Advancing the discovery of medications for autism spectrum disorder using new technologies to reveal social brain circuitry in rodents

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.

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Brain Responses Underlying Anthropomorphism, Agency, and Social Attribution in Autism Spectrum Disorder

The Open Neuroimaging Journal ◽

10.2174/1874440001812010016 ◽

2018 ◽

Vol 12 (1) ◽

pp. 16-29 ◽

Cited By ~ 1

Author(s):

Carla J. Ammons ◽

Constance F. Doss ◽

David Bala ◽

Rajesh K. Kana

Keyword(s):

Autism Spectrum Disorder ◽

Social Movement ◽

Mental States ◽

Brain Regions ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Social Brain ◽

Social Attribution ◽

Brain Responses ◽

Fmri Study

Background:Theory of Mind (ToM), the ability to attribute mental states to oneself and others, is frequently impaired in Autism Spectrum Disorder (ASD) and may result from altered activation of social brain regions. Conversely, Typically Developing (TD) individuals overextend ToM and show a strong tendency to anthropomorphize and interpret biological motion in the environment. Less is known about how the degree of anthropomorphism influences intentional attribution and engagement of the social brain in ASD.Objective:This fMRI study examines the extent of anthropomorphism, its role in social attribution, and the underlying neural responses in ASD and TD using a series of human stick figures and geometrical shapes.Methods:14 ASD and 14 TD adults watched videos of stick figures and triangles interacting in random or socially meaningful ways while in an fMRI scanner. In addition, they completed out-of-scanner measures of ToM skill and real-world social deficits. Whole brain statistical analysis was performed for regression and within and between group comparisons of all conditions using SPM12’s implementation of the general linear model.Results:ToM network regions were activated in response to social movement and human-like characters in ASD and TD. In addition, greater ToM ability was associated with increased TPJ and MPFC activity while watching stick figures; whereas more severe social symptoms were associated with reduced right TPJ activation in response to social movement.Conclusion:These results suggest that degree of anthropomorphism does not differentially affect social attribution in ASD and highlights the importance of TPJ in ToM and social attribution.

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Identification of lateralized compensatory neural activities within the social brain due to autism spectrum disorder in adolescent males

European Journal of Neuroscience ◽

10.1111/ejn.13634 ◽

2017 ◽

Vol 47 (6) ◽

pp. 631-642 ◽

Cited By ~ 6

Author(s):

Vigneshwaran Subbaraju ◽

Suresh Sundaram ◽

Sundararajan Narasimhan

Keyword(s):

Autism Spectrum Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Adolescent Males ◽

Social Brain ◽

Neural Activities ◽

The Social

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Response Patterns in the Developing Social Brain are Organized by Social and Emotion Features and Disrupted in Children Diagnosed with Autism Spectrum Disorder

10.31234/osf.io/8rcun ◽

2019 ◽

Author(s):

Hilary Richardson ◽

Hyowon Gweon ◽

David Dodell-Feder ◽

Caitlin Malloy ◽

hannah pelton ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Multivariate Analyses ◽

Developmental Change ◽

Brain Regions ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Response Patterns ◽

Social Brain ◽

Condition Model ◽

Control Models

Adults and children recruit a specific network of brain regions when engaged in “Theory of Mind” (ToM) reasoning. Recently, fMRI studies of adults have used multivariate analyses to provide a deeper characterization of responses in these regions. These analyses characterize representational distinctions within the social domain, rather than comparing responses across preferred (social) and non-preferred stimuli. Here, we conducted opportunistic multivariate analyses in two previously collected datasets (Experiment 1: n=20 5-11 year old children and n=37 adults; Experiment 2: n=76 neurotypical and n=29 5-12 year old children diagnosed with Autism Spectrum Disorder (ASD)) in order to characterize the structure of representations in the developing social brain, and in order to discover if this structure is disrupted in ASD. Children listened to stories that described characters’ mental states (Mental), non-mentalistic social information (Social), and causal events in the environment (Physical), while undergoing fMRI. We measured the extent to which neural responses in ToM brain regions were organized according to two ToM-relevant models: 1) a condition model, which reflected the experimenter-generated condition labels, and 2) a data-driven emotion model, which organized stimuli according to their emotion content. We additionally constructed two control models based on linguistic and narrative features of the stories. In both experiments, the two ToM-relevant models outperformed the control models. The fit of the condition model increased with age in neurotypical children. Moreover, the fit of the condition model to neural response patterns was reduced in the RTPJ in children diagnosed with ASD. These results provide a first glimpse into the conceptual structure of information in ToM brain regions in childhood, and suggest that there are real, stable features that predict responses in these regions in children. Multivariate analyses are a promising approach for sensitively measuring conceptual and neural developmental change and individual differences in ToM. This is a post-peer-review, pre-copyedit version of an article published in Cortex. The final authenticated version is available online at: https://doi.org/10.1016/j.cortex.2019.11.021 .

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Research Review: Constraining heterogeneity: the social brain and its development in autism spectrum disorder

Journal of Child Psychology and Psychiatry ◽

10.1111/j.1469-7610.2010.02349.x ◽

2011 ◽

Vol 52 (6) ◽

pp. 631-644 ◽

Cited By ~ 192

Author(s):

Kevin A. Pelphrey ◽

Sarah Shultz ◽

Caitlin M. Hudac ◽

Brent C. Vander Wyk

Keyword(s):

Autism Spectrum Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Research Review ◽

Social Brain ◽

The Social

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Attenuated link between the medial prefrontal cortex and the amygdala in children with autism spectrum disorder: Evidence from effective connectivity within the “social brain”

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2020.110147 ◽

2020 ◽

pp. 110147

Author(s):

Lei Li ◽

Changchun He ◽

Taorong Jian ◽

Xiaonan Guo ◽

Jinming Xiao ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Effective Connectivity ◽

Children With Autism ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Social Brain ◽

The Social

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Social Brain Functional Maturation in Newborn Infants With and Without a Family History of Autism Spectrum Disorder

JAMA Network Open ◽

10.1001/jamanetworkopen.2019.1868 ◽

2019 ◽

Vol 2 (4) ◽

pp. e191868 ◽

Cited By ~ 8

Author(s):

Judit Ciarrusta ◽

Jonathan O'Muircheartaigh ◽

Ralica Dimitrova ◽

Dafnis Batalle ◽

Lucilio Cordero-Grande ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Family History ◽

Newborn Infants ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Social Brain ◽

Functional Maturation ◽

History Of

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KEYme: Multifunctional Smart Toy for Children with Autism Spectrum Disorder

Sustainability ◽

10.3390/su13074010 ◽

2021 ◽

Vol 13 (7) ◽

pp. 4010

Author(s):

Raquel Cañete ◽

Sonia López ◽

M. Estela Peralta

Keyword(s):

Autism Spectrum Disorder ◽

New Technologies ◽

Children With Autism ◽

Well Being ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Typically Developing ◽

Functional Requirements ◽

Smart Products

The role that design engineering plays in the quality of life and well-being of people with autism spectrum disorder around the world is extremely relevant; products are highly helpful when used as “intermediaries” in social interactions, as well as in the reinforcement of cognitive, motor and sensory skills. One of the most significant challenges engineers have to face lies in the complexity of defining those functional requirements of objects that will efficiently satisfy the specific needs of children with autism within a single product. Furthermore, despite the growing trends that point toward the integration of new technologies in the creation of toys for typically developing children, the variety of specialized smart products aimed at children with autism spectrum disorder is very limited. Based on this evidence the KEYme project was created, where a multifunctional smart toy is developed as a reinforcement system for multiple needs which is adaptable to different kinds of autism for therapies, educational centers or family environments. This approach involves the knowledge transfer from the latest neuroscience, medicine and psychology contributions to the engineering and industrial design field.

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