Date of Award
5-2024
Degree Type
Thesis
Degree Name
Master of Science in Biomedical Sciences
First Advisor
Huo Lu, MD, Ph.D.
Second Advisor
Shu Zhu, MD, Ph.D.
Third Advisor
Richard White Ph.D., F.A.H.A.
Fourth Advisor
Brian DeHaven, Ph.D.
Abstract
Cerebellar ataxia is a neurological disorder that can be genetically or sporadically acquired. Ataxia is the loss of the ability to coordinate the range, rate, force, and direction of movements. Loss of gait stability, and reaching smoothness is progressively seen clinically. The non-invasive brain therapy called transcranial electric stimulation (tES) has been shown to have an impact on the behavior of humans with cerebellar dysfunction. However, the physiological and behavioral effects of tES are not well studied. Quantitative measurements were used in reaching behavior assays with head fixation using normal and ataxic mice before and after tES treatment. Frame by frame video recordings from reaching were analyzed using a markerless 3D software, DeepLabCut. The study of reaching behavior in combination with electrophysiological recording from thalamic neurons betters our understanding of the cerebello-thalamo-cerebral pathway in the effectiveness of using tES as a therapeutic method. Transcranial direct current stimulation (tDCS) is a form of tES and has been shown clinically to modulate behavior contralateral to the stimulation site. This method was chosen due to its clinical findings and past success in vivo on previous projects in our lab. Furthermore, the cerebello-thalamo-cerebral pathway can be simulated under the effects of cerebellar tDCS using NEURON. The downstream modulatory effects elicited from simulated cerebellar tDCS offers insight to the neuronal activity changes that may be seen physiologically after administration. By integrating quantitative behavioral assays, electrophysiological recordings, and computational modeling, this study extracts the potential therapeutic mechanisms of tES, particularly tDCS, in modulating cerebellar dysfunction, providing a comprehensive framework for understanding the cerebello-thalamo-cerebral pathway and advancing the effective treatment strategies for cerebellar ataxia.
Recommended Citation
Johnston, William, "Investigation of Movement Coordination in Reaching through the Modulation of the Cerebello-Thalamo-Cerebral Tract by Cerebellar tES in Awake Mice" (2024). PCOM Biomedical Studies Student Scholarship. 232.
https://digitalcommons.pcom.edu/biomed/232