{"title":"Understanding the flexibility of working memory: Compositionality, generative processing, anchors and holistic representations","authors":"Brad Wyble , Joyce Tam , Ian Deal , Howard Bowman","doi":"10.1016/j.neubiorev.2025.106387","DOIUrl":"10.1016/j.neubiorev.2025.106387","url":null,"abstract":"<div><div>The typical conception of working memory is a mechanism to temporarily hold multiple discrete objects in service of other cognitive tasks in an item-based representation. In this paper, we expand the conventional idea that working memory represents objects into a more flexible framework that uses compositional and generative mechanisms to code and then re-code visual input according to task demands. Compositionality allows complex scenes or objects to be mentally decomposed into constituents that can be individually manipulated or recombined to form new representations. Generative processing allows purely conceptual information to be reconstructed in a format akin to visual sensory representations that can be manipulated and re-processed by perceptual mechanisms. Together, compositional and generative mechanisms would enable a wide range of cognitive functions including the basis of visual imagery. In our view, working memory items do not need to correspond to discrete objects, but could serve as pointers or anchors to clusters of features that form parts of objects, or alternatively, multiple objects could be encoded as one holistic item depending on the task. We conclude with a conceptual account of such a memory system that can build and re-use information by moving it between different levels of abstraction within a perceptual hierarchy. This model is linked to experimental results from the memory and visual imagery literatures that illustrate the flexibility of such a system for performing cognitive tasks.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106387"},"PeriodicalIF":7.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226412","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}
Alex Martino Cinnera, Danny Adrian Spampinato, Valentina Pezzopane, Annibale Antonioni, Giulia Fregna, Andrea Baroni, Andrea Casarotto, Francesco Di Lorenzo, Sonia Bonnì, Sofia Straudi, Giacomo Koch
{"title":"Promoting spike-timing-dependent plasticity via paired associative stimulation: From healthy subjects to clinical applications.","authors":"Alex Martino Cinnera, Danny Adrian Spampinato, Valentina Pezzopane, Annibale Antonioni, Giulia Fregna, Andrea Baroni, Andrea Casarotto, Francesco Di Lorenzo, Sonia Bonnì, Sofia Straudi, Giacomo Koch","doi":"10.1016/j.neubiorev.2025.106314","DOIUrl":"10.1016/j.neubiorev.2025.106314","url":null,"abstract":"<p><p>Paired Associative Stimulation (PAS) protocols have been widely employed to study functional neural connections along the cortico-spinal pathways and between interconnected brain regions. PAS protocols induce spike-timing-dependent plasticity, underscoring their potential as therapeutic neurostimulation tools. Cortico-peripheral PAS is based on the temporal pairing of peripheral nerve stimulation (PNS) and cortical transcranial magnetic stimulation (TMS) pulses, applied repeatedly at specific inter-stimulus intervals, to modulate the activity of the corticospinal tract. In contrast, cortico-cortical PAS involves the application of TMS pulses at two different brain areas to induce long-term changes in functional connectivity. In this review, we provide a comprehensive overview of existing PAS protocols and the factors influencing their effects, with particular emphasis on the critical role of the inter-stimulus interval. We trace the development of PAS from initial experiments in healthy subjects to its emerging therapeutic applications in various pathological conditions. We summarize current preliminary findings, discuss limitations, outline future directions, and review ongoing clinical trials. Although still in its early stages, PAS, particularly cortico-peripheral PAS, shows promising efficacy in motor recovery for stroke and spinal cord injury patients. Furthermore, initial evidence points to potential benefits in Alzheimer's disease and generalized anxiety disorders, supporting the expanding therapeutic scope of PAS protocols.</p>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":" ","pages":"106314"},"PeriodicalIF":7.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777027","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}
Meghedi Vartanian, Azra Jahanitabesh, Julia F Christensen, Henry Staub, Daria E A Jensen, Arno Villringer, A Veronica Witte
{"title":"Neural responses to visual food cues according to weight and hunger state: A systematic review and meta-analysis.","authors":"Meghedi Vartanian, Azra Jahanitabesh, Julia F Christensen, Henry Staub, Daria E A Jensen, Arno Villringer, A Veronica Witte","doi":"10.1016/j.neubiorev.2025.106301","DOIUrl":"10.1016/j.neubiorev.2025.106301","url":null,"abstract":"<p><strong>Background: </strong>Food cue reactivity shapes eating behavior and likely relates to weight and hunger states. Functional Magnetic Resonance Imaging (fMRI) studies, however, have yielded mixed results on the underlying neural correlates. We, therefore, conducted a systematic review and meta-analysis to investigate the effect of weight and hunger on neural responses to food cues.</p><p><strong>Methods: </strong>We searched PubMed and Web of Science (2000-2022) for fMRI studies using visual food cues that reported participants' weight and hunger states (PROSPERO: CRD42022365310). The Joanna Briggs Institute critical appraisal tools and fMRI reporting standards were used to assess the risk of bias. The coordinate-based meta-analysis was conducted using GingerALE.</p><p><strong>Results: </strong>Of the 2451 screened articles, 50 were included in the systematic review (n = 1402), and 45 in the meta-analysis (n = 1162). Results are based on both whole-brain and region-of-interest (ROI) analyses. Overall, food cues consistently activated reward, frontal, and visual brain areas, in both obesity and healthy-weight groups, though selective differences in activation strength were found. A higher-order contrast meta-analysis indicated higher activations in a parahippocampal region in obesity versus healthy weight, supported by one study. Stratified analyses indicated that during fasting, individuals with obesity showed reward area activation (16 studies, n = 396), while healthy-weight individuals exhibited frontal activation (23 studies, n = 429), however, higher-order contrast analyses between groups showed no significant differences.</p><p><strong>Discussion: </strong>Neural responses to food cues were consistently found in reward, frontal and visual brain areas. Some evidence indicated variation by weight and hunger states. Additional studies are needed to further clarify these neural differences.</p>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":" ","pages":"106301"},"PeriodicalIF":7.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746134","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}
Mayerli Andrea Prado-Rivera , Verena Deddens , Annemarijn M.J. Fortuin , Kimberley E. Wever , Jocelien D.A. Olivier
{"title":"Effects of early-life stress on social functioning in depression: A systematic review and meta-analysis of mouse and rat studies","authors":"Mayerli Andrea Prado-Rivera , Verena Deddens , Annemarijn M.J. Fortuin , Kimberley E. Wever , Jocelien D.A. Olivier","doi":"10.1016/j.neubiorev.2025.106388","DOIUrl":"10.1016/j.neubiorev.2025.106388","url":null,"abstract":"<div><div>Depression is one of the most prevalent mental disorders worldwide, in which social impairments negatively impact daily functioning of those affected. Early stressful experiences have lasting effects on brain development and behavior, which further amplifies vulnerability to this disorder. While the link between early-life stress (ELS) and higher risk of depression is well-established, it remains unclear whether stress timing exposure—i.e., pregestational stress, prenatal ELS or postnatal ELS— affects social functioning severity in depressed individuals. Rodent models are of translational value to study whether stress timing modulates the ELS impact on depression-related social behaviors. Therefore, our aim was to determine whether there is an overall effect of pregestational stress, prenatal ELS and postnatal ELS exposure on a spectrum of depression-related social behaviors in mice and rats; and, whether species, sex, age at testing, and cumulative stress duration modulate such effects. After a comprehensive database search in PubMed and EMBASE, 295 publications were included. Social affiliation and attachment were reduced as a consequence of stress exposure, regardless of the timing. Social communication was not negatively affected by exposure to prenatal or postnatal ELS, while social cognition was impaired in animals exposed to postnatal ELS. Only sex mediated the effect of prenatal ELS on social affiliation and attachment, in which males but not females exhibited reduced social affiliation and attachment following prenatal exposure. These findings underscore the nuanced role of timing in the impact of ELS on depression-related social behaviors, emphasizing the need for further research considering the sex- and social-domain specific effects.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"179 ","pages":"Article 106388"},"PeriodicalIF":7.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214485","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":"Neurosteroid modulators in psychiatric disorders: Emerging evidence and therapeutic implications","authors":"Kristina M. Deligiannidis","doi":"10.1016/j.neubiorev.2025.106390","DOIUrl":"10.1016/j.neubiorev.2025.106390","url":null,"abstract":"","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"178 ","pages":"Article 106390"},"PeriodicalIF":7.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214524","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}
Alberto Bernal-Robledano , Alberto M. Parra-Perez , M.del Carmen Moleon , Jose A. Lopez-Escámez , Patricia Perez-Carpena
{"title":"Personality traits associated with tinnitus: A systematic review and contributing genetic variants","authors":"Alberto Bernal-Robledano , Alberto M. Parra-Perez , M.del Carmen Moleon , Jose A. Lopez-Escámez , Patricia Perez-Carpena","doi":"10.1016/j.neubiorev.2025.106389","DOIUrl":"10.1016/j.neubiorev.2025.106389","url":null,"abstract":"<div><div>Chronic tinnitus is multifaceted condition associated with auditory (hearing loss, hyperacusis), neurological (headache) and psychological disorders (anxiety, depression). Personality traits may determine how tinnitus is perceived, and common genetic variation contributes to shape personality. The goal of this systematic review is to analyze evidence supporting a link between personality traits and tinnitus. Published articles about tinnitus and personality related to the Big Five Traits were included. Based on 7 studies, this systematic review identified the neuroticism trait as the main potential connection between personality and tinnitus suffering. The consistency of this relationship is evident across different Big Five personality tools, with similar outcomes observed regardless of the instrument used, reinforcing the consistency of this association. In order to establish a genetics association, a GWAS based search revealed common genetic variants in the <em>GRM5</em>, <em>XKR6</em>, <em>GRM8</em>, <em>TCF4</em>, and <em>SLC39A8</em> genes, with <em>SLC39A8</em> identified as a shared missense variant rs13107325 (C/T, p.Ala391Thr) between neuroticism and tinnitus. The role of these genes in important neural functions points to possible shared mechanisms underlying both conditions.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"178 ","pages":"Article 106389"},"PeriodicalIF":7.9,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208444","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}
Robert James Blair, Ute Habel, Mikhail Votinov, Lisa Wagels, Thomas F Denson
{"title":"A Cognitive Neuroscience Approach to Understanding Aggression and its Treatment.","authors":"Robert James Blair, Ute Habel, Mikhail Votinov, Lisa Wagels, Thomas F Denson","doi":"10.1016/j.neubiorev.2025.106386","DOIUrl":"https://doi.org/10.1016/j.neubiorev.2025.106386","url":null,"abstract":"<p><p>While anyone can behave aggressively, some people are more prone to aggression than others. We present a neuro-cognitive model and consider several inter-individual differences that confer risk for aggression. Forms of atypical cognitive function include a hyperreactive acute threat response, poor emotion regulation, and mechanisms involved in choosing when to aggress. We show dysfunction in the neural systems mediating these functions may account for aggression in people high in psychopathy/callous unemotional traits, irritability/anger, hostility, impulsivity, and low in frustration tolerance. We then review promising interventions including psychological therapies and pharmaceuticals that might influence the neuro-cognitive underpinnings of these constructs. Although there is no overwhelming \"one size fits all\" approach to treating aggression, identifying the neural mechanisms implicated in these traits may improve individualized treatments.</p>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":" ","pages":"106386"},"PeriodicalIF":7.9,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187532","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}
Nada Dalloul , Connor van Huijgevoort , John Belmont , Deanna M. Barch
{"title":"Negative symptoms and resting-state functional connectivity across psychotic and mood disorders: A systematic literature review","authors":"Nada Dalloul , Connor van Huijgevoort , John Belmont , Deanna M. Barch","doi":"10.1016/j.neubiorev.2025.106385","DOIUrl":"10.1016/j.neubiorev.2025.106385","url":null,"abstract":"<div><div>Negative symptoms are strongly linked to disability and distress across psychotic and mood disorders. Current treatments are ineffective due to a limited understanding of their neurological bases. Dysconnectivity is thought to contribute to these symptoms, which makes studying resting state functional connectivity promising for developing effective interventions. This review identified 40 studies that investigated the relationships between node-based resting-state functional connectivity (specifically network and graph theory analyses) and negative symptoms across psychotic disorders (i.e., schizophrenia/schizoaffective disorder) and mood disorders with psychotic features (i.e., bipolar and major depressive disorders). There were indications that negative symptoms are related to the connectivity of several resting-state networks in schizophrenia and schizoaffective disorder, including the lateral frontoparietal, midcingulo-insular, medial frontoparietal, pericentral/somatomotor, occipital, and dorsal frontoparietal networks. There were suggestions that negative symptoms are associated with decreased functional segregation and clustering of neural connections. Nevertheless, it is important to interpret these findings with restraint, given the limitations and contradictions in the existing literature. Lastly, no studies were found that investigated negative symptoms and functional connectivity in individuals with major depressive disorder with psychotic features, and very minimal research has been done on individuals with bipolar disorder with psychotic features. Future studies should employ methods that account for negative symptoms’ heterogeneity (e.g., ecological momentary assessment), increase validity and reliability of resting state functional connectivity methods (e.g., naturalistic stimuli and individual-specific methods), and promote cohesion in the literature (e.g., consistent network taxonomy). Moreover, future research should explore the transdiagnostic nature of these relationships to inform effective clinical interventions.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"178 ","pages":"Article 106385"},"PeriodicalIF":7.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182359","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}
Valerio Ricci , Stefania Chiappini , Giovanni Martinotti , Giuseppe Maina
{"title":"Novel psychoactive substances and psychosis: A comprehensive systematic review of epidemiology, clinical features, neurobiology, and treatment","authors":"Valerio Ricci , Stefania Chiappini , Giovanni Martinotti , Giuseppe Maina","doi":"10.1016/j.neubiorev.2025.106384","DOIUrl":"10.1016/j.neubiorev.2025.106384","url":null,"abstract":"<div><h3>Background</h3><div>Novel psychoactive substances (NPS) have shown increasing prevalence worldwide, yet their relationship with psychotic disorders remains incompletely characterized despite growing clinical concern.</div></div><div><h3>Objective</h3><div>To systematically evaluate the epidemiological evidence, clinical characteristics, neurobiological mechanisms, vulnerability factors, and management approaches for NPS-associated psychosis.</div></div><div><h3>Methods</h3><div>A comprehensive systematic review following PRISMA guidelines was conducted across five major databases from January 2005 through December 2022. Quality assessment was performed using the Newcastle-Ottawa Scale and Joanna Briggs Institute checklist. Of 684 initially identified records, 85 studies met inclusion criteria, comprising case reports/series (n = 38), retrospective cohort studies (n = 25), cross-sectional studies (n = 10), case-control studies (n = 7), experimental studies (n = 3), and prospective cohort studies (n = 2).</div></div><div><h3>Results</h3><div>Epidemiological evidence consistently suggested higher psychosis risk with NPS compared to traditional substances (OR 4.4–5.2 for synthetic cannabinoids versus cannabis). Distinctive clinical profiles emerged: synthetic cannabinoid-induced \"spiceophrenia\" featured visual hallucinations (73–84 %), agitation (79–91 %), and anxiety (62–76 %); cathinone-induced psychosis presented with extreme agitation (81–94 %) and stereotyped behaviors (47–63 %); phenethylamine-induced states showed perceptual disturbances including synesthesia (37–54 %). Neurobiological investigations indicated different mechanisms across substance classes. Key vulnerability factors included pre-existing psychiatric conditions, adolescent exposure, and polysubstance use.</div></div><div><h3>Conclusion</h3><div>NPS use is associated with elevated psychosis risk and distinctive clinical presentations across substance classes. Standardized assessment approaches and rigorous longitudinal investigations are needed to better establish causality, refine substance-specific treatment protocols, and develop targeted prevention strategies.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"178 ","pages":"Article 106384"},"PeriodicalIF":7.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182377","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":"Brain biomarkers for CRPS","authors":"Martin Lotze , Sebastian Strauss","doi":"10.1016/j.neubiorev.2025.106383","DOIUrl":"10.1016/j.neubiorev.2025.106383","url":null,"abstract":"<div><h3>Summary</h3><div>For complex regional pain syndrome (CRPS), a number of brain biomarkers have been identified which show overlaps but also unique characteristics to other chronic pain syndromes. We here provide a review about possible brain biomarkers for CRPS and differentiate their role for A) diagnosis of CRPS, B) monitoring of time course of CRPS (e.g., during interventions) or C) outcome prediction and treatment stratification. In addition, the transition from the sub-chronic to the chronic phase is extremely important to investigate the development of a chronic pain syndrome. The use of these biomarkers might help to stratify patients individually for most effective interventions. Our approach involved screening of existing imaging literature on CRPS patients to identify alterations in the gray matter volume (GMV) of the brain, structural (diffusion tensor imaging) and functional connectivity (rsFMRI), and task-specific brain activity (response to sensory/painful stimuli, motor tasks, imagery). Furthermore, we will provide an overview of cortical excitability and neurotransmitter balance alterations in CRPS.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"178 ","pages":"Article 106383"},"PeriodicalIF":7.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179973","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}