Novel use of theta burst cortical electrical stimulation for modulating motor plasticity in rats

Various forms of cortical stimulation are capable of modulating motor cortical excitability through plasticity-like mechanisms and thus might have therapeutic potential for neurological diseases. To better understand the neural mechanism underlying the cortical neuromodulation effects and to enable translational research in rodent disease models, we developed a focused brain stimulation method using cortical electrical stimulation (CES) on the motor cortex in anesthetized rats. A specific stimulation scheme using theta burst stimulation (TBS) was then adopted to observe the facilitatory and inhibitory effects in motor cortical excitability. Adult male Sprague- Dawley rats were used for all experiments. Under urethane anesthesia, two epidural stainless steel screw electrodes were unilaterally implanted over the primary motor cortex targeting the forelimb area. Brachioradialis motor evoked potentials (MEPs) were obtained by single-pulse CES. Acute MEP changes were measured before and after intermittent and continuous TBS (iTBS and cTBS). For sham intervention, electrodes were implanted, but no TBS was delivered. To examine TBS-elicited plasticity responses, MEP amplitude was measured at baseline and for 30 min after iTBS or cTBS. The MEPs were significantly enhanced immediately after iTBS (p = 0.001) and remained enhanced for 30 min (p < 0.001) compared to the baseline MEP. Similarly, the MEPs were suppressed in 5 min (p = 0.035) and lasted for 30 min or more (p < 0.001) after cTBS. No effect was noted on the MEP magnitude in rats under sham stimulation (p > 0.05). The developed TBS scheme uses the focused CES method to produce consistent, rapid, and controllable electrophysiological changes in the motor cortex. In particular, the cortical plasticity can be modulated in rat models via the CES-TBS protocols. These findings may have translational relevance for establishing new therapeutic CES applications in neurological disorders.