Investigations of Amygdala Function Using Neurophysiological Recording and Stimulation

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.

Study Overview

• Status: Completed
• Conditions: PTSD; Fear; Panic Disorder
• Intervention / Treatment: Device: Amygdala recording and stimulation using Neuropace RNS; Behavioral: Behavioral tasks

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrophysiological changes in EMG	Analyze changes in amplitude of electromyography (EMG) from resting state to EMG recordings across all tasks.	2 days
Electrophysiological changes in EDA	Analyze changes in amplitude of electrodermal activity (EDA) from resting state to EMG recordings across all tasks.	2 days

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Mahendra Bhati, MD, Stanford University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2019
• Primary Completion (Actual): March 13, 2020
• Study Completion (Actual): March 13, 2020

Study Registration Dates

• First Submitted: May 20, 2019
• First Submitted That Met QC Criteria: May 20, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Responsive neurostimulation; Amygdala electrophysiology; Neuropace RNS; Temporal lobe epilepsy; closed-loop brain stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Panic Disorder
• Other Study ID Numbers: 42227; DP1MH116506 (U.S. NIH Grant/Contract); FY18 small grant fund award (Other Identifier: Department of Psychiatry, Stanford University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No