Jürgen Kayser

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.

Is Resting Anterior EEG Alpha Asymmetry a Trait Marker for Depression

Several lines of evidence suggest that asymmetric anterior brain activation is related to affective style, linking left hemisphere activation to positive affect and right hemisphere activation to negative affect. However, previous reports of left frontal hypoactivation in depressed patients were not confirmed in recent studies. This study evaluated additional characteristics of resting EEG alpha (8–13 Hz) asymmetry in 15 clinically depressed patients and 22 healthy adults by recording EEG activity on two separate occasions, 2–4 weeks apart. Across both sessions, group differences in anterior EEG asymmetry were compatible with the original hypothesis. However, groups differed in temporal stability of anterior EEG asymmetry, which was retest reliable in controls but not depressed patients. In contrast, temporal stability of posterior EEG asymmetry was acceptable in both groups. Increased variability of anterior EEG asymmetry may be a characteristic feature for depression, and, if so, this would challenge the notion that anterior EEG alpha asymmetry is a trait marker for depression.

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.

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.

Current Source Density Measures of Electroencephalographic Alpha Predict Antidepressant Treatment Response

BACKGROUND Despite recent success in pharmacologic treatment of depression, the inability to predict individual treatment response remains a liability. This study replicates and extends findings relating pretreatment electroencephalographic (EEG) alpha to treatment outcomes for serotonergic medications. METHODS Resting EEG (eyes-open and eyes-closed) was recorded from a 67-electrode montage in 41 unmedicated depressed patients and 41 healthy control subjects. Patients were tested before receiving antidepressants including a serotonergic mode of action (selective serotonin reuptake inhibitor [SSRI], serotonin and norepinephrine reuptake inhibitor, or SSRI plus norepinephrine and dopamine reuptake inhibitor). EEG was quantified by frequency principal components analysis of spectra derived from reference-free current source density (CSD) waveforms, which sharpens and simplifies EEG topographies, disentangles them from artifact, and yields measures that more closely represent underlying neuronal current generators. RESULTS Patients who did not respond to treatment had significantly less alpha CSD compared with responders or healthy control subjects, localizable to well-defined posterior generators. The alpha difference between responders and nonresponders was greater for eyes-closed than eyes-open conditions and was present across alpha subbands. A classification criterion based on the median alpha for healthy control subjects showed good positive predictive value (93.3) and specificity (92.3). There was no evidence of differential value for predicting response to an SSRI alone or dual treatment targeting serotonergic plus other monoamine neurotransmitters. CONCLUSIONS Findings confirm the value of EEG alpha amplitude as a viable predictor of antidepressant response and suggest that personalized treatments for depression may be identified using simple electrophysiologic CSD measures.

Issues and considerations for using the scalp surface Laplacian in EEG/ERP research: A tutorial review

Despite the recognition that the surface Laplacian may counteract adverse effects of volume conduction and recording reference for surface potential data, electrophysiology as a discipline has been reluctant to embrace this approach for data analysis. The reasons for such hesitation are manifold but often involve unfamiliarity with the nature of the underlying transformation, as well as intimidation by a perceived mathematical complexity, and concerns of signal loss, dense electrode array requirements, or susceptibility to noise. We revisit the pitfalls arising from volume conduction and the mandated arbitrary choice of EEG reference, describe the basic principle of the surface Laplacian transform in an intuitive fashion, and exemplify the differences between common reference schemes (nose, linked mastoids, average) and the surface Laplacian for frequently-measured EEG spectra (theta, alpha) and standard event-related potential (ERP) components, such as N1 or P3. We specifically review common reservations against the universal use of the surface Laplacian, which can be effectively addressed by employing spherical spline interpolations with an appropriate selection of the spline flexibility parameter and regularization constant. We argue from a pragmatic perspective that not only are these reservations unfounded but that the continued predominant use of surface potentials poses a considerable impediment on the progress of EEG and ERP research.

On the Reliability of Augmenting/Reducing

Abstract To investigate the impact of several methodological variations in the assessment of augmenting/reducing, auditory evoked potentials to 1000 Hz tones with varying stimulus intensity (59, 71...

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.

Cognitive ERPs in Depressive and Anxiety Disorders during Tonal and Phonetic Oddball Tasks

This report compares event-related brain potentials (ERPs) of patients having a depressive disorder alone (n=58), an anxiety disorder alone (n=22), comorbidity of these disorders (n=18), and healthy controls (n=49). ERPs were recorded from 30 electrode sites during auditory oddball tasks using consonant-vowel syllables (phonetic) or complex tones (tonal). Overlapping ERP components were identified and measured using covariance-based principal components analysis. An early P3 subcomponent (P315) was larger in patients having an anxiety disorder alone when compared to depressed patients with or without an anxiety disorder and healthy controls, whereas a late P3 subcomponent (P400) was larger in patients having comorbidity of anxiety and depressive disorders than in the other groups. Also, the N2-P3 complex showed task-dependent hemispheric asymmetries, including larger N2-P3 amplitude over left than right temporoparietal sites during the phonetic oddball task. This hemispheric asymmetry was greatest in patients having a depressive disorder alone and smallest in patients having an anxiety disorder alone. The opposite nature of the alterations of hemispheric asymmetry and early P3 amplitude in depressive and anxiety disorders underscores the importance of taking comorbidity with anxiety into account in studies of cognitive ERPs in depressive disorders.

In search of the Rosetta Stone for scalp EEG: Converging on reference-free techniques

Almost a hundred years have passed since Hans Berger’s historic discovery that electrical brain waves can be recorded from the human scalp (Berger, 1929). Since that time, the electroencephalogram (EEG) has been recognized as a real-time, noninvasive measure of both tonic (e.g., at rest or during sleep) and phasic neuronal activity (e.g., as evoked responses to physical or cognitive events). Many approaches have been developed to identify, separate, quantify, and compare the temporal and spectral properties of the EEG, as evidenced in the pages of this journal over the past 60 years. The EEG remains a valuable and cost-effective tool for a wide range of clinical and basic research purposes, regardless of the recent numerous developments of complementary neuroimaging measures. In addition to an unparalleled temporal resolution, important technological advances, such as dense electrode arrays with over a hundred channels that allow an evenly-spaced scalp coverage, offer dramatically increased topographic capacities in a recording montage with improved data quality and reduced preparation time, owing to high impedance amplifiers and miniature preamplifiers located inside the scalp sensor. However, despite the impressive advances and continued promise of these methods, we still lack an universal key to decipher the functional meaning of the scalp-recorded EEG. One well-known problem in particular arises again and again, and often in forms that may be unrecognized at first: because an EEG signal must be quantified as a potential difference between any two sites, thereby yielding relative rather than absolute measures, the properties of the reference, whether determined by its physical location or its computational characteristics, will have a fundamental impact on the signal of interest. For example, if two sites are equipotential, no EEG activity is observed between them, no matter what the absolute potential may be. Another implication is that the information provided by a difference measure is unaffected by its direction, apart from its arbitrary sign (i.e., the selection of one of a pair as reference is inherently arbitrary).