She is Not a Camel...but She Does Have Epilepsy

Maya Shenwar, executive director
of Truthout, with EEG leads
 taped to her head. 

The two most salient things about epilepsy are 1) that it sucks, and 2) that it is awesome. If you're living with seizures, of course, their awesomeness almost certainly does not make up for their suckiness. Even if you have out-of-body experiences during your seizures or hear old music, smell burning toast, or have orgasms while seizing, you still probably would rather do without them. And yet, I've met a lot of people who have a great deal of respect, if not awe, for their seizures. As they should. Epilepsy may be the enemy, as one philosophical epileptic acquaintance put it, but it is an awesome and mysterious enemy.

Not all epileptics are as enamored of their their seizures as Fyodor Dostoevsky's protagonist Prince Myshkin in The Idiot. As writer Maya Shenwar tells us in her excellent piece today on the political website Truthout, Myshkin flashes, during the auras at the outset of his seizures, to "the highest form of existence" and "the acme of harmony and beauty." Shenwar, who has had seizures for nearly a decade, has less transcendent fits than Myshkin did, but still, she is making the most of them. And she has clearly learned a lot from her epilepsy. She is courageous, funny and smart and now as fully out as an epileptic can get, a real accomplishment given the stigma and discrimination that still hounds people with this particular neurologic disorder. Read her excellent piece, and learn many things, including  why she called the essay "I am Not a Camel...But I do Have Epilepsy." 

Cyborgian Reflections

IHT illustration by Matthew Richardson

Sunday's International Herald Tribune contains a lively discussion of how our growing dependency on information technology may be changing us.  In Are We Becoming Cyborgs New York Times editor Serge Schmemann moderates three strong interlocutors: 

Susan Greenfield, professor of synaptic pharmacology at Oxford, looks at how new technology changes users' brains. She argues here that until now technologies have always "been a means to an end," whereas "current technologies have been converted from being means to being ends in themselves." She attribute some part of the explosion of new attention disorders to raising kids in an internet environment. Brains have an evolutionary mandate to adapt to their environments, she says. "If you take a young one and put it in an environment that is fast-paced, loud and sensory-laden, then it will adapt to that... My concern," Greenfield says, "is that we are heading toward a short attention span and a premium on sensationalism rather than on abstract thought and deeper reflection."

Greenfield quotes Eric Schmidt, the chairman of Google: "I still believe that sitting down and reading a book is the best way to really learn something. And I worry that we’re losing that." 

Maria Popova, the curator behind the great Brain Pickings website, is an  M.I.T. Futures of Entertainment Fellow and writes for Wired agrees that the way the web is used may be leading to diminishing attention spans and a "conflation of information and insight... The Web by and large is really well designed to help people find more of what they already know they’re looking for, and really poorly designed to help us discover that which we don’t yet know will interest us and hopefully even change the way we understand the world."

She is less pessimistic than Greenfiled about the future of web-influenced brains, though. The key, she says, is not the technology itself, but how it is employed and who determines that. Her own site, Brain Pickings, is a great example of an antidote. She also mentions apps like Instapaper and Pocket  and long-form ventures like The Atavist and Byliner as good influences preserving and promoting long-form knowledge- and focus-respecting media. 

Evengy Morozov, author of The Net Delusion: The Dark Side of Internet Freedom, fears that the internet is encouraging slactivism not activism, that it will, in moderator Schmemann's words, cultivate "people who think that clicking on a Facebook petition, for example, counts as a political act."

But "anyone who wears glasses, in one sense or another, is a cyborg," says Morozov. "And anyone who relies on technology in daily life to extend their human capacity is a cyborg as well. So I don’t think that there is anything to be feared from the very category of cyborg. We have always been cyborgs and always will be."

"The question is, what are some of the areas of our life and of our existence that should not be technologically mediated?" 

When Learning, Mattering Matters

LearningRx , a brain-training center
in Upper Montclair, N.J.,

A thought provoking story about brain training ran in the Times on October 31. Author Dan Hurley looks at both software approaches and storefront brain-training centers. It's remarkable how little has changed in the field in the three-plus years since I wrote a story about it for San Francisco Magazine in 2009. LearningRX seems to have an economic model for brain training centers that's working; that's one difference. The San Francisco-based vibrantBrain's, which I wrote about, didn't pull that off and has been homeless for over a year now. Still, the studies suggesting that this kind of training works better than other real-life activities that engage your mind (and thus your brain) are still sketchy. Truth is, as UCSF neuroscientist Alison Doupe's research suggests, brains become plastic again when they are exposed to things that matter to them:

To quote myself from the March 2009 San Francisco Magazine story, Brains of Steel:

[UCSF MD PhD neuroscientist Alison] Doupe describes what happens to the brains of finches that are first taught to sing by tape recorders. "Their songs are OK, and their development seems pretty normal on the surface," says Doupe. "But when you take one of those recorder-trained birds and stick another bird in there singing a live song, the trained bird is highly stimulated and attentive, and his critical period can actually reopen." In other words, when the bird's attention is grabbed by something that matters--in this case another living bird--he's suddenly able to learn new things.

Put another way, if students care about what they are being taught, and/or whom they are learning it from, they will be much more likely to get it. And keep it.

Fusiform Stimulation a Turn-Off for Facial Recognition

 Familiar but unrecognizable: Hillary
Clinton and Barack Obama
morphed into one

Epilepsy patients and their doctors have made huge contributions to basic brain science for thousands of years. Hippocrates' seizing patients inspired him to write the first book on neurology, and arguably the first real medical text, in which he insisted that seizures were caused not by spirits, curses, or gods, but by brain dysfunction. Drop the superstition and stick to the facts: that was a radical postion 2400 years ago.

Since then, major studies mapping the functional geography of the human brain, illuminating the mechanisms of memory, exploring the different roles of the right and left hemispheres, and investigating the neuronal mechanisms underlying language were all made possible by epilepsy patients.

With the growing reliance on intracranial studies for screening epilepsy surgery candidates, those contributions are mounting faster than ever. While patients are wired with electrodes--implanted under their skulls so they can read clearly from, and send signals directly to, the brain--for a week or so, so that their doctors can pinpoint the origin of their seizures, there is a lot of basic science that can go on in their heads. If, that is, the patients grant permission and cooperation. Which they often do. With gusto.

A few months ago I wrote about Edward Chang's amazing language experiments at UCSF. Another great example, this one focusing on brain areas devoted to facial recognition, was published in the journal Neuroscience on October 24. (The story was also covered in a good piece by the San Francisco Chronicle's Erin Allday on October 23.)

The study was authored by the brilliant Stanford neurologist and neuroscientist Josef Parvizi, whom I've also written about before. It was serendipitous that the electrodes implanted into his patient's brain were very close to a deeply-buried structure called the fusiform gyrus, long known to play a key role in human facial recognition. When Parvizi administered a brief electrical current to those electrodes, the patient, Ron Blackwell, saw Parvizi's face metamorphose, as if on a bad acid trip. Blackwell's consciousness was not disturbed in any other way, but Parvizi became completely unrecognizable. When Parvizi turned the current off, Blackwell saw his doctor's face return to normal.

It was a temporarily induced case of prosopagnosia, or face blindness, a rare disorder shared by the painter Chuck Close, the primatologist Jane Goodall, and neuroscientist Oliver Sacks. Prosopagnosics often cannot recognize close friends and are sometimes even unable to identify their own faces in the mirror.

Certain kinds of seizures can cause similar facial dysmorphia, possibly by stimulating the fusiform gyrus in the same way that Parvizi's electrical stimulation did.  Australian researcher Jim Chambliss has studied thousands of paintings by epilepsy patients and has found that morphing faces are a very common theme. Perceived facial morphing during seizures may be a more frequent symptom than is generally recognized, says Chambliss.  Some epilepsy patients may be reluctant to report the symptom to their doctors because they may fear the stigma of psychosis.

Parvizi's new research suggests no treatment for prosopagnosia, but it does suggest new avenues of research, he says. As for his patient and collaborator, Ron Blackwell: he never got his surgery. It turned out that his seizures were originating from a point in his brain adjacent to the key area responsible for peripheral vision. Removing the epileptogenic tissue might have damaged Blackwell's vision, Parvizi concluded, and that was an unacceptable risk. Strangely, and wonderfully, though, in the year since Parvizi zapped his fusiform gyrus, Blackwell's seizures seem to be much better controlled by his medication alone. There's no reason to think there's a causal connection, but Blackwell is appreciative to have participated in the study anyway. "I wouldn't take back the experience for anything," he told Allday.

That's typical of epilepsy patients who've donated their brain-time to science. So much of what we know about brains, we owe to their curiosity and generous contributions.

Smart Implants Intercept Seizures

Image by Henrik Jonsson

A good piece by Aliyah Baruchin in the July SciAm looks at how a new generation of implantable devices may help people with epilepsy squelch seizures before they get out of control. For more than a decade doctors have been implanting Vagus Nerve Stimulators (VNS) into patients who are unresponsive to anti-seizure meds. VNS either sends a periodic stimulating pulse through the vagus nerve or allows patients, when they sense a seizure coming on, to shock themselves with a magnet passed over the implanted device. The electrical stimulation defuses the mounting synchronized brain activity that would, if allowed to mount, culminate in a seizure. VNS works pretty well for a small fraction of patients whose seizures aren't responsive to anti seizure medications.

The avant-garde in implants promises to be much more subtle and targeted. The devices will read signals from the brain and "write" back to it with appropriately limited intervention. By tracking electrical activity (or temperature) in the part of the brain causing the seizures, these devices can tell when seizure activity is imminent and then can have one of three responses to intercept the seizure before it blossoms into disabling spasms or impaired consciousness.

One of these devices, under development at the University of Kansas Medical Center, address a coming seizure by cooling the area of the brain where they are kindling. Others do so by sending an electrical pulse to the offending area as a seizure mounts. A third type delivers anti-seizure medication locally and in limited doses that do not effect the entire brain.

The big advantage of all three delivery systems is that they tailor treatment to actual brain activity rather than constantly treating a brain that may only occasionally be seizure prone.

This will be a big deal for people with epilepsy. But the practice doctors get with implanted read/write devices will change the course of neuroscience and, sooner or later, it will effect everyone. The real-time data that will be collected by these implanted devices will give scientists a huge new window into all kinds of brain activity. And once installing electrodes in brains becomes routine, applications will go well beyond treating brain disorders or enabling prosthetic devices. The Brain Machine Interface is coming; fasten your seat belts.

Nocibo Effect

NYT Illustration by Scott Balmer

"Beware the Nocibo Effect," a short piece in today's Sunday Review Section of the New York Times, points again to one of the most mysterious areas of modern medicine; the effect of expectation on outcome. Usually examined through the well documented placebo effect, this piece instead examines the "nocibo effect," or the harm done by the expectation that a medication will have side bad effects.

The authors, Paul Enck, a professor psychology at the University of Boblingen and Winfried Hauser, an associate professor of psychosomatic medicine at the University of Munich, reviewed 31 studies of the nocibo effect. Their review concludes that nocibo has a potent effect on patient experience and treatment outcome. For instance, eleven percent of patients in a drug trial for a fibromyalsia drug dropped out of the study because they experienced strong dizziness and/or nausea after being warned that the sugar pills they were taking may cause those symptoms.
In another study of an anti-depressant medication, one desperate patient swallowed 26 harmless placebo tablets in an attempt to kill himself. The patient's blood pressure "dropped perilously low," the researchers report.
The point of the piece is that doctors should be mindful when describing the potential side effects of medications they are prescribing. Fair enough. But more interesting by far is the tacit acknowledgement that there is a potent and hugely influential psycho-biological mechanism at play here that we really don't understand at all.

Inflammation and Epilepsy

Inflammation and epilepsy; is there a
causal connection? Image NYT

The New York Times today describes a 400-patient, Phase 2 trial of a new medication that approaches epilepsy from a new angle: below. Currently, the drugs used to treat epilepsy patients do so from the top down, by attempting to suppress seizures. But just as sneezing is only a symptom of the flu, not the flu itself, seizing is just the most salient and acute symptom of epilepsy, not the disease itself.

Current drugs are developed and tested on animals who don't have epilepsy at all, according to Dieter Schmidt, head of the Epilepsy Research Group in Berlin. Researchers induce seizures in the animals and then try to suppress them. So these drugs don't even aim to cure epilepsy, just to quell seizures.

The study, led by Dr. Jacqueline French, a neurologist at NYU's Comprehensive Epilepsy Center, is studying a new anti-inflammatory drug that may address, she says, the causes of the epilepsy itself. If so, that would represent a major advance in treating the disorder, which affects about 2.7 million people in the US and 50 million people worldwide. 

In particular, French hopes the drug will help those epilepsy patients whose seizures are not suppressed by any current medications, the so-called "intractable" or treatment-resistant cases. That group makes up about one third of all epilepsy patients. 

The experimental medication, called VX-756 exploits recent insights into the connection between inflammation in the brain and epilepsy. For more on this, see my story about the role of glial cells in epilepsy: The Glia Club, Epilepsy USA, 2010 #3.  The excellent New York Times story, by Alastair Gee, is here. More on the inflammation connection soon.