Effects of nicotine on visuospatial attentional orienting in non-smokers.

Nicotine is a highly addictive substance, suggested to be in part due to its cognitive enhancing effects in the attentional domain. Improvements in stimulus selection with nicotine have been reported but its effects on visual-spatial selective attention are unclear. This study utilized event-related potentials (ERPs) to examine the acute effects of nicotine on selective attention in non-smokers performing a Posner-type visuo-spatial task. The attentional processing of visual-spatial locations is reflected in the P1 ERP component, which represents earlier stages of visual analysis. 24 non-smokers received nicotine gum (6 mg) in a randomized, double-blind, placebo-controlled, repeated measures design. Behavioral performance and ERPs were assessed in response to target locations preceded by valid, invalid and neutral cues. Nicotine did not affect behavioral performance indices. P1 amplitudes were greater in valid and neutral cue trials compared to invalid cue trials and acute nicotine administration (vs. placebo) was found to increase P1 amplitudes in the right hemisphere, particularly in valid cue trials. In addition, in high symptomatic subjects (as indexed by greater increases in heart rate post-administration), nicotine (vs. placebo) produced greater P1 amplitudes in valid cue trials. The study concludes that nicotine enhanced visuospatial selective attention with regards to early visual encoding and analysis. These results demonstrate support in general for the attentional effects of nicotine and nicotinic agonists and they specifically extend these effects to include orienting of visual-spatial attention.

Differential effects of nicotine on P50 amplitude, its gating, and their neural sources in low and high suppressors.

Sensory gating impairment in schizophrenia has been documented in the form of aberrant middle latency P50 event-related brain potential responses to S(1) and/or S(2) stimuli in a paired (S(1)-S(2)) auditory stimulus paradigm. Evidenced by a failure to suppress S(2) P50 or by attenuated S(1) P50s, these sensory deficits have been associated with increased smoking behaviour in this disorder, and may be related to the putative ameliorating effects of smoke-inhaled nicotine on neural mechanisms regulating gating. Comparison of healthy controls with low versus high gating efficiency has been forwarded as a model for investigating the actions of antipsychotic agents on aberrant gating functions. In the current study, the effect of a single dose (6 mg) of nicotine gum on P50, gating indices, and their cortical sources indexed with sLORETA (standardized low resolution electromagnetic tomography), was examined in healthy non-smokers (n=24) stratified for low and high gating levels. Scalp surface recordings revealed nicotine modulation of P50 and its gating to be differentially exhibited in high (decreasing gating) and low (increasing gating) suppressors while the underlying cortical sources influenced by nicotine (middle frontal gyrus, inferior/superior parietal lobules, pre- and post-central gyri) were seen only in low suppressors. These findings suggest that nicotine impacts sensory gating in healthy volunteers and as the gating enhancing effects were dependent on low baseline gating efficiency, nicotinic receptor agonists may be associated with unique P50 modulating actions in schizophrenia.

Electroencephalographic characterization of cigarette smoking behavior.

The rewarding properties of used and abused substances are related to their ability to modulate central processes subserving mood, cognition, and behavior. Research into the motivationally relevant factors mediating substance use and abuse among human beings, including tobacco smoking, can strategically benefit from the utilization of noninvasive brain function measures that are able to probe the neurobiology of brain states in concert with substance ingestion. This paper reviews investigations from my laboratory with the use of neuroelectric tools, by means of quantitative electroencephalography, for the purpose of characterizing the central response to cigarette smoking. Prominent in these strategies is the acute smoking paradigm, whereby measures are focused on the profiling of central responsivity to smoke inhalation from a single cigarette and administration of test doses of nicotine. Complementing this approach are studies (1) in which receptor antagonists are administered in an attempt to explore putative transmitter systems regulating the acute smoking-induced electroencephalographic response and (2) in which electroencephalographic profiles of acute smoking are compared with electroencephalographic profiles resulting from administration of single doses of psychotropic substances. Completing these studies are attempts to monitor the electrocortical correlates of repeated smoking exposure and smoking deprivation, which, together with investigations examining smoker vs. nonsmoker differences and the effects of chronic life-long smoking, provide objective insights into the neuroelectrophysiology underlying the smoking habit.

Effects of haloperidol pretreatment on the smoking-induced EEG/mood activation response profile.

This study examined the role of dopamine in modulating the CNS response to cigarette smoking. In a randomized, double-blind, repeated-measures design, quantitative electroencephalographic (EEG) changes and self-reports induced by the smoking of a single cigarette were assessed in 16 smokers following pretreatment with placebo and a dopamine antagonist, haloperidol (2 mg). Following placebo pretreatment, absolute (muV) and relative (%) amplitudes in slow-frequency bands (delta, theta, alpha1) were reduced and absolute and relative amplitudes in fast-frequency bands (alpha2, beta) were increased following cigarette smoking as compared to sham smoking. Haloperidol pretreatment inhibited the smoking-induced increase in absolute beta frequency. Self-ratings indicated that cigarette smoking induced increases in alertness, contentedness and calmness but not euphoria, and reduced cigarette cravings as compared to the sham smoking conditions. Smoking-induced, alpha2 increments were associated with increases in alertness and decreases in euphoria while beta increments were associated with increased calmness. Smoking-related self-ratings of mood and cigarette acceptability were not altered by haloperidol, but subjects were less content overall in the haloperidol condition as compared to placebo. Discussion of these results focuses on transmitter systems and their relationship to neuro-electric and behavioural activities associated with the smoking habit.

Smoking history and aging-associated cognitive decline: An event-related brain potential study.

Although cigarette smoking has been associated with reduced risk for dementia of the Alzheimer type, relatively little is known about the central impact of a lengthy smoking history, particularly with respect to the cognitive effects, on the normal aging brain. Given that elderly adults have been reported to exhibit poor short-term memory in conditions requiring divided attention, this study utilized behavioral performance and event-related potential (ERP) measures to compare groups (n = 10/group) of young (18-39 years) and elderly (64-81 years) adult smokers and nonsmokers during a continuous visual word recognition task carried out alone and concurrently with an auditory (oddball) tone discrimination task. Young and elderly adult smokers had average smoking histories of 9.3 and 52.0 years, respectively. Significant aging (young > elderly adults) and task (single-task > dual-task) effects were observed for performance accuracy and speed measures as well as for N400/P600 ERP waveform components elicited by 'old/new' word recognition and P300 ERP indices elicited by auditory target detection. The effects of smoking history were limited to the P600 component, which showed faster latencies in elderly smokers than elderly nonsmokers and young nonsmokers. Young smokers exhibited longer latencies than young nonsmokers. The results were discussed in relation to normal and pathological cognition in the elderly.

The effect of acute tryptophan depletion and fenfluramine on quantitative EEG and mood in healthy male subjects.

BACKGROUND: Efforts to model putative serotonergic deficits associated with affective disorders have frequently involved acute tryptophan depletion (ATD) as a manipulation strategy aimed at lowering brain serotonin synthesis. In an attempt to widen the scope of the measurement probes used in these investigations, the central actions of ATD and a subsequent dose of fenfluramine were examined via utilization of quantitative electroencephalography (EEG) and mood ratings. METHODS: Electroencephalograms (EEG) and subjective mood ratings were assessed in 28 healthy men before and after double-blind ingestion of a tryptophan-depleting (T-) amino acid mixture, or a nutritionally balanced (B) amino acid mixture containing tryptophan, and again after a single-blind oral dose of D,L-fenfluramine hydrochloride (60 mg). RESULTS: Compared to the B mixture, the T- mixture reduced total plasma tryptophan by more than 75% 5 hours after ingestion. Tryptophan depletion was associated with a modest lowering of mood and a slowing of EEG as indicated by increases in delta amplitude. Fenfluramine caused no change in mood but increased fast wave (beta) activity in anterior recordings when administered after the T-, but not after the B mixture. CONCLUSIONS: Quantitative EEG measurements may be a promising method for studying the central mechanisms underlying serotonin-mediated changes in mood and behavior.

Influence of acute tryptophan depletion on mood and immune measures in healthy males.

Depressive illness has been associated with variations of several aspects of immune functioning, as well as alterations of cytokine production in stimulated lymphocytes. In the present investigation we sought to determine whether pharmacologically-induced reductions of mood in healthy, male subjects would be associated with alterations in the levels of circulating IL-1 beta or IL-6 or to in vitro lymphocyte proliferation in response to T cell mitogens, PHA and Con A. Lowering tryptophan levels by means of a tryptophan-deficient amino acid mixture, which reduced plasma tryptophan and serotonin (5-HT) levels, produced a lowering of mood in a subset of male subjects (that had no personal or family history of depression) relative to subjects that received a balanced amino acid mixture. Correlational analyses revealed that the change of mood (particularly depression and anger) in subjects that received the tryptophan-free mixture was related to the extent of the tryptophan or 5-HT reductions. However, while fenfluramine administration resulted in recovery of tryptophan and 5-HT levels, this was not accompanied by recovery of mood. Furthermore, it was observed that the lowering of tryptophan levels and the reduced mood were not accompanied by variations of the cytokine levels or cell proliferation. Evidently, transient and modest alterations of 5-HT or mood induced by a tryptophan-free amino acid mixture were insufficient to promote variations of immune activity or circulating IL-1 beta or IL-6 levels. Even if depression were related to immune disturbances, the mood and 5-HT alterations associated with this type of manipulation may be too brief to promote immune changes comparable with those ordinarily associated with severe or chronic depressive illness.

The cholinergic basis of the smoking-induced EEG activation profile.

Acute quantitative electroencephalographic effects of cigarette smoking were examined in 15 smokers within a repeated-measures design which assessed changes in power-spectral estimates following acute pre-treatment with placebo, a dose (20 mg) of mecamylamine, a dose (0.6 mg) of scopolamine and a combined dose of mecamylamine and scopolamine. Compared to sham smoking, the smoking of a single cigarette following placebo pre-treatment reduced absolute and relative power in slow (delta, theta) frequency bands, increased absolute and relative power in alpha and beta frequency bands and accelerated mean frequency. These smoking-induced power changes in slow- and fast-frequency bands were differentially affected by the separate and combined actions of the cholinergic antagonists with treatments involving mecamylamine tending to abolish smoking-induced slow-frequency absolute power reductions and fast-frequency relative power increments. Self-ratings of smoking-induced increases in alertness were altered by mecamylamine and combined treatments while sensory aspects of cigarette smoking were only altered with combined mecamylamine and scopolamine pre-treatment. The results are discussed with respect to brain-behaviour relationships and mechanisms maintaining the smoking habit.

Aging, smoking and EEG coherence: a preliminary study.

Although the cigarette smoking habit is prevalent in young, middle aged and elderly adults, it is yet unknown whether a long term smoking history alters the aging brain and/or whether the aging brain demonstrates an altered sensitivity to acute smoking. Inter- and intrahemispheric EEG coherence was compared in 20 young (18-39 years) adults (10 smokers, 10 nonsmokers) and 20 elderly (64-81 years) adults (10 smokers, 10 nonsmokers). The acute effects of sham inhaling on a nonlighted cigarette and cigarette smoking on EEG coherence was also compared in young and elderly adult smokers. In general, elderly adults exhibited reduced interhemispheric coherence values relative to young adults and, depending on the frequency band, age effects varied with recording site. Smokers of both age groups exhibited greater interhemispheric total alpha coherence values than nonsmokers. Similar smoker status effects were found with fast alpha but this varied with recording site. Relative to sham smoking, acute cigarette smoking reduced interhemispheric slow alpha in both young and elderly smokers but reduced total alpha coherence only in elderly smokers. The results are discussed in relation to normal and pathological aging, including dementia.

Quantitative EEG correlates of panic disorder.

Quantitative analysis of electroencephalographic (EEG) signals recorded from multiple scalp sites was used to compare panic disorder patients (n = 34) with normal healthy controls. Patients exhibited greater overall absolute power in the delta, theta, and alpha frequency bands and less relative power in the beta band. Discriminant analysis of absolute power indices correctly classified 75% of the subjects, while relative power indices exhibited a 69% correct-classification rate. Absolute delta and theta power were positively correlated with observer ratings of anxiety, while relative beta power was related to self-ratings of anxiety.

Quantitative EEG in the prediction of antidepressant response to imipramine.

The purpose of this study was to examine the utility of quantitative electroencephalography (QEEG) in the prediction of response to imipramine in depressed patients. Forty patients with a diagnosis of unipolar depression were subjected to a placebo washout and were assessed at pre-drug, 3 h after their first dose of imipramine, and again 2 weeks into treatment. Following 4 weeks of open imipramine treatment, patients were separated into responder (R) and non-responder (NR) groups. Statistical analysis of the 29 patients who completed the study focused on group comparisons of power spectral estimates in four frequency bands from multi-channel recordings. Results showed that theta power differentiated R and NR groups prior to treatment, in response to an acute test dose, as well as after 2 weeks of active drug treatment. Results based on this exploratory study suggest that QEEG may be a useful early predictor of response to imipramine.

Assessing the topographic EEG changes associated with aging and acute/long-term effects of smoking.

As neuroelectric research into the smoking/nicotine habit has focused exclusively on young and middle-aged adults, this electroencephalographic (EEG) study was conducted to determine whether a long-term smoking history alters the aging brain and/or whether the aging brain demonstrates an altered sensitivity to acute smoking/nicotine. Forty healthy adults, 20 young, aged 18-39 years, and 20 elderly, aged 64-81 years, volunteered for participation. Half of the young and elderly were nonsmokers with no previous smoking history and the remaining half of the young and elderly were current smokers with average smoking histories of 9.3 and 52.0 years, respectively. Smokers attended the laboratory for two randomized test sessions during which multisite EEG recordings were collected pre and post sham and cigarette smoking. Nonsmokers attended the laboratory for one nonsmoking EEG recording session. Spectral power indices showed aging to be associated with significant reductions in absolute delta and theta power and increases in relative beta power and faster mean total band frequency. Aging effects varied with recording region but not with smoker versus nonsmoker status. Smokers did exhibit a faster mean beta frequency. Acute cigarette smoking decreased absolute delta power in young smokers and increased relative alpha 2, beta power and mean alpha frequency in both young and elderly smokers. Only the young smokers showed increase in mean theta and total frequency. The results are discussed in relation to cognition in normal and pathological aging.

Brainstem evoked potentials in panic disorder.

Patient reports and laboratory tests support the notion that panic attacks are generated by stimulation of brainstem nuclei. Scalp-recorded brainstem auditory evoked potentials may serve as a unique measurement strategy for the noninvasive assessment of the role of brainstem functioning in panic disorder. Ipsilateral and contralateral BSAEP recordings were examined in response to separate left and right ear click stimulation in 28 patients with a diagnosis of panic disorder and in 18 normal controls. Latency measures did not differentiate between the patient and control groups but amplitudes of wave III and V were found to be larger in patients. These findings are discussed in relation to pathophysiological and neurochemical theories of panic and specific emphasis is placed on serotonergic function.

Subjective and brain-evoked responses to electrical pain stimulation: effects of cigarette smoking and warning condition.

Infrahuman studies employing behavioral indices of pain reactivity have supported a central antinociceptive action of nicotine which appears to be selective and dependent on the class of pain elicited. Human investigations employing subjectively based ratings and judgments of pain intensity have been less conclusive regarding the painfulness of stimuli following nicotine/smoking administration. As the more objective brain-evoked potential (EP) measure has been shown to reflect pain intensity and to be sensitive to a variety of analgesics, this study attempted to examine, together with subjective responses, the effects of cigarette smoking on EPs to pain stimuli administered under varying warning conditions. Twelve male and twelve female smokers served as experimental subjects. In smoking and nonsmoking sessions, subjective intensity ratings (SR) and vertex EPs were assessed in response to electrical skin stimuli presented at a level 20% above pain threshold. Stimulation was either nonwarned or warned with warning conditions involving single or repeated presentations of electrical current at constant or increasing intensities 12 seconds prior to pain stimulation. SRs and peak-to-peak N1-P2 EP amplitudes were measured for each smoking session and warning condition. A significant condition effect was observed for SRs with increasing prepain warning stimulation resulting in the greatest pain ratings. Although smoking did not directly alter SRs or EPs to pain, smoking exposure, as measured by carbon monoxide, was found to be differentially correlated with EP alterations in male and female smokers depending on the warning condition.

Neurophysiological aspects of smoking behaviour: a neuroelectric perspective.

Many of the current neurobiological hypotheses of tobacco smoking concern relationships between nicotine-induced neurotransmitter alterations--events at the level of the individual neuron--and mental behavioural states. Since non-invasive physiological variables may reflect neural activity more directly than overt indices, neuroelectric studies are suggested to be particularly helpful in understanding the intermediate steps between the neuronal effects of smoke/nicotine and behavioural change. The intent of this paper is to offer direction and suggestion regarding electroencephalographic (EEG) and event-related brain potential (ERP) research into smoke/nicotine effects on mood and performance. Suggested directions revolve around multi-component measurement strategies and the employment of study designs and test paradigms which may offer a more dynamic and detailed neurobiological view of smoke/nicotine effects on these processes.

Temporal segmentation of response speed in depression: neuro-electrophysiological approaches.

1. Depressive psychomotor retardation, as observed by delayed reaction times (RT), may be related to a slowing in information processing speed. 2. Two separate studies compared indices of information processing speed in depressed patients and non-clinical controls by segmenting behavioral RT with brain event-related potentials (ERPs) and electromyographic (EMG) responses. 3. In Study I, slower behavioral RTs in depression were concomitant with slower central processing times (CPT) but not motor execution times (MET). 4. In Study II, P165, a putative early cognitive ERP related to 'stimulus evaluation time', was found to be slower but within normal range in depressed patients.

Preparatory brain potentials in major depressive disorder.

1. Psychomotor slowing in depression is frequently reflected by delayed reaction times (RT). 2. The role of central arousal mechanisms in response slowing was examined by comparing scalp-recorded slow negative potentials of depressed patients with normal controls in two separate studies. 3. Varying fore-warned RT conditions elicited contingent negative variation (CNV) waveforms and the resultant mid-point amplitudes of these waveforms together with orienting (O-wave), expectancy (E-wave) and post-imperative negative variation (PINV) component amplitudes and sensory evoked responses (N1, P2) were compared between groups. 4. RTs were significantly slowed in depressed patients and the patient group exhibited consistently larger PINV amplitudes. Depending on the RT condition, patients also exhibited larger mid-point CNV amplitudes and smaller N1 and P2 amplitudes.