Monday, January 27, 2014

Eight Years of Neurocriticism

A Mad Scientist Party Idea, from Party on Purpose.

Eight years ago, I started a blog out of sheer frustration. I decided to call it The Neurocritic. I sent out an anonymous e-mail to some of my friends to describe the project.

subject: unveiling The Neurocritic

I've started a blog to critique the most outrageous claims published in high-profile journals and discussed in the popular press:

Because The Neurocritic is not a member of the all-powerful Editorial Boards at Science, Natute, or Neuron, The Neurocritic is published under an assumed identity.  Your comments are most welcome.

Enjoy the inaugural posting! [we'll see how long it lasts.]

[I had forgotten how surprised I should be that the blog has lasted this long.]

At first, I invited others to join. Two people expressed interest in joining the party, and one was issued an account (but never posted). I soon became very proprietary and revoked that account. I had become The Neurocritic.

I didn't think anyone would read the blog. But then a funny thing happened. Several posts that discussed journal articles drew the attention of the authors, who actually commented.

Meanwhile, I tried my best to stay under the radar and hoped that no one would think of me as a real person.

Pretty colorful brains and simplified explanations of human cognition and emotion and personality had became staples of mainstream newspapers and magazines, first in the dying print media and then in purely online news sources and press release farms. Gradually, a backlash grew against studies on the neural correlates of shopping at Macy's. This blog (and others such as Mind Hacks, Neuroskeptic, and Neurobonkers) was mentioned in the same press outlets that ran outlandish opinion pieces about Loving Your iPhone:

Neuroscience: Under Attack (Nov 23, 2012)

Neuroscience Fiction (Dec 2, 2012)

Why ‘neuroskeptics’ see an epidemic of brain baloney (Apr 13, 2013)

This blog reached the height of its popularity in 2012.  Then we hit 2013... the year of decline.

What happened?? I'll explore some possible reasons in the next post, and take a glimpse into the future.

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Friday, January 24, 2014

The Brain Radio

The Brain Radio is a long-running French radio program:

THE BRAIN are Eva & Pascal Lebrain aka Puyo puyo, they run this radioshow from 1999, it deals with freaky electro, cheesy vintage, dry rock, movie themes and oddities in general. All is stuffed with absurd aphorisms, written by themselves most of the time.

The fun archive of playlists dates back to 2003 and includes 91 of the 129 radioshows.

The “Brain Radio” is also a deep brain stimulation (DBS) device that “Records and Emits Electrical Pulses,” according to an August 9, 2013 story in the MIT Technology Review:

A new brain implant that can record neural activity while it simultaneously delivers electric current has been implanted into a patient for the first time.

The new device from Medtronic, a Minneapolis-based medical device company, can also adjust its electrical output in response to the changing conditions of the brain. This automated control could one day improve deep-brain stimulation treatment and even enable doctors to use the device to treat more conditions, say experts.

This new generation device seems like what DARPA had in mind for its SUBNETS program, part of the BRAIN Initiative. The MIT Technology Review story continues:
The patient trials launched on Wednesday will test whether Medtronic’s new device can safely record electrical activity in a patient’s brain while also delivering electric currents. These tests will explore how patients’ brains respond to deep brain stimulation therapy. However, according to lab animal tests, the device is capable of not only sensing the electrical activity of the brain tissue it sits in, but of also changing its output accordingly.

The ultimate goal for the device is to provide responsive therapy by detecting brain signals and tweaking its output accordingly, says Lothar Krinke, general manager of the company’s deep brain stimulation division.

The Activa® PC+S Deep Brain Stimulation System was first implanted in a German patient with Parkinson’s disease. But now there's a new clinical trial for treatment-resistant depression (TRD) that will implant the device in the subgenual cingulate (Brodmann area 25):
The experiment described in this application is to use a new DBS device that can record the electrical activity in the brain around the site of stimulation. The electrical activity is known as Latent [sic] Field Potential (LFP) and is a reflection of the activity if the neural network. The new DBS device is an experimental device that has not been approved by the FDA, but allows for simultaneous recording of LFP while stimulation is being delivered. The device is manufactured by Medtronics and is known as Activa Primary Cell + Sensing(PC+S), but because it can be used to record the brain electrical activity it is also known as "the Brain Radio". The Brain Radio is based on an approved device commonly used for DBS for other conditions that has the added sensor capacity. The stimulation system is identical to that in the approved device. The goal of this investigation is to use the Brain Radio to study LFP in the brains of people with TRD before and during active stimulation. 

The device used in the aborted BROADEN Trial of DBS for TRD is manufactured by another company.

As I've mentioned previously, the goal of the SUBNETS program is to develop devices that both stimulate and record neural activity, and provide real-time data that can be decoded as reflecting a particular behavioral state... basically, a futuristic implant that can adjust its own stimulation parameters based on how the patient is doing.

The new DBS trial for intractable depression (which is not yet open for participant recruitment)...
...will recruit 10 patients with advanced TRD and implant them with the Brain Radio system. The recording system will be to record LFP over 3 years, while patients reesceive stimulation. A brief discontinuation study will be conducted after 6 months of stimulation when the device will be turned off and patterns of LFP changes will be recorded. All LFP measures will be correlated with the primary clinical response outcome metric, the Hamilton Depression Rating Scale.

The Journal of Neural Engineering has just published a paper outlining the results of a two year study that tested the Activa® PC+S neurostimulator in a rhesus monkey (Ryapolova-Webb et al., 2014): Chronic cortical and electromyographic recordings from a fully implantable device: preclinical experience in a nonhuman primate.

The senior author on that paper (neurosurgeon Dr. Philip Starr) was one of the first to implant the device in a Parkinson's patient in the US.

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Saturday, January 18, 2014

BROADEN Trial of DBS for Treatment-Resistant Depression Halted by the FDA

Webpage for the BROADEN™ study formerly run by St. Jude Medical

It's become mainstream these days to say that psychiatric disorders are neural circuit disorders. You can even read all about it in the New York Times! Cognitive training and neuromodulation (“electroceuticals”) are in, and pharmaceuticals are out, as explained by NIMH Director Dr. Tom Insel in a blog post about the Ten Best of 2013:
...if mental disorders are brain circuit disorders, then successful treatments need to tune circuits with precision. Chemicals may be less precise than electrical or cognitive interventions that target specific circuits.

One of the first to champion this position was Dr. Helen Mayberg and her colleagues, who conducted a small trial using deep brain stimulation (DBS) as a treatment for intractable depression (Mayberg et al., 2005). The technique has been heralded as a potential breakthrough in psychiatry, with $70 million in BRAIN Initiative funding going to DBS development. So a recent tweet announcing the failure of a major clinical trial garnered a lot of attention.

The December 13, 2013 issue of the Neurotech Business Report had the scoop:
The news that St. Jude Medical failed a futility analysis of its BROADEN trial of DBS for treatment of depression cast a pall over an otherwise upbeat attendance at the 2013 NANS meeting. Once again, the industry is left to pick up the pieces as a promising new technology gets set back by what could be many years.

It’s too early to assess blame for this failure. It’s tempting to wonder if St. Jude management was too eager to commence this trial, since that has been a culprit in other trial failures. But there’s clearly more involved here, not least the complexity of specifying the precise brain circuits involved with major depression. Indeed, Helen Mayberg’s own thinking on DBS targeting has evolved over the years since the seminal paper she and colleague Andres Lozano published in Neuron in 2005, which implicated Cg25 as a lucrative target for depression. Mayberg now believes that neuronal tracts emanating from Cg25 toward medial frontal areas may be more relevant. Research that she, Cameron McIntyre, and others are conducting on probabilistic tractography to identify the patient-specific brain regions most relevant to the particular form of depression the patient is suffering from will likely prove to be very fruitful in the years ahead.

But it was hard to find any other information about the failed trial. I can't be sure, but I think this is the study in A Clinical Evaluation of Subcallosal Cingulate Gyrus Deep Brain Stimulation for Treatment-Resistant Depression. The sponsor is St. Jude Medical. The record hasn't been updated since March 2013.

BROADEN is a tortured acronym for BROdmann Area 25 DEep brain Neuromodulation.

The July 30, 2013 version of the BROADEN website is preserved at

The BROADEN (BROdmann Area 25 DEep brain Neuromodulation) study is a study to evaluate the safety and effectiveness of deep brain stimulation in patients with a severe form of depression known as Major Depressive Disorder (MDD) who have not responded to multiple treatments. Stimulation to the brain is provided by a surgically implanted medical device called a deep brain stimulation (DBS) system. The system provides stimulation directly to an area of the brain known as Brodmann Area 25 (sometimes referred to as BA25). The study will build upon the depression work of a research team from the University of Toronto, led by neurologist Helen S. Mayberg, M.D. and neurosurgeon Andres Lozano, M.D., PhD, FRCSC.

On January 10, 2014 an Anonymous commenter at DBS Trial1 said:
Regarding the Broaden Study, I'm not writing it off entirely but things aren't looking good. The FDA has put the brakes on the study so it will not enroll any new participants.
While the study is over a year old, the results so far are not encouraging and the device manufacturer is scaling back on monitoring and programming.
It appears that a possible major misstep was made, by not including fMRI mapping prior to implanting the electrodes. 

As Neurotech Business Report (NBR) mentioned, more precise mapping of the white matter connections of the subgenual cingulate (Brodmann area 25) may be essential (e.g., Johansen-Berg et al., 2008). To determine the anatomical connectivity of the subgenual cingulate region, those authors performed tractography (using diffusion-weighted magnetic resonance imaging) to trace the pathways mediating treatment response with DBS. They compared the connections of the subgenual ACC (sACC, blue/cyan) and the perigenual ACC (pACC, red/yellow).

Fig. 3 (Johansen-Berg et al., 2008). Connectivity-based parcellation of anterior cingulate cortex (ACC) and location of electrode contacts. Effective electrode locations are mainly localized within the sACC subregion.

A July 11, 2011 News Release from St. Jude Medical announced that the FDA had approved an expansion of the BROADEN Trial so that up to 20 different sites could enroll a total of 125 patients. There were only three sites originally Chicago, New York City and Dallas. Perhaps the trial resources were getting stretched too thin.

Another possibility raised by James Cavuoto
, Editor and Publisher of NBR, is that the FDA is too darn stringent in what it considers a treatment response:
Unfortunately, much of the progress in our understanding of DBS mechanisms in depression is potentially wasted without a vibrant installed base of patients and clinicians using and perfecting DBS therapies. ... In our view, the FDA needs to understand the vital importance of getting first-generation devices into the field and move away from arbitrary standards like improving symptoms by 50 percent in 50 percent of the population. The notion that if we can’t help everybody we shouldn’t help anybody has no place in medical science, particularly when you consider that neuromodulation therapies are working with the hardest-case patients who have not responded to other therapies.

Finally, there is the unfortunate possibility that DBS treatment in this patient group doesn't work as well as initially thought...

If anyone has additional information, please leave a comment.


1 This blog [EDIT:  i.e., the DBS Trial blog] is written by another individual [not me] who for the past four years has had an implanted device for the treatment of intractible depression.


Johansen-Berg H, Gutman DA, Behrens TE, Matthews PM, Rushworth MF, Katz E, Lozano AM, Mayberg HS. (2008). Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression. Cereb Cortex. 18:1374-83.

Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH. (2005). Deep brain stimulation for treatment-resistant depression. Neuron 45:651-60.

Further Reading:

A Depression Switch?

The Sad Cingulate

Sad Cingulate on 60 Minutes and in Rats

...But My Subgenual Cingulate Is Sad

Deep Brain Stimulation for Bipolar Depression

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Saturday, January 11, 2014

Neurocrap Funded by the Masses: NeuroOn and No More Woof

Crowdfunders, get a clue! You're throwing your money away on bogus prototypes for impossible technology! Why give your hard-earned cash to the equivalent of modern-day snake oil salesman instead of funding essential projects to bring clean water and hygienic toilets to third world countries?

First we have No More Woof, which was first brought to my attention by Professor Dwayne Godwin. Writing in, a blog sponsored by the Society for Neuroscience, he considers whether an EEG-to-speech converter for dogs is plausible [HINT: of course it's not!]:
What is proposed is a gadget that on the basis of a few dry EEG electrodes will do for a creature without known speech centers what we’ve been unable to do for humans (with well-defined speech centers) using the best EEG systems yet developed.

In other words, don't you think you would have heard about a device that could translate the brain waves of a person with speech difficulties due to Broca's aphasia or ALS into fluent sentences? Gizmodo and the New York Times and even Oprah would be all over it!

Here's what the No More Woof developers have to say:
Every mammal creates and transports "thoughts" the same way, as a swarm of electrical signals through a complex neurosystem). It has long been possible to record this activity through Electroencephalogram (EEG) readings. When it comes to humans, the last decade has seen tremendous progress.

However every species uses its unique structure. You could say that all creatures speak the same language only with varying dialects. And as animal brains are less complex than humans their signal patterns are more distinct for feelings of anger, curiosity or tiredness – actually making them easier to distinguish.

There's absolutely no scientific evidence for distinguishing "anger" and "curiosity" brain signals in dogs, especially via a cheap ($65) doggie EEG headset with only one electrode.

What we really need is Professor Schwartzman's canine decoder!

The campaign has already raised $19,152 of their $10,000 goal. And there's 35 days left! So save your money!

But at least the No More Woof developers have issued a caveat. We can't say the same about our next prototype...

NeuroOn: World's first sleep mask for polyphasic sleep

Why waste any time with a trivial and unimportant activity such as sleep? The NeuroOn developers promise their device will deliver a "unique sleep schedule" that will maximizes each user's waking time... up to 22 hours a day! You'll become an efficient and brilliant productivity machine, just like Da Vinci, Tesla, Churchill and even Napoleon!
In conclusion, through great sleep efficiency, Polyphasic sleep can give you an extra 4 hours of free time every day. That’s up to 28 hours (1 day+) a week, 1460 hours a year.

That’s right - Your year now has over 420 working days!

What is polyphasic sleep? It's the division of sleep into several bouts per day, instead of the usual 8 hours or so at night. This schedule is standard in some mammals and may serve a protective purpose, according to Capellini et al. (2008):
The duration of [REM and non-REM] cycles varies extensively across mammalian species. Because the end of a sleep cycle is often followed by brief arousals to waking, a shorter sleep cycle has been proposed to function as an anti-predator strategy. Similarly, higher predation risk could explain why many species exhibit a polyphasic sleep pattern (division of sleep into several bouts per day), as having multiple sleep bouts avoids long periods of unconsciousness, potentially reducing vulnerability.

In humans, "disentrainment" protocols isolate volunteers under strict lab conditions and remove all cues to the time of day. In one study, 50 participants were allowed to eat and sleep at any desired time over a 72 hour period (Campbell & Murphy, 2007). Activity options were limited to a set playlist of recorded music, a deck of cards, and a small anthology of poetry. No strenuous exercise, TV, videos, work, study or hobbies. Why? To look at natural sleep tendencies unencumbered by that Battlestar Galactica marathon you've always wanted.

On average, the participants slept for 27.67 hrs of the 72 hour disentrainment period. That's 9.22 hrs every 24 hours, which was verified by EEG recordings (not based on self-report, as in an earlier study). There was an average of 7.6 sleep episodes per subject (instead of the standard 3 bouts each night). The mean duration of sleep episodes was 3.27 hrs but this varied wildly, with a range of 0.33-13.57 hrs. And the younger subjects (30 and under) slept longer and spent more time in REM than the middle (31-59 yrs) and older (60 and over) subjects.

What is polyphasic sleep according to the NeuroOn team?
It is a term referring to alternate sleep patterns that can reduce the required sleep time to just 2-6 hours daily. It involves breaking up your sleep into smaller parts throughout the day, which allows you to sleep less but feel as refreshed as if you slept for 8 hours or more.

Although I could be wrong, the majority of NeuroOn backers are presumably young and therefore will require more sleep than their older counterparts. Have the developers taken age differences into account?

But but,you say, these techie hipsters spend their lives on more valuable and fulfilling activities than reading poetry and playing solitaire (with an actual deck of cards)!! So of course they don't need as much sleep!

So sure, we can criticize the exaggerated claims that humans have a minimal need for sleep, with wondrous increases in productivity as a result of adopting a proprietary "unique sleep schedule". All without developing a serious psychiatric condition! While ignoring the necessity to medically screen users in the event that such a device would actually work.

The real impetus for writing this post, however, came from Justin Kiggins:

The ensuing discussion on Twitter included debunking of the entire technical premise of the device, which uses a limited number (one? three?) of ill-placed electrodes to purportedly record a wide variety of electrical signals.

Let's take a closer look at the prototype. Is that really only one electrode?? * That uses a magical "dedicated and extraordinary biological amplifier" and AI algorithms that can filter and distinguish the differing source generators and frequency bands for EEG, EMG, and EOG? Without a reference electrode connecting to the differential amplifier?

* ADDENDUM Jan 12 2014: No, that is “a part to generate physical vibration.” There are 3 electrodes, as shown in the prototype image further down.

PCB version 2.1

The developers claim:
Thanks to the use of the newest technologies we were able to create a device that will improve your effectiveness and concentration at work to the best possible levels. Measurements of EEG, EOG and EMG, coupled with the usage of artificial intelligence, allows us to create the world's first digital sleep-control system that provides accuracy close to professional polisomnographic clinics.

According to what criteria? Which published studies? Because here's a paper from a group of clinical EEG experts on how difficult it was to reach a consensus on Standardized Computer-based Organized Reporting of EEG (SCORE):
The interobserver agreement in electroencephalography (EEG) interpretation is only moderate (Van Donselaar et al., 1992; Stroink et al., 2006). The EEG signal has a high complexity. It depends on the intricate interplay between the activation of neural networks, localization and orientation (Wong, 1998) of the source (dipole), and its propagation throughout the brain (Lopes da Silva & van Rotterdam, 1993; Scherg et al., 1999; Flemming et al., 2005).

Current prototype (the backside view)

So those three gray squares sitting on your eyebrows are the recording electrodes that will distinguish eye movements like those during REM sleep (very large amplitude signals) from actual brain activity (very tiny signals)? And when the A to D output is transmitted wirelessly via bluetooth to a smartphone application, the app will wake you up precisely at the end of a REM sleep cycle? AND will induce lucid dreaming on demand, so you can literally control your dreams. Really??

No.  Dream on.

And the sad thing is that hundreds of people have pledged $250 to buy a device that will not deliver what's promised.

What is your dream?

Do you need more energy and to feel well - rested?
Do you want to pack even more into your day?
Do you want to have more control over your day?
Do you hate jet lag?
Do you just need that few extra hours every day?
Do you want to be a hero by day and a superhero by night?
Or maybe it's not so sad... people are always susceptible to snake oil and miracle cures, only now in a high tech faux-neuro guise. As of this writing, 1,901 backers have pledged $431,114, far surpassing the $100,000 goal.  Only 15 hours to go!

Don't you think it's more important to expand access to clean water and improved sanitation in poor, rural households in Vietnam? This Kiva microloan has raised 61% of its $4,750 goal, with $1,850 to go before Jan 27, 2014.

Further reading:

Dormivigilia (an actual sleep researcher) on sleep

Gaines on Brains on sleep tracking apps and why their premise is flawed

ADDENDUM #2 (Jan 12 2014): Since a commenter mentioned the Zeo headband (made by the now-defunct company Zeo, Inc.), I thought I'd say a few words about it here. The company published a paper in the Journal of Sleep Research (Shambroom et al., 2012) that examined the performance of their wireless system (WS) to professional polysomnography (PSG; see Gaines on Brains for more on sleep EEG). The Zeo agreed with the simultaneously recorded PSG sleep stages 75% of the time over the course of a night. However, the Zeo did poorly at the detecting onset of the first REM episode:
"The WS significantly and substantially underestimated REML compared to PSG. There were nine nights for which the WS scored REM within the first 6 min of sleep, possibly indicating a tendency for the technology to score REM in the early lightest stage of sleep."
The headband has 3 electrodes on the forehead like NeuroOn and used an Fp1-Fp2 bipolar recording montage (two standard left and right frontopolar sites on the forehead). EEG recorded here is particularly prone to artifacts from eye movements and muscle activity and is thus a mixture of all these signals. Analytic techniques such as independent component analysis (ICA) try to separate the sources. The Zeo group used some sort of training algorithm that used "a combination of time and frequency dependent features derived from the signal to create a best estimate of sleep stage." Interestingly, they had to filter out the very low frequencies (below 2 Hz) that comprise much of the delta wave activity seen during slow wave sleep. This was because of contamination by excessive noise in the low frequency range.

I have no idea of how any of Zeo technology relates to that used by NeuroOn, but the published paper presented some of the challenges involved in developing such a system.

ADDENDUM #3 (Jan 12 2014): While I'm at it, I should mention another neurocrap Kickstarter project -- Aurora: The Dream-Enhancing Headband, which was brought to my attention by Micah Allen. Save your money! If you want to support a worthwhile project, try OpenBCI: An Open Source Brain-Computer Interface For Makers, recommended as legit by Neurobonkers.

ADDENDUM #4 (Jan 13 2014): New post from a sleep researcher: Nonsense neurogadgets: sleep edition, at Taking a cat apart.

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