Amygdala Memory Enhancement

Epilepsy Clinical Trial

Official title:

Mechanisms of Amygdala-Mediated Memory Enhancement in Humans

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05065450
• Other study ID #: 202104033
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2021
• Est. completion date: November 1, 2027

Study information

• Verified date: March 2024
• Source: Washington University School of Medicine
• Contact: Joan Atencio
• Phone: 314-362-3114
• Email: atencio[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: November 1, 2027
• Est. primary completion date: November 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Diseases
• Brain Injuries
• Brain Injuries, Traumatic
• Cognitive Impairment
• Epilepsy
• Memory Disorders
• Post Traumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic
• Traumatic Brain Injury

Intervention

Device:
• Intracranial 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.

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	5 years
Primary	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.	5 years
Secondary	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).	5 years
Secondary	Amplitude of SPEP response to amygdala stimulation	Measured in microvolts.	5 years
Secondary	Latency of SPEP response to amygdala stimulation	Measured in milliseconds.	5 years
Secondary	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.	5 years
Secondary	LFP of bad memory state	Measured by relative power spectral frequency recorded at the time of item presentation that predicts inaccurate subsequent memory performance	5 years