Frontal cortex

A predisposition for drug addiction? Shared traits between stimulant dependents and their siblings

An exciting new study published in Science this week attempts to answer the chicken-or-egg question pervasive in drug addiction research of, "Which comes first, drug use or brain abnormalities?" Dr. Karen Ersche from the University of Cambridge* approaches this question with a new perspective, investigating the biological siblings of dependent drug users. And as is the case with most seemingly dichotomous questions in science, the answer is: both.

Dr. Ersche's group studied 50 stimulant-dependent individuals, 50 of their healthy, non-dependent biological siblings, and 50 unrelated control volunteers on a barrage of cognitive tests, personality measures, and brain imaging techniques. Throughout the assessments, there was a striking pattern of similar responding between the drug users and their siblings, significantly differing in their results from the control participants. Specifically, drug users and their siblings were both significantly more impaired on the Stop Signal Reaction Time Task (SSRT), a test of inhibitory control that measures how well an individual can stop an ongoing response when triggered. Impulse control and inhibition are traits known to be impaired in drug-dependent individuals, and poor performance on the SSRT has previously been associated with an increased risk for drug abuse. However, these dysfunctions have long been debated as to whether they can be attributed to accumulated years of drug use and its effects on the brain, or are instead a predisposing factor that places an individual at an increased risk for drug dependence. In the current study, sibling participants performed as poorly on the SSRT as drug-dependent individuals, requiring more time to inhibit their actions. This would suggest that poor impulse control is a shared trait that is present in drug-dependent individuals before the onset of abuse. However, impaired inhibition is clearly not a determining variable, as dysfunction in the siblings did not lead to subsequent drug abuse or dependency.

Did I do that? Reality monitoring in the brain

Most of us have no problem telling the real from the imagined. Or so we think. Reality monitoring, the incorporation and distinction of internal thoughts and imaginings from external experiences and memories, typically happens seamlessly for most individuals. However, there are times when we cannot recall if someone else told us about that interesting article or whether we read it ourselves, or if we remembered to lock the door before leaving the house or not. Did we actually do or hear these things, or did we only imagine them? This is a common problem in patients with schizophrenia, who at times cannot distinguish between what they think they remember or believe to be true, and what actually occurred.

A new study on reality monitoring published last week in the Journal of Neuroscience reveals that many of us are not as good at making this distinction as we might think. Additionally, the ability to discern between perceived and imagined events may be rooted in one very specific region of the brain, which nearly 30% of the population is missing. Led by Marie Buda and Dr. Jon Simons at the University of Cambridge*, researchers administered a very particular type of memory test to healthy participants who had been pre-selected based on the prominence of the paracingulate sulcus (PCS) in their brains. Running rostral-caudal (front to back) and located in the anteriomedial (middle-frontal) prefrontal cortex, this region is involved in higher level cognitive functioning and is one of the last parts of the brain to mature. Consequently, it can be relatively underdeveloped or even seemingly absent in many people. This is particularly the case in individuals with schizophrenia, where as many as 44% of patients lack this particular region.

Participants for the current study were chosen from a database of individuals who had previously undergone an MRI scan and clearly showed a presence or absence of the PCS in either one or both of the neural hemispheres. The memory task in question involved a list of common word pairs such as "yin and yang" or "bacon and eggs". These words were either presented together (perceive condition), or only one word was presented and the participant was to fill in the complimenting phrase (imagine condition). The second portion of the experiment involved the source of this information, i.e. whether the subject or the experimenter was the one to read off or verbally complete the pair. After the task, the subject was asked to report whether the pair was fully perceived or imagined, and whether this information was attributed to themselves or the experimenter. They were also asked to rate their confidence in both of these responses.

Participants with a complete absence of the PCS in both hemispheres performed significantly worse on the reality monitoring task than individuals who exhibited a definite presence of the sulcus. This difference was based on their source attribution memory (themselves vs. the experimenter); performance on the perceive or imagine condition did not differ between the groups. Interestingly, the two groups also did not differ in their confidence in their responses. Thus, even though the PCS-absent group performed significantly worse on attributing the source of the information, they were still just as confident in their answers as individuals who responded correctly, indicating a lack of interospective awareness in the absent group in regards to their memory abilities.

It should be noted that there was also a correlation between overall gray matter volume in the prefrontal and motor cortices and scores on the reality monitoring task. This is important as it may indicate that there are other regions involved in this process outside of the PCS, and the authors caution that this enhanced ability may stem from an increase in gray matter and connectivity in the medial prefrontal cortex, rather than from the PCS itself.

These findings could have useful applications in clinical psychiatry. As stated above, an impairment in reality monitoring is often associated with schizophrenia, and the absence of the PCS could serve as a potential biomarker for this disorder. Additionally, although not commonly discussed in terms of reality monitoring, another psychiatric diagnosis that could potentially benefit from this type of research is obsessive compulsive disorder (OCD). OCD often consists of obsessions and the urge for frequent compulsive checking of things, such as whether one remembered to turn off the stove. This ruminating and checking behavior could be indicative of a breakdown in reality monitoring where patients can not determine whether a target action actually occurred or not. While this problem is not encompassing of all OCD patients, reality monitoring disability could be a potential area to investigate in those patients for whom checking is a significant problem.

*Disclaimer: Marie Buda and Jon Simons are fellow members of the Department of Experimental Psychology at the University of Cambridge with me.

The neuronal defense

There's been a lot of discussion recently about structural and hormonal changes in the brain being to blame for misbehavior, whether it's a philandering husband (or senator) or a psychopath. To some extent these are valid arguments; higher testosterone levels have been linked to sensation seeking and greater sexual desire, and abnormalities in the limbic system, particularly the amygdala which processes fear and emotion, and the frontal cortex, which is in charge of inhibition and rational thought, are often seen in persons who commit crimes. However, to use these structural phenomena as excuses or arguments as in, "My brain made me do it", is the same as proclaiming, "Yes, I did this". Obviously there are times of rare and extenuating circumstances when an individual's actions are truly no longer under their own control, such as in the case of a tumor in the frontal lobe changing the temperament and personality of an individual. However, for the vast majority of individuals, we are our brains, and saying you are "pre-wired" to cheat or fight or steal is not an excuse. If anything, it is a greater indication for potential recidivism and an added incentive for either punishment or preventative measures. Excess testosterone is not a pathology like schizophrenia or mental retardation, which can be used as defenses in court for criminal actions. Additionally, if you blame chemicals like testosterone or a lack of oxytocin for misbehavior, then what is to stop us from exonerating people who commit crimes because they are on a synthetic drug, like crack cocaine or PCP? And, seeing as how presumably not all men with increased testosterone cheat and not all individuals with abnormal amygdalas commit crimes or become sociopaths, it is difficult to argue that your brain and neurotransmitters make you do something when these same conditions do not compel another to a similar path.

David Eagleman's article in The Atlantic is a particularly insightful and eloquent investigation into both sides of this issue, which I highly recommend. Instead of focusing on the question of guilt and the implications that recent advances in neuroscience and neuroimaging have on culpability, Eagleman wisely shifts his focus to sentencing and the more constructive ways to incorporate our new crude knowledge of the brain into the justice system. He suggests concentrating on the potential for recidivism and reform when determining sentencing, instead of retribution. Drug courts have already started shifting towards this perspective, supported by the recent initiative by the Global Commission on Drug Policy, marking the 40 year anniversary of the War on Drugs. Not only is it important to help drug users receive treatment instead of punishment, our economy simply can not accommodate the deluge of drug related crimes into the penal system, most strikingly demonstrated by the decision in California this month to release 3,000 prisoners before their sentences were up due to a lack of resources.

Child criminal courts have also dealt with this issue of neuroanatomical defenses for quite some time, as it is widely established that the frontal cortex is the last area of the brain to finish developing, not reaching full maturation until the mid-20s. Countless juvenile defenders have used this argument to insist that their client was not a rational individual at the time of their crime, and therefore should not be held accountable for their impulsive and illegal actions. While this is certainly a valid point, and one that is typically taken into consideration when distributing sentencing, with prolonged punishments thought to be excessive and insensitive to changes the individual will undergo in the next 5-10 years, it is important to bear in mind that not all 15 year-olds commit crimes. Therefore, this universal neural stage of adolescence that we all pass through is not necessarily a credible criminal defense, as otherwise all teenagers would be running rampant and wreaking even more havoc than they already do. Also, there are innumerable studies citing the increased risk of offense in impoverished or violent areas, yet this is not used as an excuse for a crime when poor behavior is conducted. It is absolutely a reason to reform the social system that creates these pockets of poverty and risk, but it does not compel juries to acquit defenders of their crimes simply because of the neighborhood they were raised in.

At some point, people must take responsibility for their actions and face up to the consequences, not blaming an integral part of them for going rogue and acting out of character. When you make a decision it is your brain acting and your neurons firing; you can not excuse an action because you claim you could not control these impulses. There is no outside force urging you to act or not, for that is your own will being administered and carried out. Eagleman's idea of a spectrum of culpability is a sensible one that I support, and I fully agree that in the vast majority of offenses reform and rehabilitation should be the goal, rather than retribution, however this still leaves the topic rife with ambiguity for where do you draw the line? At what point we will stand up and take responsibility for our own actions?

(Thanks to Tristan Smith for The Atlantic article.)