When a movement that has already been initiated must be suddenly stopped, a “hyperdirect” subthalamic nucleus pathway is called upon to override the primary motor control systems of the cerebral cortex, to block the action midway, a new study led by scientists at the University of Iowa has discovered.

In studies conducted on patients with Parkinson’s disease and healthy controls, researchers show when cortico-spinal excitability (CSE) is inhibited midway through an action, the inhibition extends beyond just the muscle involved in the task. This overriding pathway helps humans react to potentially dangerous or surprising situations.

The findings were published in an article in the journal Current Biology, titled, “A causal role for the human subthalamic nucleus in non-selective cortico-motor inhibition.” The identification of this hyperdirect pathway in controlling brain-body communication could advance treatment for Parkinson’s disease, where motor coordination progressively declines.

“The subthalamic nucleus is a key therapeutic target in Parkinson’s disease,” said Jan Wessel, PhD, an associate professor in the department of psychological and brain sciences, and neurology, at Iowa University and the senior author of the paper. “Indeed, just like it was done for the patient sample in our study, implantation of stimulation electrodes into the subthalamic nucleus is a highly successful treatment option for the motoric symptoms of Parkinson’s disease. Our study provides some mechanistic insights into this potential patient-care benefit.”

The subthalamic nucleus is a tiny cluster of cells that forms part of the basal ganglia, which is a key component of the neural circuit that controls movement. The basal ganglia coordinates initial motor commands by either amplifying or blocking signals or sub-signals that constitute commands from the primary motor cortex.

“You can think of the subthalamic nucleus as the core region in this ‘halting’ of extra, unwanted components of compound movements, as it is the last relay station before the output nuclei of the basal ganglia, which then communicates these commands to the wider motor system,” said Jan Wessel, PhD, an associate professor in the department of psychological and brain sciences, and neurology, at Iowa University and the senior author of the paper.

Earlier studies had hinted at the role of the subthalamic nucleus in inhibiting motor signals, but its role has not been demonstrated in humans until now.

In the current study, the scientists recruited 20 patients with Parkinson’s disease and 20 matched healthy individuals. The patients already had deep-brain stimulators implanted for therapeutic purposes, that the researchers used to transiently activate or deactivate the subthalamic nucleus.

Concurrent to the manipulation of the subthalamic nucleus using deep brain stimulation (DBS), the authors measured cortico-spinal excitability using transcranial magnetic stimulation (TMS) during a verbal stop-signal task from a hand muscle unrelated to the task.

“Deep-brain stimulation is the only method to causally and systematically influence the activity of deeply embedded brain nuclei like the subthalamic nucleus in awake, [and active] humans,” said Wessel. “However, combining deep-brain stimulation with transcranial magnetic stimulation is a highly complicated and novel technical endeavor, especially in awake, behaving humans.”

The scientists observed that in patients who did not receive DBS and controls, cortico-spinal excitability of the hand was suppressed when the verbal response was successfully stopped. This effect disappeared when the subthalamic nucleus was deactivated using DBS, in the patient group.

The combination of DBS and TMS in this study, allowed the scientists to uncover evidence that the subthalamic nucleus could be involved in nonselectively suppressing the cortico-motor pathway to stop an ongoing action abruptly.

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