Department of Psychology, Michigan State University, East Lansing, Michigan 48824.
Department of Psychiatry, University Medical Center, 3584 CX, Utrecht, The Netherlands.
J Neurosci. 2019 Mar 13;39(11):2102-2113. doi: 10.1523/JNEUROSCI.1473-18.2019. Epub 2019 Jan 10.
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. 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.
通过预测动作的感觉后果，人类可以将自身产生的感觉输入与外部引发的感觉输入区分开来。这是我们实现对自身行为的主观控制感的一种机制。相关放电（CD）信号——发送到感觉区域的运动信号的“副本”——允许进行这种预测，并且 CD 异常是精神分裂症中agency 中断的假设机制，这种中断是该病症的一部分症状的特征。事实上，已经在精神分裂症患者中观察到 CD 的改变的行为证据，包括在眼球运动系统中。一条从前上丘经由中脑背侧丘脑（MD）投射到额眼区（FEF）的通路，在非人类灵长类动物中传递与扫视眼动相关的眼球运动 CD。这项动物研究为在临床人群中研究 CD 异常提供了一个有前景的转化框架。在目前的研究中，我们研究了这条 MD-FEF 通路的结构连接是否与精神分裂症中的眼球运动 CD 功能有关。22 名精神分裂症患者和 24 名男女健康对照者接受了弥散张量成像检查，其中大部分人进行了跨扫视知觉任务，该任务可得出 CD 的测量值。我们使用概率追踪技术，在 FEF 和 MD 之间识别出解剖连接，并提取了微观结构完整性的指标。患者的 MD-FEF 通路显示出微观结构完整性受损，这与眼球运动 CD 异常更严重和更严重的精神病症状有关。这些数据强化了 MD-FEF 通路在传递眼球运动 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出现agency 异常，这可能源于对自身行为的异常感觉预测。与这一观点一致，目前的研究发现，在一种特定的大脑通路中，精神分裂症患者的结构连接减少，这种通路在非人类灵长类动物中传递这种感觉运动预测信号。结构连接减少与行为证据表明感觉运动预测受损和精神病症状有关。
