Exploration of baseline and early changes in neurocognitive characteristics as predictors of treatment response to bupropion, sertraline, and placebo in the EMBARC clinical trial.

BACKGROUND: Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner. METHODS: In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16. RESULTS: Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline. CONCLUSION: These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.

Dissociating disorders of depression, anxiety, and their comorbidity with measures of emotional processing: A joint analysis of visual brain potentials and auditory perceptual asymmetries.

In a multigenerational study of families at risk for depression, individuals with a lifetime history of depression had: 1) abnormal perceptual asymmetry (PA; smaller left ear/right hemisphere [RH] advantage) in a dichotic emotion recognition task, and 2) reduced RH late positive potential (P3RH) during an emotional hemifield task. We used standardized difference scores for processing auditory (PA sad-neutral) and visual (P3RH negative-neutral) stimuli for 112 participants (52 men) in a logistic regression to predict history of depression, anxiety or comorbidity of both. Whereas comorbidity was separately predicted by reduced PA (OR = 0.527, p = .042) or P3RH (OR = 0.457, p = .013) alone, an interaction between PA and P3RH (OR = 2.499, p = .011) predicted depressive disorder. Follow-up analyses revealed increased probability of depression at low (lack of emotional differentiation) and high (heightened reactivity to negative stimuli) levels of both predictors. Findings suggest that reduced or heightened right-lateralized emotional responsivity to negative stimuli may be uniquely associated with depression.

Predicting Depression Symptoms in Families at Risk for Depression: Interrelations of Posterior EEG Alpha and Religion/Spirituality.

BACKGROUND: Posterior EEG alpha has been identified as a putative biomarker of clinical outcomes in major depression (MDD). Separately, personal importance of religion and spirituality (R/S) has been shown to provide protective benefits for individuals at high familial risk for MDD. This study directly explored the joint value of posterior alpha and R/S on predicting clinical health outcomes of depression. METHODS: Using a mixed-effects model approach, we obtained virtual estimates of R/S at age 21 using longitudinal data collected at 5 timepoints spanning 25 years. Current source density and frequency principal component analysis was used to quantify posterior alpha in 72-channel resting EEG (eyes open/closed). Depression severity was measured between 5 and 10 years after EEG collection using PHQ-9 and IDAS-GD scales. RESULTS: Greater R/S (p = .008, η2p = 0.076) and higher alpha (p = .02, η2p = 0.056) were separately associated with fewer symptoms across scales. However, an interaction between alpha and R/S (p = .02, η2p = 0.062) was observed, where greater R/S predicted fewer symptoms with low alpha but high alpha predicted fewer symptoms with lower R/S. LIMITATIONS: Small-to-medium effect sizes and homogeneity of sample demographics caution overall interpretation and generalizability. CONCLUSIONS: Findings revealed a complementary role of R/S and alpha in that either variable exerted protective effects only if the other was present at low levels. These findings confirm the relevance of R/S importance and alpha oscillations as predictors of depression symptom severity. More research is needed on the neurobiological mechanism underlying the protective effects of R/S importance for MDD.

Frontal theta and posterior alpha in resting EEG: A critical examination of convergent and discriminant validity.

Prior research has identified two resting EEG biomarkers with potential for predicting functional outcomes in depression: theta current density in frontal brain regions (especially rostral anterior cingulate cortex) and alpha power over posterior scalp regions. As little is known about the discriminant and convergent validity of these putative biomarkers, a thorough evaluation of these psychometric properties was conducted toward the goal of improving clinical utility of these markers. Resting 71-channel EEG recorded from 35 healthy adults at two sessions (1-week retest) were used to systematically compare different quantification techniques for theta and alpha sources at scalp (surface Laplacian or current source density [CSD]) and brain (distributed inverse; exact low resolution electromagnetic tomography [eLORETA]) level. Signal quality was evaluated with signal-to-noise ratio, participant-level spectra, and frequency PCA covariance decomposition. Convergent and discriminant validity were assessed within a multitrait-multimethod framework. Posterior alpha was reliably identified as two spectral components, each with unique spatial patterns and condition effects (eyes open/closed), high signal quality, and good convergent and discriminant validity. In contrast, frontal theta was characterized by one low-variance component, low signal quality, lack of a distinct spectral peak, and mixed validity. Correlations between candidate biomarkers suggest that posterior alpha components constitute reliable, convergent, and discriminant biometrics in healthy adults. Component-based identification of spectral activity (CSD/eLORETA-fPCA) was superior to fixed, a priori frequency bands. Improved quantification and conceptualization of frontal theta is necessary to determine clinical utility.

Behavioral measures of attention and cognitive control during a new auditory working memory paradigm.

Proactive control is the ability to manipulate and maintain goal-relevant information within working memory (WM), allowing individuals to selectively attend to important information while inhibiting irrelevant distractions. Deficits in proactive control may cause multiple cognitive impairments seen in schizophrenia. However, studies of cognitive control have largely relied on visual tasks, even though the functional deficits in schizophrenia are more frequent and severe in the auditory domain (i.e., hallucinations). Hence, we developed an auditory analogue of a visual ignore/suppress paradigm. Healthy adults (N = 40) listened to a series of four letters (600-ms stimulus onset asynchrony) presented alternately to each ear, followed by a 3.2-s maintenance interval and a probe. Participants were directed either to selectively ignore (I) the to-be-presented letters at one ear, to suppress (S) letters already presented to one ear, or to remember (R) all presented letters. The critical cue was provided either before (I) or after (S) the encoding series, or simultaneously with the probe (R). The probes were encoding items presented to either the attended/not suppressed ear ("valid") or the ignored/suppressed ear ("lure"), or were not presented ("control"). Replicating prior findings during visual ignore/suppress tasks, response sensitivity and latency revealed poorer performance for lure than for control trials, particularly during the suppress condition. Shorter suppress than remember latencies suggested a behavioral advantage when discarding encoded items from WM. The paradigm-related internal consistencies and 1-week test-retest reliabilities (n = 38) were good to excellent. Our findings validate these auditory WM tasks as a reliable manipulation of proactive control and set the stage for studies with schizophrenia patients who experience auditory hallucinations.

Anxiety and anhedonia in depression: Associations with neuroticism and cognitive control.

BACKGROUND: Despite the fact that higher levels of anxiety and anhedonia in Major Depressive Disorder (MDD) are linked to poorer treatment outcomes, mechanisms contributing to these clinical presentations remain unclear. Neuroticism, impaired cognitive control, and blunted reward learning may be critical processes involved in MDD and may help to explain symptoms of anxiety and anhedonia. METHODS: Using baseline data from patients with early-onset MDD (N = 296) in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) trial, we conducted a path analysis to model relationships between neuroticism, cognitive control, and reward learning to levels of anxiety and anhedonia. RESULTS: Neuroticism was positively associated with both anhedonia (standardized coefficient = 0.26, p < .001) and anxiety (standardized coefficient = 0.40, p < .001). Cognitive control was negatively associated with anxiety (standardized coefficient = -0.18, p < .05). Reward learning was not significantly associated with either anxiety or anhedonia. LIMITATIONS: Extraneous variables not included in the model may have even more influence in explaining symptoms of anxiety and anhedonia. Restricted range in these variables may have attenuated some of the hypothesized relationships. Most important, because this was a cross-sectional analysis in a currently depressed sample, we cannot draw any causal conclusions without experimental and longitudinal data. CONCLUSIONS: These cross-sectional findings suggest that neuroticism may contribute to anxiety and anhedonia in patients with early onset and either chronic or recurrent MDD, while enhanced cognitive control may protect against anxiety.

Resting EEG Measures of Brain Arousal in a Multisite Study of Major Depression.

Several studies have found upregulated brain arousal during 15-minute EEG recordings at rest in depressed patients. However, studies based on shorter EEG recording intervals are lacking. Here we aimed to compare measures of brain arousal obtained from 2-minute EEGs at rest under eyes-closed condition in depressed patients and healthy controls in a multisite project-Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC). We expected that depressed patients would show stable and elevated brain arousal relative to controls. Eighty-seven depressed patients and 36 healthy controls from four research sites in the United States were included in the analyses. The Vigilance Algorithm Leipzig (VIGALL) was used for the fully automatic classification of EEG-vigilance stages (indicating arousal states) of 1-second EEG segments; VIGALL-derived measures of brain arousal were calculated. We found that depressed patients scored higher on arousal stability ( Z = -2.163, P = .015) and A stages (dominant alpha activity; P = .027) but lower on B1 stages (low-voltage non-alpha activity, P = .008) compared with healthy controls. No significant group differences were observed in Stage B2/3. In summary, we were able to demonstrate stable and elevated brain arousal during brief 2-minute recordings at rest in depressed patients. Results set the stage for examining the value of these measures for predicting clinical response to antidepressants in the entire EMBARC sample and evaluating whether an upregulated brain arousal is particularly characteristic for responders to antidepressants.

Temporal stability of posterior EEG alpha over twelve years.

OBJECTIVE: We previously identified posterior EEG alpha as a potential biomarker for antidepressant treatment response. To meet the definition of a trait biomarker or endophenotype, it should be independent of the course of depression. Accordingly, this report evaluated the temporal stability of posterior EEG alpha at rest. METHODS: Resting EEG was recorded from 70 participants (29 male; 46 adults), during testing sessions separated by 12 ±â€¯1.1 years. EEG alpha was identified, separated and quantified using reference-free methods that combine current source density (CSD) with principal components analysis (PCA). Measures of overall (eyes closed-plus-open) and net (eyes closed-minus-open) posterior alpha amplitude and asymmetry were compared across testing sessions. RESULTS: Overall alpha was stable for the full sample (Spearman-Brown [rSB] = .834, Pearson's r = .718), and showed excellent reliability for adults (rSB = .918; r = 0.848). Net alpha showed acceptable reliability for adults (rSB = .750; r = .600). Hemispheric asymmetries (right-minus-left hemisphere) of posterior overall alpha showed significant correlations, but revealed acceptable reliability only for adults (rSB = .728; r = .573). Findings were highly comparable between 29 male and 41 female participants. CONCLUSIONS: Overall posterior EEG alpha amplitude is reliable over long time intervals in adults. SIGNIFICANCE: The temporal stability of posterior EEG alpha oscillations at rest over long time intervals is indicative of an individual trait.

Right brain, left brain in depressive disorders: Clinical and theoretical implications of behavioral, electrophysiological and neuroimaging findings.

The right and left side of the brain are asymmetric in anatomy and function. We review electrophysiological (EEG and event-related potential), behavioral (dichotic and visual perceptual asymmetry), and neuroimaging (PET, MRI, NIRS) evidence of right-left asymmetry in depressive disorders. Recent electrophysiological and fMRI studies of emotional processing have provided new evidence of altered laterality in depressive disorders. EEG alpha asymmetry and neuroimaging findings at rest and during cognitive or emotional tasks are consistent with reduced left prefrontal activity in depressed patients, which may impair downregulation of amygdala response to negative emotional information. Dichotic listening and visual hemifield findings for non-verbal or emotional processing have revealed abnormal perceptual asymmetry in depressive disorders, and electrophysiological findings have shown reduced right-lateralized responsivity to emotional stimuli in occipitotemporal or parietotemporal cortex. We discuss models of neural networks underlying these alterations. Of clinical relevance, individual differences among depressed patients on measures of right-left brain function are related to diagnostic subtype of depression, comorbidity with anxiety disorders, and clinical response to antidepressants or cognitive behavioral therapy.

Motivated attention and family risk for depression: Neuronal generator patterns at scalp elicited by lateralized aversive pictures reveal blunted emotional responsivity.

Behavioral and electrophysiologic evidence suggests that major depression (MDD) involves right parietotemporal dysfunction, a region activated by arousing affective stimuli. Building on prior event-related potential (ERP) findings (Kayser et al. 2016 NeuroImage 142:337-350), this study examined whether these abnormalities also characterize individuals at clinical high risk for MDD. We systematically explored the impact of family risk status and personal history of depression and anxiety on three distinct stages of emotional processing comprising the late positive potential (LPP). ERPs (72 channels) were recorded from 74 high and 53 low risk individuals (age 13-59 years, 58 male) during a visual half-field paradigm using highly-controlled pictures of cosmetic surgery patients showing disordered (negative) or healed (neutral) facial areas before or after treatment. Reference-free current source density (CSD) transformations of ERP waveforms were quantified by temporal principal components analysis (tPCA). Component scores of prominent CSD-tPCA factors sensitive to emotional content were analyzed via permutation tests and repeated measures ANOVA for mixed factorial designs with unstructured covariance matrix, including gender, age and clinical covariates. Factor-based distributed inverse solutions provided descriptive estimates of emotional brain activations at group level corresponding to hierarchical activations along ventral visual processing stream. Risk status affected emotional responsivity (increased positivity to negative-than-neutral stimuli) overlapping early N2 sink (peak latency 212 ms), P3 source (385 ms), and a late centroparietal source (630 ms). High risk individuals had reduced right-greater-than-left emotional lateralization involving occipitotemporal cortex (N2 sink) and bilaterally reduced emotional effects involving posterior cingulate (P3 source) and inferior temporal cortex (630 ms) when compared to those at low risk. While the early emotional effects were enhanced for left hemifield (right hemisphere) presentations, hemifield modulations did not differ between risk groups, suggesting top-down rather than bottom-up effects of risk. Groups did not differ in their stimulus valence or arousal ratings. Similar effects were seen for individuals with a lifetime history of depression or anxiety disorder in comparison to those without. However, there was no evidence that risk status and history of MDD or anxiety disorder interacted in their impact on emotional responsivity, suggesting largely independent attenuation of attentional resource allocation to enhance perceptual processing of motivationally salient stimuli. These findings further suggest that a deficit in motivated attention preceding conscious awareness may be a marker of risk for depression.

Association of posterior EEG alpha with prioritization of religion or spirituality: A replication and extension at 20-year follow-up.

A prior report (Tenke et al., 2013 Biol. Psychol. 94:426-432) found that participants who rated religion or spirituality (R/S) highly important had greater posterior alpha after 10 years compared to those who did not. Participants who subsequently lowered their rating also had prominent alpha, while those who increased their rating did not. Here we report EEG findings 20 years after initial assessment. Clinical evaluations and R/S ratings were obtained from 73 (52 new) participants in a longitudinal study of family risk for depression. Frequency PCA of current source density transformed EEG concisely quantified posterior alpha. Those who initially rated R/S as highly important had greater alpha compared to those who did not, even if their R/S rating later increased. Furthermore, changes in religious denomination were associated with decreased alpha. Results suggest the possibility of a critical stage in the ontogenesis of R/S that is linked to posterior resting alpha.

A quick behavioral dichotic word test is prognostic for clinical response to cognitive therapy for depression: A replication study.

There are no commonly used clinical indicators of whether an individual will benefit from cognitive therapy (CT) for depression. A prior study found right ear (left hemisphere) advantage for perceiving dichotic words predicted CT response. This study replicates this finding at a different research center in clinical trials that included clinically representative samples and community therapists. Right-handed individuals with unipolar major depressive disorder who subsequently received 12-14 weeks of CT at the University of Pittsburgh were tested on dichotic fused words and complex tones tests. Responders to CT showed twice the mean right ear advantage in dichotic fused words performance than non-responders. Patients with a right ear advantage greater than the mean for healthy controls had an 81% response rate to CT, whereas those with performance lower than the mean for controls had a 46% response rate. Individuals with a right ear advantage, indicative of strong left hemisphere language dominance, may be better at utilizing cognitive processes and left frontotemporal cortical regions critical for success of CT for depression. Findings at two clinical research centers suggest that verbal dichotic listening may be a clinically disseminative brief, inexpensive and easily automated test prognostic for response to CT across diverse clinical settings.

Demonstrating test-retest reliability of electrophysiological measures for healthy adults in a multisite study of biomarkers of antidepressant treatment response.

Growing evidence suggests that loudness dependency of auditory evoked potentials (LDAEP) and resting EEG alpha and theta may be biological markers for predicting response to antidepressants. In spite of this promise, little is known about the joint reliability of these markers, and thus their clinical applicability. New standardized procedures were developed to improve the compatibility of data acquired with different EEG platforms, and used to examine test-retest reliability for the three electrophysiological measures selected for a multisite project-Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC). Thirty-nine healthy controls across four clinical research sites were tested in two sessions separated by about 1 week. Resting EEG (eyes-open and eyes-closed conditions) was recorded and LDAEP measured using binaural tones (1000 Hz, 40 ms) at five intensities (60-100 dB SPL). Principal components analysis of current source density waveforms reduced volume conduction and provided reference-free measures of resting EEG alpha and N1 dipole activity to tones from auditory cortex. Low-resolution electromagnetic tomography (LORETA) extracted resting theta current density measures corresponding to rostral anterior cingulate (rACC), which has been implicated in treatment response. There were no significant differences in posterior alpha, N1 dipole, or rACC theta across sessions. Test-retest reliability was .84 for alpha, .87 for N1 dipole, and .70 for theta rACC current density. The demonstration of good-to-excellent reliability for these measures provides a template for future EEG/ERP studies from multiple testing sites, and an important step for evaluating them as biomarkers for predicting treatment response.

Neuronal generator patterns at scalp elicited by lateralized aversive pictures reveal consecutive stages of motivated attention.

Event-related potential (ERP) studies have provided evidence for an allocation of attentional resources to enhance perceptual processing of motivationally salient stimuli. Emotional modulation affects several consecutive components associated with stages of affective-cognitive processing, beginning as early as 100-200ms after stimulus onset. In agreement with the notion that the right parietotemporal region is critically involved during the perception of arousing affective stimuli, some ERP studies have reported asymmetric emotional ERP effects. However, it is difficult to separate emotional from non-emotional effects because differences in stimulus content unrelated to affective salience or task demands may also be associated with lateralized function or promote cognitive processing. Other concerns pertain to the operational definition and statistical independence of ERP component measures, their dependence on an EEG reference, and spatial smearing due to volume conduction, all of which impede the identification of distinct scalp activation patterns associated with affective processing. Building on prior research using a visual half-field paradigm with highly controlled emotional stimuli (pictures of cosmetic surgery patients showing disordered [negative] or healed [neutral] facial areas before or after treatment), 72-channel ERPs recorded from 152 individuals (ages 13-68years; 81 female) were transformed into reference-free current source density (CSD) waveforms and submitted to temporal principal components analysis (PCA) to identify their underlying neuronal generator patterns. Using both nonparametric randomization tests and repeated measures ANOVA, robust effects of emotional content were found over parietooccipital regions for CSD factors corresponding to N2 sink (212ms peak latency), P3 source (385ms) and a late centroparietal source (630ms), all indicative of greater positivity for negative than neutral stimuli. For the N2 sink, emotional effects were right-lateralized and modulated by hemifield, with larger amplitude and asymmetry for left hemifield (right hemisphere) presentations. For all three factors, more positive amplitudes at parietooccipital sites were associated with increased ratings of negative valence and greater arousal. Distributed inverse solutions of the CSD-PCA-based emotional effects implicated a sequence of maximal activations in right occipitotemporal cortex, bilateral posterior cingulate cortex, and bilateral inferior temporal cortex. These findings are consistent with hierarchical activations of the ventral visual pathway reflecting subsequent processing stages in response to motivationally salient stimuli.

Brain laterality, depression and anxiety disorders: New findings for emotional and verbal dichotic listening in individuals at risk for depression.

Studies using dichotic listening tests and electroencephalographic (EEG) measures of hemispheric asymmetry have reported evidence of abnormal brain laterality in patients having depressive disorders. We present new findings from a multigenerational study of risk for depression, in which perceptual asymmetry was measured in dichotic listening tests of emotional and verbal processing. Biological offspring and grandchildren of probands with a major depressive disorder (MDD) who were at high risk and those of nondepressed controls who were at low risk were tested on dichotic emotional recognition and consonant-vowel syllable tests. In the emotion test, individuals with a lifetime diagnosis of MDD had a smaller right hemisphere advantage than those without a MDD, but there was no difference between high- and low-risk groups or between those with or without an anxiety disorder. In the syllable test, a smaller left hemisphere advantage was found in individuals with an anxiety disorder compared to those without an anxiety disorder, but there was no difference between high- and low-risk groups or between those with or without a MDD. This double dissociation indicates that lifetime diagnosis of MDD and anxiety disorders have a differential impact on lateralized hemispheric processing of emotional and verbal information.

Lateralization for speech predicts therapeutic response to cognitive behavioral therapy for depression.

A prior study (Bruder, G.E., Stewart, J.W., Mercier, M.A., Agosti, V., Leite, P., Donovan, S., Quitkin, F.M., 1997. Outcome of cognitive-behavioral therapy for depression: relation of hemispheric dominance for verbal processing. Journal of Abnormal Psychology 106, 138-144.) found left hemisphere advantage for verbal dichotic listening was predictive of clinical response to cognitive behavioral therapy (CBT) for depression. This study aimed to confirm this finding and to examine the value of neuropsychological tests, which have shown promise for predicting antidepressant response. Twenty depressed patients who subsequently completed 14 weeks of CBT and 74 healthy adults were tested on a Dichotic Fused Words Test (DFWT). Patients were also tested on the National Adult Reading Test to estimate IQ, and word fluency, choice RT, and Stroop neuropsychological tests. Left hemisphere advantage on the DFWT was more than twice as large in CBT responders as in non-responders, and was associated with improvement in depression following treatment. There was no difference between responders and non-responders on neuropsychological tests. The results support the hypothesis that the ability of individuals with strong left hemisphere dominance to recruit frontal and temporal cortical regions involved in verbal dichotic listening predicts CBT response. The large effect size, sensitivity and specificity of DFWT predictions suggest the potential value of this brief and inexpensive test as an indicator of whether a patient will benefit from CBT for depression.

Posterior EEG alpha at rest and during task performance: Comparison of current source density and field potential measures.

Resting and task-related EEG alpha are used in studies of cognition and psychopathology. Although Laplacian methods have been applied, apprehensions about loss of global activity dissuade researchers from greater use except as a supplement to reference-dependent measures. The unfortunate result has been continued reliance on reference strategies that differ across labs, and a systemic preference for a montage-dependent average reference over true reference-free measures. We addressed these concerns by comparing resting- and task-related EEG alpha using three EEG transformations: nose- (NR) and average-referenced (AR) EEG, and the corresponding CSD. Amplitude spectra of resting and prestimulus task-related EEG (novelty oddball) and event-related spectral perturbations were scaled to equate each transformation. Alpha measures quantified for 8-12 Hz bands were: 1) net amplitude (eyes-closed minus eyes-open) and 2) overall amplitude (eyes-closed plus eyes-open); 3) task amplitude (prestimulus baseline) and 4) task event-related desynchronization (ERD). Mean topographies unambiguously represented posterior alpha for overall, net and task, as well as poststimulus alpha ERD. Topographies were similar for the three transformations, but differed in dispersion, CSD being sharpest and NR most broadly distributed. Transformations also differed in scale, AR showing less attenuation or spurious secondary maxima at anterior sites, consistent with simulations of distributed posterior generators. Posterior task alpha and alpha ERD were positively correlated with overall alpha, but not with net alpha. CSD topographies consistently and appropriately represented posterior EEG alpha for all measures.

Neurocognitive predictors of antidepressant clinical response.

BACKGROUND: Executive dysfunction and psychomotor slowing in depressed patients have been associated with poor antidepressant clinical response, but little is known about the value of neurocognitive tests for differential prediction of response. METHODS: This report presents new findings for 70 depressed patients tested on neurocogntive tests before receiving treatment with a SSRI (escitalopram or citalopram), NDRI (bupropion) or dual mechanism therapy including a serotonergic agent, and for 57 healthy controls. RESULTS: As predicted from previous research, patients who did not respond to a SSRI or dual therapy showed poorer word fluency than responders, whereas this was not seen for patients treated with bupropion alone. Longer choice reaction time (RT) was also found in nonresponders to a SSRI or dual therapy, but the opposite trend was seen for bupropion. Using a combined index of word fluency and RT (with normative performance as a cutoff) yielded differential predictions of response. Equal to or above normal performance predicted good response to a SSRI or dual therapy, with high positive predictive value (90%) and specificity (78%) but lower sensitivity (53%). In contrast, less than normal performance predicted good response to bupropion alone (positive predictive value=82%; specificity=67%; sensitivity=90%). LIMITATIONS: Relatively small sample size, no placebo control, and combining across SSRI alone and dual treatments. CONCLUSIONS: Although findings are preliminary due to small sample size, brief tests of word fluency and psychomotor speed may help identify depressed patients who are unresponsive to a serotonergic agent, but who may respond to bupropion alone.

Identifying electrode bridging from electrical distance distributions: a survey of publicly-available EEG data using a new method.

OBJECTIVE: EEG topographies may be distorted by electrode bridges, typically caused by electrolyte spreading between adjacent electrodes. We therefore sought to determine the prevalence of electrode bridging and its potential impact on the EEG literature. METHODS: Five publicly-available EEG datasets were evaluated for evidence of bridging using a new screening method that employs the temporal variance of pairwise difference waveforms (electrical distance). Distinctive characteristics of electrical distance frequency distributions were used to develop an algorithm to identify electrode bridges in datasets with different montages (22-64 channels) and noise properties. RESULTS: The extent of bridging varied substantially across datasets: 54% of EEG recording sessions contained an electrode bridge, and the mean percentage of bridged electrodes in a montage was as high as 18% in one of the datasets. Furthermore, over 40% of the recording channels were bridged in 9 of 203 sessions. These findings were independently validated by visual inspection. CONCLUSIONS: The new algorithm conveniently, efficiently, and reliably identified electrode bridges across different datasets and recording conditions. Electrode bridging may constitute a substantial problem for some datasets. SIGNIFICANCE: Given the extent of the electrode bridging across datasets, this problem may be more widespread than commonly thought. However, when used as an automatic screening routine, the new algorithm will prevent pitfalls stemming from unrecognized electrode bridges.