Dongpyo Lee

Simultaneous Neural and Movement Recording in Large-Scale Immersive Virtual Environments

Virtual reality (VR) allows precise control and manipulation of rich, dynamic stimuli that, when coupled with on-line motion capture and neural monitoring, can provide a powerful means both of understanding brain behavioral relations in the high dimensional world and of assessing and treating a variety of neural disorders. Here we present a system that combines state-of-the-art, fully immersive, 3D, multi-modal VR with temporally aligned electroencephalographic (EEG) recordings. The VR system is dynamic and interactive across visual, auditory, and haptic interactions, providing sight, sound, touch, and force. Crucially, it does so with simultaneous EEG recordings while subjects actively move about a 20×20 ft2 space. The overall end-to-end latency between real movement and its simulated movement in the VR is approximately 40 ms. Spatial precision of the various devices is on the order of millimeters. The temporal alignment with the neural recordings is accurate to within approximately 1 ms. This powerful combination of systems opens up a new window into brain-behavioral relations and a new means of assessment and rehabilitation of individuals with motor and other disorders.

Finger tapping movements of Parkinson's disease patients automatically rated using nonlinear delay differential equations

Parkinsons disease is a degenerative condition whose severity is assessed by clinical observations of motor behaviors. These are performed by a neurological specialist through subjective ratings of a variety of movements including 10-s bouts of repetitive finger-tapping movements. We present here an algorithmic rating of these movements which may be beneficial for uniformly assessing the progression of the disease. Finger-tapping movements were digitally recorded from Parkinsons patients and controls, obtaining one time series for every 10 s bout. A nonlinear delay differential equation, whose structure was selected using a genetic algorithm, was fitted to each time series and its coefficients were used as a six-dimensional numerical descriptor. The algorithm was applied to time-series from two different groups of Parkinsons patients and controls. The algorithmic scores compared favorably with the unified Parkinsons disease rating scale scores, at least when the latter adequately matched with ratings from the Hoehn and Yahr scale. Moreover, when the two sets of mean scores for all patients are compared, there is a strong (r = 0.785) and significant (p<0.0015) correlation between them.

Dopamine function and the efficiency of human movement

To sustain successful behavior in dynamic environments, active organisms must be able to learn from the consequences of their actions and predict action outcomes. One of the most important discoveries in systems neuroscience over the last 15 years has been about the key role of the neurotransmitter dopamine in mediating such active behavior. Dopamine cell firing was found to encode differences between the expected and obtained outcomes of actions. Although activity of dopamine cells does not specify movements themselves, a recent study in humans has suggested that tonic levels of dopamine in the dorsal striatum may in part enable normal movement by encoding sensitivity to the energy cost of a movement, providing an implicit “motor motivational” signal for movement. We investigated the motivational hypothesis of dopamine by studying motor performance of patients with Parkinson disease who have marked dopamine depletion in the dorsal striatum and compared their performance with that of elderly healthy adults. All participants performed rapid sequential movements to visual targets associated with different risk and different energy costs, countered or assisted by gravity. In conditions of low energy cost, patients performed surprisingly well, similar to prescriptions of an ideal planner and healthy participants. As energy costs increased, however, performance of patients with Parkinson disease dropped markedly below the prescriptions for action by an ideal planner and below performance of healthy elderly participants. The results indicate that the ability for efficient planning depends on the energy cost of action and that the effect of energy cost on action is mediated by dopamine.

Unconstrained reaching modulates eye–hand coupling

Abstract Eye–hand coordination is a crucial element of goal-directed movements. However, few studies have looked at the extent to which unconstrained movements of the eyes and hand made to targets influence each other. We studied human participants who moved either their eyes or both their eyes and hand to one of three static or flashed targets presented in 3D space. The eyes were directed, and hand was located at a common start position on either the right or left side of the body. We found that the velocity and scatter of memory-guided saccades (flashed targets) differed significantly when produced in combination with a reaching movement than when produced alone. Specifically, when accompanied by a reach, peak saccadic velocities were lower than when the eye moved alone. Peak saccade velocities, as well as latencies, were also highly correlated with those for reaching movements, especially for the briefly flashed targets compared to the continuous visible target. The scatter of saccade endpoints was greater when the saccades were produced with the reaching movement than when produced without, and the size of the scatter for both saccades and reaches was weakly correlated. These findings suggest that the saccades and reaches made to 3D targets are weakly to moderately coupled both temporally and spatially and that this is partly the result of the arm movement influencing the eye movement. Taken together, this study provides further evidence that the oculomotor and arm motor systems interact above and beyond any common target representations shared by the two motor systems.

REACHING TO PROPRIOCEPTIVELY DEFINED TARGETS IN PARKINSON’S DISEASE: EFFECTS OF DEEP BRAIN STIMULATION THERAPY

Deep brain stimulation of the subthalamic nucleus (STN DBS) provides a unique window into human brain function since it can reversibly alter the functioning of specific brain circuits. Basal ganglia-cortical circuits are thought to be excessively noisy in patients with Parkinsons disease (PD), based in part on the lack of specificity of proprioceptive signals in basal ganglia-thalamic-cortical circuits in monkey models of the disease. PD patients are known to have deficits in proprioception, but the effects are often subtle, with paradigms typically restricted to one or two joint movements in a plane. Moreover, the effects of STN DBS on proprioception are virtually unexplored. We tested the following hypotheses: first, that PD patients will show substantial deficits in unconstrained, multi-joint proprioception, and, second, that STN DBS will improve multi-joint proprioception. Twelve PD patients with bilaterally implanted electrodes in the subthalamic nucleus and 12 age-matched healthy subjects were asked to position the left hand at a location that was proprioceptively defined in 3D space with the right hand. In a second condition, subjects were provided visual feedback during the task so that they were not forced to rely on proprioception. Overall, with STN DBS switched off, PD patients showed significantly larger proprioceptive localization errors, and greater variability in endpoint localizations than the control subjects. Visual feedback partially normalized PD performance, and demonstrated that the errors in proprioceptive localization were not simply due to a difficulty in executing the movements or in remembering target locations. Switching STN DBS on significantly reduced localization errors from those of control subjects when patients moved without visual feedback relative to when they moved with visual feedback (when proprioception was not required). However, this reduction in localization errors without vision came at the cost of increased localization variability.

Anticipatory modulation of digit placement for grasp control is affected by Parkinson's disease.

Background Successful object manipulation relies on the ability to form and retrieve sensorimotor memories of digit forces and positions used in previous object lifts. Past studies of patients affected by Parkinsons disease (PD) have revealed that the basal ganglia play a crucial role in the acquisition and/or retrieval of sensorimotor memories for grasp control. Whereas it is known that PD impairs anticipatory control of digit forces during grasp, learning deficits associated with the planning of digit placement have yet to be explored. This question is motivated by recent work in healthy subjects revealing that anticipatory control of digit placement plays a crucial role for successful manipulation. Methodology/Principal Findings We asked ten PD patients off medication and ten age-matched controls to reach, grasp and lift an object whose center of mass (CM) was on the left, right or center. The only task requirement was to minimize object roll during lift. The CM remained the same across consecutive trials (blocked condition) or was altered from trial to trial (random condition). We hypothesized that impairment of the basal ganglia-thalamo-cortical circuits in PD patients would reduce their ability to anticipate digit placement appropriate to the CM location. Consequently, we predicted that PD patients would exhibit similar digit placement in the blocked vs. random conditions and produce larger peak object rolls than that of control subjects. In the blocked condition, PD patients exhibited significantly weaker modulation of fingertip contact points to CM location and larger object roll than controls (p<0.05 and p<0.01, respectively). Nevertheless, both controls and PD patients minimized object roll more in the blocked than in the random condition (p<0.01). Conclusions/Significance Our findings indicate that, even though PD patients may have a residual ability of anticipatory control of digit contact points and forces, they fail to implement a motor plan with the same degree of effectiveness as controls. We conclude that intact basal ganglia-thalamo-cortical circuits are necessary for successful sensorimotor learning of both grasp kinematics and kinetics required for dexterous hand-object interactions.

Resolving kinematic redundancy in target-reaching movements with and without external constraint

In the context of target-reaching movements that involve the arms, trunk and legs, we have delineated rules for apportioning motions amongst body segments, which would be valid for a range of target locations that require forward bending. We further attempted to determine whether the rules are altered when motion is restricted at the knee, obliging a re-apportioning of segment motions. For each participant moving with unrestricted joints to nine target locations, principal component analysis of the changes in orientation (i.e., excursions) of six chosen segments revealed that their coupling can be described by two effective degrees of freedom (DoFs), whose weighted combinations account for the segmental excursions. Investigating the similarities and differences among individuals, we found that a set of two effective DoFs could account for the segment excursions among the group of participants who flex their knees significantly, and another set of two for the group who do not. Comparing the motions with and without the knee joints braced, we found that for each individual participant a set of two (or in some cases three) effective DoFs derived from the unrestricted segment excursions could account well for the altered segment excursions when the participant reached for the targets with the knees restricted. Our findings imply that the redundancy of kinematic DoFs can be resolved by reliance on a small number of couplings of segmental excursions, and, in light of the robustness of these couplings against mechanical restriction of joint motion, suggest a neural rather than mechanical origin for them.

Prospective Optimization with Limited Resources.

The future is uncertain because some forthcoming events are unpredictable and also because our ability to foresee the myriad consequences of our own actions is limited. Here we studied how humans select actions under such extrinsic and intrinsic uncertainty, in view of an exponentially expanding number of prospects on a branching multivalued visual stimulus. A triangular grid of disks of different sizes scrolled down a touchscreen at a variable speed. The larger disks represented larger rewards. The task was to maximize the cumulative reward by touching one disk at a time in a rapid sequence, forming an upward path across the grid, while every step along the path constrained the part of the grid accessible in the future. This task captured some of the complexity of natural behavior in the risky and dynamic world, where ongoing decisions alter the landscape of future rewards. By comparing human behavior with behavior of ideal actors, we identified the strategies used by humans in terms of how far into the future they looked (their “depth of computation”) and how often they attempted to incorporate new information about the future rewards (their “recalculation period”). We found that, for a given task difficulty, humans traded off their depth of computation for the recalculation period. The form of this tradeoff was consistent with a complete, brute-force exploration of all possible paths up to a resource-limited finite depth. A step-by-step analysis of the human behavior revealed that participants took into account very fine distinctions between the future rewards and that they abstained from some simple heuristics in assessment of the alternative paths, such as seeking only the largest disks or avoiding the smaller disks. The participants preferred to reduce their depth of computation or increase the recalculation period rather than sacrifice the precision of computation.

Scaling and coordination deficits during dynamic object manipulation in Parkinson's disease

The ability to reach for and dynamically manipulate objects in a dexterous fashion requires scaling and coordination of arm, hand, and fingertip forces during reach and grasp components of this behavior. The neural substrates underlying dynamic object manipulation are not well understood. Insight into the role of basal ganglia-thalamocortical circuits in object manipulation can come from the study of patients with Parkinsons disease (PD). We hypothesized that scaling and coordination aspects of motor control are differentially affected by this disorder. We asked 20 PD patients and 23 age-matched control subjects to reach for, grasp, and lift virtual objects along prescribed paths. The movements were subdivided into two types, intensive (scaling) and coordinative, by detecting their underlying self-similarity. PD patients off medication were significantly impaired relative to control subjects for both aspects of movement. Intensive deficits, reduced peak speed and aperture, were seen during the reach. Coordinative deficits were observed during the reach, namely, the relative position along the trajectory at which peak speed and aperture were achieved, and during the lift, when objects tilted with respect to the gravitational axis. These results suggest that basal ganglia-thalamocortical circuits may play an important role in fine motor coordination. Dopaminergic therapy significantly improved intensive but not coordinative aspects of movements. These findings are consistent with a framework in which tonic levels of dopamine in the dorsal striatum encode the energetic cost of a movement, thereby improving intensive or scaling aspects of movement. However, repletion of brain dopamine levels does not restore finely coordinated movement.