Sarah Shultz

Neural signatures of autism

Functional magnetic resonance imaging of brain responses to biological motion in children with autism spectrum disorder (ASD), unaffected siblings (US) of children with ASD, and typically developing (TD) children has revealed three types of neural signatures: (i) state activity, related to the state of having ASD that characterizes the nature of disruption in brain circuitry; (ii) trait activity, reflecting shared areas of dysfunction in US and children with ASD, thereby providing a promising neuroendophenotype to facilitate efforts to bridge genomic complexity and disorder heterogeneity; and (iii) compensatory activity, unique to US, suggesting a neural system–level mechanism by which US might compensate for an increased genetic risk for developing ASD. The distinct brain responses to biological motion exhibited by TD children and US are striking given the identical behavioral profile of these two groups. These findings offer far-reaching implications for our understanding of the neural systems underlying autism.

Inhibition of eye blinking reveals subjective perceptions of stimulus salience

Spontaneous eye blinking serves a critical physiological function, but it also interrupts incoming visual information. This tradeoff suggests that the inhibition of eye blinks might constitute an adaptive reaction to minimize the loss of visual information, particularly information that a viewer perceives to be important. To test this hypothesis, we examined whether the timing of blink inhibition, during natural viewing, is modulated between as well as within tasks, and also whether the timing of blink inhibition varies as a function of viewer engagement and stimulus event type. While viewing video scenes, we measured the timing of blinks and blink inhibition, as well as visual scanning, in a group of typical two-year-olds, and in a group of two-year-olds known for attenuated reactivity to affective stimuli: toddlers with Autism Spectrum Disorders (ASD). Although both groups dynamically adjusted the timing of their blink inhibition at levels greater than expected by chance, they inhibited their blinking and shifted visual fixation differentially with respect to salient onscreen events. Moreover, typical toddlers inhibited their blinking earlier than toddlers with ASD, indicating active anticipation of the unfolding of those events. These findings indicate that measures of blink inhibition can serve as temporally precise markers of perceived stimulus salience and are useful quantifiers of atypical processing of social affective signals in toddlers with ASD.

Social visual engagement in infants and toddlers with autism: early developmental transitions and a model of pathogenesis.

Efforts to determine and understand the causes of autism are currently hampered by a large disconnect between recent molecular genetics findings that are associated with the condition and the core behavioral symptoms that define the condition. In this perspective piece, we propose a systems biology framework to bridge that gap between genes and symptoms. The framework focuses on basic mechanisms of socialization that are highly-conserved in evolution and are early-emerging in development. By conceiving of these basic mechanisms of socialization as quantitative endophenotypes, we hope to connect genes and behavior in autism through integrative studies of neurodevelopmental, behavioral, and epigenetic changes. These changes both lead to and are led by the accomplishment of specific social adaptive tasks in a typical infants life. However, based on recent research that indicates that infants later diagnosed with autism fail to accomplish at least some of these tasks, we suggest that a narrow developmental period, spanning critical transitions from reflexive, subcortically-controlled visual behavior to interactional, cortically-controlled and social visual behavior be prioritized for future study. Mapping epigenetic, neural, and behavioral changes that both drive and are driven by these early transitions may shed a bright light on the pathogenesis of autism.

Neural Specialization for Speech in the First Months of Life.

How does the brain’s response to speech change over the first months of life? Although behavioral findings indicate that neonates’ listening biases are sharpened over the first months of life, with a species-specific preference for speech emerging by 3 months, the neural substrates underlying this developmental change are unknown. We examined neural responses to speech compared with biological non-speech sounds in 1- to 4-month-old infants using fMRI. Infants heard speech and biological non-speech sounds, including heterospecific vocalizations and human non-speech. We observed a left-lateralized response in temporal cortex for speech compared to biological non-speech sounds, indicating that this region is highly selective for speech by the first month of life. Specifically, this brain region becomes increasingly selective for speech over the next 3 months as neural substrates become less responsive to non-speech sounds. These results reveal specific changes in neural responses during a developmental period characterized by rapid behavioral changes.

The superior temporal sulcus differentiates communicative and noncommunicative auditory signals

Processing the vocalizations of conspecifics is critical for adaptive social interaction. A species-specific voice-selective region has been identified in the right STS that responds more strongly to human vocal sounds compared with a variety of nonvocal sounds. However, the STS also activates in response to a wide range of signals used in communication, such as eye gaze, biological motion, and speech. These findings raise the possibility that the voice-selective region of the STS may be especially sensitive to vocal sounds that are communicative, rather than to all human vocal sounds. Using fMRI, we demonstrate that the voice-selective region of the STS responds more strongly to communicative vocal sounds (such as speech and laughter) compared with noncommunicative vocal sounds (such as coughing and sneezing). The implications of these results for understanding the role of the STS in voice processing and in disorders of social communication, such as autism spectrum disorder, are discussed.

The posterior superior temporal sulcus is sensitive to the outcome of human and non-human goal-directed actions

Prior studies have demonstrated that the posterior superior temporal sulcus (pSTS) is involved in analyzing the intentions underlying actions and is sensitive to the context within which actions occur. However, it is debated whether the pSTS is actually sensitive to goals underlying actions, or whether previous studies can be interpreted to suggest that the pSTS is instead involved in the allocation of visual attention towards unexpected events. In addition, little is known about whether the pSTS is specialized for reasoning about the actions of social agents or whether the pSTS is sensitive to the actions of both animate and inanimate entities. Here, using functional magnetic resonance imaging, we investigated activation in response to passive viewing of successful and unsuccessful animate and inanimate goal-directed actions. Activation in the right pSTS was stronger in response to failed actions compared to successful actions, suggesting that the pSTS plays a role in encoding the goals underlying actions. Activation in the pSTS did not differentiate between animate and inanimate actions, suggesting that the pSTS is sensitive to the goal-directed actions of both animate and inanimate entities.

Goal-directed actions activate the face-sensitive posterior superior temporal sulcus and fusiform gyrus in the absence of human-like perceptual cues.

The conditions under which we identify entities as animate agents and the neural mechanisms supporting this ability are central questions in social neuroscience. Prior studies have focused upon 2 perceptual cues for signaling animacy: 1) surface features representing body forms such as faces, torsos, and limbs and 2) motion cues associated with biological forms. Here, we consider a third cue--the goal-directedness of an action. Regions in the social brain network, such as the right posterior superior temporal sulcus (pSTS) and fusiform face area (FFA), are activated by human-like motion and body form perceptual cues signaling animacy. Here, we investigate whether these same brain regions are activated by goal-directed motion even when performed by entities that lack human-like perceptual cues. We observed an interaction effect whereby the presence of either human-like perceptual cues or goal-directed actions was sufficient to activate the right pSTS and FFA. Only stimuli that lacked human-like perceptual cues and goal-directed actions failed to activate the pSTS and FFA at the same level.

Perceived animacy influences the processing of human-like surface features in the fusiform gyrus.

While decades of research have demonstrated that a region of the right fusiform gyrus (FG) responds selectively to faces, a second line of research suggests that the FG responds to a range of animacy cues, including biological motion and goal-directed actions, even in the absence of faces or other human-like surface features. These findings raise the question of whether the FG is indeed sensitive to faces or to the more abstract category of animate agents. The current study uses fMRI to examine whether the FG responds to all faces in a category-specific way or whether the FG is especially sensitive to the faces of animate agents. Animate agents are defined here as intentional agents with the capacity for rational goal-directed actions. Specifically, we examine how the FG responds to an entity that looks like an animate agent but that lacks the capacity for goal-directed rational action. Region-of-interest analyses reveal that the FG activates more strongly to the animate compared with the inanimate entity, even though the surface features of both animate and inanimate entities were identical. These results suggest that the FG does not respond to all faces in a category-specific way, and is instead especially sensitive to whether an entity is animate.

Stimulus-induced reversal of information flow through a cortical network for animacy perception

Decades of research have demonstrated that a region of the right fusiform gyrus (FG) and right posterior superior temporal sulcus (pSTS) responds preferentially to static faces and biological motion, respectively. Despite this view, both regions activate in response to both stimulus categories and to a range of other stimuli, such as goal-directed actions, suggesting that these regions respond to characteristics of animate agents more generally. Here we propose a neural model for animacy detection composed of processing streams that are initially differentially sensitive to cues signaling animacy, but that ultimately act in concert to support reasoning about animate agents. We use dynamic causal modeling, a measure of effective connectivity, to demonstrate that the directional flow of information between the FG and pSTS is initially dependent on the characteristics of the animate agent presented, a key prediction of our proposed network for animacy detection.

Neonatal Transitions in Social Behavior and Their Implications for Autism

Within the context of early infant-caregiver interaction, we review a series of pivotal transitions that occur within the first 6 months of typical infancy, with emphasis on behavior and brain mechanisms involved in preferential orientation towards, and interaction with, other people. Our goal in reviewing these transitions is to better understand how they may lay a necessary and/or sufficient groundwork for subsequent phases of development, and also to understand how the breakdown thereof, when development is atypical and those transitions become derailed, may instead yield disability. We review these developmental processes in light of recent studies documenting disruptions to early-emerging brain and behavior mechanisms in infants later diagnosed with autism spectrum disorder, shedding light on the brain-behavior pathogenesis of autism.