Motor unit discharge variability is increased in mild-to-moderate Parkinson\u27s disease

Individuals with Parkinson\u27s disease (PD) demonstrate deficits in muscle activation such as decreased amplitude and inappropriate bursting. There is evidence that some of these disturbances are more pronounced in extensor vs. flexor muscles. Surface EMG has been used widely to quantify muscle activation deficits in PD, but analysis of discharge of the underlying motor units may provide greater insight and be more sensitive to changes early in the disease. Of the few studies that have examined motor unit discharge in PD, the majority were conducted in the first dorsal interosseous, and no studies have measured motor units from extensor and flexor muscles within the same cohort. The objective of this study was to characterize the firing behavior of single motor units in the elbow flexor and extensor muscles during isometric contractions in people with mild-to-moderate PD. Ten individuals with PD (off-medication) and nine healthy controls were tested. Motor unit spike times were recorded via intramuscular EMG from the biceps and triceps brachii muscles during 30-s isometric contractions at 10% maximum voluntary elbow flexion and elbow extension torque, respectively. We selected variables of mean motor unit discharge rate, discharge variability, and torque variability to evaluate motor abnormalities in the PD group. The effects of group, muscle, and group-by-muscle on each variable were determined using separate linear mixed models. Discharge rate and torque variability were not different between groups, but discharge variability was significantly higher in the PD group for both muscles combined

Posture and Locomotion Coupling: A Target for Rehabilitation Interventions in Persons with Parkinson's Disease

Disorders of posture, balance, and gait are debilitating motor manifestations of advancing Parkinson's disease requiring rehabilitation intervention. These problems often reflect difficulties with coupling or sequencing posture and locomotion during complex whole body movements linked with falls. Considerable progress has been made with demonstrating the effectiveness of exercise interventions for individuals with Parkinson's disease. However, gaps remain in the evidence base for specific interventions and the optimal content of exercise interventions. Using a conceptual theoretical framework and experimental findings, this perspective and review advances the viewpoint that rehabilitation interventions focused on separate or isolated components of posture, balance, or gait may limit the effectiveness of current clinical practices. It is argued that treatment effectiveness may be improved by directly targeting posture and locomotion coupling problems as causal factors contributing to balance and gait dysfunction. This approach may help advance current clinical practice and improve outcomes in rehabilitation for persons with Parkinson's disease

Avoiding Virtual Obstacles During Treadmill Gait in Parkinson’s Disease

Falls often occur due to spontaneous loss of balance, but tripping over an obstacle during gait is also a frequent cause of falls (Sheldon, 1960; Stolze et al., 2004). Obstacle avoidance requires that appropriate modifications of the ongoing cyclical movement be initiated and completed in time. We evaluated the available response time to avoid a virtual obstacle in 26 Parkinson’s disease (PD) patients (in the off-medication state) and 26 controls (18 elderly and 8 young), using a virtual obstacle avoidance task during visually cued treadmill walking. To maintain a stable baseline of stride length and visual attention, participants stepped on virtual “stepping stones” projected onto a treadmill belt. Treadmill speed and stepping stone spacing were matched to overground walking (speed and stride length) for each individual. Unpredictably, a stepping stone changed color, indicating that it was an obstacle. Participants were instructed to try to step short to avoid the obstacle. By using an obstacle that appeared at a precise instant, this task probed the time interval required for processing new information and implementing gait cycle modifications. Probability of successful avoidance of an obstacle was strongly associated with the time of obstacle appearance, with earlier-appearing obstacles being more easily avoided. Age was positively correlated (p < 0.001) with the time required to successfully avoid obstacles. Nonetheless, the PD group required significantly more time than controls (p = 0.001) to achieve equivalent obstacle-avoidance success rates after accounting for the effect of age. Slowing of gait adaptability could contribute to high fall risk in elderly and PD. Possible mechanisms may include disturbances in motor planning, movement execution, or disordered response inhibition

Slow-wave sleep dysfunction in mild parkinsonism is associated with excessive beta and reduced delta oscillations in motor cortex

Increasing evidence suggests slow-wave sleep (SWS) dysfunction in Parkinson’s disease (PD) is associated with faster disease progression, cognitive impairment, and excessive daytime sleepiness. Beta oscillations (8–35 Hz) in the basal ganglia thalamocortical (BGTC) network are thought to play a role in the development of cardinal motor signs of PD. The role cortical beta oscillations play in SWS dysfunction in the early stage of parkinsonism is not understood, however. To address this question, we used a within-subject design in a nonhuman primate (NHP) model of PD to record local field potentials from the primary motor cortex (MC) during sleep across normal and mild parkinsonian states. The MC is a critical node in the BGTC network, exhibits pathological oscillations with depletion in dopamine tone, and displays high amplitude slow oscillations during SWS. The MC is therefore an appropriate recording site to understand the neurophysiology of SWS dysfunction in parkinsonism. We observed a reduction in SWS quantity (p = 0.027) in the parkinsonian state compared to normal. The cortical delta (0.5–3 Hz) power was reduced (p = 0.038) whereas beta (8–35 Hz) power was elevated (p = 0.001) during SWS in the parkinsonian state compared to normal. Furthermore, SWS quantity positively correlated with delta power (r = 0.43, p = 0.037) and negatively correlated with beta power (r = −0.65, p < 0.001). Our findings support excessive beta oscillations as a mechanism for SWS dysfunction in mild parkinsonism and could inform the development of neuromodulation therapies for enhancing SWS in people with PD

Low-frequency deep brain stimulation reveals resonant beta-band evoked oscillations in the pallidum of Parkinson’s Disease patients

IntroductionEvidence suggests that spontaneous beta band (11–35 Hz) oscillations in the basal ganglia thalamocortical (BGTC) circuit are linked to Parkinson’s disease (PD) pathophysiology. Previous studies on neural responses in the motor cortex evoked by electrical stimulation in the subthalamic nucleus have suggested that circuit resonance may underlie the generation of spontaneous and stimulation-evoked beta oscillations in PD. Whether these stimulation-evoked, resonant oscillations are present across PD patients in the internal segment of the globus pallidus (GPi), a primary output nucleus in the BGTC circuit, is yet to be determined.MethodsWe characterized spontaneous and stimulation-evoked local field potentials (LFPs) in the GPi of four PD patients (five hemispheres) using deep brain stimulation (DBS) leads externalized after DBS implantation surgery.ResultsOur analyses show that low-frequency (2–4 Hz) stimulation in the GPi evoked long-latency (>50 ms) beta-band neural responses in the GPi in 4/5 hemispheres. We demonstrated that neural sources generating both stimulation-evoked and spontaneous beta oscillations were correlated in their frequency content and spatial localization.DiscussionOur results support the hypothesis that the same neuronal population and resonance phenomenon in the BGTC circuit generates both spontaneous and evoked pallidal beta oscillations. These data also support the development of closed-loop control systems that modulate the GPi spontaneous oscillations across PD patients using beta band stimulation-evoked responses

Early and unintentional release of planned motor actions during motor cortical preparation.

Voluntary movements are often preceded by a movement-related potential beginning as much as two seconds prior to the onset of movement. In light of evidence that motor actions can be prepared and initiated in less than 200 ms, the function of this early activity has remained enigmatic. We hypothesized that the movement-related potential reflects the state of preparation of the planned movement. This was tested by delivering a startling acoustic stimulus during the preparation phase of a load-release task. The cue to release the load was presented either 3.5 seconds after a warning cue (PREDICT condition) or randomly between 4-12 seconds (REACT condition). Electroencephalographic, electromyographic and limb and load kinematic signals were recorded. In a subset of trials, a startle stimulus was delivered at -1500, -1000, -500, -250, -100 or 0 ms before the release cue. A contingent-negative variation (CNV) waveform, with a late phase of slow-rising negativity beginning an average of 1459 ms prior to movement, was observed for the PREDICT condition but not the REACT condition. For both conditions, the startle stimulus frequently evoked the early and unintentional release of the load-release sequence. The incidence of release was significantly (p<0.001) correlated with the late phase of the CNV for the PREDICT condition but not the REACT condition. For the REACT condition, the incidence of movement release was subject-specific, constant across the preparation interval, and uncorrelated with cortical activity. The onset of movement release by the startle stimulus was significantly shorter (p<0.001) for the PREDICT compared to the REACT condition. These findings provide evidence that the late phase of the CNV reflects cortical activity mediating the progressive preparation and storage of the forthcoming movement and that during this phase an intense sensory stimulus can evoke early and unintentional release of the planned action

Tremor and Dysmetria in Multiple Sclerosis: A Neurophysiological Study.

ObjectiveThe mechanisms contributing to the pathogenesis of tremor and/or dysmetria in multiple sclerosis (MS) are poorly understood. Abnormal oscillations within the olivo-cerebello-thalamo-cortical networks are believed to play an important part in tremor aetiology, but could also contribute to intention dysmetria due to disruptions in motor timing. Conversely, delayed central motor conduction times are a common feature of ataxias, but could also contribute to the expression of dysmetria in MS. This study examined the roles of central conduction delays in the manifestation of tremor and/or dysmetria in MS.MethodsTwenty-three individuals with MS participated: 8 with no movement disorder, 6 with tremor, 4 with pure dysmetria and 5 with both tremor and dysmetria. Median nerve somatosensory evoked potentials (SEPs), transcranial magnetic stimulation (TMS) over the motor cortex and cervical spine, stretch reflexes were used assess sensory and motor conduction times.ResultsCentral, but not peripheral, sensory conductions time were significantly delayed in participants with dysmetria, regardless of the presence of tremor. Similarly, the TMS evoked muscles responses and the long-latency component of stretch reflexes were significantly delayed in those with dysmetria, but not pure tremor.ConclusionDysmetria in MS is associated with delays in central conduction of sensory or motor pathways, or both, likely leading to disruption of muscle activation timing and terminal oscillations that contribute to dysmetria.SignificanceThe presence of dysmetria in MS is associated with decreased conduction velocities in central sensory and/or motor pathways likely reflects greater demyelination of these axons compared to those with no movement disorder or pure tremor

Postural instability in Parkinson’s disease assessed with clinical “pull test” and standardized postural perturbations: effect of medication and body weight support

ObjectiveThis experiment tested if balance performance differed between a standardized treadmill surface perturbation task and a clinical pull test and was affected by medication or the presence of body weight support in people with Parkinson's disease (PD).MethodsTwenty-seven individuals were tested (14 PD in both ON- and OFF-medication states). Clinical pull test and rapid forward (backward fall) translations of the support surface were applied to induce postural reactions requiring at least 1 step to restore balance. The effects of pull type (clinical vs. treadmill), partial bodyweight support (0 vs 20% body weight) and group (control, PD ON-meds and PD OFF-meds) on reactive stepping as well as practice/learning effect were examined. The number of steps taken and the first step duration were entered in linear repeated-measures mixed-effect models separately.ResultsThe effects of pull type, group, and bodyweight support were all significant in both metrics, as was ON- vs. OFF-medication. A significant interaction term (group x pull type) was found in the first step duration, showing that the group difference was greater in treadmill compared to the clinical pull test. A significant practice effect was also observed within and across testing sessions.ConclusionsA standardized treadmill perturbation performed slightly better than the classical pull test in distinguishing between groups, and partial weight support did not substantially degrade the test's performance to detect the balance deficits in people with PD

Movement-related oscillations were affected by the predictability of the imperative release cue.

<p>The upper plots show the grand average time-frequency spectrograms at the C3 electrode overlying the contralateral sensorimotor region for the PREDICT (A) and REACT (B) conditions. Magnitudes have been normalized to the power over the pre-warning cue interval (−5 to −4.25 s). Note the marked suppression of oscillations in the alpha band (8–12 Hz) immediately following the warning cue and in the beta-band (15–30 Hz) during the 1500 ms time period immediately preceding the onset of wrist extensor (EDC) muscle activity (0 ms) for the PREDICT task. In contrast, the suppression of MRCOs occurred immediately prior to EMG onset for the REACT task and was confined to the beta-band. Plots C and D show the results of the statistical analysis of the normalized time-frequency spectrograms at the C3 electrode for the PREDICT (C) and REACT (D) conditions. Significant (p<0.05) increases (red) and decreases (blue) in MRCOs relative to baseline activity are shown.</p