Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition

Summary

We describe an experimental procedure to quantify excitability and inhibition of primary motor cortex during a motor response inhibition task by using Transcranial Magnetic Stimulation throughout the course of a Stop Signal Task.

Abstract

We describe the development of a reproducible, child-friendly motor response inhibition task suitable for online Transcranial Magnetic Stimulation (TMS) characterization of primary motor cortex (M1) excitability and inhibition. Motor response inhibition prevents unwanted actions and is abnormal in several neuropsychiatric conditions. TMS is a non-invasive technology that can quantify M1 excitability and inhibition using single- and paired-pulse protocols and can be precisely timed to study cortical physiology with high temporal resolution. We modified the original Slater-Hammel (S-H) stop signal task to create a "racecar" version with TMS pulses time-locked to intra-trial events. This task is self-paced, with each trial initiating after a button push to move the racecar towards the 800 ms target. GO trials require a finger-lift to stop the racecar just before this target. Interspersed randomly are STOP trials (25%) during which the dynamically adjusted stop signal prompts subjects to prevent finger-lift. For GO trials, TMS pulses were delivered at 650 ms after trial onset; whereas, for STOP trials, the TMS pulses occurred 150 ms after the stop signal. The timings of the TMS pulses were decided based on electroencephalography (EEG) studies showing event-related changes in these time ranges during stop signal tasks. This task was studied in 3 blocks at two study sites (n=38) and we recorded behavioral performance and event-related motor-evoked potentials (MEP). Regression modelling was used to analyze MEP amplitudes using age as a covariate with multiple independent variables (sex, study site, block, TMS pulse condition [single- vs. paired-pulse], trial condition [GO, successful STOP, failed STOP]). The analysis showed that TMS pulse condition (p<0.0001) and its interaction with trial condition (p=0.009) were significant. Future applications for this online S-H/TMS paradigm include the addition of simultaneous EEG acquisition to measure TMS-evoked EEG potentials. A potential limitation is that in children, the TMS pulse sound could affect behavioral task performance.

Introduction

Response inhibition is the ability to selectively prevent those unwanted actions that can interfere with intended functional goals.¹ The cortico-striatal network is critically involved in response inhibition, which progressively becomes more efficient as children mature but is impaired in numerous neuropsychiatric conditions such as attention-deficit hyperactivity disorder (ADHD), learning disorders, obsessive compulsive disorder, and schizophrenia.^2,3 Motor response inhibition can be examined with different behavioral paradigms such as Go/NoGo (GNG) and Stop Signal tasks (SST).

Protocol

This protocol was approved by the Cincinnati Children's Hospital Medical Center and Johns Hopkins Institutional Review Boards as a minimal risk study in children and adults. Single- and paired-pulse TMS is considered as safe in children 2 years and older per international expert consensus.²⁴ After explaining the potential risks of TMS to parent/guardian and participant, consent and assent forms are signed if they agree to proceed with the study.

1. Screening and introduction

1. Screen subjects for TMS contraindication(s) using a standardized questionnaire.²⁵
2. Demonstrate ....

Results

Regression analysis is performed using a commercial statistical software package to analyze behavioral and neurophysiologic data separately. The representative data is from 23 typically developing children from Cincinnati and 15 from Baltimore (25 male, 13 female). Age did not differ between site (10.3 ± 1.3 years for Cincinnati and 10.4 ± 1.2 years for Baltimore; t test p=0.74)

We used a regression model to analyze SSRT with ag.......

Discussion

This protocol is a novel child-friendly method of combining a stop signal task and TMS to examine event-related cortical inhibition. Clinical observation of motor inhibitory deficits and poor performance in stop signal tasks have been demonstrated in numerous neuropsychiatric conditions.³ Relatively few investigators have used online fTMS to examine cortical excitability and inhibition during response inhibition tasks. Some groups have successfully used TMS during GNG task to show differences in c.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Precision Gamepad	Logitech	G-UG15
Acquisition Interface Model ACQ-16	Gould Instrument Systems Inc	ACQ-16
Micro1401-3 Data Acquisition Unit	Cambridge Electronic Design Ltd	Not applicable
Signal version 6 software (Windows)	Cambridge Electronic Design Ltd	Not applicable
Power base	Coulbourn Instruments	V15-17
Bioamplifier with filters	Coulbourn Instruments	V75-04
Conductor electrode cables (for surface EMG)	Coulbourn Instruments	V91-33
2002 TMS device	The Magstim Company Ltd	Not applicable
BiStim2 module	The Magstim Company Ltd	Not applicable
90mm circular TMS coil	The Magstim Company Ltd	Not applicable
Presentation software (Windows)	Neurobehavioral Systems Inc	Not applicable
Windows computer		Not applicable