Investigations of Amygdala Function Using Neurophysiological Recording and Stimulation

NCT03958903 | Completed

• 3 other identifiers: 42227DP1MH116506FY18 small grant fund award
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to specifically examine the in vivo electrophysiology and effects of direct stimulation of the human amygdala during conditioned and evoked fear. Investigators will also examine amygdala electrophysiology and the effects of stimulation during tasks to examine the effects of reward on fear memory. This study will recruit subjects with a history of temporal lobe epilepsy (TLE) who have undergone neurosurgical implantation with FDA-approved, NeuroPace RNS devices for treatment of seizures. These patients provide a unique cohort with (Responsive Neurostimulation) RNS devices capable of both recording and stimulating the amygdala during performance of fear-based, behavioral tasks.

Conditions

Fear; PTSD; Panic Disorder

Keywords

Responsive neurostimulation; Amygdala electrophysiology; Neuropace RNS; Temporal lobe epilepsy; closed-loop brain stimulation

Outcome Measures

Primary Outcomes (4)

• EEG(electroencephalography) amplitude changes

  Analyze change in amplitude in microvolts -in resting state EEG recording and EEG recording across all the tasks as determined clinically by the Investigator. Investigators will be analyzing stimulus-induced electrophysiological recordings, focusing on Event-Related Potentials (ERPs).

  2 days

• EEG(electroencephalography) frequency changes

  Analyze changes in frequency in Hertz- in resting state EEG recording and EEG recording across all the tasks as determined clinically by the Investigator. Investigators will be analyzing stimulus-induced electrophysiological recordings, focusing on Event-Related Spectral Potentials (ERSP).

  2 days

• ECoG (ElectroCorticoGraphy) amplitude changes

  Quantify changes in ECoG measures as determined clinically by the Investigator.- using intracranial recordings from the Neuropace devices. Analyze changes in ECoG amplitude- in resting state and ECoG throughout task and stimulation.

  2 days

• ECoG (ElectroCorticoGraphy) frequency changes

  Quantify changes in ECoG measures as determined clinically by the Investigator using intracranial recordings from the Neuropace devices. Analyze changes in ECoG frequency - in resting state and ECoG throughout task and stimulation

  2 days

Secondary Outcomes (2)

• Electrophysiological changes in EMG

  2 days

• Electrophysiological changes in EDA

  2 days

Study Arms (1)

Neurophysiological recording and stimulation of amygdala

EXPERIMENTAL

Recording and stimulation of amygdala using Neuropace RNS devices at certain points through out the behavioral tasks.

Device: Amygdala recording and stimulation using Neuropace RNS; Behavioral: Behavioral tasks

Interventions

Amygdala recording and stimulation using Neuropace RNS DEVICE

Subjects will undergo a series of different, fear-related, behavioral tasks while undergoing amygdala electrophysiology recording and stimulation using the Neuropace RNS devices.

Neurophysiological recording and stimulation of amygdala

Behavioral tasks BEHAVIORAL

Subjects perform a set of fear related behavioral tasks over 2 days, with 3 tasks each day.In addition to amygdala RNS recording and stimulation, recording of electroencephalography (EEG), electromyography (EMG), and electrodermal activity (EDA) will be performed using standard techniques to capture and quantify the fear response across all tasks.

Neurophysiological recording and stimulation of amygdala

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• be between age 18-65 years of age
• participants must have received the Neuropace RNS implant to treat their seizures
• have comprehension of instructions in the English language
• be on a stable dose of medications for their epilepsy
• have received the RNS System for Temporal Lobe Epilepsy
• have capacity to provide informed consent

You may not qualify if:

• significant cognitive impairment (Mini Mental Status Examination score of less than 20)
• DSM-V diagnosis of alcohol/substance abuse (except nicotine) within the last month or a diagnosis of alcohol/substance dependence (except nicotine) within the last 6 months
• Unable to apply EEG cap
• History of traumatic brain injury
• Active or high suicide risk
• Unable to come to study site/lack of stable housing
• is pregnant or nursing
• Patient's treating neurologist determines that the patient's epilepsy is not stable enough to participate in this study
• Any condition (including psychiatric) which in the judgment of the Investigator would prevent the subject from completion of the study

Sponsors & Collaborators

• Stanford University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Stanford University

Palo Alto, California, 94304, United States

Location

Related Publications (6)

• Gross CT, Canteras NS. The many paths to fear. Nat Rev Neurosci. 2012 Sep;13(9):651-8. doi: 10.1038/nrn3301. Epub 2012 Aug 1.

  PMID: 22850830 BACKGROUND

• Etkin A, Wager TD. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry. 2007 Oct;164(10):1476-88. doi: 10.1176/appi.ajp.2007.07030504.

  PMID: 17898336 BACKGROUND

• Morrell MJ, Halpern C. Responsive Direct Brain Stimulation for Epilepsy. Neurosurg Clin N Am. 2016 Jan;27(1):111-21. doi: 10.1016/j.nec.2015.08.012.

  PMID: 26615113 BACKGROUND

• Sato W, Kochiyama T, Uono S, Matsuda K, Usui K, Inoue Y, Toichi M. Rapid amygdala gamma oscillations in response to fearful facial expressions. Neuropsychologia. 2011 Mar;49(4):612-7. doi: 10.1016/j.neuropsychologia.2010.12.025. Epub 2010 Dec 21.

  PMID: 21182851 BACKGROUND

• Langevin JP, Koek RJ, Schwartz HN, Chen JWY, Sultzer DL, Mandelkern MA, Kulick AD, Krahl SE. Deep Brain Stimulation of the Basolateral Amygdala for Treatment-Refractory Posttraumatic Stress Disorder. Biol Psychiatry. 2016 May 15;79(10):e82-e84. doi: 10.1016/j.biopsych.2015.09.003. Epub 2015 Sep 11. No abstract available.

  PMID: 26475671 BACKGROUND

• Clarke HF, Horst NK, Roberts AC. Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making. Proc Natl Acad Sci U S A. 2015 Mar 31;112(13):4176-81. doi: 10.1073/pnas.1422440112. Epub 2015 Mar 16.

  PMID: 25775597 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Panic Disorder; Epilepsy, Temporal Lobe

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Anxiety Disorders; Epilepsies, Partial; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Study Officials

• Mahendra Bhati, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: May 20, 2019
• First Posted: May 22, 2019
• Study Start: April 24, 2019
• Primary Completion: March 13, 2020
• Study Completion: March 13, 2020
• Last Updated: September 26, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)