Application of High-Frequency Repetitive Transcranial Magnetic Stimulation to the DLPFC Alters Human Prefrontal-Hippocampal Functional Interaction
Application of High-Frequency Repetitive Transcranial Magnetic Stimulation to the DLPFC Alters Human Prefrontal-Hippocampal Functional Interaction
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DOI：
10.1523/jneurosci.3081-12.2013
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发表时间：
2013-04-17
影响因子：
5.3
通讯作者：
Tost, Heike
中科院分区：
文献类型：
--
作者：
Bilek, Edda;Schaefer, Axel;Tost, Heike
神经可塑性对于理解大脑调节回路的经验依赖性重组和精神分裂症的病理生理学至关重要。一个重要的电路水平的功能磁共振成像（fMRI）的功能是前额叶海马种子连接在工作记忆中，最好的中间连接表型的精神分裂症的风险。该表型是可塑性增强干预措施（如高频重复经颅磁刺激（rTMS））效果的一个有前途的标志物，并且可以在没有疾病相关混淆的情况下在健康志愿者中进行研究，但与大脑可塑性的关系尚未探索。我们招募了39名健康志愿者，研究5 Hz rTMS对工作记忆和静息状态下前额叶-海马耦合的影响。在一项随机和假对照实验中，将神经导航引导的rTMS应用于右背外侧前额叶皮层（DLPFC），并将fMRI和功能连接分析[种子连接和心理生理相互作用（PPI）]用作读数。此外，还对工作记忆相关连接标记的重测信度进行了评价。rTMS引起的种子功能连接的右侧DLPFC和左侧海马在工作记忆中，被证明是相对时不变的和强大的显着下降。PPI分析提供了证据的名义效应rTMS和差的重测信度。未观察到对n-back相关激活和DLPFC-海马静息状态连接的影响。这些数据提供了第一个在体内的证据，可塑性诱导对人类前额叶-海马网络动力学的影响，提供了深入了解一个成熟的中间表型与精神分裂症的生物学机制，并强调了在重测设计的结果措施的选择的重要性。
Neural plasticity is crucial for understanding the experience-dependent reorganization of brain regulatory circuits and the pathophysiology of schizophrenia. An important circuit-level feature derived from functional magnetic resonance imaging (fMRI) is prefrontal-hippocampal seeded connectivity during working memory, the best established intermediate connectivity phenotype of schizophrenia risk to date. The phenotype is a promising marker for the effects of plasticity-enhancing interventions, such as high-frequency repetitive transcranial magnetic stimulation (rTMS), and can be studied in healthy volunteers in the absence of illness-related confounds, but the relationship to brain plasticity is unexplored. We recruited 39 healthy volunteers to investigate the effects of 5 Hz rTMS on prefrontal-hippocampal coupling during working memory and rest. In a randomized and sham-controlled experiment, neuronavigation-guided rTMS was applied to the right dorsolateral prefrontal cortex (DLPFC), and fMRI and functional connectivity analyses [seeded connectivity and psychophysiological interaction (PPI)] were used as readouts. Moreover, the test-retest reliability of working-memory related connectivity markers was evaluated. rTMS provoked a significant decrease in seeded functional connectivity of the right DLPFC and left hippocampus during working memory that proved to be relatively time-invariant and robust. PPI analyses provided evidence for a nominal effect of rTMS and poor test-retest reliability. No effects on n-back-related activation and DLPFC-hippocampus resting-state connectivity were observed. These data provide the first in vivo evidence for the effects of plasticity induction on human prefrontal-hippocampal network dynamics, offer insights into the biological mechanisms of a well established intermediate phenotype linked to schizophrenia, and underscores the importance of the choice of outcome measures in test-retest designs.