Research reportHemispheric asymmetry in depression and mania: A longitudinal QEEG study in bipolar disorder
Introduction
The issue of hemispheric asymmetry in the processing of emotion has clinical as well as heuristic importance, given known asymmetries in the forebrain distributions of major neurotransmitter systems in humans (e.g., Mandell and Knapp, 1979, Flor-Henry, 1986). One theory purports a principal role of the right hemisphere in the processing of all emotion (see Flor-Henry, 1986, Silberman and Weingartner, 1986, Mandal et al., 1996, for reviews). It is likely that emotional prosody (the decoding and encoding of emotions in communication) is primarily a right hemisphere function in people with left hemisphere dominance for the grammatical elements of language (George et al., 1996). Many studies of other aspects of emotional processing support the right hemisphere specialization hypothesis as well (e.g., Blonder et al., 1991). Considerable evidence also supports the notion that the normal left hemisphere is specialized for processing positively valenced emotion, and the right, for negatively valenced emotional states (see Heilman, 1997, for review). Thus in normal infants (Davidson and Fox, 1982, Davidson and Fox, 1989, Fox and Davidson, 1986, Fox and Davidson, 1987, Fox, 1991) and adults (Reuter-Lorenz and Davidson, 1981, Schiff and McDonald, 1990, Tomarken et al., 1990, Jones and Fox, 1992), left frontal activation has been seen in association with positively valenced emotional conditions, and right frontal activation in association with negatively valenced conditions. In patients who develop mood disorders after lateralized brain injury, a complementary pattern of depressive or other negatively valenced emotional states after left unilateral destructive lesions, and euphoria or other positively valenced states after right unilateral brain injury has been observed by many investigators (Gainotti, 1972, Sackeim et al., 1982, Cummings and Mendez, 1984, Lee et al., 1990, Robinson and Starkstein, 1990, Stern and Bachman, 1991, Morris et al., 1996), although studies showing lack of association between lesion site and development of depression also exist (House et al., 1990, House, 1996). Positron emission tomographic (PET) studies in normals have revealed variable hemispheric asymmetries in association with emotion (Pardo et al., 1993George et al., 1995Partiot et al., 1995). Heilman (1997)has also commented on the asymmetrical contributions of the two hemispheres to arousal and motor activation related to emotional experience, in addition to the positive/negative valence itself.
Many investigations of primary depressed compared with control subjects employing PET or single photon emission computed tomography (SPECT) have found left frontal decrease in cerebral blood flow or metabolism, consistent with the preponderance of brain lesion data (Rush et al., 1982, Baxter et al., 1985, Kuhl et al., 1985, Delvenne et al., 1990, Martinot et al., 1990, Guze et al., 1991, Austin et al., 1992, Bench et al., 1992, Bench et al., 1993, Yazici et al., 1992, Rubin et al., 1995, Little et al., 1996). However, findings have not been entirely consistent, and a variety of other cross-sectional patient–control differences, as well as negative findings, have been reported (Risberg, 1980, Buchsbaum et al., 1984, Buchsbaum et al., 1986, Gur et al., 1984, Post et al., 1987, Schwartz et al., 1987, Cohen et al., 1989, Silfverskiold and Risberg, 1989, Amsterdam and Mozley, 1991, Drevets et al., 1992, Devous et al., 1993, Goodwin et al., 1993, Maes et al., 1993, D'Haenen and Bossuyt, 1994, Biver et al., 1994, Mayberg et al., 1994, Rubin et al., 1995, Ebert and Ebmeier, 1996, Ito et al., 1996, Ketter et al., 1996a, Ketter et al., 1996b, Little et al., 1996).
In the quantitative electroencephalography (QEEG) literature, increased left frontal alpha, suggesting decreased ipsilateral activation (Andersen and Andersson, 1968), has been reported in several cross-sectional studies of depressed compared with normal control subjects (Schaffer et al., 1983, Davidson et al., 1985, Henriquez and Davidson, 1990, Roemer et al., 1992, Allen et al., 1993). Bilaterally increased frontal alpha is also frequently reported (Schaffer et al., 1983, von Knorring et al., 1983, Brenner et al., 1988, John et al., 1988, Lieber and Newbury, 1988, Pollock and Schneider, 1990a). A variety of other depressed patient–control differences in asymmetry measures have been reported in this literature: right>left parietal alpha (Davidson et al., 1985, Henriquez and Davidson, 1990, Allen et al., 1993); L>R hemisphere delta in depressed as well as control patients, with a lower (L−R)/(L+R) laterality index in depressed than control subjects (Knott and LaPierre, 1987); increased slow-wave activity on the right (Kwon et al., 1996); decreased anterior interhemispheric coherence (Lieber and Prichep, 1988); decreased anterior and posterior slow-wave interhemispheric coherence (Lieber, 1988); and increased right hemisphere variance (Rochford et al., 1981).
PET and SPECT studies of patients finding asymmetries in the depressed state have tended to show normalization in euthymia (Baxter et al., 1985, Baxter et al., 1989, Goodwin et al., 1993; Bench et al., 1995, Ebert and Ebmeier, 1996, Matthew et al., 1996, Gyulai et al., 1997), although other studies have found trait-related hemispheric asymmetries (Martinot et al., 1990, Drevets et al., 1992). Several studies have found baseline metabolic or blood flow abnormalities in limbic frontotemporal structures to predict a positive response to somatic intervention (Ebert et al., 1991, Wu et al., 1992, Ketter et al., 1996b, Little et al., 1996). The few longitudinal QEEG studies in depressed patients have, interestingly, tended to show persistence of asymmetries on recovery (Henriquez and Davidson, 1990, Allen et al., 1993, Kwon et al., 1996). Here as well, abnormalities have been shown to predict somatic treatment response in depression (Knott et al., 1996).
Relatively few investigations of regional brain function in manic patients have been published, but hemispheric asymmetries distinguishing manic from control subjects cross-sectionally appear to be a fairly consistent finding (Flor-Henry and Koles, 1984Migliorelli et al., 1993O'Connell et al., 1995Rubin et al., 1995Al-Mousawi et al., 1996Gyulai et al., 1997).
We could find only one recent study in which a hemispheric asymmetry measure was longitudinally assessed in bipolar subjects across different mood states. Gyulai et al. (1997)found R>L anterior temporal lobe iofetamine SPECT uptake in 6/7 patients studied in depression, compared with when they were studied in euthymia, and the same finding in 2/3 patients studied in mania/hypomania compared with euthymia.
Despite inconsistencies in its presence, direction and intrahemispheric localization, emotional valence-related hemispheric asymmetry appears to be a well-replicated phenomenon across several different types of research pertinent to the question. Asymmetries have been found in prefrontal cortex, temporal lobes, basal ganglia, thalamus and cingulate. Differences in results for depressed populations with PET, SPECT and QEEG are at least in part due to differences in subject selection, neuroanatomic region of interest determination, or data analysis methodology (Gainotti, 1984, Coffey, 1987, Kahn et al., 1988, Goodwin and Jamison, 1990, Pollock and Schneider, 1990b, George et al., 1993).
Longitudinal study of the same individuals during different mood states addresses some of the methodological inconsistencies in previous studies, since it controls for inter-individual differences such as age, gender, and handedness; as well as problems associated with differences in sampling, diagnostic method, and region of interest determination. Inter-individual variation is particularly problematic with QEEG (John et al., 1988). The present study was designed to test the hypothesis that mood states of different (positive-versus-negative) valence in the same bipolar subjects at different times would be associated with state-dependent differences in the interhemispheric balance of electrical activity in homologous brain regions.
Section snippets
Experimental subjects (Table 1)
Subjects (Table 1) were 10 males (mean age 47.2; range 37–56) and three females (mean age 42.67; range 42–44) (total sample mean age 46.15) with DSM-IV (American Psychiatric Association, 1994) Bipolar I (N=11) or Bipolar II (N=2) disorder, recruited from a Veterans Affairs Medical Center Outpatient Clinic, and a County Mental Health Center, both affiliated with a major university center. Bipolar Disorder was primary in 10 and secondary to head injury in three subjects. In the latter, an
Results
Clinical characteristics of the 13 subjects who received two or more EEGs are shown in Table 1. The specific mood state pairs studied for each subject, along with the order of mood states and inter-EEG duration, are given in Table 3. ZACS for each group of patients studied in the same pair of mood states are represented in Fig. 1.
Qualitative examination of Fig. 1 reveals the following:
- 1.
A pattern of opposite direction ZACS at F3/4 and T3/4 and, to a lesser extent, C3/4 in delta, theta and alpha
Discussion
Qualitative examination of our results shows valence-based directional asymmetry changes consistent with the a priori hypothesis that the direction of interhemispheric power asymmetry at homologous QEEG lead pair locations is opposite in depression and mania/hypomania in bipolar disorder in some frontotemporal regions. Statistical confirmation of these findings was not achieved, likely due to the small sample size, large number of data points, and consequent lack of statistical power.
Diagnostic
Conclusion
We found evidence consistent with a hypothesized lateralization of cerebral activity in opposite hemispheres in association with mood states of opposite positive–negative valence in clinical bipolar mood disorder in some frontotemporal regions. Statistical significance was not achieved due to our small sample size. Confirmation of our findings must await replication in larger samples of more homogeneous subjects. Longitudinal study of hemispheric asymmetry in bipolar patients across mood states
Acknowledgements
This work was presented in preliminary form at the American Psychiatric Electrophysiology Association Annual Meeting, New York, NY, May 1996, and at the Fourth Laterality and Psychopathology Conference, London, England, June 1997. The authors wish to thank Arthur S. Kling, MD, pioneering behavioral neuroscientist who died in March 1997, for his contribution to the development of this project, Dr. Jeffrey Gornbein, UCLA SBCC/Department of Biomathematics, for expert statistical consultation, and
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