The second possible benefit of understanding the brain’s building blocks is that it could enhance instruction processes in many types of education. If we know the desired end state of the thoughts of a learner, we might be able to design the instruction to optimally provide and assemble the building blocks that compose the thought. The desired end state can be determined (using “mind reading”) from the brains of people who already have an excellent grasp of the end-state concepts. Such research is in its infancy, but it could revolutionize how we educate our young, train our workforce, and transform every child into a literate, thoughtful, productive citizen.
This vision sounds grandiose, but so would have been a description of the current state of knowledge about brain function had someone fore-shadowed it twenty-five years ago. John Elder Robison has given us here his glimpse into the future. No one can accurately predict the future of brain science, but we can be certain that it will be here soon and that it will change the world.
MARCEL ADAM JUST
D. O. Hebb Professor of Psychology and
Co-director of the Center for Cognitive Brain Imaging,
Carnegie Mellon Univerity
Findings and Further Reading
MANY READERS ASK ME where TMS therapy stands today, and whether they can sign up for treatment. As this book goes to press, in early 2016, TMS is available as an FDA-accepted therapy for depression at hundreds of hospitals and clinics across the United States. It’s also available in Canada, Europe, Australia, and parts of Asia.
TMS is not yet an FDA-approved therapy for autism or ADHD, but I suspect that will come in the next decade. Right now, the scientists described in this book are forging ahead with new studies that build on what you’ve read in the previous pages. For those of you who want to follow in my footsteps, they are always looking for volunteers. I’ve focused on a few talented researchers in this book, but they are not the only ones who are active in the field. In America, Manny Casanova continues to study autism and TMS, and as of this writing, he has actually conducted more varied trials than anyone else in America. Peter Enticott is breaking new ground in his TMS centre at Australia’s Deakin University, and Simon Baron Cohen and others study TMS and autism at Cambridge in the UK. My website (johnrobison.com) contains a more up to date list of TMS centres and studies.
Researchers are also exploring the use of very low-power electrodes to deliver energy to the brain. That technology is called TDCS, for transcranial direct current stimulation. Some studies have shown it to have an effect similar to TMS, and it’s being studied in Lindsay’s lab right now. Other scientists have found that they can deliver energy to the cortex with certain frequencies of laser light that penetrate the cranium and energize the underlying brain tissue. The thing those techniques and TMS all have in common is that they are pure-energy therapies, and they all target small regions of the brain in a safe, noninvasive manner. Collectively, they are one of the biggest—and least recognized—advances to ever happen in the field of neuroscience.
Manny Casanova is studying the convergence of TMS and neurofeed-back. By stimulating regions of the brain and using neurofeedback to optimize brain-wave patterns, he hopes to make bigger advances than TMS alone would give. One day we might see a triad of therapies—brain stimulation, cognitive therapy, and neurofeedback—all combined into one powerful package. When guided by next-generation brain imaging, the results may be beyond our wildest dreams.
Manny has agreed to write some thoughts on that, and a further elaboration of how he thinks TMS works in a piece on my website. I encourage you to look there for more information and commentary.
Most of this research is being done in labs at university medical centres, but there are also independent doctors experimenting in private clinics. Even though their treatments are not presently approved by the Food and Drug Administration and they are not yet validated by peer-reviewed studies, they may still be life-changing, as my story and the stories of others attest. It’s my opinion that TMS is inherently safer than medication. Even though medications are tested extensively before release to the public, we continue to find unexpected chemical interactions, sometimes decades later. As a pure-energy treatment, TMS doesn’t add chemicals to the body. Consequently, its potential for those kinds of side effects is near zero. TMS is finding increasingly broad acceptance in the treatment of depression, and its side effects there are usually described as markedly less than those from psychiatric medications. Still, as a prospective patient you have to make your own judgement about the skill and capability of the doctor offering TMS therapy, just as I did. Review boards oversee doctors who work at hospitals like Beth Israel; independent practitioners generally are not monitored very closely, so it’s important to check reputations.
When I talk to doctors or psychologists about TMS, I’m always asked about findings. It’s great to hear your story, they tell me, but what did the peer-reviewed journal accounts say?
In July 2011, Shirley, Lindsay, Alvaro, and others involved in the research published the results of the first TMS study in the European Journal of Neuroscience, under the heavy title “Brain Stimulation over Broca’s Area Differentially Modulates Naming Skills in Neurotypical Adults and Individuals with Asperger’s Syndrome.” The three-year lag between our participation in the TMS lab and publication of the results is typical in medical research.
Reading their paper feels funny, because it’s a very dry account of what was a very emotional and transformative time for me, and I’m sure for the other subjects. Our experiences in the hours and weeks after TMS are not mentioned at all; the published findings are limited to the results of the before and after testing in the lab, and an analysis of what they may mean.
While I can’t argue with the scientific validity of that approach, it does not come close to describing everything that went down. Here’s how the scientists summed it up:
Object naming was assessed before and after low-frequency rTMS of the left pars opercularis, left pars triangularis, right pars opercularis and right pars triangularis, and sham stimulation, as guided stereotaxically by each individual’s brain magnetic resonance imaging. In ASP participants, naming improved after rTMS of the left pars triangularis as compared with sham stimulation, whereas rTMS of the adjacent left opercularis lengthened naming latency. In healthy subjects, stimulation of parts of Broca’s area did not lead to significant changes in naming skills, consistent with published data. Overall, these findings support our hypothesis of abnormal language neural network dynamics in individuals with ASP.
But let me attempt to explain what all of that means, and what happened, in plain English. For the first TMS study, we were shown objects on a computer screen, and we had to name them as quickly as we could. It went something like this:
Bird
Stethoscope
Car
Protractor
Some of the objects were simple to name; others were not so easy. At the beginning of the study we were asked to name seventy-five objects, which were then broken down into five lists of fifteen. After each TMS session we were shown one of the lists and our responses were recorded and evaluated.
There were ten of us on the autism spectrum (all diagnosed with Asperger’s syndrome and most having above-average IQ) paired up with ten similar folks who weren’t autistic. Each of us did the tests alone, and for the most part, we did not meet or talk with one another. Interestingly, our performance on the naming test was not materially different at baseline. Differences appeared only after TMS, with one stimulation making us do better and another making us do worse. When stimulated in the left pars triangularis, those of us in the Asperger’s group outperformed the controls, who did not change. When our left pars opercularis was stimulated our performance got worse, and again the controls did not change. The stimulations on the right side of the brain didn’t affect the naming results at all, but they had a huge impact on several of us with respect to emotional insight.
It’s interesting that the m
ost profound effect of the study—that TMS stimulation of the right forebrain could unlock emotion in some of us—was not mentioned at all, because that result was not an original study objective. Neuroscience papers follow a fairly rigid form, where the experimenters describe a hypothesis to be tested, the test method, and the results. There’s little place for the unexpected surprise.
It’s funny . . . you could read that paper and have no idea it was based on the same TMS sessions I describe in this book. Or you might read that paper after reading this book and conclude that the original objectives of the study were rendered irrelevant. In that light, you might say this book describes the most important findings of those studies, at least from my perspective.
Lindsay published another TMS study entitled “Abnormal Modulation of Corticospinal Excitability in Adults with Asperger’s Syndrome” in the European Journal of Neuroscience in September 2012.
In that study, which ran concurrently with the other TMS studies I took part in, Lindsay stimulated the motor cortex and made our fingers jump as I described earlier in this book. Next she applied a burst of depressive TMS, which suppressed our fingers’ tendency to twitch when stimulated by single pulses as she’d done at the outset. Then Lindsay measured how long it took for the effect of that depressive burst to wear off.
Those results were fascinating because they showed a striking difference between the autistic and non-autistic participants. Most members of the latter group recovered finger neuron response within fifteen minutes. In contrast, the autistic people took two to three times as long to recover. As Alvaro later explained to me, that suggests that the behavioural and emotional effect of TMS may last long in autistic people—in fact long enough for TMS to change us in a lasting manner by reinforcing plastic changes, just as some of us experienced.
It is also meaningful from a safety point of view. If people “just try” TMS in unsupervised or uninformed experimentation, it might permanently modify behaviour in ways that could be undesirable.
By looking at whether a person’s response had recovered fifty minutes after the TMS burst, Lindsay was able to distinguish autistic and non-autistic individuals with an accuracy of 93 percent. That’s better than most diagnostic tests in use today, and it suggests that excess plasticity might be a distinguishing feature of the autistic brain.
The issues surrounding plasticity in autism are so important that the National Institutes of Health have funded Alvaro’s lab to study them through 2019.
If you’d like to know more about Alvaro’s theory, you can read his chapter “The Metamodal Organization of the Brain,” in Progress in Brain Research, vol. 134, edited by C. Casanova and M. Ptito (New York: Elsevier, 2001), available on the TMS lab website: http://tmslab.org/includes/alvaro_3.pdf.
One study Nick took part in was published in August 2014 in Frontiers in Human Neuroscience, with the daunting title of “Modulation of Corticospinal Excitability by Transcranial Magnetic Stimulation in Children and Adolescents with Autism Spectrum Disorder.”
The underconnectivity theory that Dr. Just and Dr. Minshew told me about was published as “Autism as a Neural Systems Disorder: A Theory of Frontal-Posterior Underconnectivity” in Neuroscience & Biobehavioral Reviews, February 6, 2012.
Dr. Just’s ideas on TMS were published as “Neurocognitive Brain Response to Transient Impairment of Wernicke’s Area” in the journal Cerebral Cortex, January 14, 2013.
Dr. Just’s study that identified autistic people on the basis of brain response was published as “Identifying Autism from Neural Representations of Social Interactions: Neurocognitive Markers of Autism” in PLoS One, December 2014.
There is an extensive index of Dr. Just’s other writings and papers on his website at psy.cmu.edu/people/just.html.
Dr. Minshew’s university profile page can be found at psychiatry.pitt.edu/node/7900.
What about the autism science work I’ve done? All the output of the Interagency Autism Coordinating Committee is available for free download from the government website iacc.hhs.gov. We produced annual reports each year in which we discussed advances and achievements and also identified questions for the future. Our meetings are also archived online. If you look at the autism sections of the National Institutes of Health and Centers for Disease Control websites you’ll find more material, including my talks before both groups during April, which is Autism Acceptance Month.
One of the activities that I’m involved with now is the development of ICF Core Sets for Autism for the World Health Organization. Our group has published several papers, including:
“Classification of Functioning and Impairment: The Development of ICF Core Sets for Autism Spectrum Disorder,” Autism Research 7, no. 1 (2014): 167–72.
“Ability and Disability in Autism Spectrum Disorder: A Systematic Literature Review Employing the International Classification of Functioning, Disability and Health—Children and Youth Version,” Autism Research, in press; published online March 2015.
A Google search will turn up videos and texts of my talks at IMFAR, the International Meeting for Autism Research. Every year, I speak at the conference to provide an autistic person’s perspective. I can’t imagine doing something like that before TMS.
The 2015 IMFAR conference took place in Salt Lake City, and I was one of the keynote panelists. In an impromptu talk, I spoke about autism, disability, and how much science and scientists had meant to my life. Difference may look like a gift, but it can be very painful to live, and science as I describe it in this book has helped me more than I can ever say. I believe my story of the personal impact of autism research came as a surprise to some of the audience, who gave me a standing ovation—the only one in IMFAR history, I was told. And, similar to the night I spoke of earlier in this book, when I addressed the doctors of my local medical society, there was not a dry eye in the house. That same thing happened seven years later at IMFAR. Connecting to the souls of others through their emotions is a powerful thing.
As this book goes to press, the International Society for Autism Research (INSAR), which hosts the IMFAR conference, is preparing to put that talk online for public viewing and it will be linked from my website.
Acknowledgments
IN THIS BOOK, I’ve done my best to translate some very complex science into something the average person can understand. I could never have done that without the help of the people listed in this section. When you read this list of credits, consider how all the people are tied together with multiple threads of connectivity, just like the strands in our brains. . . .
The first person I would like to thank is former Elms College president James H. Mullen, Jr. Dr. Mullen is now president of Allegheny College and chairman of the American Council on Education. He got this story started by inviting me to the Elms, where Dr. Kathryn James welcomed me into their autism programme. If not for them, I’d never have met Lindsay. . . .
I will always be indebted to Dr. Alvaro Pascual-Leone, his postdocs Lindsay Oberman, Ilaria Minio-Paluello, Shirley Fecteau, and all the other staff of the Berenson-Allen Center for Noninvasive Brain Stimulation at Boston’s Beth Israel Deaconess Medical Center. They are all bright, compassionate, and driven researchers. Alvaro is still very active in TMS research, and his clinic has developed a significant therapeutic practice in Boston. He remains one of the world’s leading TMS researchers.
In addition to heading the TMS lab, Alvaro is a professor in Neurology and the associate dean for clinical and translational research at Harvard Medical School.
Lindsay’s work earned her a lab of her own. Today she is director of the Neuroplasticity and Autism Spectrum Disorder Program at Bradley Hospital, the scientific director of the clinical TMS programme at Rhode Island Hospital, and an assistant professor in the Department of Psychiatry at the Warren Alpert Medical School of Brown University in Providence, Rhode Island. She works with TMS and autism and collaborates with Alvaro and others at Beth Israel, Boston Children’s, and Harvard.
Shi
rley moved back to Canada after her postdoc at Harvard. She currently holds a Canada Research Chair in Human Cognition, Decision-making, and Brain Plasticity at Laval University in Quebec. Much of her work today is focused on the use of TMS and other noninvasive brain stimulation techniques to help people with addictions.
Ilaria returned to Rome after her postdoc, where she joined the faculty of Sapienza University. She continues to be interested in TMS and autism, and I was pleased to visit her in Rome with my wife, Maripat, in the fall of 2012.
After getting involved with those Harvard scientists, I relied on my radiologist friend David Rifken, MD, to explain MRI and other brain imaging and the strange dots on my brain scans, and to answer a million other bizarre questions. Dave is a senior radiologist at Cooley Dickinson Hospital of Northampton, a Massachusetts General Hospital affiliate. Thanks again for being my friend and reading my brain scans (and all the others over the years!).
Thanks to Kimberley Hollingsworth Taylor, Michael, Nick, and family for accompanying me on the TMS journey, and for contributing memories to this account.
I’d also like to thank Dr. Nancy Minshew and Dr. Marcel Just at the University of Pittsburgh Autism Center and Carnegie Mellon University. The work they are doing is truly mind expanding and I cannot thank you enough for inviting my wife and me to be part of it.
Dr. Manny Casanova and his wife, Dr. Emily Casanova, are important people in the world of TMS and (at the time of my TMS experiences) at the University of Louisville. Both played a big role in the background by helping me understand TMS and the workings of the mind, and I greatly appreciate their contributions. Manny now holds the SmartState Endowed Chair in Translational Neurotherapeutics. He’s a professor of biomedical sciences at the University of South Carolina School of Medicine Greenville.
He is also the closest thing I know to a Renaissance man of neuroscience. While I describe researchers like Lindsay as users of TMS technology, Manny is a guy who does not hesitate to roll up his sleeves and go into the guts of the machine to get what he wants from it. As I’ve gotten to know him these past six years, I’ve often wished we lived closer together. He agreed, saying, “We would have enjoyed spending some time together building our own TMS machine with a bank of super capacitors, trying not to shock ourselves, and examining the resultant brain-wave changes as if they were on an oscilloscope.”
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