Social Cognitive and Affective Neuroscience

Fairness decisions often integrate affective responses within a social context, yet emotion regulation in this literature has been largely studied as a self-directed process rather than an interpersonal one. We examined how individual differences in other-directed emotion regulation--measured with the Emotion Regulation of Others and Self (EROS) scale--relate to behavioral and neural responses during fairness decisions in 138 adults completing a variant of the Ultimatum Game with human and computer partners during fMRI. Behaviorally, participants who more strongly endorsed worsening others emotions rejected unfair offers more frequently, and this tendency interacted with offer fairness to amplify rejection of unfair offers. At the neural level, the left anterior insula tracked offer unfairness more strongly in social versus nonsocial contexts, consistent with sociality modulating the neural encoding of fairness. Right dlPFC activation during socially unfair offers was greater among individuals who preferred to improve others emotions. Connectivity analyses revealed that social fairness sensitivity predicted stronger amygdala-orbitofrontal and amygdala-dmPFC coupling; the latter was further amplified among individuals higher in other-directed emotion worsening. Together, these findings identify interpersonal emotion regulation as an understudied source of variation in the affective and prefrontal systems supporting fairness-based social decisions.

As avatars become more commonplace, understanding how the brain processes emotional expressions in virtual faces is critical. We compared behavioral and neural responses to real and virtual faces expressing seven emotions (anger, disgust, fear, joy, sadness, surprise, neutral). In Experiment 1 (n=61), participants rated the similarity between paired faces. Expressions conveying the same emotion were rated as highly similar across face types, whereas mismatched emotions yielded substantially lower similarity ratings, indicating perceived emotional meaning was preserved despite differences in face realism. In Experiment 2 (n=91), functional near-infrared spectroscopy was used to measure brain activity while participants viewed the same stimuli. General-linear-model analyses revealed greater activation limited to visual areas for 1) virtual faces and 2) surprise and neutral expressions. Functional connectivity analyses, however, revealed network level differences between face type and emotion across the brain. Real faces elicited stronger connectivity patterns across frontal, central-temporal, and parietal regions, whereas high-arousal emotions (fear, anger, and joy) were associated with broader network engagement than other expressions. Our results suggest face-type processing occur in early visual areas, and despite perceptual similarity, different emotions on real and virtual faces are associated with distinct patterns of network level connectivity across the brain.

In task-oriented teams, long-term coordination among specialized roles may contribute to shared patterns of cognition and behavior, yet little is known about how such experience is reflected in brain functional organization. Here, we examined whether cross-individual differences in whole-brain functional connectivity were associated with court position and team membership in professional volleyball players. In the resting-state and naturalistic volleyball game-viewing conditions, we analyzed dyadic functional connectivity differences to test whether effects of shared position and team were evident across intrinsic and contextually engaged brain states, controlling for differences in playing time and performance-related statistics. We found that same-position players showed smaller functional connectivity differences. These effects were most prominent and widespread across brain networks during game viewing, whereas at rest they were specific to the somatomotor network. Team membership was also associated with smaller functional connectivity differences during game viewing, although position x team interactions varied across networks after covariate adjustment. A complementary machine learning classifier further showed that shared position could be predicted from intersubject differences in functional connectivity with accuracy exceeding a frequency-based baseline. Together, these findings suggest that shared role-specific and team-based experience may contribute to structured similarity in functional brain organization within a real-world team setting.

Flow, as defined by Mihalyi Csikszentmihalyi (1975), is a holistic sensation experienced when individuals are fully immersed in an activity, resulting in a mental state characterized by a diminished sense of self and altered perception of time. To investigate the global neural dynamics underlying flow, we employed EEG microstate analysis to capture the spatial and temporal properties of dominant transient global brain states (Lehmann et al., 1998). In a study involving 43 participants playing the video game Thumper for 25 minutes, we extracted three four-minute EEG segments from each session corresponding to reported experiences of flow, boredom, and frustration, as determined by self-reports and performance metrics. Across conditions, six distinct microstate topographies (A-F) accounted for most of the global variance. Given that reduced self-referential processing is a key feature of flow, we hypothesized that flow would modulate the properties of microstates C and E, which have been associated with brain regions resembling the default mode network (DMN). Compared to boredom and frustration, the flow condition showed significantly decreased global explained variance, mean duration, time coverage, and occurrence frequency of microstate E, as well as reduced mean duration and time coverage of microstate C. These findings suggest that microstates associated with self-referential processing are shorter and less frequent during flow than during boredom and frustration. This supports the notion that the flow experience modulates global brain dynamics, particularly within the DMN. Furthermore, our results align with previous research reporting reduced DMN activity during meditative and psychedelic states, reinforcing the idea of diminished self-awareness in such conditions.

Previous brain decoding studies indicate that an individuals pain experience can be robustly predicted from distributed patterns of brain activity. Two brain decoders have notably been associated respectively with the nociceptive and cognitive aspects of pain experience, the Neurologic Pain Signature (NPS) and the Stimulus-Intensity Independent Pain Signature (SIIPS). Yet, we still do not know if these brain patterns are also causally related to pain experience. To evaluate this possibility, we used high-field (7-Tesla) fMRI to test whether humans can alter their pain experience by bidirectionally modulating their pain-related brain activity in decoded neurofeedback paradigm. In a double-blind design, participants were trained to up- and down-regulate the NPS or the SIIPS. Our results indicate that participants can achieve bidirectional control of both signatures. NPS expression reliably increased during pain stimulation and covaried with both stimulus intensity and subjective ratings. In contrast, SIIPS expression did not show consistent stimulus-locked effects in the primary analyses. Importantly, reduction in pain rating was specific for SIIPS-training, whereas NPS has failed to show any consistent behavioral effect. Based on these preliminary findings, we hereby preregister a follow-up study, with specified rationale, hypotheses, experimental design, and analysis protocols.

Functional connectivity in network neuroscience is traditionally characterized using time-averaged correlations between brain regions. While these summaries capture stable large-scale organization, they do not fully reflect the temporal structure of moment-to-moment interactions. Here, we investigate how the order of interaction used to represent brain dynamics shapes the organization recovered from neural data. We compare three interaction representations of fMRI dynamics: regional activation (node time series), pairwise co-fluctuations (edge time series), and higher-order triplet interactions (triangle time series); within a common topological framework using Mapper from topological data analysis (TDA). Across task and resting-state data, Mapper representations derived from pairwise co-fluctuations more distinctly segregate task conditions than activation-based or higher-order representations. This organization reflects structured coordination patterns beyond activation polarity and is driven by high-amplitude interaction events. Beyond task states, modularity quality computed across all Mapper representations is highest for edge time series and selectively associated with stable individual differences: higher modularity relates to higher conscientiousness and lower internalizing and externalizing symptom dimensions. Together, these findings suggest that behaviorally relevant information is reflected in the topology of moment-to-moment brain interactions. Topological analysis of interaction-level dynamics therefore provides a complementary and interpretable framework for linking large-scale neural coordination to cognition, personality, and mental health.

BackgroundNon-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. MethodsPre-registered neuroimaging trial in recently diagnosed and treatment-naive 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. ResultsAdolescents 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. ConclusionsAdolescents 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.

Much of a typical individuals mental life is characterized by spontaneous thoughts that occur independently of external stimuli. In prior studies, ongoing mental experiences and their neural correlates have been captured using thought probes presented at random intervals during functional Magnetic Resonance Imaging (fMRI). However, this approach results in temporally imprecise estimates of brain activity relative to the arising of mental experience. In this preregistered, proof-of-concept study, we aimed to improve temporal precision using a novel method termed real-time fMRI-triggered experience-sampling (rt-fMRI-ES). We analyzed blood-oxygenation-level-dependent signals in real time during a wakeful resting state (n=60) to trigger thought probes from spontaneous activations within two regions: the dorsal anterior insular cortex (daIC; a key region within salience network) and posteromedial cortex (PMC; a key region within default mode network). We tested two preregistered hypotheses: (H1) Ratings of arousal time-locked to daIC-activation trials are higher than ratings time-locked to non-daIC-activation trials; (H2) Ratings of external-attention time-locked to PMC-activation trials are lower than ratings time-locked to non-PMC-activation trials. After applying preregistered exclusion criteria, 42 participants (1243 trials) and 49 participants (1429 trials) were included in H1 and H2 analyses, respectively. We did not find evidence in support of H1, but we did find evidence in support of H2, as external-attention ratings were significantly lower for trials triggered by PMC activation compared to other trial types. Taken together, we successfully developed and validated the rt-fMRI-ES method, offering a novel technique to efficiently capture spontaneous thoughts based on ongoing neural activity. Preregistered Stage 1 Recommendationhttps://osf.io/sd4hu (Date of in-principle acceptance: 07/24/2024; under temporary private embargo)

The thalamus is essential for learning, dynamically engaging with other subcortical and cerebral cortex regions throughout the learning process. Here, the thalamus serves as a critical connector hub and synchroniser within the thalamocortical system of the brain. However, whilst higher order thalamic nuclei are known to be particularly important for this process, the exact contributions of individual higher order and first order thalamic nuclei, alongside their individual involvement with cortical networks and subcortical regions, remains unexplored within the initial phase of learning. In light of this, we analysed fMRI data obtained within a paradigm which is designed to examine initial learning processes within feedback-driven stimulus-response learning, in order to explore thalamic contributions. We investigated dynamic learning-related functional connectivity alterations between various thalamic nuclei with other subcortical regions and cortical networks. Our results show that the initial phase of learning was associated with: (1) decreasing functional connectivity between thalamic nuclei and frontoparietal and cingulo-opercular networks, (2) increasing functional connectivity between thalamic nuclei with default mode and salience networks, (3) decreasing functional connectivity between thalamic nuclei and the putamen, and (4) decreasing functional connectivity amongst higher order thalamic nuclei. Furthermore (5) these dynamic alterations were associated primarily by mediodorsal thalamus. Altogether, these results indicate that higher order thalamic nuclei play a crucial role within initial learning and in the generation of novel goal-directed behaviour. This was demonstrated through enhanced functional connectivity with selected cortical networks which drive goal-directed behaviour, alongside decreased functional connectivity with striatal regions which drive motor selectivity.

Cognitive control is fundamental to goal-directed behavior, and its protracted maturation is a hallmark of adolescent brain development. In adulthood, the inferior frontal junction (IFJ) is functionally characterized as a critical region for updating task representations to guide the implementation of cognitive control. Yet, how its domain-general control functions emerge and mature across development remains largely underexplored. Specifically, it is unclear whether the IFJs capacity for cognitive control enhances uniformly as a single construct, or if this region matures asynchronously for distinct control processes like inhibition, switching, and working memory. To address this gap, we conducted a combined systematic review and coordinate-based neuroimaging meta-analysis. Applying multilevel kernel density analyses to fMRI studies of inhibition, switching, and working memory in youth and adults, we synthesized data from 72 contrasts (779 foci; N = 1,913). The results revealed a staggered developmental trajectory for IFJ recruitment. While adults showed consistent convergence of activation in the IFJ across all three domains, youth exhibited robust bilateral IFJ convergence exclusively during inhibitory control tasks. This suggests inhibition may be a developmentally foundational process localized to this region earlier in the lifespan. Furthermore, adults demonstrated hemispheric specialization absent in youth: left IFJ was uniquely sensitive to switching and working memory in adults, but not in youth. Together, these findings support a model where the IFJ does not mature as a static, monolithic node, but rather acts as a dynamic hub that integrates fractionated cognitive processes at different stages of development.

How does testosterone influence decisions and choice-related neural computations in competitive environments? To address this question, we administered testosterone or placebo to female participants (n = 54) in a double-blind, randomized design. Following drug treatment, participants competed in a dot estimation task that manipulated opponent status (lower, equal, or higher) and outcome feedback (win or loss), after which they decided whether to compete against the same opponent again. All participants adjusted their behavior based on opponent status and outcome feedback. Participants who received testosterone, however, showed significantly greater sensitivity to outcome feedback: they were more willing to compete after winning and less willing after losing, and made those decisions faster - suggesting that testosterone increases the weighting of immediate, salient outcome information in competitive decision-making. At the neural level, a network comprising ventral striatum, vmPFC, bilateral TPJ and ACC processed outcome-related signals during the feedback period. Critically, neural prediction analyses at the trial-level revealed that activity in left ventral striatum and TPJ predicted subsequent decisions to compete, but only in participants who received testosterone. The direction of these effects mirrored the behavioral results: striatal activity amplified the tendency to re-compete after winning, whereas TPJ activity predicted renewed competition after losing. Together, these findings demonstrate that testosterone biases competitive decisions by amplifying the influence of outcome-related activity in reward and social cognition circuits.

Humans possess an astounding ability to acquire complex movement sequences with limited practice. Motor sequence learning engages a distributed network of brain regions that show distinct learning-related changes: the prefrontal cortex (PFC) is predominantly involved early in learning, whereas the primary motor cortex (M1) becomes increasingly engaged later in learning. Because motor regions mature relatively earlier than the PFC during development, we examined how children and adults differ in the time course of neural changes underlying motor sequence learning. Using functional magnetic resonance imaging (fMRI), we compared brain activation in children (7-10 years, N = 39, 17 female) and adults (20-32 years, N = 39, 19 female) during an associative visuomotor learning task. In both age groups, response times decreased with sequence repetition, with greater reductions in adults than in children. Across age groups, early learning was associated with heightened PFC activation, whereas later learning was characterized by increased activation in left M1 and bilateral supplementary motor area. Children and adults showed comparable decreases in PFC activation and PFC-M1 connectivity with sequence repetition. In contrast, adults exhibited larger learning-related increases in activation and stability of multivariate patterns in left M1. Together, these findings indicate that although both age groups engage the PFC similarly to support increased control demands in early learning, children show less pronounced modulation of M1 activation and representational similarity, suggesting that M1s capacity to form stable, sequence-related representations may still be developing in middle childhood. Significance StatementAlthough motor sequence learning has been widely studied in adults, less is known about how brain activation changes as learning progresses during childhood. This question is particularly relevant because prefrontal cortex (PFC) and primary motor cortex (M1) both support motor learning, but mature at different rates, with PFC developing relatively later than M1. Here, we used functional MRI to compare children (7-10 years) and adults performing a motor sequence learning task. We found no age-related differences in PFC engagement early in learning; instead children showed less refinement of M1 activation and neural representations over the course of learning than adults. These findings provide new insight into how the brain supports motor learning throughout development.

Human functional magnetic resonance imaging studies of fear conditioning often average neural responses across trials, potentially obscuring transient activations that vary across learning. In this study with 139 participants, we examined finer temporal dynamics of conditioned responding by analyzing three 2s segments within the conditioned stimulus (CS) presentation period across each quarter of fear acquisition and extinction training. This approach revealed distinct, time-specific engagement of regions within fear- and safety-related networks, both within and across trials. In particular, different activation patterns emerged across the three trial segments during CS presentation, indicating that neural responses were not limited to CS onset. We observed a more classical activation pattern at 0s relative to CS onset that diverged in later trial segments, most notably involving the amygdala, hippocampus, and prefrontal cortex (PFC) structures such as vmPFC present exclusively in 2s and 4s trial segments. We also found sustained activations consistent across all blocks of trials, such as right vlPFC activation 4s after CS onset across all fear acquisition quarters. These findings suggest that conditioned fear and safety processing unfold as dynamic spatiotemporal cascades and highlight the importance of modeling later responses following CS onset rather than focusing exclusively on onset-related activation.

IntroductionWhile global topological properties of brain networks reach relative maturity early in development, functional reconfigurations at the regional level continue throughout adolescence to support cognitive maturation. However, regional age and sex-specific developmental patterns of functional reconfiguration remain incompletely understood. MethodsWe analyzed resting-state fMRI data from 528 participants aged 5-21 years from the Human Connectome Project in Development. Three regional graph-theory metrics (betweenness centrality, hub score, and local efficiency) were computed for each individuals functional network. Cognition was measured using NIH toolbox. Parallel factor analysis was employed to decompose an individual x region x metric array into factors representing distinct developmental properties in the full sample and separately for males and females. Brain-cognition associations were examined in developmental subgroups (<13, 13-18, >18 years). ResultsThree factors emerged, characterizing visual, multimodal integration, and higher-order factors. Across development, metrics capturing network integration (betweenness centrality and hubness) showed general stability, while metrics capturing segregation (local efficiency) presented distinct peaks, particularly in the visual factor. Females showed earlier peaks and declines in higher-order factor, while males exhibited greater variability and protracted maturation in multimodal and higher-order factors. Brain-cognition associations were modest with early childhood and crystallized cognition composites showed small negative correlations with hub score in entire sample (r=-0.212) and local efficiency in males aged <13 years (r=-0.215). ConclusionFindings highlight nonlinear, sex-specific functional reconfiguration at region-level during childhood and adolescence, underscoring the importance of sex-stratified analyses in developmental and providing a crucial foundation for future investigations of developmental disorders.

Subthreshold depression is associated with significant functional impairment and elevated risk of major depressive disorder. A negative self-concept may disrupt the implicit positive association evoked by ones own face, impairing incidental encoding of self-relevant information. Whether subthreshold depression involves a selective deficit in encoding self-face identity remains unclear. The attribute amnesia paradigm is well suited to address this question because it can dissociate attentional selection from working memory encoding. Using this paradigm, we examined the issue across two experiments. Experiment 1 employed nonsocial stimuli (animal drawings) and confirmed an intact attribute amnesia effect in subthreshold depression (n = 30) comparable to healthy controls (n = 30), ruling out a generalized encoding deficit. Experiment 2 replaced targets with faces (self or other) and revealed a selective enhancement of the attribute amnesia effect for self-face identity in subthreshold depression. Specifically, on the surprise trial, accuracy for self-face identity dropped to near-chance levels in the subthreshold depression group, whereas no such deficit emerged for other-faces or in controls. Encoding recovered rapidly once explicit memory expectations were introduced, indicating intact basic encoding capacity. These findings suggest that subthreshold depression is associated with a specific impairment in incidentally encoding self-face identity. This impairment likely stems from a negative self-concept that weakens self-face salience under incidental encoding conditions. By capturing this selective encoding failure, the present study reveals that the self-processing deficit in subthreshold depression can arise at the gating stage between attention and working memory consolidation.

BackgroundEmotional and cognitive difficulties often co-occur in neurodevelopmental conditions. While transdiagnostic, dimensional approaches offer a more precise framework for understanding mental health than diagnostic categories, their neural correlates in youth with learning difficulties remain poorly understood. This study investigates associations between transdiagnostic mental health dimensions and resting-state functional connectivity in struggling learners. MethodsCross-sectional behavioural data from the Centre for Attention, Learning and Memory (CALM) for struggling learners (N = 378) was used to replicate a hierarchical model of mental health from the Conners Parent Rating Short Form, the Revised Childrens Anxiety and Depression Scale and the Strengths and Difficulties Questionnaire. Functional connectomes were derived from resting-state fMRI data (N = 67), and partial least squares regression related mental health dimensions to connectivity within and between large-scale brain networks. ResultsThe replicated model comprised a general p-factor, two broad domains (internalising and externalising), and three specific dimensions (specific internalising, neurodevelopmental and social maladjustment). Symptom severity was associated with two connectivity patterns: greater default mode network coupling to frontoparietal and attention networks, and reduced connectivity between visual and somatomotor systems. These effects were strongest for the neurodevelopmental and social maladjustment dimensions, respectively. ConclusionsThese findings align with population-level evidence linking mental health dimensions to brain network organization, extending it to struggling learners and offering new insight into the neural basis of mental health vulnerability in neurodevelopmentally at-risk youth.

The proliferation of gambling advertising has intensified concerns regarding its influence on vulnerable populations, yet the neural mechanisms underlying cue-reactivity to these stimuli remain underexplored in ecologically valid settings. This study protocol proposes a novel methodological framework to investigate prefrontal cortical responses to gambling advertisements in individuals with varying degrees of gambling experience. Materials and methods: This cross-sectional study will recruit 44 participants, divided into a clinical group (individuals with high-frequency gambling or gambling disorder) and a matched control group. Neural activity will be recorded using fNIRS while participants view gambling-related, neutral, violent, and sexual stimuli. Secondary measures include validated scales for gambling severity (SOGS), impulsivity, sensation seeking, and alexithymia. Data analysis will primarily utilize inter-subject correlation (ISC) to quantify neural synchronization and multiband frequency decomposition to capture dynamic affective processing. Advanced preprocessing, including short-channel regression, will be applied to ensure signal robustness. Discussion: By combining portable neuroimaging with a data-driven ISC approach, this study aims to identify objective neural markers of gambling vulnerability. The findings will provide novel insights into the idiosyncratic processing of commercial stimuli, potentially informing public health policies and the development of more effective evidence-based regulations for gambling marketing.

Episodic memory requires integrating information across multiple scales, a process theorized to be supported by a gradient of neural timescales along the anterior-posterior axis of the hippocampus that enables both coarse-and fine-grained representations. Aging is associated with changes in hippocampal function and declines in fine-grained episodic memory, but whether this impacts the gradient organization of the hippocampus is unknown. Additionally, the relationship between the neural timescales of the hippocampus and memory specificity remains unclear. Here, we analyzed the length of timescales of individual voxels in the hippocampus during movie-viewing, along with subsequent recall data, in a sample of young and older participants. Younger adults showed the expected anterior-to-posterior timescale gradient, replicating prior work. In contrast, older adults exhibited a reversal of the expected gradient. Older adults recall was coarser and more gist-like than that of younger adults. In younger adults, longer neural timescales were associated with less specific, more gist-like recall; this was seen predominantly in the posterior-lateral hippocampus. In contrast, no relationship between neural timescales and recall were observed in older adults. An exploratory analysis revealed a similar relationship between neural timescales and memory specificity in cortical regions, in younger but not older adults. These findings suggest that aging alters the organization of neural activity throughout the hippocampus and that neural timescales in the hippocampus and cortex are related to the specificity of memory. Significance statementAs people age, episodic memories become more gist-like and less detailed. The hippocampus, which supports both gist and detailed memory, exhibits a neural timescale gradient--from slow-changing activity (longer timescales) to fast-changing activity (shorter timescales). This organization is theorized to support coarse-and fine-grained memory, respectively, yet a direct link to the age-related shift towards gist-like memory remains unestablished. Here, we identify an age-related shift in the hippocampal timescale gradient that parallels a decline in memory specificity. Furthermore, longer timescales in the hippocampus and cortical regions correlated with decreased memory specificity in younger adults. These findings demonstrate that aging is associated with a reorganization of hippocampal activity and that cortical timescales during encoding may relate to the specificity of memory.

IntroductionThe anterior limb of the internal capsule (ALIC) is a major white matter highway connecting prefrontal cortical (PFC) regions to the thalamus, brainstem, and subthalamic nucleus. Structural and functional abnormalities within the ALIC circuit have been associated with many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD) and depression, and deep brain stimulation (DBS) may provide effective treatment to some of these patients. However, it remains unclear whether the well-characterized topographic organization of the ALIC observed in healthy individuals and preclinical models is preserved in treatment-resistant psychiatric populations. MethodsWe first used diffusion tractography to evaluate the topography of PFC and subcortical fibers through the ALIC in patients with treatment-resistant OCD (n=18) and depression (n=5). In depression patients, we also evaluated ALIC topography using cerebro-cerebral evoked potentials (CCEPs) elicited by single-pulse electrical stimulation (SPES) of DBS leads in the ALIC and recordings in the ventral PFC (vPFC). ResultsThe topographic organization of PFC and subcortical projections is preserved in the ALIC among treatment-resistant psychiatric patients, consistent with patterns observed in healthy individuals and preclinical models. CCEP recordings in the ventral PFC showed a ventral ALIC to medial vPFC/dorsal ALIC to lateral vPFC response pattern in the left hemisphere, but not in the right. ConclusionOur findings confirm that topographic patterns within the ALIC previously identified using preclinical models and healthy controls are preserved in treatment-resistant psychiatric patients. Furthermore, by linking white matter topography to stimulation effects, this work supports more precise and individualized neuromodulatory strategies for neuropsychiatric disorders.

Background: While counterfactual thinking ('what could have been') guides adaptive decision-making, it remains unclear how this process is altered by the negative biases and motivational deficits characteristic of Major Depressive Disorder (MDD). Methods: We used a sequential economic decision-making task designed to emulate a volatile stock market to assess choice behavior in adults with or without MDD (Total N=178); a subset of these participants completed the task during functional MRI (N=53). The task allowed participants to make either positive ('invest') or negative ('short') bets, under either positive or negative contextual valence, defined by whether the immediately preceding stock price change was positive or negative. Fictive errors were defined as the difference between realized and best-possible outcomes. Results: Across the full cohort, group differences in behavioral adjustments to fictive error signals emerged exclusively under negative contextual valence, when stock prices decreased. Compared with controls, participants with MDD showed heightened sensitivity to invest-and-loss fictive errors, reflected in a greater reduction in subsequent bets (interaction beta = -0.63, p < .001), but blunted adjustment to short-and-gain fictive errors (beta = -0.86, p < .001). In the imaging cohort, blunted short-and-gain adjustment was accompanied by heightened anterior cingulate (ACC) activity and attenuated ventromedial prefrontal (vmPFC)-to-ACC coupling in MDD. vmPFC activity following negative market returns also tracked depression symptom severity. Conclusions: Depression selectively disrupts the use of counterfactual outcomes to guide adaptive choice under negative contextual valence, implicating altered frontocingulate function in maladaptive decision-making.