title: Devices and computational methods for preclinical mechanistic deep brain stimulation studies in freely moving rodents
Creators: name: Bisht, Anupam
Publisher: name: Graduate Studies
Year: 2025
Subjects: subject: Freely moving animals
subject: Optical recordings
subject: Brain
subject: DBS
subject: Deep brain stimulation
subject: Behaviour
subject: Neuroscience
subject: Optics

description: Deep brain stimulation (DBS) is a therapeutic technique used for the treatment of neurological and psychiatric diseases. Optimization and patient-specific application of DBS remain a challenge as mechanisms of the therapeutic action of DBS on the brain remains unknown. Currently, the instrumentation available for preclinical DBS research focused on performing freely moving animal experiments is limited. The proposed work addresses this gap through major improvements of existing devices and the development of supporting computational methods for data analysis. This work has been divided into four aims. Motivated from a previously developed gradient refractive index lens based point detector system, aim 1 involved development of a wireless miniaturized intrinsic optical imaging system (called TinyIOMS- Tiny intrinsic optical monitoring system) to measure changes in hemoglobin concentration from surface regions of the brain (e.g., motor cortex which is the main output center of DBS brain targets). A comparison of signals with a standard wide-field intrinsic optical imaging system was done to validate the signal reliability of TinyIOMS. Further, we showed the hemodynamic signals recorded could be used to distinguish between brain states (sleep vs awake) by performing continuous recordings for about 7 hours to about 2 days (via intermittent recordings). Aim 2 involved investigating motion artifacts for a single f iber system (SFS) that has shown variability in the measured hemodynamic signals (blood flow and oxygen saturation) from deep brain regions (commonly stimulated during DBS) during previous DBS studies. In this work, we showed that while the blood flow signal is sensitive to motion artifacts, oxygen saturation is not. Further, a motion artifact correction algorithm was developed to correct motion artifacts that occur during experiments using a regression-based approach utilizing light at 680 nm, a wavelength that is relatively less sensitive to hemodynamics. Since the biological interpretability of hemodynamic changes during DBS recorded in the SFS signals was limited, one approach is to compare it with well-established signals, e.g., electrophysiology or GCaMP-based fiber photometry. In aim ii 3, we have further extended the SFS design to enable stimulus-locked (e.g., footshocks, DBS) simultaneous recording of both hemodynamics and GCaMP-based fluorescence signals. In aim 4, a previously developed miniaturized DBS device was improved in mechanical and electrical design, and the software was upgraded to enable wireless programming and timed stimulation. This device was used to stimulate a novel target for DBS, the A13 region of the medial zona incerta in rats. We observed that DBS evoked a robust locomotor response with an overall non-noxious behavioral effect which is important data for clinical translation. Overall, this thesis advances the technology for performing electrical stimulation and the monitoring of hemodynamics in freely moving animals.