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说 可能是这种疾病的主要症状。具体地说，它被假设为所有的自我生成 动作产生传出副本，或运动命令的副本，从而产生感官推论 放电，或该动作的预期感觉后果的神经表示，并通过这个 预测编码行为的神经机制在神经水平上被归类为起源于自我。这 已经被提出也发生在内部过程中，这样思想也会产生传出 复印件和随之而来的退货。如果一个想法或行动缺乏这种自我生成的神经特征，那么 可能会出现控制错觉或幻觉，以解释这些表面上的外部体验。然而， 这一简约而在理论上令人信服的假说的确切神经机制尚未得到证实。 已澄清。考虑运动控制领域中的类似机制可能是有益的，其中 传出副本类似地生成以响应操作，但随后被假定为传输到 小脑，在那里一个内部模型模拟运动的动力学并输出必然的放电 (仍然是预测的感觉后果)，但目的是运动控制，而不是预测编码。 鉴于越来越多的证据表明精神分裂症患者的小脑功能障碍，以及 这两种机制，建议的研究将检查小脑是否参与预测 以及小脑异常是否导致精神分裂症的预测性编码功能障碍。这个 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 患有精神分裂症。行为测量(姿势摆动和亚秒有节奏的手指敲击)和结构性 30名精神分裂症患者将接受小脑完整性测量(解剖MRI)。 30名非精神疾病对照。先前建立的传出副本的电生理测量和 相应的放电将在脑电数据中被量化，以响应自定步速的按钮按下； 小脑异常与传出拷贝强度的关系 将对出院情况进行评估。接下来，对照组将同时接受脑电和小脑直接经颅检查。 电流刺激对小脑神经元兴奋性的调节作用及其对放电强度的影响 被评估。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 控制。对公共卫生的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准确的理解。

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.