Motor cortex stimulation enhances motor recovery and reduces peri-infarct dysfunction following ischemic insult

Abstract

Recovery of motor function following stroke is believed to be supported, at least in part, by functional compensation involving residual neural tissue. The present study used a rodent model of focal ischemia and intracortical microstimulation (ICMS) to examine the behavioral and physiological effects of cortical stimulation in combination with motor rehabilitation. Adult rats were trained to criterion on a single pellet reaching task before ICMS was used to derive maps of movement representations within forelimb motor cortex contralateral to the trained paw. All animals then received a focal ischemic infarct within the motor map. A cortical surface electrode was implanted over the motor cortex. Low levels of electrical stimulation were applied during rehabilitative training on the same reaching task for 10 days and ICMS used to derive a second motor map. Results showed that both monopolar and bipolar cortical stimulation significantly enhanced motor recovery and increased the area of cortex from which microstimulation movements could be evoked. The results demonstrate the behavioral and neurophysiological benefits of cortical stimulation in combination with rehabilitation for recovery from stroke.

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

“…This finding is in agreement with previous data indicating that monopolar or bipolar CS delivered at frequencies between 50 and 100 Hz and at 40 to 70 % of movement thresholds greatly improves reaching performance compared to unstimulated reach trained controls (Adkins-Muir and Jones, 2003;Kleim et al, 2003b;Plautz et al, 2003;Teskey et al, 2003;Adkins et al, 2006b) and rats receiving 250 Hz CS during training (Adkins-Muir and Jones, 2003). CS and motor training was initiated 2 weeks after the infarcts in the present study, but it is also effective when delivered at earlier (Kleim et al, 2003b;Teskey et al, 2003) and later (Plautz et al, 2003) time points. The present results extend the previous behavioral findings by indicating that CS also partially improves abnormalities in the movements used to perform the reaching task.…”

“…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.…”

“…Previously, CS combined with post-lesion rehabilitative training was found to increase periinfarct dendritic density (Adkins-Muir and Jones, 2003) and to induce functional alterations in the motor cortex, as revealed by expanded forelimb motor maps (Kleim et al, 2003b;Plautz et al, 2003) and neural potentiation, revealed as an increase in the late-component of motor evoked potentials (Teskey et al, 2003) compared to unstimulated rehabilitation-only controls. The present finding of CS induced increases in synaptic density provides direct support that CS influences synaptic connectivity in the motor cortex and is consistent with the general hypothesis that positive modulation of synaptic plasticity mediates the behavioral improvements resulting from CS.…”

“…Jablonka et al (2007) found that experience-dependent plasticity is impaired in the cortex near focal photothrombotic infarcts and it may be that CS can help overcome such impairment. Functionally beneficial effects of CS with training have been found using four different models of focal cortical ischemia (Adkins-Muir & Jones, 2003;Kleim et al, 2003b;Plautz et al, 2003Teskey et al, 2003. If motor cortical synaptic plasticity mediates the behavioral improvements, one would expect CS to facilitate it in the other ischemia models.…”

“…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.…”