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Component 7: Cerebral Correlates of Impulsivity in Methamphetamine Addiction

William Hoffman, M.D., Ph.D., Principal Investigator
Robert Hitzemann, Ph.D., Suzanne Mitchell, Ph.D., Alexander Stevens, Ph.D., co-investigators

Lay-language summary

How does the brain recover from methamphetamine use? How do the brain-use patterns of long-time methamphetamine users differ from people who have never tried methamphetamine?

These questions underlie the research design of Component 7, which uses functional magnetic resonance imaging (fMRI) to look inside at what's happening in different parts of the brain. We watch which regions of the brain are working while two different groups -- recovering methamphetamine users vs. non-users -- perform certain mental tasks. The tasks we have chosen explore decision-making, a function we know is affected by methamphetamine use. By comparing fMRI data from the former meth users with the non-users, we will get a picture of how the brain-use patterns in these two groups differ and learn about how methamphetamine changes the brain. In addition, we invite the former users in our study to return two more times, at three and six months of abstinence, for follow-up study. By looking following them through their early recovery, we will get an idea of how brain-use patterns change as former users stay off the drug.

Scientific abstract

The critical next step in understanding recovery from methamphetamine dependence is elucidating the neural basis of the behavioral and cognitive deficits found in methamphetamine abusers. Our model proposes that methamphetamine addiction induces neuroadaptations in the systems underlying a number of perceptual and cognitive abilities. Several brain regions, shown in Figure 1, are hypothesized to be methamphetamine’s neurobiological substrates.

Impulsivity is one behavioral trait associated with methamphetamine addiction. Using the Delay Discounting Task (DDT), a task that requires subjects to compare the values of a smaller reward obtained soon against a larger reward obtained later, we have found that recovering addicts are more impulsive than normal controls.

Functional neuroimaging allows us to view activity in the brain while people are engaged in the DDT. Results so far suggest that greater impulsivity is reflected in decreased activation of orbitofrontal cortex in methamphetamine abusers. To the extent that these deficits are due to neuroadaptations to methamphetamine addiction, the abnormalities should improve as patients recover from addiction. From this we have developed two hypotheses:

(1) Abnormalities detected with functional magnetic-resonance Imaging (fMRI) reflect methamphetamine-related neuroadaptations rather than differences in (a) degree of impulsivity as measured by DDT performance or (b) deficits in working memory.

(2) (a) Performance on the DDT in normal controls will be stable on repeated measures over six months, while (b) abstinent methamphetamine abusers become less impulsive over the same time period. Activity in methamphetamine patients brain areas showing decreased activation during DDT performance relative to controls will increase with abstinence.

To test these hypotheses, we will pursue two specific aims:

Specific Aim 1: Characterize the function (using fMRI) of the neural circuits associated with performance of the DDT as a function of task performance.

As part of this, presentation of the DDT will be systematically varied to determine the sensitivity of neuroimaging results to degree of discounting, and a working memory task will be examined as a comparator to determine the extent to which working memory deficits contribute to observed group differences.

Specific Aim 2a: Characterize the longitudinal reliability of performance of both normal controls and abstinent methamphetamine-addicted patients. We propose to evaluate the methamphetamine group monthly on the DDT and the controls at three months and six months.

Specific Aim 2b: Neural activity associated with DDT in recovering methamphetamine abusers will be assessed after two weeks, three months, and six months of abstinence. FMRI scans will be used to determine if recovery is associated with increased signal in brain regions associated with task performance in healthy controls or if they show recruitment of other brain regions.

Prospective study of the neural correlates of impulsivity in recovering patients will not only improve our insight into the mechanism by which methamphetamine addiction affects brain function, but will also provide preliminary data for future prospective study of the effects of impulsivity and cognition on treatment for addiction.

> 2008 progress report
> Component 7 publications
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