Attenuated activation of the anterior rostral medial prefrontal cortex on self-relevant social reward processing in individuals with autism spectrum disorder

Abstract Background Deletion or mutations of SHANK3 lead to Phelan-McDermid syndrome and monogenic forms of autism spectrum disorder. SHANK3 encodes its eponymous scaffolding protein at excitatory glutamatergic synapses. Altered dendritic and spine morphology in the hippocampus, cerebellum and striatum have been associated with behavioral impairments in various Shank3-deficient animal models. Given the attentional deficit reported in these animals, our study explored whether deficiency of Shank3 in a rat model alters synaptic ultrastructure in the medial prefrontal cortex. Methods We used electron microscopy to determine the density of asymmetric synapses in layer III excitatory neurons of the medial prefrontal cortex in 5 week-old Shank3-homozygous knockout ( Shank3 -KO), heterozygous ( Shank3 -Het), and wild-type (WT) rats. We also measured postsynaptic density length, postsynaptic density area, and head diameter of dendritic spines at these synapses. Results All three groups had comparable synapse density and postsynaptic density length. Spine head diameter of Shank3 -Het rats, but not Shank3 -KO, was larger than WT rats. Shank3 -Het rats had wider head diameter in non-perforated synapses compared to WT and Shank3 -KO rats. The total postsynaptic density area was significantly larger in Shank3 -Het rats compared to Shank3 -KO and WT rats. These findings represent preliminary evidence for synaptic ultrastructural alterations in the medial prefrontal cortex of rats that lack one copy of Shank3 and mimic the heterozygous loss of SHANK3 in Phelan-McDermid syndrome. Limitations The Shank3 deletion in the rat model we used does not affect all isoforms of the protein and as such, would only model the effect of the mutations resulting in loss of the N-terminus of the protein. Given the higher prevalence of ASD in males, this study focused only on synaptic ultrastructure in male Shank3 -deficient rats. Conclusions We observed increased head diameter and postsynaptic density area in rats heterozygous for Shank3 deficiency. Further investigations of the mechanisms leading to altered synaptic ultrastructure in this animal model will enable us to understand better the role that Shank3 protein plays in autism spectrum disorder and Phelan-McDermid syndrome.

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Social cognitive skills groups increase medial prefrontal cortex activity in children with autism spectrum disorder

Autism Research ◽

10.1002/aur.2603 ◽

2021 ◽

Author(s):

Karim Ibrahim ◽

Latha V. Soorya ◽

Danielle B. Halpern ◽

Michelle Gorenstein ◽

Paige M. Siper ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Cognitive Skills ◽

Social Cognitive ◽

Children With Autism ◽

Autism Spectrum ◽

Spectrum Disorder

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Social reward processing in individuals with autism spectrum disorder: A systematic review of the social motivation hypothesis

Research in Autism Spectrum Disorders ◽

10.1016/j.rasd.2017.10.001 ◽

2018 ◽

Vol 45 ◽

pp. 9-26 ◽

Cited By ~ 27

Author(s):

Summer Bottini

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorder ◽

Social Motivation ◽

Autism Spectrum ◽

Reward Processing ◽

Spectrum Disorder ◽

Social Reward ◽

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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Structural covariance between posterior cingulate cortex and medial prefrontal cortex in adolescents with autism spectrum disorder

Neuropsychiatrie de l Enfance et de l Adolescence ◽

10.1016/j.neurenf.2012.04.307 ◽

2012 ◽

Vol 60 (5) ◽

pp. S182

Author(s):

L. Liu ◽

S.S. Gau ◽

A. Pan ◽

W.I. Tseng

Keyword(s):

Autism Spectrum Disorder ◽

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Cingulate Cortex ◽

Posterior Cingulate Cortex ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Structural Covariance ◽

Posterior Cingulate ◽

Adolescents With Autism

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Reward processing in autism spectrum disorder and psychopathy: a systematic review

BJPsych Open ◽

10.1192/bjo.2021.160 ◽

2021 ◽

Vol 7 (S1) ◽

pp. S41-S42

Author(s):

Patrick McLaughlin ◽

Marija-Magdalena Petrinovic ◽

Nigel Blackwood

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorder ◽

English Language ◽

Treatment Strategies ◽

Autism Spectrum ◽

Reward Processing ◽

Spectrum Disorder ◽

Social Reward ◽

Social Dysfunction ◽

The Social

AimsEmerging research suggests that aberrant reward processing may underpin much of the social dysfunction we see in psychiatric disorders. Two conditions associated with marked social dysfunction are Autism Spectrum Disorder (ASD) and Psychopathy. However, no review to date has directly contrasted reward processing in both conditions and incorporated literature on social and non-social rewards. This systematic review aims to: (i) identify and compare reward processing abnormalities in ASD and Psychopathy as demonstrated in task-based functional magnetic resonance imaging (fMRI) studies; and (ii) identify correlations between fMRI reward processing abnormalities and manifested symptoms, with a focus on those giving rise to social dysfunction.MethodThe electronic databases PubMed, PsycINFO and EMBASE were searched to identify studies satisfying the following criteria: (i) a validated measure was used to assess ASD or Psychopathy; (ii) the study was published in an English language peer review journal; (iii) the age of participants was 18 years or older; (iv) individuals participated in a reward-based experimental paradigm; and (v) the response to the reward was measure using fMRI.ResultA total of 12 articles were identified that satisfied inclusion criteria. Six studies examined reward processing in ASD and six studies examined reward processing in Psychopathy. All studies in both conditions indicated some degree of abnormal reward-related neural response. The most replicated findings were aberrant responses in the Ventral Striatum (VS). Autism Spectrum Disorder was typified by VS hypoactivation to social and non-social reward, while Psychopathy was associated with VS hyperactivation in response to non-social reward anticipation. No studies were identified of social reward in Psychopathy.ConclusionThe reported fMRI findings correlate with clinical observations in both conditions. Reduced reward response in ASD to a range of social and non-social stimuli would provide a parsimonious account of the social and non-social deficits that characterise the condition. Enhanced responses to the anticipation of reward in Psychopathy provides an account of the ruthless and destructive pursuit of reward-driven behaviours not inhibited by immoral or aversive signals. If, as the literature suggests, reward circuitry dysfunction plays a role in the development and manifestation of symptoms in both conditions, reward processing and its underlying neural circuitry may represent important targets for the development of novel treatment strategies.

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Transcranial Direct Current Stimulation (tDCS) over the Left Dorsal Lateral Prefrontal Cortex in Children with Autism Spectrum Disorder (ASD)

Neural Plasticity ◽

10.1155/2021/6627507 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Jiujun Qiu ◽

Xuejun Kong ◽

Jihan Li ◽

Jie Yang ◽

Yiting Huang ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Prefrontal Cortex ◽

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Sleep Habits ◽

Lateral Prefrontal Cortex ◽

Direct Current Stimulation ◽

Children With Asd

Recently, transcranial direct current stimulation (tDCS) has been applied to relieve symptoms in individuals with autism spectrum disorder (ASD). In this prospective, parallel, single-blinded, randomized study, we investigate the modulation effect of three-week tDCS treatment at the left dorsal lateral prefrontal cortex (DLPFC) in children with ASD. 47 children with ASD were enrolled, and 40 (20 in each group) completed the study. The primary outcomes are Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and the Repetitive Behavior Scale-Revised (RBS-R). We found that children with ASD can tolerate three-week tDCS treatment with no serious adverse events detected. A within-group comparison showed that real tDCS, but not sham tDCS, can significantly reduce the scores of CARS, Children’s Sleep Habits Questionnaire (CSHQ), and general impressions in CARS (15th item). Real tDCS produced significant score reduction in the CSHQ and in CARS general impressions when compared to the effects of sham tDCS. The pilot study suggests that three-week left DLPFC tDCS is well-tolerated and may hold potential in relieving some symptoms in children with ASD.

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