Clinical trial NCT05065450: Amygdala Memory Enhancement
Official title: Mechanisms of Amygdala-Mediated Memory Enhancement in Humans
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Brain Diseases
Epilepsy
Memory Disorders
Traumatic Brain Injury
Cognitive Impairment
Post Traumatic Stress Disorder
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2021-10-04
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Free recall memory discriminability index (proportion recalled)
timeFrame: 5 years
measure: Recognition memory discriminability index (proportion recalled)
timeFrame: 5 years
Secondary outcomes:
measure: Location of single pulse evoked potential (SPEP) response to amygdala stimulation
timeFrame: 5 years
measure: Amplitude of SPEP response to amygdala stimulation
timeFrame: 5 years
measure: Latency of SPEP response to amygdala stimulation
timeFrame: 5 years
measure: Local field potential (LFP) of good memory state
timeFrame: 5 years
measure: LFP of bad memory state
timeFrame: 5 years
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
References:
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.
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.
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.
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.
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.