Autism Spectrum disorder (ASD) is a clinically complex and heterogeneous neurodevelopmental condition typically characterized by core deficits in social interaction (Goldson et al. 2016). ASD social dysfunctions have been associated with impairment in the first stage of emotional processing (Kana et al., 2016) and a regulatory imbalance of autonomic functions (Porges, 1995). In recent years, the classical view of the cerebellum as being primarily involved in motor control has been widely questioned due to the identification of neural circuits between the cerebellum and subcortical areas of the cerebral cortex responsible for controlling higher-order functions , including cognitive, affective/emotional and social domains. Due to its connections with the limbic system, the cerebellum, and in particular its vermal portion, has been implicated in the modulation of autonomic reactions and in the automatic component of emotional processing, i.e the emotion recognition (ER) (Clausi et al. 2017; Sacchetti et al. 2005). According to existing research, the hypothesis is that the cerebellum may have a role in vagally-mediated autonomic dysregulation in ASD and subsequent difficulties in attenuating the autonomic reactivity to stimuli during implicit emotional processing, impairing social adaptation. Specifically, we hypothesize that the ASD emotional dysregulation could be a consequence of a complex alteration of the autonomic neuronal network in which the cerebellum acts. To investigate this hypothesis an integrated behavioural, neuroimaging and physiological approach will be used. Furthermore, considering the emerging findings about the improvement effect of the cerebellar transcranial direct current stimulation (tDCS) on ER (Ferrucci et al. 2012), we postulate that the tDCS modulation of the cerebellar excitability could influence the implicit and automatic emotional processing operated by the cerebellum, opening new avenues for ASD intervention.
Although the data reported in the literature allow, at least in part, to hypothesize a role of the cerebellum in the mental disorders observed in patients with ASD, this research project is the first to use an integrate behavioural, neuroimaging and physiological approach to help the comprehension of ASD pathogenesis and open new avenues for ASD treatment. The extensive exploration of ASD subjects, the investigation of peripheral arousal accompanying the emotional experience and the analyses of functional alterations of the cerebello-cortical circuits involved in the more automatic emotional processing, will allow to identify specific MRI biomarkers of ASD autonomic and ER impairments focusing on the cerebellar role in this complex system. The implementation of tDCS protocol targeting the cerebellum and improving the autonomic response and processing of basic emotions may open the possibility to consider new ASD interventions for use in adulthood, also considering that unlike the cortex, cerebellum is NOT an ictogenic/epileptogenic structure, thus reducing potential stimulation side-effects. Generally speaking, the present project can improve the knowledge on the ASD pathogenesis. Several aspects are still unrecognized and underestimated within the scientific community, clinicians and students as well as patients and their relatives/caregivers. In particular, there is an urgent need to consider adults with ASD in research and services development to improve their mental health also including better understanding of the neurobiological causes of ASD. The limited literature on adult outcomes suggests that ASD is a lifelong condition leading to persistent and stable impairments in activities of daily living (Eaves et al. 2008). Although a growing body of studies supports the value of early diagnosis and treatment (Elder et al. 2017), many ASD adults with normal intellectual level remain unidentified or are diagnosed late in life (Klaiman et al. 2015) when social demands increases (DSM-V, 2013). As a consequence, research and health services mainly focused on children (Murphy et al. 2016). Conversely, the lack of evidence-based treatments and service for ASD adults has led to increasing prevalence rates and disease burden on people with ASD as they age, their families, and society (Ecker et al. 2013). Thus, according to the rehabilitation potentiality of the tDCS (Ferrucci et al. 2012), this research project could be crucial to evaluate new treatment approaches specifically targeting ASD adult population. Thus, a broader understanding of pathological mechanisms subtending ASD symptomatology that consider behavioural, neural and physiological interaction will be very helpful to the trainees in neurology, psychiatry, psychotherapy, with an important impact on the treatment of adult ASD subjects who lack evidence-based treatment.
The rationale for neuromodulation for social skills 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 (see van Overwalle et al, 2014). As a consequence, focal intervention in the neural network may have therapeutic effects by regulating the function of this network. Several studies have documented positive effects of non invasive brain stimulation techniques for the treatment of neurological and neuropsychiatric disorders (Finisguerra et al, 2019; To et al, 2018). In particular, cerebellar stimulation has been shown not only to improve sensorimotor functions in individuals with cerebellar ataxia (Benussi et al, 2020; Chen et al, 2020), but also to alleviate neurocognitive deficits in patients with bipolar disorder (Minichino et al, 2015; Bersani et al, 2017) or major depression (Ho et al, 2014).
The innovative aspect of the proposal is that this approach has the potential to be applied in order to address similar questions in patients with different psychopathological conditions (i.e. eating disorder, OCD, anxiety), with the future perspective to enhance the knowledge on the contribution of the cerebellum to emotional and behavioural domain, beyond the well-established motor control. Overall, the hypothesis of a cerebellar functional alteration may provide a breeding ground for various psychopathological conditions, thus enhancing the general impact of the project. Altogether, integrating knowledge and methods from different disciplines, emphasizing the connections between neurobiological findings, imaging and psychophysiological data, and behavioural/neuropsychological aspects, may have important clinical implications for patients paving the way for the development of rehabilitation protocols using non-invasive cerebellar stimulation to improve affective and social functions mediated by the cerebellum (see Oldrati and Shutter, 2018; Van Dun et al, 2018).