Frontiers in Integrative Neuroscience

Purely discovery-driven biological research \"...performed without thought of practical ends...\" establishes fundamental conceptual frameworks for technological and medical breakthroughs that often occur many years later. Despite the critical importance of discovery-driven research for scientific progress, there is increasing concern that it is increasingly less favored by funding agencies than research with explicit goals of application and innovation, resulting in a decline in discovery-driven research output. This in turn appears to promote the use of genetically modified organisms (those with advanced molecular toolkits for gene manipulation and visualization) for which genetic models of human disease can be studied at molecular and cellular resolution using state of the art methodology, and to discourage use of other experimental organisms that provide necessary evolutionary context. This field of neuroscience encompasses both applied and discovery-driven research, providing an opportunity to empirically determine whether funding and publication rates for the latter have indeed declined. Additionally, the diversity of experimental organisms traditionally employed in neuroscience research provides a means to quantify changes in use of study organisms that lack genetic tools over time. In particular, the basic research field of neuroethology is characterized by its distinct approach to selection of study organisms based on their adaptive behaviors, evolutionary history, and suitability for answering the question of interest, providing a stronger basis for the assumption that findings reflect fundamental concepts of nervous system function and behavior. A 30-year analysis of National Science Foundation (NSF) funding of neuroethology research finds that the agency has funded progressively fewer researchers with smaller average award amounts, with a decline in awards for research on non-genetically modified organisms. Neuroscience funding by the National Institutes of Health (NIH) shows the same trend but also increasing support for genetically modified organisms. The same pattern is observed in the neuroscience literature but occurs prior to changes in funding, suggesting that the shift to genetically modified organisms was likely initiated by researchers but may potentially have been later reinforced by funding agency and journal publisher preferences.

Cumulative effects of repetitive head impact have been highly associated with short and long term neurological conditions. Despite high rates of head injuries, many people in the U.S. and around the world continue to participate in collision sports. As one approach to address this concern, 2nd Skull has developed supplemental protective headgears including a skull cap, scrum cap and headband that can be utilized in both helmet and non-helmet sports. To test the effectiveness of 2nd Skull products as an adjunctive tool to reduce the severity of head impact, data were extracted from a series of tests completed at four sites under laboratory conditions using linear, projectile and rotational impactor to simulate blows to the head in sports. The majority of test cases showed the same pattern of reduced impact severity with the addition of 2nd Skull padding. It remains to be seen if these laboratory results will translate to the field.

The use of robots to help teachers to engage students in STEM subjects has been increasing in recent years, and much progress has been made in K12 schools to incorporate robots in the pedagogy. Recent studies indicate that robots can play a significant role to engage students in neuroscience subjects, but little is known about teachers perceptions of using robots to teach neuroscience. In this paper, we present a study based on a survey questionnaire conducted with 84 teachers across multiple high schools in the United States to understand their perceptions about the usefulness of using robots to teach neuroscience. To situate teachers with an example of how robots can be used in neuroscience classrooms, we describe an educational tool called the SpikerBot. Our preliminary results indicate that there is an opportunity for neuroscience-oriented robots in secondary education, provided sufficient on-boarding and training videos.

ObjectiveThis study examined whether baseline reports of adverse childhood experiences (ACEs) and early life adversity (ELA) were associated with subsequent head/neck injury or probable brain injury in the Adolescent Brain Cognitive Development (ABCD) Study(R) cohort. SettingABCD Study(R) cohort ParticipantsABCD Study(R) data release 5.0 provided baseline and partial longitudinal data through Year 4. Inclusion required at least one follow-up timepoint, data to compute the ACEs or ELA score, sex, and attention-deficit/hyperactivity disorder (ADHD) diagnosis status. The final sample included 10,853 participants for ACEs analyses and 10,850 ELA analyses. DesignProspective observational design. Main MeasuresHead and/or neck injuries and probable brain injuries were assessed using the caregiver-reported Ohio State University Traumatic Brain Injury Identification Method Short Form. We used previously published recommendations for the ABCD study to calculate a proxy ACEs score and a broader measure of ELA using both caregiver and youth report at baseline. Age, gender, race/ethnicity, primary caregiver education, childs history of ADHD, report of head/neck or probable brain injury at baseline, and broken bone injury at baseline or follow-up were covariates in logistic regression models examining the association between risk of head/neck injury or probable brain injury with ACEs or ELA. ResultsExposure to more adversity (ACES: Odds Ratio [95% Confidence Interval] OR[95%CI]=0.04[0.001,0.08]; ELA: OR[95%CI]=0.05[0.01,0.08]) was associated with higher odds of sustaining a head or neck injury at any of the follow-up time points but not of probable brain injury (ACES: OR[95%CI]=0.002[-0.08,0.08]; ELA: OR[95%CI]=0.01[-0.06,0.07]). ConclusionLimited public knowledge of and reliance on caregiver report of head/neck injury increases misclassification bias and underscores the need for improved education and measurement strategies. We observed a stronger association between ELA and head/neck injury, potentially reflecting differences in disclosure and awareness rather than due to types of exposure.

Several disciplines have approached the relationship between autism spectrum disorder (ASD) and music, but most of this understanding comes from cognitive sciences. This complex relationship has been studied by exploring how music-based interventions (MI) can benefit individuals with ASD. This systematic review and meta-analysis synthesize a range of evidence regarding the therapeutic effects of music on different aspects, including communication, behavior, social engagement, attention, and quality of life for those with ASD. Additionally, it contextualizes these effects within current research on the musical perception and processing abilities of ASD individuals, emphasizing how they perceive and process music. The studies reviewed employ a variety of methodologies, from randomized controlled trials to qualitative research, showcasing a wide array of interventions such as active music-making, music listening, and improvisational techniques. Despite substantial heterogeneity across studies, the findings point to a moderate overall benefit of MI, particularly in areas such as social interaction, expressive language, and quality of life. Given the evidence supporting the context-sensitive and domain-specific benefits of musical abilities in individuals with ASD, along with the positive outcomes highlighted in various studies, we conclude that music represents a valuable therapeutic tool for ASD. It engages individuals on emotional, cognitive, and social levels, providing a non-invasive and enjoyable way to enhance therapeutic outcomes. Future research should focus on individual differences, harmonization of outcome measures, and long-term effectiveness, paving the way for more personalized and neurodiversity-affirming intervention models.

Understanding the skill sets required for career paths is a prerequisite for preparing students for those careers. Neuroscience career paths are rapidly changing as the field expands and increasingly overlaps with computational and data-heavy job sectors. With the steady growth in neuroscience trainees and the diversification of jobs for those trainees, it is important to assess whether or not our training is matching the skill sets required in the workforce. Here, we surveyed hundreds of neuroscience professionals and graduate students to assess their use and valuation of a range of skills, from bench skills to communication and management. We find that professionals with neuroscience degrees can be clustered into three main groups based on their skill sets: academic research, industry research and technical work, and non-research. Further, we find that while graduate students do not use or highly value management and communication skills, almost all neuroscience professionals report strongly needing those skills. Finally, coding and data analysis skills are widely used in academic and industry research and predict higher salaries. Our findings can help trainees assess their own skill sets as well as encourage educational leaders to offer training in management and communication-skills which may help catapult trainees into the next stages of their careers.

ImportanceOver several decades there have been extensive debates on the use and misuse of statistical significance. It would be important to capture what P-values are reported in biomedical papers and whether their patterns have changed over time. ObjectiveTo quantify the reporting dynamics on P-values in biomedical articles in PubMed and PubMed Central(PMC) database over a 35-year period (1990-2025). DesignData were retrieved from the National Library of Medicine via PubMed and PubMed Central (PMC, full-text articles included), fetching the entire accessible corpus. Records were computationally processed using a regular expression algorithm, validated for various mathematical formats, to extract reported P-values from the text. SettingThe study includes 22,734,796 PubMed abstracts, 6,031,459 PMC abstracts and 6,397,787 PMC full-texts. Main Outcomes and MeasuresProportion of article reporting at least 1 P-value, at least 1 P-value less than thresholds (.05 and .005), distribution of P-values by magnitude and operator type. ResultsThe proportion of articles reporting P-values increased from 7.5% in 1990 to 18.3% in 2025 for PubMed abstracts, and from 5.2% to 53.3% for PMC full-texts. The median number of P-values per article increased from 2 to 7 in PMC full-text articles, with upward trends observed in all databases. A high proportion of P-values remains clustered around .05 and .001 in all databases. The proportion of articles reporting at least one P-value [≤] .05 has remained in the range 94%-98% since 1998, while the proportion reporting at least one P-value[≤] .005 has increased over time, reaching 57.0% for PubMed abstracts and 62.5% for PMC full-texts. The reporting of exact P-values increased until 2015, but with no further increase in the last 10 years (PubMed abstracts: 17.6% in 1990, 51.1% in 2015, 49.8% in 2025) Conclusions and RelevanceOur evaluation demonstrates the pervasive entrenchment of P-values, despite heavy debates and major changes in the content of the biomedical literature over time. More P-values are reported and papers using P-values almost always report some that are statistically significant. Readers should remain aware of the major issues surrounding P-value misuse and misinterpretation. Key pointsO_ST_ABSQuestionC_ST_ABSWith continuing debate regarding the use and misuse of statistical significance, how have reported P-values evolved over the past 35 years? FindingsAcross over 22 million PubMed abstracts and over 6 million full-texts, reporting of P-values became more common over time. Almost all (94-98%) abstracts and full-text reporting P-values have at least one significant at the .05 threshold. The reporting of exact P-values increased until 2015 but plateaued since then. Clustering around traditional statistical significance thresholds remains consistent. MeaningP-values reporting has become more common over time, with pervasive prevalence of significant P-values across the biomedical literature.

Preclinical research in traumatic brain injury (TBI) continues to significantly increase knowledge and yield a large number of peer-reviewed studies, but translation of these results to the clinical setting has been minimal. Rigor and transparency factors such as concealment of group allocation (e.g., "blinding) or ensuring that reagents are identifiable are critical in ensuring that scientific studies are replicable and translatable. Yet, nearly all efforts aimed at measuring these factors have concluded that reporting practices are problematic and incomplete. One way to improve transparency of reporting practices is to require that authors address a set of transparency related items in some way, such as a checklist or a paper section. Recently, Journal of Neurotrauma, a leading publisher of preclinical TBI research, instituted a required rigor-related section, which is explained to authors via a set of transparency, rigor, and reproducibility (TRR) instructions (one example for each manuscript type). These documents include specific transparency sections explaining blinding, power calculations, protocols, code, and data deposition. Experimental Neurology is a journal that is similar in size, impact and topic but the journal does not have explicit instructions to authors about transparency items. The purpose of this study was to assess the degree to which transparency reporting items were included in published manuscripts comparing reporting practices in the Journal of Neurotrauma and Experimental Neurology. We used a commercial software, SciScore, which is an AI tool tuned to detect rigor/transparency sentences in published manuscripts and count the number found (roughly dividing by the number expected) to obtain a score. Overall, SciScore found that in 6 of 8 items that were explicitly asked for, such as power calculations, investigator blinding, inclusion criteria, attrition, and data were significantly greater (more than 10%) compared to Experimental Neurology. However in Journal of Neurotrauma papers with the extra rigor section, 3 of 4 rigor items that were not explicitly asked for in the template rigor documents, such as subject demographics or transparent antibody reporting were not different from Experimental Neurology. One item, reporting of the sex of subjects was significantly better in Experimental Neurology. This shows that the Journal of Neurotrauma required rigor section is effective in improving reporting, but it would be far better if sex as a biological variable and transparent reporting of reagents (items present on major checklists including NIH rigor criteria) would be included.

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.

Infancy is a time of elevated neuroplasticity supporting rapid brain and sensory development. The gut microbiome, also undergoing extensive developmental changes in early life, may influence brain development through metabolism of neuroactive compounds. Here, we leverage longitudinal data from 194 infants across the first 18 months of life to show that microbial genes encoding enzymes that metabolize molecules playing a key role in modulating early neuroplasticity are associated with visual cortical neurodevelopment, measured by the Visual-Evoked Potential (VEP). Neuroactive compounds included neurotransmitters GABA and glutamate, the amino acid tryptophan, and short-chain fatty acids involved in myelination, including acetate and butyrate. Microbial gene sets around 4 months of age were strongly associated with the VEP from around 9 to 14 months of age and showed more associations than concurrently measured gene sets, suggesting microbial metabolism in early life may affect subsequent neural plasticity and development.

We present a deep neural network for data-driven analyses of infant rat behavior in an open field task. The network was applied to study the effect of maternal nicotine exposure prior to conception on offspring motor development. The neural network outperformed human expert designed animal locomotion measures in distinguishing rat pups born to nicotine exposed dams versus control dams. Notably, the network discovered novel movement alterations in posture, movement initiation and a stereotypy in "warm-up" behavior (the initiation of movement along specific dimensions) that were predictive of nicotine exposure. The results suggest that maternal preconception nicotine exposure delays and alters offspring motor development. In summary, we demonstrated that a deep neural network can automatically assess animal behavior with high accuracy, and that it offers a data-driven approach to investigating pharmacological effects on brain development. SignificanceRelating neuronal activity to behavior is crucial to understand brain function. Despite the staggering progress in monitoring brain activity, behavioral analyses still do not differ much from methods developed 30-50 years ago. The reason for that is the difficulty for automated video analyses to detect small differences in complex movements. Here we show that applying deep neuronal networks for automated video analyses can help to solve this problem. More importantly, knowledge extracted from the network allowed to identify subtle changes in multiple behavioral components, which were caused by maternal preconception nicotine exposure in rat pups. Thus, the examples presented here show how neuronal networks can guide the development of more accurate behavioral tests to assess symptoms of neurological disorders.

Early-life stress is known to impair neurodevelopment. Prior work from our group showed that prolonged physical and emotional separation necessitated by the medical needs of preterm infants (born <37 weeks) is associated with lower electroencephalogram (EEG) power in frontal areas, and that trend can be reversed by an intervention that enhances the physical and emotional contact between preterm infant and mother. Here we sought to model the changes in preterm infant frontal EEG power in a rodent model. We examined effects of daily maternal separation (MS) on frontal cortex electrophysiological (electrocorticography [EcoG]) activity in neonatal rats. We also explored the effects of dam-pup behavioral interactions on EcoG activity. From postnatal days (P) 2-10, rat pups were separated daily from their dam and isolated from their littermates for 3 hours. Control rats were normally reared. On P10, pups were implanted with telemetry devices and an electrode placed on the left frontal dura. EcoG activity was recorded during daily sessions over the next four days while pups remained in the home cage, as well as in response to a pup-dam isolation-reunion paradigm at P12. EcoG power was computed in 1 Hz frequency bins between 1-100 Hz. Dam and pup behavioral interactions during recording sessions were coded and synchronized to EcoG data. MS pups showed lower EcoG power during dam-pup interactions. These data parallel human and provide evidence of lower fronto-cortical activity as an early marker of early-life stress and possible mechanism for long-term effects of maternal separation on neurobehavioral development.

A study based on a survey questionnaire was conducted with 55 teachers across multiple high schools in the United States to understand their perceptions about their attitudes and confidence towards using research-based classroom exercises, which models they use to develop such exercises and their availability and preferences for an intensive summer professional development course. Our preliminary results indicate that while teachers are comfortable teaching research-based classroom activities, they are none-the-less very interested in paid professional development courses on teaching research practices to students (79%), more than two-thirds (69%) would be willing to devote at least one hour a week during the school year and three-quarters (75%) would be willing to spend 2-3 hours a week or more during the summer.

TitleStandards for Reporting of Diagnostic Accuracy using Intraoperative Neurophysiological Monitoring (STARD-IONM) ObjectiveIntraoperative neurophysiological monitoring (IONM) plays a critical role in preserving functional integrity during surgery, yet it is challenging to compare studies due to methodological heterogeneity and inconsistent reporting. We developed the STARD-IONM extension to improve the transparency, completeness, and comparability of IONM studies. MethodsThe STARD-IONM initiative followed a three-phase consensus. Phase 1 convened a IONM expert panel to discuss and define the rationale and scope. Phase 2 involved structured item-level review of existing STARD items in the context of IONM, applied to published studies with iterative feedback. Phase 3 will include broader community engagement via preprints, outreach to professional societies, and public commentary. ResultsA systematically selected review of IONM studies revealed the underreporting of at key methodological items such as handling missing data (7%), adverse events (11%), and blinding of test and outcomes (22%). A STARD-IONM checklist with recommendations for reporting IONM studies with IONM specific examples were developed. Community feedback emphasized challenges unique to IONM, including the classification of reversible IONM changes, and variability in reference standards. ConclusionsThe STARD-IONM framework addresses critical gaps in the reporting of diagnostic accuracy studies involving IONM. It represents an application of the STARD criteria, wherein the original checklist has been adapted and supplemented with guidelines for IONM studies. SignificanceStandardized reporting will facilitate enhanced adherence to methodological standards, increase reproducibility and strengthen the evidence base for the safe and effective use of IONM, which is expected to improve clinical decision-making.

Crayfish are well known to many but not often newsworthy, so cases where crayfish are covered in international news provide an example of how science journalism covers a news story about basic research. Headlines have a disproportionately large influence on peoples factual knowledge and perceptions of stories covered in media. I tracked online media coverage of one scientific paper involving marbled crayfish and analyzed the headlines used by the articles. Articles were framed as "news," but almost no headlines contained "new" facts that first appeared in the target scientific paper. The fact that appeared in the most headlines (that marbled crayfish reproduce by cloning) was over a decade old. Headlines misled readers into thinking a "breakthrough" was made by one team, rather than showing incremental advances by many teams of researchers over years.

Yips is an involuntary movement disorder seen in some professional golfers. The diagnostic challenge in yips is to distinguish symptoms of task-specific dystonia from psychological choking. We evaluated 15 professional golfers with mild symptomatic yips via anxiety tests, motion-capture and surface electromyography during a putting task. Movement instabilities were analyzed via temporal statistical methodologies (one-dimensional statistical parametric mapping). In a subset of golfers, we found significant differences in angular velocities of the putter-club rotation and altered synergy neural coefficients during the downswing phase. Our results showed that golfers with mild yips require sensitive motion-capture evaluations wherein movement instabilities become evident. Particularly the downswing is affected, and the ensuing perturbations in phasic muscle activity share dystonic features that are consistently identified as abnormal muscle synergy patterns. Despite a strong subjective feeling of yips that golfers complain of, movement analysis can reliably exclude those with choking from those with task-specific dystonias.

This study is a retrospective chart review of 200 clients who participated in a non-verbal restorative Cognitive Remediation Training (rCRT) program. The program was applied to effect proper neural functional remodeling needed to support resilient, flexible and adaptable behaviors after encountering a mild to medium closed head traumatic brain injury (mTBI). The r CRT training program focused on improving functional performance in executive cognitive control networks as defined by fMRI studies. All rCRT training activities were delivered in a semi-game-like manner, incorporating a Brain Computer Interface (BCI) that provided in-the-moment neural network performance integrity metrics (nPIMs) used to adjust the level of play required to properly engage long-term potentiation (LTP) and long term depreciation (LTD) network learning rules. This study reports on t-test and Reliable Change Index (RCI) changes found within cognitive abilities performance metrics derived from the Woodcock Johnson Cognitive Abilities III Test. We compared pre and post scores from seven cognitive abilities considered dependent on executive cognitive control networks against seven non-executive control abilities. We observed significant improvements (p values 10 to 10-22) with large Cohens d effect sizes (0.78-1.20) across thirteen cognitive ability domains with a medium effect size (.49) on the remaining. The mean percent change for pooled trained domain was double that observed for pooled untrained domain, at 17.2% versus 8.3%, respectively. To further adjust for practice effects, practice effect RCI values were computed and further supported the effectiveness of the rCRT training (RCI-trained 1.4 - 4.8; untrained RCI 0.08-0.75).

In birds, like in mammals, the hippocampus critically mediates spatial navigation through the formation of a spatial map. This study investigates the impact of active exploration of a novel environment on the hippocampus of young domestic chicks, during formation of a new spatial map. Chicks that were free to actively explore the novel environment exhibited a significantly higher neural activation (measured by c-Fos expression), compared to those that passively observed the novel environment from a restricted area. The difference was limited to the anterior and the dorsolateral parts of the intermediate hippocampus. Furthermore, the nucleus taeniae of the amygdala showed a higher c-Fos expression in the active exploration group than the passive observation group. In both brain regions, brain activation correlated with the number of locations that chicks visited during the test. This suggest that the increase of c-Fos expression in the hippocampus is related to increased firing rates of spatially coding neurons. Furthermore, our study indicates a functional linkage of the hippocampus and nucleus taeniae of the amygdala in processing spatial information. Overall, with the present study, we confirm that, in birds like in mammals, exploration of novel environments activates hippocampus, which is likely related to the formation of new spatial representations. Summary statementActive exploration of a novel environment induces stronger activation of hippocampus and taeniae of domestic chicks than pure visual, passive exploration from a restricted area.

Background: Roma, the largest ethnic minority in Europe,, are almost absent from movement-disorder research despite living in environments with biomass combustion, poor sanitation, and unprotected water, creating a high-risk neurological exposome. Objective: To describe baseline exposome profiles in a nationwide Roma screening cohort and compare exposures between marginalized and integrated communities, and between screen-positive and screen-negative participants. Methods: A nationwide community-based program combined door-to-door recruitment of marginalized Roma with recruitment of integrated Roma through neurological services. Participants completed standardized exposome questionnaires and a brief, non-diagnostic motor symptom screen. Results: Among 541 Roma (350 marginalized; 191 integrated), marginalized participants showed greater environmental and socioeconomic disadvantage, and screen-positive individuals tended to cluster at the more adverse end of this exposome spectrum. Conclusion: This nationwide Roma movement-disorder screening cohort with exposome assessment reveals substantial disparities relevant for future clinical and genetic research.

Background/Objectives: This systematic review examines how different mechanisms of Traumatic Brain Injury (TBI) influence post-injury functional independence and aims to clarify whether recovery patterns vary by injury type. A total of 105 studies (n = 59,621) involving adults with TBI were synthesized. These findings can guide clinicians and researchers in predicting outcomes and effectively customizing rehabilitation plans. Methods: A review following PRISMA standards analyzed English-language studies published from 1975 to 2025, assessed functional outcomes using the Functional Independence Measure (FIM) or the Glasgow Outcome Scale-Extended (GOSE), converted them to z-scores, and aggregated them via a random-effects model with inverse-variance weighting to demonstrate their relevance. Results: Recreational TBIs show the highest functional independence (z = +1.77), followed by MVAs (z = +1.56), with falls (z = +0.70) and assault-related TBIs (z = -0.12) showing moderate outcomes, and TBIs with penetrating trauma (z = -1.15) indicating the most adverse results. Conclusions: TBI mechanisms appear to meaningfully influence long-term post-injury functional independence. Highlighting this can inspire clinicians and researchers to trust these insights to improve prognosis and rehabilitation strategies, underscoring their crucial role in advancing patient care.