TMS - Intracranial Electrodes

• ClinicalTrials.gov Identifier: NCT03702127
• Recruitment Status: Enrolling by invitation
• First Posted: October 10, 2018
• Last Update Posted: August 6, 2021
• Sponsor: Aaron Boes
• Information provided by (Responsible Party): Aaron Boes, University of Iowa

Study Description

Brief Summary:

This is a study looking at the effects of transcranial magnetic stimulation (TMS), a form of non-invasive brain stimulation (NIBS), on the human brain as recorded by intracranial electroencephalography in neurosurgical patients. NIBS will be applied in a targeted manner and brain responses will be recorded.

Condition or disease	Intervention/treatment	Phase
Epilepsy Intractable	Device: Transcranial magnetic stimulation	Not Applicable

Detailed Description:

In the last few years, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS), transcranial current stimulation, and peripheral multi-modal stimulation have shown widespread clinical applications. Transcranial magnetic stimulation (TMS) is a noninvasive method of focally stimulating the brain that uses electromagnetic induction and does not require surgery. There is optimism that TMS and other forms of NIBS will revolutionize how we treat neurological and psychiatric disorders, evidenced by over 1000 clinical trials registered using TMS. Much of this optimism stems from the successful use of TMS as a treatment for depression. Despite the large number of clinical trials using NIBS the number of therapeutic indications has been stagnant, limited to major depression and more recently obsessive-compulsive disorder. There are fundamental questions about the underlying mechanisms of action for NIBS that will be critical to understand in order to advance this treatment modality. Here, we propose a unique collaborative project between neurology and neurosurgery that will allow an unprecedented window into understanding how NIBS impacts the human brain. Specifically, we will perform various forms of targeted TMS in neurosurgical patients with intracranial electroencephalography (iEEG) monitoring to record real time effects of NIBS on local and remote brain areas with an unparalleled combination of spatial and temporal resolution relative to other human studies. TMS may present the most risk for patients with intracranial electrodes and we have already demonstrated the safety of this approach using a gel-based phantom brain and have results from seven patients demonstrating safety and preliminary results. For the current proposal we aim to: 1) characterize the response of NIBS on the human brain as recorded from iEEG between active and sham conditions, and 2) relate remote electrophysiological responses from NIBS to measures of brain connectivity between the stimulation & recording sites assessed with resting state functional connectivity MRI (rs-fcMRI). This will allow us to evaluate the relationship between NIBS-evoked iEEG responses and the strength of functional connectivity to the stimulation site in a regression model. For the TMS portion of the study we hypothesize that 1) TMS will have focal effects detected from surface electrodes underlying the stimulation site as well as network-level engagement detected at remote sites, 2) Repetitive TMS will induce frequency-specific effects that differ between 0.5 and 10 Hz stimulation protocols, and 3) the magnitude of repetitive TMS-evoked iEEG responses across electrodes will relate to the strength of rs-fcMRI between the stimulation and recording sites. By investigating the electrophysiological responses of TMS with high spatiotemporal precision in humans, this study will provide new mechanistic insights into the effects of TMS on target engagement and relate these findings to imaging methods already in widespread use. Moreover, the TMS will be applied in a clinically meaningful way by targeting the left dorsolateral prefrontal cortex in a protocol used to treat depression. Generating results for these aims will be key to advancing our understanding of how TMS and other forms of NIBS engage brain networks, which can be leveraged to rationally develop personalized, imaging-guided therapeutic NIBS for depression and other disorders.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: Participant will receive active and sham stimulation at varying points during the study.
• Primary Purpose: Basic Science
• Official Title: Investigating the Effects of Transcranial Magnetic Stimulation With Intracranial EEG in Humans
• Actual Study Start Date: July 16, 2019
• Estimated Primary Completion Date: June 30, 2026
• Estimated Study Completion Date: July 30, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: TMS in patients with intracranial electrodes; We will administer TMS to neurosurgical patients with intracranial electroencephalography in order to better understand the effects TMS has on the human brain. Participants will receive both active and sham stimulation at varying points during the study.	Device: Transcranial magnetic stimulation; NIBS is applied to the brain.

Outcome Measures

Primary Outcome Measures :

1. Change in brain activity assessed with intracranial EEG [ Time Frame: Activity changes within seconds of the stimulation ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Eligible subjects will include neurosurgery patients (age 18 and above) who have implantation of intracranial electrodes and undergo long term (about 2 weeks) EEG monitoring in order to decide candidacy for surgical resection of seizure foci. They must have the cognitive capacity to understand the risks and benefits fo the study and provide consent.

Exclusion Criteria:

Those who are known to have neurological or psychiatric disorder other than primary disease for which patients have surgery will be excluded.

Contacts and Locations

Locations

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52242

Sponsors and Collaborators

Aaron Boes

Investigators

• Principal Investigator: Aaron Boes, MD, PhD; University of Iowa

More Information

• Responsible Party: Aaron Boes, Assistant Professor, University of Iowa
• ClinicalTrials.gov Identifier: NCT03702127
• Other Study ID Numbers: 201707763
• First Posted: October 10, 2018
• Last Update Posted: August 6, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Drug Resistant Epilepsy; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases