Autism Spectrum Disorder
Conditions
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.
Interventions
DEVICENeurofeedback using BCI
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.
Sponsors
University of Coimbra
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 30 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FEEST - Facial Expression of Emotion: Stimuli and Tests | 8 weeks (Endpoint 1) plus 6 months follow-up | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ATEC - Autism Treatment Evaluation Checklist | 8 weeks (Endpoint 1) plus 6 months follow up | 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. |
| VABS - Vineland Adaptive Behaviour Scale | 8 weeks (Endpoint 1) plus 6 months follow-up | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| POMS - Profile of Mood States | 8 weeks (Endpoint 1) plus 6 months follow-up | — |
| Debriefing Interview Questionnaire | 8 weeks (Endpoint 1) | Covers: strategies; general experience of the process; adverse effects; |
| HADS - Hospital Anxiety & Depression Scale | 8 weeks (Endpoint 1) plus 6 months follow-up | 24-item scale (7 depression & 7 anxiety items) |
| BDI - Beck Depression Inventory | 8 weeks (Endpoint 1) plus 6 months follow-up | 21-item measure of clinical depression |
Participant flow
Recruitment details
The participants, mainly recruited on a collaborative effort between the Pediatrics Hospital of Coimbra and local ASD associations, were invited for an fMRI neurofeedback feasibility clinical trial study in ASD. All participants had normal or corrected to normal vision. ). The first participant was recruited in February 2016.
Pre-assignment details
There was no significant events after participant enrollment, before group assignment.
Participants by arm
| Arm | Count |
|---|---|
| Neurofeedback Using BCI 16 (13 + 3 in case of dropoffs) ASD subjects
Neurofeedback (BCI using neuroimaging): 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. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Neurofeedback Using BCI |
|---|---|
| Age, Continuous | 19.92 years |
| ATEC - Autism Treatment Evaluation Checklist | 36.6 units on a scale STANDARD_DEVIATION 13.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 15 Participants |
| FEEST - Facial Expression of Emotion: Stimuli and Tests | 98 units on a scale STANDARD_DEVIATION 19.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment Portugal | 15 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 15 Participants |
| VABS - Vineland Adaptive Behaviour Scale Baseline [VABS ABC] | 63.4 units on a scale STANDARD_DEVIATION 13.52 |
| VABS - Vineland Adaptive Behaviour Scale Baseline [VABS COM] | 70.6 units on a scale STANDARD_DEVIATION 15.65 |
| VABS - Vineland Adaptive Behaviour Scale Baseline [VABS DLS] | 74 units on a scale STANDARD_DEVIATION 17.15 |
| VABS - Vineland Adaptive Behaviour Scale Baseline [VABS SOC] | 63.4 units on a scale STANDARD_DEVIATION 14.21 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
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.
Time frame: 8 weeks (Endpoint 1) plus 6 months follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Neurofeedback Using BCI | FEEST - Facial Expression of Emotion: Stimuli and Tests | Endpoint 1 | 100.27 units on a scale | Standard Deviation 19.29 |
| Neurofeedback Using BCI | FEEST - Facial Expression of Emotion: Stimuli and Tests | 6 months follow-up | 100.79 units on a scale | Standard Deviation 20.01 |
Secondary
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.
Time frame: 8 weeks (Endpoint 1) plus 6 months follow up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Neurofeedback Using BCI | ATEC - Autism Treatment Evaluation Checklist | Endpoint 1 | 32 units on a scale | Standard Deviation 14.66 |
| Neurofeedback Using BCI | ATEC - Autism Treatment Evaluation Checklist | 6 months follow-up | 19.64 units on a scale | Standard Deviation 8.13 |
Secondary
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.
Time frame: 8 weeks (Endpoint 1) plus 6 months follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Neurofeedback Using BCI | VABS - Vineland Adaptive Behaviour Scale | Endpoint 1 [VABS COM] | 74.87 units on a scale | Standard Deviation 14.95 |
| Neurofeedback Using BCI | VABS - Vineland Adaptive Behaviour Scale | Endpoint 1 [VABS DLS] | 76.93 units on a scale | Standard Deviation 16.46 |
| Neurofeedback Using BCI | VABS - Vineland Adaptive Behaviour Scale | 6 months follow-up [VABS COM] | 79.79 units on a scale | Standard Deviation 13.69 |
| Neurofeedback Using BCI | VABS - Vineland Adaptive Behaviour Scale | 6 months follow-up [VABS DLS] | 83.14 units on a scale | Standard Deviation 17 |
| Neurofeedback Using BCI | VABS - Vineland Adaptive Behaviour Scale | 6 months follow-up [VABS SOC] | 71.43 units on a scale | Standard Deviation 15.36 |
| Neurofeedback Using BCI | VABS - Vineland Adaptive Behaviour Scale | 6 months follow-up [VABS ABC] | 73.57 units on a scale | Standard Deviation 13.67 |
| Neurofeedback Using BCI | VABS - Vineland Adaptive Behaviour Scale | Endpoint 1 [VABS SOC] | 66.73 units on a scale | Standard Deviation 16.42 |
| Neurofeedback Using BCI | VABS - Vineland Adaptive Behaviour Scale | Endpoint 1 [VABS ABC] | 67.13 units on a scale | Standard Deviation 15.22 |
Other Pre-specified
BDI - Beck Depression Inventory
21-item measure of clinical depression
Time frame: 8 weeks (Endpoint 1) plus 6 months follow-up
Other Pre-specified
Debriefing Interview Questionnaire
Covers: strategies; general experience of the process; adverse effects;
Time frame: 8 weeks (Endpoint 1)
Other Pre-specified
HADS - Hospital Anxiety & Depression Scale
24-item scale (7 depression & 7 anxiety items)
Time frame: 8 weeks (Endpoint 1) plus 6 months follow-up
Other Pre-specified
POMS - Profile of Mood States
Time frame: 8 weeks (Endpoint 1) plus 6 months follow-up