Adolescents At Risk Of Developing A Substance-use Disorder Have Deficits In Frontal Brain Activation

"ECF is basically the control center for governing other cognitive processes," explained Rebecca Landes McNamee, assistant research professor of radiology and bioengineering at the University of Pittsburgh and corresponding author for the study. "For example, in school, ECF would be engaged in the planning and control process required in answering a question; formulating your response, raising your hand, waiting until you are called upon, and stating your answer. A person with low levels of ECF might blurt out the answer. Another example could be interacting with someone on the playground who upsets you. A person with good ECF will think through the actions and consequences of their behavior rather than responding rashly. A person with low levels of ECF may respond with violence."

McNamee and her colleagues decided to use an antisaccade task to reflect the inhibitory response required in the actions above.

"While this eye-movement task may be more basic in nature than an inhibitory response, it still requires control and response suppression, and is thought to use the same basic mechanisms in the brain as those required in more difficult suppression tasks," she said. "As response inhibition is something that may be deficient in high-risk children, we thought this task would be a beneficial way to study the workings of basic mechanisms in the brain."

The researchers employed fMRI with 25 adolescents (15 males, 10 females), ages 12 to 19 years, during a task that required inhibition of an initial eye-movement response as well as a voluntary realignment to an alternate location. The fMRI findings were categorized into regions of activation: total frontal, parietal, occipital, and temporal lobe. Additionally, each subject's neurobehavioral disinhibition (ND) -- their ability to control an immediate impulsive response to a given situation -- was assessed, and the drug use/histories were determined.

"We found that individuals who exhibit a high amount of ND -- that is, do not have a good ability to manage their impulsive responses -- have less brain activity in the frontal cortex, the region of the brain responsible for ECF, during the antisaccade task," said McNamee. "In other words, the regions of the brain responsible for these inhibitory processes engaged less energy in individuals with higher ND scores than those with lower ND scores."

Normal adolescent development involves an increase in the ability to inhibit impulsive responses, which would be reflected in an increase in brain activation in areas associated with inhibition, said McNamee.

"Since some of the children show less ability to inhibit responses -- observed as higher levels of ND -- along with less brain activity in these areas, we can hypothesize that the reason for this is a delay in the development of brain networks associated with inhibition," she said. "We cannot say for sure what may cause these deficits, but we suspect it has to do with a combination of genetics inherited from the parents and/or the environment in which the individual was raised."

One of the key implications of these findings, said McNamee, is that behaviors and actions are directly related to brain functioning.

"Teachers, caregivers, and other individuals should understand that each adolescent matures at a different rate; they do not always respond like adults because their brains are not at the same level of functioning as an adult," she said. "Responses and behaviors related to a certain situation are less easy for some adolescents to manage than others."

McNamee plans to follow these adolescents as they mature. "We would like to better understand whether the brains of subjects with higher levels of ND display increasing amounts of brain activation in the frontal lobe as they mature, or if they will continue to show reduced brain activity when compared to subjects with lower ND scores throughout later adolescence. This type of data may help to indicate whether inhibition centers in the brains of high ND subjects 'catch up' to those of the lower ND subjects, or if they will always have differences with respect to these brain centers."

Results are published in the March issue of Alcoholism: Clinical & Experimental Research.

Co-authors of the ACER paper, "Brain Activation, Response Inhibition, and Increased Risk for Substance Use Disorder," were: Kathryn L. Dunfee and Ralph E. Tarter of the Department of Pharmaceutical Sciences, Beatriz Luna of the Department of Psychiatry, and Duncan B. Clark of the Department of Pharmaceutical Sciences and the Department of Psychiatry, all at the University of Pittsburgh; as well as William F. Eddy of the Department of Statistics at Carnegie Mellon University in Pittsburgh. The study was funded by the National Institute on Drug Abuse, and the National Institute on Alcohol Abuse and Alcoholism.