The effect of peripheral nerve electrical stimulation on corticomotor excitability and motor function of the paretic hand in stroke

Abstract

Electrical stimulation to the stroke-affected paretic upper limb (UL) has been a treatment to promote its motor recovery. Despite its efficacy in promoting muscle strength and enhancing motor training, the underlying neurophysiological mechanism for such motor improvement has not been clear. It is crucial to delineate the corticomotor plasticity effects of electrical stimulation when it is applied as a single entity and as an adjunct to other forms of therapies, since the knowledge would support formulation of effective treatment for the paretic UL in stroke rehabilitation. This dissertation incorporated 4 studies to examine the corticomotor excitability modulation and motor function effects of electrical stimulation on the paretic UL due to stroke. Study 1 reviewed randomized controlled trials published before 2012 to scrutinize the efficacy of electrical stimulation on motor function improvement as well as corticomotor excitability for muscles in the paretic hand. Results of the meta-analysis showed that electrical stimulation could improve UL motor impairment but not its ability in functional task performance measured with the Action Research Arm Test. The corticomotor excitability changes associated with electrical stimulation could not be concluded because of diverse outcomes reported in only 3 studies. Study 2 was a randomized cross-over sham-controlled experiment (n = 32) set to determine a single session of 1-hour electrical stimulation delivered to the ulnar and radial nerves (PNS) of the paretic UL at an intensity of 2 to 3 sensory thresholds in modulating the corticomotor excitability in both brain hemispheres. The results confirmed that PNS could increase corticomotor excitability in terms of the recruitment curve (RC) slope and peak amplitude of motor-evoked potentials (pMEP) for the corticospinal projections to the contralateral first dorsal interosseous hand muscle (FDI) measured in both hemispheres. The PNS also enhanced better hand pincer dexterity scored by the Purdue pegboard test than the sham stimulation (PNSsham). Then Study 3 was conducted to examine if PNS could condition the corticomotor pathways for another treatment targeting motor improvement in the paretic UL. This pilot randomized cross-over study involved 20 subjects to receive 1-hour PNS paired with observation of movement demonstration in videos (termed action observation, AO) that was introduced during the last 30 minutes of PNS. PNS+AO improved the Purdue dexterity score of the paretic hand, but the change in corticomotor excitability for the contralateral FDI in the lesioned hemisphere was not significant. The control intervention PNSsham+AO did not change any of the outcome measurements. Study 4 further tested the hypothesis that PNS and/or jointly with AO might effectively condition motor training of the paretic UL in enhancing corticomotor plastic changes and hand dexterity. In this randomized sham-controlled cross-over study, 20 subjects in chronic stage of stroke were exposed to 3 separate sessions of different interventions composed of 1-hour PNS or PNSsham paired with 30 minutes of AO or sham AO (AOsham), all followed by 30-minute training of index finger abduction. The results revealed that PNS+AO+Training led to significantly increased corticomotor excitability in terms of RC slope and pMEP amplitude localized in the lesioned hemisphere but that of the intact hemisphere was not altered. This neuroplastic modulation was accompanied by enhanced hand dexterity at 24 hours post-intervention better than the control with PNSsham+AOsham+Training. On the other hand, PNS+AOsham+Training did not modulate corticomotor excitability functions but hand dexterity was increased immediately after the intervention better than after PNSsham+AOsham+Training. Training after PNSsham+AOsham conditioning was not effective on the outcome measurements. Results of the series of studies supported that (1) one-hour PNS could increase the excitability of corticomotor pathways for the contralateral hand muscle in both the lesioned and intact hemispheres similarly; (2) one-hour PNS alone, or applied as a conditioning treatment in the presence of AO or AOsham prior to movement training in the paretic hand could lead to better hand dexterity than training after sham controls; (3) Up-regulation of corticomotor excitability specifically confined to the stroke-lesioned hemisphere was evident after a session of PNS paired with AO and Training. To conclude, one session of PNS or PNS-associated interventions for the paretic UL could effectively improve dexterity of the paretic hand in people with chronic stroke. PNS might have primed the corticomotor pathways for AO and motor training to result in corticomotor excitability enhancement specifically confined to the stroke-lesioned hemisphere.