Central Lateral Thalamic Circuitry Abnormalities in Traumatic Brain Injury and Alzheimer s Disease
Abstract
Traumatic brain injury (TBI) is a leading cause of disability in military, Veteran, and civilian communities with no established medical intervention. Following a TBI, affected individuals are more at risk of developing Alzheimer’s disease (AD), which also has no medical intervention. This research lays the basic science foundation for the possible treatment of both conditions with deep brain stimulation (DBS). As yet, we know little about the changes in the brain’s connections that occur after a TBI to increase the risk of AD. A small region in the brain called the central lateral (CL) nucleus of the thalamus plays a major role in the development of commonly experienced impairments, such as fatigue and poor attention, following a TBI. Recently, we discovered evidence that CL may also lead to memory deficits following a TBI. In our clinical trial testing the use of DBS of CL to treat TBI, we found that DBS of CL not only dramatically improved fatigue and attention, but also dramatically improved the recall of personal memories. This first-in-human finding indicates that CL is also involved in memory. Furthermore, this finding suggests that the downregulation of CL following a TBI may also lead to memory deficits and other AD symptoms, thus increasing the risk for developing AD. This research investigates CL’s connectivity with memory-related brain regions and how these connections are associated with markers of AD. The AD markers examined here are personal (episodic) memory recall, the global quantity of amyloid beta in the brain, and cerebrospinal fluid levels of amyloid beta and tau protein, two neurotoxic proteins implicated in AD. This work is enabled by new tools we have developed that identify CL in neuroimaging scans for the first time. This capability will allow us to map the connections of CL in humans for the first time, instead of using invasive experiments in animals, who do not possess the same advanced cognitive regions as humans. This tool will be used to map the connections and correlate connection strength with AD markers using existing data from TBI, AD, and healthy individuals in the DoD-ADNI and ADNI databases. This research is innovative in its recognition that CL, which is typically associated with arousal and attentional focus, is involved in memory function and could be centrally involved in leading to AD following TBI. This work will provide basic knowledge of thalamic nuclei connectivity and its degeneration in TBI and AD, in humans for the first time with unprecedented specificity. This work is the direct, immediate stepping stone towards clinical treatment by identifying the connections of CL, already an investigational DBS target for TBI, that can be targeted by DBS to treat fatigue and attention and memory deficits in affected individuals of the military, Veteran, and civilian communities.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110451
Entities
People
- Eun Young Choi
Organizations
- Stanford University
- United States Army