Effects of type of emission and masking sound, and their spatial correspondence, on blind and sighted people's ability to echolocate.

Ambient sound can mask acoustic signals. The current study addressed how echolocation in people is affected by masking sound, and the role played by type of sound and spatial (i.e. binaural) similarity. We also investigated the role played by blindness and long-term experience with echolocation, by testing echolocation experts, as well as blind and sighted people new to echolocation. Results were obtained in two echolocation tasks where participants listened to binaural recordings of echolocation and masking sounds, and either localized echoes in azimuth or discriminated echo audibility. Echolocation and masking sounds could be either clicks or broad band noise. An adaptive staircase method was used to adjust signal-to-noise ratios (SNRs) based on participants' responses. When target and masker had the same binaural cues (i.e. both were monoaural sounds), people performed better (i.e. had lower SNRs) when target and masker used different types of sound (e.g. clicks in noise-masker or noise in clicks-masker), as compared to when target and masker used the same type of sound (e.g. clicks in click-, or noise in noise-masker). A very different pattern of results was observed when masker and target differed in their binaural cues, in which case people always performed better when clicks were the masker, regardless of type of emission used. Further, direct comparison between conditions with and without binaural difference revealed binaural release from masking only when clicks were used as emissions and masker, but not otherwise (i.e. when noise was used as masker or emission). This suggests that echolocation with clicks or noise may differ in their sensitivity to binaural cues. We observed the same pattern of results for echolocation experts, and blind and sighted people new to echolocation, suggesting a limited role played by long-term experience or blindness. In addition to generating novel predictions for future work, the findings also inform instruction in echolocation for people who are blind or sighted.

Increased emission intensity can compensate for the presence of noise in human click-based echolocation.

Echolocating bats adapt their emissions to succeed in noisy environments. In the present study we investigated if echolocating humans can detect a sound-reflecting surface in the presence of noise and if intensity of echolocation emissions (i.e. clicks) changes in a systematic pattern. We tested people who were blind and had experience in echolocation, as well as blind and sighted people who had no experience in echolocation prior to the study. We used an echo-detection paradigm where participants listened to binaural recordings of echolocation sounds (i.e. they did not make their own click emissions), and where intensity of emissions and echoes changed adaptively based on participant performance (intensity of echoes was yoked to intensity of emissions). We found that emission intensity had to systematically increase to compensate for weaker echoes relative to background noise. In fact, emission intensity increased so that spectral power of echoes exceeded spectral power of noise by 12 dB in 4-kHz and 5-kHz frequency bands. The effects were the same across all participant groups, suggesting that this effect occurs independently of long-time experience with echolocation. Our findings demonstrate for the first time that people can echolocate in the presence of noise and suggest that one potential strategy to deal with noise is to increase emission intensity to maintain signal-to-noise ratio of certain spectral components of the echoes.

Navigation and perception of spatial layout in virtual echo-acoustic space.

Successful navigation involves finding the way, planning routes, and avoiding collisions. Whilst previous research has shown that people can navigate using non-visual cues, it is not clear to what degree learned non-visual navigational abilities generalise to 'new' environments. Furthermore, the ability to successfully avoid collisions has not been investigated separately from the ability to perceive spatial layout or to orient oneself in space. Here, we address these important questions using a virtual echolocation paradigm in sighted people. Fourteen sighted blindfolded participants completed 20 virtual navigation training sessions over the course of 10 weeks. In separate sessions, before and after training, we also tested their ability to perceive the spatial layout of virtual echo-acoustic space. Furthermore, three blind echolocation experts completed the tasks without training, thus validating our virtual echo-acoustic paradigm. We found that over the course of 10 weeks sighted people became better at navigating, i.e. they reduced collisions and time needed to complete the route, and increased success rates. This also generalised to 'new' (i.e. untrained) virtual spaces. In addition, after training, their ability to judge spatial layout was better than before training. The data suggest that participants acquired a 'true' sensory driven navigational ability using echo-acoustics. In addition, we show that people not only developed navigational skills related to avoidance of collisions and finding safe passage, but also processes related to spatial perception and orienting. In sum, our results provide strong support for the idea that navigation is a skill which people can achieve via various modalities, here: echolocation.

Human Echolocation for Target Detection Is More Accurate With Emissions Containing Higher Spectral Frequencies, and This Is Explained by Echo Intensity.

Humans can learn to use acoustic echoes to detect and classify objects. Echolocators typically use tongue clicks to induce these echoes, and there is some evidence that higher spectral frequency content of an echolocator's tongue click is associated with better echolocation performance. This may be explained by the intensity of the echoes. The current study tested experimentally (a) if emissions with higher spectral frequencies lead to better performance for target detection, and (b) if this is mediated by echo intensity. Participants listened to sound recordings that contained an emission and sometimes an echo from an object. The peak spectral frequency of the emission was varied between 3.5 and 4.5 kHz. Participants judged whether they heard the object in these recordings and did the same under conditions in which the intensity of the echoes had been digitally equated. Participants performed better using emissions with higher spectral frequencies, but this advantage was eliminated when the intensity of the echoes was equated. These results demonstrate that emissions with higher spectral frequencies can benefit echolocation performance in conditions where they lead to an increase in echo intensity. The findings suggest that people who train to echolocate should be instructed to make emissions (e.g. mouth clicks) with higher spectral frequency content.

Human echolocators adjust loudness and number of clicks for detection of reflectors at various azimuth angles.

In bats it has been shown that they adjust their emissions to situational demands. Here we report similar findings for human echolocation. We asked eight blind expert echolocators to detect reflectors positioned at various azimuth angles. The same 17.5 cm diameter circular reflector placed at 100 cm distance at 0°, 45° or 90° with respect to straight ahead was detected with 100% accuracy, but performance dropped to approximately 80% when it was placed at 135° (i.e. somewhat behind) and to chance levels (50%) when placed at 180° (i.e. right behind). This can be explained based on poorer target ensonification owing to the beam pattern of human mouth clicks. Importantly, analyses of sound recordings show that echolocators increased loudness and numbers of clicks for reflectors at farther angles. Echolocators were able to reliably detect reflectors when level differences between echo and emission were as low as -27 dB, which is much lower than expected based on previous work. Increasing intensity and numbers of clicks improves signal-to-noise ratio and in this way compensates for weaker target reflections. Our results are, to our knowledge, the first to show that human echolocation experts adjust their emissions to improve sensory sampling. An implication from our findings is that human echolocators accumulate information from multiple samples.

Visual sensory stimulation interferes with people's ability to echolocate object size.

Echolocation is the ability to use sound-echoes to infer spatial information about the environment. People can echolocate for example by making mouth clicks. Previous research suggests that echolocation in blind people activates brain areas that process light in sighted people. Research has also shown that echolocation in blind people may replace vision for calibration of external space. In the current study we investigated if echolocation may also draw on 'visual' resources in the sighted brain. To this end, we paired a sensory interference paradigm with an echolocation task. We found that exposure to an uninformative visual stimulus (i.e. white light) while simultaneously echolocating significantly reduced participants' ability to accurately judge object size. In contrast, a tactile stimulus (i.e. vibration on the skin) did not lead to a significant change in performance (neither in sighted, nor blind echo expert participants). Furthermore, we found that the same visual stimulus did not affect performance in auditory control tasks that required detection of changes in sound intensity, sound frequency or sound location. The results suggest that processing of visual and echo-acoustic information draw on common neural resources.

Neural correlates of motion processing through echolocation, source hearing, and vision in blind echolocation experts and sighted echolocation novices.

We have shown in previous research (Thaler L, Arnott SR, Goodale MA. PLoS One 6: e20162, 2011) that motion processing through echolocation activates temporal-occipital cortex in blind echolocation experts. Here we investigated how neural substrates of echo-motion are related to neural substrates of auditory source-motion and visual-motion. Three blind echolocation experts and twelve sighted echolocation novices underwent functional MRI scanning while they listened to binaural recordings of moving or stationary echolocation or auditory source sounds located either in left or right space. Sighted participants' brain activity was also measured while they viewed moving or stationary visual stimuli. For each of the three modalities separately (echo, source, vision), we then identified motion-sensitive areas in temporal-occipital cortex and in the planum temporale. We then used a region of interest (ROI) analysis to investigate cross-modal responses, as well as laterality effects. In both sighted novices and blind experts, we found that temporal-occipital source-motion ROIs did not respond to echo-motion, and echo-motion ROIs did not respond to source-motion. This double-dissociation was absent in planum temporale ROIs. Furthermore, temporal-occipital echo-motion ROIs in blind, but not sighted, participants showed evidence for contralateral motion preference. Temporal-occipital source-motion ROIs did not show evidence for contralateral preference in either blind or sighted participants. Our data suggest a functional segregation of processing of auditory source-motion and echo-motion in human temporal-occipital cortex. Furthermore, the data suggest that the echo-motion response in blind experts may represent a reorganization rather than exaggeration of response observed in sighted novices. There is the possibility that this reorganization involves the recruitment of "visual" cortical areas.

What is the best fixation target? The effect of target shape on stability of fixational eye movements.

People can direct their gaze at a visual target for extended periods of time. Yet, even during fixation the eyes make small, involuntary movements (e.g. tremor, drift, and microsaccades). This can be a problem during experiments that require stable fixation. The shape of a fixation target can be easily manipulated in the context of many experimental paradigms. Thus, from a purely methodological point of view, it would be good to know if there was a particular shape of a fixation target that minimizes involuntary eye movements during fixation, because this shape could then be used in experiments that require stable fixation. Based on this methodological motivation, the current experiments tested if the shape of a fixation target can be used to reduce eye movements during fixation. In two separate experiments subjects directed their gaze at a fixation target for 17s on each trial. The shape of the fixation target varied from trial to trial and was drawn from a set of seven shapes, the use of which has been frequently reported in the literature. To determine stability of fixation we computed spatial dispersion and microsaccade rate. We found that only a target shape which looks like a combination of bulls eye and cross hair resulted in combined low dispersion and microsaccade rate. We recommend the combination of bulls eye and cross hair as fixation target shape for experiments that require stable fixation.

The control parameters used by the CNS to guide the hand depend on the visuo-motor task: evidence from visually guided pointing.

To perform visually guided hand movements the visuo-motor system transforms visual information into movement parameters, invoking both central and peripheral processes. Central visuo-motor processes are active in the CNS, whereas peripheral processes are active at the neuromuscular junction. A major share of research attention regarding central visuo-motor processes concerns the question which parameters the CNS controls to guide the hand from one point to another. Findings in the literature are inconsistent. Whereas some researchers suggest that the CNS controls the hand displacement vector, others suggest that it controls final hand position. The current paper introduces a paradigm and analysis method designed to identify the parameters that the CNS controls to guide the hand. We use simulations to validate our analysis in the presence of peripheral visuo-motor noise and to estimate the level of peripheral noise in our data. Using our new tools, we show that hand movements are controlled either in terms of the hand displacement vector or in terms of final hand position, depending on the way visual information relevant for movement production is specified. Interestingly, our new analysis method reveals a difference in central visuo-motor processes, even though a traditional analysis of movement endpoint distributions does not. We estimate the level of peripheral noise in our data to be less than or equal to 40%. Based on our results we conclude that the CNS is flexible with regard to the parameters it controls to guide the hand; that spatial distributions of movement endpoints are not necessarily indicative of central visuo-motor processes; and that both peripheral and central noise has to be carefully considered in the interpretation of movement data.

Diabetes in urban African-Americans. XIX. Prediction of the need for pharmacological therapy.

OBJECTIVE: To develop a prediction rule that will identify patients who will require pharmacological therapy within 6 months of first presentation to a diabetes clinic. RESEARCH DESIGN AND METHODS: Among the patients who came to the Grady Diabetes Clinic between 1991 and 1997, we randomized 557 frequent attenders to a development group and 520 frequent attenders to a validation group. Using multiple logistical regression, we derived a prediction rule in the development group to project whether patients would require pharmacological intervention to achieve HbA1c levels <7% after 6 months. The utility of the prediction rule was then confirmed in the validation group and tested prospectively on an additional group of 93 patients who presented from 1997 to 1998. Performance of the prediction rule was assessed using receiver operating characteristic (ROC) curves. RESULTS: The rule (-4.469 + 1.932 x sulfonylurea Rx + 1.334 x insulin Rx + 0.196 x duration + 0.468 x fasting glucose, where "Rx" indicates a prescription) predicted the need for pharmacological intervention in the development group (P < 0.0001). Use of insulin or sulfonylurea therapy at presentation, duration of diabetes, and fasting glucose levels were significant predictors of the future need for pharmacological management. The prediction rule also performed well in the validation group (positive predictive value 90%, correlation between predicted and observed need for medical management 0.99). ROC curves confirmed the value of the prediction rule (area under the curves was 0.91 for the development group, 0.85 for the validation group, and 0.81 for the prospective group). CONCLUSIONS: Early identification of individuals who will require pharmacological intervention to achieve national standards for glycemic control can be achieved with high probability, thus allowing for more efficient management of diabetes.

Declining bone mass in men with chronic pulmonary disease: contribution of glucocorticoid treatment, body mass index, and gonadal function.

BACKGROUND: Men with chronic lung disease (CLD) are at risk for osteoporosis, but the relative contributions of their chronic pulmonary disease, glucocorticoid therapy, and other factors toward loss of bone has not been established. Understanding the relative importance of these factors would assist in selecting patients for bone densitometry screening and in policy decisions regarding Medicare reimbursement. OBJECTIVE: To identify patients with CLD who are most likely to benefit from bone densitometry screening based on clinical and biochemical measures. DESIGN: Cross-sectional medical survey. PATIENTS: Patients with CLD who were treated with either oral, inhaled, or no glucocorticoid therapy. A control group without lung disease was recruited from the same clinic population. MEASUREMENTS: Dual-energy X-ray absorptiometry was obtained for each group, and the association between bone mass and clinical variables, glucocorticoid use, gonadal hormones, and biochemical markers of bone metabolism was determined. RESULTS: Osteoporosis (a T score < -2.5 at the hip or spine) was five times as likely in patients with CLD as in control subjects. Although the prevalence of osteoporosis was higher (ninefold) after chronic glucocorticoid therapy, patients with CLD who had never been treated with glucocorticoids had a substantial (fourfold) risk of osteoporosis. Chronic inhaled glucocorticoid therapy offered no protection from bone loss compared to treatment with oral glucocorticoids. Of the clinical and biochemical measures that were obtained, bone mass was weakly correlated with body mass index (BMI), serum estradiol-17beta, and N-telopeptide, but not with testosterone, alkaline phosphatase, bone-specific alkaline phosphatase, or osteocalcin. CONCLUSION: Patients with CLD should be considered for bone densitometry screening regardless of glucocorticoid use. Those patients with a low BMI and/or decreased serum estradiol-17beta comprise a subgroup with increased risk for osteoporosis.

Diabetes in urban African-Americans. XVII. Availability of rapid HbA1c measurements enhances clinical decision-making.

OBJECTIVE: To assess the impact of rapid-turnaround HbA1c results on providers' clinical decision-making and on follow-up HbA1c levels. RESEARCH DESIGN AND METHODS: The research design was a randomized clinical trial in which rapid HbA1c results were made available to providers on even days of the month (rapid, n = 575), but delayed by 24 h on odd days (conventional, n = 563). Adjustment of therapy for patients with type 2 diabetes was considered appropriate if therapy was intensified for HbA1c values >7% or not intensified for HbA1c values < or =7%. A post-hoc analysis was also performed using patients (n = 574) who returned for follow-up 2-7 months later to ascertain the effect of rapid HbA1c availability on subsequent glycemic control. RESULTS: Rapid HbA1c availability resulted in more appropriate management compared with conventional HbA1c availability (79 vs. 71%, P = 0.003). This difference was due mainly to less frequent intensification when HbA1c levels were < or =7% (10 vs. 22%, P < 0.0001) and slightly to more frequent intensification for patients with HbA1c values >7% (67 vs. 63%, P = 0.33). For both groups, intensification was greatest for patients on insulin (51%) compared with patients on oral agents (35%) and diet alone (14%) (P < 0.0001). Regression analysis confirmed that providers receiving conventional HbA1c results were more likely to intensify therapy in patients who already had HbA1c levels < or =7%. Over 2-7 months of follow-up, HbA1c rose more in patients with conventional HbA1c results compared with rapid results (0.8 vs. 0.4%, P = 0.02). In patients with initial HbA1c >7%, rapid HbA1c results had a favorable impact on follow-up HbA1c independent of the decision to intensify therapy (P = 0.03). CONCLUSIONS: Availability of rapid HbA1c determinations appears to facilitate diabetes management. The more favorable follow-up HbA1c profile in the rapid HbA1c group occurs independently of the decision to intensify therapy, suggesting the involvement of other factors such as enhanced provider and/or patient motivation.

The low dose (1-microg) adrenocorticotropin stimulation test in the evaluation of patients with suspected central adrenal insufficiency.

Currently, the most popular test for adrenal insufficiency is the conventional rapid ACTH stimulation test (250 microg ACTH). This method is quick and safe, but incorporates a dose of ACTH that is supraphysiological and capable of transiently stimulating the adrenal cortex in many patients with documented central adrenal insufficiency. In recent years, several investigators have published substantial evidence for a more sensitive ACTH stimulation test using a lower dose of ACTH (1 microg). Further analysis of these data, including the calculation of likelihood ratios, demonstrates that the 1-microg test performs significantly better than the 250-microg test compared to the gold standard, insulin tolerance test. We suggest that the 1-microg ACTH stimulation test replace the conventional 250-microg test when evaluating for central adrenal insufficiency. A cortisol level below 500 nmol/L after 30 min signifies impaired adrenocortical reserve. An insulin tolerance test should be performed if this low dose test results in a borderline value and the diagnosis is questioned. The 1-microg test should not be used if recent pituitary injury is suspected. Pharmaceutical companies should be encouraged to provide synthetic ACTH in 1-microg vials.

Effect of withdrawal of antihypertensive drug on depressive mood.

To evaluate the effects on depressive mood of withdrawal of antihypertensive medication, we conducted a randomized, multi-center study with clinical centers at the Albert Einstein College of Medicine, Bronx, NY, University of Alabama School of Medicine, Birmingham, and the University of Mississippi School of Medicine in Jackson. Patients were formerly active participants in the Hypertension Detection and Follow-Up Program (HDFP) whose blood pressure was controlled with drugs for a period of 5 years. Of 496 patients, 431 had both baseline and "1-year" mood scores. Patients, stratified by obesity, were randomized to one of three groups: continue the HDFP medication; discontinue medication with no dietary intervention, or with sodium restriction and potassium increase; or, for those overweight, to a weight reduction intervention. Depression was assessed using the CES-D scale (Center for Epidemiological Studies--Depressed Mood), administered at baseline and again approximately 1 year after randomization. Of the seven treatment groups, only those who continued their HDFP medication showed significant improvement in mood from baseline. The overweight continue-medication group showed significantly greater improvement compared to the no-drugs, no-diet intervention groups, and to the overweight sodium-restriction group. Patients who had their blood pressure successfully controlled with weight reduction had a significant improvement in mood from 11.0 scale points to 8.0, P = .006. Comparisons between those withdrawn from diuretic alone and those withdrawn from both diuretic plus reserpine were inconclusive. Dietary Intervention Study of Hypertension (DISH) shows no evidence that continued use of chlorthalidone has a negative impact on quality of life, while our results concerning reserpine were inconclusive.(ABSTRACT TRUNCATED AT 250 WORDS)

Genic differentiation and origin of Robertsonian populations of the house mouse (Mus musculus domesticus Rutty).

This paper examines the relation between chromosomal and nuclear-gene divergence in 28 wild populations of the house mouse semi-species, Mus musculus domesticus, in Western Europe and North Africa. Besides describing the karyotypes of 15 of these populations and comparing them to those of 13 populations for which such information was already known, it reports the results of an electrophoretic survey of proteins encoded by 34 nuclear loci in all 28 populations. Karyotypic variation in this taxon involves only centric (or Robertsonian) fusions which often differ in arm combination and number between chromosomal races. The electrophoretic analysis showed that the amount of genic variation within Robertsonian (Rb) populations was similar to that for all-acrocentric populations, i.e. bearing the standard karyotype. Moreover, divergence between the two types of populations was extremely low. These results imply that centric fusions in mice have not modified either the level or the nature of genic variability. The genetic similarity between Rb and all-acrocentric populations is not attributed to the persistence of gene flow, since multiple fusions cause marked reproductive isolation. Rather, we attribute this extreme similarity to the very recent origin of chromosomal races in Europe. Furthermore, genic diversity measures suggest that geographically separated Rb populations have in situ and independent origins. Thus, Rb translocations are probably not unique events, but originated repeatedly. Two models are presented to explain how the rapid fixation of a series of chromosomal rearrangements can occur in a population without lowering variability in the nuclear genes. The first model assumes that chromosomal mutation rates are between 10(-3) and 10(-4) and that populations underwent a series of transient bottlenecks in which the effective population size did not fall below 35. In the second model, genic variability is restored following severe bottlenecks, through gene flow and recombination.

[Genetic analysis of the hybridization zone between two subspecies Mus musculus domesticus and Mus musculus musculus in Bulgaria]. / Analyse génétique de la zone d'hybridation entre les deux sous-espèces de souris Mus musculus domesticus et Mus musculus musculus en Bulgarie.

The hybrid zone between the two subspecies of mice Mus musculus domesticus and Mus musculus musculus, which has been studied extensively in Denmark, crosses Europe to the Black Sea through the Alps and the Balkans. Two hundred and seventy-nine animals were captured in 22 localities along a transect across the Balkans. The animals were characterized for seven diagnostic nuclear loci by protein electrophoresis and by restriction pattern analysis of their mitochondrial DNA. The nuclear data show a sharp transition between the two subspecies, most of the variations in allele frequencies (from 0.9 to 0.1) occurring within a 36-km section of the transect. The introgression varies from one locus to the other and is more pronounced, in terms of distance, in M. m. musculus territory. Mitochondrial DNA introgression is important but occurs in one direction only, i.e. from M. m. musculus to M. m. domesticus, while a cytoplasmic transfer from M. m. domesticus to M. m. musculus has been reported. A previous study showed that no Y chromosome introgression occurs. The different behaviour of these three types of markers could be due to the interaction between selection against hybrid genomes and meiotic recombination. Objectively, it would appear that the genes that can introgress are neutral or nearly so and have been separated from deleterious genes they were linked to by recombination. This could explain the differential introgression between autosomal loci. The mitochondrial and Y chromosomes undergo no or very little recombination and each is transmitted as a whole. Their degree of introgression is thus indicative of the intensity of selection resulting from the amount of functional differentiation between the two taxa, which seems to be strong for the Y chromosome and weak for mitochondrial DNA. We propose that the asymmetry of nuclear introgression is due to different population structures. As M. m. musculus is relatively less structured, the rapid spreading of introgressed genes would be favoured. Such a scheme, however, can hardly account for the unidirectionality of the mitochondrial flow, which could be due to sex-dependent behaviour.

H-2 polymorphisms are more uniformly distributed than allozyme polymorphisms in natural populations of house mice.

Patterns of H-2 and allozyme polymorphism in natural populations of house mice from Europe, North Africa and South America were analyzed. The purpose of the analysis was to determine whether H-2 and allozyme polymorphisms were similarly distributed both geographically and temporally in wild mice. Two subspecies of house mice, Mus musculus domesticus and M. m. musculus were sampled and the polymorphisms of two H-2 class I genes, H-2K and H-2D, and 34 allozyme-encoding genes were surveyed. The three kinds of analyses that were conducted included a hierarchical gene diversity analysis, an analysis of the effects of barriers to gene flow, and an analysis of similarity networks. Each of the comparisons demonstrated that H-2 polymorphisms were more uniformly distributed than allozyme polymorphisms and provided additional evidence that H-2 and allozyme polymorphisms are subject to different evolutionary pressures. The analysis of similarity networks also demonstrated that H-2 genes provide little information about the phylogeny of wild mice.