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An accumulating body of evidence indicates a tight relationship between the endocrine system and abnormal social behavior. Two evolutionarily conserved hypothalamic peptides, oxytocin and arginine-vasopressin, because of their extensively documented function in supporting and regulating affiliative and socio-emotional responses, have attracted great interest for their critical implications for autism spectrum disorders (ASD). A large number of controlled trials demonstrated that exogenous oxytocin or arginine-vasopressin administration can mitigate social behavior impairment in ASD. Furthermore, there exists long-standing evidence of severe socioemotional dysfunctions after hypothalamic lesions in animals and humans. However, despite the major role of the hypothalamus for the synthesis and release of oxytocin and vasopressin, and the evident hypothalamic implication in affiliative behavior in animals and humans, a rather small number of neuroimaging studies showed an association between this region and socioemotional responses in ASD. This review aims to provide a critical synthesis of evidences linking alterations of the hypothalamus with impaired social cognition and behavior in ASD by integrating results of both anatomical and functional studies in individuals with ASD as well as in healthy carriers of oxytocin receptor (OXTR) genetic risk variant for ASD. Current findings, although limited, indicate that morphofunctional anomalies are implicated in the pathophysiology of ASD and call for further investigations aiming to elucidate anatomical and functional properties of hypothalamic nuclei underlying atypical socioemotional behavior in ASD.

Background and objectiveThe presence of executive deficits in patients with Amyotrophic Lateral Sclerosis is well established, even if standardized measures are difficult to obtain due to progressive physical disability of the patients. We present clinical data concerning a newly developed measure of cognitive flexibility, administered by means of Eye-Tracking (ET) technology in order to bypass verbal-motor limitations.Methods21 ALS patients and 21 age-and education-matched healthy subjects participated in an ET-based cognitive assessment, including a newly developed test of cognitive flexibility (Arrows and Colors Cognitive Test–ACCT) and other oculomotor-driven measures of cognitive functions. A standard screening of frontal and working memory abilities and global cognitive efficiency was administered to all subjects, in addition to a psychological self-rated assessment. For ALS patients, a clinical examination was also performed.ResultsACCT successfully discriminated between patients and healthy controls, mainly concerning execution times obtained at different subtests. A qualitative analysis performed on error distributions in patients highlighted a lower prevalence of perseverative errors, with respect to other type of errors. Correlations between ACCT and other ET-based frontal-executive measures were significant and involved different frontal sub-domains. Limited correlations were observed between ACCT and standard ‘paper and pencil’ cognitive tests.ConclusionsThe newly developed ET-based measure of cognitive flexibility could be a useful tool to detect slight frontal impairments in non-demented ALS patients by bypassing verbal-motor limitations through the oculomotor-driven administration. The findings reported in the present study represent the first contribution towards the development of a full verbal-motor free executive test for ALS patients.

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