Noise estimation for head-mounted 3D binocular eye tracking using Pupil Core eye-tracking goggles.

Head-mounted, video-based eye tracking is becoming increasingly common and has promise in a range of applications. Here, we provide a practical and systematic assessment of the sources of measurement uncertainty for one such device - the Pupil Core - in three eye-tracking domains: (1) the 2D scene camera image; (2) the physical rotation of the eye relative to the scene camera 3D space; and (3) the external projection of the estimated gaze point location onto the target plane or in relation to world coordinates. We also assess eye camera motion during active tasks relative to the eye and the scene camera, an important consideration as the rigid arrangement of eye and scene camera is essential for proper alignment of the detected gaze. We find that eye camera motion, improper gaze point depth estimation, and erroneous eye models can all lead to added noise that must be considered in the experimental design. Further, while calibration accuracy and precision estimates can help assess data quality in the scene camera image, they may not be reflective of errors and variability in gaze point estimation. These findings support the importance of eye model constancy for comparisons across experimental conditions and suggest additional assessments of data reliability may be warranted for experiments that require the gaze point or measure eye movements relative to the external world.

The digital signature of emergent tremor in Parkinson's disease.

Background: Emergent tremor in Parkinson's disease (PD) can occur during sustained postures or movement that is different from action tremor. Tremor can contaminate the clinical rating of bradykinesia during finger tapping. Currently, there is no reliable way of isolating emergent tremor and measuring the cardinal motor symptoms based on voluntary movements only. Objective: Investigate whether emergent tremor during repetitive alternating finger tapping (RAFT) on a quantitative digitography (QDG) device can be reliably identified and distinguished from voluntary tapping. Methods: Ninety-six individuals with PD and forty-two healthy controls performed a thirty-second QDG-RAFT task and the Movement Disorders Society - Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III). Visual identification of tremor during QDG-RAFT was labelled by an experienced movement disorders specialist. Two methods of identifying tremor were investigated: 1) physiologically-informed temporal thresholds 2) XGBoost model using temporal and amplitude features of tapping. Results: The XGBoost model showed high accuracy for identifying tremor (area under the precision-recall curve of 0.981) and outperformed temporal-based thresholds. Percent time duration of classifier-identified tremor showed significant correlations with MDS-UPDRS III tremor subscores (r = 0.50, P < 0.0001). There was a significant change in QDG metrics for bradykinesia, rigidity and arrhythmicity after tremor strikes were excluded (p < 0.01). Conclusions: Emergent tremor during QDG-RAFT has a unique digital signature and the duration of tremor correlated with the MDS-UPDRS III tremor items. When involuntary tremor strikes were excluded, the QDG metrics of bradykinesia and rigidity were significantly worse, demonstrating the importance of distinguishing tremor from voluntary movement when rating bradykinesia.

A Comparison of Walking Behavior during the Instrumented TUG and Habitual Gait.

The timed up and go test (TUG) is a common clinical functional balance test often used to complement findings on sensorimotor changes due to aging or sensory/motor dysfunction. The instrumented TUG can be used to obtain objective postural and gait measures that are more sensitive to mobility changes. We investigated whether gait and body coordination during TUG is representative of walking. We examined the walking phase of the TUG and compared gait metrics (stride duration and length, walking speed, and step frequency) and head/trunk accelerations to normal walking. The latter is a key aspect of postural control and can also reveal changes in sensory and motor function. Forty participants were recruited into three groups: young adults, older adults, and older adults with visual impairment. All performed the TUG and a short walking task wearing ultra-lightweight wireless IMUs on the head, chest, and right ankle. Gait and head/trunk acceleration metrics were comparable across tasks. Further, stride length and walking speed were correlated with the participants' age. Those with visual impairment walked significantly slower than sighted older adults. We suggest that the TUG can be a valuable tool for examining gait and stability during walking without the added time or space constraints.

Bradykinesia and Its Progression Are Related to Interhemispheric Beta Coherence.

OBJECTIVE: Bradykinesia is the major cardinal motor sign of Parkinson disease (PD), but its neural underpinnings are unclear. The goal of this study was to examine whether changes in bradykinesia following long-term subthalamic nucleus (STN) deep brain stimulation (DBS) are linked to local STN beta (13-30 Hz) dynamics or a wider bilateral network dysfunction. METHODS: Twenty-one individuals with PD implanted with sensing neurostimulators (Activa® PC + S, Medtronic, PLC) in the STN participated in a longitudinal 'washout' therapy study every three to 6 months for an average of 3 years. At each visit, participants were withdrawn from medication (12/24/48 hours) and had DBS turned off (>60 minutes) before completing a repetitive wrist-flexion extension task, a validated quantitative assessment of bradykinesia, while local field potentials were recorded. Local STN beta dynamics were investigated via beta power and burst duration, while interhemispheric beta synchrony was assessed with STN-STN beta coherence. RESULTS: Higher interhemispheric STN beta coherence, but not contralateral beta power or burst duration, was significantly associated with worse bradykinesia. Bradykinesia worsened off therapy over time. Interhemispheric STN-STN beta coherence also increased over time, whereas beta power and burst duration remained stable. The observed change in bradykinesia was related to the change in interhemispheric beta coherence, with greater increases in synchrony associated with further worsening of bradykinesia. INTERPRETATION: Together, these findings implicate interhemispheric beta synchrony as a neural correlate of the progression of bradykinesia following chronic STN DBS. This could imply the existence of a pathological bilateral network contributing to bradykinesia in PD. ANN NEUROL 2023;93:1029-1039.

A low-cost robotic oculomotor simulator for assessing eye tracking accuracy in health and disease.

Eye tracking accuracy is affected in individuals with vision and oculomotor deficits, impeding our ability to answer important scientific and clinical questions about these disorders. It is difficult to disambiguate decreases in eye movement accuracy and changes in accuracy of the eye tracking itself. We propose the EyeRobot-a low-cost, robotic oculomotor simulator capable of emulating healthy and compromised eye movements to provide ground truth assessment of eye tracker performance, and how different aspects of oculomotor deficits might affect tracking accuracy and performance. The device can operate with eccentric optical axes or large deviations between the eyes, as well as simulate oculomotor pathologies, such as large fixational instabilities. We find that our design can provide accurate eye movements for both central and eccentric viewing conditions, which can be tracked by using a head-mounted eye tracker, Pupil Core. As proof of concept, we examine the effects of eccentric fixation on calibration accuracy and find that Pupil Core's existing eye tracking algorithm is robust to large fixation offsets. In addition, we demonstrate that the EyeRobot can simulate realistic eye movements like saccades and smooth pursuit that can be tracked using video-based eye tracking. These tests suggest that the EyeRobot, an easy to build and flexible tool, can aid with eye tracking validation and future algorithm development in healthy and compromised vision.

Quantitative Digitography Measures Motor Symptoms and Disease Progression in Parkinson's Disease.

BACKGROUND: Assessment of motor signs in Parkinson's disease (PD) requires an in-person examination. However, 50% of people with PD do not have access to a neurologist. Wearable sensors can provide remote measures of some motor signs but require continuous monitoring for several days. A major unmet need is reliable metrics of all cardinal motor signs, including rigidity, from a simple short active task that can be performed remotely or in the clinic. OBJECTIVE: Investigate whether thirty seconds of repetitive alternating finger tapping (RAFT) on a portable quantitative digitography (QDG) device, which measures amplitude and timing, produces reliable metrics of all cardinal motor signs in PD. METHODS: Ninety-six individuals with PD and forty-two healthy controls performed a thirty-second QDG-RAFT task and clinical motor assessment. Eighteen individuals were followed longitudinally with repeated assessments for an average of three years and up to six years. RESULTS: QDG-RAFT metrics showed differences between PD and controls and provided correlated metrics for total motor disability (MDS-UPDRS III) and for rigidity, bradykinesia, tremor, gait impairment, and freezing of gait (FOG). Additionally, QDG-RAFT tracked disease progression over several years off therapy and showed differences between akinetic-rigid and tremor-dominant phenotypes, as well as people with and without FOG. CONCLUSIONS: QDG is a reliable technology, which could be used in the clinic or remotely. This could improve access to care, allow complex remote disease management based on data received in real time, and accurate monitoring of disease progression over time in PD. QDG-RAFT also provides the comprehensive motor metrics needed for therapeutic trials.

Differential Effects of Pathological Beta Burst Dynamics Between Parkinson's Disease Phenotypes Across Different Movements.

Background: Resting state beta band (13-30 Hz) oscillations represent pathological neural activity in Parkinson's disease (PD). It is unknown how the peak frequency or dynamics of beta oscillations may change among fine, limb, and axial movements and different disease phenotypes. This will be critical for the development of personalized closed loop deep brain stimulation (DBS) algorithms during different activity states. Methods: Subthalamic (STN) and local field potentials (LFPs) were recorded from a sensing neurostimulator (Activa® PC + S, Medtronic PLC.) in fourteen PD participants (six tremor-dominant and eight akinetic-rigid) off medication/off STN DBS during 30 s of repetitive alternating finger tapping, wrist-flexion extension, stepping in place, and free walking. Beta power peaks and beta burst dynamics were identified by custom algorithms and were compared among movement tasks and between tremor-dominant and akinetic-rigid groups. Results: Beta power peaks were evident during fine, limb, and axial movements in 98% of movement trials; the peak frequencies were similar during each type of movement. Burst power and duration were significantly larger in the high beta band, but not in the low beta band, in the akinetic-rigid group compared to the tremor-dominant group. Conclusion: The conservation of beta peak frequency during different activity states supports the feasibility of patient-specific closed loop DBS algorithms driven by the dynamics of the same beta band during different activities. Akinetic-rigid participants had greater power and longer burst durations in the high beta band than tremor-dominant participants during movement, which may relate to the difference in underlying pathophysiology between phenotypes.

Lack of progression of beta dynamics after long-term subthalamic neurostimulation.

OBJECTIVE: To investigate the progression of neural and motor features of Parkinson's disease in a longitudinal study, after washout of medication and bilateral subthalamic nucleus deep brain stimulation (STN DBS). METHODS: Participants with clinically established Parkinson's disease underwent bilateral implantation of DBS leads (18 participants, 13 male) within the STN using standard functional frameless stereotactic technique and multi-pass microelectrode recording. Both DBS leads were connected to an implanted investigative sensing neurostimulator (Activa™ PC + S, Medtronic, PLC). Resting state STN local field potentials (LFPs) were recorded and motor disability, (the Movement Disorder Society-Unified Parkinson's Disease Rating Scale - motor subscale, MDS-UPDRS III) was assessed off therapy at initial programming, and after 6 months, 1 year, and yearly out to 5 years of treatment. The primary endpoint was measured at 3 years. At each visit, medication had been held for over 12/24 h and DBS was turned off for at least 60 min, by which time LFP spectra reached a steady state. RESULTS: After 3 years of chronic DBS, there were no increases in STN beta band dynamics (p = 0.98) but there were increases in alpha band dynamics (p = 0.0027, 25 STNs). Similar results were observed in a smaller cohort out to 5 years. There was no increase in the MDS-UPDRS III score. INTERPRETATION: These findings provide evidence that the beta oscillopathy does not substantially progress following combined STN DBS plus medication in moderate to advanced Parkinson's disease.

Eye, head, and gaze contributions to smooth pursuit in macular degeneration.

Macular degeneration (MD) often leads to the loss of the fovea and surrounding central visual field. This type of visual loss is very common and can present particular challenges for oculomotor tasks that may rely on the fovea. For certain tasks, individuals develop a new, eccentric fixational locus. Our previous work has shown that smooth pursuit is impaired in MD. However, extent of retinal lesion size and eccentricity of fixation do not directly contribute to changes in smooth pursuit gain. Oculomotor limitations due to eccentric eye position in the orbit may be another culprit. Here we test the hypothesis that deficits in smooth pursuit in MD would be reduced under head-unrestrained conditions. To that end, we examined eye, head, and gaze movements in eight individuals with MD and seven age-matched controls in response to a step-ramp pursuit stimulus. We found that despite variability across participants, both groups had similar smooth pursuit head movements (P = 0.76), while both had significantly higher pursuit gains in the head-restrained condition (P < 0.0001), suggesting that in older populations, head movements may lead to a decrease in pursuit gain. Furthermore, we did not find a correlation between eccentricity of fixation and amount of head displacement during the trial (P = 0.25), suggesting that eccentric eye position does not lead to higher reliance on head movements in smooth pursuit. Our finding that individuals with MD have lower pursuit gains, despite similar head movements as controls, suggests a difference in how MD affects mechanisms underlying eye versus head movements in smooth pursuit.NEW & NOTEWORTHY This article is the first to look at eye and head movements in observers with macular degeneration. It is the first to show that in older individuals, regardless of central field defect, freedom of head movement may reduce pursuit gain. Despite oculomotor limitations due to eccentric fixation, individuals with macular degeneration do not rely on head movements more than age-matched controls, with both groups having a similarly heterogenous eye and head movement strategy for pursuit.

Neuromodulation targets pathological not physiological beta bursts during gait in Parkinson's disease.

Freezing of gait (FOG) is a devastating axial motor symptom in Parkinson's disease (PD) leading to falls, institutionalization, and even death. The response of FOG to dopaminergic medication and deep brain stimulation (DBS) is complex, variable, and yet to be optimized. Fundamental gaps in the knowledge of the underlying neurobiomechanical mechanisms of FOG render this symptom one of the unsolved challenges in the treatment of PD. Subcortical neural mechanisms of gait impairment and FOG in PD are largely unknown due to the challenge of accessing deep brain circuitry and measuring neural signals in real time in freely-moving subjects. Additionally, there is a lack of gait tasks that reliably elicit FOG. Since FOG is episodic, we hypothesized that dynamic features of subthalamic (STN) beta oscillations, or beta bursts, may contribute to the Freezer phenotype in PD during gait tasks that elicit FOG. We also investigated whether STN DBS at 60 Hz or 140 Hz affected beta burst dynamics and gait impairment differently in Freezers and Non-Freezers. Synchronized STN local field potentials, from an implanted, sensing neurostimulator (Activa® PC + S, Medtronic, Inc.), and gait kinematics were recorded in 12 PD subjects, off-medication during forward walking and stepping-in-place tasks under the following randomly presented conditions: NO, 60 Hz, and 140 Hz DBS. Prolonged movement band beta burst durations differentiated Freezers from Non-Freezers, were a pathological neural feature of FOG and were shortened during DBS which improved gait. Normal gait parameters, accompanied by shorter bursts in Non-Freezers, were unchanged during DBS. The difference between the mean burst duration between hemispheres (STNs) of all individuals strongly correlated with the difference in stride time between their legs but there was no correlation between mean burst duration of each STN and stride time of the contralateral leg, suggesting an interaction between hemispheres influences gait. These results suggest that prolonged STN beta burst durations measured during gait is an important biomarker for FOG and that STN DBS modulated long not short burst durations, thereby acting to restore physiological sensorimotor information processing, while improving gait.

Subthalamic neural entropy is a feature of freezing of gait in freely moving people with Parkinson's disease.

The goal of this study was to investigate subthalamic (STN) neural features of Freezers and Non-Freezers with Parkinson's disease (PD), while freely walking without freezing of gait (FOG) and during periods of FOG, which were better elicited during a novel turning and barrier gait task than during forward walking. METHODS: Synchronous STN local field potentials (LFPs), shank angular velocities, and ground reaction forces were measured in fourteen PD subjects (eight Freezers) off medication, OFF deep brain stimulation (DBS), using an investigative, implanted, sensing neurostimulator (Activa® PC+S, Medtronic, Inc.). Tasks included standing still, instrumented forward walking, stepping in place on dual forceplates, and instrumented walking through a turning and barrier course. RESULTS: During locomotion without FOG, Freezers showed lower beta (13-30Hz) power (P=0.036) and greater beta Sample Entropy (P=0.032), than Non-Freezers, as well as greater gait asymmetry and arrhythmicity (P<0.05 for both). No differences in alpha/beta power and/or entropy were evident at rest. During periods of FOG, Freezers showed greater alpha (8-12Hz) Sample Entropy (P<0.001) than during walking without FOG. CONCLUSIONS: A novel turning and barrier course was superior to FW in eliciting FOG. Greater unpredictability in subthalamic beta rhythms was evident during stepping without freezing episodes in Freezers compared to Non-Freezers, whereas greater unpredictability in alpha rhythms was evident in Freezers during FOG. Non-linear analysis of dynamic neural signals during gait in freely moving people with PD may yield greater insight into the pathophysiology of FOG; whether the increases in STN entropy are causative or compensatory remains to be determined. Some beta LFP power may be useful for rhythmic, symmetric gait and DBS parameters, which completely attenuate STN beta power may worsen rather than improve FOG.

Subthalamic oscillations and phase amplitude coupling are greater in the more affected hemisphere in Parkinson's disease.

OBJECTIVE: Determine the incidence of resting state oscillations in alpha/beta, high frequency (HFO) bands, and their phase amplitude coupling (PAC) in a large cohort in Parkinson's disease (PD). METHODS: Intra-operative local field potentials (LFPs) from subthalamic nucleus (STN) were recorded from 100 PD subjects, data from 74 subjects were included in the analysis. RESULTS: Alpha/beta oscillations were evident in >99%, HFO in 87% and PAC in 98% of cases. Alpha/beta oscillations (P<0.01) and PAC were stronger in the more affected (MA) hemisphere (P=0.03). Alpha/beta oscillations were primarily found in 13-20Hz (low beta). Beta and HFO frequencies with the greatest coupling, were positively correlated (P=0.001). Tremor attenuated alpha (P=0.002) and beta band oscillations (P<0.001). CONCLUSIONS: STN alpha/beta band oscillations and PAC were evident in ⩾98% cases and were greater in MA hemisphere. Resting tremor attenuated underlying alpha/beta band oscillations. SIGNIFICANCE: Beta band LFP power may be used to drive adaptive deep brain stimulation (aDBS), augmented by a kinematic classifier in tremor dominant PD.

Sixty-hertz stimulation improves bradykinesia and amplifies subthalamic low-frequency oscillations.

BACKGROUND: The objective of this study was to investigate the hypothesis that attenuation of subthalamic nucleus (STN) alpha-/beta-band oscillations is causal to improvement in bradykinesia. METHODS: STN local field potentials from a sensing neurostimulator (Activa® PC+S; Medtronic, Inc.) and kinematics from wearable sensors were recorded simultaneously during 60- and 140-Hz deep brain stimulation (DBS) in 9 freely moving PD subjects (15 STNs) performing repetitive wrist flexion-extension. Kinematics were recorded during 20-Hz DBS in a subgroup. RESULTS: Both 60- and 140-Hz DBS improved the angular velocity and frequency of movement (P = 0.002 and P = 0.029, respectively, for 60 Hz; P < 0.001 and P < 0.001, respectively, for 140 Hz), but 60-Hz DBS did not attenuate beta-band power (13-30 Hz). In fact, 60-Hz DBS amplified alpha/low-beta (11-15 Hz, P = 0.007) and attenuated high-beta power (19-27 Hz, P < 0.001), whereas 140-Hz DBS broadly attenuated beta power (15-30 Hz, P < 0.001). Only 60-Hz DBS improved the regularity of angular range (P = 0.046) and 20-Hz DBS did not worsen bradykinesia. There was no correlation between beta-power modulation and bradykinesia. CONCLUSIONS: These novel results obtained from freely moving PD subjects demonstrated that both 140- and 60-Hz DBS improved bradykinesia and attenuated high beta oscillations; however, 60-Hz DBS amplified a subband of alpha/low-beta oscillations, and DBS at a beta-band frequency did not worsen bradykinesia. Based on recent literature, we suggest that both 140- and 60-Hz DBS decouple the cortico-STN hyperdirect pathway, whereas 60-Hz DBS increases coupling within striato-STN circuitry. These results inform future algorithms for closed-loop DBS in PD. © 2016 International Parkinson and Movement Disorder Society.

Subthalamic beta oscillations are attenuated after withdrawal of chronic high frequency neurostimulation in Parkinson's disease.

Subthalamic nucleus (STN) local field potential (LFP) recordings demonstrate beta (13-30Hz) band oscillations in Parkinson's disease (PD) defined as elevations of spectral power. The amount of attenuation of beta band power on therapeutic levels of high frequency (HF) deep brain stimulation (DBS) and/or dopaminergic medication has been correlated with the degree of improvement in bradykinesia and rigidity from the therapy, which has led to the suggestion that elevated beta band power is a marker of PD motor disability. A fundamental question has not been answered: whether there is a prolonged attenuation of beta band power after withdrawal of chronic HF DBS and whether this is related to a lack of progression or even improvement in the underlying motor disability. Until now, in human PD subjects, STN LFP recordings were only attainable in the peri-operative period and after short periods of stimulation. For the first time, using an investigational, implanted sensing neurostimulator (Activa® PC+S, Medtronic, Inc.), STN LFPs and motor disability were recorded/assessed after withdrawal of chronic (6 and 12month) HF DBS in freely moving PD subjects. Beta band power was similar within 14s and 60min after stimulation was withdrawn, suggesting that "off therapy" experiments can be conducted almost immediately after stimulation is turned off. After withdrawal of 6 and 12months of STN DBS, beta band power was significantly lower (P<0.05 at 6 and 12months) and off therapy UPDRS scores were better (P<0.05 at 12months) compared to before DBS was started. The attenuation in beta band power was correlated with improvement in motor disability scores (P<0.05). These findings were supported by evidence of a gradual increase in beta band power in two unstimulated STNs after 24months and could not be explained by changes in lead impedance. This suggests that chronic HF DBS exerts long-term plasticity in the sensorimotor network, which may contribute to a lack of progression in underlying motor disability in PD.

Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation.

BACKGROUND: Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner. METHODS: Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa(®) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states. RESULTS: Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P < 0.003, n = 14), and this was voltage dependent (P < 0.001). CONCLUSIONS: Beta power was conserved during resting and forward walking states and was attenuated in a voltage-dependent manner during 140-Hz DBS. Phenotype may be an important consideration if this is used for closed-loop DBS.

Sixty hertz neurostimulation amplifies subthalamic neural synchrony in Parkinson's disease.

High frequency subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal motor signs of Parkinson's disease (PD) and attenuates STN alpha/beta band neural synchrony in a voltage-dependent manner. While there is a growing interest in the behavioral effects of lower frequency (60 Hz) DBS, little is known about its effect on STN neural synchrony. Here we demonstrate for the first time that during intra-operative 60 Hz STN DBS, one or more bands of resting state neural synchrony were amplified in the STN in PD. We recorded intra-operative STN resting state local field potentials (LFPs) from twenty-eight STNs in seventeen PD subjects after placement of the DBS lead (model 3389, Medtronic, Inc.) before and during three randomized neurostimulation sets (130 Hz/1.35V, 130 Hz/2V, 60 Hz/2V). During 130 Hz/2V DBS, baseline (no DBS) STN alpha (8-12 Hz) and beta (13-35 Hz) band power decreased (N=14, P < 0.001 for both), whereas during 60 Hz/2V DBS, alpha band and peak frequency power increased (P = 0.012, P = 0.007, respectively). The effect of 60 Hz/2V DBS opposed that of power-equivalent (130 Hz/1.35V) DBS (alpha: P < 0.001, beta: P = 0.006). These results show that intra-operative 60 Hz STN DBS amplified whereas 130 Hz STN DBS attenuated resting state neural synchrony in PD; the effects were frequency-specific. We demonstrate that neurostimulation may be useful as a tool to selectively modulate resting state resonant bands of neural synchrony and to investigate its influence on motor and non-motor behaviors in PD and other neuropsychiatric diseases.

Arrhythmokinesis is evident during unimanual not bimanual finger tapping in Parkinson's disease.

BACKGROUND: Arrhythmokinesis, the variability in repetitive movements, is a fundamental feature of Parkinson's disease (PD). We hypothesized that unimanual repetitive alternating finger tapping (AFT) would reveal more arrhythmokinesis compared to bimanual single finger alternating hand tapping (SFT), in PD. METHODS: The variability of inter-strike interval (CVISI) and of amplitude (CVAMP) during AFT and SFT were measured on an engineered, MRI-compatible keyboard in sixteen PD subjects off medication and in twenty-four age-matched controls. RESULTS: The CVISI and CVAMP of the more affected (MA) and less affected (LA) sides in PD subjects were greater during AFT than SFT (P < 0.05). However, there was no difference between AFT and SFT for controls. Both CVISI and CVAMP were greater in the MA and LA hands of PD subjects versus controls during AFT (P < 0.01). The CVISI and CVAMP of the MA, but not the LA hand, were greater in PDs versus controls during SFT (P < 0.05). Also, AFT, but not SFT, detected a difference between the MA and LA hands of PDs (P < 0.01). CONCLUSIONS: Unimanual, repetitive alternating finger tapping brings out more arrhythmokinesis compared to bimanual, single finger tapping in PDs but not in controls. Arrhythmokinesis during unimanual, alternating finger tapping captured a significant difference between both the MA and LA hands of PD subjects and controls, whereas that during a bimanual, single finger tapping task only distinguished between the MA hand and controls. Arrhythmokinesis underlies freezing of gait and may also underlie the freezing behavior documented in fine motor control if studied using a unimanual alternating finger tapping task.