Karen I. Bolla

Dose-related neurocognitive effects of marijuana use

Background: Although about 7 million people in the US population use marijuana at least weekly, there is a paucity of scientific data on persistent neurocognitive effects of marijuana use. Objective: To determine if neurocognitive deficits persist in 28-day abstinent heavy marijuana users and if these deficits are dose-related to the number of marijuana joints smoked per week. Methods: A battery of neurocognitive tests was given to 28-day abstinent heavy marijuana abusers. Results: As joints smoked per week increased, performance decreased on tests measuring memory, executive functioning, psychomotor speed, and manual dexterity. When dividing the group into light, middle, and heavy user groups, the heavy group performed significantly below the light group on 5 of 35 measures and the size of the effect ranged from 3.00 to 4.20 SD units. Duration of use had little effect on neurocognitive performance. Conclusions: Very heavy use of marijuana is associated with persistent decrements in neurocognitive performance even after 28 days of abstinence. It is unclear if these decrements will resolve with continued abstinence or become progressively worse with continued heavy marijuana use.

Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task

Cocaine abusers demonstrate faulty decision-making as manifested by their inability to discontinue self-destructive drug-seeking behaviors. The orbitofrontal cortex (OFC) plays an important role in decision-making. In this preliminary study we tested whether 25-day-abstinent cocaine abusers show alterations in normalized cerebral blood flow (rCBF) in the OFC using PET with (15)O during the Iowa Gambling Task (a decision-making task). This task measures the ability to weigh short-term rewards against long-term losses. A control task matched the sensorimotor aspects of the task but did not require decision-making. Cocaine abusers (N = 13) showed greater activation during performance of the Iowa Gambling Task in the right OFC and less activation in the right dorsolateral prefrontal cortex (DLPFC) and left medial prefrontal cortex (MPFC) compared to a control group (N = 13). Better Iowa Gambling Task performance was associated with greater activation in the right OFC in both groups. Also, the amount of cocaine used (grams/week) prior to the 25 days of enforced abstinence was negatively correlated with activation in the left OFC. Greater activation in the OFC in cocaine abusers compared to a control group may reflect differences in the anticipation of reward while less activation in the DLPFC and MPFC may reflect differences in planning and working memory. These findings suggest that cocaine abusers show persistent functional abnormalities in prefrontal neural networks involved in decision-making and these effects are related to cocaine abuse. Compromised decision-making could contribute to the development of addiction and undermine attempts at abstinence.

Decision-making in a Risk-taking Task: A PET Study

As decision-making is central to motivated behavior, understanding its neural substrates can help elucidate the deficits that characterize various maladaptive behaviors. Twenty healthy adults performed a risk-taking task during positron emission tomography with 15O-labeled water. The task, a computerized card game, tests the ability to weigh short-term rewards against long-term losses. A control task matched all components of the risk-taking task except for decision-making and the difference between responses to contingent and non-contingent reward and punishment. Decision-making (2 runs of the active task minus 2 runs of the control task) activated orbital and dorsolateral prefrontal cortex, anterior cingulate, insula, inferior parietal cortex and thalamus predominantly on the right side, and cerebellum predominantly on the left side. In an exploratory analysis, guessing (run 1 minus run 2 of the active task) accompanied activation of sensory-motor associative areas, and amygdala on the left side, whereas informed decision-making (run 2 minus run 1) activated areas that subserve memory (hippocampus, posterior cingulate) and motor control (striatum, cerebellum). The findings provide a framework for future investigations of decision-making in maladaptive behaviors.

Frontal cortical tissue composition in abstinent cocaine abusers: a magnetic resonance imaging study.

Cocaine abusers exhibit impairment of executive cognitive functions that are mediated by the frontal cortex. This work tested for structural (i.e., tissue composition) abnormalities that may underlie such performance deficits. Research participants were cocaine abusers (n = 14) abstinent for 20 days and a non-drug-using comparison group (n = 11), who underwent magnetic resonance imaging (T1-weighted scans of the brain). Gray matter and white matter tissue densities were determined using voxel-based morphometry with small volume correction based on a priori hypotheses derived from functional imaging of the same subjects. Cocaine abusers had significantly lower gray matter tissue density than did the non drug users in 10 of 13 small volumes analyzed in the frontal cortex [bilateral anterior cingulate gyrus (infragenual and perigenual regions) and medial orbitofrontal cortex and the lateral orbitofrontal cortex and middle/dorsal cingulate gyrus in the right hemisphere]. No group differences were found in white matter density of the frontal cortex. These results extend our previous findings of defective frontal cortical activation (indexed by cerebral blood flow) in cocaine abusers to include abnormalities in gray matter tissue density in the same frontal cortical regions.

Abnormal brain activity in prefrontal brain regions in abstinent marijuana users

We used PET (15)O and a modified version of the Stroop task to determine if 25-day abstinent heavy marijuana (MJ) users have persistent deficits in executive cognitive functioning (ECF) and brain activity. Performance on a modified version of the Stroop task and brain activity was compared between 25-day abstinent, heavy marijuana users (n = 11), and a matched comparison group (n = 11). The 25-day abstinent marijuana users showed no deficits in performance on the modified version of the Stroop task when compared to the comparison group. Despite the lack of performance differences, the marijuana users showed hypoactivity in the left perigenual anterior cingulate cortex (ACC) and the left lateral prefrontal cortex (LPFC) and hyperactivity in the hippocampus bilaterally, when compared to the comparison group. These results suggest that marijuana users display persistent metabolic alterations in brain regions responsible for ECF. It may be that marijuana users recruit an alternative neural network as a compensatory mechanism during performance on a modified version of the Stroop task. These differences in brain activity may be a common denominator in the evolution of maladaptive behaviors such as substance abuse and other neuropsychiatric disorders.

Past adult lead exposure is associated with longitudinal decline in cognitive function

Objective: To determine whether adults with past exposure to neurotoxicants have progressive declines in cognitive function years after exposure has ceased, and whether tibia lead is a predictor of the magnitude of change. Methods: A total of 535 former organolead manufacturing workers with a mean age of 55.6 years, a mean duration of 16 years since last occupational lead exposure, and low blood lead levels at the first study visit and 118 controls were evaluated with neurobehavioral tests two to four times over 4 years. “Peak” tibia lead levels, estimated from current levels measured by X-ray fluorescence, were used to predict changes in cognitive function over time. Results: In former lead workers, peak tibia lead ranged from −2.2 to 98.7 μg Pb/g bone mineral. Compared to controls, former lead workers performed worse over time for three tests of visuo-constructive ability and verbal memory and learning (p < 0.05). In former lead workers, peak tibia lead predicted declines for six tests of verbal memory and learning, visual memory, executive ability, and manual dexterity (p < 0.05 for four tests and < 0.10 for two additional tests). On average, for these six tests, an increase of 15.7 μg/g of peak tibia lead was equivalent in its effects on annual test decline to 5 more years of age at baseline. Conclusions: These are the first data to suggest that cognitive function can progressively decline due to past occupational exposures to a neurotoxicant.

Differential effects of cocaine and cocaine alcohol on neurocognitive performance.

Objective: To investigate the dose-related effects of cocaine with or without alcohol use on the CNS by measuring performance on neurobehavioral tests. Background: Chronic use of cocaine is associated with persistent decrements in cognitive function that are most pronounced in heavy users. Specific neurobehavioral deficits in areas such as executive function and impulsivity would make it difficult for the cocaine abuser to discontinue using drugs. Because alcohol is often used in conjunction with cocaine, the CNS effects of alcohol when taken with cocaine deserve further investigation. Method: The authors evaluated the dose-related effects of cocaine and alcohol use on performance in a variety of neuropsychological tests after 1 to 3 days of abstinence and again after 4 weeks of abstinence. Fifty-six chronic cocaine abusers who had used cocaine during the past 24 to 48 hours volunteered to perform a battery of neuropsychological tests on two separate occasions during a period of enforced abstinence. In addition to using cocaine, most of the volunteers consumed alcohol. Approximately half of the participants consumed more than 10 alcohol-containing drinks per week. Results: After controlling for the effects of age, sex, and intelligence on performance, the authors found dose-related associations between neurobehavioral performance and cocaine dose and alcohol dose. When the influences of cocaine and alcohol on neurobehavioral performance were taken separately, cocaine and alcohol each selectively affected performance on different neurobehavioral tests after 1 to 3 days of abstinence, with these effects persisting after 4 weeks of abstinence. Conclusion: The concomitant use of cocaine and alcohol may have additive negative effects on the brain as compared to the use of only one of these two substances.

Cannabis use before age 15 and subsequent executive functioning

BACKGROUND Many studies have suggested that adolescence is a period of particular vulnerability to neurocognitive effects associated with substance misuse. However, few large studies have measured differences in cognitive performance between chronic cannabis users who started in early adolescence (before age 15) with those who started later. AIMS To examine the executive functioning of individuals who started chronic cannabis use before age 15 compared with those who started chronic cannabis use after 15 and controls. METHOD We evaluated the performance of 104 chronic cannabis users (49 early-onset users and 55 late-onset users) and 44 controls who undertook neuropsychological tasks, with a focus on executive functioning. Comparisons involving neuropsychological measures were performed using generalised linear model analysis of variance (ANOVA). RESULTS The early-onset group showed significantly poorer performance compared with the controls and the late-onset group on tasks assessing sustained attention, impulse control and executive functioning. CONCLUSIONS Early-onset chronic cannabis users exhibited poorer cognitive performance than controls and late-onset users in executive functioning. Chronic cannabis use, when started before age 15, may have more deleterious effects on neurocognitive functioning.

Predictors of verbal fluency (FAS) in the healthy elderly

The Verbal Fluency Task (FAS), sensitive indicator of brain injury, was examined in a population of healthy elderly (N = 199, aged 40 to 89 years). The present study was conducted to examine the relative contributions of age, sex, education, verbal intelligence, and specific cognitive abilities to FAS performance. Significant effects were found for vocabulary and sex, although no aging effect was found. Separate norms for sex and level of verbal intelligence are presented. Results indicated that ability to quickly organize information and formulate effective recall strategies played a critical role in good FAS performance.

Homocysteine and Cognitive Function in a Population‐Based Study of Older Adults

Objectives: To assess the relations between homocysteine levels and neurobehavioral test scores representing a broad range of cognitive domains in a population‐based study of older adults.