One of my publications just became available to the public on PubMed. The publication deals with the use of transcranial magnetic stimulation in autism spectrum disorders, more specifically, why I thought it could offer a good therapeutic intervention, and some of the results from our laboratory. Having had the idea and written the article I can only offer my eternal gratitude to a wonderful group of collaborators capable of making dreams come true.
In the following paragraphs I offer both the abstract and the conclusions to the article.
Abstract
Despite growing knowledge about autism spectrum disorder (ASD), research findings have not been translated into curative treatment. At present, most therapeutic interventions provide for symptomatic treatment. Outcomes of interventions are judged by subjective endpoints (e.g., behavioral assessments) which alongside the highly heterogeneous nature of ASD account for wide variability in the effectiveness of treatments. Transcranial magnetic stimulation (TMS) is one of the first treatments that targets a putative core pathological feature of autism, specifically the cortical inhibitory imbalance that alters gamma frequency synchronization. Studies show that low frequency TMS over the dorsolateral prefrontal cortex (DLPC) of individuals with ASD decreases the power of gamma activity and increases the difference between gamma responses to target and non-target stimuli. TMS improves executive function skills related to self-monitoring behaviors and the ability to apply corrective actions. These improvements manifest themselves as a reduction of stimulus bound behaviors and diminished sympathetic arousal. Results become more significant with increasing number of sessions and bear synergism when used along with neurofeedback. When applied at low frequencies in individuals with ASD, TMS appears to be safe and to improve multiple patient-oriented outcomes. Future studies should be conducted in large populations to establish predictors of outcomes (e.g., genetic profiling), length of persistence of benefits, and utility of booster sessions.
Conclusions
In summary, the cerebral cortex’s inherent excitatory/inhibitory bias demands the presence of dampening mechanisms to maintain a proper set point when acquiring and processing stimuli. This bias is altered in ASD individuals and manifested as gamma oscillation abnormalities, deficits in executive function, and stimulus bound behaviors. TMS is a non-invasive therapeutic intervention capable of modulating evoked and induced gamma oscillations and altering maladaptive behaviors83. Recent reviews of the literature suggest that TMS is safe and effective when used in ASD54,84–91. Selecting appropriate outcome measures is of importance due to limitations in presently available sham procedures that help define differences between active and control populations92. It is therefore of importance that the selection process for outcome measures extends beyond subjective methods, such as behavioral screening, and into unbiased electrophysiological measures that maximize both internal and statistical validity. In addition, objective measures of quality care should be instituted and analyzed by themselves rather than being considered surrogate measures of outcomes. We have found that autonomic measures, themselves related to behavior problems and emotional regulation, help define functional changes associated with ASD while simultaneously monitoring adverse experiences80,81. At present, efforts should focus on developing large sample clinical trials with targeted inclusionary/exclusionary criteria and longitudinal follow-up. This will allow testing critical questions regarding possible predictors of outcome (e.g., genetic profiling), length of persistence of benefits, assessing outcome according to severity of phenotypic presentation, and utility of booster sessions.
Cortical Chauvinism 
Manny, this post and the journal paper it points to are wonderful! Thank you so much! This is fertile material for additional blog posts and further, very valuable research. I might be able to help a bit with future research.
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Thank you. Really appreciate the comment.
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I may well be the only researcher today to challenge the autism spectrum approach. I concluded over some time the “spectrum” theory was adopted by psychologists Wing and Goulde in the mid 1980s. The initial theory seems to have been derived from Kretschmer’s essays in the 1920s. I think the spectrum conception was challenged (prior to Wing) by several elite researchers, led by S.Suhareva. I suppose my point is that Wing’s interpretation was accepted at face value and not properly analysed in context. Of course, my approach heavily relies upon psychology and less neurology.
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Difficult to calculate the power. Even in evoked potentials, the measure is usually a proxy of the real power as we know the voltage (crudely and only for superficial layers of the cerebral cortex) but not the current. As an aside many of my best ideas (e.g., a way to synthesize optically active amines) came to me in dreams.
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Hi Dr. Casanova,
I just stumbled upon your work on TMS and autism.
I am a young adult just recently diagnosed with high functioning autism
Since you are one of the foremost researchers on this topic, I was wondering if you are able to answer a few of my questions.
1. Do you think it is advisable for me to pursue TMS off-label for my autism with the current state TMS is in?
2. In your opinion is there any hope for TMS to be approved by the FDA for autism treatment like it has for depression and OCD in the near future? And if so, in what time frame do you see it happening?
3. Are there any other lines of research for autism cures that you think are promising like stem cell therapy, gut flora transplants, fatty acid treatments etc.?
Thank you so much for your work in improving the lives of so many with autism and I hope you see this comment.
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Hi Reyhan,
TMS remains an experimental technique, not approved by the FDA, for the treatment of autism. Although it has been the object of many studies, the FDA requires a phase III trial with a large population before considering it for approval. The problem being that many of the previous studies vary from each other in anatomical target, energy, frequency of the stimulation, etc. I do believe that it may be approved in the future, but it may require funding from the federal government to carry on the necessary studies.
I did some 15 clinical trials for TMS in autism and treated hundreds of patients with good results. Never charged anybody for participation. I retired a couple of years ago. You may find out who is conducting clinical trials by going to clinicaltrials.gov. In addition, you may check with tertiary care hospitals (academic centers) to see if they have a section specialized in the technique.
If you are interested in some articles about the technique I will gladly send you copies (my email i m0casa02@louisville.edu).
Best regards,
Manuel
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TMS may improve executive function, which to me is like giving sight to someone who is completely blind, but it would be like a very imperfect sight to say the least if I still did things in an autistic (inferior) manner.
I’ll echo what the above person said, how promising are the prospects for eliminating the autism in it’s entirity? Will it ever be done?
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My main concern has always been to try to improve those aspects of autism that may handicap the individual or decrease the quality of life. In this regard we are using symptomatic rather than curative treatment. Improving executive functions, diminishing anxiety, dysautonomia and prophylaxis of sudden death. should be major concerns of physicians that are trying to help their patients.
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Thank you for replying to my question. I’ve been reading your articles about autistic psychology and possible treatments and your insights are stunning and your soluitions seem promising.
Can’t blame me for asking the question that I asked, even though I was almost certain your answer would amount to “no, it’s not possible.” I suppose my brain is of a an autistic phenotyope, and to somehow reconstruct it and convert it into a normal brain would be in the realms of high fatanasy right?
Well, I’ll still never give up hope that it can and will be done, if not in my lifetime then sometime in the future. Meantime I’ll look into some of the real life things that you propose on this blog.
A lot of it’s common sense really, positive attidtue, regular sleep, good diet and excercise etc. The TMS looks promising too. I hope that it becomes an available treatment that I can try sometime in the near future.
The problem is that my executive function is so terrible it feels like I have none at all. I battle fiercly for months to complete a basic laundry list of things that I’m certain a regular person could do within a week.
I’m trying to take those basic, common sense steps to life improvment and the difficulty is astranomoical. While I’m still holding out for a magical Jesus cure, and still trying to tackle my problems of an earthly basis, if you could respond briefly to any questions I have on any of your blog articles that would be grand.
Cheers.
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