Modulation of Cortical Motor Evoked Potential After Stroke During Electrical Stimulation of the Lateral Cerebellar Nucleus

Abstract

Background Deep brain stimulation (DBS) targeting the dentato-thalamo-cortical (DTC) pathway at its origin in the lateral cerebellar nucleus (LCN) has been shown to enhance motor recovery in a rodent model of cortical ischemia. LCN DBS also yielded frequency specific changes in motor cortex excitability in the normal brain, indexed by motor evoked potential (MEP) amplitude. Objective To investigate the effect of cortical stroke on cortical motor excitability in a rodent ischemia model and to measure the effects of LCN DBS on post-ischemia excitability as a function of stimulation parameters. Methods Adult Sprague-Dawley rats were divided into two groups: naïve and stroke, with cortical ischemia induced through multiple, unilateral endothelin-1 injections. All animals were implanted with a bipolar electrode in the LCN opposite the affected hemisphere. MEPs were elicited from the affected hemisphere using intracortical microstimulation (ICMS) techniques. Multiple LCN DBS parameters were examined, including isochronal stimulation at 20, 30, 50, and 100 Hz as well as a novel burst stimulation pattern. Results ICMS-evoked MEPs were reduced in stroke (n=10) relative to naïve (n=12) animals. However, both groups showed frequency-dependent augmentation of cortical excitability in response to LCN DBS. In the naïve group, LCN DBS increased MEPs by 22–58%, while in the stroke group, MEPs were enhanced by 9–41% compared to OFF DBS conditions. Conclusions Activation of the DTC pathway increases cortical excitability in both naïve and post-stroke animals. These effects may underlie, at least partially, functional reorganization and therapeutic benefits associated with chronic LCN DBS in post-stroke animals.

Visual feedback alters force control and functional activity in the visuomotor network after stroke

“…In the context of these previous findings, one interpretation is that during visuomotor processing, age may lead to an increase in the engagement of the cerebellum to support the error correction process, and that the engagement of these cerebellar regions is augmented after stroke. Such a position is consistent with other observations which demonstrate a central role for the cerebellum in motor adaptation ( Bastian, 2006 , Bastian, 2008 , Rabe et al, 2009 , Thach et al, 1992 ), and recent stimulation paradigms that target cerebellar activity to influence motor function in rodent models ( Park et al, 2015 ), as well as humans ( Ferrucci and Priori, 2014 , Jalali et al, 2017 , Jayaram et al, 2011 , Samaei et al, 2017 ).…”

Deep Brain Stimulation rescues memory and synaptic activity in a rat model of global ischemia

“…Therefore, changes in synaptic activities after DBS treatment cannot be ruled out through other nonsynaptic ongoing events might also contribute to the increase in amplitude of LFPs. These results are supported by previous studies in a rat model of cerebral ischemia, which shows DBS targeting the DTC pathway enhances cortical plasticity and excitability, and promotes perilesional cortical reorganization (Cooperrider et al, 2014;Park et al, 2015).…”

Neurorestoration after stroke

“…14 Invasive cerebellar stimulation has also been studied. Deep brain stimulation of the cerebello-thalamo-cortical pathway, specifically of the lateral cerebellar nucleus, 119 has been shown in preclinical rodent models to modulate cerebral cortex excitability 7 and improve postischemia motor recovery. 106 More recently, chronic cerebellar DBS demonstrated promotion of long-term potentiation, neuroplasticity, and reparative reorganization.…”