Understanding Autonomic Control via Human Deep Brain Stimulation

The Central Autonomic Network (CAN) consists of higher cortical areas, basal ganglia, and brainstem areas that are important in the control of the autonomic nervous system (ANS). This thesis concentrates on the control of the respiratory and cardiovascular systems both alone and in combination in the context of exercise. Deep Brain Stimulation (DBS) is a type of therapy in patients in which electrodes are inserted into the brain to treat neurological disorders such as Parkinson’s disease. The presence of electrodes allows the study of the effects of stimulation of components of the CAN, as well as measurement of electrical activity (local field potentials (LFPs)) to assess whether a nucleus is integral to a specific change in autonomic output. The sum of my work outlined in this thesis demonstrates that common DBS targets such as subthalamic nucleus (STN) and pedunculopontine nucleus (PPN) alter both cardiovascular and respiratory control. Furthermore, these changes have clinical implications not previously highlighted. This includes the relief of breathlessness for some nuclei (such as the motor thalamus) and induction of breathlessness for others (such as STN). In addition to clinical implications, insights are provided into the ‘central command’ system of autonomic control in the brain, such as the role of the anterior cingulate cortex (ACC) in the cardiovascular response to intermittent exercise. Besides advancing understanding of the regulation of these autonomic processes, this work has also directly resulted in first in-human clinical trials of DBS for the treatment of autonomic symptoms of multiple systems atrophy.