Brownian thought space

Cognitive science, mostly, but more a sometimes structured random walk about things.

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Location: Rochester, United States

Chronically curious モ..

Wednesday, February 28, 2007

New Location!

Finally, it's time to transfer out to the green arrow on this page... :)

Tuesday, February 20, 2007

Kid Stuff!

One brilliant site..

Monday, February 19, 2007

The Mystery of the BOLD Signal

I've been pretty much bugged about trying to understand the physiological basis of the BOLD signal in fMRI. In a previous post, I sketched an initial attempt to undertsand the vascular changes, mainly in relation to Optical Topography. But then, I realise I don't understand the BOLD response very well, after all...
So here's an update.

MR Basics1
  • Inside the magnet, anything with a magnetic moment will align itself with the big stationary magnetic field (B0), along the z-axis, and all spins will be in phase.
  • A radio-frequency pulse makes a second magnetic axis (e.g.) perpendicular to the main magnet axis, and several molecules/atoms use this as an excuse to spin away from the main axis and into the transverse (x-y) axis.
  • When the RF pulse is turned off, {a} the spins start coming back to their equilibrum position along B0 with a time constant T1, and {b} in the absence of an external driving force, the spins in the x-y plane lose coherence (and so lose a net magnetic moment) with a time constant T2*. (There's also another decay time constant in this transverse field, the T2, which is the decay constant during repeatedly refocusing the phase of the transverse spins).
  • The presence of a paramagnetic substance like deoxy-Hemoglobin (HbR) creates magnetic inhomogeneities, such that the going-out-of-phase in the x-y plane happens much quicker. So, a much smaller signal is produced. Thus, the more the HbR, the smaller the signal. In contrast (heh!) HbO is diamagnetic, and for all magnetic purposes behaves like water, so doesn't contribute much to the (T2*-dependent) BOLD signal.
So far so good.

The basic reason why one would use the BOLD signal is because of certain findings that indicated to Messrs. Roy and Sherrington (1980):
...the existence of an automatic mechanism by which the blood supply of any part of the cerebral tissue is varied in accordance with the activity of the chemical changes which underlie the functional action of that part. Bearing in mind that strong evidence exists of localisation of function in the brain, we are of opinion that an automatic mechanism, of the kind just referred to, is well fitted to provide for a local variation of the blood supply in accordance with local variations of the functional activity.
In short, a neurovascular coupling.
Naively, one would expect the following sequence of events2: a stimulus comes in, the relevant neurons hike up their activity, they require more energy, and so start burning more glucose and turning more HbO into HbR. Therefore, there should be an increase in HbR in the area close to the activity. This means that the BOLD signal should be smaller following stimulation.

Now, other things seem to happen when the stimulus arrives: an increase in the blood-flow rate, and an increase in the blood volume. Again, both of these increase the amount of HbR, and so should decrease the BOLD signal.

BUT, as it happens, over and over again (something like 90% of the studies, according to one source), one finds an increase in the BOLD signal!

Actually, that's not strictly true. There is evidence for an initial "dip" in the BOLD signal, as one would expect3. One possible sequence reconstructed by Malonek et al goes something like this:
  • sensory stimulus
  • blood flow increase
  • as soon as blood flow increases, HbO increases
  • simultaneously with blood flow change, HbR starts to decrease
But then what causes the much larger BOLD signal? Simultaneous recordings of spikes, local field potentials, blood oxymetry and so on favour a view in which the BOLD somehow reflects
"...population synaptic activity (including inhibitory and excitatory activity), with a secondary and potentially more variable connection with cellular action potentials."
In short, not the spikes, but the more widespread synaptic signalling, whether or not it leads to spiking4.

So, one might wonder, how does the big BOLD signal come about?? Clearly, there is much less HbR per unit volume post-stimulation that there was before. How can THAT be? One possibility is that, somehow, the incoming blood is (a) plentiful = large volumes and (b) progressively enriched in HbO.

So, larger quantities of greater HbO-containing blood can both satisfy both the observations - that volume increases and that HbR goes down.

Luckily (for me, at any rate), last year there was a paper in Nature Neuroscience: "Astrocyte-mediated control of cerebral blood flow" by Takano et al. The abstract reads:
Local increase in blood flow during neural activity forms the basis for functional brain imaging, but its mechanism remains poorly defined. Here we show that cortical astrocytes in vivo possess a powerful mechanism for rapid vasodilation. We imaged the activity of astrocytes labeled with the calcium (Ca2+)-sensitive indicator rhod-2 in somatosensory cortex of adult mice. Photolysis of caged Ca2+ in astrocytic endfeet ensheathing the vessel wall was associated with an 18% increase in arterial cross-section area that corresponded to a 37% increase in blood flow. Vasodilation occurred with a latency of only 1–2 s, and both indomethacin and the cyclooxygenase-1 inhibitor SC-560 blocked the photolysis-induced hyperemia. These observations implicate astrocytes in the control of local microcirculation and suggest that one of their physiological roles is to mediate vasodilation in response to increased neural activity.
The crème de la crème is the finding that the astrocytes selectively open up the arterial flow! Here's the graph from their paper, showing the relative changes for arteries, veins and capillaries.

This explains both the increased oxygenation of the blood (and so the lower [HbR]) and the larger volume. Add to this the finding from last year that pericytes - cells sitting around the capillaries - can bidirectionally squeeze capillaries, and you might also understand why local blood velocity goes up.

  1. For an excellent online source, look at
  2. See this previous post.
  3. Malonek, D. & Grinvald, A. (1996) Science 272, 551–554
  4. Arthurs, OJ & Boniface, S. (2002) TINS 25(1), 27-31

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The kind of Pokemon I am

Starmie You scored 53% Fire vs Water, 47% Grass vs Flying, 43% Electric vs Bug, and 64% Fight v Psychic! You are Starmie! You're happy to go with the flow and use your brain power rather than brute strength. You're logical and outgoing and altogether quite charming. You don't like to fight, that much is obvious, but you aren't afraid to face a challenge and will take it head-on. But you're more laid-back, and are rather calm in your approach to life. Your special attack is minimize. You don't exactly shrink from a battle, but you know when to hold them and when to fold them, and you'd rather spend your time doing something more fun than fighting silly battles. You are a water and psychic type, easy going and intelligent. Your trainer will find these qualities have many benefits in battle.
Link: The What Kind of Pokemon Are You Test written by AaronJJ on OkCupid.

Thursday, February 15, 2007

The Adventures of Sherlock Holmes!

What a find! The opening theme from the bestest adaptation of a fictional person for the telly: Jeremy Brett as Sherlock Holmes in the Granada production The Adventures of Sherlock Holmes.

Wednesday, February 14, 2007


A casual statement in a Journal Club article in the Journal of Neuroscience set me thinking: what if an infant were confronted with two people doing some common action, e.g., tying shoelaces. However, while one of them is an expert, the other is not. (a) would the infant be able to discriminate the two? (b) would it choose to imitate one adult over the other? (c) would infants exposed to the expert be more faithful in their reproduction of the action? The point is, if imitation is "dumb", then one shold imitate anything at all. But, if imitation is smart (a la György/Gergely), then infants might be able to compute efficiency and prefer to imitate the expert.

Tuesday, February 06, 2007

Blood in the brain

Over the last few days we had a remarkable series of talk on funtional neuroimaging of the human brain by Hellmuth Obrig; a most likeable and clever person. The main lessons learnt from these talks (for me), was what exactly is being measured by functional neuroimaging methods. I should 'fess up - my ideas were pretty crap on the topic.

Anyhow. What's clear is why it is called a Blood-Oxygen-Level-Dependent measure. What's far from clear is what causes the change in blood oxygenation in local pieces of the brain tissue. There is some serious energetic stock-taking to be done in brain tissue, and it's time to look at the literature.

What I Learnt: Here's a model. The brain cells are idling, sending the occasional spike and so on, breaking down glucose through the TCA cycle and making ATP through oxidative phosphorylation. Along comes a stimulus, and the cell tries to step up ox. pho.; and in the meantime uses some anaerobic means to break down glucose, which is energetically demanding, and produces lactic acid. [although, neurons also seem to use lactate, presumably produced by astroctytes, as an energy source; ref1, but see ref2]. The cells somehow signal the need for more oxygenated blood, and so the blood flow rate goes up. This brings about an increase in the concentration of oxygenated hemoglobin (Oxy-Hb), presumably because the concentration is something like an integral over time in a certain volume, so faster rate = higher concentration.

Clearly, the higher flow rate is to supply more O2, so more Oxy-Hb should be getting converted to Deoxy-Hb. But, since overall Oxy-Hb seems to increase, it looks like the extent of Oxy-Hb increase is greater than its conversion to Deoxy-Hb. Consequently, the increase in [Deoxy-Hb] is smaller than the increase in [Oxy-Hb] (square brackets - concentration), and as a result, because conversion to Deoxy-Hb cannot keep up with the increased flow-rate, the [Deoxy-Hb] goes down a little, explaining the observation from Optical Topography as in this figure (courtesy of Herr Obrig; thanks!): the red dots are [Oxy-Hb], blue dots are [Deoxy-Hb]; the x-scale is seconds of visual stimulation, the data is recorded from a near-infrared emitter-detector pair over the visual cortex (back of the head).
Presumably, once the stimulus is switched off, the balance between energetic need and enhanced blood flow is re-established, with some overshoot, and the neurons are back to idling.

Another cool thing was about the difference between volume changes and flow-rate changes. You could imagine that either the flow-rate speeds up, somehow, or that the local volume diminishes: both lead to faster blood flow. But how do you get local changes in blood velocity?

Two things: first, several blood vessels in the brain, specially the larger ones, have smoothmuscle control. Even cooler, the very smallest capillaries, which don't have muscles, have pericytes, which grasp the capillaries and squeeze them when required (ref)!

Thursday, February 01, 2007


If I give you the article, will you keep in indefinitely...?