Investigating the role of cerebellar abnormalities in dysfunctional predictive coding in individuals with schizophrenia

项目摘要 预测编码失败是关于精神分裂症神经机制的一个有影响力的假设， 可以解释这种疾病的主要症状具体来说，有人假设，所有自我生成的 动作产生一个输出拷贝，或运动指令的拷贝，这导致感觉推论 放电，或该行动的预期感官后果的神经表征，并通过此 预测性编码动作的神经机制在神经水平上被分类为起源于自我。这 也被认为发生在内部过程中，这样思想也会产生一种输出。 副本和相应的解除。如果一个想法或行动缺乏这种自我生成的神经信号， 控制妄想或幻觉可能会出现，以解释这些看似外部的经验。然而，在这方面， 这种简约而理论上令人信服的假设的精确神经机制还有待于进一步研究。 阐明。考虑运动控制领域中的类似机制可能是有益的，其中 传出副本类似地响应于动作而生成，但是随后被假设为行进到 小脑，其中内部模型模拟运动的动力学并输出必然的放电 （仍然是预测的感觉结果），但用于运动控制而不是预测编码。 鉴于精神分裂症患者小脑功能障碍的证据越来越多， 这两种机制，拟议的研究将检查小脑是否参与预测 小脑异常是否有助于精神分裂症的预测编码功能障碍。的 将在对照组和个体中评估小脑完整性与预测编码测量的关系 精神分裂症行为测量（姿势摇摆和亚秒级手指敲击）和结构测量（ 将对30名精神分裂症患者进行小脑完整性测量（解剖MRI）， 30个非精神病对照组。先前建立的传出复制的电生理测量， 将在EEG数据中量化响应自起搏按钮按压的必然放电; 小脑异常与传出复制强度的关系及其推论 将评估出院情况。接下来，对照组将同时进行EEG和小脑经颅直接 电流刺激调节小脑神经元的兴奋性，对相应放电强度的影响将 进行评估。结果将揭示小脑异常是否有助于预测编码功能障碍， 精神分裂症，以及小脑神经元兴奋性的调制是否影响预测编码， 对照公共卫生影响包括更好地阐明精神分裂症的病理生理机制 并对小脑在预测编码中的作用有了更精确的理解。

Project Summary Failure in predictive coding is an influential hypothesis regarding the neural mechanisms of schizophrenia that may account for cardinal symptoms of the disorder. Specifically, it has been hypothesized that all self-generated actions produce an efference copy, or a copy of the motor command, which results in a sensory corollary discharge, or a neural representation of the expected sensory consequences of that action, and that through this neural mechanism of predictive coding actions are classified at the neural level as originating from the self. This has been proposed to occur for internal processes as well, such that thoughts would also generate an efference copy and a corollary discharge. If a thought or action lacked this neural signature of self-generation, then delusions of control or hallucinations could arise to account for these seemingly external experiences. However, the precise neural mechanisms of this parsimonious and theoretically compelling hypothesis have yet to be elucidated. It may be informative to consider an analogous mechanism in the domain of motor control, wherein an efference copy is similarly generated in response to an action, but is then hypothesized to travel to the cerebellum, where an internal model simulates the dynamics of movement and outputs a corollary discharge (still the predicted sensory consequences), but for the purpose of motor control rather than predictive coding. Given the accumulating evidence of cerebellar dysfunction in schizophrenia and the striking similarities between these two mechanisms, the proposed research will examine whether the cerebellum is involved in predictive coding and whether cerebellar abnormalities contribute to predictive coding dysfunction in schizophrenia. The relationship of cerebellar integrity to measures of predictive coding will be assessed in controls and individuals with schizophrenia. Behavioral measures (postural sway and subsecond paced finger tapping) and a structural measure (anatomical MRI) of cerebellar integrity will be administered to 30 individuals with schizophrenia and 30 non-psychiatric controls. Previously established electrophysiological measures of the efference copy and corollary discharge will be quantified in EEG data in response to self-paced button presses; the effect of cerebellar abnormalities on the relationship between the strength of the efference copy and the corollary discharge will be assessed. Next, controls will undergo simultaneous EEG and cerebellar transcranial direct current stimulation to modulate cerebellar neuronal excitability, and the effect on corollary discharge strength will be assessed. Results will reveal whether cerebellar abnormalities contribute to predictive coding dysfunction in schizophrenia, as well as whether modulation of cerebellar neuronal excitability impacts predictive coding in controls. Public health implications include better elucidating pathophysiological mechanisms of schizophrenia and gaining a more precise understanding of the role of the cerebellum in predictive coding.