Robert Mcmanus

Background:  Deep brain stimulation (DBS) is a well-established tool in functional neurosurgery with several FDA-cleared indications. Given its established safety profile and growing market, repurposing DBS for cognitive decline is a promising therapy. However, the literature on DBS for cognitive decline is limited and has obtained mixed results. This review aims to demonstrate how the combination of DBS reinforced with mathematical modeling could be a powerful new tool for improving memory in patients with cognitive decline.

Methods: PubMed was searched for the period between 2016 and 2024 using the keywords “Deep brain stimulation” and “Cognitive decline”.

Results: Several studies have shown a paradoxical effect of DBS on memory, and the answer to that problem is likely a function of neurogenesis, altered neurotransmitter concentrations, and timing of stimulation⁵. A landmark paper utilizing deep brain stimulation of the entorhinal region and hippocampus in humans impaired memory, demonstrating a causal role for the medial temporal lobe in memory encoding⁴. Improving upon this, using mathematical models to learn how the hippocampus encodes memory and then stimulating according to the natural process resulted in a significant improvement (35%) in both short-term and long-term retention of visual information across subjects². Improving the algorithm allowed researchers to improve memory in as 37.9% in patients with cognitive decline³. Using a similar approach, another team of researchers were able to significantly improve memory by stimulating the lateral temporal lobe, an area that could be non-invasively stimulated¹. These results demonstrate a promising future for using DBS and other forms of neurostimulation in cognitive decline.

Conclusions: DBS is a safe and well-established treatment for many pathologies and repurposing it for memory-related disorders would be highly beneficial. Mathematical models learning how the brain encodes memories and then bolstering the natural process using stimulation, resulted in improved memory. This combination of a classification algorithm based on a patient’s own data and applied stimulation to improve memory encoding has shown significant promise. While the underlying mechanisms still need to be studied, DBS could offer a much-needed treatment for the cognitive decline seen in dementia.

Works Cited:

1. Ezzyat Y, Wanda PA, Levy DF, et al. Closed-loop stimulation of temporal cortex rescues functional networks and improves memory. Nat Commun. 2018;9(1):365. doi:1038/s41467-017-02753-0
2. Hampson RE, Song D, Robinson BS, et al. Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall. J Neural Eng. 2018;15(3):036014. doi:1088/1741-2552/aaaed7
3. Roeder BM, She X, Dakos AS, et al. Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall of stimulus features and categories. Front Comput Neurosci. 2024;18. doi:3389/fncom.2024.1263311
4. Jacobs J, Miller J, Lee SA, et al. Direct Electrical Stimulation of the Human Entorhinal Region and Hippocampus Impairs Memory. Neuron. 2016;92(5):983-990. doi:1016/j.neuron.2016.10.062
5. Tan SZK, Fung ML, Koh J, Chan YS, Lim LW. The Paradoxical Effect of Deep Brain Stimulation on Memory. Aging Dis. 2020;11(1):179-190. doi:14336/AD.2019.0511