Spatial coordinates of human auditory working memory.

The accuracy of localizing remembered sound sources was investigated by employing a delayed-response task, where a small light spot, projected onto a screen by a laser diode attached to the head, had to be spatially aligned with either actual or remembered stimulus positions. Systematic errors indicated overestimation of the eccentricity of remembered targets compared to direct stimulus localization. This overestimation increased with prolonged response delay, suggesting that the coordinates of memorized space are distorted with respect to perceived actual sound location and that this distortion increases as a function of time.

Sound lateralization during passive whole-body rotation.

The effect of passive whole-body rotation about the earth-vertical axis on the lateralization of dichotic sound was investigated in human subjects. Pure-tone pulses (1 kHz; 0.1 s duration) with various interaural time differences were presented via headphones during brief, low-amplitude rotation (angular acceleration 400 degrees/s2; maximum velocity 90 degrees/s; maximum displacement 194 degrees ). Subjects made two-alternative forced-choice (left/right) judgements on the acoustic stimuli. The auditory median plane of the head was shifted opposite to the direction of rotation, indicating a shift of the intracranial auditory percept in the direction of rotation. The mean magnitude of the shift was 10.7 micros. This result demonstrates a slight, but significant, influence of rotation on sound lateralization, suggesting that vestibular information is taken into account by the brain for accurate localization of stationary sound sources during natural head and body motion.

Spatio-temporal constraints for auditory--visual integration.

The perceptual coherence of auditory and visual information is achieved by integrative brain processes. Specialized single neurons with spatial and temporal interactions of auditory and visual stimuli have been demonstrated by several neurophysiological studies. The present, psychophysical, study investigates possible perceptual correlates of these neuronal features. Subjects had to indicate the point of subjective spatial alignment (PSSA) for a horizontally moving visual stimulus that crossed the position of a stationary sound source. Auditory and visual stimuli consisted of periodic pulses that were systematically varied in their phase relationship or repetition rate. PSSAs obtained for continuous visual stimuli served as a reference. When sound and light pulses were coincident in phase at a repetition rate of 2 Hz, PSSAs were shifted by approximately 3 degrees in a direction opposite to the movement of the visual stimulus (with respect to the reference condition). This shift markedly decreased when the temporal disparity exceeded approximately 100 ms and disappeared near phase opposition (250 ms disparity). With 4 Hz repetition rate (temporal disparity < or =125 ms), there was no significant effect of phase relationship on PSSAs, but still an approximately constant shift with respect to the reference value. Variation of the repetition rate resulted in almost constant shifts in PSSA of approximately 3 degrees between 1 and 4 Hz and a linear decrease (slope 0.27 degrees /Hz) with higher repetition rates. These results suggest a spatio-temporal 'window' for auditory-visual integration, that extends over approximately 100 ms and approximately 3 degrees : when auditory and visual stimuli are within this window, they are always perceived as spatially coincident. These psychophysical findings may be related to properties of bimodal neurons such as have been demonstrated by neurophysiological recordings in midbrain and cortex.

Effect of gaze direction on sound localization in rear space.

The effect of eccentric eye position on the localization of sound in rear space was investigated, using a two-alternative forced-choice method in combination with a visual fixation task. The azimuthal position of the rear sound was perceived as shifted slightly (mean 1.2 degrees ) to the left of the subjects' median plane when fixation was 30 degrees to the right, or to the right when fixation was 30 degrees to the left. Combined with previous studies on localization in frontal space, this finding suggests that eye-position signals influence processing of binaural, but not monaural spectral, cues for directional hearing.

Vestibular influence on human auditory space perception.

We investigated the effect of vestibular stimulation on the lateralization of dichotic sound by cold-water irrigation of the external auditory canal in human subjects. Subjects adjusted the interaural level difference of the auditory stimulus to the subjective median plane of the head. In those subjects in whom dizziness and nystagmus indicated sufficient vestibular stimulation, these adjustments were significantly shifted toward the cooled ear compared with the control condition (irrigation with water at body temperature); i.e., vestibular stimulation induced a shift of the sound image toward the nonstimulated side. The mean magnitude of the shift was 7.3 dB immediately after vestibular stimulation and decreased to 2.5 dB after 5 min. As shown by an additional control experiment, this effect cannot be attributed to a unilateral hearing loss induced by cooling of the auditory periphery. The results indicate the involvement of vestibular afferent information in the perception of sound location during movements of the head and/or the whole body. We thus hypothesize that vestibular information is used by central-nervous mechanisms generating a world-centered representation of auditory space.

Visual and proprioceptive shifts in perceived egocentric direction induced by eye-position.

The relation of three main effects of eye-position on perceived direction was investigated using a method of hand pointing in the horizontal plane: (1) Retinal eccentricity is overestimated with respect to the fovea by a constant factor of 2.6 degrees; (2) an extraretinal signal induces a shift in perceived visual direction (slope 0.12) that is opposite to the direction of eccentric gaze; and (3) the perceived position of the median plane of the head shifts toward the direction of eccentric eye-position (slope 0.23) while perceived trunk position remains unchanged.

Sound localization with eccentric head position.

This study investigates the influence of head-to-trunk position on auditory localization in humans. Various methods of head pointing, of two-alternative forced choice, and hand pointing were employed. Head-pointing toward actual sound sources in darkness, by using only the subjective median plane of the head as a reference, resulted in systematic underestimations of target eccentricity. The deviations of the terminal head position from the target shifted with a mean slope of approximately 0.1 degrees per degree change in head position. A corresponding shift in the localization of virtual sound sources (presented via headphones during eccentric head positions) was demonstrated by requiring forced-choice (left or right) responses with respect to the subjective median plane of the head. Head pointing toward remembered auditory targets in darkness resulted in undershoots similar to those found with actual targets. However, when a visual marker of the actual median plane of the head was additionally presented to the subject during these tasks (by a laser attached to the head that projected a spot onto a screen), sound localization was fairly accurate. Localization of eccentric auditory targets by using a swivel hand pointer also showed systematic errors similar to those found with head pointing in darkness when the head was simultaneously oriented toward the sound. When the head remained in alignment with the trunk, hand pointing resulted in overshooting responses. These results may be related to neural processes, presumably in the posterior parietal cortex, that transform auditory and visual spatial coordinates into a common, trunk-centered, frame of reference.

CD87-positive tumor cells in bone marrow aspirates identified by confocal laser scanning fluorescence microscopy.

Dissemination of single tumor cells to the bone marrow is a common event in cancer. The clinical significance of cytokeratin-positive cells detected in the bone marrow of cancer patients is still a matter of debate. In gastric cancer, overexpression of the receptor (uPAR or CD87) for the serine protease urokinase-type plasminogen activator (uPA) in disseminated cancer cells indicates shorter survival of cancer patients. A new immunofluorescence approach, applying confocal laser scanning microscopy, is introduced to locate CD87 antigen in cytokeratin-positive tumor cells and to quantify the CD87 antigen by consecutive scanning. At first, cytokeratin 8/18/19-positive carcinoma cells are identified at excitation wavelength 488 nm using monoclonal antibody A45B/B3 to the cytokeratins and goat anti-mouse IgG labeled with the fluorochrome Alexa488. Next, CD87 in tumor cells is identified by chicken antibody HU277 to the uPA-receptor and goat anti-chicken IgY labeled with fluorochrome Alexa568 (excitation wavelength 568 nm) and the fluorescence signal quantified on a single cell basis using fluorescently labeled latex beads as the fluorescence reference. From 16 patients with gastric or esophageal carcinoma, bone marrow aspirates were obtained, stained for cytokeratins and CD87 and then subjected to laser scanning fluorescence microscopy. Three of six gastric cancer patients had tumor cells present in the bone marrow of which 2 stained for CD87. Three of ten esophageal carcinoma patients had tumor cells in the bone marrow, all three samples stained for CD87. CD87-positive tumor cells were also dissected from stained bone marrow aspirates by laser microdissection microscope to allow analysis of single cells at the gene level.

Neck-proprioceptive influence on auditory lateralization.

The effect of transcutaneous vibration of the posterior neck muscles on the lateralization of dichotic sound was investigated in human subjects. Two-alternative forced-choice (left/right) judgements were made on acoustic stimuli presented with different interaural level differences via headphones during neck-muscle vibration. A shift of the subjective auditory median plane toward the side contralateral of vibration was found, indicating that the sound was perceived as shifted toward the side of vibration. The mean magnitude of the vibration-induced intracranial shift was 1.5 dB. The results demonstrate a neck-proprioceptive influence on sound lateralization and suggest that this proprioceptive input is used for a central-nervous transformation of auditory spatial coordinates onto a body-centered frame of reference.

Auditory-visual spatial integration: a new psychophysical approach using laser pointing to acoustic targets.

The alignment of auditory and visual spatial perception was investigated in four experiments, employing a method of laser pointing toward acoustic targets in combination with various tasks of visual fixation in six subjects. Subjects had to fixate either a target LED or a laser spot projected on a screen in a dark, anechoic room and, while doing so, direct the laser beam toward the perceived azimuthal position of the sound stimulus (bandpass-filtered noise; bandwidth 1-3 kHz; 70 dB sound pressure level, duration 10 s). The sound was produced by one of nine loudspeakers, located behind the acoustically transparent screen between 22 degrees to the left and 22 degrees to the right of straight ahead. Systematic divergences between sound azimuth and laser adjustment were found, depending on the instructions given to the subjects. The eccentricity of acoustic targets was generally overestimated by up to 10.4 degrees with an only slight influence of gaze direction on this effect. When the sound source was straight ahead, gaze direction had a substantial influence in that the laser adjustments deviated by up to 5.6 degrees from sound azimuth, toward the side to which the gaze was directed. This effect of eye position decreased with increasing eccentricity of the sound. These results can be explained by the interactive effects of four distinct factors: the lateral overestimation of the auditory eccentricity, the effect of eye position on sound localization, the effect of the retinal eccentricity on visual localization, and the extraretinal effect of eye position on visual localization.

Influence of head-to-trunk position on sound lateralization.

The effect of horizontal head position on the lateralization of dichotic sound stimuli was investigated in four experiments. In experiment 1, subjects adjusted the interaural level difference (ILD) of a stimulus (band-pass noise) to the subjective auditory median plane (SAMP) while simultaneously directing the beam of a laser attached to the head to visual targets in various directions. The adjustments were significantly correlated with head position, shifting in a direction toward the side to which the head was turned. This result was replicated in experiment 2, which employed a two-alternative forced-choice method, in which stimuli of different ILD were presented and left/right judgments were made. In both experiments, the average magnitude of the shift of the SAMP was about 1 dB over the range of head positions from straight ahead to 60 degrees to the side. The shift of the SAMP indicates that any shift in head position induces a change in sound lateralization in the opposite direction, i.e., the intracranial sound image is shifted slightly to the left when the head is directed to the right and to the right when the head is to the left. In experiments 3 and 4, the effect of head position was compared with that of eye position by using the same methods as in experiment 2. Both shifts in SAMP, induced by either head- or eye-position changes, are in the same direction and, on average, of about the same magnitude (experiment 3), and head- and eye-position effects compensate approximately for each other during variations of head position when the gaze remains fixed to a visual target in space (experiment 4).

Spatial-tuning properties of auditory neurons in the optic tectum of the pigeon.

We studied the auditory neurons in the optic tectum of the unanesthetized pigeon, using single-unit recordings and acoustic free-field stimulation. Most units showed spatial tuning, with best areas located in the contralateral hemifield. All units responded also to visual stimuli, the auditory best areas being in rough alignment with visual receptive fields.

The effect of gaze eccentricity on perceived sound direction and its relation to visual localization.

This study investigates the influence of eye position on the localization of a free-field sound source by employing a pointing method. While fixating visual targets in various directions, the subjects indicated the perceived direction of a sound source by adjusting the azimuthal angle of a swivel pointer. The perceived sound azimuth shifted consistently opposite to the direction of eccentric gaze. i.e. to the left when gaze was to the right and vice versa. This shift resembled an approximately linear function of horizontal gaze direction. The mean magnitude of the shift was 3.1 degrees when the gaze was 45 degrees to the side (mean slope 0.069 degrees per degree eccentricity in gaze direction). An additional experiment investigated the relation of this effect to visual localization. Using the same method, the shift of perceived visual azimuth was measured as a function of gaze direction. The results indicate a shift in the same direction as the auditory shift (opposite to the direction of eccentric gaze), but with a significantly greater magnitude, which was 5.7 degrees for 45 degrees eccentricity in gaze direction. The perceived shifts of sound direction depending on gaze eccentricity may result from incomplete transformations of the auditory spatial coordinates from a craniocentric to an oculocentric frame of reference within neural maps of space, as has been suggested by previous neurophysiological investigations.

Eye-position effects in directional hearing.

The influence of gaze direction on azimuthal sound localization was investigated by presenting free-field acoustical stimuli in combination with a visual fixation task. In Experiment 1, a two-alternative forced-choice method was employed. While fixating visual targets, subjects judged whether noise bursts, presented from various directions, were perceived as being on the left or right of either a visual reference indicating straight ahead or the subjective straight-ahead direction. The psychometric functions measured with the first task shifted consistently opposite to the direction of eccentric gaze, i.e., the location of the auditory stimulus was perceived as shifted toward the direction of gaze. The mean magnitude of the shift was 4.7 degrees over a range of fixation angles up to 45 degrees on either side. Without an external reference indicating straight ahead, shifts of sound localization were inconsistent, either opposite or toward the direction of fixation in individual subjects. In Experiment 2, subjects orientated their head toward sound stimuli while fixating visual targets in various directions. As in Experiment 1, head position as a measure of sound localization shifted significantly toward the direction of eccentric gaze when a visual reference of the head median plane was present, and the results were inconsistent across subjects when it was absent. The results indicate a significant effect of gaze direction on the spatial agreement of auditory and visual perception which may be based on the superposition of distinct auditory and visual eye-position effects. The effect is in agreement with previous neurophysiological results that have suggested an incomplete neural transformation of auditory spatial coordinates from a craniocentric into an oculocentric frame of reference.

Auditory-visual shift in localization depending on gaze direction.

The effect of eye position on the spatial congruence of the perceived direction of auditory and visual cues was investigated, using a two-alternative forced choice method in combination with a visual fixation task. The azimuth of the sound was perceived as slightly shifted to the left of a visual reference when the gaze was directed to the left, and to the right when the gaze was to the right. The maximum magnitude of this relative auditory-visual shift was 4.7 degrees over a range of fixation angles from 45 degrees to the left to 45 degrees to the right. The observed auditory-visual shift may reflect an incomplete transformation of spatial coordinates within auditory and visual neural representations, as suggested by neurophysiological recordings in the primate midbrain.

The effect of eye position on auditory lateralization.

The present study examines whether the direction of gaze can influence sound lateralization. For this purpose, dichotic stimuli with variable interaural level difference (ILD) were presented under different conditions of visual fixation. In experiment 1, subjects with their head fixed directed their gaze to a given target, simultaneously adjusting the ILD of continuous pure tone or noise stimuli so that their location was perceived in the median plane of the head. The auditory adjustments were significantly correlated with gaze direction. During eccentric fixation, the psychophysical adjustments to the median plane shifted slightly toward the direction of gaze. The magnitude of the shift was about 1-3 dB, over a range of fixation angles of 45 degrees to either side. The eye position effect, measured as a function of pure-tone frequency, was most pronounced at 2 kHz and showed a tendency to decrease at lower and higher frequencies. The effect still occurred, although weaker, even when the eyes were directed to eccentric positions in darkness and without a fixation target. In experiment 2, the adjustment method was replaced by a two-alternative forced-choice method. Subjects judged whether sound bursts, presented with variable ILDs, were perceived on the left or right of the median plane during fixation of targets in various directions. Corresponding to experiment 1, the psychometric functions shifted significantly with gaze direction. However, the shift was only about half as large as that found in experiment 1. The shift of the subjective auditory median plane in the direction of eccentric gaze, observed in both experiments, indicates that dichotic sound is localized slightly to the opposite side, i.e., to the left when the gaze is directed to the right and vice versa. The effect may be related to auditory neurons which exhibit spatially selective receptive fields that shift with eye position.

Structure of the Arabidopsis RPM1 gene enabling dual specificity disease resistance.

Plants can recognize pathogens through the action of disease resistance (R) genes, which confer resistance to pathogens expressing unique corresponding avirulence (avr) genes. The molecular basis of this gene-for-gene specificity is unknown. The Arabidopsis thaliana RPM1 gene enables dual specificity to pathogens expressing either of two unrelated Pseudomonas syringae avr genes. Despite this function, RPM1 encodes a protein sharing molecular features with recently described single-specificity R genes. Surprisingly, RPM1 is lacking from naturally occurring, disease-susceptible Arabidopsis accessions.

The contribution of GABA-mediated inhibition to response properties of neurons in the nucleus of the optic tract in the rat.

The contribution of GABA-mediated inhibition to the generation of directional selectivity of neurons in the nucleus of the optic tract (NOT) and the dorsal terminal nucleus of the accessory optic system (DTN) was examined in anaesthetized rats by iontophoretic application of the GABAA receptor antagonist bicuculline methiodide. Spontaneous and visually evoked NOT-DTN cell activities were always increased by bicuculline application. The directional selectivity of NOT-DTN cells to slowly moving whole-field stimuli, expressed as the direction index, was reduced for most neurons. However, the difference between firing rates during stimulus movements in the preferred and in the non-preferred direction did not change systematically. On average, this difference was not significantly affected in the majority of the neurons, although bicuculline more strongly increased the activity during movement in the preferred or non-preferred direction in some of the neurons. These results indicate that directionally selective neurons in the rat NOT-DTN receive GABAergic inhibition which is most likely tonic and independent of the stimulus direction.

GABA-like and glutamate-like immunoreactivity in the pretecto-olivary pathway in the rat.

The identities of neurotransmitters of the pretecto-olivary projection neurons and of the nerve terminals contacting them were investigated using a double-label method with retrograde labelling in combination with gamma-aminobutyric acid (GABA) and glutamate immunocytochemistry in the nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic system in the rat both light and electron microscopically. At the light microscopic level, the somata of all projection neurons identified by a label of horseradish peroxidase reaction product were stained moderately but reliably for glutamate immunoreactivity. In no case, any retrogradely labelled neuron was found to be stained for GABA immunoreactivity. However, the somata and proximal dendrites of these cells were surrounded with many intensively stained puncta, indicating strong reactions with the anti-GABA antibodies. In contrast, no immunostaining with anti-glycine or anti-taurine antibodies was obtained. Electron microscopic investigations demonstrated that immunogold-positive axosomatic or axodendritic synapses on the retrogradely labelled neurons corresponded to some of the GABA-positive puncta in semithin sections. The results suggest that the projection neurons receive a strong inhibitory input mediated by GABA and send their directionally selective information to the inferior olive by glutamatergic projections.

Neural mechanisms of directional hearing in the pigeon.

The directional sensitivity of single auditory neurons in the midbrain (Nucleus mesencephalicus lateralis pars dorsalis) of the pigeon (Columba livia) was studied, using acoustic free-field stimulation (usually pure tones) in the frontal hemifield. Of a total of 337 units, 84.6% showed statistically significant changes of their responses as a function of sound azimuth. Of these, most units respond maximally to sounds in a particular azimuthal range, each has its "best area". These neurons were classified into four classes according to the properties of their best areas: (1) contralateral neurons (53.4%); (2) ipsilateral neurons (6.2%); (3) frontal neurons (18.1%); and (4) complex neurons (3.3%). The first two showed only one border of the best area within the frontal hemifield, with an increase of response strength towards the contralateral and the ipsilateral side, respectively; with frontal neurons, the best area was bounded towards both sides within the frontal hemifield, whereas the complex neurons had two or more separated best areas or extensive frontal inhibitory areas. In the remaining units (3.6%), termed weakly directional neurons, changes of their discharge rate depending on sound azimuth were statistically significant, but too poor to determine any best areas. There was a significant under-representation of best frequencies in the mid-frequency range (1-2 kHz) with a minimum in the relative number of MLD neurons recorded from at 2 kHz. However, the directional sensitivity of the neurons quantified by analysing different parameters of the directional diagrams (dynamic range, roll-off steepness, best area width) was undiminished in the mid-frequency range. In several experiments, in addition to the neurons' directional sensitivity in free-field sound, their sensitivity to interaural ongoing time (phase) differences (OTDs) and interaural intensity differences (IIDs) were also tested, using dichotic stimulation (pure tones) by headphones. Directional sensitive neurons tuned to low frequencies (best frequency less than 2 kHz) were either sensitive exclusively to OTDs or to both OTDs and IIDs; the ranges of best OTDs were correlated significantly with the azimuthal position of the best area. "High frequency" units (best frequency greater than 2 kHz) were sensitive to IIDs but not to OTDs.(ABSTRACT TRUNCATED AT 400 WORDS)