Functional and Structural Optical Brain Imaging

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We are using functional near infrared spectroscopy (fNIRS) to study brain activity in 2 distinct lines of research:1) developmental trajectories of cognitive abilities in children and 2) validity of fNIRS using cognitive tasks previously evaluated using fMRI. Under the developmental studies, we have continued the collaboration with Dr. Audrey Thurm (NIMH) and Dr. Nathan Fox (University of Maryland), on the mirror neuron network in infants (IRB # 18-CH-0001). The mirror neuron network (MNN) is associated with the development of sophisticated social behaviors that emerge in typical human infants (e.g., complex imitation, decoding emotional states). Modeling MNN development will create a sensitive measure of deviations in social communication development before clinical behavioral deficits can be detected. We have finished data collection in adult pilot subjects (N=40) who underwent a motor observation and execution paradigm while their brain activity measured through EEG/fNIRS simultaneously. MNN activation has already been associated with Mu suppression using EEG. By using EEG (with high temporal resolution) in conjunction with fNIRS will provide a more precise spatial resolution of neural activity based on hemodynamic activation to investigate the MNN. Within this protocol several manuscripts are currently under preparation/ submission. We conducted a review on the current fNIRS literature examining the action-observation network. The purpose of the review was to assess and critique the methodological and analytic approaches that have been used to study the action-observation network in healthy adults using fNIRS. In addition to being an important preparatory step in planning our empirical approach for our mirror neuron project, we felt that integrating this literature into a review paper was an important contribution to the field that could encourage other researchers to consider integration fNIRS measurement into these types of studies. The manuscript will be submitted to Neuroimage by September 2020. In addition, we have also examined the feasibility of fNIRS for the study of MNS (also referred to action-observation network- AON) in a subsample of 30 subjects. Overall, our results indicated that the parietal regions, including bilateral superior parietal lobule (SPL), bilateral inferior parietal lobule (IPL), right supra-marginal region (SMG) and right angular gyrus (AG) are candidate regions of the human AON. Moreover, we demonstrated that the paradigm is sensitive to differences in subclinical levels of autistic traits, which can be used in future studies with clinical populations who present deficits in action understanding and action representation, namely autism spectrum disorders (ASD). This work in now under revision and will be submitted to publication by October 2020. Additional analysis is being conducted using a connectivity approach to determine if increases in observation and execution conditions are distinct at an individual level. For this purpose, we are examining the correlation of activity across all subjects. We found 8 within region connections including the right and left precentral, postcentral, and angular, right supramarginal, left parietal inferior, and left parietal superior regions, and 7 between regions connections including precentral and postcentral (both sides), right precentral and left parietal superior, left supramarginal and left angular, left parietal inferior and left postcentral, left parietal inferior and left parietal superior, and left postcentral and left parietal superior, which can potentially be candidates of the MNN. These connections satisfy conditions of 1) having a strong connectivity in both action-observation and action-execution task and 2) a significant correlation between the connectivity during both tasks. Furthermore, to fully characterize the MNN network using concurrent signals (EEG and fNIRS) we are conducting multimodal multiset data-fusion analysis with the goal of letting the modalities fully interact. After applying mCCA on the integrated datasets we observed consistent results with previous literature. Action execution/observation showed a similar pattern of activity across regions of interest indicating higher brain activity in regions in the left hemisphere (paracentral region, precentral region, and parietal inferior and superior regions) while subjects were performing an action. For the observation condition also higher brain activity was also found in left regions of the brain, namely the postcentral, paracentral, precentral, and parietal superior and inferior regions. This preliminary analysis is very relevant, as it is the first report that uses distinct brain metrics (hemodynamic response function and electrical activity) to characterize the MNN in the human brain. As our pilot study validates the MNN paradigm, we have now started recruiting typically developing infants (9-12 months) (n=60). Once we have tested the paradigm in a subset of infants in this sample, we will start recruiting infants at-risk. We have continued the collaboration with Dr. Andrea Gropman at Childrens National Medical Center examining developmental deficits in children with Urea Cycle Disorders (UCD), especifically Ornithine transcarbamylase deficiency (OTCD) characterized by presence of hyperammonia (HA). HA is known to cause impairments of executive function and working memory. Monitoring OTCD progression and investigating neurocognitive biomarkers can become critical in examining the underlying brain function in OTCD. Using fNIRS we examined the hemodynamics of PFC in OTCD population and fraternal twin with and without OTCD. Results revealed a distinction in left PFC activation between controls and patients with OTCD, where controls showed higher task related activation increase while performing the Stroop task. Subjects with OTCD also exhibited bilateral increase in PFC activation. We quantified the hemodynamic variations in total-hemoglobin, while twins performed the N-Back Working Memory task. Our preliminary results showed that the sibling with OTCD had higher variations in a very low frequency band (<0.03 Hz, related to mechanism of cerebral autoregulation) compared to the control sibling, possibly due to effect of HA. Functional connectivity (FC) analysis also revealed lower interhemispheric FC in an OTCD sibling as the task load increased. Lastly, as part of our ongoing fNIRS calibration protocol (IRB #10-CH-0198), one manuscript is currently in the revise and resubmit phase at Frontiers in Neuroscience. Through the use of simultaneously collected functional near-infrared spectroscopy (fNIRS) of the prefrontal cortex and high frequency heart rate variability (HF-HRV; as derived from electrocardiogram), we examined the connection between prefrontal activation and parasympathetic nervous system activity (as measured HF-HRV) during a behavioral flexibility task (the go/no-go task). The relationship between these measures has been previously described by the neurovisceral integration model (Thayer & Lane, 2000); however, no study to date had examined these measures simultaneously. These data were collected in 38 healthy adult controls at rest and during the go/no-go task. The time course of HF-HRV and prefrontal fNIRS activation over the baseline period and the task period were then compared to determine whether they were related over time. Results indicated that at rest, HF-HRV was negatively related to prefrontal activation, consistent with previous studies that had collected HF-HRV and brain activity during separate resting state sessions (Allen et al., 2015). These results support the tenets of the neurovisceral integration model and the utility of fNIRS in future studies examining the model and its relation to cognitive functions.