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Electrophysiological Read-Out of Interoceptive Processing

Primary Purpose

Drug-resistant Epilepsy

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Stereoelectroencephalography
Sponsored by
Icahn School of Medicine at Mount Sinai
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Drug-resistant Epilepsy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Epileptologists at Mount Sinai West have identified the patient as having drug-resistant epilepsy that may benefit from surgery Patient has or will undergo invasive monitoring as part of routine surgical management Patient has or will be implanted with a minimum of 6-8 bilateral SEEG pairs, including posterior and anterior insula, and at least four of the following targets: ventral lateral prefrontal cortex dorsal medial prefrontal cortex mid-cingulate subcallosal cingulate amygdala hippocampus fusiform gyrus Sufficient use of hands to complete self-report questionnaires and tasks, as determined during pre-surgical neuropsychological assessment Normal or corrected to normal vision, determined by patient report Use of anti-epileptic drugs (AEDs) with known psychiatric complications will not be an exclusion criterion Exclusion Criteria: Pre-operative neuropsychological testing indicates a Montreal Cognitive Assessment (MOCA) score < 26. English language proficiency insufficient to complete psychometric questionnaires and receive task instructions (<6th grade reading level) as determined by neuropsychologist at pre-operative assessment Vulnerable populations such as minors, pregnant women, cognitive impaired individuals and prisoners will not be included in the study

Sites / Locations

  • Mount Sinai WestRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Interoceptive Challenge Battery

Arm Description

During simultaneous stereoelectroencephalography recording (n=30) patients will complete a series of three computer-based tasks designed to evoke changes in interoceptive attention, arousal and anticipation.

Outcomes

Primary Outcome Measures

Heartbeat Evoked Potential (HEP) for attention
The heartbeat evoked potential is a brain electrophysiological signal time locked to the "rpeak" of the cardiac signal and thought to reflect interoceptive sensation of baroreceptor firing in the chest cavity. The population average magnitude of the change in HEP following the experimental manipulation (mean, standard deviation, 95% confidence interval) will be reported.
Heartbeat Evoked Potential (HEP) for arousal
The heartbeat evoked potential is a brain electrophysiological signal time locked to the "rpeak" of the cardiac signal and thought to reflect interoceptive sensation of baroreceptor firing in the chest cavity. The population average magnitude of the change in HEP following the experimental manipulation (mean, standard deviation, 95% confidence interval) will be reported.
Heartbeat Evoked Potential (HEP) for decision making
The heartbeat evoked potential is a brain electrophysiological signal time locked to the "rpeak" of the cardiac signal and thought to reflect interoceptive sensation of baroreceptor firing in the chest cavity. The population average magnitude of the change in HEP following the experimental manipulation (mean, standard deviation, 95% confidence interval) will be reported.

Secondary Outcome Measures

Full Information

First Posted
March 3, 2023
Last Updated
March 3, 2023
Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT05769634
Brief Title
Electrophysiological Read-Out of Interoceptive Processing
Official Title
Electrophysiological Read-Out of Interoceptive Processing in the Insula
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 10, 2022 (Actual)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
Interoception, or sensation from inside the body, is involved in a variety of clinical symptoms, such as tics, compulsions and negative mood. This study uses invasive recordings of brain activity and brain stimulation to better understand basic neural mechanisms of interoception and related behaviors. Outcomes of this study provide critical tools for future investigation into clinical symptoms that emerge from abnormal interoception.
Detailed Description
Abnormal interoceptive processing is observed across psychiatric and neurological conditions wherein core symptoms are motivated by diffuse bodily feeling: pervasive negative mood in Major Depression, compulsive urge in Obsessive Compulsive Disorder, urge to tic in Tourette Syndrome, and craving in addiction. Despite the prevalence of interoceptive abnormality, there is a scarcity of data on neurovisceral interactions in clinical populations. This knowledge gap can be attributed in part to a need for objective, neural measures of interoceptive processing. A candidate neural measure is the heartbeat evoked potential (HEP), a brain electrophysiological signal that is time-locked to the heartbeat and thought to index baroreceptor sensation in the chest cavity. While promising, basic characteristics of this signal are unknown, which limits its application to mechanistic and clinical research. Cortical sources of the HEP have been identified in the insula, yet spatial and temporal characteristics diverge across experimental paradigms. This suggests multiple functional correlates and cortical sources of the HEP index, including the insula. An added challenge is that the insula may be too deep for non-invasive recording and modulation, which necessitates invasive neural recording to explain non-invasive measures. Aim 1 validates neural source generators of the HEP with simultaneous invasive stereoelectroencephalography and dense array EEG on the scalp surface, while patients complete a battery of interoceptive tasks. Aim 2 investigates neural network dynamics during interoceptive attention, arousal and anticipation: theorizing that key clinical symptoms (e.g., tic, compulsions, negative mood) are learned behaviors in response to interoceptive cues, the research team tests the specific hypothesis that interoceptive activity is a predictor of reward-based decisions, particularly when decision-making demands a go with your gut strategy as reward outcomes are learned. Critically, Aim 3 then applies a deep breathing strategy to strategically perturb cardiac dynamics and disambiguate functional correlates of the HEP signal. Outcomes define properties of the HEP signal that must be known for this measurement strategy to inform and validate models of abnormal interoceptive circuit dynamics involving maladaptive responses to bodily distress.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Drug-resistant Epilepsy

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Interoceptive Challenge Battery
Arm Type
Experimental
Arm Description
During simultaneous stereoelectroencephalography recording (n=30) patients will complete a series of three computer-based tasks designed to evoke changes in interoceptive attention, arousal and anticipation.
Intervention Type
Behavioral
Intervention Name(s)
Stereoelectroencephalography
Intervention Description
Three computer-based tasks designed to evoke changes in interoceptive attention, arousal and anticipation will be completed. The first asks patients to attend to their heartbeat to manipulate interoceptive attention. The second asks patients to judge affective pictures to manipulate states of arousals. The third engages patients in a probabilistic reward-learning task, or gambling task, and anticipate the outcomes of risky decision-making. A final task guides patients to slow their breathing to 6 breaths per minute.
Primary Outcome Measure Information:
Title
Heartbeat Evoked Potential (HEP) for attention
Description
The heartbeat evoked potential is a brain electrophysiological signal time locked to the "rpeak" of the cardiac signal and thought to reflect interoceptive sensation of baroreceptor firing in the chest cavity. The population average magnitude of the change in HEP following the experimental manipulation (mean, standard deviation, 95% confidence interval) will be reported.
Time Frame
15 minutes
Title
Heartbeat Evoked Potential (HEP) for arousal
Description
The heartbeat evoked potential is a brain electrophysiological signal time locked to the "rpeak" of the cardiac signal and thought to reflect interoceptive sensation of baroreceptor firing in the chest cavity. The population average magnitude of the change in HEP following the experimental manipulation (mean, standard deviation, 95% confidence interval) will be reported.
Time Frame
15 minutes
Title
Heartbeat Evoked Potential (HEP) for decision making
Description
The heartbeat evoked potential is a brain electrophysiological signal time locked to the "rpeak" of the cardiac signal and thought to reflect interoceptive sensation of baroreceptor firing in the chest cavity. The population average magnitude of the change in HEP following the experimental manipulation (mean, standard deviation, 95% confidence interval) will be reported.
Time Frame
15 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Epileptologists at Mount Sinai West have identified the patient as having drug-resistant epilepsy that may benefit from surgery Patient has or will undergo invasive monitoring as part of routine surgical management Patient has or will be implanted with a minimum of 6-8 bilateral SEEG pairs, including posterior and anterior insula, and at least four of the following targets: ventral lateral prefrontal cortex dorsal medial prefrontal cortex mid-cingulate subcallosal cingulate amygdala hippocampus fusiform gyrus Sufficient use of hands to complete self-report questionnaires and tasks, as determined during pre-surgical neuropsychological assessment Normal or corrected to normal vision, determined by patient report Use of anti-epileptic drugs (AEDs) with known psychiatric complications will not be an exclusion criterion Exclusion Criteria: Pre-operative neuropsychological testing indicates a Montreal Cognitive Assessment (MOCA) score < 26. English language proficiency insufficient to complete psychometric questionnaires and receive task instructions (<6th grade reading level) as determined by neuropsychologist at pre-operative assessment Vulnerable populations such as minors, pregnant women, cognitive impaired individuals and prisoners will not be included in the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Allison Waters
Phone
212-523-8832
Email
allison.waters@mssm.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allison Waters
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mount Sinai West
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Allison Waters, PhD
Phone
212-523-8832
Email
allison.waters@mssm.edu
First Name & Middle Initial & Last Name & Degree
Allison Waters

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
IPD Sharing Time Frame
Beginning 3 months and ending 5 years following article publication.
IPD Sharing Access Criteria
Researchers who provide a methodologically sound proposal. Any purpose. Proposals should be directed to Allison.Waters@mssm.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (Link to be included in the URL field below).
IPD Sharing URL
https://labs.icahn.mssm.edu/waterslab/

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Electrophysiological Read-Out of Interoceptive Processing

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