This proposal regards the continuation of a previously approved K99 fellowship, with Northwestern University as the proposed R00-phase institution. Memory impairments are common to many neurological and psychiatric disorders, including Alzheimer’s disease and depression, and impose a heavy burden on patients and their families. Brain stimulation is a potentially powerful therapeutic strategy with the potential to elicit lasting improvements in episodic memory. However, its efficacy depends on precise targeting of stimulation to brain regions, in a manner that respects the idiosyncrasies of each individual’s functional brain anatomy. Recent advances in functional magnetic resonance imaging (fMRI) have allowed brain networks to be mapped with precision within individuals. Of particular relevance to memory disorders, a distributed network was identified within individuals that includes regions of posterior parietal and parahippocampal cortices – regions which form prominent stimulation targets for modulation of memory – in combination with regions distributed throughout frontal, parietal, temporal and midline cortices. It is not known whether stimulation of these distributed regions can also lead to memory improvements, but if so this could provide additional and potentially more accessible targets for stimulation-based therapy. In this project, individual-level network mapping with fMRI will be performed on epilepsy patients who are scheduled to undergo intracranial monitoring and stimulation. The distributed network which includes parahippocampal and posterior parietal cortex will be delineated with precision in individual patients and the resulting network maps will be used to select candidate implanted electrodes for stimulation. The involvement of the distributed brain network in episodic memory will be characterized at high temporal and spatial resolution through recordings obtained during an episodic memory task. Direct cortical stimulation will be applied to individual sites with the aim of testing the causal influence of distributed network regions on episodic memory. To achieve this project, the PI will establish a research program at the Northwestern University Feinberg School of Medicine, building on procedures, protocols and experience gained at Stanford University during the K99 training, and in collaboration with neuroscientists (Joel Voss, Ph.D.) and epileptologists (Stephan Schuele, Ph. D.) at Northwestern University. The resulting data will refine the current understanding of the neural systems involved in episodic memory, and importantly provide a proof-of-principle for the use of individual-level network mapping to guide intracranial brain recording and stimulation, which could have important implications for stimulation therapies for a range of mental health disorders.
|Effective start/end date||8/28/20 → 7/31/23|
- National Institute of Mental Health (4R00MH117226-03)