included. ExposureComputational simulation of published sub-scalp device montages using standard 10-20 EEG channels. Main Outcomes and MeasuresThe primary outcome was event-based F1 scores evaluated for three published seizure detectors--a one-class support vector machine (SVM), a convolutional neural network (SPaRCNet), and a long short-term memory autoregressive model (NDD)--across montages. ResultsA total of 466 admissions from 436 patients (mean [SD] age, 39.0 [14.4] years; 54.4% female) met inclusion criteria, comprising 1683 seizures and 1527 interictal clips. SPaRCNet achieved the highest performance (mean [SD] F1, 0.61 [0.30]), followed by NDD (0.56 [0.28]) and SVM (0.39 [0.25]). Performance decreased by at most 0.09 with reduced montages, depending on detectors. Patient factors accounted for the largest proportion of performance variance (29.2%), followed by detector choice (10.3%). Montage effects were minimal (0.4%), despite variation in optimal montage across detectors. Reduced-montage performance correlated moderately to highly with full-montage performance ({rho}=0.29-0.73), suggesting full-montage performance could help identify patients suitable for sub-scalp devices. Missed seizures were associated with lower amplitude and bandpowers than detected seizures, though they remained distinguishable from interictal data. Conclusions and RelevanceAutomated seizure detection achieved comparable accuracy, with only modest reductions, under simulated reduced montages. Performance differences were driven primarily by detector- and patient-level factors rather than montage. These findings support the feasibility of accurately detecting seizures with published sub-scalp devices and highlight the need for improved algorithms to optimize performance. Key FindingsO_ST_ABSQuestionC_ST_ABSHow do automated seizure detection algorithms perform with reduced-channel montages simulating published sub-scalp devices? FindingsIn this retrospective cross-sectional study, seizure detection performance decreased only modestly on reduced montages relative to the full montage (absolute F1 change -0.09 to 0.014), whereas patient- and algorithm-level factors accounted for most of performance variance (29.2% and 10.3%, respectively). Algorithm performance on full montage recordings was moderately correlated with performance on reduced channel montages ({rho}=0.29-0.73). MeaningReduced-montage sub-scalp devices are promising for ultra-long-term monitoring, but best performance requires selecting the right patients. Patient-specific seizure detectors will likely be required to optimize long-term performance.

The rodent accessory olfactory system (AOS) detects chemosignals emitted by conspecifics and other species to support beneficial behaviors. Peripheral vomeronasal sensory neurons (VSNs), the AOS chemical sensors, detect fecal bile acids in patterns that have unknown significance to the animal. We used a combination of mass spectrometry and VSN calcium imaging to investigate the AOS capacity to use bile acid information to discriminate between fecal samples from captive reptiles and mice with varying gut microbiome states. Mass spectrometry analysis revealed bile acid patterns that distinguished biologically relevant samples from one another, representing theoretical discrimination axes. We measured VSN response patterns to bile acid stimuli aligned with theoretical discrimination axes. We found that VSNs perform stimulus "whitening" via an inverse relationship between natural bile acid abundance and population response magnitude. VSNs showed maximum sensitivity to taurine-conjugated bile acids, which have high theoretical discriminatory value, but were found at low natural abundance levels. Individual taurine-conjugated bile acids drove threat assessment behavior when added to familiar mouse fecal extracts, suggesting high behavioral significance. Finally, we analyzed the degree to which the AOS utilizes the theoretical information about species, diet, and gut microbiome status from bile acids. We found that VSN tuning patterns align with theoretical axes for discriminating reptilian predators from vegetarians, and between mice with different gut microbiome states. VSN tuning was especially well-aligned with the information available about conspecific gut microbiome status. These results show that AOS bile acid chemosensation supports discrimination of multiple biologically relevant states. Short abstractThe rodent accessory olfactory system (AOS) detects fecal bile acids via combinatorial codes with unknown biological significance. We investigated whether AOS bile acid chemosensation supports species and gut microbiome evaluation using mass spectrometry, calcium imaging in vomeronasal sensory neurons (VSNs), and analytical modeling. Bile acid excretion patterns theoretically supported discrimination of reptilian predators from vegetarians, and germ-free mice from conventionally raised counterparts. VSNs demonstrated stimulus "whitening" via an inverse relationship between natural bile acid abundance and population response magnitude. VSNs had highest sensitivity to taurine-conjugated bile acids, a novel class of chemosignals that elicited behavioral aversion. VSN tuning aligned with ideal discrimination axes, which was especially strong for gut microbiome-associated bile acid abundance patterns. These results show that AOS bile acid chemosensation supports discrimination of multiple biologically relevant states.

Summary paragraphA hallmark of learning is the need for sensory stimuli (Ginns, 2015; McGraw et al., 2009; Reinwein, 2012; Spence, 1950) so that learning is fundamentally based on sensory input signals affecting behaviour, physiology, and neurology. If behavioural measures of learning can be causally linked to physiological and neurological variables, a broader understanding of the mechanisms related to learning in schools, learning disabilities, and learning and health issues may emerge (McGraw et al., 2009). Despite decades of research on the physiological/neurological variable of sympathetic activation, learning, and achievement (Horvers et al., 2021), any causal relation remains unclear (Cowley et al., 2014; Mason et al., 2020; Pijeira-Diaz et al., 2016; Sung et al., 2023; Yu et al., 2024) and issues with instrument validation remain (Costantini et al., 2023; Hu et al., 2024; Milstein & Gordon, 2020; Van Der Mee et al., 2021). Here we investigate the effect of sensory input on sympathetic activation by using validated instruments for skin conductance measurement (Batista et al., 2019) and whether sympathetic activation is connected to learning in a cognitive laboratory context and an ecologically valid classroom context. In both contexts, we found a physiological variable which correlated with learning and that sensory input affected this variable while student movement did not. These sensory inputs varied depending on the different instructional activities the students participated in. Together, these findings bring us one step closer to a model linking sensory input to behavioural, physiological, and neurological variables.

BackgroundNeonatal cerebral venous sinus thrombosis (CVST) is associated with intracranial hemorrhage (ICH) and ischemic lesions. There is no scale to characterize the spectrum of brain injury secondary to neonatal CVST. ObjectiveTo develop the Neonatal CVST Hemorrhage Score (NeoCVST Score) to characterize ICH and brain injury in neonates with CVST. MethodsThis was a retrospective cohort study of neonates with CVST diagnosed using brain MRI/MRV. The NeoCVST Score was developed using the study cohort, integrating elements from previous hemorrhage classification systems and expert consensus. Logistic regression examined associations between NeoCVST score and neurodevelopmental outcomes (Pediatric Stroke Outcome Measure). Interrater reliability was assessed with intraclass correlation coefficient. ResultsThe study included 100 neonates (77% term and 23% preterm) with CVST. Thrombosis of multiple venous sinuses was present in 62%. ICH was present in 63%. Supratentorial hemorrhage was present in 57% and included germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) grades 1-2 (22%), GMH-IVH grade 3 (15%), parenchymal (43%) and thalamic (18%) hemorrhage. Infratentorial hemorrhage was present in 19% and included cerebellar (18%) and brainstem (4%) hemorrhage. Extra-axial hemorrhage was present in 32% and included epidural (2%), subdural (26%) and subarachnoid hemorrhage (6%). Ischemic brain injury was present in 67% and included lesions in the medullary vein distribution (13%), white matter (54%), basal ganglia (17%) and thalamus (25%). Neurodevelopmental outcomes included 40% with normal outcomes and 60% with neurodevelopmental impairments. NeoCVST total score (OR=1.1, P=0.02) and subscores for thalamic hemorrhage (OR=1.9, P=0.04), thalamic ischemia (OR=2.2, P=0.005) and bilateral thalamic ischemia (OR=2.8, P=0.01) were predictors of adverse neurodevelopmental outcome. Inter-rater reliability showed moderate-good agreement between reviewers with an intraclass correlation coefficient of 0.71. ConclusionsThe NeoCVST Score is a simple clinical tool to characterize ICH and brain injury secondary to neonatal CVST. Increasing NeoCVST total score and subscores for thalamic hemorrhage and ischemia were associated with worse neurodevelopmental outcomes.

High-density electrophysiological recording using Neuropixels probes enables single-unit resolution of human neural activity. However, integrating these systems into clinical environments remains challenging. Reported human recordings have been limited to a few centres in the United States utilising variable regulatory, sterilisation and operative techniques. Here, we present human Neuropixels recordings under a nationally managed ethical and regulatory framework in the United Kingdom. We provide a reproducible roadmap to overcome regulatory and equipment constraints. Guided by the IDEAL Stage 2a (Development) framework, we established a frameless intraoperative workflow utilising manufacturer-sterilised probes and a commercially available, clinical-grade setup for Neuropixels insertion including micromanipulator and endoscope holder. We prospectively evaluated this workflow across six participants (mean age 62.5 years) undergoing elective ventriculoperitoneal shunt surgery. Iterative failure-mitigation cycles successfully resolved key technical barriers, including neuronavigation interference and hardware instability. Assessed across three predefined endpoints (clinical safety, procedural timing, and neural data yield), the workflow achieved zero research-related adverse events and maintained a strict 30-minute procedural extension. Progressive technical refinements increased single-unit yield from 25 units during early development to 146 manually curated units. This approach provides a scalable, clinically integrated workflow to safely perform high-density electrophysiology in routine neurosurgical environments.

Multimodal communication plays a central role in animal behavior, particularly when individuals must integrate information from different sensory channels to make rapid decisions. In aquatic environments, chemical and visual cues differ markedly in their spatial and temporal properties, such that chemical signals may be constrained by limited spatial resolution and temporal instability, potentially requiring visual information to reliably guide social decisions. In decapod crustaceans, both cue types are known to mediate reproduction, yet their relative contribution to mate-location behavior remains unclear. Here, we tested how visual and chemical cues from males influence mate-location behavior in females of the prawn Macrobrachium rosenbergii. Females were placed in a central arena and exposed to four stimulus configurations combining visual cues (a life-size photograph of a male or a control background) and chemical cues (water from an aquarium with or without a male). Attraction was quantified as the time spent in each half of the arena. Females showed no directional preference when exposed to chemical cues alone or when visual and chemical cues were spatially incongruent. In contrast, females spent significantly more time near male-associated stimuli only when visual and chemical cues were spatially congruent. These results indicate that mate-location behavior in this species depends on multimodal integration with a strong contextual dependence on visual information, which appears to gate the effectiveness of chemical cues. Spatially congruent multimodal signals are therefore necessary to guide orientation during mate search, suggesting that disruption of visual or chemical information in aquaculture systems may impair mating efficiency.

Background: High school students may be able to communicate health topics to peers and adults. Yet, few studies have evaluated the role of high school students in community health initiatives, making them an underutilized group for disseminating health information. We pilot tested stroke education across five high schools using varied delivery approaches as a preliminary step toward evaluating youth stroke education to improve community health. Methods: In April-May 2025, five high schools in Connecticut and New York participated in stroke education. The format was designed to fit the needs of each school and included an 8-session classroom curriculum (Derby, CT), after-school club meetings (New Haven, CT; Long Island, NY), and one large assembly (Bridgeport, CT). Developed by teachers and neurology providers, the curriculum covered stroke risk factors, symptoms, and emergency response. Students completed a 15-point assessment adapted from the validated Stroke Action Test before, immediately after, and 4-6 weeks post-intervention; data were collected between April and July 2025. Results: Of 112 students completing the pre-test, 99 (88%) completed the immediate post-test and 51 (46%) the delayed follow-up. Average scores rose from 47% pre-intervention to 75% post and 70% at 4-6 weeks. All schools scored <50% on pre-tests suggesting poor baseline stroke knowledge. Conclusion: This pilot suggests that stroke education can be delivered to high school students across varied settings and may support knowledge gains up to 6 weeks. Limitations included small sample sizes and missing follow-up data. If validated in larger studies, this adaptable, teacher-supported approach could offer a scalable public health strategy for improving community stroke preparedness.

The hippocampal CA2 region is critical for social novelty recognition memory--the discrimination of whether a conspecific is novel or familiar. However, its role in forming a memory of a pair-bonded mate is unknown. To examine how social memories of pair-bonded individuals are encoded, we sought to understand if CA2 and the neighboring CA1 region participate in the memorization and recognition of a pair-bonded mate in monogamous Peromyscus californicus (California mice). Here, we report that CA2 and CA1 show distinct changes in social encoding of an opposite sex conspecific following pair-bonding. Using multi-channel silicon probes, we recorded single units from CA2 and CA1 in freely behaving male mice before and after pair bond formation during interactions with novel and partner females. We found that the strength of CA2 representations of a novel female mouse weakened after pair bond formation, indicating that CA2 may be preferentially important for novelty detection. In contrast, CA1 demonstrated an increase in the strength of encoding a female partner after pair-bond formation, suggesting that CA1 may encode partner memory. These findings indicate that pair bonding shifts the discrimination of social information from CA2 to CA1.

Perinatal hypoxia is a major contributor to neurodevelopmental disorders; however, the consequences of mild-to-moderate perinatal hypoxia (MPH) remain insufficiently characterized. Here, we investigated cortical plasticity following MPH using a multimodal approach that combines behavioral assessment, histological analysis, and in vivo magnetic resonance imaging (MRI). Fifty-six Wistar Han rats were exposed to hypoxia or normoxia at postnatal day 1 (P1). Neurodevelopmental assessment from P3 to P14 revealed impaired rooting and vibrissae-placing reflexes in hypoxic rats. Histological analysis demonstrated: altered expression of microtubule-associated protein-2, apical dendrite bundling, reduced neurofilament-H expression, and decreased dendritic arbor complexity in large pyramidal neurons, indicating disrupted maturation of excitatory circuits. Increased parvalbumin expression, higher interneuron density, and its enhanced neurite elaboration indicated precocious development of inhibitory circuits, consistent with a compensatory response. MRI at P15, combined with whole-brain voxel-wise analysis, revealed a significant increase in fractional anisotropy in the anterior cingulate cortex (ACC). Convergent behavioral, histological, and imaging findings identified the ACC as the most vulnerable region following MPH, followed by the somatosensory cortex. These findings reveal early cytoarchitectural and MRI detectable correlates of a single episode of MPH, which, together with previous findings from this model, support the neurodevelopmental origin of persistent alterations in cortical structure and circuit function, characterized by an excitatory-inhibitory imbalance. The study identifies and defines a framework for understanding region-specific vulnerability and plasticity in the immature brain, with implications for improving the early detection of subtle perinatal brain injury, as a prerequisite for timely therapeutic intervention.

Importance: Leukodystrophies are a heterogeneous group of genetic disorders affecting the white matter of the brain, often presenting with overlapping clinical features but differing in neuroanatomical involvement. There is a critical need for quantitative tools to characterize disease burden and support diagnosis, severity stratification, and clinical trial readiness. Objective: To characterize shared and distinct neuroanatomical patterns across six genetically confirmed leukodystrophies using anatomical MRI-derived phenotypes benchmarked against brain growth charts, and to assess the utility of this methodological approach for identifying imaging biomarkers of disease severity. Design, Setting, and Participants: Cross-sectional neuroimaging study using retrospective clinical MRI data. Setting: Multicenter study incorporating data from the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN) and control data from the Childrens Hospital of Philadelphia. Participants: The study included 434 MRI scan sessions from 274 patients with genetically confirmed leukodystrophies (Pelizaeus-Merzbacher disease, Metachromatic leukodystrophy, Alexander disease, Aicardi-Goutieres syndrome, TUBB4A-related leukodystrophies, and POLR3-related leukodystrophy). Control MRI data (7628 scans from 7205 subjects) were drawn from the Scans with Limited Imaging Pathology cohort at the Children's Hospital of Philadelphia. Exposures: All MRI scans underwent automated segmentation using deep learning segmentation tools to derive global and regional brain volumes. Normative models of brain development ("brain growth charts") were generated for the control cohort using generalized additive models for location, scale, and shape. Centile scores were then calculated for leukodystrophy subjects to quantify deviations from typical development. Main Outcomes and Measures: Centile scores for global and regional brain volumes were compared across leukodystrophy subtypes to identify disease-specific neuroanatomical patterns and to evaluate their potential utility for severity stratification. Results: Distinct patterns of neuroanatomical deviation were observed across leukodystrophy subtypes. Certain leukodystrophies showed preferential involvement of specific cortical or subcortical regions, while others displayed more diffuse volume loss. Centile scores demonstrated potential for differentiating disease subtypes and stratifying individuals by severity. Preliminary longitudinal data suggest centile scores may also track progression over time. Conclusions and Relevance:This study demonstrates the feasibility and utility of MRI profiling of individuals with leukodystrophy using anatomical MRI-derived phenotypes benchmarked against brain growth charts. The approach enables data-driven, quantitative characterization of structural brain abnormalities, offering a scalable method for phenotyping, diagnosis, and future use in clinical trials.

Interval timing (IT) is the ability to time events in the range from seconds to a few minutes, allowing animals to organize behavior in time at short durations. IT relies on two cognitive functions: 1) Measuring the passage of time; 2) Storing and retrieving temporal memories in a context appropriate manner. The hippocampus (HC) and medial prefrontal cortex (mPFC) have been shown critical to the accuracy and precision of time-contingent instrumental responses in IT. The anatomy supporting mPFC-HC interactions, required for memory encoding and retrieval, include projections from HC to mPFC, and indirect bidirectional connections through the ventral midline thalamus (VMT), most notably reuniens. Here, we explored VMTs role in retrieving fixed-interval (FI) temporal memories. Rats were trained on a 5s FI signaled by an auditory cue and demonstrated temporal memory by poking predominantly at the time of the expected reward. Timing responses on individual trials were classified into on-time, early, and random response. Across sessions, random response trials decreased following training. Next, we switched training to longer intervals (20s or 80s; daily sessions for weeks). To probe the role of the VMT in temporal memory retrieval, we infused the GABAA-agonist muscimol, or saline, before training sessions. Results show that VMT muscimol infusions decreased timing precision. Also, at both intervals, the number of on-time response trials decreased, and the number of random response trials significantly increased. The number of early response trials had no significant change at 20s, and significantly decreased at 80s. Overall, our results suggest that the VMT is critical for precise retrieval of temporal memories. We also describe per-trial response patterns with characteristics consistent across all trained intervals, suggesting multiple behavioral strategies at play during interval timing.