A remarkable article in today's NYT Magazine describes what appears to be evidence of scientific malfeasance in the treatment of data from one of the most influential studies in neuroscience history. The article, by Luke Dittrich, suggests that MIT neuroscientist Suzanne Corkin either ignored or actively suppressed evidence that the brain of Henry Molaison  had damage to its left frontal lobe. 

Decades of research presumed that Molaison's only brain damage was the product of a temporal lobectomy in which his hippocampus, amygdala, and entorhinal cortex were removed in a desperate effort to quell his epileptic seizures. 

Studies of Molaison serve as the foundation for a huge body of memory research spanning decades. It stands to reason that this new evidence could throw into question at least some of that fundamental work.

Dittrich's grandfather was the surgeon who removed Molaison's hippocampus in 1953. The writer's 2010 Esquire piece about HM is also excellent and his book on the subject, Patient H.M.: A Story of Memory, Madness, and Family Secrets, to be released August 9, will surely shed more light on what appears to be a troubling history, some of it, I expect, implicating his own grandfather, neurosurgeon William Beecher Scoville. 

Cal field hockey player Keats Iwanaga
examined on the field by Dr. Jaqueline Theis 

About 500 concussions are diagnosed by the UC Berkeley student health center each year. And yet the injury is notoriously tricky to diagnose and treat. Two UC Berkeley doctors--sports physician Casey Batten and optometrist Jaqueline Theis--are deploying the tools of optometry to help bring greater clarity to the field and to ease the way for all students, whether athletes or not, back into their academic saddles. I wrote a piece about the subject for the print-only Berkeley Optometry magazine in December; it was republished, online, by CalBears.  

Ketogenic Diet Helps Schizophrenic Rats

High-fat butter sculpture of an ear mouse.

Almost a century ago, the high-fat, low-carb ketogenic diet (KD) was invented as a way to help people with epilepsy control their seizures. It works better than any known medicine at reducing or eliminating even the most refractory seizures. As if that weren't enough, recent studies show its promise for treating a host of other neurologic and psychiatric disorders as well: Parkinson's, Alzheimer's, MS, and depression. A new study now suggests the KD might one day help people with schizophrenia, too.

The research, conducted at Australia's James Cook University and published in the December 2015 issue of Schizophrenia Research, found that rats on the high-fat, low-carb diet show "fewer behaviors that resemble schizophrenia" than other rats, says the study's lead author, professor Zoltan Sarnyai.

In addition to its positive psychiatric effects, says Sarnyai, the diet has another suite of benefits, too: rats on the treatment also lost weight. "It works against the weight gain, cardiovascular issues and type-two diabetes we see as common side-effects of drugs given to control schizophrenia," says Sarnyai in a James Cook University press release. This is still very early stage research, but the  JCU team is hoping to launch a controlled clinical trial on humans suffering from schizophrenia,the release reports.

Navy SEALS May Dive Deep on Ketones

Research on oxygen toxicity suggests Navy SEALS
may benefit from higher ketone levels during deep dives.

A few days ago I linked to a study showing that a particular fatty acid, decanoic acid, could be responsible for at least some of the seizure-suppressing power of one version of the ketogenic diet. According to SeaPower Magazine, the Office of Naval Research (ONR) is banking on an alternative explanation by funding research on ketone-ester oral supplements in the hope that they can quell the potentially deadly seizures sometimes experienced by special ops scuba divers.

For stealth, NAVY seals, for instance, use closed-circuit rebreathers on their oxygen supplies. While these devices minimize bubbles visible on the water's surface (a giveaway to SEAL-wary enemies) and allow for very deep dives, they also increase the risk of hyperbaric oxygen poisoning. Seizures are an occasional and usually lethal side effect oxygen toxicity. 

The research,  led by University of South Florida  neuroscientist  Dominic D'Agostino, is based on the theory that the ketone esters themselves are hefting the weight of seizure control. Underlying that idea is the observation that when brain cells burn ketones instead of glucose they become less seizure prone. The association between ketosis and seizure suppression is well established, but the causal mechanism--or mechanisms--is still hotly debated.

D'Agostino fed ketone esters to rats that were then put in deep-dive-simulating hyperbaric chambers. Compared to a control group that did not get the ketones, the first group was significantly less likely to have seizures. What's more, they also performed better on other physical and cognitive tests.

So, it seems that while specific ketogenic-diet-related fats reduce seizures, so do the presence of ketones, even when those fats are not present. At least in rodents. This suggest that the ketogenic diet may have more than one seizure-suppression mechanism going for it.

D'Agostino hopes to move his research into human trials next year.

Crowdsourcing Seizure Prediction

I wrote a short piece for the December issue of Discover Magazine about  freelance coders  recruited by epilepsy researchers to help advance the tricky art of seizure prediction.

For many of the 50 million people with epilepsy, seizures are brutally unpredictable. They can strike out of the clear blue sky at any time; those who suffer them have to be ready all the time. Even people who average only a seizure a month can't drive and shouldn't swim or bicycle alone. Cooking is treacherous. Every sharp corner, high place, or moving vehicle poses risk.  What’s more, to keep seizures at a minimum, many patients suffer the side effects of constant medication. If seizures were predictable, people with epilepsy could conduct business as usual most of the time, getting out of harm’s way when a seizure approaches, or, better still, taking medical action to forestall it.

Over the past 15 years the NIH and several other funding entities have spent about $40 million trying to devise algorithms that detect signs of a brewing neurologic storm early enough to intervene. A driving patient could get off the road. Or a device could deliver anti-seizure medication or a subtle, seizure-aborting electric current.

Seizure prediction proved a tough nut to crack; all that investment produced algorithms little better than a coin flip. Frustrated, a group of neuroscientist epilepsy docs--backed by the NIH, Epilepsy Foundation, and American Epilepsy Society--invited computational geeks and hackers around the world to take a shot. Over 500 teams competed; each was given data sets recorded from the brains of human epilepsy patients and epileptic dogs.

Three months—and $30,000 of prize money--later, winners had produced algorithms predicting seizures with better than 84% accuracy; good enough to one day transform millions of lives.

The new predictive tools are of special interest to three companies already manufacturing implantable stimulation devices that interrupt seizures. Currently, these devices detect seizures but can’t predict them. Adding prediction will allow now tentative patients to seize the day.

What Makes the Ketogenic Diet Work? It's The Fat! (At Least Partly)

The MCT-suppliment diet is just one of many
effective high-fat, low-carb epilepsy treatments

A new study in the journal Brain reveals one mechanism by which a variant of the ketogenic diet treatment seems to work. The MCT (medium-chain triglyceride) ketogenic diet is a relatively easy to follow version of the diet that is more popular in the UK than in the US, where other lower-carb varieties predominate. It was thought that ingested MCT oil produced ketones more easily than other kinds of fats, and that the extra ketones produced were hefting the weight of seizure control. The new study, though, reveals the effectiveness of a particular fatty acid, decanoic acid, at quelling seizures in animal models. Like ketones, decanoic acid is produced by the liver when the body runs out of carbohydrates to burn and converts fat into fuel for the brain. In the animal studies at University College London, and reported in Brain, decanoic acid was shown to directly decrease the excitability of neurons and thus reduce the risk of seizures. The presence of ketones themselves didn't seem to matter much.

High-fat, low-carb, ketogenic diets have been effectively used to treat epilepsy since the 1920s.  In the late 20s and 30s it was the most popular and most effective treatment available, and was especially good for treating children, whose eating habits could be more easily controlled than those of adults. The popularity of ketogenic diets as a first-line treatment took a nose dive, though, with the discovery of the anti-seizure drug Dilantin in the late 1940s. The diet's effectiveness (better than Dilantin for hard-to-treat cases) was clear to clinicians who used it, but because it was labor intensive for patients, care givers, and doctors, and also because no one knew how it worked, it fell from fashion. Fortunately, the treatment was kept alive in a few epilepsy centers, most notably at Johns Hopkins in Baltimore, where hundreds of so-called "intractable" pediatric epilepsy patients found relief over the decades.

Ketogenic treatments became popular again in the 1990s, largely because of the publicity following an NBC Dateline documentary about the effectiveness (and lack of negative side effects) associated with the under-used treatment. Still, though, the mechanisms by which the treatment supressed seizures remained mysterious. Only in the past decade has research on how the diet works really begun to bear fruit. Different theories have spawned variations of the diet, some focusing on raising ketone levels in patients, others focusing on the beneficial effects of the fats themselves, and still others on the positive effects of minimizing carbohydrates. According to the top researchers in the field, there may well be more than one mechanism at play. That would help explain the surprisingly broad effects of the diet, which is also currently being studied as a treatment for Parkinson's, Alzheimer's, and even cancer.

This New Scientist Piece by Clare Wilson is  good, but it confuses the MCT ketogenic diet for all ketogenic treatments and assumes that the mechanism reported in the Brain paper explains all of the ketogenic diet effects. Fortunately, it's much more likely that other mechanisms will also be revealed in  months and years to come.  And each of those will open new clinical possibilities and shed light on basic metabolic processes in the brain.

Try & Try Again: Sam Vogelstein & CBD

Fred Vogelstein wrote about his son's epilepsy in a fine 2010 New York Times Magazine article. That piece,  "Epilepsy's Big Fat Miracle," focused on the high-fat ketogenic diet; Fred's son Sam, who was nine years old at the time, had once been buffeted by hundreds of  absence seizures a day. Medications weren't helping. The ketogenic diet, described by Vogelstein as a "desperate" treatment, seemed to work. He was only having about six seizures a day. Sam was finally "a happy, healthy, and independent kid," Fred wrote. Hence the Big Fat Miracle;  Sam's life was back on track.

In the July 2015 issue of WIRED, though, Sam and Fred are back on the therapy trail in a piece titled "One Man's Desperate Quest to Cure His Son's Epilepsy--With Weed."  Between the two features, Sam's seizures returned again. With a vengeance. This time, having tried everything else, they head off to London, in 2012,  to try another desperate treatment: this one is an extract of the marijuana plant known as cannabidiol, or CBD. The compelling piece is largely about the hoops the Vogelsteins have to go through to try the compound at all.

"It had taken four months of phone calls, emails, and meetings with doctors and pharmaceutical company executives on two continents to get permission to try this drug," writes Fred. "Sam wasn’t joining an ongoing clinical trial. The company made the pills just for him" By the time the Vogelstein's win approval from the DEA to import CBD into the US, they have spent more than $120,000 of their own money on the effort. Their expense and efforts seem to have paid off. Both for Sam, whose seizures are again under control, and for many others who still suffer from medication-resistant epilepsy in the US. Sam's story seems to have helped pave the way for several sizable studies of CBD in major US research centers. A CBD-based drug made by the British company GW Pharmaceuticals may be on the shelves less than three years from now.