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.

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.

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.

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.

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?

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.

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.

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.

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).

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.

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.

Evidence for asymmetric inhibitory activity during motor planning phases of sensorimotor synchronization.

Sensorimotor synchronization (SMS) is frequently dependent on coordination of excitatory and inhibitory activity across hemispheres, as well as the cognitive control over environmental distractors. However, the timing (motor planning versus execution) and cortical regions involved in these processes remain actively debated. Functional magnetic resonance imaging data were therefore analyzed from 34 strongly right-handed healthy adults performing a cued (to initiate motor planning) SMS task with either their right or left hand (motor execution phase) based on spatially congruent or incongruent visual stimuli. Behavioral effects of incongruent stimuli were limited to the first stimulus. Functionally, greater activation was observed in left sensorimotor cortex (SMC) and right cerebellar Lobule V for congruent versus incongruent stimuli. A negative blood-oxygen level dependent response, a putative marker of neural inhibition, was present in bilateral SMC, right supplemental motor area (SMA) and bilateral cerebellar Lobule V during the motor planning, but not execution phase. The magnitude of the inhibitory response was greater in right cortical regions and cerebellar Lobule V. Homologue connectivity was associated with inhibitory activity in the right SMA, suggesting that individual differences in intrinsic connectivity may mediate transcallosal inhibition. In summary, results suggest increased inhibition (i.e., greater negative BOLD response) within the right relative to left hemisphere, which was released once motor programs were executed. Both task and intrinsic functional connectivity results highlight a critical role of the left SMA in interhemispheric inhibition and motor planning.

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).

Not So Automatic Imitation: Expectation of Incongruence Reduces Interference in Both Autism Spectrum Disorder and Typical Development.

Research has observed evidence for both hypo-(supposedly due to a broken mirror neuron system) and hyper-(thought to be the result of deficits in adaptive control) imitation in autism spectrum disorder (ASD). This work sought to adjudicate between these findings using an automatic imitation (AI) paradigm with the novel manipulation of the need to engage adaptive control of imitation. Results demonstrated that ASD participants do not display a specific deficit in AI capability, are able to engage in proactive control of AI, and that relative to a well-matched effector condition, AI is not selectively associated with ASD symptom severity. These data cast doubt upon the notion of impairments in imitation or its control in ASD.

Compensatory Hippocampal Recruitment Supports Preserved Episodic Memory in Autism Spectrum Disorder.

BACKGROUND: The degree to which individuals with autism spectrum disorder (ASD) evidence impairments in episodic memory relative to their typically developing (TD) counterparts remains unclear. According to a prominent view, ASD is associated with deficits in encoding associations between items and recollecting precise context details. Here, we evaluated behavioral and neural evidence for this impaired relational binding hypothesis using a task involving relational encoding and recollection during functional magnetic resonance imaging. METHODS: Adolescents and young adults (nASD = 47, nTD = 60) performed the Relational and Item-Specific Encoding task during functional magnetic resonance imaging, including item and associative recognition testing. We modeled functional recruitment within the medial temporal lobes (MTLs), and connectivity between MTL and the posterior medial (PM) network thought to underlie relational memory. The impaired relational binding model would predict a behavioral deficit driven by aberrant recruitment and connectivity of MTL and the PM network. RESULTS: The ASD and TD groups showed indistinguishable item and associative recognition performance. During relational encoding, the ASD group demonstrated increased hippocampal recruitment, and decreased connectivity between MTL and PM regions relative to the TD group. Within ASD, hippocampal recruitment and MTL-PM connectivity were inversely correlated. CONCLUSIONS: The lack of a behavioral deficit in ASD does not support the impaired relational binding hypothesis. Instead, the current data suggest that increased recruitment of the hippocampus compensates for decreased MTL-PM connectivity to support preserved episodic memory in ASD. These findings suggest a compensatory neurodevelopmental mechanism that may support preserved cognitive domains in ASD: local hyperrecruitment may offset connectivity aberrations in individuals with ASD relative to TD subjects.

Proactive control as a double-edged sword in autism spectrum disorder.

Proactive control refers to the active representation of contextual information to bias cognitive processing and facilitate goal-directed behavior. Despite research suggesting that proactive control may be impaired in autism spectrum disorder (ASD), the associations between proactive control and clinical symptoms of ASD remain underspecified. Here, we combined a children's version of the AX Continuous Performance Task (AX-CPT) with gold standard clinical assessments in children with ASD (N = 34) or typical development (TYP; N = 45). After controlling for full-scale IQ (FSIQ), measures of proactive control were similar between ASD and TYP. However, specifically within ASD we observed paradoxical relationships between proactive control and clinical symptoms. Increased reliance on proactive control was associated with reduced attention problems and increased restricted and repetitive behaviors in ASD. Therefore, proactive control appears to represent a double-edged sword in ASD: improved attentional control at the cost of heightened behavioral inflexibility. This represents a compelling and new characterization of the specific association between cognitive control processes isolated in computerized laboratory tasks and the multidimensional cognitive symptoms characteristic of ASD. (PsycINFO Database Record

Insula-Retrosplenial Cortex Overconnectivity Increases Internalizing via Reduced Insight in Autism.

BACKGROUND: Internalizing symptoms like anxiety and depression are common and impairing in autism spectrum disorder (ASD). Here, we test the hypothesis that aberrant functional connectivity among three brain networks (salience network [SN], default mode network [DMN], and frontoparietal network [FPN]) plays a role in the pathophysiology of internalizing in ASD. METHODS: We examined the association between resting-state functional connectivity and internalizing in 102 adolescents and young adults with ASD (n = 49) or typical development (n = 53). Seed-to-target functional connectivity was contrasted between adolescents and young adults with ASD and typically developing subjects using a recent parcellation of the human cerebral cortex, and connections that were aberrant in ASD were analyzed dimensionally as a function of parent-reported internalizing symptoms. RESULTS: Three connections demonstrated robust overconnectivity in ASD: 1) the anterior insula to the retrosplenial cortex (i.e., SN-DMN), 2) the anterior insula to the frontal pole (i.e., SN-FPN), and 3) the dorsolateral prefrontal cortex to the retrosplenial cortex (i.e., FPN-DMN). These differences remained significant after controlling for age, and no age-related effects survived correction. The SN-DMN connection was associated with greater internalizing in ASD, mediated by a bigger difference between self- and parent-reported internalizing. Control analyses found that the other two connections were not associated with internalizing, and SN-DMN connectivity was not associated with a well-matched control measure (externalizing symptoms). CONCLUSIONS: The present findings provide novel evidence for a specific link between SN-DMN overconnectivity and internalizing in ASD. Further, the mediation results suggest that intact anterior insula-retrosplenial connectivity may play a role in an individual's generating insight into his or her own psychopathology.

Language and alexithymia: Evidence for the role of the inferior frontal gyrus in acquired alexithymia.

The clinical relevance of alexithymia, a condition associated with difficulties identifying and describing one's own emotion, is becoming ever more apparent. Increased rates of alexithymia are observed in multiple psychiatric conditions, and also in neurological conditions resulting from both organic and traumatic brain injury. The presence of alexithymia in these conditions predicts poorer regulation of one's emotions, decreased treatment response, and increased burden on carers. While clinically important, the aetiology of alexithymia is still a matter of debate, with several authors arguing for multiple 'routes' to impaired understanding of one's own emotions, which may or may not result in distinct subtypes of alexithymia. While previous studies support the role of impaired interoception (perceiving bodily states) in the development of alexithymia, the current study assessed whether acquired language impairment following traumatic brain injury, and damage to language regions, may also be associated with an increased risk of alexithymia. Within a sample of 129 participants with penetrating brain injury and 33 healthy controls, neuropsychological testing revealed that deficits in a non-emotional language task, object naming, were associated with alexithymia, specifically with difficulty identifying one's own emotions. Both region-of-interest and whole-brain lesion analyses revealed that damage to language regions in the inferior frontal gyrus was associated with the presence of both this language impairment and alexithymia. These results are consistent with a framework for acquired alexithymia that incorporates both interoceptive and language processes, and support the idea that brain injury may result in alexithymia via impairment in any one of a number of more basic processes.