Electrophysiological Read-Out of Interoceptive Processing

Drug-resistant Epilepsy Clinical Trial

Official title:

Electrophysiological Read-Out of Interoceptive Processing in the Insula

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05769634
• Other study ID #: STUDY-22-00529
• Secondary ID: R21MH126968-01A1
• Status: Recruiting
• Phase: Early Phase 1
• Start date: August 10, 2022
• Est. completion date: March 31, 2024

Study information

• Verified date: March 2023
• Source: Icahn School of Medicine at Mount Sinai
• Contact: Allison Waters
• Phone: 212-523-8832
• Email: allison.waters[@]mssm.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Drug Resistant Epilepsy
• Drug-resistant Epilepsy

Intervention

Behavioral:
• Stereoelectroencephalography
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.

Locations

Country	Name	City	State
United States	Mount Sinai West	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	15 minutes
Primary	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.	15 minutes
Primary	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.	15 minutes