Some Thoughts about Transcranial Magnetic Stimulation in Autism

There are several hundred studies of transcranial magnetic stimulation (TMS) in autism. Trying to make sense out of them would entail gathering the results of comparable studies that adhered to proper scientific standards.  In this regard we would have to eliminate from consideration case reports, single session treatments, those made only for mechanistic considerations, and those who did not provide enough data for proper criticism. When all of these studies are eliminated, we are left with a couple of dozen studies from where to draw our conclusions. The most notable aspect from the reduced number of studies is that they are highly variable among themselves.  They have used different populations of patients (age, gender, functioning level), select different regions in the brain for stimulation, use different protocols (some meant for excitation others for inhibition), and they all seem to vary in their equipment (figure eight coil, H-coil, picoTesla helmet). Curiously enough, I believe that this variability represents both the strengths and the weaknesses about the possible effectiveness of TMS in autism.  Let me explain.

Despite the variability in patient’s profiles, study protocols, equipment used, blinding methods, etc. results have shown positive improvements in patients, that are reproducible among different laboratories. Patients have shown improvements in irritability, repetitive behaviors, sociability, and even in terms of their executive functions.  Alternatively, the negative aspect ingrained in interstudy variability is the difficulty in drawing adequate conclusions.  Are the results significant?  Indeed, the conclusions for most review articles on the subject uniformly reads the same:  “the results are suggestive of positive improvements, but more research to this area is required before drawing meaningful conclusions”.

What is the reason for this variability among different studies?  The primary reason, I would say, is that you can not buy how a researcher thinks!  Researchers will change their stimulation protocols and outcome measures depending on the hypothesis that they are trying to prove.  Depending on whether they believe that autism is due to a cortical excitatory-inhibitory imbalance, language abnormality, faulty mirror neurons, or abnormal motor planning (dyspraxia), their underlying hypothesis will lead them to stimulate different regions of the brain and the use different outcome measures to gauge their results. To illustrate the difficulties that we are facing take for example the stimulation frequency used in TMS studies. Low frequencies are known to promote inhibition while higher frequencies promote excitation.  There is a body of literature claiming that both inhibitory cells and receptors are reduced in the cerebral cortex of autistic individuals.  The findings make clinical sense and have been used to explain why many autistic individuals suffer from convulsions and sensory abnormalities.  This has led many groups to use low frequency (inhibitory) TMS in autism.  Other researchers believe that autism is due to a dopaminergic deficit and cite abnormalities in the conducting pathways of this neurotransmitter.  High frequency TMS applied to the prefrontal cortex is known to release and increase the levels of dopamine in those subcortical regions claimed to be affected in autism.  So, while some researchers are trying to provoke inhibition in the prefrontal cortex of autistic individuals, others are targeting the same region and using excitatory frequencies. Different ideas about autism leading to diametrically opposite treatments.

In our own studies we selected the dorsolateral prefrontal cortex for stimulation.  This region of the brain is involved in those executive functions that provide for the cognitive control of behavior, monitors the same, and facilitates the attainment of goals.  Psychological tests, neuropathological studies and a multitude of neuroimaging reports all claim that executive dysfunction plays a prominent role in autism.  The problem being is whether we should stimulate the dorsolateral prefrontal cortex on the left hemisphere, on the right hemisphere, alternate in stimulating left and right hemisphere, or stimulate both simultaneously?  Each one of these is a different intervention and a different experiment. Still, depending on the hypothesis of other individuals and whatever findings they select from the research literature, other areas of the brain may be selected for stimulation: the midline bilateral prefrontal cortex, inferior prefrontal cortex (home of the mirror neurons), motor and supplementary motor cortices, and the posterior portion of the superior temporal gyrus.

Unfortunately, the variability among studies has detracted researchers from being able to answer some of the more pressing questions in TMS research. Do benefits extend to lower functioning individuals?  How long does the beneficial effects last? How come some people have positives results and others don’t, -what differentiates them?  As many research reviews have stated, -more research needs to be done. Unfortunately, the federal government rather than helping solve problems has placed roadblocks on research dealing with interventions that could improve the quality of life of patients. Instead, a lot of the funding goes to animal research and genetics exploration that will provide little, if any, immediate benefits to the patients.

I have been reading about the manipulation of stock prices by Wall Street hedge funds and how the Reddit crowd revolted causing some hedge funds to close their positions (GameStop saga is about ‘working class vs hedge funds’: Reddit WSB user (yahoo.com). I do believe that, in similar fashion, stakeholders of the autism community should take over dictating research initiatives from the federal government. This is throwback to Leo Kanner who decades ago argued for parental participation in all aspects related to the medical care of their children, including defining diagnostic criteria. It has been remarkably frustrating and painful to watch first-hand the mishandling of research initiatives related to autism by the federal government. Much more could have been done.

References

The National Database for Autism Research (NDAR): Playing Favorites in Autism Research | Cortical Chauvinism

Federally funded autism research | Cortical Chauvinism

Of Mice and Men: Complications of Animal Models in Autism Research | Cortical Chauvinism

Translating TMS: From Autism Science to Autism Therapy | Cortical Chauvinism

Autism Updated: Symptoms, Treatments and Controversies: Empowering parents and autistic individuals through knowledge: Casanova MD, Manuel F: 9781079144109: Amazon.com: Books

4 responses to “Some Thoughts about Transcranial Magnetic Stimulation in Autism

    • Yes. They both have a long history within the medical literature of positive results. Treatment of depression was approved by the FDA in 2008 (being limited to treatment resistant depression).

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  1. If you feel that way you should be in favor of abolishing the IACC as I am. The government has been completely taken over by neurodiversity I was not aware that anyone besides Endicott in australia and your group had done any treatment studies with TMS and autism so i guess i need to read more I thought the harvard TMS group and Lindsay oberman and others were just using it to assess various brain functions and plasticity in autism, but I may have thought wrong

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    • I would have to agree with you on everything. I have been displeased with the IACC. It has taken autism research nowhere. Quite a shame. In regards to TMS, my group did most of the clinical studies and reported on more patients than the rest of the world put together. Again, you are correct, the Harvard group did mostly mechanistic studies, not clinical trials. Overall I am frustrated, always thought that much more could have been done.

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