Rt-fMRI NF Intervention Study in ASD

Study Overview
=================
Brief Summary
-----------------
This study aims to demonstrate that fMRI neurofeedback training improves the identification and comprehension of emotional facial expressions (and overall social behaviour) in subjects with ASD. The intervention setup provides structured presentation of emotional facial expressions and the associated tools for mental imagery. The investigators hypothesize that the accomplishment of the proposed competence training improves the subjects ability to comprehend facial expressions, identify emotions and be able to correctly express them. Intervention Type is a Device (brain computer interface using brain imaging signals) and the specific Intervention Name is Neurofeedback. Structure: (1) initial eligibility screening, (2) pre-intervention (first week of study, baseline outcome measures and additional evaluations), (3) intervention process (8 weeks), (4) post-intervention (outcome measures and additional evaluations), and (5) follow-up (outcome measures at 6 months).

Detailed Description
-----------------
Clinical research has demonstrated that ASD children have deficits in the identification and interpretation of the emotional and mental state of others (Baron-Cohen 2001). An important skill to this end (impaired in ASD patients), is to appropriately recognize and discriminate emotional expressions. The main brain regions involved in face processing the inferior occipital gyri, lateral portion of the fusiform gyrus (especially a region deemed the fusiform face area or FFA), and posterior superior temporal sulcus (pSTS) (Haxby et al. 2000). STS plays a key role on several basic aspects in social information processing, and deficits in ASD have been found associated to this region. The purpose of the study is to determine the effect of neurofeedback considering a social cognition brain region (i.e. pSTS) on the identification of facial expressions in ASD patients. The intervention comprehends seven BCI sessions spread over four months. The first four sessions are weekly, and the rest monthly. In each session, the subjects are asked to imagine different facial expressions and their brain activity (i.e. BOLD activation in the pSTS region) is interpreted and used to estimate a feedback signal.The hypothesis is that the training induced up-regulation of the target region, improves clinical symptoms.

Official Title
-----------------
Improving Facial Expression Identification in ASD: a Real-time fMRI Neurofeedback Approach

Conditions
-----------------
Autism Spectrum Disorder

Intervention / Treatment
-----------------
* Device: Neurofeedback using BCI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Positive diagnostic results for ASD in: Autism Diagnostic Interview-Revised; Autism Diagnostic Observation Schedule; The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Exclusion Criteria: Global Intelligence Quotient < 80 Associated medical condition such as epilepsy, neurocutaneous or other genetic syndromes, or other usual comorbidity in ASD samples

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 30 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neurofeedback using BCI<br>16 (13 + 3 in case of dropoffs) ASD subjects | Device: Neurofeedback using BCI<br>* This group will undergo five sessions of neurofeedback intervention in the fMRI scanner. Each subject will also undergo neuropsychological evaluations before the first neurofeedback session (week 0) and after the last neurofeedback session (week 7). The first four sessions are weekly while the last one is one month later. The intervention will take a total of four months. Follow up will be performed in the the first week and 6 months after the last intervention session.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEEST - Facial Expression of Emotion: Stimuli and Tests | The Emotion Hexagon test represents the primary outcome measure. The assessment based on this test will be performed before (baseline), after the intervention - endpoint 1 (at 8 weeks) and at the 6 months follow-up. The Emotion Hexagon test uses stimuli of graded difficulty, created using computer image manipulation techniques (morphing is used to modify photographs from the Ekman and Friesen (1976) series, creating examples that lie close to or more distant from the prototype expression). The 120 test trials with unambiguous stimuli (4 pictures for each of the 6 emotions across the 5 test blocks) can be used to derive an overall (total) score out of a possible maximum of 120 expressions correctly recognized. | 8 weeks (Endpoint 1) plus 6 months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ATEC - Autism Treatment Evaluation Checklist | Autism Treatment Evaluation Checklist (ATEC) evaluates the effectiveness of autism treatments - a 1-page form designed to be completed by parents or caretakers. It consists of 4 subtests: I. Speech/Language Communication (14 items, min.0-max.28); II. Sociability (20 items, min.0-max.40); III. Sensory/Cognitive Awareness (18 items, min.0-max.36); and IV. Health/Phys./Behavior (25 items, min.0-max.75). Total score (sum) ranges from min.0-max.179. The results reported here correspond to the total ATEC score to be used for comparison at a later date. The lower the score, the fewer the problems. | 8 weeks (Endpoint 1) plus 6 months follow up | 
| VABS - Vineland Adaptive Behaviour Scale | The Vineland Adaptive Behaviour Scale (VABS) is a semi-structured interview designed to assess global adaptive functioning, composed by 3 main domains: Communication COM, Daily Living Skills DLS and Socialization SOC (all reported here in terms of standard scores as described in the VABS manual, i.e. mean 100 and standard deviation 15). The Adaptive Behaviour Composite ABC (total score, also reported here) is the sum of the raw scores from the three main domains. These are transformed in standard scores (m.=100;std.=15). The higher the score, better is the adaptive behavior. | 8 weeks (Endpoint 1) plus 6 months follow-up |