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

ABSTRACT

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.     

Perceptive and affective impairments in emotive eye-region processing in alexithymia

Alexithymia is characterized by impairments in emotion processing, frequently linked to facial expressions of emotion. The eye-region conveys information necessary for emotion processing. It has been demonstrated that alexithymia is associated with reduced attention to the eyes, but little is known regarding the cognitive and electrophysiological mechanisms underlying emotive eye-region processing in alexithymia. Here, we recorded behavioral and electrophysiological responses of individuals with alexithymia (ALEX; n = 25) and individuals without alexithymia (NonALEX; n = 23) while they viewed intact and eyeless faces with angry and sad expressions during a dual-target rapid serial visual presentation task. Results showed different eye-region focuses and differentiating N1 responses between intact and eyeless faces to anger and sadness in NonALEX, but not in ALEX, suggesting deficient perceptual processing of the eye-region in alexithymia. Reduced eye-region focus and smaller differences in frontal alpha asymmetry in response to sadness between intact and eyeless faces were observed in ALEX than NonALEX, indicative of impaired affective processing of the eye-region in alexithymia. These findings highlight perceptual and affective abnormalities of emotive eye-region processing in alexithymia. Our results contribute to understanding the neuropsychopathology of alexithymia and alexithymia-related disorders.     

Abnormal functional brain asymmetry in depression: evidence of biologic commonality between major depression and dysthymia

Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having "pure" dysthymia show the same abnormality of perceptual asymmetry as MDD. It also examined gender differences in lateralization, and the extent to which abnormalities of perceptual asymmetry in depressed patients are dependent on gender. Unmedicated patients having either a MDD (n=96) or "pure" dysthymic disorder (n=42) and healthy controls (n=114) were tested on dichotic fused-words and complex-tone tests. Patient and control groups differed in right hemisphere advantage for complex tones, but not left hemisphere advantage for words. Reduced right hemisphere advantage for tones was equally present in MDD and dysthymia, but was more evident among depressed men than depressed women. Also, healthy men had greater hemispheric asymmetry than healthy women for both words and tones, whereas this gender difference was not seen for depressed patients. Dysthymia and MDD share a common abnormality of hemispheric asymmetry for dichotic listening.     

Regional patterns of brain activity in adults with a history of childhood-onset depression: gender differences and clinical variability

OBJECTIVE: The study investigated the hypothesis that EEG asymmetry scores (indicating higher right and lower left frontal brain activity) are associated with vulnerability to negative mood states and depressive disorders. Gender and clinical history variables were examined as factors that may influence the relation between EEG and depression. METHOD: EEG measures of asymmetrical alpha frequency (7.5-12.5 Hz) suppression were analyzed in 55 young adults with a documented clinical history of childhood-onset depression and 55 comparison subjects with no history of major psychopathology. EEG patterns were examined in relation to operational diagnoses of mental disorders during childhood and adulthood. RESULTS: Differences in EEG asymmetry between childhood depression probands and comparison subjects varied with gender, diagnostic history, and current symptoms. Women with childhood depression had higher right midfrontal alpha suppression, and men with childhood depression had higher left midfrontal alpha suppression, relative to comparison subjects. At all scalp sites, women showed greater alpha power than men. Probands with a bipolar spectrum course had the most extreme midfrontal asymmetry. Frontal asymmetry was more extreme in probands with current depressive symptoms than in those without current symptoms. CONCLUSIONS: Regional brain activity is influenced by gender and variability in clinical course. The findings have implications for investigating brain correlates of mood disorder and may help to develop more refined phenotypes.     

Resting and reactive frontal brain electrical activity (EEG) among a non-clinical sample of socially anxious adults: Does concurrent depressive mood matter?

A number of studies have noted that the pattern of resting frontal brain electrical activity (EEG) is related to individual differences in affective style in healthy infants, children, and adults and some clinical populations when symptoms are reduced or in remission. We measured self-reported trait shyness and sociability, concurrent depressive mood, and frontal brain electrical activity (EEG) at rest and in anticipation of a speech task in a non-clinical sample of healthy young adults selected for high and low social anxiety. Although the patterns of resting and reactive frontal EEG asymmetry did not distinguish among individual differences in social anxiety, the pattern of resting frontal EEG asymmetry was related to trait shyness after controlling for concurrent depressive mood. Individuals who reported a higher degree of shyness were likely to exhibit greater relative right frontal EEG activity at rest. However, trait shyness was not related to frontal EEG asymmetry measured during the speech-preparation task, even after controlling for concurrent depressive mood. These findings replicate and extend prior work on resting frontal EEG asymmetry and individual differences in affective style in adults. Findings also highlight the importance of considering concurrent emotional states of participants when examining psychophysiological correlates of personality.     

Finding a way in: A review and practical evaluation of fMRI and EEG for detection and assessment in disorders of consciousness

Diagnoses and assessments of cognitive function in disorders of consciousness (DOC) are notoriously prone to error due to their reliance on behavioural measures. As a result, researchers have turned to functional neuroimaging and electrophysiological techniques with the goal of developing more effective methods of detecting awareness and assessing cognition in these patients. This article reviews functional magnetic resonance imaging (fMRI) and electroenchphalography (EEG)-based studies of cognition and consciousness in DOC, including assessment of basic sensory, perceptual, language, and emotional processing; studies for detection of conscious awareness; paradigms for the establishment of communication in the absence of behaviour; and functional connectivity studies. The advantages and limitations of fMRI and EEG-based measures are examined as research and clinical tools in this population and an explanation offered for the rediscovery of the unique advantages of EEG in the study of DOC.     

Abnormal cerebral laterality in bipolar depression: convergence of behavioral and brain event-related potential findings.

Cerebral laterality in bipolar and unipolar major depression was compared using visual half-field and dichotic listening measures of perceptual asymmetry. The results replicate our prior finding of abnormal laterality in bipolar depressed patients on a visuospatial test. Bipolar patients (n = 11) failed to show the left visual field (right hemisphere) advantage for dot enumeration seen for both unipolar patients (n = 43) and normal controls (n = 24). Bipolar patients performed significantly poorer than unipolar patients on normal controls for left visual field, but not right visual field stimuli. An electrophysiological correlate of abnormal visual field asymmetry in bipolar depression was found in brain event-related potentials recorded during audiospatial and temporal discrimination tasks. Bipolar patients had smaller N100 amplitudes for test stimuli in the left than right hemifield, whereas unipolar patients and normals did not. The origins of left hemifield deficits in bipolar depression are discussed in terms of right-sided dysfunction of an arousal/attentional system involving temporoparietal and possibly frontal regions.     

Grandchildren at high and low risk for depression differ in EEG measures of regional brain asymmetry.

BACKGROUND: Electrophysiologic studies have found abnormalities of alpha asymmetry in depressed adults and offspring of depressed parents, which have been hypothesized to be vulnerability markers of depression. Resting electroencephalogram (EEG) was measured in grandchildren participating in a multigenerational high-risk study. METHODS: Electroencephalogram from 12 electrodes at six homologous sites over each hemisphere (digitally linked-ears reference) was compared in right-handed grandchildren in three groups: 1) both parent and grandparent having major depressive disorder (MDD; n = 19); 2) either parent or grandparent having MDD (n = 14); and 3) neither having MDD (n = 16). RESULTS: Grandchildren with both depressed parent and grandparent showed greater alpha asymmetry, with relatively less right than left hemisphere activity, when compared with those with neither depressed parent nor grandparent. This difference was present over the parietal region in the eyes-closed condition. Grandchildren having either depressed parent or grandparent also tended to show heightened alpha asymmetry at parietal sites, but they did not differ significantly from those with neither depressed parent nor grandparent. Low-risk grandchildren with neither depressed parent nor grandparent showed no significant alpha asymmetry. CONCLUSIONS: High-risk grandchildren displayed a parietal alpha asymmetry similar to that seen in adolescents or adults having a MDD and in second-generation offspring of parents concordant for MDD. Its presence in high-risk offspring and grandchildren without a lifetime history of MDD supports the hypothesis that an alpha asymmetry indicative of relatively less right than left parietal activity is an endophenotypic marker of vulnerability to a familial form of major depression.     

Neuronal dynamics enable the functional differentiation of resting state networks in the human brain

Intrinsic brain activity is organized in spatial–temporal patterns, called resting‐state networks (RSNs), exhibiting specific structural–functional architecture. These networks presumably reflect complex neurophysiological processes and have a central role in distinct perceptual and cognitive functions. In this work, we propose an innovative approach for characterizing RSNs according to their underlying neural oscillations. We investigated specific electrophysiological properties, including spectral features, fractal dimension, and entropy, associated with eight core RSNs derived from high‐density electroencephalography (EEG) source‐reconstructed signals. Specifically, we found higher synchronization of the gamma‐band activity and higher fractal dimension values in perceptual (PNs) compared with higher cognitive (HCNs) networks. The inspection of this underlying rapid activity becomes of utmost importance for assessing possible alterations related to specific brain disorders. The disruption of the coordinated activity of RSNs may result in altered behavioral and perceptual states. Thus, this approach could potentially be used for the early detection and treatment of neurological disorders.     

Beyond frontal alpha: investigating hemispheric asymmetries over the EEG frequency spectrum as a function of sex and handedness

Frontal alpha EEG asymmetry, an indirect marker of asymmetries in relative frontal brain activity, are widely used in research on lateralization of emotional processing. While most authors focus on frontal electrode pairs (e.g., F3/F4 or F7/F8), several recent studies have indicated that EEG asymmetries can also be observed outside the frontal lobe and in frequency bands other than alpha. Because the focus of most EEG asymmetry research is on the correlations between asymmetry and other traits, much less is known about the distribution of patterns of asymmetry at the population level. To systematically assess these asymmetries in a representative sample, we determined EEG asymmetries across the head in the alpha, beta, delta and theta frequency bands in 235 healthy adults. We found significant asymmetries in all four frequency bands and across several brain areas, indicating that EEG asymmetries are not limited to frontal alpha. Asymmetries were not modulated by sex. They were modulated by direction of hand preference, with stronger right-handedness predicting greater right (relative to left) alpha power, or greater left (relative to right) activity. Taken together, the present results show that EEG asymmetries other than frontal alpha represent markers of asymmetric brain function that should be explored further.     

Electroencephalographic measures of regional hemispheric activity in offspring at risk for depressive disorders.

BACKGROUND: Electroencephalographic (EEG) studies have found abnormal regional hemispheric asymmetries in depressive disorders, which have been hypothesized to be vulnerability markers for depression. In a longitudinal high-risk study, resting EEG was measured in primarily adult offspring of depressed or nondepressed probands. METHODS: Electroencephalograms from12 homologous sites over each hemisphere (digitally linked-ears reference) were analyzed in right-handed offspring for whom both parents (n = 18), one parent (n = 40), or neither parent (n = 29) had a major depressive disorder (MDD). RESULTS: Offspring with both parents having MDD showed greater alpha asymmetry at medial sites, with relatively less activity (more alpha) over right central and parietal regions, compared with offspring having one or no parent with MDD. Relatively less left frontal activity at lateral sites was associated with lifetime MDD in offspring but not with parental MDD. Offspring with both parents having a MDD also showed markedly greater anterior-to- posterior increase in alpha with eyes closed compared with those with one or no parent with a MDD. CONCLUSIONS: Alpha asymmetry indicative of right parietotemporal hypoactivity, previously reported for depressed adolescents and adults, and heightened anterior-to-posterior gradient of alpha are present in high-risk offspring having parents concordant for MDD.     

Emotion effects on attention, amygdala activation, and functional connectivity in schizophrenia

Emotional abnormalities are a critical clinical feature of schizophrenia (SCZ), but complete understanding of their underlying neuropathology is lacking. Numerous studies have examined amygdala activation in response to affective stimuli in SCZ, but no consensus has emerged. However, behavioral studies examining 'in-the-moment' processing of affect have suggested intact emotional processing in SCZ. To examine which aspects of emotional processing may be impaired in SCZ, we combined behavior and neuroimaging to investigate effects of aversive stimuli during minimal cognitive engagement, at the level of behavior, amygdala recruitment, and its whole-brain task-based functional connectivity (tb-fcMRI) because impairments may manifest when examining across-region functional integration. Twenty-eight patients and 24 matched controls underwent rapid event-related fMRI at 3 T while performing a simple perceptual decision task with negative or neutral distraction. We examined perceptual decision slowing, amygdala activation, and whole-brain amygdala tb-fcMRI, while ensuring group signal-to-noise profile matching. Following scanning, subjects rated all images for experienced arousal and valence. No significant group differences emerged for negative vs neutral reaction time, emotional ratings across groups, or amygdala activation. However, even in the absence of behavioral or activation differences, SCZ subjects demonstrated significantly weaker amygdala-prefrontal cortical coupling, specifically during negative distraction. Whereas in-the-moment perception, behavioral response, and amygdala recruitment to negative stimuli during minimal cognitive load seem to be intact, there is evidence of aberrant amygdala-prefrontal integration in SCZ subjects. Such abnormalities may prove critical for understanding disturbances in patients' ability to use affective cues when guiding higher level cognitive processes needed in social interactions.     

Relationship of resting EEG with anatomical MRI measures in individuals at high and low risk for depression

Studies have found abnormalities of resting EEG measures of hemispheric activity in depressive disorders. Similar EEG findings and a prominent thinning of the cortical mantle have been reported for persons at risk for depression. The correspondence between EEG alpha power and magnetic resonance imaging (MRI) measures of cortical thickness was examined in a multigenerational study of individuals at risk for depression. Seventy-five participants underwent resting EEG and approximately 5 years later underwent MRI scanning. High-risk participants (n = 37) were biological descendants of probands having major depression and low-risk participants (n = 38) were descendants of individuals without a history of depression. EEG alpha power was interpolated across the surface of a template brain and coregistered with measures of cortical thickness. Voxel-wise correlations of cortical thickness and alpha power were computed while covarying for age and gender. The high-risk group, when compared to the low-risk group, showed greater alpha asymmetry in an eyes-closed condition, with relatively less activity over right parietal cortex. Alpha power correlated inversely with cortical thickness, particularly over the right posterior region, indicating that EEG evidence of reduced cortical activity was associated with increased cortical thinning. This is the first report of widespread correlation of EEG alpha activity with MRI measures of cortical thickness. Although both EEG and MRI measures are associated with risk for depression, we did not detect evidence that cortical thickness mediated the alpha asymmetry findings. Thus, alpha asymmetry, alone or in combination with MRI, may be a marker of vulnerability for a familial form of depression.     

Visual function in infants with West syndrome: correlation with EEG patterns

PURPOSE: Several studies have reported behavioral and electrophysiological evidence of visual impairment during the active stage of West syndrome. The underlying mechanisms are, however, poorly understood, and little has been reported about the correlation between visual impairment, EEG patterns, and brain lesions. The aim of the study was to assess visual function at the onset of spasm and 2 months thereafter and relate visual findings to brain lesions and EEG features. METHODS: Twenty-five infants with West syndrome were enrolled and studied with (a) a full clinical assessment including a battery of tests specifically designed to assess visual function, (b) a video-polygraphic study, and (c) brain magnetic resonance imaging (MRI). Besides brain neuroimaging and EEG comparison with visual function, an intra-EEG analysis was performed to investigate the possible relation of EEG patterns to fluctuating visual behavior (fixation and following). RESULTS: Twenty-two children had at least one abnormal result on one or more of the tests assessing visual function at T0. Visual impairment at the spasm onset was related to the sleep disorganization rather than to the hypsarrhythmic pattern in awake EEG. After 2 months, both EEG features become significantly linked to visual function. Visual function improved in several cases after 2 months, in parallel with the seizure regression. No relation was found between EEG patterns and fluctuating visual behavior. CONCLUSIONS: The study supplies new evidence of the involvement of visual function in West syndrome. The presence of abnormal visual findings in infants without lesions on brain MRI suggests that visual abnormalities are due not only to brain injury but also to epileptic disorder per se. New insight is also provided into the possible mechanisms underlying clinical and EEG abnormalities.     

L’analyse des visages dans la dépression

Depression is a mood disorder associated with impairments in the processing of social and emotional messages. This article presents a review of the literature of behavioral, clinical, pharmacological, and neuro-imaging studies dealing with a particular kind of stimuli: faces. Overall, these studies report on the existence of deficits in the processing of emotional faces in patients with major depressive disorder, especially for happiness and sadness. At the behavioral level, studies show a reduction in the recognition of positive expressions together with an enhancement in the recognition of negative emotions, in particular sadness. Attentional and memory biases have also been observed with these stimuli. At the clinical level, impairments in facial expression processing seem to improve following antidepressant treatment. However, subtle deficit may remain, which might also be present in subjects at risk for major depressive disorder. Pharmacological studies suggest that anomalies in the serotonin signalling may be involved. Finally, these deficits have been associated with structural and functional anomalies in a network of brain regions including the amygdala, prefrontal cortex (medial, orbitofrontal and anterior cingulate) and hippocampus. Studies investigating the neural dynamics of facial expression processing in depression are consistent with anomalies in the early stages of attentional orienting toward emotional stimuli in depressed patients. Recent advances in pharmacogenetics and genetic neuro-imaging relating functional and pharmacological anomalies with cognitive or emotional disorders observed in depressed patients offer new promising perspectives.     

Depression and modern neuroimaging

Modern neuroimaging like PET, SPECT, MR-Volumetry, functional MRI and MR-Spectroscopy has effectively advanced research on aetiology, pathogenesis and therapy options of depressive disorders. This review highlights the status of current research on this topic. Consistent with morphological findings, which report alterations in regions of emotionally relevant networks of the brain in depressive disorders, findings of functional studies point to changes in the basal ganglia, the frontal cortex and the limbic system involving the hippocampus and the amygdala. During processing of emotional cues depressive patients show different activation patterns in the regions of the frontal lobe and the amygdala. In our study of a subgroup we were also able to show deficits in processing cues independently from the emotional quality of the stimulus - especially in posterior-parietal and prefrontal areas. In healthy subjects affective modulation correlates with an ordered interaction of ventral-limbic and dorsal-neocortical regions of the brain, which become unbalanced in depressive disorders. In the future, modern neuroimaging will open promising fields of research, which aim at the identification of valid neurofunctional subgroups of the heterogeneous affective disorders and the development of more adjusted and efficient therapy strategies.     

Developing an integrated brain, behavior and biological response profile in posttraumatic stress disorder (PTSD)

The present study sought to determine a profile of integrated behavioral, brain and autonomic alterations in PTSD. Previous findings suggest that PTSD is associated with changes across electrophysiological (EEG and ERP), autonomic and cognitive/behavioral measures. In particular, PTSD has been associated with reduced cognitive performance, altered cortical arousal (measured by EEG), diminished late ERP component to oddball task targets (reduced P3 amplitude) and increased autonomic arousal relative to healthy controls. The present study examined measures of cognitive function, auditory oddball ERP components, autonomic function (heart rate and skin conductance) and EEG during resting conditions in 44 individuals with PTSD and 44 non-trauma-exposed controls, and predicted that an integrated profile of changes across a number of these measures would show a high level of sensitivity and specificity in discriminating PTSD from controls. Nine variables showing strongly significant (p < 0.002) between-group differences were entered into a discriminant function analysis. Four of these measures successfully discriminated the PTSD and non-PTSD groups: change in tonic arousal, duration of attention switching, working memory reaction time and errors of commission during visuospatial maze learning. Tonic arousal change contributed the most variance in predicting group membership. These results extend previous findings and provide an integrated biomarker profile that characterizes both PTSD and non-PTSD groups with a high degree of sensitivity and specificity. This outcome provides a platform for future studies to test how this profile of disturbances in autonomic and information processing may be unique to PTSD or may occur generically across clinical and/or other anxiety disorders.     

Fleeting images: rapid affect discrimination in the visual cortex

Converging electrophysiological and hemodynamic findings indicate sensory processing of emotional pictures is preferred to that of neutral pictures. Whereas neuroimaging studies of emotional picture perception have employed stimulus durations lasting several seconds, recent electrocortical investigations report early visual cortical discrimination between emotionally arousing and neutral picture processing. Here, we use a hybrid picture presentation paradigm covering a range of rapid presentation rates (0.75-6 Hz), while visual system activity is recorded with functional magnetic resonance imaging. Results demonstrate widespread sensitivity to emotional arousal in the secondary and inferior temporal visual cortex. Furthermore, activity in the lateral inferior occipital and medial inferior temporal visual cortex revealed equivalent emotion-sensitive activation across all presentation rates. Results further support the notion that attention and perceptual processing are in part directed by underlying motivational systems.     

Lateral Asymmetries in Infancy: Implications for the Development of the Hemispheres

TREVARTHEN, C., Lateral asymmetries in infancy: implications for the development of the hemispheres. NEUROSCI BIOBEHAV REV 20 (4)571–586, 1996.—Cerebral asymmetry of cognitive processing of stimulus information is commonly viewed as a neocortical phenomenon. However, a number of lines of evidence give innate asymmetry of brainstem motivating systems, which anticipate experience, a key role.

Spontaneous asymmetries of gesture and emotion can be observed in infants, who entirely lack language and visuo-constructive skills. Motives for communication in early life may direct subsequent development of complementary cognitive systems in left and right hemispheres. In split-brain monkeys, lateralized motive sets, intentions for manipulation by one hand, can determine which hemisphere will see and learn. Evolutionary antecedents of cerebral appear to affect motivation, social signalling and bimanual coordination, with secondary effects in perceptual processing and learning.

The hemispheres of adult humans differ in links with neurochemical systems that regulate motor initiatives, exploration and attention, and the approach/withdrawal balance in social encounters. Asymmetries in emotional and communicative behaviour in infancy support evidence that an Intrinsic Motive Formation emerging in the embryo human brain stem regulates asymmetries in development and in functioning of the cerebral cortex. Copyright © 1996 Elsevier Science Ltd.     

Neuroimaging studies of mood disorders.

Neuroimaging studies of major depression have identified neurophysiologic abnormalities in multiple areas of the orbital and medial prefrontal cortex, the amygdala, and related parts of the striatum and thalamus. Some of these abnormalities appear mood state-dependent and are located in regions where cerebral blood flow increases during normal and other pathologic emotional states. These neurophysiologic differences between depressives and control subjects may thus implicate areas where physiologic activity changes to mediate or respond to the emotional, behavioral, and cognitive manifestations of major depressive episodes. Other abnormalities persist following symptom remission, and are found in orbital and medial prefrontal cortex areas where postmortem studies demonstrate reductions in cortex volume and histopathologic changes in primary mood disorders. These areas appear to modulate emotional behavior and stress responses, based upon evidence from brain mapping, lesion analysis, and electrophysiologic studies of humans and/or experimental animals. Dysfunction involving these regions is thus hypothesized to play a role in the pathogenesis of depressive symptoms. Taken together, these findings implicate interconnected neural circuits in which pathologic patterns of neurotransmission may result in the emotional, motivational, cognitive, and behavioral manifestations of primary and secondary affective disorders.