Activity In Medial Prefrontal Cortex Research Articles

Medial prefrontal activity during self-other judgments is modulated by relationship need fulfillment

ABSTRACT The medial prefrontal cortex (MPFC) plays an important role in representing semantic self-knowledge. Studies comparing semantic self-judgments with judgments of close others suggest that interpersonal closeness may influence the degree to which the MPFC differentiates self and other. We used optical neuroimaging to examine if support for competence, relatedness, and autonomy from relationship partners moderates MPFC activity during a personality judgment task. Participants (N = 109) were asked to judge the descriptive accuracy of trait adjectives for both themselves and a friend. Participants who reported lower need fulfillment with their friend showed elevated activity only in the self-judgment condition; in contrast, participants who reported higher need fulfillment with their friend showed similarly high levels of MPFC activity across the conditions. These results are consistent with the idea that the MPFC differentially represents others on the basis of the need fulfillment experienced within the relationship.

Not the Master of Your Volitional Mind? The Roles of the Right Medial Prefrontal Cortex and Personality Traits in Unconscious Introjections Versus Self-Chosen Goals.

Humans are unconditionally confronted with social expectations and norms, up to a degree that they, or some of them, have a hard time recognizing what they actually want. This renders them susceptible for introjection, that is, to unwittingly or “unconsciously” mistake social expectations for self-chosen goals. Such introjections compromise an individual’s autonomy and mental health and have been shown to be more prevalent in individuals with rumination tendencies and low emotional self-awareness. In this brain imaging study, we draw on a source memory task and found that introjections, as indicated by imposed tasks that are falsely recognized as self-chosen, involved the bilateral medial prefrontal cortex (MPFC) and the dorsal anterior cingulate cortex (ACC). Notably, reduced right MPFC activation within this condition correlated with trait scores of ruminations and reduced emotional self-awareness, but also introversion. Moreover, correct recognition of tasks as self-chosen involved the right MPFC. Accordingly, the right MPFC may play a role in supporting the maintenance of psychological autonomy and counteract introjection, which individuals with certain personality traits seem to be prone to. This research has significant implications for the study of mechanisms underlying autonomous motivation, goal and norm internalization, decision-making, persuasion, education, and clinical conditions such as depression and burnout.

P231. Medial Prefrontal Cortex Activation to Reward Outcome Moderates Influence of Sexual Orientation Victimization in Adolescents and Young Adults

Sexual minority youth (SMY) are at greater risk for depression than heterosexual counterparts. Minority stress theory posits that sexual orientation victimization acts as a chronic stressor to influence depression. For those responsive to stress, stress may worsen depression by altering activity in neural reward systems. This study examines whether orientation victimization impacts neural reward activity and depression, and whether these relationships differ by SMY status.

Differences in working memory coding of biological motion attributed to oneself and others.

The question how the brain distinguishes between information about self and others is of fundamental interest to both philosophy and neuroscience. In this functional magnetic resonance imaging (fMRI) study, we sought to distinguish the neural substrates of representing a full‐body movement as one's movement and as someone else's movement. Participants performed a delayed match‐to‐sample working memory task where a retained full‐body movement (displayed using point‐light walkers) was arbitrarily labeled as one's own movement or as performed by someone else. By using arbitrary associations we aimed to address a limitation of previous studies, namely that our own movements are more familiar to us than movements of other people. A searchlight multivariate decoding analysis was used to test where information about types of movement and about self‐association was coded. Movement specific activation patterns were found in a network of regions also involved in perceptual processing of movement stimuli, however not in early sensory regions. Information about whether a memorized movement was associated with the self or with another person was found to be coded by activity in the left middle frontal gyrus (MFG), left inferior frontal gyrus (IFG), bilateral supplementary motor area, and (at reduced threshold) in the left temporoparietal junction (TPJ). These areas are frequently reported as involved in action understanding (IFG, MFG) and domain‐general self/other distinction (TPJ). Finally, in univariate analysis we found that selecting a self‐associated movement for retention was related to increased activity in the ventral medial prefrontal cortex.

Activity Subspaces in Medial Prefrontal Cortex Distinguish States of the World.

Medial prefrontal cortex (mPfC) activity represents information about the state of the world, including present behavior, such as decisions, and the immediate past, such as short-term memory. Unknown is whether information about different states of the world are represented in the same mPfC neural population and, if so, how they are kept distinct. To address this, we analyze here mPfC population activity of male rats learning rules in a Y-maze, with self-initiated choice trials to an arm end followed by a self-paced return during the intertrial interval (ITI). We find that trial and ITI population activity from the same population fall into different low-dimensional subspaces. These subspaces encode different states of the world: multiple features of the task can be decoded from both trial and ITI activity, but the decoding axes for the same feature are roughly orthogonal between the two task phases, and the decodings are predominantly of features of the present during the trial but features of the preceding trial during the ITI. These subspace distinctions are carried forward into sleep, where population activity is preferentially reactivated in post-training sleep but differently for activity from the trial and ITI subspaces. Our results suggest that the problem of interference when representing different states of the world is solved in mPfC by population activity occupying different subspaces for the world states, which can be independently decoded by downstream targets and independently addressed by upstream inputs.SIGNIFICANCE STATEMENT Activity in the medial prefrontal cortex plays a role in representing the current and past states of the world. We show that during a maze task, the activity of a single population in medial prefrontal cortex represents at least two different states of the world. These representations were sequential and sufficiently distinct that a downstream population could separately read out either state from that activity. Moreover, the activity representing different states is differently reactivated in sleep. Different world states can thus be represented in the same medial prefrontal cortex population but in such a way that prevents potentially catastrophic interference between them.

Using fNIRS to Identify Transparency- and Reliability-Sensitive Markers of Trust Across Multiple Timescales in Collaborative Human-Human-Agent Triads.

Intelligent agents are rapidly evolving from assistants into teammates as they perform increasingly complex tasks. Successful human-agent teams leverage the computational power and sensory capabilities of automated agents while keeping the human operator's expectation consistent with the agent's ability. This helps prevent over-reliance on and under-utilization of the agent to optimize its effectiveness. Research at the intersection of human-computer interaction, social psychology, and neuroergonomics has identified trust as a governing factor of human-agent interactions that can be modulated to maintain an appropriate expectation. To achieve this calibration, trust can be monitored continuously and unobtrusively using neurophysiological sensors. While prior studies have demonstrated the potential of functional near-infrared spectroscopy (fNIRS), a lightweight neuroimaging technology, in the prediction of social, cognitive, and affective states, few have successfully used it to measure complex social constructs like trust in artificial agents. Even fewer studies have examined the dynamics of hybrid teams of more than 1 human or 1 agent. We address this gap by developing a highly collaborative task that requires knowledge sharing within teams of 2 humans and 1 agent. Using brain data obtained with fNIRS sensors, we aim to identify brain regions sensitive to changes in agent behavior on a long- and short-term scale. We manipulated agent reliability and transparency while measuring trust, mental demand, team processes, and affect. Transparency and reliability levels are found to significantly affect trust in the agent, while transparency explanations do not impact mental demand. Reducing agent communication is shown to disrupt interpersonal trust and team cohesion, suggesting similar dynamics as human-human teams. Contrasts of General Linear Model analyses identify dorsal medial prefrontal cortex activation specific to assessing the agent's transparency explanations and characterize increases in mental demand as signaled by dorsal lateral prefrontal cortex and frontopolar activation. Short scale event-level data is analyzed to show that predicting whether an individual will trust the agent, with data from 15 s before their decision, is feasible with fNIRS data. Discussing our results, we identify targets and directions for future neuroergonomics research as a step toward building an intelligent trust-modulation system to optimize human-agent collaborations in real time.

The effects of age-bias on neural correlates of successful and unsuccessful response inhibition

Response inhibition is important for adherence to social norms, especially when norms conflict with biases based on one’s social identity. While previous studies have shown that in-group bias generally modulates neural activity related to stimulus appraisal, it is unclear whether and how an in-group bias based on age affects neural information processing during response inhibition. To assess this potential influence, young adults completed a Go/NoGo task incorporating younger face (in-group) and older face (out-group) stimuli while undergoing functional magnetic resonance imaging (fMRI). Our results replicated previous findings by demonstrating higher accuracy in successful Go compared to NoGo trials, as well as the engagement of nodes of the response inhibition network during successful response inhibition, and brain regions comprising the salience network during unsuccessful response inhibition. Importantly, despite a lack of behavioural differences, our results showed that younger and older face stimuli modulated activity in the response inhibition and salience networks during successful and unsuccessful inhibition, respectively. Interestingly, these effects were not uniform across networks. During successful response inhibition, in-group stimuli increased activity in medial prefrontal cortex and temporo-parietal junction, whereas out-group stimuli more strongly engaged pre-supplemental motor area. During unsuccessful response inhibition, in-group stimuli increased activity in posterior insula, whereas out-group stimuli more strongly engaged angular gyrus and intraparietal sulcus. Consequently, the results infer the presence of an age-bias effect in the context of inhibitory control, which has substantial implications for future experimental design and may also provide the means of investigating the neural correlates of implicit beliefs that contribute to ageism.

Cognitive neural mechanisms underlying the impact of oxytocin on fear acquisition and extinction

<p id="p00005">Fear is a biologically adaptive response to environmental threats, and fear learning plays a key role in adaptive function. However, maladaptive fear learning underlies emotional disorders, such as anxiety and posttraumatic stress disorder (PTSD). Together with the development of cognitive neuroscience and the integration of multidisciplinary research, the study on the cognitive neural mechanism of fear has become a hot topic in the field of emotion. Using the classical fear conditioning paradigm, researchers have identified the brain circuits of fear learning and extinction. Specifically, extensive imaging researches have revealed several key regions involved in fear acquisition, including the amygdala, insula, dorsal anterior cingulate (dACC) and thalamus. Moreover, the amygdala, hippocampus and ventromedial prefrontal cortex (vmPFC) served key roles in fear memory consolidation and reconsolidation, and the amygdala, hippocampus, vmPFC, and dACC are required for fear extinction. Cumulative evidence has suggested that oxytocin plays a crucial role in the process of fear acquisition, fear consolidation and fear extinction. Therefore, firstly, we summarized the paradigms of fear acquisition and fear extinction as well as the cognitive neural mechanisms of fear acquisition and fear extinction based on the fingdings of corresponding meta-analyses. Secondly, we focused on the cognitive neural mechanisms underlying the impact of oxytocin on fear acquisition and fear extinction. Next, we summarized the neurobiological circuits of oxytocin influence on fear emotion processing. Finally, we prospected the future researches on the cognitive neural mechanisms underlying the impact of oxytocin on fear processing. The present study sheds insights into the cognitive neural mechanisms underlying the impact of oxytocin on fear processing. Moreover, the present study provides an potential treatment for the fear-related disorders. <p id="p00006">Oxytocin has been shown to facilitate fear acquisition as it affects brain activity in several regions including amygdala, prefrontal cortex, anterior cingulate gyrus, insula and hippocampus, as well as the functional connectivity between them. Oxytocin also enhances fear extinction by regulating amygdala and medial prefrontal cortex activity, as well as enhancing the functional connectivity between prefrontal cortex and amygdala. Furthermore, oxytocin can regulate the activity of the amygdala, anterior cingulate gyrus, insula, hippocampus, vmPFC and other fear-related brain regions, thus affecting the processes of fear acquisition and extinction. Specifically, cumulative evidence has indicated that intranasal oxytocin attenuates amygdala (hyper)activity and enhances functional coupling of the amygdala with the vmPFC and hippocampus, resulting in increased top-down control over the fear response. In addition, intranasal oxytocin has also been found to attenuate amygdala—brainstem connectivity and to change activity and connectivity in nodes of the salience network (i.e., insula and dACC). Furthermore, oxytocin administration may enhance social behavior through modulating the hypothalamus—pituitary—adrenal (HPA) axis and autonomic nervous system (ANS) function, which may provide a potential treatment for the fear-related disorders. However, it should be noted that the dose, time and location of oxytocin injection might have different effects on the processes of fear acquisition and extinction. <p id="p00007">Future studies should focus on gender differences, neural network underlying the impact of oxytocin on fear consolidation and reconsolidation and the pathological study examining oxytocin effect on fear emotion processing to better reveal the cognitive neural mechanisms underlying the impact of oxytocin on.

Distinct stress-related medial prefrontal cortex activation in women with depression with and without childhood maltreatment.

Emerging evidence has highlighted the moderating effect of childhood maltreatment (CM) in shaping neurobiological abnormalities in major depressive disorder (MDD). However, whether neural mechanisms underlying stress sensitivity in MDD are affected by the history of CM is unclear. Two hundred and thirteen medication-free female participants were recruited for a functional magnetic resonance imaging study assessing the effects of psychosocial stress on neural responses. The Montreal Imaging Stress Task was administrated to 44 female MDD patients with CM (MDD/CM), 32 female MDD patients without CM (MDD/noCM), 43 female healthy controls (HCs) with CM (HC/CM), and 94 female HCs without CM (HC/noCM). A CM (CM, noCM) × diagnosis (MDD, HC) whole-brain voxel-wise analysis was run to assess putative group differences in neural stress responses. A significant CM × Diagnosis interaction emerged in the medial prefrontal cortex (mPFC). Bonferroni-corrected simple effects analysis clarified that (1) the MDD/CM group had less mPFC deactivation than the HC/CM group, (2) the MDD/noCM group exhibited greater mPFC deactivation than the HC/noCM group, and (3) the MDD/CM group exhibited less mPFC deactivation relative to the MDD/noCM group. In addition, the mPFC-seed psychophysiological interaction analysis revealed that individuals in the CM groups had significantly greater stress-related mPFC-left superior frontal gyrus and mPFC-right posterior cerebellum connectivity relative to the noCM groups. Findings highlight distinct neural abnormalities in MDD depending on prior CM history, particularly potentiated stress-related mPFC recruitment among MDD individuals reporting CM. Moreover, CM history was generally associated with the disruption in functional connectivity centered on the mPFC.

The acute effects of different doses of tramadol on neuronal activity of medial prefrontal cortex in rats

Background:Tramadol is an opioid analgesic with monoamine reuptake inhibitory effects. Although tramadol has been widely used to control pain, there is controversy about the risk of abuse. Therefore, in the present study, the acute effects of tramadol on neuronal activity in the medial prefrontal cortex (mPFC), which is one of the important centers of the reward system, were investigated electrophysiologically.Materials and Methods:Tramadol was injected interperitoneally (12.5 and 25 mk/kg) or subcutaneously (40 mg/kg) and its effect on the firing of mPFC neurons was investigated, using in vivo extracellular single unit recording.Results:Tramadol could not significantly affect neural activity in mPFC, suggesting no acute and rapid effect on mPFC.Conclusions:The present results showed that neural activity in mPFC was not rapidly affected by acute application of tramadol. Since the role of mPFC in tramadol addiction has been elucidated, it can be concluded that these effects may be due to delayed responses or chronic use of tramadol.

Benefit from retrieval practice is linked to temporal and frontal activity in healthy young and older humans.

Retrieval practice improves retention of information in long-term memory more than restudy, but the underlying neural mechanisms of this “retrieval practice effect” (RPE) remain poorly understood. Therefore, we investigated the behavioral and neural differences between previously retrieved versus restudied items at final retrieval. Thirty younger (20–30 years old) and twenty-five older (50+ years old) adults learned familiar and new picture stimuli either through retrieval or restudy. At final recognition, hemodynamic activity was measured using functional magnetic resonance imaging (fMRI). Behaviorally, younger and older adults showed similar benefits of retrieval practice, with higher recollection, but unchanged familiarity rates. In a univariate analysis of the fMRI data, activation in medial prefrontal cortex and left temporal regions correlated with an individual’s amount of behavioral benefit from retrieval practice, irrespective of age. Compatible with this observation, in a multivariate representational similarity analysis (RSA), retrieval practice led to an increase in pattern similarity for retested items in a priori defined regions of interest, including the medial temporal lobe, as well as prefrontal and parietal cortex. Our findings demonstrate that retrieval practice leads to enhanced long-term memories in younger and older adults alike, and this effect may be driven by fast consolidation processes.

Treadmill Walking Maintains Dual-Task Gait Performance and Reduces Medial Prefrontal Cortex Activation in Healthy Adults

Treadmill Walking Maintains Dual-Task Gait Performance and Reduces Medial Prefrontal Cortex Activation in Healthy Adults

The passive recipient: Neural correlates of negative self‐view in depression

IntrodctionPrevious studies have argued that people tend to isolate themselves from negative information. This tendency is modulated by the individual's role in social interaction, that is, as an initiative actor (e.g., “I hit Tom”) or a passive recipient (e.g., “Paul hits me”). Depressed patients tend to focus on negative aspects of themselves and cope with situations passively. It is still an open question how the actor/recipient role affects the behavioral and neural responses to self in depression.MethodsThe present study adopted functional magnetic resonance imaging (fMRI) technology to investigate behavioral and neural responses to self (as an actor/recipient) in depressed patients and the matched healthy controls when attributing negative events.ResultsCompared with healthy controls, depressed patients showed more self‐attribution for negative events. Depressed patients showed increased brain activity in the dorsal medial prefrontal cortex (dmPFC) subsystem of the default mode network (DMN) when they played recipient role in self‐related negative events. Activity of the dmPFC subsystem was negatively correlated with depressed patients’ self‐attribution for negative events in recipient condition. While decreased brain activity in the medial temporal lobe (MTL) subsystem was observed in depressed patients when they played the actor or recipient role in self‐related negative events. Activity of the MTL subsystem was negatively correlated with depressed patients’ reaction time when they played recipient role in selfrelated negative events.ConclusionThese results implicated that depressed patients manifested the negative self‐view. Actor/recipient role affected their activation patterns in the DMN which were different from the healthy controls. The correlation between the abnormal brain activations of the DMN and the behavioral performances might manifest more easily when depressed patients played recipient role in negative events.

Neuronal discharge activity in mouse medial prefrontal cortex during associative motor learning

Neuronal discharge activity in mouse medial prefrontal cortex during associative motor learning

Information about others’ choices selectively alters risk tolerance and medial prefrontal cortex activation across adolescence and young adulthood

Adolescence is associated with major changes in the cognitive, emotional and social domains. One domain in which these processes intersect is decision-making. Previous research has shown that individuals’ attitudes towards risk and ambiguity shape their decision-making, and information about others’ choices can influence individuals’ decisions. However, it is currently unknown how information about others’ choices influences risk and ambiguity attitudes separately, and the degree to which others’ choices shape decision-making differentially across development from adolescence to young adulthood. The current study used a computational modeling framework to test how information about others’ choices influences these attitudes. Participants, aged 14–22 years, made a series of risky and ambiguous choices while undergoing fMRI scanning. On some trials, they viewed risky or safe choices of others. Results showed that participants aligned their choices toward the choice preferences of others. Moreover, the tendency to align choices was expressed in changes in risk attitude, but not ambiguity attitude. The change in risk attitude was positively related to neural activation in the medial prefrontal cortex. Results did not show age related differences in behavior and corresponding neural activation, indicating that the manner in which adolescents are influenced by peers is not ubiquitous but rather, is highly context-dependent.

Neural responses to facial attractiveness in the judgments of moral goodness and moral beauty.

The judgments of moral goodness and moral beauty objectively refer to the perception and evaluation of moral traits, which are generally influenced by facial attractiveness. For centuries, people have equated beauty with the possession of positive qualities, but it is not clear whether the association between beauty and positive qualities exerts a similarly implicit influence on people's responses to moral goodness and moral beauty, how it affects those responses, and what is the neural basis for such an effect. The present study is the first to examine the neural responses to facial attractiveness in the judgments of moral goodness and moral beauty. We found that beautiful faces in both moral judgments activated the left ventral occipitotemporal cortices sensitive to the geometric configuration of the faces, demonstrating that both moral goodness and moral beauty required the automatic visual analysis of geometrical configuration of attractive faces. In addition, compared to beautiful faces during moral goodness judgment, beautiful faces during moral beauty judgment induced unique activity in the ventral medial prefrontal cortex and midline cortical structures involved in the emotional-valenced information about attractive faces. The opposite comparison elicited specific activity in the left superior temporal cortex and premotor area, which play a critical role in the recognition of facial identity. Our results demonstrated that the neural responses to facial attractiveness in the process of higher order moral decision-makings exhibit both task-general and task-specific characteristics. Our findings contribute to the understanding of the essence of the relationship between morality and aesthetics.

Post-error Slowing During Instrumental Learning is Shaped by Working Memory-based Choice Strategies

Post-error slowing (PES) – a relative increase in response time for a decision on trialtgiven an error on trialt − 1 – is a well-known effect in studies of human decision-making. Post-error processing is reflected in neural signatures such as reduced activity in sensorimotor regions and increased activity in medial prefrontal cortex. PES is thought to reflect the deployment of executive resources to get task performance back on track. This provides a general account of PES that cuts across perceptual decision-making, memory, and learning tasks. With respect to PES and learning, things are complicated by the fact that learning often reflectsmultiple qualitatively different processes with distinct neural correlates. It is unclear if multiple processes shape PES during learning, or if PES reflects a policy for reacting to errors generated by one particular process (e.g., cortico-striatal reinforcement learning). Here we provide behavioral and computational evidence that PES is influenced by the operation of multiple distinct processes. Human subjects learned a simple visuomotor skill (arbitrary visuomotor association learning) under low load conditionsmore amenable to simple working memory-based strategies, and high load conditions that were putatively more reliant on trial-by-trial reinforcement learning. PES decreased withload, even when the progress of learning (i.e., reinforcement history) was accounted for. This result suggested that PES during learning is influenced by the recruitment of working memory. Indeed, observed PES effects were approximated by a computational model with parallel working memory and reinforcement learning systems that are differentially recruited according to cognitive load.

Modulating medial prefrontal cortex activity using real-time fMRI neurofeedback: Effects on reality monitoring performance and associated functional connectivity

Neuroimaging studies have found ‘reality monitoring’, our ability to distinguish internally generated experiences from those derived from the external world, to be associated with activity in the medial prefrontal cortex (mPFC) of the brain. Here we probe the functional underpinning of this ability using real-time fMRI neurofeedback to investigate the involvement of mPFC in recollection of the source of self-generated information. Thirty-nine healthy individuals underwent neurofeedback training in a between groups study receiving either Active feedback derived from the paracingulate region of the mPFC (21 subjects) or Sham feedback based on a similar level of randomised signal (18 subjects). Compared to those in the Sham group, participants receiving Active signal showed increased mPFC activity over the course of three real-time neurofeedback training runs undertaken in a single scanning session. Analysis of resting state functional connectivity associated with changes in reality monitoring accuracy following Active neurofeedback revealed increased connectivity between dorsolateral frontal regions of the fronto-parietal network (FPN) and the mPFC region of the default mode network (DMN), together with reduced connectivity within ventral regions of the FPN itself. However, only a trend effect was observed in the interaction of the recollection of the source of Imagined information compared with recognition memory between participants receiving Active and Sham neurofeedback, pre- and post- scanning. As such, these findings demonstrate that neurofeedback can be used to modulate mPFC activity and increase cooperation between the FPN and DMN, but the effects on reality monitoring performance are less clear.

Effects of sensory distraction and salience priming on emotion identification in autism: an fMRI study

BackgroundSocial interaction often occurs in noisy environments with many extraneous sensory stimuli. This is especially relevant for youth with autism spectrum disorders (ASD) who commonly experience sensory over-responsivity (SOR) in addition to social challenges. However, the relationship between SOR and social difficulties is still poorly understood and thus rarely addressed in interventions. This study investigated the effect of auditory sensory distracters on neural processing of emotion identification in youth with ASD and the effects of increasing attention to social cues by priming participants with their own emotional faces.MethodsWhile undergoing functional magnetic resonance imaging (fMRI), 30 youth with ASD and 24 typically developing (TD) age-matched controls (ages 8–17 years) identified faces as happy or angry with and without simultaneously hearing aversive environmental noises. Halfway through the task, participants also viewed videos of their own emotional faces. The relationship between parent-rated auditory SOR and brain responses during the task was also examined.ResultsDespite showing comparable behavioral performance on the task, ASD and TD youth demonstrated distinct patterns of neural activity. Compared to TD, ASD youth showed greater increases in amygdala, insula, and primary sensory regions when identifying emotions with noises compared to no sounds. After viewing videos of their own emotion faces, ASD youth showed greater increases in medial prefrontal cortex activation compared to TD youth. Within ASD youth, lower SOR was associated with reduced increased activity in subcortical regions after the prime and greater increased activity in the ventromedial prefrontal cortex after the prime, particularly in trials with noises.ConclusionsThe results suggest that the sensory environment plays an important role in how ASD youth process social information. Additionally, we demonstrated that increasing attention to relevant social cues helps ASD youth engage frontal regions involved in higher-order social cognition, a mechanism that could be targeted in interventions. Importantly, the effect of the intervention may depend on individual differences in SOR, supporting the importance of pre-screening youth for sensory challenges prior to social interventions.

Social cognitive skills groups increase medial prefrontal cortex activity in children with autism spectrum disorder.

Few studies have examined the neural mechanisms of change following social skills interventions for children with autism spectrum disorder (ASD). This study examined the neural effects of social cognitive skills groups during functional MRI (fMRI) tasks of irony comprehension and eye gaze processing in school-aged children with ASD. Verbally fluent children (ages 8-11) were randomized to social cognitive skills groups or facilitated play comparison groups. Behavioral assessments and fMRI scans were obtained at baseline and endpoint (12 weeks). During fMRI, children completed two separate tasks to engage social cognition circuitry: comprehension of potentially ironic scenarios (n= 34) and viewing emotionally expressive faces with direct or averted gaze (n= 24). Whole-brain analyses were conducted to examine neural changes following treatment. Regression analyses were also conducted to explore the relationship between neural and behavioral changes. When comparing the two groups directly, the social cognitive skills group showed greater increases in activity in the medial prefrontal cortex (mPFC), implicated in theory of mind, relative to the comparison group for both irony comprehension and gaze processing tasks. Increased mPFC activity during the irony task was associated with improvement in social functioning on the Social Responsiveness Scale across both groups. Findings indicate that social cognitive skills interventions may increase activity in regions associated with social cognition and mentalizing abilities. LAY SUMMARY: Social skills groups are a common intervention for school-aged children with ASD. However, few studies have examined the neural response to social skills groups in school-aged children with ASD. Here, we report on a study evaluating neural outcomes from an empirically supported social cognitive skills training curriculum using fMRI. This study seeks to understand the effects of targeting emotion recognition and theory of mind on the brain circuitry involved in social cognition in verbally fluent children ages 8-11. Results indicate increased neural activity in the mPFC, a region considered to be a central hub of the "social brain," in children randomized to social cognitive skills groups relative to a comparison group that received a high-quality, child-directed play approach. In addition, increased activation in the mPFC during an irony comprehension task was associated with gains in social functioning across both groups from pre- to post-treatment. This is the first fMRI study of social skills treatment outcomes following a randomized trial with an active treatment condition in school-aged children with ASD.