Memory impairment occurs in a variety of neuropsychiatric conditions (e.g., depression and schizophrenia) and in many neurologic disorders (e.g., neurodegenerative disease and brain injury). Unfortunately, memory impairments have devastating consequences for life quality and there are no current treatments that reliably improve memory function. The goal of this project is to better understand a new procedure for the noninvasive enhancement of human hippocampal-cortical brain networks that are thought to critically support memory. This noninvasive brain-stimulation procedure can produce robust and lasting (at least ~24 hours) enhancement of hippocampal-cortical networks and concomitant improvement in long-term associative memory. However, relevant brain mechanisms must be more fully specified before this procedure can be more broadly applied to better understand and treat memory impairments. We therefore propose a collection of experiments that aim to answer three standing mechanistic questions. First, we aim to test whether distinct hippocampal-cortical brain networks can be selectively enhanced, which would determine whether stimulation acts on discrete targeted memory networks. Second, we aim to determine the timecourse and duration of these enhancements, which is essential for evaluation of putative neural mechanisms and of potential for clinical utility. Finally, we aim to test whethe the hippocampus is the key site of stimulation-induced enhancement of hippocampal-cortical networks by targeting intact versus surgically removed hippocampal tissue in individuals with unilateral medial temporalobectomy performed for treatment of refractory epilepsy. Impairments in stimulation-induced enhancement of hippocampal-cortical networks and memory when missing hippocampal tissue is targeted would confirm the necessary/causal role of hippocampus in the effects of stimulation. All proposed experiments involve sophisticated assessments of hippocampal-dependent memory function and of hippocampal-cortical brain networks. Findings will thus deeply inform understanding of stimulation effects while at the same time producing important information on the role of hippocampal-cortical networks in memory. Insights from this research could propel understanding of memory impairment and its treatment by noninvasive stimulation.

Public Health Relevance

Memory impairments occur in a variety of neuropsychiatric and neurologic disorders, and currently there are no effective treatments. This project seeks to better understand a new method involving noninvasive improvement of hippocampal-cortical brain networks, which are critical for memory function. This research seeks to discover the brain mechanisms for these memory-enhancing effects, which will provide better understanding and refinement of procedures for noninvasive stimulation of memory-related brain networks and for treatment of memory impairments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH106512-02
Application #
9134216
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Buhring, Bettina D
Project Start
2015-09-01
Project End
2020-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Kim, Sungshin; Nilakantan, Aneesha S; Hermiller, Molly S et al. (2018) Selective and coherent activity increases due to stimulation indicate functional distinctions between episodic memory networks. Sci Adv 4:eaar2768
Warren, Kristen N; Hermiller, Molly S; Nilakantan, Aneesha S et al. (2018) Increased fMRI activity correlations in autobiographical memory versus resting states. Hum Brain Mapp 39:4312-4321
Nilakantan, Aneesha S; Bridge, Donna J; Gagnon, Elise P et al. (2017) Stimulation of the Posterior Cortical-Hippocampal Network Enhances Precision of Memory Recollection. Curr Biol 27:465-470