What Does the Frontopolar Cortex Contribute to Goal-Directed Cognition and Action?

Understanding the unique functions of different subregions of primate prefrontal cortex has been a longstanding goal in cognitive neuroscience. Yet, the anatomy and function of one of its largest subregions (the frontopolar cortex) remain enigmatic and underspecified. Our Society for Neuroscience minisymposium Primate Frontopolar Cortex: From Circuits to Complex Behaviors will comprise a range of new anatomic and functional approaches that have helped to clarify the basic circuit anatomy of the frontal pole, its functional involvement during performance of cognitively demanding behavioral paradigms in monkeys and humans, and its clinical potential as a target for noninvasive brain stimulation in patients with brain disorders. This review consolidates knowledge about the anatomy and connectivity of frontopolar cortex and provides an integrative summary of its function in primates. We aim to answer the question: what, if anything, does frontopolar cortex contribute to goal-directed cognition and action?

Neighborhood Deprivation Shapes Motivational-Neurocircuit Recruitment in Children.

Implementing motivated behaviors on the basis of prior reward is central to adaptive human functioning, but aberrant reward-motivated behavior is a core feature of neuropsychiatric illness. Children from disadvantaged neighborhoods have decreased access to rewards, which may shape motivational neurocircuits and risk for psychopathology. Here, we leveraged the unprecedented neuroimaging data from the Adolescent Brain Cognitive Development (ABCD) study to test the hypothesis that neighborhood socioeconomic disadvantage shapes the functional recruitment of motivational neurocircuits in children. Specifically, via the ABCD study's monetary-incentive-delay task (N = 6,396 children; age: 9-10 years), we found that children from zip codes with a high Area Deprivation Index demonstrate blunted recruitment of striatum (dorsal and ventral nuclei) and pallidum during reward anticipation. In fact, blunted dorsal striatal recruitment during reward anticipation mediated the association between Area Deprivation Index and increased attention problems. These data reveal a candidate mechanism driving elevated risk for psychopathology in children from socioeconomically disadvantaged neighborhoods.

Differing functional mechanisms underlie cognitive control deficits in psychotic spectrum disorders.

Background: Functional underpinnings of cognitive control deficits in unbiased samples (i.e., all comers) of patients with psychotic spectrum disorders (PSD) remain actively debated. While many studies suggest hypofrontality in the lateral prefrontal cortex (PFC) and greater deficits during proactive relative to reactive control, few have examined the full hemodynamic response. Methods: Patients with PSD (n = 154) and healthy controls (n = 65) performed the AX continuous performance task (AX-CPT) during rapid (460 ms) functional neuroimaging and underwent full clinical characterization. Results: Behavioural results indicated generalized cognitive deficits (slower and less accurate) across proactive and reactive control conditions in patients with PSD relative to healthy controls. We observed a delayed/prolonged neural response in the left dorsolateral PFC, the sensorimotor cortex and the superior parietal lobe during proactive control for patients with PSD. These proactive hemodynamic abnormalities were better explained by negative rather than by positive symptoms or by traditional diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR), with subsequent simulations unequivocally demonstrating how these abnormalities could be erroneously interpreted as hypoactivation. Conversely, true hypoactivity, unassociated with clinical symptoms or DSM-IV-TR diagnoses, was observed within the ventrolateral PFC during reactive control. Limitations: In spite of guidance for AX-CPT use in neuroimaging studies, one-third of patients with PSD could not perform the task above chance and were more clinically impaired. Conclusion: Current findings question the utility of the AX-CPT for neuroimaging-based appraisal of cognitive control across the full spectrum of patients with PSD. Previously reported lateral PFC "hypoactivity" during proactive control may be more indicative of a delayed/prolonged neural response, important for rehabilitative purposes. Negative symptoms may better explain certain behavioural and hemodynamic abnormalities in patients with PSD relative to DSM-IV-TR diagnoses.

Impaired Valuation Leads to Increased Apathy Following Ventromedial Prefrontal Cortex Damage.

Apathy is defined by reduced goal-directed behavior, and is common in patients with damage to the ventromedial prefrontal cortex (vmPFC). Separately, in neuroeconomics research, the vmPFC has been shown to play a role in reward processing-namely, in "stimulus valuation," or the computation of the subjective reward value of a stimulus. Here, we used a sample of patients with focal brain lesions (N = 93) and matched healthy controls (N = 21) to determine whether the association between vmPFC damage and increased apathy is driven by impaired valuation. An auction task was used to measure valuation, and apathy was assessed via caregiver ratings of patients' day-to-day behavior. Lesion-symptom mapping identified the locus of impaired valuation in the vmPFC, and patients with damage to this region demonstrated increased apathy relative to patients with damage to dorsomedial prefrontal cortex (dmPFC), patients with damage to other brain regions, and healthy controls. Critically, the association between vmPFC damage and apathy was mediated by impaired valuation, with no effect as a function of dmPFC damage. Our results implicate a valuation-based mechanism underlying the relationship between vmPFC integrity and apathy, bridging findings from both the clinical literature and neuroeconomics research.

Social Mimicry Enhances Mu-Suppression During Action Observation.

During social interactions, there is a tendency for people to mimic the gestures and mannerisms of others, which increases liking and rapport. Psychologists have extensively studied the antecedents and consequences of mimicry at the social level, but the neural basis of this behavior remains unclear. Many researchers have speculated that mimicry is related to activity in the human mirror system (HMS), a network of parietofrontal regions that are involved in both action execution and observation. However, activity of the HMS during reciprocal social interactions involving mimicry has not been demonstrated. Here, we took an electroencephalographic (EEG) index of mirror activity-mu-suppression during action observation-in a pretest/post-test design with 1 of 3 intervening treatments: 1) social interaction in which the participant was mimicked, 2) social interaction without mimicry, or 3) an innocuous computer task, not involving another human agent. The change in mu-suppression from pre- to post-test varied as a function of the intervening treatment, with participants who had been mimicked showing an increase in mu-suppression during the post-treatment action observation session. We propose that this specific modulation of HMS activity as a function of mimicry constitutes the first direct evidence for mirror system involvement in real social mimicry.

Exploration versus exploitation decisions in the human brain: A systematic review of functional neuroimaging and neuropsychological studies.

Thoughts and actions are often driven by a decision to either explore new avenues with unknown outcomes, or to exploit known options with predictable outcomes. Yet, the neural mechanisms underlying this exploration-exploitation trade-off in humans remain poorly understood. This is attributable to variability in the operationalization of exploration and exploitation as psychological constructs, as well as the heterogeneity of experimental protocols and paradigms used to study these choice behaviours. To address this gap, here we present a comprehensive review of the literature to investigate the neural basis of explore-exploit decision-making in humans. We first conducted a systematic review of functional magnetic resonance imaging (fMRI) studies of exploration-versus exploitation-based decision-making in healthy adult humans during foraging, reinforcement learning, and information search. Eleven fMRI studies met inclusion criterion for this review. Adopting a network neuroscience framework, synthesis of the findings across these studies revealed that exploration-based choice was associated with the engagement of attentional, control, and salience networks. In contrast, exploitation-based choice was associated with engagement of default network brain regions. We interpret these results in the context of a network architecture that supports the flexible switching between externally and internally directed cognitive processes, necessary for adaptive, goal-directed behaviour. To further investigate potential neural mechanisms underlying the exploration-exploitation trade-off we next surveyed studies involving neurodevelopmental, neuropsychological, and neuropsychiatric disorders, as well as lifespan development, and neurodegenerative diseases. We observed striking differences in patterns of explore-exploit decision-making across these populations, again suggesting that these two decision-making modes are supported by independent neural circuits. Taken together, our review highlights the need for precision-mapping of the neural circuitry and behavioural correlates associated with exploration and exploitation in humans. Characterizing exploration versus exploitation decision-making biases may offer a novel, trans-diagnostic approach to assessment, surveillance, and intervention for cognitive decline and dysfunction in normal development and clinical populations.

Hypoactivation of ventromedial frontal cortex in major depressive disorder: an MEG study of the Reward Positivity.

Background: The Reward Positivity (RewP) is sensitive and specific electrophysiological marker of reward receipt. These characteristics make it a compelling candidate marker of dysfunctional reward processing in major depressive disorder. We previously proposed that the RewP is a nexus of multiple aspects of reward variance, and that a diminished RewP in depression might only reflect a deficit in some of this variance. Specifically, we predicted a diminished ventromedial contribution in depression in the context of maintained reward learning. Methods: Here we collected magnetoencephalographic (MEG) recordings of reward receipt in 43 individuals with major depressive disorder (MDD group) and 38 healthy controls (CTL group). MEG allows effective source estimation due to the absence of volume conduction that compromises electroencephalographic recordings. Results: The MEG RewP analogue was generated by a broad set of cortical areas, yet only right ventromedial and right ventral temporal areas were diminished in MDD. These areas correlated with a principal component of anhedonia derived from multiple questionnaires. Compellingly, BA25 was the frontal region with the largest representation in both of these effects. Conclusions: These findings not only advance our understanding underlying the computation of the RewP, but they also dovetail with convergent findings from other types of functional source imaging in depression, as well as from deep brain stimulation treatments. Together, these discoveries suggest that the RewP may be a valuable marker for objective assessment of reward affect and its disruption in major depression.

Multifaceted neural and vascular pathologies after pediatric mild traumatic brain injury.

Dynamic changes in neurodevelopment and cognitive functioning occur during adolescence, including a switch from reactive to more proactive forms of cognitive control, including response inhibition. Pediatric mild traumatic brain injury (pmTBI) affects these cognitions immediately post-injury, but the role of vascular versus neural injury in cognitive dysfunction remains debated. This study consecutively recruited 214 sub-acute pmTBI (8-18 years) and age/sex-matched healthy controls (HC; N = 186), with high retention rates (>80%) at four months post-injury. Multimodal imaging (functional MRI during response inhibition, cerebral blood flow and cerebrovascular reactivity) assessed for pathologies within the neurovascular unit. Patients exhibited increased errors of commission and hypoactivation of motor circuitry during processing of probes. Evidence of increased/delayed cerebrovascular reactivity within motor circuitry during hypercapnia was present along with normal perfusion. Neither age-at-injury nor post-concussive symptom load were strongly associated with imaging abnormalities. Collectively, mild cognitive impairments and clinical symptoms may continue up to four months post-injury. Prolonged dysfunction within the neurovascular unit was observed during proactive response inhibition, with preliminary evidence that neural and pure vascular trauma are statistically independent. These findings suggest pmTBI is characterized by multifaceted pathologies during the sub-acute injury stage that persist several months post-injury.

Social interaction enhances motor resonance for observed human actions.

Understanding the neural basis of social behavior has become an important goal for cognitive neuroscience and a key aim is to link neural processes observed in the laboratory to more naturalistic social behaviors in real-world contexts. Although it is accepted that mirror mechanisms contribute to the occurrence of motor resonance (MR) and are common to action execution, observation, and imitation, questions remain about mirror (and MR) involvement in real social behavior and in processing nonhuman actions. To determine whether social interaction primes the MR system, groups of participants engaged or did not engage in a social interaction before observing human or robotic actions. During observation, MR was assessed via motor-evoked potentials elicited with transcranial magnetic stimulation. Compared with participants who did not engage in a prior social interaction, participants who engaged in the social interaction showed a significant increase in MR for human actions. In contrast, social interaction did not increase MR for robot actions. Thus, naturalistic social interaction and laboratory action observation tasks appear to involve common MR mechanisms, and recent experience tunes the system to particular agent types.

Automatic imitation is automatic, but less so for narcissists.

Imitation is a fundamentally important human capability and has been the topic of considerable research in the behavioural sciences. One paradigm for investigating the basic nature of imitation is the "automatic imitation" paradigm. In this paradigm, participants are symbolically cued to make a particular response, whilst being incidentally exposed to a congruent or incongruent motor action performed by another person. The robust finding is that when the incidental action is incongruent with the cued action, participants are slower to respond than when it is congruent. Despite the name given to this paradigm, the extent to which the imitative tendency involved is actually automatic remains unclear. Here, we manipulated the probability of congruent and incongruent trials within blocks to assess the effects of expectation on the imitative process. In addition, we determined whether an individual difference variable related to how people process others' behaviour-narcissism-affected the automaticity of imitation. Our results confirm that imitation as observed in this paradigm is robust in the face of expectation. However, the degree to which expectation modulates automatic imitation was enhanced for individuals who scored higher on a narcissism inventory. Together, these results suggest that imitation in the automatic imitation paradigm is indeed largely automatic, but that individual differences in narcissism can change the extent to which imitative behaviour manifests.

Affective imagery boosts the reward related delta power in hazardous drinkers.

The Reward Positivity (RewP) is an event-related potential component with a delta band spectral representation that is elicited by reward receipt. Evidence suggests that RewP is modulated by both reward probability as well as affective valuation ("liking"). Here we determined whether RewP is a marker of enhanced hedonic salience of alcohol images in hazardous drinkers. We recruited 54 participants (Hazardous Drinkers = 28, Control = 26) who completed a reinforcement learning task with affective versus alcohol imagery during feedback. The learning task used images of puppies vs. alcohol paired with reinforcing feedback. Both groups rated categories of affective images (puppies, scenery, babies, neutral) similarly, but the hazardous drinking group rated alcohol significantly higher. There were no group differences in performance or in RewP amplitudes, even as a function of alcohol imagery. Contrary to prior findings, we did not observe a significant correlation between alcohol image rating and alcohol-specific RewP amplitude, although we did observe this relationship with the alcohol-specific delta band spectral representation of RewP. Within hazardous drinking group, there was significant correlation between hazardous drinking (AUDIT score) and alcohol-specific RewP indicating an inter-individual influence of drinking habits on affect specific RewP. These findings suggest a domain-specific enhancement of reward responsiveness in hazardous drinkers.

Electrophysiological Markers of Aberrant Cue-Specific Exploration in Hazardous Drinkers.

Background: Hazardous drinking is associated with maladaptive alcohol-related decision-making. Existing studies have often focused on how participants learn to exploit familiar cues based on prior reinforcement, but little is known about the mechanisms that drive hazardous drinkers to explore novel alcohol cues when their value is not known. Methods: We investigated exploration of novel alcohol and non-alcohol cues in hazardous drinkers (N = 27) and control participants (N = 26) during electroencephalography (EEG). A normative computational model with two free parameters was fit to estimate participants' weighting of the future value of exploration and immediate value of exploitation. Results: Hazardous drinkers demonstrated increased exploration of novel alcohol cues, and conversely, increased probability of exploiting familiar alternatives instead of exploring novel non-alcohol cues. The motivation to explore novel alcohol stimuli in hazardous drinkers was driven by an elevated relative future valuation of uncertain alcohol cues. P3a predicted more exploratory decision policies driven by an enhanced relative future valuation of novel alcohol cues. P3b did not predict choice behavior, but computational parameter estimates suggested that hazardous drinkers with enhanced P3b to alcohol cues were likely to learn to exploit their immediate expected value. Conclusions: Hazardous drinkers did not display atypical choice behavior, different P3a/P3b amplitudes, or computational estimates to novel non-alcohol cues-diverging from previous studies in addiction showing atypical generalized explore-exploit decisions with non-drug-related cues. These findings reveal that cue-specific neural computations may drive aberrant alcohol-related decision-making in hazardous drinkers-highlighting the importance of drug-relevant cues in studies of decision-making in addiction.

Resonating with others: the effects of self-construal type on motor cortical output.

"Self-construal" refers to how individuals view and make meaning of the self, and at least two subtypes have been identified. Interdependent self-construal is a view of the self that includes relationships with others, and independent self-construal is a view of the self that does not include relations with others. It has been suggested that priming these two types of self-construal affects the cognitive processing style that an individual adopts, especially with regard to context sensitivity. Specifically, an interdependent self-construal is thought to promote attention to others and social context to a greater degree than an independent self-construal. To investigate this assertion, we elicited motor-evoked potentials with transcranial magnetic stimulation during an action observation task in which human participants were presented with either interdependent or independent self-construal prime words. Priming interdependent self-construal increased motor cortical output whereas priming independent self-construal did not, compared with a no-priming baseline condition. These effects, likely mediated by changes in the mirror system, essentially tune the individual to, or shield the individual from, social input. Interestingly, the pattern of these self-construal-induced changes in the motor system corroborates with previously observed self-construal effects on overt behavioral mimicry in social settings, and as such, our results provide strong evidence that motor resonance likely mediates nonconscious mimicry in social settings. Finally, these self-construal effects may lead to the development of interventions for disorders of deficient or excessive social influence, like certain autism spectrum and compulsive imitative disorders.

The neurocomputational bases of explore-exploit decision-making.

Flexible decision-making requires animals to forego immediate rewards (exploitation) and try novel choice options (exploration) to discover if they are preferable to familiar alternatives. Using the same task and a partially observable Markov decision process (POMDP) model to quantify the value of choices, we first determined that the computational basis for managing explore-exploit tradeoffs is conserved across monkeys and humans. We then used fMRI to identify where in the human brain the immediate value of exploitative choices and relative uncertainty about the value of exploratory choices were encoded. Consistent with prior neurophysiological evidence in monkeys, we observed divergent encoding of reward value and uncertainty in prefrontal and parietal regions, including frontopolar cortex, and parallel encoding of these computations in motivational regions including the amygdala, ventral striatum, and orbitofrontal cortex. These results clarify the interplay between prefrontal and motivational circuits that supports adaptive explore-exploit decisions in humans and nonhuman primates.

Alexithymia.

Humans are highly adept at differentiating, regulating, and responding to their emotions. At the core of all these functions is emotional awareness: the conscious feeling states that are central to human mental life. Disrupted emotional awareness-a subclinical construct commonly referred to as alexithymia-is present in a range of psychiatric and neurological disorders and can have a deleterious impact on functional outcomes and treatment response. This chapter is a selective review of the current state of the science on alexithymia. We focus on two separate but related issues: (i) the functional deficits associated with alexithymia and what they reveal about the importance of emotional awareness for shaping normative human functioning, and (ii) the neural correlates of alexithymia and what they can inform us about the biological bases of emotional awareness. Lastly, we outline challenges and opportunities for alexithymia research, focusing on measurement issues and the potential utility of formal computational models of emotional awareness for advancing the fields of clinical and affective science.

Association between alexithymia and impaired reward valuation in patients with fronto-insular damage.

Humans compute the anticipated reward value of stimuli in their environment in order to behave in an adaptive, goal-directed manner. This reward valuation ability is vital, and its disruption in a range of clinical populations has profound personal and social consequences. However, research has often failed to consider the reward-related functions of a central component of human emotion: conscious emotional experience. Alexithymia-a condition characterized by diminished conscious awareness of one's emotions-offers a unique opportunity to examine the link between emotional awareness and reward valuation. In the present study, we measured both acquired alexithymia and reward valuation ability in a large sample of patients with traumatic brain injuries (N = 112). Behavioral analyses provided evidence for a negative association between alexithymia and reward valuation ability. This association remained significant after controlling for several covariates in the model (anxiety, depression, posttraumatic stress disorder, and IQ). Voxel-based lesion-symptom mapping was carried out to identify brain regions-of-interest (ROIs) that, when damaged, lead to increased alexithymia and impaired reward valuation. Importantly, mediation models computed using the ROIs identified through the voxel-based lesion-symptom mapping revealed a specific indirect effect of left frontoinsular damage on impaired valuation that was mediated by increased levels of alexithymia. This indirect effect was not observed for any of the other candidate ROIs. The present study identifies a network of brain regions likely to be involved in the integration of subjective feelings and reward processes critical for the adaptive control of goal-directed behavior. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Components of Executive Control in Autism Spectrum Disorder: A Functional Magnetic Resonance Imaging Examination of Dual-Mechanism Accounts.

BACKGROUND: It remains unclear whether executive control (EC) deficits in autism spectrum disorder (ASD) represent a failure in proactive EC (engaged and maintained before a cognitively demanding event) or in reactive EC (engaged transiently as the event occurs). We addressed this question by administering a paradigm investigating components of EC in a sample of individuals with ASD and typically developing individuals during functional magnetic resonance imaging. METHODS: During functional magnetic resonance imaging, 141 participants (64 ASD, 77 typically developing) completed a rapid preparing to overcome prepotency task that required participants to respond to an arrow probe based on the color of an initially presented cue. We examined functional recruitment and connectivity in the frontoparietal task control, cingulo-opercular task control, salience, and default mode networks during cue and probe phases of the task. RESULTS: ASD participants showed evidence of behavioral EC impairment. Analyses of functional recruitment and connectivity revealed that ASD participants showed significantly greater activity during the cue in networks associated with proactive control processes, but on the less cognitively demanding trials. On the more cognitively demanding trials, cue activity was similar across groups. During the probe, connectivity between regions associated with reactive control processes was uniquely enhanced on more-demanding (relative to less-demanding) trials in individuals with ASD but not in typically developing individuals. CONCLUSIONS: The current data suggest that rather than arising from a specific failure to engage proactive or reactive forms of EC, the deficits in EC commonly observed in ASD may be due to reduced proactive EC and a consequent overreliance on reactive EC on more cognitively demanding tasks.

Ventromedial Prefrontal-Anterior Cingulate Hyperconnectivity and Resilience to Apathy in Traumatic Brain Injury.

Apathy is a common and impairing sequela of traumatic brain injury (TBI). Yet, little is known about the neural mechanisms determining in which patients apathy does or does not develop post-TBI. We aimed to elucidate the impact of TBI on motivational neural circuits and how this shapes apathy over the course of TBI recovery. Resting-state functional magnetic resonance imaging data were collected in patients with subacute mild TBI (n = 44), chronic mild-to-moderate TBI (n = 26), and nonbrain-injured control participants (CTRL; n = 28). We measured ventromedial prefrontal cortex (vmPFC) functional connectivity (FC) as a function of apathy, using an a priori vmPFC seed adopted from a motivated decision-making study in an independent TBI study cohort. Patients reported apathy using a well-validated tool for assaying apathy in TBI. The vmPFC-to-wholebrain FC was contrasted between groups, and we fit regression models with apathy predicting vmPFC FC. Subacute and chronic TBI caused increased apathy relative to CTRL, replicating previous work suggesting that apathy has an enduring impact in TBI. The vmPFC was functionally connected to the canonical default network, and this architecture did not differ between subacute TBI, chronic TBI, and CTRL groups. Critically, in TBI, increased apathy scores predicted decreased vmPFC-dorsal anterior cingulate cortex (dACC) FC. Last, we subdivided the TBI group based on patients above versus below the threshold for "clinically significant apathy," finding that TBI patients with clinically significant apathy demonstrated comparable vmPFC-dACC FC to CTRLs, whereas TBI patients with subthreshold apathy scores demonstrated vmPFC-dACC hyperconnectivity relative to both CTRLs and patients with clinically significant apathy. Post-TBI vmPFC-dACC hyperconnectivity may represent an adaptive compensatory response, helping to maintain motivation and enabling resilience to the development of apathy after neurotrauma. Given the role of vmPFC-dACC circuits in value-based decision making, rehabilitation strategies designed to improve this ability may help to reduce apathy and improve functional outcomes in TBI.

Incidental action observation modulates muscle activity.

Similar circuits in the brain are engaged during the performance and observation of identical actions. Such engagement manifests in priming effects, where observation of an action leads to faster production of that action and slower production of an action involving a different movement of the same effector (e.g. observed finger flexion vs. produced finger extension), or a completely different effector (e.g. observed hand action vs. produced leg action). Here, we asked whether priming occurs for actions involving identical muscle groups where the degree of muscle contraction in observed actions was the same or different to that underlying an instructed response and whether patterns of muscle activation were also affected. Participants held an unseen rubber ball between their forefinger and thumb and responded to colour cues instructing a hard or a soft squeeze, whilst EMG activity from the first dorsal interosseous and the abductor pollicis brevis was recorded. The colour cues were superimposed on videos depicting a hard or soft squeeze of an identical rubber ball. Thus, there were two congruent (observe hard, produce hard; observe soft, produce soft) and two incongruent (observe hard, produce soft; observe soft, produce hard) conditions. Results showed that reaction time was slowed and EMG activity was modulated in the direction of the difference between observed and instructed squeezing movements. Hence, neural circuits underlying action observation are sensitive not only to differences in the actual muscle groups underlying observed actions but also to different extents of activation of the same muscle groups.

Proactive control in adolescents and young adults with autism spectrum disorder: Unimpaired but associated with symptoms of depression.

Although autism spectrum disorder (ASD) is characterized by deficits in cognitive control, our previous work has shown that preparatory, goal-directed cognitive processing (proactive control) may be preserved in children with ASD. We investigated whether proactive control is intact in adolescents and young adults with ASD, as well as how symptoms of ASD (repetitive behaviors) and psychopathology (Depressive, Anxiety, and Attention-Deficit/Hyperactivity Problems) are related to proactive control. Participants were adolescents and young adults with ASD (N = 44) and typical development (TD; N = 44). Proactive control was assessed using a picture-word Stroop paradigm where participants named animals depicted in drawings while ignoring a superimposed written animal word. Interference effects (reaction time (RT) differences between more difficult incongruent trials, where animal pictures and words prompted different responses, and simpler congruent trials, where animal pictures and words prompted the same response) were calculated for two versions of the Stroop Task: a mostly congruent (MC) block, where the majority of trials were congruent, and a mostly incongruent (MI) block, where most trials were incongruent. Proactive control was calculated as the reduction in interference in the MI block in comparison to the MC block. Proactive control did not differ between groups, indicating that proactive control is not impaired in adolescents and young adults with ASD. In ASD, depression symptoms were associated with reduced proactive control. Future research should investigate the effects of interventions targeting depression as well as interventions targeting proactive control processes in individuals with ASD and comorbid depression. (PsycInfo Database Record (c) 2020 APA, all rights reserved).