Response- and stimulus-related ERP asymmetries in a tonal oddball task: a Laplacian analysis.

Previous studies have found greater P3 amplitude over right than left hemisphere sites in a tonal oddball task with a reaction time (RT) response. This asymmetry had a central topography, and interacted with response hand. Identification of the processes underlying these asymmetries requires the use of additional methods for separating response- and stimulus-related contributions. We applied local Hjorth and spherical spline algorithms to compute surface Laplacian topographies of ERP data recorded from 30 scalp electrodes in a pooled sample of 46 right-handed healthy adults. For both methods, the current sources underlying the late positive complex were largest at medial parietal regions, but were asymmetric at central and frontocentral sites. Although a frontocentral sink contralateral to the response hand contributed to the asymmetry of the classic P3 peak, the source asymmetry was most robust after the sink had resolved. The late source was largest at electrode C4 for right hand responses, and was further enhanced in subjects showing a dichotic left ear advantage, but was unrelated to response speed. We conclude that the right hemisphere source reflects an interaction of response-related asymmetries with right hemisphere processes responsible for pitch discrimination.

Brain ERPs of depressed patients to complex tones in an oddball task: relation of reduced P3 asymmetry to physical anhedonia.

Event-related potentials to binaural complex tones were recorded from 40 depressed outpatients and 22 normal control participants at 30 electrode sites. Patients did not differ from control participants in N1 or P3 amplitude but showed greater N2. N2 was greater over right than over the left hemisphere at lateral sites in patients and control participants. A P3 asymmetry was found for control participants and patients with low scores on a physical anhedonia scale, but not for patients with high anhedonia scores. Topographic (local Laplacian) maps corresponding to P3 showed greater radial current flow over right than over left central regions in control participants. Patients with high anhedonia did not show this asymmetry, whereas patients with low anhedonia showed an intermediate asymmetry. These findings support the hypothesis that anhedonic depression is associated with dysfunction of right hemisphere mechanisms mediating the processing of complex pitch information.

Regional brain asymmetries in major depression with or without an anxiety disorder: a quantitative electroencephalographic study.

Studies of brain activity in affective disorders need to distinguish between effects of depression and anxiety because of the substantial comorbidity of these disorders. Based on a model of asymmetric hemispheric activity in depression and anxiety, it was predicted that anxious and nonanxious depressed patients would differ on electroencephalographic (EEG) measures of parietotemporal activity. Resting EEG (eyes closed and eyes open) was recorded from 44 unmedicated outpatients having a unipolar major depressive disorder (19 with and 25 without an anxiety disorder), and 26 normal controls using 30 scalp electrodes (13 homologous pairs over the two hemispheres and four midline sites). As predicted, depressed patients with an anxiety disorder differed from those without an anxiety disorder in alpha asymmetry. Nonanxious depressed patients showed an alpha asymmetry indicative of less activation over right than left posterior sites, whereas anxious depressed patients showed evidence of greater activation over right than left anterior and posterior sites. The findings are discussed in terms of a model in which specific symptom features of depression and anxiety are related to different patterns of regional brain activity.

Brain event-related potentials to complex tones in depressed patients: relations to perceptual asymmetry and clinical features.

Brain event-related potentials (ERPs) to probe tones in a dichotic complex tone test were recorded from right-handed depressed patients (n = 44) and normal subjects (n = 19) at homologous sites over left and right hemispheres (F3, F4; C3, C4; P3, P4; O1, O2). There were no differences between groups N1 or P2 amplitude, but patients had smaller P3 amplitude than did normal subjects. Depressed patients failed to show either the left ear advantage or behavior-related hemispheric asymmetry of P3 seen for normal subjects. Depressed patients also showed less difference in hemispheric asymmetry between same and different judgments. These findings indicate that the abnormal behavioral asymmetry for dichotic pitch discrimination in depressed patients reflects a reduction in hemispheric asymmetry and is related to relatively late stages of cognitive processing.

Brain event-related potential correlates of overfocused attention in obsessive-compulsive disorder.

A hypothesis of overfocused attention in obsessive-compulsive disorder was investigated by measuring auditory event-related potentials (ERPs) during a selective attention task. Unmedicated patients (n = 18) with this disorder showed significantly larger attention-related processing negativity (PN), with earlier onset and longer duration, than did normal controls (n = 15). In the N200 region (160-250 ms), PN was larger in patients with fewer nonspecific neurological soft signs. This task, however, did not yield any group differences in mismatch negativity (N2a) or classical N200 (N2b). P300 amplitudes for attended targets were smaller for patient than normal groups, but the reverse was true for P300 and positive slow wave amplitudes for unattended nontargets. Collectively, these ERP abnormalities suggest a misallocation of cognitive resources. Because of the importance of the frontal lobe in the control of selective attention, PN enhancement in patients with obsessive-compulsive disorder may reflect hyperactivation of this region. This conceptualization is consistent with recent functional neuroimaging findings.

Correspondence between brain ERP and behavioral asymmetries in a dichotic complex tone test.

Electrophysiologic correlates of perceptual asymmetry for dichotic pitch discrimination were investigated in 20 normal subjects. Brain event-related potentials (ERPs) elicited by dichotic pairs and binaural probe tones in the Complex Tone Test (Sidtis, 1981) were recorded from homologous scalp locations over left and right hemispheres (F3, F4; C3, C4; P3, P4; O1, O2). Baseline-to-peak amplitudes were measured for N100, P200, and a late positive complex consisting of P350, P550, and slow wave. A left ear advantage (LEA) was evident in 70% of the subjects, and hemispheric asymmetries related to this behavioral asymmetry were found for P350 and P550 amplitudes to probe stimuli. Subjects with a strong LEA had greater amplitudes over the right hemisphere than the left, whereas subjects with little or no LEA showed a nonsignificant trend toward the opposite hemispheric asymmetry. Hemispheric asymmetry of these late ERPs at parietal and occipital sites was highly correlated with behavioral asymmetry. These findings suggest the utility of electrophysiological measures in assessing hemispheric asymmetries for processing complex pitch information.

Abnormal cerebral laterality in bipolar depression: convergence of behavioral and brain event-related potential findings.

Cerebral laterality in bipolar and unipolar major depression was compared using visual half-field and dichotic listening measures of perceptual asymmetry. The results replicate our prior finding of abnormal laterality in bipolar depressed patients on a visuospatial test. Bipolar patients (n = 11) failed to show the left visual field (right hemisphere) advantage for dot enumeration seen for both unipolar patients (n = 43) and normal controls (n = 24). Bipolar patients performed significantly poorer than unipolar patients on normal controls for left visual field, but not right visual field stimuli. An electrophysiological correlate of abnormal visual field asymmetry in bipolar depression was found in brain event-related potentials recorded during audiospatial and temporal discrimination tasks. Bipolar patients had smaller N100 amplitudes for test stimuli in the left than right hemifield, whereas unipolar patients and normals did not. The origins of left hemifield deficits in bipolar depression are discussed in terms of right-sided dysfunction of an arousal/attentional system involving temporoparietal and possibly frontal regions.

Event-related potentials in depression: influence of task, stimulus hemifield and clinical features on P3 latency.

P3 latency, a brain event-related potential (ERP) correlate of stimulus evaluation time, was measured in 25 unmedicated depressed patients and 27 normal controls during auditory temporal and spatial discrimination tasks. Patients were divided into two subgroups, one having a typical major depression (melancholia or simple mood reactive depression) and one having an atypical depression. Typical depressives had abnormally long P3 latency for the spatial task but not the temporal task. They also showed an abnormal lateral asymmetry, with longer P3 latency for stimuli in the right hemifield than the left. In contrast, atypical depressives did not differ from normals in either respect. Longer P3 latency correlated with ratings of insomnia, while abnormal lateral asymmetry correlated with reduced right visual field advantage for syllables. The P3 latency findings point to a task-related slowing of perceptual decisions in a subgroup of depression.

Methadone during pregnancy: assessment of behavioral effects in the rat offspring.

Pregnant rats were administered methadone hydrochloride by gastric intubation. Beginning on day 8 of gestation, a drug group received 5 mg/kg/day; the daily maintenance dose was increased to 10 mg/kg after 4 days with the final dose given on day 22. An intubation control group received sterile water alone on the same gestation days and a nontreated control group was left undisturbed, All experimental and control litters were fostered at birth to untreated mothers, Body weights were low at birth among the methadone offspring but were similar to controls by weaning. During adulthood, offspring were tested on several operant tasks that included acquisition of a lever-pressing response, performance on a variable interval reinforcement schedule, acquisition and performance of an auditory-visual discrimination and response inhibition in a "punishment" paradigm. None of these measures revealed any learning or inhibitory impairments among the methadone-exposed offspring. The major behavioral effect produced by the treatment was a high response output which emerged for each sex in different phases of testing.

Methadone during pregnancy in the rat: dose level effects on maternal and perinatal mortality and growth in the offspring.

Four groups of pregnant rats were administered methadone hydrochloride orally on days 8 through 22 of gestation. Each group initially received 5 mg/kg for 4 days. One group was maintained at this level and the remaining groups were increased to maintenance doses of 10, 15 or 20 mg/kg increments at 4-day intervals. An intubation control group received the vehicle only. Nontreated control mothers were left undisturbed. All offspring were fostered to other nontreated mothers at birth. Methadone, particularly at the higher dose levels, reduced maternal weight gain during pregnancy and increased both maternal mortality and total mortality among the young (resorptions plus stillbirths). Birth weight covaried with dose level and litter size: the 5, 10 and 15 mg/kg doses yielded litter sizes comparable, to, or somewhat smaller than, controls, but with lower birth weights; the 20 mg/kg doses yielded the smallest litter sizes but with birth weights greater than any other treated or control group. Beyond day 1 of life, treated and control offspring did not differ in mortality. By weaning, the low offspring weights seen at birth had been compensated for and were no longer evident. Body weights of offspring of mothers in the 20 mg/kg group remained well above average through weaning. In a second experiment, blood levels of methadone were determined for both mothers and litters in the 5, 10 and 15 mg/kg groups, sacrificed 24 hours before expected parturition. Blood levels were dose-related and corresponded to those found in human subjects receiving daily maintenance doses of approximately 30, 60 and 100 mg, respectively.