Deep brain stimulation and the regulation of autonomic functions, including micturition

Describing the anatomy and behaviour of neural structures that support physiological functions, and understanding their susceptibility to injury through disease processes, is one of the goals of neuroscience research today. The control of autonomic function, including micturition, involves the interaction of highly distributed neural systems to maintain homeostatic balance within the internal milieu of the body and to optimise survival within the hostile environment of the world. Autonomic control is relevant to many diseases of the peripheral and central nervous system and also appears to have implications for cognitive functions, both in the sense that impaired autonomic performance can result in temporary or permanent cognitive impairment due to poor perfusion of the brain, but also in the sense that autonomic input has a major role in our emotional processing and decision making. Better understanding the organisation of this system, then, will have relevance for clinical medicine as well as cognitive neuroscience and physiological science. In this thesis I use three different approaches to better understand the organisation of autonomic and bladder control, all based loosely around the specific insights that can be gained from working with a certain clinical population (patients undergoing deep brain stimulation (DBS)). In the early chapters, I use brain imaging techniques to investigate correlations between white and grey matter structural changes and autonomic symptoms in patients with Parkinson’s disease (PD) and other movement disorders. These analyses identify the left hippocampus as a key grey matter structure relevant to autonomic dysfunction in Parkinson’s disease, and suggest that white matter structural changes associated with autonomic dysfunction are more widespread and less specific than grey matter changes. In addition to this, I investigate whether connectivity to any particular brain regions is associated with improvements or deterioration in autonomic symptoms in PD patients following DBS surgery of the subthalamic nucleus. Significant regions are identified and discussed. In the second main part of the thesis, the focus turns to the control of the urinary bladder. Here, I use local field potential (LFP) analysis to investigate the changes in oscillatory activity of small populations of neurons in the vicinity of implanted DBS electrodes associated with bladder related behaviours. In the first LFP chapter I describe correlations between oscillatory signatures in the basal ganglia and lower urinary tract symptoms in patients with Parkinson’s disease, demonstrating that the beta oscillation may be linked to dysfunctional voiding in this patient population, and that voiding dysfunction is likely to be distinct from the other urinary problems experienced by Parkinson’s disease sufferers. In the second LFP chapter I describe two case studies focussing on the role of alpha oscillations in the periaqueductal grey area (PAG) and ventral posterolateral thalamic nucleus (VPL) during bladder filling, urinary voiding and other bladder-related tasks. Finally, moving to a more translational approach, in the last chapter I investigate the effect of deep brain stimulation of the pedunculopontine nucleus (PPN) on bladder filling capacity in a series of patients with Parkinson’s disease, demonstrating that stimulation at this nucleus increases bladder filling capacity. This chapter is appropriately placed at the end of the thesis, to represent the hope that study of the neural control of the bladder, both at a structural level using MRI techniques, but also critically at a more local level using local field potential and allied electrophysiological techniques, could lead to interventions such as neuromodulation that improve urinary symptoms in patients with bladder dysfunction.