Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group.

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE < 0.001; right: d = -0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.

Facial and neural mechanisms during interactive disclosure of biographical information.

Pairs of participants mutually communicated (or not) biographical information to each other. By combining simultaneous eye-tracking, face-tracking and functional near-infrared spectroscopy, we examined how this mutual sharing of information modulates social signalling and brain activity. When biographical information was disclosed, participants directed more eye gaze to the face of the partner and presented more facial displays. We also found that spontaneous production and observation of facial displays was associated with activity in the left SMG and right dlPFC/IFG, respectively. Moreover, mutual information-sharing increased activity in bilateral TPJ and left dlPFC, as well as cross-brain synchrony between right TPJ and left dlPFC. This suggests that a complex long-range mechanism is recruited during information-sharing. These multimodal findings support the second-person neuroscience hypothesis, which postulates that communicative interactions activate additional neurocognitive mechanisms to those engaged in non-interactive situations. They further advance our understanding of which neurocognitive mechanisms underlie communicative interactions.

Frontal temporal and parietal systems synchronize within and across brains during live eye-to-eye contact.

Human eye-to-eye contact is a primary source of social cues and communication. In spite of the biological significance of this interpersonal interaction, the underlying neural processes are not well-understood. This knowledge gap, in part, reflects limitations of conventional neuroimaging methods, including solitary confinement in the bore of a scanner and minimal tolerance of head movement that constrain investigations of natural, two-person interactions. However, these limitations are substantially resolved by recent technical developments in functional near-infrared spectroscopy (fNIRS), a non-invasive spectral absorbance technique that detects changes in blood oxygen levels in the brain by using surface-mounted optical sensors. Functional NIRS is tolerant of limited head motion and enables simultaneous acquisitions of neural signals from two interacting partners in natural conditions. We employ fNIRS to advance a data-driven theoretical framework for two-person neuroscience motivated by the Interactive Brain Hypothesis which proposes that interpersonal interaction between individuals evokes neural mechanisms not engaged during solo, non-interactive, behaviors. Within this context, two specific hypotheses related to eye-to-eye contact, functional specificity and functional synchrony, were tested. The functional specificity hypothesis proposes that eye-to-eye contact engages specialized, within-brain, neural systems; and the functional synchrony hypothesis proposes that eye-to-eye contact engages specialized, across-brain, neural processors that are synchronized between dyads. Signals acquired during eye-to-eye contact between partners (interactive condition) were compared to signals acquired during mutual gaze at the eyes of a picture-face (non-interactive condition). In accordance with the specificity hypothesis, responses during eye-to-eye contact were greater than eye-to-picture gaze for a left frontal cluster that included pars opercularis (associated with canonical language production functions known as Broca's region), pre- and supplementary motor cortices (associated with articulatory systems), as well as the subcentral area. This frontal cluster was also functionally connected to a cluster located in the left superior temporal gyrus (associated with canonical language receptive functions known as Wernicke's region), primary somatosensory cortex, and the subcentral area. In accordance with the functional synchrony hypothesis, cross-brain coherence during eye-to-eye contact relative to eye-to-picture gaze increased for signals originating within left superior temporal, middle temporal, and supramarginal gyri as well as the pre- and supplementary motor cortices of both interacting brains. These synchronous cross-brain regions are also associated with known language functions, and were partner-specific (i.e., disappeared with randomly assigned partners). Together, both within and across-brain neural correlates of eye-to-eye contact included components of previously established productive and receptive language systems. These findings reveal a left frontal, temporal, and parietal long-range network that mediates neural responses during eye-to-eye contact between dyads, and advance insight into elemental mechanisms of social and interpersonal interactions.

Greater anterior cingulate activation and connectivity in response to visual and auditory high-calorie food cues in binge eating: Preliminary findings.

Obese individuals show altered neural responses to high-calorie food cues. Individuals with binge eating [BE], who exhibit heightened impulsivity and emotionality, may show a related but distinct pattern of irregular neural responses. However, few neuroimaging studies have compared BE and non-BE groups. To examine neural responses to food cues in BE, 10 women with BE and 10 women without BE (non-BE) who were matched for obesity (5 obese and 5 lean in each group) underwent fMRI scanning during presentation of visual (picture) and auditory (spoken word) cues representing high energy density (ED) foods, low-ED foods, and non-foods. We then compared regional brain activation in BE vs. non-BE groups for high-ED vs. low-ED foods. To explore differences in functional connectivity, we also compared psychophysiologic interactions [PPI] with dorsal anterior cingulate cortex [dACC] for BE vs. non-BE groups. Region of interest (ROI) analyses revealed that the BE group showed more activation than the non-BE group in the dACC, with no activation differences in the striatum or orbitofrontal cortex [OFC]. Exploratory PPI analyses revealed a trend towards greater functional connectivity with dACC in the insula, cerebellum, and supramarginal gyrus in the BE vs. non-BE group. Our results suggest that women with BE show hyper-responsivity in the dACC as well as increased coupling with other brain regions when presented with high-ED cues. These differences are independent of body weight, and appear to be associated with the BE phenotype.

Shared space, separate processes: Neural activation patterns for auditory description and visual object naming in healthy adults.

Historically, both clinicians and cognitive scientists have used visual object naming measures to study naming, and lesion-type studies have implicated the left posterior, temporo-parietal region as a critical component of naming circuitry. However, recent results from behavioral and cortical stimulation studies using auditory description naming as well as visual object naming in left temporal lobe epilepsy patients suggest that discrete sites in anterior temporal cortex are critical for description naming, whereas posterior temporal regions mediate both visual object naming and description naming. To determine whether this task specificity reflects normal cerebral organization and processing, 13 healthy adults performed description naming and visual naming during functional neuroimaging. In addition to standard univariate analysis, multivariate, ordinal trend analysis examined the network character of the regions involved in task-specific naming. Univariate analysis indicated posterior temporal activation for both visual naming and description naming, whereas multivariate analysis revealed broader networks for both tasks, with both overlapping and task-specific regions, as well as task-related differences in the way the tasks utilized common regions. Additionally, multivariate analysis revealed unique, task-specific, regionally covarying activation patterns that were strikingly consistent in all 13 subjects for visual naming and 12/13 subjects for description naming. Results suggest a common neural substrate, yet differentiable neural processes underlying visual naming and description naming in neurologically intact individuals. These findings support the use of both types of tasks for clinical assessment and may have application in the treatment of neurologically based naming deficits. Inc.

Support vector machine prediction of individual Autism Diagnostic Observation Schedule (ADOS) scores based on neural responses during live eye-to-eye contact.

Social difficulties during interactions with others are central to autism spectrum disorder (ASD). Understanding the links between these social difficulties and their underlying neural processes is a primary aim focused on improved diagnosis and treatment. In keeping with this goal, we have developed a multivariate classification method based on neural data acquired by functional near infrared spectroscopy, fNIRS, during live eye-to-eye contact with adults who were either typically developed (TD) or individuals with ASD. The ASD diagnosis was based on the gold-standard Autism Diagnostic Observation Schedule (ADOS) which also provides an index of symptom severity. Using a nested cross-validation method, a support vector machine (SVM) was trained to discriminate between ASD and TD groups based on the neural responses during eye-to-eye contact. ADOS scores were not applied in the classification training. To test the hypothesis that SVM identifies neural activity patterns related to one of the neural mechanisms underlying the behavioral symptoms of ASD, we determined the correlation coefficient between the SVM scores and the individual ADOS scores. Consistent with the hypothesis, the correlation between observed and predicted ADOS scores was 0.72 (p < 0.002). Findings suggest that multivariate classification methods combined with the live interaction paradigm of eye-to-eye contact provide a promising approach to link neural processes and social difficulties in individuals with ASD.

The temporal derivative of expected utility: a neural mechanism for dynamic decision-making.

Real world tasks involving moving targets, such as driving a vehicle, are performed based on continuous decisions thought to depend upon the temporal derivative of the expected utility (∂V/∂t), where the expected utility (V) is the effective value of a future reward. However, the neural mechanisms that underlie dynamic decision-making are not well understood. This study investigates human neural correlates of both V and ∂V/∂t using fMRI and a novel experimental paradigm based on a pursuit-evasion game optimized to isolate components of dynamic decision processes. Our behavioral data show that players of the pursuit-evasion game adopt an exponential discounting function, supporting the expected utility theory. The continuous functions of V and ∂V/∂t were derived from the behavioral data and applied as regressors in fMRI analysis, enabling temporal resolution that exceeded the sampling rate of image acquisition, hyper-temporal resolution, by taking advantage of numerous trials that provide rich and independent manipulation of those variables. V and ∂V/∂t were each associated with distinct neural activity. Specifically, ∂V/∂t was associated with anterior and posterior cingulate cortices, superior parietal lobule, and ventral pallidum, whereas V was primarily associated with supplementary motor, pre and post central gyri, cerebellum, and thalamus. The association between the ∂V/∂t and brain regions previously related to decision-making is consistent with the primary role of the temporal derivative of expected utility in dynamic decision-making.

Decoding unattended fearful faces with whole-brain correlations: an approach to identify condition-dependent large-scale functional connectivity.

Processing of unattended threat-related stimuli, such as fearful faces, has been previously examined using group functional magnetic resonance (fMRI) approaches. However, the identification of features of brain activity containing sufficient information to decode, or "brain-read", unattended (implicit) fear perception remains an active research goal. Here we test the hypothesis that patterns of large-scale functional connectivity (FC) decode the emotional expression of implicitly perceived faces within single individuals using training data from separate subjects. fMRI and a blocked design were used to acquire BOLD signals during implicit (task-unrelated) presentation of fearful and neutral faces. A pattern classifier (linear kernel Support Vector Machine, or SVM) with linear filter feature selection used pair-wise FC as features to predict the emotional expression of implicitly presented faces. We plotted classification accuracy vs. number of top N selected features and observed that significantly higher than chance accuracies (between 90-100%) were achieved with 15-40 features. During fearful face presentation, the most informative and positively modulated FC was between angular gyrus and hippocampus, while the greatest overall contributing region was the thalamus, with positively modulated connections to bilateral middle temporal gyrus and insula. Other FCs that predicted fear included superior-occipital and parietal regions, cerebellum and prefrontal cortex. By comparison, patterns of spatial activity (as opposed to interactivity) were relatively uninformative in decoding implicit fear. These findings indicate that whole-brain patterns of interactivity are a sensitive and informative signature of unattended fearful emotion processing. At the same time, we demonstrate and propose a sensitive and exploratory approach for the identification of large-scale, condition-dependent FC. In contrast to model-based, group approaches, the current approach does not discount the multivariate, joint responses of multiple functional connections and is not hampered by signal loss and the need for multiple comparisons correction.

Neural systems for speech and song in autism.

Despite language disabilities in autism, music abilities are frequently preserved. Paradoxically, brain regions associated with these functions typically overlap, enabling investigation of neural organization supporting speech and song in autism. Neural systems sensitive to speech and song were compared in low-functioning autistic and age-matched control children using passive auditory stimulation during functional magnetic resonance and diffusion tensor imaging. Activation in left inferior frontal gyrus was reduced in autistic children relative to controls during speech stimulation, but was greater than controls during song stimulation. Functional connectivity for song relative to speech was also increased between left inferior frontal gyrus and superior temporal gyrus in autism, and large-scale connectivity showed increased frontal-posterior connections. Although fractional anisotropy of the left arcuate fasciculus was decreased in autistic children relative to controls, structural terminations of the arcuate fasciculus in inferior frontal gyrus were indistinguishable between autistic and control groups. Fractional anisotropy correlated with activity in left inferior frontal gyrus for both speech and song conditions. Together, these findings indicate that in autism, functional systems that process speech and song were more effectively engaged for song than for speech and projections of structural pathways associated with these functions were not distinguishable from controls.

Neural mechanisms for emotional contagion and spontaneous mimicry of live facial expressions.

Viewing a live facial expression typically elicits a similar expression by the observer (facial mimicry) that is associated with a concordant emotional experience (emotional contagion). The model of embodied emotion proposes that emotional contagion and facial mimicry are functionally linked although the neural underpinnings are not known. To address this knowledge gap, we employed a live two-person paradigm (n = 20 dyads) using functional near-infrared spectroscopy during live emotive face-processing while also measuring eye-tracking, facial classifications and ratings of emotion. One dyadic partner, 'Movie Watcher', was instructed to emote natural facial expressions while viewing evocative short movie clips. The other dyadic partner, 'Face Watcher', viewed the Movie Watcher's face. Task and rest blocks were implemented by timed epochs of clear and opaque glass that separated partners. Dyadic roles were alternated during the experiment. Mean cross-partner correlations of facial expressions (r = 0.36 ± 0.11 s.e.m.) and mean cross-partner affect ratings (r = 0.67 ± 0.04) were consistent with facial mimicry and emotional contagion, respectively. Neural correlates of emotional contagion based on covariates of partner affect ratings included angular and supramarginal gyri, whereas neural correlates of the live facial action units included motor cortex and ventral face-processing areas. Findings suggest distinct neural components for facial mimicry and emotional contagion. This article is part of a discussion meeting issue 'Face2face: advancing the science of social interaction'.

Neural and visual processing of social gaze cueing in typical and ASD adults.

Atypical eye gaze in joint attention is a clinical characteristic of autism spectrum disorder (ASD). Despite this documented symptom, neural processing of joint attention tasks in real-life social interactions is not understood. To address this knowledge gap, functional-near infrared spectroscopy (fNIRS) and eye-tracking data were acquired simultaneously as ASD and typically developed (TD) individuals engaged in a gaze-directed joint attention task with a live human and robot partner. We test the hypothesis that face processing deficits in ASD are greater for interactive faces than for simulated (robot) faces. Consistent with prior findings, neural responses during human gaze cueing modulated by face visual dwell time resulted in increased activity of ventral frontal regions in ASD and dorsal parietal systems in TD participants. Hypoactivity of the right dorsal parietal area during live human gaze cueing was correlated with autism spectrum symptom severity: Brief Observations of Symptoms of Autism (BOSA) scores (r = âˆ'0.86). Contrarily, neural activity in response to robot gaze cueing modulated by visual acquisition factors activated dorsal parietal systems in ASD, and this neural activity was not related to autism symptom severity (r = 0.06). These results are consistent with the hypothesis that altered encoding of incoming facial information to the dorsal parietal cortex is specific to live human faces in ASD. These findings open new directions for understanding joint attention difficulties in ASD by providing a connection between superior parietal lobule activity and live interaction with human faces. Lay Summary: Little is known about why it is so difficult for autistic individuals to make eye contact with other people. We find that in a live face-to-face viewing task with a robot, the brains of autistic participants were similar to typical participants but not when the partner was a live human. Findings suggest that difficulties in real-life social situations for autistic individuals may be specific to difficulties with live social interaction rather than general face gaze.

Rejection Distress Suppresses Medial Prefrontal Cortex in Borderline Personality Disorder.

BACKGROUND: Borderline personality disorder (BPD) is characterized by an elevated distress response to social exclusion (i.e., rejection distress), the neural mechanisms of which remain unclear. Functional magnetic resonance imaging studies of social exclusion have relied on the classic version of the Cyberball task, which is not optimized for functional magnetic resonance imaging. Our goal was to clarify the neural substrates of rejection distress in BPD using a modified version of Cyberball, which allowed us to dissociate the neural response to exclusion events from its modulation by exclusionary context. METHODS: Twenty-three women with BPD and 22 healthy control participants completed a novel functional magnetic resonance imaging modification of Cyberball with 5 runs of varying exclusion probability and rated their rejection distress after each run. We tested group differences in the whole-brain response to exclusion events and in the parametric modulation of that response by rejection distress using mass univariate analysis. RESULTS: Although rejection distress was higher in participants with BPD (F1,40 = 5.25, p = .027, η2 = 0.12), both groups showed similar neural responses to exclusion events. However, as rejection distress increased, the rostromedial prefrontal cortex response to exclusion events decreased in the BPD group but not in control participants. Stronger modulation of the rostromedial prefrontal cortex response by rejection distress was associated with higher trait rejection expectation, r = -0.30, p = .050. CONCLUSIONS: Heightened rejection distress in BPD might stem from a failure to maintain or upregulate the activity of the rostromedial prefrontal cortex, a key node of the mentalization network. Inverse coupling between rejection distress and mentalization-related brain activity might contribute to heightened rejection expectation in BPD.

Cortical functional connectivity decodes subconscious, task-irrelevant threat-related emotion processing.

It is currently unclear to what extent cortical structures are required for and engaged during subconscious processing of biologically salient affective stimuli (i.e. the 'low-road' vs. 'many-roads' hypotheses). Here we show that cortical-cortical and cortical-subcortical functional connectivity (FC) contain substantially more information, relative to subcortical-subcortical FC (i.e. 'subcortical alarm' and other limbic regions), that predicts subliminal fearful face processing within individuals using training data from separate subjects. A plot of classification accuracy vs. number of selected whole-brain FC features revealed 92% accuracy when learning was based on the top 8 features from each training set. The most informative FC was between right amygdala and precuneus, which increased during subliminal fear conditions, while left and right amygdala FC decreased, suggesting a bilateral decoupling of this key limbic region during processing of subliminal fear-related stimuli. Other informative FC included angular gyrus, middle temporal gyrus and cerebellum. These findings identify FC that decodes subliminally perceived, task-irrelevant affective stimuli, and suggest that cortical structures are actively engaged by and appear to be essential for subliminal fear processing.

Conceptual representations of perceptual knowledge.

Many neuroimaging studies of semantic memory have argued that knowledge of an object's perceptual properties are represented in a modality-specific manner. These studies often base their argument on finding activation in the left-hemisphere fusiform gyrus-a region assumed to be involved in perceptual processing-when the participant is verifying verbal statements about objects and properties. In this paper, we report an extension of one of these influential papers-Kan, Barsalou, Solomon, Minor, and Thompson-Schill (2003 )-and present evidence for an amodal component in the representation and processing of perceptual knowledge. Participants were required to verify object-property statements (e.g., "cat-whiskers?"; "bear-wings?") while they were being scanned by functional magnetic resonance imaging (fMRI). We replicated Kan et al.'s activation in the left fusiform gyrus, but also found activation in regions of left inferior frontal gyrus (IFG) and middle-temporal gyrus, areas known to reflect amodal processes or representations. Further, only activations in the left IFG, an amodal area, were correlated with measures of behavioural performance.

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.

An Approach to Neuroimaging Interpersonal Interactions in Mental Health Interventions.

BACKGROUND: Conventional paradigms in clinical neuroscience tend to be constrained in terms of ecological validity, raising several challenges to studying the mechanisms mediating treatments and outcomes in clinical settings. Addressing these issues requires real-world neuroimaging techniques that are capable of continuously collecting data during free-flowing interpersonal interactions and that allow for experimental designs that are representative of the clinical situations in which they occur. METHODS: In this work, we developed a paradigm that fractionates the major components of human-to-human verbal interactions occurring in clinical situations and used functional near-infrared spectroscopy to assess the brain systems underlying clinician-client discourse (N = 30). RESULTS: Cross-brain neural coupling between people was significantly greater during clinical interactions compared with everyday life verbal communication, particularly between the prefrontal cortex (e.g., inferior frontal gyrus) and inferior parietal lobule (e.g., supramarginal gyrus). The clinical tasks revealed extensive increases in activity across the prefrontal cortex, especially in the rostral prefrontal cortex (area 10), during periods in which participants were required to silently reason about the dysfunctional cognitions of the other person. CONCLUSIONS: This work demonstrates a novel experimental approach to investigating the neural underpinnings of interpersonal interactions that typically occur in clinical settings, and its findings support the idea that particular prefrontal systems might be critical to cultivating mental health.

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.

Investigation of functional near-infrared spectroscopy signal quality and development of the hemodynamic phase correlation signal.

Significance: There is a longstanding recommendation within the field of fNIRS to use oxygenated ( HbO 2 ) and deoxygenated (HHb) hemoglobin when analyzing and interpreting results. Despite this, many fNIRS studies do focus on HbO 2 only. Previous work has shown that HbO 2 on its own is susceptible to systemic interference and results may mostly reflect that rather than functional activation. Studies using both HbO 2 and HHb to draw their conclusions do so with varying methods and can lead to discrepancies between studies. The combination of HbO 2 and HHb has been recommended as a method to utilize both signals in analysis. Aim: We present the development of the hemodynamic phase correlation (HPC) signal to combine HbO 2 and HHb as recommended to utilize both signals in the analysis. We use synthetic and experimental data to evaluate how the HPC and current signals used for fNIRS analysis compare. Approach: About 18 synthetic datasets were formed using resting-state fNIRS data acquired from 16 channels over the frontal lobe. To simulate fNIRS data for a block-design task, we superimposed a synthetic task-related hemodynamic response to the resting state data. This data was used to develop an HPC-general linear model (GLM) framework. Experiments were conducted to investigate the performance of each signal at different SNR and to investigate the effect of false positives on the data. Performance was based on each signal's mean T -value across channels. Experimental data recorded from 128 participants across 134 channels during a finger-tapping task were used to investigate the performance of multiple signals [ HbO 2 , HHb, HbT, HbD, correlation-based signal improvement (CBSI), and HPC] on real data. Signal performance was evaluated on its ability to localize activation to a specific region of interest. Results: Results from varying the SNR show that the HPC signal has the highest performance for high SNRs. The CBSI performed the best for medium-low SNR. The next analysis evaluated how false positives affect the signals. The analyses evaluating the effect of false positives showed that the HPC and CBSI signals reflect the effect of false positives on HbO 2 and HHb. The analysis of real experimental data revealed that the HPC and HHb signals provide localization to the primary motor cortex with the highest accuracy. Conclusions: We developed a new hemodynamic signal (HPC) with the potential to overcome the current limitations of using HbO 2 and HHb separately. Our results suggest that the HPC signal provides comparable accuracy to HHb to localize functional activation while at the same time being more robust against false positives.

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.

Decreased Exercise-Induced Changes in Prefrontal Cortex Hemodynamics Are Associated With Depressive Symptoms.

People with a depressed mood tend to perform poorly on executive function tasks, which require much of the prefrontal cortex (PFC), an area of the brain which has also been shown to be hypo-active in this population. Recent research has suggested that these aspects of cognition might be improved through physical activity and cognitive training. However, whether the acute effects of exercise on PFC activation during executive function tasks vary with depressive symptoms remains unclear. To investigate these effects, 106 participants were given a cardiopulmonary exercise test (CPET) and were administered a set of executive function tests directly before and after the CPET assessment. The composite effects of exercise on the PFC (all experimental blocks) showed bilateral activation changes in dorsolateral (BA46/9) and ventrolateral (BA44/45) PFC, with the greatest changes occurring in rostral PFC (BA10). The effects observed in right ventrolateral PFC varied depending on level of depressive symptoms (13% variance explained); the changes in activation were less for higher levels. There was also a positive relationship between CPET scores (VO2peak) and right rostral PFC, in that greater activation changes in right BA10 were predictive of higher levels of aerobic fitness (9% variance explained). Since acute exercise ipsilaterally affected this PFC subregion and the inferior frontal gyrus during executive function tasks, this suggests physical activity might benefit the executive functions these subregions support. And because physical fitness and depressive symptoms explained some degree of cerebral upregulation to these subregions, physical activity might more specifically facilitate the engagement of executive functions that are typically associated with hypoactivation in depressed populations. Future research might investigate this possibility in clinical populations, particularly the neural effects of physical activity used in combination with mental health interventions.