Serotonin (5-HT) critically regulates cognitive and emotional functions, and both stable and transient variations in 5-HT signaling have been associated with emotional dysregulations. However, findings regarding the neurofunctional effects of transient 5-HT variations have been highly inconsistent. Therefore, we examined whether individual variations in a central 5-HT-regulating genetic polymorphism (tryptophan hydroxylase 2, TPH2) represent a vulnerability or resilience factor for the effects of acute tryptophan depletion (ATD) on functional brain architecture. The current study utilized a pharmacogenetic within-subject randomized placebo-controlled resting-state fMRI design with N = 53 healthy male participants in combination with spontaneous intrinsic neural activity, functional connectivity, and connectome gradient analyses to compare the neurofunctional effects of ATD-induced transient reduction in central 5-HT signaling between TPH2 genotypes (a priori genotyping for rs4570625, GG n = 25 vs. TT n = 23). ATD induced significant increases in spontaneous neural activity in hippocampal CA1 irrespective of genotype and enhanced communication of this region with the bilateral amygdala and the vmPFC specifically in GG carriers. ATD sharpened the intrinsic connectome gradient architecture in several large-scale networks, including the salience, frontoparietal, and default mode network. Our results identify a potential genetic marker for an increased vulnerability to the neural effects of transient variations in 5-HT signaling on the functional architecture of an anxiety- and stress-related brain circuit in men. Gradient architecture results underscore the regulatory role of 5-HT on the intricate organization of large-scale networks involved in emotional reactivity and regulation.

Posttraumatic stress disorder (PTSD) is associated with dysfunctional engagement of frontal control and subcortical emotion processing regions, which may compromise adaptive affect regulation. Real-time fMRI neurofeedback (rt-fMRI NF) offers a neuroscience-informed approach to strengthen self-regulation of cognitive control regions, yet its effects on transient resting-state (RS) connectivity within symptom-specific networks remain unclear.This study examined the impact of a single rt-fMRI NF-guided cognitive reappraisal session on RS connectivity in 41 participants (20 PTSD; 21 healthy controls). RS scans were acquired at baseline, after active NF, and after a control condition (NoNF). NF targeted self-regulation of an individually defined region in the left inferior frontal gyrus (lIFG).At baseline, group differences in connectivity were limited to the cerebellum. After NF compared to the control condition, participants showed significant connectivity changes between the left IFG and pre- and postcentral gyri, superior parietal lobe, occipital cortex, and a limbic cluster enompassing the amygdala, nucleus accumbens, and putamen. ROI-to-ROI analyses confirmed fronto-amygdala network modulation, particularly involving the superficial (SF) and basolateral (BL) amygdala nuclei. No group differences were observed in NF-related connectivity changes. Notably, post-NF connectivity between the amygdala and superior parietal lobe was associated with increased positive affect at four-week follow-up in PTSD. Baseline connectivity between the putamen and posterior cingulate cortex (PCC) predicted regulation success during NF.Overall, a single rt-fMRI NF session may modulate networks supporting adaptive emotion regulation, attention, and sensory processing in both PTSD and healthy individuals. Future randomized, double-blind controlled trials are needed to establish clinical relevance.

Abstract Adaptive emotion regulation is essential for mental health. Reappraisal and acceptance are effective yet cognitively distinct emotion regulation strategies. A key unanswered question is whether their neural implementations are supported by common overarching or distinct neurofunctional processes, especially under dynamic, naturalistic conditions that mirror real-life scenarios. Here, we combined naturalistic fMRI with multivariate predictive modeling to develop neurofunctional signatures that accurately and comprehensively characterize negative affect and its regulation via acceptance and reappraisal in dynamic, immersive contexts (n = 59). These signatures demonstrated process-specificity and generalizability across cohorts, cultures, and modalities (n = 33, 358, 45, and 33, respectively). Emotion regulation strategies were encoded in distributed, distinguishable neural representations, with shared contributions from the default mode network and strategy-specific contributions from the amygdala, somatomotor and attention (acceptance), and the frontoparietal control (reappraisal) networks. The neuromarkers precisely identified strategy-specific ER impairments in male cannabis users (nhealthy_controls = 48, ncannabis_users = 49), underscoring their potential clinical translational relevance. Collectively, these findings demonstrate shared and distinct neural signatures of reappraisal and acceptance, highlight the critical role of whole-brain integration in emotion regulation, and provide comprehensive, clinically relevant brain models of emotion regulation and dysregulation in naturalistic contexts.

Sustained affect shapes well-being, yet its neural architecture across externally elicited and internally generated experience remains unclear. Using whole-brain functional connectivity during minutes-long naturalistic movie viewing, we derived positive and negative affective experience signatures and their underlying neural architecture. These signatures predicted valence-specific affective intensity and generalized to independent movie-viewing data and internally generated affect, discriminating sad memory and rumination from neutral distraction while tracking subjective experience. Importantly, their expression showed little relation to vigilance or cognitive demand. Characterization of these signatures revealed coherent community structure and a shared distributed backbone, alongside valence-preferential components, consistent with a partially separable architecture. Extending beyond experimentally evoked states, in four resting-state depression cohorts, these signatures distinguished patients from controls with reduced positive and elevated negative signature expression, and predicted symptom burden and anhedonia. These findings identify a generalizable distributed architecture bridging external and internal affective experience and extending to clinically relevant affective dysregulation.

Background The renin-angiotensin system (RAS) has been increasingly recognized as potent modulator of cognitive and affective functions, with angiotensin II type 1 receptor (AT1R) antagonists emerging as repurposing candidate for anxiety and stress-related disorders. However, it remains unclear whether transient AT1R blockade modulates emotional attentional control and whether these effects are sex-dependent. Methods We conducted a preregistered, randomized, double-blind, placebo-controlled pharmacological eye-tracking study in 79 healthy adults (males and females) and determined effects of transient AT1R blockade via losartan (50 mg) on emotional attention control using a validated anti-saccade paradigm with social (emotional faces) and non-social stimuli. Treatment effects on state anxiety and oculomotor responses were characterized using traditional metrics and a novel trial-history informed dynamic control framework. Results Losartan reduced state anxiety irrespective of sex but induced sexually dimorphic effects on attentional control. In females, losartan enhanced performance by reducing endpoint error without altering latency. Conversely, in males, losartan increased endpoint error and prolonged latency of the first correct saccade. Trial-history analyses revealed losartan reduced error probabilities following errors and repeat trials in both sexes. Yet, following correct trials, females receiving losartan maintained lower error probabilities, while males exhibited higher errors, potentially reflecting failure to disengage from effortful control. Conclusions The RAS modulates anxiety and attentional control, the latter sex-dependently. AT1R blockade reconfigures attentional processing and adaptive control, suggesting sex-specific therapeutic potential in disorders characterized by excessive anxiety and attentional dysregulation. Clinical trials registration ClinicalTrials.gov; https://clinicaltrials.gov/; NCT06329050.

BACKGROUND:Non-suicidal self-injury (NSSI) in adolescents represents a critical public health issue. While symptomatic links between NSSI and alterations in pain and social processing have been established, changes in neural responses and everyday reactivity to others' pain remain unknown. METHODS:This pre-registered study examined pain empathic processing in unmedicated adolescents with NSSI (n = 29) and healthy controls (n = 33) using functional magnetic resonance imaging (fMRI). A validated paradigm assessed neural responses to physical pain versus affective pain observation and was combined with both univariate and machine learning analytic approaches. RESULTS:NSSI participants exhibited significantly increased neural reactivity during physical pain empathy in lateral prefrontal, insular, temporal, and somatomotor network regions (all p < 0.05, FDR-corrected), while affective pain processing remained intact. Machine learning analysis revealed distinguishable whole-brain signatures, with a physical pain empathic pattern achieving superior discrimination in NSSI. NSSI participants reported elevated personal distress to others' negative experiences in everyday life, which was associated with enhanced limbic reactivity during physical pain empathy. CONCLUSIONS:Findings identify domain-specific neural hyperreactivity to others' physical pain in NSSI adolescents and elevated personal distress in daily life. These characteristics may represent predisposing alterations that facilitate engagement in self-harm or consequences of repeated engagement in NSSI that impact everyday social behavior.

Overarching conceptualizations propose a critical role of the default mode network (DMN) in self-referential mental time travel, particularly in autobiographical memory retrieval and episodic future thinking, and internal (intrinsic) emotion generation and regulation. However, these conceptualizations have not been directly evaluated. Against this background, the present fMRI study aimed to identify both shared and distinct neural systems underlying autobiographical episodic processing across different temporal contexts - specifically, episodic memory retrieval (EMR) and episodic future thinking (EFT) - and to examine how these systems interact with affective experiences, including valence and arousal. Our findings demonstrated the central role of the DMN - encompassing the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and medial temporal lobe (MTL) - in both EMR and EFT. Importantly, we identified a functional dissociation along both valence and temporal dimensions: the ventromedial prefrontal cortex (vmPFC) was more strongly associated with positive experiences and simulations, whereas the dorsomedial prefrontal cortex (dmPFC) was consistently engaged during the processing of negative affect across past and future contexts. Moreover, representational similarity and parametric analyses indicated that the hippocampus supports differential processing of valence and arousal across temporal domains. Together, these findings provide empirical evidence for the involvement of cortical midline core DMN systems in autobiographical processing across time and suggest overlapping and distinct systems for the integration of emotional experiences across mental time travel. ### Competing Interest Statement The authors have declared no competing interest. National Natural Science Foundation of China, 82271583 Ministry of Science and Technology of China, 2022ZD0208500 Hong Kong University Grants Council, 17615525 University of Hong Kong seed funding and start-up schemes, 2407102536

BACKGROUND:Dysfunctional emotion regulation (ER) strategies may represent a promising treatment target for heroin use disorder (HUD). The therapeutic potential of transcranial magnetic stimulation to improve ER in HUD remains to be evaluated. METHODS:The present randomized sham-controlled pre-registered clinical trial determined the therapeutic efficacy of intermittent theta-burst transcranial magnetic stimulation (iTBS) over the left dorsolateral prefrontal cortex (DLPFC) for 10 days in 39 HUD patients (21 real iTBS; 18 sham). The ER performance-associated electroencephalographic indices obtained by event-related potential, time-frequency, source localization, and connectivity analysis techniques served as outcomes and were assessed pre- and post-intervention, and one month later, follow-up for the real iTBS group. RESULTS:Compared to the sham iTBS group, the intervention group exhibited significantly more positive difference waves (DW) at 400-600 ms, which was significantly related to reduced craving. The real iTBS group specifically showed changes over the intervention, with enhanced event-related synchronization in the delta/theta band during viewing neutral pictures and expressing suppression of unpleasant pictures (US); lower activation in the left supramarginal gyrus and right posterior cingulate cortex (PCC) in the above conditions, separately; and lower connectivity between left DLPFC and right PCC under the US condition. During 1000-1200 ms, their DW amplitudes at the follow-up period were significantly more negative than baseline. CONCLUSIONS:The iTBS can improve the ER ability of HUD patients to use ER strategies, particularly expressive suppression, which are maintained following the intervention. Improved ER capability is associated with reduced craving, which may involve alterations in frontal-limbic connectivity.

Emotional stimuli may have positive effects in cognitive processes that allows for temporary storage and manipulation of information. However, the influence of emotional stimuli, along with its neural correlates have not been fully analysed so far. This study aimed at investigating the neural and behavioral effect that the emotional content of stimuli has on working memory performance. In this functional magnetic resonance imaging (fMRI) study, we induced different emotional faces pictures while participants (n = 17) performed an n-back visual working memory task. Data were analyzed using Statistical Parametric Mapping 12 (SPM-12). Result showed emotional working memory n-back tasks activated motor, occipital, frontal, parietal regions. Frontal and parietal regions showed more activation in 1-back task association with increased working memory load. This showed that additional component need in maintaining a representation of the previous stimuli.

Although contemporary models of obsessive-compulsive disorder (OCD) have primarily emphasized fear, recent accounts suggest that abnormal disgust learning may also contribute to OCD pathology, particularly in contamination-related OCD (C-OCD). The present study examined the neural correlates of disgust learning in individuals with elevated contamination-related obsessive-compulsive symptoms. Event-related potentials (ERPs) were recorded while 28 participants high in contamination-related obsessive-compulsive symptoms (HC) and 30 participants low in such symptoms (LC) completed disgust acquisition and extinction tasks. Behavioral measures included unconditioned stimulus (US) expectancy and conditioned stimulus (CS) disgust ratings, alongside electrophysiological indices of conditioned disgust. During acquisition, the HC group showed higher US expectancy for the CS+ than the LC group. At the neural level, both groups showed larger P3 amplitudes to the CS+ than to the CS-, indicating enhanced attentional significance. However, the HC group exhibited smaller overall P3 amplitudes than the LC group, which may reflect greater avoidance during disgust learning. During extinction, US expectancy differences between the CS+ and CS- remained evident in both groups, whereas P3 differences were no longer observed, suggesting a dissociation between self-reported and neural responses. Overall, these findings indicate that individuals with elevated contamination fear show enhanced disgust acquisition and altered neural processing during disgust learning, which may help clarify how maladaptive disgust responses are formed and maintained in contamination-related OCD.

In this opinion article, we critically evaluate the widespread discussion of proposed phenomena such as AI Psychosis and Brain Rot. These terms lack empirical support but have gained traction in news media and scientific communication. We argue that society bears significant costs when scientific debates and public discourse become dominated by sensationalized terminology which perpetuates pseudo-science and distract from the real harm of technology use. Using such terms in the context of AI phenomena may also contribute to public panic about AI content and technologies, and undermine balanced discussions of the risks and benefits of these innovations.

Mood disorders, including Major Depressive Disorder (MDD) and Bipolar Disorder (BD), are highly prevalent conditions. These disorders are characterized by persistent emotional dysregulation and substantial functional impairments. Despite extensive neuroimaging research, reliable neurofunctional markers remains elusive. To address this gap, we propose a novel approach that utilizes Divergent Emotional Functional Networks (DEFN), derived from functional magnetic resonance imaging (fMRI) in naturalistic contexts.By integrating naturalistic emotion induction, dynamic functional connectivity (dFC), and machine learning, we identified emotion-specific functional patterns in healthy individuals with an accuracy of 83.99%. The DEFN was subsequently validated in clinical datasets, including a multi-site MDD cohort (Hiroshima University: MDDs = 63, HCs = 111; University of Tokyo: MDDs = 62, HCs = 96) and an independently BD cohort (BDs = 59, HCs = 50). Using static functional connectivity (sFC) and nested 10-fold cross-validation, DEFN-based models (MDD: 70.33%, BD: 75.18%) significantly outperformed baseline models in classifying patients and HCs (MDD: 70.33% vs. 57.58%; BD: 75.18% vs. 63.18%). Additionally, DEFN demonstrates highly reproducibility across age and sex, supporting the robustness of DEFN model. In conclusion, the DEFN approach presents a promising, reproducible, and clinically relevant neural marker for diagnosing, offering potential for more effective and timely interventions.

BACKGROUND:Acute stress plays a key role in mental health, and there is a pressing need for accessible, brain-based interventions that strengthen stress regulation by directly targeting the underlying brain mechanisms. We therefore developed a real-time functional near-infrared spectroscopy (fNIRS)-informed neurofeedback training targeting a prefrontal region involved in cognitive emotion regulation (left lateral prefrontal cortex, PFC) and evaluated its potential to enhance stress regulation using the socially evaluated cold pressor test, an acute stress paradigm that combines physical and social stressors. METHODS:In a randomized double-blind, sham yoked feedback-controlled parallel-group trial, 60 young healthy adults underwent pretraining of cognitive emotion regulation with reappraisal strategies, then completed four neurofeedback runs applying reappraisal strategies to drive regulation, preceded and followed by baseline and maintenance runs without feedback. The training combined continuous neurofeedback from individualized lateral PFC channels to guide neurofunctional control. The primary outcome assessed activity at trained channels, while secondary outcomes assessed stress and pain regulation during the socially evaluated cold pressor test. RESULTS:Neurofeedback significantly promoted upregulation of lateral PFC activity throughout the training runs. Participants in the training group exhibited lower subjective stress - yet not pain - experience during the cold pressor test, as well as reduced post-training anxiety, reflecting a successful and domain-specific transfer of regulatory control. CONCLUSIONS:This study demonstrates the efficacy of real-time fNIRS lateral PFC neurofeedback in facilitating adaptive learning of regulatory skills, which transferred robustly to regulation of subjective stress under acute stressors. These findings point to neurofeedback training as a promising translational strategy for enhancing stress regulation.

BACKGROUND:Depression is associated with pathological dysregulations affecting both the brain and the body, with the latter being reflected in plasma proteins. While plasma protein signatures of depression have been increasingly recognized, a holistic examination of interactions with brain features is lacking. METHODS:Leveraging data from 3,966 UK Biobank participants, we identified a multimodal neuroimaging-plasma protein component of depression (NeuroPro-Dep) by integrating plasma proteins and five brain modalities via an ICD-10 diagnosis-constrained multimodal fusion approach. RESULTS:Notably, NeuroPro-Dep demonstrates detectable associations with depression symptoms across datasets from diverse populations, underscoring its clinical potential. This capability is anchored in its five brain modalities alterations, including hippocampal atrophy, reduced cortical sensorimotor network functional connectivity, and impaired internetwork structural connectivity of the frontoparietal network. The multimodal neuroimaging-derived plasma protein modality of NeuroPro-Dep is enriched in metabolic pathways, as further supported by association analysis linking this modality to body mass index (BMI), type 2 diabetes, and other metabolic indicators. Crucially, two-step Mendelian randomization analysis revealed that the NeuroPro-Dep plasma protein modality exerts a causal effect on depression through BMI (plasma protein to BMI: or=0.28, p=0.035; BMI to depression: or=1.14, p=4.37×10-11). CONCLUSIONS:Overall, this study underscores metabolic dysfunction as a bridge between brain changes, depression, and physical diseases, while providing a novel multimodal biological signature and valuable insights that may inform future treatment strategies.

Abstract Background Non-suicidal self-injury (NSSI) represents a growing public health concern, particularly in adolescents. Emotion dysregulation is central to prevailing NSSI models, yet it remains unclear whether acceptance-based emotion regulation (ER) and its underlying neural processes are disrupted in naturalistic, dynamic contexts. Methods Pre-registered neuroimaging trial in recently diagnosed and treatment-naïve adolescents with NSSI (n=25) and healthy controls (n=25) using an ER paradigm with dynamic video clips and concomitant functional magnetic resonance imaging. Behavioral, neural activity, and connectivity indices during emotion reactivity and acceptance-based regulation were compared between groups. Results Adolescents with NSSI experienced elevated negative feelings during neutral clips, reflecting heightened baseline negativity. In comparison to controls, they displayed reduced temporal and ventrolateral prefrontal engagement during emotional reactivity, but increased engagement of regions implicated in both emotion reactivity (right amygdala, insula) and ER (right dlPFC, dmPFC, vlPFC) when utilizing acceptance. Higher activation in the right dlPFC was positively associated with difficulties in accessing ER strategies in everyday life. Adolescents with NSSI showed reduced functional connectivity between the right amygdala and left dlPFC. Conclusions Adolescents with NSSI exhibited a baseline negativity bias and altered neural engagement during both negative emotional reactivity and acceptance-based regulation, characterized by increased activation and reduced amygdala–dlPFC connectivity. These findings highlight atypical emotion processing in real-life contexts in individuals with NSSI. Targeting acceptance-based regulation and prefrontal–limbic circuitry may represent a promising intervention approach for adolescents with NSSI.

Aesthetic experience shapes behaviours ranging from everyday consumer choices to art appreciation. Although theoretical accounts propose that such experiences emerge from interactions among core brain systems, the dimensions organising this mental process remain unclear. Here, we introduce a data-driven framework to characterise the latent neural architecture of shared aesthetic evaluations. Participants viewed traditional paintings during 7T functional magnetic resonance imaging (fMRI), and we applied dimensionality reduction to the similarity structure of their aesthetic ratings to identify the dominant axes of variation. Two principal dimensions emerged, visual semantics and hedonic valuation, each predicted by dissociable multivariate neural signatures. Category-selective regions along the ventral visual stream tracked variation in visual semantics, whereas medial prefrontal and subcortical circuitry tracked hedonic valuation. Moreover, individual differences in this latent aesthetic space, particularly within default mode network regions, scaled with visual art expertise. Together, these findings reveal how core brain systems synergistically organise shared aesthetic evaluations of visual artworks.

BackgroundNonsuicidal self-injury (NSSI) and suicide attempt (SA) are two major self-injurious behaviors causing substantial suffering and socioeconomic burden. However, it remains unclear whether NSSI and SA are characterized by common or distinct brain dysregulations. Here, we aimed to identify shared and separable neurofunctional alterations during task engagement between NSSI and SA.MethodA coordinate-based meta-analysis was employed using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) by capitalizing on task-based functional magnetic resonance imaging (fMRI) studies comparing the brain activation between NSSI/SA individuals and controls.ResultThe search identified 10 studies for NSSI (n = 200, mean age: 22.89 years) and 16 studies for SA (n = 343, mean age: 28.65 years). After threshold-free cluster enhancement correction, NSSI individuals exhibited increased right amygdala activation relative to both controls and the SA group, as well as heightened left middle frontal gyrus and reduced left paracentral lobule activation compared to the SA group. No significant activation differences were found between SA and controls, though a less conservative threshold revealed increased left postcentral gyrus activation in the SA group. No shared functional abnormalities were identified between NSSI and SA under either corrected or uncorrected thresholds. Importantly, subgroup analyses revealed that the neurofunctional abnormalities in NSSI were primarily driven by adolescent cohorts, whereas no significant clusters emerged for the SA group across age-stratified analyses.ConclusionThese results suggest that neurofunctional abnormalities are evident in adolescent NSSI, particularly in fronto−limbic regions, with no robust findings in adult NSSI or SA subgroups. This highlights a unique developmental trajectory that necessitates age-tailored risk assessment and interventions for self-injurious behaviors.

While basal threat processing dynamics (e.g., visual looming) are well characterized in animals, the underlying mechanisms and their modulation by neuropeptide systems with different modulatory roles in threat processing (vasopressin, angiotensin II) remain poorly understood in humans. In a randomized, placebo-controlled eye-tracking study (N = 111), we administered vasopressin (AVP) or an angiotensin II receptor blocker (via Losartan, LT) during a time-to-collision threat paradigm. This study was prospectively registered at ClinicalTrials.gov (NCT06329076, NCT06329063) on April 11, 2024, prior to participant enrollment. Behaviorally, AVP induced a systematic time overestimation while LT induced temporal compression and reduced state anxiety. Pupillometry revealed distinguishable profiles: AVP induced sustained constriction during stimulus approach followed by post-stimulus threat-specific dilation, LT maintained sustained pupillary constriction throughout both approach and occlusion phases yet preserving threat-specificity, while placebo (PLC) showed no threat-specific modulation. A computational framework (combining Functional Principal Component Analysis, clustering, and Markov chain analysis) underscored the distinct modulations: AVP stabilized a high-arousal state characterized by the co-activation of vigilance, threat-proactive preparation and a shift from perception to internal simulation. LT suppressed transitions to high-arousal states and exhibited maximal sequence entropy, reflecting flexible response patterns-contrasting with placebo's lowest entropy dynamics. These results demonstrate that AVP and LT differentially regulate basal threat processing via separable neuropeptide pathways: AVP sustains hypervigilance while LT promotes anxiolysis and adaptive flexibility. Our findings suggest neuropeptide pathway-specific targets maladaptive threat processing in trauma- or anxiety-related disorders.

Disgust constitutes an evolutionary adaptive defensive-avoidance response, yet humans vary markedly in their dispositional tendency to experience disgust (disgust propensity) and in their negative appraisal of such experience (disgust sensitivity). Conceptual frameworks and neuroimaging studies suggest that these traits may differentially modulate neural responses to disgust-eliciting stimuli; however, methodological constraints have left their precise roles unresolved. Our comparably large fMRI study (n = 142) therefore aimed to systematically determine how trait disgust modulates neural responses to carefully selected and validated disgust-specific visual stimuli across varying levels of subjective disgust experience. The whole-brain voxel-wise regression analyses revealed a differential pattern of neural associations between the two disgust traits, with disgust propensity, but not disgust sensitivity, modulating disgust-related neural activity in the anterior, middle, and posterior insula, as well as the caudate, putamen, thalamus, hippocampus, and parahippocampal gyrus. Mediation and network-level analyses further supported this partly dissociable pattern by showing that disgust propensity shapes disgust experience via insula-striatal-hippocampal pathways. Together, these findings provide evidence for a differential association between disgust propensity and disgust sensitivity with disgust-related neural responses and elucidate how trait disgust shapes subjective experiences. They further suggest that disgust propensity and the identified systems may represent promising targets for the regulation of disgust-related pathology.

Problematic smartphone use (PSU) is highly prevalent among college students and robustly associated with broad social functioning impairments. However, the impacts of PSU on cooperation and competition—two core forms of interpersonal interaction underpinning daily social adaptation—and their underlying neural mechanisms remain largely uncharacterized, creating a critical gap in understanding PSU-related social dysfunction.We employed a two-phase study design: an online prescreening of 532 college students using validated scales for PSU severity, cooperative willingness, and competitive traits; followed by a laboratory experiment with 84 participants (42 in the PSU group, 42 healthy controls, 21 dyads per group) completing cooperative, competitive, and single-player tasks, with functional near-infrared spectroscopy hyperscanning recording dyads’ behavioral performance and interpersonal brain synchronization (IBS).Behaviorally, higher PSU severity correlated with lower cooperative willingness (r=-0.086, p<0.05) and stronger competitive traits (r=0.402, p<0.001). The PSU group exhibited significant cooperative performance deficits (p<0.01, Cohen’s d=0.55), with no group differences in competitive or single-task behavior. Neurally, controls showed robust bilateral dorsolateral prefrontal cortex (dlPFC) IBS during cooperation, while the PSU group had no significant IBS; dlPFC IBS alterations positively correlated with PSU severity (r=0.373, p<0.05).These findings demonstrate that elevated PSU is linked to selective cooperative impairments in college students, with absent dlPFC IBS as a potential neural marker of PSU-related social dysfunction, advancing theoretical understanding of PSU psychopathology and informing targeted interventions.