Neuroscience & Biobehavioral Reviews

Background: Chronic pain is a multidimensional condition that often persists despite conventional treatment and adversely affects multiple domains of daily life. Music listening has emerged as a promising non-pharmacological intervention, with accumulating evidence supporting its beneficial effects on pain and associated psychological outcomes. However, despite growing evidence of efficacy, the translation of music listening into routine clinical practice remains limited, partly because intervention reporting has received comparatively little attention. Objective: To evaluate the effectiveness of music listening interventions for chronic pain and systematically assess the methodological quality and completeness of intervention reporting to identify barriers to reproducibility and clinical implementation. Methods: Systematic searches were conducted in PubMed, Cochrane Library, CINAHL, and Web of Science through June 2025, with no date restrictions on publication. Randomized controlled trials involving adults with chronic pain receiving music listening interventions were included. Two independent reviewers screened studies, extracted data, and assessed risk of bias. Intervention reporting was evaluated using the TIDieR checklist, and a random-effects meta-analysis was performed for pain intensity outcomes. Results: Ten RCTs involving 538 participants were included. Music listening interventions varied substantially in delivery, duration, and music selection procedures, reflecting considerable heterogeneity in intervention design. Most studies reported significant improvements in pain and psychological outcomes. Meta-analysis of eight trials (10 effect estimates), demonstrated a moderate reduction in pain intensity (SMD = -0.53, 95% CI: -0.96 to -0.11, p = 0.014; I2 = 76.2%). Although intervention rationale and procedures were generally well described, reporting of intervention modifications, treatment fidelity, and adherence was frequently incomplete. These reporting deficiencies may compromise reproducibility and limit translation into clinical practice. Conclusions: Music listening appears to be a safe, accessible, and scalable non-pharmacological intervention for chronic pain management, with benefits extending beyond pain reduction to psychological wellbeing, quality of life, and functioning. However, incomplete reporting of key intervention components may limit reproducibility and hinder clinical implementation. Future trials should adopt standardized and transparent reporting standards to facilitate implementation into clinical practice.

Background: The ability to remember object locations in real life is a fundamental cognitive process that supports goal-directed behavior and is particularly vulnerable to aging and neurodegenerative disease. Despite a growing body of functional magnetic resonance imaging (fMRI) research on object-location memory (OLM), the neural substrates of establishing and retrieving location information are largely unknown. Objective: This systematic review and coordinate-based meta-analysis aimed to identify brain regions consistently activated during OLM in healthy adults, primarily for encoding and - on an exploratory basis - for retrieval, and to characterize age-related differences in OLM-related neural activity. Methods: A systematic search was conducted across three databases (PubMed, PsycInfo, Cochrane Library) up to February 2026. Studies employing task-based fMRI during the encoding and retrieval of object-location associations in healthy adults were eligible. Age-related differences in OLM-related brain activity were examined via narrative synthesis. An activation likelihood estimation (ALE) meta-analysis was performed on studies reporting stereotactic peak coordinates. The review was pre-registered on PROSPERO (CRD420251023695). Results: Twenty-one studies comprising 637 participants were included in the systematic review, with 12 studies being eligible for the encoding ALE meta-analysis. The retrieval ALE meta-analysis was not possible due to the limited number of included studies and reported foci. The systematic review indicated that OLM encoding consistently recruited bilateral fusiform gyri and parahippocampal cortices, with additional engagement of parietal and prefrontal regions across individual studies, whereas OLM retrieval recruited mainly the hippocampus and precuneus. The coordinate-based ALE meta-analysis revealed two significant clusters of activation during OLM encoding: a left-lateralized cluster encompassing the fusiform gyrus, parahippocampal gyrus, and inferior temporal gyrus (peak MNI: -28, -38, -16), and a right-hemisphere cluster spanning the parahippocampal gyrus and fusiform gyrus (peak MNI: 30, -46, -16). Age-related differences, based on a small number of studies with direct age comparison, pointed toward reduced activity in posterior cortical regions coupled with increased activity in prefrontal and midline regions. Additionally, younger adults showed greater hippocampal activation for successful than unsuccessful spatial retrieval, whereas older adults showed the opposite pattern. Conclusion: The systematic review and meta-analysis identify the fusiform gyri and parahippocampal cortices as the most reliably activated regions during OLM encoding, locating OLM formation primarily within the ventral visual-to-medial-temporal processing stream. Retrieval additionally engaged the hippocampus and precuneus, consistent with their established roles in episodic memory. Age-related differences included reduced posterior cortical encoding activity in older adults, a reversal of the hippocampal activation pattern during retrieval, and weaker suppression of midline regions during task performance. The identified encoding pathway may inform targeted network-level interventions such as non-invasive brain stimulation to counteract cognitive decline in aging and neurodegenerative disease.

Abstract Background Negative symptoms are persistent determinants of disability in schizophrenia and often respond incompletely to antipsychotic treatment. Objective To compare the efficacy of pharmacological and non-pharmacological add-on treatments for prominent or persistent negative symptoms using network meta-analysis. Methods This systematic review followed PRISMA 2020 and PRISMA-NMA and was registered in PROSPERO (CRD420261422218). PubMed, Europe PMC, Semantic Scholar and Crossref were searched from inception to 29 July 2026, supplemented by citation chasing. Eligible studies were randomized controlled trials in adults with DSM/ICD schizophrenia or schizoaffective disorder, prominent or persistent negative symptoms, stable antipsychotic treatment and an adjunctive intervention. Outcomes were Positive and Negative Syndrome Scale negative subscale or Scale for the Assessment of Negative Symptoms scores. Random-effects frequentist networks estimated standardized mean differences (SMDs) with 95% confidence intervals (CIs); negative values favoured add-on treatment. Risk of bias was assessed with Cochrane RoB 2. Results Forty-nine unique RCTs met the clinical and design criteria, of which 28 (2,067 randomized; 1,933 analysable participants) contributed to the locked quantitative dataset. The primary connected network included 24 trials, 25 treatments and 31 comparison estimates. Fourteen add-ons had CIs excluding the null versus a broad control node. The highest P-scores were observed for mirtazapine (SMD -2.38, 95% CI -3.55 to -1.21), granisetron (-1.96, -2.74 to -1.17), tropisetron (-1.82, -2.59 to -1.05), minocycline (-1.78, -2.55 to -1.01) and memantine (-1.54, -2.28 to -0.80). Heterogeneity was low ({tau} = 0.119; {tau}2= 0.014), but the predominantly star-shaped network had zero inconsistency degrees of freedom. Overall RoB 2 judgements were low for eight trials, some concerns for 15 and high for five. Conclusions Several pharmacological and non-pharmacological add-ons showed potentially important efficacy signals. Because most nodes were informed by single small trials, direct active comparisons were scarce, inconsistency could not be evaluated and risk-of-bias concerns were common, the treatment hierarchy should be considered hypothesis-generating rather than a basis for firm clinical recommendations. Registration: PROSPERO CRD420261422218 Keywords: schizophrenia; negative symptoms; adjunctive treatment; network meta-analysis; randomized controlled trial; neurostimulation Key Points This review compares pharmacological and non-pharmacological adjuncts in adults selected for prominent or persistent negative symptoms while receiving stable antipsychotic medication. Mirtazapine, granisetron, tropisetron, minocycline and memantine had the highest P-scores, while tDCS, rTMS and body-oriented psychotherapy also showed efficacy signals versus broad control. The evidence network was sparse and star-shaped, most interventions were supported by one small trial, and inconsistency was not estimable; rankings therefore require cautious interpretation.

Background: Altered gamma-aminobutyric acid (GABA) neurotransmission is a proposed mechanism underlying autism spectrum disorder (ASD), prompting evaluation of several GABA-modulating pharmacotherapies. However, it remains unclear whether these interventions improve ASD broadly or preferentially affect specific symptom domains. Methods: We conducted a systematic review and random-effects meta-analysis of randomized controlled trials evaluating GABA-modulating pharmacotherapies in individuals with ASD. PubMed/MEDLINE, Embase, Scopus, and CENTRAL were searched from inception to April 1, 2026. Outcomes were prespecified as global autism severity, social communication, functional communication, restricted and repetitive behaviours (RRBs), adaptive behaviour, and irritability. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and certainty of evidence was evaluated using GRADE. Results: Thirteen randomized controlled trials evaluating three GABA-modulating interventions (bumetanide, arbaclofen, and valproate) were included. GABA-modulating therapies were associated with statistically significant improvements in global autism severity (Hedges' g = -0.25, 95% CI -0.46 to -0.03; p = 0.028) and adaptive behaviour (Hedges' g = -0.09, 95% CI -0.15 to -0.02; p = 0.023). No significant pooled effects were observed for social communication (Hedges' g = -0.26, p = 0.077), functional communication (Hedges' g = -0.01, p = 0.869), RRBs (Hedges' g = -0.21, p = 0.126), or irritability (Hedges' g = -0.07, p = 0.543). After Holm-Bonferroni step down procedure, neither global autism severity nor adaptive behaviour remained statistically significant (Holm-adjusted p = .140 and .138, respectively). Adverse events were predominantly gastrointestinal, neurological, metabolic, and appetite-related. Overall risk of bias was variable, and the certainty of evidence ranged from very low to moderate. Conclusions: GABA-modulating pharmacotherapies did not demonstrate a robust, multiplicity-corrected benefit in any of the six prespecified ASD symptom domains. Nominal, unadjusted improvements in global autism severity and adaptive behaviour did not withstand correction for multiple comparisons and should be regarded as hypothesis-generating rather than confirmatory. Larger, adequately powered randomized trials using standardized domain-specific outcome measures are needed to determine whether individual GABA-modulating agents provide clinically meaningful benefit.

Objectives To evaluate the positive and adverse effects of parent-mediated interventions (PMIs) versus care as usual for children with autism. Setting Systematic review and meta-analysis and Trial Sequential Analyses (TSA), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methods We searched for randomised clinical trials of PMIs for children with autism in the databases CENTRAL, EMBASE, LILACS, PsycINFO, MEDLINE, and SCI-EXPANDED (up to 13 August, 2025), complemented with manual searches. 12,359 articles were screened. Data were synthesised using meta-analyses and Trial Sequential Analyses (TSA), and risks of bias and certainty of the evidence were evaluated. Primary and secondary outcome measures The primary outcome was autism characteristics. Secondary outcomes were adverse effects, child adaptive functioning, child language, child and parent quality of life, and parental stress. Ten exploratory outcomes were included. Results 32 trials (N=1,625) comparing PMIs to usual care, waiting list, or no intervention were included. All trials had a high risk of bias. The multiplicity-adjusted threshold for statistical significance was p = 0.013 due to the number of outcomes. Meta-analyses and TSAs showed it could be rejected that PMIs reduced autism characteristics (MD = -0.88; 95% confidence interval -2.92 to 1.15; p = 0.05, 4 trials, N=353, low certainty), child adaptive functioning (7 trials, N=408), child language (4 trials, N=308), or parental stress (7 trials, N=385). Due to insufficient data, the remaining secondary meta-analyses could not be conducted. Meta-analyses of exploratory outcomes showed beneficial effects concerning child behaviour problems and parent sensitivity/synchronicity. Conclusions This meta-analysis found no benefits of PMIs on child autism characteristics, child adaptive functioning, child language, or parental stress. Benefits were found in reduction of child behaviour problems and improved parent sensitivity/synchronicity. The evidence remains uncertain, and more trials including outcomes of adverse effects and quality of life are needed.

Background: Placebo responding involves the reduction of symptoms in response to contextual features of an intervention (e.g., verbal suggestions), yet it is characterized by pronounced heterogeneity. Although verbal suggestions are widely recognised as a hallmark method for inducing placebo responses, an open question is whether variability in placebo responding can be partly attributed to individual differences in trait responsiveness to verbal suggestions (REVS). We conducted a pre-registered meta-analysis (PROSPERO registration number CRD420250654692) to quantitatively synthesize available research on the association between trait REVS and placebo responding. Methods: PsycInfo, PubMed, MEDLINE, and Embase were searched up to June 2026 for original clinical or experimental studies involving both the assessment of REVS and symptom measures (self-report, behavioural, and/or physiological) in response to an inactive intervention (placebo). Results: Of 1,512 search results, 24 articles presenting 66 correlations between REVS and placebo responding were analysed (N = 1,137). A multi-level meta-analysis revealed a significant, albeit weak, positive correlation between REVS and placebo responses, r = 0.18 [95% CI: 0.13, 0.24], such that individuals with higher REVS reported greater symptom relief in response to the placebo. Meta-regression analyses did not identify any significant moderators of the correlation between REVS and placebo responding and sensitivity analyses based on Bayesian subgroup estimates indicated that the aggregate correlation was stable across methodological quality indicators and study features. Conclusion: These findings suggest that individual differences in REVS may partly explain variability in symptom reduction in response to placebos, with implications for the sources of variance in placebo effects in experimental and applied contexts.

Background: Serotonin has been implicated in cognitive flexibility and pathological perseverative thinking (PT), including rumination, worry, and obsessions. However, evidence remains fragmented across pharmacological manipulations, clinical populations, and outcome measures. This multilevel meta-analysis examined whether serotonergic interventions influence PT and cognitive flexibility. Methods: Preregistered and following PRISMA guidelines, we synthesized studies investigating three classes of serotonergic manipulations: acute tryptophan depletion (ATD), serotonin elevation via selective serotonin reuptake inhibitors (SSRIs), and classic serotonergic psychedelics. Three multilevel random-effects meta-analyses with cluster-robust variance estimation were conducted: (A) effects of ATD on cognitive flexibility (N = 266; 10 effect sizes), (B) effects of serotonin elevation on cognitive flexibility (N = 654; 15 effect sizes), and (C) effects of serotonin elevation on pathological perseverative thinking (N = 1,100; 20 effect sizes). Across analyses, the total sample comprised 2,030 participants and 45 effect sizes. Results: ATD did not significantly impair cognitive flexibility (g = 0.15, 95% CI [-0.07, 0.38], p = .23), and no moderation by task type, sex, or age was observed. Serotonin elevation similarly did not improve cognitive flexibility (g = -0.07, 95% CI [-0.36, 0.22], p = .63), with no significant performance differences emerging between SSRIs, classical psychedelics, or tryptophan enrichment. In contrast, serotonin elevation was associated with a significant medium-to-large reduction in perseverative thinking (g = -0.58, 95% CI [-0.76, -0.41], p < .001). Notably, while both pharmacological classes effectively reduced cognitive rigidity, SSRIs demonstrated a marginally smaller magnitude of symptom reduction compared to acute psilocybin interventions (p = .081). Furthermore, samples with a higher proportion of female participants showed larger reductions in perseverative thinking ({beta} = -1.86, p = .014), while worries exhibited marginally smaller reductions relative to obsessions ({beta} = 0.42, p = .055). Publication bias tests were non-significant across analyses. Conclusions: Serotonergic interventions robustly reduce perseverative thinking but do not consistently alter performance on laboratory measures of cognitive flexibility. These findings suggest that serotonin may influence cognitive-emotional rigidity and the subjective experience of repetitive thought more strongly than objective executive task performance. The dissociation between task-based and phenomenological outcomes aligns with contemporary models of serotonergic plasticity and highlights perseverative thinking as a potentially transdiagnostic therapeutic target of serotonergic interventions.

Background: Psychotic illnesses are among the most debilitating classes of psychiatric disorders, requiring targeted and effective treatment strategies. Although antipsychotics are the primary pharmacological therapy for psychosis, their full range of effects remain unclear, including effects within the frontal cortex, a brain region linked structurally and functionally to psychotic disorders. Methods: To examine the effects of antipsychotic treatment on the frontal cortex, we conducted a meta-analysis of publicly available rodent (rat, mice) transcriptional profiling datasets (microarray, RNA-Seq). Five datasets (GSE45229, GSE93918, GSE2547, GSE4031.1, GSE66275) were identified within the Gemma database using pre-specified search terms and inclusion/exclusion criteria (date: 7/7/2024), yielding differential expression results for eight drug vs. control comparisons (collective n=68). A random-effects meta-analysis model was fit to the log2 fold changes for each gene, and p-values adjusted for false discovery rate (FDR), with follow-up analyses exploring robustness, heterogeneity, and publication bias. To increase the power and generalizability of our findings, an exploratory meta-analysis was also run incorporating antipsychotic effects from both rodents and nonhuman primates (collective n=101), and compared to findings from individuals with schizophrenia. Results: Our meta-analysis yielded stable estimates for 12,190 genes, identifying 63 genes that were differentially expressed following antipsychotic treatment ("DEGs", FDR<0.05). Differential expression included genes important for serotonergic and cholinergic signalling, and was enriched within pathways linked to oligodendrocyte development and myelination, physiological and cellular stress responses, and cardiovascular function. An exploratory meta-analysis combining rodent and nonhuman primate results confirmed these observations and yielded additional findings (117 DEGs total). Comparisons with human post-mortem findings suggested that some schizophrenia-related gene expression may instead reflect antipsychotic treatment. Conclusion: Further validation is necessary, but our findings suggest that antipsychotics may assist in the regulation of specific structural and functional changes within the frontal cortex linked to psychotic disorders.

Background Vitamin D may influence bone healing and recovery after spine surgery, but its clinical effects remain uncertain. Objective To evaluate clinical, functional, and bone-related outcomes associated with vitamin D status and supplementation in patients undergoing spine surgery. Methods This systematic review and meta-analysis was registered in PROSPERO (CRD420261467482) and reported according to PRISMA 2020. PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Library were searched from inception through 1 June 2026. Random-effects meta-analyses used mean differences (MDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes. Direct supplementation analyses were prioritized, while analyses combining supplementation, baseline vitamin D status, or co-interventions were considered exploratory. Risk of bias was assessed using design-specific Joanna Briggs Institute tools. Results Thirteen studies were included. Four supplementation studies involving 177 participants showed no significant reduction in postoperative pain (MD -0.82, 95% CI -2.50 to 0.86; I2 = 84.3%). Three studies involving 277 participants showed lower Oswestry Disability Index scores in an exploratory analysis (MD -6.40, 95% CI -10.41 to -2.39; I2 = 96.8%). Three supplementation studies involving 128 participants showed no significant improvement in fusion rate (RR 1.17, 95% CI 0.78 to 1.74; I2 = 31.5%). An exploratory four-study fusion analysis was also not statistically significant (RR 1.24, 95% CI 0.98 to 1.57; I2 = 45.5%). Conclusion Current evidence does not establish that vitamin D supplementation independently improves postoperative pain or fusion rates after spine surgery. Possible benefits for disability and other bone-related outcomes remain uncertain because of small study numbers, heterogeneity, co-interventions, and residual confounding. Larger randomized trials stratified by baseline vitamin D status are needed.

A long-standing debate surrounding the neural bases of social concepts concerns the role of anterior temporal lobe (ATL). One perspective suggests ATL subregions are dedicated specifically to social knowledge; another suggests the ATLs constitute a domain-general hub for conceptual knowledge, but with graded functional specialisation depending on connectivity to modality specific spokes. The positions have been difficult to adjudicate due to many confounding factors in tests of social and non-social knowledge. We address these challenges via three innovations in assessment of knowledge in frontotemporal dementia (FTD). First, we introduce a new task that controls for several potential confounds. Second, we apply mixed linear models to behavioural data analysis, allowing further control over confounding factors. Third, we extend the mixed-model approach to lesion-symptom mapping, identifying cortical regions where structural pathology yields a disproportionate impairment on social versus non-social knowledge when other factors are controlled. We used these techniques to probe social and non-social knowledge in FTD subtypes: semantic dementia (SD), associated with asymmetric-bilateral ATL atrophy (n=21), and behavioural-variant (bvFTD), characterised by frontoinsular atrophy (n=24). When confounding factors were controlled, people with SD showed an equal impairment for social and non-social concepts, whereas those with bvFTD were disproportionately impaired on social concepts. The differential impairment of social concepts was associated with atrophy in the insula, orbitofrontal and ventromedial prefrontal cortex and other regions implicated in social knowledge generally. The results suggest that the bilateral ATLs constitute a domain-general semantic hub, whereas ventral prefrontal and insula cortex contribute preferentially to knowledge about people.

Neurobiological mechanisms underlying child maltreatment perpetration remain poorly understood, and the role of immune dysregulation has rarely been examined. Here, we tested whether peripheral inflammatory signatures are linked to brain structural alterations in mothers who have perpetrated maltreatment, and whether such alterations mediate this link to perpetration. In this cross-sectional study integrating structural MRI and inflammatory proteomics, 16 mothers with histories of maltreatment perpetration and 145 age-matched control mothers underwent brain imaging; a subgroup (n = 52; 11 maltreatment, 41 control) also completed plasma proteomic profiling using the Olink Target 96 Inflammation panel. Whole-brain voxel-based morphometry revealed significantly reduced gray matter volume (GMV) in the right middle/inferior temporal gyri, a region implicated in social cognition and contextual interpretation, in the maltreatment group. Proteomic analysis identified 16 inflammation-related proteins differentially expressed between groups; among these, nine were significantly associated with GMV in this temporal region. Lower GMV was associated with higher levels of pro-inflammatory proteins (CCL20, IL-17C) and with lower levels of immune-regulatory and metabolic proteins (CXCL1, CXCL6, SIRT2, STAMBP, MCP-2, MCP-4, 4E-BP1). Mediation analyses revealed that both protein sets were indirectly associated with perpetration through this regional GMV, with opposing patterns of direct association. These findings suggest that peripheral immune imbalance, characterized by elevated inflammatory signaling and diminished immune-regulatory capacity, is linked to structural vulnerability in a temporal cortical region involved in social cognition, specifically in perpetrating mothers. This neuroimmune pathway may contribute to maladaptive interpretation of child signals during caregiving and represents a potential target for biomarker-informed preventive intervention.

Alzheimer's disease (AD) is clinically marked by difficulty retaining newly learned information, yet routine memory scores often conflate poor initial encoding with failure to stabilise information after encoding. This ambiguity limits the mechanistic interpretability of cognitive assessment during the transition from mild cognitive impairment to AD. Here we propose a Hippocampal Cortical Consolidation Bottleneck (HCCB) model to computationally separate these two components of new memory failure. The model represents newly presented information as a rapidly formed hippocampal trace and a slowly stabilised cortical trace, predicting a residual bottleneck when delayed recall falls below the level expected from immediate recall. We operationalised this prediction as Consolidation Bottleneck Index*(CBI*), a cognitively normal reference normalised residual index, and evaluated it using Alzheimer's Disease Neuroimaging Initiative (ADNI) cognitive and MRI data, with independent dynamical support from OpenNeuro EEG. Simulations showed recent memory vulnerability when hippocampal vulnerability exceeded cortical vulnerability. In ADNI, CBI* increased from cognitively normal participants to mild cognitive impairment nonconverters, reached Alzheimer like levels in mild cognitive impairment converters, and was associated with hippocampal atrophy. CBI* added minimal discrimination beyond established clinical and structural predictors, supporting its role as a mechanistic phenotype rather than a replacement prognostic model. OpenNeuro EEG further showed increased neurodynamic rigidity in AD. Our findings provide a computational framework for quantifying failed stabilisation of newly encoded information in AD progression.

Individuals with schizophrenia show well-documented impairment in metaphor comprehension, often exhibiting a bias toward concrete, literal interpretations. While this tendency has traditionally been linked to psychopathological and cognitive factors, the contribution of perceptual processes remains underexplored. Here, we tested the hypothesis that figurative language impairment reflects altered perceptual processing, whereby the visual representations evoked by metaphors remain abnormally active and hinder abstraction. A sample of 143 individuals with schizophrenia and healthy controls was administered a novel paradigm where metaphors (e.g., Wisdom is a flashlight) served as primes for target words related to the metaphor vehicle based on visual (e.g., microphone), action (e.g., remote), or semantic features (e.g., lamp). While in healthy participants metaphors activated semantically associated words, individuals with schizophrenia showed sustained visual priming, emerging 1000 ms after metaphor presentation and persisting up to 1400 ms, with both groups showing reverse priming for action targets. Critically, greater visual priming predicted lower metaphor comprehension in patients, whereas greater semantic priming was correlated with better metaphor skills in controls. These results suggest that visual-perceptual representations are not only overactivated in patients compared to controls during metaphor processing but may also interfere with figurative comprehension. We argue that concretism arises from an imbalance between bottom-up sensory signals and top-down contextual priors, leading to the persistence of the visual representations and impaired abstraction. More broadly, these results support multimodal and predictive accounts of metaphor processing and point to altered perceptual dynamics as a previously unappreciated mechanism contributing to pragmatic impairment in schizophrenia.

Background Brain abnormalities related to childhood adversity (CA) have been reported across clinical presentations in psychotic disorder (PD) and bipolar disorder (BD). This systematic review and meta-analysis examined gray matter volume (GMV) alterations linked to CA in PD and BD. Methods A PRISMA-compliant systematic review was conducted (PROSPERO ID: CRD42022351133). The EMBASE, MEDLINE, and PsycINFO databases were searched from inception to June 2024 for studies investigating CA and structural brain imaging in PD and BD. Study quality was assessed with the Newcastle Ottawa Scale (NOS). Data were extracted and synthesized accounting for sex differences and CA subtypes with brain findings categorized by the presence and direction of associations. Meta-analyses were performed for hippocampal and amygdala volumes. Results In the systematic review (k = 29), 3,056 participants with PD and BD (mean age = 36.6; SD =16.1; 47% female), published between 2011 and 2023, were included. Study quality was fair, with high heterogeneity. Most studies reported significant negative associations between CA and GMV, especially in prefrontal regions, while findings for the hippocampus and amygdala were largely null or inconsistent. Meta-analyses of a study subset identified no significant association between CA and hemisphere-specific and combined volumes of the hippocampus (k = 5; p [&ge;] 8805; 0.66) or amygdala (k = 4; p [&ge;] 8805; 0.87). Conclusion CA was not consistently associated with hippocampal or amygdala volume alterations in PD and BD. More consistent evidence emerged for reduced GMV in prefrontal regions, suggesting that neurobiological impact of CA may be more robustly captured at the cortical level.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) improves levodopa-induced motor complications and cardinal motor symptoms of Parkinson's disease (PD), but stimulation frequency may differentially shape outcomes. This is evident for axial and gait symptoms, which may respond differently to lower-frequency stimulation. Whether frequency-dependent effects extend to cognition remains unclear. Objective: To investigate the cognitive effects of DBS at distinct frequencies in PD. Methods: We conducted a systematic review and meta-analysis (PROSPERO - CRD42024618253). PubMed, Web of Science, and EMBASE were searched for studies assessing cognitive outcomes under different stimulation frequencies. Eight cognitive domains were defined: verbal fluency, cognitive flexibility, executive control, working memory, attention, processing speed, episodic memory, and time processing. Multilevel random-effects meta-analyses were performed, with effect sizes expressed as Hedges' g. Results: Forty-three studies met the inclusion criteria, the majority (n = 31) involving STN-DBS. Twenty-one STN-DBS studies, including 355 patients, were included in the meta-analysis. Compared with HFS ([&ge;] 130 Hz), lower frequencies (4-80 Hz) were associated with better verbal fluency (g = 0.27) and cognitive flexibility (g = 0.38), with consistent effects across sensitivity and leave-one-out analyses. Accuracy-based executive control measures also favored lower-frequency stimulation. OFF-stimulation comparisons showed a concordant pattern. Evidence for other targets (PPN and NBM) was limited. Conclusions: Lower-frequency STN-DBS was associated with modest benefits in specific cognitive domains compared with HFS. These findings highlight the need for future research to determine how frequency interacts with stimulation location and symptom-specific networks to shape cognitive and cognitive-motor outcomes in PD.

Background Although mental illness is primarily regarded as a disorder of the brain, body system dysfunction is increasingly recognized as a salient biomarker in psychiatry, often emerging before the onset of overt symptoms. Here, we systematically review studies on peripheral organ systems (cardiovascular, metabolic, immune, liver, kidneys, lungs and muskeloskeletal) in schizophrenia, major depressive disorder (MDD), bipolar disorder (BD) and generalized anxiety disorder (GAD), aiming to synthesize findings on the function of multiple body systems in the early stages of mental illness. Methods EMBASE, MEDLINE and PsycINFO were searched from inception until 19 November 2024, identifying case-control studies comparing physiological markers of peripheral organ systems (i.e., cardiovascular, metabolic, immune, liver, kidney, lung and muskeloskeletal) in adults with one of the four mental illnesses at first-episode and drug naive, with healthy controls. We followed the PRISMA 2020 guidelines (PROSPERO: CRD42023408594). Results Of 2,637 citations retrieved, 138 studies met inclusion criteria for review with 52 markers of immune (n=32), metabolic (n=11), cardiovascular (n=6), liver (n=2) and musculoskeletal (n=1) function identified. 105 studies were eligible for meta-analysis, including 80, 26, 4 and 0 studies on schizophrenia, MDD, BD and GAD respectively. Meta-analysis revealed increased HDL-cholesterol, waist-hip-circumference ratio, triglycerides, insulin, insulin resistance, 2-hr glucose, neutrophil, monocyte, white blood cell, IL-4 and systolic blood pressure, and reduced albumin in schizophrenia; increased TNF- and IL-10 in MDD; and increased IL-6 and IFN-{gamma} in both schizophrenia and MDD. Other results were narratively discussed. Conclusions Alterations in peripheral organ function across multiple systems characterizes the onset of psychiatric disorders. However, research on peripheral organ function in psychiatry is limited and primarily focusses on the immune and metabolic systems.

Reconciling the anatomical observation that the human brain comprises two asymmetrical halves with the phenomenal unity of the mind is a puzzle that has challenged neuroscientists since the dawn of research in the field. White-matter commissural fibres of the corpus callosum constitute a critical anatomical substrate for the functional resolution of this anatomical duality. However, the extent of the functional involvement of the callosum in different domains of cognition represents, to this day, a mostly uncharted territory. Here we present a probabilistic characterization of callosal involvement in a set of cognitive functions. In particular, we estimated structural callosal connections by means of the Disconnectome approach applied to a reference sample of healthy participants while using the macro-anatomical cortical areas contained in the Harvard-Oxford template as seeds. By multiplying structural connectivity by the involvement of each cortical area in a set of cognitive functions (as derived from Neurosynth meta-analyses), we produced a voxel-wise characterization of the corpus callosum in different functional domains. We were able to highlight greater involvement of posterior callosal regions in vision and episodic memory, greater involvement of more anterior callosal regions in decision making and working memory, with somatosensory and motor functions more related to the central dorsal portion of the callosum.

Objective: This systematic review and meta-analysis examined 1) the effects of stress management interventions on changes in stress eating for women, and 2) the longevity of these effects, by summarizing and assessing evidence from controlled and non-equivalent pretest-posttest intervention studies. Method: Five databases (PsycINFO, PubMed, Medline, Web of Science, CINAHL), existing sources, and grey literature were searched (February - June 2025). Studies that assessed stress eating or emotional eating, included a stress management intervention, and comprised at least 70% women were included. The primary outcome was reduction in stress eating. Data were pooled in meta-analyses using multi-level random-effects models and subset by follow-up period. Risk of bias was assessed via funnel plots and sensitivity analyses. Results: Sixty studies with 119 effect size estimates were included in the primary analysis. Pooled estimates indicated that stress management interventions significantly reduced stress eating (Hedges g = -0.4174, p < 0.001), with pre-post designs having larger effects than controlled trials. Subgroup analyses of follow-up periods found small effects in the short-term (before 3 months; Hedges g = -0.4202, p < 0.0001) and moderate effects for mid-term (3-6 months; Hedges g = -0.5886, p < 0.0001). Effects beyond 6 months were small and nonsignificant (Hedges g = -0.4370, p = 0.0660). Conclusion and Relevance: Stress management interventions appear to be effective for reducing stress eating for women, suggesting the potential to incorporate stress management in interventions targeting obesity. Effects may be only sustained 6 months post-intervention, suggesting the need for strategies to bolster long-term effectiveness.

Background: Neuropathic pain (NP) remains a therapeutic challenge, with conventional repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) yielding a response rate of approximately 40%. Personalised targeting based on dysfunctional neurocircuitry offers a promising strategy to enhance efficacy, yet its application in NP is unexplored. This open-label trial investigated a novel targeting approach guided by the recently described cingulo-opercular and somato-cognitive action (CON-SCAN) network, a circuit integrating cognitive and affective dimensions of pain. Methods: Twenty patients with NP received 10 sessions of M1-rTMS over two weeks, with the stimulation site individually localised based on maximal functional connectivity to a CON template. Results: Increased CON-SCAN connectivity from baseline to post-treatment was associated with reduction in pain interference, anxiety and depression scores. The response rate was 50% post-treatment, which was maintained at the 1-month follow-up. Improvements were also observed in neuropathic pain symptoms, negative affect, and overall health. Conclusions: As the first connectivity-guided rTMS trial for NP, this study provides preliminary evidence that personalised targeting of the CON-SCAN network is feasible and associated with the analgesic effects of M1-rTMS, supporting further investigation in randomised controlled trials. Trial registration: Chinese Clinical Trial Registry, ChiCTR2500104679. Registered 20 June 2025, http://www.chictr.org.cn. Chinese Clinical Trial Registry, ChiCTR2400094568. Registered 24 December 2024, http://www.chictr.org.cn. Keywords: Personalised TMS; Pain; M1; CON; SCAN

Empirical conclusions can depend on the many individual choices researchers make when analyzing data. Multiverse-style analyses address this by computing results across a set of specifications rather than a single one, but it is unclear how widely they are being used and how they are being implemented. We searched the Web of Science Core Collection (May 2026) for articles citing six foundational papers on different variants of multiverse-style methods and classified each of the citing articles as implementing such methods or only discussing them. For implementations, we recorded the framework used, the number of specifications, which of four decision nodes (measurement, data processing, modeling, and estimation) were varied, and other aspects such as how results were visualized and interpreted. Of the 1545 classifiable articles, 613 (39.7%) implemented a multiverse-style analysis (primarily multiverse n = 336, specification curve n = 175, vibration of effects n = 20, multimodel n = 59, and multi-analyst/many-analyst n = 23). Uptake spanned many disciplines, most often psychology (39.8%), the social sciences (20.7%), and medicine (19.2%). The number of specifications ranged from fewer than ten to more than ten thousand (median = 144, IQR 24-1248). Modeling (75%) and data-processing (62%) choices were included most often. Interpretation was predominantly descriptive, whereas formal inference (10.5%), preregistration (8.6%), and explicit attention to the defensibility of specifications (3.9%) were uncommon. Multiverse-style analyses are increasingly becoming established across the quantitative sciences, but some implementation practices can be strengthened so that these analyses become more fully transparent and more genuinely informative about the robustness of research findings.