Hippocampal Involvement in Safety Signal Learning Varies With Anxiety Among Healthy Adults.

Background: Safety signal learning (SSL), based on conditioned inhibition of fear in the presence of learned safety, can effectively attenuate threat responses in animal models and humans. Difficulty regulating threat responses is a core feature of anxiety disorders, suggesting that SSL may provide a novel mechanism for fear reduction. Cross-species evidence suggests that SSL involves functional connectivity between the anterior hippocampus and the dorsal anterior cingulate cortex. However, the neural mechanisms supporting SSL have not been examined in relation to trait anxiety or while controlling for the effect of novelty. Methods: Here, we investigated the neural mechanisms involved in SSL and associations with trait anxiety in a sample of 64 healthy (non-clinically anxious) adults (ages 18-30 years; 43 female, 21 male) using physiological, behavioral, and neuroimaging (functional magnetic resonance imaging) data collected during an SSL task. Results: During SSL, compared with individuals with lower trait anxiety, individuals with higher trait anxiety showed less fear reduction as well as altered hippocampal activation and hippocampal-dorsal anterior cingulate cortex functional connectivity, and lower inferior frontal gyrus and ventrolateral prefrontal cortex activation. Importantly, the findings show that SSL reduces threat responding, across learning and over and above the effect of novelty, and involves hippocampal activation. Conclusions: These findings provide new insights into the nature of SSL and suggest that there may be meaningful variation in SSL and related neural correlates as a function of trait anxiety, with implications for better understanding fear reduction and optimizing interventions for individuals with anxiety disorders.

Responding to threat: Associations between neural reactivity to and behavioral avoidance of threat in pediatric anxiety.

BACKGROUND: Despite broad recognition of the central role of avoidance in anxiety, a lack of specificity in its operationalization has hindered progress in understanding this clinically significant construct. The current study uses a multimodal approach to investigate how specific measures of avoidance relate to neural reactivity to threat in youth with anxiety disorders. METHODS: Children with anxiety disorders (ages 6-12 years; n = 65 for primary analyses) completed laboratory task- and clinician-based measures of avoidance, as well as a functional magnetic resonance imaging task probing neural reactivity to threat. Primary analyses examined the ventral anterior insula (vAI), amygdala, and ventromedial prefrontal cortex (vmPFC). RESULTS: Significant but distinct patterns of association with task- versus clinician-based measures of avoidance emerged. Clinician-rated avoidance was negatively associated with right and left vAI reactivity to threat, whereas laboratory-based avoidance was positively associated with right vAI reactivity to threat. Moreover, left vAI-right amygdala and bilateral vmPFC-right amygdala functional connectivity were negatively associated with clinician-rated avoidance but not laboratory-based avoidance. LIMITATIONS: These results should be considered in the context of the restricted range of our treatment-seeking sample, which limits the ability to draw conclusions about these associations across children with a broader range of symptomatology. In addition, the limited racial and ethnic diversity of our sample may limit the generalizability of findings. CONCLUSION: These findings mark an important step towards bridging neural findings and behavioral patterns using a multimodal approach. Advancing understanding of behavioral avoidance in pediatric anxiety may guide future treatment optimization by identifying individual-specific targets for treatment.

Multivariate links between the developmental timing of adversity exposure and white matter tract integrity in adulthood.

Early-life adversity is pervasive worldwide and represents a potent risk factor for increased mental health burden across the lifespan. However, there is substantial individual heterogeneity in associations between adversity exposure, neurobiological changes, and mental health problems. Accounting for key features of adversity such as the developmental timing of exposure may clarify associations between adversity, neurodevelopment, and mental health. The present study leverages sparse canonical correlation analysis to characterize modes of covariation between age of adversity exposure and the integrity of white matter tracts throughout the brain in a sample of 107 adults. We find that adversity exposure during middle childhood (ages 5-6 and 8-9 in particular) is consistently linked with alterations in white matter tract integrity, such that tracts supporting sensorimotor functions display higher integrity in relation to adversity exposure while tracts supporting cortico-cortical communication display lower integrity. Further, latent patterns of tract integrity linked with adversity experienced across preschool age and middle childhood (ages 4-9) were associated with trauma-related symptoms in adulthood. Our findings underscore that adversity exposure may differentially affect white matter in a function- and developmental-timing specific manner and suggest that adversity experienced between ages 4-9 may shape the development of global white matter tracts in ways that are relevant for adult mental health.

Extinction Learning Across Development: Neurodevelopmental Changes and Implications for Pediatric Anxiety Disorders.

Alterations in extinction learning relate to the development and maintenance of anxiety disorders across the lifespan. While exposure therapy, based on principles of extinction, can be highly effective for treating anxiety, many patients do not show sufficient improvement following treatment. In particular, evidence suggests that exposure therapy does not work sufficiently for up to 40% of children who receive this evidence-based treatment.Importantly, fear learning and extinction, as well as the neural circuitry supporting these processes, undergo dynamic changes across development. An improved understanding of developmental changes in extinction learning and the associated neural circuitry may help to identify targets to improve treatment response in clinically anxious children and adolescents. In this chapter, we provide a brief overview of methods used to study fear learning and extinction in developmental populations. We then review what is currently known about the developmental changes that occur in extinction learning and related neural circuitry. We end this chapter with a discussion of the implications of these neurodevelopmental changes for the characterization and treatment of pediatric anxiety disorders.

Neural effects of controllability as a key dimension of stress exposure.

Cross-species evidence suggests that the ability to exert control over a stressor is a key dimension of stress exposure that may sensitize frontostriatal-amygdala circuitry to promote more adaptive responses to subsequent stressors. The present study examined neural correlates of stressor controllability in young adults. Participants (N = 56; Mage = 23.74, range = 18-30 years) completed either the controllable or uncontrollable stress condition of the first of two novel stressor controllability tasks during functional magnetic resonance imaging (fMRI) acquisition. Participants in the uncontrollable stress condition were yoked to age- and sex-matched participants in the controllable stress condition. All participants were subsequently exposed to uncontrollable stress in the second task, which is the focus of fMRI analyses reported here. A whole-brain searchlight classification analysis revealed that patterns of activity in the right dorsal anterior insula (dAI) during subsequent exposure to uncontrollable stress could be used to classify participants' initial exposure to either controllable or uncontrollable stress with a peak of 73% accuracy. Previous experience of exerting control over a stressor may change the computations performed within the right dAI during subsequent stress exposure, shedding further light on the neural underpinnings of stressor controllability.

Neural circuitry involved in conditioned inhibition via safety signal learning is sensitive to trauma exposure.

Exposure to trauma throughout the lifespan is prevalent and increases the likelihood for the development of mental health conditions such as anxiety and post-traumatic stress disorder (PTSD). Safety signal learning (SSL)--a form of conditioned inhibition that involves reducing fear via conditioned safety--has been shown to effectively attenuate fear responses among individuals with trauma exposure, but the association between trauma exposure and the neural mechanisms of SSL remains unknown. Adults with varied prior exposure to trauma completed a conditioned inhibition task during functional MRI scanning and collection of skin conductance response (SCR). Conditioned safety signals reduced psychophysiological reactivity (i.e., SCR) in the overall sample. Although exposure to a higher number of traumatic events was associated with elevated SCR across all task conditions, SCR did not differ between threat in the presence of conditioned safety (i.e., SSL) relative to threat alone in a trauma-related manner. At the neural level, however, higher levels of trauma exposure were associated with lower hippocampal, amygdala, and dorsolateral prefrontal cortical activation during SSL. These findings suggest that while conditioned safety signals can reduce fear in the presence of threat even among individuals exposed to higher degrees of trauma, the neural circuitry involved in SSL is in fact sensitive to trauma exposure. Future research investigating neural processes during SSL among individuals with PTSD or anxiety can further elucidate the ways in which SSL and its neural correlates may reduce fear and link trauma exposure with later mental health conditions.

Lack of robust associations between prepandemic coping strategies and frontolimbic circuitry with depression and anxiety symptoms during the COVID-19 pandemic: A preregistered longitudinal study.

The COVID-19 pandemic is an ongoing stressor that has resulted in the exacerbation of mental health problems worldwide. However, longitudinal studies that identify preexisting behavioral and neurobiological factors associated with mental health outcomes during the pandemic are lacking. Here, we examined associations between prepandemic coping strategy engagement and frontolimbic circuitry with internalizing symptoms during the pandemic. In 85 adults (71.8% female; age 18-30 years), we assessed prototypically adaptive coping strategies (Connor-Davidson Resilience Scale), resting-state functional magnetic resonance imaging functional connectivity (FC) of frontolimbic circuitry, and depression and anxiety symptoms (Beck Depression Inventory, Screen for Child Anxiety-Related Emotional Disorders-Adult, respectively). We conducted general linear models to test preregistered hypotheses that (1) lower coping engagement prepandemic and (2) weaker frontolimbic FC prepandemic would predict elevated symptoms during the pandemic; and (3) coping would interact with FC to predict symptoms during the pandemic. Depression and anxiety symptoms worsened during the pandemic (ps < .001). Prepandemic adaptive coping engagement and frontolimbic FC were not associated with depression or anxiety symptoms during the pandemic (uncorrected ps > .05). Coping interacted with insula-rostral anterior cingulate cortex (ACC) FC (p = .003, pFDR = .014) and with insula-ventral ACC FC (p < .001, pFDR < .001) to predict depression symptoms, but these findings did not survive FDR correction after removal of outliers. Findings from our preregistered study suggest that specific prepandemic factors, particularly adaptive coping and frontolimbic circuitry, are not robustly associated with emotional responses to the pandemic. Additional studies that identify preexisting neurobehavioral factors implicated in mental health outcomes during global health crises are needed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Associations between early-life stress exposure and internalizing symptomatology during the COVID-19 pandemic: Assessing the role of neurobehavioral mediators.

Background: The ongoing COVID-19 pandemic is a major stressor that has been associated with increased risk for psychiatric illness in the general population. Recent work has highlighted that experiences of early-life stress (ELS) may impact individuals' psychological functioning and vulnerability for developing internalizing psychopathology in response to pandemic-related stress. However, little is known about the neurobehavioral factors that may mediate the association between ELS exposure and COVID-related internalizing symptomatology. The current study sought to examine the mediating roles of pre-pandemic resting-state frontoamygdala connectivity and concurrent emotion regulation (ER) in the association between ELS and pandemic-related internalizing symptomatology. Methods: Retrospective life-stress histories, concurrent self-reported ER strategies (i.e., reappraisal and suppression), concurrent self-reported internalizing symptomatology (i.e., depression- and anxiety-related symptomatology), and resting-state functional connectivity data from a sample of adults (N = 64, M age = 22.12, female = 68.75%) were utilized. Results: There were no significant direct associations between ELS and COVID-related internalizing symptomatology. Neither frontoamygdala functional connectivity nor ER strategy use mediated an association between ELS and COVID-related internalizing symptomatology (ps > 0.05). Exploratory analyses identified a significant moderating effect of reappraisal use on the association between ELS and internalizing symptomatology (ß = -0.818, p = 0.047), such that increased reappraisal use buffered the impact of ELS on psychopathology. Conclusions: While frontoamygdala connectivity and ER do not appear to mediate the association between ELS and COVID-related internalizing symptomatology, our findings suggest that the use of reappraisal may buffer against the effect of ELS on mental health during the pandemic.

Migration-related trauma and mental health among migrant children emigrating from Mexico and Central America to the United States: Effects on developmental neurobiology and implications for policy.

Children make up over half of the world's migrants and refugees and face a multitude of traumatic experiences prior to, during, and following migration. Here, we focus on migrant children emigrating from Mexico and Central America to the United States and review trauma related to migration, as well as its implications for the mental health of migrant and refugee children. We then draw upon the early adversity literature to highlight potential behavioral and neurobiological sequalae of migration-related trauma exposure, focusing on attachment, emotion regulation, and fear learning and extinction as transdiagnostic mechanisms underlying the development of internalizing and externalizing symptomatology following early-life adversity. This review underscores the need for interdisciplinary efforts to both mitigate the effects of trauma faced by migrant and refugee youth emigrating from Mexico and Central America and, of primary importance, to prevent child exposure to trauma in the context of migration. Thus, we conclude by outlining policy recommendations aimed at improving the mental health of migrant and refugee youth.

Learning About Safety: Conditioned Inhibition as a Novel Approach to Fear Reduction Targeting the Developing Brain.

Adolescence is a peak time for the onset of psychiatric disorders, with anxiety disorders being the most common and affecting as many as 30% of youths. A core feature of anxiety disorders is difficulty regulating fear, with evidence suggesting deficits in extinction learning and corresponding alterations in frontolimbic circuitry. Despite marked changes in this neural circuitry and extinction learning throughout development, interventions for anxious youths are largely based on principles of extinction learning studied in adulthood. Safety signal learning, based on conditioned inhibition of fear in the presence of a cue that indicates safety, has been shown to effectively reduce anxiety-like behavior in animal models and attenuate fear responses in healthy adults. Cross-species evidence suggests that safety signal learning involves connections between the ventral hippocampus and the prelimbic cortex in rodents or the dorsal anterior cingulate cortex in humans. Particularly because this pathway follows a different developmental trajectory than fronto-amygdala circuitry involved in traditional extinction learning, safety cues may provide a novel approach to reducing fear in youths. In this review, the authors leverage a translational framework to bring together findings from studies in animal models and humans and to bridge the gap between research on basic neuroscience and clinical treatment. The authors consider the potential application of safety signal learning for optimizing interventions for anxious youths by targeting the biological state of the developing brain. Based on the existing cross-species literature on safety signal learning, they propose that the judicious use of safety cues may be an effective and neurodevelopmentally optimized approach to enhancing treatment outcomes for youths with anxiety disorders.

Comparing neural correlates of conditioned inhibition between children with and without anxiety disorders - A preliminary study.

Cognitive-behavioral therapy (CBT), a first-line treatment for pediatric anxiety disorders, is based on principles of threat learning and extinction. However, CBT does not work sufficiently for up to 40% of clinically anxious youth. The neural and behavioral correlates of conditioned inhibition might provide promising targets for attempts to improve CBT response. During conditioned inhibition, threat and safety cues appear together, forming a safety compound. Here, we test whether this safety compound elicits a reduced fear response compared to pairing the threat cue with a novel cue (novel compound). The current pilot study compares behavioral, physiological, and neural correlates of conditioned inhibition between children with (n = 17, Mage = 13.09, SDage = 3.05) and without (n = 18, Mage = 14.49, SDage = 2.38) anxiety disorders. Behavioral and physiological measures did not differ between children with and without anxiety disorders during fear acquisition. During testing, children with anxiety disorders showed overall higher skin conductance response and expected to hear the aversive sound following the novel compound more often than children without anxiety disorders. Children with anxiety disorders showed more activity in the right ventromedial prefrontal cortex (vmPFC) to the safety versus novel compound. Children without anxiety disorders showed the opposite pattern - more right vmPFC activity to the novel versus safety compound (F(1,31) = 5.40, p = 0.03). No group differences manifested within the amygdala, dorsal anterior cingulate cortex, or hippocampus. These pilot findings suggest a feasible approach for examining conditioned inhibition in pediatric anxiety disorders. If replicated in larger samples, findings may implicate perturbed conditioned inhibition in pediatric anxiety disorders and provide targets for CBT.

Neural Responses to a Putative Set-shifting Task in Children with Autism Spectrum Disorder.

While much progress has been made toward understanding the neurobiology of social and communication deficits associated with autism spectrum disorder (ASD), less is known regarding the neurobiological basis of restricted and repetitive behaviors (RRBs) central to the ASD diagnosis. Symptom severity for RRBs in ASD is associated with cognitive inflexibility. Thus, understanding the neural mechanisms underlying cognitive inflexibility in ASD is critical for tailoring therapies to treat this understudied yet pervasive symptom. Here we used a set-shifting paradigm adopted from the developmental cognitive neuroscience literature involving flexible switching between stimulus categories to examine task performance and neural responses in children with ASD. Behaviorally, we found little evidence for group differences in performance on the set-shifting task. Compared with typically developing children, children with ASD exhibited greater activation of the parahippocampal gyrus during performance on trials requiring switching. These findings suggest that children with ASD may need to recruit memory-based neural systems to a greater degree when learning to flexibly associate stimuli with responses. LAY SUMMARY: Children with autism often struggle to behave in a flexible way when faced with unexpected challenges. We examined brain responses during a task thought to involve flexible thinking and found that compared with typically developing children, those with autism relied more on brain areas involved in learning and memory to complete the task. This study helps us to understand what types of cognitive tasks are best suited for exploring the neural basis of cognitive flexibility in children with autism. Autism Res 2020, 13: 1501-1515. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Measuring Cognitive Flexibility with the Flexible Item Selection Task: From fMRI Adaptation to Individual Connectome Mapping.

Cognitive flexibility, the ability to appropriately adjust behavior in a changing environment, has been challenging to operationalize and validate in cognitive neuroscience studies. Here, we investigate neural activation and directed functional connectivity underlying cognitive flexibility using an fMRI-adapted version of the Flexible Item Selection Task (FIST) in adults (n = 32, ages 19-46 years). The fMRI-adapted FIST was reliable, showed comparable performance to the computer-based version of the task, and produced robust activation in frontoparietal, anterior cingulate, insular, and subcortical regions. During flexibility trials, participants directly engaged the left inferior frontal junction, which influenced activity in other cortical and subcortical regions. The strength of intrinsic functional connectivity between select brain regions was related to individual differences in performance on the FIST, but there was also significant individual variability in functional network topography supporting cognitive flexibility. Taken together, these results suggest that the FIST is a valid measure of cognitive flexibility, which relies on computations within a broad corticosubcortical network driven by inferior frontal junction engagement.

Novel insights from actigraphy: Anxiety is associated with sleep quantity but not quality during childhood.

Anxiety and sleep function change dynamically across development, and sleep dysfunction has emerged as a correlate and predictor of anxiety in pediatric clinical samples. Despite this, previous research has not investigated how associations between qualitative and quantitative measures of sleep function change with anxiety across development, specifically from childhood to adolescence. The present study used actigraphy collection to examine whether associations between quantitative and qualitative sleep function and anxiety differed as a function of developmental stage in a community pediatric sample (8-17 years old; N = 92). Age moderated the association between anxiety and sleep quantity, but not sleep quality. Contrary to hypotheses, higher anxiety was related to increased sleep for children, but not adolescents. Results suggest age-related changes in the association between sleep function and anxiety across development, with implications for targeting sleep-related interventions for youth with anxiety.

Ventral hippocampus interacts with prelimbic cortex during inhibition of threat response via learned safety in both mice and humans.

Heightened fear and inefficient safety learning are key features of fear and anxiety disorders. Evidence-based interventions for anxiety disorders, such as cognitive behavioral therapy, primarily rely on mechanisms of fear extinction. However, up to 50% of clinically anxious individuals do not respond to current evidence-based treatment, suggesting a critical need for new interventions based on alternative neurobiological pathways. Using parallel human and rodent conditioned inhibition paradigms alongside brain imaging methodologies, we investigated neural activity patterns in the ventral hippocampus in response to stimuli predictive of threat or safety and compound cues to test inhibition via safety in the presence of threat. Distinct hippocampal responses to threat, safety, and compound cues suggest that the ventral hippocampus is involved in conditioned inhibition in both mice and humans. Moreover, unique response patterns within target-differentiated subpopulations of ventral hippocampal neurons identify a circuit by which fear may be inhibited via safety. Specifically, ventral hippocampal neurons projecting to the prelimbic cortex, but not to the infralimbic cortex or basolateral amygdala, were more active to safety and compound cues than threat cues, and activity correlated with freezing behavior in rodents. A corresponding distinction was observed in humans: hippocampal-dorsal anterior cingulate cortex functional connectivity-but not hippocampal-anterior ventromedial prefrontal cortex or hippocampal-basolateral amygdala connectivity-differentiated between threat, safety, and compound conditions. These findings highlight the potential to enhance treatment for anxiety disorders by targeting an alternative neural mechanism through safety signal learning.

Investigating functional brain network integrity using a traditional and novel categorical scheme for neurodevelopmental disorders.

BACKGROUND: Current diagnostic systems for neurodevelopmental disorders do not have clear links to underlying neurobiology, limiting their utility in identifying targeted treatments for individuals. Here, we aimed to investigate differences in functional brain network integrity between traditional diagnostic categories (autism spectrum disorder [ASD], attention-deficit/hyperactivity disorder [ADHD], typically developing [TD]) and carefully consider the impact of comorbid ASD and ADHD on functional brain network integrity in a sample adequately powered to detect large effects. We also assess the neurobiological separability of a novel, potential alternative categorical scheme based on behavioral measures of executive function. METHOD: Five-minute resting-state fMRI data were obtained from 168 children (128 boys, 40 girls) with ASD, ADHD, comorbid ASD and ADHD, and TD children. Independent component analysis and dual regression were used to compute within- and between-network functional connectivity metrics at the individual level. RESULTS: No significant group differences in within- or between-network functional connectivity were observed between traditional diagnostic categories (ASD, ADHD, TD) even when stratified by comorbidity (ASD + ADHD, ASD, ADHD, TD). Similarly, subgroups classified by executive functioning levels showed no group differences. CONCLUSIONS: Using clinical diagnosis and behavioral measures of executive function, no differences in functional connectivity were observed among the categories examined. Despite our limited ability to detect small- to medium-sized differences between groups, this work contributes to a growing literature suggesting that traditional diagnostic categories do not define neurobiologically separable groups. Future work is necessary to ascertain the validity of the executive function-based nosology, but current results suggest that nosologies reliant on behavioral data alone may not lead to discovery of neurobiologically distinct categories.

Impaired voice processing in reward and salience circuits predicts social communication in children with autism.

Engaging with vocal sounds is critical for children's social-emotional learning, and children with autism spectrum disorder (ASD) often 'tune out' voices in their environment. Little is known regarding the neurobiological basis of voice processing and its link to social impairments in ASD. Here, we perform the first comprehensive brain network analysis of voice processing in children with ASD. We examined neural responses elicited by unfamiliar voices and mother's voice, a biologically salient voice for social learning, and identified a striking relationship between social communication abilities in children with ASD and activation in key structures of reward and salience processing regions. Functional connectivity between voice-selective and reward regions during voice processing predicted social communication in children with ASD and distinguished them from typically developing children. Results support the Social Motivation Theory of ASD by showing reward system deficits associated with the processing of a critical social stimulus, mother's voice, in children with ASD. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that minor issues remain unresolved (see decision letter).

Atypical frontoamygdala functional connectivity in youth with autism.

Functional connectivity (FC) between the amygdala and the ventromedial prefrontal cortex underlies socioemotional functioning, a core domain of impairment in autism spectrum disorder (ASD). Although frontoamygdala circuitry undergoes dynamic changes throughout development, little is known about age-related changes in frontoamygdala networks in ASD. Here we characterize frontoamygdala resting-state FC in a cross-sectional sample (ages 7-25) of 58 typically developing (TD) individuals and 53 individuals with ASD. Contrary to hypotheses, individuals with ASD did not show different age-related patterns of frontoamygdala FC compared with TD individuals. However, overall group differences in frontoamygdala FC were observed. Specifically, relative to TD individuals, individuals with ASD showed weaker frontoamygdala FC between the right basolateral (BL) amygdala and the rostral anterior cingulate cortex (rACC). These findings extend prior work to a broader developmental range in ASD, and indicate ASD-related differences in frontoamygdala FC that may underlie core socioemotional impairments in children and adolescents with ASD.

Neural circuits underlying mother's voice perception predict social communication abilities in children.

The human voice is a critical social cue, and listeners are extremely sensitive to the voices in their environment. One of the most salient voices in a child's life is mother's voice: Infants discriminate their mother's voice from the first days of life, and this stimulus is associated with guiding emotional and social function during development. Little is known regarding the functional circuits that are selectively engaged in children by biologically salient voices such as mother's voice or whether this brain activity is related to children's social communication abilities. We used functional MRI to measure brain activity in 24 healthy children (mean age, 10.2 y) while they attended to brief (<1 s) nonsense words produced by their biological mother and two female control voices and explored relationships between speech-evoked neural activity and social function. Compared to female control voices, mother's voice elicited greater activity in primary auditory regions in the midbrain and cortex; voice-selective superior temporal sulcus (STS); the amygdala, which is crucial for processing of affect; nucleus accumbens and orbitofrontal cortex of the reward circuit; anterior insula and cingulate of the salience network; and a subregion of fusiform gyrus associated with face perception. The strength of brain connectivity between voice-selective STS and reward, affective, salience, memory, and face-processing regions during mother's voice perception predicted social communication skills. Our findings provide a novel neurobiological template for investigation of typical social development as well as clinical disorders, such as autism, in which perception of biologically and socially salient voices may be impaired.