Nicotine enhances alerting, but not executive, attention in smokers and nonsmokers.

INTRODUCTION: Difficulty concentrating is a symptom of nicotine withdrawal that can contribute to relapse in individuals trying to quit smoking. The purpose of this study was to determine the effects of nicotine on executive and alerting attention in smokers and nonsmokers. METHODS: Thirty daily smokers who were not tobacco deprived and 30 nonsmokers participated in the study. Participants received a single dose of intranasal nicotine (0, 0.5, or 1.5 mg) at each of 3 experimental sessions on separate days. Participants completed subjective ratings and 3 attention tasks before and after nicotine administration. RESULTS: Nicotine had no effect on executive attention as assessed by a Rapid Serial Visual Presentation (RSVP) task or the Attention Network Test in smokers and nonsmokers. In contrast, nicotine enhanced alerting attention by decreasing errors on a Continuous Performance Test (CPT) in nonsmokers and improving the correct identification of target words on the RSVP task in smokers. Nonsmokers were more sensitive than smokers to the subjective, but not the cardiovascular, effects of nicotine. CONCLUSIONS: The acute administration of intranasal nicotine improved alerting attention in nonsmokers as measured by the CPT, and in smokers as measured by the RSVP. Understanding the elements of attention enhanced by nicotine might guide the development of novel medications for tobacco dependence.

Dose-related enhancement of mood and cognition in smokers administered nicotine nasal spray.

The discovery of the role of nicotinic receptors in attention and memory has led to the testing of nicotinic analogs as cognitive enhancing agents in patient populations. Empirical information about nicotine's ability to enhance elements of attention and memory in normal individuals might guide development of therapeutic uses of nicotine in cognitively impaired populations. The purpose of this study was to determine the effect of nicotine on continuous attention, working memory, and computational processing in tobacco-deprived and nondeprived smokers. A total of 28 smokers (14 men, 14 women) participated in a double-blind, placebo-controlled, within-subject study, in which they were overnight (12 h) tobacco deprived at one session and smoked ad libitum before the other session. At each session, participants received 0, 1, and 2 mg nicotine via nasal spray in random order at 90 min intervals. Before and after each dose, a battery of cognitive, subjective, and physiological measures was administered, and blood samples were taken for plasma nicotine concentration. Overnight tobacco deprivation resulted in impaired functioning on all cognitive tests and increased self-reports of tobacco craving and negative mood; nicotine normalized these deficits. In the nondeprived condition, nicotine enhanced performance on the continuous performance test (CPT) and an arithmetic test in a dose-related manner, but had no effect on working memory. In general, women were more sensitive than men to the subjective effects of nicotine. These results provide an unequivocal determination that nicotine enhanced attentional and computational abilities in nondeprived smokers and suggest these cognitive domains as substrates for novel therapeutic indications.

Divided versus selective attention: evidence for common processing mechanisms.

The current study revisited the question of whether there are brain mechanisms specific to divided attention that differ from those used in selective attention. Increased neuronal activity required to simultaneously process two stimulus dimensions as compared with each separate dimension has often been observed, but rarely has activity induced by a divided attention condition exceeded the sum of activity induced by the component tasks. Healthy participants performed a selective-divided attention paradigm while undergoing functional Magnetic Resonance Imaging (fMRI). The task required participants to make a same-different judgment about either one of two simultaneously presented stimulus dimensions, or about both dimensions. Performance accuracy was equated between tasks by dynamically adjusting the stimulus display time. Blood Oxygenation Level Dependent (BOLD) signal differences between tasks were identified by whole-brain voxel-wise comparisons and by region-specific analyses of all areas modulated by the divided attention task (DIV). No region displayed greater activation or deactivation by DIV than the sum of signal change by the two selective attention tasks. Instead, regional activity followed the tasks' processing demands as reflected by reaction time. Only a left cerebellar region displayed a correlation between participants' BOLD signal intensity and reaction time that was selective for DIV. The correlation was positive, reflecting slower responding with greater activation. Overall, the findings do not support the existence of functional brain activity specific to DIV. Increased activity appears to reflect additional processing demands by introducing a secondary task, but those demands do not appear to qualitatively differ from processes of selective attention.

Consistency of subjective responses to imagery-induced tobacco craving over multiple sessions.

Although studies have demonstrated the validity of imagery procedures to elicit tobacco craving responses in single sessions, few studies have examined the consistency of responding in the same individuals over multiple experimental sessions. In this study, nondeprived smokers were presented with a randomized series of imagery scripts that varied in the intensity of smoking-urge content. At each of five sessions spaced over several weeks, participants were exposed to six imagery trials (two each of no-, low-, and high-intensity imagery scripts). After each trial, participants completed subjective measures of tobacco craving and mood. Ratings of craving and negative mood significantly increased as a function of smoking-urge intensity, which was consistent across the five sessions. Further, significant intraclass correlations indicated that craving and mood responses were highly reliable over the five sessions, as well as across two, three, and four sessions. These results have practical implications for examining individual differences in sensitivity to smoking cues and for studies involving repeated measurement of elicited craving over time.

Deficits on the Continuous Performance Test within the schizophrenia spectrum and the mediating effects of family history of schizophrenia.

Individuals with schizophrenia spectrum personality disorders (SSPD) and schizophrenia show similar cognitive impairments. The authors examined the contributions of SSPD symptoms and familial risk for schizophrenia to impairments on the Continuous Performance Test--Identical Pairs Version. Participants included 103 schizophrenia patients, 66 first-degree relatives (29 SSPD), and 103 community controls (26 SSPD) screened for family history of psychosis. Patients and SSPD relatives performed significantly worse than non-SSPD relatives and SSPD and non-SSPD community controls. No differences in performance were observed among non-SSPD relatives and SSPD and non-SSPD community controls. Results suggest a continuum in which risk for schizophrenia-related cognitive impairments is highest among patients and SSPD relatives, intermediate among non-SSPD relatives, and lowest among SSPD and non-SSPD community controls. Results suggest that SSPD in the absence of a family history of psychosis may be a phenocopy.

Effects of nicotine on leading saccades during smooth pursuit eye movements in smokers and nonsmokers with schizophrenia.

Several studies have shown that schizophrenic patients and their biological relatives generate a greater number of leading saccades during smooth pursuit eye movement (SPEM) tasks. This abnormality may reflect a failure of cortical and/or cerebellar areas to coordinate saccadic and pursuit eye movements during visual tracking. The pharmacology of this phenomenon is not known. Here, we sought to replicate and extend the findings of Olincy et al (1998), who found that nicotine transiently reduced the number of leading saccades during SPEMs. A total of 27 subjects with schizophrenia (17 males; 14 smokers), and 25 healthy comparison subjects (nine males; 14 smokers) completed an eye-tracking task after receiving a 1.0 mg nasal spray of nicotine and during drug-free conditions. Results confirm that nicotine reduces the number of leading saccadic eye movements during visual tracking in schizophrenic patients. Baseline impairments and the beneficial effects of nicotine were not restricted to patient smokers, as nonsmoker patients exhibited the greatest number of leading saccades in the no drug condition and exhibited the most pronounced improvements after nicotine administration. Improvement in patient nonsmokers was not a function of previous smoking history. No effect of nicotine was observed in control nonsmokers. In contrast to the previous study, nicotine appeared to improve performance in control smokers. Overall, the study results support a functional role of nACh receptors in improving eye-tracking performance, and are consistent with the hypothesis, articulated by several investigators, that nACh receptor system abnormalities are responsible for a number of schizophrenia-related neurophysiological deficits.

Nicotine improves delayed recognition in schizophrenic patients.

RATIONALE: Nicotine has been shown to enhance some aspects of memory, attention and cognition in normal subjects and in some patient populations such as Alzheimer's and Parkinson's disease groups. OBJECTIVES: Memory disorders are consistently observed in schizophrenic patients, so it is of interest to determine whether nicotine might improve memory performance in these patients. METHODS: Delayed recognition was assessed using yes/no recognition of visuospatial designs. Working memory was assessed in a delayed match-to-sample paradigm using unfamiliar faces. Nicotine (1.0 mg delivered via nasal spray) was administered to schizophrenic patients and normal volunteers prior to testing in the nicotine condition. Results were compared to a baseline condition in which no nicotine was given. RESULTS: On both tasks, normal volunteers performed better overall than schizophrenic patients. Significant improvement following nicotine administration was obtained only on the delayed recognition task and only for the subset of schizophrenic patients who were smokers. This improvement reflected a reduction in false alarm rates in the nicotine condition; hit rates were unaffected by nicotine. CONCLUSIONS: These results suggest that nicotine enhances delayed recognition memory in schizophrenic patients who smoke, but that similar performance enhancement is not observed for working memory.

Cervical cancer screening and acute care visits among Medicaid enrollees with mental and substance use disorders.

OBJECTIVE: This study compared rates of cervical cancer screening and acute care (primary or gynecological) visits among women with and without a diagnosis of psychosis, substance use disorder, bipolar disorder or mania, or depression. METHODS: Using data about women (N=105,681) enrolled in Maryland's Medicaid program in fiscal year 2005, the authors constructed logistic models with cancer screening and acute care visits as dependent variables and serious mental illness flags as independent variables. Covariates were age, race, geography, Medicaid eligibility category, and sexually transmitted diseases. The logistic model of cervical cancer screening outcomes was repeated with acute care visits as a covariate. RESULTS: Women with psychosis (N=4,747), bipolar disorder or mania (N=3,319), or depression (N=5,014) were significantly (p<.05) more likely than women in a control group without such disorders (N=85,375) to receive cancer screening (adjusted odds ratio (AOR) range=1.46-1.78) and to have associated acute care visits (AOR range=1.45-2.15). Compared with those in the control group, women with a substance use disorder, with (N=1,104) or without (N=6,122) psychosis, demonstrated reduced odds of cancer screening (AOR=.80) but similar odds of acute care visits (AOR=1.04). Acute care visits were strongly correlated with cancer screens. Genital cancer prevalence did not significantly differ among diagnostic groups. CONCLUSIONS: In Maryland Medicaid, the odds of cancer screening and related acute care visits were greater for women with major mental disorders compared with women in the control group. For women with substance use disorders, however, screening was reduced and acute care visits were similar compared with women in the control group. Providers should encourage and support their patients with substance use disorders to increase use of preventive care services by primary care physicians and gynecologists.

Group independent component analysis reveals consistent resting-state networks across multiple sessions.

Group independent component analysis (gICA) was performed on resting-state data from 14 healthy subjects scanned on 5 fMRI scan sessions across 16 days. The data were reduced and aggregated in 3 steps using Principal Components Analysis (PCA, within scan, within session and across session) and subjected to gICA procedures. The amount of reduction was estimated by an improved method that utilizes a first-order autoregressive fitting technique to the PCA spectrum. Analyses were performed using all sessions in order to maximize sensitivity and alleviate the problem of component identification across session. Across-session consistency was examined by three methods, all using back-reconstruction of the single-session or single-subject/session maps from the grand (5-session) maps. The gICA analysis produced 55 spatially independent maps. Obvious artifactual maps were eliminated and the remainder were grouped based upon physiological recognizability. Biologically relevant component maps were found, including sensory, motor and a 'default-mode' map. All analysis methods showed that components were remarkably consistent across session. Critically, the components with the most obvious physiological relevance were the most consistent. The consistency of these maps suggests that, at least over a period of several weeks, these networks would be useful to follow longitudinal treatment-related manipulations.

Effect of tobacco deprivation on the attentional blink in rapid serial visual presentation.

When two targets are imbedded in rapid serial visual presentation (RSVP), identification of the second target (T2) is impaired if it occurs within 500 ms of the first target (T1). This attentional blink (AB) is thought to involve interference of resources in processing T1 and T2. The deleterious effect of tobacco deprivation on attention has been documented, but no studies have examined the AB. Nonsmokers (n=30), 12-h tobacco-deprived smokers (n=30), and nondeprived smokers (n=30) were randomly assigned to perform the RSVP with one of three stimulus-duration conditions (96, 113, or 130 ms). Participants completed 48 RSVP trials. Each trial consisted of 16 individually presented words (T1, T2, and 14 distractors), and T2 lagged T1 at serial positions 1-8. Participants verbalized T1 and T2 in order immediately after each trial. Identification of T2 (for correct T1 trials) was impaired at early versus late lag positions, which was especially pronounced in the most difficult (96 ms) condition. There was no evidence for group differences on the AB; however, deprived smokers were worse identifying T1 in the 113-ms condition. These results suggest that the AB is influenced by stimulus duration, but not by 12 h of tobacco deprivation.

Regional expression of RGS4 mRNA in human brain.

Regulators of G-protein signalling (RGS) proteins are a recently discovered class of proteins that modulate G-protein activity. More than 20 RGS proteins have been identified and are expressed throughout the body and brain. In particular, RGS4 appears to regulate dopamine receptor function and has been implicated in several dopamine related diseases, including schizophrenia. This study presents an extensive examination of the regional distribution of RGS4 mRNA in postmortem human brain. Using in situ hybridization, the expression levels of RGS4 mRNA were determined in human hemicoronal (Talairach sections +8 and -20) brain sections. In the rostral slice (Talairach +8) highest levels were found in the inferior frontal cortex, the superior frontal, and the cingulate cortex. Slightly lower levels were found in the insular cortex and inferior temporal cortex. The caudate, putamen and nucleus accumbens had lower levels. In the caudal slice (-20), the cortical layers showed the highest levels, with moderate levels observed in the parahippocampal gyrus, low levels in the CA-pyramidal region, and almost undetectable levels in the thalamus. In the frontal cortex a dense band was apparent near one of the inner layers of the cortex. In conclusion, RGS4 mRNA distribution in human postmortem tissue from normal persons was very dense in most cortical layers examined, with lower density in the basal ganglia and thalamus.