Background: Cortical damage after stroke can drastically impair sensory and motor function of the upper limb, affecting the execution of activities of daily living and quality of life. Motor impairment after stroke has been thoroughly studied, however sensory impairment and its relation to movement control has received less attention. Integrity of the somatosensory system is essential for feedback control of human movement, and compromised integrity due to stroke has been linked to sensory impairment. Methods: The goal of this study is to assess the integrity of the somatosensory system in individuals with chronic hemiparetic stroke with different levels of sensory impairment, through a combination of robotic joint manipulation and high-density electroencephalogram (EEG). A robotic wrist manipulator applied continuous periodic disturbances to the affected limb, providing somatosensory (proprioceptive and tactile) stimulation while challenging task execution. The integrity of the somatosensory system was evaluated during passive and active tasks, defined as ‘relaxed wrist’ and ‘maintaining 20% maximum wrist flexion’, respectively. The evoked cortical responses in the EEG were quantified using the power in the averaged responses and their signal-to-noise ratio. Results: Thirty individuals with chronic hemiparetic stroke and ten unimpaired individuals without stroke participated in this study. Participants with stroke were classified as having severe, mild, or no sensory impairment, based on the Erasmus modification of the Nottingham Sensory Assessment. Under passive conditions, wrist manipulation resulted in contralateral cortical responses in unimpaired and chronic stroke participants with mild and no sensory impairment. In participants with severe sensory impairment the cortical responses were strongly reduced in amplitude, which related to anatomical damage. Under active conditions, participants with mild sensory impairment showed reduced responses compared to the passive condition, whereas unimpaired and chronic stroke participants without sensory impairment did not show this reduction. Conclusions: Robotic continuous joint manipulation allows studying somatosensory cortical evoked responses during the execution of meaningful upper limb control tasks. Using such an approach it is possible to quantitatively assess the integrity of sensory pathways; in the context of movement control this provides additional information required to develop more effective neurorehabilitation therapies.@en

Cortical responses to continuous stimuli as recorded using either magneto- or electroencephalography (EEG) have shown power at harmonics of the stimulated frequency, indicating nonlinear behavior. Even though the selection of analysis techniques depends on the linearity of the system under study, the importance of nonlinear contributions to cortical responses has not been formally addressed.The goal of this paper is to quantify the nonlinear contributions to the cortical response obtained fromcontinuous sensory stimulation. EEG was used to record the cortical response evoked by continuousmovement of the wrist joint of healthy subjects applied with a robotic manipulator. Multisine stimulus signals (i.e., the sum of several sinusoids) elicit a periodic cortical response and allowto assess the nonlinear contributions to the response.Wrist dynamics (relation between joint angle and torque) were successfully linearized, explaining 99% of the response. In contrast, the cortical response revealed a highly nonlinear relation; where most power ( ∼ 80%) occurred at non-stimulated frequencies. Moreover, only 10% of the response could be explained using a nonparametric linear model. These results indicate that the recorded evoked cortical responses are governed by nonlinearities and that linear methods do not suffice when describing the relation between mechanical stimulus and cortical response.@en

Joint manipulation elicits a response from the sensors in the periphery which, via the spinal cord, arrives in the cortex. The average evoked cortical response recorded using electroencephalography was shown to be highly nonlinear; a linear model can only explain 10% of the variance of the evoked response, and over 80% of the response is generated by nonlinear behavior. The goal of this study is to obtain a nonparametric nonlinear dynamic model, which can consistently explain the recorded cortical response requiring little a priori assumptions about model structure. Wrist joint manipulation was applied in ten healthy participants during which their cortical activity was recorded and modeled using a truncated Volterra series. The obtained models could explain 46% of the variance of the evoked cortical response, thereby demonstrating the relevance of nonlinear modeling. The high similarity of the obtained models across participants indicates that the models reveal common characteristics of the underlying system. The models show predominantly high-pass behavior, which suggests that velocity-related information originating from the muscle spindles governs the cortical response. In conclusion, the nonlinear modeling approach using a truncated Volterra series with regularization, provides a quantitative way of investigating the sensorimotor system, offering insight into the underlying physiology.@en

A continuous somatosensory stimulation evokes a steady state response in the cortex, which can be measured using electroencephalography. We applied mechanical multisine stimulation of the wrist to investigate the properties of the steady state response in the frequency domain. Our results show a response in the contralateral sensorimotor cortex at the stimulated frequencies yet with more power at their even harmonics, indicating substantial nonlinear behavior. The observed cortical response to a mechanical somatosensory stimulation is time invariant and nonlinear, however shows no subharmonics, allowing for the application of a broad range of (non)linear system identification tools.@en

Dedicated pairs of isometric wrist flexion tasks, with and without visual feedback of the exerted torque, were designed to target activation of the CBL and BG in healthy subjects during functional magnetic resonance imaging (fMRI). Selective activation of the cerebellum (CBL) and basal ganglia (BG), often implicated in movement disorders such as tremor and dystonia, may help identify pathological changes and expedite diagnosis. A prototyped MR-compatible wrist torque measurement device, free of magnetic and conductive materials, allowed safe execution of tasks during fMRI without causing artifacts. A significant increase of activity in CBL and BG was found in healthy volunteers during a constant torque task with visual feedback compared to a constant torque task without visual feedback. This study shows that specific pairs of motor tasks using MR-compatible equipment at the wrist allow for targeted activation of CBL and BG, paving a new way for research into the pathophysiology of movement disorders.@en

Dedicated pairs of isometric wrist flexion tasks, with and without visual feedback of the exerted torque, were designed to target activation of the CBL and BG in healthy subjects during functional magnetic resonance imaging (fMRI). Selective activation of the cerebellum (CBL) and basal ganglia (BG), often implicated in movement disorders such as tremor and dystonia, may help identify pathological changes and expedite diagnosis. A prototyped MR-compatible wrist torque measurement device, free of magnetic and conductive materials, allowed safe execution of tasks during fMRI without causing artifacts. A significant increase of activity in CBL and BG was found in healthy volunteers during a constant torque task with visual feedback compared to a constant torque task without visual feedback. This study shows that specific pairs of motor tasks using MR-compatible equipment at the wrist allow for targeted activation of CBL and BG, paving a new way for research into the pathophysiology of movement disorders.@en

Cortical damage after a stroke often affects movement control, resulting in impairments such as paresis and synergies. Although some recover, most stroke survivors are left with reduced function of the upper limb, which has a severe impact on their activities of daily living. People who have suffered a stroke demonstrate heterogeneous impairments due to large variability in lesion location and extent; thus, rehabilitation should be tailored to each individual. Design and evaluation of rehabilitation programs requires a thorough understanding of the healthy and impaired sensorimotor system. Impairments to the motor system have been extensively investigated. On the contrary, the sensory aspects of impaired motor control have received less attention. This thesis intends to characterize the relation between somatosensory information from the periphery and the corresponding cortical responses using electroencephalography (EEG).@en