Clinical trial NCT03958903: Investigations of Amygdala Function Using Neurophysiological Recording and Stimulation
Official title: Investigations of Amygdala Function Using Neurophysiological Recording and Stimulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fear
PTSD
Panic Disorder
Keywords: Responsive neurostimulation
Amygdala electrophysiology
Neuropace RNS
Temporal lobe epilepsy
closed-loop brain stimulation
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2019-05-22
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: EEG(electroencephalography) amplitude changes
timeFrame: 2 days
measure: EEG(electroencephalography) frequency changes
timeFrame: 2 days
measure: ECoG (ElectroCorticoGraphy) amplitude changes
timeFrame: 2 days
measure: ECoG (ElectroCorticoGraphy) frequency changes
timeFrame: 2 days
Secondary outcomes:
measure: Electrophysiological changes in EMG
timeFrame: 2 days
measure: Electrophysiological changes in EDA
timeFrame: 2 days
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Mahendra Bhati, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.