Another lesion results in lost addiction, new model of addiction

What is the deal with the stories showing brain lesions that end addiction? First, there was this one. Then, today in Nature there was another one:

Strokes often change a person's character, depending on where the damage hits. Some may become more impulsive, others depressed. Now researchers have shown that damage to a small but very specific brain area can wipe out an addiction to smoking.

Antoine Bechera, of the University of Iowa in Iowa City, has identified 14 patients who all stopped smoking immediately after having a stroke that damaged their insular cortex. This seems to be not because they were concerned about their health, but because they had lost all interest in cigarettes, he told the Federation of Neuroscience Societies in Vienna this week. "One or two had even forgotten that they used to smoke," says Bechera.

The insular cortex is a relatively primitive part of the brain whose functions include providing an emotional context for experiences, such as drug taking, along with some higher-level, decision-making functions involved, for example, in forming memories.

The other story I mentioned showed a case of someone with a lesion to their globus pallidus that resulted in a loss of their addiction. This is to a different part of the brain. This difference in brain regions actually highlights two different views of how addiction works in the brain.

The more traditional view would hold that addiction results from a potentiation of the reward pathway involving dopamine. This is supported by lesion and pharmacological studies involving rats where interfering with this pathway prevents them from becoming addicted.

The researcher from the article, Antoine Bechera, has a slightly different view of how addiction works on the brain. His view is more nuanced in that it includes the process of decision in succumbing to addiction.

Basically, he highlights two opposing systems in the brain. The "impulsive" system is that part of the brain that identifies the immediate affective salience of a particular stimulus -- whether it is rewarding or aversive. It is short-lived, habituates rapidly, and involves structures at the base of the brain like the amygdala. The "reflective" system identifies the long-term affective consequences of a stimulus based on memory and hypotheticals. It is long-lived and involves the prefrontal cortex.

I hate to be all Freudian but if you want you could think of the impulsive system as a sort of id and the reflective system as a sort of superego.

In deciding whether to use drugs, there is a competitive process between the impulsive system and the reflective system that is winner take all. The decision to do drugs occurs when the impulsive system's positive reward signal exceeds the reflective system's aversive evaluation to the long-term consequences of the act.

This model makes several concrete predictions about addiction, many of which are supported by the evidence. Here is an excerpt from a review by Bechara -- which I recommend in its entirety if you want more information about his model:

Normal functioning of the VMPC [ventromedial prefrontal cortex] is contingent upon the integrity of other neural systems. One system involves the insula and other somatosensory cortices, especially on the right side, that are critical for representing patterns of emotional/affective states. Patients with right parietal damage (encompassing insula and somatosensory cortex) show impairments in decision making; addicts show functional abnormalities in these parietal regions when performing decision making tasks. The other system involves the dorsolateral sector of the prefrontal cortex and the hippocampus, which are critical for memory. Indeed, maintaining an active representation of memory over a delay period involves the dorsolateral sector of the prefrontal cortex, and patients with damage to this structure show compromised decision making; addicts who have deficits in working memory also show compromised decision making. Thus, decision making depends on systems for memory as well as for emotion and affect. Damage to any of these systems compromises the ability to make decisions that are advantageous in the long term. The VMPC region links these systems together, and therefore when it is damaged, there are many manifestations, including alterations of emotional/affective experience, poor decision making and abnormal social functioning.

Several voxel-brain-morphometry studies of brain scans of addicts found varying degrees of structural abnormalities in main components of the reflective system (Fig. 1), including the VMPC, anterior cingulate, insular cortex, dorsolateral prefrontal cortex and lateral orbitofrontal/inferior frontal gyrus. Abnormalities have also been detected in white matter pathways connecting these structures. Convergent results have also been obtained from functional neuroimaging studies...However, it is difficult to determine whether these abnormalities preceded or were the consequences of drug use. My view is that a degree of abnormality pre-existed the addiction state, by facilitating the progress from experimentation to addiction. However, any subsequent excessive and chronic use of drugs can exacerbate these abnormalities. (Citations have been omitted. Emphasis mine.)

It is not clear whether poor function in what he would call the reflective system precedes addiction. Also, Bechara concedes that addicts are a mixed group:

One subgroup of addicts appeared normal and did not show behavioral or physiological signs of decision making deficits. This suggests that not every drug user has impaired decision making. We have described these addicts as 'functional' addicts, because a closer inspection of their everyday lives has shown that they have suffered minimal social and psychological harm as a consequence of their drug use: for example, they manage to keep their jobs. Therefore, my view is that poor decision making in addiction is evident only when individuals persist in escalating their drug use in the face of rising adverse consequences. According to this view, people described as addicted to coffee, sweets, the internet and so on do not necessarily have impaired decision making, unless their choices bring increasing social, physical or psychological harms. However, an alternate possibility is that the lack of evidence for decision making deficits in this subgroup of addicts is a limitation of the proposed somatic marker framework, in that it does not capture all instances of addiction.

Finally, one subgroup of normal controls shows behavioral and physiological profiles that matches VMPC patients. This raises the question of whether these individuals are predisposed, or at higher risk, for addiction than individuals with normal decision making capabilities. This suggestion is reasonable in light of the evidence that one predisposing factor to addiction is heredity, and genes can act in general fashion (such as the serotonin transporter gene) to predispose individuals to multiple, as opposed to specific, drug addictions. Future research using functional imaging methods could focus on relationships between (i) genotypes related to specific neurotransmitter systems (for example, the serotonin transporter gene) (ii) the level of neural activity in specific neural circuits, and (iii) quality of choice, as shown by complex laboratory tasks of decision making. This will reveal whether genetic factors lead to suboptimal function in specific neural systems, which then leads to behaviors reflecting poor decision making.

However, not all predisposing factors are necessarily genetic; other factors could be environmental (such as drug neurotoxicity), or the product of gene-environment interactions. Although the evidence for neurotoxicity resulting from drug use remains questionable, the potential for harm remains relatively higher if drugs were abused during adolescence. Indeed, evidence suggests that the functions of the prefrontal cortex may not develop fully until the age of 21, and until such a time, the development of neural connections that underlie decision making, and the control over powerful temptations, is still taking place. Therefore, exposing the prefrontal cortex to drugs before its maturity could be harmful to decision making, just like exposing the fetus to drugs during pregnancy. However, the fact remains that not every adolescent who tries drugs ends up addicted; it takes more than mere exposure to drugs to become addicted. Therefore, my hypothesis is that poor decision making in addiction is not the product of drug use; rather, poor decision making is what leads to addiction. (Citations have been omitted. Emphasis mine.)

Simply because this model can account for the possibility of both a risk predating drug use and an increasing risk that follows from drug use, I think it does a much better job explaining the evidence than the other model. Also, it concedes the existence of high functioning drug addicts, who we may want to pretend don't exist but certainly do.

This is definitely an area of research to watch, so I thought I would summarize some of the newer models. I imagine it is also an area of research that is bound to spawn contreversy. Several commenters have taken issue with an article that I posted on the ill-effects of early alcohol use. If early drug use capitalizes on existing vulnerability, what strategies can we use to prevent young people from using drugs? If drug use is partly the consequence of a genetic vulnerability, should we be imprisoning drug users? Bechara believes that decision -- albeit a decision with a sometimes stacked deck -- initiates addiction. Is he right? How culpable are we?

I think all of these are reasonable concerns that will recieve more and more scrutiny as the evidence comes in.

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A very interesting clinical observation, (the insular cortex lesions) it's a shame, however, that it wasn't tagged together with an animal lesionning study (you know, do insular cortex lesions stop formation, expression or re-expression of addiction).

It's also interesting that there is such a strong link to the ventromedial prefrontal cortex, I wonder if the insular cortex has strong links to the dopaminergic midbrain neurons and ventral striatum and other reward related regions...