Late Emergence of the Whisker Direction Selectivity Map in the Rat Barrel Cortex

Kremer Y, Léger JF, Goodman DF, Brette R, Bourdieu L (2011).Late Emergence of the Whisker Direction Selectivity Map in the Rat Barrel Cortex. J Neurosci 31(29):10689-700.

Abstract. In the neocortex, neuronal selectivities for multiple sensorimotor modalities are often distributed in topical maps thought to emerge during a restricted period in early postnatal development. Rodent barrel cortex contains a somatotopic map for whisker identity, but the existence of maps representing other tactile features has not been clearly demonstrated. We addressed the issue of the existence in the rat cortex of an intra-barrel map for whisker movement direction using in vivo two photon imaging. We discovered that the emergence of a direction map occurs long after all known critical periods in the somatosensory system. This map is remarkably specific, taking a pinwheel form centered near the barrel center and aligned to the barrel cortex somatotopy. We suggest that this map may arise from intra-cortical mechanisms and demonstrate by simulation that the combination of spike-timing-dependent plasticity at synapses between layer 4 and layer 2/3 and realistic pad stimulation is sufficient to produce such a map. Its late emergence long after other classical maps suggests that experience-dependent map formation and refinement continue throughout adult life.

Supplementary movie (20 MB). Spikes of L2/3 neurons and evolution of their direction selectivity during the stimulation with random moving bars. The movie shows the spikes of all neurons in L2/3 during the stimulation with random moving bars (left) and the evolution of their direction selectivity (right), as estimated from the average selectivity of their presynaptic neurons in L4, weighted by the synaptic weights. Initial conditions and parameters are identical to those used in the Figure 6. In these conditions, the simulation lasted 1500 seconds. Only 3% of all frames are included in the movie. Note that when a moving bar activates a sequence of whiskers, the first barrel column reached by the bar is almost homogeneously activated (at least at the beginning of the simulation) whereas subsequent barrel columns already exhibit inhomogeneous activity. This inhomogeneous activation of the second, third, etc barrel columns is not a consequence of the existence of a radial direction selectivity map, as this map does not have enough time to develop for instance at the first presentation of the moving bar. It is just due to horizontal connections within layer 2/3, which propagate the activation of the first column to the next adjacent columns, inhibiting predominantly the closest regions to the first column. This inhomogeneous activation of barrel columns becomes reinforced as the direction selectivity map develops, but this contribution only comes in second.

Code. In the examples of the Brian simulator, there is a script that stimulates a plastic model of the barrel cortex with randomly moving bars, and shows the selectivity map after learning.

Perceiving and knowing

Perceiving space is knowing where things are in the world. Or is it?

I am sitting in my living room, and there are big windows on a courtyard. The windows are sound-proof and so if I open just one, acoustical waves mostly enter the room through that window. Now someone enters the courtyard on the right, walks across it and arrives at the door on the left. If I close my eyes, I know that the person is walking from right to left. However, what I hear is the sound of someone walking, always coming from the same direction, that of the window. If someone asks me where the person is at a given moment time, I could point to the more or less correct direction, by inference. But this is not what I perceive. I always perceive the sound coming from the same direction. There is a difference between perceiving (phenomenological) and knowing (conceptual). And there is a difference between phenomenology and behavior.

Another striking example is referred pain. Referred pain is a pain that one feels at a location away from the cause of the injury. For example, in a heart attack, one may feel pain in the arm rather than in the chest. This is a known phenomenon and if you know it, you may correctly identify the location of injury in the heart when you feel pain in the arm. But it doesn't change the fact that you feel pain in the arm. You may entirely convince yourself that the injury is in the heart, and all your behavior might be consistent with that belief, but still you will feel the pain in the arm.

There are several interesting conclusions we can draw from these remarks. First, perception is not entirely reducible to behavior. Here we are touching the hard problem of consciousness (qualia): you could observe a cat turning its head to a sound source and you would think that the cat perceives that the sound came from the source, but in reality you don't know. Maybe the cat perceives it somewhere else but it corrects its movement because it knows its perception tends to be biased. With humans, you could perhaps distinguish between these possibilities because humans speak. But without this option, a purely functionalist approach to perception (in terms of relationships between sensory stimuli and behavior) misses part of the phenomenon.

Second, inference is not the same as perception. Spatial perception is not just the process of inferring where something is from sensory inputs. There is also the experience of perception, which is not captured by the objectivist view.

Spatial perception of pain (III) How can we feel pain inside the body?

I will first start with a summary of the different propositions I made in the previous post about where it hurts.

- Proposition A (independent channels): there are two independent channels, one that provides pain information (intensity or quality of pain, through pain receptors) and another one that provides spatial information (through tactile receptors or vision). The two channels are bound by co-occurrence.
- Proposition B (sensorimotor): you feel pain at a particular location because specific movements that you make produce that pain.
- Proposition B2 (sensorimotor): you feel pain at a particular location because whenever this particular activation pattern of pain receptors is present, you can manipulate this pattern or the intensity of pain by specific movements or actions.
- Proposition C (learned association): the localization of pain is inferred from the activation pattern of pain receptors (which must be spatially selective), by association with another channel that carries spatial information (e.g. tactile receptors).

Note that in A and C, I have moved the problem of spatial information to another modality, either touch or vision. We may consider that spatial information in touch and vision is constituted by sensorimotor contingencies, but it is not an important assumption here. The puzzle is the following: we can only touch our skin, the surface of our body, and we cannot see inside our body. If touch is central to the spatial perception of pain, then how is it possible that we can feel pain inside the body (say, in the stomach or in the head)?

I have discussed a similar example in spatial perception: when one hears music or speech through headphones, it usually feels like the sound comes from “inside the head”. First of all, there is a simple argument why sounds should feel as coming from your body in this case: when you move the head, the sound is unaffected, which means the source is part of your head – either on the surface (skin) or inside the head. The same argument applies to pain felt inside the body: rigid displacements of the body do not change the pain or any information associated with it. Therefore the pain is in you, not in the external world. However, this remark does not explain why pain feels inside the body and not on the skin.

I mentioned another possibility for sounds, inside as a default hypothesis: if you cannot identify the source as coming from somewhere outside, then the sound feels located inside. The default hypothesis raises a question: why does it feel located inside rather than not located at all? There is also another problem here: pain does not simply feel inside, it feels at a particular place inside the body (e.g. the stomach).

A first answer is proposition B2. Perhaps you feel a headache in the head and not in the stomach because the pain is only affected by movements of the head. In the same way, touching your stomach may alter the intensity of pain but not touching other parts. This explanation is a combination of default hypothesis (it's not on the skin so it's inside) and sensorimotor theory (B2). It is appealing but let's see how it applies to the perception of sounds inside the head. Here again, sounds do not simply feel inside the head, but at a particular place inside the head (say on the left or on the right). But no movement that you make has any impact on the sound, and so proposition B2 only explains why the sound is inside the head, but not where in the head it is.

Let us formalize the problem more precisely. Your stomach hurts. There is a pattern of activation of receptors that is characteristic of this condition, but no movement that you can make generates this pattern. In addition, in the case of auditory perception inside the head, no movement may alter this pattern. The default hypothesis is logical inference: since it is a new pattern, it must be located where I cannot produce it: in my body. But as we saw, this not sufficiently precise. To make some progress, I will start with an experiment of thought.

Imagine that in your life, you have touched only two points on your skin, points A and B. When something touches point A, you feel it located at A because you recognize the activation pattern of the tactile receptors. But what if something touches a point between A and B? One possibility would be that you don't feel it located at all, you just feel that something touches you. But it contradicts the fact that you feel sounds inside the head or pain inside the body. Another possibility is the default hypothesis: since you have never encountered the activation pattern, then you know it is neither A nor B, so you feel the touch somewhere outside of A and B. But this logical inference does not produce anything more precise. It seems to contradict the fact that we can hear sounds in our head on the left or on the right. To feel the touch somewhere between A and B requires some form of interpolation: if the new activation pattern resembles the pattern that is characteristic of A, then the touch was probably located somewhere near A; if it resembles both A and B, then it was probably located between A and B.

More generally, we can only have a finite number of experiences, and so t is unlikely that the exact activation pattern of receptors is encountered twice. Even if physical stimuli were identical, the body changes over time. Thus, it appears that we could not have any perceptual experience at all unless there is some form of interpolation. A natural proposition is then that detailed perception inside our body results from perceptual interpolation. This is not the same as logical inference, as in the case of the default hypothesis, because it necessary involves some arbitrariness: there is no way you can logically know where exactly between A and B your skin was touched if you have never encountered the activation pattern before, so the perceived location is a guess.

Now let us go back to our specific problem. How can pain be located inside our body? The idea of interpolation seems to imply that the pattern of receptor activation induced by such pains should resemble that of pains induced on the skin at opposite locations on the body. For example, pain in a joint, say the knee, should produce activation patterns resembling those of pains induced at the skin all around the knee.

There are two interesting points to note about the interpolation idea:
1) Sounds and pains located inside the body tend be less precisely localized, the location is “vague”. This means that the concept of interpolation as in picking a particular point between two points is incorrect: somehow the process of perceptual interpolation also affects the uncertainty of the location, or perhaps the perceived size.
2) How specifically are perceptual locations interpolated? In other words, what is the topology of spatial perception?

Spatial perception of pain (II)

Where does it hurt? A common answer to this question is: it hurts at the location of the pain receptors in the body. I will discuss three counter-arguments to this proposition, starting with the simple one. The simple argument is that there is a discrete set of pain receptors on the skin, but the spatial perception of pain is not discrete (the same argument applies to touch): we do not feel pain at discrete locations on our skin. It seems that the phenomenal space of pain is continuous, and this observation does not match anatomy. Then there are the anecdotical arguments: we have headaches but there is no pain receptor in the head; when you lose a limb (say a hand), the non-existent limb can hurt (phantom limb pain); there are systematic mislocalizations of the causes of pain, for example heart pains are felt in the arm. Finally there is a more sophisticated argument. Let us assume that we do feel pain at the location of our pain receptors. But then how do you know where your pain receptors are? One answer would be: we know it because it is somehow encoded in our genes. The “somehow” would deserve some precise explanation, but this is not necessary for this argument. This proposition requires that there is a systematic mapping between our genes and our body at a fine level of detail. That is, the precise location of pain receptors should depend only on our genes. But we know that this is not true. For example the size of our body depends on the diet we had when we were kids, and therefore so does the location of nerves. Therefore, even if we felt pain at the location of the receptors, we would still need to find out where these receptors are.

Another common answer to the question “where does it hurt?” is the objectivist answer: it hurts where the cause of the pain is, or where the injury is. An important difference with the previous one is that it does not imply discrete spatial perception. From our experience, this proposition seems to be correct most of the time but a simple objection is that there are cases of mislocalizations of pain (e.g. heart pains). The same argument as above leads us to the same question: how do you know where the injury or cause of pain is?

If genes are not sufficient, then it must be based on experience. Let us imagine that you hit your knee against a wall. You can see the knee hitting the wall; you also have a tactile experience; you feel an intense pain at the moment of contact, which perhaps gradually fades out. I start with proposition A: there are two independent channels, one that provides pain information (intensity of pain, through pain receptors) and another one that provides spatial information (through tactile receptors or vision). The same question now applies to the spatial channel: how do you know where something touches you? This is simpler to answer because you can touch yourself: you can associate your movements with activation patterns of tactile receptors when you touch your skin. You know where a tactile stimulus is in the sense that you know how to make movements to touch it. An objection to proposition A is: what if there is no external stimulus that activates the tactile receptors? For example, your stomach could hurt because of acidity or a tooth could hurt because of bacteria. There is nothing you can see, and all the tactile receptors are on the skin, so there is no independent source of spatial information, and yet the pain feels precisely localized. The only way to save proposition A is to assume that there actually is another source of spatial information. For example, in the case of tooth pain, maybe tactile receptors (or the nerves) are actually activated. In the case of stomach ache, it is harder to imagine that these receptors on the skin are activated (but I leave it as an open question), and in this case you would need to hypothesize that there are other types of receptors, perhaps acidity receptors, that carry spatial information. But then we are back to the same problem as before: how do these receptors get to carry any spatial information at all? (how do you know where these neurons are?) You would then need to assume that these receptors inside your body can also be activated with your own movements. I leave this as an open possibility. There is still one difficulty, which I will address later because it is shared with other propositions: how can pain be localized inside the body?

I will now discuss two other related propositions. Proposition B is purely sensorimotor: you feel pain at a particular location because specific movements that you make produce that pain. This explanation only requires pain receptors, but these receptors must be activated in a way that is spatially specific (i.e., which varies systematically with the location of the pain stimulus). For example, by pinching yourself, you associate the pattern of pain receptor activation with the location of the skin where you pinched yourself. This proposition implies that you cannot feel any localized pain unless you have previously produced it yourself. But what about when a tooth aches? It seems that you could feel tooth ache without having hurt your tooth yourself before. To save proposition B, it seems necessary to assume that the pain receptors can be activated at a “subthreshold” level that does not produce pain. In this case, to feel pain at a particular location requires previously producing specific movements that produce a similar (but possibly less intense) pattern of activation of the pain receptors.

There is a variation of B, which I will call proposition B2, which goes as follows. You feel the pain at a particular location because whenever this particular activation pattern of pain receptors is present, you can manipulate this pattern or the intensity of pain by specific movements or actions. For example, you hurt your knee and then you know you will feel a bit better if you put your hand on it, maybe because of the heat. Proposition B2 is slightly different from B by the fact that it is how you can manipulate pain, rather than how you can cause pain, that provides spatial information. The example of the tooth would then be: your tooth aches, and you know where it aches because by moving your tongue on your teeth you alter the intensity of pain.

Proposition C is learned association: the localization of pain is inferred from the activation pattern of pain receptors (which must be spatially selective), by association with another channel that carries spatial information (e.g. tactile receptors). For example: you hit your knee against the wall, the tactile receptors carry information about the location of pain, which you associate with the activation pattern of pain receptors. Later, you knee hurts but there is no mechanical contact with anything: you still feel the pain in the knee because it is the same activation pattern as when it was hit by the wall. In proposition C, you could not experience the location of a pain unless you have previously experienced the same pain in conjunction with an independent cue of location. So we have the same problem as in proposition A: what if a tooth aches for the first time? The proposition can be saved in the same way by assuming that pain receptors can be activated at a subthreshold level that does not induce pain.

There are now two questions I want to address: 1) How can we feel pain inside the body? 2) Why do we make systematic errors in localizing pain?

Spatial perception of pain (I)

Pain is a great example of many important themes in philosophy of perception. Here I want to focus on spatial perception, but I will start with a few general comments.

First of all, why do we feel pain in the first place? Scientists tend to offer two types of explanations. One is expressed in terms of efficient causes: you hit your knee against a wall, it activates receptors in your skin, these receptors make some neurons in a particular region of the brain fire, and then these neurons produce a substance (molecules) that is characteristic of pain experience (material cause). Such an explanation has some value, for example it might suggest pharmacological targets for pain relief. However, it does not explain the experience of pain at all. Why is it that a particular molecule induces the experience of pain? This does not seem to be a much better explanation than to say that the contact of the wall induces pain (it is somewhat better because it is more universally associated with pain – i.e., pain caused by other events). This problem is what philosophers call the problem of “qualia”: to explain how pain feels like, why pain hurts rather than just being some information about the state of your body. It is notoriously difficult to explain qualia in terms of efficient causes (see Thomas Nagel's famous paper, “What is it like to be a bat?”). It is much easier to explain the informative content of pain (what is going on in your body), than to explain the phenomenal content of pain (how it feels like).

A second type of explanation is in terms of final cause: it hurts because it is an experience you should avoid. It is useful for you to feel pain because then you will learn to avoid dangerous stimuli: pain has a survival value, which is why it has been selected by evolution. But again this type of explanation fails to address the phenomenal content of pain, because what it requires is a modification of behavior with dangerous stimuli, not necessarily an emotional experience. You could well imagine that when your knee is hit, you get the information that this is something that you should avoid in the future, without carrying an unpleasant feeling. You could also imagine that the event triggers a series of cognitive responses (e.g. negative conditioning) without producing any feeling at all. You could imagine that you hit your knee while sleeping, without being conscious of the event, and that your body reacts to it, perhaps even with negative conditioning (e.g. avoiding to turn in the same direction again), without you actually experiencing pain. So why does it hurt?

I do not know why it hurts. So in this series I want to address another question: where does it hurt? This is also quite an interesting question, because although it sounds obvious to us what is meant by the location of pain, we are really asking about the perceived location in the world of a feeling. What kind of weird question is this?