Colleen Mahoney

EEG power, frequency, asymmetry and coherence in male depression

Quantitative electroencephalographic (EEG) power topography has served as a useful tool for investigating brain regional mechanisms underlying affective disorders. In an attempt to examine the role of gender and widen the scope of the measurement probes used in these investigations, the traditional power and inter-hemispheric power ratio indices were supplemented with intra-hemispheric power ratios, mean frequency and both inter and intra-hemispheric coherence indices, in the comparison of depressed male patients and healthy controls. Resting (eyes closed), vigilance controlled EEG recordings from 21 scalp sites were collected from 70 male, unmedicated, unipolar major depressive disorder outpatients and 23 normal control male subjects. Absolute and relative power, frequency, asymmetry and coherence measures derived from spectrally analyzed EEGs were subjected to univariate analyses for group comparisons as well as to discriminant function analysis to examine their utility as classification indices. Compared with controls, patients evidenced greater overall relative beta power and, at bilateral anterior regions, greater absolute beta power and faster mean total spectrum frequency. Inter-hemispheric alpha power asymmetry index differences were noted, with controls exhibiting relatively reduced left hemisphere activation, and widespread reduced delta, theta, alpha and beta coherence indices. Whereas intra-hemispheric theta power asymmetry reduction was exhibited in patients bilaterally at all regions, group differences with intra-hemispheric beta power asymmetry were unilateral, being restricted to the right hemisphere. Discriminant analysis correctly classified 91.3% of the patients and controls. Quantitative EEG measurements in male depression appear to describe a pattern of aberrant inter-hemispheric synchrony/asymmetry and a profile of frontal activation.

Quantitative EEG in schizophrenia and in response to acute and chronic clozapine treatment.

Topographic quantitative electroencephalographic (EEG) power and frequency indices were collected in 17 treatment refractory, DSM-III diagnosed schizophrenic patients, before and after acute (single dose) and chronic (six weeks) clozapine treatment, as well as in 17 healthy volunteers. Prior to treatment, patients exhibited greater overall absolute theta power, slower mean alpha frequency and elevated absolute delta and total power in anterior regions. Acute dosing increased total spectrum power globally, slow wave power posteriorally, mean alpha frequency and beta power anteriorally and decreased alpha power posteriorally. Six weeks of clozapine treatment significantly reduced clinical ratings of positive and negative symptoms as well as symptoms of global psychopathology. Chronic treatment resulted in EEG slowing as shown by decreases in relative alpha power, mean beta/total spectrum frequency and by widespread increases in absolute total and delta/theta power. The preliminary findings suggest that brain electric profiling may be a promising tool for assessing and understanding the central impact of pharmacotherapeutic interventions in schizophrenia.

Acute nicotine effects on auditory sensory memory in tacrine-treated and nontreated patients with Alzheimer's disease: an event-related potential study.

The auditory mismatch negativity (MMN) event-related brain potential (ERP) reflects the storage of information in acoustic sensory memory. Thirteen patients with Alzheimers disease (AD), 6 receiving treatment with the cholinesterase inhibitor, tacrine [tetrahydroaminoacridine (THA)], and 7 receiving no treatment, were administered 2 mg of nicotine polacrilex and placebo. MMNs were recorded with 1- and 3-s interstimulus intervals (ISIs) during pre- and post-placebo/nicotine administration. Amplitudes decreased from pre- to post-placebo recordings in nontreated patients but remained stable in THA-treated patients. Comparison of pre- and post-nicotine MMNs found amplitude increases with nicotine in nontreated but not in THA-treated patients. MMN latencies were shortened by nicotine in both treatment groups. These exploratory findings suggest that nicotine-improved strength of acoustic sensory memory traces and speed of acoustic sensory discrimination in AD are differentially affected by chronic tacrine treatment.

EEG correlates of acute and chronic paroxetine treatment in depression

Single dose administration of efficacious antidepressant agents elicit characteristic pharmaco-electroencephalographic (EEG) profiles in healthy volunteers but acute and chronic pharmaco-EEG profiling of antidepressant action in depressed patients has been relatively lacking. This study sought to examine the quantitative topographic EEGs of depressed patients in response to paroxetine treatment. Thirty male patients, meeting DSM-IV criteria for major depression, were examined before and after a single 20 mg dose. These, and an additional 40 patients, were also assessed following 6 weeks of treatment. Eyes-closed resting EEG, collected from 21 scalp sites, was spectrally analyzed to yield regional measures of absolute/relative power and mean frequency in delta, theta, alpha, beta and total spectrum frequency bands. Chronic treatment resulted in a significant reduction in scores on the Hamilton Rating Scale for Depression (HAM-D), with 80% of treatment completers exhibiting a >50% reduction in depression ratings at the end of the 6th week. Acute paroxetine did not alter EEG in patients but chronic treatment was associated with significant alterations as shown by diffuse decreases in alpha power and increases in slow (delta and theta) and anterior fast (beta) wave power, Mean theta and alpha (occipital) frequency were slowed while mean total frequency was accelerated at frontal sites and decreased at occipital sites. The chronic pharmaco-EEG response pattern reflects both sedating and activating actions in regional specific areas which are relevant to the pathophysiology and the pharmacotherapeutic treatment of depression.

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.

Event-related potentials in schizophrenic patients during a degraded stimulus version of the visual continuous performance task

Previous studies of the auditory P300 event-related potential (ERP) have reported smaller amplitudes in chronic schizophrenics but similar consistencies have not been observed with visual P300s. This study examined P300s in symptomatically stable, medicated, chronic schizophrenics (n = 14) and normal controls (n = 14) performing a visual continuous performance task utilizing degraded stimuli to burden encoding processes. Performance analysis found slower response times, fewer target detections and more false alarms in patients than in controls. Analysis of ERPs showed P300 amplitudes of schizophrenics to be significantly smaller than those of controls and, unlike controls, schizophrenics failed to exhibit significant target vs. non-target P300 amplitude differences. Discriminant analysis indicated target and non-target midline (Fz, Cz, Pz) P300 amplitudes together correctly classified all patients and controls. Exploratory topographic analysis indicated that P300 amplitudes were not asymmetrical in patients, as has been observed with auditory P300s, and, unlike the performance measures, the P300s did not correlate with the patients positive or negative symptom ratings. The implications of these findings are described in relation to attentional disturbances and trait versus state issues in schizophrenics.

Effects of Acute Nicotine Administration on Cognitive Event-Related Potentials in Tacrine-Treated and Non-Treated Patients with Alzheimer’s Disease

Earlier studies of cognitive event-related brain potentials (ERPs) reporting diminished amplitudes and delayed latencies of the P300 potential in dementia of the Alzheimer type (DAT), together with independent findings of the P300- and performance-enhancing properties of nicotine in normal adults, stimulated this study to explore the single-dose effects of nicotine on auditory and visual P300s in DAT. Thirteen patients, 6 currently receiving treatment with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine; THA) and the remaining being medication free, were administered 2 mg of nicotine polacrilex under double-blind, randomized, placebo-controlled conditions. Prior to nicotine administration, THA-treated patients exhibited shorter auditory P300 latencies than non-treated patients. Acutely administered nicotine failed to alter auditory P300, but increased the amplitudes of visual P300s in both DAT patient groups. Neither THA treatment nor single-dose nicotine altered behavioural performance in the visual and auditory task paradigms. The results are discussed in relation to nicotinic cholinergic, attentional and cognitive processes in DAT.

Acute nicotine administration in Alzheimer's disease: an exploratory EEG study.

Previous findings of cognitive deficits and EEG slowing in Alheimer’s patients, together with independent reports of the performance enhancing and electrocortical activating properties of nicotine in normal adults, stimulated this study to examine the acute effects of nicotine on spectrum-analyzed EEG in patients with dementia of the Alzheimer type (DAT). Thirteen patients, 6 currently receiving cholinesterase inhibitor treatment and the remaining being medication free, were administered 2 mg of nicotine polacrilex under randomized, placebo-controlled conditions. Compared to age-regressed EEG norms, the pretreatment EEG spectrums of patients in general were characterized by excessive slow (delta and theta)-wave power, diminished fast (alpha and beta)-wave power and slow mean alpha and total band frequencies. Although postnicotine EEG indices remained within the abnormal range, nicotine, compared to placebo, significantly shifted EEG towards normal values by reducing slow wave (relative delta and theta) power and augmenting fast (relative alpha-1, alpha-2, beta-1) wave power. No differences were observed between treated and nontreated patients in response to nicotine. The results are discussed in relation to cholinergic and brain arousal systems and their relationship to cognitive processes.

EEG hemispheric asymmetry as a predictor and correlate of short-term response to clozapine treatment in schizophrenia.

In search of early neuroleptic response predictors in schizophrenia, functional interhemispheric and intrahemispheric asymmetry indices, derived from spectrally analyzed resting electroencephalographic (EEG) activity, were examined in 17 schizophrenic patients prior to open label treatment with the atypical neuroleptic clozapine. Compared to EEG asymmetry indices derived from a normative data bank, patients exhibited significant interhemispheric (left greater than right) and intrahemispheric (anterior greater than posterior) deviations in delta, theta, alpha and beta frequency bands. Intrahemispheric indices were positively correlated with clinical ratings of positive symptoms and global psychopathology. Clozapine-induced improvements in positive and negative symptoms and global psychopathology symptom ratings were related to pretreatment intrahemispheric asymmetry only, with relationships varying with symptom, recording region and frequency band. The results are discussed in relation to the neurobiology of schizophrenia and the utility of EEG as an informative predictor of treatment response.

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 (µV) and relative (%) amplitudes in slow-frequency bands (δ, Θ, α1) were reduced and absolute and relative amplitudes in fast-frequency bands (α2, β) were increased following cigarette smoking as compared to sham smoking. Haloperidol pretreatment inhibited the smoking-induced increase in absolute β 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, α2 increments were associated with increases in alertness and decreases in euphoria while β 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.