Microplastics (MPs) and nanoplastics (NPs) pose serious environmental and health risks and have made plastic pollution a major concern worldwide. They have been detected in terrestrial and aquatic species, including humans, and have been linked to increased risks of cardiovascular, respiratory and metabolic diseases. However, a critical question remains regarding whether plastic pollution also affects brain function and behavior. This review summarizes the current state of knowledge on the neurotoxic effects of MPs and NPs (MNPs) in the brain and their impact on behavior in both humans and rodents. We analyzed recent studies across multiple experimental approaches, including in vitro assays, animal models, human biomonitoring, and emerging technologies (i.e., brain organoids) to provide a comprehensive overview of MNP-induced effects. Findings are organized and discussed in terms of their influence on behavior, brain neurotransmission and function, and mechanistic pathways underlying neurotoxicity. We conclude that clarifying how MNPs affect neural systems and behavior, and exploring strategies to prevent or reverse their neurotoxic effects, will be crucial for safeguarding brain health in an increasingly plastic-contaminated world.
The computational units of large language models (LLMs)-artificial neurons, attention heads, and weight matrices-differ from biological neurons not merely in degree but in kind. This paper develops that empirical argument across three levels of biological organization: the single neuron, the local circuit, and whole-brain dynamics. At the single-neuron level, biological neurons are self-maintaining electrochemical processes sustained by continuous ATP-dependent ion pumping, activity-dependent morphological remodeling, and spike-timing-dependent plasticity (STDP) grounded in local calcium dynamics at individual synapses; artificial units are stateless, memoryless scalar transformations with no metabolic basis. At the circuit level, cortical columns implement laminar excitatory-inhibitory balance and self-organized collective oscillatory dynamics that are absent from the feedforward, batch-normalized layer stacks of transformer architectures. At the systems level, the brain sustains always-on intrinsic dynamics, homeostatic regulation, and circadian entrainment; LLMs are stateless between inferences and possess no equivalent of resting-state activity. Across all three levels, the differences are organizational rather than scalar: they concern the mode of existence of the processing units, not merely the quantity or speed of processing. We conclude that the term "artificial neuron" is a historical metaphor that has outlived its usefulness as a scientific description, and that the conflation of artificial units with biological neurons is a source of persistent confusion in both AI research and public understanding. Replacing the metaphor with precise empirical description is a precondition for accurate evaluation of what LLMs can and cannot do.
Psychiatric disorders arise from dysfunctions of neural systems that are deeply conserved across mammals, yet contemporary psychiatric classification remains fundamentally anthropocentric, relying heavily on subjective experience, symbolic language and self-report. This creates a major challenge for veterinarian psychiatrists and for comparative neuroscience: how can psychopathology be characterized across species when introspective access is unavailable? The domestic dog provides a uniquely powerful model for addressing this question, combining conserved affective and cognitive neural circuitry with species-specific socio-emotional adaptations shaped by domestication and exceptional phenotypic diversity generated by selective breeding. Here, we review the comparative neurobiology of cognitive and emotional regulation in dogs and humans, highlighting both shared neural architectures and critical species-specific differences in cognition, communication and social organization that limit direct transposition of human diagnostic categories. We then examine the principal methodological obstacles currently preventing canine psychiatry from becoming a mature neuroscience discipline, including the absence of standardized behavioral phenotyping, objective biomarkers, harmonized neuroimaging frameworks and operational diagnostic criteria. Building on recent advances in comparative neuroscience, evolutionary biology and dimensional psychiatry, we propose a species-centered syndromic framework in which canine psychopathology is defined through multidimensional profiles integrating behavior, physiology, neural circuits and developmental trajectories. This framework illustrates how comparative neuroscience can contribute to a broader evolutionary psychiatry, shifting psychiatric classification from language-dependent phenomenology toward biologically grounded, cross-species mechanisms of brain dysfunction. We argue that dogs are not merely translational models of human psychiatric disorders but a model system for developing an objective neuroscience of psychopathology.
Brain oscillations represent frequency-specific neural phenomena essential for coordinating distributed brain activity and supporting cognition. The endocannabinoid system (ECS), particularly via cannabinoid receptor 1 (CB1R), plays a pivotal role in modulating neural oscillations through inhibitory circuit modulation, synaptic plasticity regulation, and long-range connectivity coordination. This review synthesizes current understanding of cannabinoid-oscillation interactions from a primarily mechanistic perspective, organized along a temporal framework: acute cannabinoid effects that directly engage CB1R-mediated circuit modulation; chronic adaptations that produce persistent oscillatory changes outlasting drug exposure; developmental vulnerability during prenatal and adolescent periods when cannabinoid exposure disrupts oscillatory circuit maturation; and aging-related ECS dysfunction in neurodegenerative conditions. Within this temporal structure, we examine specific cognitive domains and clinical conditions where mechanistic insights have translational relevance. Understanding the role of ECS as a modulator of oscillations will improve development of targeted cannabinoid-based therapeutics. We conclude by identifying critical knowledge gaps, including incomplete characterization of cell-type-specific CB1R functions and the mechanistic links between oscillatory dysregulation and specific psychiatric symptoms.
Functional brain connectivity (FC) research in attention-deficit/hyperactivity disorder (ADHD) has been dominated by functional magnetic resonance imaging (fMRI). However, electroencephalography (EEG) offers a more clinically accessible alternative with lower cost, easier in-practice implementation, and better temporal resolution. Despite these advantages, clinical translation of FC findings has been hindered by substantial methodological heterogeneity. It is unclear whether coherent, disorder-relevant patterns can be extracted across this diverse literature. We conducted a systematic review and narrative synthesis of EEG FC studies in ADHD, examining whether consistent alterations emerge across analytic families (linear/non-linear; lagged/non-lagged), spatial domains (sensor-/source-spaced) and recording conditions (rest/task). Thirty-seven studies meeting inclusion criteria were identified, encompassing paediatric, adolescent, and adult samples (n=4038, 65.8% male, 30.0% female, 4.2% not specified). Despite pronounced methodological diversity, several convergent themes emerged. Across approaches, ADHD was commonly characterised by reduced posterior integration with relative frontal compensation, altered interactions between large-scale networks, fragmented or compartmentalised network organisation, and a shift toward increased local connectivity alongside weakened global integration. These patterns were most robust in slower frequency bands and often accentuated under cognitive or affective demands. Importantly, these EEG-derived network features closely parallel established fMRI findings of large-scale functional dysconnectivity in ADHD. Together, these results demonstrate that meaningful, region-level network signatures of ADHD can be identified across heterogeneous EEG FC methodologies. These findings support the viability of EEG as a translational tool for characterising brain network dysfunction in ADHD, while also highlighting the importance of standardised, lag-aware, and source-informed approaches for future clinical and biomarker-oriented research.
Empathy, the capacity to understand and share others' emotions, relies on two complementary components: cognitive empathy, involving perspective-taking and inferential understanding, and affective empathy, grounded in bodily resonance with others' states. Both depend on the ability to maintain a clear boundary between self and other because, when this is blurred, individuals might experience emotional contagion, a simpler form of emotional engagement with the other. Evidence suggests that autobiographical memory supports cognitive empathy by enabling individuals to simulate others' experiences through recollection, while interoceptive processes contribute to affective empathy by providing access to internal bodily representations that are appraised and interpreted based on first-hand previous experiences. We propose that memory and empathy are interconnected through a shared mechanism of self-other distinction, primarily mediated by the precuneus and its interactions with hippocampus, anterior insula and cingulate cortex. Damage to these networks may differentially impair empathic components, depending on whether memory-based self-referential processes or bodily self-representations are compromised. We suggest that the weakening of self-other distinction may represent a key mechanism linking memory loss to empathy impoverishment. Future studies should explicitly investigate this relationship by integrating assessments of memory, interoception, and self-other distinction-using approaches such as virtual reality, lesion mapping, and neuromodulation-to clarify how memory deficits affect empathy. Understanding these processes may reconcile inconsistent findings in the literature and advance models of social cognition across aging and disease.
Many people eat at around the same times each day. This may result in meal times becoming predictive of eating's potential to be rewarding at that time (i.e., hunger). Time as a predictor of food reward has received much attention in animals but less in humans, even though many people organise eating around breakfast, lunch and dinner - words implying particular times of day. In this narrative review we examine if and how habitual meal times might cause hunger in people. We start by addressing a basic premise, can time-of-day predict food availability outside of modern clock-driven societies? We find it can, with moderate-to-strong evidence. We then turn to a harder question, is there evidence that habitual meal times can cause hunger? In animals, this focusses on the behavioral and physiological correlates of hunger, which provide positive weak-to-moderate and strong support, respectively. In humans, this means finding studies that control a key confound, namely people often eat after a period without food. This can generate other cues (e.g., an empty stomach) that may cause hunger, potentially resulting in cue competition. Currently, the human evidence is supportive, but weak. Finally, we evaluate models of how habitual meal times might cause hunger in animals, and then critically apply these to humans - noting that several key questions remain (i.e., cue competition). The implications for the human cephalic phase literature, the health impacts of regular/irregular eating patterns, how time may develop as a hunger cue and cause hunger, and its neural basis, are discussed.
BACKGROUND:Contact with the criminal legal system (CLS) is a prevalent and socially patterned exposure in the United States with well-documented health consequences. Growing research suggests that CLS contact may be associated with biological aging, but evidence remains variable across biomarker domains, forms of exposure, and study designs. This systematic review synthesized literature on CLS contact and biomarkers relevant to biological aging in the U.S. METHODS:We systematically searched seven electronic databases and Google Scholar. Eligible studies examined direct or vicarious CLS contact in relation to at least one biomarker domain relevant to biological aging, including epigenetic measures, telomere length, inflammatory markers, or allostatic load. Retrieved references were imported into Covidence for deduplication and screening. Data were extracted using a standardized form and evidence quality was assessed using an adapted Newcastle-Ottawa Scale. RESULTS:Twenty-two studies met inclusion criteria. Sixteen studies (72.7%) reported findings consistent with accelerated biological aging in association with CLS contact. The most consistent evidence was observed for epigenetic outcomes, with all seven studies reporting significant accelerated epigenetic aging in association with CLS contact. Evidence for inflammatory markers, allostatic load, and telomere length was less consistent, although several studies linked CLS contact with elevated inflammation, greater multisystem physiological dysregulation, and shorter telomere length. Associations varied by form of CLS contact, timing, and context, including violence during incarceration and racialized exposure to policing. CONCLUSIONS:CLS contact may be associated with multiple biological systems relevant to biological aging. More research is needed to clarify temporality, heterogeneity, and underlying pathways.
(235 words)Acute aerobic exercise (AAE) has been shown to influence motor learning outcomes, but previous studies have typically focused on overall performance measures, leaving it unclear whether spatial and temporal components are differentially affected. In addition, the impact of exercise timing and intensity on these effects has not yet been investigated. This pre-registered meta-analysis aimed to evaluate these effects. A systematic search of four databases (Web of Science, ERIC, MEDLINE, SPORTDiscus) identified 18 studies including 657 participants. Spatial and temporal outcomes of motor learning were analyzed separately, considering whether AAE was performed before or after motor task practice. A random-effects meta-analysis was performed, with Hedges’ g as the effect size. Overall, our findings demonstrated that AAE performed before motor task practice selectively enhanced spatial outcomes of motor learning (g = 0.30, 95%CI [0.14; 0.47], p = 0.0003), whereas temporal components showed no significant change (g = 0.01, 95%CI [-0.15; 0.17], p = 0.911). A meta-regression indicated that high AAE intensity significantly moderated this effect (g = 0.48, 95% CI [0.28; 0.69], p < 0.001). These findings indicate that spatial and temporal components of motor learning are differentially sensitive to AAE, with spatial outcomes preferentially enhanced by AAE performed before motor task practice and at high AAE intensities. This distinction has important implications for sports training and clinical rehabilitation, suggesting that interventions can be tailored to prioritize spatial precision over temporal aspects, thereby enhancing specific motor learning outcomes.
Communication enables social connection, autonomy and identity, making it a fundamental domain of human functioning. In lysosomal storage diseases (LSDs), progressive neurological dysfunction can severely disrupt speech, language and social communication, resulting in profound isolation and reduced quality of life. LSDs are a heterogeneous group of more than 70 inherited metabolic disorders caused by lysosomal dysfunction and substrate accumulation, leading to severe neurological consequences and multisystem pathology. LSDs are classified according to the biochemical nature of the accumulating substrate, reflecting both the underlying enzymatic defect and clinical phenotype. Disease groups include sphingolipidoses (e.g., Gaucher disease), mucopolysaccharidoses (e.g., Hurler syndrome [MPS I]), glycoproteinoses (e.g., aspartylglycosaminuria), gangliosidoses (e.g., Tay-Sachs disease), neuronal ceroid lipofuscinoses (e.g., Batten Disease [CLN3]) and other lipid storage disorders such as Pompe disease or Niemann Pick Type C. Clinical presentations are highly variable, with neurodevelopmental symptoms presenting in infancy or early childhood for many. In this review, we synthesize evidence on speech, language, and social communication phenotypes across lysosomal storage diseases, examining how they can mirror underlying neurodegenerative processes and provide insight into disease progression and neurological vulnerability. We discuss the potential of communication phenotyping to improve diagnosis and prognostic stratification, inform therapeutic monitoring, and guide timely, targeted interventions to preserve social connection and quality of life.
Background The Fusiform Gyrus (FG), a brain region relevant for the interaction between cognitive processes and emotional behavior, especially emotion recognition and interpretation of social cues, has been linked to the pathophysiology of schizophrenia conceptualized as a disorder of aberrant synaptic function and brain connectivity as well as characterized by disruptions in thought processes, perceptions, emotional responsiveness, and Theory of Mind (ToM). Disrupted FG connectivity has been reported in schizophrenia; however, no systematic review has addressed this issue in a comprehensive and critical manner. Methods We conducted a systematic review of PubMed, Embase, and Scopus from database inception to February 2026 following PRISMA guidelines. We included peer-reviewed neuroimaging studies using functional magnetic resonance imaging to assess functional connectivity or task-related activation of the FG in patients with schizophrenia compared with healthy controls. Results We identified 2765 articles from different sources. After duplicate removal, 959 articles were screened at the title-abstract level, 269 articles were reviewed for full-texts, and 86 eligible articles were included. Across fMRI studies, the FG emerged as a central node of dysconnectivity. Drug-naïve patients showed heterogeneous FG alterations, with increased local activity and network centrality reported in some studies and reduced interhemispheric and functional connectivity in others, alongside reduced FG activation on visual, affective, and sensory tasks reported more broadly across schizophrenia samples. First-episode psychosis patients were characterized by FG hypoconnectivity associated with negative symptoms and socio-cognitive impairment. Treatment-responsive patients demonstrated partial normalization or modulation of fusiform connectivity and network centrality following antipsychotic treatment. In contrast, treatment-resistant schizophrenia patients showed persistent hypoactivation and reduced connectivity, correlating with cognitive deficits and negative symptoms. Conclusions The FG appears to function as a dynamic, state-sensitive hub underlying perceptual, emotional, and cognitive disturbances in schizophrenia, in line with impaired ToM.
We performed the first coordinate-based meta-analysis of functional neuroimaging studies using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to investigate the neural correlates of loss aversion, defined as the tendency to overweight potential losses relative to equivalent gains in decision-making under risk. We aimed both to identify its core functional neurocognitive correlates, and to characterize the roles of the identified regions across behavioral domains. Among the studies reporting λ, mean estimates ranged from 1.12 to 2.20 (overall mean = 1.71), confirming the typical overweighting of losses relative to equivalent gains. Meta-analytic findings revealed the consistent involvement of the striatum, anterior insula and dorsal anterior/middle cingulate cortex (dACC/MCC). We complemented these findings with a functional characterization of these regions in terms of their associated behavioral domains, including reward processing, emotion, interoception, pain and higher-order reasoning. This characterization supports a model in which loss aversion reflects the integration of affective and cognitive mechanisms. By contrast, we found no consistent meta-analytic evidence for amygdala involvement in loss aversion. This negative finding likely reflects both methodological constraints inherent in coordinate-based meta-analyses, including the selective inclusion of whole-brain results, and the sensitivity of amygdala responses to task and/or stimulus characteristics. In addition to providing a foundational framework for understanding the neural correlates of human choice and loss aversion, these findings offer a benchmark for investigating clinical conditions characterized by altered evaluative processes and for assessing the effects of therapeutic interventions.
Interpersonal distance (IPD), the physical proximity individuals maintain during face-to-face interaction, is disrupted across a range of disorders involving distorted or threat-biased body representation, from eating disorders to social anxiety and schizophrenia. The dominant mechanistic account links this disruption to peripersonal space (PPS), modeling IPD as the output of the perceiver's own defensive boundary. This account is egocentric: it treats the approaching person as a source of threat rather than as a body whose size, kinematics, and spatial requirements must themselves be represented. IPD regulation, however, is a two-body problem that no current single-body model addresses. Drawing on recent evidence that the spatial properties of another person's body enter the same sensorimotor system that codes one's own PPS, the present article extends the body-representation framework of Möllmann et al., (2024) into a process model of IPD regulation. The model specifies how self-body and other-body representations are coupled across action-guiding, metric, and evaluative stages within a continuous control loop, and proposes how this coupling could render otherwise contradictory findings (most notably the inconsistent IPD effects in anorexia nervosa) more tractable. I further argue that markerless multi-person motion capture is a suitable platform for measuring this process, and outline a research agenda that moves beyond static stop distances toward the approach-avoidance kinematics through which body-representation-based IPD dysregulation is most directly expressed.
Adipokines are proteins synthesized and secreted by several tissues, predominantly adipose tissue, which regulate multiple physiological functions. Historically, they have been mainly associated with regulating energy homeostasis, including glucose metabolism and body weight control. However, accumulating evidence over the past decade indicates that their actions extend far beyond metabolic processes. Adipokines are now recognized as pleiotropic hormonal mediators exerting systemic effects on various organs, including the central nervous system, where they modulate neuroendocrine circuits essential for complex physiological functions. Understanding the mechanisms that regulate reproductive function is crucial for elucidating reproductive physiology and improving fertility-related clinical outcomes. In this review, we focus on an underexplored aspect of adipokines' function: their role as modulators of reproduction and sexual behavior. Recent data demonstrate that several adipokines, including leptin and apelin-13, modulate hypothalamic-pituitary-gonadal axis function and neural circuits involved in reproductive physiology and sexual behavior. Peripheral reproductive actions, including effects on steroidogenesis and gametogenesis, are discussed as complementary mechanisms that interact with central neuroendocrine regulation. Furthermore, dysregulation of adipokine signaling pathways has been linked to various reproductive disorders and fertility impairments in both males and females. These findings underscore the importance of considering adipokines within the broader context of reproductive physiology.
Lifelong antiretroviral therapy extends the lifespan of individuals with human immunodeficiency virus (HIV). However, HIV-associated neurocognitive disorders (HAND) remain with age-linked comorbidities. Despite viral suppression, the co-development of Alzheimer's disease (AD) remains a concern. Both HAND and AD share key mechanisms, including chronic neuroinflammation, glial dysfunction, and progressive neurodegeneration. Microglial activation is a key contributor that generates persistent proinflammatory neurotoxins, promoting amyloid-β aggregation, disrupting clearance, and accelerating neurodegeneration. Persistent viral reservoirs and low-level viral protein expression disrupt glial homeostasis, enhancing oxidative stress, tau hyperphosphorylation, and synaptic damage in the brain. This review highlights the intersections between both disorders and discusses emerging rodent models to investigate convergent pathways with the goal of improving therapeutic strategies to preserve cognitive health.
The intersection of gaming and gambling has gained increasing attention due to their role in addictive behaviours and their effects on brain function. Disadvantageous decision-making, involving continued engagement despite adverse consequences, may reflect dysregulations in positive and negative valence processing common to both gaming and gambling disorders. After conducting a thorough literature search (3773 records identified), we included 56 studies focusing on valence-related processes during functional magnetic resonance imaging (fMRI) with a total of 952 individuals with Internet Gaming Disorder (IGD) and 469 with Gambling Disorder (GD). We performed several meta-analyses using GingerAle software to identify patterns of task-related functional brain activity within IGD and GD (IGD vs controls: 22 experiments, 562 IGD and 530 control participants; GD vs controls: 18 experiments, 341 GD and 365 control participants) and to conduct exploratory comparisons between disorders. Our analysis identified spatial convergence of case-control activation in the right putamen across IGD studies, as well as in the caudate and globus pallidus across GD studies. Exploratory cross-disorder contrast identified shared spatial convergence in the right caudate head across IGD and GD studies while greater spatial convergence was found in the right globus pallidus and left caudate in GD. However, systematic comparison of the two literatures identified substantial differences in reporting conventions, diagnostic approaches, participant characteristics and task paradigms. Consequently, the exploratory between-literature contrast cannot establish disorder-specific basal-ganglia differences and should be regarded as hypothesis-generating. Future studies would benefit from harmonised diagnostic criteria and reporting conventions to enable more robust transdiagnostic comparisons.
Layer IV (L4) is the primary target of thalamic input to the neocortex. Its development varies from the thick L4 of primary sensory cortex to the thin L4 of primary motor cortex, which Nissl staining does not resolve. Why the gradient takes the values it does has remained unexplained. I propose the Input Canonicalization (IC) theory: L4 development is set by the demand for IC - the computation converting inputs into the canonical form downstream intracortical processing presupposes. IC demand is the cross-condition variability of the dominant input, and falls as Canonicalization Fixation proceeds: input statistics stabilize through development and learning. The theory asks what sets the gradient of laminar differentiation that the Structural Model takes as given. With the LPP Conservation Assumption - the laminar architecture of corticocortical projections is preserved between cortical types - I derive the motor areas' projection patterns (aFF/aFB). For termination layers it agrees with the Structural Model and macaque data; for origin layers it accounts for the loss of feedforward-feedback asymmetry in those data, and reverses the hierarchical assignment drawn from them. The postnatal course of L4 in area 4, and its persistence in cerebral palsy, fit the prediction. Active Inference has been offered for reduced L4 in motor cortex; IC theory is broader, and explains features that accounts of cortical type leave open, among them the three separate islands of most differentiated cortex in adult primates. IC demand can be estimated independently of L4, and I state the theory's failure conditions.
Complex motor behaviour, such as bimanual coordination, plays an important role in daily-life activities and specialist skills, relying on a highly refined motor system that interacts with cognitive, emotional and motivational processes. In this review, we propose that handedness, dexterity and expertise are key complementary modulators of motor skill organisation, steering neural and behavioural interactions, with an optimal performance emerging from a synergy between predispositions and acquired abilities. We further demonstrate the implications for surgical practice, where outcomes emerge within high-performance environments. In these settings, motor behaviour follows core principles of motor skill organisation, although its expression strongly relies on cognitive demands due to multiple factors such as procedural and environmental complexity, multitasking, and high-precision requirements. Accounting for these constraints is a critical determinant of how the brain optimises behaviour and mindset during surgical performance. Through extensive training, experts develop adaptive control that promotes an advanced level of motor skill organisation, enabling them to translate their skill, knowledge and experience into superior outcomes. Advancing our understanding of how complex specialist motor skills are performed, acquired and refined is essential for strengthening theoretical models of motor control and learning, enhancing training opportunities, and informing objective assessment criteria and curriculum development.
As the field more actively recognizes the unique facets of adolescent neural, social, and behavioral development, it is clear that adult models of addiction are incongruent with the nature of the developing brain, adolescent substance use behavior, and behavioral outcomes in substance use treatment with adolescents. The present review highlights how developmental translational neuroscience can address this gap by informing and guiding the creation and implementation of more effective, neurodevelopmentally-targeted treatment programming for adolescents. This is illustrated with the example of Adolescent Developmentally-Appropriate health Promotion Therapy (ADAPT), a novel substance use treatment grounded in developmental translational (integrated human brain and behavioral) empirical research. Ultimately, this review aims to provide clinicians working in direct care settings with adolescents engaged in substance use a contemporary perspective on how and why developmental translational neuroscience is relevant to the clinical context, as well as a concrete example of how developmental translational neuroscience can inform substance use treatment for this high need and underserved age group.
