Parkinson's disease patients show impaired corrective grasp control and eye-hand coupling when reaching to grasp virtual objects.

The effect of Parkinson's disease (PD) on hand-eye coordination and corrective response control during reach-to-grasp tasks remains unclear. Moderately impaired PD patients (n=9) and age-matched controls (n=12) reached to and grasped a virtual rectangular object, with haptic feedback provided to the thumb and index fingertip by two 3-degree of freedom manipulanda. The object rotated unexpectedly on a minority of trials, requiring subjects to adjust their grasp aperture. On half the trials, visual feedback of finger positions disappeared during the initial phase of the reach, when feedforward mechanisms are known to guide movement. PD patients were tested without (OFF) and with (ON) medication to investigate the effects of dopamine depletion and repletion on eye-hand coordination online corrective response control. We quantified eye-hand coordination by monitoring hand kinematics and eye position during the reach. We hypothesized that if the basal ganglia are important for eye-hand coordination and online corrections to object perturbations, then PD patients tested OFF medication would show reduced eye-hand spans and impoverished arm-hand coordination responses to the perturbation, which would be further exasperated when visual feedback of the hand was removed. Strikingly, PD patients tracked their hands with their gaze, and their movements became destabilized when having to make online corrective responses to object perturbations exhibiting pauses and changes in movement direction. These impairments largely remained even when tested in the ON state, despite significant improvement on the Unified Parkinson's Disease Rating Scale. Our findings suggest that basal ganglia-cortical loops are essential for mediating eye-hand coordination and adaptive online responses for reach-to-grasp movements, and that restoration of tonic levels of dopamine may not be adequate to remediate this coordinative nature of basal ganglia-modulated function.

Mechanisms of neural reorganization in chronic stroke subjects after virtual reality training.

This study investigates patterns of brain reorganization in chronic stroke subjects after two weeks of robot-assisted arm and hand training in virtual reality (VR). Four subjects were studied with event-related fMRI while doing simple paretic hand finger movements before (double baseline) and after training. Bilateral hand movements were recorded and used to provide real-time feedback to subjects during scanning to eliminate performance confounds on fMRI results. The kinematic parameters of each movement were also used in the general linear model with the BOLD signal to investigate training-induced changes in neuromotor coupling. Univariate analysis showed an increase in BOLD signal in the ipsilesional hemisphere in two subjects and a decrease in activity in the other two subjects. Seed voxel based functional connectivity analysis revealed an increase in connectivity between ipsilesional motor cortex and bilateral sensorimotor cortex during finger movements in all four subjects. Hemispheric laterality index values showed a tendency to decrease reflecting a reduction in the over-dominance of the contralesional hemisphere. The study is novel in terms of 1) tracking finger movement during a motor task in the scanner, 2) monitoring motor performance during the experiment and 3) giving online visual feedback of subjects' movement. This pilot study introduces a novel approach to study neural plasticity by combining measures of regional intensity, interregional interactions (using functional connectivity analysis and hemispheric laterality index), and modulation in the strength of neuromotor coupling.

A virtual reality-based system integrated with fmri to study neural mechanisms of action observation-execution: a proof of concept study.

PURPOSE: Emerging evidence shows that interactive virtual environments (VEs) may be a promising tool for studying sensorimotor processes and for rehabilitation. However, the potential of VEs to recruit action observation-execution neural networks is largely unknown. For the first time, a functional MRI-compatible virtual reality system (VR) has been developed to provide a window into studying brain-behavior interactions. This system is capable of measuring the complex span of hand-finger movements and simultaneously streaming this kinematic data to control the motion of representations of human hands in virtual reality. METHODS: In a blocked fMRI design, thirteen healthy subjects observed, with the intent to imitate (OTI), finger sequences performed by the virtual hand avatar seen in 1st person perspective and animated by pre-recorded kinematic data. Following this, subjects imitated the observed sequence while viewing the virtual hand avatar animated by their own movement in real-time. These blocks were interleaved with rest periods during which subjects viewed static virtual hand avatars and control trials in which the avatars were replaced with moving non-anthropomorphic objects. RESULTS: We show three main findings. First, both observation with intent to imitate and imitation with real-time virtual avatar feedback, were associated with activation in a distributed frontoparietal network typically recruited for observation and execution of real-world actions. Second, we noted a time-variant increase in activation in the left insular cortex for observation with intent to imitate actions performed by the virtual avatar. Third, imitation with virtual avatar feedback (relative to the control condition) was associated with a localized recruitment of the angular gyrus, precuneus, and extrastriate body area, regions which are (along with insular cortex) associated with the sense of agency. CONCLUSIONS: Our data suggest that the virtual hand avatars may have served as disembodied training tools in the observation condition and as embodied "extensions" of the subject's own body (pseudo-tools) in the imitation. These data advance our understanding of the brain-behavior interactions when performing actions in VE and have implications in the development of observation- and imitation-based VR rehabilitation paradigms.

Innovative approaches to the rehabilitation of upper extremity hemiparesis using virtual environments.

AIM: Upper-extremity interventions for hemiparesis are a challenging aspect of stroke rehabilitation. Purpose of this paper is to report the feasibility of using virtual environments (VEs) in combination with robotics to assist recovery of hand-arm function and to present preliminary data demonstrating the potential of using sensory manipulations in VE to drive activation in targeted neural regions. METHODS: We trained 8 subjects for 8 three hour sessions using a library of complex VE's integrated with robots, comparing training arm and hand separately to training arm and hand together. Instrumented gloves and hand exoskeleton were used for hand tracking and haptic effects. Haptic Master robotic arm was used for arm tracking and generating three-dimensional haptic VEs. To investigate the use of manipulations in VE to drive neural activations, we created a "virtual mirror" that subjects used while performing a unimanual task. Cortical activation was measured with functional MRI (fMRI) and transcranial magnetic stimulation. RESULTS: Both groups showed improvement in kinematics and measures of real-world function. The group trained using their arm and hand together showed greater improvement. In a stroke subject, fMRI data suggested virtual mirror feedback could activate the sensorimotor cortex contralateral to the reflected hand (ipsilateral to the moving hand) thus recruiting the lesioned hemisphere. CONCLUSION: Gaming simulations interfaced with robotic devices provide a training medium that can modify movement patterns. In addition to showing that our VE therapies can optimize behavioral performance, we show preliminary evidence to support the potential of using specific sensory manipulations to selectively recruit targeted neural circuits.

Beyond grasping: representation of action in human anterior intraparietal sulcus.

The fronto-parietal network has been implicated in the processing of multisensory information for motor control. Recent methodological advances with both fMRI and TMS provide the opportunity to dissect the functionality of this extensive network in humans and may identify distinct contributions of local neural populations within this circuit that are not only related to motor planning, but to goal oriented behavior as a whole. Herein, we review and make parallels between experiments in monkeys and humans on a broad array of motor as well as non-motor tasks in order to characterize the specific contribution of a region in the parietal lobe, the anterior intraparietal sulcus (aIPS). The intent of this article is to review: (1) the historical perspectives on the parietal lobe, particularly the aIPS; (2) extend and update these perspectives based on recent empirical data; and (3) discuss the potential implications of the revised functionality of the aIPS in relationship to complex goal oriented behavior and social interaction. Our contention is that aIPS is a critical node within a network involved in the higher order dynamic control of action, including representation of intended action goals. These findings may be important not only for guiding the design of future experiments investigating related issues but may also have valuable utility in other fields, such social neuroscience and biomedical engineering.

Dopamine replacement therapy does not restore the ability of Parkinsonian patients to make rapid adjustments in motor strategies according to changing sensorimotor contexts.

The ability of dopamine replacement to restore rapid motor adjustments in Parkinson's disease (PD) was investigated. Medicated and non-medicated patients performed finger-to-nose movements while simultaneously bending the trunk forward, without vision. Trunk motion was blocked unexpectedly, necessitating rapid adjustments in arm trajectories. Patients exhibited irregular hand paths, plateaus in hand velocity, and prolonged movement times, which were significantly greater in perturbed trials. Medication improved kinematics but perturbation-induced disturbances persisted and did not approximate the levels of non-perturbed trials nor those of controls. Dopaminergic replenishment in PD may therefore have limited restorative benefits for rapid context-specific motor control.

Deficits in adaptive upper limb control in response to trunk perturbations in Parkinson's disease.

The ability of patients with Parkinson's disease (PD) to compensate for unexpected perturbations remains relatively unexplored. To address this issue PD subjects were required to compensate at the arm for an unexpected mechanical perturbation of the trunk while performing a trunk-assisted reach. Twelve healthy and nine PD subjects (off medication) performed trunk-assisted reaching movements without vision or knowledge of results to a remembered target in the ipsilateral (T1) or contralateral (T2) workspace. On 60% of the trials trunk motion was unrestrained (free condition). On the remaining 40% of randomly selected trials trunk motion was arrested at movement onset (blocked condition). If subjects appropriately changed arm joint angles to compensate for the trunk arrest, there should be spatial and temporal invariance in the hand trajectories and in the endpoint errors across conditions. The control group successfully changed their arm configuration in a context-dependent manner which resulted in invariant hand trajectory profiles across the free and blocked conditions. More so, they initiated these changes rapidly after the trunk perturbation (group mean 70 ms). Some PD subjects were unable to maintain invariant hand paths and movement errors across conditions. Their hand velocity profiles were also more variable relative to those of the healthy subjects in the blocked-trunk trials but not in the free-trunk trials. Furthermore, the latency of compensatory changes in arm joint angles in movements toward T1 was longer in the PD group (group mean 153 ms). Finally, PD subjects' arm and trunk were desynchronized at movement onset, confirming our previous findings and consistent with PD patients' known problems in the sequential or parallel generation of different movement components. The findings that individual PD subjects were unsuccessful or delayed in producing context-dependent responses at the arm to unexpected perturbations of the trunk suggests that the basal ganglia are important nodes in the organization of adaptive behavior.

Arm-trunk coordination in the absence of proprioception.

During trunk-assisted reaching to targets placed within arm's length, the influence of trunk motion on the hand trajectory is compensated for by changes in the arm configuration. The role of proprioception in this compensation was investigated by analyzing the movements of 2 deafferented and 12 healthy subjects. Subjects reached to remembered targets (placed approximately 80 degrees ipsilateral or approximately 45 degrees contralateral to the sagittal midline) with an active forward movement of the trunk produced by hip flexion. In 40% of randomly selected trials, trunk motion was mechanically blocked. No visual feedback was provided during the experiment. The hand trajectory and velocity profiles of healthy subjects remained invariant whether or not the trunk was blocked. The invariance was achieved by changes in arm interjoint coordination that, for reaches toward the ipsilateral target, started as early as 50 ms after the perturbation. Both deafferented subjects exhibited considerable, though incomplete, compensation for the effects of the perturbation. Compensation was more successful for reaches to the ipsilateral target. Both deafferented subjects showed invariance between conditions (unobstructed or blocked trunk motion) in their hand paths to the ipsilateral target, and one did to the contralateral target. For the other deafferented subject, hand paths in the two types of trials began to deviate after about 50% into the movement, because of excessive elbow extension. In movements to the ipsilateral target, when deafferented subjects compensated successfully, the changes in arm joint angles were initiated as early as 50 ms after the trunk perturbation, similar to healthy subjects. Although the deafferented subjects showed less than ideal compensatory control, they compensated to a remarkably large extent given their complete loss of proprioception. The presence of partial compensation in the absence of vision and proprioception points to the likelihood that not only proprioception but also vestibulospinal pathways help mediate this compensation.