Training the social brain: Clinical and neural effects of an 8-week real-time functional magnetic resonance imaging neurofeedback Phase IIa Clinical Trial in Autism

Abstract

Autism spectrum disorder is characterized by abnormal function in core social brain regions. Here, we demonstrate the feasibility of real-time functional magnetic resonance imaging volitional neurofeedback. Following up the demonstration of neuromodulation in healthy participants, in this repeated-measure design clinical trial, 15 autism spectrum disorder patients were enrolled in a 5-session training program of real-time functional magnetic resonance imaging neurofeedback targeting facial emotion expressions processing, using the posterior superior temporal sulcus as region-of-interest. Participants were able to modulate brain activity in this region-of-interest, over multiple sessions. Moreover, we identified the relevant clinical and neural effects, as documented by whole-brain neuroimaging results and neuropsychological measures, including emotion recognition of fear, immediately after the intervention and persisting after 6 months. Neuromodulation profiles demonstrated subject-specificity for happy, sad, and neutral facial expressions, an unsurprising variable pattern in autism spectrum disorder. Modulation occurred in negative or positive directions, even for neutral faces, in line with their often-perceived ambiguity in autism spectrum disorder. Striatal regions (associated with success/failure of neuromodulation), saliency (insula/anterior cingulate cortex), and emotional control (medial prefrontal cortex) networks were recruited during neuromodulation. Recruitment of the operant learning network is consistent with participants’ engagement. Compliance, immediate intervention benefits, and their persistence after 6 months pave the way for a future Phase IIb/III, randomized controlled clinical trial, with a larger sample that will allow to conclude on clinical benefits from neurofeedback training in autism spectrum disorder (NCT02440451). Lay abstract Neurofeedback is an emerging therapeutic approach in neuropsychiatric disorders. Its potential application in autism spectrum disorder remains to be tested. Here, we demonstrate the feasibility of real-time functional magnetic resonance imaging volitional neurofeedback in targeting social brain regions in autism spectrum disorder. In this clinical trial, autism spectrum disorder patients were enrolled in a program with five training sessions of neurofeedback. Participants were able to control their own brain activity in this social brain region, with positive clinical and neural effects. Larger, controlled, and blinded clinical studies will be required to confirm the benefits.

Motor Cortex Excitation/Inhibition Imbalance in Young Adults With Autism Spectrum Disorder: A MRS-TMS Approach

“…ASD participants were recruited from a database used in previous studies ( 47 , 48 ) and in collaboration with local ASD associations. All ASD participants obtained positive results on the gold standard diagnostic instruments, namely parental or caregiver interview [Autism Diagnostic Interview-Revised, ADI-R ( 49 )] and direct structured proband assessment [Autism Diagnostic Observation Schedule, ADOS ( 50 )], and met the current diagnostic criteria for ASD as assessed by the Diagnostic and Statistical Manual of Mental Disorders [5th ed.…”

Real-time fMRI neurofeedback as a new treatment for psychiatric disorders: A meta-analysis

“…In contrast, one study on ASD targeted social processing via the connectivity between the left superior temporal sulcus (STS) and the left somatosensory cortex (SC) (54). The other targeted the facial emotion expression processing via the right posterior STS activity (56). Trauma and stressor-related disorders studies focused on the modulation of AMY (41,49,50,52) and the ACC (51) because of their implication in emotion dysregulation, a key symptom in PTSD.…”

“…The optimal duration of the follow-up is not yet well established. Some studies reported a sustained improvement after RT-fMRI-NF training for a month(35,36,53,56,59,61,62), while others only after one week(38,43,44,47).Despite the importance of these measures, only 10 studies out of the 30 reviewed collected and reported follow-up data. This leads to a reduction of the clinical relevance of this technique and may lead to an underestimation of the size of the NF effect.…”

Designing Mobile EEG Neurofeedback Games for Children with Autism: Implications from Industry Practice

“…These collaborative tasks were also supported by prior research and our domain experts' knowledge. Attending to interpersonal collaboration has been proven to be effective stimuli for autistic children's mirror neuron activation [5,6,14]. The core project team consists of one neuroscientist, two algorithmic engineers (for signal processing and machine learning), two developers (for front-end and back-end development), and three designers (for interaction design and product design).…”