The neuroethical and epistemological examination of closed-loop deep brain stimulation for neuropsychiatric illnesses

<p dir="ltr">Contemporary investigators have long striven to better understand and interact with the brain and its quintessential role in the formation of an individual’s personality, self, consciousness, etc. In this quest, different approaches to examining the nervous system, whether at the level of neurotransmitters, genetics, neurons, neuropathways, behaviors, subjective experiences, or social influences, have been pursued. Some findings provided from this research have then aided in the medical amelioration of various neurologic and psychiatric disorders. Nonetheless, each treatment developed has come with a particular risk profile; the rule of thumb being those with higher risk are generally the more invasive methods, such as neurosurgical interventions. First line therapies therefore typically prioritize non-invasive modalities; however, in recent decades the use of more invasive brain stimulation therapies, involving deep brain stimulation (DBS) devices, have increased to better address severe treatment resistant neurological disorders, such as Parkinson’s Disease, Epilepsy, Essential Tremor, and Dystonia. To better tailor DBS to also treat severe psychiatric disorders, these devices have shifted away from merely stimulating neural tissue at an automated rate and instead to utilizing the patient’s own neurological states to trigger stimulation. However, these “closed-loop” stimulation devices, utilizing neuromonitoring and computational systems not seen in the original “open-loop” design, complicate an already ethically intricate treatment with possibly new and unknown risks. This is in part because of their transition from a standardized intervention to a personalized one, much like neuro-oncological therapies for brain tumors. In order to better assess and address the resulting neuroethical dilemmas with regard to closed-loop DBS (cDBS) devices, this thesis examines both the practical and ethical challenges this novel technology faces in research, regulatory, and clinical settings. Firstly, there are ethical challenges of classifying cDBS as an innovative treatment versus a research-driven intervention during its application in psychiatric surgery. Dissolving this distinction demonstrates the ethical balancing act required for such a non-validated intervention for psychiatric disorders with the risk profile of course being elevated due to the invasive nature of DBS. Secondly, the evaluative criteria for medical devices, including neurostimulatory systems both in the Australian federal jurisdiction and globally, have been identified as being biased towards requiring quantitative criteria in the assessment of a treatment’s safety and efficacy. This focus subsequently deprioritizes alternative measurement modalities, like qualitative assessments, that may provide alternative insights into the efficacy and risks of cDBS interventions. Lastly, the gradual improvements of DBS’s risk profile and concurrent growth in efficacy for neurological disorders arguably foreshadows a future in which they may be utilized earlier in a disease’s treatment timeline. Since the contemporary heuristic is to consider neurosurgical interventions as a ‘last resort’ treatment, a revision has been proposed so as to ensure DBS is accurately characterized. In particular, this adjustment of the ‘last resort’ phrasing may also break down as psychiatric surgeries with cDBS become indicated at earlier disease stages as their clinical efficacy for disorders like Obsessive-Compulsive Disorder improve. In sum, these investigations have helped to spur insights into some alternative paths of inquiry, notably in addressing the tensions between the epistemological and ethical standards needed to produce generalizable knowledge of neurostimulatory treatments in patients with rare diseases. The examination of the actual data sets obtained by DBS clinical researchers, especially those sets of data that are not submitted for formal regulatory review, presents an additional tension in holistically assessing these treatments. It is hoped that by examining these topics, this thesis will better support the next generation of patients treated with cDBS interventions, while also assisting in the ongoing challenge of the mind to better understand the technology it interacts with.</p>