Impulsivity Markers in Parkinsonian Subthalamic Single-Unit Activity

Impulsive-compulsive behaviors are common in Parkinson's disease (PD) patients. However, the basal ganglia dysfunctions associated with high impulsivity have not been fully characterized. The objective of this study was to identify the features associated with impulsive-compulsive behaviors in single neurons of the subthalamic nucleus (STN)

Comparing the effects of augmented virtual reality treadmill training versus conventional treadmill training in patients with stage II-III Parkinson’s disease: the VIRTREAD-PD randomized controlled trial protocol

BackgroundIntensive treadmill training (TT) has been documented to improve gait parameters and functional independence in Parkinson’s Disease (PD), but the optimal intervention protocol and the criteria for tailoring the intervention to patients’ performances are lacking. TT may be integrated with augmented virtual reality (AVR), however, evidence of the effectiveness of this combined treatment is still limited. Moreover, prognostic biomarkers of rehabilitation, potentially useful to customize the treatment, are currently missing. The primary aim of this study is to compare the effects on gait performances of TT + AVR versus TT alone in II-III stage PD patients with gait disturbance. Secondary aims are to assess the effects on balance, gait parameters and other motor and non-motor symptoms, and patient’s satisfaction and adherence to the treatment. As an exploratory aim, the study attempts to identify biomarkers of neuroplasticity detecting changes in Neurofilament Light Chain concentration T0-T1 and to identify prognostic biomarkers associated to blood-derived Extracellular Vesicles.MethodsSingle-center, randomized controlled single-blind trial comparing TT + AVR vs. TT in II-III stage PD patients with gait disturbances. Assessment will be performed at baseline (T0), end of training (T1), 3 (T2) and 6 months (T3, phone interview) from T1. The primary outcome is difference in gait performance assessed with the Tinetti Performance-Oriented Mobility Assessment gait scale at T1. Secondary outcomes are differences in gait performance at T2, in balance and spatial–temporal gait parameters at T1 and T2, patients’ satisfaction and adherence. Changes in falls, functional mobility, functional autonomy, cognition, mood, and quality of life will be also assessed at different timepoints. The G*Power software was used to estimate a sample size of 20 subjects per group (power 0.95, α < 0.05), raised to 24 per group to compensate for potential drop-outs. Both interventions will be customized and progressive, based on the participant’s performance, according to a predefined protocol.ConclusionThis study will provide data on the possible superiority of AVR-associated TT over conventional TT in improving gait and other motor and non-motor symptoms in persons with PD and gait disturbances. Results of the exploratory analysis could add information in the field of biomarker research in PD rehabilitation

Transcranial magnetic stimulation over the cerebellum and eye movements: state of the art

Transcranial magnetic stimulation (TMS) transiently induces an electrical field in the tissues beneath the area of application, thereby perturbing local cortical activity if applied over the scalp. It can therefore be used to modulate cerebellar function in healthy humans. Even though the role of the cerebellum in eye movement control and adaptation is well known, few experiments have used eye movements to evaluate the effect of TMS over the cerebellum. Single-pulse TMS over the posterior vermis resulted in impaired accuracy of reflexive saccades, acceleration of smooth pursuit, and coordination of saccades and head movements. TMS over the cerebellar hemisphere decreased pursuit gain. Repetitive TMS (rTMS) over the posterior vermis impaired saccade adaptation in a double-step paradigm. Comparing the effects of TMS on different behavioural paradigms could be useful to test cerebellar control of reflexive and voluntary eye movements, and as a probe of cerebellar plasticity. rTMS appears to be especially interesting since its effects outlast the stimulation period and its behavioural consequences can therefore be measured without interfering with the execution of eye movements or with the experimental procedure

New insights into vestibular-saccade interaction based on covert corrective saccades in patients with unilateral vestibular deficits

In response to passive high-acceleration head impulses patients with low vestibulo-ocular reflex (VOR) gains often produce covert (executed while the head is still moving) corrective saccades in the direction of deficient slow phases. Here we examined 23 patients using passive, and nine also active, head impulses with acute (< 10 days from onset) unilateral vestibular neuritis and low VOR gains. We found that when corrective saccades are larger than 10\ub0, the slow-phase component of the VOR is inhibited, even though inhibition increases further the time to reacquire the fixation target. We also found that saccades are faster and more accurate if the residual VOR gain is higher, saccades also compensate for the head displacement that occurs during the saccade, and the amplitude-peak velocity relationship of the larger corrective saccades deviates from that of head-fixed saccades of the same size. We propose a mathematical model to account for these findings hypothesizing that covert saccades are driven by a desired gaze-position signal based on a prediction of head displacement using vestibular and extra-vestibular signals, covert saccades are controlled by a gaze feedback loop, and the VOR command is modulated according to predicted saccade amplitude. A central and novel feature of the model is that the brain develops two separate estimates of head rotation, one for generating saccades while the head is moving and the other for generating slow phases. Furthermore the model, while developed for gaze-stabilizing behavior during passively-induced head impulses, also simulates both active gaze-stabilizing and active gaze-shifting eye movements

Impulse control disorders in Parkinson’s disease: a systematic review on the psychometric properties of the existing measures

Background A significant percentage of patients suffering from Parkinson’s Disease (PD) experience Impulse Control Disorders (ICDs), contributing to reduced quality of life. As they can be managed by reducing the dopamine dosage, the detection of their presence is crucial for PD treatment plan. Nevertheless, they tend to be under-recognized in clinical practice, since routine screening is not common–despite existing instruments that may support clinicians. This work presents a systematic review on the psychometric properties of instruments measuring ICDs in PD, to test whether clinicians dispose of valid tools that may help them in clinical assessment. Method A systematic literature search in three databases (EMBASE, MEDLINE, and PsycINFO) was conducted. Quality of the instruments’ psychometric properties was evaluated with Terwee et al.’s criteria, and methodological quality of the studies was evaluated with the COSMIN Checklist. Results Ten studies examining seven instruments were selected. The Questionnaire for Impulsive- Compulsive Disorders in Parkinson’s Disease (QUIP) and the Ardouin Scale of Behavior in Parkinson’s Disease (ASBPD) resulted to be the best from a psychometric point of view. Conclusions Though the gold standard for diagnosis remains a detailed diagnostic interview, this review will encourage clinicians to use validated tools to accurately assess ICDs