Quantitative EEG biomarkers for STXBP1-related disorders.

OBJECTIVE: EEG patterns and quantitative EEG (qEEG) features have been poorly explored in monogenic epilepsies. Herein, we investigate regional differences in EEG frequency composition in patients with STXBP1 developmental and epileptic encephalopathy (STXBP1-DEE). METHODS: We conducted a retrospective study collecting electroclinical data of patients with STXBP1-DEE and two control groups of patients with DEEs of different etiologies and typically developing individuals matched for age and sex. We performed a (1) visual EEG assessment, (b) qEEG analysis, and (c) electrical source imaging (ESI). We quantified the relative power (RP) of four frequency bands (α ß, θ, δ), in two electrode groups (anterior/posterior), and compared their averages and dynamics (standard deviation [SD] over time). The ESI was performed by applying the standard Distributed Source Modeling algorithm. RESULTS: We analyzed 42 EEG studies in 19 patients with STXBP1-DEE (10 female), with a median age at recordings of 9.6 years (range 9 months to 29 years). The δRP was higher in recordings of STXBP1-DEE (p < .001) compared to both control groups, suggesting the pathogenicity and STXBP1-specificity of these findings. In STXBP1-DEE, the δRP was significantly higher in the anterior electrode group compared to the posterior one (p = .003). There was no correlation between the anterior δRP and the epilepsy focus, age at recordings, and concomitant medications The ESI modeling of this activity showed a widespread involvement of the dorsomesial frontal cortex, suggesting a large corticosubcortical pathologic network. Finally, we identified two groups of recordings: cluster.1 with higher anterior δRP and low dynamics and cluster.2 with lower δRP and higher dynamics. Patients in cluster.1 had a more severe epilepsy and neurological phenotype compared to patients in cluster 2. SIGNIFICANCE: The qEEG analysis showed a predominant frontal slow activity as a specific STXBP1 feature that correlates with the severity of the phenotype and may represent a biomarker for prospective longitudinal studies of STXBP1-DEE.

Examining Brain Activity Responses during Rat Ultrasonic Vocalization Playback: Insights from a Novel fMRI Translational Paradigm.

Despite decades of preclinical investigation, there remains limited understanding of the etiology and biological underpinnings of anxiety disorders. Sensitivity to potential threat is characteristic of anxiety-like behavior in humans and rodents, but traditional rodent behavioral tasks aimed to assess threat responsiveness lack translational value, especially with regard to emotionally valenced stimuli. Therefore, development of novel preclinical approaches to serve as analogues to patient assessments is needed. In humans, the fearful face task is widely used to test responsiveness to socially communicated threat signals. In rats, ultrasonic vocalizations (USVs) are analogous social cues associated with positive or negative affective states that can elicit behavioral changes in the receiver. It is therefore likely that when rats hear aversive alarm call USVs (22 kHz), they evoke translatable changes in brain activity comparable with the fearful face task. We used functional magnetic resonance imaging in male and female rats to assess changes in BOLD activity induced by exposure to aversive 22 kHz alarm calls emitted in response to threatening stimuli, prosocial (55 kHz) USVs emitted in response to appetitive stimuli, or a computer-generated 22 kHz tone. Results show patterns of regional activation that are specific to each USV stimulus. Notably, limbic regions clinically relevant to psychiatric disorders (e.g., amygdala, bed nucleus of the stria terminalis) are preferentially activated by either aversive 22 kHz or appetitive 55 kHz USVs. These results support the use of USV playback as a promising translational tool to investigate affective processing under conditions of distal threat in preclinical rat models.

Considerations for developing complex post-stroke upper limb behavioural interventions: An international qualitative study.

OBJECTIVE: To simultaneously explore the perspectives and opinions of different invested participant groups on the important considerations for development of upper limb behavioural interventions that drive optimal post-stroke upper limb motor recovery. DESIGN: A qualitative descriptive study in a constructivist epistemology. PARTICIPANTS: Purposively selected participant groups (preclinical research n = 9, clinical research n = 9, clinical experience n = 9 and lived experience n = 10). SETTING: Research participants were selected from top internationally published authors. Experiential participants were recruited internationally, through networks. RESULTS: Four themes were identified with embedded subthemes. Theme 1: 'Clinical relevance should be the core of a "good" research question' with two subthemes: 'Breaking down silos: forging interdisciplinary research teams', and 'Beyond the pipeline: bench to bedside and back'; theme 2: 'Balance restitution and compensation to maximise outcomes' with three subthemes: 'Good outcome: going beyond an outcome measure', 'Recovery is a puzzle: measure all the pieces', and 'Optimising capacity: knowing when and how'; theme 3: 'Stroke demands personalised solutions' with two subthemes: 'Condition-specific considerations', and 'Person-specific considerations'; theme 4: 'Upper limb recovery requires complex interventions' with four subthemes: 'Fuelling engagement', 'Content is crucial', 'Multidimensional dose', and 'Therapist sway'. CONCLUSIONS: This study suggests that post-stroke upper limb motor interventions are the interactions of multiple intervention elements (e.g. dose and content) shaped by different contextual considerations (e.g. stroke and personal factors). Development of such interventions may need to consider both content and context of the intervention to drive optimal recovery.

Comparing mouse and human cingulate cortex organization using functional connectivity.

The subdivisions of the extended cingulate cortex of the human brain are implicated in a number of high-level behaviors and affected by a range of neuropsychiatric disorders. Its anatomy, function, and response to therapeutics are often studied using non-human animals, including the mouse. However, the similarity of human and mouse frontal cortex, including cingulate areas, is still not fully understood. Some accounts emphasize resemblances between mouse cingulate cortex and human cingulate cortex while others emphasize similarities with human granular prefrontal cortex. We use comparative neuroimaging to study the connectivity of the cingulate cortex in the mouse and human, allowing comparisons between mouse 'gold standard' tracer and imaging data, and, in addition, comparison between the mouse and the human using comparable imaging data. We find overall similarities in organization of the cingulate between species, including anterior and midcingulate areas and a retrosplenial area. However, human cingulate contains subareas with a more fine-grained organization than is apparent in the mouse and it has connections to prefrontal areas not present in the mouse. Results such as these help formally address between-species brain organization and aim to improve the translation from preclinical to human results.

Linking Cognitive Integrity to Working Memory Dynamics in the Aging Human Brain.

Aging is accompanied by a decline of working memory, an important cognitive capacity that involves stimulus-selective neural activity that persists after stimulus presentation. Here, we unraveled working memory dynamics in older human adults (male and female) including those diagnosed with mild cognitive impairment (MCI) using a combination of behavioral modeling, neuropsychological assessment, and MEG recordings of brain activity. Younger adults (male and female) were studied with behavioral modeling only. Participants performed a visuospatial delayed match-to-sample task under systematic manipulation of the delay and distance between sample and test stimuli. Their behavior (match/nonmatch decisions) was fit with a computational model permitting the dissociation of noise in the internal operations underlying the working memory performance from a strategic decision threshold. Task accuracy decreased with delay duration and sample/test proximity. When sample/test distances were small, older adults committed more false alarms than younger adults. The computational model explained the participants' behavior well. The model parameters reflecting internal noise (not decision threshold) correlated with the precision of stimulus-selective cortical activity measured with MEG during the delay interval. The model uncovered an increase specifically in working memory noise in older compared with younger participants. Furthermore, in the MCI group, but not in the older healthy controls, internal noise correlated with the participants' clinically assessed cognitive integrity. Our results are consistent with the idea that the stability of working memory contents deteriorates in aging, in a manner that is specifically linked to the overall cognitive integrity of individuals diagnosed with MCI.

The mouse motor system contains multiple premotor areas and partially follows human organizational principles.

While humans are known to have several premotor cortical areas, secondary motor cortex (M2) is often considered to be the only higher-order motor area of the mouse brain and is thought to combine properties of various human premotor cortices. Here, we show that axonal tracer, functional connectivity, myelin mapping, gene expression, and optogenetics data contradict this notion. Our analyses reveal three premotor areas in the mouse, anterior-lateral motor cortex (ALM), anterior-lateral M2 (aM2), and posterior-medial M2 (pM2), with distinct structural, functional, and behavioral properties. By using the same techniques across mice and humans, we show that ALM has strikingly similar functional and microstructural properties to human anterior ventral premotor areas and that aM2 and pM2 amalgamate properties of human pre-SMA and cingulate cortex. These results provide evidence for the existence of multiple premotor areas in the mouse and chart a comparative map between the motor systems of humans and mice.

Comparative neuroimaging of sex differences in human and mouse brain anatomy.

In vivo neuroimaging studies have established several reproducible volumetric sex differences in the human brain, but the causes of such differences are hard to parse. While mouse models are useful for understanding the cellular and mechanistic bases of sex-specific brain development, there have been no attempts to formally compare human and mouse neuroanatomical sex differences to ascertain how well they translate. Addressing this question would shed critical light on the use of the mouse as a translational model for sex differences in the human brain and provide insights into the degree to which sex differences in brain volume are conserved across mammals. Here, we use structural magnetic resonance imaging to conduct the first comparative neuroimaging study of sex-specific neuroanatomy of the human and mouse brain. In line with previous findings, we observe that in humans, males have significantly larger and more variable total brain volume; these sex differences are not mirrored in mice. After controlling for total brain volume, we observe modest cross-species congruence in the volumetric effect size of sex across 60 homologous regions (r=0.30). This cross-species congruence is greater in the cortex (r=0.33) than non-cortex (r=0.16). By incorporating regional measures of gene expression in both species, we reveal that cortical regions with greater cross-species congruence in volumetric sex differences also show greater cross-species congruence in the expression profile of 2835 homologous genes. This phenomenon differentiates primary sensory regions with high congruence of sex effects and gene expression from limbic cortices where congruence in both these features was weaker between species. These findings help identify aspects of sex-biased brain anatomy present in mice that are retained, lost, or inverted in humans. More broadly, our work provides an empirical basis for targeting mechanistic studies of sex-specific brain development in mice to brain regions that best echo sex-specific brain development in humans.

Can I see it in the eyes? An investigation of freezing-like motion patterns in response to avoidable threat.

Freezing is one of the most extensively studied defensive behaviors in rodents. Both reduced body and gaze movements during anticipation of threat also occur in humans and have been discussed as translational indicators of freezing but their relationship remains unclear. We thus set out to elucidate body and eye movements and concomitant autonomic dynamics in anticipation of avoidable threat. Specifically, 50 participants viewed naturalistic pictures that were preceded by a colored fixation cross, signaling them whether to expect an inevitable (shock), no (safety), or a potential shock (flight) that could be avoided by a quick button press. Body sway, eye movements, the heart rate and skin conductance were recorded. We replicated previously described reductions in body sway, gaze dispersion, and the heart rate, and a skin conductance increase in flight trials. Stronger reductions in gaze but not in body sway predicted faster motor reactions on a trial-wise basis, highlighting their functional role in action preparation. We failed to find a trait-like relationship between body and gaze movements across participants, but their temporal profiles were positively related within individuals, suggesting that both metrics partly reflect the same construct. However, future research is desirable to assess these response patterns in naturalistic environments. A more ethological examination of different movement dynamics upon threat would not only warrant better comparability between rodent and human research but also help determine whether and how eye-tracking could be implemented as a proxy for fear-related movements in restricted brain imaging environments.

The explore/exploit trade-off: An ecologically valid and translational framework that can advance mechanistic understanding of eating disorders.

The explore/exploit trade-off is a decision-making process that is conserved across species and balances exploring unfamiliar choices of unknown value with choosing familiar options of known value to maximize reward. This framework is rooted in behavioral ecology and has traditionally been used to study maladaptive versus adaptive non-human animal foraging behavior. Researchers have begun to recognize the potential utility of understanding human decision-making and psychopathology through the explore/exploit trade-off. In this article, we propose that explore/exploit trade-off holds promise for advancing our mechanistic understanding of decision-making processes that confer vulnerability for and maintain eating pathology due to its neurodevelopmental bases, conservation across species, and ability to be mathematically modeled. We present a model for how suboptimal explore/exploit decision-making can promote disordered eating and present recommendations for future research applying this framework to eating pathology. Taken together, the explore/exploit trade-off provides a translational framework for expanding etiologic and maintenance models of eating pathology, given developmental changes in explore/exploit decision-making that coincide in time with the emergence of eating pathology and evidence of biased explore/exploit decision-making in psychopathology. Additionally, understanding explore/exploit decision-making in eating disorders may improve knowledge of their underlying pathophysiology, informing targeted clinical interventions such as neuromodulation and pharmacotherapy. PUBLIC SIGNIFICANCE STATEMENT: The explore/exploit trade-off is a cross-species decision-making process whereby organisms choose between a known option with a known reward or sampling unfamiliar options. We hypothesize that imbalanced explore/exploit decision-making can promote disordered eating and present preliminary data. We propose that explore/exploit trade-off has significant potential to advance understanding of the neurocognitive and neurodevelopmental mechanisms of eating pathology, which could ultimately guide revisions of etiologic models and inform novel interventions.

El balance entre explorar y explotar es un proceso de toma de decisiones que se conserva a través de las especies y equilibra la exploración de opciones desconocidas de valor desconocido con la elección de opciones familiares de valor conocido para maximizar la recompensa. Este marco está arraigado en la ecología del comportamiento y tradicionalmente se ha utilizado para estudiar el comportamiento de forrajeo no adaptativo versus adaptativo en animales no humanos. Los investigadores han comenzado a reconocer la utilidad potencial de entender la toma de decisiones humanas y la psicopatología a través del balance entre explorar y explotar. En este artículo, proponemos que el balance entre explorar y explotar ofrece promesas para avanzar en nuestra comprensión mecanicista de los procesos de toma de decisiones que confieren vulnerabilidad y mantienen la patología alimentaria debido a sus bases neurodesarrolladoras, su conservación a través de las especies y su capacidad de ser modelado matemáticamente. Presentamos un modelo de cómo la toma de decisiones subóptima entre explorar y explotar puede promover la alimentación disfuncional y presentamos recomendaciones para futuras investigaciones que apliquen este marco a la patología alimentaria. En conjunto, el balance entre explorar y explotar proporciona un marco translacional para expandir los modelos etiológicos y de mantenimiento de la patología alimentaria, dadas los cambios en el desarrollo de la toma de decisiones entre explorar y explotar que coinciden en el tiempo con la aparición de la patología alimentaria y la evidencia de una toma de decisiones entre explorar y explotar sesgada en la psicopatología. Además, comprender la toma de decisiones entre explorar y explotar en los trastornos alimentarios puede mejorar el conocimiento de su fisiopatología subyacente, informando intervenciones clínicas dirigidas como la neuromodulación y la farmacoterapia.

Integrating direct electrical brain stimulation with the human connectome.

Neurological and neurodevelopmental conditions are a major public health concern for which new therapies are urgently needed. The development of effective therapies relies on the precise mapping of the neural substrates causally involved in behaviour generation. Direct electrical stimulation (DES) performed during cognitive and neurological monitoring in awake surgery is currently considered the gold standard for the causal mapping of brain functions. However, DES is limited by the focal nature of the stimulation sites, hampering a real holistic exploration of human brain functions at the network level. We used 4137 DES points derived from 612 glioma patients in combination with human connectome data-resting-state functional MRI, n = 1000 and diffusion weighted imaging, n = 284-to provide a multimodal description of the causal macroscale functional networks subtending 12 distinct behavioural domains. To probe the validity of our procedure, we (i) compared the network topographies of healthy and clinical populations; (ii) tested the predictive capacity of DES-derived networks; (iii) quantified the coupling between structural and functional connectivity; and (iv) built a multivariate model able to quantify single subject deviations from a normative population. Lastly, we probed the translational potential of DES-derived functional networks by testing their specificity and sensitivity in identifying critical neuromodulation targets and neural substrates associated with postoperative language deficits. The combination of DES and human connectome data resulted in an average 29.4-fold increase in whole brain coverage compared to DES alone. DES-derived functional networks are predictive of future stimulation points (97.8% accuracy) and strongly supported by the anatomical connectivity of subcortical stimulations. We did not observe any significant topographical differences between the patients and the healthy population at both group and single subject level. Showcasing concrete clinical applications, we found that DES-derived functional networks overlap with effective neuromodulation targets across several functional domains, show a high degree of specificity when tested with the intracranial stimulation points of a different stimulation technique and can be used effectively to characterize postoperative behavioural deficits. The integration of DES with the human connectome fundamentally advances the quality of the functional mapping provided by DES or functional imaging alone. DES-derived functional networks can reliably predict future stimulation points, have a strong correspondence with the underlying white matter and can be used for patient specific functional mapping. Possible applications range from psychiatry and neurology to neuropsychology, neurosurgery and neurorehabilitation.

A precision neuroscience approach to estimating reliability of neural responses during emotion processing: Implications for task-fMRI.

Recent work demonstrating low test-retest reliability of neural activation during fMRI tasks raises questions about the utility of task-based fMRI for the study of individual variation in brain function. Two possible sources of the instability in task-based BOLD signal over time are noise or measurement error in the instrument, and meaningful variation across time within-individuals in the construct itself-brain activation elicited during fMRI tasks. Examining the contribution of these two sources of test-retest unreliability in task-evoked brain activity has far-reaching implications for cognitive neuroscience. If test-retest reliability largely reflects measurement error, it suggests that task-based fMRI has little utility in the study of either inter- or intra-individual differences. On the other hand, if task-evoked BOLD signal varies meaningfully over time, it would suggest that this tool may yet be well suited to studying intraindividual variation. We parse these sources of variance in BOLD signal in response to emotional cues over time and within-individuals in a longitudinal sample with 10 monthly fMRI scans. Test-retest reliability was low, reflecting a lack of stability in between-person differences across scans. In contrast, within-person, within-session internal consistency of the BOLD signal was higher, and within-person fluctuations across sessions explained almost half the variance in voxel-level neural responses. Additionally, monthly fluctuations in neural response to emotional cues were associated with intraindividual variation in mood, sleep, and exposure to stressors. Rather than reflecting trait-like differences across people, neural responses to emotional cues may be more reflective of intraindividual variation over time. These patterns suggest that task-based fMRI may be able to contribute to the study of individual variation in brain function if more attention is given to within-individual variation approaches, psychometrics-beginning with improving reliability beyond the modest estimates observed here, and the validity of task fMRI beyond the suggestive associations reported here.

Prefrontal photobiomodulation produces beneficial mitochondrial and oxygenation effects in older adults with bipolar disorder.

There is growing evidence of mitochondrial dysfunction and prefrontal cortex (PFC) hypometabolism in bipolar disorder (BD). Older adults with BD exhibit greater decline in PFC-related neurocognitive functions than is expected for age-matched controls, and clinical interventions intended for mood stabilization are not targeted to prevent or ameliorate mitochondrial deficits and neurocognitive decline in this population. Transcranial infrared laser stimulation (TILS) is a non-invasive form of photobiomodulation, in which photons delivered to the PFC photo-oxidize the mitochondrial respiratory enzyme, cytochrome-c-oxidase (CCO), a major intracellular photon acceptor in photobiomodulation. TILS at 1064-nm can significantly upregulate oxidized CCO concentrations to promote differential levels of oxygenated vs. deoxygenated hemoglobin (HbD), an index of cerebral oxygenation. The objective of this controlled study was to use non-invasive broadband near-infrared spectroscopy to assess if TILS to bilateral PFC (Brodmann area 10) produces beneficial effects on mitochondrial oxidative energy metabolism (oxidized CCO) and cerebral oxygenation (HbD) in older (≥50 years old) euthymic adults with BD (N = 15). As compared to sham, TILS to the PFC in adults with BD increased oxidized CCO both during and after TILS, and increased HbD concentrations after TILS. By significantly increasing oxidized CCO and HbD concentrations above sham levels, TILS has the potential ability to stabilize mitochondrial oxidative energy production and prevent oxidative damage in the PFC of adults with BD. In conclusion, TILS was both safe and effective in enhancing metabolic function and subsequent hemodynamic responses in the PFC, which might help alleviate the accelerated neurocognitive decline and dysfunctional mitochondria present in BD.

Unraveling the Thread of Aphasia Rehabilitation: A Translational Cognitive Perspective.

Translational neuroscience is a multidisciplinary field that aims to bridge the gap between basic science and clinical practice. Regarding aphasia rehabilitation, there are still several unresolved issues related to the neural mechanisms that optimize language treatment. Although there are studies providing indications toward a translational approach to the remediation of acquired language disorders, the incorporation of fundamental neuroplasticity principles into this field is still in progress. From that aspect, in this narrative review, we discuss some key neuroplasticity principles, which have been elucidated through animal studies and which could eventually be applied in the context of aphasia treatment. This translational approach could be further strengthened by the implementation of intervention strategies that incorporate the idea that language is supported by domain-general mechanisms, which highlights the impact of non-linguistic factors in post-stroke language recovery. Here, we highlight that translational research in aphasia has the potential to advance our knowledge of brain-language relationships. We further argue that advances in this field could lead to improvement in the remediation of acquired language disturbances by remodeling the rationale of aphasia-therapy approaches. Arguably, the complex anatomy and phenomenology of aphasia dictate the need for a multidisciplinary approach with one of its main pillars being translational research.

Data Mining of Microarray Datasets in Translational Neuroscience.

Data mining involves the computational analysis of a plethora of publicly available datasets to generate new hypotheses that can be further validated by experiments for the improved understanding of the pathogenesis of neurodegenerative diseases. Although the number of sequencing datasets is on the rise, microarray analysis conducted on diverse biological samples represent a large collection of datasets with multiple web-based programs that enable efficient and convenient data analysis. In this review, we first discuss the selection of biological samples associated with neurological disorders, and the possibility of a combination of datasets, from various types of samples, to conduct an integrated analysis in order to achieve a holistic understanding of the alterations in the examined biological system. We then summarize key approaches and studies that have made use of the data mining of microarray datasets to obtain insights into translational neuroscience applications, including biomarker discovery, therapeutic development, and the elucidation of the pathogenic mechanisms of neurodegenerative diseases. We further discuss the gap to be bridged between microarray and sequencing studies to improve the utilization and combination of different types of datasets, together with experimental validation, for more comprehensive analyses. We conclude by providing future perspectives on integrating multi-omics, to advance precision phenotyping and personalized medicine for neurodegenerative diseases.

Integrative multi-omics and systems bioinformatics in translational neuroscience: A data mining perspective.

Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information, with its application to neuroscience termed neuroinformatics. Data mining of omics datasets has enabled the generation of new hypotheses based on differentially regulated biological molecules associated with disease mechanisms, which can be tested experimentally for improved diagnostic and therapeutic targeting of neurodegenerative diseases. Importantly, integrating multi-omics data using a systems bioinformatics approach will advance the understanding of the layered and interactive network of biological regulation that exchanges systemic knowledge to facilitate the development of a comprehensive human brain profile. In this review, we first summarize data mining studies utilizing datasets from the individual type of omics analysis, including epigenetics/epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, and spatial omics, pertaining to Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We then discuss multi-omics integration approaches, including independent biological integration and unsupervised integration methods, for more intuitive and informative interpretation of the biological data obtained across different omics layers. We further assess studies that integrate multi-omics in data mining which provide convoluted biological insights and offer proof-of-concept proposition towards systems bioinformatics in the reconstruction of brain networks. Finally, we recommend a combination of high dimensional bioinformatics analysis with experimental validation to achieve translational neuroscience applications including biomarker discovery, therapeutic development, and elucidation of disease mechanisms. We conclude by providing future perspectives and opportunities in applying integrative multi-omics and systems bioinformatics to achieve precision phenotyping of neurodegenerative diseases and towards personalized medicine.

Bridging the Gap between Basic Research and Clinical Practice: The Growing Role of Translational Neurorehabilitation.

Translational neuroscience is intended as a holistic approach in the field of brain disorders, starting from the basic research of cerebral morphology and with the function of implementing it into clinical practice. This concept can be applied to the rehabilitation field to promote promising results that positively influence the patient's quality of life. The last decades have seen great scientific and technological improvements in the field of neurorehabilitation. In this paper, we discuss the main issues related to translational neurorehabilitation, from basic research to current clinical practice, and we also suggest possible future scenarios.

Introducing individual sentience profiles in nonhuman primate neuroscience research.

The Animal Research Declaration is committed to establishing cohesive and rigorous ethical standards to safeguard the welfare of nonhuman primates (NHPs) engaged in neuroscience research (Petkov et al., 2022 this issue). As part of this mission, there is an expanding dialogue amongst neuroscientists, philosophers, and policymakers, that is centred on diverse aspects of animal welfare and scientific practice. This paper emphasises the necessity of integrating the assessment of animal sentience into the declaration. Animal sentience, in this context, refers to the recognized capacity that animals have for various kinds of subjective experience, with an associated positive or negative valence (Browning and Birch, 2022). Accordingly, NHP neuroscience researchers should work toward instituting a standardised approach for evaluating what can be termed "individual sentience profiles," representing the unique manner in which an individual NHP experiences specific events or environments. The adoption of this novel parameter would serve a triad of indispensable purposes: enhancing NHP welfare throughout research involvement, elevating the quality of life for NHPs in captivity, and refining the calibre of research outcomes.

The Pig as a Translational Animal Model for Biobehavioral and Neurotrauma Research.

In recent decades, the pig has attracted considerable attention as an important intermediary model animal in translational biobehavioral research due to major similarities between pig and human neuroanatomy, physiology, and behavior. As a result, there is growing interest in using pigs to model many human neurological conditions and injuries. Pigs are highly intelligent and are capable of performing a wide range of behaviors, which can provide valuable insight into the effects of various neurological disease states. One area in which the pig has emerged as a particularly relevant model species is in the realm of neurotrauma research. Indeed, the number of investigators developing injury models and assessing treatment options in pigs is ever-expanding. In this review, we examine the use of pigs for cognitive and behavioral research as well as some commonly used physiological assessment methods. We also discuss the current usage of pigs as a model for the study of traumatic brain injury. We conclude that the pig is a valuable animal species for studying cognition and the physiological effect of disease, and it has the potential to contribute to the development of new treatments and therapies for human neurological and psychiatric disorders.