Friday, May 9, 2025
5/9/2025
Cortical and subcortical neurophysiology in terminating movement - ABSTRACT Our ability to stop and control movements is an integral part of human behavior. This behavior is disrupted in several disorders such as Parkinson’s disease, attention deficit disorder, obsessive compulsive disorder, and addiction. Previous work has often used motor inhibition tasks such as the stop signal task to study this behavior. In this task, participants are instructed to respond to a stimuli (such as an arrow) with a button press. On most trials the response is executed as planned. However, on a minority of trials a second stimuli – a stop signal – is presented that indicates the participant should attempt to stop their movement. This task, combined with neuroscientific techniques, has pointed to the importance of a network of cortical and subcortical regions. However, the stop signal task has several limitations. First, because the stop task requires contrasting successful stopping with trials that include a response – disentangling motoric cessation of movement from the cognitive inhibitory component is challenging. Second, although examples of stopping in daily life often focus on stopping ongoing movements (i.e. stopping walking when you see a car rounding the corner), the traditional stop signal task focuses on single, discrete, movements. It is unclear if the same neural network and physiological processes are involved in stopping continuous movements. Finally, the time it takes to stop cannot be calculated for individual trials and instead is estimated over the entire task, complicating certain analyses/interpretations. To address these limitations, we have designed a new task. Here participants perform a continuous movement during a countdown. On the majority of trials, the countdown proceeds to 0 as expected and then a stop signal appears, but on a minority of trials, the stop signal occurs early and the participant must stop a response before they expected. In this proposal, participants will perform this novel task while their brain activity is recorded. We will first use two different approaches to probe both cortical and subcortical activity. First, to examine cortical activity we will record intracranial electrophysiology from epilepsy patients undergoing invasive monitoring. Then, to examine subcortical activity (and its influence on cortex) we will record scalp EEG in a special cohort of Parkinson’s disease patients with deep brain stimulation electrodes implanted in different subcortical nodes (subthalamic nucleus, STN and globus pallidus interna, GPi). These patients will be tested with their stimulation turned both on and off to examine the effect of subcortical stimulation of particular nodes on behavior and cortical activity. Finally, we will establish the ecological validity and clinical reliability of this task by comparing behavioral measures derived from the task to validated scales of cognition and inhibitory control in a large cohort of controls and nicotine dependent individuals (smokers). This cohort is appropriate because models of addiction have identified inhibitory control deficits as an important factor in addictive behavior. Overall, these experiments will disentangle roles of cortical and subcortical nodes in stopping continuous movements and link these behaviors to clinically validates measures.
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