The effects of psychotherapy for anhedonia on subcortical brain volumes measured with ultra-high field MRI.

BACKGROUND: Anhedonia is a transdiagnostic symptom often resistant to treatment. The identification of biomarkers sensitive to anhedonia treatment will aid in the evaluation of novel anhedonia interventions. METHODS: This is an exploratory analysis of changes in subcortical brain volumes accompanying psychotherapy in a transdiagnostic anhedonic sample using ultra-high field (7-Tesla) MRI. Outpatients with clinically impairing anhedonia (n = 116) received Behavioral Activation Treatment for Anhedonia, a novel psychotherapy, or Mindfulness-Based Cognitive Therapy (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). Subcortical brain volumes were estimated via the MultisegPipeline, and regions of interest were the amygdala, caudate nucleus, hippocampus, pallidum, putamen, and thalamus. Bivariate mixed effects models estimated pre-treatment relations between anhedonia severity and subcortical brain volumes, change over time in subcortical brain volumes, and associations between changes in subcortical brain volumes and changes in anhedonia symptoms. RESULTS: As reported previously (Cernasov et al., 2023), both forms of psychotherapy resulted in equivalent and significant reductions in anhedonia symptoms. Pre-treatment anhedonia severity and subcortical brain volumes were not related. No changes in subcortical brain volumes were observed over the course of treatment. Additionally, no relations were observed between changes in subcortical brain volumes and changes in anhedonia severity over the course of treatment. LIMITATIONS: This trial included a modest sample size and did not have a waitlist-control condition or a non-anhedonic comparison group. CONCLUSIONS: In this exploratory analysis, psychotherapy for anhedonia was not accompanied by changes in subcortical brain volumes, suggesting that subcortical brain volumes may not be a candidate biomarker sensitive to response to psychotherapy.

Bilingualism Predicts Affective Theory of Mind in Autistic Adults.

PURPOSE: This study examined the impact of bilingualism on affective theory of mind (ToM) and social prioritization (SP) among autistic adults compared to neurotypical comparison participants. METHOD: Fifty-two (25 autistic, 27 neurotypical) adult participants (ages 21-35 years) with varying second language (L2) experience, ranging from monolingual to bilingual, completed an affective ToM task. A subset of this sample also completed a dynamic eye-tracking task designed to capture differences in time spent looking at social aspects of a scene (SP). Four language groups were compared on task performance (monolingual autism and neurotypical, bilingual autism and neurotypical), followed by analyses examining the contribution of L2 experience, autism characteristics, and social face prioritization on affective ToM, controlling for verbal IQ. Finally, we conducted an analysis to identify the contribution of SP on affective ToM when moderated by autism status and L2 experience, controlling for verbal IQ. RESULTS: The monolingual autism group performed significantly worse than the other three groups (bilingual autism, monolingual neurotypical, and bilingual neurotypical) on the affective ToM task; however, there were no significant differences between the bilingual autism group compared to the monolingual and bilingual neurotypical groups. For autistic individuals, affective ToM capabilities were positively associated with both verbal IQ and L2 experience but did not relate to autism characteristics or SP during eye tracking. Neurotypical participants showed greater SP during the eye-tracking task, and SP did not relate to L2 or autism characteristics for autistic individuals. SP and verbal IQ predicted affective ToM performance across autism and neurotypical groups, but this relationship was moderated by L2 experience; SP more strongly predicted affective ToM performance among participants with lower L2 experience (e.g., monolingual) and had less of an impact for those with higher L2 experience. CONCLUSION: This study provides support for a bilingual advantage in affective ToM for autistic individuals. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25696083.

Depressive symptoms and activity engagement in autistic adolescents and those with other developmental disabilities.

BACKGROUND: Autistic adults and those with other developmental disabilities (DD) have increased depressive symptoms and decreased activity engagement when compared to those with no DD. Few studies explore activities related to depressive symptoms in autistic people and those with other DD during adolescence. OBJECTIVE: The objectives of this analysis were to describe depressive symptoms and activity engagement among autistic adolescents and those with other DD and no DD and explore types of activities associated with depressive symptoms, stratified by study group. METHODS: Parents of adolescents completed a multi-site case-control study of autism and other DD when their child was 2-5 years of age and a follow-up survey when their child was 12-16 years of age. Questions asked about the adolescent's current diagnoses, depressive symptoms (i.e., diagnosis, medication use, or symptoms), and engagement in club, social, sport, vocational, volunteer, and other organized activities. RESULTS: Autistic adolescents (N = 238) and those with other DD (N = 222) were significantly more likely to have depressive symptoms than adolescents with no DD (N = 406), (31.9 %, 30.6 %, and 15.0 % respectively). Lower percentages of autistic adolescents participated in activities than peers with other DD, who had lower percentages than peers with no DD. Participation in sports was associated with lower likelihood of depressive symptoms in all groups. CONCLUSIONS: Autistic adolescents and those with other DD are at increased risk for depressive symptoms and reduced activity engagement. Participation in sports may be especially important for adolescent mental health regardless of disability status. Implications for public health education and intervention are discussed.

Neural Markers of Emotion Reactivity and Regulation Before and After a Targeted Social Rejection: Differences Among Girls With and Without Suicidal Ideation and Behavior Histories.

BACKGROUND: Suicidal thoughts and behaviors (STBs) are common among adolescent girls and increase risk for suicide death. Emotion regulation difficulties are linked with STBs, particularly in response to targeted social rejection. However, neural correlates of this link have not been investigated and may identify novel targets for interventions. Here, we examined neural correlates of emotion regulation before and after an experimentally delivered targeted social rejection in adolescent girls with STBs and girls without STBs (i.e., control participants). METHODS: Girls (N = 138; age range, 9-15 years; mean [SD] age = 11.6 [1.79] years) completed a functional neuroimaging emotion regulation task. In the middle of the task, participants were socially rejected by an unfamiliar confederate whom the participants had elected to meet. Participants also completed a multimethod STB assessment. RESULTS: Before rejection, girls with a history of STBs, compared with control participants, showed greater activation in the right superior frontal gyrus when passively viewing negative stimuli, and girls with suicidal behavior (SB) versus those without SB showed less activation in the right frontal pole during emotion regulation attempts. Following the rejection, girls with STBs, compared with control participants, showed greater activation in the right inferior frontal gyrus during emotion regulation. CONCLUSIONS: Before social rejection, girls with SB versus without SB may not activate brain regions implicated in emotion regulation, suggesting a vulnerability to poor regulation at their baseline emotional state. After social rejection, girls with any history of STBs showed altered activation in a brain region strongly associated with inhibition and emotion regulation success, possibly reflecting increased effort at inhibiting emotional responses during regulation following stress exposure.

Hormone sensitivity predicts the beneficial effects of transdermal estradiol on reward-seeking behaviors in perimenopausal women: A randomized controlled trial.

Depression is highly prevalent during the menopause transition (perimenopause), and often presents with anxious and anhedonic features. This increased vulnerability for mood symptoms is likely driven in part by the dramatic hormonal changes that are characteristic of the menopause transition, as prior research has linked fluctuations in estradiol (E2) to emergence of depressed mood in at risk perimenopausal women. Transdermal estradiol (TE2) has been shown to reduce the severity of depression in clinically symptomatic women, particularly in those with recent stressful life events. This research extends prior work by examining the relation between E2 and reward seeking behaviors, a precise behavioral indicator of depression. Specifically, the current study utilizes a randomized, double blind, placebo-controlled design to investigate whether mood sensitivity to E2 flux ("hormone sensitivity") predicts the beneficial effects of TE2 interventions on reward seeking behaviors in perimenopausal women, and whether recent stressful life events moderate any observed associations. METHOD: Participants were 66 women who met standardized criteria for being early or late perimenopausal based on bleeding patterns. Participants were recruited from a community sample; therefore, mood symptoms varied across the continuum and the majority of participants did not meet diagnostic criteria for a depressive or anxiety disorder at the time of enrollment. Hormone sensitivity was quantified over an 8-week baseline period, using within-subjects correlations between repeated weekly measures of E2 serum concentrations and weekly anxiety (State Trait Anxiety Inventory) and anhedonia ratings (Snaith-Hamilton Pleasure Scale). Women were then randomized to receive 8 weeks of TE2 (0.1 mg) or transdermal placebo, and reward-seeking behaviors were assessed using the Effort-Expenditure for Rewards Task (EEfRT). RESULTS: Participants who were randomized to receive transdermal estradiol and who demonstrated greater anxiety sensitivity to E2 fluctuations at baseline, demonstrated more reward seeking behaviors on the EEfRT task. Notably, the strength of the association between E2-anxiety sensitivity and post-randomization EEfRT for TE2 participants increased when women experienced more recent stressful life events and rated those events as more stressful. E2-anhedonia sensitivity was not associated with reward-seeking behaviors. CONCLUSION: Perimenopausal women who are more sensitive to E2 fluctuations and experienced more recent life stress may experience a greater benefit of TE2 as evidenced by an increase in reward seeking behaviors.

Striatal dopamine in anhedonia: A simultaneous [11C]raclopride positron emission tomography and functional magnetic resonance imaging investigation.

BACKGROUND: Anhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample. METHODS: Participants with (n = 25) and without (n = 12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [11C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors. RESULTS: Relative to controls, the anhedonia group exhibited decreased task-related DA release in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC. CONCLUSIONS: Results provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia.

Parsing within & between-person dynamics of therapy homework completion and clinical symptoms in two cognitive behavioral treatments for adults with anhedonia.

OBJECTIVE: Homework is a key theoretical component of cognitive-behavioral therapies, however, the effects of homework on clinical outcomes have largely been evaluated between-persons rather than within-persons. METHODS: The effects of homework completion on treatment response were examined in a randomized trial comparing Behavioral Activation Treatment for Anhedonia (BATA, n = 38), a novel psychotherapy, to Mindfulness-Based Cognitive Therapy (MBCT, n=35). The primary endpoint was consummatory reward sensitivity, measured weekly by the Snaith Hamilton Pleasure Scale (SHAPS), up to 15 weeks. Multilevel models evaluated change in SHAPS scores over time and the effects of clinician-reported and participant-reported homework. RESULTS: BATA and MBCT resulted in significant, equivalent reductions in SHAPS scores. Unexpectedly, participants who completed greater mean total amounts of homework did not improve at a faster rate (i.e., no between-person effect). However, sessions with greater than average participant-reported homework completion were associated with greater than average reductions in SHAPS scores (i.e., a within-person effect). For clinician-reported homework, this effect was only evident within the BATA condition. CONCLUSION: This study shows psychotherapy homework completion relates to symptomatic improvement in cognitive-behavioral treatments for anhedonia when session-to-session changes are examined within-person. On the contrary, we found no evidence that total homework completion predicted greater improvements between-person. When possible, psychotherapy researchers should evaluate their constructs of interest across multiple sessions (not just pre/post) to allow more direct tests of hypotheses predicted by theoretical models of individual change processes.

Longitudinal associations between perceived stress and anhedonia during psychotherapy.

BACKGROUND: Chronic stress alters reward sensitivity and contributes to the emergence of anhedonia. In clinical samples, the perception of stress is a strong predictor of anhedonia. While there is substantial evidence demonstrating psychotherapy reduces perceived stress, little is known regarding the effects of treatment-related decreases in perceived stress on anhedonia. METHODS: The current study investigated reciprocal relations between perceived stress and anhedonia using a cross-lagged panel model approach in a 15-week clinical trial examining the effects of Behavioral Activation Treatment for Anhedonia (BATA), a novel psychotherapy to treat anhedonia, compared to a Mindfulness-Based Cognitive Therapy (MBCT) comparison intervention (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). RESULTS: Treatment completers (n = 72) experienced significant reductions in anhedonia (M = -8.94, SD = 5.66) on the Snaith-Hamilton Pleasure Scale (t(71) = 13.39, p < .0001), and significant reductions in perceived stress (M = -3.71, SD = 3.88) on the Perceived Stress Scale (t(71) = 8.11, p < .0001) following treatment. Across all treatment-seeking participants (n = 87), a longitudinal autoregressive cross-lagged model revealed significant paths showing that higher levels of perceived stress at treatment Week 1 predicted reductions in anhedonia at treatment Week 4; lower levels of perceived stress at Week 8 predicted reductions in anhedonia at Week 12. Anhedonia did not significantly predict perceived stress at any stage of treatment. CONCLUSIONS: This study showed specific timing and directional effects of perceived stress on anhedonia during psychotherapy treatment. Individuals with relatively high perceived stress at the start of treatment were more likely to report relatively lower anhedonia a few weeks into treatment. At mid-treatment, individuals with low perceived stress were more likely to report lower anhedonia towards the end of treatment. These results demonstrate that early treatment components reduce perceived stress, thus allowing for downstream changes in hedonic functioning during mid-late treatment. The findings presented here suggest it will be critically important for future clinical trials evaluating novel interventions for anhedonia to measure stress levels repeatedly, as an important mechanism of change. TRIAL NAME: Development of a Novel Transdiagnostic Intervention for Anhedonia - R61 Phase. TRIAL URL: https://clinicaltrials.gov/ct2/show/NCT02874534. TRIAL REGISTRATION NUMBER: NCT02874534.

Perimenopausal Effects of Estradiol on Anhedonia and Psychosis Study (PEEPs): study protocol for a neural and molecular mechanistic clinical trial.

BACKGROUND: The perimenopausal transition is accompanied by psychiatric symptoms in over 10% of women. Symptoms commonly include depressed mood and anhedonia and less commonly include psychosis. Psychiatric symptoms have been linked to the depletion and/or variability of circulating estradiol, and estradiol treatment reduces perimenopausal anhedonia and psychosis in some women. Estrogen fluctuations may disrupt function in the mesolimbic reward system in some women, leading to psychiatric symptoms like anhedonia or psychosis. The Perimenopausal Effects of Estradiol on Anhedonia and Psychosis Study (PEEPs) is a mechanistic clinical trial that aims to (1) identify relationships between perimenopausal-onset anhedonia and psychosis and neuromolecular markers of mesolimbic reward responses and (2) determine the extent to which estradiol treatment-induced changes in mesolimbic reward responses are associated with alleviation of perimenopausal onset anhedonia or psychosis. METHODS: This study will recruit 100 unmedicated women ages 44-55 in the late-stage perimenopausal transition, sampling across the range of mild-to-high anhedonia and absent-to-moderate psychosis symptoms. Patients will be randomized to receive either estradiol or placebo treatment for 3 weeks. Clinical outcome measures will include symptoms of anhedonia (measured with Snaith-Hamilton Pleasure Scale; SHAPS) and psychosis (measured with Brief Psychiatric Rating Scale; BPRS psychosis subscale) as well as neural markers of mesolimbic reward system functioning, including reward-related fMRI activation and PET-derived measure of striatal dopamine binding. Pre-treatment associations between (1) SHAPS/BPRS scores and (2) reward-related striatal dopamine binding/BOLD activation will be examined. Furthermore, longitudinal mixed models will be used to estimate (1) symptom and neuromolecular trajectories as a function of estradiol vs. placebo treatment and (2) how changes in reward-related striatal dopamine binding and BOLD activation predict variability in symptom trajectories in response to estradiol treatment. DISCUSSION: This clinical trial will be the first to characterize neural and molecular mechanisms by which estradiol treatment ameliorates anhedonia and psychosis symptoms during the perimenopausal transition, thus laying the groundwork for future biomarker research to predict susceptibility and prognosis and develop targeted treatments for perimenopausal psychiatric symptoms. Furthermore, in alignment with the National Institute for Mental Health Research Domain Criteria initiative, this trial will improve our understanding of a range of disorders characterized by anhedonia, psychosis, and reward system dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov NCT05282277.

Social goals in girls transitioning to adolescence: associations with psychopathology and brain network connectivity.

The motivation to socially connect with peers increases during adolescence in parallel with changes in neurodevelopment. These changes in social motivation create opportunities for experiences that can impact risk for psychopathology, but the specific motivational presentations that confer greater psychopathology risk are not fully understood. To address this issue, we used a latent profile analysis to identify the multidimensional presentations of self-reported social goals in a sample of 220 girls (9-15 years old, M = 11.81, SD = 1.81) that was enriched for internalizing symptoms, and tested the association between social goal profiles and psychopathology. Associations between social goals and brain network connectivity were also examined in a subsample of 138 youth. Preregistered analyses revealed four unique profiles of social goal presentations in these girls. Greater psychopathology was associated with heightened social goals such that higher clinical symptoms were related to a greater desire to attain social competence, avoid negative feedback and gain positive feedback from peers. The profiles endorsing these excessive social goals were characterized by denser connections among social-affective and cognitive control brain regions. These findings thus provide preliminary support for adolescent-onset changes in motivating factors supporting social engagement that may contribute to risk for psychopathology in vulnerable girls.

Anhedonia and Hyperhedonia in Autism and Related Neurodevelopmental Disorders.

Although autism spectrum disorder (ASD) is defined by impaired social communication and restricted and repetitive behaviors and interests, ASD is also characterized by impaired motivational processes. The "social motivation theory of autism" describes how social motivation disruptions in ASD in early childhood may impede the drive to engage in reciprocal social behaviors and ultimately interfere with the development of neural networks critical for social communication (Chevallier et al., Trends Cogn Sci 16:231-239, 2012b). Importantly, clinical studies and preclinical research using model organisms for ASD indicate that motivational impairments in ASD are not constrained to social rewards but are evident in response to a range of nonsocial rewards as well. Additionally, translational studies on certain genetically defined neurodevelopmental disorders associated with ASD indicate that these syndromic forms of ASD are also characterized by motivational deficits and mesolimbic dopamine impairments. In this chapter we summarize clinical and preclinical research relevant to reward processing impairments in ASD and related neurodevelopmental disorders. We also propose a nosology to describe reward processing impairments in these disorders that uses a three-axes model. In this triaxial nosology, the first axis defines the direction of the reward response (i.e., anhedonic, hyperhedonic); the second axis defines the construct of the reward process (e.g., reward liking, reward wanting); and the third axis defines the context of the reward response (e.g., social, nonsocial). A more precise nosology for describing reward processing impairments in ASD and related neurodevelopmental disorders will aid in the translation of preclinical research to clinical investigations which will ultimately help to speed up the development of interventions that target motivational systems for ASD and related neurodevelopmental disorders.

Multilevel growth curve analyses of behavioral activation for anhedonia (BATA) and mindfulness-based cognitive therapy effects on anhedonia and resting-state functional connectivity: Interim results of a randomized trial✰.

BACKGROUND: The neural mechanisms associated with anhedonia treatment response are poorly understood. Additionally, no study has investigated changes in resting-state functional connectivity (rsFC) accompanying psychosocial treatment for anhedonia. METHODS: We evaluated a novel psychotherapy, Behavioral Activation Therapy for Anhedonia (BATA, n = 38) relative to Mindfulness-Based Cognitive Therapy (MBCT, n = 35) in a medication-free, transdiagnostic, anhedonic sample in a parallel randomized controlled trial. Participants completed up to 15 sessions of therapy and up to four 7T MRI scans before, during, and after treatment (n = 185 scans). Growth curve models estimated change over time in anhedonia and in rsFC using average region-of-interest (ROI)-to-ROI connectivity within the default mode network (DMN), frontoparietal network (FPN), salience network, and reward network. Changes in rsFC from pre- to post-treatment were further evaluated using whole-network seed-to-voxel and ROI-to-ROI edgewise analyses. RESULTS: Growth curve models showed significant reductions in anhedonia symptoms and in average rsFC within the DMN and FPN over time, across BATA and MBCT. There were no differences in anhedonia reductions between treatments. Within-person, changes in average rsFC were unrelated to changes in anhedonia. Between-person, higher than average FPN rsFC was related to less anhedonia across timepoints. Seed-to-voxel and edgewise rsFC analyses corroborated reductions within the DMN and between the DMN and FPN over time, across the sample. CONCLUSIONS: Reductions in rsFC within the DMN, FPN, and between these networks co-occurred with anhedonia improvement across two psychosocial treatments for anhedonia. Future anhedonia clinical trials with a waitlist control group should disambiguate treatment versus time-related effects on rsFC.

Health Status and Health Care Use Among Adolescents Identified With and Without Autism in Early Childhood - Four U.S. Sites, 2018-2020.

Persons identified in early childhood as having autism spectrum disorder (autism) often have co-occurring health problems that extend into adolescence (1-3). Although only limited data exist on their health and use of health care services as they transition to adolescence, emerging data suggest that a minority of these persons receive recommended guidance* from their primary care providers (PCPs) starting at age 12 years to ensure a planned transition from pediatric to adult health care (4,5). To address this gap in data, researchers analyzed preliminary data from a follow-up survey of parents and guardians of adolescents aged 12-16 years who previously participated in the Study to Explore Early Development (https://www.cdc.gov/ncbddd/autism/seed.html). The adolescents were originally studied at ages 2-5 years and identified at that age as having autism (autism group) or as general population controls (control group). Adjusted prevalence ratios (aPRs) that accounted for differences in demographic characteristics were used to compare outcomes between groups. Adolescents in the autism group were more likely than were those in the control group to have physical difficulties (21.2% versus 1.6%; aPR = 11.6; 95% confidence interval [CI] = 4.2-31.9), and to have additional mental health or other conditions† (one or more condition: 63.0% versus 28.9%; aPR = 1.9; 95% CI = 1.5-2.5). Adolescents in the autism group were more likely to receive mental health services (41.8% versus 22.1%; aPR = 1.8, 95% CI = 1.3-2.6) but were also more likely to have an unmet medical or mental health service need§ (11.0% versus 3.2%; aPR = 3.1; 95% CI = 1.1-8.8). In both groups, a small percentage of adolescents (autism, 7.5%; control, 14.1%) received recommended health care transition (transition) guidance. These findings are consistent with previous research (4,5) indicating that few adolescents receive the recommended transition guidance and suggest that adolescents identified with autism in early childhood are more likely than adolescents in the general population to have unmet health care service needs. Improved provider training on the heath care needs of adolescents with autism and coordination of comprehensive programs¶ to meet their needs can improve delivery of services and adherence to recommended guidance for transitioning from pediatric to adult health care.

A simultaneous [11C]raclopride positron emission tomography and functional magnetic resonance imaging investigation of striatal dopamine binding in autism.

The social motivation hypothesis of autism posits that autism spectrum disorder (ASD) is characterized by impaired motivation to seek out social experience early in life that interferes with the development of social functioning. This framework suggests that impaired mesolimbic dopamine function underlies compromised responses to social rewards in ASD. Although this hypothesis is supported by functional magnetic resonance imaging (fMRI) studies, no molecular imaging study has evaluated striatal dopamine functioning in response to rewards in ASD. Here, we examined striatal functioning during monetary incentive processing in ASD and controls using simultaneous positron emission tomography (PET) and fMRI. Using a bolus + infusion protocol with the D2/D3 dopamine receptor antagonist [11C]raclopride, voxel-wise binding potential (BPND) was compared between groups (controls = 12, ASD = 10) in the striatum. Striatal clusters showing significant between-group BPND differences were used as seeds in whole-brain fMRI general functional connectivity analyses. Relative to controls, the ASD group demonstrated decreased phasic dopamine release to incentives in the bilateral putamen and left caudate, as well as increased functional connectivity between a PET-derived right putamen seed and the precuneus and insula. Within the ASD group, decreased phasic dopamine release in the putamen was related to poorer theory-of-mind skills. Our findings that ASD is characterized by impaired striatal phasic dopamine release to incentives provide support for the social motivation hypothesis of autism. PET-fMRI may be a suitable tool to evaluate novel ASD therapeutics targeting the striatal dopamine system.

Dynamic Eye Tracking as a Predictor and Outcome Measure of Social Skills Intervention in Adolescents and Adults with Autism Spectrum Disorder.

To evaluate an eye tracking task as a predictor and outcome measure of treatment response for autism spectrum disorder (ASD) social skills interventions, adolescents and young adults with ASD completed the eye tracking task before, immediately after, and two months after completing Social Cognition and Interaction Training for Autism (SCIT-A). The study compared SCIT-A participants (n = 20) to participants with ASD who received treatment as usual (TAU; n = 21). Overall, increased visual attention to faces and background objects and decreased attention to hands playing with toys at baseline were associated with improved social functioning immediately following intervention, suggesting this eye tracking task may reliably predict ASD social intervention outcomes.

A Nexus Model of Restricted Interests in Autism Spectrum Disorder.

Restricted interests (RIs) in autism spectrum disorder (ASD) are clinically impairing interests of unusual focus or intensity. They are a subtype of restricted and repetitive behaviors which are one of two diagnostic criteria for the disorder. Despite the near ubiquity of RIs in ASD, the neural basis for their development is not well understood. However, recent cognitive neuroscience findings from nonclinical samples and from individuals with ASD shed light on neural mechanisms that may explain the emergence of RIs. We propose the nexus model of RIs in ASD, a novel conceptualization of this symptom domain that suggests that RIs may reflect a co-opting of brain systems that typically serve to integrate complex attention, memory, semantic, and social communication functions during development. The nexus model of RIs hypothesizes that when social communicative development is compromised, brain functions typically located within the lateral surface of cortex may expand into social processing brain systems and alter cortical representations of various cognitive functions during development. These changes, in turn, promote the development of RIs as an alternative process mediated by these brain networks. The nexus model of RIs makes testable predictions about reciprocal relations between the impaired development of social communication and the emergence of RIs in ASD and suggests novel avenues for treatment development.

Neural Mechanisms of Vicarious Reward Processing in Adults with Autism Spectrum Disorder.

Previous studies examining the neural substrates of reward processing in ASD have explored responses to rewards for oneself but not rewards earned for others (i.e., vicarious reward). This omission is notable given that vicarious reward processing is a critical component of creating and maintaining social relationships. The current study examined the neural mechanisms of vicarious reward processing in 15 adults with ASD and 15 age- and gender-matched typically developing controls. Individuals with ASD demonstrated attenuated activation of reward-related regions during vicarious reward processing. Altered connectivity was also observed in individuals with ASD during reward receipt. These findings of altered neural sensitivity to vicarious reward processing may represent a mechanism that hinders the development of social abilities in ASD.

Neural Mechanisms of Social and Nonsocial Reward Prediction Errors in Adolescents with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is characterized by impaired predictive abilities; however, the neural mechanisms subsuming reward prediction errors in ASD are poorly understood. In the current study, we investigated neural responses during social and nonsocial reward prediction errors in 22 adolescents with ASD (ages 12-17) and 20 typically developing control adolescents (ages 12-18). Participants performed a reward prediction error task using both social (i.e., faces) and nonsocial (i.e., objects) rewards during a functional magnetic resonance imaging scan. Reward prediction errors were defined in two ways: (a) the signed prediction error, the difference between the experienced and expected reward; and (b) the thresholded unsigned prediction error, the difference between expected and unexpected outcomes regardless of magnitude. During social reward prediction errors, the ASD group demonstrated the following differences relative to the TD group: (a) signed prediction error: decreased activation in the right precentral gyrus and increased activation in the right frontal pole; and (b) thresholded unsigned prediction error: increased activation in the right anterior cingulate gyrus and bilateral precentral gyrus. Groups did not differ in brain activation during nonsocial reward prediction errors. Within the ASD group, exploratory analyses revealed that reaction times and social-communication impairments were related to precentral gyrus activation during social prediction errors. These findings elucidate the neural mechanisms of social reward prediction errors in ASD and suggest that ASD is characterized by greater neural atypicalities during social, relative to nonsocial, reward prediction errors in ASD. Autism Res 2020, 13: 715-728. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We used brain imaging to evaluate differences in brain activation in adolescents with autism while they performed tasks that involved learning about social and nonsocial information. We found no differences in brain responses during the nonsocial condition, but differences during the social condition of the learning task. This study provides evidence that autism may involve different patterns of brain activation when learning about social information.

Social Stimuli Induce Activation of Oxytocin Neurons Within the Paraventricular Nucleus of the Hypothalamus to Promote Social Behavior in Male Mice.

Oxytocin (OT) is critical for the expression of social behavior across a wide array of species; however, the role of this system in the encoding of socially relevant information is not well understood. In the present study, we show that chemogenetic activation of OT neurons within the paraventricular nucleus of the hypothalamus (PVH) of male mice (OT-Ires-Cre) enhanced social investigation during a social choice test, while chemogenetic inhibition of these neurons abolished typical social preferences. These data suggest that activation of the OT system is necessary to direct behavior preferentially toward social stimuli. To determine whether the presence of a social stimulus is sufficient to induce activation of PVH-OT neurons, we performed the first definitive recording of OT neurons in awake mice using two-photon calcium imaging. These recordings demonstrate that social stimuli activate PVH-OT neurons and that these neurons differentially encode social and nonsocial stimuli, suggesting that PVH-OT neurons may act to convey social salience of environmental stimuli. Finally, an attenuation of social salience is associated with social disorders, such as autism. We therefore also examined possible OT system dysfunction in a mouse model of autism, Shank3b knock-out (KO) mice. Male Shank3b KO mice showed a marked reduction in PVH-OT neuron number and administration of an OT receptor agonist improved social deficits. Overall, these data suggest that the presence of a social stimulus induces activation of the PVH-OT neurons to promote adaptive social behavior responses.SIGNIFICANCE STATEMENT Although the oxytocin (OT) system is well known to regulate a diverse array of social behaviors, the mechanism in which OT acts to promote the appropriate social response is poorly understood. One hypothesis is that the presence of social conspecifics activates the OT system to generate an adaptive social response. Here, we selectively recorded from OT neurons in the paraventricular hypothalamic nucleus (PVH) to show that social stimulus exposure indeed induces activation of the OT system. We also show that activation of the OT system is necessary to promote social behavior and that mice with abnormal social behavior have reduced numbers of PVH-OT neurons. Finally, aberrant social behavior in these mice was rescued by administration of an OT receptor agonist.

Reward Network Modulation as a Mechanism of Change in Behavioral Activation.

Behavioral Activation (BA) is a contemporary third-wave psychosocial treatment approach that emphasizes helping individuals become more active in ways that are meaningful to them as a means of improving mood and quality of life. BA has been designated as a well-established, validated treatment for depression by the American Psychological Association following several decades of accumulated empirical support demonstrating that BA techniques successfully reduce depression symptoms and produce other desirable outcomes across a variety of populations and contexts. The purported mechanism of change underlying BA treatment lies in increasing activation, which in turn increases contact with positive reinforcement thereby reversing the cycle of depression. Current studies are further investigating how increasing activation and subsequent contact with mood reinforcers can influence mood and behavior. Specifically, there is growing evidence that BA modifies function of reward-related networks in the brain, and that these changes are associated with clinical improvement. Herein, we provide a brief history of BA, describe the primary components of BA treatment, and describe BA's purported mechanisms of change at behavioral, neural, and subjective activation levels. We present limitations as well as gaps in the current state of knowledge regarding mechanisms of action of BA.