To evaluate the effects of cerebellar transcranial alternating current stimulation (tACS) delivered at cerebellar-resonant frequencies, i.e., theta (θ) and gamma (γ), on upper limb motor performance and cerebellum-primary motor cortex (M1) connectivity, as assessed by cerebellar-brain inhibition (CBI), in healthy subjects. Participants underwent cerebellar-tACS while performing three cerebellar-dependent motor tasks: (i) rhythmic finger-tapping, (ii) arm reaching-to-grasp ('grasping') and (iii) arm reaching-to-point ('pointing') an object. Also, we evaluated possible changes in CBI during cerebellar-tACS. θ-tACS decreased movement regularity during the tapping task and increased the duration of the pointing task compared to sham- and γ-tACS. Additionally, θ-tACS increased the CBI effectiveness (greater inhibition). The effect of θ-tACS on movement rhythm correlated with CBI changes and less tapping regularity corresponded to greater CBI. Cerebellar-tACS delivered at the θ frequency modulates cerebellar-related motor behavior and this effect is, at least in part, mediated by changes in the cerebellar inhibitory output onto M1. The effects of θ-tACS may be due to the modulation of cerebellar neurons that resonate to the θ rhythm. These findings contribute to a better understanding of the physiological mechanisms of motor control and provide new evidence on cerebellar non-invasive brain stimulation.

In patients with Parkinson’s disease, the connectivity between the two primary motor cortices may be altered. However, the correlation between asymmetries of abnormal interhemispheric connections and bradykinesia features has not been investigated. Furthermore, the potential effects of dopaminergic medications on this issue remain largely unclear. The aim of the present study is to investigate the interhemispheric connections in Parkinson’s disease by transcranial magnetic stimulation and explore the potential relationship between interhemispheric inhibition and bradykinesia feature asymmetry in patients. Additionally, we examined the impact of dopaminergic therapy on neurophysiological and motor characteristics. Short- and long-latency interhemispheric inhibition was measured in 18 Parkinson’s disease patients and 18 healthy controls, bilaterally. We also assessed the corticospinal and intracortical excitability of both primary motor cortices. We conducted an objective analysis of finger-tapping from both hands. Correlation analyses were performed to explore potential relationships among clinical, transcranial magnetic stimulation and kinematic data in patients. We found that short- and long-latency interhemispheric inhibition was reduced (less inhibition) from both hemispheres in patients than controls. Compared to controls, finger-tapping movements in patients were slower, more irregular, of smaller amplitudes and characterized by a progressive amplitude reduction during movement repetition (sequence effect). Among Parkinson’s disease patients, the degree of short-latency interhemispheric inhibition imbalance towards the less affected primary motor cortex correlated with the global clinical motor scores, as well as with the sequence effect on the most affected hand. The greater the interhemispheric inhibition imbalance towards the less affected hemisphere (i.e. less inhibition from the less to the most affected primary motor cortex than that measured from the most to the less affected primary motor cortex), the more severe the bradykinesia in patients. In conclusion, the inhibitory connections between the two primary motor cortices in Parkinson’s disease are reduced. The interhemispheric disinhibition of the primary motor cortex may have a role in the pathophysiology of specific bradykinesia features in patients, i.e. the sequence effect.

Over the past three decades, substantial advancements have occurred in non-invasive brain stimulation (NIBS). These developments encompass various non-invasive techniques aimed at modulating brain function. Among the most widely utilized methods today are transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES), which include direct- or alternating-current transcranial stimulation (tDCS/tACS). In addition to these established techniques, newer modalities have emerged, broadening the scope of non-invasive neuromodulation approaches available for research and clinical applications in movement disorders, particularly for Parkinson’s disease (PD) and, to a lesser extent, atypical Parkinsonism (AP). All NIBS techniques offer the opportunity to explore a wide range of neurophysiological mechanisms and exert influence over distinct brain regions implicated in the pathophysiology of Parkinsonism. This paper’s first aim is to provide a brief overview of the historical background and underlying physiological principles of primary NIBS techniques, focusing on their translational relevance. It aims to shed light on the potential identification of biomarkers for diagnostic and therapeutic purposes, by summarising available experimental data on individuals with Parkinsonism. To date, despite promising findings indicating the potential utility of NIBS techniques in Parkinsonism, their integration into clinical routine for diagnostic or therapeutic protocols remains a subject of ongoing investigation and scientific debate. In this context, this paper addresses current unsolved issues and methodological challenges concerning the use of NIBS, focusing on the importance of future research endeavours for maximizing the efficacy and relevance of NIBS strategies for individuals with Parkinsonism.

Background: Essential tremor (ET) is one of the most prevalent movement disorders. However, the complete understanding of ET pathophysiology remains elusive. Objective: To explore the pathophysiological role of primary motor cortex (M1) in ET, specifically exploring its neurophysiological changes and their correlation with voluntary motor abnormalities. Methods: We recruited 30 ET patients and 18 healthy controls (HC). Evaluations were conducted on patients using clinical scales. Transcranial magnetic stimulation (TMS) was used to assess M1 excitability, including motor thresholds and motor evoked potentials (MEPs) input/output curve, together with intracortical excitability measures. Long‐term potentiation (LTP)‐like plasticity of M1 was tested using intermittent theta‐burst stimulation (iTBS). Objective assessments of tremor and voluntary movement execution during finger‐tapping were conducted through kinematic analysis. Finally, we explored the potential relationship between TMS, clinical, and kinematic data. Results: Compared with HC, ET patients had lower excitability, intracortical inhibition, and lower LTP‐like plasticity of M1. ET patients also exhibited slower finger‐tapping performance compared with HC. Among ET patients, the degree of movement slowing during finger‐tapping correlated with alterations in corticospinal excitability. Specifically, reduced M1 excitability was associated with lower finger‐tapping velocity. No other correlations were found. Conclusions: The study findings reveal neurophysiological alterations of M1 in ET and demonstrate correlations between excitability measures and voluntary motor performance. These results provide novel insight into the pathophysiology of ET, emphasizing the role of M1 changes in this condition. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Bradykinesia is the hallmark sign of parkinsonism. We recently proposed redefining bradykinesia as a complex of motor abnormalities, each reflecting separate pathophysiological elements. Objective: To analyze the ‘bradykinesia complex’ in Parkinson's disease (PD) and healthy elderly individuals. Methods: We conducted a finger‐tapping kinematic analysis in 350 individuals (192 PD patients OFF medication and 158 healthy controls). A subsample of 129 patients was also tested ON medication. Group comparisons were followed by unsupervised clustering. Receiver operating characteristic (ROC) analyses defined optimal kinematic cut‐offs to detect individual motor abnormalities. We then quantified the prevalence and combinations of these features per subject. Using Bayes' theorem, we estimated the probability of PD based on the observed combination of bradykinesia features. Regression analyses served to identify predictors of kinematic alterations. Results: Patients exhibited reduced velocity and amplitude as well as altered rhythm and sequence effect compared with controls (all P‐ values < 0.001). Cluster analysis revealed substantial group overlap. ROC analyses showed that bradykinesia (movement slowness) was the most common and accurate feature for distinguishing PD, with its diagnostic power improving when combined with other motor abnormalities (hypokinesia, dysrhythmia, sequence effect). The likelihood of correctly identifying PD increased with the number of observed abnormalities, reaching up to 95% when all features were present. Levodopa improved motor performance, but the motor abnormality patterns remained unchanged. Conclusions: The detailed bradykinesia features assessment was crucial for differentiating PD individuals from controls. Diagnostic accuracy requires considering multiple motor abnormalities together, irrespective of the specific combination. Advancing our understanding of the ‘bradykinesia complex’ has clinical and pathophysiological implications. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.