Robert B. Duckrow

EEG coherence has structure in the millimeter domain: subdural and hippocampal recordings from epileptic patients

Subdural recordings from 8 patients and depth recordings from 3 patients via rows of electrodes with 5-10 mm spacing were searched for signs of significant local differentiation of coherence calculated between all possible pairs of loci. EEG samples of 2-4 min were taken during 4 states: alertness, stage 2-3 sleep, light surgical anesthesia permitting the patient to respond to questions and electrical seizures. Coherence was computed for all frequencies from 1 to 50 Hz or 0.3-100 Hz; for comparisons the mean coherence over each of 6 or 7 narrower bands between 2 and 70 Hz was used. Whereas the literature supports the view that EEG coherence is usually substantial over many centimeters, the hypothesis here tested--and found to be well above stochastic expectations--is that significant structure occurs in the millimeter domain for EEG recorded subdurally or within the brain. In both the subdural surface samples and those from temporal lobe depth electrode arrays coherence declines with distance between electrodes of the pair, on the average quite severely in millimeters. This is nearly the same for all frequency bands. For middle bands like 8-13 and 13-20 Hz, mean coherence typically declines most steeply in the first 10 mm, from values indistinguishable from 1.0 at < 0.5 mm distance to 0.5 at 5-10 mm and to 0.25 in another 10-20 mm in the subdural surface data. Temporal lobe depth estimates decline about half as fast; coherence > or = 0.5 extends for 9-20 mm and > or = 0.25 for another 20-35mm. Low frequency bands (1-5, 5-8 Hz) usually fall slightly more slowly than high frequency bands (20-35, 35-50 Hz but the difference is small and variance large. The steepness of decline with distance in humans is significantly but only slightly smaller than that we reported earlier for the rabbit and rat, averaging less than one half. Local coherence, for individual pairs of loci, shows differentiation in the millimeter range, i.e., nearest neighbor pairs may be locally well above or below average and this is sustained over minutes. Local highs and lows tend to be similar for widely different frequency bands. Coherence varies quite independently of power, although they are sometimes correlated. Regional differentiation is statistically significant in average coherence among pairs of loci on temporal vs frontal cortex or lateral frontal vs. subfrontal strips in the same patient, but such differences are usually small.(ABSTRACT TRUNCATED AT 400 WORDS)

Regional coherence and the transfer of ictal activity during seizure onset in the medial temporal lobe.

Epileptiform activity requires that large aggregates of neurons act synchronously. The process of neuronal synchronization during seizure onset was studied in the human medial temporal lobe by measuring the coherence of EEG activity. Records were obtained from 10 consecutive patients with hippocampal depth electrodes being evaluated for possible resective surgery. Coherence and phase spectra were calculated from all possible pairs of contacts in the medial temporal lobe of seizure onset using the method of Gotman applied to successive 6.4 sec epochs. Signals derived from adjacent contacts within definable brain regions were coherent during both the preictal and ictal period. Transitions in the level of coherence were measured between contacts presumed to span the boundaries of these regions. Time delays were measured early in the development of the seizure discharge but were not sustained. These time delays spanned the borders of regions of differing coherence, especially in the posterior hippocampus, and were interpreted to represent a transient increase in the functional linkage between structural elements. We conclude that the process of neuronal entrainment during seizure onset involves a transient interaction between brain regions but the maintenance of this interaction is not required for sustained seizure activity.

Measuring the coherence of intracranial electroencephalograms.

OBJECTIVEnPrevious coherence studies of human intracranial electroencephalograms (EEGs) can be faulted on two methodological issues: (1) coherence estimates in a majority were formed from a very small number of independent sample spectra, and (2) the statistical significance of coherence estimates was either not reported or was poorly evaluated. Coherence estimator performance may be poor when a small number of independent sample spectra are employed, and the coupling of poor estimation and statistical testing can result in inaccuracy in the measurement of coherence. The performance characteristics of the coherence estimator and statistical testing of coherence estimates are described in this manuscript.nnnMETHODSnThe bias, variance, probability density functions, and confidence intervals of the estimate of magnitude squared coherence (MSC); and power analysis for the test of zero MSC were developed from the exact analytic form of the probability density function of the estimate of MSC for Gaussian random processes. The coherence of a single epoch of background EEG, recorded from a patient with intractable seizures, was evaluated with different parameter values to aid in the exposition of the concepts developed here.nnnRESULTSnThe statistical characteristics of WOSA coherence estimates are a function of a single estimator parameter, the number of independent sample spectra employed in the estimation. Bias and variance are high, confidence intervals may be large, and the probability of Type II errors is high if a small number of independent sample spectra are employed. A considerable improvement in measurement accuracy is possible with careful selection of estimator parameter values.nnnCONCLUSIONSnCoherence measurement accuracy can be improved over previous applications by attention to estimator performance and accurate statistical testing of coherence estimates.

BICOHERENCE OF INTRACRANIAL EEG IN SLEEP, WAKEFULNESS AND SEIZURES

The hypothesis that the intracranial EEG has local structure and short-term non-stationarity is tested with a little-studied measure of non-linear phase coupling, the bicoherence in human subdural and deep temporal lobe probe data from 11 subjects during sleeping, waking and seizure states. This measure of cooperativity estimates the proportion of energy in every possible pair of frequency components, F1, F2 (from 1 to 50 Hz in this study), that satisfies the definition of quadratic phase coupling (phase of component at F3, which is F1 + F2, equals phase of F1 + phase of F2). Derived from the bispectrum, which segregates the non-Gaussian energy, auto-bicoherence uses the frequency components in one channel; cross-bicoherence uses one channel for F1 and F2 and another for F3. These higher order spectra are used in physical systems for detection of episodes of non-linearity and transients, for pattern recognition and robust classification, relatively immune to Gaussian components and low signal to noise ratios. Bicoherence is found not to be a fixed character of the EEG but quite local and unstable, in agreement with the hypothesis. Bicoherence can be quite different in adjacent segments as brief as 1.6 s as well as adjacent intracranial electrodes as close as 6.5 mm, even when the EEG looks similar. It can rise or fall steeply within millimeters. It is virtually absent in many analysis epochs of 17s duration. Other epochs show significant bicoherence with diverse form and distribution over the bifrequency plane. Isolated peaks, periodic peaks or rounded mountain ranges are either widely scattered or confined to one or a few parts of the plane. Bicoherence is generally an invisible feature: one cannot usually recognize the responsible form of non-linearity or any obvious correlate in the raw EEG. During stage II/III sleep overall mean bicoherence is generally higher than in the waking state. During seizures the diverse EEG patterns average a significant elevation in bicoherence but have a wide variance. Maximum bispectrum, maximum power spectrum, maximum and mean bicoherence, skewness and asymmetry all vary independently of each other. Cross-bicoherence is often intermediate between the two auto-bicoherence spectra but commonly resembles one of the two. Of the known factors that contribute to bicoherence, transient as distinct from ongoing wave forms can be more important in our data sets. This measure of non-linear higher moments is very sensitive to weak quadratic phase coupling; this can come from several kinds of waveforms. New methods are needed to evaluate their respective contributions. Utility of this descriptor cannot be claimed before more carefully defined and repeatable brain states are studied.

A brief hypoperfusion precedes spreading depression if nitric oxide synthesis is inhibited

Spreading cortical depression (SCD) alters cerebral blood flow by mechanisms that are not well understood. To investigate the role of the likely endothelium-derived relaxing factor, nitric oxide, in the blood flow changes occurring during SCD in awake rats, nitric oxide synthesis was blocked using N omega-nitro-L-arginine methyl ester (L-NAME). During SCD there is an initial hyperperfusion followed by a longer-lasting hypoperfusion. Treatment with L-NAME, 30 mg/kg, reduced resting cerebral blood flow globally. During SCD, L-NAME treatment produced an additional brief phase of hypoperfusion which preceded the initial hyperperfusion. The magnitude of the initial hyperperfusion was less than expected. The subsequent longer-lasting hypoperfusion was unchanged. Nitric oxide plays an important role in the regulation of cerebral blood flow during SCD.

Localization of muscarinic receptor subtypes in brain stem areas regulating sleep.

Muscarinic cholinergic receptors (mAChRs) within the pontine brain stem play a key role in generating rapid eye movement (REM) sleep. Using an in vitro autoradiographic technique that permits selective labeling of mAChR subtypes by radioligand binding, this study provides the first quantitative map of mAChR subtypes in cat brain stem areas important for REM sleep generation. M1, M2 and M3 mAChR subtypes were distributed heterogeneously throughout the brain stem. For all 3 mAChR subtypes, the greatest levels of binding were found in the dorsal raphe and locus coeruleus, and the least amount of binding was in the reticular formation. These findings are consistent with data from in vivo studies showing that multiple mAChR subtypes are involved in REM sleep generation.

Decreased cerebral blood flow during acute hyperglycemia.

Cerebral blood flow (CBF) decreases during acute hyperglycemia but the mechanism of this change is unknown. The role that plasma osmolality plays in this effect was reexamined in pentobarbital-anesthetized rats using a continuous measure of CBF, laser-Doppler flowmetry. CBF decreased 25% during acute elevation of plasma osmolality induced by intraperitoneal injection of concentrated solutions of glucose or mannitol. In addition there were brief transient increases of CBF with peak magnitude 2-4-times the baseline level that were not accompanied by transient depression of electroencephalographic activity. These transient CBF increases may explain why discontinuous methods of CBF measurement fail to detect flow decreases after mannitol injection. Decreased CBF measured during acute hyperglycemia may be the result of increased plasma osmolality.

The effect of a scalp reference signal on coherence measurements of intracranial electroencephalograms

OBJECTIVEnTo determine the effect of a scalp reference signal, such as that recorded from the mastoid or ear, on the coherence of referential intracranial electroencephalograms (EEGs).nnnMETHODSnThe relationship between reference signal power and magnitude squared coherence (MSC) was determined from the theoretical expression of the coherence of referential recordings, obtained under the assumption that the reference signal is not correlated with the signals being studied. The effect of a contaminated reference signal on the coherence of intracranial EEGs was determined by measuring the MSC of both a recording of background EEGs with a simulated contaminated reference signal and a contaminated recording of a seizure.nnnRESULTSnThe MSC of referential intracranial EEGs is inflated due to the reference signal. This inflation is a function of the true MSC of the intracranial signals and the power of the reference and intracranial signals. The inflation is limited where reference signal power is smaller than the power of the intracranial signals; maximum inflation <0.1 when reference signal power=0.2xpower of intracranial EEGs and </=0.2 when reference signal power=0.5xpower of intracranial EEGs. A contaminated reference signal may have a considerable effect on MSC, however. The changes to the MSC spectrum that result from a contaminated reference primarily occur in an open-ended high-frequency band and may create an elevated plateau in this part of the MSC spectrum.nnnCONCLUSIONSnThe findings presented here suggest a scalp reference signal is suitable, with careful monitoring of the reference signal, for coherence analysis of intracranial EEGs. A reference signal will have a limited effect on the coherence of intracranial EEGs except when it is contaminated. In the event the reference signal is contaminated it should be possible to detect this from the stereotyped features of the coherence spectrum.

Distinguishing Subtypes of Temporal Lobe Epilepsy with Background Hippocampal Activity

Summary: u2002Purpose: Two subtypes of temporal lobe epilepsy (TLE) can be defined through clinical observations and analysis of hippocampal tissue resected during surgical procedures for intractable TLE: (a) mesial temporal sclerosis (MTS), which is characterized by extensive changes to the hippocampus and good surgical outcome; and (b) paradoxical temporal lobe epilepsy (PTLE), which is characterized by minimal cell loss and comparatively poorer surgical outcome. Patients in both subtypes have seizures that appear to begin in the medial temporal lobe, but documented differences in substrate and outcome between these subtypes has defined a need to distinguish MTS and PTLE patients before surgery. This report describes a retrospective study to investigate the feasibility of doing so during intracranial monitoring.

Development of a research interface for image guided intervention: initial application to epilepsy neurosurgery

This paper describes the development and application of methods to integrate research image analysis methods and software with a commercial image guided surgery navigation system (the BrainLAB VectorVision Cranial System.) The integration was achieved using a custom designed client/server architecture termed VectorVision Link (VV Link) which extends functionality from the Visualization Toolkit. VV Link enables bi-directional data transfer such as image data sets, visualizations and tool positions in real time. The system was tested in both laboratory experiments and in real epilepsy neurosurgeries with highly promising results