Sensory Habituation in Autism Spectrum Disorders (ASD_VR_RE)

Neurobiological Mechanisms of Sensory Hyper-sensitivity and Habituation in Autism Spectrum Disorders

Autism spectrum disorder (ASD) is one of the most common developmental disabilities and often people with ASD have sensory processing disorders. These sensory processing disorders are often associated with problem behaviors and, more recently, have been connected to anxiety disorders in people with ASD. While it has been suggested that sensory processing responses in ASD could be malleable, current treatment strategies for sensory processing disorders in ASD have inconsistent results or lack large-sample sized data. This investigation will explore changes in neurophysiological activity in people with ASD and neurotypical peers after they are exposed to an unpleasant visual stimulus through a virtual reality systematic desensitization protocol. 30 people with ASD and 30 neurotypical people between the ages 7 - 35 will be recruited. The study have, 1) a practice magnetic resonance imaging (MRI) visit with questionnaires, 2) a per-exposure MRI with structural and functional MRI collections, 3) a virtual reality systematic desensitization session where we will record the participant's physiological response using an Emotibit device, and 4) a post-exposure MRI session with structural and functional MRI collections. This investigation aims to quantify changes in neurophysiological responses in order to determine the effect of systematic desensitization.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder; Sensory Processing Disorder; Autism; Sensory Over-Responsivity
• Intervention / Treatment: Behavioral: Sensory Habituation Protocol

Detailed Description

Autism Spectrum Disorder (ASD) is one of the most common developmental disabilities, with an estimated 1 in 54 children receiving a diagnosis. The total economic burden of ASD in the United States is estimated to be $268 billion and will increase to $461 billion by 2025. People with ASD have deficiencies in social relationships and communications and an increased rate of anxiety disorders, with some estimates suggesting 84% of people with ASD have anxiety. This anxiety can lead to an individual with ASD to exhibit avoidant behavior, which can include exclusion from activities to escalated behaviors that could be self-injurious or harmful to others. These avoidant behaviors can make participation in activities of daily living challenging for people with ASD, as the avoidant behavior is often considered socially-unacceptable behavior. While there has been increasing interest in anxiety in ASD, there is still a major knowledge gap in understanding how sensory processing disorders play a role in anxiety and if this can be treated.

Sensory Processing in ASD: Sensory processing disorders were added to ASD diagnosis in The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition in 2013. Since then, there has been little research into the role that sensory processing disorders plays in the anxiety of people with ASD. Functional magnetic resonance imaging (fMRI) studies have demonstrated that people with ASD have greater brain activity in relevant sensory areas, the amygdala, and the orbital frontal cortex when exposed to combinations of unpleasant auditory, tactile, or visual stimuli. Further, people with ASD have a reduced ability to habituate to the same unpleasant stimuli in the relevant sensory cortices and amygdala, differences in the changes of brain activity in the orbital-frontal cortex, and differences in functional connectivity between the amygdala and orbital-frontal cortex. These brain responses have also been connected with physiological responses in children with ASD, as those with greater skin conductivity having reduced neural response in the orbital-frontal cortex and heart rate being positively correlated with activity in the inferior and medial frontal gyrus.

Even though the neurophysiological evidence supports sensory processing differences in ASD, current treatment strategies are sparse and the results are often inconsistent. The most successful paradigm is exposure therapy through systematic desensitization, which has been used in both ASD and people with anxiety. While multisensory integration skills may be malleable, it has been suggested that exposure therapy may not be an effective long-term strategy, as the clinical team cannot perform exposure to every stimulus in every environment. With this in mind, new therapeutic techniques need to be designed to enable personalization of exposure experiences.

Virtual Reality for ASD: One emerging technique that could enable quick personalization of unpleasant stimulus and environments is virtual reality (VR). Therapeutic VR software has shown to be an effective platform for skill training, mainly focusing on behavioral skills in social or educational environments. Two investigations demonstrated changes in neural activity after participating in VR social cognition training. However, the effects of using VR as a sensory exposure platform on the physiological response to unpleasant stimuli has not been explored.

Purpose The research objectives of this application are to quantify the neurophysiological changes that occur after participating in a virtual reality systematic desensitization protocol. The following aims will be achieved the top physiological recording devices for ASD to collect physiological responses, front-line virtual reality systems to provide automated desensitization exposure therapy, and University of Nebraska Medical Center's research MRI system. 30 people with ASD and 30 neurotypical peers will be recruited to utilize this software. This proposal will be the first step in developing evidence-based therapies aimed at addressing sensory processing differences in ASD.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: James E Gehringer, PhD; Phone Number: 402-559-2562; Email: james.gehringer@unmc.edu

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • Recruiting
      • University of Nebraska Medical Center, Munroe-Meyer Insitute
      • Contact: James E Gehringer, PhD; Phone Number: 402-559-2562; Email: james.gehringer@unmc.edu
      • Principal Investigator: James E Gehringer, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• For our patient population

  1. people with a diagnosis of autism spectrum disorder
  2. people who have sensory over-responsivity
  3. can wear a VR headset for up to 20 minutes
  4. can understand and follow directions

For neurotypical participants

1. can wear a VR headset for up to 20 minutes
2. can understand and follow directions

Exclusion Criteria:

• 1) if you have any known visual impairment that will make it difficult to watch an object in a VR headset 2) inability to wear a VR headset 3) a history of seizures 4) A subject with orthodontic braces or metallic implants, such as prostheses, shrapnel, or aneurysm clips, or persons with electronic implants, such as cardiac pacemakers. The magnetic field generated by the MRI machine can cause a displacement or malfunctioning of these devices; 5) A subject who is claustrophobic, unable to stay still in the scanner for 40 minutes, or unable to be in the MRI scanner room alone;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autism Spectrum Disorder Habituation Group; This will be the group of subjects with Autism and sensory over-responsivity. This group will go through a mock-MRI, a pre-habituation MRI, the habituation protocol in virtual reality, and a post-habituation MRI.	Behavioral: Sensory Habituation Protocol; The first session continues with the Mock MRI, which lasts 10 minutes. Participant's comfort level in VR will be evaluated. At the pre-exposure visit, participants complete an MRI scan on a 3 Tesla MRI, which takes approximately 1 hour & 15 minutes. It consists of structural & functional MRI scans. Structural scans require the participant to stay still with eyes closed. Functional scans will require the participant to lie with eyes closed or watch and listen to sensory stimulation. VR exposure will occur across 3 1-hour sessions at most. Participants will be asked to complete a sensory habituation protocol, in which they will watch and listen to sensory stimuli in VR for an increasing amount of time. Between the sensory stimuli, the participant will watch a self-selected video. Finally, the subject will be asked to do a post-exposure MRI visit, which is the same as the pre-exposure visit.; Other Names: Repeated Exposure
Active Comparator: Neurotypical Habitation Group; This will be the group of subjects who are neurotypical peers. This group will go through a mock-MRI, a pre-habituation MRI, the habituation protocol in virtual reality, and a post-habituation MRI.	Behavioral: Sensory Habituation Protocol; The first session continues with the Mock MRI, which lasts 10 minutes. Participant's comfort level in VR will be evaluated. At the pre-exposure visit, participants complete an MRI scan on a 3 Tesla MRI, which takes approximately 1 hour & 15 minutes. It consists of structural & functional MRI scans. Structural scans require the participant to stay still with eyes closed. Functional scans will require the participant to lie with eyes closed or watch and listen to sensory stimulation. VR exposure will occur across 3 1-hour sessions at most. Participants will be asked to complete a sensory habituation protocol, in which they will watch and listen to sensory stimuli in VR for an increasing amount of time. Between the sensory stimuli, the participant will watch a self-selected video. Finally, the subject will be asked to do a post-exposure MRI visit, which is the same as the pre-exposure visit.; Other Names: Repeated Exposure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in neural response to the sensory stimulation	This will be the change in the bold response as measured by the fMRI scan.	There are two 1 hour sessions in which the bold response will be measured. The first time point will be during visit 2 of the study. The second time point will be the final visit of the study.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Galvanic Skin Response as measured by a physiological recording devices, either an Emotibit or the MRI scanner	Galvanic skin response is a measure of how sweaty the skin is and can be used as a measure of the body's stress. We will look at this before during and after the habituation protocol to measure how the body adapts to the sensory stimulation.	Galvanic skin response will be measured at 3 - 5 time points, ranging from 1 hour and 30 minutes to 3 hours and 30 minutes of data. 15 minutes will be measured at the 2nd and last visit. 1 hour will be collected at each VR visit.
Changes in skin temperature after going through a sensory habituation protocol, measured by an Emotibit	This will look at the change in the skins temperature before, during, and after the sensory habituation protocol. This is a measure of the body's response to a stressor.	Skin temperature will be measured at 1 - 3 time points, ranging from 1 hour to 3 hours of data. 1 hour will be collected at each VR visit.
Heart rate changes as measured by a physiological recording devices, either an Emotibit or the MRI scanner	Changes in heart rate can give an indication of stress and habituation. This will be recorded before, during, and after the habituation protocol to assess how the body reacts.	Heart rate will be measured at 3 - 5 time points, ranging from 1 hour and 30 minutes to 3 hours and 30 minutes of data. 15 minutes will be measured at the 2nd and last visit. 1 hour will be collected at each VR visit.

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: James E Gehringer, PhD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: January 22, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): February 7, 2024

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Autism; Virtual Reality; Autism Spectrum Disorder; Sensory Sensitivity; Sensory Processing; Sensory Over-Responsivity; Sensory Hyper-reactivity
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: 0709-22-EP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified MRI scans and physiological responses will be made available after completion of the study.
• IPD Sharing Time Frame: De-identified data will be released after conclusion of data collections (planned for end of 2025), conclusion of data analysis (planned for end of 2026), and submission of publication (planned for end of 2026/early 2027)
• IPD Sharing Access Criteria: Data will be made available upon reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No