Consciousness and how it got to be that way

Friday, December 30, 2011

HDAC Inhibitors and Neuropsychiatric Illness

The mechanism of valproic acid (Depakote) is inhibition of histone de-acetylases. For a mood-stabilizer and anti-epileptic, this has struck many people as unexpected. A paper by Tang at Scripps in Translational Psychiatry now strengthens the link, showing the acetylation levels at some promoter regions of genes implicated in schizophrenia and bipolar disorder (samples were taken from PFC). In non-psychiatric patients the levels drop consistently with age, but in the psychiatric patients they didn't. Treatment with a novel HDAC inhibitor altered expression of the homologous genes in treated mice.

Maybe a heavy epigenetic bias to the pathophysiology of schizophrenia is the reason we've had such trouble making schizophrenia markers stick.

Tuesday, December 6, 2011

Novartis Bails Out of Neuroscience

Novartis follows several other drugmakers' footsteps; medicinal chemist Derek Lowe provides perspective, and maybe even some optimism for small companies (i.e. San Diego biotech scene).

Tuesday, August 9, 2011

Help Downs Syndrome Families - The Trisomy 21 Act

The Trisomy 21 Act which was introduced in Congress a couple of years ago. (Down Syndrome is usually caused by having an extra copy of the twenty-first chromosome, hence the name.) Unfortunately the bill died in committee. It has been resurrected by a bipartisan team of legislators, two of whom have kids with Down Syndrome.

What will this bill do? Expand and intensify Down Syndrome programs at NIH and the CDC; create a research database; and create at least six Translational Research Centers of Excellence. Translational research is research that can go from the lab to the clinic - in other words, medicine. This is truly an exciting time to be working on Down Syndrome.

More information is available at this website. At the bottom of the page is an easy to use template to send an e-mail message to your congressperson requesting co-sponsorship of the bill. It will automatically insert your representative based on your address (just in case you don't know who it is). I completed this before I wrote this blog post.

Please share this with colleagues, friends and family members!

More information: The Trisomy 21 Act

Thursday, July 21, 2011

Neuroeconomics and Delusions

Previously I posted about semantic reasoning and severity of delusions. Part of the severity of delusion can be thought of as the degree to which the delusional belief affects the individual's actions. However, frequently people's non-verbal behavior seems unaffected by their delusions. Informally speaking, there would seem to be two types of delusions that do not affect behavior. The first type are not-fully-endorsed delusions, and the second are abstract, behaviorally-contentless delusions. There are insights about both that behavioral economics can offer.

The first type of less-behavior-affecting delusions (not-fully-endorsed) occurs when a delusional person has developed a coping strategy to avoid dangerous or unpleasant behavior that their delusional belief would otherwise seem to require of them, if they fully accepted its implications (this is known as not endorsing their delusion). That is, someone believes the CIA is following them and planning to harm them, but they don't attempt to move, or stop using trackable electronic communications devices, or alter their schedule. The content of the delusion could also have internally consistent components that prevent it from affecting their behavior; i.e. if they start changing their schedule, the CIA will know they know, triggering an assassination.

From the standpoint of the effect on behavior, this type of delusion would not be considered severe (again speaking informally) because although the person's social relationships may suffer, their life is not otherwise disrupted. In my previous post I stated that one way to measure the severity of the delusion would be to measure how much discomfort the individual was willing to endure to make decisions that accord with the delusion. For a not-fully-endorsed delusion, not very much. Such an approach of course would be extremely unethical and therefore not useful to consider. However, an article in Neuroscience and Biobehavioral Reviews suggests this question can be approached non-interventionally, from a neuroeconomics standpoint by looking at how suboptimal a psychotic individual's decision-making is. Less-fully-endorsed delusions would be expected to have less impact on utility maximization than more fully endorsed ones. The neuroeconomics approach is potentially a very productive one for psychiatry because it can measure utility maximization along the entire spectrum from healthy function to badly psychotic, does not get bogged down in epistemology, and most importantly, is a good proxy indicator for the overall well-being of the individual.

The second type of less-severe delusion (again, in an informal sense of the degree to which it affects behavior) is those which are behaviorally contentless; i.e., the delusion is mostly or entirely abstract and does not contain actionable content. (Whether such a belief is really a delusion is actually questionable, since an abstract belief with no external behavioral impact could be argued to be meaningless, but this is more a question for logicians or epistemologists.) These delusions cannot be endorsed, because it has no concrete implications that would make the believer behave differently. Many of these are not technically (by DSM-IV) delusions, because they are "culturally appropriate". That is, if someone believes that a statue is alive and can cry figuratively, that at a certain place someone once rode a horse into the sky, or that people are on a mission from a supernatural being to perform some act in their life, these beliefs might actually not be delusions if they are commonly held in the believers' culture. At first this exception seems an outrageous concession to political correctness, but there are salient characteristics that set "culturally-appropriate" believers apart from isolated cases. For one thing, the type of person who has decided that a statue is alive and cries figuratively - and has decided this in isolation, without meeting anyone else who believes it - is probably different from someone who believes it as a result of being brought up and repeatedly told this by trusted friends and family. Indeed, not holding or at least professing such beliefs in many cultures could be seen as irrational in the sense that failing to do so can carry a risk of ostracism or even material harm to property or person.

But what is truly interesting is that these culturally-appropriate false beliefs tend to be behaviorally-contentless, about which observation a good economic argument can be made. Culture-specific beliefs of the type described above seem to be curiously free of direct, concrete behavioral manifestations, aside from very specific rituals at certain times. The beliefs concern entities that the believer cannot define, or cannot agree upon with others who claim to hold the same beliefs (though the believer may strenuously object when told that they are unable to define their beliefs). Furthermore, the beliefs are circumscribed in the sense that their implications are not generalized to the world at large. That is, a statue-crying-believer will not generally be curious to investigate what other measurable properties of the statue might be different from a normal statue, or whether there are other crying statues with similar properties. The crying-statue believer may even find these kinds of questions offensive and actively refuse to discuss them. This behavior seems to defend a behaviorally contentless belief from being recognized as such. The question then becomes: what is the purpose of such beliefs?

One answer is that they are primarily cultural loyalty signals with no semantic content (equivalent to "Go team!" or a verbal salute), but cannot be recognized as such by the believers because then they somehow lose their function. But if that's the case, it still doesn't explain why these beliefs are behaviorally contentless. This is where a neuroeconomic argument again applies. We should expect such beliefs to tend to be behaviorally contentless because otherwise they would damage the individuals' ability to maximize utility, and they would be selected against over time. The extent to which the belief does actually affect behavior will be partly offset by the loyalty signal value, so we should expect culturally-appropriate false beliefs to correlate in terms of their contentfulness and their loyalty-signal value. That is, the more that they're useful to signal your solidarity to receive in-group benefits and avoid punishment, the more these kinds of beliefs will actually make you do things instead of just say things. At the same time, when populations with two sets of cultural beliefs come into contact, the aggregate effect of the population with more severe behavior-affecting false beliefs will become apparent, because the loyalty-signal value of the beliefs is zero between populations that do not share it.

There are clear test cases for this theory in the world today where culture-specific-false-belief areas border each other, and where there are differences in terms of utility maximization as seen in economic development. I probably don't need to point them out because several have already been written about extensively in geopolitics books.

Hasler G. Can the neuroeconomics revolution revolutionize psychiatry? Neuroscience and Biobehavioral Reviews. 2011 Apr 29. [Epub ahead of print]

Saturday, June 25, 2011

The Linguistics of Bugs Bunny

We can infer that Bugs Bunny's native language probably has a small phoneme inventory, so that most utterances in Bunnese would be longer than their counterparts in English (as his first statement is). I always thought this was clever and it probably is one of the things that interested me at an early age in how languages differ.

There's also a great Porky Pig cartoon where Porky insists to Daffy Duck that "buenos dias" just means "bonjour" and vice versa. The self-referentiality of this implies through comedy that something like Pinker's mentalese must exist, but I can't find the clip.

Wednesday, June 1, 2011

Twittering and Tweeting

An early-adopter friend of mine, way back in '07 or '08, announced by Facebook that he was Twittering. At the time I hadn't heard of Twitter, and worried that he was publicly confessing he had developed an amphetamine habit. But we don't use Twitter as a verb. We tweet and re-tweet, right?

Actually, we do use Twitter as a verb - when we're speaking about
habitual use. "I'm Twittering" means "These days, I'm using Twitter" as opposed to "I'm sending a message on Twitter at the moment" - that latter sentence would be abbreviated by saying "I'm tweeting."

Many languages preserve a morphosyntactically encoded distinction between present and habitual - in fact, that's even one distinction between standard American English and the oft-villified ebonics (ebonics has it, standard Am English doesn't.) Here it's marked by requiring separate verbs. Minor observation, but interesting nonetheless.

Thursday, May 26, 2011

John P. Harrington and California Native Languages

John P. Harrington is known for taking copious notes on Southern California native languages. In the early twentieth century, many of these languages were already moribund. In at least one case - Tataviam, a Uto-Aztecan language spoken in the Santa Clara River basin which empties into the Pacific between Oxnard and Ventura - Harrington's notes constitute the only attestation the now-extinct language left to posterity.

It always amazes me when languages go extinct, not in isolation in the wilderness, but in the midst of booming humanity. Yes, I understand that the more numerous and economically-overbearing the new language community is (English in this case), the more likely the old language is to go extinct. But it always seems that out of all these people that settled Southern California, more than one would have been interested in recording them before they disappeared into the dust.

Tuesday, March 29, 2011

Button-Pushing Experiments Disprove Only One Fragile Model of Freewill

Experimental evidence continues accumulating which shows that human motor behavior, and conscious awareness of the decision to perform the behavior, are often preceded by neuronal activity. This has sometimes been taken as a disproof of free will. This reasoning is flawed. If we believe "if free will exists, then it applies to all human motor behavior, and all neuronal activity engaged with this motor behavior must be conscious". Therefore, for these experiments to be a disproof, at least two assumptions must be true: 1) the entire chain of events from deciding to act to performing the act must take place within consciousness to be called free will, and 2) this simple motor task model must be generalizeable to all decision-making and motor behavior taking place on all time scales.

To #1: it is possible that the decision is made, relative to the depolarization path of the motor act, "prior" to consciousness. If this is always the case, then epiphenomenalism is the correct description of consciousness, even though we could still have free will, because we can still affect future belief states and motor acts. Consequently it's worth asking if in these models, the "originating" neuron(s) is/are really the originating neuron. Acts of apparent free will merely passing through an unconscious pathway would be even less troublesome to the idea of free will than one originating in unconscious neurons.

Analogously, we cannot choose beliefs - we don't have free will about what we perceive and believe, because perception and belief follow necessarily from sense data and from the model of the universe that exists in our brains. When we encounter sense data, we interpret it immediately as representing something and as being causally related to other things in reality. For example, you cannot see someone smile, and DECIDE consciously whether or not to believe that they are smiling, and whether or not to believe that this means something about their emotional state. But this doesn't mean that we are prisoner to those beliefs and that we cannot influence future perceptions and beliefs. If you cross-check those beliefs, you can engage in behaviors the outcomes of which can differ in obvious
ways that then will allow you to update those beliefs.

At the very least, concluding that experimental results of this sort invalidate the idea of free will, you must carry other assumptions about the nature of consciousness and free will besides just "some objects' motions cannot be predicted from prior states, and those objects have conscious experience which in some way influences those motions". The separability of these two parts of free will - the idea of unpredictable output on the one hand and input from conscious experience on the other - is important. What are the requirements for non-conscious objects with unpredictable output? Are there conscious objects with completely predictable output? Another way of asking is whether things without nervous systems can have free will.

To #2, it's worth asking whether there are classes of decisions that are more or less subject to free will; i.e., how much can we generalize these results? Certainly there are cases where free will can be an illusion, but this falls short of disproving the possibility of free will in general. By all means experimenters should continue asking this question in more settings, although a button-push model wouldn't seem to give the nervous system a chance to shine. My suspicion is that if free will exists in any action it's in long-term executive planning.

It's worth mentioning that it seems strange very strange that our own lack of free will is not obvious to us, given that prediction of the behavior of conspecifics is evolutionarily extremely important. Why the inability to do so exactly, or why the strong appearance that we are the source of action? One speculation is game-theory oriented, that the input-output chain must necessarily be clouded by introducing randomness (which wouldn't really be free will), and our sense of free will falls out of that.

Another attack on the concept is Churchland-like, and questions whether free will isn't just a bad folk idea about human behavior (which I think many enthusiasts of these experiments which agree to). It's worth asking whether belief in something like free will is universal even among non-Western humans - do Solomon Islanders and pygmies have the same belief? - and if so, what it is that predisposes humans to believing this. Do humans with a different conception of agency have different beliefs about this (Aspergers spectrum people)? Finally, do nonhuman animals also believe in free will? I encourage inventive experimentalists to think of a way to support or discredit this hypothesis. If we know different kinds of nervous systems have the same belief we can start understanding what it is we have in common with them that makes us think this.

Tuesday, January 11, 2011

Signing Off Until Late June

As above. To study for a big test as well as maybe to get some actual original neuroscience research done. Thanks for reading, see you then. -Mike