Electrophysiological measures of regional neural interactive coupling. Linear and non-linear dependence relationships among multiple channel electroencephalographic recordings.

Linear spectral coherence (Sklar et al., 1973) measures have been used in the neurosciences to test hypotheses which address the question of whether multiple EEG recording sites are independent or whether they are activated by common sources of neurophysiological activity. This measure is appropriate when regional neural sources interact and thereby electrically activate several recording sites through linear transmission pathways which may or may not be different in their linear transformation properties. However, if the transmission media are non-linear, then interactive dependency is not necessarily revealed by a linear coherence test. Therefore, if common sources are activating EEG recording sites through nonlinear media, evaluating the resulting relationships among the signals recorded from these sites requires a test which reveals the presence of such nonlinear relationships. In neurophysiological applications, a polycoherence cross-spectral measure provides such a test for nonlinear dependency (similar to the linear coherence test) among EEG recording sites. The data requirements and statistical properties of these linear and non-linear measures are described and results of a linear coherence analysis are presented in the context of an EEG pilot study of learning-disabled children.

Moments of the power spectral density estimated from samples of the autocorrelation function (a robust procedure for monitoring changes in the statistical properties of lengthy non-stationary time series such as the EEG.

Accurate estimates of the statistical moments of the power spectral density (PSD) are obtained without computing the Fourier transform of the associated time series. An innovative analytical procedure is derived which reduces the problem to that of summing a small number of weighted samples of the autocorrelation function (ACF). This result significantly reduces the computational requirements for generating meaningful PSD shape descriptors and thus is especially important in biomedical applications where the cost and effort of monitoring lengthy non-stationary time series is a serious practical limitation. In addition the procedure is robust and therefore can be rigorously applied to any stochastic process to estimate its fundamental statistical properties.

Effects of carbamazepine on plasma haloperidol levels.

Plasma haloperidol levels were monitored in three schizophrenic patients when carbamazepine was either added or discontinued. The percent decrease in plasma haloperidol levels due to concomitant carbamazepine therapy was between 59% and 61%. The effects of carbamazepine on plasma haloperidol levels were noted to occur in 2 to 3 weeks. Although no adverse effects occurred in the patients during therapy, careful monitoring of clinical symptoms and plasma haloperidol levels is recommended.

Haloperidol and reduced haloperidol plasma levels in selected schizophrenic patients.

The first measurements of haloperidol (HL) and its reduced metabolite hydroxyhaloperidol (RH) in plasma versus clinical response in five chronic schizophrenic patients are reported. HL and RH were measured by a radioimmunoassay with a low coefficient of variation. Patients were selected based on poor response or the need for high dosage and were rated with the Clinical Global Impression Scale. Daily HL dosage range was 0.5 to 1.5 mg/kg. HL plasma concentrations ranged from 14 to 98 ng/ml. RH plasma concentrations ranged from 10 to 319 ng/ml. Four patients did not respond to HL therapy; two of these improved dramatically when switched to fluphenazine. The four nonresponding patients had higher RH than HL concentrations. RH seems to be present in plasma in significant concentrations, and further investigation of the relationships of RH and HL plasma levels versus response is needed.

Evoked potential studies of the effects of impact acceleration on the motor nervous system.

The initial results of a continuing investigation into the effects of various levels of impact acceleration on the functional integrity of the motor nervous system are summarized. The results are based on the measurement of alterations in neural transmission along the motor pathway of the Rhesus monkey as revealed by latency and amplitude changes in the motor pathway evoked potential (EP) following the delivery of various levels of impact acceleration to a test vehicle. The EPs were produced by electrical stimulation of and recording from the motor pathway of experimental animals subjected to -Y (lateral impact) acceleration and animals subjected to -X (frontal impact) acceleration. High resolution latency and amplitude measures of the EP recorded from these animals before and after impact were tracked so that the time course of recovery of nerve propagation following impact could be accurately assessed. Analysis of these EP measures revealed that the time course of recovery to preimpact values is directly related to the intensity of the acceleration impulse delivered to the test vehicle.

Changes in the rhesus monkey's EEG responses to ethanol during chronic exposure.

This study was designated to document the changes in the CNS response to ethanol during chronic exposure in 5 male, 3.5--5.0 kg rhesus monkeys. Electrodes were implanted bilaterally into the amygdala, hippocampus and the calvarium over the frontal and temporal cortex. Ethanol or control solutions were administered intragastrically through indwelling cannulae. The 1.25 g/kg ethanol challenge dose was administered during EEG recordings. After one challenge dose, the animals received 60 days of chronic alcohol exposure (3.0 g/kg/day increasing to 8.0 g/kg/day). EEG was recorded every 10 days and analyzed by period analysis. Changes in the effect of the challenge dose were assessed by determining the percentage change of the EEG from pre-dose levels to selected times post-dose throughout the chronic alcohol exposure. The EEG response changed significantly during chronic alcohol treatment. Although each structure exhibited a slightly different pattern of change, the overall change was a shift from an excitatory response in the non-tolerant animal to an EEG slowing during chronic exposure. We suggest that such a change may be useful as a diagnostic marker for alcohol tolerance. In addition, the differential nature of the in vivo expression of alcohol tolerance in each brain area suggests that such analysis may provide a valuable tool for understanding the mechanism and expression of alcohol tolerance in the CNS.