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Postural instability (PI) in Parkinson's disease (PD) exposes patients to an increased risk of falls (RF). While dopaminergic therapy and deep brain stimulation (DBS) improve motor performance in advanced PD patients, their effects on PI and RF remain elusive. PI and RF were assessed using a stabilometric platform in six advanced PD patients. Patients were evaluated in OFF and ON dopaminergic medication and under four DBS settings: with DBS off, DBS bilateral, and unilateral DBS of the more- or less-affected side. Our findings indicate that dopaminergic medication by itself exacerbated PI and RF, and DBS alone led to a decline in RF. No combination of medication and DBS yielded a superior improvement in postural control compared to the baseline combination of OFF medication and the DBS-off condition. Yet, for ON medication, DBS significantly improved both PI and RF. Among DBS conditions, DBS bilateral provided the most favorable outcomes, improving PI and RF in the ON medication state and presenting the smallest setbacks in the OFF state. Conversely, the more-affected side DBS was less beneficial. These preliminary results could inform therapeutic strategies for advanced PD patients experiencing postural disorders.

Paired associative stimulation (PAS) is a non-invasive brain stimulation technique that modulates synaptic plasticity in the human motor cortex (M1). Since previous studies have primarily used motor-evoked potentials (MEPs) as outcome measure, cortical correlates of PAS-induced plasticity remain unknown. Therefore, the aim of this observational study was to investigate cortical correlates of a standard PAS induced plasticity in the primary motor cortex by using a combined TMS-EEG approach in a cohort of eighteen healthy subjects. In addition to the expected long-lasting facilitatory modulation of MEPs amplitude, PAS intervention also induced a significant increase in transcranial magnetic stimulation-evoked potentials (TEPs) P30 and P60 amplitude. No significant correlation between the magnitude of PAS-induced changes in TEP components and MEP amplitude were observed. However, the linear regression analysis revealed that the combined changes in P30 and P60 component amplitudes significantly predicted the MEP facilitation after PAS. The findings of our study offer novel insight into the neurophysiological changes associated with PAS-induced plasticity at M1 cortical level and suggest a complex relationship between TEPs and MEPs changes following PAS.

Background : The ability to perceive two tactile stimuli as asynchronous can be measured using the somatosensory temporal discrimination threshold (STDT). In healthy humans, the execution of a voluntary movement determines an increase in STDT values, while the integration of STDT and movement execution is abnormal in patients with basal ganglia disorders. Sensorimotor integration can be modulated using focal muscle vibration (fMV), a neurophysiological approach that selectively activates proprioceptive afferents from the vibrated muscle. Method : In this study, we investigated whether fMV was able to modulate STDT or STDT-movement integration in healthy subjects by measuring them before, during and after fMV applied over the first dorsalis interosseous, abductor pollicis brevis and flexor radialis carpi muscles. Results : The results showed that fMV modulated STDT-movement integration only when applied over the first dorsalis interosseous, namely, the muscle performing the motor task involved in STDT-movement integration. These changes occurred during and up to 10 min after fMV. Differently, fMV did not influence STDT at rest. We suggest that that fMV interferes with the STDT-movement task processing, possibly disrupting the physiological processing of sensory information. Conclusions : This study showed that FMV is able to modulate STDT-movement integration when applied over the muscle involved in the motor task. This result provides further information on the mechanisms underlying fMV, and has potential future implications in basal ganglia disorders characterized by altered sensorimotor integration.

Variability in the response of individuals to various non-invasive brain stimulation protocols is a major problem that limits their potential for clinical applications. Baseline motor-evoked potential (MEP) amplitude is the key predictor of an individual's response to transcranial magnetic stimulation protocols. However, the factors that predict MEP amplitude and its variability remain unclear. In this study, we aimed to identify the input-output curve (IOC) parameters that best predict MEP amplitude and its variability. We analysed IOC data from 75 subjects and built a general linear model (GLM) using the IOC parameters as regressors and MEP amplitude at 120% resting motor threshold (RMT) as the response variable. We bootstrapped the data to estimate variability of IOC parameters and included them in a GLM to identify the significant predictors of MEP amplitude variability. Peak slope, motor threshold, and maximum MEP amplitude of the IOC were significant predictors of MEP amplitude at 120% RMT and its variability was primarily driven by the variability of peak slope and maximum MEP amplitude. Recruitment gain and maximum corticospinal excitability are the key predictors of MEP amplitude and its variability. Inter-individual variability in motor output may be reduced by achieving a uniform IOC slope.

Studies using transcranial magnetic stimulation (TMS) have demonstrated the importance of direction and intensity of the applied current when the primary motor cortex (M1) is targeted. By varying these, it is possible to stimulate different subsets of neural elements, as demonstrated by modulation of motor evoked potentials (MEPs) and motor behaviour. The latter involves premotor areas as well, and among them, the presupplementary motor area (pre-SMA) has recently received significant attention in the study of motor inhibition. It is possible that, similar to M1, different neuronal populations can be activated by varying the direction and intensity of TMS; however, the absence of a direct electrophysiological outcome has limited this investigation. The problem can be solved by quantifying direct cortical responses by means of combined TMS and electroencephalography (TMS-EEG). We investigated the effect of variable coil orientations (0°, 90°, 180° and 270°) and stimulation intensities (100%, 120% and 140% of resting motor threshold) on local mean field potential (LMFP), transcranial evoked potential (TEP) peaks and TMS-related spectral perturbation (TRSP) from pre-SMA stimulation. As a result, early and late LMFP and peaks were larger, with the coil handle pointing posteriorly (0°) and laterally (90°). This was true also for TRSP in the β-γ range, but, surprisingly, θ-α TRSP was larger with the coil pointing at 180°. A 90° orientation activated the right M1, as shown by MEPs elicitation, thus limiting the spatial specificity of the stimulation. These results suggest that coil orientation and stimulation intensity are critical when stimulating the pre-SMA.