Thresholds of microwave-evoked warmth sensations in human skin.

We measured thresholds for microwave-evoked skin sensations of warmth at frequencies of 2.45, 7.5, 10, 35, and 94 GHz. In the same subjects, thresholds of warmth evoked by infrared radiation (IR) were also measured for comparison. Detection thresholds were measured on the skin in the middle of the back in 15 adult male human subjects at all microwave (MW) frequencies and with IR. Long duration (10-s), large area (327-cm2) stimuli were used to minimize any differential effects of temporal or spatial summation. Sensitivity increased monotonically with frequency throughout the range of microwave frequencies tested. The threshold at 94 GHz (4.5 +/- 0.6 mW/cm2) was more than an order of magnitude less than at 2.45 GHz (63.1 +/- 6.7 mW/cm2), and it was comparable to the threshold for IR (5.34 +/- 1.07 mW/cm2).

Lack of behavioral effects in non-human primates after exposure to ultrawideband electromagnetic radiation in the microwave frequency range.

The effect of acute exposure to ultrawideband (UWB) electromagnetic radiation on the Primate Equilibrium Platform (PEP) task, where the monkey's task is to manipulate a joystick control to compensate for the random perturbations in the pitch plane that are generated by a computer at unpredictable intervals, was examined. The duration of the UWB exposure was 2 min at a pulse repetition rate of 60 Hz (total of 7200 pulses). The bandwidth of the pulse was 100 MHz to 1.5 GHz (peak power between 250-500 MHz) with a peak E-field strength of 250 kV/m. Each monkey was exposed twice. The interval between exposures was 6 days. The exposure to UWB electromagnetic radiation had no effect on PEP performance when tested immediately after exposure.

No detectable bioeffects following acute exposure to high peak power ultra-wide band electromagnetic radiation in rats.

A wide range assessment of the possible bioeffects of an acute exposure to high peak power ultra-wide band (UWB) electromagnetic radiation was performed in rats. The UWB-exposure consisted of 2 min of pulsed (frequency: 60 Hz, pulse width: 5-10 ns) UWB (bandwidth: 0.25-2.50 GHz) electromagnetic radiation. Rats were examined using one of the following: 1) a functional observational battery (FOB); 2) a swimming performance test; 3) a complete panel of blood chemistries; or 4) determination of the expression of the c-fos protein in immunohistologically-stained sections of the brain. No significant differences were found between UWB- or sham-exposed rats on any of the measured parameters.

A possible feline model for human blepharospasm.

'Benign essential blepharospasm' is a human eyelid disorder of unknown aetiology characterized by involuntary, bilateral, and disabling spasmodic contracture of the orbicularis oculi muscle. Treatments are frequently disappointing. Here we report what might be a first step toward developing an animal model for exploring mechanisms of the disorder and potential treatments. We surgically implanted stimulating electrodes into brain areas known to supply input to the lateral division of the facial nerve nucleus to induce blinking by electrical stimulation. Single-pulse stimuli at or near the facial, parabrachial, red, and interstitial nuclei produced consistent stimulus-induced eyelid contractions. Responses were ipsilateral to stimulation, except for the interstitial nucleus where contralateral responses occurred. Little or no other movements of the face, head, or body occurred at eye-blink threshold voltages. When these sites were stimulated with pulse trains, eyelid closures followed stimulus frequency and tended to fuse into constant closure. Thresholds at each stimulus site remained constant during three days of testing. Drug treatments produced no consistent effect on eye-blink threshold from any stimulation site, even when general behaviour was affected. We conclude that these input pathways to the facial nucleus may contribute to blepharospasm and that future neurochemical and electrophysiological study of these pathways may produce a suitable animal model for understanding this disorder.

Innervation of the feline eyelids.

The innervation of the eyelids is incompletely understood. This is a particular problem for those who wish to develop animal models of eyelid dysfunction in humans. Blepharospasm, for example, is a disease of uncontrolled eyelid spasm that is difficult to manage clinically because the aetiology is not understood. The anatomical literature on eyelid innervation is sparse and even conflicting. We attempted to study eyelid innervation, both sensory and motor, with injection of horseradish peroxidase (HRP) into the superior eyelid, inferior eyelid, and bulbar conjunctiva. We used 13 anesthetized weanling cats. Shape and structure of the facial nucleus varied along its rostrocaudal extent, but there was a clear demarcation of lateral and medial division. HRP-filled facial nucleus cells were ipsilateral to the injection site, and label appeared throughout the rostrocaudal length. All injection sites, including bulbar conjunctiva, labelled facial nucleus neurons located with overlapping distribution, predominantly in the dorsal part of the lateral division. Likewise, heavy labelling occurred throughout the entire ipsilateral cranial cervical ganglion and the trigeminal ganglion in all kittens. Injection of upper or lower eyelids caused some labelling in the second through the fourth cervical spinal ganglia.

An applied model for the evaluation of multiple physiological stressors.

In everyday life, a human is likely to be exposed to the combined effects of a number of different stressors simultaneously. Consequently, if an applied model is to ultimately provide the best 'fit' between the modeling and modeled phenomena, it must be able to accommodate the evaluation of multiple stressors. Therefore, a multidimensional, primate model is described that can fully accommodate a large number of conceivably stressful, real life scenarios that may be encountered by civilian or military workers. A number of physiological measurements were made in female rhesus monkeys in order to validate the model against previous reports. These evaluations were further expanded to include the experimental perturbation of physical work (exercise). Physiological profiles during activity were extended with the incorporation of radio telemetry. In conclusion, this model allows maximal extrapolation of the potential deleterious or ergogenic effects on systemic physiological function under conditions of realistic operational demands and environments.

Electrographic recording from bovine vomeronasal capsule under spontaneous and stimulated conditions.

The vomeronasal organ ( VNO ) is an accessory olfactory system which in many vertebrates seems to be involved in reproductive behavior, particularly in permitting males to detect estrus in conspecific females. We postulated that EEG-like field potentials could be recorded from the VNO because the organ has a sensory epithelium that can discharge in response to odorants, and because VNO receptor cells are structurally similar to cells in the olfactory mucosa that produce field potentials (the "electro- olfactogram "). We examined this postulate in male cattle by surgically implanting recording/perfusion cannulae into the ducts leading to each VNO . Both bipolar (between VNOs ) and reference recording revealed continuous spontaneous voltage fluctuations that were similar to an EEG, except that amplitudes were larger and frequencies slower. Simultaneous recording of the EEG and VNO , using the same nasal reference electrode revealed that neither signal was "contaminated" by voltages from the other. Perfusions of one VNO with whole urine, urine condensate, or aqueous reconstituted urine extracts, whether from females in estrus or in anestrus, produced massive transient electrical responses from both VNOs . Perfusion with penicillin or local anesthetics caused more sustained large electrical responses from both VNOs , except that activity became quiescent about 15 min after local anesthesia. These results suggest that it is feasible to use direct recording of VNO responses to stimulation to investigate the behavioral physiology of the VNO .(ABSTRACT TRUNCATED AT 250 WORDS)

What is the meaningful measure of neuronal spike train activity?

Neuronal spike train activity is conventionally viewed in terms of certain measures of central tendency (mean or median of intervals between discrete events or mean rate of such events) and their associated measures of variability (S.D., skew, etc.). Less commonly, investigators will compute the probabilities of occurrence in an Information Theory context. Another rarely considered measure of spike trains is serial ordering. Seldom is more than one of these approaches applied to the same spike train, and we are unaware of any case where all 3 have been applied to the same train. In order to test the inter-relationships among these approaches, we examined the same spike trains with all 3 analytic methods. Measures of central tendency were taken from the original absolute interval values, whereas entropy and serial order (Markov order) were computed from the sequences of patterns of adjacent intervals, expressed in the same non-parametric format. We found that entropy (measure of uncertainty) did not correlate well with the degree of serial ordering (Markov order). Entropy also did not correlate well with measures of central tendency (median or mean interval, or impulses/s) nor with the variability of such measures. An inverse correlation was seen between Markov order and several measures of central tendency (mean interval and rate) as well as with several measures of variability. The implications of these analyses extend beyond the analysis of spike trains to most all biological and physical time series. For neurophysiologists, these analyses may challenge our common assumptions about the most appropriate way to describe and interpret neuronal spike train activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of large doses of ethanol to eliminate Markovian serial dependencies in neuronal spike train intervals.

The effect of drug-induced state changes on serial ordering of interaction potential intervals was evaluated by determining if the intervals were generated by a Markov process, and if they were, determining the Markov level (the degree of serial ordering) of the process before and after the injection of an intoxicating dose of ethanol. When categorizing intervals as short, medium, or long, a Markov process of level 4 (i.e., the process has a "memory" for 4 preceding adjacent intervals) was noted for most neurons; this level of serial ordering remained constant after ethanol injections. Many of the specific clusters that made the major contributions to the statistical significance before ethanol did not contribute after ethanol and a new set of clusters made the major contribution. This suggests that neurons may process intervals as "clusters" and the "cluster-length" may be a basic function of the neuron and not dependent on the general state of the organism. This methodology allows us to determine the "cluster-length" of the processor and detect and isolate the specific "clusters" that may be important state-sensitive "information carriers" (signal) in the nervous system.

Divergence from statistical independence in specified clusters of adjacent neuronal spike train intervals before and after ethanol state changes.

In order to test the influence of drug-induced state changes on serial ordering of interaction potential intervals, we evaluated divergence from statistical independence of specific "clusters" of various numbers of adjacent intervals. Such divergence, which was highly significant statistically, was noted using two different methods, one based on relative interval duration, and the other based on categorizing intervals as to short, medium, or long. Before ethanol, significant divergence was seen for clusters of as many as 5-6 adjacent intervals, and this same degree of serial ordering was seen after ethanol. While the apparent cluster length remained unchanged by ethanol, the specific clusters which contributed most to the statistical significance, were generally not the same after ethanol. This suggests that neurons process intervals as "clusters" of a given length but that specific "clusters" may be important "information carriers" in the nervous system. The methodology outlined herein may allow us to identify these important "clusters."

The pharmacological effects of the ligroin extract of nutmeg (Myristica fragrans).

A ligroin extract of nutmeg (Myristica fragrans) caused a significant increase in the duration of light and deep sleep in the young chicken. The presence of trimyristin tended to increase the effect of the extract. The extract did not contain detectable amounts of myristicin, elemicin, safrole, or eugenol, which either individually or collectively have been suggested to be the active agent of nutmeg.

Serial dependencies and Markov properties of neuronal interspike intervals from rat cerebellum.

Using three different approaches, each with different theoretical assumptions, we showed that mammalian neuronal spike trains contain serial ordering. We demonstrated that: (1) when intervals are categorized according to whether their durations are short, medium, or long, sequential groupings of adjacent interval categories exhibit Markov dependencies, extending to at least the 4th order; (2) the observed incidence of specified patterns of these groups of adjacent interval categories differs from the independent case, based on Chi square goodness-of-fit tests, and by using similar procedures; (3) there is divergence from independence when adjacent interval patterns are described in terms of relative lengths of adjacent intervals. The statistical indicators of serial dependence were significantly greater when applied to the original data than when applied to the same data after shuffling. Each of these approaches leads to the notion that "information" is carried in clusters of adjacent intervals ("bytes" or "words") and moreover, we can identify which specific patterns of interspike intervals contribute most to the statistical significance (i.e., those clusters that are potential candidates for "information carriers"). In most of the ten neurons, the "memory" of the system appears to be at least 36--45 msecs.

Do neurons process information by relative intervals in spike trains?

We suggest the possibility that neurons process information in terms of the relative duration of clusters of adjacent and successive inter-action potential intervals ("bytes" of intervals). If this concept is plausible, as is supported by research from several laboratories which have specifically addressed this possibility, one should be able to see evidence for such patterning in the published illustrations from studies in which this concept was not considered. We present some of this evidence here, along with some illustrations from the original publications. Byte patterns are evident in these examples, even though they went unrecognized by authors and readers alike. It is true that interval patterns are not obvious in all published illustrations of spike trains, and we suggest that this can be explained by one or more of the following: (1) some neurons may operate with an interval-pattern code while others do not, (2) a given neuron may use an interval-pattern code only under certain conditions, and (3) even when such a code exists, it may be difficult to detect for identifiable technical reasons. Therefore, we believe that the relative-internal-pattern concept is a valid scientific hypothesis which merits specific testing of its validity and range of applicability.

Structures of the bovine vomeronasal complex and its relationships to the palate: tongue manipulation.

The rostral part of the bovine vomeronasal complex was examined to determine its relation structures of the palate which are compressed by the tongue during investigative sexual behavior. The rostral vomeronasal cartilage (VNC) is C-shaped and contains the incisive duct (ID). The hilus of the cartilage is directed medially, approximately 0.5 cm dorsal to the palate. Just caudal to the origin of the vomeronasal duct, the VCN lies approximately 1 cm above the palate with a ventrally oriented hilus containing the ID. Further caudally, the hilus is directed laterally, toward the nasal cavity. Palatal mucosa occupies the intervomeronasal, cartilaginous area below the nasal septum and caudal to the incisive papilla. This mucosa and the ID appear to be compressed by the bull's everted tongue, forcing fluid samples into the vomeronasal system.

Entropy as an index of the informational state of neurons.

Techniques were developed for using the classical information theory descriptor, entropy, to quantify the "uncertainty" present in neuronal spike trains. Entropy was calculated on the basis of a method that describes the relative relationships of serially ordered interspike intervals by encoding the intervals as a series of symbols, each of which depicts the relative duration of two adjacent spike intervals. Each symbol, or set of symbols has a specific fractional entropy value, derived from its probability of occurrence; moreover, fractional entropy can describe the relative amount of "information" that is associated with the relative location of a given symbol in a string of symbols. Using spike trains from 12 single neurons in the cerebellar cortex of rats, we determined: (1) the mean and S.D. of information content of each symbol in each specific position in a group of symbols (2-4 symbols/group, based on 3-5 adjacent intervals), (2) the 4-symbol groups which had the least and the most average fractional entropy, (3) that the 4-symbol groups with both low and high fractional entropy had significant positive correlations with the probability of occurrence of those groups after a drug treatment (ethanol), and (4) that the degree of drug-induced change in the incidence of both low- and high-fractional entropy groups did not correlate with predrug entropy. Thus, the entropy of clusters of 3-5 adjacent spike intervals, when computed in this particular way, seems to be a useful measure or index of the informational state of neurons.

Entropy measures of signal in the presence of noise: evidence for 'byte' versus 'bit' processing in the nervous system.

A method for detecting signal in the presence of noise in a highly specific way is described. Using action potential interval data from 12 neurons in rat cerebellum, we have demonstrated that the sequential ordering of spike intervals contains both noise and signal. We have identified and quantified the magnitude of relative entropy (uncertainty) of specified sets of interval patterns, ranging in length from 3-5 successive intervals. Some of these sets have exceptionally low entropy and thus seem to be especially meaningful as a set ('word') to the brain.

Serial ordering in spike trains: what's it "trying to tell us"?

Summarized herein is the evidence that supports the hypothesis that neuronal action potentials (spike trains) are coded not only in terms of simple discharge rate but also can be serially coded by certain patterns of spike intervals. Based on the relative interval description method of Sherry and Marczynski (1972), our analyses of single-unit activity from cerebellar cortex neurons of rats seem to support three principal categories of conclusions; (1) Serial dependence of intervals does exist. This has been demonstrated with a variety of conventional statistical tests. These serial dependencies have also been shown to be independent of the (nonsequential) interval distribution variability. (2) Information theory is appropriate for evaluating spike trains. We have developed and tested methods for computing a fractional entropy for a given number of adjacent intervals, for assessing the relative fractional entropy of any one interval in a set of intervals, for computing for a group of neurons the mean and standard deviation of fractional entropy for specified clusters or intervals, and for transforming these values so that interval clusters of differing number can all be compared on the same numerical entropy scale (percentage maximum fractional entropy). In addition to the descriptive and quantitative value of such measures, we have also demonstrated their utility in testing hypotheses and in making empirical correlations. (3) The nervous system seems to process spike train intervals in "bytes", not "hits", of adjacent, serially ordered intervals. Among the several lines of evidence for this conclusion is the demonstration that drug-induced (ethanol) changes in fractional entropy of specific interval clusters seem to involve a "linked" combination of certain interval clusters, some which increase and others which decrease in incidence. Also, by using n-dimensional Chi-Square methodology, we have demonstrated that the relationships of adjacent intervals represent a Markovian process in which the duration of a given interval is partially determined by the duration of as many as four immediately preceding intervals. Finally, we showed that the relative fractional entropy (% maximum) of interval clusters of different numbers does not have a Gaussian distribution but rather is distributed in surprising ways by the specific number and relative durations of adjacent intervals. So just what is the serial ordering and information content of spike train intervals trying to tell us?. Perhaps it is trying to say that the nervous system processes information on a moment-by-moment basis in terms of "bytes" of short sequences of spikes with specific patterns of relative interspike durations. If so, we should be able to identify and characterize those "bytes". Much further testing must be done before we can claim that "neural codes" operate on the principles described herein. Nonetheless, we have made the issues explicit, and in our opinion have provided enough evidence to warrant further investigation.