Novel Use of Theta Burst Cortical Electrical Stimulation for Modulating Motor Plasticity in Rats

Abstract

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 SpragueDawley 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.

Neuromodulatory Effects of Transcranial Direct Current Stimulation on Motor Excitability in Rats

“…A previous study demonstrated the polarity effects of tDCS on MEPs, where MEPs were evoked by electric current that was delivered through same stimulation montage as tDCS [25]. In contrast to that study using the brain-thorax montage, we used a bipolar CES, which induced current similar to that by TMS in the cortex, to evoke MEPs in the current study [15]. The CES-MEP method provided a more focal stimulation than the brain-thorax montage for targeting the motor cortex and allowed better quantitative measurements of neuromodulation in motor excitability after tDCS [15,16].…”

“…All animal procedures were conducted in accordance with the guidelines of the Institutional Animal Care and Use Committee at Chang Gung University. Procedures followed for measuring motor plasticity in the rat model were similar to those described in a previous study [15].…”

“…The major limitation of an animal model for recording MEPs is the low focalization because the TMS coil is considerably larger than the brain of small animals. To overcome this limitation, we developed a focused cortical electrical stimulation (CES) method by using epidural electrodes on the motor cortex in place of TMS in anesthetized rats for evoking MEPs [15,16]. In this study, we developed a platform to test the polarity effects of tDCS on MEPs in rats based on the CES technique.…”

“…The reference electrode was positioned distally in the paw. The ground electrode was inserted into the base of the tail of a rat [15]. The EMG signal was amplified (gain = 2000) and filtered using 60 Hz notch and 10-1000 Hz bandpass filters prior to digitization at 10 kHz (MP36, BIOPAC System, California, USA).…”

“…Anodal tDCS (+) at 0.1 and 0.8 mA, cathodal tDCS (-) at 0.1 and 0.8 mA, and sham tDCS protocols were used to induce long-term potentiation-(LTP-), long-term depression-(LTD-) like changes, and the control condition, respectively. Biphasic singlepulse CES (amplitude: 1-10 V; pulse duration: 1 ms with 10 s intervals) was delivered to determine the resting motor threshold (RMT), which was defined as the intensity of electrical stimulation required to elicit peak-to-peak MEPs greater than 20 μV in five out of 10 consecutive trials [15]. Baseline MEP was measured as the average of 12 MEPs evoked by a standard CES pulse delivered every 10 s at 120% RMT intensity.…”