Spatiotemporal Entrainment as Innovative Neuromodulation Targeting Cerebello-cerebral Circuits for Enhancing Rehabilitation Outcomes of Cognitive and Social Skills in Progressive and Acquired Cerebellar Diseases
Trial ID: NCT07500103
Status: RECRUITING
Study type: INTERVENTIONAL
Phase: NA
Start date: 2025-01-15
Completion date: 2027-04
Sponsor: I.R.C.C.S. Fondazione Santa Lucia
Collaborators: IRCCS National Neurological Institute "C. Mondino" Foundation
Conditions: Cerebellar Degeneration; Cerebellar Malformation
Interventions: EEg-guided High-Definition transcranial alternate current stimulation (HD-tACS); Immersive Virtual Reality (IVR) Social Prediction training
Locations: IRCCS National Neurological Institute "C. Mondino" Foundation; I.R.C.C.S. Fondazione Santa Lucia
Countries: Italy; Italy
Enrollment: 60
Age range: 12 Years - None
Sex: ALL

Summary:
The cerebellum is increasingly recognized for its crucial role in high-level cognitive processes, particularly in the domain of social cognition and action prediction. Disruptions in cerebellar circuits can lead to significant impairments in anticipating others' intentions and behaviors, affecting daily social interactions. This randomized, double-blind, sham-controlled trial protocol investigates the combined effects of personalized cerebellar High-Definition transcranial Alternating Current Stimulation (HD-tACS) and Immersive Virtual Reality (IVR) training on social prediction abilities. The study involves two clinical populations: adolescents and young adults with congenital cerebellar malformations (CM) and adults with acquired neurodegenerative cerebellar atrophy (CA). Participants undergo eight daily sessions of IVR training designed to enhance internal models of social events through interactive scenarios. Simultaneously, they receive either active or sham HD-tACS delivered at their Individual Gamma Frequency (IGF), determined via baseline EEG. The primary outcomes include behavioral responses to context-based social prediction tasks (action intentions, emotions, and personality traits). Secondary outcomes encompass electrophysiological measures, neuropsychological functioning, and adaptive behavior. By integrating neuromodulation with embodied virtual experiences, the project aims to facilitate cerebello-cerebral plasticity and provide a novel transdiagnostic rehabilitative approach for socio-cognitive impairments.

Eligibility criteria:
Inclusion Criteria for patients with cerebellar malformation include:

* Documented malformations confined to the cerebellum confirmed by a 3T brain MRI scan;
* Age ranging from 12 to 32 years old;
* IQ \>= 50;
* Absence of extra-cerebellar malformations on conventional brain MRI scan.

Inclusion Criteria for patients with degenerative cerebellar atrophy include:

* Evidence of diffuse cerebellar atrophy;
* More than 6 months of illness;
* IQ \>=75;
* Absence of any cortical lesion on conventional brain MRI scans

Exclusion Criteria for both groups include:

* Presence of severe motor and visual impairments, as well as neurodevelopmental (i.e., autism), neurological or psychiatric disorders that could interfere with task execution and protocol compliance;
* Presence of any contraindication for tACS.

Outcomes:
Context-based social prediction task