Deep Brain Stimulation in Alzheimer’s Disease
Post by Lincoln Tracy
The takeaway
New research suggests targeting the intersection of the fornix and the bed nucleus of the stria terminalis with deep brain stimulation may have promising results in Alzheimer’s disease.
What's the science?
Alzheimer’s disease is a common and highly debilitating neurodegenerative disorder. Numerous attempts to modify the disease have had limited success. Following the success of deep brain stimulation (DBS) in treating other conditions such as Parkinson’s disease, targeting the fornix has been trialed in Alzheimer’s disease. However, the benefits of deep brain stimulation to the fornix are yet to be conclusively proven, with patients reporting inconsistent results. This week in Nature Communications, Rios and colleagues explored how variation in DBS electrode placement influenced its effectiveness, thereby identifying brain structures and fiber tracks associated with optimal outcomes.
How did they do it?
The authors undertook a post-hoc analysis of data collected from 46 individuals with mild Alzheimer’s disease (23 females, mean age 67 years) from seven international centers who received DBS to the fornix between 2007 and 2019. First, they aimed to determine which white matter fiber tract stimulation was associated with maximal clinical improvement by performing DBS fiber filtering on a normative connectome obtained through a whole-brain diffusion scan. Second, they undertook a voxel-wise mapping analysis to identify target coordinates for an optimal DBS sweet spot that can be targeted during surgery. Finally, they used DBS network mapping to identify regions functionally connected with optimal stimulation volume sites, by generating a fingerprint of functional connectivity seeding to estimate the whole-brain response to optimal DBS. Patients were pseudorandomly split into training and hold-out cohorts for each component as a means of cross-validation.
What did they find?
First, the authors identified that stimulating specific white matter tracts in the circuit of Papez and the stria terminalis resulted in optimal clinical improvement. Second, they found the intersection of the fornix and the bed nucleus of the stria terminalis was the optimal stimulation site on a localized voxel level, suggesting that targeting DBS more superiorly and medially than the currently used target may result in better clinical outcomes. Finally, functional connectivity to the precuneus, prefrontal regions, cingulate, thalamus, basal ganglia, and insula were most strongly correlated with the optimal response following DBS.
What's the impact?
These findings provide a framework for the neural mechanisms involved in successful DBS of the fornix, giving the opportunity to influence and improve surgical targeting and stimulation optimization for future trials in Alzheimer’s disease patients. Further research is required to determine other optimal stimulation parameters beyond electrode placement. Utilizing these findings could result in improved and more consistent clinical benefits for millions of individuals affected by Alzheimer’s disease.
