過去研究中，在身體周邊施予自然型式的刺激並記錄神經反應，是研究腦部如何處理感覺訊號的主要方式。然而，對某些類型的自然刺激而言，隨著刺激時間或次數的增加所產生的反應，不易有穩定的再現性，如重複的觸覺刺激所造成的周邊受器之適應(adaptation)等。若利用微電刺激直接刺激腦內神經元及控制其興奮程度，可避免上述自然刺激之問題，而能對單一神經元本身進行定量的分析研究。因此，本研究之目的為研發一腦內微電刺激(deep-brain microstimulation)方法，並評估此方法是否適用於探討腦部神經元功能。
本研究以大鼠為實驗動物，進行刺激及神經訊號記錄。觸覺刺激施於後肢，並在視丘(thalamus)及大腦皮質(cerebral cortex)分別以兩根玻璃電極記錄反應之訊號。微電刺激則透過上述視丘所用之相同記錄電極施於視丘，而記錄在大腦皮質所產生之反應。觸覺及電刺激引發之大腦皮質動作電位(action potentials, APs)，予以詳細比對。
微電刺激所引發之大腦皮質動作電位，與觸覺刺激相當類似，而其視丘至大腦皮質之訊號傳遞時間，與觸覺刺激亦相當符合。因此，此方法可引發與自然型式刺激相當類似之反應，可應用於腦中微電刺激以模擬自然刺激。基於此一效果，未來可將其利用於腦功能研究，針對活體腦部神經元功能，進行更深入之探討。

Conventionally, recording neural responses to adequate stimuli in peripheral has been the principle method for studying brain functions of somatosensory. However, under prolonged or repeated stimulation, adaptation or sensitization in peripheral may make it difficult to consistently evoke neuronal responses. By utilizing the technique of electrical stimulation instead, neurons can be directly stimulated to evoke controllable excitation and thus analyzed quantitatively, without the limitations of adequate stimulation. In this study, a deep-brain electrical microstimulation method was established and evaluated to verify whether it can be used as a tool to explore neuronal function in the brain.
Male Wistar rats were used in this study. Tactile stimulation (TS) was applied to the hindpaw, and the TS-evoked responses in the thalamus and cerebral cortex were recorded independently with two glass microelectrodes. Then, electrical microstimulation (ES) was applied through the same microelectrode previously used for recording in the thalamus, and the ES-evoked cortical responses were recorded also by the same microelectrode in the cortex. The evoked cortical action potentials (APs) of both types of stimulation were carefully compared.
The waveforms of ES-evoked APs were similar to those of TS-evoked APs. The transmission latency from thalamus to cortex of the ES-evoked response was also compatible with that of the TS-evoked response. These results suggested that ES can be used to directly stimulate the tactile neuron and mimic the effect of TS. With its precision and fidelity, this method may contribute to the exploration of neuronal functions in the brain.

中文摘要 i
Abstract ii
List of Figures vi
1. Introduction 1
1.1 Background 1
1.2 The aim of this study 3
2. Materials and Methods 5
2.1 Experiment procedures 5
2.2 Animal preparation 5
2.3 Signal searching and recording 6
2.4 Tactile stimulation 8
2.5 Electrical microstimulation 9
2.6 Data analysis 9
3. Results 18
3.1 TS-evoked responses 18
3.2 ES-evoked responses 18
3.3 Comparison of TS- and ES-evoked responses 19
3.3.1 Multi-unit action potentials 19
3.3.2 Identification of single-unit action potential 20
4. Discussion 29
4.1 Cortical responses evoked by electrical microstimulation 29
4.2 Effectiveness of mimicking tactile stimulation by electrical microstimulation 30
5. Conclusion 34
References 35

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