Modulation of Emotion Perception in Humans Via Amygdala Stimulation

Neuromodulation of Affective Valence in Humans by Amygdala Stimulation

This study will enroll patients with epilepsy who are being evaluated for epilepsy surgery and have intracranial EEG electrodes. In this study, the aim is to record brain signals from areas important in social and emotional processing and to understand how electrical brain stimulation - called neuromodulation - affects such processing. Patients enrolled in this study will be asked to view images depicting a variety of emotionally positive, negative, or neutral themes. As the patient views these images, a small amount of imperceptible and painless electric current will be used to map function of certain parts of a human brain. The overarching goal of the study is to determine if neuromodulation can be used in certain areas of the brain to treat cognitive disorders such as memory loss and post-traumatic stress disorder.

Study Overview

• Status: Completed
• Conditions: Refractory Epilepsy
• Intervention / Treatment: Other: Electrical Stimulation

Detailed Description

One to two study tasks will be performed by each participant to help us understand how the brain processes emotion and how stimulation effects emotional processing.

These study tasks will last up to several minutes each, and generally require participants to view pictures while EEG recordings are made from the electrodes placed in specific areas of the brain. The routine video/EEG monitoring and brain function testing should not be disrupted or prolonged by the study testing, and if a participant has a seizure during the testing, it will be recorded as usual for review by participant's providers.

The following study procedures will likely be carried out in each individual case:

1. Recording from areas important in social and emotional processing.

   A computer monitor will be used to present pictures of people engaged in social interaction. Additionally, the researchers will present individual participants with well standardized tasks designed to understand the nature of emotions. Some of these images may be emotionally disturbing. Should participants become uncomfortable with viewing such images, participants would be provided with a choice to not participate in this study.

2. Using brain stimulation to map function of certain parts of your brain.

   A brain stimulator will be used -normally used to map where important brain regions are located-to understand new functions of the brain. Each participant will be presented with pictures on a computer screen. As participant(s) views these pictures, the brain stimulator may be activated (this is not something that is felt by a person) and an electrical stimulation through the implanted electrodes will be delivered to specific regions of the brain. Research team will be measuring how brain stimulation may affect each individual's emotional response to a specific stimulus.

3. Completing the Emotion Self-Rating (ESR) Scale.

This questionnaire will be given to ensure the stimulation doesn't increase any unpleasant emotional experience for participants. This will take place before and during the stimulation of a specific part of the brain.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03776
      • Dartmouth-Hitchcock Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age of 18 years or older
• FSIQ 75 and above or any equivalent test of generalized intelligence as determined by the PI to adequately predict engagement in the task
• Able to give independent consent for participation in the study

Exclusion Criteria:

• Additional neurological disorders (such as dementia, stroke, brain tumor, etc.)
• Any psychiatric condition that would limit their ability to provide consent and/or perform study tasks within normal limits. This would be based on presurgical psychiatric assessment.
• Anything else, that in the opinion of the principal investigator, might preclude them from participating in the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stimulation; This part will include 24 randomly chosen images from each of four categories (total of 96 images varying in valence and arousal) and will be presented block-randomized amygdala stimulation.	Other: Electrical Stimulation; We will use a computer randomized stimulation of specific areas in the amygdala while showing a computer randomized set of pictures.
No Intervention: No stimulation; This part will include 24 randomly chosen images from each of four categories (total of 96 images varying in valence and arousal) and will be presented without amygdala stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Z-score Gamma Power in Amygdala Per Valence Category	Valence of each image is assessed by each subject using a Likert-type rating scale with a range of 1 to 7, where 1 represents most negative valence, 4 as neutral, and 7 as most positive. Valence categories are defined in the following manner: negative = 1.0 to 3.0, neutral = 3.1 to 5.0, negative = 5.1 to 7.0. Activation is measured by gamma frequency power (mµV²/30-100 Hz) at 0-1000 msec following image presentation in the basolateral amygdala electrode contact and compared to baseline defined as -500 msec to 0 of image presentation. Gamma power is transformed to z-score (baseline to following image presentation) for individual observations. Z-score of 0 indicates no change from baseline. Positive z-score indicates activation of the basolateral amygdala compared to baseline. Gamma frequency range is defined as 30-100 Hz in intracranial EEG. Power was estimated via a multitaper time-frequency transformation approach. Statistics was done using linear-mixed effects models (LMEs).	0 to 1000 MS following image presentation
Effect of Amygdala Stimulation on Perception of Valence	Here we assess the effect of basolateral amygdala stimulation on valence ratings. Participants rate the emotional valence of each image in a Likert scale range of 1-7 (1= maximum negative valence, 4=maximum neutral valence, and 7 maximum positive valence) for each of the 96 images. We randomly apply electrical stimulation during perception and of 50% of the images presented. We analyze the effect of stimulation on image rating in the following manner: we grouped the images into three categories, negative (1 to 3), neutral (3.1 to 5), and positive (5.1 to 7) based on subject specific ratings. 2. We then used a multivariate model to assess the effect of stimulation on perception of neutral, negative, and positive categories across 9 patients.	Valence ratings were assessed immediately following the viewing of each image during performance of the task.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure whether amygdala can be a suitable DBS target through comparison of EEG and reported perceptions.	Through administration of the electrical stimulation to the human amygdala while presenting participants with emotion producing pictures, researchers hope to analyze the differences in effects on reported perceptions by individual participants. These findings would allow to further determine whether the human amygdala is a suitable DBS target to treat certain psychiatric disorders.	Evaluated for each patient during monitoring period of approximately 2 weeks.

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Krzysztof A Bujarski, MD, Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2022
• Primary Completion (Actual): February 16, 2024
• Study Completion (Actual): February 16, 2024

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: March 14, 2022
• First Posted (Actual): March 23, 2022

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Deep Brain Stimulation; Psychiatric Disorders; Human Amygdala
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Drug Resistant Epilepsy; Mental Disorders; Investigative Techniques; Physical Stimulation; Electric Stimulation
• Other Study ID Numbers: STUDY02001399; 1R21MH124674-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study results will be available on ClinicalTrials.gov and will be published in appropriate clinical journal upon completion.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No