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

https://doi.org/10.1016/j.neubiorev.2017.04.021Get rights and content

Highlights

  • EEG alpha asymmetry and fRMI indicative of left frontal hypoactivity in depression.

  • Asymmetry in non-verbal/emotional dichotic and visual tasks abnormal in depression.

  • ERPs to emotional stimuli indicate right parietotemporal hypoactivity in depression.

  • Frontal and parietotemporal asymmetries modulated by anxiety and anxious arousal.

  • Right-left asymmetry related to diagnostic and treatment responsive subtypes.

Abstract

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.

Introduction

Studies in healthy adults and neurological patients have provided considerable evidence for asymmetries of right and left brain function (Springer and Deutsch, 1998, Hugdahl and Davidson, 2003). For over 30 years, studies have reported abnormalities of right-left asymmetry in depressive disorders. We review the findings of these studies and, in particular, examine how they are relevant to diagnosis and treatment of these disorders. Numerous studies have reported evidence of abnormal frontal and parietotemporal asymmetries in depressive disorders. The bulk of findings for frontal asymmetry have come from electroencephalographic (EEG) studies measuring alpha, which has received considerable attention in prior reviews and meta-analyses (Jesulola et al., 2015, Peltola et al., 2014, Thibodeau et al., 2006), and also in studies measuring glucose metabolism with positron emission tomography (PET) and regional cerebral blood flow (rCBF) with functional magnetic resonance imaging (fMRI). Although parietotemporal asymmetries have received less attention (Stewart et al., 2011), behavioral and event-related potential (ERP) studies using dichotic listening or visual hemifield tasks that tap functions mediated by this region have found considerable evidence of abnormal lateralized cognitive and emotional processing in patients having depressive disorders (see Bruder, 2003 for an earlier review). More recent studies have provided additional evidence of altered laterality in depression, particularly for processing emotional information. The present report gives particular attention to reviewing converging evidence from behavioral, EEG, ERP, and neuroimaging studies, which support hypotheses of reduced left frontal and right parietotemporal function in depression, and provide a new understanding of neural networks that may underlie this altered laterality. The relevance of right-left asymmetries for risk of developing a depressive disorder, diagnostic subtypes of depression, and clinical responsiveness to pharmacological and cognitive-behavioral treatments will also be a focus.

Section snippets

EEG alpha asymmetry

The EEG alpha rhythm (8–12 Hz) is maximal when one is in a relaxed, wakeful state with eyes closed, but is reduced when one becomes alert or opens the eyes. Alpha power has been found to be inversely related to cortical activity as measured by rCBF (Cook et al., 1998) or blood oxygen level in posterior regions where alpha is greatest (Feige et al., 2005). This inverse relation can lead to some confusion as to whether one is referring to hemispheric asymmetry of alpha power or cortical activity.

Dichotic listening asymmetry (Behavioral and ERP studies)

Early behavioral studies using neuropsychological tests of cognitive function in depressed patients reported greater deficits in functions related to the right (non-dominant) than left (dominant) hemisphere (Flor-Henry, 1976, Abrams et al., 1981). The greater right hemisphere deficits in depressed patients were more evident among women than men and clinical improvement during treatment was associated with improved cognitive function (Fromm-Auch, 1983). More recent studies have found deficits in

Visual hemifield asymmetry (Behavioral and ERP findings)

Differences in PA were found between patients having a bipolar (primarily Bipolar II) and unipolar depressive disorders who were tested in a dot enumeration task, which requires subjects to report the number of dots projected to either the right or left of fixation (Bruder et al., 1989). Patients having a unipolar depressive disorder and controls showed the expected right hemisphere advantage seen previously for the dot enumeration test (McClone and Davidson, 1973), whereas bipolar depressed

PET, MRI and NIRS neuroimaging findings

Neuroimaging studies using PET and MRI measures have found evidence of abnormalities involving multiple brain regions in depressed patients, including prefrontal cortex (PFC), superior temporal cortex, anterior cingulate cortex (ACC), amygdala, insula, basal ganglia and cerebellum (Fitzgerald et al., 2008, Pizzagalli, 2011, Rive et al., 2013, Sacher et al., 2012), but the extent to which these are lateralized to the right or left hemisphere has received less attention. Most imaging studies were

Conclusions

Studies using dichotic listening, visual hemifield, electrophysiological, and neuroimaging (PET, fMRI, NIRS) measures have found abnormalities of right-left asymmetries of brain function in depressive disorders. The bulk of evidence across studies using these diverse measures is consistent with reductions of left frontal and right parietotemporal function in depressive disorders. Relatively less left than right frontal activity in depression is in accordance with valence or approach/withdrawal

Acknowledgements

This work was supported by the New York State Office of Mental Health and the National Institute of Mental Health (MH36295).

References (192)

  • G.E. Bruder et al.

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

    Biol. Psychiatry

    (2008)
  • G.E. Bruder et al.

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

    Psychiatry Res.

    (2012)
  • G.E. Bruder et al.

    Predicting therapeutic response to secondary treatment with bupropion: dichotic listening tests of functional brain asymmetry

    Psychiatry Res.

    (2007)
  • G.E. Bruder et al.

    Electroencephalographic and perceptual asymmetry differences between responders and nonresponders to an SSRI antidepressant

    Biol. Psychiatry

    (2001)
  • G.E. Bruder et al.

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

    Biol. Psychiatry

    (1992)
  • G. Bruder et al.

    Lateralized auditory processing in depression: dichotic click detection

    Psychiatry Res.

    (1981)
  • G.E. Bruder et al.

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

    Biol. Psychiatry

    (2005)
  • G.E. Bruder et al.

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

    Biol. Psychiatry

    (2007)
  • J.A. Coan et al.

    A capability model of individual differences in frontal EEG asymmetry

    Biol. Psychol.

    (2006)
  • J. Cole et al.

    Hippocampal atrophy in first episode depression: a meta-analysis of magnetic resonance imaging studies

    J. Affect. Disord.

    (2011)
  • M.E. Connolly et al.

    Reduced striatal activation in females with major depression during the processing of affective stimuli

    J. Psychiatr. Res.

    (2015)
  • I.A. Cook et al.

    Assessing the accuracy of topographic EEG mapping for determining local brain function

    Electroencephalogr. Clin. Neurophysiol.

    (1998)
  • C. Cotrena et al.

    Executive function impairments in depression and bipolar disorder: association with functional impairment and quality of life

    J. Affect. Disord.

    (2016)
  • R.J. Davidson et al.

    While a phobic waits: regional brain electrical and autonomic activity in social phobics during anticipation of public speaking

    Biol. Psychiatry

    (2000)
  • G.S. Dichter et al.

    A systematic review of relations between resting-state functional- MRI and treatment response in major depressive disorder

    J. Affect. Disord.

    (2015)
  • M.A. Diego et al.

    Withdrawn and intrusive maternal interaction style and infant frontal EEG asymmetry shifts in infants of depressed and non- depressed mothers

    Infant Behav. Dev.

    (2006)
  • C. Diener et al.

    A meta-analysis of neurofunctional imaging studies of emotion and cognition in major depression

    Neuroimage

    (2012)
  • C.L. Ehlers et al.

    EEG asymmetry: Relationship to mood and risk for alcoholism in Mission Indian youth

    Biol. Psychiatry

    (2001)
  • A.S. Fischer et al.

    The clinical applicability of functional connectivity in depression: Pathways toward more targeted intervention

    Biol. Psychiatry Cogn. Neurosci. Neuroimaging

    (2016)
  • K.N. Fountoulakis et al.

    The relationship of regional cerebral blood flow with subtypes of major depression

    Prog. Neuropsychopharmacol. Biol. Psychiatry

    (2004)
  • M. Gadea et al.

    The sad, the angry, and the asymmetrical brain: dichotic listening studies of negative affect and depression

    Brain Cogn.

    (2011)
  • N. Gordon et al.

    Understanding alterations in serotonin connectivity in a rat model of depression within the monoamine-deficiency and the hippocampal-neurogenesis frameworks

    Behav. Brain Res.

    (2016)
  • S. Grimm et al.

    Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment: an fMRI study in severe major depressive disorder

    Biol. Psychiatry

    (2008)
  • N.A. Groenewold et al.

    Emotional valence modulates brain functional abnormalities in depression: evidence from a meta-analysis of fMRI studies

    Neurosci. Biohav. Rev.

    (2013)
  • E. Harmon-Jones et al.

    The role of asymmetric frontal cortical activity in emotion-related phenomena: a review and update

    Biol. Psychol.

    (2010)
  • W. Heller

    Gender differences in depression: perspectives from neuropsychology

    J. Affect. Disord.

    (1993)
  • K. Hugdahl et al.

    Attentional and executive dysfunctions in schizophrenia and depression: Evidence from dichotic listening performance

    Biol. Psychiatry

    (2003)
  • N. Jaworska et al.

    Subgenual anterior cingulate cortex and hippocampal volumes in depressed youths: the role of comorbidity and age

    J. Affect. Disord.

    (2016)
  • E. Jesulola et al.

    Frontal alpha asymmetry as a pathway to behavioural withdrawal depression: Research findings and issues

    Behav. Brain Res.

    (2015)
  • J. Kayser et al.

    Event related potentials (ERPs) to hemifield presentations of emotional stimuli: Differences between depressed patients and healthy adults in P3 amplitude and asymmetry

    Int. J. Psychophysiol.

    (2000)
  • J. Kayser et al.

    Principal components analysis of Laplacian waveforms as a generic method for identifying ERP generator patterns: II Adequacy of low-density estimates

    Clin. Neurophysiol.

    (2006)
  • J. Kayser et al.

    On the benefits of using surface Laplacian (current source density) methodology in electrophysiology

    Int. J. Psychophysiol.

    (2015)
  • R. Abrams et al.

    Cognitive dysfunction in schizophrenia, affective disorder and organic brain disease

    Brit. J. Psychiatry

    (1981)
  • H. Alhaj et al.

    The use of the EEG in measuring therapeutic drug action: focus on depression and antidepressants

    J. Psychopharmacol.

    (2011)
  • J.J.B. Allen et al.

    The stability of resting frontal electroencephalographic asymmetry in depression

    Psychophysiology

    (2004)
  • L. Baxter et al.

    Cerebral metabolic rates for glucose in mood disorders

    Arch. Gen. Psychiatry

    (1985)
  • L.R. Baxter et al.

    Reduction of prefrontal cortex glucose metabolism common to three types of depression

    Arch. Gen. Psychiatry

    (1989)
  • M. Beauregard et al.

    Dysfunction in the neural circuitry of emotional self-regulation in major depressive disorder

    Neuroreport

    (2006)
  • C.J. Bench et al.

    Regional cerebral blood flow in depression measured by positron emission tomography: the relationship with clinical dimensions

    Psychol. Med.

    (1993)
  • K.F. Berman et al.

    Is the mechanism of prefrontal hypofunction in depression the same as in schizophrenia?

    Br. J. Psychiatry

    (1993)
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