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In contrast to the current state of knowledge of cardiac and of gastrointestinal electrophysiology, our current knowledge of the physiology of the uterus during pregnancy is still very rudimentary. Despite seminal work performed in the past decades, there are still significant areas that we know little about. In this review, some of these areas are explored. For example, although many studies have tried to find the site of the uterus pacemaker, such a site has not yet been found and its mechanism and location remain, to date, a mystery. Similarly, there is much confusion as to the mechanism of propagation of the electrical impulse. Although the existence of gap junctions, connecting neighboring myometrial cells to each other, have been known since 1977, alternative or additional mechanisms are being suggested such as the potential existence of a network of interstitial cells, similar to the one that is functioning in the gut, or the involvement of stretch receptors to synchronize activity and contraction. In recent years, high-resolution studies have been introduced enabling detailed analysis of the location and spatial patterns of propagation. This work is being developed at the in-vitro level in isolated tissues, in the whole organ and in several animal species. Most recently, a surge in new technology enabling high fidelity and high resolution recording from the human uterus through the abdominal wall are being explored which could ultimately lead to new diagnostic tools and a clearer understanding of the physiology of pregnancies and (premature) labor.

Background: A periodic electrical activity, termed "slow waves", coordinates gastrointestinal contractions. Slow-wave dysrhythmias are thought to contribute to dysmotility syndromes such as postoperative gastroparesis, but the clinical significance of these dysrhythmias remains poorly defined. Electrogastrography (EGG) has been unable to characterize dsyrhythmic activity reliably, and the most accurate method for evaluating slow waves is to record directly from the surface of the target organ. This study presents a novel laparoscopic device for recording serosal slow-wave activity, together with its validation., Methods: The novel device consists of a shaft (diameter, 4 mm; length, 300 mm) and a flexible connecting cable. It contains four individual electrodes and is fully shielded. Validation was performed by comparing slow-wave recordings from the laparoscopic device with those from a standard electrode platform in an open-abdomen porcine model. An intraoperative human trial of the device also was performed by recording activity from the gastric antrum of a patient undergoing a laparoscopic cholecystectomy., Results: Slow-wave amplitudes were similar between the laparoscopic device and the standard recording platform (mean 0.38 ± 0.03 mV vs range 0.36-0.38 ± 0.03 mV) (p = 0.94). The signal-to-noise ratio (SNR) also was similar between the two types of electrodes (13.7 dB vs 12.6 dB). High-quality antral slow-wave recordings were achieved in the intraoperative human trial (amplitude, 0.41 ± 0.04 mV; SNR, 12.6 dB), and an activation map was constructed showing normal aboral slow-wave propagation at a velocity of 6.3 ± 0.9 mm/s., Conclusions: The novel laparoscopic device achieves high-quality serosal slow-wave recordings. It is easily deployable and atraumatic. It is anticipated that this device will aid in the clinical investigation of normal and dsyrhythmic slow-wave activity. In particular, it offers new potential for investigating the effect of surgical procedures on slow-wave activity.

Myoelectric recordings from the gastrointestinal (GI) tract in conscious animals have been limited in duration and site. Recently, we have implanted 24 electrodes and obtained electrograms from these sites simultaneously (200 Hz sampling rate; 1.1 MB/min data stream). An automated electrogram analysis was developed to process this large amount of data. Myoelectrical recordings from the GI tract often consist of slow wave deflections followed by one or more action potentials (=spike deflections) in the same traces. To analyze these signals, a first module separates the signal into one containing only slow waves and a second one containing only spikes. The timings of these waveforms were then detected, in real time, for all 24 electrograms, in a separate slow wave detection module and a separate spike-detection module. Basic statistics such as timing and amplitudes and the number of spikes per slow wave were performed and displayed on-line. In summary, with this online analysis, it is possible to study for long periods of time and under various experimental conditions major components of gastrointestinal motility.

Myoelectric recordings from the intestines in conscious animals have been limited to a few electrode sites with relatively large inter-electrode distances. The aim of this project was to increase the number of recording sites to allow high-resolution reconstruction of the propagation of myoelectrical signals. Sets of six unipolar electrodes, positioned in a 3x2 array, were constructed. A silver ring close to each set served as the reference electrodes. Inter-electrode distances varied from 4 to 8 mm. Electrode sets, to a maximum of 4, were implanted in various configurations allowing recording from 24 sites simultaneously. Four sets of 6 electrodes each were implanted successfully in 11 female Beagles. Implantation sites evaluated were the upper small intestine (n=10), the lower small intestine (n=4) and the stomach (n=3). The implants remained functional for 7.2 months (median; range 1.4-27.3 months). Recorded signals showed slow waves at regular intervals and spike potentials. In addition, when the sets were positioned close together, it was possible to re-construct the propagation of individual slow waves, to determine their direction of propagation and to calculate their propagation velocity. No signs or symptoms of interference with normal GI-function were observed in the tested animals. With this approach, it is possible to implant 24 extracellular electrodes on the serosal surface of the intestines without interfering with its normal physiology. This approach makes it possible to study the electrical activities of the GI system at high resolution in vivo in the conscious animal.

We assessed depression, anxiety, and relevant cognitions in persons with mental retardation by administering modified versions of the Reynolds Child Depression Scale, the Beck Anxiety Inventory, the Automatic Thoughts Questionnaire, and the Cognitions Checklist to 46 persons with borderline to moderate mental retardation. Consistent with research with other groups, self-reports of depression and anxiety were highly correlated (r = .74) in these individuals, and cognitions were strong predictors of negative affect. Subscales measuring cognitions related to depression and anxiety were also highly related, limiting the "cognitive-specificity" hypothesis. Hierarchical multiple regression analyses offered mixed support for cognitive-specificity. We discuss the implications of these findings for the cognitive and affective assessment of persons with intellectual limitations.

In the isolated pregnant myometrium of the rat, the pattern of propagation was investigated by recording simultaneously from 240 different extracellular sites while the contraction of the tissue was recorded isometrically. Analysis of all recorded electrograms allowed the two-dimensional spread of activity in the myometrium to be reconstructed. From these activation maps, the conduction velocities were measured in the longitudinal, oblique and transversal directions. At low concentrations (10(-9 )and 5x10(-9) M), oxytocin significantly increased the frequency and duration of electrical bursts and the average spike intervals, without affecting the homogeneity of action potential propagation, concomitant with a significant increase in the amplitude of contractions. At high concentrations (10(-8) and 5x10(-8) M), oxytocin induced conduction blocks and the size of inexcitable areas was increased, concomitantly with an increase in muscle contractures. In contrast, the conduction velocities in the longitudinal, oblique and circular directions were not influenced by oxytocin at any concentrations.

The propagation of individual action potentials during spontaneous bursts of activity in isolated pregnant rat myometrium in the final stage of pregnancy was analyzed. Simultaneous recordings from 240 extracellular recording sites (inter-electrode distance 1 mm) made it possible to reconstruct, in spatial and temporal details, the conduction of the electrical impulse. On several occasions, the impulse was seen to be conducted in a circular fashion whereby the impulse repeatedly re-excited the myometrium. No evidence was found of circuits rotating around an area of depressed excitability or anatomical obstacle, suggesting that these circuits are similar to those proposed to occur in cardiac muscle by the "leading circuit" model. Because of the anisotropic conduction properties of the myometrium, several circuits revolved in an ellipse with the long axis parallel to the longitudinal fiber direction, similar to functional re-entry in the anisotropic ventricle. Of a total of 46 bursts analyzed, myometrial re-entry occurred in 10 of the bursts. Furthermore, re-entries were found at day 17, day 19 and day 21 ( = term) stages of pregnancy suggesting that re-entry may occur throughout the final stage of gestation. In conclusion, functional re-entry, previously shown in the myocardium, may also occur in the pregnant myometrium. The presence of re-entry in the uterus could underlie the mechanism for uterine tachysystole, leading to dysfunctional labor.

High-resolution mapping makes it possible to reconstruct and display the conduction pattern of the action potential as it propagates through cardiac or smooth muscles. During slow and regular activity, time mapping of the spread of activation muscles. During slow and regular activity, time mapping of the spread of activation is relatively simple and straightforward. However, when frequencies are high or conduction is slow, such as seen during atrial fibrillation or found in the pregnant uterus, the tracking of individual waves may become more difficult and uncertain. In order to reconstruct the pathway of a single wave, a search and sorting routine was developed which makes it possible to distinguish, track and display individual wavelets. The algorithm is able to detect variations in conduction block, spontaneous shifts in the location of the pacemaker and changes in the direction of conduction. It is less sensitive when two or more wavefronts intermingle in space and time, such as during collision or fusion. Wave mapping is especially useful, in addition to current time mapping, in sorting quickly through the large amount of data produced by high-resolution mapping of electrical activities in cardiac and smooth muscle.

In the isolated right atrium of the rabbit heart the influence of the atrial myocardium on impulse formation in the sinus node was investigated. Under normal conditions the pacemaker (earliest activation) was located in the center of the node where fibers with the highest rate of diastolic depolarization were found. After disconnection of the atrium from the sinus node spontaneous cycle length decreased from a mean of 348 ms to a mean of 288 ms (-18%) in all experiments (n = 15). This was accompanied by a shift of the pacemaker from the nodal center towards the border zone. By means of multiple microelectrode impalements changes in action potential configuration were studied. After disconnection of atrium and sinus node the rate of diastolic depolarization of fibers in the border zone was increased from a mean of 26 mV/s to a mean of 78 mV/s, whereas in the center of the sinus node no increase was found (mean: 52 mV/s). It was concluded that the fibers in the border zone of the sinus node are better pacemaker fibers than in the nodal center. However under normal conditions the intrinsic pacemaker properties of the border zone fibers are electronically depressed by the connected atrial myocardium.