Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction and repetitive behaviour or restricted interests (American Psychiatric Association, 2013). Recent findings have implicated the cerebellum in this syndrome. Post-mortem studies showed a cerebellar Purkinje cells loss in ASD patients and neuroimaging data evidenced cerebellar gray and white matter alterations in these patients (Amaral et al. 2008; Scott et al. 2009; Olivito et al, 2017; 2018). The ASD diagnosis is based on a pervasive social interaction disorder (World Health Organization 1993) and its main behavioral hallmark is an impairment in Theory of Mind (ToM), the ability to recognize and attribute mental states to others to explain and predict their behaviour (Baron-Cohen 1995).
Intriguingly, ToM alterations have been reported in patients with cerebellar degenerative diseases (CDD) (Sokolovsky et al. 2010; D'Agata et al. 2011; Clausi et al., 2019; Van Overwalle et al, 2019) and neuroimaging studies have shown a cerebellar activation during tasks implying social cognitive abilities (Habel et al. 2005; see Clausi et al, 2017 for a review).
These evidences, supported by cerebellar connections with limbic and associative areas (Schmahmann, Pandya, 1997), suggest a role of cerebellum in ASD mentalizing impairment.
In the present study, ToM profile and neuro-anatomical substrate of CDD and ASD patients will be directly compared. It will allow to elucidate the cerebellar involvement in specific ToM aspects (Coricelli, 2005) and clarify the role of cerebello-cerebral circuits in ASD pathogenesis, opening new perspectives on ASD treatment.
ASD are highly prevalent neurodevelopment disorders (Levy et al, 2009), with complex aetiology, multiple contributing factors, and high social cost. Moreover, isolated cerebellar injury has been associated with a higher incidence of ASD (Limperopoulos et al. 2007).
The anatomical and functional characterization of the cerebello-cortical alterations in CCD and ASD patients related with ToM deficits will provide a crucial insight on the comprehension of ASD pathogenesis.
Studies showed the rehabilitation potentiality of the tDCS in stroke patients (Ayache et al. 2012) and in patients affected by mood disorders (Galvez et al. 2011; Berlim et al. 2012). For an overview of this topic see the Consensus Paper by Miterko et al. (2019).
Moreover, Ferrucci et al. (2012) showed that the cerebellar tDCS results in a facilitation of the emotion recognition ability. Neuromodulation-based approaches have showed promise for treating several neuropsychiatric conditions including schizophrenia and depression (Szymkowicz et al., 2016). A tDCS study in schizophrenia found that anodic (excitatory) stimulation of the left dorsolateral prefrontal cortex (DLPFC) in conjunction with cathodic (inhibitory) stimulation of the left temporal-parietal junction could significantly reduce the occurrence of auditory verbal hallucinations in patients (Brunelin et al., 2012), while anodic stimulation of the left DLPFC can significantly reduce depression scores (Fregni et al., 2006).
Although a growing body of evidence supports the value of early diagnosis and treatment with evidence-based interventions (Elder et al., 2017), many subjects remain unidentified as having ASD or are diagnosed late in life (Klaiman et al., 2015). In particular, while severe forms of ASD are often diagnosed in early childhood, high-functioning individuals may not be diagnosed until much later in life. Considerable evidences suggest that vocational and independent living outcomes are suboptimal for the majority of ASD adults (Seltzer et al., 2004; Roux et al., 2015).
Thus, future studies aiming to investigate the effectiveness of novel and focused therapeutic approach in adulthood are challenging, in particular for those ASD subjects who were diagnosed later in adulthood and did not receive any treatment during childhood or adolescence.
In this view, the rationale for neuromodulation of ToM ability is based on a neural network theory that posits a specific set of functionally connected brain regions that work together to achieve functional optimal outcomes in terms of ToM. As consequence, focal intervention in the neural network may have therapeutic effects by regulating the function of this network.
To reach this objective it is necessary: - characterize ToM profiles in adults with ASD; - identify brain networks that show a correlation with ToM scores in terms of functional properties, detecting the abnormal brain process that may underlie and maintain maladaptive conditions; -verify the neuromodulation effects on these specific networks.
Taking into account all these aspects, the present proposal has the potential to provide a breeding ground for alternative therapeutic indications, such as neuromodulation, to improve suboptimal outcomes and likelihood of independent living in adults with ASD.