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

B. Direito, S. Mouga, A. Sayal, M. Simoes, H. Quental, I. Bernardino, R. Playle, R. McNamara, D.E.J. Linden, G. Oliveira, M.C. Branco*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Web of Science)


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 abstractNeurofeedback 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.
Original languageEnglish
Article number13623613211002052
Pages (from-to)1746-1760
Number of pages15
Issue number6
Publication statusPublished - 1 Aug 2021


  • autism spectrum disorder
  • neurofeedback
  • neurorehabilitation
  • posterior superior temporal sulcus
  • real-time functional magnetic resonance imaging
  • social cognition

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