Effects of cigarette smoking and abstinence on Stroop task performance.

RATIONALE: Smokers report enhanced concentration after cigarette smoking and difficulty concentrating when abstinent from smoking. These perceived effects may contribute to smoking cessation failures, and if so, clarification of their cognitive bases could inform treatment strategies. Selective attention may be important in this regard, but earlier literature presents inconsistent findings on how smoking abstinence and resumption of smoking influence this cognitive function. OBJECTIVES: We aimed to compare smokers and nonsmokers on selective attention, and in smokers, to test the effects of overnight abstinence from smoking and of acute smoking on selective attention. MATERIALS AND METHODS: Smokers and nonsmokers (n = 43) performed a Stroop test (two test days, two test blocks per day). Smokers participated after overnight abstinence and also within 1-h of ad libitum smoking. Smokers each smoked a cigarette between test blocks on each day; nonsmokers did not. RESULTS: Smokers demonstrated longer response latencies for both congruent and incongruent stimuli after overnight than brief abstinence, but no deficit specifically related to selective attention. Whereas nonsmokers showed no changes in performance in the second test block, smoking between blocks reduced the Stroop effect when smokers were abstinent overnight. CONCLUSIONS: These data are consistent with the hypothesis that abstinence from smoking among nicotine-dependent individuals has deleterious effects on cognitive performance, but do not indicate that selective attention is adversely effected. Improvement in selective attention after terminating abstinence with one cigarette may also contribute to smokers' perceived enhanced ability to concentrate after smoking.

Working memory in cigarette smokers: comparison to non-smokers and effects of abstinence.

The present study was designed to examine the effect of cigarette smoking and withdrawal on working memory. Participants included 15 smokers and 22 matched non-smokers. For both groups the N-Back Task (of working memory) was administered in two test blocks on each of two days. On one day, smokers were tested after >or=13 h abstinence; on the other day, testing began or=13 h but not

Structural abnormalities in the brains of human subjects who use methamphetamine.

We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations associated with chronic MA abuse in human subjects and related these deficits to cognitive impairment. We used high-resolution MRI and surface-based computational image analyses to map regional abnormalities in the cortex, hippocampus, white matter, and ventricles in 22 human subjects who used MA and 21 age-matched, healthy controls. Cortical maps revealed severe gray-matter deficits in the cingulate, limbic, and paralimbic cortices of MA abusers (averaging 11.3% below control; p < 0.05). On average, MA abusers had 7.8% smaller hippocampal volumes than control subjects (p < 0.01; left, p = 0.01; right, p < 0.05) and significant white-matter hypertrophy (7.0%; p < 0.01). Hippocampal deficits were mapped and correlated with memory performance on a word-recall test (p < 0.05). MRI-based maps suggest that chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance. MA may selectively damage the medial temporal lobe and, consistent with metabolic studies, the cingulate-limbic cortex, inducing neuroadaptation, neuropil reduction, or cell death. Prominent white-matter hypertrophy may result from altered myelination and adaptive glial changes, including gliosis secondary to neuronal damage. These brain substrates may help account for the symptoms of MA abuse, providing therapeutic targets for drug-induced brain injury.

Brain activity in cigarette smokers performing a working memory task: effect of smoking abstinence.

BACKGROUND: When nicotine-dependent human subjects abstain from cigarette smoking, they exhibit deficits in working memory. An understanding of the neural substrates of such impairments may help to understand how nicotine affects cognition. Our aim, therefore, was to identify abnormalities in the circuitry that mediates working memory in nicotine-dependent subjects after they initiate abstinence from smoking. METHODS: We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study eight smokers while they performed a letter version of the N-Back working memory task under satiety (< or = 1.5 hours abstinence) and abstinence (> or = 14 hours abstinence) conditions. RESULTS: Task-related activity in the left dorsal lateral prefrontal cortex (DLPFC) showed a significant interaction between test session (satiety, abstinence) and task load (1-back, 2-back, and 3-back). This interaction reflected the fact that task-related activity in the satiety condition was relatively low during performance of the 1-back task but greater at the more difficult task levels, whereas task-related activity in the abstinence condition was relatively high at the 1-back level and did not increase at the more difficult task levels. CONCLUSIONS: We conclude that neural processing related to working memory in the left DLPFC is less efficient during acute abstinence from smoking than at smoking satiety.

Cerebral metabolic dysfunction and impaired vigilance in recently abstinent methamphetamine abusers.

BACKGROUND: Methamphetamine (MA) abusers have cognitive deficits, abnormal metabolic activity and structural deficits in limbic and paralimbic cortices, and reduced hippocampal volume. The links between cognitive impairment and these cerebral abnormalities are not established. METHODS: We assessed cerebral glucose metabolism with [F-18]fluorodeoxyglucose positron emission tomography in 17 abstinent (4 to 7 days) methamphetamine users and 16 control subjects performing an auditory vigilance task and obtained structural magnetic resonance brain scans. Regional brain radioactivity served as a marker for relative glucose metabolism. Error rates on the task were related to regional radioactivity and hippocampal morphology. RESULTS: Methamphetamine users had higher error rates than control subjects on the vigilance task. The groups showed different relationships between error rates and relative activity in the anterior and middle cingulate gyrus and the insula. Whereas the MA user group showed negative correlations involving these regions, the control group showed positive correlations involving the cingulate cortex. Across groups, hippocampal metabolic and structural measures were negatively correlated with error rates. CONCLUSIONS: Dysfunction in the cingulate and insular cortices of recently abstinent MA abusers contribute to impaired vigilance and other cognitive functions requiring sustained attention. Hippocampal integrity predicts task performance in methamphetamine users as well as control subjects.

Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers.

BACKGROUND: Mood disturbances in methamphetamine (MA) abusers likely influence drug use, but the neurobiological bases for these problems are poorly understood. OBJECTIVE: To assess regional brain function and its possible relationships with negative affect in newly abstinent MA abusers. DESIGN: Two groups were compared by measures of mood and cerebral glucose metabolism ([18F]fluorodeoxyglucose positron emission tomography) during performance of a vigilance task. SETTING: Participants were recruited from the general community to a research center. PARTICIPANTS: Seventeen abstaining (4-7 days) MA abusers (6 women) were compared with 18 control subjects (8 women). MAIN OUTCOME MEASURES: Self-reports of depressive symptoms and anxiety were measured, as were global and relative glucose metabolism in the orbitofrontal, cingulate, lateral prefrontal, and insular cortices and the amygdala, striatum, and cerebellum. RESULTS: Abusers of MA provided higher self-ratings of depression and anxiety than control subjects and differed significantly in relative regional glucose metabolism: lower in the anterior cingulate and insula and higher in the lateral orbitofrontal area, middle and posterior cingulate, amygdala, ventral striatum, and cerebellum. In MA abusers, self-reports of depressive symptoms covaried positively with relative glucose metabolism in limbic regions (eg, perigenual anterior cingulate gyrus and amygdala) and ratings of state and trait anxiety covaried negatively with relative activity in the anterior cingulate cortex and left insula. Trait anxiety also covaried negatively with relative activity in the orbitofrontal cortex and positively with amygdala activity. CONCLUSIONS: Abusers of MA have abnormalities in brain regions implicated in mood disorders. Relationships between relative glucose metabolism in limbic and paralimbic regions and self-reports of depression and anxiety in MA abusers suggest that these regions are involved in affective dysregulation and may be an important target of intervention for MA dependence.

Quantitative EEG Correlates of Outcome in Older Psychiatric Patients: Part II: Two-Year Follow-Up of Patients With Depression.

The authors examined quantitative electroencephalographc (QEEG) coherence in 37 depressed elderly patients and performed 2-year follow-up evaluations. All subjects had equivocal cognitive impairment, but none had delirium or dementia. More than 40% (16/37) recovered from depression, and 38% (14/37) remained well for 2 years. Twenty-four percent (n = 9) had died within 2 years, most from cardiac causes. Low trans-Rolandic coherence from the left hemisphere was strongly associated with mortality: 44% (7/16) of those with low coherence died, and 78% (7/9) of those who died had low coherence. Among survivors (n = 28) at follow-up, low coherence was significantly associated with lower functional status. These findings suggest that the coherence variable measures actual neurophysiology differences between groups of depressed patients and these differences are associated with the heterogeneous outcomes of depression in elderly patients.

Quantitative EEG Correlates of Outcome in Older Psychiatric Patients: Part I: Cross-Sectional and Longitudinal Assessment of Patients With Dementia.

Using quantitative electroencephalographic coherence (a measure of synchronized electrical activity between brain regions) the authors examined heterogeneity in clinical presentation and outcome inpatients with dementia. Patients (N = 114) with mild-to-moderate dementia of the Alzheimer's type (DAT) or multi-infarct dementia (MID) were examined for coherence from the left hemisphere. More than 70% diagnostic accuracy in distinguishing between DAT and MID subjects was achieved using coherence measures alone. Also, decreased coherence measured across the Rolandic fissure in the left hemisphere was significantly associated with poorer functional status of subjects at 2-year follow-up, despite similar levels of cognitive impairment at baseline. These findings suggest that coherence is a useful measure for assessment and for prediction of the course of illness inpatients with dementia.

The effect of relapse on cognition in abstinent methamphetamine abusers.

Data from 75 participants in a longitudinal study of methamphetamine (MA) abuse were used to differentiate the cognitive performance of those who remained abstinent, relapsed, or continued to use during treatment. Participants were divided into three groups: continuous abstinence, initial abstinence but relapse, and continuous use. Groups did not differ on age, education, gender or ethnicity. Participants in the longitudinal study completed a battery of cognitive tests within 7 days of their last use of MA, then were re-tested monthly for up to 6 months (average time for this analysis was 92 days). For episodic memory, the relapse groups performance was worse than the abstinent and significantly worse than that of the continued use group who had the best performance on all measures. Relapse to methamphetamine use may affect episodic memory differently than it affects the other cognitive functions measured.

Cognitive performance of current methamphetamine and cocaine abusers.

Forty currently using methamphetamine (MA) abusers, 40 currently using cocaine (COC) abusers, and 80 comparison participants who did not use psychostimulants received a cognitive battery and questionnaires covering medical history and stimulant use patterns. Forty comparison participants were matched to the 40 MA users on age, education, ethnicity, and gender. The other 40 comparison participants were matched to the cocaine users on the same variables. This design was chosen because there were significant differences in age and ethnicity between COC and MA users that precluded a direct comparison between the groups. The COC group was older and predominantly African American compared to the predominantly Caucasian MA group. When compared to their matched non-using control groups, both MA and COC abusers were impaired on cognitive measures, but the type and degree of impairments were somewhat different.

Cognitive deficits among methamphetamine users with attention deficit hyperactivity disorder symptomatology.

Understanding the association between attention deficit hyperactivity disorder (ADHD) and substance abuse, specifically methamphetamine (MA) abuse, is challenging, partly because little is known about the specific constellation of cognitive impairments produced by MA. The present investigation serves to address this relationship by comparing the cognitive performance of MA abusers with ADHD symptomatology (n = 28) and MA abusers without ADHD symptomatology (n = 41) on tests of attention, memory and general intellectual functioning, executive functioning, problem solving, verbal fluency, and abstract thinking. Both MA samples had deficiencies in measures of memory and learning function, psychomotor speed and abstract thinking when compared to a control group (n = 40). Additional deficits were noted on tasks involving executive functioning, attention, and general intellectual functioning in MA abusers with ADHD symptomatology. The preliminary data suggests that executive function deficits and some of the symptoms associated with long-term MA use may be due to the fact that a large proportion of MA addicts had ADHD symptomatology as children.

A comparison of patterns of methamphetamine and cocaine use.

Typical use patterns of methamphetamine (MA) users were examined using self-report measures from 120 MA and 63 cocaine users. Twenty (14 MA and 6 cocaine) of the participants also took part in structured interviews designed to provide more specific descriptions of their drug use. The typical MA user uses more than 20 days a month. Use is evenly spaced throughout the day, and although the amount of drug used per day is not different, MA users use fewer times per day than do cocaine users. Fewer of the cocaine users are continuous users, and they use in the evening rather than the daytime. The cocaine pattern of fewer days of use, evening use, and more frequent doses per day fits a picture of recreational use, whereas the all-day-most-days methamphetamine pattern does not.

Methamphetamine dependence and neuropsychological functioning: evaluating change during early abstinence.

OBJECTIVE: The purpose of this work was to assess neuropsychological functioning of individuals in early abstinence from methamphetamine dependence and to test for cognitive change over the first month of abstinence. METHOD: Methamphetamine-dependent subjects in very early abstinence from methamphetamine (4-9 days; n = 27) were compared with healthy comparison subjects (n = 28) on a test battery that evaluated five cognitive domains (attention/processing speed, learning/memory, working memory, timed executive functioning, and untimed executive functioning). A subsample of the methamphetamine-dependent subjects (n =18), who maintained abstinence for 1 month, as well as a subsample of the comparison subjects (n = 21), were retested. RESULTS: At the first assessment, the methamphetamine-dependent subjects showed significantly worse performance than the comparison group on a test of processing speed; they also performed 0.31 SDs worse than the control group on a global battery composite score (p < .05). After a month of abstinence, methamphetamine-dependent subjects demonstrated slightly more cognitive improvement than healthy control subjects on the entire cognitive battery, but this difference did not approach statistical significance (p = .33). CONCLUSIONS: Our findings suggest that methamphetamine-dependent subjects do not show considerable cognitive gains in the first month of abstinence. A greater length of abstinence may be needed for cognitive improvement.

Severity of nicotine dependence moderates performance on perceptual-motor tests of attention.

Acute abstinence from cigarette smoking by nicotine-dependent smokers has been linked with cognitive deficits, but the role of nicotine dependence per se in these effects is not known. We therefore tested the relationships of nicotine dependence and smoking history with performance in perceptual-motor, timed tests of attention. Nicotine-dependent smokers (n = 37) and nonsmokers (n = 48), 18-55 years old, took both the d2 Test of Attention and the Digit Symbol Test on each of 2 test days. For smokers, testing on one day began after ad libitum smoking (<45 min since last cigarette); and on the other day, it began after overnight abstinence (>13 hr since last cigarette). On each test day, there were two test blocks with an intervening break, when only the smokers each smoked one cigarette. There were no significant effects of abstinence or of smoking one cigarette on the performance of smokers; however, across conditions, the smokers' performance on both tests correlated negatively with severity of nicotine dependence but not lifetime cigarette consumption or cigarette craving. Smokers with high nicotine dependence performed more slowly on both tests than less dependent smokers or nonsmokers. The findings suggest that severity of nicotine dependence and slowness in perceptual-motor tasks of attention share an underlying basis.

Variation in neurophysiological function and evidence of quantitative electroencephalogram discordance: predicting cocaine-dependent treatment attrition.

Cocaine treatment trials suffer from a high rate of attrition. We examined pretreatment neurophysiological factors to identify participants at greatest risk. Twenty-five participants were divided into concordant and discordant groups following electroencephalogram (EEG) measures recorded prior to a double-blind, placebo-controlled treatment trial. Three possible outcomes were examined: successful completion, dropout, and removal. Concordant (high perfusion correlate) participants had an 85% rate of successful completion, while discordant participants had a 15% rate of successful completion. Twenty-five percent of dropouts and 50% of participants removed were discordant (low perfusion correlate), while only 25% of those who completed were discordant. Failure to complete the trial was not explained by depression, craving, benzoylecgonine levels or quantitative electroencephalogram (QEEG) power; thus cordance may help identify attrition risk.