Monitoring and Treating Neurological Conditions Through Focal Interfacing with the Brain

Abstract

Neurological dysregulation serves as the fundamental basis for a spectrum of debilitating disorders such as Parkinson's disease and epilepsy. Despite considerable efforts, our current comprehension of these disorders and ability to treat them remains limited. Neurochemical sampling of the affected tissue can be used to monitor pathological states, but existing tools are limited by tissue reactivity and suboptimal spatiotemporal resolution. Additionally, methods for treating neurological disorders predominantly rely on systemic drug administration which is hampered by inadequate targeting and off-target effects.

There is a need for minimally invasive modalities to both monitor and treat neurological disorders that have high spatial resolution, maintain chronic functionality, and preserve overall brain function. This thesis presents the development and implementation of neural implants capable of both infusing and sampling sub-microliter volumes of fluid with exceptional spatial precision. These implants utilize micron-scale technology to minimize scarring following implantation and allow for sustained chronic functionality. We use these devices to answer two key questions: (1) Can the localized delivery of drugs to specific neural circuits provide effective treatment for neurological diseases? and (2) Can micro-invasive sampling of brain interstitial fluid facilitate disease diagnosis and monitoring?

We assessed our ability to treat focal epilepsy with this platform by delivering antiseizure medications directly to the seizure focus in a mouse model of temporal lobe epilepsy. We found that localized drug delivery effectively suppressed seizure activity without adverse effects. We also explored micro-invasive, membrane-free sampling of interstitial fluid from different brain regions using our device. We detected hundreds of distinct proteins from minute sample volumes with high spatial resolution and minimal tissue damage. The results from both studies highlight the platform’s potential for targeted drug delivery and biomarker detection across a variety of disease states.