Autism Oxytocin Brain Project

The main goal of the study is to look at the effects of intranasal oxytocin on the brain in Autism Spectrum Disorder (ASD). Oxytocin is a hormone that exists naturally in the body and the brain, affecting a wide range of social behaviors and emotions. The investigators will study the effects of different treatments (3 doses of oxytocin and one dose of placebo) on brain functional connectivity at rest in patients with ASD, using functional magnetic resonance imaging (fMRI). Investigators also seek to study how the effects of oxytocin treatment can be affected by genetic, immune and environmental factors.

This study consists of investigating the effects of several doses of acute administration of intranasal oxytocin on brain activity in adults with Autism Spectrum Disorder (ASD). There is increasing evidence for the role of intranasal oxytocin (IN-OT) in enhancing social skills in ASD. Nevertheless, there is still a need of determining target engagement for oxytocin's action on brain and behavior. Here, investigators are studying the effects of different doses of IN-OT on the modulation of behavioral outcomes and neural responses in a double blind crossover study in individuals with ASD. The aims of the research are to: Study the effects of IN-OT doses on the modulation of brain functional connectivity between key socio-emotional brain regions during resting state in ASD Study the effects of IN-OT doses on the blood-oxygen-level dependent (BOLD) activity of key emotional and perceptual brain networks in response to social cues (such as faces) Study the effects of IN-OT on the BOLD activity of brain regions during an interactive social environment (ball game) in ASD Investigators will compare the neuroimaging and behavioral results of individuals with ASD to control healthy males who will receive intranasal placebo. Investigators are also investigating the role of genetic factors, behavioral or clinical sub-groups of ASD, immune and environmental factors in modulating the effect of IN-OT on brain and behavior. Participants with ASD will undergo 4 clinical visits during which they receive various randomly assigned doses of intranasal oxytocin and placebo. Both participants and the experimenter will be blind to the type of the treatment administered. There will be only one visit for healthy controls who will all receive placebo spray. The visit for healthy controls will be conducted in a single-blind design. The experimenter will be aware that the subject is receiving placebo. However, the participant will be told that he might receive oxytocin or placebo.

Male participants diagnosed with ASD will receive 12 puffs (6 in each nostril) of intranasal oxytocin (syntocinon) and placebo (assigned randomly) during 4 study visits.

Age matched healthy controls will receive placebo intranasal spray (12 puffs, 6 per nostril) during one study visit.

Resting State Functional Connectivity (rsFC) Salience Network (Anterior Cingulate Cortex (ACC) and Insula Versus Visual Cortex)

Investigators will study the effects of intranasal oxytocin (IN-OT) on the resting state functional connectivity between key socio-emotional and social salience brain regions using functional magnetic resonance imaging (fMRI). Resting state functional connectivity is a task-independent metric of brain activity that is based on correlations between low-frequency fluctuations of the blood oxygen level-dependent signal between several brain regions. It reflects the strength of a functional connection that is in good agreement with the underlying neuroanatomy and provides a system-level understanding of brain function. Z-scores represent the number of standard deviations from the mean of 0 and range from -3 to +3, and z-scores greater than 0 indicate greater than average resting state functional connectivity.

BOLD activity level was assessed via fMRI during completion of the face perception task (FPT) of emotional and neutral faces. BOLD scores are reported on a z-scale, with the mean, standard deviation and the minimum and the maximum. This refers to the non-thresholded z-scores that are obtained for each dose before conducting small volume correction analysis.

BOLD activity in social-emotional brain regions during the perception of emotional facial videos were measured during the ball-game task. Mean percent change in contrast of parameter estimates in anatomical regions of interest are presented here. A positive value indicates increased BOLD activity while a negative value indicates decreased BOLD activity.

Plasma concentration of oxytocin prior to administration of study intervention and after administration of study intervention will be compared between the different dose levels and placebo. Plasma concentration of oxytocin is expected to increase following administration of intranasal oxytocin.

Clinical improvements will be rated by a clinician as based on a videotaped interview conducted after the MRI scanning session. Values between the different treatment conditions will be assessed to study the effect of intranasal oxytocin on ASD at the clinical level. The improvement will be assessed based on the quality of social interaction between the experimenter and the participant, specifically as the amount of smiling behavior displayed by participants. Larger values indicate that participants are smiling more frequently.

Eye gaze will be recorded via an eye tracker inside the MRI scanner during the face perception task (FPT). Visual fixation between different treatment conditions will be assessed in ASD participants.

During the SLT, participants complete an implicit association test using faces and words. The faces that are presented in this task are partners' faces with whom participants played during the ball-game inside the MRI scanner. In this task, there are congruent blocks where neutral faces of "positive" partners are presented with friendly words and neutral faces of "negative" partners are presented with unfriendly words. During incongruent blocks, neutral faces of "positive" partners are presented with unfriendly words and neutral faces of "negative" partners are presented with friendly words. Participants match the face or the word to one of two categories. Longer reaction time indicates difficulty with selecting a category. Longer reaction time in incongruent trials signifies implicit biases were formed for the positive and negative players such that "positive" partners from the ball-game are now perceived as friendly and "negative" partners are now perceived as unfriendly.

Inclusion Criteria for ASD Participants: Have an ASD diagnosis based on the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview (ADI) criteria, gold standards of research-based autism diagnosis Intelligence quotient (IQ) > 70 Normal or corrected-to-normal vision Exclusion Criteria for ASD Participants: Recent occurrence of seizures (past 5 years) Brain damage or head trauma (can be included at discretion of PI and sponsor) Color blind Cardiovascular disease Presence of a severe medical problem Severe mental retardation Alcoholism or substance abuse Asthma (can be included at the discretion of study physician/nurse practitioner if episodes are infrequent and no active problems at time of the study) Migraine headaches (at the discretion of the nurse practitioner or the study physician) Claustrophobia (at discretion of study physician/designee/PI) Pacemakers, cochlear implants, surgical clips or metal fragments Inclusion Criteria for Healthy Age-Matched Controls: IQ > 70 Normal or corrected-to-normal vision Exclusion Criteria for Healthy Age-Matched Controls: History of seizures Neurological disorder Current psychiatric disorder Previous psychiatric disorder (can be included at discretion of PI) Current use of psychoactive drugs Previous use of psychoactive drugs (can be included at discretion of PI) Head trauma (can be included at discretion of PI) Alcoholism or substance abuse Cardiovascular disease Color blind Asthma (can be included at the discretion of study physician/nurse practitioner if episodes are infrequent and no active problems at time of the study) Migraine headaches (at the discretion of the nurse practitioner or the study physician) Claustrophobia (at discretion of study physician/designee/PI) Presence of a severe medical problem Severe mental retardation Pacemakers, cochlear implants, surgical clips or metal fragments