Alcoholism

Brendan Koerner has a really fantastic article in the latest Wired on Alcoholics Anonymous (AA). It's a fascinating exploration of the organization, from its hallucinogen inspired birth (Bill Wilson was tripping on belladonna when he found God in a hospital room) to the difficulty of accurately measuring the effectiveness of AA:

The group's "cure rate" has been estimated at anywhere from 75 percent to 5 percent, extremes that seem far-fetched. Even the most widely cited (and carefully conducted) studies are often marred by obvious flaws. A 1999 meta-analysis of 21 existing studies, for example, concluded that AA members actually fared worse than drinkers who received no treatment at all. The authors acknowledged, however, that many of the subjects were coerced into attending AA by court order. Such forced attendees have little shot at benefiting from any sort of therapy--it's widely agreed that a sincere desire to stop drinking is a mandatory prerequisite for getting sober.

Yet a growing body of evidence suggests that while AA is certainly no miracle cure, people who become deeply involved in the program usually do well over the long haul. In a 2006 study, for example, two Stanford psychiatrists chronicled the fates of 628 alcoholics they managed to track over a 16-year period. They concluded that subjects who attended AA meetings frequently were more likely to be sober than those who merely dabbled in the organization. The University of New Mexico's Tonigan says the relationship between first-year attendance and long-term sobriety is small but valid: In the language of statistics, the correlation is around 0.3, which is right on the borderline between weak and modest (0 meaning no relationship, and 1.0 being a perfect one-to-one relationship).

Koerner also investigates AA from the perspective of the brain. He focuses on the prefrontal cortex, that chunk of tissue behind the forehead that allows us to exert self-control, to order club soda instead of whiskey:

As dependence grows, alcoholics also lose the ability to properly regulate their behavior. This regulation is the responsibility of the prefrontal cortex, which is charged with keeping the rest of the brain apprised of the consequences of harmful actions. But mind-altering substances slowly rob the cortex of so-called synaptic plasticity, which makes it harder for neurons to communicate with one another. When this happens, alcoholics become less likely to stop drinking, since their prefrontal cortex cannot effectively warn of the dangers of bad habits.

This is why even though some people may be fully cognizant of the problems that result from drinking, they don't do anything to avoid them. "They'll say, 'Oh, my family is falling apart, I've been arrested twice,'" says Peter Kalivas, a neuroscientist at the Medical University of South Carolina in Charleston. "They can list all of these negative consequences, but they can't take that information and manhandle their habits."The loss of synaptic plasticity is thought to be a major reason why more than 90 percent of recovering alcoholics relapse at some point.

It's now possible to see these changes in the prefrontal cortex at an extremely precise level. Interestingly, one of the most important changes has to do with how alcoholics (and addicts in general) process "prediction error" signals. In essence, a prediction error signal occurs when we expect to get a reward - and it doesn't matter if the reward is money, sex, praise or drugs - and we instead get nothing (or maybe even a negative outcome). The brain processes this disappointment as a prediction error. As Wolfram Schultz and others have demonstrated, such prediction errors are an incredibly efficient way to learn about the world, allowing us to update our internal models (all those predictions of good stuff) in light of our mistakes.

This is an essential aspect of decision-making, as it allows us to avoid the mindless repetition of mistakes. Just look at what happens to monkeys when their prediction error pathway is surgically disrupted. The experiment went like this: monkeys were given a joystick that moved in two different directions. At any given moment, only one of the movements would trigger a reward (a pellet of food). To make things more interesting, the scientists switched the direction every twenty-five trials. If the monkeys had previously gotten in the habit of lifting the joystick in order to get a food pellet, they now had to shift their strategy.

So what did the monkeys do? Animals with an intact prediction error pathway had no problem with the task. As soon as they stopped receiving rewards for lifting the joystick - this generated a prediction error - they started turning it in the other direction, which meant they continued to receive their pellets of food. However, monkeys that were missing their prediction error machinery demonstrated a telling defect. When they stopped being rewarded for moving the joystick in a certain direction, they were still able (most of the time) to change directions, just like a normal monkey. However, they were unable to persist in this successful strategy, and soon went back to moving the joystick in the direction that garnered no reward. They never learned how to consistently find the food, to turn a mistake into an enduring lesson.

What do prediction errors have to do with addiction? One way to think about addiction is the abuse of a substance despite serious adverse consequences. We think the alcohol will make us happy - and it does, for a few minutes - but the drug will also lead to withdrawal, hangovers, ruined relationships, an empty wallet, etc. In other words, the costs of the drink far exceed its fleeting rewards. Why, then, do addicts keep on drinking? One possible explanation is that addicts can't properly process their prediction errors, so that all those negative outcomes get ignored. (In other words, we're like those monkeys who keep on pressing the joystick in the wrong direction.) The end result is that we never learn from our very costly decision-making mistakes.

A new paper in the Journal of Neuroscience by Soyoung Q Park, et. al. provides compelling support for this hypothesis. The scientists began by giving twenty "abstinent alcohol-dependent patients" a simple reinforcement learning task featuring green smiling faces (positive feedback) and red frowning faces (negative feedback).

The first thing to note is that it took the alcoholic patients significantly longer to figure out the game than a group of control subjects. Because the game was played inside an fMRI machine, the scientists were able to analyze the neural differences that led to the learning problems. Interestingly, the alcoholic patients didn't have a problem generating prediction errors in the striatum, the dopaminergic source of the prediction error signal. When they made a bad guess and saw the red frowning face, their addicted brains looked identical to brains of control subjects. Both groups instantly and automatically recognized their mistakes.

It's what happened next that begins to explain the errant behavior of addicts. In the control group, this prediction error signal was quickly passed along to the prefrontal cortex, which used this new information to modulate future decisions. As a result, the control brain was able to quickly learn from its mistakes and minimize the number of red frowning faces.

The alcoholic brain wasn't nearly as adept. Park et. al. found that, at least in this small group of addicted patients, there appeared to a connectivity problem between the striatum and the prefrontal cortex. As a result, when these subjects made a mistake, their prefrontal cortex wasn't fully informed - there was a reduced amount of "feedback-rela
ted modulation" - and this
lack of modulation correlated with 1) an inability to succeed at the simple learning task and 2) the magnitude of their alcohol craving. (This data extends similar results observed in smokers.) In other words, the addicts who couldn't internalize their prediction errors were the most addicted. This suggests that it is the inability to learn from mistakes - even when these mistakes are destroying our life - that makes addiction so damn hard to escape.

Now here's some blatant speculation. I think one reason AA is successful, at least for many of those who commit to the program, is that it's designed to force people to confront their prediction errors. Just look at the twelve steps, many of which are all about the admission of mistakes, from step number 1 ("We admitted we were powerless over alcohol--that our lives had become unmanageable") to step number 8 ("Made a list of all persons we had harmed, and became willing to make amends to them all") to step number 10 ("Continued to take personal inventory and when we were wrong promptly admitted it"). I'd suggest that the presence of these steps helps people break through the neuromodulatory problem of addiction, as the prefrontal cortex is forced to grapple with its massive failings and flaws. Because unless we accept our mistakes we will keep on making them.