Research Spotlight: Mapping Cognitive Effects of Deep Brain Stimulation
Lead author Calvin William Howard, MD and senior author Michael Fox, MD, PhD, both of the Department of Neurology at Brigham and Women’s Hospital, published a paper in Alzheimer’s & Dementia, “Cognitive Outcomes of Deep Brain Stimulation Depend on Age and Hippocampal Connectivity in Parkinson’s and Alzheimer’s Disease.”
Q: How would you summarize your study for a lay audience?
Cognitive dysfunction is a common problem in individuals with both Parkinson’s disease (PD) or Alzheimer’s disease (AD). Despite advances in treatment, options for improving memory and thinking for these patients remain limited.
We looked at whether deep brain stimulation (DBS) can impact cognitive function in these neurodegenerative diseases. Our team found that DBS can either improve or worsen cognitive function and that the effect depends on two key factors:
- Neural connectivity – how strongly the electrode is connected to the hippocampus (the brain’s memory center).
- Brain atrophy – the extent to which the hippocampus has been damaged by the disease.
Q: What knowledge gap does your study help to fill?
We aimed to understand why DBS connected to the hippocampus appears to impair cognitive function in patients with PD, but improve it in those with AD. This paradox, observed in previous studies, raised important questions about how DBS affects cognition across different neurodegenerative conditions.
Our goal in this study was to understand whether factors such as age and brain structure—specifically, the degree of hippocampal atrophy (a loss of volume in the brain’s memory center often linked to aging and dementia)—could explain these opposing outcomes.
By doing so, we hoped to uncover whether DBS could be more precisely tailored to support cognitive function in patients with Parkinson’s or Alzheimer’s disease.
Q: What methods or approach did you use?
Our team used a technique called DBS network mapping, which starts by identifying the exact area of the brain being stimulated by the implanted electrode in each patient. Then, we combine that information with a detailed map of how different parts of the brain are connected—known as the human connectome.
By overlaying stimulation sites onto this brain wiring map, we can see whether the sites are connected to brain regions involved in memory such as the hippocampus. This approach allowed us to explore how changes in cognitive function after DBS depend on brain connectivity, patient age, and brain health.
Q: What did you find?
DBS can either improve or worsen cognition in patients with Parkinson’s or Alzheimer’s, depending on a few key factors.
When the hippocampus is already damaged, stimulation sites more strongly connected to the hippocampus tend to improve cognitive function.
In contrast, when the hippocampus appears healthy, stimulation sites more strongly connected to the hippocampus tend to impair cognitive function.
This finding was similar in patients with Parkinson’s disease or Alzheimer’s disease.
Q: What are the implications?
Our findings show that DBS can influence cognition similarly across different neurodegenerative diseases. However, whether the cognitive effect of DBS is positive or negative depends upon if the electrical stimulation site is connected to a healthy or an atrophic hippocampus. Because each patient has multiple potential stimulation sites on their DBS electrodes, it may be possible to change the location of stimulation to improve cognitive outcomes.
Q: What are the next steps?
We’ve built an AI algorithm to reprogram DBS for patients to potentially improve their cognitive function. We are assessing the feasibility of a clinical trial to test if this can help patients. Interested patients can contact bwhdbscognitionresearch@mgb.org for more information.
Authorship: In addition to Howard and Fox, Mass General Brigham authors include Lan Luo, Niels Pacheco-Barrios, Helen Friedrich, Andrew Pines, Leila Montaser-Kouhsari, William Drew, Lauren Hart, Garance Meyer, Nanditha Rajamani, Maximillian U. Friedrich and Andreas Horn.
Paper cited: Howard, C W, et al. “Cognitive Outcomes of Deep Brain Stimulation Depend on Age and Hippocampal Connectivity in Parkinson’s and Alzheimer’s Disease” Alzheimer’s & Dementia. DOI: 10.1002/alz.70498
Funding: This work was supported by grants from the Canadian Clinician Investigator Program. Author Michael D. Fox was supported by grants from the NIH (R01MH113929, R21MH126271, R21NS123813, R01NS127892, R01MH130666, UM1NS132358), the Kaye Family Research Endowment, the Ellison / Baszucki Family Foundation, the Once Upon a Time Foundation, the Manley Family, Donna and Tom May, and Chuck and Kerri Bean.
Disclosures: Author Michael D. Fox discloses honoraria from Boston Scientific and Medtronic and has intellectual property on the use of brain connectivity imaging to analyze lesions and guide brain stimulation, has consulted for Magnus Medical, Soterix, Abbott, Boston Scientific, Tal Medical, MDC Venture Capital, and is on the Scientific Advisory Board of Salma Health. He has received research support from Neuronetics and Boston Scientific.
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