A series of four experiments by neuroscientists at Georgetown University Medical Center are helping researchers zero in on what puts teens at risk of alcohol use and abuse even before they start drinking.
The experiments are part of the Adolescent Development Study, an effort funded by the National Institutes of Health (NIH) to understand how a teen brain “still under construction,”as NIH officials put it, can lead to risky behaviors such as alcohol and drug use.
The study, a collaboration between researchers at Georgetown and the University of Maryland School of Medicine (UMSOM), is directed by John VanMeter, Ph.D., director of the Center for Functional and Molecular Imaging, and associate professor of neurology at GUMC, and Diana Fishbein, Ph.D., director of the Center for Translational Research on Adversity, Neurodevelopment, and Substance Abuse (C-TRANS) at UMSOM.
“What this study is attempting to do is identify the differences in the brains of adolescents who go on to misuse alcohol and other drugs,” said VanMeter. “If we know what is different, we may be able to develop strategies that can prevent the behavior.”
For the studies, researchers recruited 135 preteen and teenage boys and girls, with an average age of 12.6 years. All 135 underwent structural and functional MRIs to investigate the connection between brain development and behavior.
The researchers also used questionnaires and several tests of neurocognitive function. Two of those tests — the Continuous Performance Task (CPT), which measures impulsivity, and the Temporal Discounting Task (TD), which quantifies preference for immediate rather than delayed reward — were conducted while the adolescents were scanned in the MRI.
The first study examines a long-standing question: Is a lack of connectivity in the brain’s Executive Control Network (ECN) a contributor to, or the result of, teen alcohol use?
For this study, Tomas Clarke, a research assistant, and Stuart Washington, Ph.D., a postdoctoral fellow in VanMeter’s laboratory, looked at the association between the Drug Use Screening Inventory questionnaire filled out by the 32 participants’ parents and brain connectivity within the ECN, which includes the areas that process emotion, impulsivity, and self-control.
According to the researchers, the questionnaire predicts future alcohol misuse. It does not ask parents about their alcohol or drug use, but does ask about social behaviors in their children, such as irritability, anger, and sadness.
Based on the questionnaire, Clarke divided the participants into two groups, 16 at high/medium risk for alcohol abuse and 16 at low risk. He then used fMRI scans to look at connectivity in the ECN. He discovered that ECN connectivity was significantly lower in the high/medium risk groups compared to the low risk group.
“We know impaired functioning in the ECN is linked to an earlier age of drinking onset and higher frequency of drinking, but it was unclear whether this dysfunction occurred before drinking or was a consequence of alcohol use,” Clarke said.
“Our findings suggest reduced prefrontal cortex development predates alcohol use and may be related to future alcohol use disorders.”
The next study examined levels of impulsivity in relation to the connection between executive control in the prefrontal cortex and the insular cortex, which is involved in processing emotions.
Benson Stevens, a graduate student in Georgetown’s Interdisciplinary Program in Neuroscience, used the Drug Use Screening Inventory to establish a high/medium risk and a low risk group, each with 17 participants.
He then administered the CPT test while the participants underwent fMRI. He found that, compared with the low risk group, participants in the high/medium risk group had reduced connectivity between the prefrontal cortex and the insular cortex.
“Less connectivity predicted higher levels of impulsivity,” Stevens said. “Importantly, these effects were observed before the onset of alcohol use. The reduced connectivity between these brain regions could be an important factor in adolescent alcohol use given that reduced inhibitory control has been found to be a factor in alcohol use disorders.”
A third study investigated the relationship between sugar intake — as self-reported by the adolescents in a food questionnaire — and performance on two tests, the CPT and the TD, which measure impulsivity and ability to delay gratification. The CPT was used while participants were being scanned by fMRI.
“We know that, compared to healthy individuals, adults with alcoholism have a stronger preference for sweet tastes, are more impulsive and are less able to delay gratification,” explained Dana Estefan, a former research assistant in VanMeter’s lab who is now a student at New York University.
“We wanted to know if this profile fits youth deemed to be at risk for early alcohol use by the Drug Use Screening Inventory.”
The TD task confirmed the expected relationship — kids with high amounts of added sugar in their diets preferred immediate rewards more than kids with lower levels of added sugar in their diets.
Additionally, the CPT task revealed that kids with increased sugar intake also showed greater activation in the right superior temporal gyrus and right insula, areas linked to impulsivity and emotional affect, the researchers reported. Their hypothalamus was also highly activated, which, in adults, is linked to overeating, reward seeking and drug addiction, Estefan added.
“Our findings could potentially mean a positive correlation between impulsivity and sugar intake in adolescents, but more research needs to be done on this,” she said.
In the last experiment, Valerie Darcey, a registered dietitian and a graduate student in the Interdisciplinary Program in Neuroscience, examined the relationship between the intake of DHA, an essential omega-3 fatty acid, and impulsivity. DHA, found in cold-water fish, is important for neuronal function, she explained.
She used a food questionnaire to measure, in 81 participants, ingestion of DHA and arachidonic acid (AA), which is omega-6 fatty acid found in vegetable oil, among other foods. AA competes with DHA for a place in cell membranes, so the more AA consumed, the less DHA is used, she explained.
She then gave the adolescents the CPT test while scanning their brains with fMRI.
“My preliminary findings show that while impulsivity levels are the same for kids with high and low levels of DHA in their diets, the brains of kids with low DHA appear to be more active — working harder to compensate — in a region involved in paying attention to the task and a region that participates in executive function,” she says.
“This tells us that the brains of the kids eating less DHA may not be developing like those eating more DHA.”