tACS-combined motor training for the rehabilitation of the upper limb in children and adolescents with cerebral palsy: A randomized, sham-controlled trial protocol Viola Oldrati, Andrea Ciricugno, Renato Borgatti, Simona Orcesi, Elisa Fazzi, et al. Plos One, 2025 Background Children with cerebral palsy (CP) commonly face gross motor function impairments and manual dexterity deficits, significantly affecting their activity level and independence and, ultimately, quality of life. Rehabilitation often targets improving manual dexterity and activity levels, but standard therapies have limited efficacy. Hence, exploring novel methods to enhance upper limb functionality is crucial. Transcranial alternating current stimulation (tACS), by delivering currents oscillating at specific frequencies syncing with the brain’s electrical rhythms, has been demonstrated to modulate neural oscillations and motor behavior. Method This randomized, double-blind, sham-controlled, pre-post test study involves 44 children and adolescents (6–17 yo) with CP treated in pairs, which will be randomly allocated to the experimental or control group receiving, respectively, active or sham fronto-cerebellar tACS delivered at the individual gamma frequency. After tACS, both groups will undergo bimanual training, including lower extremities (HABIT-ILE). Primary outcome measures will include the Assisting Hand Assessment, Box and Block Test, and a Visuomotor Task administered via computer for manual visuomotor control evaluation. Secondary outcomes will encompass the Children’s Hand Experience Questionnaire, Canadian Occupational Performance Measure, Melbourne Assessment of Unilateral Upper Limb Function, Gross Motor Function Measure, Vineland version 2, Pediatric Quality of Life Inventory, and EEG power recorded in fronto-central regions at rest before (at T0), soon after (at T1), and 3 months after the end of (T2) the training. Safety and tolerability will be assessed by pre- and post-tACS recordings of oxygen saturation and heart rate, along with self-report questionnaires on sensations and side-effects. Discussion This study investigates whether an intensive HABIT-ILE program combined with fronto-cerebellar gamma tACS can boost training effects on manual dexterity in children and adolescents with CP, while ensuring safety and tolerability throughout the intervention period. Trial registration ClinicalTrials.gov NCT06372041
Advances in Cerebellar TMS Therapy: An Updated Systematic Review on Multi-Session Interventions Andrea Ciricugno, Sonia Paternò, Nicole Barbati, Renato Borgatti, Zaira Cattaneo, et al. Biomedicines, 2025 Introduction: Cerebellar transcranial magnetic stimulation (TMS) has emerged as a promising neuromodulatory intervention for addressing motor, cognitive, and socio-affective deficits across a range of clinical populations. Materials and Methods: This systematic review aimed to synthesize recent evidence (2015–2025) on the efficacy, safety, and methodological characteristics of multi-session cerebellar TMS protocols used in rehabilitation settings. Following PRISMA guidelines, a comprehensive search of PubMed and Scopus was conducted to identify peer-reviewed studies applying multi-session cerebellar TMS in clinical populations for motor, cognitive, or affective rehabilitation. A total of 1750 records were screened, and 46 studies met the inclusion criteria. Data extraction included sample characteristics, study design, TMS protocol, targeted symptoms, outcomes, and risk of bias. Results: The results show that repeated sessions of cerebellar TMS are safe, well-tolerated, and associated with functional improvements primarily in motor disorders—such as spinocerebellar ataxia, Parkinson’s disease, multiple system atrophy, essential tremor, and post-stroke deficits—as well as in psychiatric populations, particularly patients with schizophrenia. Discussion: Evidence regarding the effects of cerebellar TMS on cognitive functions remains limited, though promising. Despite overall positive findings, the literature is limited by variability in stimulation parameters, protocol designs, and outcome measures, small sample sizes and potential publication bias. Conclusions: The review highlights the need for further large-scale and well-controlled trials to refine stimulation protocols, explore long-term effects, and clarify the underlying mechanisms of cerebellar TMS across motor, cognitive, and affective domains. This systematic review has been registered on PROSPERO (registration number: CRD420251067308).
Cerebellar Neurostimulation for Boosting Social and Affective Functions: Implications for the Rehabilitation of Hereditary Ataxia Patients Andrea Ciricugno, Viola Oldrati, Zaira Cattaneo, Maria Leggio, Cosimo Urgesi, et al. Cerebellum, 2024 Beyond motor deficits, spinocerebellar ataxia (SCA) patients also suffer cognitive decline and show socio-affective difficulties, negatively impacting on their social functioning. The possibility to modulate cerebello-cerebral networks involved in social cognition through cerebellar neurostimulation has opened up potential therapeutic applications for ameliorating social and affective difficulties. The present review offers an overview of the research on cerebellar neurostimulation for the modulation of socio-affective functions in both healthy individuals and different clinical populations, published in the time period 2000–2022. A total of 25 records reporting either transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) studies were found. The investigated clinical populations comprised different pathological conditions, including but not limited to SCA syndromes. The reviewed evidence supports that cerebellar neurostimulation is effective in improving social abilities in healthy individuals and reducing social and affective symptoms in different neurological and psychiatric populations associated with cerebellar damage or with impairments in functions that involve the cerebellum. These findings encourage to further explore the rehabilitative effects of cerebellar neurostimulation on socio-affective deficits experienced by patients with cerebellar abnormalities, as SCA patients. Nevertheless, conclusions remain tentative at this stage due to the heterogeneity characterizing stimulation protocols, study methodologies and patients’ samples.
Pairing transcutaneous vagus nerve stimulation with an intensive bimanual training in children and adolescents with cerebral palsy: study protocol of a randomized sham-controlled trial Viola Oldrati, Verusca Gasparroni, Arianna Michelutti, Andrea Ciricugno, Renato Borgatti, et al. Frontiers in Neurology, 2024 BackgroundGross motor function impairments and manual dexterity deficits are frequently observed in children and adolescents with Cerebral Palsy (CP), having a major impact on their activity level and autonomy. Improving manual dexterity and activity level of patients with CP is often the focus of rehabilitation. Novel and adjuvant treatment methods that could support the standard training also in chronic conditions are a research priority. The transcutaneous Vagus Nerve Stimulation (tVNS) is a non-invasive brain stimulation technique, which provides a bottom-up stimulation of subcortical and cortical brain structures, enhancing brain GABA and Noradrenaline levels. This technique may play a pivotal role in brain plasticity, which has not been tested in CP patients before.Methods44 children and adolescents with CP will be involved, treated in pairs in a randomized, double-blind, pre-post test study. The two groups will undergo the Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) for 2 consecutive weeks, with 3 h daily sessions for 5 days per week, for an overall time interval of 30 h; the training will be combined with the application for 75 min/day of active or sham tVNS, in separate, randomly allocated groups. The primary outcome measure will include the scores at the Assisting Hand Assessment and Box and Block Test, and at an ad-hoc visuomotor task evaluating manual visuomotor control. Secondary outcomes will include the scores at the Children’s Hand Experience Questionnaire, Canadian Occupational Performance Measure, Melbourne Assessment of Unilateral Upper Limb Function, Gross Motor Function Measure, Vineland, Pediatric quality of life inventory. The evaluation points will include pre (T0), post (T1) and 3-month follow up (T2) assessments. Safety and tolerability will also be assessed.ResultsThe results of this trial will assess whether tVNS can effectively boost the effects of an intensive two-week bimanual training, in improving manual dexterity in children and adolescents with cerebral palsy, ensuring safety and tolerability throughout the intervention period.Clinical trial registration: ClinicalTrials.gov, NCT06372028.
How Untidiness Moves the Motor System Francesca Fiori, Andrea Ciricugno, Maria Luisa Rusconi, Ryan J. Slaby, Zaira Cattaneo Perceptual and Motor Skills, 2022
