Name: online transcranial magnetic stimulation protocol for measuring cortical physiology associated with response inhibition
Uploaded: 2018-02-08T13:00:00
Description: Watch this Scientific Journal Video about Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition at JoVE.com

This study was funded by the National Institute of Mental Health (R01MH095014).

This protocol was approved by the Cincinnati Children&#39;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 intro...

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...

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).1,4 Behavioral data alone does not provide information about potentially modifiable, quantifiable biological mechanisms. The overarching goal in the present study was to develop a child friendly method to evaluate motor cortex physiology during the execution of response inhibition, in order to develop a brain-based quantitative biomarker of the neural substrate of this task. Such biomarkers could have wide application in predictive studies of prognosis or treatment of neurobehavioral disorders.
For this purpose, the investigators selected and modified the Slater-Hammel (S-H) task5. This is a stop signal task that requires participants to inhibit an internally generated pre-programmed action. This self-paced task consists of both GO and STOP trials. GO trials are initiated by the subject pressing and maintaining pressure on a button, with the instruction to lift finger off the button (i.e. GO action) as close to but before the 800 ms target. In the original paradigm, time is indicated on a clock with a rapidly rotating hand. STOP trials are randomly interspersed amongst GO trials during which the person must inhibit the pre-planned GO action (i.e. prevent finger lift). The stop signal task is more difficult because subjects have to inhibit a response in the context of a pre-programmed GO signal, whereas in GNG task, the decision is whether to initiate or not initiate an action with no prior commands.6 Furthermore, it may be more accurate to investigate response inhibition by using stop signal tasks because in the GNG task, consistent correlations between signal and responses may result in automatic inhibition.7 Automatic inhibition is the theory that consistent mapping between signal and response (i.e. GO signal always results in a GO response and vice versa) leads to an automatic processing throughout the course of the experiment such that the STOP trials are partly processed through memory retrieval and bypasses certain executive controls.8,9
Transcranial magnetic stimulation (TMS) is a non-invasive technology that can be used to measure cortical physiology. Using single- and paired-pulse stimulation paradigms, one can quantify cortical excitability and inhibition. Although most published TMS studies investigate cortical physiology at rest, some groups have examined cortical excitability/inhibition during mental preparation for action10 and during different cognitive states that may be reflected in motor cortex physiology.11,12,13,14 This functional TMS (fTMS) approach requires online TMS measurements while participants are performing behavioral tasks, thus allowing one to probe cortical changes that are state-dependent with high temporal resolution. Providing real-time information on neurophysiologic changes in such a manner broadens the physiologic investigation of motor control15,16 and neuropsychiatric conditions17,18,19,20.
Prior fTMS studies have explored cortical mechanisms of response inhibition in healthy adults using GNG14 and SST tasks15,16,21. Furthermore, one study showed that a single dose of methylphenidate changed motor cortical physiology of healthy adults during an fTMS/GNG experiment.22 To date, there are two groups that have published pediatric fTMS studies using GNG task to characterize cortical physiology of ADHD23 and Tourette Syndrome17. There is currently no published fTMS study utilizing SST in the pediatric population.
A critical issue in fTMS studies, to a much greater extent than rest-alone TMS studies, is muscle artifact. Standardized surface electromyography (EMG) measures of amplitude and latency from motor-evoked potentials (MEP) must not be contaminated by muscle artifact. So, for example, to study cortical changes in preparation for a movement in a reaction time study, TMS pulses must be precisely timed to occur after a GO signal but prior to an individual&#39;s reaction time. Thus in any task, it is critical to ensure that TMS pulses are occurring at a time when the motor response has not yet begun, and that the participant is comfortable and able to maintain the relevant muscle at rest. This can be exceptionally problematic with hyperkinetic children who may naturally have extraneous movements and who may keep their arm and hand tensed throughout a reaction time game.
The aim of the present study is to develop a version of the Slater-Hammel SST that is child-friendly and suitable for studying primary motor cortex (M1) physiology. This task should be 1) easily understandable for children, 2) relatively easy to complete for children and 3) compatible with online TMS.

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online transcranial magnetic stimulation protocol for measuring cortical physiology associated with response inhibition

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 &#34;racecar&#34; 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&#60;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&#160;affect behavioral task performance.

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 &#177; 1.3 years for Cincinnati and 10.4 &#177; 1.2 years for Baltimore; t test p=0.74)
We used a regression model to analyze SS...

Watch this Scientific Journal Video about Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition at JoVE.com

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

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.

We describe the development of a reproducible, child-friendly motor response inhibition task suitable for online Transcranial Magnetic Stimulation (TMS) ...

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