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Using Deep Brain Stimulation to Unravel the Mysteries of Cardiorespiratory Control

Alexander L. Green, David J. Paterson

10.1002/cphy.c190039

Source: Volume 10, Issue 3, July 2020

Published online: July 2020

Full Article on Wiley Online Library



Abstract

This article charts the history of deep brain stimulation (DBS) as applied to alleviate a number of neurological disorders, while in parallel mapping the electrophysiological circuits involved in generating and integrating neural signals driving the cardiorespiratory system during exercise. With the advent of improved neuroimaging techniques, neurosurgeons can place small electrodes into deep brain structures with a high degree accuracy to treat a number of neurological disorders, such as movement impairment associated with Parkinson's disease and neuropathic pain. As well as stimulating discrete nuclei and monitoring autonomic outflow, local field potentials can also assess how the neurocircuitry responds to exercise. This technique has provided an opportunity to validate in humans putative circuits previously identified in animal models. The central autonomic network consists of multiple sites from the spinal cord to the cortex involved in autonomic control. Important areas exist at multiple evolutionary levels, which include the anterior cingulate cortex (telencephalon), hypothalamus (diencephalon), periaqueductal grey (midbrain), parabrachial nucleus and nucleus of the tractus solitaries (brainstem), and the intermediolateral column of the spinal cord. These areas receive afferent input from all over the body and provide a site for integration, resulting in a coordinated efferent autonomic (sympathetic and parasympathetic) response. In particular, emerging evidence from DBS studies have identified the basal ganglia as a major sub‐cortical cognitive integrator of both higher center and peripheral afferent feedback. These circuits in the basal ganglia appear to be central in coupling movement to the cardiorespiratory motor program. © 2020 American Physiological Society. Compr Physiol 10:1085‐1104, 2020.

Figure 1. Figure 1. Brain areas are known to be involved in autonomic control. Shaded areas are approximate regions. Note that the insula is in the mesial temporal lobe lateral to the basal ganglia which is not shown and the area, therefore, appears out of the picture. Midline structures are surrounded by a broken line.
Figure 2. Figure 2. (A,B) To perform deep brain stimulation, the target is accurately planned on an MRI scan and custom targeting software (such as Renishaw Neuroinspire® depicted here). (C) Surgery is performed to insert the electrode using a stereotactic frame. Intraoperative testing may be used in awake patients. (D) The brain electrodes are connected via a subcutaneous extension wire to an implantable pulse generator placed in a subcutaneous pocket. Courtesy of Dr. Binith Cheeran, Abbott Neuromodulation.
Figure 3. Figure 3. Looking at the mechanisms of the effect of DBS on autonomic parameters. A microneurographer (inset) can record from the autonomic fibers within the peroneal muscle. Comparing DBS On and Off shows that stimulation of the dorsal subthalamic nucleus increases muscle sympathetic nerve activity and is associated with a small increase in BP. Adapted, with permission, from Sverrisdottir YB, et al., 2014 236.
Figure 4. Figure 4. Study of DBS patients allows a number of investigations to elucidate brain function in the context of cardiorespiratory function. This particular study used subjects with indwelling DBS electrodes in the pedunculopontine nucleus (PPN) for the treatment of Parkinson's disease. (A) Position of electrode contacts studied in a group of patients undergoing PPN stimulation. (B) Local field potentials (LFPs) tell us how the PPN is changing electrically. Here, the patient undergoes head‐up tilt testing (HUTT) (blue vertical line) and there is a resultant reduction in alpha (8–12 Hz) activity in the PPN. (C) Physiological testing demonstrates that PPN stimulation reduces the postural drop in BP on HUTT. “On” refers to stimulation “On” rather than levodopa effects. (D) DTI analysis demonstrates connections between PPN and other brain areas. Adapted, with permission, from Hyam JARH, et al., 2019 131.
Figure 5. Figure 5. BP changes resulting from intraoperative stimulation of two different areas of the PAG in a single subject. (A) BP reduction resulted from ventral stimulation in the first position studied. (B) As the electrode was advanced, stimulation posteriorly in the dorsal PAG resulted in increased BP. (C) An axial MRI showing an electrode contact in the left PAG (arrow). (D) A schematic sagittal section in the midline to show the electrode position relative to surrounding structures.


Figure 1. Brain areas are known to be involved in autonomic control. Shaded areas are approximate regions. Note that the insula is in the mesial temporal lobe lateral to the basal ganglia which is not shown and the area, therefore, appears out of the picture. Midline structures are surrounded by a broken line.


Figure 2. (A,B) To perform deep brain stimulation, the target is accurately planned on an MRI scan and custom targeting software (such as Renishaw Neuroinspire® depicted here). (C) Surgery is performed to insert the electrode using a stereotactic frame. Intraoperative testing may be used in awake patients. (D) The brain electrodes are connected via a subcutaneous extension wire to an implantable pulse generator placed in a subcutaneous pocket. Courtesy of Dr. Binith Cheeran, Abbott Neuromodulation.


Figure 3. Looking at the mechanisms of the effect of DBS on autonomic parameters. A microneurographer (inset) can record from the autonomic fibers within the peroneal muscle. Comparing DBS On and Off shows that stimulation of the dorsal subthalamic nucleus increases muscle sympathetic nerve activity and is associated with a small increase in BP. Adapted, with permission, from Sverrisdottir YB, et al., 2014 236.


Figure 4. Study of DBS patients allows a number of investigations to elucidate brain function in the context of cardiorespiratory function. This particular study used subjects with indwelling DBS electrodes in the pedunculopontine nucleus (PPN) for the treatment of Parkinson's disease. (A) Position of electrode contacts studied in a group of patients undergoing PPN stimulation. (B) Local field potentials (LFPs) tell us how the PPN is changing electrically. Here, the patient undergoes head‐up tilt testing (HUTT) (blue vertical line) and there is a resultant reduction in alpha (8–12 Hz) activity in the PPN. (C) Physiological testing demonstrates that PPN stimulation reduces the postural drop in BP on HUTT. “On” refers to stimulation “On” rather than levodopa effects. (D) DTI analysis demonstrates connections between PPN and other brain areas. Adapted, with permission, from Hyam JARH, et al., 2019 131.


Figure 5. BP changes resulting from intraoperative stimulation of two different areas of the PAG in a single subject. (A) BP reduction resulted from ventral stimulation in the first position studied. (B) As the electrode was advanced, stimulation posteriorly in the dorsal PAG resulted in increased BP. (C) An axial MRI showing an electrode contact in the left PAG (arrow). (D) A schematic sagittal section in the midline to show the electrode position relative to surrounding structures.
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Article Title: Using Deep Brain Stimulation to Unravel the Mysteries of Cardiorespiratory Control
 

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Alexander L. Green, David J. Paterson. Using Deep Brain Stimulation to Unravel the Mysteries of Cardiorespiratory Control. Compr Physiol 2020, 10: 1085-1104. doi: 10.1002/cphy.c190039