Nicotinic receptor modulation of the default mode network.
Nicotinic receptor modulation of the default mode network.
复制标题
默认模式网络的烟碱受体调节。
DOI：
10.1007/s00213-020-05711-9
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发表时间：
2021
影响因子：
3.4
通讯作者：
Stein,ElliotA
中科院分区：
文献类型：
--
作者：
Hahn,Britta;Harvey,AlexanderN;Concheiro-Guisan,Marta;Huestis,MarilynA;Ross,ThomasJ;Stein,ElliotA
先前的神经成像研究涉及烟碱乙酰胆碱受体（nAChR）激动剂管理的认知一再发现增强的任务诱导的默认模式网络（DMN）区域的失活，这是一组大脑系统，在休息时更活跃，并介导任务无关的思维过程。目的本研究试图测试DMN的nAChR调节是否是双向的，即，是否nAChR拮抗剂将减少任务诱导的deactivation.MethodsEighteen健康的非吸烟者进行功能磁共振成像，同时执行一个字母N-回任务。在给予尼古丁（7 mg/24 h，透皮）后，给予nAChR拮抗剂美加明（7.5 mg，p.o.）后，在双重安慰剂后，以平衡顺序。血氧水平依赖（BOLD）的信号进行了分析腹内侧前额叶皮层（vmPFC）和后扣带皮层（PCC）区域的利益，中央枢纽的DMN.ResultsNicotine一致nAChR激动剂诱导的变化已被确定在0-回和2-回的条件下，提高命中率，而美加明减慢反应时间在2-回的条件。美加明减少了vmPFC和PCC的任务诱导的失活。尼古丁没有显着影响BOLD signal.ConclusionsThe发现，nAChR音减少美加明削弱任务引起的DMN失活表明，一个恒定的音调nAChR激活有助于调节DMN活动在健康个体。这表明低nAChR张力可能在轻度认知障碍或阿尔茨海默病等疾病中观察到的DMN失调中发挥因果作用。
RationalePrevious neuroimaging studies of cognition involving nicotinic acetylcholine receptor (nAChR) agonist administration have repeatedly found enhanced task-induced deactivation of regions of the default mode network (DMN), a group of brain systems that is more active at rest and mediates task-independent thought processes. This effect may be related to pro-cognitive nAChR agonist effectsObjectivesThe present study sought to test whether nAChR modulation of the DMN is bi-directional, i.e., whether a nAChR antagonist would reduce task-induced deactivation.MethodsEighteen healthy non-smokers underwent functional magnetic resonance imaging while performing a letter N-back task. Scans were performed after nicotine administration (7 mg/24 h, transdermally), after administration of the nAChR antagonist mecamylamine (7.5 mg, p.o.), and after double placebo, in counterbalanced sequence. Blood-oxygen-level-dependent (BOLD) signal was analyzed within ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC) regions of interest—central hubs of the DMN in which consistent nAChR agonist–induced changes had previously been identified.ResultsNicotine enhanced hit rate in both the 0-back and 2-back condition, while mecamylamine slowed reaction time in the 2-back condition. Mecamylamine reduced task-induced deactivation of vmPFC and PCC. Nicotine had no significant effects on the BOLD signal.ConclusionsThe finding that nAChR tone reduction by mecamylamine weakened task-induced DMN deactivation indicates that a constant tone of nAChR activation helps regulate DMN activity in healthy individuals. This suggests that low nAChR tone may play a causal role in DMN dysregulation seen in conditions such as mild cognitive impairment or Alzheimer’s disease.