NEUROIMAGING CENTER

Cognitive and Clinical Neuroimaging Core (CCNC): Overview

The Cognitive and Clinical Neuroimaging Core is dedicated to the examination of cognitive and affective correlates of neural systems, which may mediate symptoms in psychiatric disorders and behaviors related to substance abuse. Techniques used in these investigations include measures of neuropsychological performance, clinical and diagnostic rating scales and instruments and various magnetic resonance imaging methods, including functional magnetic resonance imaging (fMRI), structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). The aim of these studies has been to identify brain abnormalities, particularly disruptions of frontally and temporally mediated networks, which may represent risk factors for psychiatric illness or substance abuse, or which may be the site of pathology in these illnesses. Recent investigations have combined results from neurocognitive testing and brain imaging in healthy subjects, substance abusers, and subjects with psychiatric disorders as a means of clarifying the possible dysfunctional neural network processes associated with these illnesses. Clinical and neurocognitive assessments, as well as functional and spectroscopic imaging pre and post treatment with a variety of pharmacologic agents have also provided a means for understanding the effect of specific naturopathic and more conventional pharmacological agents on brain function.

CCNC In the News:

World's Federation Against Drugs (11/19/2010)
McLean study shows greater cognitive deficits in marijuana users who start young
www.wfad.se/latest-news/1-articles/432-mclean-study-shows-greater-cognitive-deficits-in-marijuana-users-who-start-young
Science Daily (11/17/2010)
Human Study Shows Greater Cognitive Deficits in Marijuana Users Who Start Young
www.sciencedaily.com/releases/2010/11/101116104202.htm
AOL.com (11/16/2010)
Smoking 3,000 Joints Is Bad for Your Brain, Study Finds
www.aolnews.com/surge-desk/article/smoking-3-000-joints-is-bad-for-your-brain-study-finds/19720740
The Boston Globe (11/16/2010)
Brain-damage risks higher for younger marijuana users, study says
www.boston.com/news/health/articles/2010/11/16/brain_damage_risks_higher_for_younger_marijuana_users_study_says/
The Denver Post (11/16/2010)
Pot smoking changes teens' brains, study shows
www.denverpost.com/news/marijuana/ci_16623489
FoxNews (11/16/2010)
Early Marijuana Use May Increase Brain Damage
www.foxnews.com/health/2010/11/16/study-early-marijuana-use-increase-brain-damage/
Gainesville.com from The Gainesville Sun (11/16/2010)
Marijuana Smokers Who Start Early Are at Greatest Risk, Study Finds
www.gainesville.com/article/20101115/ZNYT04/11153018/-1/obituaries?p=1&tc=pg
Harvard Gazette (11/16/2010)
Brain-damage risks higher for younger marijuana users, study says
news.harvard.edu/gazette/story/2010/11/brain-damage-risks-higher-for-younger-marijuana-users-study-says/
ABC News (11/15/2010)
Early and Chronic Marijuana Use May Damage Brain Function, Says Study
abcnews.go.com/Health/MindMoodNews/smoking-pot-early-age-impair-brain-function/story?id=12152238
Bloomberg Business Week (11/15/2010)
Teens Smoking Pot Before Age 16 Show Brain Changes
www.businessweek.com/news/2010-11-15/teens-smoking-pot-before-age-16-show-brain-changes.html
CNN (11/15/2010)
Teen brain more prone to drug, alcohol damage
pagingdrgupta.blogs.cnn.com/2010/11/15/teen-brain-more-prone-to-drug-alcohol-damage/?iref=allsearch
eScience (11/15/2010)
Early marijuana use a bigger problem
esciencenews.com/sources/harvard.science/2010/11/15/early.marijuana.use.a.bigger.problem
Harvard Gazette (11/15/2010)
Early marijuana use a bigger problem
news.harvard.edu/gazette/story/2010/11/marijuana-study/
Health.com (11/15/2010)
Early 'Pot' Use May Harm Brain More: Study
news.health.com/2010/11/15/early-pot-use-may-harm-brain-more-study/
HealthGrades.com (11/15/2010)
Early 'Pot' Use May Harm Brain More: Study
www.healthgrades.com/health-news/ArticleDetail.aspx?id=645879
Health News (11/15/2010)
Teenage Marijuana Use May Damage Cognitive Function
www.healthnews.com/en/news/Teenage-Marijuana-Use-May-Damage-Cognitive-Function/3LtMNRCCrA7uJDXhSJ4M5z/
The New York Times (11/15/2010)
Marijuana Smokers Who Start Early Are at Greatest Risk, Study Finds
www.nytimes.com/2010/11/15/health/research/15marijuana.html?_r=1&scp=8&sq=roni&st=cse
The Seattle Times (11/15/2010)
Early use of pot may change the brain
seattletimes.nwsource.com/html/nationworld/2013443066_pot16.html
U.S. News & World Report (11/15/2010)
Early 'Pot' Use May Harm Brain More: Study
Smoking before age 16 tied to greater executive function problems
health.usnews.com/health-news/family-health/brain-and-behavior/articles/2010/11/15/early-pot-use-may-harm-brain-more-study.html
WBUR - National Public Radio (NPR) (11/15/2010)
Early Marijuana Use May Impair Brain Function
radioboston.wbur.org/2010/11/15/marijuana-study
ATVN.org USC's News (11/16/2010)
Marijuana impacts younger users more severly
www.atvn.org/index.php/news/story/111610_marijuana_impacts_youth_severely
Harvard Gazette (04/26/2009)
A mother’s criticism touches nerve in formerly depressed
news.harvard.edu/gazette/story/2009/04/a-mothers-criticism-touches-nerve-in-formerly-depressed/

Summaries of Selected Ongoing Projects:

Early Marijuana Use Impacts Executive Function and Use Patterns Overall
Marijuana (MJ) remains the most widely abused illicit substance in the United States, and in recent years, a decline in perceived risk of MJ use has been accompanied by a simultaneous increase in rates of use among adolescents. In the current study, we hypothesized that chronic MJ smokers would perform tasks of executive function more poorly than control subjects, and that individuals who started smoking MJ regularly prior to age 16 (early onset) would have more difficulty than those who started after age 16 (late onset). Thirty-four chronic, heavy MJ smokers separated into early and late onset groups and 28 non-MJ smoking controls completed a battery of neurocognitive measures. As hypothesized, MJ smokers performed more poorly than controls on several measures of executive function including the Wisconsin Card Sorting Test (WCST), Stroop Color Word Test, and the Trail Making Test.

MJ smokers as a group performed the WCST, a “gold standard” measure of executive function and set shifting abilities, more poorly than controls. Moreover, early onset smokers performed significantly worse than later onset smokers, achieving fewer categories and making more perseverative errors. During the Stroop Color Word Test, a task used to measure the ability to inhibit inappropriate responses and resist interference, MJ smokers made more commission errors and achieved lower percent accuracy relative to control subjects. Additionally, early onset smokers displaying impaired performance, reflected in lower task accuracy and significantly higher commission errors relative to late onset smokers. In addition to impairments on these tasks, we found that early onset smokers smoked twice as often per week and nearly three times as many grams of MJ per week reative to the late onset smokers. Findings suggest that earlier MJ onset is related to poorer executive function and increased frequency and magnitude of MJ use relative to later MJ onset. Exposure to marijuana during a period of neurodevelopmental vulnerability, such as adolescence, may result in altered brain development and enduring neuropsychological changes.

Chronic Marijuana Smokers are Impaired on the Trail Making Test (TMT)
Over 3 million people aged twelve and older use marijuana (MJ) daily and despite reports of cognitive impairments related to MJ use, the current deliberations over the legalization of MJ may reduce concern regarding the potential negative impact of MJ on cognition. This study was designed to evaluate the effects of MJ on executive function using the Trail Making Test (TMT). We administered the TMT, parts A and B, to 27 non-MJ smoking healthy controls and 33 chronic, heavy MJ smokers. Trails A is a measure of psychomotor function in which subjects must connect a series of dots in numerical order (i.e. 1, 2, 3...) as quickly as possible, while Trails B is a uses an alternating set demand to measure cognitive flexibility and executive functioning; subjects must connect the dots by alternating between connecting numbers and letters (i.e. 1, A, 2, B...) as quickly as possible.
Despite similar task performance on Trails A, MJ smokers took significantly longer to complete Trails B and had significantly longer derived interference (Trails B-A) time relative to controls indicating that MJ users do not have difficulty with the psychomotor component of Trails A, but struggle with the demands of Trails B. Interestingly, grams of MJ used per week was positively correlated with B time and errors. To assess the potential impact of age of onset of MJ use, smokers were divided into early (MJ use before age 16) and late (MJ use at age 16 or later) onset groups. Early onset smokers reported using 2.5 times more grams of MJ per week than late onset smokers and made significantly more errors on Trails B. Taken together, these findings suggest that MJ use impacts cognitive processing and in particular, that both a higher magnitude and earlier onset of MJ use is related to greater executive function impairment. Earlier onset of use was significantly associated with higher MJ use and increased errors, thus highlighting the importance of early intervention and education regarding the potential negative outcomes associated with heavy MJ use.

Serial List Learning Strategies Are Related to Impulsivity in Chronic MJ Smokers
As part of a larger study, 30 chronic, heavy MJ smokers and 26 non-MJ smoking control subjects completed the standard California Verbal Learning Test (CVLT) in order to examine overall learning and encoding strategies. In this task, subjects are read a 16-item grocery list and asked to recall as many words as possible for a total of 5 trials and must also complete a short delay and long delay free recall trial. Subjects also completed the Barratt Impulsivity Scale 11 (BIS-11) in order to assess their level of behavioral impulsivity. Our analyses focused on variables related to learning, specifically Trials 1-5 correct, as well as semantic clusters and perseverations. Although no significant difference between MJ smokers and controls were found for total number of words recalled, MJ smokers made significantly more perseverations and had fewer semantic clusters than controls. In addition, scores on the BIS-11 were significantly higher in MJ smokers relative to controls. Findings from this study suggest that while overall learning was not different between MJ smokers and controls, encoding strategies differed between the groups. MJ smokers made significantly more repetitive, incorrect responses and had fewer semantic clusters, suggesting that they don't organize information as efficiently. Additionally, it appears that impulsivity further hinders the ability to utilize semantic strategies in MJ smokers. These data underscore the importance of assessing qualitative differences in MJ smokers which may clarify issues related to drug use.

Altered Brain Activation during an Inhibitory Task in Early Onset Marijuana Smokers
Difficulties in the ability to successfully inhibit impulsive behaviors have been reported in marijuana (MJ) smokers, yet few studies have made direct comparisons between early (prior to age 16) and late (age 16 or later) onset MJ smokers, specifically during behavioral inhibition tasks. We recently utilized the Multisource Interference Task (MSIT) during functional magnetic resonance imaging (fMRI) in order to examine potential differences in non-MJ smoking controls (HCs) and early vs late onset chronic, heavy MJ smokers. During the task, subjects were presented with sets of three numbers (1, 2, 3, or 0), with one (target) always different from the other two (distractor) numbers. Subjects were instructed to report the identity of the number that differed from the distractors using a button box. Results showed that MJ smokers and HCs displayed differences in activation patterns during the MSIT, although there were no behavioral performance differences between the two groups. While HCs exhibited a very focal pattern of activation, MJ smokers demonstrated a much more diffuse pattern. The comparison between MJ subgroups revealed that early onset smokers activated a more focal region of ACC during the task, and in fact appeared more similar to the single sample analysis of healthy controls relative to the late onset smokers, who demonstrated a pattern more similar to MJ smokers overall. Furthermore, analyses approaching statistical significance showed that while early onset smokers had faster reaction times, they made nearly twice as many errors of commission relative to the later onset smokers, which is indicative of a failure to inhibit inappropriate responses. Taken together, these data may reflect both a neural compensation for early exposure to MJ during a vulnerable neurodevelopmental period and a behavioral inability to execute cognitive control. Further investigation is warranted, as early exposure to MJ may result in reorganization of critical brain regions.

Why So Impulsive? White Matter Alterations and Impulsivity in Chronic Marijuana Smokers
Difficulty monitoring and inhibiting impulsive behaviors has been reported in marijuana (MJ) smokers, and neuroimaging studies, which examined frontal systems in chronic MJ smokers, have reported alterations during inhibitory tasks. Diffusion tensor imaging (DTI) provides a quantitative estimate of white matter integrity at the microstructural level. We applied DTI, clinical ratings and impulsivity measures to explore the hypotheses that chronic, heavy MJ smokers would demonstrate alterations in white matter microstructure and a different association between white matter measures and impulsivity relative to non-smoking control subjects (NS). Fractional anisotropy (FA), a measure of directional coherence, and trace, a measure of overall diffusivity were calculated using manual voxel-based methods for six locations including bilateral frontal regions in 15 chronic MJ smokers and 15 NS. Subjects completed clinical rating scales, including the Barratt Impulsivity Scale (BIS). Analyses revealed significant reductions in left frontal FA in MJ smokers relative to NS and significantly higher levels of trace in the right genu. MJ smokers also had significantly higher BIS total and motor subscale scores relative to NS, which were positively correlated with left frontal FA values. Finally, age of onset of MJ use was positively correlated with frontal FA values and inversely related to trace. These data represent the first report of significant alterations in frontal white matter tracts associated with measures of impulsivity in chronic MJ smokers. Early MJ use may result in reduced FA and increased diffusivity, which may predict increased impulsivity, and ultimately contribute to the initiation of MJ use or the inability to discontinue use.

Age of Onset of Marijuana Use is Related to White Matter and Behavioral Impulsivity
We recently completed analyses of white matter from a new group of chronic, heavy MJ smokers and control subjects which utilized more advanced tract based spatial statistics (TBSS) techniques which increase the sensitivity and the interpretability of the results compared with voxel-based approaches. As in our previous analysis, we found significantly reduced FA in both the left and right genu of the corpus callosum for the MJ smokers relative to the control subjects. In addition, within the same regions, mean diffusivity was significantly higher in MJ smokers relative to controls. Correlation analyses revealed a significant relationship between the age of MJ onset and FA in both the left and right genu for early but not late onset smokers. Further, scores on the Barratt Impulsivity Scale (BIS) were inversely correlated with FA in both regions for the early onset smokers, suggesting a specific relationship between FA and behavioral impulsivity. Overall, MJ smokers have lower FA relative to controls, but perhaps more importantly, the earlier the age of MJ onset, the lower the FA level. Similarly, lower FA is related to higher levels of impulsivity. Taken together, these findings are consistent with previous DTI studies and reinforce the idea that early onset MJ use impacts white matter development (earlier onset = lower FA, higher diffusivity) and is associated with behavioral impulsivity, a combination likely to have devastating effects on the developing brain.

Marijuana and Mood: A Role in Bipolar Disorder
Bipolar disorder (BPD) remains a leading cause of disability across the world, and individuals with co-occurring BPD and substance abuse often experience poor treatment response, relapse of mood symptoms and psychosocial difficulties. While precise reasons for comorbidity remain unclear, some studies of bipolar patients report that substance use is directly related to at least one symptom, and that the majority of patients report symptom improvement as a result of substance use. As twenty to fifty percent of patients with BPD report using MJ, we examined the impact of MJ use on mood symptoms in MJ-smoking bipolar patients (MJBP) and pure MJ smokers (MJ) in order to test the hypothesis that bipolar patients would experience improved mood after smoking MJ. To assess mood changes multiple times per day and before and after smoking MJ, subjects were given Palm Pilot devices uploaded with an application containing electronic versions of several clinical rating scales, including the Profile of Mood States (POMS), Hamilton Anxiety Scale (HAM-A), Montgomery-Asberg Depression Rating Scale (MADRS), and the Young Mania Rating Scale (YMRS). In addition, subjects recorded episodes of smoking, including amount, frequency and mode of MJ use. A difference score was calculated from pre-MJ scales as compared to post-MJ scales, completed within 4 hours of smoking MJ. T-tests for within and between-group differences on the change scores were computed. Significant improvement in mood symptoms was noted in the MJBP group after smoking MJ for the POMS, HAM-A and MADRS scales, while the MJ group appeared to have a slight worsening of symptoms. Notably, total mood disturbance (TMD), a composite measure of the POMS, was significantly reduced from 23.13 to 12.22 in the MJBP group but increased from -6.19 to -2.45 in the pure MJ group. These pilot data suggest that MJBP subjects experience a significant improvement in mood symptoms after smoking MJ while pure MJ smokers exhibit a slight worsening of clinical state. Consistent with previous reports of BPD patients using drugs to improve mood-related symptoms, these data underscore the likelihood that MJ may act as a mood stabilizer for some patients with BPD, and highlight the importance of examining cannabinoid-based therapies.

Personnel

Staci Gruber, Ph.D. - Director
Atilla Gönenc, Ph.D. - Assistant Physicist
Mary Kathryn (Kate) Dahlgren, B.A. - Senior Clinical Research Coordinator
Kelly Sagar, B.A. - Clinical Research Assistant
Megan Racine, B.S. - Clinical Research Assistant
Margaret Ricciuti, B.A. - Administrative Assistant

Collaborators