張鈞惠Chun-hui Chang

國立清華大學系統神經科學研究所副教授

面對挑戰時 大腦的黑盒子如何調節行為？

Obsessive-compulsive disorder ( OCD ) is usually accompanied with hyperactivity of the orbitofrontal cortex ( OFC ) . Many OCD patients have anxiety issues, and there is high comorbidity of OCD and post-traumatic stress disorder (PTSD). This clinical evidence suggested that at the circuitry level, related brain structures must have interacted.


One of the candidates for the interaction is the amygdala, the key emotion center in the brain, which receives inputs from neocortical areas including the medial prefrontal cortex ( mPFC ) and lateral orbitofrontal cortex (lOFC). Indeed, it is well documented that input from the mPFC to the amygdala is critical for proper fear regulation after extinction, and malfunction of the mPFCamygdala pathway has been suggested as the leading cause of PTSD.


In a series of studies, we examined how activation of the lOFC mimicking OCD condition may interfere the extinction processes at the neurobiological and behavioral level. Using in vivo extracellular single unit recordings in anesthetized rats, we found that activation of the lOFC exerted an inhibitory modulation on the mPFC-amygdala pathway and was mediated through an intraamygdala feed-forward inhibition.


We next examined the hypothesis that hyperactivity of the lOFC negatively affects fear extinction, a behavioral procedure critically relied on integrated mPFC-amygdala activities. We found that when we brought the lOFC on-line before extinction training, there was a general initial suppression of fear expression, which was followed by development of nonspecific fear response. Moreover, preextinction activation of the lOFC impaired the encoding of extinction demonstrated by a general upshift of fear levels during retrieval test compared to controls.


Extinction based exposure therapy is widely used in many anxiety disorders, and failure of extinction may result in PTSD. From neural circuitry to behavior, this series of studies unveiled a potential mechanism of comorbid OCD and PTSD etiology.

得獎感言

謝謝科技部的肯定，謝謝國立清華大學研究發展處、生命科學院及腦科學研究中心，對於研究的支持，謝謝國立交通大學實驗動物中心的協助，讓實驗得以進行，謝謝我的家人。


知識的延續是一代一代的傳承，謝謝引領我進入學術研究的恩師們，臺大動物系的嚴震東老師、臺大心理系的梁庚辰老師、博士班指導教授 Dr. Stephen Maren ，以及博士後指導教授 Dr. Anthony Grace 。而做研究最開心的部分，是和實驗室一群非常認真的年輕學生們，一起發現新知及成長，謝謝他們。

個人勵志銘

達賴喇嘛：能解決的事，不必去擔心；不能解決的事，擔心也沒用。