Cerebellar Transcranial Direct Current Stimulation in Children with Autism Spectrum Disorder: A Pilot Study on Efficacy, Feasibility, Safety, and Unexpected Outcomes in Tic Disorder and Epilepsy.

Giordano D’Urso,Roberta Ferrucci,Elena Toscano,Carmela Bravaccio,Andrea De Bartolomeis,Christine E Sheffer,Maria Pia Riccio,Felice Iasevoli,Alberto Priori,Anne Sauvaget,Veronica Sanges

doi:10.3390/jcm11010143

Abstract

Patients with autism spectrum disorder (ASD) display distinctive neurophysiological characteristics associated with significant cognitive, emotional, and behavioral symptoms. Transcranial direct current stimulation (tDCS) applied to the frontal or temporoparietal lobes has demonstrated potential to reduce the severity of ASD-related symptoms. Recently, the cerebellum has been identified as a brain area involved in ASD pathophysiology. In this open-label pilot study, seven ASD patients aged between 9 and 13 years underwent 20 daily sessions of 20 min cathodal stimulation of the right cerebellar lobe. At the end of the treatment, the Aberrant Behavior Checklist (ABC) scores showed a 25% mean reduction in global severity of symptoms, with a more pronounced reduction in the “social withdrawal and lethargy” (−35%), “hyperactivity and noncompliance” (−26%), and “irritability, agitation, and crying” (−25%) subscales. Minor and no improvement were observed in the “stereotypic behavior” (−18%) and “inappropriate speech” (−0%) subscales, respectively. Improvements were not detected in the two patients who were taking psychotropic drugs during the study. Clinical response showed a symptom-specific time course. Quality of sleep and mood improved earlier than hyperactivity and social withdrawal. The treatment was generally accepted by patients and well tolerated. No serious adverse events were reported. Stimulation also appeared to markedly reduce the severity of tics in a patient with comorbid tic disorder and led to the disappearance of a frontal epileptogenic focus in another patient with a history of seizures. In conclusion, cerebellar tDCS is safe, feasible, and potentially effective in the treatment of ASD symptoms among children. Strategies to improve recruitment and retention are discussed.

Highlights

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, the prevalence of which has increased significantly in the past 20 years [1]
In morphometric brain imaging studies, compared to neurotypical children, children with autism spectrum disorder (ASD) showed hemispheric asymmetry with greater volume in several right hemispheric structures compared with homologous contralateral structures, in brain regions associated with language and social abilities [8,9,10,11]
A functional magnetic resonance imaging study found hypoactivation of specific brain areas of the left hemisphere relative to the right hemisphere among children with ASD compared with neurotypical children [12], while a proton magnetic resonance spectroscopic study showed a reduced N-acetylaspartate/creatine/phosphocreatine ratio, a marker of neuronal density, in the left but not in the right dorsolateral prefrontal cortex (DLPFC) of autistic patients [13]

Summary

Introduction

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, the prevalence of which has increased significantly in the past 20 years [1]. In morphometric brain imaging studies, compared to neurotypical children, children with ASD showed hemispheric asymmetry with greater volume in several right hemispheric structures compared with homologous contralateral structures, in brain regions associated with language and social abilities [8,9,10,11]. A functional magnetic resonance imaging study found hypoactivation of specific brain areas of the left hemisphere (i.e., amygdala and fusiform gyrus) relative to the right hemisphere among children with ASD compared with neurotypical children [12], while a proton magnetic resonance spectroscopic study showed a reduced N-acetylaspartate/creatine/phosphocreatine ratio, a marker of neuronal density, in the left but not in the right dorsolateral prefrontal cortex (DLPFC) of autistic patients [13]. The left DLPFC is key to cognitive, social, and emotional functioning [14]

Results

Discussion

Conclusion