Cortical Excitability in Cyclic Vomiting Syndrome

Study Overview
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Brief Summary
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This exploratory study will determine if there are differences in cortical excitability between patients suffering from cyclic vomiting syndrome (CVS) and healthy control subjects, as assessed by a non-invasive method of brain stimulation (Transcranial Magnetic Stimulation, TMS).

Detailed Description
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This exploratory study will determine if there are differences in cortical excitability between patients suffering from cyclic vomiting syndrome (CVS) and healthy control subjects, as assessed by a non-invasive method of brain stimulation (Transcranial Magnetic Stimulation, TMS). Using the paired-pulse TMS paradigm, intracortical inhibition and facilitation of cortical circuitry will be assessed by stimulating the motor cortex and using the electromyographic (EMG) response of a target muscle as readout. In such studies, a conditioning stimulus modulates the amplitude of the motor-evoked potential (MEP) produced by the test stimulus. Depending on the inter-stimulus interval, effects can be attributed to different aspects of cortical processing. Brief intervals (1-5 ms) will be used to assess short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF), intermediate intervals (7-20 ms) to assess intracortical facilitation (ICF) and long intervals (50-200 ms) to assess long-interval intracortical inhibition (LICI). Some clinical, demographic, and autonomic data (i.e. EKG) will be recorded and used as covariates to investigate any systematic impact on cortical excitability measures collected with the paired-pulse protocols.

Official Title
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Cortical Excitability in Cyclic Vomiting Syndrome

Conditions
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Cyclic Vomiting Syndrome

Intervention / Treatment
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* Other: TMS Paired-Pulse assessment of cortical excitability
* Other: Autonomic activity


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of CVS Exclusion Criteria: history of CVS (for healthy control population only) psychosis or altered cognitive status history of head injury, metal in the skull, stroke, or a history of seizures implantable devices, such as a pacemaker or nerve stimulator current use of the following medications or use of substances which are known to lower the seizure threshold: clozapine (Clozaril), chlorpromazine (Thorazine), amphetamines or methamphetamine, Ecstasy, Ketamine, Angel Dust/PCP, cocaine, or 3 or more alcoholic drinks per day pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a comparative study looking at differences in electrophysiologic measures of cortical excitability between those with Cyclic Vomiting Syndrome and healthy controls.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CVS subjects<br>Subjects diagnosed with Cyclic Vomiting Syndrome (CVS) | Other: TMS Paired-Pulse assessment of cortical excitability<br>* Using the paired-pulse TMS paradigm, intracortical inhibition and facilitation of cortical circuitry will be assessed by stimulating the motor cortex and using the electromyographic (EMG) response of a target muscle as readout. In such studies, a conditioning stimulus modulates the amplitude of the motor-evoked potential (MEP) produced by the test stimulus. Depending on the inter-stimulus interval, effects can be attributed to different aspects of cortical processing. Brief intervals (1-5 ms) will be used to assess short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF), intermediate intervals (7-20 ms) to assess intracortical facilitation (ICF) and long intervals (50-200 ms) to assess long-interval intracortical inhibition (LICI).<br>Other: Autonomic activity<br>* Autonomic function will be determined using continuously recorded EKG and used as covariates to investigate any systematic impact on cortical excitability measures collected with the paired-pulse protocols.<br>|
| Active Comparator: healthy, non-CVS subjects<br>Subjects not diagnosed with CVS | Other: TMS Paired-Pulse assessment of cortical excitability<br>* Using the paired-pulse TMS paradigm, intracortical inhibition and facilitation of cortical circuitry will be assessed by stimulating the motor cortex and using the electromyographic (EMG) response of a target muscle as readout. In such studies, a conditioning stimulus modulates the amplitude of the motor-evoked potential (MEP) produced by the test stimulus. Depending on the inter-stimulus interval, effects can be attributed to different aspects of cortical processing. Brief intervals (1-5 ms) will be used to assess short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF), intermediate intervals (7-20 ms) to assess intracortical facilitation (ICF) and long intervals (50-200 ms) to assess long-interval intracortical inhibition (LICI).<br>Other: Autonomic activity<br>* Autonomic function will be determined using continuously recorded EKG and used as covariates to investigate any systematic impact on cortical excitability measures collected with the paired-pulse protocols.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Paired-pulse ratios | Percentage Change in Paired Pulse (PP) TMS induced MEP responses with inhibitory or facilitatory stimulation. | Multiple study sessions spanning up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TMS motor threshold | TMS stimulator output necessary to elicit 200 microvolt MEP responses | Multiple study sessions spanning up to 12 months | 
| Cortical silent period | Length (milliseconds) of EMG inactivity following TMS stimulation | Multiple study sessions spanning up to 12 months | 
| Heart rate variability | Spectral frequency analysis (via Fast Fourier Transformation) of R-R intervals | Multiple study sessions spanning up to 12 months |