Parr Thomas, Oswal Ashwini, Manohar Sanjay G
Nuffield Department of Clinical Neurosciences, University of Oxford, UK.
Nuffield Department of Clinical Neurosciences, University of Oxford, UK.
Neurosci Biobehav Rev. 2025 Feb;169:105984. doi: 10.1016/j.neubiorev.2024.105984. Epub 2024 Dec 17.
Most of our movement consists of sequences of discrete actions at regular intervals-including speech, walking, playing music, or even chewing. Despite this, few models of the motor system address how the brain determines the interval at which to trigger actions. This paper offers a theoretical analysis of the problem of timing movements. We consider a scenario in which we must align an alternating movement with a regular external (auditory) stimulus. We assume that our brains employ generative world models that include internal clocks of various speeds. These allow us to associate a temporally regular sensory input with an internal clock, and actions with parts of that clock cycle. We treat this as process of inferring which clock best explains sensory input. This offers a way in which temporally discrete choices might emerge from a continuous process. This is not straightforward, particularly if each of those choices unfolds during a time that has a (possibly unknown) duration. We develop a route for translation to neurology, in the context of Parkinson's disease-a disorder that characteristically slows down movements. The effects are often elicited in clinic by alternating movements. We find that it is possible to reproduce behavioural and electrophysiological features associated with parkinsonism by disrupting specific parameters-that determine the priors for inferences made by the brain. We observe three core features of Parkinson's disease: amplitude decrement, festination, and breakdown of repetitive movements. Our simulations provide a mechanistic interpretation of how pathology and therapeutics might influence behaviour and neural activity.
我们的大多数动作都由一系列有规律间隔的离散动作组成,包括说话、行走、演奏音乐,甚至咀嚼。尽管如此,很少有运动系统模型探讨大脑如何确定触发动作的间隔时间。本文对动作计时问题进行了理论分析。我们考虑一种情景,即必须使交替动作与有规律的外部(听觉)刺激同步。我们假设大脑使用生成式世界模型,其中包括各种速度的内部时钟。这些时钟使我们能够将时间上有规律的感官输入与内部时钟联系起来,并将动作与该时钟周期的各个部分联系起来。我们将此视为推断哪个时钟最能解释感官输入的过程。这提供了一种方式,使时间上离散的选择可能从连续过程中产生。这并非易事,尤其是如果每个选择都在一个(可能未知)持续时间内展开。我们在帕金森病(一种典型地会使动作变慢的疾病)的背景下,开发了一条向神经学转化的途径。临床症状通常由交替动作引发。我们发现,通过破坏特定参数(这些参数决定大脑进行推断的先验条件),有可能重现与帕金森症相关的行为和电生理特征。我们观察到帕金森病的三个核心特征:幅度递减、慌张步态和重复动作的中断。我们的模拟为病理和治疗如何影响行为和神经活动提供了一种机制性解释。