Craig E. Tenke

Principal components analysis of Laplacian waveforms as a generic method for identifying ERP generator patterns. I. Evaluation with auditory oddball tasks

OBJECTIVE To evaluate the effectiveness and comparability of PCA-based simplifications of ERP waveforms versus their reference-free Laplacian transformations for separating task- and response-related ERP generator patterns during auditory oddball tasks. METHODS Nose-referenced ERPs (31 sites total) were recorded from 66 right-handed adults during oddball tasks using syllables or tones. Response mode (left press, right press, silent count) and task was varied within subjects. Spherical spline current source density (CSD) waveforms were computed to sharpen ERP scalp topographies and eliminate volume-conducted contributions. ERP and CSD data were submitted to separate covariance-based, unrestricted temporal PCAs (Varimax) to disentangle temporally and spatially overlapping ERP and CSD components. RESULTS Corresponding ERP and CSD factors were unambiguously related to known ERP components. For example, the dipolar organization of a central N1 was evident from factorized anterior sinks and posterior sources encompassing the Sylvian fissure. Factors associated with N2 were characterized by asymmetric frontolateral (tonal: frontotemporal R > L) and parietotemporal (phonetic: parietotemporal L > R) sinks for targets. A single ERP factor summarized parietal P3 activity, along with an anterior negativity. In contrast, two CSD factors peaking at 360 and 560 ms distinguished a parietal P3 source with an anterior sink from a centroparietal P3 source with a sharply localized Fz sink. A smaller parietal but larger left temporal P3 source was found for silent count compared to button press. Left or right press produced opposite, region-specific asymmetries originating from central sites, modulating the N2/P3 complex. CONCLUSIONS CSD transformation is shown to be a valuable preprocessing step for PCA of ERP data, providing a unique, physiologically meaningful solution to the ubiquitous reference problem. By reducing ERP redundancy and producing sharper, simpler topographies, and without losing or distorting any effects of interest, the CSD-PCA solution replicated and extended previous task- and response-related findings. SIGNIFICANCE Eliminating ambiguities of the recording reference, the combined CSD-PCA approach systematically bridges between montage-dependent scalp potentials and distinct, anatomically-relevant current generators, and shows promise as a comprehensive, generic strategy for ERP analysis.

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.

Striate cortical contribution to the surface-recorded pattern-reversal VEP in the alert monkey.

The striate cortical contribution to the surface pattern-reversal visual evoked potential (VEP) was investigated in awake monkeys during performance of a visual fixation task, by examining laminar profiles of VEP, current source density (CSD) and concomitant multiunit activity (MUA) in Area 17, recorded simultaneously at incremental depths using multicontact electrodes. Stimuli were black/white bar gratings centered on the fixation point. The typical surface pattern-reversal VEP over striate cortex consists of a prominent positivity peaking at 50-70 msec (P60), followed by a large negativity peaking at approx. 80 msec (N80), and then by a late broad positivity, peaking between 120 and 150 msec (P125). P60 is often preceded by a small negativity peaking at 45-55 msec (N50), and on rare occasions a small positivity (P40) is also observed. N50 is generated primarily by current sinks in Lamina 4C. P60 arises from large current sources in the supragranular laminae. N80 and P125 appear to be composite waveforms reflecting complex contributions from local activity and from activity occurring outside of the foveal/immediate parafoveal representation in Area 17. The basic physiologic sequence elicited by patterned stimulation is similar to that elicited by diffuse luminance or by electrical stimulation, but is characterized by more prominent supra- and infragranular activation. It is consistent with the cellular and synaptic anatomy of Area 17: initial activation of the thalamorecipient subdivisions of Lamina 4C, followed by activation of mid/upper Lamina 4 and of supra- and infragranular laminae. Our results suggest the possibility of differentiating synaptic stages and cellular processes reflected in the human VEP, based on homologies with simian VEP components.

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 alpha measures predict therapeutic response to a selective serotonin reuptake inhibitor antidepressant: pre- and post-treatment findings.

BACKGROUND There is growing evidence that individual differences among depressed patients on electrophysiologic (EEG), neuroimaging, and neurocognitive measures are predictive of therapeutic response to antidepressant drugs. This study replicates prior findings of pretreatment differences between selective serotonin reuptake inhibitor (SSRI) responders and nonresponders in EEG alpha power or asymmetry and examines whether these differences normalize or are stable after treatment. METHODS Resting EEG (eyes open and closed) was recorded from 28 electrodes (nose reference) in 18 depressed patients when off medication and at the end of 12 weeks of fluoxetine treatment. Clinical response was assessed by an independent rater with the Clinical Global Impression Improvement scale. The EEG data were also obtained for 18 healthy adults matched to patients in gender and age. RESULTS Treatment responders had greater alpha power compared with nonresponders and healthy control subjects, with largest differences at occipital sites where alpha was largest. There were also differences in alpha asymmetry between responders and nonresponders at occipital sites. Responders showed greater alpha (less activity) over right than left hemisphere, whereas nonresponders tended to show the opposite asymmetry. Neither alpha power nor asymmetry changed after treatment, and test-retest correlations were high, particularly for alpha power. Alpha power and asymmetry showed reasonable positive predictive value but less negative predictive value. CONCLUSIONS The findings confirm reports of alpha differences between antidepressant responders and nonresponders and raise hopes for developing EEG tests for selecting effective treatments for patients. The stability of alpha power and asymmetry differences between SSRI responders and nonresponders after treatment suggests that they represent state-independent characteristics.

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.

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.

Reference-free quantification of EEG spectra: Combining current source density (CSD) and frequency principal components analysis (fPCA)

OBJECTIVE Definition of appropriate frequency bands and choice of recording reference limit the interpretability of quantitative EEG, which may be further compromised by distorted topographies or inverted hemispheric asymmetries when employing conventional (non-linear) power spectra. In contrast, fPCA factors conform to the spectral structure of empirical data, and a surface Laplacian (2-dimensional CSD) simplifies topographies by minimizing volume-conducted activity. Conciseness and interpretability of EEG and CSD fPCA solutions were compared for three common scaling methods. METHODS Resting EEG and CSD (30 channels, nose reference, eyes open/closed) from 51 healthy and 93 clinically-depressed adults were simplified as power, log power, and amplitude spectra, and summarized using unrestricted, Varimax-rotated, covariance-based fPCA. RESULTS Multiple alpha factors were separable from artifact and reproducible across subgroups. Power spectra produced numerous, sharply-defined factors emphasizing low frequencies. Log power spectra produced fewer, broader factors emphasizing high frequencies. Solutions for amplitude spectra showed optimal intermediate tuning, particularly when derived from CSD rather than EEG spectra. These solutions were topographically distinct, detecting multiple posterior alpha generators but excluding the dorsal surface of the frontal lobes. Instead a low alpha/theta factor showed a secondary topography along the frontal midline. CONCLUSIONS CSD amplitude spectrum fPCA solutions provide simpler, reference-independent measures that more directly reflect neuronal activity. SIGNIFICANCE A new quantitative EEG approach affording spectral components is developed that closely parallels the concept of an ERP component in the temporal domain.

Cellular generators of the cortical auditory evoked potential initial component

Cellular generators of the initial cortical auditory evoked potential (AEP) component were determined by analyzing laminar profiles of click-evoked AEPs, current source density, and multiple unit activity (MUA) in primary auditory cortex of awake monkeys. The initial AEP component is a surface-negative wave, N8, that peaks at 8-9 msec and inverts in polarity below lamina 4. N8 is generated by a lamina 4 current sink and a deeper current source. Simultaneous MUA is present from lower lamina 3 to the subjacent white matter. Findings indicate that thalamocortical afferents are a generator of N8 and support a role for lamina 4 stellate cells. Relationships to the human AEP are discussed.

Religiosity and Major Depression in Adults at High Risk: A Ten-Year Prospective Study

OBJECTIVE Previously the authors found that personal importance of religion or spirituality was associated with a lower risk for major depression in a study of adults with and without a history of depression. Here the authors examine the association of personal importance of religion or spirituality with major depression in the adult offspring of the original sample using a 10-year prospective longitudinal design. METHOD Participants were 114 adult offspring of depressed and nondepressed parents, followed longitudinally. The analysis covers the period from the 10-year to the 20-year follow-up assessments. Diagnosis was assessed with the Schedule for Affective Disorders and Schizophrenia-Lifetime Version. Religiosity measures included personal importance of religion or spirituality, frequency of attendance at religious services, and denomination (all participants were Catholic or Protestant). In a logistic regression analysis, major depression at 20 years was used as the outcome measure and the three religiosity variables at 10 years as predictors. RESULTS Offspring who reported at year 10 that religion or spirituality was highly important to them had about one-fourth the risk of experiencing major depression between years 10 and 20 compared with other participants. Religious attendance and denomination did not significantly predict this outcome. The effect was most pronounced among offspring at high risk for depression by virtue of having a depressed parent; in this group, those who reported a high importance of religion or spirituality had about one-tenth the risk of experiencing major depression between years 10 and 20 compared with those who did not. The protective effect was found primarily against recurrence rather than onset of depression. CONCLUSIONS A high self-report rating of the importance of religion or spirituality may have a protective effect against recurrence of depression, particularly in adults with a history of parental depression.