Wednesday, October 8, 2014

Location! Location! Location!

Where are you? And how do you know? The answers find their most fundamental satisfaction through a mechanism in the temporal lobe discovered and explored by the three winners of this year's Nobel Prize for Physiology or Medicine. On Monday, the Nobel committee announced that John O'Keefe, May-Britt Moser, and Edvard Moser will share this year's prize for explaining the brain's global positioning system, a network of cells in the temporal lobe. In 1971, O'Keefe, now a professor of cognitive neuroscience at the University College London, first described what he called "place cells," neurons that identify specific places where a rat has been; the same neurons consistently activate whenever the rat walks by that location. Thirty four years later, the Mosers, who are a married couple and both professors at the Norwegian University of Science and Technology in Trondheim, discovered "grid cells." These neurons form clusters of triangular grids into which the place cells register their locations relative to each other.  Together, these two systems allow rats, humans, non-human primates, and probably most other brainy creatures, to determine their position in space, to store location information, and to navigate.

Last year, the first human grid cells were directly identified via electrodes temporarily implanted in the temporal lobes of epilepsy patients. The implants were put in place to study the patients' brains in preparation for surgery aimed at quelling their seizures. That work was done by Joshua Jacobs at Drexel University and appeared in  Nature Neuroscience.

The same area of the brain occupied by the grid cell navigation system is often hit by early Alzheimer's disease. Easily getting lost is a common early symptom of Alzheimer's.

James Gorman's good profile of the Mosers--who are both brilliant and adorable--was published in the Times last April.

Friday, August 22, 2014

New Study Shows Autism May Be Caused by Inadequate Synaptic Pruning? How About Epilepsy?

An infant's brain is chock full of connections. The average one has many times more synapses per neuron than the typical adult's. It is with the pruning of those extra neurons that networks enabling specific functions emerge. A story in today's New York Times describes research, published Thursday in the journal Neuron,  suggesting that the brains of autistic children are failing to prune away synapses as aggressively as they should.

David Sulzer, at Columbia University Medical Center, analyzed tissue from the brains of 20 children who had died between the ages of 2 and 20. Ten of those children had autism. The other ten did not. Both groups had about the same number of synaptic connections when they were very young. By the time the non-autistic children turned 19, they had 41 percent fewer synapses than when they were infants. The children with autism had only 16 percent fewer synapses.

Sulzer and colleagues found the same trends in rat models. Administering a drug used to prevent organ transplant rejection, to rats caused their brains to restore normal levels of synaptic pruning.

From the Columbia University press release:

"Although the drug, rapamycin, has side effects that may preclude its use in people with autism, “the fact that we can see changes in behavior suggests that autism may still be treatable after a child is diagnosed, if we can find a better drug,” said the study’s senior investigator, David Sulzer, PhD, professor of neurobiology in the Departments of Psychiatry, Neurology, and Pharmacology at CUMC."

More than a third of kids with autism also have epilepsy, and it is thought that reduced synaptic pruning, and the neural over-excitation it may cause, could also play a key role in some forms of epilepsy. See my story about epilepsy and autism in Epilepsy USA. I'll investigate this further from the epilepsy researcher's point of view and report back soon.

Wednesday, May 28, 2014

CNEP Wins $26M from DARPA for Neural Implants

UCSF neurosurgeon Edward
Chang developing read/write
neural implants to treat neuro-
psychiatric illness. (Photo by
Eric Millette) 
NPR's Morning Edition yesterday featured a good story about the work of Eddie Chang, the brilliant neurosurgeon/scientist at UCSF, and his cohorts at CNEP. These guys--whom I've written about  for Discover, San Francisco Magazine, and Berkeley Engineer--are on fire. The NPR piece reported on CNEP's part of a five-year $70-million DARPA project using brain implants to identify, study, and reform errant neural circuitry behind depression, PTSD, and addiction. The UCSF/Berkeley CNEP team is getting about $26 million of the funding to work on both the implants and the algorithms needed to 1) read and make sense of the brain's activity and 2) know when and how to apply subtle electrical impulses to lead the brain to "unlearn dysfunction" in areas causing psychiatric symptoms. It would be an entirely new way of treating mental  illness...unless you count electroconvulsive therapy (ECT), which also used electrical stimulation to interrupt pathological symptoms. Let's hope the new approach is a little more nuanced in its application and effects. Whether the implant approach will even work at all is unclear, but in just trying to find out the CNEP group will surely make huge strides toward directly linking brains and computers. 

I don't question DARPA's interest in helping millions of vets and others to overcome disabling and agonizing mental illness, but nor do I doubt the military research organization's incentive to develop brain-machine interfaces for a host of other purposes, too. More to come on this soon. 

Listen to NPR's Morning Edition story, Military Plans to Test Brain Implants to Fight Mental Disorders, by Jon Hamilton. Here's a link to DARPA's announcement. And a UC Berkeley release about the project.

Tuesday, April 1, 2014

Audible Seizures

Chris Chafe and a student
examining readouts of brain
activity. Photo by Linda Cicero

I have a piece in the May issue of Discover describing a device that converts EEG readings into sound, which is much easier to interpret than the cryptic visual EEG scrolls that even many neurologists can't properly read. Stanford inventors Josef Parvizi and Chris Chafe call the device a "brain stethoscope" because users can move its sensors around a patient's head to listen for seizure activity in all the key parts of the brain. It is a rough-and-ready tool for distinguishing non-convulsive seizures--which can present quite subtly--from other neurological or psychological conditions. The inventors hope that parents and other care takers of epilepsy patients will even be able to use it at home. The most interesting part of the Discover package is an audio piece that Molly Bentley and I produced; it is a narrative voice-over of one of the "seizure cantatas" recorded with the device. Josef Parvizi describes the onset, peak, and postictal phases of the event in a way that listeners can feel as well as understand. I find the recording upsetting, but also quite beautiful.

Thursday, March 27, 2014

Neurostimulator by Neuropace.
An interesting piece in this week's Science Times describes an increasingly popular way of treating intractable epilepsy with an implanted stimulation device. The surgical implant, called an RNS device, reads signals from electrodes placed deep in the brain. When its processors determines that a seizure is mounting, the device delivers a strategically-placed current custom designed to interrupt the attack.

Approved by the FDA for marketing in 2013, the system seems to be particularly helpful in quieting epilepsies with a one or two foci, or spots in the brain where the seizures start. Electrodes are implanted near those foci--the hippocampus is often one--and deliver a limited shock just to those parts of the brain. A much older technology, called Vegus Nerve Stimulation, or VNS, gives the brain a much more distributed shock that is periodic, and not tied to specific brain activity.

In addition to reducing seizures in about half of the patients who receive them (which is a big deal, since these are very difficult cases!), the RNS may have a side effect not mentioned in the story. Data are constantly being gathered from the brain by the device and are wirelessly downloadable with a wandlike reader that is waved over the skull near the implant. Having a continuous live stream of data from the seizure focus of an epileptic brain presents a huge research opportunity as well as an important clinical one.

Friday, February 14, 2014

Sorting the Crop from the Weed

An editorial in Wednesday's Times calls for caution from parents considering using marijuana extracts to treat their children's seizures and, just as importantly, for a full-speed-ahead study of the compounds that may make such treatment effective.  As states like Colorado and California begin to legalize marijuana, it becomes easier to administer the drug to epileptic children outside of the clinic. Unfortunately, federal regulations designating even CBD--the non-psychoactive component of marijuana that may inhibit seizures--as a Schedule 1 drug, make it very difficult to conduct scientific studies. The compound may work, says Orrin Devinsky, an epileptologist at NYU and one of the op-ed's authors, but the science just isn't yet in. Nor has the safety of the compound been proven.  "This concern is especially relevant in children, for whom there is good evidence that marijuana use can increase the risk of serious psychiatric disorders and long-term cognitive problems," writes Davinsky, one of the country's top epilepsy doctors and researchers.

Devinsky and Daniel Friedman, his co-author and colleague at NYU, are not anti-pot ideologues. They are scientists making an urgent plea for the study of a set of promising but complicated compounds. Apparently (from the avalanche of outraged comments) the piece was misunderstood by many legalization advocates. The authors are not calling for pursuit or persecution of patients using CBD but rather for an urgent and rigorous scientific study, and the update of federal regulations that would make that possible. Of course such study will be skeptical; science always should be.

Friday, October 25, 2013

DARPA to Spend $70M on Deep Brain Stimulation

DARPA yes, but are they combat
satellites or brain dust? 
James Gorman in today's NYT reports a plan of the federal Defense Advanced Research Projects Agency (known as Darpa) to spend $70 million on deep brain stimulation research and technology. Although DBS is already deployed as a treatment for Parkinson's disease, it also has promise for the treatment of epilepsy (often a consequence of traumatic brain injuries experienced by soldiers), depression, and other common neurological and psychiatric maladies suffered by soldiers and vets. From the initial report, it looks like research will focus on reading signals from the brain more than sending stimulation in, though. Gorman quotes Darpa program manager Justin Sanchez saying they are looking for technology that can “tell them precisely what is going on with the brain.” Gorman goes on: "The next step is to create a device that can monitor the signs of illness or injury in real time, treat them appropriately, and measure the effects of the treatment."

That would be great. But beware, by the time you could monitor and treat mental illness through implanted wireless electrodes you could monitor and influence all kinds of other "mental events" as well.

Darpa may have made a mark on history by giving us GPS and the Internet, but with read-write brain-machine interfaces it would bring about more than a technological revolution; more like a human speciation event! Keep your seat belts on...and your skull caps closed.