Verner J. Knott

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 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.

Transdermal Nicotine: Single Dose Effects on Mood, EEG, Performance, and Event-Related Potentials

A 21-mg dose of nicotine was administered transdermally to 16 overnight smoking-deprived smokers in a double-blind, placebo-controlled design. Mood ratings, electroencephalography (EEG), behavioral performance and event-related potential (ERP: P300) indices of attention and information processing speed were assessed before and 4 h after placebo/nicotine treatment. Although nicotine, relative to placebo, failed to alter mood, it increased absolute and relative power indices of EEG arousal, shortened reaction times, and increased P300 amplitudes. The results are discussed in relation to nicotines actions on cholinergic transmission and its role in smoking behavior.

Dynamic EEG Changes during Cigarette Smoking

Electroencephalograms were monitored before, during and after smoking a single cigarette. Quantitative analysis indicated that smoking produced a characteristic psychostimulant profile involving power reductions in delta and theta and increases in both alpha power and peak alpha frequency. Puff-by-puff analysis yielded similar patterns with the effects emerging by the fourth puff. Delta reductions were evident during the act of puffing and following inhalation. The results are discussed in relation to motivational theories of smoking.

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.

Computerized EEG correlates of depression and antidepressant treatment

Quantitative EEG was used to examine: differences between non-medicated depressives and normal controls; chronic effects of antidepressant drug treatment. Spectral analysis of cortical EEG activity revealed: significant group differences in slow and fast wave activity and significant differences in hemispheric asymmetry; limited effects of antidepressants which were restricted to slow wave activity. Group differences are supportive of cortical disactivation of the right-hemisphere in depressive disorders and the limited drug-EEG effects in depressives argue for additional studies on multi-lead oriented pharmaco-EEG profiles in psychiatric populations.

The right profile: mismatch negativity in schizophrenia with and without auditory hallucinations as measured by a multi-feature paradigm.

OBJECTIVE To examine pre-attentive acoustic change detection in schizophrenia patients with and without auditory hallucinations via mismatch negativity (MMN) extracted from a multi-feature paradigm. METHODS This study examined the electroencephalograph (EEG)-derived MMN, recorded across 32 sites, in 12 hallucinating patients (HPs) with schizophrenia, 12 non-hallucinating patients (NPs) with schizophrenia and 12 healthy controls (HCs). MMN was recorded in response to a multi-feature MMN paradigm [Näätänen, R., et al., 2004. The mismatch negativity (MMN): towards the optimal paradigm. Clin. Neurophys. 115, 140-144] which employs frequency, duration, intensity, location and gap deviants. Differences in source localization were probed using standardized low resolution brain electromagnetic tomography (sLORETA). RESULTS HPs showed significantly smaller MMNs to duration deviants compared to HCs and NPs, as well as smaller MMNs to intensity deviants compared to HCs. Regionalized differences between HCs and each of the patient groups were observed in response to frequency deviants. There were no significant group effects for location or gap deviants, or for MMN latency. Source localization using sLORETA showed no significant differences in MMN generator location across groups for any of the deviant stimuli. CONCLUSIONS The often-reported robust MMN deficit to duration deviants may be specific to schizophrenia patients afflicted with auditory hallucinations. Furthermore, by using symptom-specific groups, novel deficits of pre-attentive auditory processing, such as that observed to intensity deviants in HPs, may be revealed. SIGNIFICANCE The differential responding observed between both groups of patients with schizophrenia has implications for automatic processing within the auditory cortex of hallucinating patients and suggests that care must be taken when recruiting participants in studies involving schizophrenia to ensure consistent, replicable results.

Alpha Power, Alpha Asymmetry and Anterior Cingulate Cortex Activity in Depressed Males and Females

Left fronto-cortical hypoactivity, thought to reflect reduced activity in approach-related systems, and right parietal hypoactivity, associated with emotional under-arousal, have been noted in major depressive disorder (MDD). Altered theta activity in the anterior cingulate cortex (ACC) has also been associated with the disorder. We assessed resting frontal and parietal alpha asymmetry and power in non-medicated MDD (N = 53; 29 females) and control (N = 43; 23 females) individuals. Theta activity was examined using standardized low-resolution electromagnetic tomography (sLORETA) in the ACC [BA24ab and BA32 comprising the rostral ACC and BA25/subgenual (sg) ACC]. The MDD group, and particularly depressed males, displayed increased overall frontal and parietal alpha power and left midfrontal hypoactivity (alpha(2)-indexed). They also exhibited increased sgACC theta(2) activity. MDD females had increased right parietal activity, suggesting increased emotive arousal. Thus, unmedicated depressed adults were characterized by lower activity in regions implicated in approach/positive affective tendencies as well as diffuse cortical hypoarousal, though sex specific modulations emerged. Altered theta in the sgACC may reflect emotion regulation abnormalities in MDD.

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.

Sensory gating and source analysis of the auditory P50 in low and high suppressors

Impairments in sensory gating in schizophrenia have been reflected by diminished suppression of the scalp-recorded middle latency auditory P50 event-related potential (MLAERP) elicited by the second (S(2)) of a pair (S(1)-S(2)) of clicks. As understanding the functional neural substrates of aberrant gating would have important implications for schizophrenia, this study examined the location and time-course of the neural generators of the P50 MLAERP and its gating on subgroups of healthy volunteers exhibiting low (n=12) and high (n=12) P50 suppression. Suppressor differences were observed with S(1) P50 (high>low) and S(2) P50 (high<low) amplitudes, and current source density analysis with standardized Low Resolution Electromagnetic Tomography (sLORETA) evidenced an S(1) P50-related activation of limbic, temporal and parietal regions in the high but not the low suppressors. Distributed source localization of the Gating Difference Wave (GDW), obtained by subtracting the S(2) P50 response from the S(1) P50 response, also revealed a later and sustained frontal activation to characterize high suppressors. These findings suggest that impaired gating of the kind evident in schizophrenia may involve the deficient functioning of multiple interconnected and temporally overlapping activated brain regions.