8/12/2009

Localizing ASD: Locus Coeruleus Links Sensory Processing, Cognition, Attention, & Fight or Flight Systems

I've read a number of studies that attempt to localize ASD in the brain, and none of them thrill me. They focus on a couple of symptoms, such as face reading deficits or problems understanding other's behavior. They make sweeping statements like "such and such wiring problem seems to cause ASD" when they fail to even address how, say, face reading deficits would cause pragmatic language issues or obsessive and narrow interests. They just seem to assume that, once you explain the social skills issues, everything else falls into place.

ASD involves problems with sensory processing, social cognition and interpretation, social language, and narrow, obsessive interests. Thus, cognitive, sensory, and probably attention and executive systems are likely involved in ASD. These systems are all connected, but they're also dissociable. So, if you're going to localize ASD, you have to find some brain region that communicates with, and affects, all of these.

Amazingly, someone has actually done this. Mark Mehler and Dominick Purpura actually paid attention to decades of anecdotal observations showing that some autistic kids seem to improve when they have a fever, but relapse to normal when the fever ends. Only one brain system is involved both in producing fever and controlling behavior: the LC-NA system.

The LC-NA system has its roots in the locus coeruleus, a bundle of neurons in the brain stem that are more widely connected than any other neurons in the brain. Here are some too-perfect properties of the LC-NA system...
  • It has "widespread connections to brain regions that process sensory information," taking in "sensory signals from all areas of the body."
  • In fact, the more connected the LC-NA system is to certain visual areas, the better a person is at "global visual spatial analysis and elaboration of visuomotor responses," as opposed to an autistic person's "greater focus on stimulus feature extraction and pattern analysis." To unpack the jargon: a neurotypical person's LC-NA system seems to be involved in global visual processing. It's also involved in exactly what Lily has trouble doing: acting on visual stimuli. We've already seen that people with ASD are biased towards local rather than global processing, although it's not clear yet exactly what this means.
  • "It secrets most of the brain's noradrenaline, a neurotransmitted that plays a key role in arousal mechanisms, such as the 'fight or flight' response." (Fight or flight responses are common in Asperger's syndrome. Adam was considered a "problem child" at several schools because, frightened by a social world that seemed hostile and senseless, he continually went into fight-or-flight mode).
  • The "preeminent role of the LC-NA system in arousal and attention" has been known for a while. Differences in attention combined with sensory processing likely produces caetextia, or context-blindness, in people with ASD.
  • Not only does the LC connect with these more basic, earlier-evolved brain areas, but it also "activates almost all higher-order brain centers that are involved in complex cognitive tasks," Dr. Mehler says. (This finding recalls a study suggesting that complex tasks are a problem for kids and adults with ASD. While they succeeded at simple cognitive and perceptual tasks involving only one area of the brain, they "had difficulty performing certain complex tasks that involved brain areas working together.")
Mehler and Purpura emphasize that there is no actual damage to the LC-NA system in ASD kids. Instead, the locus coeruleus activates a lot less than it's supposed to, probably because of genetic abnormalities. Fever temporarily helps people with ASD because the LC activates a lot more during a fever, and this activation seems to spread throughout the LC-NA system to connected areas. That there is no damage, and the LC-NA system can be reactivated in some cases, shows that ASD is reversible and treatable.

These researchers propose studying the tens, hundreds or thousands of genes that impair LC activation in people with ASD. I think that's a great idea. But if the problem is with activation, I wouldn't be surprised if we start seeing therapies that electrically stimulate the LC. It'll be a while before we understand the genetics of the LC-NA, but I think we have the knowledge and technology to stimulate it now.