Guller Yelena, Ferrarelli Fabio, Shackman Alexander J, Sarasso Simone, Peterson Michael J, Langheim Frederick J, Meyerand Mary E, Tononi Giulio, Postle Bradley R
Department of Psychiatry, University of Wisconsin–Madison, 53706, USA.
Arch Gen Psychiatry. 2012 Jul;69(7):662-71. doi: 10.1001/archgenpsychiatry.2012.23.
Schizophrenia is a devastating illness with an indeterminate pathophysiology. Several lines of evidence implicate dysfunction in the thalamus, a key node in the distributed neural networks underlying perception, emotion, and cognition. Existing evidence of aberrant thalamic function is based on indirect measures of thalamic activity, but dysfunction has not yet been demonstrated with a causal method.
To test the hypothesis that direct physiological stimulation of the cortex will produce an abnormal thalamic response in individuals with schizophrenia.
We stimulated the precentral gyrus with single-pulse transcranial magnetic stimulation (spTMS) and measured the response to this pulse in synaptically connected regions (thalamus, medial superior frontal cortex, insula) using concurrent functional magnetic resonance imaging. The mean hemodynamic response from these regions was fit with the sum of 2 gamma functions, and response parameters were compared across groups.
Academic research laboratory.
Patients with schizophrenia and sex- and age-matched psychiatrically healthy subjects were recruited from the community.
Peak amplitude of the thalamic hemodynamic response to spTMS of the precentral gyrus.
The spTMS-evoked responses did not differ between groups at the cortical stimulation site. Compared with healthy subjects, patients with schizophrenia showed a reduced response to spTMS in the thalamus (P=1.86 × 10(-9)) and medial superior frontal cortex (P=.02). Similar results were observed in the insula. Sham TMS indicated that these results could not be attributed to indirect effects of TMS coil discharge. Functional connectivity analyses revealed weaker thalamus-medial superior frontal cortex and thalamus-insula connectivity in patients with schizophrenia compared with control subjects.
Individuals with schizophrenia showed reduced thalamic activation in response to direct perturbation delivered to the cortex. These results extend prior work implicating the thalamus in the pathophysiology of schizophrenia and suggest that the thalamus contributes to the patterns of aberrant connectivity characteristic of this disease.
精神分裂症是一种具有不确定病理生理学机制的毁灭性疾病。多条证据表明丘脑功能失调，丘脑是感知、情感和认知所依赖的分布式神经网络中的一个关键节点。现有的丘脑功能异常证据基于对丘脑活动的间接测量，但尚未通过因果方法证实功能失调。
检验皮层直接生理刺激会在精神分裂症患者中产生异常丘脑反应这一假设。
我们使用单脉冲经颅磁刺激（spTMS）刺激中央前回，并使用同步功能磁共振成像测量在突触连接区域（丘脑、内侧额上回、岛叶）对该脉冲的反应。这些区域的平均血液动力学反应与两个伽马函数的总和拟合，并比较各组的反应参数。
学术研究实验室。
从社区招募精神分裂症患者以及性别和年龄匹配的精神健康受试者。
中央前回spTMS刺激后丘脑血液动力学反应的峰值幅度。
在皮层刺激部位，两组之间的spTMS诱发反应没有差异。与健康受试者相比，精神分裂症患者对spTMS在丘脑（P = 1.86×10⁻⁹）和内侧额上回（P = 0.02）的反应降低。在岛叶也观察到类似结果。假TMS表明这些结果不能归因于TMS线圈放电的间接影响。功能连接分析显示，与对照组相比，精神分裂症患者的丘脑 - 内侧额上回和丘脑 - 岛叶连接较弱。
精神分裂症患者在接受传递至皮层的直接扰动时，丘脑激活减少。这些结果扩展了先前将丘脑与精神分裂症病理生理学相关联的研究工作，并表明丘脑促成了该疾病特征性的异常连接模式。
