TMS: Using the Theta-Burst Protocol to Explore Mechanism of Plasticity in Individuals with Fragile X Syndrome and Autism

Summary

In this article, we examine the effects of Theta-Burst TMS stimulation on cortical plasticity in individuals suffering from Fragile X syndrome and individuals on the autistic spectrum.

Abstract

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome.^1,2 Individuals suffering from FXS display abnormalities in the expression of FMR1 - a protein required for typical, healthy neural development.³ Recent data has suggested that the loss of this protein can cause the cortex to be hyperexcitable thereby affecting overall patterns of neural plasticity.^4,5

In addition, Fragile X shows a strong comorbidity with autism: in fact, 30% of children with FXS are diagnosed with autism, and 2 - 5% of autistic children suffer from FXS.⁶

Transcranial Magnetic Stimulation (a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability via the application of localized magnetic field pulses ^7,8) represents a unique method of exploring plasticity and the manifestations of FXS within affected individuals. More specifically, Theta-Burst Stimulation (TBS), a specific stimulatory protocol shown to modulate cortical plasticity for a duration up to 30 minutes after stimulation cessation in healthy populations, has already proven an efficacious tool in the exploration of abnormal plasticity.^9,10

Recent studies have shown the effects of TBS last considerably longer in individuals on the autistic spectrum - up to 90 minutes.¹¹ This extended effect-duration suggests an underlying abnormality in the brain's natural plasticity state in autistic individuals - similar to the hyperexcitability induced by Fragile X Syndrome.

In this experiment, utilizing single-pulse motor-evoked potentials (MEPs) as our benchmark, we will explore the effects of both intermittent and continuous TBS on cortical plasticity in individuals suffering from FXS and individuals on the Autistic Spectrum.

Protocol

1. Determine Resting Motor Threshold:

1. To begin, seat your subject in a comfortable chair.
2. Next, apply EMG surface electrodes over the first dorsal inerosseus muscle of the subject's right hand. (INSERT FIGURE1) If you are having trouble locating this muscle, ask the subject to make a pinching motion or to move his/her index finger back and forth - this should make the muscle easier to locate.
3. Place a ground electrode on the meaty portion of the subject's forearm.
4. Determine the location of the subject's left motor cortex. Although this area differs slightly for everyone, it will generally ....

Discussion

Knowing that prolonged duration of TMS after-effects is reflective of atypical neural plasticity, studies such as this could serve to create better and more precise diagnostic protocols for Autism and related disorders.

Similarly, with more data, we may be able to find temporal biological markers for other neurological pathologies - including Fragile X syndrome. In this case, although there is not yet a therapeutic remediation option, early detection could help parents and educators determin.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Alcohol Swabs
EMG Electrodes
EMG Measuring Equipment/Software
Ear Plugs
Marker or Grease Pen
Any Single Pulse Capable TMS Device
Any rTMS Capable TMS Device (for TBS)
Any Compatible Figure-of-Eight Coil
Frameless Stereotactic Equipment (Optional)