Wednesday, May 30, 2012

A new TMS study, this one involving teenagers

Over the past few years many of you have asked about the transcranial magnetic stimulation (TMS) research that I’ve been involved with.  Some of you have even asked about enrolling teenagers in behavioral experiments involving TMS.  Today, researchers at Boston Children’s Hospital are conducting a TMS study that may provide short-term improvement in visuomotor processing, social skills, and pragmatic language skills

They are seeking male volunteers, 8-15 years of age, with good verbal skills, an autism spectrum diagnosis and IQ over 80. 

Participation in the study involves 4 visits. Visit 1 will be a screening visit. Visits 2, 3, and 4 will have subjects doing behavioral tasks in conjunction with measures of brain activity by TMS, which is a noninvasive method that measures and influences brain activity. In TMS, a strong magnet is pulsed next to the patient's head, and small electrical currents are induced in the patient's brain. TMS is painless and well-tolerated, even by young children.

There will be no cost to participate in the research and participants will be compensated with a small token of appreciation.   If the researchers or participants see a short-term improvement, the participants will be offered the opportunity to receive TMS as a therapy through the department of Neurology at Children's Hospital.

If you are interested or for more information about the study please contact Dr. Lindsay Oberman at 617-667-5247.

Monday, May 28, 2012

More thoughts on ultrasound, questions about risk, and autism

Last week's essay on ultrasound generated a great deal of commentary.  Some of the questions raised by readers were beyond my expertise, so I turned to Dr. Manny Casanova from the University of Louisville. He and his colleague Emily williams have spent a good bit of time studying ultrasound and its effects on cells.  They were kind enough to write the following essay and will respond to your questions here on the blog:

One problem of which we've become poignantly aware is that ultrasound, especially since the early 1990s, has been deregulated and is nowadays used to excess. Ultimately we would like to see more research into its safety, as well as tighter regulations on its use so that its risks don't outweigh the benefits. We'd also like to clarify that we're not proposing that ultrasound is "the" cause of autism. What we're proposing instead is that ultrasound may be one of many risk factors for those who have a selective vulnerability.

Many people when they first hear about ultrasound as a possible risk factor in the development of autism think it sounds like pseudoscience. Who can blame them? We've been subjected to many different hypotheses about what may be causing autism.  It seems like everyone is ultimately seeking the "holy grail" of causation. So we're all skeptical when we hear something new, especially something which seems to contradict our understanding of how we view the world-- or in this case, how we perceive the safety of ultrasound. After all, ultrasound is just a picture, right?

That's what we in our laboratory used to think until we began studying what mediates the effects of ultrasound. In the following paragraphs we hope to offer a simple explanation on the rather complex effect of ultrasound on the living cell.

Ultrasound refers to sound that has a frequency above that which can be detected by the human ear. Sound itself is the force of pressure through a solid, liquid, or gas; it causes the movement of those particles. In the case of prenatal ultrasound, the ultrasound transducer emits sonic waves into the abdomen, the sound enters the body including that of the developing embryo/fetus, bounces off the tissue, reflecting back, and that echo is measured by the transducer to form a representative visual image.
Ultrasound is currently used in a variety of ways in medicine and research, and some of these include:

1) the production of lesions in neurosurgery, similar to the use of laser;
2) transcranial (across the skull) stimulation of brain activity, similar to transcranial magnetic stimulation (TMS) or the use of electrodes;
3) vasodilation, or the widening of blood vessels, which helps in both visualization of the vasculature as well as the delivery of important medications to tissue;
4) transdermal (across the skin) delivery of medications which would normally be unable to cross the skin barrier;
5) wound healing, such as on certain bone fractures and ulcers;
6) the purification of foods via its oxidative potential;
7) the purification of metals also due to its oxidative capacity;
8) transmembrane delivery of nonviral genes into target cells (mainly used in research).

These are just a few examples of how science and medicine apply ultrasound. As you can probably guess by now, given its capacity at different levels of intensity to promote cell growth, cell destruction, alter membrane fluidity (e.g., poke temporary holes in cell membranes), and alter a cell's activity such as causing a neuron to fire, ultrasound has an incredible range of effects. It turns out it's not just a picture after all.

The physical effects of ultrasound include both its pressure on the water within and surrounding a given cell, and through the creation, oscillation (spinning), and implosion of bubbles in that same liquid. The latter is referred to as "cavitation" or the creation of a gaseous cavity within the liquid. Cavitation and noncavitational effects together can poke transient holes in cells, activate certain molecular pathways within those cells, cause temperature increases when the bubble violently implodes, promote the creation of free radicals (oxidation) when that gas escapes into the surrounding medium which can subsequently damage or even kill a cell, can cause general disarray within the cell, and at certain intensities may even promote mutations of DNA.

Most of the deadly effects on cells are generally not seen at diagnostic intensities levels. However, there is still the potential that ultrasound is altering how these cells develop and behave; i.e., it doesn't kill them, it changes them. In the case of autism, we frequently find abnormalities in neuron number and growth patterns in the brain. Given that ultrasound has the capacity to promote cellular growth, as well as its overuse in obstetrics and the apparent rising numbers of autism diagnoses, this is a prime area for scientific study. Needless to say, this is a gross simplification of our hypothesis, so for anyone interested in more detailed accounts, please contact us for further materials and we'd be glad to supply them (see

Back in the 1960s, '70s, and '80s, the scientific community was very cautious about using prenatal ultrasound. As much as science knew in the day, they expressed due concern and performed a good number of safety studies. From these studies, they decided that ultrasound was ultimately safe to use in obstetrics. However, science is ever-changing and continually learning more about development. Back in the 1970s, the height of concern over ultrasound was whether it promoted spontaneous abortion or reduced postnatal survival rates, whether it promoted macroscopic growth abnormalities like differences in birth weight and overall size, and whether it caused genetic mutations. Nowadays, we know much more about the molecular biology of the cell, and more as to how development can be affected in microscopic ways which can have very big effects on behavior. Let's face it: when a postmortem examination is performed on an autistic person's brain, usually one of the most striking things about it from a macroscopic level is that there isn't anything unusual. So the differences in an autistic person's brain are indeed very subtle; they need to be teased out with various technologies, with a knowledge of the complexity of anatomical, cellular, and molecular biology, and a nuanced understanding of early development. Our science has continued to mature, but unfortunately the early safety studies on ultrasound were never updated to include this new understanding.

It's time we go back and reassess, with new knowledge, techniques, and technology, whether or not ultrasound is truly as safe as we assume it is. It's also time that the regulations on ultrasound be refined so that we can be doubly sure we're not putting our unborn infants at risk, be it for autism or some other condition.

Again, what we want to stress is that we're not advocating the disuse of ultrasound. It's an extremely vital and useful tool in medicine. But we are advocating that it be used more wisely. For those who are pregnant, we recommend that ultrasound should not be performed during the first trimester unless it is an at-risk pregnancy, and especially not within the first 8 weeks of gestation. The first 8 weeks is the period when the greatest intensity of growth occurs-- and therefore when the greatest damage can be done. Be cautious of early and unnecessary ultrasounds. In addition, don't use fetal heart rate monitors for private use because these are handheld ultrasounds.

                                                                                                            Manuel F. Casanova, M.D.
                                                                                                            Emily L. Williams

Sunday, May 20, 2012

The best thing about IMFAR 2012

Above:  Descending into Toronto for IMFAR 2012

In my opinion, the best thing about this year’s IMFAR autism science conference was the degree to which the community has become involved.  Four years ago there was hardly a spectrumite to be seen there, geek scientists excepted.   This year we were everywhere.

Just a few years ago, autistic bloggers and writers gazed in from the outside and wondered what was discussed in the IMFAR meetings, and what INSAR (the organization who puts on the conference) really did.  Scientists wondered about the wisdom of admitting the public to what are often highly technical presentations and discussions.  In the absence of openness, conspiracy theory and contempt ran rampant.

Things changed recently, thanks to the INSAR board and the folks on the Community committee.   We have seen more community involvement each of the past three years as we’ve added programming to serve the autism community as well as the researchers.

Autistic artists and entertainers have delighted us with their performances, and their work.  Not only has that made an enjoyable addition to the conference, it’s provided an important humanizing element, especially to younger researchers who may be new to the field.  The arts build community, all round.

I am especially happy to see bloggers and writers from our community of all points of view.  People who might never have spoken to one another now share meals together and become friends, thanks to meetings that take place here.

In their writing and other communications, many new ideas emerge, all with a common theme:  We need to direct our best scientific efforts to alleviate disability, improve quality of life, and create the best possible opportunities for our population.

Some writers are critical while others are laudatory.  I’m pleased to see it all.

Our pre-conference for the community was standing room only, as was the stakeholder luncheon and Q&A.  Attendance at those events has gone up every year.

INSAR and its sponsors have continued to offer scholarships, admission fee waivers, and travel grants to encourage community members to attend.  That’s a great thing, and it’s made possible by the conservative governance of the INSAR organization that generated the financial surplus to pay for benefits like these.

It may surprise you to read that some of the community openness at IMFAR was inspired by the example set by three US government groups:  the IACC, whose meetings are fully open, and NIH and CDC who make more and more of their discussions public as well.  Not only are those events open to the public physically, many are webcast and archived online, something INSAR is doing now as well.

I’m proud to have served on committees for INSAR and the government groups above.  I’ve learned more than I can tell you here and I’m most pleased at the way others have joined me to explore and share what we find with the wider world.

I’ll look forward to an even bigger community presence, next year in Spain.

John Elder Robison
Writing from IMFAR 2012
Toronto, Ontario, Canada

Ultrasound and Autism - a possible link?

Could the increased use of ultrasound during pregnancy be implicated in autism?

That’s a question I discussed yesterday with University of Louisville researcher Manny Casanova.

A few stories have raised this question in recent years, but none have elaborated on the possible process, as he did for me yesterday.   Here’s what he said:

Ultrasonic energy is known to affect cellular membranes and cell growth.  In fact, ultrasound is used as a therapy to accelerate bone growth following certain traumatic injuries.  In stem cell research, ultrasound has been shown to accelerate development of cells.  Knowing that stems cells are developing into neurons early in the fetal development, it’s quite possible that addition of ultrasound energy might shift that balance.  

Those were questions that I’d not heard before, when it came to ultrasound.  

When I got back to my hotel room, I discovered a number of scientific papers supporting each of his points, but none really put the ideas together in the context of autism. I found that fascinating, and somewhat disturbing.

What I had heard were these questions:

Heating and vibration might also affect a fetus.  Ultrasound will heat water, and the operation of ultrasonic cleaning systems is familiar to many of us.  Either of those processes might affect fetal development adversely too.

Like many people, I took for granted the idea that whomever approved ultrasound for clinical use made sure the power levels were low enough that the developing baby wasn’t cooked by its operation, or disintegrated like dirt on jewelry in the cleaning tank.

Not so fast, Manny cautioned me . . .

When ultrasound was developed, it was first used late in pregnancy, when all these risk factors are minimized.  It was also used by trained staff and the machines, being new, were likely well calibrated.  Most moms did not get ultrasound at all, and those who did typically received one or two.

The situation today is totally different.  Many doctors do ultrasound much earlier in an effort to spot other problems, like Down’s syndrome.  It’s common for moms to get three, four, or more ultrasounds done.  Finally and most disturbing, many states have “ultrasound boutiques” in malls where moms can get ultrasounds as art; for the new baby scrapbook. 

When the goal is a pretty picture, power levels may be turned up unwittingly.  Safety is assumed by operators who are not always medical people, and who may have little knowledge of the underlying processes.

So we have the confluence of more ultrasounds, done earlier, and possibly with poorly calibrated equipment and inadequately trained people.  I always associated ultrasound with professional staff in a hospital, but to hear Manny, it can be a lot more like a tattoo parlor experience. 

In fact, several states have no regulation at all over the use of ultrasound imaging equipment.  Anyone can buy it and make pretty pictures of your innards, perhaps cooking or altering you in the process.  In the hands of the wrong operator, it's like taking your developing baby and stepping into the microwave oven.  That's something none of you would do, yet the mall ultrasound parlors reportedly do a brisk business.  

Ultrasound Zeke has a wall full of beautiful fetal art, but it may have come at a high cost.  

I hesitate to say that’s a frightening prospect, but it’s certainly one I’d study more carefully.  If I were pregnant today, I’d be thinking hard if my doctor advised ultrasound early on, and I’d be reluctant to do it very often.

An energy process that makes broken femurs heal faster is not the sort of thing you want to fire into the brain of a developing fetus.  His brain is developing fast enough, all on its own.  We don’t need to amp up the rate of neuron development.

Remember . . . outside of evolution and the natural appearance of autistic people throughout history, we may never find a single pathway into autism.  There may be a hundred other causative factors.  I'm not suggesting this is THE CAUSE and neither is Manny.  This may or may not be involved . . . I simply suggest it's worth exploring further.

This is the second interesting question from IMFAR 2012.  What are your thoughts?

John Elder Robison
Writing from IMFAR 2012
Toronto, Ontario, Canada

Saturday, May 19, 2012

Autism and Sexuality - IMFAR 2012

Now that IMFAR has wound down and I have a moment to gather my thoughts I’d like to describe a few of the less-noticed findings from this year’s conference.

One concerned autism and sexuality.  I found that quite interesting because it’s a topic I had not seen at IMFAR before, and it raised interesting and probably controversial new questions.  The key finding:  Several studies reported a marked increase in the rate of LGBT identity as compared to the NT population.

In some studies identity was classified by self-report, while other studies scored identity based on responses to a standardized questionnaire.  Interestingly, the results seemed similar between the two methods.

When I talked to one of the researchers, I was struck by her description of what she called “flexibility.”  Others might call that bisexuality but she seemed to see it as different from bisexuality in the NT community.  She described the one as a choice while the other was more “no preference.”  She further suggested that our diminished theory of mind might leave us both uncertain and vulnerable to sexual exploitation. 

I don’t know if theory of mind is the answer but the “exploitation” certainly hit home for me, as I recalled all the female spectrumites who have told me awful stories from their own lives.  At the same time, I consider the males, who mostly talk of dating failure.

When I have written about that issue in the past, I suggested that females are the principal choosers in our society, so a male who acts strange (due to autism or anything else) does not get chosen and has a zero result.  But a female whose choosing instinct is weakened by autism runs the risk of choosing wrong which can lead to a very bad outcome.

I know it’s not totally cut and dried, and both parties have to pick each other, but the evidence I’ve seen on college campuses where I’ve spoken certainly corroborates that.  Yet none of the observations from my own life have suggested that LGBT identity is more common among the AS population, nor have I ever sensed we are “flexible” in that regard.

Of course, that may simply be because I am not very perceptive in that area, either because I am autistic or for some other reason.  The data presented described some hundreds of people; enough to have a meaningful sample and the consistency of that particular finding between the studies leads me to think it’s probably valid.  But why?

Why do we autistics have such a different distribution of expressed sexual preferences?  That is the question researchers asked, and several possible answers were posited:
1 – We might have more “masculinized brains,” whatever that means.  I quote those words from one of the summaries.  I know Simon Baron Cohen has advanced the idea before but I’d not heard it in the context of sexual identity.
2 – Since our ability to read other people are limited, we may be freer to think independently.  So freed we might make choices that NTs would be inhibited from making.
3- Our sexual identify might be inherently more flexible for as-yet unknown reasons related to our autistic differences.
4- Our penchant for directness may cause us to be more truthful in surveys of this type; in that case we may report truer percentages while the NT group had many respondents who hid their true feelings.  The difference may not be great at all; we just answer differently.

While the reasons remain an open question, our willingness to embrace LGBT choices seems undisputed.  All the studies agreed on that.  I’ll be very curious to see where this leads.

When I look at my own family, my brother has always been gay, and I have always been straight.  I am not aware of any “lifestyle choice” either of us made to be the way we are.  I’m not sure if or why being autistic would influence that; it’s a curious finding for sure. 

One final point from this research:  A significant fraction of the AS population chooses asexuality, a choice that’s not really found in the NT population.  I’ve long known AS people who felt that way but until now I have never wondered why, or what it may mean.

Here are a few of the questions I had, when it comes to these studies:

If we believe there really are more LGBT autistics - What sort of changes might be needed in our social skills training to optimize or be more inclusive for a LGBT audience? 

If indeed we are more vulnerable to sexual exploitation how might we protect young people from that outcome?  To answer, we’d have to know how it comes about.

Growing up LGBT presents any kid with additional complications. When we combine that with the knowledge that autistic kids are already very much at-risk for bullying, it paints a disturbing picture.  What should or could we do to help?

If we believe autistics are simply more truthful about disclosing their identifies in surveys, does that directness subject us to ridicule and harassment, and if so, what could we do about it?

It’s an interesting question and I’ll be curious to see what your thoughts are . . .

John Elder Robison
Writing from IMFAR 2012
Toronto, Ontario, Canada

Thursday, May 10, 2012

News from China

Xi’an, China – Archaeologists in this Chinese city have reportedly found what may be the earliest terra-cotta figures of domestic dogs.  The dog figurines, each about ten inches high, are believed to represent Imperial War Pugs.  They were discovered by accident during excavations at an 11th century BCE Zhou Dynasty site last week.

According to Chinese legend, War Pugs were first bred by Emperor Ku, who was said to bestow the dogs on his most favored generals.  The dogs were not meant to be warlike; indeed their serenity was said to exert a calming influence on his generals, who were otherwise known for their ruthless efficiency in battle.

The image of a War Pug standing by his General’s side, gazing impassively over a field of fallen soldiers, is iconic in Chinese literature of the period. 

Though ordinary Pug dogs were exported from China legally, the purebred War Pugs remained a closely guarded secret until a few specimens were captured by British soldiers during the looting of the Summer Palace in Beijing, in 1860.    Even today, few dog fanciers know the history of this remarkable breed.

Archaeologists plan to return to the site where the figurines were discovered next month in hopes of making additional discoveries.