# Inactivation of the hippocampus by electrical stimulation to preview post-surgical verbal recognition memory deficits

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $509,819

## Abstract

PROJECT SUMMARY
Patients who have undergone hippocampal resection to treat mesial temporal lobe epilepsy (MTLE) frequently
experience memory deficits. Clinicians have few tools to preview these deficits when planning surgeries; the
Wada test, which anesthetizes each hemisphere to test memory function available in the contralateral
hemisphere, is the current medical standard. It was developed when temporal lobectomy was the primary
surgical treatment for MTLE. In contrast, modern surgical techniques such as open selective
amygdalohippocampectomy (AH) and laser interstitial thermal therapy (LITT) enable precise, selective lesions
while minimizing damage to surrounding tissue. The difference in scale between the preview and the resection
is one variable contributing to inconsistency in the utility of the Wada test to accurately preview memory deficits.
Clinicians need a test which more precisely targets the tissue to be removed, and thus more accurately predicts
functional consequences of losing the tissue. We propose using electrical stimulation (ES) through
stereoelectroencephalography (SEEG) depth electrodes, placed in the hippocampus for clinical seizure
monitoring, to generate temporary memory deficits at the spatial scale of intended surgical resection. Although
ES of the hippocampus has been frequently employed to study the hippocampus' role in memory processes, its
clinical utility to preview the memory deficits after hippocampectomy is less studied. Because the Wada test
remains the clinical standard, we have designed our study to match its testing paradigm. Within this framework,
our proposal will study where (Aim 1), when (Aim 2), and how (Aim 3) to stimulate the hippocampus to produce
memory impairment. While the involvement of the hippocampus in memory function is undisputed, it is not clear
which subregion(s) of the hippocampus should be stimulated to impair memory function. We believe stimulating
both the head and body of the hippocampus will lead to impairment, but in Aim 1 we will also test stimulation of
the head and body individually to see whether more localized stimulation can produce the desired effect.
Similarly, the hippocampus has been implicated in both encoding and retrieval memory processes, but it is not
known which of these processes should be disrupted by ES to impair memory function. In Aim 2 we will test
stimulation in these phases individually and in both phases to determine which leads to the best impairment.
Finally, in Aim 3 we will examine how the frequency of stimulation affects impairment of memory function. The
literature reports studies using a wide range of frequencies, from 5 to 200 Hz. Because higher frequencies are
more likely to generate epileptic activity, we limit our testing to a lower range of frequencies. We will evaluate ES
at 5 Hz, which matches endogenous neurophysiological modulation within the hippocampus, and 50 Hz, which
has long been a clinical standard used to disrupt function throughout n...

## Key facts

- **NIH application ID:** 10764796
- **Project number:** 5R01NS129542-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Spencer Kellis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $509,819
- **Award type:** 5
- **Project period:** 2023-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764796

## Citation

> US National Institutes of Health, RePORTER application 10764796, Inactivation of the hippocampus by electrical stimulation to preview post-surgical verbal recognition memory deficits (5R01NS129542-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10764796. Licensed CC0.

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