Cerebellum and Autism: Regional Specialization for Social and Executive Functions

Study Overview
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Brief Summary
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The goal of this study is to determine the impact of neuromodulation to the cerebellum on social and executive functions in neurotypical young adults and young adults with autism.

Detailed Description
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Autism spectrum disorder is a prevalent neurodevelopmental condition characterized by deficits in social communication and the presence of repetitive and inflexible behaviors. There are currently few biologically-targeted treatment options for autism, in part because the underlying neurobiology is not well understood. One region of the brain that is consistently implicated in autism is the cerebellum. Specifically, two cerebellar subregions show structural and functional differences in autism: right cerebellar lobule VII (RVII) and the posterior cerebellar vermis. Based on the different anatomical connectivity of these regions, the investigators hypothesize that RVII and the posterior vermis regulate different core deficits in autism. In this study, the investigators combine cerebellar neuromodulation with functional neuroimaging to test the hypothesis that neuromodulation targeting RVII will selectively alter social learning and neural networks supporting social behavior, while neuromodulation targeting the posterior vermis will impact cognitive flexibility and neural networks involved in the allocation of attention. Neurotypical adults and adults with autism will complete social and cognitive flexibility tasks after excitatory, inhibitory, or sham neuromodulation in a within-subjects design. Some participants will receive neuromodulation targeting RVII and others will receive neuromodulation targeting the posterior vermis. The investigators will acquire functional brain imaging data during and after cerebellar neuromodulation, which will allow the team to better understand the mechanisms by which non-invasive neuromodulation might impact behavior in clinical disorders.

Official Title
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Cerebellum and Autism: Regional Specialization for Social and Executive Functions

Conditions
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Autism, Autism Spectrum Disorder

Intervention / Treatment
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* Device: Transcranial direct current stimulation


Participation Criteria
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Eligibility Criteria
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Please note: This study takes place at American University and Georgetown University in Washington, DC. We do not have funds for travel and lodging available for this study, so participants should be local to the DC region. Inclusion Criteria: All participants Aged 18-35 Able to provide written, informed consent NIH Toolbox age-adjusted Cognitive Function Composite standard score ≥ 85 Native English speaker Right-handed Not pregnant Able to attend all study sessions Pass safety screening for MRI and neuromodulation (e.g. no metal in body, implanted devices, history of seizure, claustrophobia) Additional INCLUSION criteria for adults with autism Either Prior research-reliable diagnosis of autism spectrum disorder (ASD) Or Meet DSM-5 criteria for ASD confirmed with ADOS-2 via research-reliable clinical assessment Exclusion Criteria: Neurotypical adults Age <18 or >35 NIH Toolbox age-adjusted Cognitive Function Composite standard score < 85 Contraindications for MRI or neuromodulation with tDCS (e.g. metal in body, pacemaker or other implanted device, history of seizure, claustrophobia) Current or prior history of neurological or neurodevelopmental condition or brain injury Psychotropic medication Pregnancy Adults with autism Age <18 or >35 Participants with a legal authorized representative NIH Toolbox age-adjusted Cognitive Function Composite standard score < 85 Contraindications for MRI or neuromodulation with tDCS (e.g. metal in body, pacemaker or other implanted device, history of seizure, claustrophobia) Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Within-subjects design (active, sham tDCS) with separate groups receiving tDCS targeting cerebellar right lobule VII and the posterior cerebellar vermis.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Right cerebellum<br>Participants (neurotypical, autistic) in this arm will receive tDCS targeting the right posterolateral cerebellum (lobule VII). All participants will receive anodal, cathodal and sham tDCS. | Device: Transcranial direct current stimulation<br>* TDCS involves applying small (1-2 mA) electric currents to the scalp in order to transiently modify local neuronal electrical potentials in the brain.<br>* Other names: tDCS;|
| Experimental: Posterior vermis<br>Participants (neurotypical, autistic) in this arm will receive tDCS targeting the posterior cerebellar vermis. All participants will receive anodal, cathodal and sham tDCS. | Device: Transcranial direct current stimulation<br>* TDCS involves applying small (1-2 mA) electric currents to the scalp in order to transiently modify local neuronal electrical potentials in the brain.<br>* Other names: tDCS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reading the Mind in the Eyes Test Adult Version |  | Within 30min post-tDCS | 
| Cyberball social ball-playing task |  | Within 30min post-tDCS | 
| Flexible Item Selection Test |  | Within 30min post-tDCS | 
| Functional MRI data | Functional MRI task data and resting state functional connectivity data | Within 45min post-tDCS |