Long-Term High Frequency Deep Brain Stimulation of the Nucleus Accumbens Drives Time-Dependent Changes in Functional Connectivity in the Rodent Limbic System

Long-Term High Frequency Deep Brain Stimulation of the Nucleus Accumbens Drives Time-Dependent Changes in Functional Connectivity in the Rodent Limbic System
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DOI:
10.1016/j.brs.2012.07.007
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发表时间:
2013-05-01
期刊:
影响因子:
7.7
通讯作者:
Grace, Anthony A.
Grace, Anthony A.
中科院分区:
医学1区
文献类型:
--
作者:
Ewing, Samuel G.;Grace, Anthony A.

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脑深部刺激腹侧纹状体是治疗多种难治性精神疾病的有效方法,但其作用机制尚不明确。我们研究了五天的刺激如何影响自由运动大鼠的有节奏的大脑活动,在选择的两侧边缘区域内的振荡功率和一致性方面。定制的双极刺激/记录电极被植入伏隔核的双侧核心。局部场电位(LFP)记录电极被植入双侧的前额叶和眶额皮质以及丘脑中背核。使用定制的刺激装置,以100 μ a振幅、130 Hz频率、持续时间100 μ s的恒流脉冲对双侧进行刺激。在刺激之前、期间和之后,从动物的家庭笼子中收集同步视频和LFP数据。对信号进行处理以去除运动和刺激伪影,并分析以确定区域内光谱功率的变化和区域之间的一致性。对伏隔核进行为期五天的刺激,在多个脑区的多个带宽上产生了LFP功率的暂时动态调制。丘脑中背侧核与伏隔核之间的α带一致性减弱。在5天的刺激期内,伏隔核各核之间的一致性表现出丰富的时间动态。停止刺激在多个大脑区域的能力和连贯性方面显示出显著的“反弹”效应。总的来说,短期刺激下观察到的初始功率变化被相干性改变所取代,这可能反映了DBS的功能作用。(c) 2013爱思唯尔公司版权所有。
Deep brain stimulation of the ventral striatum is an effective treatment for a variety of treatment refractory psychiatric disorders yet the mechanism of action remains elusive. We examined how five days of stimulation affected rhythmic brain activity in freely moving rats in terms of oscillatory power within, and coherence between, selected limbic regions bilaterally. Custom made bipolar stimulating/recording electrodes were implanted, bilaterally, in the nucleus accumbens core. Local field potential (LFP) recording electrodes were implanted, bilaterally in the prelimbic and orbitofrontal cortices and mediodorsal thalamic nucleus. Stimulation was delivered bilaterally with 100 mu s duration constant current pulses at a frequency of 130 Hz delivered at an amplitude of 100 mu A using a custom-made stimulation device. Synchronized video and LFP data were collected from animals in their home cages before, during and after stimulation. Signals were processed to remove movement and stimulation artifacts, and analyzed to determine changes in spectral power within, and coherence between regions. Five days stimulation of the nucleus accumbens core yielded temporally dynamic modulation of LFP power in multiple bandwidths across multiple brain regions. Coherence was seen to decrease in the alpha band between the mediodorsal thalamic nucleus and core of the nucleus accumbens. Coherence between each core of the nucleus accumbens bilaterally showed rich temporal dynamics throughout the five day stimulation period. Stimulation cessation revealed significant "rebound" effects in both power and coherence in multiple brain regions. Overall, the initial changes in power observed with short-term stimulation are replaced by altered coherence, which may reflect the functional action of DBS. (c) 2013 Elsevier Inc. All rights reserved.