INVESTIGATING THE NEUROPHYSIOLOGICAL EFFECTS OF OXYTOCIN ADMINISTRATION ON HEALTHY SUBJECTS AND INDIVIDUALS WITH SCHIZOPHRENIA USING MAGNETO-ENCEPHALOGRAPHY IMAGING.

INTRODUCTION Schizophrenia-spectrum disorders (SZ) are characterized by disturbances of early information processing across various sensory modalities that originate from disrupted spatial and temporal linkage in critical neural networks that include the limbic system and sensory cortices. These disturbances are known to underlie impairments in social cognition, i.e. the ability to understand the thoughts and behaviors of others, which is a critical skill for effectively navigating the social world. Patients with SZ have widespread social cognitive deficits that interfere with social relationships and impair occupational functioning. Current pharmacological treatments are ineffective in remediating social cognitive deficits and in regulating their neurophysiological underpinnings. The oxytocin (OT) system, which is critically involved in social behavior and cognition in mammals and is dysregulated in SZ, is a promising target. Intranasal administration of exogenous OT is well tolerated and improves social cognition in patients with SZ. Additionally, neuroimaging studies in healthy individuals suggest that OT improves information processing and social cognition by modulating regional activity within those neural networks that are impaired in SZ. While work on healthy individuals is promising, no studies investigated the effects induced by OT on spatiotemporal neural oscillatory patterns in patients with SZ. MATERIAL & METHODS. In this study, I used Magnetoencepholagraphy Imaging (MEG-I) to examine the effects of OT. I administered a single intranasal dose of OT (40 IU) or placebo (PL) in a randomized, doubleblind, counterbalanced order with a cross-over, within-subject design to 25 males with SZ and 25 matched healthy controls (HC). Participants\u2019 brain activity was recorded using MEG-I while they completed an auditory deviance task and a facial emotion processing task that robustly activate neural networks underlying information processing and social cognition. Change in auditory mismatch negativity induced by OT/PL in SZ and HC was assessed repeated measures ANOVA. Induced oscillatory activity in regions displaying early activation patterns was examined using adaptive spatial filtering techniques. Broadband activity estimated at each time point in a trial was averaged across trials, root-mean-square transformed, and z-normalized. Average amplitude from early time windows post-stimulus onset was calculated to assess early responses in the bilateral occipital face area (OFA) and the right amygdala. The Neurodynamic Utility Toolbox for MEG-I was used to conduct an exploratory time-frequency analysis of the neural sources during the processing of facial emotions. Task-induced neural oscillatory power changes were localized and examined after OT and PL administration. RESULTS. Compared to HC, SZ showed reduced amplitude of the mismatch negativity under PL. This impairment was normalized after OT administration. Under the effects of PL, the exploratory time-frequency analysis found differential early activations in SZ subjects relative to HC in several regions of interest, including the bilateral OFA and the right amygdala. In the OFA, SZ subjects showed impaired M100 responses that were normalized by OT, while HC showed no effects of OT on M100 response. In the right amygdala, SZ showed aberrant theta activity and impaired M100 under PL. These responses were normalized by OT. CONCLUSION. MEG-I analysis provided detailed measures of the location and time course of neural activations induced by OT. In SZ, OT remediated impaired facial emotion processing and auditory deviance processing, by normalizing the aberrant underlying early activation patterns. Future analyses will examine the neurophysiological effects of OT on late activation patterns in associative and cognitive control areas. This knowledge is critical to optimizing the use of OT as a treatment for social cognitive impairments in SZ and other neuropsychiatric illnesses