The Development and Functions of the Frontal/Prefrontal lobes: Role in Drug Abuse

United States

Summary of Conference

The conference participants discussed and reviewed research themes that were identified as particularly important for understanding 1) the development and functions of the frontal/prefrontal lobes and 2) how these functions might play their role in drug abuse. There was unanimous agreement that frontal lobe functions play an important role in drug abuse but this area of research has not been effectively exploited in NIDA sponsored research. Listed, in the table below are some of the themes that should be supported both in terms of basic research that can be applied to the study of drug abuse in the near future as well as science that is well developed enough to be applied and translated now in drug abuse research.

Research Themes

Choice and decision processes-basic research

Use of animal models for the development of pilot experimental tasks that might be effectively used in humans (adults, children and teenagers). Animal models allow more invasive investigations of the neurobiology of decision-making. As much as possible, we should encourage neuroscience studies that 1) investigate neural substrates (synaptic, cellular, systems) of direct relevance to adaptive decision-making, and 2) examine decision-making in behavioral tasks with close analogies to human decision-making. It is important, however, to remember that animals have species-specific cognitive capacities - they may pass or fail behavioral tests for different reasons than humans or other animal species.

Choice and decision making in development and in drug abuse patients.

What is altered in the decision-making of substance abusers? Is their maladaptive decision-making specific to learned drug-related behaviors, or is it a manifestation of a more generalized deficit? To address this, novel, well-defined behavioral tasks assessing various aspects of decision-making would be useful. Tasks that assess adaptive decision making in more realistic, emotional or stressful conditions may be of particular value. Development of behavioral tasks should be guided by, and used to inform, neurobiological studies. As a long-term goal, it would be useful to have a battery of tasks that could be effectively used to either diagnose or predict vulnerability to substance abuse, and perhaps be used to guide interventions.

Adaptive planning and decision-making has multiple functional components, each of which may be altered in substance abuse. These include defining goals, accurate conceptualization of the consequences of distinct actions, and inhibition of competing/short-term responses. In addition, many of the actions we perform are automatic, occurring rapidly without conscious planning. Choosing adaptively can therefore also require the pre-decision to make a conscious, evaluated choice. These executive processes involve multiple brain systems, but the frontal lobes are known to be of particular importance.

Frontal and PFC normal and aberrant development

Are their key stages in development when cognitive treatment interventions may be most successful in lowering the risk for drug abuse? How do the decision-making capacities of children and adolescents develop, and how is this mirrored in their developing functional brain organization and neurochemistry? It is important to have a solid 'baseline' from which to assess alterations in individual decision-making capacities. Studies that evaluate both cognitive capacities and brain development in the same individuals over time would be particularly useful. Such baseline studies would be of interest to multiple NIH institutes and may be best approached as inter-institute initiatives.

Inhibition (but must be understood that this is a very general term/concept that covers all kinds of processes and operations)

There are different forms and patterns of inhibition. PFC in inhibition, patterns of inhibition. Should continue to be studied from a number of perspectives; neurochemistry, electrophysiology and molecular biology. Need to support integrative research (from the cellular to the systems levels) Since inhibition may not be a generalized process, task design may be quite important. One of the themes that should also be considered as part of the inhibition theme is aggression.

Circuitry of frontal and PFC in relation to other brain regions including relationship between frontal cortex and reward systems

The prefrontal cortex is critical for normal planning and execution of adaptive choices. Distinct types of information must be gathered from other brain regions, utilized in an evaluative selection process, and appropriate output generated to guide activity in various other brain regions. A greater understanding of the relationship between PFC and other brain regions, as well as the internal circuitry within PFC, is therefore desirable. For example, how exactly is information about previous experiences, current cues in the environment, and rewards, used to guide choices? How is the PFC able to inhibit well-established 'habits' to allow flexible, adaptive behavior?

Frontal and PFC acute and chronic effects of abused drugs

This type of research would include development of ecologically valid tasks as well as a consideration of "hot" and "cold" emotions in cognitive effects. Ecologically valid tests means tests that would also make use of social cognition paradigms.

Shift from controlled to automatic operations and back again.

We know a good deal about how controlled cognitive tasks become automated but are not nearly as knowledgeable about how to de-automate a cognitive task so that it can be "re-tooled" in a controlled manner. This theme may be particularly important in drug abuse (for functions such as inhibition).

Longitudinal studies of kids (through college) who use and abuse (vulnerability) or do not abuse drugs/ (resilience).

Longitudinal studies that evaluate populations before, during and after periods of high vulnerability to substance abuse would potentially lend insight into individual risk factors. As an example, heavy/binge drinking is common in college-age populations, but the majority gives up this behavior; what's different about those who do not? Who are the survivors of drug experimentation? Use of fMRI and other methods for assessment.

Children and adolescents may be particularly vulnerable to acquiring drug habits, because their planning/decision-making capabilities are not fully developed, because their understanding of the consequences of their actions is incomplete, and because their social and biological context may lead them to prioritize goals differently to adults.

Use of potential treatment interventions as a means of testing models. rather than simply about efficacy in the clinic

Think of potential treatment interventions in terms of studies that can elucidate the features of the etiology of drug abuse but also as a perspective for answering basic science questions related to frontal/PFC functioning.

Additional issues that were considered at this meeting

1. Environmental/social context and frontal/PFC functioning. This theme may be particularly relevant in the study of inhibition and aggression.
2. Stress and PFC and impact on frontal/PFC functions and its clinical implications. There can be dissociation between the actions individuals say they would perform in hypothetical situations, and what they actually do in the real world. This dissociation is likely in part due to the different emotional states in which laboratory vs. real-world decisions are made. In particular, social pressures and stress can provoke acquisition or relapse to drug-taking behavior.
3. Translational research groups should supported that can work together on problems that represent different levels of analysis (human and animal work).
4. Develop rewards that can compete with drugs (using what we know from cognitive neuroscience research)
5. Imaging studies of animals in parallel with humans of different ages. There are several groups beginning to use PET and fMRI with nonhuman primates. These are critical with respect to the use of animals as models, and for comparison with humans.
6. Development of experimental/observational assays that can be used across species and age groups. This is relevant for most of the themes outlined above.