Seizure Dogs: An Alternate Explanation

I’ve been wanting to write a story about seizure dogs for years, ever since I heard about their ability to sense the onset of epileptic seizures before their masters have any idea that they are going to seize. There’s so little documented material, though, that I kept putting off the story. So I was surprised and fascinated (panicked, actually) to see a piece about dog intelligence in the Sunday NYT that opens with tell of Jet, a seizure dog in New Jersey that, among other amazing talents, puts its body in a position on the floor to break the seizure fall of his master before she even knows she’s going to have one.

The Times piece, by Sarah Kershaw, acknowledges that there is still “mystery” about how dogs can detect seizures before they occur, but it fails to look skeptically at whether the dogs are really able to predict--in a way that no neurologists can—when a seizure is going to occur.

The piece goes on, credulously, I think, to cite “Hungarian researchers [who] reported in a study last year that a guide dog for a blind and epileptic person became anxious before its master suffered a seizure and was taught to bark and lick the owner’s face and upper arm when it detected an onset, three to five minutes before the seizure.” The dog not only “knows more than we thought,” he knows more than any neurologist I’ve ever met or heard of and is more sensitive to the subtle electrical happening in the brain before a seizure than any fMRI or EEG. As explanation for this amazing feat of prediction, Kenshaw suggests, maybe that the dog may be “picking up on behavioral changes or smelling something awry.”

I hate to throw a wet, skeptical blanket on dog lovers, romantics, and telepathy fans, but there might be another, and really fascinating and important, explanation for how the Hungarian dog knows that seizures are coming. I think the dog can predict seizures because its predictions bring them on.

I know how crazy that sounds. But consider this fact, which blew my mind when I read it earlier this year: tens of thousands, possibly hundreds of thousands, of Americans who are diagnosed with uncontrolled epilepsy do not have epilepsy at all. They have real seizures all right, and those seizures look like epileptic seizures, but they aren’t caused by uncontrolled electrical activity in their brains, like epileptic seizures are. Rather, they are what neurologists call “psychogenic non-epileptic seizures,” or PNES, which can only be definitively diagnosed using video-monitored EEG. The patient is hooked up to an EEG, which monitors the electrical activity in his or her brain, and is also video taped so that the seizure behavior can be compared to the EEG. The patients are in no way putting on a show; they fully believe they have epilepsy and generally accept diagnosis and treatment when the real roots of their seizures are exposed.

Here’s the thing, patients with PNES tend to be highly suggestible. When they are told, in an epilepsy clinic, while attached to an EEG and while being videotaped, that a seizure will be provoked, say, by flashing lights, or the administration of a saline solution, the procedures do tend to bring on PNES-type seizures.  Such strategies do not tend to catalyze epileptic seizures. The PNES patients, whose seizures have psychological rather than neurological roots, follow the lead of their examiners and can often be fairly easily “guided” toward seizing.

Here’s the Freakanomics moment: Undoubtedly, some of the seizure-dog-owning patients who believe they have epilepsy are actually suffering from PNES. And these very suggestible patients could well be seizing in response to their dog's behavior. When that Hungarian dog starts to lick his master’s forearm, warning her that she is going to have a seizure, that suggestion could well be enough to induce a psychogenic seizure. The dog and the patient are engaging in a kind of folie à deux.

All you’d need to trash this hypothesis is one patient whose seizure dog could be proved to reliably predict real epileptic seizures, as opposed to apparently-epileptic-but-actually-psychogenic ones. If my hunch is right, though, and I have a hunch it is, it would certainly behoove anyone with a working seizure dog who they think can predict the future, to get themselves to an epilepsy clinic for a video EEG to see if the root of their seizures might be something other than epilepsy. Psychogenic seizures are treatable, but not with anti-seizure medications. And if you are unnecessarily suffering the side-effects and expenses of treatment for epilepsy, but don’t have it, that would be very, very good to know.

I’m not opposed to researching miracle dogs that can smell seizures that haven’t happened, though I’d rather not have to pay for it. But if I’m right, the research projects worth spending real money on are those that would lead to an understanding of how PNES works and how better to better treat it.
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Illustration by Ross Macdonald, from NYT, Oct. 31, 2009

Schitzophrenic Phenobarb: Good, Bad, and Ugly

Phenobarbital is one of the oldest and most potent pharmacological treatments for epilepsy, and it is still, nearly a century after its discovery, the most widely used anti-seizure med in the world. But it has a checkered past. And now it's use in young, developing brains has been linked, in animal models, to an increased likelihood of schizophrenia later in life.

Phenobarb was invented in early 20th-century Germany and used as a potent tranquilizer for more than a decade before a young German doctor, Alfred Hauptmann,  discovered that it not only calmed his epileptic patients' nerves, but, in many cases, it also suppressed their seizures. In the 80-plus years since, phenobarb has prevented more seizures--probably by several orders of magnitude--than any other anti-epileptic drug. Its widespread adoption marked a huge step forward in the treatment of epilepsy. When phenobarb replaced bromide--which was both nasty and ineffective--as the treatment of choice for seizure disorders, many patients gained complete control of their seizures and many more were able to leave institutions and resume normal--even if not completely seizure-free--lives.

The barbiturate has has relieved huge amounts of suffering. But it has caused suffering, too.

In one of the sickest mis-applications in pharmacological history, overdoses of phenobarbital, then under the brand name Luminal, were used by German eugenicists, many of whom were doctors, in the state-sponsored program of killing children born with deformities or diseases (including epilepsy.)

Now, according to a paper just presented in Chicago by a team of researchers from Georgetown University Medical Center, phenobarbital has been linked to a rise in schizophrenia-like conditions in the developing brains of animals. Guillermo Palchik, a doctoral student at Georgetown's department of pediatrics, said that the study raises doubts about the long-term safety of prescribing phenobarbital to infants.

According to Palchik and colleagues, an association between early childhood seizures and an increased likelihood of schizophrenia later in life has long been recognized. But do the seizures cause brain damage that leads to schizophrenia? Or does brain damage caused by phenobarb in regions of the brain associated with schizophrenia explain the trend? The question remains unanswered, but the new Georgetown study suggests an urgent need to take a longer, harder look at the drug end.

Epilepsy's Window to the Brain

Los Angeles Times writer Karen Kaplan wrote a good description of an experiment designed to see whether Broca's area really does divide the task of uttering a word with Wernicke's area, as long claimed in neuroanatomy texts. The researchers, at Harvard and UC San Diego, showed subjects a series of 240 distinct words and asked them to "pronounce" the words in their minds. Some of the words required conversion into another tense before being "pronounced." Meanwhile, the researchers watched what happened in Brocas's area, and found that there was activity there associated with 1) selecting a word, 2) deciding on a tense, and 3) mapping out how that word will be pronounced with the mouth. Nothing at all interesting happened in Wernicke's area. Broca's does it all! In less than half a second!

"The finding will make many textbooks obsolete," writes Kaplan.

The result is interesting enough on its own, but  more remarkable to me is the methodology employed. See, fMRI   doesn't picture the brain at a high enough resolution, or quickly enough,  to record this kind of activity. Instead, the researchers needed tiny electrodes implanted deep into the brains of the subjects to measure super fast and subtle reactions at ultra-high resolutions. But no review board was going to--nor should it--approve an experiment that requires brain surgery, no matter how interesting the results might be. Once again, epilepsy steps in to drive neuro-discovery as generous patients, and ingenious, multi-tasking neurosurgeons, offer their services (and/or their brains). The surgeons, in preparation for surgical treatment of epilepsy, are conducting a procedure called intracranial electrophysiology (ICE), in which they implant dozens of electrodes in the area of an epileptic patient's brain to precisely detect where the patient's seizures are starting and where healthy neurons are just doing their thing. The procedure allows neurosurgeons to cut only the pathogenic tissue, leaving behind all the important, good stuff. It takes several days, during which there is a wide open window into the portions of the patient's brain where the electrodes are inserted. If the patient is willing, and if the surgeon is interested, and if the part of the brain being explored is of interest to a neurobiologist who gets word of the surgery, the situation is ripe for research, like the Brooca's area study. Such a scene also led to discovery of the first mirror neurons in human brains (see my news piece in New Scientist) and many other cutting-edge studies. As ICE becomes more common, and as researchers increasingly include it in their repertoire of tools, other textbook chapters will be laid to rest as well.

For centuries, since Hippocrates at least, efforts to understand, describe, and treat epilepsy have been nudging, or hurtling, neuroscience forward. In fact, the reason we know as much as we do about the functional geography of most parts of the human brain--including the general functions of Broca's and Wernicke's areas, is because of earlier explorations inside the brains of epileptics. And there's no sign the trend is turning.

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Photo caption: Neurosurgeons implant electrodes deep into the human brain in order to locate the foci of seizures.  While the electrodes are in, they can be used for basic research, such as the study described in Karan Kaplan's LA Times, piece. This remarkable X-ray photo is by Ned T. Sahin, the UC San Diego neurobiologist who was the lead author on the Broca's Area study, which appeared in last Friday's issue of Science.

Brooks on the Brain: The Young and the Neuro

In today’s column,  David Brooks reports on the Social and Affective Neuroscience Society’s conference last week in NYC. He says  about the crack young neuro-scientists there, “When you spoke with them, you felt yourself near the beginning of something long and important.”  Let’s hope so. But let's not lose our heads yet. 

While the kinds of studies these guys conduct will stir up interesting clues and insights about what makes us tick--and what sometimes makes us explode, and what sometimes makes us blow other people up--and that is thrilling, unless you’re trying to raise funds for your own research, it seems best to resist irrational exuberance about the value of consigning various brain states to emotions and behaviors. Brooks suggests that “this work will someday give us new categories, which will replace misleading categories like ‘emotion’ and ‘reason.’” Maybe. Maybe not. 

He gives the example of Saaid A. Mendoza and David M. Amodio of New York University, whose work shows that reminding people to be fair may correct for reflexive prejudice that occurs in as little as 170 milliseconds in the anterior cingulate cortices when people racially discriminate. But what does that tell us that we don’t already know? That we should remind ourselves to be fair? Okay. And where would we be left if the study showed us otherwise? Would we give up trying to teach journalists to be fair, to compensate for their own prejudices? Would we stop bothering to try to make our kids aware of their biases? 

Brooks is right to be enthusiastic. Neuroscience is in a thrilling stage. Absolutely. But it would be a big mistake to bank on the idea that the study of brain states will show us a way toward solving the crisis in the Middle East, or toward solving the social injustice we've come to take in stride here in the US. We can't just blame those problems on our brains. Nor are we likely to find ultimate solutions there. Brains don't go to war, people do.

Epilepsy and the Mind-Brain Problem

In his good essay, "Reflections On Epilepsy," in the current issue of Philosophy Now, neurologist Raymond Tallis looks at what epilepsy may reveal about the argument that consciousness boils down to various brain states. An excerpt:

“If neural impulses in a solitary brain were sufficient to make up a world – as opposed to simulating bits of worlds under very abnormal circumstances – then we should not be able to distinguish between having a series of epileptic fits and living with epilepsy – or, indeed, living without epilepsy. I used to shudder when I heard people with epilepsy referred to as ‘epileptics’. By identifying the patient with his brain condition, it collapsed the distance between the latter and the person who coped with it (and decided whether my advice was any good or not). This was not only dehumanizing but also metaphysically wrong.”

Tallis makes the old, basic, and I find convincing, point that brains are necessary but not sufficient conditions for consciousness. His approach is resonant with the thoughtful Berkeley philosopher Alva Noe, who argued in his book "Out of Our Heads," that we are not our brains. (See my Salon interview with Noe.) But I especially like the way Tallis, who used to run an epilepsy clinic and is also a novelist and poet, exploits his experience watching patients with seizure disorders lose and regain consciousness. Having seen hundreds of generalized seizures myself, I concur that it is when the seizing person’s mind reassembles, after the electrical storm is over and the necessary neural orchestration has been resumed, that consciousness becomes possible. But at that early postictal point, consciousness is only a possibility. Only when the person who's had the seizure is back in the world with you--maybe they blink, say a few words, ask where they are--is anyone ready to call them actually conscious.  

While Tallis’s essay hardly settles the question of the identity of brain and mind, it does suggest a fresh and fascinating way to get some traction on the subject by looking at real consciousness in real people with a real disorder (epilepsy), which conducts all kinds of natural experiments that, for my research money, blow Hilary Putnam's "Brain in a Vat" out of the water. 

Twenty four hundred years ago, Hippocrates’ book “On the Sacred Disease,” argued that epilepsy should be treated as a physical phenomenon and not a spiritual one. It was the birth of medical science. And efforts to understand and treat epilepsy have remained at the center of progress in neuroscience ever since. So it makes sense that epilepsy would have a lot of teach us today as science and philosophy continue to struggle to clarify the relationship between brains and minds.

None So Blind: Anton’s Syndrome

We  fill in blind spots all the time to keep our perception of the  world flowing and making sense. Earlier this week I interviewed Stanford neuroscientist Ben Barres, who recounted a staggering feat of such patching.

An elderly patient was brought into the ER by her family because she'd been "bumping into things and acting strange." Barres, a Cornell medical resident at the time, gave her a full neurological exam, which she passed with flying colors, until, that is, he asked her how many fingers he held up. "Five," she said. He’d been holding up three. He kept his hand down and asked again. "Three," she said. Barres passed his hand near the patient’s face; she didn’t blink. "How's your vision?" he asked. "Fine," she said. But her vision wasn't fine. She was totally blind.

A recent stroke had whacked her visual cortex so that although her brain was getting visual data, it couldn’t interpret it. The stroke had also cut off communication between the visual cortex and the speech-language areas of the brain causing a kind of cortical blindness called Anton’s syndrome. The patient could not see a thing, but she didn’t know it yet. And, not believing she was blind, the patient’s brain invented a plausible visual "patch," from other sensory data… and a strong dose of imagination. "The power of denial," says Barres, "is also at play." (I guess so!) Amazing the hoops the brain goes through to fill in blind spots (in this case, the entire visual field) and preserve a coherent, and tolerable, picture of the world.

Remember to Forget

Mental Floss Magazine posted a fascinating article about super-autobiographical memory last week. The piece profiles four adults who share the ability to recall tiny, seemingly insignificant details from long ago. The possibility that everything we experience is stored somewhere in our brain goes back to experiments by British neurosurgeon Wilder Penfield, who provoked specific, long-forgotten memories in his patients by touching parts of their temporal lobes with an electric probe. One epileptic patient relived a childhood experience of smelling burnt toast each time Penfield stimulated a particular location on her cortex.
     If the people profiled in Mental Floss can control their access to the huge database in their brains, why can’t the rest of us? The coming decades may explain why, or they may show us how we can recover long-forgotten details, too. But I suspect that we will also learn that our ability to forget—to flush destructive or superfluous data or memories--is at least as important as our ability to remember.  Especially if the data we’re talking about contains viral components that can keep our brains pinwheeling while other key bits of data--our lives-- pass us by.  Those of us who can’t remember every episode of Flipper should  thank our lucky stars.
   One hot and relevant area of current research focuses on the role of attention in helping the brain decide what to hold onto and what to flush. Take a look, for instance, at this Journal of Neuroscience paper by Adam Gazzaley and Theodore P. Zanto showing how "top-down" attention is related to memory acquisition. Choosing what to remember and what to let slide sounds good, but  I wonder if our conscious minds can always be trusted to know what's important to remember and what's not?