Optimal deep brain stimulation sites and networks for stimulation of the fornix in Alzheimer's disease.
Ana Sofía RíosSimón OxenfordClemens NeudorferKonstantin ButenkoNingfei LiNanditha RajamaniAlexandre BoutetGavin J B EliasJurgen GermannAaron LohWissam DeebFuyixue WangKawin SetsompopBryan SalvatoLeonardo Brito de AlmeidaKelly D FooteRobert AmaralPaul B RosenbergDavid F Tang-WaiDavid A WolkAnna D BurkeStephen P SallowayMarwan N SabbaghM Mallar ChakravartyGwenn S SmithConstantine G LyketsosMichael S OkunWilliam S AndersonZoltan MariFrancisco A PonceAndres M LozanoChristos GanosPublished in: Nature communications (2022)
Deep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer's Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neural circuits. To investigate this, we performed a post-hoc analysis on a multi-center cohort of 46 patients with DBS to the fornix (NCT00658125, NCT01608061). Using normative structural and functional connectivity data, we found that stimulation of the circuit of Papez and stria terminalis robustly associated with cognitive improvement (R = 0.53, p < 0.001). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.48, p < 0.001). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.48, p < 0.001). Findings were robust to multiple cross-validation designs and may define an optimal network target that could refine DBS surgery and programming.
Keyphrases
- deep brain stimulation
- functional connectivity
- parkinson disease
- resting state
- obsessive compulsive disorder
- end stage renal disease
- ejection fraction
- cognitive decline
- minimally invasive
- newly diagnosed
- chronic kidney disease
- prognostic factors
- high resolution
- white matter
- adipose tissue
- coronary artery bypass
- social media
- metabolic syndrome
- randomized controlled trial
- machine learning
- electronic health record
- patient reported outcomes
- acute coronary syndrome
- blood brain barrier
- weight loss
- combination therapy
- open label
- atrial fibrillation
- deep learning
- double blind
- data analysis
- network analysis
- smoking cessation