{"title":"How the body and brain process time","authors":"Alice Teghil , Marc Wittmann","doi":"10.1016/j.neubiorev.2025.106416","DOIUrl":"10.1016/j.neubiorev.2025.106416","url":null,"abstract":"<div><div>Recent evidence from two independent meta-analyses reveals that subjective time is processed in the insular cortex alongside the supplementary motor area (SMA). The insula is suggested to function as the primary sensory interoceptive cortex which receives and processes signals from bodily organs and tissues. In this review, we highlight growing evidence from functional neuroimaging, electrophysiological and psychophysiological studies, as well as from neuropsychological and neuropsychiatric research, which indicate that subjective time judgments are rooted in both bodily and emotional aspects of the self. Highlighting the still underrepresented role of the insula in time perception, we propose that the perception of time passage and the judgment of duration rely on brain regions that support the interaction between the body and the external environment (SMA), as well as the processing of internal signals originating from the body (insula).</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106416"},"PeriodicalIF":7.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wouter A J Vints, Evrim Gökçe, Antoine Langeard, Iuliia Pavlova, Özge Selin Çevik, Mohammad Mosaferi Ziaaldini, Jasemin Todri, Orges Lena, Salit Bar Shalom, Suzanne Jak, Ioanna Zorba Zormpa, Christina Karatzaferi, Oron Levin, Nerijus Masiulis, Yael Netz
{"title":"Corrigendum to 'Investigating the mediating effect of myokines on exercise-induced cognitive changes in older adults: A living systematic review and meta-analysis' [Neurosci. Biobehav. Rev., vol. 178, (November 2025) 106381].","authors":"Wouter A J Vints, Evrim Gökçe, Antoine Langeard, Iuliia Pavlova, Özge Selin Çevik, Mohammad Mosaferi Ziaaldini, Jasemin Todri, Orges Lena, Salit Bar Shalom, Suzanne Jak, Ioanna Zorba Zormpa, Christina Karatzaferi, Oron Levin, Nerijus Masiulis, Yael Netz","doi":"10.1016/j.neubiorev.2025.106405","DOIUrl":"10.1016/j.neubiorev.2025.106405","url":null,"abstract":"","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":" ","pages":"106405"},"PeriodicalIF":7.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sofia Domeij , Ellie Sandberg Larsson , Mike Gilbert , Anders Rasmussen
{"title":"Interspecies variations in eyeblink conditioning","authors":"Sofia Domeij , Ellie Sandberg Larsson , Mike Gilbert , Anders Rasmussen","doi":"10.1016/j.neubiorev.2025.106398","DOIUrl":"10.1016/j.neubiorev.2025.106398","url":null,"abstract":"<div><div>A central assumption in neuroscience is that learning mechanisms are conserved across species. Eyeblink conditioning, a cornerstone paradigm for studying associative learning and cerebellar function, has been widely used in humans and animal models alike. Yet direct cross-species comparisons remain rare. In this systematic review, we analyzed 484 eyeblink conditioning experiments reported in 271 studies spanning humans, rabbits, rats, mice, as well as individual studies in other species. Our findings reveal consistent interspecies differences in acquisition rates, timing parameters, and stimulus protocols, with notable variation even within species. These results challenge the assumption of mechanistic equivalence across species and highlight the limitations of generalizing neural mechanisms from one species to another.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106398"},"PeriodicalIF":7.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spinal glia-driven neuroinflammation as a therapeutic target for neuropathic pain: Rational development of novel analgesics","authors":"Zhonghua Zhang , Zhanyu Niu , Shouliang Dong","doi":"10.1016/j.neubiorev.2025.106404","DOIUrl":"10.1016/j.neubiorev.2025.106404","url":null,"abstract":"<div><div>Neuropathic pain caused by a lesion or disease of the somatosensory nervous system is a suffering and prevalent chronic pain condition with a major impact on the quality of patients’ lives. Current pharmacotherapeutic interventions deliver insufficient pain relief, and thus the development of effective analgesics for neuropathic pain represents a significant clinical demand. Notably, accumulating evidence demonstrates that neuroinflammation mediated by microglia and astrocytes within the central nervous system plays a pivotal role in driving the pathological progression of neuropathic pain. Nerve injury or neuropathy triggers alterations in receptor and ion channel expression on microglia and astrocytes, including upregulation or downregulation. These alterations drive glial proliferation, mediate neuroinflammatory cascades, and facilitate the progression of neuropathic pain. In preclinical studies, clinical drugs or analgesic molecules targeting these glial receptors or ion channels have demonstrated significant neuropathic pain relief and suppression of neuroinflammation. The suppression includes inhibition of gliosis, reduction of pro-inflammatory mediator release, and transition toward anti-inflammatory microglia or neuroprotective astrocytes. Therefore, targeting glial receptors or ion channels involved in neuropathic pain to inhibit neuroinflammatory progression represents a promising therapeutic strategy for developing analgesics with potential long-term pharmacotherapy.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106404"},"PeriodicalIF":7.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dana Shamai-Leshem , Tamar Radai , Simone Shamay-Tsoory
{"title":"The oxytocin-attention loop of loneliness","authors":"Dana Shamai-Leshem , Tamar Radai , Simone Shamay-Tsoory","doi":"10.1016/j.neubiorev.2025.106395","DOIUrl":"10.1016/j.neubiorev.2025.106395","url":null,"abstract":"<div><div>Loneliness is a biological signal urging us to reconnect with others. However, some people fail to do so and become trapped in chronic loneliness, which leads to adverse physical and mental consequences. Here, we propose a theoretical bio-behavioral model explaining how loneliness becomes chronic through a self-reinforcing oxytocin-attention loop. We suggest that acute loneliness leads to increased oxytocin release, which projects to the mesolimbic reward system, increasing the salience of social cues. In most individuals, attention is normally biased toward affiliative social cues, thus oxytocin heightens attention toward affiliative cues, promoting reconnection and alleviating loneliness. By contrast, loneliness-vulnerable individuals show attention bias toward signs of rejection. For them, oxytocin-related social salience leads to heightened rejection vigilance, which may result in increased social avoidance and persistent loneliness. Over time, chronic loneliness causes a reduction in oxytocin system reactivity, weakening the motivational drive for reconnection, and diminishing individual’s ability to recover. This model offers an integrative perspective of neurobiological and cognitive factors and provides potential targets for therapeutic interventions for loneliness.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106395"},"PeriodicalIF":7.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Defending the self: The role of oxytocin in responses to psychological threat","authors":"Chunliang Feng , Wenbo Luo , Ruida Zhu","doi":"10.1016/j.neubiorev.2025.106406","DOIUrl":"10.1016/j.neubiorev.2025.106406","url":null,"abstract":"<div><div>Oxytocin (OT) is widely characterized as a prosocial neuropeptide, yet its effects are context-dependent and extend beyond affiliation. Drawing on recent evolutionary perspectives, we advance a framework in which OT supports the defense and enhancement of positively biased self-views. This function is distinctly human because it relies on self-reflection and symbolic self-representation. To assess this account, we synthesize evidence across intrapersonal, social comparison, and social evaluation contexts. Converging findings indicate that OT modulates affective, cognitive, and behavioral processes relevant to self-protection. In particular, OT impacts both proactive (e.g., information selection, non-cooperation) and reactive (e.g., aggression, cognitive distortion) strategies that serve to protect desirable self-views. This self-protection account offers a unifying explanation for heterogeneous and sometimes paradoxical OT effects by reframing them as context-sensitive expressions of self-defense. Common and distinct mechanisms through which OT and the structurally homologous neuropeptide vasopressin contribute to self‑protection are delineated. We conclude by situating the account relative to prevailing theoretical models, delineating priorities for future research, and outlining clinical implications for conditions characterized by self‑protection deficits.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106406"},"PeriodicalIF":7.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reina A. Mendoza , Michael A. Grandner , Lana S. Elali , Fabian-Xosé Fernandez
{"title":"Concerning the circadian rhythms of prolactin, its secretion timing, and regulation of the affiliative mind","authors":"Reina A. Mendoza , Michael A. Grandner , Lana S. Elali , Fabian-Xosé Fernandez","doi":"10.1016/j.neubiorev.2025.106403","DOIUrl":"10.1016/j.neubiorev.2025.106403","url":null,"abstract":"<div><div>Prolactin, traditionally regarded as a lactation hormone, is now understood to be a multifunctional modulator of physiology and behavior, integrating reproductive, metabolic, immune, and affective processes. A defining feature of prolactin is its circadian rhythmicity: in humans, levels peak during the early hours of the night—between 2:00 and 4:00 a.m.—a time closely aligned with caregiving, physical intimacy, and co-sleeping. This review synthesizes the neuroendocrine mechanisms underlying prolactin’s secretion, highlighting the roles of dopaminergic inhibition, hypothalamic signaling, photoperiodic input, and circadian regulation via the suprachiasmatic nucleus, alongside interactions with sleep–wake cycles. Beyond its well-established physiological roles, prolactin appears to attenuate activity in the hypothalamic-pituitary-adrenal axis, promote neural plasticity, and enhance social bonding in mothers and fathers, as well as in non-parental cooperative caregivers. Integrating these data, we propose that prolactin’s nocturnal rise may scaffold a circadian-gated neurobehavioral state – what we term the affiliative mind – characterized by calm affect, empathic attunement, and approach-oriented prosocial motivation. This state is potentiated by oxytocin and endorphin release during close social interactions, forming an amplifying feedback loop. As part of our general hypothesis, we also suggest that prolactin may influence higher-order social cognition through effects on the brain’s default mode network, and that its rhythms may become partially synchronized among individuals who cohabitate. Evolutionarily, prolactin’s nocturnal action may have transformed nighttime vulnerabilities into opportunities for solidifying trust and group cohesion. Together, plausible extensions of available data position prolactin as a chronobiological scaffold for affiliative behavior within and across individuals and social groups.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106403"},"PeriodicalIF":7.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy, effectiveness, and safety/tolerability of lithium in children and adolescents up to 18 years of age with conditions other than mood disorders: A scoping review","authors":"Emilia Matera , Maria Giuseppina Petruzzelli , Lucia Margari , Gabriele Masi , Simone Pisano , Federica Annecchini , Valeria Carruolo , Roberta Melibeo , Fabio Tarantino , Miguel Garcia-Argibay , Samuele Cortese","doi":"10.1016/j.neubiorev.2025.106402","DOIUrl":"10.1016/j.neubiorev.2025.106402","url":null,"abstract":"<div><div>In youth, lithium is an effective medication for mood disorders, particularly for mixed and manic episodes of bipolar disorder, and is generally well-tolerated. In some clinical contexts, lithium is used off-label to manage other conditions. We conducted a scoping review of studies on the efficacy/effectiveness and safety/tolerability of lithium for treating youths with psychiatric conditions other than mood disorders or neurological disorders. We searched EMBASE, MEDLINE, PsycINFO, PubMed, and ClinicalTrials.gov up to March 31, 2025, with no restrictions on language or document type. We included studies of any design involving children and adolescents (mean age up to 18) treated with lithium, either as monotherapy or in combination with other psychotropic agents. We assessed study quality using the appropriate NHLBI tools and visually summarized the results with a heat map displaying sample size by study design and conditions, as well as the timeline of included studies’ publication years. From 2687 records initially identified, after de-duplication removal and screening, 367 full-text reports were assessed, and 41 studies were included in the review, grouped by type of psychiatric or neurological disorder, most of which had a small sample. Among the assessed studies, 60 % of were considered of “fair” quality and 40 % of “poor” quality. Overall, although the clinical use of lithium beyond bipolar disorder in youth is increasing, the underlying evidence base remains limited. More rigorous research based on RCTs and observational studies with designs aimed at reducing confounding are needed to guide clinical practice.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106402"},"PeriodicalIF":7.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rethinking ambiguity across species","authors":"Marlen Fröhlich , Gerhard Jäger , Asya Achimova","doi":"10.1016/j.neubiorev.2025.106401","DOIUrl":"10.1016/j.neubiorev.2025.106401","url":null,"abstract":"<div><div>Ambiguity—the capacity for a signal to support multiple interpretations—has long been regarded as a hallmark of human language, linked to sophisticated syntax and pragmatics. Yet recent evidence shows that ambiguity is also widespread in non-human communication systems, especially among primates, where signals are routinely disambiguated through social and interactional context. We maintain that ambiguity is not a communicative flaw but an evolved strategy that enhances efficiency and flexibility across species. Drawing on cross-species data and probabilistic modelling, we argue that ambiguity offers adaptive benefits: balancing signal cost, informativeness, and interpretive flexibility. We propose that pragmatic ambiguity resolution likely predates language and reflects shared cognitive capacities for social inference. Recognising ambiguity as a comparative phenomenon reframes debates on language evolution and highlights shared adaptive pressures shaping communication systems.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106401"},"PeriodicalIF":7.9,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Classification of neurological and mental health disorders based on multimodal approaches: A comprehensive review","authors":"Hivi I. Dino , Masoud M. Hassan","doi":"10.1016/j.neubiorev.2025.106399","DOIUrl":"10.1016/j.neubiorev.2025.106399","url":null,"abstract":"<div><div>Disorders of the nervous system and mental health are among the most prevalent, complex, and devastating health challenges globally, with a significant<!--> <!-->impact on quality of life. Recently, advances in deep learning-based multimodal methodologies have transformed the classification<!--> <!-->and detection of these disorders through the utilization of diverse data types including neuroimaging, bio-signals, and clinical evaluations. These multimodal techniques provide a more holistic understanding of complex conditions, addressing the limitations of traditional unimodal methods, which often fail to capture the multifaceted nature of these disorders. Despite the growing body of research, a comprehensive review focusing on the application of deep learning-based multimodal approaches to both neurological and mental health disorders remains lacking. This review fills this gap by offering an in-depth analysis of recent advancements in machine learning and deep learning-based multimodal classification for ten major disorders: five neurological and five mental health-related. It examined key modalities, explored fusion strategies, and provided insights into the strengths and weaknesses of existing multimodal approaches. Additionally, this review highlighted the challenges associated with multimodal data integration, such as data imbalance, model interpretability, and the need for large-scale, high-quality datasets. Furthermore, the review discussed emerging trends and future directions, emphasizing the potential of advanced fusion and computational techniques to enhance the clinical applicability of these models. By synthesizing the current state of research, this review aims to guide future studies and contribute to the development of more accurate, reliable, and accessible diagnostic tools for neurological and mental health disorders.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106399"},"PeriodicalIF":7.9,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}