Improved method for computation of potentials in a realistic head shape model.

The Lead Field Analysis (LFA) algorithm, a new computational technique for the calculation of potentials on the surface of a realistic head shaped volume conductor model based on the Boundary Element Method and the Reciprocity Theorem, is presented. The new algorithm, in comparison to the Standard Boundary Element Method, offers improved computational efficiency and lower storage requirements. It also yields more accurate surface potential results in the face of varying dipole source locations for a head shape Boundary Element model with a given number of nodes. Additionally, the algorithm results in quasi-analytic expressions of the derivatives of the surface potential with respect to the location of the sources, allowing the use of optimization techniques with better convergence properties. A set of simulations demonstrating the increased robustness of the LFA Algorithm in the face of varying dipole source parameters is also described.

Multiple-generator errors are unavoidable under model misspecification.

Model misspecification poses a major problem for dipole source localization (DSL) because it causes insidious multiple-generator errors (MulGenErrs) to occur in the fitted dipole parameters. This paper describes how and why this occurs, based upon simple algebraic considerations. MulGenErrs must occur, to some degree, in any DSL analysis of real data because there is model misspecification and mathematically the equations used for the simultaneously active generators must be of a different form than the equations for each generator active alone.

DSL and MUSIC under model misspecification and noise-conditions.

The concepts of both the traditional DSL (Dipole Source Localization) and MUSIC (MUltiple SIgnal Classification) are explained using simple vectors. DSL and MUSIC differ in the way the weighting functions are found. In both DSL and MUSIC, the fitted generator magnitudes are found by projecting the recorded potential map onto the fitted weighting functions, and the model transfers the weighting functions into generator locations/orientations. Both DSL and MUSIC will cause errors in the fitted dipole parameters when there is model misspecification, noise, or both. Therefore, an accurate head model is essential for either method to give reliable results.

Model misspecification detection by means of multiple generator errors, using the observed potential map.

Due to model misspecification, currently-used Dipole Source Localization (DSL) methods may contain Multiple-Generator Errors (MulGenErrs) when fitting simultaneously-active dipoles. The size of the MulGenErr is a function of both the model used, and the dipole parameters, including the dipoles' waveforms (time-varying magnitudes). For a given fitting model, by examining the variation of the MulGenErrs (or the fit parameters) under different waveforms for the same generating-dipoles, the accuracy of the fitting model for this set of dipoles can be determined. This method of testing model misspecification can be applied to evoked potential maps even when the parameters of the generating-dipoles are unknown. The dipole parameters fitted in a model should only be accepted if the model can be shown to be sufficiently accurate.

Insidious errors in dipole parameters due to shell model misspecification using multiple time-points.

Insidious errors in dipole modeling due to shell model misspecification in a spherical model were examined analyzing multiple time-points using the constraints of a commonly-used DSL (Dipole Source Localization) method. The computer simulation examined the differences in the fit dipole parameters for the same generator under two circumstances: 1) when computed as a single dipole active alone, and 2) when computed as a member of a simultaneously-active dipole pair. The computations were done using a simplification by which the dipole parameters computed from multiple time-points can be correctly assessed by computing dipole parameters at only two virtual time-points. Using multiple time-points in the DSL generally resulted in less error than if only a single time-point was used. However, how much improvement cna be achieved by using multiple time-points, as compared with a single time-point, is a function of many factors, such as the location and orientation of the dipoles, and the relative magnitudes and overlap of the waveforms (i.e., time-varying magnitudes) of the dipoles, as well as the model used in the fitting. Further, it was shown that it is incorrect to assume that a multiple-time-point DSL will compute a zero magnitude for generators during quiescent intervals. Additionally, it was shown that a "correction" to reduce error for one pair of waveforms will not be applicable to other waveforms. Also, even if location errors are eliminated, magnitude and orientation errors can still be shown to be present. Finally, iterative reduction of the least-square error between the observed and predicted surface maps leads to increasing errors in dipole parameters. We conclude that a DSL with model misspecification can contain insidious (undetectable) errors.

Exposure to blood-containing aerosols in the operating room: a preliminary study.

A personal sampling study was conducted to assess exposure to blood aerosols in the operating room. The breathing zones of primary and assistant surgeons were monitored using a personal cascade impactor configured with three stages corresponding to effective cut-off aerodynamic diameters of 14.8 microns, 3.5 microns, and 0.52 microns, respectively. Hemastix was used to assess the hemoglobin content of each particle size fraction. The arithmetic mean exposure concentration for primary surgeons (n = 14) was 1.4 micrograms Hb/m3 (range, none detected to 7.4 micrograms Hb/m3), while that for assistant surgeons (n = 12) was 1.8 micrograms Hb/m3 (range, 0.3 to 4.8 micrograms Hb/m3). Hemoglobin was detected in Stage 2 in 26 (90%) of the samples, in Stage 5 in 19 (66%) of the samples, and in Stage 8 in 11 (38%) of the samples. These data show that the mucous membrane lining of the upper respiratory tract and alveolar macrophages in the gas-exchange region are likely to be exposed to aerosolized blood in the operating room. Until further research determines the potential of infected blood aerosols to transmit disease, the authors recommend the proper use of respiratory protection equipment instead of surgical masks because the latter do not offer adequate protection.

Far-field potentials.

Far-field potentials are produced by neural generators located at a distance from the recording electrodes. These potentials were initially characterized incorrectly as being of positive polarity, widespread distribution, and constant latency; however, recent advances have clearly demonstrated that far-field potentials may be either positive or negative depending upon the location of the electrodes with respect to the orientation of the dipole generator. Additionally, peak latencies in the far-field can vary with alterations in body position and the spatial distribution of far-field potentials, while widespread, is not uniform. Recent studies of far-field potentials suggest how such waveforms are produced when the symmetry of an action potential, as recorded by distant electrodes, is broken by such factors as differing conductivities of volume conductor compartments, direction of action potential propagation, size differentials in adjoining body segments, or the termination of action potential propagation in excitable tissue. Human, animal, and computer experiments support the preceding generalizations. These new explanations are directly applicable to such far-field potentials as the short latency somatosensory-evoked potential. Furthermore, since far-field potentials can also occur in muscle tissue, one should expect that these generalizations will hold with respect to electromyographic potentials.

Insidious errors in dipole localization parameters at a single time-point due to model misspecification of number of shells.

Insidious errors (unexpected and difficult-to-detect under usual conditions) were found using a single time-point dipole localization method, when two dipoles were simultaneously active and there was misspecification of the number of shells (usually intended to mimic the conductivity differences of the brain, skull, and scalp). The errors involved all dipole parameters (i.e., location, orientation, and magnitude). Potentials at 65 "electrode" locations on the surface of a 3-shell sphere were computed for dipoles of known location, orientation, and magnitude. These "maps" were then used to compute the best-least-squares-fit of the surface potentials based upon dipole parameters in a 1-shell sphere when either one or two dipoles were active. The dipole parameters were often significantly different when computed with two equal-magnitude dipoles active, compared with only one dipole, with location errors of 0-36 mm, orientation errors of 0-63 degrees, and magnitude errors of 2-98%. When the two dipole magnitudes were not the same, the errors in the computed dipole parameters were even larger. All these errors occurred when the LSE (least-square-error) was small and at or near minimum. Moreover, location errors increased as LSE decreased over iterations. These errors generally occur because the fitted dipole parameters under different potential maps do not obey the superposition law when there is shell model misspecification, which is also the reason that presently used "correction" methods cannot satisfactorily remove these errors from the analyses. This problem must be dealt with when analyzing evoked response "maps" from simultaneously active generators, if correspondence to anatomy and physiology is desired.

Blood-containing aerosols generated by surgical techniques: a possible infectious hazard.

The aerosols generated in an operating room during surgery were simulated in the laboratory by using a variety of common surgical power tools. A Stryker bone saw, a Hall drill, and a Shea drill were used on bone, and a Bovie electrocautery was used in both the cutting and coagulation modes on tendon, all in the presence of a thin film of blood. A 10-stage, low-pressure cascade impactor was used to determine the particle size distribution of each aerosol, and Hemastix was used to assess the hemoglobin content of each particle size fraction. The same assessment was done for another series of blood aerosols that had previously shown the ability to infect human T-cell cultures. All of the tools tested produced blood-containing aerosol particles in the respirable size range (less than 5 microns). Because surgical masks offer little protection against such particles, personal sampling is indicated to define the risk of exposure to bloodborne pathogens by this route.

A double-blind study of symptom provocation to determine food sensitivity.

BACKGROUND: Some claim that food sensitivities can best be identified by intradermal injection of extracts of the suspected allergens to reproduce the associated symptoms. A different dose of an offending allergen is thought to "neutralize" the reaction. METHODS: To assess the validity of symptom provocation, we performed a double-blind study that was carried out in the offices of seven physicians who were proponents of this technique and experienced in its use. Eighteen patients were tested in 20 sessions (two patients were tested twice) by the same technician, using the same extracts (at the same dilutions with the same saline diluent) as those previously thought to provoke symptoms during unblinded testing. At each session three injections of extract and nine of diluent were given in random sequence. The symptoms evaluated included nasal stuffiness, dry mouth, nausea, fatigue, headache, and feelings of disorientation or depression. No patient had a history of asthma or anaphylaxis. RESULTS: The responses of the patients to the active and control injections were indistinguishable, as was the incidence of positive responses: 27 percent of the active injections (16 of 60) were judged by the patients to be the active substance, as were 24 percent of the control injections (44 of 180). Neutralizing doses given by some of the physicians to treat the symptoms after a response were equally efficacious whether the injection was of the suspected allergen or saline. The rate of judging injections as active remained relatively constant within the experimental sessions, with no major change in the response rate due to neutralization or habituation. CONCLUSIONS: When the provocation of symptoms to identify food sensitivities is evaluated under double-blind conditions, this type of testing, as well as the treatments based on "neutralizing" such reactions, appears to lack scientific validity. The frequency of positive responses to the injected extracts appears to be the result of suggestion and chance.

Far-field potentials generated by action potentials of isolated frog sciatic nerves in a spherical volume.

Previous results in cylindrical volumes have shown that action potentials generate far-field potentials when experimental conditions are such that quadrupolar components of the action potential are reduced to an equivalent dipole. We now show that the same conclusions are also reached within a spherical volume, again recording far-field potentials from isolated bullfrog nerves. A mathematical proof is given that shows that in a sphere, antipodal electrodes primarily detect far-field potentials from dipole generators and not quadrupole generators. A revised conception of the 'far-field' in evoked responses is discussed which equates far-field recordings with dipole detection.

Autonomic components of the human pupillary light reflex.

To investigate the autonomic components of the pupillary light reflex in humans, we used infrared pupillometry combined with a partial local cholinergic (tropicamide) or alpha-adrenergic (thymoxamine) blockade. The pupillary response curve was analyzed using parameters identical or similar to those employed previously to study the autonomic components of the pupillary light reflex. Tropicamide increased baseline pupil area and affected five of the eight measured parameters. Thymoxamine lowered baseline pupil area but did not affect any of the parameters. We found the expected cholinergic contribution to the constrictive phase of the pupillary light reflex but no evidence for peripheral alpha-adrenergic activity during redilation. We propose that redilation primarily involves parasympathetic relaxation, modulated by cholinergic inhibition of the dilator muscle and central sympathetic inhibition of the Edinger-Westphal nucleus.

Far-field potentials recorded from action potentials and from a tripole in a hemicylindrical volume.

There is growing evidence in support of the hypothesis that far-field potentials are recorded when action potentials encounter discontinuities in the surrounding volume. The present study found further support for this hypothesis using two methods of experimentation. The first method recorded potentials when the action potential from an isolated bullfrog sciatic nerve in a hemicylindrical volume (i) encountered a change in the shape of the surrounding volume, (ii) crossed a boundary between 2 volumes of differing resistivities, (iii) reached a bend in the nerve, or (iv) reached the functional end of the nerve. In the second method, potentials were recorded when an electrical tripole, constructed in a way to produce the electrical equivalent of an action potential, encountered the same discontinuities as well as when it was configured to simulate a curved nerve. These results are consistent with the hypothesis that dipole components of an action potential predominant in far-field recordings.

Far-field potentials due to action potentials traversing curved nerves, reaching cut nerve ends, and crossing boundaries between cylindrical volumes.

A previously published computer simulation was tested in a biological preparation by recording action potentials from frog sciatic nerves within a volume conductor filled with Ringer's solution. Traveling in a straight line, nerve action potentials traversed a constricted cylinder before crossing into a larger, hemicylindrical volume. Recordings from widely spaced electrodes in the larger volume demonstrated a potential associated with the action potential crossing the boundary between the two volumes. Another potential was associated with the action potential reaching the nerve's cut end. These potentials did not diminish in amplitude with increasing distance from the source. In other recordings, a potential associated with a bend in the nerve was found which was dependent upon the angle of the bend. These results indicate that the simple model of a dipole in a bounded sphere in which potentials decrease as a function of distance from the generator does not explain all potentials that can be observed under conditions that approximate human and animal recordings.