Differential Responses to Low- and High-Frequency Subthalamic Nucleus Deep Brain Stimulation on Sensor-Measured Components of Bradykinesia in Parkinson's Disease.

INTRODUCTION: The current approach to assessing bradykinesia in Parkinson's Disease relies on the Unified Parkinson's Disease Rating Scale (UPDRS), which is a numeric scale. Inertial sensors offer the ability to probe subcomponents of bradykinesia: motor speed, amplitude, and rhythm. Thus, we sought to investigate the differential effects of high-frequency compared to low-frequency subthalamic nucleus (STN) deep brain stimulation (DBS) on these quantified facets of bradykinesia. METHODS: We recruited advanced Parkinson's Disease subjects with a chronic bilateral subthalamic nucleus (STN) DBS implantation to a single-blind stimulation trial where each combination of medication state (OFF/ON), electrode contacts, and stimulation frequency (60 Hz/180 Hz) was assessed. The Kinesia One sensor system was used to measure upper limb bradykinesia. For each stimulation trial, subjects performed extremity motor tasks. Sensor data were recorded continuously. We identified STN DBS parameters that were associated with improved upper extremity bradykinesia symptoms using a mixed linear regression model. RESULTS: We recruited 22 subjects (6 females) for this study. The 180 Hz STN DBS (compared to the 60 Hz STN DBS) and dopaminergic medications improved all subcomponents of upper extremity bradykinesia (motor speed, amplitude, and rhythm). For the motor rhythm subcomponent of bradykinesia, ventral contacts yielded improved symptom improvement compared to dorsal contacts. CONCLUSION: The differential impact of high- and low-frequency STN DBS on the symptoms of bradykinesia may advise programming for these patients but warrants further investigation. Wearable sensors represent a valuable addition to the armamentarium that furthers our ability to conduct objective, quantitative clinical assessments.

Short-term effects of Pilates-based exercise on upper limb strength and function in people with Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PD) have impaired upper limb motor coordination, limiting the execution of activities of daily living. This study investigated the feasibility and safety of a short-term Pilates-based exercise program in the treatment of upper limb motor coordination for people with PD. METHODS: Fifteen patients - n (%) 4 women/11 men (27/73), median [interquartile range] age 66 [9] years - participated in this quasi-experimental (before-and-after) clinical trial. Patients underwent a 6-week (30 min/day, 3 days/week) Pilates exercise program using Reformer, Cadillac, Chair, and Barrel equipment. Feasibility was evaluated by adherence to the program and the ability to perform the exercises including progressions on difficulty. Safety was evaluated based on self-reported adverse events. Clinical and functional trends before and after the intervention were also computed regarding handgrip strength (HGS), fine motor coordination (9 Hole Peg Test; 9HPT), bradykinesia (Movement Disorder Society - Unified Parkinson's disease Rating Scale; MDS-UPDRS), and upper limb functionality (Test D'évaluation des Membres Supérieurs des Personnes Âgées, TEMPA). RESULTS: Of the 18 Pilates sessions, exercise adherence was 100%. The only adverse event observed was mild muscle pain. Pre-post differences were observed only for body bradykinesia and hypokinesia (1.0 [0.0] vs. 0.0 [1.0] s, adjusted p = 0.048). CONCLUSIONS: A short-term Pilates-based exercise program in the treatment of upper limb muscle strength, manual dexterity, bradykinesia, and functionality is feasible and safe for people with PD. Changes in upper limb bradykinesia encourage randomized clinical trials.

Why so slow? Models of parkinsonian bradykinesia.

Bradykinesia, or slowness of movement, is a defining feature of Parkinson disease (PD) and a major contributor to the negative effects on quality of life associated with this disorder and related conditions. A dominant pathophysiological model of bradykinesia in PD has existed for approximately 30 years and has been the basis for the development of several therapeutic interventions, but accumulating evidence has made this model increasingly untenable. Although more recent models have been proposed, they also appear to be flawed. In this Perspective, I consider the leading prior models of bradykinesia in PD and argue that a more functionally related model is required, one that considers changes that disrupt the fundamental process of accurate information transmission. In doing so, I review emerging evidence of network level functional connectivity changes, information transfer dysfunction and potential motor code transmission error and present a novel model of bradykinesia in PD that incorporates this evidence. I hope that this model may reconcile inconsistencies in its predecessors and encourage further development of therapeutic interventions.

Characterizing Disease Progression in Parkinson's Disease from Videos of the Finger Tapping Test.

INTRODUCTION: Parkinson's disease (PD) is characterized by motor symptoms whose progression is typically assessed using clinical scales, namely the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Despite its reliability, the scale is bounded by a 5-point scale that limits its ability to track subtle changes in disease progression and is prone to subjective interpretations. We aimed to develop an automated system to objectively quantify motor symptoms in PD using Machine Learning (ML) algorithms to analyze videos and capture nuanced features of disease progression. METHODS: We analyzed videos of the Finger Tapping test, a component of the MDS-UPDRS, from 24 healthy controls and 66 PD patients using ML algorithms for hand pose estimation. We computed multiple movement features related to bradykinesia from videos and employed a novel tiered classification approach to predict disease severity that employed different features according to severity. We compared our video-based disease severity prediction approach against other approaches recently introduced in the literature. RESULTS: Traditional kinematics features such as amplitude and velocity changed linearly with disease severity, while other non-traditional features displayed non-linear trends. The proposed disease severity prediction approach demonstrated superior accuracy in detecting PD and distinguishing between different levels of disease severity when compared to existing approaches.

Disentangling Bradykinesia and Rigidity in Parkinson's Disease: Evidence from Short- and Long-Term Subthalamic Nucleus Deep Brain Stimulation.

OBJECTIVE: Bradykinesia and rigidity are considered closely related motor signs in Parkinson disease (PD), but recent neurophysiological findings suggest distinct pathophysiological mechanisms. This study aims to examine and compare longitudinal changes in bradykinesia and rigidity in PD patients treated with bilateral subthalamic nucleus deep brain stimulation (STN-DBS). METHODS: In this retrospective cohort study, the clinical progression of appendicular and axial bradykinesia and rigidity was assessed up to 15 years after STN-DBS in the best treatment conditions (ON medication and ON stimulation). The severity of bradykinesia and rigidity was examined using ad hoc composite scores from specific subitems of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III). Short- and long-term predictors of bradykinesia and rigidity were analyzed through linear regression analysis, considering various preoperative demographic and clinical data, including disease duration and severity, phenotype, motor and cognitive scores (eg, frontal score), and medication. RESULTS: A total of 301 patients were examined before and 1 year after surgery. Among them, 101 and 56 individuals were also evaluated at 10-year and 15-year follow-ups, respectively. Bradykinesia significantly worsened after surgery, especially in appendicular segments (p < 0.001). Conversely, rigidity showed sustained benefit, with unchanged clinical scores compared to preoperative assessment (p > 0.05). Preoperative motor disability (eg, composite scores from the UPDRS-III) predicted short- and long-term outcomes for both bradykinesia and rigidity (p < 0.01). Executive dysfunction was specifically linked to bradykinesia but not to rigidity (p < 0.05). INTERPRETATION: Bradykinesia and rigidity show long-term divergent progression in PD following STN-DBS and are associated with independent clinical factors, supporting the hypothesis of partially distinct pathophysiology. ANN NEUROL 2024;96:234-246.

Hyperkinetic and Hypokinetic Movement Disorders in SSPE: A Systematic Review of Case Reports and Case Series.

Background: Subacute Sclerosing Panencephalitis (SSPE) typically presents with periodic myoclonus; however, a spectrum of movement disorders including dystonia, chorea, tremor, and parkinsonism have also been described. This review aims to evaluate the array of movement disorders in SSPE, correlating them with neuroimaging findings, disease stages, and patient outcomes. Methods: A comprehensive review of published case reports and case series was conducted on patients with SSPE exhibiting movement disorders other than periodic myoclonus. PRISMA guidelines were followed, and the protocol was registered with PROSPERO (2023 CRD42023434650). A comprehensive search of multiple databases yielded 37 reports detailing 39 patients. Dyken's criteria were used for SSPE diagnosis, and the International Movement Disorders Society definitions were applied to categorize movement disorders. Results: The majority of patients were male, with an average age of 13.8 years. Approximately, 80% lacked a reliable vaccination history, and 39% had prior measles infections. Dystonia was the most common movement disorder (49%), followed by parkinsonism and choreoathetosis. Rapid disease progression was noted in 64% of cases, with a disease duration of ≤6 months in 72%. Neuroimaging showed T2/FLAIR MR hyperintensities, primarily periventricular, with 26% affecting the basal ganglia/thalamus. Brain biopsies revealed inflammatory and neurodegenerative changes. Over half of the patients (56%) reached an akinetic mute state or died. Conclusion: SSPE is associated with diverse movement disorders, predominantly hyperkinetic. The prevalence of dystonia suggests basal ganglia dysfunction.

Deep brain stimulation of symptom-specific networks in Parkinson's disease.

Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson's disease. Potentially, improving each symptom may require stimulation of different white matter tracts. Here, we study a large cohort of patients (N = 237 from five centers) to identify tracts associated with improvements in each of the four symptom domains. Tremor improvements were associated with stimulation of tracts connected to primary motor cortex and cerebellum. In contrast, axial symptoms are associated with stimulation of tracts connected to the supplementary motor cortex and brainstem. Bradykinesia and rigidity improvements are associated with the stimulation of tracts connected to the supplementary motor and premotor cortices, respectively. We introduce an algorithm that uses these symptom-response tracts to suggest optimal stimulation parameters for DBS based on individual patient's symptom profiles. Application of the algorithm illustrates that our symptom-tract library may bear potential in personalizing stimulation treatment based on the symptoms that are most burdensome in an individual patient.

Impaired performance of rapid grip in people with Parkinson's disease and motor segmentation.

Bradykinesia, or slow movement, is a defining symptom of Parkinson's disease (PD), but the underlying neuromechanical deficits that lead to this slowness remain unclear. People with PD often have impaired rates of motor output accompanied by disruptions in neuromuscular excitation, causing abnormal, segmented, force-time curves. Previous investigations using single-joint models indicate that agonist electromyogram (EMG) silent periods cause motor segmentation. It is unknown whether motor segmentation is evident in more anatomically complex and ecologically important tasks, such as handgrip tasks. Aim 1 was to determine how handgrip rates of force change compare between people with PD and healthy young and older adults. Aim 2 was to determine whether motor segmentation is present in handgrip force and EMG measures in people with PD. Subjects performed rapid isometric handgrip pulses to 20-60% of their maximal voluntary contraction force while EMG was collected from the grip flexors and extensors. Dependent variables included the time to 90% peak force, the peak rate of force development, the duration above 90% of peak force, the number of segments in the force-time curve, the number of EMG bursts, time to relaxation from 90% of peak force, and the peak rate of force relaxation. People with PD had longer durations and lower rates of force change than young and older adults. Six of 22 people with PD had motor segmentation. People with PD had more EMG bursts compared to healthy adults and the number of EMG bursts covaried with the number of segments. Thus, control of rapid movement in Parkinson's disease can be studied using isometric handgrip. People with PD have impaired rate control compared to healthy adults and motor segmentation can be studied in handgrip.

Bradykinesia in Neurodegenerative Disorders: A Blinded Video Analysis of Pathology-Proven Cases.

BACKGROUND: Bradykinesia is a cardinal feature in parkinsonisms. No study has assessed the differential features of bradykinesia in patients with pathology-proven synucleinopathies and tauopathies. OBJECTIVE: We examined whether bradykinesia features (speed, amplitude, rhythm, and sequence effect) may differ between pathology-proven synucleinopathies and tauopathies. METHODS: Forty-two cases who underwent autopsy were included and divided into synucleinopathies (Parkinson's disease and dementia with Lewy bodies) and tauopathies (progressive supranuclear palsy). Two raters blinded to the diagnosis retrospectively scored the Movement Disorders Society-Unified Parkinson's Disease Rating Scale Part III and Modified Bradykinesia Rating Scale on standardized videotaped neurological examinations. Bradykinesia scores were compared using the Mann-Whitney test and logistic regression models to adjust for disease duration. RESULTS: Demographic and clinical parameters were similar between synucleinopathies and tauopathies. There were no differences between speed, amplitude, rhythm, and sequence effect in synucleinopathies and tauopathies in unadjusted comparisons and adjusted models (all P > 0.05). CONCLUSIONS: Clinical bradykinesia features do not distinguish the underlying neuropathology in neurodegenerative parkinsonisms. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Shrew's venom quickly causes circulation disorder, analgesia and hypokinesia.

Multiple representatives of eulipotyphlan mammals such as shrews have oral venom systems. Venom facilitates shrews to hunt and/or hoard preys. However, little is known about their venom composition, and especially the mechanism to hoard prey in comatose states for meeting their extremely high metabolic rates. A toxin (BQTX) was identified from venomous submaxillary glands of the shrew Blarinella quadraticauda. BQTX is specifically distributed and highly concentrated (~ 1% total protein) in the organs. BQTX shares structural and functional similarities to toxins from snakes, wasps and snails, suggesting an evolutional relevancy of venoms from mammalians and non-mammalians. By potentiating thrombin and factor-XIIa and inhibiting plasmin, BQTX induces acute hypertension, blood coagulation and hypokinesia. It also shows strong analgesic function by inhibiting elastase. Notably, the toxin keeps high plasma stability with a 16-h half-life in-vivo, which likely extends intoxication to paralyze or immobilize prey hoarded fresh for later consumption and maximize foraging profit.

Long-Term Persistence of Increased Number of γH2AX+ Peripheral Blood Lymphocytes in Monkeys Exposed to Negative Factors of Space Flights: Ionizing Radiation and Simulated Hypogravity.

We studied the influence of ionizing radiation and hypogravity as negative factors of space flights on DNA damage in peripheral blood lymphocytes of rhesus monkeys at different times after exposure (from 1 to 446 days). The proportion of cells with high numbers of DNA double-strand breaks (DSB), positive for the surrogate DSB marker-protein γH2AX, was monitored using flow cytometry. Some animals were exposed to 7-day antiorthostatic hypokinesia simulating hypogravity, the others to a combined effect of antiorthostatic hypokinesia, whole-body γ-irradiation (2.34 cGy/h, dose 1 Gy), and irradiation of the head with 12C ions (450 MeV, dose 1 Gy). Exposure to antiorthostatic hypokinesia led to a significant increase in the proportion of γH2AX+ lymphocytes only on the first day after exposure, whereas after combined exposure, increased numbers of damaged lymphocytes were recorded up to 42 days after exposure.

Bradykinesia in motoneuron diseases.

OBJECTIVE: Only few studies investigated voluntary movement abnormalities in patients with motoneuron diseases (MNDs) or their neurophysiological correlates. We aimed to kinematically assess finger tapping abnormalities in patients with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), as compared to healthy controls (HCs), and their relationship with motoneuron involvement. METHODS: Fourteen ALS and 5 PLS patients were enrolled. Finger tapping was assessed by a motion analysis system. Patients underwent a central motor conduction time assessment, a motor nerve conduction study, and needle electromyography. Data were compared to those of 79 HCs using non-parametric tests. Possible relationships between clinical, kinematic, and neurophysiological data were assessed in patients. RESULTS: As a major finding, ALS and PLS patients performed finger tapping slower than HCs. In both conditions, movement slowness correlated with muscle strength. In ALS, movement slowness also correlated with the amplitude of the compound muscle action potential recorded from the muscles involved in the task and with denervation activity. No correlations were found between slowness, measures of upper motoneuron involvement, and other clinical and neurophysiological data. CONCLUSIONS: This study provides novel information on voluntary movement abnormalities in MNDs. SIGNIFICANCE: The results highlight the pathophysiological role of motoneurons in generating movement slowness.

Comparison of the Parkinson's KinetiGraph to off/on levodopa response testing: Single center experience.

BACKGROUND AND OBJECTIVE: Levodopa off/on testing is frequently performed to assess medication response in patients with Parkinson's disease (PD) as an aid in determining best medical management or potential surgical candidacy. The Parkinson's Kinetigraph (PKG) is a wearable device which generates tremor, bradykinesia (BKS) and dyskinesia (DKS) scores representing motor symptoms over a six-day period. In this study, we compared off/on testing with PKG motor scores. METHODS: Patients were enrolled as part of an observational study: Assessing the Longitudinal Signs in PD, a three-year study evaluating clinical and biomarker evolution in patients with PD taking levodopa. Patients underwent off/on testing at baseline and 6-month visits. A greater than 30% improvement between off and on MDS-Unified Parkinson's Disease Rating Scale scores was considered a robust response. After each visit, patients wore the PKG for 6 days. A bradykinesia score (BKS) greater than 26 and dyskinesia score (DKS) greater than 9 were considered poorly controlled bradykinesia and dyskinesia, respectively. RESULTS: The median BKS at the baseline and 6-month visits were 27.15 and 27.55, respectively, despite a robust median off/on improvement at both visits. In addition, 10/18 (66%) and 7/13 (53.8%) patients with robust off/on improvement at the baseline and 6-month visits, respectively, demonstrated a BKS > 26 or DKS > 9. CONCLUSION: A robust off/on response during a clinic visit does not necessarily reflect adequately controlled motor symptoms. The PKG, by virtue of its continuous recording of motor movements, may provide additional clinically relevant data on motor symptoms which may be useful for prospective observational studies.

DNAJC6 mutation causing cranial-onset dystonia with tremor dominant levodopa non-responsive parkinsonism: A novel phenotype.

DNAJC6 mutation causes two types of phenotypes: slowly progressive parkinsonism with levodopa response and rapidly progressive parkinsonism with additional manifestations like intellectual disability, epilepsy etc. We report a new phenotype wherein an adolescent girl developed blepharospasm followed by jaw opening, lingual and cervical dystonia followed by tremors of limbs (rest and action) with rigidity, bradykinesia. The dystonia-parkinsonism phenotype has not been described. She had novel homozygous missense mutation in DNAJC6 gene.

Beta power and movement-related beta modulation as hallmarks of energy for plasticity induction: Implications for Parkinson's disease.

Extensive work on movement-related beta oscillations (~13-30 Hz) over the sensorimotor areas in both humans and animals has demonstrated that sensorimotor beta power decreases during movement and transiently increases after movement. This beta power modulation has been interpreted as reflecting interactions between sensory and motor cortical areas with attenuation of sensory afferents during movement and their subsequent re-activation for internal models updating. More recent studies in neurologically normal subjects have demonstrated that this movement-related modulation as well as mean beta power at rest increase with practice and that previous motor learning enhances such increases. Conversely, patients with Parkinson's disease (PD) do not show such practice-related increases. Interestingly, a 2-h inactivity period without sleep can restore beta power values to baseline in normal subjects. Based on these results and on those of biochemical and electrophysiological studies in animals, we expand the current interpretation of beta activity and propose that the practice-related increases of beta power over sensorimotor areas are local indices of energy used for engaging plasticity-related activity. This paper provides some preliminary evidence in this respect linking findings of biochemical and electrophysiological studies in both humans and animals. This novel interpretation may explain the high level of beta power at rest, the deficient modulation during movement as well as the decreased skill formation in PD as resulting from deficiency in energy consumption, availability and regulation that are altered in this disease.

Evaluation of neurogenic bladder outlet obstruction mimicking sphincter bradykinesia in male patients with Parkinson's disease.

BACKGROUND: Lower urinary tract symptoms are one of the most common groups of non-movement symptoms in patients with Parkinson's disease (PD). Storage symptoms are well-acknowledged, but neurogenic voiding dysfunction caused by PD remains a knowledge gap. This study aimed to evaluate the neurogenic bladder outlet obstruction in male patients with PD and its clinical significance. METHODS: Male patients who were diagnosed with PD and underwent urodynamic studies were retrospectively reviewed. The patients with prostate size < 30 ml and bladder outlet obstruction index ≥40 were included in the study. Lower urinary tract symptoms were evaluated by International Prostate Symptom Score (IPSS). Free flowmetry was performed and post void residual (PVR) volume was measured by ultrasound at follow-up. RESULTS: Six patients were included in the final analysis. The mean age was 68.2 and the mean movement symptom duration was 70.7 months. The patients had a mean IPSS of 12.5 and mean PVR volume of 70.8 ml. All patients had slow stream but none of them reported significant voiding difficulty. Urodynamic studies showed the delayed urinary sphincter relaxation and the special trace pattern. After a mean follow-up of 20 months, they had a mean IPSS of 12.5 and mean PVR volume of 73.3 ml. None of them complained of significant voiding difficulty at follow-up. CONCLUSION: The delayed urinary sphincter relaxation is a rare but repeatable phenomenon in male patients with PD. It is unlikely to cause disturbing voiding dysfunction, as reported by the patients, and does not progress prominently during the course of PD. Further studies are needed to investigate the nature of this special type of neurogenic BOO and whether it is peculiar to PD in a larger patient cohort.

Continuous home monitoring of Parkinson's disease using inertial sensors: A systematic review.

Parkinson's disease (PD) is a progressive neurological disorder of the central nervous system that deteriorates motor functions, while it is also accompanied by a large diversity of non-motor symptoms such as cognitive impairment and mood changes, hallucinations, and sleep disturbance. Parkinsonism is evaluated during clinical examinations and appropriate medical treatments are directed towards alleviating symptoms. Tri-axial accelerometers, gyroscopes, and magnetometers could be adopted to support clinicians in the decision-making process by objectively quantifying the patient's condition. In this context, at-home data collections aim to capture motor function during daily living and unobstructedly assess the patients' status and the disease's symptoms for prolonged time periods. This review aims to collate existing literature on PD monitoring using inertial sensors while it focuses on papers with at least one free-living data capture unsupervised either directly or via videotapes. Twenty-four papers were selected at the end of the process: fourteen investigated gait impairments, eight of which focused on walking, three on turning, two on falls, and one on physical activity; ten articles on the other hand examined symptoms, including bradykinesia, tremor, dyskinesia, and motor state fluctuations in the on/off phenomenon. In summary, inertial sensors are capable of gathering data over a long period of time and have the potential to facilitate the monitoring of people with Parkinson's, providing relevant information about their motor status. Concerning gait impairments, kinematic parameters (such as duration of gait cycle, step length, and velocity) were typically used to discern PD from healthy subjects, whereas for symptoms' assessment, researchers were capable of achieving accuracies of over 90% in a free-living environment. Further investigations should be focused on the development of ad-hoc hardware and software capable of providing real-time feedback to clinicians and patients. In addition, features such as the wearability of the system and user comfort, set-up process, and instructions for use, need to be strongly considered in the development of wearable sensors for PD monitoring.

Machine Learning-Based Automatic Rating for Cardinal Symptoms of Parkinson Disease.

OBJECTIVE: We developed and investigated the feasibility of a machine learning-based automated rating for the 2 cardinal symptoms of Parkinson disease (PD): resting tremor and bradykinesia. METHODS: Using OpenPose, a deep learning-based human pose estimation program, we analyzed video clips for resting tremor and finger tapping of the bilateral upper limbs of 55 patients with PD (110 arms). Key motion parameters, including resting tremor amplitude and finger tapping speed, amplitude, and fatigue, were extracted to develop a machine learning-based automatic Unified Parkinson's Disease Rating Scale (UPDRS) rating using support vector machine (SVM) method. To evaluate the performance of this model, we calculated weighted κ and intraclass correlation coefficients (ICCs) between the model and the gold standard rating by a movement disorder specialist who is trained and certified by the Movement Disorder Society for UPDRS rating. These values were compared to weighted κ and ICC between a nontrained human rater and the gold standard rating. RESULTS: For resting tremors, the SVM model showed a very good to excellent reliability range with the gold standard rating (κ 0.791; ICC 0.927), with both values higher than that of nontrained human rater (κ 0.662; ICC 0.861). For finger tapping, the SVM model showed a very good reliability range with the gold standard rating (κ 0.700 and ICC 0.793), which was comparable to that for nontrained human raters (κ 0.627; ICC 0.797). CONCLUSION: Machine learning-based algorithms that automatically rate PD cardinal symptoms are feasible, with more accurate results than nontrained human ratings. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that machine learning-based automated rating of resting tremor and bradykinesia in people with PD has very good reliability compared to a rating by a movement disorder specialist.

Modulation of beta bursts in subthalamic sensorimotor circuits predicts improvement in bradykinesia.

No biomarker of Parkinson's disease exists that allows clinicians to adjust chronic therapy, either medication or deep brain stimulation, with real-time feedback. Consequently, clinicians rely on time-intensive, empirical, and subjective clinical assessments of motor behaviour and adverse events to adjust therapies. Accumulating evidence suggests that hypokinetic aspects of Parkinson's disease and their improvement with therapy are related to pathological neural activity in the beta band (beta oscillopathy) in the subthalamic nucleus. Additionally, effectiveness of deep brain stimulation may depend on modulation of the dorsolateral sensorimotor region of the subthalamic nucleus, which is the primary site of this beta oscillopathy. Despite the feasibility of utilizing this information to provide integrated, biomarker-driven precise deep brain stimulation, these measures have not been brought together in awake freely moving individuals. We sought to directly test whether stimulation-related improvements in bradykinesia were contingent on reduction of beta power and burst durations, and/or the volume of the sensorimotor subthalamic nucleus that was modulated. We recorded synchronized local field potentials and kinematic data in 16 subthalamic nuclei of individuals with Parkinson's disease chronically implanted with neurostimulators during a repetitive wrist-flexion extension task, while administering randomized different intensities of high frequency stimulation. Increased intensities of deep brain stimulation improved movement velocity and were associated with an intensity-dependent reduction in beta power and mean burst duration, measured during movement. The degree of reduction in this beta oscillopathy was associated with the improvement in movement velocity. Moreover, the reduction in beta power and beta burst durations was dependent on the theoretical degree of tissue modulated in the sensorimotor region of the subthalamic nucleus. Finally, the degree of attenuation of both beta power and beta burst durations, together with the degree of overlap of stimulation with the sensorimotor subthalamic nucleus significantly explained the stimulation-related improvement in movement velocity. The above results provide direct evidence that subthalamic nucleus deep brain stimulation-related improvements in bradykinesia are related to the reduction in beta oscillopathy within the sensorimotor region. With the advent of sensing neurostimulators, this beta oscillopathy combined with lead location could be used as a marker for real-time feedback to adjust clinical settings or to drive closed-loop deep brain stimulation in freely moving individuals with Parkinson's disease.

Changes in Total Cholesterol and Heart Rate in Normotensive and Hypertensive Rats under Combined Influence of Cold Exposure and Hypokinesia.

We studied the effect of hypokinesia alone and in combination with cold exposure on HR and total cholesterol content in the blood serum of Wistar, WKY, and SHR rats. Irrespectively of the season, hypokinesia was associated with a decrease in HR, which is probably a result of reduced body needs due to deceleration of metabolic processes. A significant increase in total cholesterol was found under conditions of cold exposure combined with hypokinesia, which indicates qualitative structural rearrangement of energy metabolism under the influence of environmental factors. In winter, the increase in total cholesterol concentration was more pronounced (by 51.5%) in the group of hypertensive animals. Presumably, the increase in the serum concentration of total cholesterol under conditions of hypokinesia and cold exposure is a predictor of structural changes in the heart.