Theory of Mind Deficits and Neurophysiological Operations in Autism Spectrum Disorders: A Review

Ανδρέου, Μαρία; Skrimpa, Vasileia

doi:10.3390/brainsci10060393

Cited by 65 publications

(45 citation statements)

References 75 publications

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“…Here, we employed a novel experimental system designed for directly monitoring social investigation behavior to examine the behavior of these mice in a battery of four social discrimination tests. Of these tests, the ESP test is a novel test, which is similar in principle to the affective state discrimination test recently described (12), and seems to be highly relevant to ASD symptoms which involve impaired theory of mind (22,23). In agreement with our previous paper, we found normal behavior of A350V mice in the SP test which assesses social motivation, as well as in the SNP test which assesses social cognition.…”

Section: Discussionsupporting

confidence: 90%

Precision medicine for the rescue of specific impairments in social behavior associated with the A350VIqsec2mutation

Jabarin

Levy

Abergel

et al. 2020

Preprint

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In this study we tested the hypothesis that precision medicine guided therapy targeting glutamatergic neurotransmission could rescue behavioral deficits exhibited by mice carrying a specific mutation in the Iqsec2 gene. The IQSEC2 protein plays a key role in glutamatergic synapses and mutations in the IQSEC2 gene are a frequent cause of neurodevelopmental disorders. We have recently reported on the molecular pathophysiology of one such mutation A350V and demonstrated that this mutation downregulates AMPA type glutamatergic receptors (AMPAR) in A350V mice. Here we sought to identify behavioral deficits in A350V mice and hypothesized that we could rescue these deficits by PF-4778574, a positive AMPAR modulator. We found that A350V Iqsec2 mice exhibit specific deficits in sex preference and emotional state preference behaviors as well as in vocalizations when encountering a female mouse. The social discrimination deficits, but not the impaired vocalization, were rescued with PF-4778574. We conclude that social behavior deficits associated with the A350V Iqsec2 mutation may be rescued by enhancing AMPAR mediated synaptic transmission.

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Section: Discussionsupporting

confidence: 90%

Precision medicine for the rescue of specific impairments in social behavior associated with the A350VIqsec2mutation

Jabarin

Levy

Abergel

et al. 2020

Preprint

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“…Nevertheless, progress in investigating complex symptoms of ASD patients has lagged, owing to inherent limitation of traditional behavioral analyses. For instance, the lack of emotional reciprocity is frequently observed in ASD patients, who have difficulty in performing a set of executive functions, including impaired theory of mind, imitation, or joint attention of other people [ 6 , 7 ]. Deficits in these higher cognitive functions, particularly, empathy, are likely to lead to abnormalities in complex social behaviors, such as social competition and cooperation [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…For instance, the lack of emotional reciprocity is frequently observed in ASD patients, who have difficulty in performing a set of executive functions, including impaired theory of mind, imitation, or joint attention of other people [ 6 , 7 ]. Deficits in these higher cognitive functions, particularly, empathy, are likely to lead to abnormalities in complex social behaviors, such as social competition and cooperation [ 6 , 7 ]. Indeed, major symptoms of high-functioning autism include empathic incapacity, reactive aggression and impaired complex social behaviors [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice

et al. 2020

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Background Recent progress in genomics has contributed to the identification of a large number of autism spectrum disorder (ASD) risk genes, many of which encode synaptic proteins. Our understanding of ASDs has advanced rapidly, partly owing to the development of numerous animal models. Extensive characterizations using a variety of behavioral batteries that analyze social behaviors have shown that a subset of engineered mice that model mutations in genes encoding Shanks, a family of excitatory postsynaptic scaffolding proteins, exhibit autism-like behaviors. Although these behavioral assays have been useful in identifying deficits in simple social behaviors, alterations in complex social behaviors remain largely untested. Methods Two syndromic ASD mouse models—Shank2 constitutive knockout [KO] mice and Shank3 constitutive KO mice—were examined for alterations in social dominance and social cooperative behaviors using tube tests and automated cooperation tests. Upon naïve and salient behavioral experience, expression levels of c-Fos were analyzed as a proxy for neural activity across diverse brain areas, including the medial prefrontal cortex (mPFC) and a number of subcortical structures. Findings As previously reported, Shank2 KO mice showed deficits in sociability, with intact social recognition memory, whereas Shank3 KO mice displayed no overt phenotypes. Strikingly, the two Shank KO mouse models exhibited diametrically opposed alterations in social dominance and cooperative behaviors. After a specific social behavioral experience, Shank mutant mice exhibited distinct changes in number of c-Fos+ neurons in the number of cortical and subcortical brain regions. Conclusions Our results underscore the heterogeneity of social behavioral alterations in different ASD mouse models and highlight the utility of testing complex social behaviors in validating neurodevelopmental and neuropsychiatric disorder models. In addition, neural activities at distinct brain regions are likely collectively involved in eliciting complex social behaviors, which are differentially altered in ASD mouse models.

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“…Similarly, a recent study in ADHD patients versus healthy controls by Abdel-Hamid et al, 2019 [47], found significant positive correlations between theory of mind (ToM) and empathy competences and EF performances in the ADHD group but not in the control group. In a recent review, which analyzed fifteen studies conducted on ADHD samples, with or without comorbidities and included mostly male children, Pineda-Alhucema et al, 2018 [48], found the EF most correlated with ToM were inhibitory control, working memory, cognitive flexibility and attention (for further updated details on the relationship between EF and ToM please refer to Andreou et al 2020 [49]).…”

Section: Introductionmentioning

confidence: 99%

The Role of Executive Functions in the Development of Empathy and Its Association with Externalizing Behaviors in Children with Neurodevelopmental Disorders and Other Psychiatric Comorbidities

et al. 2020

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Executive functions have been previously shown to correlate with empathic attitudes and prosocial behaviors. People with higher levels of executive functions, as a whole, may better regulate their emotions and reduce perceived distress during the empathetic processes. Our goal was to explore the relationship between empathy and executive functioning in a sample of children and adolescents diagnosed with Attention Deficit and Hyperactivity Disorder alone or associated with comorbid Disruptive Behavior Disorders and/or Autism Spectrum Disorder. We also aimed to examine the role of empathic dimensions and executive skills in regulating externalizing behaviors. The 151 participants with ADHD were assigned to four groups according to their psychiatric comorbidity (either “pure” or with ASD and/or ODD/CD) and assessed by means of either parent- or self-reported questionnaires, namely the BRIEF−2, the BES, and the IRI. No questionnaire was found to discriminate between the four groups. Affective Empathy was found to positively correlate with Emotional and Behavioral Regulation competences. Furthermore, Aggressiveness and Oppositional Defiant Problems were positively associated with Executive Emotional and Behavioral Regulation competences. On the other hand, Rule-Breaking Behaviors and Conduct Problems were negatively associated with Affective Empathy and with Behavioral skills. Our study provides an additional contribution for a better understanding of the complex relationship between empathic competence and executive functions, showing that executive functioning and empathic attitudes interact with each other to regulate aggressive behaviors. This study further corroborates developmental models of empathy and their clinical implications, for which externalizing behaviors could be attenuated by enhancing executive functioning skills.

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Theory of Mind Deficits and Neurophysiological Operations in Autism Spectrum Disorders: A Review

Cited by 65 publications

References 75 publications

Precision medicine for the rescue of specific impairments in social behavior associated with the A350VIqsec2mutation

Precision medicine for the rescue of specific impairments in social behavior associated with the A350VIqsec2mutation

Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice

The Role of Executive Functions in the Development of Empathy and Its Association with Externalizing Behaviors in Children with Neurodevelopmental Disorders and Other Psychiatric Comorbidities

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