Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Hum Brain Mapp. 2014 Jan;35(1):140-51. doi: 10.1002/hbm.22165. Epub 2012 Sep 11.
Neuronal plasticity is crucial for flexible interaction with a changing environment and its disruption is thought to contribute to psychiatric diseases like schizophrenia. High-frequency repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool to increase local excitability of neurons and induce short-time functional reorganization of cortical networks. While this has been shown for the motor system, little is known about the short-term plasticity of networks for executive cognition in humans. We examined 12 healthy control subjects in a crossover study with fMRI after real and sham 5 Hz rTMS to the right dorsolateral prefrontal cortex (DLPFC). During scanning, subjects performed an n-back working memory (WM) task and a flanker task engaging cognitive control. Reaction times during the n-back task were significantly shorter after rTMS than after sham stimulation. RTMS compared with sham stimulation caused no activation changes at the stimulation site (right DLPFC) itself, but significantly increased connectivity within the WM network during n-back and reduced activation in the anterior cingulate cortex during the flanker task. Reduced reaction times after real stimulation support an excitatory effect of high-frequency rTMS. Our findings identified plastic changes in prefrontally connected networks downstream of the stimulation site as the substrate of this behavioral effect. Using a multimodal fMRI-rTMS approach, we could demonstrate changes in cortical plasticity in humans during executive cognition. In further studies this approach could be used to study pharmacological, genetic and disease-related alterations.
神经可塑性对于灵活地与不断变化的环境相互作用至关重要，其破坏被认为是导致精神分裂症等精神疾病的原因之一。高频重复经颅磁刺激（rTMS）是一种非侵入性工具，可以增加神经元的局部兴奋性，并诱导皮质网络的短期功能重组。虽然这在运动系统中已经得到证实，但对于人类执行认知网络的短期可塑性知之甚少。我们在一项交叉研究中检查了 12 名健康对照者，在对右侧背外侧前额叶皮层（DLPFC）进行真实和假 5 Hz rTMS 后进行 fMRI。在扫描过程中，受试者执行 n-back 工作记忆（WM）任务和执行认知控制的侧抑制任务。与假刺激相比，rTMS 后 n-back 任务的反应时间明显缩短。与假刺激相比，rTMS 刺激本身并未引起刺激部位（右侧 DLPFC）的激活变化，但在 n-back 期间显着增加了 WM 网络内的连接性，并在侧抑制任务期间减少了前扣带皮层的激活。真实刺激后的反应时间缩短支持高频 rTMS 的兴奋性效应。我们的发现确定了刺激部位下游前额叶连接网络中的可塑性变化是这种行为效应的基础。使用多模态 fMRI-rTMS 方法，我们可以证明人类在执行认知过程中皮质可塑性的变化。在进一步的研究中，这种方法可用于研究药理学、遗传学和疾病相关的改变。
