Marika C. Coffman

Recent advances in understanding the neural bases of autism spectrum disorder.

Purpose of review This article reviews current work investigating the neural bases of autism spectrum disorder (ASD) within the discipline of electrophysiological brain research. The manuscript focuses primarily on advances in understanding related to social information processing and interconnectivity among brain systems in ASD. Recent findings Recent research indicates anomalous function of social brain regions in ASD and highlights the specificity of processing problems to these systems. Atypical activity in this circuitry may reflect genetic susceptibility for ASD, with increased activity in compensatory areas marking the distinction between developing and not developing the disorder. Advances in understanding connectivity in ASD are highlighted by novel work providing initial evidence of atypical interconnectivity in infancy. Summary Emerging understanding of neural dysfunction in ASD indicates consistent but heterogeneous dysfunction across brain systems in ASD. Key objectives for the immediate future include the use of multimethod approaches that encompass temporal and spatial imaging; behavioral phenotyping carried out in developmental context to reveal subgroups defined uniquely by trajectories; and individual-specific profiles of behavioral performance and brain function.

Sex differences in the development of brain mechanisms for processing biological motion.

Disorders related to social functioning including autism and schizophrenia differ drastically in incidence and severity between males and females. Little is known about the neural systems underlying these sex-linked differences in risk and resiliency. Using functional magnetic resonance imaging and a task involving the visual perception of point-light displays of coherent and scrambled biological motion, we discovered sex differences in the development of neural systems for basic social perception. In adults, we identified enhanced activity during coherent biological motion perception in females relative to males in a network of brain regions previously implicated in social perception including amygdala, medial temporal gyrus, and temporal pole. These sex differences were less pronounced in our sample of school-age youth. We hypothesize that the robust neural circuitry supporting social perception in females, which diverges from males beginning in childhood, may underlie sex differences in disorders related to social processing.

Diminished social reward anticipation in the broad autism phenotype as revealed by event-related brain potentials

Diminished responsivity to reward incentives is a key contributor to the social-communication problems seen in autism spectrum disorders (ASDs). Social motivation theories suggest that individuals with ASD do not experience social interactions as rewarding, leading to negative consequences for the development of brain circuitry subserving social information. In this study, we examined neural responses to social and non-social reward anticipation in 35 typically developing young adults, examining modulation of reward sensitivity by level of autistic traits. Using an Event-related potential incentive-delay task incorporating novel, more ecologically valid forms of reward, higher expression of autistic traits was associated with an attenuated P3 response to the anticipation of social (simulated real-time video feedback from an observer), but not non-social (candy), rewards. Exploratory analyses revealed that this was unrelated to mentalizing ability. The P3 component reflects motivated attention to reward signals, suggesting attenuated motivation allocation specific to social incentives. The study extends prior findings of atypical reward anticipation in ASD, demonstrating that attenuated social reward responsiveness extends to autistic traits in the range of typical functioning. Results support the development of innovative paradigms for investigating social and non-social reward responsiveness. Insight into vulnerabilities in reward processing is critical for understanding social function in ASD.

Neural Mechanisms of Emotion Regulation in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is characterized by high rates of comorbid internalizing and externalizing disorders. One mechanistic account of these comorbidities is that ASD is characterized by impaired emotion regulation (ER) that results in deficits modulating emotional responses. We assessed neural activation during cognitive reappraisal of faces in high functioning adults with ASD. Groups did not differ in looking time, pupilometry, or subjective ratings of faces during reappraisal. However, instructions to increase positive and negative emotional responses resulted in less increase in nucleus accumbens and amygdala activations (respectively) in the ASD group, and both regulation instructions resulted in less change in dorsolateral prefrontal cortex activation in the ASD group. Results suggest a potential mechanistic account of impaired ER in ASD.

Sex differences in social perception in children with ASD.

Autism spectrum disorder (ASD) is more common in males than females. An underrepresentation of females in the ASD literature has led to limited knowledge of differences in social function across the sexes. Investigations of face perception represent a promising target for understanding variability in social functioning between males and females. The current study analyzed electrophysiological brain recordings during face perception to investigate sex differences in the neural correlates of face perception and their relationship to social function. Event related potentials (ERP) were recorded from children with ASD while viewing faces, inverted faces, and houses. Relative to males, females showed attenuated response at an ERP marker of face perception, the N170. Among females, but not males, atypical face response was associated with symptom severity. Observed sex differences reflect influential differences in social information processing, and impairment in these features correlates with deficits in social information processing in females, but not males, with ASD. These findings hold significance for future treatment protocols, which should account for differences in males and females with ASD in clinical presentation and neural phenotypes.

The Promise of Neurotechnology in Clinical Translational Science

Neurotechnology is broadly defined as a set of devices used to understand neural processes and applications that can potentially facilitate the brain’s ability to repair itself. In the past decade, an increasingly explicit understanding of basic biological mechanisms of brain-related illnesses has produced applications that allow a direct yet noninvasive method to index and manipulate the functioning of the human nervous system. Clinical scientists are poised to apply this technology to assess, treat, and better understand complex socioemotional processes that underlie many forms of psychopathology. In this review, we describe the potential benefits and hurdles, both technical and methodological, of neurotechnology in the context of clinical dysfunction. We also offer a framework for developing and evaluating neurotechnologies that is intended to expedite progress at the nexus of clinical science and neural-interface designs by providing a comprehensive vocabulary to describe the necessary features of neurotechnology in the clinic.

Validation of the NIMH-ChEFS adolescent face stimulus set in an adolescent, parent, and health professional sample.

Attention to faces is a fundamental psychological process in humans, with atypical attention to faces noted across several clinical disorders. Although many clinical disorders onset in adolescence, there is a lack of well‐validated stimulus sets containing adolescent faces available for experimental use. Further, the images comprising most available sets are not controlled for high‐ and low‐level visual properties. Here, we present a cross‐site validation of the National Institute of Mental Health Child Emotional Faces Picture Set (NIMH‐ChEFS), comprised of 257 photographs of adolescent faces displaying angry, fearful, happy, sad, and neutral expressions. All of the direct facial images from the NIMH‐ChEFS set were adjusted in terms of location of facial features and standardized for luminance, size, and smoothness. Although overall agreement between raters in this study and the original development‐site raters was high (89.52%), this differed by group such that agreement was lower for adolescents relative to mental health professionals in the current study. These results suggest that future research using this face set or others of adolescent/child faces should base comparisons on similarly‐aged validation data. Copyright

Brain electrophysiology reveals intact processing of speech sounds in deformational plagiocephaly.

Background: The prevalence of deformational plagiocephaly has risen dramatically in recent years, now affecting 15 percent or more of infants. Prior research using developmental scales suggests that these children may be at elevated risk for developmental delays. However, the low positive predictive value of such instruments in identifying long-term impairment, coupled with their poor reliability in infants, warrants the development of methods to more precisely measure brain function in craniofacial patients. Event-related potentials offer a direct measure of cortical activity that is highly applicable to young populations and has been implemented in other disorders to predict long-term cognitive functioning. The current study used event-related potentials to contrast neural correlates of auditory perception in infants with deformational plagiocephaly and typically developing children. Methods: Event-related potentials were recorded while 16 infants with deformational plagiocephaly and 18 nonaffected controls passively listened to speech sounds. Given prior research suggesting their association with subsequent functioning, analyses focused on the P150 and N450 event-related potential components. Results: Deformational plagiocephaly patients and normal controls showed comparable cortical responses to speech sounds at both auditory event-related potential components. Conclusions: Children with deformational plagiocephaly demonstrate neural responses to language that are consistent with normative expectations and comparable to those of typical children. These results indicate that head shape deformity secondary to supine sleep is not associated with impairments in auditory processing. The applicability of the current methods in early infancy suggests that electrophysiologic brain recordings represent a promising method of monitoring brain development in children with cranial disorders. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Spatiotemporal dissociation of brain activity underlying threat and reward in social anxiety disorder

Abstract Social anxiety disorder (SAD) involves abnormalities in social motivation, which may be independent of well-documented differences in fear and arousal systems. Yet, the neurobiology underlying motivational difficulties in SAD is not well understood. The aim of the current study was to spatiotemporally dissociate reward circuitry dysfunction from alterations in fear and arousal-related neural activity during anticipation and notification of social and non-social reward and punishment. During fMRI acquisition, non-depressed adults with social anxiety disorder (SAD; N = 21) and age-, sex- and IQ-matched control subjects (N = 22) completed eight runs of an incentive delay task, alternating between social and monetary outcomes and interleaved in alternating order between gain and loss outcomes. Adults with SAD demonstrated significantly reduced neural activity in ventral striatum during the anticipation of positive but not negative social outcomes. No differences between the SAD and control groups were observed during anticipation of monetary gain or loss outcomes or during anticipation of negative social images. However, consistent with previous work, the SAD group demonstrated amygdala hyper-activity upon notification of negative social outcomes. Degraded anticipatory processing in bilateral ventral striatum in SAD was constrained exclusively to anticipation of positive social information and dissociable from the effects of negative social outcomes previously observed in the amygdala. Alterations in anticipation-related neural signals may represent a promising target for treatment that is not addressed by available evidence-based interventions, which focus primarily on fear extinction and habituation processes.

A computer-generated animated face stimulus set for psychophysiological research

Human faces are fundamentally dynamic, but experimental investigations of face perception have traditionally relied on static images of faces. Although naturalistic videos of actors have been used with success in some contexts, much research in neuroscience and psychophysics demands carefully controlled stimuli. In this article, we describe a novel set of computer-generated, dynamic face stimuli. These grayscale faces are tightly controlled for low- and high-level visual properties. All faces are standardized in terms of size, luminance, location, and the size of facial features. Each face begins with a neutral pose and transitions to an expression over the course of 30 frames. Altogether, 222 stimuli were created, spanning three different categories of movement: (1) an affective movement (fearful face), (2) a neutral movement (close-lipped, puffed cheeks with open eyes), and (3) a biologically impossible movement (upward dislocation of eyes and mouth). To determine whether early brain responses sensitive to low-level visual features differed between the expressions, we measured the occipital P100 event-related potential, which is known to reflect differences in early stages of visual processing, and the N170, which reflects structural encoding of faces. We found no differences between the faces at the P100, indicating that different face categories were well matched on low-level image properties. This database provides researchers with a well-controlled set of dynamic faces, controlled for low-level image characteristics, that are applicable to a range of research questions in social perception.