Cortical electrical stimulation combined with rehabilitative training: Enhanced functional recovery and dendritic plasticity following focal cortical ischemia in rats

Abstract

This study assessed the behavioral and dendritic structural effects of combining subdural motor cortical electrical stimulation with motor skills training following unilateral sensorimotor cortex lesions in adult male rats. Rats were pre-operatively trained on a skilled forelimb reaching task, the Montoya staircase test, and then received endothelin-1 induced ischemic lesions of the sensorimotor cortex. Ten to 14 days later, electrodes were implanted over the peri-lesion cortical surface. Rats subsequently began 10 days of rehabilitative training on the reaching task in 1 of 3 conditions: 1. 50 Hz stimulation during training, 2. 250 Hz stimulation during training or 3. no stimulation. No significant difference in performance was found between the 250 Hz and no stimulation groups. The 50 Hz stimulation group had significantly greater rates of improvement with the impaired forelimb in comparison to 250 Hz and no stimulation groups combined. Fifty Hz stimulated animals also had a significant increase in the surface density of dendritic processes immunoreactive for the cytoskeletal protein, microtubule-associated protein 2, in the peri-lesion cortex compared to the other groups. These results support the efficacy of combining rehabilitative training with cortical electrical stimulation to improve functional outcome and cortical neuronal structural plasticity following sensorimotor cortical damage.

Motor cortical stimulation promotes synaptic plasticity and behavioral improvements following sensorimotor cortex lesions

“…Nevertheless, movement threshold were similar to a previous study using epidural electrodes and between groups. Also consistent with previous findings (Adkins-Muir and Jones, 2003;Teskey et al, 2003), movement thresholds declined over days (F(2,84) = 4.19, p = 0.02). The severely impaired group tended to show less of a decline in movement threshold current levels, but there was no significant difference between groups (p = 0.81) or group by day interaction effect (p = 0.09).…”

“…4). Unlike the subdural electrodes used in our previous study (Adkins-Muir and Jones, 2003), epidural electrodes did not produce detectable indentation of the cortex nor additional tissue damage. In all groups, there were one to two animals with relatively superficial infarcts that did not produce noticeable damage to layer V of the SMC.…”

“…The neural mechanisms of these functional effects are unknown, but we hypothesize that CS recruits neurons that may otherwise be insufficiently activated during task performance and that this enables activitydependent synaptic plasticity that mediates recovery of skilled movements in the impaired forelimb. Consistent with this possibility, CS-induced improvements in reaching success coincide with neuroplastic changes in the stimulated region of the SMC, including increased surface density of layer V dendritic processes (Adkins-Muir and Jones, 2003), expansion of movement representations detected using intracortical microstimulation mapping (in rats: Kleim et al, 2003b;in monkeys: Plautz et al, 2003) and enlargement of the polysynaptic component of motor cortical evoked potentials (Teskey et al, 2003) compared to animals receiving rehabilitation alone. Because plasticity of synaptic connectivity is thought to underlie motor learning and re-learning (Monfils et al, 2005), a major purpose of the present study was to directly determine whether training combined with CS induces greater structural plasticity of synapses in remaining motor cortex than training alone.…”

“…The platinum contacts were placed in a consistent manner relative to skull landmarks on dura and were orientated approximately parallel to midline. This electrode placement has been found to reliably enable post-operative stimulation-evoked contralesional forelimb, face and/ or upper body movement (Adkins-Muir and Jones, 2003;Adkins et al, 2006b). Cathodal current was delivered to the contacts on cortex and anodal current flowed through a small metal disk implanted subcutaneously (contact facing skin) near Lambda to ground the current (Northstar Neuroscience, Inc., Seattle, WA).…”

“…Recent studies in humans indicate that stimulation of select cortical regions might be used to improve the efficacy of rehabilitative training (Brown and Pilitsis, 2006;Hummel and Cohen, 2006;Pascual-Leone, 2006). In support of this possibility, recent studies in monkeys (Plautz et al, 2003) and rats (Adkins-Muir and Jones, 2003;Kleim et al, 2003b;Teskey et al, 2003; Adkins et al, 2006b) with infarcts of the sensorimotor cortex (SMC) indicate that the efficacy of rehabilitation can be greatly enhanced by coupling it with cortical stimulation (CS) of the peri-infarct region. In this approach, as animals are undergoing daily training on a skilled reaching task, subthreshold (to evoke movements) current is passed through electrodes positioned over remaining motor cortex.…”