On Circadian Rhythms & Physiology

from reference 1


Circadian rhythms govern our state of arousal, informing us when to go to sleep and (for some) pulling us up from the pleasant depths of slumber. Further, because the physiological goals of sleep are so different from wakefulness (learning while awake & consolidating memories while asleep, using muscles to do work during the day & repairing them at night, et cetera), the circadian rhythm is also used to regulate many bodily properties and dynamics. An example of this can be found in a recent paper published in the journal Cell¹. The authors of this study found that the degree of electrical coupling between rod cells and cone cells in mice and goldfish is modulated by circadian rhythms.

Rod cells are relatively color-insensitive cells in the eye while cone cells are color-sensitive (with different subtypes having being sensitive to different parts of the spectrum). Thus, for the purposes of accurate perception of the visual world, one wouldn't normally want to link the activity of rods and cones because this would mix the color-insensitive responses with the color-sensitive ones, effectively washing out color information. However, as the day goes on and it gets dark, the argument goes, color matters less, and the paucity of light leads to the strategy of pooling responses across all light-responsive retinal cells. This is what is achieved by such circadian-rhythm-induced electrical coupling, pooling of responses to illumination.

References:
1. Ribelayga C, Cao Y, Mangel SC. The circadian clock in the retina controls rod-cone coupling. Neuron, 59: 790-801, 2008.

On Martian Snow

As reported in the Washington Post, NASA's Phoenix Lander (pictured above) has detected snowfall on Mars. Using LASER based scanning technology, the remote probe was able to spot flakes in the atmosphere and track their descent for more than a mile. However, Phoenix was not able to discern whether the snow actually landed on the surface of the planet. The idea, however, of snow-fall on Mars is a romantic and beautiful one, it just blossoms in my imagination.

On the 2007 Science and Engineering Visualization Challenge

A runner-up in the photography category.

Each year, Science magazine and the National Science Foundation hold a competition to select the best of the best in scientific imagery. Awards are given in several categories, and the contents range from tiny sub-domains to entire galaxies. These renderings are freely available to all on Science Magazine's website.

On The Genetic Basis of Schizophrenia

"... what a narrow ridge of normality we all inhabit, with the abysses of mania and depression yawning to either side."¹


from reference 2


Schizophrenia is a debilitating condition, chronic in nature, that affects approximately 1 in a hundred people worldwide. Although able to strongly suggest a genetic basis, past research has not been truly successful in determining the hereditary underpinnings of this combined neurological and psychiatric disorder.


from reference 3


Two papers, published in the journal Nature, have pushed this field of research farther than ever before, establishing schizophrenia-relevant chromosomal loci and using larger numbers of patients than in the past, for stronger statistical power^2,3. These studies focused on two types of chromosomal abnormalities, single nucleotide polymorphisms (SNPs; changes to single bases) and copy-number variations (CNVs; changes in the number of copies of one or more whole genes). Both studies confirmed previous findings of a CNV locus associated with schizophrenia, and validated each other's implication of two new CNV loci. Although it is still unclear how such information might be used, this is a cause for enthusiasm regarding the treatment of schizophrenia, and the possibility of determining genetic basis for other psychiatric disorders.

References:
1. Sacks, O. A Summer of Madness. The New York Review of Books, LV(14): 57-61, 2008.

2. Stefansson H, Rujescu D, Cichon S, Pietiläinen OP, Ingason A, Steinberg S, Fossdal R, Sigurdsson E, Sigmundsson T, Buizer-Voskamp JE, Hansen T, Jakobsen KD, Muglia P, Francks C, Matthews PM, Gylfason A, Halldorsson BV, Gudbjartsson D, Thorgeirsson TE, Sigurdsson A, Jonasdottir A, Jonasdottir A, Bjornsson A, Mattiasdottir S, Blondal T, Haraldsson M, Magnusdottir BB, Giegling I, Möller HJ, Hartmann A, Shianna KV, Ge D, Need AC, Crombie C, Fraser G, Walker N, Lonnqvist J, Suvisaari J, Tuulio-Henriksson A, Paunio T, Toulopoulou T, Bramon E, Di Forti M, Murray R, Ruggeri M, Vassos E, Tosato S, Walshe M, Li T, Vasilescu C, Mühleisen TW, Wang AG, Ullum H, Djurovic S, Melle I, Olesen J, Kiemeney LA, Franke B, Sabatti C, Freimer NB, Gulcher JR, Thorsteinsdottir U, Kong A, Andreassen OA, Ophoff RA, Georgi A, Rietschel M, Werge T, Petursson H, Goldstein DB, Nöthen MM, Peltonen L, Collier DA, St Clair D, Stefansson K, Kahn RS, Linszen DH, van Os J, Wiersma D, Bruggeman R, Cahn W, de Haan L, Krabbendam L, Myin-Germeys I; Genetic Risk and Outcome in Psychosis (GROUP). Large recurrent microdeletions associated with schizophrenia. Nature, 455(7210):232-236, 2008.

3. Stone JL, O'Donovan MC, Gurling H, Kirov GK, Blackwood DH, Corvin A, Craddock NJ, Gill M, Hultman CM, Lichtenstein P, McQuillin A, Pato CN, Ruderfer DM, Owen MJ, St Clair D, Sullivan PF, Sklar P, Purcell SM, Stone JL, Ruderfer DM, Korn J, Kirov GK, Macgregor S, McQuillin A, Morris DW, O'Dushlaine CT, Daly MJ, Visscher PM, Holmans PA, O'Donovan MC, Sullivan PF, Sklar P, Purcell SM, Gurling H, Corvin A, Blackwood DH, Craddock NJ, Gill M, Hultman CM, Kirov GK, Lichtenstein P, McQuillin A, O'Donovan MC, Owen MJ, Pato CN, Purcell SM, Scolnick EM, St Clair D, Stone JL, Sullivan PF, Sklar P, O'Donovan MC, Kirov GK, Craddock NJ, Holmans PA, Williams NM, Georgieva L, Nikolov I, Norton N, Williams H, Toncheva D, Milanova V, Owen MJ, Hultman CM, Lichtenstein P, Thelander EF, Sullivan P, Morris DW, O'Dushlaine CT, Kenny E, Waddington JL, Gill M, Corvin A, McQuillin A, Choudhury K, Datta S, Pimm J, Thirumalai S, Puri V, Krasucki R, Lawrence J, Quested D, Bass N, Curtis D, Gurling H, Crombie C, Fraser G, Kwan SL, Walker N, St Clair D, Blackwood DH, Muir WJ, McGhee KA, Pickard B, Malloy P, Maclean AW, Van Beck M, Visscher PM, Macgregor S, Pato MT, Medeiros H, Middleton F, Carvalho C, Morley C, Fanous A, Conti D, Knowles JA, Ferreira CP, Macedo A, Azevedo MH, Pato CN, Stone JL, Ruderfer DM, Korn J, McCarroll SA, Daly M, Purcell SM, Sklar P, Purcell SM, Stone JL, Chambert K, Ruderfer DM, Korn J, McCarroll SA, Gates C, Daly MJ, Scolnick EM, Sklar P. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature, 455(7210):237-241, 2008

On Subconscious Action

from reference 1


The subconscious components of our minds are more powerful than many admit, or feel comfortable admitting. As we go about our lives, our subconsciousness learns about aspects of our existence that might otherwise clutter our thoughts with a distracting chatter of activity: what pressure must I apply to the coffee cup in order for it to remain in my grasp, what route must I take through the throng of commuters in Penn-station to avoid colliding with others, has my blood-sugar dropped below the threshold where I experience hunger, et cetera. In fact, to some extent, the subconscious mind has access to information that the conscious mind does not, as in the muscle tension and blood-sugar examples. Understanding how these abilities are segregated between conscious and unconscious, and to what extent that question even makes sense to ask at both a behavioral and neurophysiological level are of fundamental interest to the understanding of consciousness and human neurological function in general.

A recent study speaks to this topic by probing the extent to which the subconscious can learn about the association between briefly presented visual cues and a monetary reward¹. Specifically, Chris Frith & colleagues had subjects play a game where the ability to win money in a given turn of the game was predicted by a visual cue which was presented too briefly to be consciously perceived (see instructions below²). The results of this study suggest that humans are reliably able to subconsciously learn the rewarding value of these visual cues. Importantly, in a control experiment, the researchers demonstrated that the subjects were unable to discriminate between the stimuli without the monetary reward/punishment scheme.

Given the abilities of humans (sketched above) to relegate processing to the subconscious, this finding isn't that surprising. However, this paper demonstrates the importance of feedback (reward or punishment) for instructing the subconscious. Furthermore, the fact that something as arbitrary as the conscious perception of promised financial reward can serve as the feed-back signal suggests a fundamental role for this type of learning that isn't limited to certain acts, but might underlie the learning abilities of humans in general.

References/Notes:
1. Pessiglione M, Petrovic P, Daunizeau J, Palminteri S, Dolan RJ, Frith CD. Subliminal instrumental conditioning demonstrated in the human brain. Neuron, 59(4): 561-567, 2008.

2. "The aim of the game is to win money, by guessing the outcome of a button press.

At the beginning of each trial you must orient your gaze towards the central cross and pay attention to the
masked cue. You will not be able to perceive the cue which is hidden behind the mask.

When the interrogation dot appears you have 3 seconds to make your choice between
- holding the button down
- leaving the button up
If you change your mind you can still release or press the button until the 3 seconds have elapsed.

‘GO!’ will be written in yellow if, at the end of the 3 seconds delay, the button is being pressed.

Then we will display the outcome of your choice. Not pressing the button is safe: you will always get a
neutral outcome (£0). Pressing the button is of interest but risky: you can equally win £1, get nil (£0) or
lose £1. This depends on which cue was hidden behind the mask.

There is no logical rule to find in this game. If you never press the button, or if you press it every trial,
your overall payoff will be nil. To win money you must guess if the ongoing trial is a winning or a losing
trial. Your choices should be improved trial after trial by your unconscious emotional reactions. Just
follow your gut feelings and you will win, and avoid losing, a lot of pounds! "

On Tree Drinking

from reference 1


Plants don't have hearts to pump fluids throughout their systems, so how do they generate the pressure to move water against the force of gravity from their roots to their shoots (leaves)? Capillary action (the tendency of a fluid to move through small spaces due to it's molecular constituents cohesive properties or surface tension) can explain the movement of water over small distances, but it cannot account for the large scale movement of water from the bases to the tips of tall trees like the Giant Sequoia of Redwood Forest.

Instead, it has long been thought that evaporation of water at the leaves draws water up in a long continuous column from the root, a process known as transpiration. This hypothesis was recently verified in the form of an artificial model¹. Abraham Stroock and his graduate student at Cornell University built a small (10 cm) proof-of-concept tree model with artificial membranes representing roots and leaves and small "microfluidic" channels connecting them. Though small, this device demonstrates the functional capacity of the evaporation/water-column idea, and might eventually be used to test failures of this model (such as when air-bubbles intervene in the column) and to draw small amounts of water out of hard to reach places.

References:
1. Wheeler TD, Stroock AD. The transpiration of water at negative pressures in a synthetic tree. Nature, 455(7210): 208-212, 2008.

On the nth Sense

from reference 1


It is widely documented that pheromones effect the behavior of insects, fish and mammals. However, locating both the pheromone molecules themselves and the anatomy for detecting them has proven challenging. A recent study, however, has identified the cells responsible for detecting so-called 'alarm pheromones' in mice¹.

The image above shows the implicated structures at various levels of detail. In the upper left, you can see a section of a mouse head, with a box around the GG: the Gruenberg ganglion, named for Hans Gruenberg, who first identified the set of cells in 1973.

There is every reason to assume that human beings are susceptible to the effects of pheromones, especially since the ganglion identified in the study mentioned above is present in humans. The prospect of having our behavior (or physiology in general) manipulated by artificial use of these molecules is both exciting and scary.

References:

1. Brechbühl J, Klaey M, Broillet M-C. Grueneberg ganglion cells mediate alarm pheromone detection in mice. Science 321: 1092-1095, 2008.

On Memory and Experience

from reference 1

As reported in the New York Times, a new study has demonstrated an aspect of memory that has long been hypothesized. That being: the same neurons that fire during an experience fire during the memory of that experience. The research, published in the journal Science, relies on recordings from the brains of epileptic patients undergoing surgery to remove the parts of their brain which cause excesses of neuronal activity, essentially the only way to record the activity of neurons in awake human beings¹.

The authors of the study took an approach where they recorded the activity of single hippocampal brain cells while subjects were watching a variety of video clips. Unsurprisingly, certain cells responded best to certain clips. Then, after a brief interim during which the experimenters distracted the patients, they asked the subjects to recall the video clips. Not only did the activity of the neurons during recollection correlate with activity during first viewing, the experimenters were able to predict which video clip the subjects were remembering based on the recorded activity! Interestingly, however, the hippocampus (the area of the brain being recorded from in this study) is not required for the recall of long term memories. Thus, in some ways this work further deepens the mystery of how short term versus long term memories are encoded in the brain and the involvement of hippocampus in these processes; a subject previously touched on in this forum.

Reading about this research reminded me of my favorite definition of memory, as the ability to:

"repeat a mental or physical act after some time despite a changing context.... We stress repetition after some time in this definition because it is the ability to re-create an act separated by a certain duration from the original signal set that is characteristic of memory. And in mentioning a changing context, we pay heed to a key property of memory in the brain: that it is, in some sense, a form of constructive recategorization during ongoing experience, rather than a precise replication of a previous sequence of events.

...the key conclusion is that whatever its form, memory itself is a [property of a system]. It cannot be equated exclusively with circuitry, with synaptic changes, with biochemistry, with value constraints, or with behavioral dynamics. Instead, it is the dynamic result of the interactions of all these factors acting together, serving to select an output that repeats a performance or an act.

The overall characteristics of a particular performance may be similar to previous performance, but the ensembles of neurons underlying any two similar performances at different times can be and usually are different. This property ensures that one can repeat the same act, despite remarkable changes in background and context, with ongoing experience."²

References:

1. Gelbard-Sagiv H, Mukamel R, Harel M, Malach R, Fried I (2008) Internally Generated Reactivation of Single Neurons in Human Hippocampus During Free Recall. Science 10.1126/science.1164685
2. Edelman GM, Tononi G (2000) A Universe of Consciousness: How Matter Becomes Imagination, Basic Books, New York

On the Importance of Single Spikes

from reference 1


As mentioned numerous times before in this forum, neurons in the brain communicate by action potentials: pulses of voltage that usually propagate from the cell body (soma) down a specialized outcropping of membrane called the axon which synapses onto other neurons. Usually, these synapses link pre-synaptic axons to post-synaptic dendrites, cellular structures specialized for recieving input.

Until recently, it was thought impossible for a single action potential, initiated in soma, to cause a second, post-synaptic neuron to fire an action potential; rather, as has been extensively documented, single neurons require many simultaneous dendritic inputs which are summed together to cause an action potential to be initiated in the soma. Recent research, however, has identified a cell type found exclusively in the cerebral cortex of human beings which seems to contradict this generalization. These neurons, termed "chandelier cells" are able to cause a chain of post-synaptic events (action potentials in several cells) lasting up to, on average, 37 milliseconds, ten times longer than had been previously assumed possible¹.

The article reporting these findings, published in the estimable journal PLoS Biology, describes one feature that the authors feel is of paramount importance to this phenomenon. Apparently chandelier cells are much more likely to make axo-axonic connections. That is, they send their pulses of activity not to dentrites, but to other axons. The reason for this somewhat exotic type of connectivity is that chandelier cells normally turn off the output of other neurons by sending inhibitory signals that cancel action potentials being sent down axons of the chandelier's targets. It seems then, that single chandelier cell action potentials inhibit other cells which are themselves inhibitory, indirectly exciting the targets of these secondary inhibitory cells.

The relevance of these findings to human cognition or consciousness is unclear, but this represents a significant advancement for our understanding of the functional connectivity of the human brain.

References:
1. Molnár G, Oláh S, Komlósi G, Füle M, Szabadics J, et al. (2008) Complex Events Initiated by Individual Spikes in the Human Cerebral Cortex. PLoS Biol 6(9): e222 doi:10.1371/journal.pbio.0060222

On Behavioral Genetics (II)

from reference 1


Once again, an example of a gene that plays some role in determining a human behavior has been found. Vasopressin, a neuropeptide, has long been known to regulate monogamous behavior in male voles. As with all signalling molecules in the brain, the effects of vasopressin can be changed by variations in its receptors (the molecules that recognize the signal; the lock to the key). Interestingly, recent research indicates that vasopressin plays a similar regulatory role in humans. Specifically, research published in PNAS aimed to determine if there was variability in the pair-bonding behavior amongst men possessing variable copies (none, one or two) of a version of a gene that codes for one subtype of the vasopressin receptor. As can be read from the table above, the work reports that men with more copies of this gene were less likely to be married, and more likely to answer yes to the question: "Have you experienced marital crisis or threat of divorce within the last year?"

References:
1. Walum, H, Westberg, L, Henningsson, S, Neiderhiser, JM, Reiss, D, Igl, W, Ganiban, JM, Spotts, EL, Pedersen, NL, Eriksson, E, & Lichtenstein, P. (2008) Genetic variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans. PNAS doi: 10.1073/pnas.0803081105

On Self Recognition

from reference 1


Ascribing human characteristics to animals based on behaviors that resemble our own is a dangerous game. However, scientists studying the brain and behavior are often left with little choice. Thus, the "spot-test" has become the best experiment we have for answering the question: "does a given species have the capacity for self-recognition." In this test, a colored spot is put on an animal, the animal is placed in front of a mirror, and the experimenter looks to see if the animal will attempt to remove the spot, thus associating the figure in the mirror with itself. So far, the four great apes, bottlenose dolphins, and Asian elephants have shown the ability to pass this test. New research adds the magpie to this list¹. An interesting commentary was also published in the same issue of PLoS Biology as the study itself, and I reproduce an excerpt from that commentary here:

"From an evolutionary perspective, it must be added that MSR [mirror self recognition] seems hardly interesting. It cannot be an important adaptation, since animals lacking this capacity have no trouble with reflective surfaces, such as standing pools of water. Animals certainly do not need to recognize themselves to survive. The importance of the mirror test rather resides in what it may tell us about how animals perceive themselves in relation to their environment, including their social partners. In other words, the mirror test is interesting not because it shows that an animal has the capacity for self-recognition but because of the cognitive abilities that are associated with MSR.

It has been speculated that MSR coincides with advanced social relationships, including the capacity to look at the world from another's viewpoint. Gallup already speculated about this connection, and more recently this idea has been connected to the various levels of empathy reached by mammals. The higher levels of empathy require individuals to grasp the situation in which another finds itself, hence looking at the situation from another's perspective. The same capacity may be reflected in MSR. This is known as the “co-emergence hypothesis,” according to which the capacities for MSR and perspective-taking appear in tandem during both evolution and development.

With regards to human development, this hypothesis is well-supported. Children begin to show perspective-taking abilities at around the same time that they first pass the mirror mark test, even after age has been controlled for. In the future, researchers may be able to address this issue more directly through neural investigation. In humans, for example, the right inferior parietal cortex, at the temporoparietal junction, underpins advanced empathy by helping distinguish between self- and other-produced actions. If mirror responses tap into the same self–other distinction, the mark test is obviously more than it appears.²"

References:
1. Prior H, Schwarz A, Güntürkün O (2008) Mirror-Induced Behavior in the Magpie (Pica pica): Evidence of Self-Recognition . PLoS Biol 6(8): e202 doi:10.1371/journal.pbio.0060202
2. de Waal FBM (2008) The Thief in the Mirror. PLoS Biol 6(8): e201 doi:10.1371/journal.pbio.0060201

On Rodent Parkinsons

The cover of the journal Brain


Therapies based on stem cells rely heavily on our ability to coax these blank-cellular-slates into taking on specific forms. Stem cells are exciting as possible sources of medicinal therapy because they have the potential to become any type of cell in the body, but in order for their utility to be realized, we must be able to reliably effect their fates. The process of turning a stem cell into a specific cell type is called, logically, differentiation. With the exception of the immune system, the brain has more cell-types than any other organ, not to mention some of the most differentiated (exotic or distinct) types. Thus, many scientists are busily engaged in the activity of deducing molecular algorithms for deterministic control of their cellular end-state.

One disease where there seems to be a clear connection between cell-type-specific disfunction and pathology is Parkinson's Disease. In this debilitating condition, the afflicted progressively loose motor function due to a lack of stimulation of their motor corticies (the area responsible for directing movement in the human brain) by dopaminergic neurons found in the amygdala (another brain region associated with emotion and reward). Further, it appears to be the case that the reason for this lack of stimulation is simply a lack of production of dopamine by these dopaminergic amygdalar neurons. The cell-type specificity of the disease makes it an an excellent candidate for treatment by replacing the existing hypoactive neurons with newly differentiated stem cell versions of their kind, which should have normal dopamine production abilities.

A recent paper appearing in the journal Brain reports the results of a study in which the researchers have achieved just such a therapeutic cell-type replacement in rats with a "model" of human Parkinson's disease (ref. 1). They report that motor function was restored by this approach, and further that the longevity of the differentiated cells was related to their restorative efficacy. Further examples of work like this promise to revolutionize the treatment of a host of diseases.

References:
1. Sanchez-Pernaute R, Lee H, Patterson M, Reske-Nielsen C, Yoshizaki T, Sonntag KC, Studer L, Isacson O. (2008) Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson's disease. Brain.

On Curvature in Saccades

I study Saccade Adaptation, the process by which our saccades (rapid, point-to-point eye movements) are kept accurate. I am proud to report that something that I wrote (with a Post-Doc in the lab I currently do my work in) was published today in the Journal of Neuroscience. Take a look at the PDF if you're so inclined.

On the Positive Effects of Variability

from reference 1

An emerging idea in neuroscience is that noise is a good thing, in moderation. Neural activity is very noisy, there is a large degree of variability in the temporal and frequency domains of the spiking of brain cells. It is thought that this variability actually contributes to the robustness of the system. One concrete example is stochastic resonance. In that phenomenon, randomly perturbing neural activity can push it over some threshold such that a sensory event is detected, or an ambiguous decision is made, one way or the other. It may be difficult to see this as beneficial, but especially as we are fantastic learning machines, simply making a decision, or having a perceptual event occur (even when there has been none) contributes to the system's learning abilities far more than indecision or non-detection.

In a more macroscopic example, a recent paper analyzing variability in brain activity across several age groups has found it to be quite positive. "Behaviorally, children showed slower, more variable response times (RT), and less accurate recognition than adults. However, brain signal variability increased with age, and showed strong negative correlations with intrasubject RT variability and positive correlations with accuracy. Thus, maturation appears to lead to a brain with greater functional variability, which is indicative of enhanced neural complexity. This variability may reflect a broader repertoire of metastable brain states and more fluid transitions among them that enable optimum responses. Our results suggest that the moment-to-moment variability in brain activity may be a critical index of the cognitive capacity of the brain.¹"

References:
1. McIntosh AR, Kovacevic N, Itier RJ. (2008) Increased brain signal variability accompanies lower behavioral variability in development. PLoS Comput Biol. 4(7):e1000106.

On Language Influencing Non-verbal Thought

from reference 1

Does the language we speak influence our non-verbal thoughts? This question is a stratifying one: some think that language is synonymous with thought, while others consider it a component of our mental abilities or a type of output, no more representative of underlying cogitation than the way we walk or move our arms.

A paper published in the Proceedings of the National Academy of Science weighs in on this matter with experimental results indicating that individuals who speak very different languages (English, Turkish, Chinese, & Spanish) seem to non-verbally represent events in similar ways.

Specifically, in one task, the researchers asked their subjects to communicate an event such as "boy tilts glass" (read in each individual's native language) with gestures. In a second task, they were asked to reconstruct an event using pictures. In order to quantify performance in these tasks, the researchers examined the ordering that gestures or pictures were used. They reasoned that because grammatical structures dictate that words be used in potentially divergent ways depending on language, that this structure might extend to the order in which gestures or pictures are used as well. Interestingly, they found that there was no quantitative difference in performance between speakers of different languages, suggesting that there is a common underlying mode of event representation which is minimally influenced by spoken language.

References:
1. Goldin-Meadow S, So WC, Ozyürek A, Mylander C. (2008) The natural order of events: how speakers of different languages represent events nonverbally. Proc Natl Acad Sci USA. 105(27):9163-8.

On The Wiring Diagram

From reference 1


The human brain has roughly 100 Billion neurons and each neuron has between 1000 and 10000 synapses (connections), thus approximately 500 Trillion synapses. This makes the problem of determining the connectivity, or the wiring diagram of the brain absurdly complex. This is one of the most fundamental problems confronting neuroscientists today because the solution to many problems of how the brain works would be made much easier if we simply knew the structure that it is built on.

A recent piece of computational research (published a wonderful PLOS journal) suggests a novel statistical method to identify which synapses of a given neuron are active at a given time. The author of this study simulated the output of many single neurons when a particular subset of it's synapses were active. This characterization was based on the number of action potentials the neuron fired in response to the activity of these many specific synapses. Next, the author examined the changes in the output when a single additional synapse was activated along with the baseline subset. He found that if he simulated the addition of one synapse ~80 times, he could measure significant changes in the output of the simulated neuron such that it was possible in subsequent tests to reliably predict when this synapse was active.

The authors suggestion is that taking this technique out of the computer and into the world of real brains (or small slices of brain, as is commonly employed), would facilitate the task of elucidating the numerous connections in the brain. While this is true, it must be said that this method is good for asking the following question: Which neurons are connected to one neuron that I know very well? In other words, somebody interested in applying this work would have to have one neuron of interest and then stimulate every other neuron that might be connected to it in order to determine the connectivity. In this sense, the approach is a far cry from revealing the wiring of the brain, but it certainly does help.

References:
1. Bhalla US. (2008) How to record a million synaptic weights in a hippocampal slice. PLoS Comput Biol. 4(6):e1000098.

On The Brain In Your Face

Figure 1 (from reference 1) showing the employed stimuli (a) and a schematic of the model they used (b).

Commonly held wisdom says that processing of visual features such as lines, forms, and motion is limited to higher cortical areas (for example, the medial temporal lobe, or area MT). Recent research shows, however, that the retina itself can extract motion signals, underscoring the subtle computational prowess of the bit of your brain that lives in your eye.

References:
1. Baccus, S. A., Olveczky, B. P., Manu, M. & Meister, M. (2008) A Retinal Circuit That Computes Object Motion. The Journal of Neuroscience, 28(27):6807-6817

On Context & Priming

From Reference 1

Part of the paradox of free will is that it not only liberates us by giving us control over our own actions, it also requires us to take responsibility for decisions which we make subconsciously. Thus, it is important to be vigilant in monitoring and understanding ones own psychology, one's implicit rationale and underlying systematic reasoning so that taking responsibility for all acts is useful in correcting or maintaining patterns of behavior. However, we must also remember that there are things that will effect the way we interact with the world that may lie beyond our awareness. In this sense we must be able to forgive ourselves when those factors play a role in decisions we deem inappropriate in retrospect. Metaphysics aside, there is a great deal of research documenting the effects of context and priming on human behavior. The latest is from a study on how voting location can affect the way people vote¹. Specifically, psychology researchers found that those voting on a education tax increase initiative were significantly more likely to vote for the initiative if they were voting in a school. The values (in the table above) indicate that the differences were small, but the statistics indicate that these differences are real.

References:
1. Berger J, Meredith M, Wheeler SC. (2008) Contextual priming: Where people vote affects how they vote. Proc Natl Acad Sci U S A. 105(26):8846 – 8849

On, Robot Prosthetics

From Reference 1


Using signals from the brain to control robotic arms is no longer cutting edge, having been achieved several times in the last decade. However, in the latest research into this topic, the authors present a novelty: rapidly training monkeys to control an anthropomorphic (having a shoulder, elbow, and wrist joint as well as a gripper) in order to feed themselves¹. This kind of technology promises to eventually revolutionize prosthetics and give untold freedom to those who can no longer use their own limbs but do retain the brain areas that generate the signals that once controlled them. In order for this to become feasible, the implants used to record brain activity must be vastly improved (at present they are reliable for only a matter of weeks or months), the processing power must be reduced in size (it presently requires several computers), and the process must be automated (the systems must at present be tuned by a technician online).

References:
1. Velliste M, Perel S, Spalding MC, Whitford AS, Schwartz AB. (2008) Cortical control of a prosthetic arm for self-feeding. Nature. 453(7198):1098-101.

On Time Perception & Sleep

Courbet's Sleep


Why is it that our perception of the passage of time changes around and during periods of sleep? While it is known that there are diurnal variations in time perception¹, and that insomniacs have irregular perception of duration of sleep², this basic question remains.

In an article concerning regular and pathological conscious perception of time, Oliver Sacks speculates that "visual perception might in a very real way be analogous to cinematography, taking in the visual environment in brief, instantaneous, static frames, or 'stills,' and then, under normal conditions, fusing these to give visual awareness its usual movements and continuity³."

This suggests the possibility that our perception of time is a function of our ability to impose a sense of continuity on our own perceptions. Thus, in the absence of external stimuli for this continuity system to act on, we have no mechanism to calculate the passage of time, and instead estimate this variable in a noisy, post-hoc manner.

In any case, the fact that it's possible to drastically misestimate how long one a bout of sleep has lasted implies that there is something fundamental about the state of consciousness (wakefullness) and judgement of time perception which remains to be understood.

References:

1. Pöppel E, Giedke H. (1970) Diurnal variation of time perception. Psychol Forsch. 34(2):182-98.
2. Knab B, Engel RR. (1988) Perception of waking and sleeping: possible implications for the evaluation of insomnia. Sleep. 11(3):265-72.
3. Sacks, O. (2004) In the River of Consciousness. The New York Review of Books. 51(1):