Multichannel electroencephalographic assessment of auditory evoked response suppression in schizophrenia.

Reduced auditory evoked response (AER) suppression in a paired-stimulus paradigm (where suppression equals the difference between S1 and S2 amplitudes divided by S1 amplitude) may index genetic liability for schizophrenia. The present report is a multiple-channel electroencephalographic (EEG) study of AER suppression among 20 normal and 20 schizophrenia subjects. The typical paired-stimulus paradigm was used to evoke time-locked AERs. AER responses were scored at P50 and N100 in the time domain using both single (Cz) and multichannel data (after reduction using principal components analysis, PCA), and were scored for information in the gamma (20-50 Hz) and low-frequency (1-20 Hz) ranges using multichannel information (also after PCA). The time domain analyses demonstrated that schizophrenia patients differ from normal in amplitude of response to the first, but not to the second, stimulus for both P50 and N100. The frequency domain data demonstrated that schizophrenia patients differed from normal on amplitude of the low-frequency response (LFR) to the first, but not to the second, stimulus. The groups did not differ significantly on amplitudes of the gamma-band responses. Group separations were largest for the multichannel N100 and LFR data, with the LFR demonstrating a modestly better risk ratio for differentiating schizophrenia from normal subjects. The present results suggest two novel differences from previous AER suppression studies: (1) S1 amplitudes largely determine differences between normal and schizophrenia groups on AER suppression, and (2) frequency domain analyses may provide important complimentary information when studying AERs in schizophrenia.

Response to the first stimulus determines reduced auditory evoked response suppression in schizophrenia: single trials analysis using MEG.

OBJECTIVE: Reduced auditory evoked response (AER) suppression in a paired-stimulus paradigm may index genetic liability for schizophrenia. In most published studies of AER suppression, scores are based on data averaged over numerous stimulus presentations and recorded from few channels. It is unclear whether averaged data are equally representative of single trial responses in normal and schizophrenia subjects. In the present report, we used 148 channel magnetoencephalography to investigate grand-average and single trial responses on AER suppression. METHODS: The typical paired-stimulus paradigm was used to evoke time-locked AERs from 20 normal and 20 schizophrenia patients. Gamma band response (GBR) and low frequency response (LFR) characteristics were measured on grand-averaged and single trial data. Generalized eigenvalue decomposition was used to reduce the multiple channel information to a vector that accounted for the most AER variance for the GBR and LFR. RESULTS: Group performances on grand-average and single trials were similar. A remarkable difference, which replicates previous studies, was that schizophrenia subjects had smaller LFR amplitudes in response to the first stimulus than normal. CONCLUSIONS: These findings are inconsistent with the "poor suppression" theory often used to explain schizophrenia-normal group differences when using the paired-stimulus paradigm.

Cervimetry: a review of methods for measuring cervical dilatation during labor.

Several different methods of measuring cervical dilatation have been described. In this article, we review those methods and examine findings from studies using them. Although many instruments have been developed to measure cervical dilatation during labor and their use as a research tool has been established, no device has yet been successfully used for clinical obstetrics. The ideal device has not yet been developed; however, because repeated digital cervical examinations are time consuming for the clinician, are poorly reproducible, and are uncomfortable for the patient, continued efforts to develop a cervimeter suitable for clinical use is a worthwhile endeavor.

Hemispheric differences on auditory evoked response suppression in schizophrenia.

Using binaural stimuli, schizophrenia subjects have worse auditory evoked response (AER) suppression than normals in a paired-click paradigm. In this study we investigated hemispheric differences in AER suppression between groups using monaural and binaural stimulus presentation. Auditory evoked responses from 12 schizophrenia and 12 normal subjects were recorded with a 148-channel whole-head biomagnetometer. One hundred and twenty pairs of clicks were presented in three counterbalanced blocks (left, right, binaural). With monaural stimuli, patients had worse M100 suppression than normals in ipsilateral (effect size -2.13) but not in contralateral hemisphere (effect size -0.43). The groups did not differ on gamma band response suppression. Overall, the best group separations were obtained with binaural stimulus presentation on M100 suppression (effect size -4.14).

Retinopathy of prematurity in multiple-gestation pregnancies.

PURPOSE: To determine differences in incidence of retinopathy of prematurity between neonates of multiple-gestation and single-gestation pregnancies and to analyze differences in severity of retinopathy of prematurity among siblings of multiple-gestation pregnancies. METHODS: We reviewed the records of 149 neonates of multiple-gestation pregnancies and 691 single-gestation neonates screened for retinopathy of prematurity at one hospital from January 1, 1992, through December 31, 1995. The peak stage of retinopathy of prematurity was recorded for all infants. The multiple-gestation infants were then separated into concordant and discordant retinopathy of prematurity groups, with discordance defined as a difference of at least 2 stages of retinopathy of prematurity between siblings. Between siblings with discordant retinopathy of prematurity, multiple factors were compared. RESULTS: Retinopathy of prematurity was present in 69 (46%) of the multiple-gestation neonates. Retinopathy of prematurity was present in 312 (45%) of single-birth neonates. The percentage of multiple-gestation neonates with stages 1, 2, or 3 (prethreshold) or threshold retinopathy of prematurity was similar to that of single-gestation neonates. Stage 4 or 5 retinopathy of prematurity did not occur in either group. CONCLUSIONS: There was no significant difference in stage of retinopathy of prematurity between infants of single-gestation pregnancies vs those of multiple-gestation pregnancies. The majority (84%) of infants of multiple-gestation pregnancies had concordant retinopathy of prematurity. In those infants with discordant disease, zygosity and postgestational factors other than lowest serum glucose were not related to severity of retinopathy of prematurity.

Failure of dominant left-hemispheric activation to right-ear stimulation in schizophrenia.

Schizophrenia is associated with an absence of the lateralizations that typify the human brain. Previous evidence emphasized structural changes, particularly reduced asymmetry in extension and surface of the planum temporale, although gross structural deviations occur only in a minority of patients. The present study describes an absence of lateralization on a robust functional measure that characterized schizophrenia patients: healthy subjects but not schizophrenics displayed a contralateral left-hemispheric dominance of the auditory evoked magnetic field to right-ear auditory stimulation. Absence of contralateral dominance in response to auditory stimuli among schizophrenia patients may indicate a failure to establish unequivocal left-hemispheric dominance of the phonological loop as hypothesized by Crow.

The Phenomenology of Attention

The effect of attention on perceived brightness and contrast was investigated in eight experiments. Attention was manipulated by engaging observers in an attention-demanding concurrent task (letter detection) or by directing attention to a location with a peripheral cue. In all of the dual-task manipulations, attention reduced the variability of responses. However, attention did not affect the brightness of stimuli, nor did it affect the amount of simultaneous brightness contrast. Results with peripheral location cues were similar; however, the effect of attention in these experiments could be attributed to nonperceptual factors. The metaphorical "spotlight" of attention reduces observers' uncertainty about the brightness of a stimulus, but it does not "illuminate" in terms of brightness or contrast.

The phenomenology of attention. 2. Brightness and contrast.

The effect of attention on perceived brightness and contrast was investigated in eight experiments. Attention was manipulated by engaging observers in an attention-demanding concurrent task (letter detection) or by directing attention to a location with a peripheral cue. In all of the dual-task manipulations, attention reduced the variability of responses. However, attention did not affect the brightness of stimuli, nor did it affect the amount of simultaneous brightness contrast. Results with peripheral location cues were similar; however, the effect of attention in these experiments could be attributed to nonperceptual factors. The metaphorical "spotlight" of attention reduces observers' uncertainty about the brightness of a stimulus, but it does not "illuminate" in terms of brightness or contrast.

The gamma band response may account for poor P50 suppression in schizophrenia.

The relationship between gamma band response (GBR) and P50 suppression was investigated among 10 DSM-IV schizophrenia patients and 10 normal comparison subjects using neuromagnetic and electrical recordings. In a paired-click paradigm, the neuromagnetic GBR and M100 suppression data improved schizophrenia-normal group separations over the typical electrical, vertex-recorded P50 suppression measure. The neuromagnetic GBR was also superior to the magnetic equivalent of P50 (M50) for discriminating schizophrenia and normal subjects. Our data are consistent with the hypothesis that P50 may be a subcomponent of the GBR, and that P50 suppression may be a proxy for GBR suppression. Measurement of the GBR should be given consideration as another, and perhaps better, means for evaluating auditory-evoked response abnormalities among schizophrenia patients.

Physical mechanism of ATP formation in biomembranes.

Membrane-bound and isolated H+ ATPases of various origin are able to synthesize ATP from ADP and Pi after a jump-like pH increase. In the course of this increase the pH of solution (or suspension) must cross a value corresponding to pK of certain acid groups in the catalytic component of ATPase. In the case of isolated soluble enzymes it is possible to obtain up to 10 ATP molecules per one pH jump per one enzyme molecule. A physical mechanism of this phenomenon as well as of oxidative and photosynthetic phosphorylation is suggested.

A model of the mechanism of enzyme action in terms of protein conformational relaxation.

A theoretical model of enzymatic reaction is formulated in which the modulation of the reaction coordinates by low-frequency conformational motions of the enzyme molecule causes the lowering of the activation energy barriers until they completely disappear. If the rates of electron transitions in the enzyme-substrate complex exceed the characteristic frequencies of conformational motions then the rate of the elementary enzymatic reaction shows hysteresis dependence on temperature and substrate concentration.

PH-jump-induced ADP phosphorylation in mitochondria.

Mitochondria, uncoupled by aging or by freeze-thaw treatment, are able to synthesize ATP from ADP and Pi after a fast increase (but not decrease) in the external pH. The maximal ATP yield (approx. 2.5 ATP molecules/electron-transport chain per pH jump) can be obtained under the following conditions: (1) the pH change during the jump must exceed 0.7 pH units; (2) in the course of this change, the pH of the mitochondrial suspension must cross the pH 8.1-8.3 value. This pH-jump-induced ATP synthesis is completely inhibited by oligomycin.

Spectral properties of nonequilibrium states in cytochrome P-450 formed by reduction at subzero temperatures.

Nonequilibrium conformational states in cytochrome P-450 in the presence and absence of substrates formed by reduction at subzero temperatures with hydrates electrons were obtained and characterized by their absorption spectra. Different absorption spectra between the relaxed (298 K) and the non-relaxed enzyme forms (77 K) indicate conformational changes proceeding in the relaxed form after reduction of the heme iron which lead to altered interactions between the active centre and its environment in the protein. The two maxima of the nonequilibrium form of cytochrome P-450 without substrate in the visible absorption spectrum (alpha-band, beta-band) and the ratio of their intensities indicate the low-spin character of the heme iron. These spectral properties give evidence for a reduced cytochrome P-450 with two heme-linked axial ligands.