Low-intensity contralesional electrical theta burst stimulation modulates ipsilesional excitability and enhances stroke recovery

Abstract

Targeting interhemispheric inhibition using brain stimulation has shown potential for enhancing stroke recovery. Following stroke, increased inhibition originating from the contralesional hemisphere impairs motor activation in ipsilesional areas. We have previously reported that low-intensity electrical theta burst stimulation (TBS) applied to an implanted electrode in the contralesional rat motor cortex reduces interhemispheric inhibition, and improves functional recovery when commenced three days after cortical injury. Here we apply this approach at more clinically relevant later time points and measure recovery from photothrombotic stroke, following three weeks of low-intensity intermittent TBS (iTBS), continuous TBS (cTBS) or sham stimulation applied to the contralesional motor cortex. Interhemispheric inhibition and cellular excitability were measured in the same rats from single pyramidal neurons in the peri-infarct area, using in vivo intracellular recording. A minimal dose of iTBS did not enhance motor function when applied beginning one month after stroke. However both a high and a low dose of iTBS improved recovery to a similar degree when applied 10 days after stroke, with the degree of recovery positively correlated with ipsilesional excitability. The final level of interhemispheric inhibition was negatively correlated with excitability, but did not independently correlate with functional recovery. In contrast, contralesional cTBS left recovery unaltered, but decreased ipsilesional excitability. These data support focal contralesional iTBS and not cTBS as an intervention for enhancing stroke recovery and suggest that there is a complex relationship between functional recovery and interhemispheric inhibition, with both independently associated with ipsilesional excitability.