Isis Gastaldo-Jordan, Claudia Villalba-Pita, José Martínez-Raga, Yolanda Sanz, Eva M Medina-Rodríguez
{"title":"ARE CONVENTIONAL ANTIDEPRESSANTS ENOUGH? THE GUT MICROBIOME AND NANOCARRIER-BASED DELIVERY SYSTEMS AS FUTURE PROSPECTS FOR DEPRESSION TREATMENT.","authors":"Isis Gastaldo-Jordan, Claudia Villalba-Pita, José Martínez-Raga, Yolanda Sanz, Eva M Medina-Rodríguez","doi":"10.1016/j.neubiorev.2025.106421","DOIUrl":"https://doi.org/10.1016/j.neubiorev.2025.106421","url":null,"abstract":"<p><p>Depression is the leading cause of disability worldwide and thus a major contributor to the economic burden of disease. In addition to genetic and epigenetic factors, sustained psychological stress linked to modern lifestyles (often characterized by high social expectations, elevated workload and increasing financial needs) may trigger psychiatric diseases such as depression. The effective treatment of this psychiatric condition represents one of the major challenges of our time, due to its skyrocketing increase in prevalence. While conventional antidepressants often provide low response rates and have frequent adverse effects, emerging research is revealing novel and more efficient therapeutic approaches. Notably, the bacteria that populates our intestinal tract, also known as the gut microbiota, is highly susceptible to stress and other factors associated with depression. Therefore, gut microbiota-targeting interventions based on lifestyle modifications or direct supplementation with biotherapeutic agents are being proposed as monotherapy or as adjuvants to conventional treatments. In addition, novel delivery systems, such as nanocarriers, for current antidepressants are being explored to improve drug bioavailability and therapeutic efficiency. This review summarizes the role of the gut microbiota in the pathogenesis of depression and its link with current antidepressant treatments. Furthermore, it explores how strategies like nanoparticle-based delivery systems are paving the way for the next generation of treatments.</p>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":" ","pages":"106421"},"PeriodicalIF":7.9,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304562","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}
Nicola Brunello , Lorenzo Diana , Jothini Sritharan , Marija Glisic , Tobias Nef , Rajeev K. Verma , Giuseppe A. Zito
{"title":"A systematic review and meta-analysis on the neural correlates of bodily self-consciousness","authors":"Nicola Brunello , Lorenzo Diana , Jothini Sritharan , Marija Glisic , Tobias Nef , Rajeev K. Verma , Giuseppe A. Zito","doi":"10.1016/j.neubiorev.2025.106420","DOIUrl":"10.1016/j.neubiorev.2025.106420","url":null,"abstract":"<div><div>The sense of one's own body, also referred to as bodily self-consciousness (BSC), is an important aspect of self-consciousness, that allows us to experience our body as our own. Previous research has identified the distinct components of BSC (i.e., body ownership, sense of agency, and self-location), and investigated their neural correlates separately. However, a consensus on the brain regions involved in BSC has not been found, and whether the experience of BSC goes beyond the sum of its components is still unknown. This study aims to identify the neural correlates of the components of manipulated BSC, as well as their shared patterns of activation. We conducted a meta-analysis employing multi-level kernel density analysis on 56 neuroimaging studies investigating manipulated BSC (primarily body ownership and sense of agency) in healthy individuals, to determine their neural correlates individually, as well as shared activations across them. Our analyses revealed activations in left premotor, bilateral posterior parietal, and left occipital cortices for altered body ownership, whereas altered sense of agency engaged the right temporoparietal junction, bilateral inferior parietal lobule, right frontal gyri, left postcentral gyrus, and left insula. The conjunction analysis revealed activations around the bilateral posterior parietal cortex, precentral gyrus, and temporo-occipito-parietal junction. These results support the presence of an interactive relationship between the components of manipulated BSC, tapping into the domain of self-recognition and detection of discrepancies across sensory inputs. Our findings point to a critical role of multisensory integration and self-attribution processes to the experience of manipulated BSC.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106420"},"PeriodicalIF":7.9,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304508","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}
Neville Magielse , Aikaterina Manoli , Simon B. Eickhoff , Peter T. Fox , Amin Saberi , Sofie L. Valk
{"title":"A bias-accounting meta-analytic approach refines and expands the cerebellar behavioral topography","authors":"Neville Magielse , Aikaterina Manoli , Simon B. Eickhoff , Peter T. Fox , Amin Saberi , Sofie L. Valk","doi":"10.1016/j.neubiorev.2025.106418","DOIUrl":"10.1016/j.neubiorev.2025.106418","url":null,"abstract":"<div><div>The cerebellum plays important roles in motor, cognitive, and emotional behaviors. Previous cerebellar coordinate-based meta-analyses (CBMAs) have complemented precision-mapping and parcellation approaches by finding generalizable cerebellar activations across the largest possible set of behaviors. However, cerebellar CBMAs face challenges due to inherent methodological limitations, exacerbated by historical cerebellar neglect in neuroimaging studies. Here, we show overrepresentation of superior activations, rendering the null hypothesis of standard activation likelihood estimation (ALE) unsuitable. Our new method, cerebellum-specific ALE (C-SALE), finds behavioral convergence beyond baseline activation rates. It does this by testing experimental activations versus null models sampled from a data-driven probability distribution of finding activations at any cerebellar location. Task-specific mappings in the BrainMap meta-analytic database illustrated improved specificity of the new method. Multiple (sub)domains reached convergence in specific cerebellar subregions, supporting dual motor representations and placing cognition in posterior-lateral regions. We show our method and findings are replicable using the NeuroSynth database. Across both databases, 54/138 task domains or behavioral terms, including sustained attention, somesthesis, inference, anticipation and rhythm, reached convergence in specific cerebellar subgregions. Our meta-analyic maps largely corresponded with cerebellar atlases but also showed many complementary mappings. Repeated subsampling analysis showed that motor behaviors, and to a lesser extent language and working memory, mapped to especially consistent cerebellar subregions. Lastly, we found that cerebellar clusters were parts of brain-wide coactivation networks with cortical and subcortical regions implied in these behaviors. Together, our method further complements and expands understanding of cerebellar involvement in human behavior, highlighting regions for future investigation in both basic and clinical applications.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106418"},"PeriodicalIF":7.9,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294410","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":"The cognitive neuroscience of memory representations","authors":"Michael D. Rugg , Louis Renoult","doi":"10.1016/j.neubiorev.2025.106417","DOIUrl":"10.1016/j.neubiorev.2025.106417","url":null,"abstract":"<div><div>The present paper considers the cognitive neuroscience of memory from a representational perspective with the aim of shedding light on current empirical and theoretical issues. We focus on episodic memory, differentiating active versus latent, and cognitive versus neural memory representations. We adopt a causal perspective, according to which a memory representation must have a causal connection to a past event to count as a memory. We note that retrieved episodic information may nonetheless only partially determine the content of an active memory representation, which can comprise a combination of the retrieved information with semantic, schematic and situational information. We further note that, especially in the case of memories for temporally remote events, re-encoding operations likely lead to a causal chain that extends from the original experience of the event to its currently accessible memory trace. We discuss how the reinstatement framework provides a mechanistic basis for the causal linkage between an experience, the memory trace encoding it, and the episodic memory of the experience, highlighting the crucial role of hippocampal engrams in encoding patterns of neocortical activity that, when active, constitute the neural representation of an episodic memory. Finally, we discuss some of the ways in which a memory can become modified and hence distanced from the episode that precipitated it.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106417"},"PeriodicalIF":7.9,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287838","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}
Amel Bouloufa , Sarah Delcourte , Thomas Delannay , Renaud Rovera , Thorsten Lau , Lionel Mouledous , Ouria Dkhissi-Benyahya , Bruno P. Guiard , Nasser Haddjeri
{"title":"LSD: Mechanisms and relevance to the treatment of depression","authors":"Amel Bouloufa , Sarah Delcourte , Thomas Delannay , Renaud Rovera , Thorsten Lau , Lionel Mouledous , Ouria Dkhissi-Benyahya , Bruno P. Guiard , Nasser Haddjeri","doi":"10.1016/j.neubiorev.2025.106407","DOIUrl":"10.1016/j.neubiorev.2025.106407","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is one of the most prevalent psychiatric conditions worldwide, affecting over 350 million people. Standard treatments, primarily antidepressants targeting serotonin, noradrenaline, and/or dopamine, are based on the monoamine hypothesis, which links depression to imbalances in these neurotransmitters. A sizable fraction of patients, however, does not get enough relief, which highlights the limits of current drug treatments. Treatment-resistant depression (TRD), a mainly intractable subtype of MDD, affects around 30 % of MDD sufferers, therefore it is imperative that better effective therapies be found. Recent research has focused on psychedelic medicines including lysergic acid diethylamide (LSD), which affects serotonergic as well as glutamatergic systems. These drugs have demonstrated potential to induce rapid and long-term antidepressant responses, possibly by the facilitation of neuroplasticity and adjustment of long-term neural communication, even after the drug is cleared from the body. Ongoing clinical trials are testing the efficacy and safety of LSD in TRD and simultaneously resolving problems of placebo design and risk minimization. This narrative review examines the neurobiological mechanisms of LSD, assesses its potential as an antidepressant and anxiolytic agent, and discusses the safety issues associated with its utilization. Although still experimental, psychedelic therapies could demonstrate a significant shift in psychiatric treatment, offering new hope for patients who have not responded to conventional antidepressants. Sustained research is essential to validate these results and guide their integration into clinical practice.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106407"},"PeriodicalIF":7.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276635","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}
Yuet Ruh Dan , Anastasia Christakou , Karin Roelofs
{"title":"Systematic review: Effects of cholinergic signaling on cognition in human pharmacological studies","authors":"Yuet Ruh Dan , Anastasia Christakou , Karin Roelofs","doi":"10.1016/j.neubiorev.2025.106408","DOIUrl":"10.1016/j.neubiorev.2025.106408","url":null,"abstract":"<div><div>Acetylcholine (ACh) is one of the main neurotransmitters in central nervous systems across species. It has been extensively studied in animal models, and is known for its profound role in attention processes and adaptive responses to changing environments. Recent theories propose that this occurs by modulating the relative influence of top-down and bottom-up inputs during perceptual inference and regulating cue-validity updating in uncertain environments. However, the role of ACh in human cognition has mostly been investigated in memory and is less well established in other domains. Here we provide a systematic review of human studies investigating effects of ACh on cognitive functions using pharmacological modulators, with a focus on the cognitive processes needed for acute behavioural adaptation to situational changes. Results revealed that ACh is involved in sustained attention, perceptual detection, the updating of cue-response relationships and the speed of information processing, with differential cognitive effects associated with muscarinic and nicotinic modulators. This supports a role of ACh in prioritizing top-down and bottom-up information in humans, potentially enabling rapid updating of behavioural responses to situational changes. However, efforts to parse out the molecular roles of ACh signaling with pharmacological methodologies may be limited by their relative nonspecificity and an inability to mimic signaling dynamics. Integration of pharmacological findings with neuroimaging data such as functional magnetic resonance spectroscopy may be helpful to identify the effects of cholinergic modulators on whole-brain pharmacodynamics.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106408"},"PeriodicalIF":7.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276650","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":"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}