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Amygdala Memory Enhancement

Primary Purpose

Brain Diseases, Epilepsy, Memory Disorders

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Intracranial Stimulation
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Diseases

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

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

Sites / Locations

  • Washington University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Brain Stimulation

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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).
Amplitude of SPEP response to amygdala stimulation
Measured in microvolts.
Latency of SPEP response to amygdala stimulation
Measured in milliseconds.
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.
LFP of bad memory state
Measured by relative power spectral frequency recorded at the time of item presentation that predicts inaccurate subsequent memory performance

Full Information

First Posted
August 17, 2021
Last Updated
January 27, 2023
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT05065450
Brief Title
Amygdala Memory Enhancement
Official Title
Mechanisms of Amygdala-Mediated Memory Enhancement in Humans
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2021 (Actual)
Primary Completion Date
November 1, 2026 (Anticipated)
Study Completion Date
November 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Diseases, Epilepsy, Memory Disorders, Traumatic Brain Injury, Cognitive Impairment, Post Traumatic Stress Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Brain Stimulation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Intracranial Stimulation
Other Intervention Name(s)
Device: ACTIVE basal lateral amygdala electrical stimulation (Active-BLAES), Device: SHAM basal lateral amygdala electrical stimulation (Sham-BLAES)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Free recall memory discriminability index (proportion recalled)
Description
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
Title
Recognition memory discriminability index (proportion recalled)
Description
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 Outcome Measure Information:
Title
Location of single pulse evoked potential (SPEP) response to amygdala stimulation
Description
Measured by presence of the evoked potential in different brain subregions (hippocampus, entorhinal cortex, perirhinal cortex, and parahippocampal cortex).
Time Frame
5 years
Title
Amplitude of SPEP response to amygdala stimulation
Description
Measured in microvolts.
Time Frame
5 years
Title
Latency of SPEP response to amygdala stimulation
Description
Measured in milliseconds.
Time Frame
5 years
Title
Local field potential (LFP) of good memory state
Description
Measured by relative power spectral frequency recorded at time of item presentation that predicts accurate subsequent memory performance.
Time Frame
5 years
Title
LFP of bad memory state
Description
Measured by relative power spectral frequency recorded at the time of item presentation that predicts inaccurate subsequent memory performance
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Unable to understand and speak English. Unable to provide informed consent. Not diagnosed with epilepsy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Evans, RN
Phone
314-574-8065
Email
johnaevans@wustl.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Sophie Church
Phone
917-699-9097
Email
sophie.church@wustl.edu
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Evans, RN
Phone
314-574-8065
Email
johnaevans@wustl.edu
First Name & Middle Initial & Last Name & Degree
Jon T Willie, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29255054
Citation
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.
Results Reference
background
PubMed Identifier
27721578
Citation
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.
Results Reference
background
PubMed Identifier
26030426
Citation
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.
Results Reference
background
PubMed Identifier
24211699
Citation
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.
Results Reference
background
PubMed Identifier
22141467
Citation
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.
Results Reference
background

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Amygdala Memory Enhancement

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