Electrophysiologic Studies of Cognition in Epilepsy Patients

NCT ID: NCT05769634

Last Updated: 2025-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-10
• Study Completion Date: 2024-05-28

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.

Conditions

Drug-resistant Epilepsy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Interoceptive Challenge Battery

During simultaneous stereoelectroencephalography recording (n=20) patients will complete a series of three computer-based tasks designed to evoke changes in interoceptive attention and arousal.

Group Type: EXPERIMENTAL

Stereoelectroencephalography

Intervention Type: BEHAVIORAL

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.

Interventions

Stereoelectroencephalography

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.

Intervention Type: BEHAVIORAL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Allison Waters

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Allison Waters

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Mount Sinai West

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R21MH126968-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY-22-00529

Identifier Type: -

Identifier Source: org_study_id