Marco Cavicchioli , Alberto Caruso , Andrea Scalabrini , Alessandro Torelli , Sara Bottiroli , Anna Pichiecchio , Elena Prodi , Martina Cangelosi , Carlo Lai , Paolo Vitali , Luca Maria Sconfienza , Piercarlo Sarzi-Puttini , Federica Galli
{"title":"An ALE meta-analysis of pain processing alterations in fibromyalgia: Toward an evidence-based process model","authors":"Marco Cavicchioli , Alberto Caruso , Andrea Scalabrini , Alessandro Torelli , Sara Bottiroli , Anna Pichiecchio , Elena Prodi , Martina Cangelosi , Carlo Lai , Paolo Vitali , Luca Maria Sconfienza , Piercarlo Sarzi-Puttini , Federica Galli","doi":"10.1016/j.neubiorev.2025.106303","DOIUrl":"10.1016/j.neubiorev.2025.106303","url":null,"abstract":"<div><div>It has been hypothesized that core pain-related symptoms of fibromyalgia (FM) might be associated with alterations of pain processing mechanisms. On the one hand, several fMRI studies were conducted to evaluate possible alterations of neural responsiveness toward the presentation of different kinds of noxious stimuli among patients with FM. On the other hand, a quantitative summary of these findings is still lacking. Accordingly, it was conducted an ALE meta-analysis (FWE, p < .05) of studies comparing brain responsiveness to the administration of painful stimuli between patients with FM and healthy controls (HCs). Twenty-one studies were included for meta-analytic procedures. Results showed 3 main findings: i) key areas of the pain matrix (i.e., dorsal anterior cingulate cortex [dACC], basal ganglia and thalamic nuclei) were commonly involved in pain processing in both FM patients and HCs; ii) pain processing in FM patients were characterized by a recruitment of the right insula; whereas, HCs mainly recruited prefrontal areas; iii) patients with FM, compared to HCs, showed an increased magnitude of dACC and supplementary motor area responsiveness toward the presentation of painful stimuli. These findings suggest that altered pain processing in FM is characterized by: i) an increased salience of painful stimuli, which are processed at a viscero-somatic non-mentalized level; ii) high intensity and low granularity of painful experiences accompanied by a negative valence, and modulated through maladaptive avoidance strategies; iii) the development of hypervigilance toward any potential harmful stimuli</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"176 ","pages":"Article 106303"},"PeriodicalIF":7.9,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735578","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}
Zoey Yutong Li , Jeremy Rui Chang , Cong Wang , Minxia Jin , Ian Hoyin Cheng , Suk-yu Yau , Waiming Cheung , Hector Winghong Tsang
{"title":"The effects of non-pharmacological interventions on vagally-mediated heart rate variability (vmHRV) in individuals with depression: A systematic review and meta-analysis","authors":"Zoey Yutong Li , Jeremy Rui Chang , Cong Wang , Minxia Jin , Ian Hoyin Cheng , Suk-yu Yau , Waiming Cheung , Hector Winghong Tsang","doi":"10.1016/j.neubiorev.2025.106300","DOIUrl":"10.1016/j.neubiorev.2025.106300","url":null,"abstract":"<div><h3>Objectives</h3><div>This study seeks to explore the impact of non-pharmacological interventions (NPIs) on vagally-mediated heart rate variability (vmHRV) in subjects experiencing depression. Additionally, it aims to delineate the relationship between vmHRV alterations and the severity of depressive symptoms.</div></div><div><h3>Methods</h3><div>Search was systematically performed on RCTs studies across various databases. These included Embase, the Cochrane Central Register of Controlled Trials, Medline via EBSCO, PsycINFO accessed through ProQuest, and the Web of Science, capturing all entries until March 11, 2024.</div></div><div><h3>Results</h3><div>The analysis revealed that NPIs generally exerted small to moderate beneficial effects on cardiac parasympathetic nervous system (PNS) markers such as the root mean square of successive differences (RMSSD) ([SMD] = 0.266, 95 % confidence interval [CI] 0.029–0.503) and high-frequency power (HF) (SMD = 0.178, 95 % CI 0.018–0.337). Specifically, mind-body exercises demonstrated moderate to large enhancements in RMSSD (SMD = 0.689, 95 % CI 0.265–1.112) and a moderate improvement in HF (SMD = 0.498, 95 % CI 0.134–0.863) immediately following the interventions. Conversely, psychological interventions did not show significant immediate post-intervention vmHRV enhancements; however, subsequent assessments revealed a moderate increase in HF (SMD = 0.477, 95 % CI 0.177–0.786) during short-term follow-ups. Moreover, substantial correlations were observed between vmHRV improvements and reductions in depression severity.</div></div><div><h3>Conclusions</h3><div>Our findings indicated that NPIs effectively enhance vmHRV and reduce depressive symptoms. This underscores the effectiveness of both mind-body exercises and psychological interventions. Furthermore, alterations in vmHRV may serve as viable predictors for the success of depression treatments.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"176 ","pages":"Article 106300"},"PeriodicalIF":7.9,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735579","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}
Qian Dong , Xinyu Cheng , Yoshihiro Noda , Georg S. Kranz , Xiaoyun Guo , Ti-Fei Yuan , Di Zhao
{"title":"Therapeutic potential of non-invasive brain stimulation in alleviating suicidal ideation and depressive symptoms in major depressive disorder: A systematic review and meta-analysis","authors":"Qian Dong , Xinyu Cheng , Yoshihiro Noda , Georg S. Kranz , Xiaoyun Guo , Ti-Fei Yuan , Di Zhao","doi":"10.1016/j.neubiorev.2025.106299","DOIUrl":"10.1016/j.neubiorev.2025.106299","url":null,"abstract":"<div><h3>Importance</h3><div>Suicidal ideation, intricately associated with depressive symptoms, poses a significant public health challenge. Previous clinical studies of non-invasive brain stimulation (NIBS) as a therapeutic modality have demonstrated encouraging efficacy, underscoring its potential to address both suicidal and depressive manifestations.</div></div><div><h3>Objective</h3><div>The present study aims to integrate the anti-suicidal and antidepressant effects of NIBS in depressive patients and examined the complex interplay and underlying correlations between these effects.</div></div><div><h3>Methods</h3><div>Adopting the PICOS framework and adhering to PRISMA guidelines, we conducted a comprehensive systematic review and meta-analysis, prospectively registered with PROSPERO (CRD42024506889). Our search, spanning six databases from inception to June 2025, targeted terms related to suicidal ideation, depression, and NIBS, with a focus on randomized controlled trials. Following independent screening by two assessors, we assessed the methodological rigor of the included studies using the Jadad score and the Cochrane Collaboration Risk of Bias Tool version 2 (RoB2).</div></div><div><h3>Findings</h3><div>The meta-analysis included 21 clinical trials from 19 articles (with two articles each reporting two trials), totaling 1329 participants. Results revealed a small effect size for the anti-suicide effect (SMD = −0.28, 95 % CI [−0.43, −0.14], <em>I</em><sup><em>2</em></sup> = 38.8 %, p < 0.001) and a medium effect size for the antidepressant effect (SMD = −0.46, 95 % CI [−0.64, −0.28], <em>I</em><sup><em>2</em></sup> = 22.9 %, p < 0.001). Subgroup analysis and meta-regression highlighted cultural background (Western or Non-western) as the most significant contributor to the heterogeneity of suicidal outcomes (<em>R</em><sup><em>2</em></sup> = 100 %). Furthermore, a positive linear correlation was observed between the two therapeutic effects (R = 0.74, p < 0.001), suggesting a synergistic interplay.</div></div><div><h3>Interpretation</h3><div>Our findings emphasized the dual therapeutic potential of NIBS in mitigating suicidality and depression, offering outcome-driven evidence for clinical practice and mathematical correlation into the underlying neurobiological mechanisms. Notably, the heterogeneity analysis revealed the profound influence of sociodemographic factors, particularly cultural context, on psychological states, indicating the need for culturally tailored interventions.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"176 ","pages":"Article 106299"},"PeriodicalIF":7.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714316","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":"Commentary: Neuroactive steroids and the dopaminergic system","authors":"Roberto Cosimo Melcangi","doi":"10.1016/j.neubiorev.2025.106298","DOIUrl":"10.1016/j.neubiorev.2025.106298","url":null,"abstract":"","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"176 ","pages":"Article 106298"},"PeriodicalIF":7.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696548","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}
Lorenza Colzato , Hongchi Zhang , Veit Roessner , Christian Beste , Bernhard Hommel
{"title":"Non-bivalent psychopathology: Rethinking mental disorders through metacontrol","authors":"Lorenza Colzato , Hongchi Zhang , Veit Roessner , Christian Beste , Bernhard Hommel","doi":"10.1016/j.neubiorev.2025.106297","DOIUrl":"10.1016/j.neubiorev.2025.106297","url":null,"abstract":"<div><div>Traditional approaches to psychopathology are based on a bivalent or binary view (healthy vs. ill), oftentimes obscuring an understanding of the heterogeneity of symptoms, fluctuations, comorbidities, and of relationships/boundaries between psychopathologies. The recent Research Domain Criteria (RDoC) approach recognizes these problems without providing mechanistic solutions. We propose a novel non-binary approach based on neurocognitive principles derived from the well-established, mechanistically transparent Metacontrol State Model of psychopathology (<em>MSMp)</em>. We suggest (1) abandoning phenomenologically-derived classifications of psychopathologies altogether; (2) explaining functional and dysfunctional behavior by means of the same theory; and (3) reconstructing behavioral observations from basic mechanisms. In line with the ambitions of RDoC, our mechanistic account allows addressing, analyzing, and treating malfunctioning at its very core—the responsible mechanism, rather than focusing on observable symptoms that may not indicate a common problem. Our theory-guided, evidence-based approach has the potential to foster a novel mechanistic understanding of psychopathology, improve diagnostic criteria weighting, and make interventions more effective.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"176 ","pages":"Article 106297"},"PeriodicalIF":7.9,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700450","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}
Zekun Wu , Jiteng Shao , Russell Gill , Woo Jae Kim
{"title":"Mating duration of male Drosophila melanogaster – A novel genetic model to study interval timing function of human brain","authors":"Zekun Wu , Jiteng Shao , Russell Gill , Woo Jae Kim","doi":"10.1016/j.neubiorev.2025.106294","DOIUrl":"10.1016/j.neubiorev.2025.106294","url":null,"abstract":"<div><div>Time perception is essential for survival, enabling animals to estimate and control intervals between events, which underlies complex behaviors. While the brain efficiently processes temporal information across various timescales, the neural and genetic mechanisms governing this ability remain poorly understood. Although research has identified brain regions involved in timing information, genetic exploration of temporal perception lags behind, particularly outside circadian rhythms. Advances in neuroscience now allow genetic manipulation of neurotransmitters and neuropeptides to study neural circuits, but a comprehensive understanding of the molecular basis of timing remains elusive. This gap persists due to the lack of a model system that integrates behavioral, neural, and genetic data. In this context, we propose male mating duration as a novel interval timing model, as it provides a unique framework to study the interplay between genetic factors and temporal processing. Establishing such a system requires multidisciplinary efforts across computational neuroscience, molecular genetics, and behavioral genetics to uncover unifying principles of timing processes.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"176 ","pages":"Article 106294"},"PeriodicalIF":7.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692572","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}
Marek Kotas , Bartłomiej Stańczykiewicz , Bartłomiej Sporniak , Edyta Pawlak , Błażej Misiak
{"title":"A systematic review of miRNA expression in schizophrenia spectrum disorders across the blood and the brain","authors":"Marek Kotas , Bartłomiej Stańczykiewicz , Bartłomiej Sporniak , Edyta Pawlak , Błażej Misiak","doi":"10.1016/j.neubiorev.2025.106292","DOIUrl":"10.1016/j.neubiorev.2025.106292","url":null,"abstract":"<div><div>Several studies have investigated whether individuals with schizophrenia spectrum disorders (SSD) show altered microRNA expression. However, findings in this field have not been synthesized so far. Therefore, we performed a systematic review of studies measuring microRNA levels in the peripheral blood and brain samples of individuals with SSD and healthy controls. We searched electronic databases for studies comparing the expression of microRNAs between individuals with SSD and healthy controls. We synthesized findings with respect to concordance of alterations across the brain and peripheral blood, observations in early psychosis, medication effects, treatment resistance, molecular pathways and the utility of microRNAs as potential biomarkers. Altogether, 77 studies measuring the expression of 124 dysregulated microRNAs were included. Among them, 35 microRNAs were upregulated and 11 were downregulated in brain samples while 69 microRNAs were up-regulated and 37 were downregulated in blood samples of individuals with SSD. The most consistent finding was the overexpression of miR-181b-5p and miR-34a-5p in 8 out of 10 studies with concordant results across both types of biological materials. Both microRNAs are involved in apoptosis, neurodevelopment, and cell survival. The area under the curve (AUC) values were 0.84 ± 0.08 with the highest AUC observed for miR-199–3p (0.979). The overexpression of miR-181b-5p and miR-34a-5p is the most consistent dysregulation of microRNA expression in SSD, suggesting the significance of apoptotic, neurodevelopmental, and cell survival processes. The analysis of microRNA expression might be promising for the development of potential biomarkers for SSD.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"176 ","pages":"Article 106292"},"PeriodicalIF":7.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663139","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}
Sandhiya Vijayabaskaran, Xiangshuai Zeng, Behnam Ghazinouri, Laurenz Wiskott, Sen Cheng
{"title":"A taxonomy of spatial navigation in mammals: Insights from computational modeling","authors":"Sandhiya Vijayabaskaran, Xiangshuai Zeng, Behnam Ghazinouri, Laurenz Wiskott, Sen Cheng","doi":"10.1016/j.neubiorev.2025.106282","DOIUrl":"10.1016/j.neubiorev.2025.106282","url":null,"abstract":"<div><div>Spatial navigation is a vital cognitive process in nearly all animals, relying on complex neuronal mechanisms to extract, process, and act upon spatial representations. To advance the understanding of spatial navigation and its neural mechanisms, Parra-Barrero et al. (2023) have proposed a taxonomy of spatial navigation processes based on extensive behavioral and neural studies. These processes are hierarchically organized in two levels with navigation strategies at the top and behaviors at the bottom. Building upon this taxonomy, here, we review computational modeling studies on spatial navigation in mammals to provide an overview of the current state of the art and further analyze the navigation processes within the proposed taxonomy. We specifically focus on the representations required by navigation processes, how these representations are extracted, and the computations necessary to execute each strategy and behavior. We propose that the key to understanding what representations and computations are being used by agents lies in testing their ability to generalize to novel situations. We identify three types of generalization relevant for navigation and analyze to what extent current computational models are capable of achieving these types of generalization. Our review shows that while significant progress has been made in modeling navigation, substantial work remains to model and fully understand spatial navigation in mammals.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"176 ","pages":"Article 106282"},"PeriodicalIF":7.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683660","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 Pepe , Alessandro von Gal , Greta Fabiani , Laura Piccardi
{"title":"Common brain areas in spatial navigation and visuo-spatial planning: A meta-analysis","authors":"Sofia Pepe , Alessandro von Gal , Greta Fabiani , Laura Piccardi","doi":"10.1016/j.neubiorev.2025.106295","DOIUrl":"10.1016/j.neubiorev.2025.106295","url":null,"abstract":"<div><div>Planning is a fundamental function of both spatial navigation and visuo-spatial tasks, supported by overlapping and distinct neural substrates that remain partially unclear. We conducted an Activation Likelihood Estimation (ALE) meta-analysis on fMRI studies examining active, goal-directed navigation and visuo-spatial planning tasks (i.e., the Tower of London paradigm). Conjunction and contrast analyses revealed a shared network encompassing bilateral frontal regions, including the superior frontal gyrus (SFG), middle frontal gyrus (MFG), anterior insula (INS), and clusters in the left supplementary motor area (SMA) and triangular part of the inferior frontal gyrus (IFGtriang). Contrast analyses highlighted greater involvement of the hippocampus (HIP) and parahippocampal gyrus (PHG) in navigation, and posterior parietal and dorsolateral prefrontal regions in visuo-spatial planning. These findings clarify the neural mechanisms underlying these processes, emphasizing shared amodal regions contributing to both visuo-spatial planning and spatial navigation. This work provides insights on the underlying deficits associated with neurodevelopmental disorders and brain injuries.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"176 ","pages":"Article 106295"},"PeriodicalIF":7.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683661","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}
Pallavi Sharma , Brittany D. Elliott , Randy J. Nelson
{"title":"Effects of air and light pollution on brain and behavioral function: Potential synergy","authors":"Pallavi Sharma , Brittany D. Elliott , Randy J. Nelson","doi":"10.1016/j.neubiorev.2025.106293","DOIUrl":"10.1016/j.neubiorev.2025.106293","url":null,"abstract":"<div><div>The growing global prevalence of artificial light at night (ALAN) and air pollution has raised concerns regarding their effects on human health. Several epidemiological, preclinical, and clinical studies suggest that both ALAN and air pollution can independently contribute to adverse brain health outcomes, including cognitive decline, increased risk of neurodegenerative diseases, and behavioral disorders. Air pollutants can enter the bloodstream and reach the brain, leading to potential neuropathology. Exposure to ALAN disrupts circadian rhythms, suppresses melatonin production, and alters sleep patterns, causing detrimental health consequences. Recent research highlights a complex interaction between these two pollutants and emphasizes the need for future studies exploring their synergistic effects. The current review provides an overview of how air and light pollution influence brain health and lead to different physiological and behavioral issues. We explored the potential mechanisms that may underlie their combined effects, such as oxidative stress, inflammation, disruption of circadian rhythms, blood-brain barrier disruption, and genetic alterations. This review also calls for future research in order to investigate the biological pathways at play and identifies critical research gaps. Understanding the interaction between ALAN and air pollution is crucial for developing effective health care strategies to mitigate their harmful effects on the brain and central nervous system.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"176 ","pages":"Article 106293"},"PeriodicalIF":7.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661120","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}