McCracken Clinton B, Grace Anthony A
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
J Neurosci. 2009 Apr 22;29(16):5354-63. doi: 10.1523/JNEUROSCI.0131-09.2009.
Deep brain stimulation of the nucleus accumbens (NAC) region is an effective therapeutic avenue for several psychiatric disorders that are not responsive to traditional treatment strategies. Nonetheless, the mechanisms by which DBS achieves therapeutic effects remain unclear. We showed previously that high-frequency (HF) NAC DBS suppressed pyramidal cell firing and enhanced slow local field potential (LFP) oscillations in the orbitofrontal cortex (OFC) via antidromic activation of corticostriatal recurrent inhibition. Using simultaneous multisite LFP recordings in urethane-anesthetized rats, we now show that NAC DBS delivered for 90 min at high or low frequency (LF) selectively affects spontaneous and evoked LFP oscillatory power and coherence within and between the medial prefrontal cortex (mPFC), lateral OFC, mediodorsal thalamus (MD), and NAC. Compared with LF or sham DBS, HF DBS enhanced spontaneous slow oscillations and potentiated evoked LFP responses only in OFC. HF DBS also produced widespread increases in spontaneous beta and gamma power and enhanced coherent beta activity between MD and all other regions. In contrast, LF DBS elevated theta power in MD and NAC. Analysis of acute NAC-induced oscillations showed that HF DBS increased and LF DBS decreased induced relative gamma coherence compared with sham DBS. These data suggest that HF (therapeutic) and LF (possibly deleterious) NAC DBS produce distinct region-specific and frequency band-specific changes in LFP oscillations. NAC DBS may achieve therapeutic effects by enhancing rhythmicity and synchronous inhibition within and between afferent structures, thereby normalizing function of a neural circuit that shows aberrant activity in obsessive-compulsive disorder and depression.
伏隔核(NAC)区域的深部脑刺激是治疗几种对传统治疗策略无反应的精神疾病的有效治疗途径。尽管如此,深部脑刺激实现治疗效果的机制仍不清楚。我们之前表明,高频(HF)NAC深部脑刺激通过皮质纹状体反复抑制的逆向激活,抑制眶额皮质(OFC)中的锥体细胞放电并增强慢局部场电位(LFP)振荡。我们现在在乌拉坦麻醉的大鼠中使用同步多部位LFP记录表明,高频或低频(LF)给予90分钟的NAC深部脑刺激选择性地影响内侧前额叶皮质(mPFC)、外侧OFC、背内侧丘脑(MD)和NAC内以及它们之间的自发和诱发LFP振荡功率及相干性。与低频或假深部脑刺激相比,高频深部脑刺激仅在OFC中增强自发慢振荡并增强诱发的LFP反应。高频深部脑刺激还使自发的β和γ功率普遍增加,并增强了MD与所有其他区域之间的相干β活动。相比之下,低频深部脑刺激提高了MD和NAC中的θ功率。急性NAC诱导振荡的分析表明,与假深部脑刺激相比,高频深部脑刺激增加而低频深部脑刺激降低了诱导的相对γ相干性。这些数据表明,高频(治疗性)和低频(可能有害)NAC深部脑刺激在LFP振荡中产生不同的区域特异性和频段特异性变化。NAC深部脑刺激可能通过增强传入结构内和之间的节律性和同步抑制来实现治疗效果,从而使在强迫症和抑郁症中表现出异常活动的神经回路功能正常化。