When acronyms are not

From a current Journal of Neuroscience abstract:

To identify genes downstream of BDNF that may play roles in psychiatric disorders, we examined a subset of BDNF-induced genes also regulated by 5-HT (serotonin), which includes the neuropeptide VGF (nonacronymic)

Neuropeptide VGF (nonacronymic)? WTF? As if crazy acronyms like BDNF (brain derived neurotrophic factor) weren't confusing and non-mnemonic enough. And who, given a rare opportunity to name something, squanders it on a random sequence of letters? Clearly, there's some in-joke here that I'm missing.

Improve your memory by pharmacologically disabling it when it is not needed

And you thought resveratrol was hot...

Paradoxical Facilitatory Effect of Low-Dose Alcohol Consumption on Memory Mediated by NMDA Receptors

Maggie L. Kalev-Zylinska and Matthew J. During

Epidemiological studies have suggested a negative correlation between alcohol intake and Alzheimer's disease. In vitro, ethanol negatively modulates NMDA receptor function. We hypothesized that chronic moderate alcohol intake leads to improved memory via adaptive responses in the expression of NMDA receptors and downstream signaling. We fed liquid diets containing no, moderate, or high amounts of ethanol to control and matched rats with hippocampal knock-down of the NR1 subunit. Rats with increased hippocampal NR1 expression were also generated to determine whether they had a phenotype similar to that of ethanol-fed animals. We found that moderate ethanol intake improved memory, increased NR1 expression, and changed some aspects of neurotrophin signaling. NR1 knock-down prevented ethanol's facilitatory effects, whereas hippocampal NR1 overexpression mimicked the effect of chronic low-dose ethanol intake on memory. In contrast, high-dose ethanol reduced neurogenesis, inhibited NR2B expression, and impaired visual memory. In conclusion, adaptive changes in hippocampal NMDA receptor expression may contribute to the positive effects of ethanol on cognition.

Boris: Wandering through Plato's cave

Boris is something of a chameleon in the drone doom community. Indeed, they might well object to any label being put on their creative output. While they do have songs in which single notes are drawn out until it seems they must snap and percussion is dispensed with as an unnecessary adulterant of pure tones and feedback, they also frequently display distinctly punk sensibilities, and are comfortable within the psychedelic rock idiom. Their vocals in particular display an intensity which seems rooted in political or personal concerns, rather than the existential terror or universal hatred which drip from the ragged edges of most black metal rasps. Being a drone doom aficionado myself, I think Boris reaches their peak when they veer towards the abstract and leave out the more quotidian vocals.

Their collaborations with Merzbow deserve particular mention. Merzbow seems to provide a textured but emotionally neutral backdrop against which Boris' pure tones can shine out like jewels. I've sometimes compared Ulver's Nattens Madrigal to being awoken late at night by a ringing telephone and picking up the receiver only to find God Himself on the line. The connection is poor and the line full of static, but it is abundantly clear that this is not the all forgiving God of the new testament, nor even the vengeful but rationally-minded God of the old testament. Rather, this is a being of wrath divorced from mortal notions of reason. Lovecraft's idiot flutist Azathoth blares into the line, barely constrained by the medium's bandpass filter, calling down an apocalypse which represents not moral judgment but the inevitable triumph of entropy. Just as Ulver conjures a deranged deity thrust into the modern world through the most banal tool of communication, Boris and Merzbow bring us into Plato's cave. The rough-hewn walls are solid, but devoid of intellectual or emotional presence. Against their mindless physicality dance pure ideas, freed from their earthly trappings by the stabilizing matrix of rock surrounding them. While the mental and the physical are inextricably wed, Boris and Merzbow draw the connection into a thin thread. The abstract and corporeal move independently, throwing each other into deeper contrast.

In their independent efforts, Boris provides this tension with the abstract through alternative routes. Mental and physical intertwine more tightly, but the result is a dance between yin and yang, rather than a uniform composite. Soaring notes reach out, only to be drawn under by the crash of cymbals and feedback. Their music often has an agitated energy which feels almost carnal, like the buzz of amphetamines, limbs vibrating and twitching of their own accord while the mind wanders elsewhere, only loosely coupled to the pumping pistons of the body. Other times, the music retreats into a contemplative fugue, acoustically fleshing out quiet corners of the world, speaking to lost moments spent alone, almost divorced from the self. In all cases, the result screams craftsmanship and quality.

Computational horsepower: Natural vs artificial systems

An interesting exercise in dimensional analysis:

There are about 10^11 neurons in the brain, with about 10,000 synapses per neuron, yielding approximately 10^15 synapses total. Extracellular electrophysiology would have you believe that the average pyramidal (excitatory) neuron fires at about 10-20 Hz (inhibitory neurons fire even more rapidly), but there is a strong bias towards recording from more active neurons. It's hard to locate silent neurons with an extracellular electrode, since you can only determine that you are near a neuron when it fires. Intracellular electrodes may also be biased towards larger cells, since they are probably easier to spear (or clamp onto, depending upon technique), but almost all in vivo recordings are performed using extracellular electrodes. Arguments based upon metabolic rates suggest that the average firing rate is closer to 1 Hz, but I don't have the actual papers at my fingertips. I'll fish it out the reference if challenged. The traditional leaky-integrate-and-fire model of neural activity suggests that depolarization / shunting / hyperpolarization delivered to synapses throughout the dendritic tree and soma sum linearly in the soma (subject to a low-pas filter), and the neuron fires an action potential when its membrane potential exceeds some threshold. Polsky, Mel, and Schiller (2004), amongst other recent papers, implies that individual dendrites or dendritic compartments actually contain separate computational subunits, utilizing the nonlinear voltage-gated and NMDA channels to perform a thresholding operation similar to that normally ascribed to the axon hillock (where action potentials are initiated).

Let's be generous and assume that each thresholding operation roughly corresponds to a single floating point operation. We can also reasonably estimate that there are 100 such thresholding sites in the dendritic tree, and they perform thresholding operations (i.e., floating point operations) at the same rate that their inputs fire. The human brain then runs at approximately 10^11 neurons * 10^2 thresholding sites / neuron * 1 Hz = 10^13 flops. Bounding our estimate on the other side by assuming that each synapse performs a floating point operation each time it receives a spike and that the average neuron fires at 10 Hz, we find that the brain performs at most about 10^15 synapses * 10 Hz = 10^16 flops. The world's fastest supercomputers run at about 100 teraflops, or 10^14 flops, whereas desktop computers can achieve about 10^10 flops. Furthermore, Moore's law implies that computer performance should double approximately every 24 months. This suggests that computers are very close to the computational capacity of the brain.

Of course, this doesn't imply that we can simulate such a brain. The biophysics underlying these abstract computations is orders of magnitude more complex than the computations themselves. The blue brain project is currently struggling to simulate a single cortical column with a scant 10,000 neurons. To make efficient use of our available computational power to simulate the high-level activity of the brain, we would first need to know the basic algorithms the brain is computing.

Top search keywords

For your amusement, here are some of the search terms which led people to this blog:

amps that really go to 11
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wolves in the thrown room (the band is wolves in the throne room; the homophone leads to a slightly different mental image)

Seek and ye shall find.

Oliver Sacks, on mountains of amphetamine, mescaline, and cannabis

Stolen without remorse from a Wired interview with Oliver Sacks about his new book on music and the brain:

Hume wondered whether one can imagine a color that one has never encountered. One day in 1964, I constructed a sort of pharmacological mountain, and at its peak, I said, "I want to see indigo, now!" As if thrown by a paintbrush, a huge, trembling drop of purest indigo appeared on the wall — the color of heaven. For months after that, I kept looking for that color. It was like the lost chord.

Then I went to a concert at the Metropolitan Museum of Art. In the first half, they played the Monteverdi Vespers, and I was transported. I felt a river of music 400 years long running from Monteverdi's mind into mine. Wandering around during the interval, I saw some lapis lazuli snuffboxes that were that same wonderful indigo, and I thought, "Good, the color exists in the external world." But in the second half I got restless, and when I saw the snuffboxes again, they were no longer indigo — they were blue, mauve, pink. I've never seen that color since.

It took a mountain of amphetamine, mescaline, and cannabis to launch me into that space. But Monteverdi did it too.

Apophenia, take 2

After some additional consideration, I think my Apophenia post was unfair. Humans, and indeed mammals in general, are ridiculously good at detecting and utilizing correlations. But only particular types of correlations which they have been evolutionarily prepared to expect and process. Consider that darling of experimental neuroscience, the rat. Rats will learn to associate a tone with a foot-shock in only a few trials, if the tone is brief, co-terminates with the foot-shock, and if the tone predicts the shock with high reliability. If the tone is more than a few seconds long before the shock occurs, if there is a substantial gap between the tone and the shock, or if the tone occurs often without a shock, the rat will not learn the relationship. Similarly, rats can learn that water with a distinctive taste is correlated with nausea after only a single pairing, even if the nausea occurs hours after the water is consumed, but they cannot learn that lights and sounds are correlated with nausea.

You might now quite reasonably be thinking that learning to associate tones and shocks is not very impressive, and that I promised quality correlation detection. The tone-shock combinations are unnatural and thus akin to the correlations in the Apophenia post. Rats rarely encounter electrified grids hooked up to speakers in the wild. The ability to associate foods with illness is no mean feat, given the time spans involved (although it can go awry - if you've ever eaten a distinctive-tasting food while sick and later vomited, you likely found that you had lost your taste for that food. I didn't care much for lobster for most of my youth after my father brought home a special treat one evening when I had an ear infection. Cancer patients undergoing chemotherapy are often left staring down the business end of this phenomenon). But the brain (and the cortex in particular) really comes into its own when processing complex instantaneous sensory stimuli.

Consider the same rat which couldn't remember that it was going to receive a shock after hearing a bell because we nefariously inserted a five-second delay between the two stimuli. If you stick that rat in a big pool of opaque water (they use some sort of latex beads, I think) with a small platform hidden just below the surface of the water, the rat will swim around at random until stumbling upon the platform, at which point it will immediately climb up and out of the water (this is called a Morris water maze. It's generally used to test spatial memory. Note that while they're pretty good swimmers, rat's don't bathe recreationally). If you now pick the rat up, blindfold it, swing it around your head a few times to disorient it, and put it back in the pool at some random location, it will immediately swim back to the platform.

Amazing! After a single trial, the rat learned to associate the complex visual stimulus perceived at a particular location in the pool with the position of the platform. Even though this visual stimulus changes completely depending upon the direction in which the rat is facing (they don't have to approach the platform from the same direction each time). Even though the visual stimulus associated with other positions in the pool is virtually identical to that at the platform. Even though rats are not very visual animals (they rely primarily upon olfaction and tactile sensation (remember the whiskers!)). How the hell was the rat able to figure out that some subtle variation in the pattern of light falling on its retina indicates a nice dry spot to chill out, whereas almost identical patterns would leave it treading water until it drowned from exhaustion? (Of course, as the benevolent experimenter, you would rescue our friend the rat before it met its untimely demise in a kiddy-pool of milky water. Right? Right!?!?!)

Neither neuroscientists nor computer scientists have a convincing answer to this question. If you've ever tried to use voice-recognition software on a computer, you are familiar with how bad computers are at processing sensory input. The reason you've never even seen a computer vision recognition system is that they're even worse. State-of-the-art algorithms can recognize perhaps dozens of different categories of objects, but they are much less nuanced in their discriminations than a rat. For instance, most such systems are baffled by objection rotations and partial occlusion. The brain, in contrast, detects the necessary high-order correlations with such ease that you don't even realize how difficult the task is.

Remember Clive Wearing

Every introductory course on neuroscience or psychology makes mention of H.M., a man who's medial temporal lobes (including the hippocampus and surrounding structures) were removed to treat drug-resistant epilepsy. After the operation, H.M. lost the ability to form new long-term memories, as well as most of his memory for the ten or so years before the surgery. (Ironically, H.M. has made a greater contribution to human knowledge than all but a handful of professional scientists, but he will never be able to appreciate the impact he's had.) H.M.'s case is canonical because it is the only instance where the connection between brain damage and subsequent amnesia is so clear. Indeed, no surgeon would have taken such drastic action had they known the effects, and no equivalent operation has been performed since (at least on humans). But H.M. is not alone in suffering from anterograde (can't form new memories) and graded retrograde (loss of memories of the recent past) amnesia. Korsakoff's amnesia is brought on by thiamine (vitamin B1) deficiency, primarily in alcoholics who derive a large percentage of their caloric intake from alcohol. The hippocampus can also be damaged by stroke, hypoxia, and infections.

One of the most acute known cases of amnesia is that of Clive Wearing (chronicled recently in this article by Oliver Sacks), whose temporal and frontal lobes were damaged by herpes encephalitis. Unlike H.M. and other amnesiacs, Mr. Wearing remembers nothing at all; his entire experience is restricted to the minute or two available through working memory (the short term memory which underlies active though processes, often believed to have a capacity of 7 +/- 2 "chunks"). Every time Mr. Wearing is distracted, he awakens to an entirely new and unfamiliar reality. For years, Mr. Wearing has kept a diary. Each entry contains the current time and a record of the profound realization that he is now, for the first time, alive and conscious. He then notices the previous entries. Pages of them. All making the same claim. All in his own familiar handwriting. All written by some unremembered stranger. He goes back, systematically crosses out these false entries, and underlines the current entry. The first true entry. He sets the diary down, glances out the window, and awakens for the first time.



Mr. Wearing has more to teach us than the dependency of memory formation and access on certain brain structures. His condition is not so different from our own. Consciousness is inextricably tied to the present moment. Our past and our future belong to other people. People who occupy the same body, in the same world, but who are tied together only by the hallucination of memory.

Apophenia

Humans are horrible at noticing unexpected connections between large number of variables. When I was living in LA, driving took on an added measure of excitement during a heavy rainfall. Not because of reduced visibility or the slickness of the road as months of impacted dust and oil were finally loosened and left to form a thin, low-viscosity film over the asphalt. Rain has those effects on roadways across the world. In New York or Boston, the dangers of driving in the rain are hammered into new motor vehicle operators before the first drop of precipitation taps their moving windshields. Southern Californian drivers, in contrast, are faced with rain so infrequently that the subject seems to be passed over in high school driver's ed. Many are slow to discover the relationship between rain and reduced traction on their own. Even the occasional skid while blasting through tight curves at 60 mph or faster doesn't seem to clue them in to a possible causal interaction. On the evening after a heavy rainfall, there is inevitably a car or two lying inoperable on the sides of the 110. The stories I heard about cars spinning 360 in the middle of the roadway were even more disturbing.

Another example: One summer in college, I was baffled by the seemingly unpredictable variations in my level of motivation when working in the afternoons. Some days I was hungry and tired and disengaged as the afternoon wore into the evening. Other days, I was consumed by my research and barely thought about dinner. I thought the difference might be due to some aspect of my diet or sleep pattern, but I couldn't find any consistent covariations. I even considered the possibility that I was going into ketosis (which of course is patently absurd). Only after the fact did I come to realize that the difference must have been due to the color of the coffee pot. I had always assumed that caffeine had relatively little effect on me and drank coffee because I liked the taste. So I didn't really pay attention to whether I poured my coffee from the brown (caffeinated) pot, or the orange (decaffeinated) pot. In retrospect, I was as naive as the LA drivers who refuse to ease up on the gas peddle during a downpour.

Which brings us to the present day. Up until last Tuesday, I was in a multi-week funk, feeling not just tired, but less conscious than usual. I was sleeping long and deeply, but it just wasn't doing me any good. Philosophers refer to entities that behave just like people but which aren't conscious as zombies. That's what I felt like, perhaps with the addition of a little homunculus sealed off behind one-way, sound-proof glass, allowed to watch the proceedings but unable to exert any control. Then on Tuesday, the funk magically lightened. I can't say I feel 100%, but it's certainly better. What brought on this descent into the voodoo nether-world? What precipitated my slow return? Here we are once again faced with a superflux of variables and no sign of a correlation. I'm sure there's a simple explanation, but I'm equally sure that I will never find it. My best guesses are:

a) After spending a week or two going all hard-core on the German learning, I gave up again. I can't remember the citation off the top of my head, but I'm pretty sure that REM sleep has been shown to be correlated with language learning. That is, immersion in a foreign language increases the amount of REM sleep, and the magnitude of this increase is correlated with the amount of learning. Perhaps my foolish attempts to learn the local language were saturating my REM sleep time, leaving me semi-sleep deprived despite eight hours in bed.

b) The gym finally reopened. It had been closed for the previous two weeks. For cleaning. In the US, the cleaning would have been done at night. Or one section of the facility would have been closed off at a time, leaving the rest functional and open. I can only assume that a phalanx of temporary employees was brought in, issued toothbrushes, and spent ten eight-hour days on their hands and knees, scouring every surface. Either that or they sealed off all the entrances and flooded the building with dilute hydrogen peroxide. When I was finally allowed back in Monday night, the gym was indeed clean. But it was clean before they shut down. Which is to say, I couldn't see that their extensive efforts made any difference. Regardless, I was finally able to lift heavy things and put them down again, after two weeks of just running in circles. This change in my exercise routines may have directly or indirectly affected my energy level.

In the end, I'm probably just an obsessive-compulsive hypochondriac, and it was all in my head to begin with. But the point remains that people are bad at detecting unexpected correlations.

Coffee machine: The legend continues

So I managed to get to the Migros on Saturday with a few minutes to spare before the 5pm closing time. I don't think my roommate bought my story that the coffee machine's great aunt was a phoenix, and that it was consumed in a burst of flame and born anew from the ashes. The slag of its predecessor in the sink might have tipped her off.

On Sunday, I set out to make my first cup of coffee with the gleaming new aluminum marvel. I even managed to read the instructions in German only to discover that, for the past year, I've been packing in the coffee grounds too tight and brewing the coffee over excessive heat. With my ground coffee loosely set in the filter and the flame turned down to medium, I awaited the black nectar that would soon gush from the top of the spout. Except that it didn't. Rather, it bubbled out of the side of the machine and pooled on the top of the oven. I did manage to extract enough juice to have my morning cup of coffee, but the residue in the bottom of the pot revealed a rift extending along perhaps a quarter of the bottom edge of the pot.

Made in Italy. Worthless. Apparently, Italian aluminum is very delicate and tears when subjected to too much force. Even when it is a couple of millimeters thick.

So I'm now on my third coffee machine in three days. Folk wisdom holds that this attempt should be charmed, but I'm not holding my breath.