Joy Hirsch - US grants

brain morphology; functional magnetic resonance imaging; biomedical resource; clinical research;

? DESCRIPTION (provided by applicant): Social interaction and communication are fundamental human functions and are conserved across cultures and other mammalian species. Yet little is known about the underlying neural dynamics that drive these behaviors. Conventional functional imaging studies using fMRI and PET that investigate the neural underpinnings of spoken language have generally been limited to investigations of single subjects and non-interactive paradigms. Thus, questions of the neural mechanisms specialized for interpersonal exchanges remain understudied. The motivating hypothesis for this investigation is that interpersonal dialogue between two individuals engages a neural complex that extends beyond the functional specializations of Broca's and Wernicke's Areas known as the canonical language system and serves as a paradigm to investigate social behavior in real-time paradigms. Specifically, we hypothesize that a neural complex specialized for multi-agent interpersonal communication incorporates synchronizing information shared between the partners (transmission), using meaningful visual and auditory input cues (reception), and integrates functions that guide turn-taking behavior (regulation) between speakers. Near-infrared spectroscopy (NIRS) provides a non- invasive imaging technique that acquires the Blood Oxygen Level Dependent (BOLD) signals using absorbance spectra, and is suitable for the study of brain function in pairs of behaving subjects which is enabled by the use of portable and wearable optodes located on the surface of the head. We propose to use fNIRS and interacting pairs of subjects to compare neural responses during monologue, dialogue, and simultaneous recitation conditions, as well as face-to-face and occluded conditions that systematically limit visual and auditory input. Computational approaches will be based on coherence measures determined by wavelet analyses between homologous regions of the two interacting brains as evidence for the neural response to social engagement and of the associated underlying neural circuitry. We anticipate that dialogue tasks will activate the canonical language system more than monologue tasks, as well as additional social brain systems that receive facial information and are associated with regulatory and control functions. For example, these areas may include fusiform gyrus (interpretation of facial information) and dorsal lateral prefrontal cortex (regulation and control of neural events) respectively. Findings will provide the basis for a transceiver model of human communication including the neural underpinnings of a transmitter (speech production), a receiver (visual and auditory input), and a regulator (control of turn-taking in a conversation). The aims of this proposal are intended to provide a foundation that enables extended studies of inter-brain synchronization during social behavior and interpersonal communication in socially-healthy individuals that can be applied to social disorders in subsequent studies.

PROJECT SUMMARY Social interaction and communication begin in early infancy, and, although these are fundamental human functions, little is known about the underlying neural mechanisms that regulate them particularly in Autism Spectrum Disorder (ASD). ASD is a neurodevelopmental disorder characterized by significant disabilities in language and social skills, and the specific neural mechanisms that lead to these disabilities remain active topics for investigation. Emerging theoretical directions converge on problems with eye-contact as a salient component of these communication and social disabilities. Technical limitations, however, associated with imaging of two or more individuals during natural communication and mutual eye contact have been a primary obstacle to these investigations. To overcome this technical impasse, we employ a rapidly developing brain imaging technology, functional near-infrared spectroscopy (fNIRS) allowing simultaneous neural imaging of two individuals during valid interactions to observe the neural effects of eye-to-eye contact and actual dialogue. Functional NIRS detects active neural tissue based on the blood-oxygen-level-dependent (BOLD) signal by measuring variations in the absorption spectra associated with oxyhemoglobin and deoxyhemoglobin. Because detectors and emitters are surface mounted on the head, they are relatively insensitive to head movement, and, as such, fNIRS is well suited for investigations of neural events engaged during active interpersonal interactions between two participants. The neural mechanisms that underlie atypical interpersonal interactions and eye contact in adult ASD are the focus of this proposal. Pilot studies confirm the feasibility of all aspects of this research project. Dyads consisting of a confederate and a participants with typical development (TYP) or ASD will be compared during neuroimaging while engaged in natural interaction and communication. We introduce a computational approach based on wavelet analysis to quantify regional cross-brain coherence between the two participants and hypothesize that cross-brain coherence associated with speech and eye contact will be reduced in ASD relative to the TYP cohort. Cross-brain computations also form the basis for a model of dynamic neural processes based on neural ?send and receive? functions during communication. We hypothesize that these dynamic ?cross-brain communication? systems unify and coordinate the roles of language production and reception (Broca's and Wernicke's Areas), respectively, with visual reception involving face specializations (fusiform gyrus). Computational comparison of cross-brain connectivity effects as well as conventional functional connectivity and segregation/contrast effects during live communication both with and without direct eye contact provides a transformational technical, empirical, computational, and theoretical advance toward understanding the dynamic neural mechanisms associated with social and communication disabilities in ASD.

PROJECT SUMMARY Little is known about the neural mechanisms that regulate natural dynamic cues during human social and emotional interactions, although these mechanisms are impaired in many psychiatric and neurological disorders. Although it is widely understood that social signals such as facial expressions carry salient, but implicit, emotional and social cues, these ?real-time? pathways have not been investigated with dual-brain neuroimaging techniques. This unmet need is largely due to technological limitations that prevent neuroimaging of two or more individuals during natural interactive situations. We overcome this technical ?roadblock? with recent advances in an emerging human brain imaging technology, functional near-infrared spectroscopy (fNIRS). This non-invasive technique detects active neural tissue based on hemodynamic signals measured by variations in the absorption spectra associated with oxyhemoglobin and de-oxyhemoglobin. Because detectors and emitters are surface mounted on the head, absent a high magnetic field, they are relatively insensitive to head movement and thus successfully applied to dyadic experiments. The focus of this proposal is to gain a comprehensive understanding of the mechanisms that underlie dynamic cross-brain neural coupling during real interpersonal interactions. Cross-brain neural coupling is defined as the correlation between the temporal patterns of the signals of two brains. It has been proposed that these matched patterns represent shared neural processes including dynamic exchanges of information. However, the basic assumptions of shared information and temporal resonance patterns between specific brain-to-brain regions has not been tested. We pioneer tests of these hypothesis using eye-to-eye contact as a metric of shared information and predict that dynamic neural coupling between the two brains will increase with increasing numbers of eye-to-eye contact events. Mimicry of facial expressions is also a metric of emotional contagion as well as shared information between brains. We further test the hypothesis that neural coupling will increase with the level of mimicry also by virtue of the shared information Confirmation of the hypothesis that neural coupling represents shared information between the two brains would provide a singular advance for understanding mechanisms for dynamic interactions. Both approaches include variations of emotive expressions to test the additional hypothesis that content as well as shared information might influence dynamic coupling mechanisms. Findings from these studies are expected to open a new direction for the study of live and dynamic interactions between individuals, and provide foundational components to a general framework for models of face-to-face interactions. A long-term goal is to understand the neural underpinnings of affective disorders as they present in clinically-relevant and real-world situations.