Spatiotemporal Entrainment Neuromodulation Targeting Cerebello-Cerebral Circuits to Enhance Cognitive and Social Rehabilitation in Cerebellar Diseases
Spatiotemporal Entrainment as Innovative Neuromodulation Targeting Cerebello-cerebral Circuits for Enhancing Rehabilitation Outcomes of Cognitive and Social Skills in Progressive and Acquired Cerebellar Diseases
I.R.C.C.S. Fondazione Santa Lucia
60 participants
Jan 15, 2025
INTERVENTIONAL
Conditions
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
Inclusion Criteria8
- 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.
- Evidence of diffuse cerebellar atrophy;
- More than 6 months of illness;
- IQ \>=75;
- Absence of any cortical lesion on conventional brain MRI scans
Exclusion Criteria2
- 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.
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Interventions
EEG-guided HD-tACS is delivered via a CE-marked Starstim® 8-channel device using a multifocal montage with the active ring electrode centered over the left cerebellar hemisphere (2 cm below and 3 cm left of the inion) and four equidistant references (4 cm). This configuration, validated by SimNIBS 4.1 electric field modeling, targets cerebellar regions linked to mentalizing connectivity. Stimulation is applied for 20 minutes daily at 1 mA peak-to-peak intensity-selected for its safety and efficacy in younger participants-including 30-second ramp-up/down phases. In the sham condition, current is deactivated after the initial ramp-up to maintain blinding through transient tingling. The stimulation frequency is individually tailored to each participant's Individual Gamma Frequency (IGF), identified as the peak power within the 30-80 Hz band via Welch's PSD estimation of 19-channel EEG data (10/10 system) recorded at 500 Hz and processed using FIR filtering.
The protocol employs age-matched, immersive virtual scenarios developed in Blender and Unity, delivered via Meta Quest 2 HMD (120 Hz, 110° FOV) to ensure a high sense of presence. To maximize ecological validity through personalized settings, adolescents interact with school-based environments (library/playground), while adults use a supermarket or restaurant. From a first-person perspective with synchronous hand-tracking, participants observe three objects on a counter as an avatar approaches. Each session (40 mins) includes 88 trials where participants must infer and predict the avatar's preferred object category (e.g., beverages, books) and grasp it first. Three avatars follow specific preferences, while a fourth acts randomly; mappings are pseudo-randomized across eight sessions to ensure identity-based learning. Feedback is provided via auditory cues.
Locations(2)
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NCT07500103