Emotion recognition deficits as predictors of transition in individuals at clinical high risk for schizophrenia: a neurodevelopmental perspective.

BACKGROUND: Schizophrenia is characterized by profound and disabling deficits in the ability to recognize emotion in facial expression and tone of voice. Although these deficits are well documented in established schizophrenia using recently validated tasks, their predictive utility in at-risk populations has not been formally evaluated. METHOD: The Penn Emotion Recognition and Discrimination tasks, and recently developed measures of auditory emotion recognition, were administered to 49 clinical high-risk subjects prospectively followed for 2 years for schizophrenia outcome, and 31 healthy controls, and a developmental cohort of 43 individuals aged 7-26 years. Deficit in emotion recognition in at-risk subjects was compared with deficit in established schizophrenia, and with normal neurocognitive growth curves from childhood to early adulthood. RESULTS: Deficits in emotion recognition significantly distinguished at-risk patients who transitioned to schizophrenia. By contrast, more general neurocognitive measures, such as attention vigilance or processing speed, were non-predictive. The best classification model for schizophrenia onset included both face emotion processing and negative symptoms, with accuracy of 96%, and area under the receiver-operating characteristic curve of 0.99. In a parallel developmental study, emotion recognition abilities were found to reach maturity prior to traditional age of risk for schizophrenia, suggesting they may serve as objective markers of early developmental insult. CONCLUSIONS: Profound deficits in emotion recognition exist in at-risk patients prior to schizophrenia onset. They may serve as an index of early developmental insult, and represent an effective target for early identification and remediation. Future studies investigating emotion recognition deficits at both mechanistic and predictive levels are strongly encouraged.

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.

Perceptual asymmetries in schizophrenia: subtype differences in left hemisphere dominance for dichotic fused words.

OBJECTIVE: Dichotic listening techniques have been used to study hemispheric dominance for language in schizophrenia. The authors' goal was to compare subjects with paranoid and undifferentiated subtypes of schizophrenia. METHOD: The Fused Rhymed Words Test was used to compare perceptual asymmetries in 16 patients with paranoid schizophrenia, 28 patients with undifferentiated schizophrenia, and 29 healthy comparison subjects. RESULTS: Patients with paranoid schizophrenia had the largest left hemisphere advantage and patients with undifferentiated schizophrenia had the smallest. The asymmetry of healthy subjects was intermediate. Hemisphere advantage varied as a function of gender only in the patients with undifferentiated schizophrenia. CONCLUSIONS: The findings support the hypotheses that undifferentiated schizophrenia is associated with underactivation of left hemisphere resources for verbal processing and that paranoid schizophrenia is characterized by preserved left hemisphere processing.

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.

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.

Cerebral laterality in adolescent major depression.

This study tests the hypothesis that adolescents with major depression exhibit abnormalities in cerebral asymmetry previously found among adults. Perceptual asymmetry was assessed through tests of verbal and non-verbal dichotic listening in four groups - 48 adolescents with major depression, 22 adolescent comparisons with no history of Axis I disorders, 149 adults with major depression, and 57 comparison adults with no history of Axis I disorders. Data from adults have been previously reported. In both age groups, subjects with major depression were further divided based on the presence or absence of an anxiety disorder. Procedures used to collect perceptual asymmetry data in adolescents and adults were identical. In both age groups, depressed and healthy subjects showed perceptual asymmetry in expected directions for verbal and non-verbal dichotic tasks. Depressed and comparison subjects differed in performance on the Fused-Word Test, though these differences varied as a function of anxiety and developmental level. Relative to comparisons, both adolescents and adults with major depression exhibited an increased right ear/left hemisphere advantage for fused words. Adults but not adolescents with comorbid major depressive and anxiety disorders exhibited a reduced right ear/left hemisphere advantage for fused words. These findings suggest similarities and differences across development in the relationship between cerebral laterality and psychopathology. Further studies using longitudinal and family-based designs, as well as various measures of regional brain activity, are needed to enhance understanding of associations between cerebral laterality and psychopathology across development.

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.

Do tricyclic responders have different brain laterality?

A previous study showed that depressed patients who improved with tricyclic antidepressant medication had dichotic complex tones test results suggesting right-hemisphere dysfunction relative to nonresponders and controls (G. E. Bruder et al., 1990). A new sample of 68 depressed patients completed dichotic consonant-vowel (CV) and complex tones (CT) tests and then were treated with imipramine or placebo. A significant Ear x Test x Treatment x Response interaction was accounted for by significantly poorer left-ear accuracy for CVs among imipramine responders compared with nonresponders, placebo responders, and controls. CV left-ear accuracy was also significantly greater among placebo responders than placebo nonresponders and controls. The results only partially replicate the prior study in that evidence of right-hemisphere dysfunction in tricyclic responders was seen for the CV test but not the CT test.

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.

Dichotic listening deficits and the prediction of substance use in young boys.

OBJECTIVE: Prior studies note relationships among verbal deficits, disruptive psychopathology, and substance use. The current study examines the relationship between verbal deficits, assessed through a dichotic listening test, and children's substance use. METHOD: A series of 87 young boys was prospectively followed over a 1- to 2-year period. A prior study in these boys noted a cross-sectional relationship between disruptive psychopathology and deficits on a dichotic consonant-vowel listening test. The current study examines the predictive relationship between this language-related deficit at one study wave and substance use assessed during a follow-up study wave. RESULTS: Reduced right ear accuracy, reflecting a deficit in left hemisphere processing ability, predicted substance use at follow-up. This association was independent of any other predictors, including cognitive or behavioral indices of substance use risk. CONCLUSIONS: A lateralized deficit in verbal processing on a dichotic listening task predicts change in substance use by follow-up. Findings are consistent with other evidence linking early childhood lateralization abnormalities to development of disruptive psychopathology.

Perceptual asymmetry differences between major depression with or without a comorbid anxiety disorder: a dichotic listening study.

Predictions that anxious and nonanxious depression would differ in perceptual asymmetry (PA), as well as in sensitivity for perceiving emotional words, were evaluated using dichotic listening tasks. A total of 149 patients having a major depressive disorder (51 with and 98 without an anxiety disorder) and 57 healthy controls were tested on fused-word and complex tone tasks. The anxious and nonanxious depression groups showed a consistent difference in PA across tasks; that is, the anxious group had a larger left-ear advantage for tones and a smaller right-ear advantage for words when compared with the nonanxious group. There was no group difference in sensitivity for perceiving emotional words. Patients having an anxious depression appear to have a greater propensity to activate right than left-hemisphere regions during auditory tasks, whereas those having a nonanxious depression have the opposite hemispheric asymmetry.

Monorhinal odor identification and depression scores in patients with seasonal affective disorder.

BACKGROUND: Visual and olfactory pathways are interconnected. Olfactory deafferentation unmasks photoperiodic responsiveness in some nonphotoperiodic animals such as laboratory rats. By analogy, we hypothesized that olfactory deficits may unmask seasonal rhythms in certain individuals, namely those with seasonal affective disorder (SAD). Since previous studies suggest lateralized hemispheric dysfunction in SAD, and since olfactory neurons' primary projections are largely ipsilateral, we assessed olfactory identification performance on both the right and left side of the nose. METHODS: Twenty-four patients with SAD and 24 matched controls were studied using a phenyl ethyl alcohol detection threshold test bilaterally and the University of Pennsylvania Smell Identification Test unilaterally. Subjects rated their mood using the Self Assessment Mood Scale for SAD. Patients' testing was done in both 'depressed' and 'improved on light' states. RESULTS: No difference in olfactory performance was found between patients and controls or between patients before and after light treatment. However, right-side identification scores were negatively correlated with 'typical' depression scores (r = -0.56, P = 0.006), while left-side olfactory scores were not. Atypical depression scores were unrelated to olfactory performance. Similar correlations emerged between the olfactory identification laterality quotient (Right - Left)/(Right + Left) and typical depressive scores (r = - 0.64, P < 0.001) and total depression scores (r = - 0.59, P < 0.004). LIMITATIONS: We studied a demographically heterogeneous sample and did not control for menstrual factors. DISCUSSION: Our results add to previous evidence of lateralized hemispheric involvement in SAD and suggest that olfaction may be related to seasonal emotional rhythms in humans.

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.