Neural correlates of eye contact and social function in autism spectrum disorder.

Reluctance to make eye contact during natural interactions is a central diagnostic criterion for autism spectrum disorder (ASD). However, the underlying neural correlates for eye contacts in ASD are unknown, and diagnostic biomarkers are active areas of investigation. Here, neuroimaging, eye-tracking, and pupillometry data were acquired simultaneously using two-person functional near-infrared spectroscopy (fNIRS) during live "in-person" eye-to-eye contact and eye-gaze at a video face for typically-developed (TD) and participants with ASD to identify the neural correlates of live eye-to-eye contact in both groups. Comparisons between ASD and TD showed decreased right dorsal-parietal activity and increased right ventral temporal-parietal activity for ASD during live eye-to-eye contact (p≤0.05, FDR-corrected) and reduced cross-brain coherence consistent with atypical neural systems for live eye contact. Hypoactivity of right dorsal-parietal regions during eye contact in ASD was further associated with gold standard measures of social performance by the correlation of neural responses and individual measures of: ADOS-2, Autism Diagnostic Observation Schedule, 2nd Edition (r = -0.76, -0.92 and -0.77); and SRS-2, Social Responsiveness Scale, Second Edition (r = -0.58). The findings indicate that as categorized social ability decreases, neural responses to real eye-contact in the right dorsal parietal region also decrease consistent with a neural correlate for social characteristics in ASD.

Activation in Right Dorsolateral Prefrontal Cortex Underlies Stuttering Anticipation.

People who stutter learn to anticipate many of their overt stuttering events. Despite the critical role of anticipation, particularly how responses to anticipation shape stuttering behaviors, the neural bases associated with anticipation are unknown. We used a novel approach to identify anticipated and unanticipated words, which were produced by 22 adult stutterers in a delayed-response task while hemodynamic activity was measured using functional near infrared spectroscopy (fNIRS). Twenty-two control participants were included such that each individualized set of anticipated and unanticipated words was produced by one stutterer and one control participant. We conducted an analysis on the right dorsolateral prefrontal cortex (R-DLPFC) based on converging lines of evidence from the stuttering and cognitive control literatures. We also assessed connectivity between the R-DLPFC and right supramarginal gyrus (R-SMG), two key nodes of the frontoparietal network (FPN), to assess the role of cognitive control, and particularly error-likelihood monitoring, in stuttering anticipation. All analyses focused on the five-second anticipation phase preceding the go signal to produce speech. The results indicate that anticipated words are associated with elevated activation in the R-DLPFC, and that compared to non-stutterers, stutterers exhibit greater activity in the R-DLPFC, irrespective of anticipation. Further, anticipated words are associated with reduced connectivity between the R-DLPFC and R-SMG. These findings highlight the potential roles of the R-DLPFC and the greater FPN as a neural substrate of stuttering anticipation. The results also support previous accounts of error-likelihood monitoring and action-stopping in stuttering anticipation. Overall, this work offers numerous directions for future research with clinical implications for targeted neuromodulation.

Bidirectional Connectivity Between Broca's Area and Wernicke's Area During Interactive Verbal Communication.

Aim: This investigation aims to advance the understanding of neural dynamics that underlies live and natural interactions during spoken dialogue between two individuals. Introduction: The underlying hypothesis is that functional connectivity between canonical speech areas in the human brain will be modulated by social interaction. Methods: Granger causality was applied to compare directional connectivity across Broca's and Wernicke's areas during verbal conditions consisting of interactive and noninteractive communication. Thirty-three pairs of healthy adult participants alternately talked and listened to each other while performing an object naming and description task that was either interactive or not during hyperscanning with functional near-infrared spectroscopy (fNIRS). In the noninteractive condition, the speaker named and described a picture-object without reference to the partner's description. In the interactive condition, the speaker performed the same task but included an interactive response about the preceding comments of the partner. Causality measures of hemodynamic responses from Broca's and Wernicke's areas were compared between real, surrogate, and shuffled trials within dyads. Results: The interactive communication was characterized by bidirectional connectivity between Wernicke's and Broca's areas of the listener's brain. Whereas this connectivity was unidirectional in the speaker's brain. In the case of the noninteractive condition, both speaker's and listener's brains showed unidirectional top-down (Broca's area to Wernicke's area) connectivity. Conclusion: Together, directional connectivity as determined by Granger analysis reveals bidirectional flow of neuronal information during dynamic two-person verbal interaction for processes that are active during listening (reception) and not during talking (production). Findings are consistent with prior contrast findings (general linear model) showing neural modulation of the receptive language system associated with Wernicke's area during a two-person live interaction. Impact statement The neural dynamics that underlies real-life social interactions is an emergent topic of interest. Dynamically coupled cross-brain neural mechanisms between interacting partners during verbal dialogue have been shown within Wernicke's area. However, it is not known how within-brain long-range neural mechanisms operate during these live social functions. Using Granger causality analysis, we show bidirectional neural activity between Broca's and Wernicke's areas during interactive dialogue compared with a noninteractive control task showing only unidirectional activity. Findings are consistent with an Interactive Brain Model where long-range neural mechanisms process interactive processes associated with rapid and spontaneous spoken social cues.

Comparison of short-channel separation and spatial domain filtering for removal of non-neural components in functional near-infrared spectroscopy signals.

Significance: With the increasing popularity of functional near-infrared spectroscopy (fNIRS), the need to determine localization of the source and nature of the signals has grown. Aim: We compare strategies for removal of non-neural signals for a finger-thumb tapping task, which shows responses in contralateral motor cortex and a visual checkerboard viewing task that produces activity within the occipital lobe. Approach: We compare temporal regression strategies using short-channel separation to a spatial principal component (PC) filter that removes global signals present in all channels. For short-channel temporal regression, we compare non-neural signal removal using first and combined first and second PCs from a broad distribution of short channels to limited distribution on the forehead. Results: Temporal regression of non-neural information from broadly distributed short channels did not differ from forehead-only distribution. Spatial PC filtering provides results similar to short-channel separation using the temporal domain. Utilizing both first and second PCs from short channels removes additional non-neural information. Conclusions: We conclude that short-channel information in the temporal domain and spatial domain regression filtering methods remove similar non-neural components represented in scalp hemodynamics from fNIRS signals and that either technique is sufficient to remove non-neural components.

Joint Attention During Live Person-to-Person Contact Activates rTPJ, Including a Sub-Component Associated With Spontaneous Eye-to-Eye Contact.

Eye-to-eye contact is a spontaneous behavior between interacting partners that occurs naturally during social interactions. However, individuals differ with respect to eye gaze behaviors such as frequency of eye-to-eye contacts, and these variations may reflect underlying differences in social behavior in the population. While the use of eye signaling to indicate a shared object of attention in joint attention tasks has been well-studied, the effects of the natural variation in establishing eye contact during joint attention have not been isolated. Here, we investigate this question using a novel two-person joint attention task. Participants were not instructed regarding the use of eye contacts; thus all mutual eye contact events between interacting partners that occurred during the joint attention task were spontaneous and varied with respect to frequency. We predicted that joint attention systems would be modulated by differences in the social behavior across participant pairs, which could be measured by the frequency of eye contact behavior. We used functional near-infrared spectroscopy (fNIRS) hyperscanning and eye-tracking to measure the neural signals associated with joint attention in interacting dyads and to record the number of eye contact events between them. Participants engaged in a social joint attention task in which real partners used eye gaze to direct each other's attention to specific targets. Findings were compared to a non-social joint attention task in which an LED cue directed both partners' attention to the same target. The social joint attention condition showed greater activity in right temporoparietal junction than the non-social condition, replicating prior joint attention results. Eye-contact frequency modulated the joint attention activity, revealing bilateral activity in social and high level visual areas associated with partners who made more eye contact. Additionally, when the number of mutual eye contact events was used to classify each pair as either "high eye contact" or "low eye contact" dyads, cross-brain coherence analysis revealed greater coherence between high eye contact dyads than low eye contact dyads in these same areas. Together, findings suggest that variation in social behavior as measured by eye contact modulates activity in a subunit of the network associated with joint attention.

Optimization of wavelet coherence analysis as a measure of neural synchrony during hyperscanning using functional near-infrared spectroscopy.

Significance: The expanding field of human social interaction is enabled by functional near-infrared spectroscopy (fNIRS) that acquires hemodynamic signals during live two-person interactions. These advances call for development of methods to quantify interactive processes. Aim: Wavelet coherence analysis has been applied to cross-brain neural coupling. However, fNIRS-specific computations have not been explored. This investigation determines the effects of global mean removal, wavelet equation, and choice of oxyhemoglobin versus deoxyhemoglobin signals. Approach: We compare signals with a known coherence with acquired signals to determine optimal computational approaches. The known coherence was calculated using three visual stimulation sequences of a contrast-reversing checkerboard convolved with the canonical hemodynamic response function. This standard was compared with acquired human fNIRS responses within visual cortex using the same sequences. Results: Observed coherence was consistent with known coherence with highest correlations within the wavelength range between 10 and 20 s. Removal of the global mean improved the correlation irrespective of the specific equation for wavelet coherence, and the oxyhemoglobin signal was associated with a marginal correlation advantage. Conclusions: These findings provide both methodological and computational guidance that enhances the validity and interpretability of wavelet coherence analysis for fNIRS signals acquired during live social interactions.

Real-Time Eye-to-Eye Contact Is Associated With Cross-Brain Neural Coupling in Angular Gyrus.

Direct eye contact between two individuals is a salient social behavior known to initiate and promote interpersonal interaction. However, the neural processes that underlie these live interactive behaviors and eye-to-eye contact are not well understood. The Dynamic Neural Coupling Hypothesis presents a general theoretical framework proposing that shared interactive behaviors are represented by cross-brain signal coherence. Using functional near-infrared spectroscopy (fNIRS) adapted for hyper scanning, we tested this hypothesis specifically for neural mechanisms associated with eye-to-eye gaze between human participants compared to similar direct eye-gaze at a dynamic video of a face and predicted that the coherence of neural signals between the two participants during reciprocal eye-to-eye contact would be greater than coherence observed during direct eye-gaze at a dynamic video for those signals originating in social and face processing systems. Consistent with this prediction cross-brain coherence was increased for signals within the angular gyrus (AG) during eye-to-eye contact relative to direct eye-gaze at a dynamic face video (p < 0.01). Further, activity in the right temporal-parietal junction (TPJ) was increased in the real eye-to-eye condition (p < 0.05, FDR corrected). Together, these findings advance a functional and mechanistic understanding of the AG and cross-brain neural coupling associated with real-time eye-to-eye contact.

Co-localization of theta-band activity and hemodynamic responses during face perception: simultaneous electroencephalography and functional near-infrared spectroscopy recordings.

Face-specific neural processes in the human brain have been localized to multiple anatomical structures and associated with diverse and dynamic social functions. The question of how various face-related systems and functions may be bound together remains an active area of investigation. We hypothesize that face processing may be associated with specific frequency band oscillations that serve to integrate distributed face processing systems. Using a multimodal imaging approach, including electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS), simultaneous signals were acquired during face and object picture viewing. As expected for face processing, hemodynamic activity in the right occipital face area (OFA) increased during face viewing compared to object viewing, and in a subset of participants, the expected N170 EEG response was observed for faces. Based on recently reported associations between the theta band and visual processing, we hypothesized that increased hemodynamic activity in a face processing area would also be associated with greater theta-band activity originating in the same area. Consistent with our hypothesis, theta-band oscillations were also localized to the right OFA for faces, whereas alpha- and beta-band oscillations were not. Together, these findings suggest that theta-band oscillations originating in the OFA may be part of the distributed face-specific processing mechanism.

A cross-brain neural mechanism for human-to-human verbal communication.

Neural mechanisms that mediate dynamic social interactions remain understudied despite their evolutionary significance. The interactive brain hypothesis proposes that interactive social cues are processed by dedicated brain substrates and provides a general theoretical framework for investigating the underlying neural mechanisms of social interaction. We test the specific case of this hypothesis proposing that canonical language areas are upregulated and dynamically coupled across brains during social interactions based on talking and listening. Functional near-infrared spectroscopy (fNIRS) was employed to acquire simultaneous deoxyhemoglobin (deOxyHb) signals of the brain on partners who alternated between speaking and listening while doing an Object Naming & Description task with and without interaction in a natural setting. Comparison of interactive and non-interactive conditions confirmed an increase in neural activity associated with Wernicke's area including the superior temporal gyrus (STG) during interaction (P = 0.04). However, the hypothesis was not supported for Broca's area. Cross-brain coherence determined by wavelet analyses of signals originating from the STG and the subcentral area was greater during interaction than non-interaction (P < 0.01). In support of the interactive brain hypothesis these findings suggest a dynamically coupled cross-brain neural mechanism dedicated to pathways that share interpersonal information.

Comparison of oxyhemoglobin and deoxyhemoglobin signal reliability with and without global mean removal for digit manipulation motor tasks.

Functional near-infrared spectroscopy (fNIRS) could be well suited for clinical use, such as measuring neural activity before and after treatment; however, reliability and specificity of fNIRS signals must be ensured so that differences can be attributed to the intervention. This study compared the test-retest and longitudinal reliability of oxyhemoglobin and deoxyhemoglobin signals before and after spatial filtering. In the test-retest experiment, 14 participants were scanned on 2 days while performing four right-handed digit-manipulation tasks. Group results revealed greater test-retest reliability for oxyhemoglobin than deoxyhemoglobin signals and greater spatial specificity for the deoxyhemoglobin signals. To further characterize reliability, a longitudinal experiment was conducted in which two participants repeated the same motor tasks for 10 days. Beta values from the two tasks with the lowest and highest test-retest reliability, respectively, in the spatially filtered deoxyhemoglobin signal are reported as representative findings. Both test-retest and longitudinal methods confirmed that task and signal type influence reliability. Oxyhemoglobin signals were more reliable overall than deoxyhemoglobin, and removal of the global mean reduced reliability of both signals. Findings are consistent with the suggestion that systemic components most prevalent in the oxyhemoglobin signal may inflate reliability relative to the deoxyhemoglobin signal, which is less influenced by systemic factors.

Signal processing of functional NIRS data acquired during overt speaking.

Functional near-infrared spectroscopy (fNIRS) offers an advantage over traditional functional imaging methods [such as functional magnetic resonance imaging (fMRI)] by allowing participants to move and speak relatively freely. However, neuroimaging while actively speaking has proven to be particularly challenging due to the systemic artifacts that tend to be located in the critical brain areas. To overcome these limitations and enhance the utility of fNIRS, we describe methods for investigating cortical activity during spoken language tasks through refinement of deoxyhemoglobin (deoxyHb) signals with principal component analysis (PCA) spatial filtering to remove global components. We studied overt picture naming and compared oxyhemoglobin (oxyHb) and deoxyHb signals with and without global component removal using general linear model approaches. Activity in Broca's region and supplementary motor cortex was observed only when the filter was applied to the deoxyHb signal and was shown to be spatially comparable to fMRI data acquired using a similar task and to meta-analysis data. oxyHb signals did not yield expected activity in Broca's region with or without global component removal. This study demonstrates the utility of a PCA spatial filter on the deoxyHb signal in revealing neural activity related to a spoken language task and extends applications of fNIRS to natural and ecologically valid conditions.

Neural correlates of conflict between gestures and words: A domain-specific role for a temporal-parietal complex.

The interpretation of social cues is a fundamental function of human social behavior, and resolution of inconsistencies between spoken and gestural cues plays an important role in successful interactions. To gain insight into these underlying neural processes, we compared neural responses in a traditional color/word conflict task and to a gesture/word conflict task to test hypotheses of domain-general and domain-specific conflict resolution. In the gesture task, recorded spoken words ("yes" and "no") were presented simultaneously with video recordings of actors performing one of the following affirmative or negative gestures: thumbs up, thumbs down, head nodding (up and down), or head shaking (side-to-side), thereby generating congruent and incongruent communication stimuli between gesture and words. Participants identified the communicative intent of the gestures as either positive or negative. In the color task, participants were presented the words "red" and "green" in either red or green font and were asked to identify the color of the letters. We observed a classic "Stroop" behavioral interference effect, with participants showing increased response time for incongruent trials relative to congruent ones for both the gesture and color tasks. Hemodynamic signals acquired using functional near-infrared spectroscopy (fNIRS) were increased in the right dorsolateral prefrontal cortex (DLPFC) for incongruent trials relative to congruent trials for both tasks consistent with a common, domain-general mechanism for detecting conflict. However, activity in the left DLPFC and frontal eye fields and the right temporal-parietal junction (TPJ), superior temporal gyrus (STG), supramarginal gyrus (SMG), and primary and auditory association cortices was greater for the gesture task than the color task. Thus, in addition to domain-general conflict processing mechanisms, as suggested by common engagement of right DLPFC, socially specialized neural modules localized to the left DLPFC and right TPJ including adjacent homologous receptive language areas were engaged when processing conflicting communications. These findings contribute to an emerging view of specialization within the TPJ and adjacent areas for interpretation of social cues and indicate a role for the region in processing social conflict.

Shindigs, brunches, and rodeos: the neural basis of event words.

Events (e.g., "running" or "eating") constitute a basic type within human cognition and human language. We asked whether thinking about events, as compared to other conceptual categories, depends on partially independent neural circuits. Indirect evidence for this hypothesis comes from previous studies showing elevated posterior temporal responses to verbs, which typically label events. Neural responses to verbs could, however, be driven either by their grammatical or by their semantic properties. In the present experiment, we separated the effects of grammatical class (verb vs. noun) and semantic category (event vs. object) by measuring neural responses to event nouns (e.g., "the hurricane"). Participants rated the semantic relatedness of event nouns, as well as of two categories of object nouns-animals (e.g., "the alligator") and plants (e.g., "the acorn")-and three categories of verbs-manner of motion (e.g., "to roll"), emission (e.g., "to sparkle"), and perception (e.g., "to gaze"). As has previously been observed, we found larger responses to verbs than to object nouns in the left posterior middle (LMTG) and superior (LSTG) temporal gyri. Crucially, we also found that the LMTG responds more to event than to object nouns. These data suggest that part of the posterior lateral temporal response to verbs is driven by their semantic properties. By contrast, a more superior region, at the junction of the temporal and parietal cortices, responded more to verbs than to all nouns, irrespective of their semantic category. We concluded that the neural mechanisms engaged when thinking about event and object categories are partially dissociable.

People can understand descriptions of motion without activating visual motion brain regions.

What is the relationship between our perceptual and linguistic neural representations of the same event? We approached this question by asking whether visual perception of motion and understanding linguistic depictions of motion rely on the same neural architecture. The same group of participants took part in two language tasks and one visual task. In task 1, participants made semantic similarity judgments with high motion (e.g., "to bounce") and low motion (e.g., "to look") words. In task 2, participants made plausibility judgments for passages describing movement ("A centaur hurled a spear … ") or cognitive events ("A gentleman loved cheese …"). Task 3 was a visual motion localizer in which participants viewed animations of point-light walkers, randomly moving dots, and stationary dots changing in luminance. Based on the visual motion localizer we identified classic visual motion areas of the temporal (MT/MST and STS) and parietal cortex (inferior and superior parietal lobules). We find that these visual cortical areas are largely distinct from neural responses to linguistic depictions of motion. Motion words did not activate any part of the visual motion system. Motion passages produced a small response in the right superior parietal lobule, but none of the temporal motion regions. These results suggest that (1) as compared to words, rich language stimuli such as passages are more likely to evoke mental imagery and more likely to affect perceptual circuits and (2) effects of language on the visual system are more likely in secondary perceptual areas as compared to early sensory areas. We conclude that language and visual perception constitute distinct but interacting systems.

A sensitive period for language in the visual cortex: distinct patterns of plasticity in congenitally versus late blind adults.

Recent evidence suggests that blindness enables visual circuits to contribute to language processing. We examined whether this dramatic functional plasticity has a sensitive period. BOLD fMRI signal was measured in congenitally blind, late blind (blindness onset 9-years-old or later) and sighted participants while they performed a sentence comprehension task. In a control condition, participants listened to backwards speech and made match/non-match to sample judgments. In both congenitally and late blind participants BOLD signal increased in bilateral foveal-pericalcarine cortex during response preparation, irrespective of whether the stimulus was a sentence or backwards speech. However, left occipital areas (pericalcarine, extrastriate, fusiform and lateral) responded more to sentences than backwards speech only in congenitally blind people. We conclude that age of blindness onset constrains the non-visual functions of occipital cortex: while plasticity is present in both congenitally and late blind individuals, recruitment of visual circuits for language depends on blindness during childhood.