Edward L. Merrin

Common reference coherence data are confounded by power and phase effects

Coherence analysis of the EEG is used to study the coupling between cortical regions. High coherence between signals recorded at 2 electrodes is interpreted as evidence for neuroanatomic connections between the cortical areas underlying the electrodes. When common reference recordings are used, coherence measures the relationship between 2 time series, each of which is the difference between 2 signals measured at the scalp and is confounded by spectral power and phase at the recording and reference electrodes. Using multi-channel EEG data from 3 subjects, we illustrate the confounding of common reference data coherence computations and demonstrate the extreme effects of power and phase changes on coherence by simulating these changes in the EEG data. Common reference coherence data can be either inflated or deflated as a consequence of activity (i.e., spectral power) at the reference. Phase relationships among the reference and recording time series modulate the power effects on coherence. Both the power and phase effects can vary dramatically across frequencies, having profound and complicated effects on the shape of the coherence function. Based on these considerations, we conclude that common reference coherence data must be interpreted very cautiously and recommend that a new body of EEG coherence data must be gathered using reference-free recording methods before the utility of EEG coherence analysis for understanding brain function can be determined.

Lateral eye movement and cognitive mode

The direction of lateral eye movement elicited by reflective questions is strongly modified by the cognitive demands of the question; verbal and arithmetical questions elicit more movements to the right than do spatial and musical questions. This is consistent with the lateral specialization of the human brain for these cognitive processes. These results support the hypothesis that the direction of the lateral eye movement indicates the activation of the contralateral cerebral hemisphere.

EEG coherence in unmedicated schizophrenic patients

We have recently shown that electroencephalogram (EEG) coherence data recorded with common reference methods, including those obtained from schizophrenics, are confounded by power and phase effects. Three published reports using bipolar recordings found that EEG coherence was higher in schizophrenics; however, only medicated patients were studied. To extend these findings, we measured EEG coherence from bipolar EEG recordings in unmedicated schizophrenics (n = 10), affective disorder patients (n = 8), and normal controls (n = 13) during resting and task conditions. Seven schizophrenics were restudied after a period of neuroleptic treatment. Schizophrenics had higher across-task interhemispheric (p less than 0.05) and intrahemispheric (p less than 0.04) coherence in the theta band and tended to have higher intrahemispheric alpha coherence (p less than 0.08). Medication treatment was associated with clinical improvement and increases in spectral power, but not with changes in coherence values. These results confirm those obtained by earlier investigations and suggest that increased coherence reflects the presence of anomalous cortical organization in schizophrenics rather than medication effects or transient states related to acute clinical disturbance.

31Phosphorus magnetic resonance spectroscopy of the frontal and parietal lobes in chronic schizophrenia

In vivo 31Phosphorus magnetic resonance spectroscopic imaging (31P MRSI) was performed on 20 chronic schizophrenic patients and 16 normal controls to determine if there were specific changes in high energy phosphorus and phospholipid metabolism in the frontal lobes of schizophrenic patients. Phosphorous metabolites were assessed in each of the left and right frontal as well as the left and right parietal lobes. Frontal lobe phosphorous metabolites were also correlated with severity of psychiatric symptomatology as assessed by the Brief Psychiatric Rating Scale (BPRS). Schizophrenics demonstrated higher phosphodiesters (PDE) and lower phosphocreatine (PCr) in both the left and right frontal regions compared to controls. There was also lower left frontal inorganic phosphate (Pi) in the schizophrenic group. No group differences were noted in the left or right parietal regions. In addition, right frontal PDE and right frontal PCr were highly correlated with the hostility-suspiciousness and anxiety-depression subscales of the BPRS. This study provides further support for altered frontal lobe phosphorous metabolism in schizophrenia.

Negative symptoms and EEG alpha in schizophrenia : a replication

The authors previously reported that negative symptoms were associated with reduced EEG alpha power and coherence in medication-free schizophrenic inpatients. These post-hoc findings were based on resting EEG data in an eyes open condition. This report describes the replication of these results in a new sample of 17 male veterans (aged 38 +/- 8) recently hospitalized with DSM-III-R schizophrenia. All patients had been free of neuroleptic medication at least 12-14 days. The relationships between resting alpha (7.5-12.5 Hz) power and coherence and symptom ratings (as measured by subscales derived from the Brief Psychiatric Rating Scale) were examined with multivariate repeated measure analyses of covariance. Results were similar to those obtained earlier, with a main effect of negative symptoms (p = 0.05) on log alpha power, a localized effect on right frontal-parietal alpha coherence (p < 0.02), and a main effect (p < 0.03) on between-hemisphere alpha coherence. There was also a trend for an asymmetrical effect on power favoring the right side in parietal leads. Negative symptoms were associated with reduced alpha power and less alpha coherence between hemispheres and between right parietal and frontal regions. The authors discuss the implications of these results on neurodevelopmental, genetic, and attentional aspects of schizophrenia.

Correlation between left frontal phospholipids and Wisconsin Card Sort Test performance in schizophrenia

The relationship between frontal lobe phospholipid measures as measured by in vivo 31phosphorus magnetic resonance spectroscopic imaging and performance on the Wisconsin Card Sort Test was examined in 16 chronic schizophrenic patients and 13 normal controls. Lower left frontal phosphomonoester levels in the schizophrenics were associated with fewer categories achieved, lower percent conceptual level, and greater total errors. No significant correlations between frontal phospholipid measures and performance on the WCST were noted in the controls. The results suggest a relationship between altered left frontal phospholipid metabolism and a specific measure of frontal lobe neuropsychological functioning.

31Phosphorus magnetic resonance spectroscopy of the temporal lobes in schizophrenia

Eleven schizophrenic patients and nine normal controls were studied using in vivo 31Phosphorous magnetic resonance spectroscopy (31P MRS) to test the hypothesis of metabolic asymmetry in the temporal lobes in schizophrenia. The controls did not demonstrate any asymmetry of phosphorous metabolite ratios, percentage of phosphorous metabolites, or pH. In the schizophrenics, however, phosphocreatine/beta-adenosine triphosphate (PCr/beta-ATP) and phosphocreatine/inorganic phosphate (PCr/Pi) effects appeared to primarily reflect higher ratios on the right side, while the percentage of beta-ATP appeared to primarily reflect higher relative concentrations in the left temporal lobe. Moreover, significant negative correlations were noted between total Brief Psychiatric Rating Scale scores and PCr/beta-ATP in both the right and left temporal lobes. These results support the hypothesis of an asymmetric distribution of 31P metabolites in the temporal lobe of schizophrenic patients, and also show an association between temporal lobe phosphorous metabolism and the severity of psychiatric symptomatology.

Negative symptoms and EEG alpha activity in schizophrenic patients.

Quantitative analyses of electroencephalographic (EEG) recordings in schizophrenic patients have often demonstrated reduced alpha band (8-13 Hz) activity. However, this finding is not universal and there is some evidence that subgroups of schizophrenics may differ in overall or lateralized levels of EEG alpha activity. To investigate this issue, the authors examined relationships between clinical ratings performed at the time of EEG recording and resting alpha power and coherence in 14 medication free schizophrenic patients. Nine channels of previously recorded resting (eyes open) EEG were transformed to average reference prior to spectral analysis and transformed to source derivation prior to calculation of inter-electrode coherences. Patients were rated with the Brief Psychiatric Rating Scale (BPRS), from which subscales corresponding to negative symptoms, positive symptoms, paranoia, and anxiety/depression were derived. Ratings and EEG measures were also obtained on 10 of the schizophrenic patients after neuroleptic treatment. Multiple regression with repeated measures was used to examine the influence of the subscale scores on bilateral log alpha power and both within- and between-hemisphere alpha coherence at selected locations. Prior to treatment, negative symptoms varied inversely with alpha power (p < 0.02), within-hemisphere alpha coherence (p < 0.03), and between-hemisphere coherence (p = 0.053). The effect of negative symptoms on alpha power was bilateral, but the effect on within-hemisphere coherence tended (p = 0.053) to be right-sided. After treatment these relationships were no longer present. The possible implications of and the effects of drug treatment on an association between negative symptoms and reduced alpha activity are discussed.

Asymmetry of temporal lobe phosphorous metabolism in schizophrenia: A 31Phosphorous magnetic resonance spectroscopic imaging study

In vivo 31Phosphorous magnetic resonance spectroscopic imaging (31P MRSI) was performed on 18 chronic schizophrenic patients and 14 normal controls to determine if there was asymmetry of high-energy phosphorous metabolism in the temporal lobes of schizophrenic patients. Temporal lobe phosphorous metabolites were also correlated with severity of psychiatric symptomatology as assessed by the Brief Psychiatric Rating Scale (BPRS). Schizophrenics demonstrated significantly higher right relative to left temporal phosphocreatine/adenosine triphosphate (PCr/ATP), phosphocreatine/inorganic phosphate (PCr/Pi), and PCr as well as significantly lower right relative to left temporal ATP. There were no asymmetries of temporal lobe phosphorous metabolites in the control group. In addition, both left temporal PCr and the degree of asymmetry of temporal lobe PCr were highly correlated with the thinking disturbance subscale of the BPRS. This study provides further support for temporal lobe metabolic asymmetry in schizophrenia and its possible association with clinical symptoms.

EEG asymmetry in schizophrenic patients before and during neuroleptic treatment

Lateral asymmetry of electroencephalographic (EEG) spectra was assessed in schizophrenic patients compared to normal controls. Ten predominantly unmedicated schizophrenic inpatients and nine normal controls performed monitored cognitive tasks during bilateral recording of EEG from parietal and temporal sites. Lateralization of EEG power in five frequency bands was compared between the groups; separate analyses were performed for linked ears and vertex references. A subsample of schizophrenic patients was restudied after a period of neuroleptic treatment. All significant group differences were obtained with the linked ears reference only. Pretreatment schizophrenics manifested relatively less alpha power over the right hemisphere during all conditions than controls, particularly in the parietal leads. After treatment, there was a significant shift in alpha lateralization toward the control values. These latter effects were also present in the theta frequency band to a lesser extent.