Division of Neurosurgery, Toronto Western Hospital, Toronto, Ontario, Canada.
Exp Neurol. 2010 Sep;225(1):154-62. doi: 10.1016/j.expneurol.2010.06.007. Epub 2010 Jun 14.
Deep brain stimulation (DBS) of the anterior thalamic nucleus (AN), an important relay in the circuitry of memory, is currently being proposed as a treatment for epilepsy. Despite the encouraging results with the use of this therapy, potential benefits and adverse effects are yet to be determined. We show that AN stimulation at relatively high current disrupted the acquisition of contextual fear conditioning and impaired performance on a spatial alternating task in rats. This has not been observed at parameters generating a charge density that approximated the one used in clinical practice. At settings that impaired behavior, AN stimulation induced a functional depolarization block nearby the electrode, increased c-Fos expression in cerebral regions projecting to and receiving projections from the AN, and influenced hippocampal activity. This suggests that complex mechanisms might be involved in the effects of AN DBS, including a local target inactivation and the modulation of structures at a distance. Though translating data from animals to humans has to be considered with caution, our study underscores the need for carefully monitoring memory function while selecting stimulation parameters during the clinical evaluation of AN DBS.
丘脑前核（AN）的深部脑刺激（DBS）是记忆回路中的一个重要中继站，目前被提议作为治疗癫痫的一种方法。尽管这种治疗方法的结果令人鼓舞，但潜在的益处和不良反应仍有待确定。我们发现，在相对较高的电流刺激下，AN 会干扰情境性恐惧条件反射的获得，并损害大鼠在空间交替任务中的表现。而在产生类似于临床实践中使用的电荷密度的参数下，并没有观察到这种情况。在行为受损的设置下，AN 刺激在电极附近引起功能性去极化阻断，增加了投射到 AN 并接收 AN 投射的脑区中的 c-Fos 表达，并影响了海马体的活动。这表明，在 AN DBS 的作用中可能涉及复杂的机制，包括局部靶标失活和远距离结构的调制。尽管将动物数据转化为人类数据需要谨慎考虑，但我们的研究强调了在临床评估 AN DBS 时选择刺激参数时，需要仔细监测记忆功能。
