Unifying multisensory signals across time and space.

The brain integrates information from multiple sensory modalities and, through this process, generates a coherent and apparently seamless percept of the external world. Although multisensory integration typically binds information that is derived from the same event, when multisensory cues are somewhat discordant they can result in illusory percepts such as the "ventriloquism effect." These biases in stimulus localization are generally accompanied by the perceptual unification of the two stimuli. In the current study, we sought to further elucidate the relationship between localization biases, perceptual unification and measures of a participant's uncertainty in target localization (i.e., variability). Participants performed an auditory localization task in which they were also asked to report on whether they perceived the auditory and visual stimuli to be perceptually unified. The auditory and visual stimuli were delivered at a variety of spatial (0 degrees, 5 degrees, 10 degrees, 15 degrees ) and temporal (200, 500, 800 ms) disparities. Localization bias and reports of perceptual unity occurred even with substantial spatial (i.e., 15 degrees ) and temporal (i.e., 800 ms) disparities. Trial-by-trial comparison of these measures revealed a striking correlation: regardless of their disparity, whenever the auditory and visual stimuli were perceived as unified, they were localized at or very near the light. In contrast, when the stimuli were perceived as not unified, auditory localization was often biased away from the visual stimulus. Furthermore, localization variability was significantly less when the stimuli were perceived as unified. Intriguingly, on non-unity trials such variability increased with decreasing disparity. Together, these results suggest strong and potentially mechanistic links between the multiple facets of multisensory integration that contribute to our perceptual Gestalt.

Quantitative measurement of airborne allergens from dust mites, dogs, and cats using an ion-charging device.

BACKGROUND: Increasing evidence suggests that children raised with an animal(s) in the house have a decreased risk of becoming sensitized. However, it is not clear whether this phenomenon is related to airborne exposure. OBJECTIVE: To estimate airborne exposure to animal dander and dust mite allergens using a device that can sample large volumes of air silently. METHODS: The device, which uses an ion-charging technique to move air and to collect particles, was run at 1.7 m3/min for 24 h in 44 homes with and without animals. The allergen collected was measured by ELISA for Fel d 1, Can f 1, Der p 1, and Der f 1. RESULTS: Airborne Fel d 1 was present in all homes with a cat (n=27). The quantities measured, i.e. 0.5-20 microg in 24 h, represent 0.01-0.3 microg Fel d 1 inhaled/day at normal breathing rates (20 L/h). Values for houses without a cat were 0.01-0.05 microg inhaled/day. Airborne Fel d 1 correlated significantly with floor Fel d 1 (r=0.58, P<0.001). Results for Can f 1 were similar in houses with a dog, but this allergen was only detected airborne in two houses without a dog. Neither Der p 1 nor Der f 1 (i.e. <0.01 microg) was detected, which represents < or =1 ng inhaled/day during normal domestic activity. During disturbance airborne mite was detected with both the ion-charging device and a filter run in parallel. For cat and mite allergens there was a close correlation between the two techniques (r=0.84, P<0.001). CONCLUSION: Exposure to cat or dog allergen airborne in homes with an animal can be up to 100 times higher than exposure to mite allergen. The results are in keeping with a model where immunological tolerance to animal dander allergens results from high exposure.

Visual localization ability influences cross-modal bias.

The ability of a visual signal to influence the localization of an auditory target (i.e., "cross-modal bias") was examined as a function of the spatial disparity between the two stimuli and their absolute locations in space. Three experimental issues were examined: (a) the effect of a spatially disparate visual stimulus on auditory localization judgments; (b) how the ability to localize visual, auditory, and spatially aligned multisensory (visual-auditory) targets is related to cross-modal bias, and (c) the relationship between the magnitude of cross-modal bias and the perception that the two stimuli are spatially "unified" (i.e., originate from the same location). Whereas variability in localization of auditory targets was large and fairly uniform for all tested locations, variability in localizing visual or spatially aligned multisensory targets was much smaller, and increased with increasing distance from the midline. This trend proved to be strongly correlated with biasing effectiveness, for although visual-auditory bias was unexpectedly large in all conditions tested, it decreased progressively (as localization variability increased) with increasing distance from the midline. Thus, central visual stimuli had a substantially greater biasing effect on auditory target localization than did more peripheral visual stimuli. It was also apparent that cross-modal bias decreased as the degree of visual-auditory disparity increased. Consequently, the greatest visual-auditory biases were obtained with small disparities at central locations. In all cases, the magnitude of these biases covaried with judgments of spatial unity. The results suggest that functional properties of the visual system play the predominant role in determining these visual-auditory interactions and that cross-modal biases can be substantially greater than previously noted.

The influence of visual and auditory receptive field organization on multisensory integration in the superior colliculus.

The spatial register of the different receptive fields of multisensory neurons in the superior colliculus (SC) plays a significant role in determining the responses of these neurons to cross-modal stimulus combinations. Spatially coincident visual-auditory stimuli fall within these overlapping receptive fields and generally produce response enhancements that exceed the individual modality-specific responses and can exceed their sum. Yet, in this context, it has not been clear how "spatial coincidence" is operationally defined. Given the large size of SC receptive fields, visual and auditory stimuli could be within their respective receptive fields even when there are substantial spatial disparities between them. Indeed, previous observations have raised the possibility that there may be a second level of determinism in how SC neurons deal with the relative spatial locations of within-field cross-modal stimuli; specifically, that multisensory response enhancements become progressively weaker as the within-field visual and auditory stimuli become increasingly disparate. While the present experiments demonstrated that SC multisensory neurons have heterogeneous receptive fields, and that the greatest number of impulses evoked were by stimuli that fell within the area of cross-modal receptive field overlap, they also indicate that there is no systematic relationship between cross-modal stimulus disparity and the magnitude of multisensory response enhancement. Thus, two within-field cross-modal stimuli produced the same proportionate change (i.e., multisensory response enhancement) when they were widely disparate as they did when they overlapped one another in space. These observations indicate that cross-modal spatial coincidence can be defined operationally by the borders of an SC neuron's receptive fields regardless of the size of those receptive fields and/or the absolute spatial disparity between within-field cross-modal stimuli.

Serum IgG and IgG4 antibodies to Fel d 1 among children exposed to 20 microg Fel d 1 at home: relevance of a nonallergic modified Th2 response.

Exposure to foreign antigens is an essential element of all immune responses, including allergic sensitization. For some allergens (e.g. mite and cockroach), the prevalence of sensitization is directly correlated with exposure. However, for allergens derived from domestic animals, several studies have suggested that children with a cat in the home have a decreased risk of sensitization and asthma. We have now shown that many children exposed to greater than 20 microg of Fel d 1/g of dust at home made an IgG and IgG4 antibody response to Fel d 1 without IgE antibody. This modified Th2 response is not associated with symptoms and should be regarded as a form of immunological tolerance. The fact that the dose-response relationship between cat exposure and sensitization is bell shaped, while that for mite exposure and sensitization is linear, is highly relevant to understanding the role of allergens in the increase in allergic disease.

Two cortical areas mediate multisensory integration in superior colliculus neurons.

The majority of multisensory neurons in the cat superior colliculus (SC) are able to synthesize cross-modal cues (e.g., visual and auditory) and thereby produce responses greater than those elicited by the most effective single modality stimulus and, sometimes, greater than those predicted by the arithmetic sum of their modality-specific responses. The present study examined the role of corticotectal inputs from two cortical areas, the anterior ectosylvian sulcus (AES) and the rostral aspect of the lateral suprasylvian sulcus (rLS), in producing these response enhancements. This was accomplished by evaluating the multisensory properties of individual SC neurons during reversible deactivation of these cortices individually and in combination using cryogenic deactivation techniques. Cortical deactivation eliminated the characteristic multisensory response enhancement of nearly all SC neurons but generally had little or no effect on a neuron's modality-specific responses. Thus, the responses of SC neurons to combinations of cross-modal stimuli were now no different from those evoked by one or the other of these stimuli individually. Of the two cortical areas, AES had a much greater impact on SC multisensory integrative processes, with nearly half the SC neurons sampled dependent on it alone. In contrast, only a small number of SC neurons depended solely on rLS. However, most SC neurons exhibited dual dependencies, and their multisensory enhancement was mediated by either synergistic or redundant influences from AES and rLS. Corticotectal synergy was evident when deactivating either cortical area compromised the multisensory enhancement of an SC neuron, whereas corticotectal redundancy was evident when deactivation of both cortical areas was required to produce this effect. The results suggest that, although multisensory SC neurons can be created as a consequence of a variety of converging tectopetal afferents that are derived from a host of subcortical and cortical structures, the ability to synthesize cross-modal inputs, and thereby produce an enhanced multisensory response, requires functional inputs from the AES, the rLS, or both.

The role of intervention in established allergy: avoidance of indoor allergens in the treatment of chronic allergic disease.

Avoidance of exposure to indoor allergens is an important element in the treatment of allergic disease. The results of several studies provide strong evidence in support of a role for allergen avoidance; however, strategies that optimize allergen reduction in houses have not been determined. Complex issues regarding the efficacy of physical and chemical measures that target house dust mite, pet, and cockroach allergens in the home are discussed. The greatest challenge is to educate allergic patients so that they can play an important role in controlling their own disease.

Assessment of vacuum cleaners and vacuum cleaner bags recommended for allergic subjects.

BACKGROUND: High-quality vacuum cleaners and vacuum cleaner bags are often recommended to allergic patients as a means of reducing indoor allergen exposure. A number of vacuum cleaners on the market today claim to capture 99.9% of particles 0.3 microm or larger entering the vacuum cleaner, and many vacuum cleaner bags are now being sold as microfiltration bags. OBJECTIVE: The purpose of this study was to compare the allergen-trapping abilities of vacuum cleaners and to use a new technique for testing vacuum cleaner bags that are recommended for allergic patients. METHODS: Vacuum cleaners were tested in an 18-m(3) laboratory room permeated with dust containing high levels of cat allergen by using techniques previously described. Air was sampled with parallel filters in conjunction with a particle counter. The filters were assayed by ELISA for cat allergen (Fel d 1). Vacuum cleaner bags were tested by using a modified dust trap to pull sieved house dust containing a known amount of Fel d 1 across the material used for the bag. Allergen passing through the bag was trapped on a filter covering the exit of the trap and analyzed for Fel d 1. RESULTS: In general, vacuum cleaners designed for allergic patients leaked lower amounts of allergen (<0.5-4.04 ng/m(3)) than that found in our previous studies (<0.5-100 ng/m(3)). Single-layer vacuum cleaner bags performed poorly (1250-2640 ng recovered) compared with most of the 2- and 3-layer microfiltration bags (0.53-2450 ng recovered). The range of allergen recovered from the 2-layer bags (0.93-2450 ng recovered) highlighted the variability found between manufacturers. CONCLUSION: The results suggest that although allergen leakage has been reduced, there is still room for improvement. A method of testing allergen leakage by using Fel d 1 should be applied to vacuum cleaners and bags recommended for allergic patients.

Evaluation of materials used for bedding encasement: effect of pore size in blocking cat and dust mite allergen.

BACKGROUND: Mattress and pillow encasings are recommended for patients allergic to dust mites. Many encasements block allergen and are vapor permeable but do not allow free passage of air through the material. Recently, breathable fabrics made from tightly woven synthetic fibers or nonwoven synthetics have been recommend as encasements. OBJECTIVE: The purpose of this study was to develop a method for testing encasement materials made of breathable fabrics. METHODS: Dust samples containing a known quantity of allergen (Der f 1, Der p 1, and Fel d 1) were pulled across a variety of fabrics using a modified dust trap. Airflow through the dust trap was controlled with a vacuum pump. Five minutes after dust was introduced, the pump was shut off. A filter located downstream of the fabric collected allergen passing through the fabric during the test and was assayed with ELISA for the relevant allergen. Fabrics to be tested were obtained from manufacturers and specialty catalogs. RESULTS: As the average pore size decreases, the airflow through a fabric becomes restricted, and the pressure differential created by the vacuum pump increases. Dust mite allergens (Der f 1 and Der p 1) were blocked below detectable limits by fabrics of less than 10 microm in pore size. Fabrics with an average pore size of 6 microm or less blocked cat allergen (Fel d 1). CONCLUSION: The method we developed provided a rigorous and reliable test for leakage of common indoor allergens through breathable barrier fabrics. Our results show that tightly woven fabrics and nonwoven synthetic fabrics can block common indoor allergens but still allow airflow.

Mechanisms of within- and cross-modality suppression in the superior colliculus.

The present studies were initiated to explore the basis for the response suppression that occurs in cat superior colliculus (SC) neurons when two spatially disparate stimuli are presented simultaneously or in close temporal proximity to one another. Of specific interest was examining the possibility that suppressive regions border the receptive fields (RFs) of unimodal and multisensory SC neurons and, when activated, degrade the neuron's responses to excitatory stimuli. Both within- and cross-modality effects were examined. An example of the former is when a response to a visual stimulus within its RF is suppressed by a second visual stimulus outside the RF. An example of the latter is when the response to a visual stimulus within the visual RF is suppressed when a stimulus from a different modality (e. g., auditory) is presented outside its (i.e., auditory) RF. Suppressive regions were found bordering visual, auditory, and somatosensory RFs. Despite significant modality-specific differences in the incidence and effectiveness of these regions, they were generally quite potent regardless of the modality. In the vast majority (85%) of cases, responses to the excitatory stimulus were degraded by >/=50% by simultaneously stimulating the suppressive region. Contrary to expectations and previous speculations, the effects of activating these suppressive regions often were quite specific. Thus powerful within-modality suppression could be demonstrated in many multisensory neurons in which cross-modality suppression could not be generated. However, the converse was not true. If an extra-RF stimulus inhibited center responses to stimuli of a different modality, it also would suppress center responses to stimuli of its own modality. Thus when cross-modality suppression was demonstrated, it was always accompanied by within-modality suppression. These observations suggest that separate mechanisms underlie within- and cross-modality suppression in the SC. Because some modality-specific tectopetal structures contain neurons with suppressive regions bordering their RFs, the within-modality suppression observed in the SC simply may reflect interactions taking place at the level of one input channel. However, the presence of modality-specific suppression at the level of one input channel would have no effect on the excitation initiated via another input channel. Given the modality-specificity of tectopetal inputs, it appears that cross-modality interactions require the convergence of two or more modality-specific inputs onto the same SC neuron and that the expression of these interactions depends on the internal circuitry of the SC. This allows a cross-modality suppressive signal to be nonspecific and to degrade any and all of the neuron's excitatory inputs.

Metabotropic glutamate receptors switch visual response mode of lateral geniculate nucleus cells from burst to tonic.

1. Metabotropic glutamate receptors (mGluRs) on relay cells of the lateral geniculate nucleus appear to be activated exclusively by cortical inputs. We thus sought to manipulate these receptors in an effort to gain insight into the possible role of the corticogeniculate pathway. We used in vivo recording and pharmacological techniques in cats to activate or inactivate these receptors on geniculate neurons while analyzing their response properties. 2. Iontophoretic application of the mGluR agonist 1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) to X and Y cells in the geniculate A laminae diminished or abolished burst activity characteristic of low-threshold Ca2+ spikes. This was accompanied by pronounced changes in the visual response, including a decrease in signal detectability as measured with receiver operating characteristic curves. 3. ACPD effects appear specific to mGluRs, because a specific antagonist of ionotropic glutamate receptors (iGluRs) failed to affect the ACPD-evoked responses, and antagonists of ACPD failed to affect iGluR-mediated responses. We found that 3,5-dihydroxyphenylglycine, an agonist reported to be specific for phosphatidylinositol (PI)-linked mGluRs, had effects similar to those of ACPD, implying that these effects are mediated by PI-coupled mGluRs. Furthermore, antagonists reported to be effective against PI-linked mGluRs were effective in antagonizing the ACPD-mediated effects, and substances reported to be agonists to mGluRs coupled to the adenosine 3',5'-cyclic monophosphate cascade did not affect neuronal responses on their own. These data, when added to our preliminary anatomic data, indicate that the receptor responsible for the observed effects may be mGluR1, or a functionally equivalent mGluR. 4. Activation of mGluRs produces changes in geniculate relay cell activity consistent with depolarization of these cells seen during in vitro studies. Such membrane depolarization has been shown to control the activation state of a voltage-dependent Ca2+ conductance, and this, in turn, determines whether the relay cell fires in tonic or burst mode. Our data show that application of ACPD produces a shift in response mode from burst to tonic. Because response mode is an important characteristic of the geniculate relay and because the activation state of certain mGluRs, which helps determine response mode may be controlled by corticogeniculate input, we conclude that an important function of this input is to provide a visuotopically discrete transition from burst to tonic response mode.

Receiver operating characteristic (ROC) analysis of neurons in the cat's lateral geniculate nucleus during tonic and burst response mode.

Relay cells of the lateral geniculate nucleus respond to visual stimuli in one of two modes: burst and tonic. The burst mode depends on the activation of a voltage-dependent, Ca2+ conductance underlying the low threshold spike. This conductance is inactivated at depolarized membrane potentials, but when activated from hyperpolarized levels, it leads to a large, triangular, nearly all-or-none depolarization. Typically, riding its crest is a high-frequency barrage of action potentials. Low threshold spikes thus provide a nonlinear amplification allowing hyperpolarized relay neurons to respond to depolarizing inputs, including retinal EPSPs. In contrast, the tonic mode is characterized by a steady stream of unitary action potentials that more linearly reflects the visual stimulus. In this study, we tested possible differences in detection between response modes of 103 geniculate neurons by constructing receiver operating characteristic (ROC) curves for responses to visual stimuli (drifting sine-wave gratings and flashing spots). Detectability was determined from the ROC curves by computing the area under each curve, known as the ROC area. Most cells switched between modes during recording, evidently due to small shifts in membrane potential that affected the activation state of the low threshold spike. We found that the more often a cell responded in burst mode, the larger its ROC area. This was true for responses to optimal and nonoptimal visual stimuli, the latter including nonoptimal spatial frequencies and low stimulus contrasts. The larger ROC areas associated with burst mode were due to a reduced spontaneous activity and roughly equivalent level of visually evoked response when compared to tonic mode. We performed a within-cell analysis on a subset of 22 cells that switched modes during recording. Every cell, whether tested with a low contrast or high contrast visual stimulus exhibited a larger ROC area during its burst response mode than during its tonic mode. We conclude that burst responses better support signal detection than do tonic responses. Thus, burst responses, while less linear and perhaps less useful in providing a detailed analysis of visual stimuli, improve target detection. The tonic mode, with its more linear response, seems better suited for signal analysis rather than signal detection.

Latency variability of responses to visual stimuli in cells of the cat's lateral geniculate nucleus.

We constructed average histograms from responses evoked by flashing stimuli and noted previously described variations in the shape of the response profile, particularly with respect to sharpness of the peak. To express this variable, we measured the half-rise latency, which is the latency from stimulus onset required to reach half the maximum response. A short half-rise latency, which is characteristic of nonlagged cells, is associated with a brisk response and sharp peak; a long half-rise latency, characteristic of lagged cells, is associated with a sluggish response and broad peak. Nonlagged cells were readily seen; we attempted to identify cells with long latencies as lagged, but we were unable to do so unambiguously due to failure to observe lagged properties other than latency. We thus refer to these latter cells as having "lagged-like" responses to indicate that we are not certain whether these are indeed lagged cells. In addition to the histograms, we analyzed the individual response trials that were summed to create each histogram, and we used spike density analysis to estimate the initial response latency to the flashing spot for each trial. We found that lagged-like responses were associated with more variability in initial response latency than were nonlagged responses. We then employed an alignment procedure to eliminate latency variation from individual trials; that is, responses during individual trials were shifted in time as needed so that each had a latency equal to the average latency of all trials. We used these "aligned" trials to create a second, "aligned" response histogram for each cell. The alignment procedure had little effect on nonlagged responses, because these were already well aligned due to consistent response latencies amongst trials. For lagged-like responses, however, the alignment made a dramatic difference. The aligned histograms looked very much like those for nonlagged responses: the responses appeared brisk, with a sharply rising peak that was fairly high in amplitude. We thus conclude that the slow build up to a relatively low peak of firing of the lagged-like response histogram is not an accurate reflection of responses on single trials. Instead, the sluggishness of lagged-like responses inferred from average response histograms results from temporal smearing due to latency variability amongst trials. We thus conclude that there is relatively little difference in briskness between nonlagged and lagged-like responses to single stimuli.