Structural Thalamofrontal Hypoconnectivity Is Related to Oculomotor Corollary Discharge Dysfunction in Schizophrenia
Structural Thalamofrontal Hypoconnectivity Is Related to Oculomotor Corollary Discharge Dysfunction in Schizophrenia
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DOI：
10.1523/jneurosci.1473-18.2019
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发表时间：
2019-01
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通讯作者：
Beier Yao;S. Neggers;M. Rolfs;L. Rösler;Ilse A Thompson;H. Hopman;Livon Ghermezi;R. Kahn;Katharine N. Thakkar
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文献类型：
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作者：
Beier Yao;S. Neggers;M. Rolfs;L. Rösler;Ilse A Thompson;H. Hopman;Livon Ghermezi;R. Kahn;Katharine N. Thakkar
通过预测行为的感官后果，人类可以区分自我产生的感官输入和外部引发的感官输入。这是一种机制，通过这种机制，我们对自己的行为产生了主观的能动性。推论放电（CD）信号-发送到感觉区域的运动信号的“副本”-允许这样的预测，CD异常是精神分裂症中表征症状子集的代理中断的假设机制。事实上，在精神分裂症患者中已经观察到CD改变的行为证据，包括眼神经系统。在非人灵长类动物中，从上级丘经由内侧背丘脑（MD）投射到额眼野（FEF）的通路传递与扫视眼球运动相关的眼CD。这项动物研究提供了一个有前途的翻译框架，在其中研究CD异常的临床人群。在目前的研究中，我们研究了是否结构连接的MD-FEF通路与眼CD功能在精神分裂症。22名精神分裂症患者和24名健康对照男女参与者进行了弥散张量成像，一个大的子集进行了跨扫视知觉任务，产生CD的措施。使用概率纤维束成像，我们确定了FEF和MD之间的解剖连接，并提取了显微结构完整性指数。患者在MD-FEF通路中表现出受损的微结构完整性，这与更大的眼部CD异常和更严重的精神病症状相关。这些数据加强了MD-FEF通路在传递眼CD信号中的作用，并表明该通路的紊乱可能与患者的精神病症状表现有关。精神分裂症患者有时会经历一种代理感的异常，这可能源于对自己行为的异常感官预测。与这一观点一致，目前的研究发现，精神分裂症患者在一个特定的大脑通路中的结构连接性降低，该通路在非人类灵长类动物中被发现传递这种感觉运动预测信号。结构连接性降低与感觉运动预测受损和精神病症状的行为证据相关。
By predicting sensory consequences of actions, humans can distinguish self-generated sensory inputs from those that are elicited externally. This is one mechanism by which we achieve a subjective sense of agency over our actions. Corollary discharge (CD) signals—“copies” of motor signals sent to sensory areas—permit such predictions, and CD abnormalities are a hypothesized mechanism for the agency disruptions in schizophrenia that characterize a subset of symptoms. Indeed, behavioral evidence of altered CD, including in the oculomotor system, has been observed in schizophrenia patients. A pathway projecting from the superior colliculus to the frontal eye fields (FEFs) via the mediodorsal thalamus (MD) conveys oculomotor CD associated with saccadic eye movements in nonhuman primates. This animal work provides a promising translational framework in which to investigate CD abnormalities in clinical populations. In the current study, we examined whether structural connectivity of this MD–FEF pathway relates to oculomotor CD functioning in schizophrenia. Twenty-two schizophrenia patients and 24 healthy control participants of both sexes underwent diffusion tensor imaging, and a large subset performed a trans-saccadic perceptual task that yields measures of CD. Using probabilistic tractography, we identified anatomical connections between FEF and MD and extracted indices of microstructural integrity. Patients exhibited compromised microstructural integrity in the MD–FEF pathway, which was correlated with greater oculomotor CD abnormalities and more severe psychotic symptoms. These data reinforce the role of the MD–FEF pathway in transmitting oculomotor CD signals and suggest that disturbances in this pathway may relate to psychotic symptom manifestation in patients. SIGNIFICANCE STATEMENT People with schizophrenia sometimes experience abnormalities in a sense of agency, which may stem from abnormal sensory predictions about their own actions. Consistent with this notion, the current study found reduced structural connectivity in patients with schizophrenia in a specific brain pathway found to transmit such sensorimotor prediction signals in nonhuman primates. Reduced structural connectivity was correlated with behavioral evidence for impaired sensorimotor predictions and psychotic symptoms.