Neuronal generators of posterior EEG alpha reflect individual differences in prioritizing personal spirituality.

Prominent posterior EEG alpha is associated with depression and clinical response to antidepressants. Given that religious belief was protective against depression in a longitudinal study of familial risk, we hypothesized that individuals who differed by strength of spiritual beliefs might also differ in EEG alpha. Clinical evaluations and self-reports of the importance of religion or spirituality (R/S) were obtained from 52 participants, and again at 10-y followup when EEG was measured. EEG alpha was quantified using frequency PCA of current source densities (CSD-fPCA). Participants who rated R/S as highly important at initial assessment showed greater alpha compared to those who did not. Those who rated R/S important in both sessions showed greater alpha than those who changed their ratings. EEG differences were particularly well-defined for participants with lifetime depression. Findings extend the view of alpha as a marker for affective processes, suggesting an association with the ontogenesis of spirituality.

Event-related potentials in schizophrenia during tonal and phonetic oddball tasks: relations to diagnostic subtype, symptom features and verbal memory.

BACKGROUND: This study compares event-related potentials for paranoid patients (n = 13) versus matched undifferentiated patients and unmedicated patients (n = 14) versus matched healthy adults. METHODS: Event-related potentials of right-handed patients and control subjects were recorded from 30 electrodes during oddball tasks using consonant-vowel syllables or complex tones. Patients were also assessed using the Positive and Negative Syndrome Scale, the Thought Disorder Index, and the Wechsler Memory Scale. RESULTS: Paranoid patients did not differ from undifferentiated patients in N1 or P3 amplitude but showed larger N2 at frontocentral sites to phonetic stimuli, as well as larger N2 over left than right hemisphere. Unmedicated patients showed reduced N2, but not N1 or P3, compared to control subjects. CONCLUSIONS: The N2 findings are consistent with neuropsychological evidence of greater verbal abilities and left hemisphere dominance in paranoid than nonparanoid schizophrenia. The findings also confirm the relationship of P3 to total Brief Psychiatric Rating Scale score, negative symptoms, and verbal associative memory.

Event-related brain potentials (ERPs) in schizophrenia for tonal and phonetic oddball tasks.

BACKGROUND: Prior studies using simple target detection ("oddball") tasks with pure tones have reported asymmetric reduction of the P3 event-related potential (ERP). This study investigated the time course and topography of ERPs recorded during both tonal and phonetic oddball tasks. METHODS: Event-related potentials of 66 patients (14 unmedicated) diagnosed with schizophrenia (n = 46) or schizoaffective disorder (n = 20) and 32 healthy adults were recorded from 30 scalp electrodes during two oddball tasks using consonant-vowel syllables or complex tones. Overlapping ERP components were identified and measured by covariance-based principal components analysis. RESULTS: Schizophrenic patients showed marked, task-independent reductions of early negative potentials (N1, N2) but not reduced P3 amplitude or abnormal P3 asymmetry. Task-related hemispheric asymmetries of the N2/P3 complex were similar in healthy adults and schizophrenic patients. Poorer task performance in patients was related to ERP amplitudes, but could not account for reductions of early negativities. CONCLUSIONS: The findings suggest that both patients and control subjects activated lateralized cortical networks required for pitch (right frontotemporal) and phoneme (left parietotemporal) discrimination. Task-independent reductions of negativities between 80 and 280 msec after stimulus onset suggest a deficit of automatic stimulus classification in schizophrenia, which may be partly compensated by later effortful processing.

Electroencephalographic and perceptual asymmetry differences between responders and nonresponders to an SSRI antidepressant.

BACKGROUND: Recent reports suggest the value of electroencephalographic and dichotic listening measures as predictors of response to antidepressants. This study examines the potential of electroencephalographic alpha asymmetry and dichotic measures of perceptual asymmetry as predictors of clinical response to 12 weeks of treatment with fluoxetine (Prozac). METHODS: Resting electroencephalography (eyes open and eyes closed) and dichotic listening with word or complex tone stimuli were assessed in depressed outpatients during a pretreatment period. RESULTS: Fluoxetine responders (n = 34) differed from nonresponders (n = 19) in favoring left over right hemisphere processing of dichotic stimuli. They also differed in their resting electroencephalographic alpha asymmetry, particularly in the eyes open condition. Nonresponders showed an alpha asymmetry indicative of overall greater activation of the right hemisphere than the left, whereas responders did not. The relationship between hemispheric asymmetry and treatment response interacted with gender, being evident among depressed women but not men. CONCLUSIONS: The results are consistent with the hypothesis that a characteristic tendency toward greater left than right hemisphere activation is associated with favorable response to fluoxetine, whereas the opposite hemispheric asymmetry predicts poor response.

A convenient method for detecting electrolyte bridges in multichannel electroencephalogram and event-related potential recordings.

Dense electrode arrays offer numerous advantages over single channel electroencephalogram/event-related potential (EEG/ERP) recordings, but also exaggerate the influence of common error sources arising from the preparation of scalp placements. Even with conventional low density recordings (e.g. 30-channel Electro-Cap), over-application of electrode gel may result in electrolyte leakage and create low impedance bridges, particularly at vertically-aligned sites (e.g. inferior-lateral). The ensuing electrical short produces an artificial similarity of ERPs at neighboring sites that distorts the ERP topography. This artifact is not immediately apparent in group averages, and may even go undetected after visual inspection of the individual ERP waveforms. Besides adding noise variance to the topography, this error source also has the capacity to introduce systematic, localized artifacts (e.g. add or remove evidence of lateralized activity). Electrolyte bridges causing these artifacts can be easily detected by a simple variant of the Hjorth algorithm (intrinsic Hjorth), in which spatial interelectrode distances are replaced by an electrical analog of distance (i.e. the variances of the difference waveforms for all pairwise combinations of electrodes). When a low impedance bridge exists, the Hjorth algorithm identifies all affected sites as flat lines that are readily distinguishable from Hjorth waveforms at unbridged electrodes.

Symptom provocation alters behavioral ratings and brain electrical activity in obsessive-compulsive disorder: a preliminary study.

Regional brain activity was measured using quantitative electroencephalography (EEG) in six patients with obsessive-compulsive disorder (OCD) during live and imaginal exposure to feared contaminants. OCD symptoms increased significantly from baseline levels during live and imaginal exposures. However, live exposure provoked significantly more OCD symptoms than imaginal exposure. There was a significant change in the anterior-to-posterior scalp distribution of alpha power during live exposure. These preliminary results suggest that: (1) live exposure is more effective than imaginal exposure in altering behavioral and electrophysiological measures; and (2) live exposure is associated with regional EEG changes in OCD.

Event-related potentials (ERPs) to hemifield presentations of emotional stimuli: differences between depressed patients and healthy adults in P3 amplitude and asymmetry.

Depression may involve dysfunction of right parietotemporal cortex, a region activated during perception of affective stimuli. To further test this hypothesis, event-related brain potentials (ERPs) were measured in a paradigm previously shown to produce ERP asymmetries to affective stimuli over parietal sites in healthy adults. Pictures of patients with dermatological diseases showing disordered or healed facial areas before (negative) or after (neutral) surgical treatment were briefly exposed for 250 ms to either the left or right hemifield. ERPs of 30 unmedicated, unipolar depressed patients and 16 healthy adults, all right-handed, were recorded from 30 electrodes. A principal components analysis extracted factors which closely corresponded to distinctive ERP components previously reported for this task (N1, N2, early P3, late P3, slow wave). Significant effects of emotional content, i.e. enhanced amplitudes to negative than neutral stimuli, were found for early and late P3. Control subjects showed significant hemispheric asymmetries of emotional processing for late P3 (peak latency 460 ms), with the largest emotional content effects over the right parietal region. In striking contrast to control subjects, depressed patients did not show an increase in late P3 for negative compared to neutral stimuli over either hemisphere and had smaller late P3 amplitude than control subjects. Patients did, however, show larger early P3 (peak latency 330 ms) to negative than neutral stimuli. Results suggest intact early discrimination but abnormal late appraisal of affective content in depression, which may arise from selective inhibition of right parietal regions integral for perceiving and evaluating emotional stimuli.

Electroencephalographic asymmetries in adolescents with major depression: influence of comorbidity with anxiety disorders.

This study examined whether adolescents with major depressive disorder (MDD) display the abnormal electroencephalographic (EEG) alpha asymmetries found in depressed adults. Resting EEG was recorded in 25 right-handed female outpatients (19 with MDD, 11 of whom also had a current anxiety disorder; 6 with anxiety disorders only) and 10 non-ill controls. In contrast to the non-ill controls, adolescents having MDD but no anxiety disorder showed alpha asymmetry indicative of less activation over right than over left posterior sites. Within the MDD patient group, comorbid anxiety disorders reduced the posterior alpha asymmetry, supporting the potential importance of evaluating anxiety in studies of regional brain activation in adolescent MDD. These preliminary findings are similar to those from adult studies that suggest that MDD is associated with right parietotemporal hypoactivation.

Brain event-related potentials (ERPs) in schizophrenia during a word recognition memory task.

Impairments of recognition memory for words and attenuation of the ERP 'old-new' effect have been found in patients with left medial temporal lobe damage. If left temporal lobe dysfunction in schizophrenia involves medial structures (e.g. hippocampus), then schizophrenic patients might show similar abnormalities of verbal recognition memory. This study recorded ERPs from 30 electrode sites while subjects were engaged in a continuous word recognition memory task. Results are reported for 24 patients having a diagnosis of schizophrenia (n = 16) or schizoaffective disorder (n = 8) and 19 age-matched healthy controls. Both patients and controls showed the expected 'old-new' effect, with greater late positivity to correctly recognized old words at posterior sites, and there was also no significant difference between groups in P3 amplitude. However, accuracy of word recognition memory was poorer in patients than controls, and patients showed markedly smaller N2 amplitude. Reduced amplitudes of N2 and N2-P3 were associated with poorer performance, with highest correlations over the left inferior parietal (N2) and left medial parietal (N2-P3) region. Moreover, patients failed to show significantly greater left than right hemisphere amplitude of N2-P3 at posterior sites, which was seen for healthy controls. These findings suggest that impaired word recognition in schizophrenia may arise from a left lateralized deficit at an early stage of processing, beginning at 200-300 ms after word onset.

Predictors of therapeutic response to treatments for depression: a review of electrophysiologic and dichotic listening studies.

There are few clinical or biologic predictors of response to treatments for depression. This article reviews growing evidence that electrophysiologic and neurocognitive measures of brain function may be of value as predictors of therapeutic response to antidepressants. Initial studies using dichotic listening, quantitative electroencephalography, or event-related brain potential measures have found differences between treatment responsive and nonresponsive subgroups of depressed patients. The neurophysiologic basis for these differences and the potential clinical utility of electrophysiologic and dichotic predictors of treatment outcome remain to be determined in future studies.

Dissociation of brain ERP topographies for tonal and phonetic oddball tasks.

ERP topographies for 30 scalp electrodes were examined in 26 healthy right-handed volunteers during oddball tasks (20% targets) using binaurally presented consonant-vowel syllables or complex tones. Response hand was counterbalanced across participants. Both window averages and a principal components analysis (PCA) with Varimax rotation revealed task-related (tonal/phonetic) hemispheric asymmetries for N2, early P3, and particularly for N2-P3 amplitude. In the tonal task, N2 was maximal over right lateral-temporal regions, and early P3 over right medial-parietal regions. For the phonetic task, N2 was maximal over the left lateral-parietal regions, and late P3/N3 over left medial-parietal regions. A response-related frontal negativity (N3) interacted with task-related asymmetries in an unbalanced fashion. The distinct, asymmetric N2 and P3 topographies for tonal and phonetic tasks presumably reflect differential involvement of cortical structures in pitch (right frontotemporal) and phoneme (left parietotemporal) discrimination.

Identification of emotion in a dichotic listening task: event-related brain potential and behavioral findings.

The lateralization of emotion perception has been examined using stimuli in both auditory and visual modalities. Studies using dichotic stimuli have generally supported the hypothesis of right-hemisphere dominance for emotion perception, whereas studies of facial and verbal emotion perception have provided evidence for the right-hemisphere and valence hypotheses. A dichotic target detection task was developed to enable acquisition of event-related potentials (ERP) from subjects engaged in emotion detection. Nonsense syllables (e.g., ba, pa) stated in seven different emotional intonations were dichotically presented to 24 young adults, in a target detection task during four separate blocks (target emotions: happiness, interest, anger, or sadness). Accuracy and reaction time and ERP measures were also collected. ERPs were recorded from 14 scalp electrodes with a nose reference and quantified for N100, sustained negativity, late positivity, and slow wave. Significantly greater left- than right-ear accuracy was obtained for the identification of target prosodic emotion. Hemispheric asymmetries of N100 and sustained negativity were found, with left-hemisphere amplitudes greater than right-hemisphere amplitudes. These ERP asymmetries were not significantly correlated with the left-ear dichotic advantage and may be related more to early phonetic processing than to emotion perception. Since the behavioral evidence supports the right-hemisphere hypothesis for emotion perception, behavioral and ERP asymmetries evident in this task reflect separable patterns of brain lateralization.

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.

Interpretation of high-resolution current source density profiles: a simulation of sublaminar contributions to the visual evoked potential.

Current source density (CSD) analysis provides an index of the location, direction, and density of transmembrane currents that arise with synchronous activation of neural tissue and that generate an evoked potential profile in the extracellular medium. In neocortex and other laminated structures, a simplified, one-dimensional CSD analysis can be computed by differentiation of voltages sampled at discrete points in a linear array. One-dimensional CSD analysis is a practical and accurate method for defining both regional activity patterns and neural generators of surface-recorded evoked and event-related potentials. In computing the CSD, common practices of differentiating across spatial grids of 200 microns or more and use of spatial smoothing routines help to reduce noise, but severely limit the spatial resolution available to the analysis. High-resolution CSD procedures (i.e., 3 point differentiation using a spatial grid of 100 microns or less) are more suited to identification of processes within individual cortical laminae or sublaminae, but can magnify the contributions of computational artifacts. Despite the inclusion of independent indices of cellular activity (e.g., multiunit activity), both high- and low-resolution analyses may indicate current source and sink configurations for which there is more than one plausible physiological interpretation. In the present study we examined the resolving capacity and pitfalls of common CSD procedures using simulated ensembles of current dipoles. These were positioned and oriented to model the depolarization of lamina 4C stellate cells and thalamocortical afferents in macaque striate cortex. Empirically, the surface N40 appears in association with a CSD configuration which includes current sinks within the thalamorecipient (stellate) subdivisions of lamina 4C and a large current source extending considerably below 4C. Dipole ensemble contributions to the CSD profile were computed and compared to physiological data from this region. Small asymmetries in activation of model stellate laminae were sufficient to produce substantial open field contributions. However, the best fit with empirical CSD profile was found when the simulation included contributions from thalamocortical axons, along with both open and closed field contributions from dual stellate cell sublaminae. High-resolution CSD profiles were shown to be interpretable when computational artifacts characteristic of closed and open fields were identified using a series of differentiation grids.

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.