Join 3,375 readers in helping fund MetaFilter (Hide)


Deus Ex Now
April 28, 2012 4:24 AM   Subscribe

"Jolts to the brain boosts memory!" Via deep brain stimulation technique, patients in a UCLA study (Full PDF)were able to significantly improve their ability to remember and find their way through a virtual environment. Although the study was small, it offers tantalizing clues toward potential treatments of disease such as Alzheimer's and raises the specter of artificial neuro-enhancements in the future.

In the words of the authors of the paper, "Our results show that spatial learning in humans can be enhanced by electrical stimulation of the entorhinal region, a specific site within the medial temporal lobe and the chief gateway into the hippocampus." This is the first instances that I know of where a human neuroprothesis led to improvement in solving cognitive problems closely modeled on real-life situations.

So how does it work? An accompanying editorial notes that in animal studies electrical stimulation of the same brain regions appears to generate new neurons, which gets hooked up to exisiting neural circuitry.

The subject of memory-related neuroprosthesis has been discussed in mefi before.
posted by Pantalaimon (17 comments total) 10 users marked this as a favorite

 
I wonder how they did the control. It seems like having electrodes implanted in your brain would make anything memorable. If the subject was able to consciously sense the stimulation, then wouldn't you need to a similar sensation generation to avoid people simply remembering things due to the sheer strangeness of the experience?
posted by delmoi at 4:54 AM on April 28, 2012


From the paper: "The subjects were unaware of the stimulation condition, and no subject reported noticing any effect of stimulation."
posted by Pantalaimon at 5:04 AM on April 28, 2012


Is this permission to electrocute the wife if she keeps forgetting things?
posted by Splunge at 6:36 AM on April 28, 2012


Is this permission to electrocute the wife if she keeps forgetting things?

I'm sure you'll get off on the charge.
posted by furtive at 6:51 AM on April 28, 2012 [9 favorites]


I was wondering if this would make it to the blue. I am part of a lab that does a lot of work with Fried's group at UCLA. My boss was quoted at some length in the NYT article about the study (IMO a better summary), and our lab was even incorrectly credited with the find in the picture caption. The headline is a more exciting than the actual study (though the finding is exciting), but I figured I'd give some background on this type of study. Please forgive my verbosity.

A little background: Our lab developed this "VR"/video game-type paradigm many years ago (before I joined) as an analogue to rodent studies of spatial memory and cognition. It's easy to implant an electrode in a rat or mouse and let them run around an enclosure; that's a tougher prospect with a patient recovering from brain surgery mostly confined to a hospital bed. Even so, using the "YellowCab" paradigm, we (and others) have been able to find some really cool stuff in humans that had only been seen in rodents before: place cells (Ekstrom et al., 2003, Nature), hippocampal theta (Ekstrom et al., 2005, Hippocampus), clockwise/counterclockwise direction cells (Jacobs et al., 2010, PNAS), and grid cells (Jacobs et al., forthcoming). (Itzhak Fried, whose lab conducted the OP stim research, is an author on all of these; we still regularly collaborate with him to collect single-unit -- single-cell spiking -- data.) Plus a wealth of behavioral (non-electrophysiology) studies detailing human spatial memory and cognition.

Cognitive testing with these patients (who have intractable epilepsy and are undergoing invasive intracranial EEG monitoring prior to resection surgery) is sort of a funny thing. It's laughable that we would be able to do this kind of study with healthy controls (it's brain surgery!); we're just piggybacking on a clinical procedure and giving the patients something to do while they're in the epilepsy monitoring unit. We collaborate really closely with two nearby functional neurosurgery units, but we're still at the mercy of the clinical neurologists and neurosurgeons to be able to collect this (incredibly valuable) sort of data. Not to mention that the patients that we're working with are not exactly ideal-- aforementioned brain surgery, morphine drips, cognitive impairments from (sometimes debilitating) epilepsy. The most we can do it walk into their room and ask, "Feel like testing today...?" The difference at UCLA is that Fried is the neurosurgeon. I'm absolutely not saying that he does anything that's clinically irresponsible to further research interests. That's totally untrue. But he does have a different sort of mindset than our (primarily clinical) neurosurgeons, so all else being equal (that's the key part), the clinical decisions he makes allow him to collect research-oriented data. He will go out of his way (i.e., additional time or cost) to be set up to collect research data, while other neurosurgeons do their normal thing and if it happens to be useful for cognitive or basic neuroscience research, yahtzee. He's also really good at "getting units"--- setting the patients up in the OR in such a way that he can detect single action potentials in the brain. We can find collaborators who are interested in our research, but ones who are interested enough to have this kind of involvement are thin on the ground. Again, and I want to stress this, nothing clinically questionable is being done in the pursuit of research data.

This is an exciting finding, no doubt. My boss is quoted in the NYT saying that groups should run to reproduce this finding; we're likely going to be one of the labs that tries to do just that. We do stim studies of free recall and paired associates currently, but our stimulation sites tend to be on the surface of the brain for those. In a recent AskMe I talked about a funny case study of (clinical) stimulation evoking particularly vivid memories for one patient. We were able to use that phenomenon for further analysis of the patient.

I also talked about the fact that, for the most part, we don't know why brain stimulation has the effects that it does. We don't know what kinds of cells it affects (inhibitory interneurons or excitatory pyramidal cells, e.g.). Current theory is that it temporarily "knocks out" a section of tissue, creating a temporary focal lesion, but it's often difficult to interpret stimulation results, like the one in the OP here, in that light. Previous research has shown place-responsive cells in entorhinal cortex and the hippocampus; if that's the case, why would knocking them out improve spatial learning? The paper is light on that sort of theorizing. They mention that micro-stimulation of the perforant pathway in rodents leads to better spatial learning. The PP is the input to the hippocampus from the EC, but stimulating the hippocampus directly leads to mixed results. A key point is that they really can't be sure where the stimulating electrodes are; they have post-op MRIs and/or CTs to go on, and that's it.

Forgive the academic snobbery, but one also has to look at where they published this finding. Don't get me wrong-- NEJM is a great journal, but it's a clinical journal. We never publish there, because we're a cognitive lab. This is a cognitive study. Sure, it has clinical implications, but so does almost everything in this field. The measure of performance used -- excess path length -- is a good one, but there are others that would be appropriate. From what I can see, it's a bit light on data to be published in, say, Nature Neuro, Neuron, or Journal of Neuroscience, which are dedicated research journals. Did they publish in NEJM to get the attention of clinicians (the generous interpretation) or because their results and methods weren't rigorous enough?

Sniping aside, I really do like what I see... but I'd like to see more, and it makes me wonder why I don't. In short, I'm skeptical of the headlines, but I'm eagerly awaiting replication studies, and I hope I get to be part of one myself.
posted by supercres at 7:46 AM on April 28, 2012 [43 favorites]


Important: Boot to the head does *not* equal jolt to the brain.
posted by eriko at 7:59 AM on April 28, 2012


So how does it work? An accompanying editorial notes that in animal studies electrical stimulation of the same brain regions appears to generate new neurons, which gets hooked up to exisiting neural circuitry.

This doesn't explain the Fried finding. Neurogenesis doesn't work on this timescale.
posted by supercres at 8:18 AM on April 28, 2012 [1 favorite]


I have a terrible sense of direction and enjoy confusing and annoying the TSA. Sign me up! I've done worse things to my brain, I'm sure.

Also please sidebar supercres up there, that was fascinating.
posted by Blue Meanie at 9:46 AM on April 28, 2012


superces, thank you very much - and be as verbose as wish!

Are there any non-evasive techniques for such brain stimulation that show promise? Assume that this type of stimulation ends up being a net plus and side-effect free or close enough to it to be seen as beneficial, how long until such stimulation can be one without the surgery?
posted by Bort at 10:26 AM on April 28, 2012


Are there any non-evasive techniques for such brain stimulation that show promise?

Not yet. The problem is that these structures -- the ones implicated in memory -- are buried deep in the brain. (I'm mostly speaking about the hippocampus, but the entorhinal region of cortex is right next to it.) The two non-invasive techniques commonly used today are TMS (transcranial magnetic stimulation) and tDCS (transcranial direct current stimulation). TMS is now a pretty well-established research technique, as well as a clinical one. The problem is that it really only depolarizes surface tissue. For various reasons, the electric field that the magnetic field induces is thought to activate tissue, for the most part. (Perhaps by depolarizing inhibitory interneurons. I've done TMS before, and I can pretty reliably find the spot over motor cortex to make people's hands twitch. But again, motor cortex is on the surface of the brain.) The advantage of Fried's studies, and others like it, is that they use depth electrodes that don't just sit on the surface of the brain: they get deep, directly into HC/EC/amygdala. (There are surface -- subdural -- electrodes as well; they look like this -- warning: gory surgery picture.)

So yeah, not yet. Surgery & implanted electrodes are currently necessary to reliably record from or stimulate these structures. Same for midbrain structures, like vACC for depression or STN for Parkinson's. But this is an engineering problem, and the technology is constantly evolving. I think TMS will get there sooner rather than later.

I should add, though, that one really has to think hard about how to implement stimulation, assuming that it does aid memory formation, Fried's group's conclusion, and that you can get it focused to the EC. Would you keep it on all the time? Doubtful-- it almost necessarily disrupts other brain functions. And I'll quote myself from the previous neuroprosthetic thread: "statistically significant [often] isn't all that significant to real life." We do the same thing with other memory paradigms (paired associates to be precise) and it's tough to get a solid result (or else I'd cite it :) ).

So again, I'm excited, but still skeptical. Extraordinary claims require extraordinary evidence, and I don't think this study makes it. The stats and methods aren't quite there yet.
posted by supercres at 11:08 AM on April 28, 2012 [1 favorite]


supercres,

What's your take on tDCS? Your comments above seem to discuss TMS.
posted by effugas at 12:25 PM on April 28, 2012


What's your take on tDCS?

I honestly don't know much about it, beyond popular science-type stuff. When I was working with non-invasive stim, three years ago or so, I only read about and worked with TMS. It's a slower type of effect-- TMS has a very transient effect; same with stimulation along clinical intracranial electrodes. The sort of thing I'm interested in requires a sharp, temporally-isolated effect, for reasons that probably aren't generally interesting. (Our stim tends to come right when the to-be-remembered stimulus appears on screen.) In that way, maybe the OP study is closer to tDCS effect, given that it wasn't locked to stimulus? The stimulation here took place in spans of five second on-and-off blocks, which might not be the ideal stim parameters, since the block division adds another variable, but that's a different question.

If anyone here knows a good tDCS/cognitive review article, let me know!
posted by supercres at 12:39 PM on April 28, 2012


I'm not any kind of neural or cognitive scientist, but when a friend posted a tDCS video on Facebook a couple of days ago, the first thing I thought of was , Up the voltage.
posted by ob1quixote at 2:38 PM on April 28, 2012


From what I can see, it's a bit light on data to be published in, say, Nature Neuro, Neuron, or Journal of Neuroscience, which are dedicated research journals. Did they publish in NEJM to get the attention of clinicians (the generous interpretation) or because their results and methods weren't rigorous enough?

Correct me if I'm wrong, but the impact factor for the New England is an order of magnitude greater than those listed journals. Short of Science, Nature, and Cell, all things equal I'm not sure anyone would really opt to publish in another journal if they have a shot at NEJM.
posted by drpynchon at 6:29 PM on April 28, 2012 [1 favorite]


As deep brain stimulation, sex is cheaper.
posted by Twang at 8:20 PM on April 28, 2012


Correct me if I'm wrong, but the impact factor for the New England is an order of magnitude greater than those listed journals.

I believe it, but it's still about who reads the journals. Cognitive neuro people publish in Science, Nature, Nature Neuro, Neuron, Cerebral Cortex, J Neurosci. Publishing cognitive studies in a clinical journal just looks like you're trying to sneak something weak into the literature because clinical journals aren't as rigorous for analysis.

A coworker reminded me of an example of this: the OP study reports theta phase reset; it's a major tie-in to previous literature. They didn't show, however, that phase reset doesn't happen in alpha, beta, etc. That wouldn't sneak by a neuroscience journal or its reviewers. But clinical journals have clinician reviewers. And clinician reviewers don't know the neuro literature as well, or the state of the art for signal analysis, or advanced statistics. Nothing against clinicians or clinical journals; it's just a different audience with different implicit requirements. Cognitive folks like me are skeptical.

I really hate sounding like I'm bashing the study. It's an interesting study. But it doesn't meet the burden of proof in the cognitive neuroscience community.
posted by supercres at 9:41 PM on April 28, 2012 [2 favorites]


Just to jump in with supercres, the trustability of a result does not perfectly corelate with the impact factor of a journal. The quality of review would indeed be different at NEJM than Neuron or J Neurosci. Those clinicians would be not idiots, hopefully, and have more perspective on the more global value of the work being outside of the field, but they can also be expected to have less familiarity with the specific techniques and expectations of another field, exactly like supercres is mentioning.

For example, if I were to read a paper claiming to have found and characterized an RNA polymerase that transcribes backwards, I would trust it a lot more published in J. Bact than in Science or Nature. There is a surprising amount of absolute shit that gets published in those journals and it is in large part because they generally have two thirds of the reviewers from other fields to make sure that the paper is notable enough.
posted by Blasdelb at 7:52 AM on April 29, 2012 [2 favorites]


« Older In Bed With Invader One night in Paris with street...  |  Is Some Homophobia Self-Phobia... Newer »


This thread has been archived and is closed to new comments