Neural pathways associated with reduced rigidity during pallidal deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) can markedly reduce muscle rigidity in people with Parkinson's disease (PD); however, the mechanisms mediating this effect are poorly understood. Computational modeling of DBS provides a method to estimate the relative contributions of neural pathway activations to changes in outcomes. In this study, we generated subject-specific biophysical models of GPi DBS (derived from individual 7-T MRI), including pallidal efferent, putamenal efferent, and internal capsule pathways, to investigate how activation of neural pathways contributed to changes in forearm rigidity in PD.

Different descending pathways mediate early and late portions of lower limb responses to transcranial magnetic stimulation.

Although recent studies in nonhuman primates have provided evidence that transcranial magnetic stimulation (TMS) activates cells within the reticular formation, it remains unclear whether descending brain stem projections contribute to the generation of TMS-induced motor evoked potentials (MEPs) in skeletal muscles. We compared MEPs in muscles with extensive direct corticomotoneuronal input (first dorsal interosseous) versus a prominent role in postural control (gastrocnemius) to determine whether the amplitudes of early and late MEPs were differentially modulated by cortical suppression. Suprathreshold TMS was applied with and without a preceding suprathreshold TMS pulse at two interstimulus intervals (50 and 80 ms).

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.

Excessive cortical beta oscillations are associated with slow-wave sleep dysfunction in mild parkinsonism.

Increasing evidence associates slow-wave sleep (SWS) dysfunction with neurodegeneration. Using a within-subject design in the nonhuman primate model of Parkinson's disease (PD), we found that reduced SWS quantity in mild parkinsonism was accompanied by elevated beta and reduced delta power during SWS in the motor cortex. Our findings support excessive beta oscillations as a mechanism for SWS dysfunction and will inform development of neuromodulation therapies for enhancing SWS in PD.

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

Introduction: Evidence suggests that 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.

Startle-induced rapid release of a gait initiation sequence in Parkinson's disease with freezing of gait.

Objective: Freezing of gait (FOG) in Parkinson's disease (PD) is characterized by the inability to initiate stepping, despite the intention to do so. This study used a startling acoustic stimulus paradigm to examine if the capacity to select, prepare and initiate gait under simple and choice reaction time conditions are impaired in people with PD and FOG.

Methods: Thirty individuals (10 PD with FOG, 10 PD without FOG, and 10 controls) performed an instructed-delay gait initiation task under simple and choice reaction time conditions.

Parkinsonian daytime sleep-wake classification using deep brain stimulation lead recordings.

Excessive daytime sleepiness is a recognized non-motor symptom that adversely impacts the quality of life of people with Parkinson's disease (PD), yet effective treatment options remain limited. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for PD motor signs. Reliable daytime sleep-wake classification using local field potentials (LFPs) recorded from DBS leads implanted in STN can inform the development of closed-loop DBS approaches for prompt detection and disruption of sleep-related neural oscillations.

Postural instability in Parkinson's disease assessed with clinical "pull test" and standardized postural perturbations: effect of medication and body weight support.

Objective: This 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).

Methods: Twenty-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.

Basal ganglia engagement during REM sleep movements in Parkinson's disease.

To elucidate the role of the basal ganglia during REM sleep movements in Parkinson's disease (PD) we recorded pallidal neural activity from four PD patients. Unlike desynchronization commonly observed during wakeful movements, beta oscillations (13-35 Hz) synchronized during REM sleep movements; furthermore, high-frequency oscillations (150-350 Hz) synchronized during movement irrespective of sleep-wake states. Our results demonstrate differential engagement of the basal ganglia during REM sleep and awake movements.

Postural support requirements preferentially modulate late components of the gastrocnemius response to transcranial magnetic stimulation.

Mounting evidence suggests that motor evoked potentials (MEPs) recorded in upper limb muscles with postural support roles following transcranial magnetic stimulation receive contributions from both corticospinal and non-corticospinal descending pathways. We tested the hypothesis that neural structures responsible for regulating upright balance are involved in transmitting late portions of TMS-induced MEPs in a lower limb muscle. MEPs were recorded in the medial gastrocnemius muscles of each leg, while participants supported their upright posture in five postural conditions that required different levels of support from the target muscles.

Modulation of Beta Oscillations in the Pallidum During Externally Cued Gait.

Freezing of gait (FOG) is a particularly debilitating symptom of Parkinson's disease (PD) and is often refractory to treatment. A striking feature of FOG is that external sensory cues can be used to overcome freezing and improve gait. Local field potentials (LFPs) recorded from the subthalamic nucleus (STN) and globus pallidus (GP) show that beta-band power modulates with gait phase.

White matter microstructure in Parkinson's disease with and without elevated rapid eye movement sleep muscle tone.

People with Parkinson's disease who have elevated muscle activity during rapid eye movement sleep (REM sleep without atonia) typically have a worse motor and cognitive impairment compared with those with normal muscle atonia during rapid eye movement sleep. This study used tract-based spatial statistics to compare diffusion MRI measures of fractional anisotropy, radial, mean and axial diffusivity (measures of axonal microstructure based on the directionality of water diffusion) in white matter tracts between people with Parkinson's disease with and without rapid eye movement sleep without atonia and controls and their relationship to measures of motor and cognitive function. Thirty-eight individuals with mild-to-moderate Parkinson's disease and 21 matched control subjects underwent ultra-high field MRI (7 T), quantitative motor assessments of gait and bradykinesia and neuropsychological testing.

Overground versus treadmill walking in Parkinson's disease: Relationship between speed and spatiotemporal gait metrics.

Background: Treadmills provide a safe and convenient way to study the gait of people with Parkinson's disease (PD), but outcome measures derived from treadmill gait may differ from overground walking.

Objective: To investigate how the relationships between gait metrics and walking speed vary between overground and treadmill walking in people with PD and healthy controls.

Methods: We compared 29 healthy controls to 27 people with PD in the OFF-medication state.

Can People with Parkinson's Disease Self-Trigger Gait Initiation? A Comparison of Cueing Strategies.

Background: An external cue can markedly improve gait initiation in people with Parkinson's disease (PD) and is often used to overcome freezing of gait (FOG). It is unknown if the effects of external cueing are comparable if the imperative stimulus is triggered by the person receiving the cue (self-triggered) or an external source.

Objective: Two experiments were conducted to compare the effects of self- versus externally triggered cueing on anticipatory postural adjustments (APAs) during gait initiation in people with PD.

Tremor and Dysmetria in Multiple Sclerosis: A Neurophysiological Study.

Objective: The 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.

Semi-automated approaches to optimize deep brain stimulation parameters in Parkinson's disease.

Background: Deep brain stimulation (DBS) is a treatment option for Parkinson's disease patients when medication does not sufficiently manage their symptoms. DBS can be a highly effect therapy, but only after a time-consuming trial-and-error stimulation parameter adjustment process that is susceptible to clinician bias. This trial-and-error process will be further prolonged with the introduction of segmented electrodes that are now commercially available.

Motor Dysfunction in REM Sleep Behavior Disorder: A Rehabilitation Framework for Prodromal Synucleinopathy.

Parkinson disease (PD) and other related diseases with α-synuclein pathology are associated with a long prodromal or preclinical stage of disease. Predictive models based on diagnosis of idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) make it possible to identify people in the prodromal stage of synucleinopathy who have a high probability of future disease and provide an opportunity to implement neuroprotective therapies. However, rehabilitation providers may be unaware of iRBD and the motor abnormalities that indicate early motor system dysfunction related to α-synuclein pathology.

REM Sleep Without Atonia and Gait Impairment in People with Mild-to-Moderate Parkinson's Disease.

Background: Subtle gait deficits can be seen in people with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), a prodromal stage of Parkinson's disease (PD) and related alpha-synucleinopathies. It is unknown if the presence and level of REM sleep without atonia (RSWA, the electromyographic hallmark of RBD) is related to the severity of gait disturbances in people with PD.

Objective: We hypothesized that gait disturbances in people with mild-to-moderate PD would be greater in participants with RSWA compared to those without RSWA and matched controls, and that gait impairment would correlate with measures of RSWA.

Comparison of forward and backward postural perturbations in mild-to-moderate Parkinson's disease.

Background: Assessing postural stability in Parkinson's disease (PD) often relies on measuring the stepping response to an imposed postural perturbation. The standard clinical technique relies on a brisk backwards pull at the shoulders by the examiner and judgement by a trained rater. In research settings, various quantitative measures and perturbation directions have been tested, but it is unclear which metrics and perturbation direction differ most between people with PD and controls.

Motor Unit Discharge Variability Is Increased in Mild-To-Moderate Parkinson's Disease.

Individuals with Parkinson's 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.

Morphological changes in the subthalamic nucleus of people with mild-to-moderate Parkinson's disease: a 7T MRI study.

This project investigated whether structural changes are present in the subthalamic nucleus (STN) of people with mild-to-moderate severity of Parkinson's disease (PD). Within-subject measures of STN volume and fractional anisotropy (FA) were derived from high-resolution 7Tesla magnetic resonance imaging (MRI) for 29 subjects with mild-to-moderate PD (median disease duration = 2.3±1.

REM sleep without atonia is associated with increased rigidity in patients with mild to moderate Parkinson's disease.

Objective: Increased muscle activity during rapid eye movement (REM) sleep (i.e. REM sleep without atonia) is common in people with Parkinson's disease (PD).