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External sensory cues can reduce freezing of gait in people with Parkinson's disease (PD), yet the role of the basal ganglia in these movements is unclear. We used microelectrode recordings to examine modulations in single unit (SU) and oscillatory local field potentials (LFP) during auditory-cued rhythmic pedaling movements of the feet. We tested five blocks of increasing cue frequencies (1 Hz, 1.5 Hz, 2 Hz, 2.5 Hz, and 3 Hz) in 24 people with PD undergoing deep brain stimulation surgery of the subthalamic nucleus (STN) or globus pallidus internus (GPi). Single unit firing and beta band LFPs (13–30 Hz) in response to movement onsets or cue onsets were examined. We found that the timing accuracy of foot pedaling decreased with faster cue frequencies. Increasing cue frequencies also attenuated firing rates in both STN and GPi neurons. Peak beta power in the GPi and STN showed different responses to the task. GPi beta power showed persistent suppression with fast cues and phasic modulation with slow cues. STN beta power showed enhanced beta synchronization following movement. STN beta power also correlated with rate of pedaling. Overall, we showed task-related responses in the GPi and STN during auditory-cued movements with differential roles in sensory and motor control. The results suggest a role for both input and output basal ganglia nuclei in auditory rhythmic pacing of gait-like movements in PD. • Single neurons in STN (72%) and GPi (52%) responded to auditory cued foot pedaling at rates from 1 to 3 Hz in awake PD persons OFF-drug • Accuracy of pedaling with respect to cues progressively decreased as cue frequencies increased, particularly above 1.5 Hz. • GPi showed decrease in tonic beta LFP power with fast auditory cues. STN showed tonic increases in beta power after onset of foot movement. • STN is involved in motor aspects of auditory cued pedaling while the GPi may play a role in sensory processing of the task. [ABSTRACT FROM AUTHOR]

Postural control requires effective sensory integration. People with Parkinson's disease (PD) are reported to have impaired visual and vestibular perception. While self-motion perception is a key aspect of locomotion, visual-vestibular integration has not been directly characterized in people with PD during gait. We compared the ability of people with PD and healthy older adults (OA) to integrate multi-sensory information during straight-line walking in response to visual and vestibular perturbations, using continuous translations of the visual surround and galvanic vestibular stimulation within a virtual reality environment. We measured their endpoint deviations from midline and changes in gait parameters. We found that people with PD deviated more than OA when walking in a dark environment but did not show differences in deviations when walking in a virtual room with visual information. With visual and vestibular perturbations, people with PD did not differ from OA in endpoint deviations nor variabilities. However, people with PD did not adopt a more cautious gait when GVS was applied in a virtual room, unlike OA. Overall, we showed that people with mild PD did not perform worse than OA but did show differences in gait patterns, suggesting that visual-vestibular integration is relatively preserved during gait in PD. • People with PD deviate more than older adults when walking with reduced visual information (i.e., in the dark). • People with PD do not deviate more than age-matched older adults with sensory perturbations. • Visual-vestibular sensory integration may be preserved in PD. [ABSTRACT FROM AUTHOR]

Bradykinesia is a disabling symptom of Parkinson's disease (PD) which presents with slowness of movement. Visual assessment using clinical rating scales is currently the gold standard to assess bradykinesia. Such assessments require multiple separate movements, are subjective, and rely on the ability of the rater to determine frequency and amplitude features of excursion of multiple joints simultaneously. The current study introduces the use of wearable inertial measurement units (IMUs) to characterize full-arm repetitive movements and provide a new index score for bradykinesia severity (BKI) in the upper limbs. The BKI provides an approach to measuring bradykinesia reliably and objectively. Importantly, this index is needed to demonstrate separability between healthy individuals and PD participants, and also between bradykinetic and non-bradykinetic PD participants. Thirteen PD participants and ten age-matched healthy control participants were studied. Using a single upper limb task that activated multiple joints and recordings from angular displacements from all joints, features relevant to demonstrating bradykinesia were extracted and systematically combined to create the total BKI. A strong correlation coefficient was obtained comparing BKI to upper limb UPDRS bradykinesia scores ( r s = − 0.626, p = 0.001). The BKI successfully identified differences between control and PD participants ( p = 0.018). The BKI was also sensitive enough to identify differences within the PD population, separating PD participants with and without bradykinesia ( p < 0.001). This study demonstrates the feasibility of using IMU-based motion capture systems and employing the new BKI for quantitative assessment of bradykinesia. This approach when generalized to lower extremity and truncal movements would be able to provide an objective and reproducible whole body bradykinesia index. [ABSTRACT FROM AUTHOR]

Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) characterized by paroxysmal episodes in which patients are unable to step forward. A research priority is identifying cortical changes before freezing in PD-FOG. We tested 19 patients with PD who had been assessed for FOG (n =14 with FOG and 5 without FOG). While seated, patients stepped bilaterally on pedals to progress forward through a virtual hallway while 64-channel EEG was recorded. We assessed cortical activities before and during lower limb motor blocks (LLMB), defined as a break in rhythmic pedaling, and stops, defined as movement cessation following an auditory stop cue. This task was selected because LLMB correlates with FOG severity in PD and allows recording of high-quality EEG. Patients were tested after overnight withdrawal from dopaminergic medications ("off" state) and in the "on" medications state. EEG source activities were evaluated using individual MRI and standardized low resolution brain electromagnetic tomography (sLORETA). Functional connectivity was evaluated by phase lag index between seeds and pre-defined cortical regions of interest. EEG source activities for LLMB vs. cued stops localized to right posterior parietal area (Brodmann area 39), lateral premotor area (Brodmann area 6), and inferior frontal gyrus (Brodmann area 47). In these areas, PD-FOG (n =14) increased alpha rhythms (8-12 Hz) before LLMB vs. typical stepping, whereas PD without FOG (n =5) decreased alpha power. Alpha rhythms were linearly correlated with LLMB severity, and the relationship became an inverted U-shape when assessing alpha rhythms as a function of percent time in LLMB in the "off" medication state. Right inferior frontal gyrus and supplementary motor area connectivity was observed before LLMB in the beta band (13-30 Hz). This same pattern of connectivity was seen before stops. Dopaminergic medication improved FOG and led to less alpha synchronization and increased functional connections between frontal and parietal areas. Right inferior parietofrontal structures are implicated in PD-FOG. The predominant changes were in the alpha rhythm, which increased before LLMB and with LLMB severity. Similar connectivity was observed for LLMB and stops between the right inferior frontal gyrus and supplementary motor area, suggesting that FOG may be a form of "unintended stopping." These findings may inform approaches to neurorehabilitation of PD-FOG. • Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD). • EEG source activity localized to right frontal and parietal areas in PD-FOG. • Alpha rhythms in these areas increased with severity of lower limb motor blocks. • Dopaminergic medications improved FOG and led to fewer alpha rhythms. • These brain signals may be useful for neurorehabilitation of PD-FOG. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation of the subthalamic nucleus is effective to alleviate motor symptoms in advanced Parkinson's disease. Using a novel conditioning paradigm, it has been shown that deep brain stimulation pulses from electrodes in the subthalamic nucleus modulate corticospinal excitability as determined with transcranial magnetic stimulation applied to the motor cortex. The mechanism of action is unclear.Objective: To investigate the effects of subthalamic nucleus and dorsal premotor cortex conditioning on corticospinal excitability as a function of interstimulus intervals between target areas and deep brain stimulation frequencies.Methods: In 19 patients with Parkinson's disease with subthalamic nucleus deep brain stimulation, the premotor-motor interaction was investigated in four different deep brain stimulation conditions (off, clinically used settings, 3 Hz, 20 Hz). Transcranial magnetic pulses were applied to the premotor and motor cortex and paired at certain intervals with deep brain stimulation pulses. The volume of tissue activated by deep brain stimulation was correlated with neurophysiological findings.Results: There was distinct motor cortex inhibition by premotor cortex conditioning at an interstimulus interval of 1 ms before the motor cortex stimulation. Subthalamic nucleus conditioning with deep brain stimulation frequencies of 3 and 20 Hz at an interstimulus interval of 10 ms between subthalamic nucleus and primary motor cortex reduced premotor-motor inhibition. The volume of tissue activated by deep brain stimulation correlated positively with this effect. Corticospinal excitability was not affected by subthalamic nucleus conditioning as used here.Conclusions: Premotor-motor inhibition is modulated by subthalamic nucleus conditioning, presumably through the monosynaptic hyperdirect pathway. [ABSTRACT FROM AUTHOR]