Graded defragmentation of cortical neuronal firing during recovery of consciousness in rats.

State-dependent neuronal firing patterns reflect changes in ongoing information processing and cortical function. A disruption of neuronal coordination has been suggested as the neural correlate of anesthesia. Here, we studied the temporal correlation patterns of ongoing spike activity, during a stepwise reduction of the volatile anesthetic desflurane, in the cerebral cortex of freely moving rats. We hypothesized that the recovery of consciousness from general anesthesia is accompanied by specific changes in the spatiotemporal pattern and correlation of neuronal activity. Sixty-four contact microelectrode arrays were chronically implanted in the primary visual cortex (contacts spanning 1.4-mm depth and 1.4-mm width) for recording of extracellular unit activity at four steady-state levels of anesthesia (8-2% desflurane) and wakefulness. Recovery of consciousness was defined as the regaining of the righting reflex (near 4%). High-intensity firing (HI) periods were segmented using a threshold (200-ms) representing the minimum in the neurons' bimodal interspike interval histogram under anesthesia. We found that the HI periods were highly fragmented in deep anesthesia and gradually transformed to a near-continuous firing pattern at wakefulness. As the anesthetic was withdrawn, HI periods became longer and increasingly correlated among the units both locally and across remote recording sites. Paradoxically, in 4 of 8 animals, HI correlation was also high at the deepest level of anesthesia (8%) when local field potentials (LFP) were burst-suppressed. We conclude that recovery from desflurane anesthesia is accompanied by a graded defragmentation of neuronal activity in the cerebral cortex. Hypersynchrony during deep anesthesia is an exception that occurs only with LFP burst suppression.

Ballistocardiogram artifact reduction in the simultaneous acquisition of auditory ERPS and fMRI.

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are now being combined to analyze brain function. Confounding the EEG signal acquired in the MR environment is a ballistocardiogram artifact (BA), which is predominantly caused by cardiac-related body movement. The objective of this study was to develop and evaluate a method for reducing these MR-induced artifacts to retrieve small auditory event-related potentials (ERPs) from EEG recorded during fMRI. An algorithm for BA reduction was developed that relies on timing information obtained from simultaneous electrocardiogram (ECG) recordings and subsequent creation of an adaptive BA template. The BA template is formed by median-filtering 10 consecutive BA events in the EEG signal. The continuously updated template is then subtracted from each BA in the EEG. The auditory ERPs are obtained through signal averaging of the remaining EEG signal. Experimental and simulated ERP data were estimated to assess effectiveness of the BA reduction. Simulation showed that the algorithm reduced BA without significantly altering the morphology of a signal periodically inserted in the EEG. Auditory ERP data, obtained in a 1.5-T scanner during a passive auditory oddball paradigm and processed with the BA reduction algorithm, were comparable to data recorded in a mock scanner outside the magnetic field with the same experimental paradigm. It is concluded that through adequate reduction of the BA, relatively small auditory ERPs can be acquired in the MR environment.

Halothane augments event-related gamma oscillations in rat visual cortex.

Cortical gamma oscillations have been associated with neural processes supporting cognition and the state of consciousness but the effect of general anesthesia on gamma oscillations is controversial. Here we studied the concentration-dependent effect of halothane on gamma (20-60 Hz) power of event-related potentials (ERP) in rat primary visual cortex. ERP to light flashes repeated at 5-s intervals was recorded with chronically implanted, bipolar, intracortical electrodes at selected steady-state halothane concentrations between 0 and 2%. gamma-Band power was calculated for 0-1000, 0-300 and 300-1000 ms poststimulus periods and corresponding prestimulus (PS) periods. Multitaper power spectral analysis was used to estimate gamma power from both single-trial and average ERP in order to differentiate between phase-locked (evoked) and non-phase-locked (induced) gamma activities. Significant PS gamma power was present at all halothane concentrations. Flash elicited an increase in gamma power that lasted up to 1 s poststimulus at all halothane concentrations. Halothane at intermediate concentrations (0.5-1.2%) augmented both PS and ERP gamma power two to four times relative to the waking baseline. gamma Power was not different between waking and deeply anesthetized (2%) levels. gamma Power reached maximum, as predicted by a Gaussian fit of power-concentration data, at halothane concentration (0.86%) similar to the concentration (0.73%) that abolished the righting reflex, a behavioral index of loss of consciousness. Evoked, i.e. stimulus-locked, gamma power was present during the first 300 ms poststimulus but not later, and was approximately 50% of single-trial ERP gamma power. Single-trial gamma power was present also at 300-1000 ms poststimulus, reflecting ERP not phase-locked to the stimulus. In summary, these observations suggest that (1) gamma activity is present in states ranging from waking to deep halothane anesthesia, (2) halothane does not prevent the transfer of visual input to striate cortex even at surgical plane of anesthesia, and (3) anesthetic-induced loss of consciousness, as reflected by the loss of righting reflex, is not correlated with a reduction in gamma power. Variance with other studies may be due to an underestimation of gamma power by ERP signal averaging as compared with single-trial analysis.

A syntactic methodology for automatic diagnosis by analysis of continuous time measurements using hierarchical signal representations.

In this paper, we present a methodology for automatic diagnosis of systems characterized by continuous signals. For each condition considered, the methodology requires the development of an alphabet of signal primitives, and a set of hierarchical fuzzy automatons (HFAs). Each alphabet is adaptively obtained by training an adaptive resonance theory (ART2) architecture with signal segments from a particular condition. Then, the original signal is transformed into a string of vectors of primitives, where each vector of primitives replaces a signal segment in the original signal. The string, in turn, is presented to the HFA characterizing that particular condition. Each set of HFA consists of a main automaton identifying the entire signal, and several sub-automata each identifying a particular significant structure in the signal. A transition in the main automaton occurs (i.e., the main automaton moves from one state to another) if the corresponding subautomaton recognizes a token where a token is a portion of the string of vectors of signal primitives with a significant structure. The fuzziness in automaton operation adds flexibility to the operation of the automaton, enabling the processing of imperfect input, allowing for toleration measurement noise and other ambiguities. The methodology is applied to the problem of automatic electrocardiogram diagnosis.

Analysis and use of FMRI response delays.

In this study, we implemented a new method for measuring the temporal delay of functional magnetic resonance imaging (fMRI) responses and then estimated the statistical distribution of response delays evoked by visual stimuli (checkered annuli) within and across voxels in human visual cortex. We assessed delay variability among different cortical sites and between parenchyma and blood vessels. Overall, 81% of all responsive voxels showed activation in phase with the stimulus while the remaining voxels showed antiphase, suppressive responses. Mean delays for activated and suppressed voxels were not significantly different (P < 0.001). Cortical flat maps showed that the pattern of activated and suppressed voxels was dynamically induced and depended on stimulus size. Mean delays for blood vessels were 0.7-2.4 sec longer than for parenchyma (P < 0.01). However, both parenchyma and blood vessels produced responses with long delays. We developed a model to identify and quantify different components contributing to variability in the empirical delay measurements. Within-voxel changes in delay over time were fully accounted for by the effects of empirically measured fMRI noise with virtually no measurable variability associated with the stimulus-induced response itself. Across voxels, as much as 47% of the delay variance was also the result of fMRI noise, with the remaining variance reflecting fixed differences in response delay among brain sites. In all cases, the contribution of fMRI noise to the delay variance depended on the noise power at the stimulus frequency. White noise models significantly underestimated the fMRI noise effects.

Frequency domain analysis of endocardial signals.

Frequency domain analysis, applied to atrial endocardial electrograms during atrial fibrillation, has been used to develop automated arrhythmia detection schemes for implantable devices and to investigate electrophysiologic mechanisms. Such analysis may be used to quantify both temporal and spatial organization during atrial fibrillation. Specifically, autopower spectra and coherence spectra reveal electrogram characteristics that are powerful in discriminating atrial fibrillation from sinus rhythm and regular atrial tachycardias. Furthermore, changes in spectral characteristics with drug administration reveal nonstationarities in spatial organization and in underlying electrophysiologic mechanism. The usefulness of frequency domain analysis in the study of atrial fibrillation is influenced by electrode configuration, the method of spectral estimation and other clinical variables.

Time-frequency coherence analysis of atrial fibrillation termination during procainamide administration.

A time-frequency coherence estimator is developed and applied to study changes in signal characteristics as atrial fibrillation converts to sinus rhythm during administration of procainamide. A coherence spectrogram (CS) using multiple sinusoidal tapers is used in this study to assess phase relations between electrogram recordings at multiple atrial sites of seven patients who received procainamide to terminate atrial fibrillation. CSs are calculated (0 to 60 Hz) with 1 sec time resolution and 6.2 Hz frequency resolution. In agreement with previous studies, CSs generally exhibit low coherence during atrial fibrillation. Conversion to sinus rhythm is concomitant with an increase in coherence and emergence of structured time-frequency topography. Transition from atrial fibrillation to sinus rhythm is associated with a variety of time-frequency dynamics. Both gradual and abrupt increases in coherence coincide with conversion. Results suggest transient electrical organization in the atria during atrial fibrillation not seen in previous low-resolution coherence studies. CSs permit investigation of rhythm organization with unparalleled time and frequency resolution and thus are useful for studying transient changes in cardiac rhythms that may reflect underlying mechanisms.

Observations from intraatrial recordings on the termination of electrically induced atrial fibrillation in humans.

BACKGROUND: The circulating wavelet hypothesis suggests that atrial fibrillation could terminate by either progressive fusion or simultaneous block of all wavelets. METHODS: Intraatrial recordings from the right atrial free wall were made during procainamide induced (n = 8) or spontaneous (n = 7) termination of electrically induced atrial fibrillation in 14 patients. Atrial rate, mean magnitude squared coherence, and direction of activation during sequential electrograms were measured. Rate and coherence were calculated from the earliest point within 5 minutes prior to termination as well as from the 4-second interval just prior to termination. RESULTS: Termination was directly to sinus rhythm (13 episodes) or to atrial flutter (2 episodes). For the eight procainamide induced terminations, rate decreased between the first measurement and the measurement just prior to termination, from 443 +/- 127 beats/min to 322 +/- 119 beats/min. For the seven spontaneous terminations, rate also decreased from 373 +/- 119 beats/min to 323 +/- 88 beats/min; however, a slight increase in atrial rate prior to termination was observed in three episodes. No specific patterns of atrial cycle lengths were seen during the final few seconds of fibrillation. No increase in coherence was observed. In seven episodes, recordings were made using orthogonal bipoles in the x, y, and z directions, allowing direction of activation of wavefronts to be measured. Three episodes showed multiple instances where direction of activation remained similar over several electrograms as we have previously reported for chronic fibrillation. However, no such instances precipitated termination in any of the seven episodes. CONCLUSIONS: Atrial fibrillation usually terminates directly to sinus rhythm and does so abruptly and without forewarning. While we and others have previously reported that the rate of atrial fibrillation decreases with procainamide infusion, a decrease in the rate of atrial fibrillation is not required for the rhythm to terminate and consequently may not be a part of the termination process at all. Coherence does not demonstrate a progressive increase in the organization of atrial fibrillation prior to termination. Lack of stabilization in the direction of activation of wavefronts in the final few seconds also fails to support fusion of wavefronts as the mechanism of termination of atrial fibrillation. Simultaneous block of all wavelets is consistent with, but not proven by, our observations.

Detection of changes in atrial endocardial activation with use of an orthogonal catheter.

The ability of a catheter with an orthogonal electrode configuration to sense differences in the direction of local atrial endocardial activation was tested in 18 consecutive patients with intact retrograde conduction. In all 18, discrimination of anterograde from retrograde conduction at a single atrial site was examined; in 5 of the 18, multiple sites were examined to determine if the discriminatory ability of the catheter was site dependent. The catheter was specially designed with bipoles in the x, y and z directions. A vector was computed for each electrogram during anterograde and retrograde conduction. Electrogram amplitude along the standard bipole was also compared for anterograde and retrograde conduction. Mean electrogram amplitude for the standard bipole was significantly different for anterograde than for retrograde conduction in 17 of 18 patients (mean +/- SD 4 +/- 1.9 vs. 2.7 +/- 1.3 mV; p less than 0.005), with complete separation of amplitude distributions in 4 patients. The electrogram vector during anterograde conduction was significantly different from that during retrograde conduction in all 18 patients (p less than 0.0001), with complete separation of vector distributions in 14. In some patients with multiple site recordings, the choice of site greatly affected separation based on electrogram amplitude or vector, or both. The orthogonal catheter can be used to sense directional differences in local endocardial activation. The catheter shows promise for discriminating anterograde from retrograde conduction and examining the direction of endocardial activation in the heart during an electrophysiologic examination.

Differentiation of ventricular tachyarrhythmias.

Implantable devices capable of several modes of therapy will require differentiation of various ventricular tachyarrhythmias. Three methods of arrhythmia analysis, magnitude-squared coherence, ventricular rate, and irregularity of cycle length were performed for 45 episodes of induced ventricular tachyarrhythmia in 15 patients. Differentiation of monomorphic ventricular tachycardia from polymorphic ventricular tachycardia and ventricular fibrillation was possible by mean magnitude-squared coherence, less possible by rate, and not possible by beat-to-beat irregularity. Faster monomorphic ventricular tachycardia overlapped with rates of polymorphic ventricular tachycardia and ventricular fibrillation. Differentiation of polymorphic ventricular tachycardia and ventricular fibrillation was not possible by rate or irregularity. A progressive decrease in mean magnitude-squared coherence from monomorphic ventricular tachycardia to polymorphic ventricular tachycardia to ventricular fibrillation strengthens previous observations that coherence is a measure of rhythm "organization."

Effect of bipole configuration on atrial electrograms during atrial fibrillation.

Despite an increasing body of work on the nature of fibrillatory rhythms, and the application of different bipole configurations in antifibrillatory devices, little published work has assessed the effect of bipole configuration on the endocardial recordings of fibrillatory rhythms. To address this issue, a specially designed 6 Fr decapolar catheter was used to record intra-atrial electrograms during sustained atrial fibrillation in 15 patients. Simultaneous filtered (30-500 Hz) and unfiltered (0.05-5,000 Hz) recordings of atrial fibrillation were performed of four different bipole configurations: (a) 1-mm interelectrode spacing adjacent to the atrial wall; (b) 10-mm interelectrode spacing adjacent to the atrial wall; (c) 10-mm inter-electrode spacing 24 mm from the distal catheter tip; (d) 1-mm interelectrode spacing 24 mm from the distal catheter tip. One minute of such data was recorded, and each 4.27-second segment (x 14 segments) was analyzed for atrial rate, electrogram amplitude, amplitude probability density function (apdf), median frequency in the 2-9 Hz band, and electrogram morphology. Changes in bipole configuration resulted in profound changes in calculated atrial rate, amplitude, and apdf (P less than 0.001 by two-way ANOVA in each instance). Specifically, closer interbipole spacing and closer proximity to the atrial wall resulted in lower calculated atrial rates, higher electrogram amplitudes, and higher apdf values. In contrast, median frequency proved to be a more robust measure despite multiple configurations (P greater than 0.10 by two-way ANOVA). These changes significantly affected the predictive value of previously published detection criteria for rate (P less than 0.01) and apdf (P less than 0.00001). Bipole location also affected morphology, with locations adjacent to the atrial wall and with closer interbipole spacing having more discrete electrograms and greater apparent organization (P less than 0.0001). Further, when data segments from all patients and bipole configurations were grouped, rate and apdf were found to be strongly inversely correlated (r = -0.808). (r = -0.808).(ABSTRACT TRUNCATED AT 400 WORDS)

Measuring the organization of cardiac rhythms using the magnitude-squared coherence function.

The application of the magnitude-squared coherence (MSC) spectrum as a measure of the degree of organization of the cardiac electrical activity is explored. The MSC spectrum is a frequency-domain measure of the linear relationship between two signals. In the work described the two signals are two bipolar electrograms from either acutely placed catheter(s) or automatic implantable cardioverter/defibrillator electrodes. It is shown that the MSC is a dimensionless (no units), real-valued spectrum that is always in the range of zero to unity. The case of zero is found at frequencies where there is no linear relationship between the signals, and the case of unity implies a linear, noise-free relationship. The way the MSC spectrum is normalized makes it insensitive to gain or gain differences between the two signals. Example MSC spectra are presented and discussed. Striking differences in the spectra for fibrillatory and nonfibrillatory rhythms are seen.

The coherence spectrum. A quantitative discriminator of fibrillatory and nonfibrillatory cardiac rhythms.

Previous work has suggested that a comparison of electrograms from two or more sites may best differentiate fibrillatory from nonfibrillatory rhythms. The coherence spectrum is a measure by which two signals may be compared quantitatively in the frequency domain. In the present study, the coherence spectrum was used to quantify the relation between spectral components of electrograms from two sites in either the atrium or ventricle during both fibrillatory and nonfibrillatory rhythms. Bipolar recordings of 35 rhythms from 20 patients were analyzed for coherence in the 1-59 Hz band. The 17 nonfibrillatory rhythms were sinus rhythm (six), paroxysmal supraventricular tachycardia (two), atrial flutter (four), and monomorphic ventricular tachycardia (five). The 18 fibrillatory rhythms were atrial fibrillation (12) and ventricular fibrillation (six). Nonfibrillatory rhythms exhibited moderate-to-high levels of coherence throughout the 1-59 Hz band, with peaks concentrated at the rhythm's fundamental frequency and its harmonics. Fibrillatory rhythms exhibited little coherence throughout the 1-59 Hz band, and harmonics were not evident. The mean magnitude-squared coherence (scale of 0 to 1) for the 1-59 Hz band ranged from 0.22 to 0.86 (mean +/- SD, 0.52 +/- 0.19) for nonfibrillatory rhythms and from 0.042 to 0.12 (0.067 +/- 0.021) for fibrillatory rhythms. Separation of fibrillatory and nonfibrillatory rhythms was possible whether signals were recorded by floating or fixed-electrode configurations. These findings indicate that comparison of two electrograms with magnitude-squared coherence measurements differentiates fibrillatory from nonfibrillatory rhythms. A recognition algorithm based on coherence spectra may provide a major variations in lead configuration.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of procainamide on intra-atrial [corrected] electrograms during atrial fibrillation: implications [corrected] for detection algorithms.

The effects of antiarrhythmic drugs on electrograms have implications for arrhythmia-detection algorithms in implantable antitachycardia devices. Filtered and unfiltered intra-atrial electrograms were analyzed in eight patients who received procainamide (50 mg/min iv, up to 1000 mg) during 11 episodes of atrial fibrillation. Continuous recordings were made before, during, and after the infusion. The recordings were digitized, divided into 4.27 sec segments, and analyzed for atrial rate, median frequency and amplitude probability density function. Significant differences were noted before and after infusion of procainamide for atrial rate (498 +/- 97 vs 356 +/- 146 beats/min; p less than .005), median frequency (5.50 +/- 1.22 vs 4.24 +/- 0.99 Hz; p less than .0005), and density (58.3 +/- 13.9% vs 69.1 +/- 15.0%; p less than .005). Pre- and postprocainamide values were compared with published criteria for detection of atrial fibrillation. Before procainamide, only 2.3%, 5.7%, and 3.4% of the data segments failed to meet criteria for atrial fibrillation by rate, frequency content, and density, respectively. In contrast, after procainamide, 50%, 36.4%, and 28.4% of the data segments failed to meet these same criteria, despite electrograms still meeting morphologic criteria for atrial fibrillation. Thus procainamide resulted in changes sufficient to cause failure of published criteria for detection of atrial fibrillation. These findings have broad implications for the function of antitachycardia devices in patients receiving antiarrhythmic drug therapy.