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RecruitingNCT05065450Updated Jul 17, 2025

Amygdala Memory Enhancement

An interventional study of Intracranial Stimulation in Brain Diseases, Epilepsy and Memory Disorders, sponsored by Washington University School of Medicine. Recruiting at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-07-17.

Sponsored by Washington University School of Medicine · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
90
Allocation
Not applicable
Ages
18 Years to 75 Years
Sex
All
01

Study summary

The objective is to understand how amygdala activation affects other medial temporal lobe structures to prioritize long-term memories. The project is relevant to disorders of memory and to disorders involving affect and memory, including traumatic brain injury and post-traumatic stress disorder.

Read the detailed description

Direct electrical stimulation (DES) of the basolateral complex of the amygdala (BLA) can improve declarative memory, reflecting the role of the BLA in modulating memory processes in medial temporal lobe (MTL) regions as a function of emotional arousal. Thus, DES can reveal mechanisms of BLA-mediated memory enhancement relevant to human mental health and disease. DES of the BLA can be used to interrogate the function of memory circuits, especially how neuronal oscillations in the MTL support declarative memory. First, BLA is hypothesized to wield the capacity to prioritize long-term retention of information initially encountered adjacent in time over days and weeks after encoding. Second, the BLA preferentially projects to anterior MTL regions and thus is hypothesized to preferentially modulate memory processes in those anatomic regions, processes thought to support memory for non-spatial items more so than memory for spatial locations. Third, although emotional arousal, amygdala activity, MTL activity, and memory performance are typically correlated, the investigators hypothesize that DES will reveal that BLA outputs to other MTL regions cause improved memory performance by directly eliciting pro-memory oscillatory states in those networks. The expected outcomes represent a significant advancement for the basic science of normal memory function and significant movement towards novel therapeutics designed to emulate endogenous mechanisms of memory enhancement.

02

Conditions studied

  • Brain Diseases
  • Epilepsy
  • Memory Disorders
  • Traumatic Brain Injury
  • Cognitive Impairment
  • Post Traumatic Stress Disorder
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Must be able to understand and speak English.
  • Able to provide informed consent.
  • Diagnosed with epilepsy.
  • Scheduled to undergo long-term intra-cranial video monitoring for seizure onset localization.
  • Must be implanted with intracranial depth electrodes to the left or right amygdala, hippocampus, and parahippocampal/perirhinal cortices.

Exclusion criteria

Exclusion Criteria:

  • Unable to understand and speak English.
  • Unable to provide informed consent.
  • Not diagnosed with epilepsy.
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
90 participants (estimated)

Study arms

  • Experimental
    Brain Stimulation

    Neurosurgical epilepsy patients that undergo placement of medial temporal electrode for seizure localizations will be recruited. All participants will view a series of images of emotionally-neutral objects on a computer screen. After each item presentation, they will randomly undergo either active-BLAES or sham-stimulation. Over subsequent days, free recall and recognition memory for these items, relative to new distractor items will be tested. Memory for items presented with and without stimulation will be compared. Brain activity recorded in the medial temporal lobe during item presentations will be used to predict subsequent memory. Such good and bad memory states (biomarkers) will be used to perform closed-loop stimulation when bad memory states are detected in order to enhance subsequent memory.

    Device: Intracranial Stimulation

Interventions

  • DeviceIntracranial Stimulation

    Electrodes localized to the BLA will be stimulated with either active-BLAES (0.5-3.5 mA, theta-modulated gamma burst) electrical stimulation for a 1-sec duration immediately following item image presentation or sham-BLAES (zero-amplitude). At later stages of the project, stimulation parameters and timing will be varied and triggered not at random, but by real-time closed-loop analysis of memory biomarkers in the medial temporal lobe.

    Also known as: Device: ACTIVE basal lateral amygdala electrical stimulation (Active-BLAES), Device: SHAM basal lateral amygdala electrical stimulation (Sham-BLAES)

05

What researchers measure

Primary outcomes

  1. Free recall memory discriminability index (proportion recalled)

    Proportion of items (objects, associations, and scenes) accurately recalled during the delayed recall trial will be compared with and without BLAES for each participant in a within subject design. Subsets of items may be tested after durations up to a month after initial presentation.

    Time frame: 5 years

  2. Recognition memory discriminability index (proportion recalled)

    Proportion of items (objects, associations, and scenes) accurately recognized during the delayed recognition trial will be compared with and without BLAES for each participant in a within subject design. Subsets of items may be tested after durations up to a month after initial presentation.

    Time frame: 5 years

Secondary outcomes

  1. Location of single pulse evoked potential (SPEP) response to amygdala stimulation

    Measured by presence of the evoked potential in different brain subregions (hippocampus, entorhinal cortex, perirhinal cortex, and parahippocampal cortex).

    Time frame: 5 years

  2. Amplitude of SPEP response to amygdala stimulation

    Measured in microvolts.

    Time frame: 5 years

  3. Latency of SPEP response to amygdala stimulation

    Measured in milliseconds.

    Time frame: 5 years

  4. Local field potential (LFP) of good memory state

    Measured by relative power spectral frequency recorded at time of item presentation that predicts accurate subsequent memory performance.

    Time frame: 5 years

  5. LFP of bad memory state

    Measured by relative power spectral frequency recorded at the time of item presentation that predicts inaccurate subsequent memory performance

    Time frame: 5 years

06

Study locations

1 of 1 sites recruiting
  • Washington University School of Medicine
    St Louis, Missouri 63110, United States
    • Joan Atencio · Contact · atencio@wustl.edu · 314-362-3114
    • Jon T Willie, MD, PhD · Principal investigator
    Recruiting
07

References and documents

Publications

  • Inman CS, Manns JR, Bijanki KR, Bass DI, Hamann S, Drane DL, Fasano RE, Kovach CK, Gross RE, Willie JT. Direct electrical stimulation of the amygdala enhances declarative memory in humans. Proc Natl Acad Sci U S A. 2018 Jan 2;115(1):98-103. doi: 10.1073/pnas.1714058114. Epub 2017 Dec 18. PubMed 29255054 ↗
  • Manns JR, Bass DI. The amygdala and prioritization of declarative memories. Curr Dir Psychol Sci. 2016 Aug;25(4):261-265. doi: 10.1177/0963721416654456. PubMed 27721578 ↗
  • Bass DI, Manns JR. Memory-enhancing amygdala stimulation elicits gamma synchrony in the hippocampus. Behav Neurosci. 2015 Jun;129(3):244-56. doi: 10.1037/bne0000052. PubMed 26030426 ↗
  • Bass DI, Nizam ZG, Partain KN, Wang A, Manns JR. Amygdala-mediated enhancement of memory for specific events depends on the hippocampus. Neurobiol Learn Mem. 2014 Jan;107:37-41. doi: 10.1016/j.nlm.2013.10.020. Epub 2013 Nov 8. PubMed 24211699 ↗
  • Bass DI, Partain KN, Manns JR. Event-specific enhancement of memory via brief electrical stimulation to the basolateral complex of the amygdala in rats. Behav Neurosci. 2012 Feb;126(1):204-8. doi: 10.1037/a0026462. Epub 2011 Dec 5. PubMed 22141467 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT05065450
Lead sponsor
Washington University School of Medicine
Responsible party
Sponsor
First posted
Oct 4, 2021
Start date
Nov 1, 2021
Primary completion
Nov 1, 2026 (estimated)
Completion
Nov 1, 2027 (estimated)
Last update
Jul 17, 2025

Study contacts

Joan Atencio
Contact
atencio@wustl.edu
314-362-3114
Sophie Church
Contact
sophie.church@wustl.edu
917-699-9097

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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