Electrical Stimulation on Anterior Cingulate Cortex Modulates Pain-related Neural Activities

Abstract

본 논문에서는 뇌의 Anterior cingulate cortex (ACC) 영역에 전기자극이 가해지는 동안, 통증과 관련된 뇌 영역인 Ventral posterolateral nucleus (VPL) 와 Primary somatosensory cortex (S1) 사이에서의 synchrony가 어떻게 변하는지 혹은 각 영역에서 신경신호가 어떻게 변하는지 알아보았다. 이를 위해 마취된 쥐의 뒷발에 클립을 사용하여 다리자극을 인가하는 동안, 전기자극이 있을 때와 없을 때의 신경신호를 비교하며 분석하였다. 그 결과, spike firing rate의 경우, 다리자극에 의해서 증가된 값이 ACC 전기자극에 의해서 감소되었고 이는 VPL과 S1 신경신호에서 모두 나타났다. 또한 VPL과 S1 신경신호 간의 spike synchrony도 다리자극에 의해 증가된 값이 ACC 전기자극에 의해 값이 감소되었다. Local field potential의 경우, 낮은 주파수 파워(1-10Hz)가 다리자극에 의해 감소했고 감소된 정도는 ACC 전기자극에 의해서 완화되었다. VPL과 S1간의 phase synchrony는 높은 주파수에서 (120-135Hz) 다리자극 동안 증가되었지만 ACC전기자극에 의해서 오히려 감소되었다. 본 연구는 ACC 전기자극 동안 통증 관련된 영역의 신경 신호 억제와 신호간의 synchrony 억제가 일어나는 것을 보였다. 이 연구를 통해 ACC 전기자극이 신경병증성 통증에 효과적인 치료 방법이 될 것으로 기대하고 있다.; The electrical stimulation on a specific brain area has become an effective treatment for neurological diseases such as Parkinson’s diseases, obsessive compulsive disorder, dystonia and essential tremor. Recently, it was reported that the electrical stimulation on anterior cingulate cortex (ACC) modulates pain-related neural activities. However, there has been no study investigating the synchronization between pain-related brain regions during electrical stimulation on ACC. In this dissertation, the neural activities and the synchronization were monitored between pain-related brain regions of rats; somatosensory cortex (S1) and ventral posterolateral nucleus (VPL). The single unit activities and local field potentials (LFPs) were recorded simultaneously from both VPL and S1 of anesthetized rats. To induce the sensation response of S1 and VPL neurons, a mechanical pressure was applied on the hindpaw of rats using a clip. Along with the mechanical pressure, at the same time, electrical stimulation was delivered to ACC to examine the effect of electrical stimulation on the pain-related neural signals. The parameters of electrical stimulation were 10-50 Hz pulse frequency, 100 μA pulse amplitude, 60 μs pulse duration and biphasic pulses for 20 seconds. In this experiment, the results were obtained in four categories; spike firing rate, spike synchrony based on single unit activities, and spectral power and phase synchrony based on LFPs. Spike firing rate was significantly increased during the mechanical pressure but suppressed by ACC electrical stimulation in both S1 and VPL. Spike synchrony between VPL and S1 was significantly increased while applying the mechanical stimulation but decreased by ACC electrical stimulation. In LFPs, spectral power was decreased in low frequency band (1-10 Hz) during mechanical pressure in both VPL and S1 but the effect was reversed by ACC stimulation. Similar to the spike synchrony, phase synchrony was also significantly increased in high frequency band (120-135 Hz) during the mechanical pressure and ACC electrical stimulation also reversed the phase synchrony change. In summary, we successfully showed that the electrical stimulation on ACC modulates pain-related neural activities in rats. In our knowledge, this is the first report which measured the alteration of spikes and phase synchrony during electrical stimulation. Ultimately, our goal is to employ ACC stimulation as a treatment for modulating neuropathic pain by decreasing the synchronization between VPL and S1 in the pain pathway.