fMRI assessment of upper extremity related brain activation with an MRI-compatible manipulandum

Purpose: Longitudinal studies to evaluate the effect of rehabilitative therapies require an objective, reproducible and quantitative means for testing function in vivo. An fMRI assessment tool for upper extremity related brain activation using an MRI-compatible manipulandum was developed and tested for use in neurorehabilitation research. Methods: Fifteen healthy, right-handed subjects participated in two fMRI sessions, which were three to four weeks apart. A block design paradigm, composed of three conditions of subject-passive movement, subject-active movement and rest, was employed for the fMRI recordings. During the rest condition, subjects simply held the device handle without applying any force or movement. The same type of auditory and visual instructions were given in all the three conditions, guiding the subjects to perform the motor tasks interactively with the MRI-compatible arm manipulandum. The tasks were controlled across the fMRI sessions. The subjects' brain activation was recorded by fMRI, and their behavioral performance was recorded by the manipulandum. The brain network activated by the subjects' interaction with the manipulandum was identified, and the reproducibility and reliability of the obtained activation were determined. Results: All subjects completed the trial protocol. Two subjects were excluded from analysis due to head motion artifacts. All passive movements were performed well. Four out of the total 780 active movements were missed by two subjects. Brain activation was found in the contralateral sensorimotor cortex, secondary somatosensory cortex and non-primary motor cortex as well as in subcortical areas in the thalamus, basal ganglia and the cerebellum. These activations were consistent across the two fMRI sessions. Conclusion: The MRI-compatible manipulandum elicited robust and reproducible brain activations in healthy subjects during the subject-active and subject-passive upper extremity motor tasks with a block design paradigm. This system is promising for many applications in neurorehabilitation research and may be useful for longitudinal studie

Design and Validation of a MR-compatible Pneumatic Manipulandum

The combination of functional MR imaging and novel robotic tools may provide unique opportunities to probe the neural systems underlying motor control and learning. Here, we describe the design and validation of a MR-compatible, 1 degree-of-freedom pneumatic manipulandum along with experiments demonstrating its safety and efficacy. We first validated the robot\u27s ability to apply computer-controlled loads about the wrist, demonstrating that it possesses sufficient bandwidth to simulate torsional spring-like loads during point-to-point flexion movements. Next, we verified the MR-compatibility of the device by imaging a head phantom during robot operation. We observed no systematic differences in two measures of MRI signal quality (signal/noise and field homogeneity) when the robot was introduced into the scanner environment. Likewise, measurements of joint angle and actuator pressure were not adversely affected by scanning. Finally, we verified device efficacy by scanning 20 healthy human subjects performing rapid wrist flexions against a wide range of spring-like loads. We observed a linear relationship between joint torque at peak movement extent and perturbation magnitude, thus demonstrating the robot\u27s ability to simulate spring-like loads in situ. fMRI revealed task-related activation in regions known to contribute to the control of movement including the left primary sensorimotor cortex and right cerebellum

Design and Validation of an MR Conditional Upper Extremity Evaluation System to Study Brain Activation Patterns after Stroke

Stroke is the third leading cause of death and second most frequent cause of disability in the United States. Stroke rehabilitation methods have been developed to induce the cortical reorganization and motor-relearning that leads to stroke recovery. In this thesis, we designed and developed an MR conditional upper extremity reach and grasp movement evaluation system for the stroke survivors to study their kinematic performances in reach and grasp movement and the relationship between kinematic metrics and the recovery level measured by clinical assessment methods. We also applied the system into the functional MRI experiments to identify the ability to study motor performance with the system inside the scanner and the reach, grasp and reach-to-grasp movements related brain activation patterns. Our experiments demonstrates that ours system is an MR conditional system in the 3.0 Tesla magnetic field. It is able to measure the stroke survivors\u27 reach and grasp movement in terms of grasp aperture and elbow joint angles. We used the Mann Whitney U test to examine the significant metrics in each tasks and principle component analysis to decide the major metrics that are associated with the outcome. Then we discovered better recovery scores are associated with these major kinematic metrics such as larger maximal velocity, larger mean velocity, larger maximal movement angle, and longer time to peak velocity. Additional to these metrics, time to maximal angle, time to target and time to peak velocity could also be used as additional metrics to help predict the recovery and assess robot-assisted therapy and optimize task-oriented rehabilitation strategy. We also identified the movement related brain activations in the motor and sensory areas as well as cerebellum in both normal and stroke survivors

The cortical activation pattern by a rehabilitation robotic hand: a functional NIRS study

Introduction: Clarification of the relationship between external stimuli and brain response has been an important topic in neuroscience and brain rehabilitation. In the current study, using functional near infrared spectroscopy (fNIRS), we attempted to investigate cortical activation patterns generated during execution of a rehabilitation robotic hand. Methods: Ten normal subjects were recruited for this study. Passive movements of the right fingers were performed using a rehabilitation robotic hand at a frequency of 0.5 Hz. We measured values of oxy-hemoglobin (HbO), deoxy-hemoglobin (HbR) and total-hemoglobin (HbT) in five regions of interest: the primary sensory-motor cortex (SM1), hand somatotopy of the contralateral SM1, supplementary motor area (SMA), premotor cortex (PMC), and prefrontal cortex (PFC). Results: HbO and HbT values indicated significant activation in the left SM1, left SMA, left PMC, and left PFC during execution of the rehabilitation robotic hand (uncorrected, p < 0.01). By contrast, HbR value indicated significant activation only in the hand somatotopic area of the left SM1 (uncorrected, p < 0.01). Conclusions: Our results appear to indicate that execution of the rehabilitation robotic hand could induce cortical activation. © 2014 Chang, Lee, Gu, Lee, Jin, Yeo, Seo and Jang.1

An fMRI Study on Supra-Spinal Contributions to Upper and Lower Limb Motor Control

The differences in the neural mechanisms contributing to upper and lower extremity movement have not been fully elucidated, and this might be a factor that leads to the ineffectiveness of rehabilitation techniques for most stroke survivors. It is unclear whether therapies designed for upper extremities should also be used for the lower extremities, and vice versa. In this study, fMRI was used to examine the supraspinal control of UE and LE movement in both neurologically intact individuals and people with post-stroke hemiparesis. We compared the location, volume, and intensity of brain activity associated with upper and lower extremity pedaling and unilateral flexion/extension of the hand and ankle. We hypothesized that if the supraspinal control strategies were the same for upper and lower extremities, then the pattern of brain activity would be the same across upper and lower limb movement. Alternatively, if the strategies were not the same, then brain activation would differ for each task. We found movement related brain activity in three cortical regions (S1, M1, and Brodmann Area 6) among healthy subjects. The location of activity complied with the somatotopic order in the sensorimotor cortex, but upper extremity produced greater activities during both pedaling and flexion/extension movement compared to the lower extremities. These observations suggested that the general brain activation strategies were similar between upper and lower extremities, while the involvement of cortical structures was more substantial for upper than lower limb movements. The four stroke subjects showed activity in the same regions as compared to the healthy group, yet the volume, intensity and symmetry of activation varied across the subjects and motor tasks. These observations suggested that there were multiple strategies for cortical reorganization after stroke and the controlling strategies for the effectors differed

Neural and Electromyographic Correlates of Wrist Posture Control

In identical experiments in and out of a MR scanner, we recorded functional magnetic resonance imaging and electromyographic correlates of wrist stabilization against constant and time-varying mechanical perturbations. Positioning errors were greatest while stabilizing random torques. Wrist muscle activity lagged changes in joint angular velocity at latencies suggesting trans-cortical reflex action. Drift in stabilized hand positions gave rise to frequent, accurately directed, corrective movements, suggesting that the brain maintains separate representations of desired wrist angle for feedback control of posture and the generation of discrete corrections. Two patterns of neural activity were evident in the blood-oxygenation-level-dependent (BOLD) time series obtained during stabilization. A cerebello-thalamo-cortical network showed significant activity whenever position errors were present. Here, changes in activation correlated with moment-by-moment changes in position errors (not force), implicating this network in the feedback control of hand position. A second network, showing elevated activity during stabilization whether errors were present or not, included prefrontal cortex, rostral dorsal premotor and supplementary motor area cortices, and inferior aspects of parietal cortex. BOLD activation in some of these regions correlated with positioning errors integrated over a longer time-frame consistent with optimization of feedback performance via adjustment of the behavioral goal (feedback setpoint) and the planning and execution of internally generated motor actions. The finding that nonoverlapping networks demonstrate differential sensitivity to kinematic performance errors over different time scales supports the hypothesis that in stabilizing the hand, the brain recruits distinct neural systems for feedback control of limb position and for evaluation/adjustment of controller parameters in response to persistent errors

EEG During Motor Tasks in Stroke: The Effects of Remote Ischemic Conditioning and Fatigue on Brain Activity

This dissertation aimed to use electroencephalography (EEG) to identify the effects of fatigue and remote ischemic conditioning on brain activity. Lesions due to stroke directly or indirectly affect regions of the brain and the descending corticospinal pathways. Cortical reorganization and alternate descending neural pathways are used during recovery from stroke as compensation mechanisms for motor deficits. These mechanisms exacerbate the deficits by worsening the ability to terminate muscle activity, individuate muscles for fine motor control and minimize abnormal muscle synergy and coactivation patterns to conserve resources during movement. Even though imaging and muscle activation studies have documented the existence and impact of cortical reorganization and the use of alternate descending pathways, temporal changes in cortical activation during long motor tasks are not well understood. We expect that potential changes in cerebrovascular function and physiology of brain metabolism after stroke might impact the ability of the brain to produce extended activity. We used EEG for its high temporal resolution compared to other imaging modalities to document temporal changes in brain activity when people with stroke performed various motor tasks. We first documented the changes in activation during and at the end of a simple cued finger tap task between people with stroke and controls. We then pushed the neuromuscular system to its limits using a fatiguing contraction of the wrist to visualize changes in brain activation patterns after extended muscle contraction. Lastly, we tested a neurorehabilitation therapy protocol, remote ischemic conditioning (RIC), that has shown functional improvements in people with stroke to determine if cortical activation is changed during a complex, multijoint visuomotor task. The results show that cortical activation in people with stroke is divergent from controls. People with stroke continue brain activation at the end of a simple task but cannot increase activation at the end of a fatiguing task. RIC, however, increases activation during a multijoint elbow/shoulder task. This research has improved our understanding of brain activation during a simple task and in response to fatigue in people with stroke. The knowledge of cortical changes due to RIC demonstrates the therapy’s ability to “prime” the brain for neurorehabilitation, which might lead to better therapeutic outcomes post-rehabilitation in people with stroke

EEG Characterization of Sensorimotor Networks: Implications in Stroke

The purpose of this dissertation was to use electroencephalography (EEG) to characterize sensorimotor networks and examine the effects of stroke on sensorimotor networks. Sensorimotor networks play an essential role in completion of everyday tasks, and when damaged, as in stroke survivors, the successful completion of seemingly simple motor tasks becomes fantasy. When sensorimotor networks are impaired as a result of stroke, varying degrees of sensorimotor deficits emerge, most often including loss of sensation and difficulty generating upper extremity movements. Although sensory therapies, such as the application of tendon vibration, have been shown to reduce the sensorimotor deficits after stroke, the underlying sensorimotor mechanisms associated with such improvements are unknown. While sensorimotor networks have been studied extensively, unanswered questions still surround their role in basic control paradigms and how their role changes after stroke. EEG provides a way to probe the high-speed temporal dynamics of sensorimotor networks that other more common imaging modalities lack. Sensorimotor network function was examined in controls during a task designed to differentiate potential mechanisms of arm stabilization and determine to what degree the sensorimotor network is involved. After sensorimotor network function was characterized in controls, we examined the effect of stroke on the sensorimotor network during rest and described the reorganization that occurs. Lastly, we explored tendon vibration as a sensory therapy for stroke survivors and determined if sensorimotor network mechanisms underlie improvements in arm tracking performance due to wrist tendon vibration. We observed cortical activity and connectivity that suggests sensorimotor networks are involved in the control of arm stability, cortical networks reorganize to more asymmetric, local networks after stroke, and tendon vibration normalizes sensorimotor network activity and connectivity during motor control after stroke. This dissertation was among the first studies using EEG to characterize the high-speed temporal dynamics of sensorimotor networks following stroke. This new knowledge has led to a better understanding of how sensorimotor networks function under ordinary circumstances as well as extreme situations such as stroke and revealed previously unknown mechanisms by which tendon vibration improves motor control in stroke survivors, which will lead to better therapeutic approaches

An fMRI Study of Command Following and Communication Using Overt and Covert Motor Responses: Implications for Disorders of Consciousness

We used functional magnetic resonance imaging (fMRI) to explore neural mechanisms of command following or communicating using executed or imagined movements, in order to understand why most covertly aware patients cannot communicate. 15 healthy participants executed or imagined arm movements that were either selected by them or pre-determined. We also explored non-volitional motor activity by passively moving participants. Response selection involved greater activity in high-level associative areas in frontal and parietal regions than following commands. Furthermore, there was no interaction between response and modality. Neural activity during passive movement exceeded that of active (volitional) movement in sensorimotor regions. Our results suggest that the ability to select between motor responses is not dependent on how that response is expressed (via motor execution/imagery). They also suggest a potential neural basis of the distinction in cognitive abilities seen in DOCs. Finally, passive movement could be applied to study unresponsive patients’ motor systems