Inhibition of Parkinsonian tremor with cutaneous afferent evoked by transcutaneous electrical nerve stimulation.

BACKGROUND: Recent study suggests that tremor signals are transmitted by way of multi-synaptic corticospinal pathway. Neurophysiological studies have also demonstrated that cutaneous afferents exert potent inhibition to descending motor commands by way of spinal interneurons. We hypothesize in this study that cutaneous afferents could also affect the transmission of tremor signals, thus, inhibit tremor in patients with PD. METHODS: We tested this hypothesis by activating cutaneous afferents in the dorsal hand skin innervated by superficial radial nerve using transcutaneous electrical nerve stimulation (TENS). Eight patients with PD having tremor dominant symptom were recruited to participate in this study using a consistent experimental protocol for tremor inhibition. Resting tremor and electromyogram (EMG) of muscles in the upper extremity of these subjects with PD were recorded, while surface stimulation was applied to the dorsal skin of the hand. Fifteen seconds of data were recorded for 5 s prior to, during and post stimulation. Power spectrum densities (PSDs) of tremor and EMG signals were computed for each data segment. The peak values of PSDs in three data segments were compared to detect evidence of tremor inhibition. RESULTS: At stimulation intensity from 1.5 to 1.75 times of radiating sensation threshold, apparent suppressions of tremor at wrist, forearm and upper arm and in the EMGs were observed immediately at the onset of stimulation. After termination of stimulation, tremor and rhythmic EMG bursts reemerged gradually. Statistical analysis of peak spectral amplitudes showed a significant difference in joint tremors and EMGs during and prior to stimulation in all 8 subjects with PD. The average percentage of suppression was 61.56% in tremor across all joints of all subjects, and 47.97% in EMG of all muscles. The suppression appeared to occur mainly in distal joints and muscles. There was a slight, but inconsistent effect on tremor frequency in the 8 patients with PD tested. CONCLUSIONS: Our results provide direct evidence that tremor in the upper extremity of patients with PD can be inhibited to a large extent with evoked cutaneous reflexes via surface stimulation of the dorsal hand skin area innervated by the superficial radial nerve.

Contribution of inter-muscular synchronization in the modulation of tremor intensity in Parkinson's disease.

BACKGROUND: Involuntary central oscillations at single and double tremor frequencies drive the peripheral neuromechanical system of muscles and joints to cause tremor in Parkinson's disease (PD). The central signal of double tremor frequency was found to correlate more directly to individual muscle EMGs (Timmermann et al. 2003). This study is aimed at investigating what central components of oscillation contribute to inter-muscular synchronization in a group of upper extremity muscles during tremor in PD patients. METHODS: 11 idiopathic, tremor dominant PD subjects participated in this study. Joint kinematics during tremor in the upper extremity was recorded along with EMGs of six upper arm muscles using a novel experimental apparatus. The apparatus provided support for the upper extremity on a horizontal surface with reduced friction, so that resting tremor in the arm can be recorded with a MotionMonitor II system. In each subject, the frequencies of rhythmic firings in upper arm muscles were determined using spectral analysis. Paired and pool-averaged coherence analyses of EMGs for the group of muscles were performed to correlate the level of inter-muscular synchronization to tremor amplitudes at shoulder and elbow. The phase shift between synchronized antagonistic muscle pairs was calculated to aid coherence analysis in the muscle pool. RESULTS: Recorded EMG revealed that rhythmic firings were present in most recorded muscles, which were either synchronized to form phase-locked bursting cycles at a subject specific frequency, or unsynchronized with a random phase distribution. Paired coherence showed a stronger synchronization among a subset of recorded arm muscles at tremor frequency than that at double tremor frequency. Furthermore, the number of synchronized muscles in the arm was positively correlated to tremor amplitudes at elbow and shoulder. Pool-averaged coherence at tremor frequency also showed a better correlation with the amplitude of resting tremor than that of double tremor frequency, indicating that the neuromechanical coupling in peripheral neuromuscular system was stronger at tremor frequency. CONCLUSIONS: Both paired and pool-averaged coherences are more consistent indexes to correlate to tremor intensity in a group of upper extremity muscles of PD patients. The central drive at tremor frequency contributes mainly to synchronize peripheral muscles in the modulation of tremor intensity.

An Experimental Protocol for Evaluating Pulse Width Modulation Ranges of Evoked Tactile Sensory Feedback in Amputees.

The objective of this study is to develop an experimental protocol to define the range of modulation for different sensory modalities elicited by transcutaneous electrical nerve stimulation (TENS) in amputees with evoked tactile sensation (ETS). Modulation ranges of sensory modalities, such as vibration, buzz, tingling etc., are essential for designing a coding strategy for incoming sensory information from prosthetic hands for each amputee. Here, the modulation ranges of different modalities in pulse width at fixed stimulus frequencies were evaluated. Four healthy subjects and three transradial amputee subjects were recruited to participate in this preliminary test. A single skin site in healthy subjects and five finger areas of the projected finger map (PFM) on the stump skin in amputee subjects were stimulated for evaluation. Then, a finger identification test was conducted to show the feasibility of this sensory coding strategy in one amputee subject. The sensitivity of different sensory modalities was also measured to quantify the minimum pulse width change that subject could distinguish. Results showed that vibration and buzz sensations had wider modulation ranges in pulse width for both healthy and amputee subjects at 20Hz and 50Hz of stimulation, respectively. The average accuracy of finger identification was 91.66% in the amputee subject. The minimum pulse width changes distinguishable for both vibration and buzz sensation were below 20 (us). Results indicated that the protocol of evaluating pulse width modulation ranges for different sensory modalities was effective, and the coding strategy could provide accurate finger-specific sensory information for amputees with ETS.Clinical Relevance- This protocol establishes a guideline for customizing the coding strategy of evoked tactile sensory feedback for each amputee.

Neural Correlation between Evoked Tactile Sensation and Central Activities in the Somatosensory Cortex.

Evoked tactile sensation (ETS) is induced with stimulation of areas in the projected finger map (PFM) in the stump skin of forearm amputees. The aim of the present study is to further explore the neural correlation of the ETS with central activities in the somatosensory cortex (SI). Two forearm amputees were recruited to participate in this study. The neuroimaging technique of Magnetoencephalography (MEG) was employed to reveal the activities in the somatosensory cortex (SI), while the thumb and little finger areas in the PFM and the thumb and little finger of the contralateral hand were stimulated with a bi-phasic current pulse train. In one subject, local anesthesia was applied to the skin areas of the thumb and little finger of the PFM to examine the effects of blocking peripheral nerve transmission on the central activities in SI. Results obtained in the two subjects indicated that stimulation of the thumb and little finger areas in the PFM of amputated side produced the similar neural activities in the somatosensory cortex as those of stimulating the thumb and little finger of the contralateral hand, both of which were consistent with the homunculus organization of the SI cortex. The intensity of SI cortical activities was proportional to the intensity of the amplitude of peripheral stimulation. In particular, local anesthesia reduced the intensity of central activities in SI as revealed by the MEG response, as well as the sensitivity of ETS as reported by the subject. This neural correlation appears to suggest that the finger areas in the PFM in the stump skin are neuroanatomically connected to the finger areas of the somatosensory cortex. Thus, electrical stimulation of the PFM can induce natural sensation as that of normal fingers. This establishes the neural basis of natural sensory feedback from the prosthetic hand to the forearm amputee with finger-to-finger specificity.

Neural computational modeling reveals a major role of corticospinal gating of central oscillations in the generation of essential tremor.

Essential tremor, also referred to as familial tremor, is an autosomal dominant genetic disease and the most common movement disorder. It typically involves a postural and motor tremor of the hands, head or other part of the body. Essential tremor is driven by a central oscillation signal in the brain. However, the corticospinal mechanisms involved in the generation of essential tremor are unclear. Therefore, in this study, we used a neural computational model that includes both monosynaptic and multisynaptic corticospinal pathways interacting with a propriospinal neuronal network. A virtual arm model is driven by the central oscillation signal to simulate tremor activity behavior. Cortical descending commands are classified as alpha or gamma through monosynaptic or multisynaptic corticospinal pathways, which converge respectively on alpha or gamma motoneurons in the spinal cord. Several scenarios are evaluated based on the central oscillation signal passing down to the spinal motoneurons via each descending pathway. The simulated behaviors are compared with clinical essential tremor characteristics to identify the corticospinal pathways responsible for transmitting the central oscillation signal. A propriospinal neuron with strong cortical inhibition performs a gating function in the generation of essential tremor. Our results indicate that the propriospinal neuronal network is essential for relaying the central oscillation signal and the production of essential tremor.