Alex Martino Cinnera

Matching brain stimulation to the brain’s natural rhythms can drive plasticity, yet this principle has rarely been tested in humans. We targeted the cerebellum, a key hub for motor coordination and learning, using a rhythm-tuned protocol that pairs theta-frequency transcranial alternating current stimulation with intermittent theta-burst stimulation to engage plasticity of cerebello-cortical circuits. In young healthy adults, this pairing enhanced fine motor control and hand dexterity, with gains closely tracking physiological markers of cerebellar-driven plasticity. Applying the same approach in chronic stroke survivors yielded parallel behavioral and neural gains, demonstrating preserved rhythm-plasticity coupling despite injury. Control experiments confirmed both frequency specificity and site specificity, underscoring the mechanistic precision of the intervention. By linking theta-frequency cerebellar stimulation to circuit-level and functional outcomes, these findings establish a biologically grounded framework for targeted neurorehabilitation. Rhythm-specific cerebellar stimulation provides a scalable strategy for enhancing plasticity and improving motor function across movement disorders and motor impairments.

Constraint-Induced Movement Therapy in Children With Hemiplegic Cerebral Palsy: A Scoping Review of Functional Outcomes and Neuroplasticity-Related Evidence

Cerebellar ataxia (CA) is a neurodegenerative disorder characterized by progressive impairments in coordination, balance, and gait disturbances. Conventional rehabilitation therapies offer only limited benefits, driving interest toward exploring alternative non-invasive interventions. Among these, non-invasive brain stimulation techniques, such as cerebellar transcranial alternating current stimulation (tACS) and intermittent theta burst stimulation (iTBS) have emerged as promising approaches. This study aims to investigate the effectiveness of a combined cerebellar tACS-iTBS protocol in alleviating symptoms of CA, specifically targeting improvements in motor coordination, balance control, and quality of life. In this randomized, sham-controlled crossover study, 31 patients diagnosed with CA will participate in two experimental conditions (real and sham stimulation), each lasting 2 weeks (phase A and B) and separated by a 3-week washout period. In the real condition, patients will receive cerebellar tACS at 5 Hz (2 mA, 190 s) delivered simultaneously with iTBS (600 pulses at 50 Hz; 80% of active motor threshold). In the sham condition, TMS will be applied without active stimulation, and cerebellar tACS will be applied only briefly for participant blinding. Following each stimulation session, patients will perform sensor-based balance training using an adaptive system with a force platform for a total of 30 min. Outcome assessments will take place at baseline of each phase (A and B) (T0_a, T0_b) and after completion of each 2-week intervention period (T1_a, T1_b). Primary and secondary outcome measures will include the Scale for the Assessment and Rating of Ataxia (SARA), International Cooperative Ataxia Rating Scale (ICARS), Short Form-36 Health Survey (SF-36), postural control (center of pressure trajectory), Motor Evoked Potentials (MEPs) for assessing corticospinal excitability, and cerebellar brain inhibition (CBI) to evaluate cerebellar-motor cortex connectivity. This study will provide valuable insights into the therapeutic potential of cerebellar tACS-iTBS as a non-invasive intervention for CA. By assessing its effects on balance, coordination, and overall quality of life, the findings could help establish whether this combined stimulation method serves as a beneficial aid to sensor-based balance training. If successful, cerebellar tACS-iTBS could offer a promising new strategy to enhance clinical outcomes and improve the quality of life in individuals with CA. ClinicalTrial.gov NCT06420271. Registered on 2024-05-20.

Background and Objectives: Children with Developmental Coordination Disorder (DCD) show substantial motor and balance difficulties that affect daily activities. Although action observation (AO) and motor imagery (MI) are effective in other neurological conditions, their impact in DCD remains underinvestigated. This review explores the preliminary evidence of AO- and MI-based interventions for improving motor and functional outcomes in children with DCD. Methods: A systematic search of PubMed, Scopus, and Web of Science identified randomized controlled trials and controlled trials published in the last 15 years evaluating AO and MI interventions in children with DCD. Two independent reviewers conducted the screening of the studies, data extraction, and the risk-of-bias assessment using RoB2 and ROBINS-I. The review followed PRISMA reporting guidelines and was pre-registered on the PROSPERO database (CRD420251084196). Results: Of 320 records initially identified, seven studies, involving 199 children with DCD (aged 5–12 years), were included. Interventions varied from single-session to multi-session protocols (1–16 sessions) and included AO, MI, or a combination of both (AO + MI), with heterogeneous control conditions. Within these studies, the outcomes were primarily assessed using standardized motor coordination measures (MABC/MABC-2, DCDQ), planning tasks, and performance-based activities of daily living (ADLs) measures. Improvements were reported in motor imagery tasks, planning, and functional task performance. However, RCTs and CTs were identified to have a moderate and high risk of bias, respectively. Conclusions: The present review suggests that AO and MI, either alone or in combination, may enhance motor planning, coordination, and daily functional skills in children with DCD, supporting internal motor representations and predictive motor control, reflecting functional gain in motor skills and ADL performance. Interestingly, these mental training approaches can be applied in clinical and everyday settings and are suitable for supporting these processes, with VR-based combinations representing a promising, but exploratory, approach. Although critical heterogeneity and a moderate risk of bias remain, the findings need to be interpreted with caution and require further investigation.

Article: Rehabilitation enhanced by artificial intelligence: introducing the living systematic mapping review from REHALISE initiative - European Journal of Physical and Rehabilitation Medicine 2025 October;61(5):691-3 - Minerva Medica - Journals

Artificial intelligence (AI) is revolutionizing many fields of science, including medicine, by enhancing diagnostic, therapeutic, and decision-making processes. However, understanding how AI can be truly useful in everyday clinical practice remains challenging. This living review systematically investigates current clinical applications of AI in the rehabilitation field, clarifies key concepts, and identifies knowledge gaps. PubMed, Scopus, WOS/Embase, and PEDro were systematically searched from December 1, 2014, to December 1, 2024. Retrieved articles were independently screened by two reviewers, with a third reviewer resolving any disagreements. Extracted data (including bibliometric, clinical, and AI-related variables) were synthesized into a synoptic table using a semi-automated Python pipeline. Reporting adhered to PRISMA guidelines, and the review protocol was registered in the PROSPERO database (CRD420250622434). Of 4193 records identified, 240 studies applying AI for rehabilitative purposes met the inclusion criteria. Most studies focused on neurological (57.9%) and orthopedic (22.7%) rehabilitation, particularly involving stroke, Parkinson's disease, and amputation, with research activity mainly concentrated in China (24.6%) and the USA (16.7%). AI has been tested across all stages of the medical process, with a slight predominance in intervention (23.8%), followed by prognosis (17.5%), assessment (16.7%), diagnosis (12.9%), and monitoring (12.5%). It was frequently integrated with wearable sensors, robotic systems, and digital technologies, especially inertial measurement units, surface EMG, mobile apps and EEG. Most AI studies in rehabilitation used raw (37.9%) or tabular data (27.5%), with multimodal inputs in only 11.3%. Over half lacked a comparator (50.8%). Supervised learning (70.8%) and classical machine learning (43.8%) predominated, while external validation (5.8%) and explainability (10.2%) were rarely applied. AI applications in rehabilitation are rapidly expanding, particularly in neurological and orthopedic fields where data-driven and technology-assisted approaches prevail. While this progress is promising, current evidence remains largely based on supervised learning with small, single-type datasets, limited external validation, and scarce explainability, critical issues that must be addressed to enable reliable translation into clinical practice.

Background/Objectives: Limited research has examined the relationship between preoperative health status and health-related quality of life (HRQoL) in patients with lumbar spinal stenosis (LSS) undergoing surgery. This study aims to assess the role of clinical, preoperative health and demographic factors on short-term HRQoL and functional outcomes following LSS surgery. Methods: A longitudinal study was conducted on 61 LSS patients (mean age 72.2 ± 8.8 years) undergoing surgery, assessing HRQoL and clinical outcomes before and 30 days post-surgery. Demographic and preoperative health status data were collected at baseline. HRQoL was measured using the Short Form Health Survey 36 (SF-36); clinical evaluations included assessments of disability, pain, and psychological status. Changes in HRQoL and clinical scores were analyzed with repeated measures ANOVA. HRQoL improvement was correlated with demographic and clinical variables, using Pearson’s correlation. Results: Spinal surgery for LSS led to significant improvements in HRQoL, with notable gains in both physical and mental health components (both p < 0.001), and in particular, in the body pain (+34%) and physical functioning, role physical, and social functioning (+20%) subscales of SF-36. Clinical scores also showed significant post-surgery improvements, strongly correlating with HRQoL. Correlations between ΔSF-36 subscale scores and preoperative factors revealed negative associations with BMI, smoking, comorbidities, and psychological distress. Conversely, physical activity was positively correlated with HRQoL improvements, especially in items showing the greatest score increases. Conclusions: Surgical treatment for LSS determines a significant improvement in HRQoL and functional outcome, which are however influenced by preoperative factors such as psychological distress, high BMI, smoking, and comorbidities. Conversely, regular physical activity is associated with better daily functioning, work performance, and social engagement. A comprehensive preoperative assessment may be a useful and appropriate tool to identify patients who are most likely to benefit and optimize quality of life after LSS surgery.

Introduction: Cerebral palsy (CP) is a group of permanent disorders of movement development that may cause activity limitations. In this context, robot-assisted therapy might play a key role in clinical management. This comprehensive systematic review aimed to investigate the efficacy of robotic systems in improving upper limb (UL) functions in children with CP.Methods: PubMed, EMBASE, Scopus, and PEDro were searched from inception to February 2024. The risk of bias was assessed with the Joanna Briggs Institute critical appraisal tools battery.Results: Of 756 articles identified, 14 studies involving 193 children with CP with a judged to be of good methodological quality, but with a lack in the study design, were included in the final synthesis. In the included studies a wide range of devices was used, both exoskeletons and end-effectors, both wearable and non-wearable. The CP children who underwent robot-assisted therapy reported a significant overall increase in clinical assessment, specifically in UL movements and manual dexterity. The clinical improvement was often accompanied by a gain also in instrumental assessments (i.e., kinematic analysis, EMG).Discussion: The present review suggested that robot-assisted therapy can improve UL motor functions in children with CP. Moreover, the availability of different devices with adjustable parameters can represent an important resource in proposing patient-centered-personalized rehabilitation protocols to enhance the efficacy of rehabilitation and integration into daily life. However, the limited sample size and lack of standardized and clearly reproducible protocols impose to recommend the use of robot-assisted therapy as an integration to usual rehabilitation and not as a replacement.Systematic review registration: https://osf.io/a78zb/.

Background: Children with cerebral palsy (CP) may present motor and gait impairment. Objective: This systematic review aims to assess the potential of robot-assisted gait training (RAGT) with Lokomat^® exoskeleton to improve gait in children with CP. Methods: The search was conducted and repoted according to PRISMA guidelines on PubMed, Scopus, Cochrane Library and PEDro databases. All randomised controlled trials (RCT) including children with CP who underwent RAGT with Lokomat^® were considered eligible. Risk of bias was assessed with the Rob2 tool by two blinded reviewers. The review was previously registered on the PROSPERO database (CRD42023488699). Results: 948 articles were found, and 9 studies involving 403 children with CP met the inclusion criteria. We found a heterogeneity in the RAGT protocol and a higher risk of bias for two included studies. Seven out nine studies reported a statistically significant improvement ( p < 0.05) on gait, balance, or global functions with respect to control groups. Specifically, walking speed and stride length were improved after RAGT. Conclusions: Children with CP can benefit from the add-on therapy with RAGT through Lokomat^® to improve walking and balance function. There is a need for RCTs with better patient stratification and with less heterogeneity in outcomes to improve the quality of the pooled evidence.

Background: Guillain–Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy that represents a leading cause of motor impairment. Robot-assisted therapy (RAT) has been widely applied in various neurological conditions. However, the use of RAT in GBS remains underexplored. This systematic review (SR) aims to evaluate the preliminary evidence regarding the efficacy of RAT in terms of motor recovery in people with GBS (pwGBSs). Secondly, the study protocol for a randomized RCT is reported. Methods: A comprehensive SR was conducted on PubMed, Scopus, EMBASE, Cochrane Library, and Epistemikos. Risk of bias was assessed using the National Institute of Health (NIH) study quality assessment. The SR’s protocol was recorded in the PROSPERO database. Results: Out of 116 articles found, four studies published in the past four years met the inclusion criteria. These studies investigated the effects of RAT on lower limbs (three studies) and upper limbs (one study) in four pwGBSs. The results showed improvements in motor function and patient engagement, but it is impossible to generalize the findings. Conclusions: Our SRs supports the rationale for an RCT to assess the efficacy of RAT in pwGBSs. We present the protocol for a double-blind RCT to evaluate the effects of RAT on upper limb motor function in pwGBSs.