Striatum

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.

Impaired adolescent decision-making

I am pleased to announce that my first first-author publication has recently been released online by the journal Developmental Psychology. The article, on decision-making in children and adolescents, looks at the developmental trajectory of affective decision-making abilities using the Iowa Gambling Task (IGT) in children between the ages of 8 and 17. It compares this type of "hot" executive function with more typical "colder" cognitive abilities, such as impulse control and working memory. Contrary to the accepted belief that children improve universally on cognitive tasks as they age, we discovered that early adolescents (ages 11-13) are actually more impaired on this task than some of the younger participants, making riskier decisions and failing to learn from their mistakes.

The IGT requires participants to choose between four decks of cards that give out varying amounts of wins and losses. Two of the decks issue low wins but also low losses, resulting in an overall net gain, whereas the other two decks are riskier options, giving high payoffs but also higher losses, making them ultimately disadvantageous. A net score is calculated by subtracting the total number of disadvantageous choices from the total advantageous decisions. Early adolescents had significantly lower mean net scores on the task than older participants, but did not differ from the younger children in their ability. However, the total trajectory of mean scores across all ages resulted in a significant J-shaped curve, signifying a dip in ability in early adolescence.

We speculate that this curvilinear trajectory is due to the varying developmental schedules of different regions of the brain, particularly the striatum (involved in reward processing) and the prefrontal cortex, which is responsible for more inhibitory control. Structures in the basal ganglia typically develop earlier in adolescence,  whereas the prefrontal cortex is not fully matured until the early 20s. This earlier development of the striatum could lead adolescents to place undue emphasis on the initially high reward, but ultimately disadvantageous options in the IGT. Coupled with the delayed development of the prefrontal cortex, this group could also lack the necessary inhibitory control to offset this reward-driven urge. Supporting this theory, other imaging studies investigating developing cognitive ability have shown adolescents to disproportionately recruit from subcortical regions, particularly the basal ganglia, on tasks involving monetary rewards.

Conversely, younger children performed neither overtly advantageously nor disadvantageously on the task, choosing between the decks more randomly. This could be due to an earlier neurodevelopmental stage, before the striatum and other limbic regions had fully developed, making them less sensitive to the risky high reward options. Also supporting this J-shape trajectory theory, older adolescents performed the most advantageously on the task, improving their performance and successfully inhibiting the urge to make impulsive choices. This improvement presumably correlates with the continued maturation of their prefrontal cortices, as these inhibitory abilities come on-line.

Notably, all other cognitive tasks administered during the course of testing improved linearly across age, demonstrating that affective decision-making is a unique process that taps into the limbic regions, rather than just relying on the cortical cognitive network.

Importantly, these results are not implying that all adolescents are impulsive risk-seekers doomed to make lasting poor decisions. We all go through these stages of neurodevelopment and the vast majority of us emerge from adolescence relatively unscathed. Also, as this was not an imaging study the neural correlates of the abnormal decision-making development is speculative. However, this study does provide an interesting glimpse into how we develop in our affective decision-making tendencies and how they change as we mature.