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.

Human Echolocators Have Better Localization Off Axis.

Here, we report novel empirical results from a psychophysical experiment in which we tested the echolocation abilities of nine blind adult human experts in click-based echolocation. We found that they had better acuity in localizing a target and used lower intensity emissions (i.e., mouth clicks) when a target was placed 45° off to the side compared with when it was placed at 0° (straight ahead). We provide a possible explanation of the behavioral result in terms of binaural-intensity signals, which appear to change more rapidly around 45°. The finding that echolocators have better echo-localization off axis is surprising, because for human source localization (i.e., regular spatial hearing), it is well known that performance is best when targets are straight ahead (0°) and decreases as targets move farther to the side. This may suggest that human echolocation and source hearing rely on different acoustic cues and that human spatial hearing has more facets than previously thought.

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.

Contrasting the processes of texture segmentation and discrimination with static and phase-reversing stimuli.

Regions of visual texture can be automatically segregated from one another when they abut but also discriminated from one another if they are separated in space or time. A difference in mean orientation between two textures serves to facilitate their segmentation, whereas a difference in orientation variance does not. The present study further supports this notion, by replicating the findings of Wolfson and Landy (1998) in showing that judgments (odd-one-out) made for textures that differ in mean orientation were more accurate (and more rapid) when the textures were abutting than when separated, whereas judgments of variance were made no more accurately for abutting relative to separated textures. Interestingly, however, responses were overall faster for textures differing in variance when they were separated compared to when they were abutting. This is perhaps due to the clear separation boundary, which serves to delineate the regions on which to perform some regional estimation of orientation variance. A second experiment highlights the phase-insensitivity of texture segmentation, in that locating a texture edge (defined by a difference in mean orientation) in high frequency orientation-reversing stimuli can be performed at much higher frequencies than the discrimination of the same regions but with the texture contour masked. Textures that differed in variance did not exhibit this effect. A final experiment demonstrates that the phase-insensitive perception of texture borders improves with eccentric viewing relative to the fovea, whereas perception of the texture regions does not. Together, these experiments show dissociations between edge- and region-based texture analysis mechanisms and suggest a fast, sign-invariant contour extraction system mediating texture segmentation, which may be closely linked to the magnocellular subdivision of visual processing.

Methylation of two Homo sapiens-specific X-Y homologous genes in Klinefelter's syndrome (XXY).

An increased incidence of psychiatric and structural brain abnormalities in individuals with Klinefelter syndrome (KS, 47 XXY) could be due to the presence of extra copies of X-Y homologous genes that escape X inactivation. Of particular interest are the two brain-expressed genes Protocadherin11XY (PCDH11XY) and the Synaptobrevin-like gene (SYBL1) which have been duplicated from the X chromosome to the Y chromosome to give X-Y homologous gene pairs that are specific to modern humans. We examined the DNA of KS individuals reported recently by DeLisi et al. 2005 and determined the parental origin of the X alleles, the degree of skewed X inactivation and investigated the CpG island methylation status of PCDH11XY and SYBL1 by bisulphite sequencing and quantification of methylated HpaII sites. We used a novel method for quantification of unmethylated CpGs with the restriction enzyme McrBC which cuts methylated but not unmethylated CpGs. The results showed that KS individuals have two methylated and one unmethylated SYBL1 allele whereas PCDH11XY is unmethylated and escapes X inactivation on the extra X chromosome. Overexpression of PCDH11XY in KS is probable and variable escape from inactivation of this Homo sapiens-specific gene could account for some abnormalities in KS. The origin of the parental alleles or their preferential X inactivation was not associated with psychotic symptoms.

Quantitation of X-Y homologous genes in patients with schizophrenia by multiplex polymerase chain reaction.

OBJECTIVES: The genetic basis of schizophrenia is obscure. In an XX male patient with schizophrenia we previously showed that one X;Y translocation breakpoint was in pseudoautosomal region 1 (PAR1) with the effect that the proximal segment of PAR1 from the PAR1 boundary to acetylserotonin N-methyl transferase (ASMT) distally was triplicated in this patient. This study determined whether dosage imbalances of X-Y homologous regions in general are associated with schizophrenia. METHODS: A multiplex semi-quantitative polymerase chain reaction assay was developed to quantify MIC2 gene as a representative of PAR1 and compare it with the SYBL1 gene which maps in pseudoautosomal region 2 (PAR2) and protocadherin XY (PCDHXY), located at Xq21.3. Each of these three loci was co-amplified with the autosomal gene MSX2 using Cy5-labelled primers and the products separated by electrophoresis in polyacrylamide gels. Results were expressed as ratios of peak area of the target gene to MSX2 which served as an internal dosage control. RESULTS: Using genomes with sex chromosome aneuploidies, the method was found sensitive enough to detect a two-fold difference in gene copy number. We confirmed the MIC2 triplication in the XX male patient but found no significant difference in gene dosage of MIC2, PCDHXY and SYBL1 in a panel of 17 patients with schizophrenia compared to controls. CONCLUSIONS: No evidence was obtained for gene dosage imbalances in MIC2, PCDHXY and SYBL1 in patients with schizophrenia.

Nutrition and growth in relation to severity of renal disease in children.

Practical joint medical/dietetic guidelines are required for children with chronic renal insufficiency (CRI). Nutritional status and growth were compared in 95 children (59 male) > 2 years age with CRI, grouped following [51Cr]-labelled EDTA glomerular filtration rate (GFR, ml/min/1.73 m2) estimations into 'normal' kidney function [GFR > 75 (mean 104 (SD 18.9), n = 35], mild (GFR 51-75, n = 23), moderate (GFR 25-50, n = 19) and severe CRI (GFR < 25, n = 18). Anthropometry [weight (wt.), height (ht.), and body mass index (BMI)], laboratory investigations and a 3-day dietary record were obtained. All anthropometric indices deteriorated with worsening renal function, from mean SD scores for wt., ht. and BMI in 'normal' children of 0.32 (SD 1.2), 0.4 (SD 1.0) and 0.1 (SD 1.3), respectively, to values of -1.28 (SD 1.1; P < 0.001), -1.52 (SD 1.1; P < 0.001) and -0.42 (SD 1.1; NS) in severe CRI. Mean total energy intake decreased from 103% (SD 17) estimated average requirement (EAR) in 'normal' children to 85% EAR (SD 27; P = 0.004) in severe CRI. Mean serum PTH concentrations (normal laboratory range 12-72 ng/l) were higher in moderate [67 ng/l (SD 58), P < 0.001] and severe CRI [164 ng/l (SD 164), P < 0.001] and mean serum phosphate concentrations were higher in severe CRI (1.54 mmol/l (SD 0.17), P = 0.009) compared to 'normal'. Disturbances in nutritional intakes, bone biochemistry and growth occur early in CRI and suggest the need for joint medical/dietetic intervention in children with mild and moderate CRI, in addition to those with more severe CRI.

Provision of dietetic care in children on chronic peritoneal dialysis.

OBJECTIVE: To estimate the provision of dietetic care necessary to manage and support children receiving chronic peritoneal dialysis (CPD) with/without nutritional support via a gastrostomy button (GB) and their families. DESIGN: Three-year prospective, longitudinal study documenting dietetic contacts (direct: inpatient/outpatient, telephone, home, school, and family practitioner visits; and indirect: with other health professionals). SETTING: Regional Pediatric Renal Unit. PARTICIPANTS: Thirteen children (7 male; 5 <5 yrs of age) commenced CPD at a mean age of 7.7 years (range, 0.2 to 8.5 years). Eight children received tube feeding (7 GB, 1 nasogastric [NG]) in combination with CPD at a mean age of 4.3 years (range, 0.2 to 8.2 years). MAIN OUTCOME MEASURES: Quantitative data regarding dietetic contacts and growth parameters. RESULTS: Seven hundred eighty-one dietetic contacts were recorded during 182 patient months of observation, with a mean of 5.9 (standard deviation [SD] 1.9) contacts per patient, per month in children <5 years of age, compared with 3.1 (SD 1.6) contacts in children >5 years of age. Eighty-two percent of contacts were with children receiving nutritional support via a GB. Telephone contact accounted for 41% of all contacts in the less than 5 years of age group, compared with 7% in children greater than 5 years of age. Mean standard deviation scores (SDS) for height and weight at the start of the study were -1.2 and -1.32, and at the end were -1.14 and -0. 73. Body mass index (BMI) SDS significantly improved from -0.91 to 0. 17 (P = 0.03). CONCLUSION: This study illustrates the number and nature of dietetic contacts that we felt were required to support children and families on CPD. Attempts to achieve adequate nutritional intakes for growth require frequent adjustments of nutritional prescriptions, particularly in preschool children.

Chronic renal failure in infancy. Two dietetic case reports.

Dietetic care of infants with end stage renal disease (ESRD) involving intensive nutritional support and frequent monitoring in attempts to optimise growth has not been previously quantified. We describe the progress of two male infants born with ESRD due to renal dysplasia. Child A and child B were commenced on continuous cyclic peritoneal dialysis at mean age of 3 months and required nutritional support via a gastrostomy button. Energy intakes pre-dialysis (147 kcal/kg) and energy and protein intakes during the first year of life on CCPD (137 kcal/kg, 2.6 g/kg actual body weight) were greater than recommended for the healthy population. Over the 2 year period without growth hormone, height SDS increased from -1.66 to -0.17 and 0.67 to 0.78 and weight SDS increased from -1.26 to -0.43 and 0.31 to 1.75 for Child A and Child B respectively. Mean dietetic contacts (in/out patient and telephone) over the 2 years were 11.8 contacts/mth pre-dialysis, 8.4 contacts during the first year on CCPD and 4.3 contacts during the second year. We conclude that infants with end stage renal disease require frequent dietetic contact in combination with early dialysis and tube feeding to achieve nutritional goals and optimise growth. In addition, dietetic advice provides valuable family support.

Dose-dependent effects of arginine vasopressin on endocrine and blood gas responses of fetal sheep during the last third of pregnancy.

Arginine vasopressin (AVP) is released in fetal sheep in response to various intrauterine stresses such as hypoxaemia, hypotension, and haemorrhage. We have examined the effects of exogenous AVP injected at two doses (200 ng and 2 micrograms) on the plasma concentrations of ACTH and cortisol, and on arterial blood PO2, PCO2, and pH in chronically catheterized fetal sheep at d110-115, d125-130, and at d135-140 of pregnancy. AVP (2 micrograms) provoked a significant elevation in the plasma ACTH and cortisol concentration at all three stages of gestation, whereas the administration of 200 ng AVP raised plasma ACTH and cortisol only at d110-115 and at d125-130. The increment in plasma cortisol after 200 ng AVP at the two earlier stages of pregnancy was similar to that after 2 micrograms AVP, despite a dose-dependent difference in the change in ACTH concentration. AVP stimulated a rise in PaO2 at each time of study, although the time course of response was shorter at d135-140 than at the previous stages of pregnancy. The effect of AVP on PaCO2 was more variable, showing a transient decrease at +5 min after injection in the two oldest groups of fetuses. pH fell after AVP at d110-115 and at d125-130, but it rose transiently in the oldest fetuses. We conclude that at high concentrations systemic administration of AVP provokes endocrine and blood gas changes in fetal sheep. ACTH was consistently elevated by AVP. PaO2 also rose at each stage of pregnancy, but the effects on PaCO2 and pH varied as a function of fetal age.(ABSTRACT TRUNCATED AT 250 WORDS)

Dexamethasone inhibits ovine corticotrophin-releasing factor (oCRF), arginine vasopressin (AVP), and oCRF + AVP stimulated release of ACTH during the last third of pregnancy in the sheep fetus.

We examined the hypothesis that in fetal sheep during late pregnancy exogenous glucocorticoids might affect differentially the pituitary response, measured as changes in plasma ACTH concentrations, to the systemic administration of ovine corticotrophin-releasing factor (oCRF), arginine vasopressin (AVP), or oCRF + AVP. At d 113-116 of pregnancy, equimolar injections of oCRF and AVP given separately provoked similar significant increases in plasma ACTH; the change in ACTH over basal values was significantly greater than the sum of the two separate responses when AVP + oCRF were given together. Exogenous dexamethasone did not affect basal ACTH concentrations, but suppressed significantly the responses to oCRF, AVP, and oCRF + AVP. At d 126-130, there was a significant ACTH response to CRF alone and to AVP + oCRF, but not to AVP alone. The response during the first 30 min postinjection to oCRF was significantly less than that to AVP + oCRF. Plasma cortisol rose after each peptide injection. Exogenous dexamethasone suppressed both basal and stimulated responses to each peptide. At the amounts injected, there was no significant ACTH or cortisol response to oCRF, AVP, or oCRF + AVP at d 136-140, but dexamethasone suppressed basal ACTH and cortisol concentrations at this time. We conclude that stimulated, but not basal, release of ACTH is subject to the negative feedback effect of exogenous glucocorticoid by d 113-116 of gestation in fetal sheep. Both basal and stimulated release of ACTH and cortisol are suppressed after d 125. At the amount of exogenous dexamethasone given, oCRF, AVP, and oCRF + AVP-stimulated responses are affected similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

Pituitary and adrenal responses to pulsatile ovine corticotropin-releasing factor administered to fetal sheep.

In fetal sheep a bolus injection of ovine CRF (oCRF) elevates plasma immunoreactive ACTH (IR-ACTH) during the last 5 weeks of gestation. However, the effects of long term administration of oCRF to fetal sheep have not been studied. We examined the effects of pulsatile administration of oCRF (1 microgram every 4 h) for 7 days on fetal pituitary and adrenal responses, as reflected by plasma concentrations of IR-ACTH and cortisol (F). In addition, we examined the effects of oCRF on cAMP accumulation by dispersed pituitary cells in vitro after treatment in vivo with either oCRF or saline. Pulsed oCRF (P-CRF) treatment resulted in a significant (P less than 0.05) increase in basal IR-ACTH and F concentrations on all days of treatment. However, the pituitary response (change in IR-ACTH in response to a pulse of oCRF) decreased, and the adrenal response (change in F in response to endogenously secreted ACTH) increased as treatment progressed. A significant inverse correlation (r = 0.962) between basal F and the IR-ACTH response to oCRF was seen over the 7 days of treatment. Although P-CRF treatment resulted in an increase in fetal adrenal weight, it did not lead to premature parturition. There was a dose-dependent accumulation of cAMP in response to oCRF in vitro by dispersed pituitary cells from both groups of fetuses. However, this response was significantly greater when the fetuses had been pretreated with oCRF in vivo than after saline treatment. We conclude that the P-CRF regimen employed in this study stimulates the fetal pituitary-adrenal axis and the ability of fetal pituitary cells to accumulate cAMP in response to further oCRF in vitro. The reduced plasma IR-ACTH response after continued P-CRF in vivo may be attributed to increasing negative feedback effects of elevated endogenous F.

Synergism between systemic corticotropin-releasing factor and arginine vasopressin on adrenocorticotropin release in vivo varies as a function of gestational age in the ovine fetus.

In sheep, parturition is associated with maturation of fetal pituitary-adrenal function, and with rises in the concentrations of ACTH and cortisol (F) in fetal plasma. We examined the hypothesis that pituitary ACTH output in response to arginine vasopressin (AVP) and CRF separately and together might change during late pregnancy as a function of fetal age. Fetal sheep were chronically catheterized, and bolus iv injections of equimolar AVP, CRF, AVP plus CRF, or saline (controls) were given on days 110-115, 125-130, and 135-140 of gestation. AVP evoked significant rises in plasma ACTH on days 110-115 and 125-130, but not on days 135-140. After AVP, the peak plasma concentrations of ACTH were attained at 5-10 min, and basal (preinjection) values were reestablished by 30-60 min. After CRF treatment, plasma ACTH rose progressively throughout the 240 min of the study. Evidence was obtained in support of an increase in pituitary responsiveness to CRF between days 110-115 and 125-130 and a decrease in response on days 135-140, when basal F concentrations were higher. The ACTH response to AVP, relative to that to CRF, was greatest in the youngest fetuses. On days 110-115 only, CRF and AVP showed a synergistic response in ACTH output, especially during the first 30 min after agonist injection. Plasma F rose in response to the changes in endogenously released ACTH in a manner consistent with progressive fetal adrenal maturation between days 110-140 of pregnancy. We conclude that in vivo the ovine fetal pituitary responds separately and synergistically to AVP and CRF on days 110-115 of gestation, but the relative role of AVP in stimulating ACTH release decreases with progressive gestational age.

Changes in pituitary responses to synthetic ovine corticotrophin releasing factor in fetal sheep.

The rise in cortisol in fetal sheep during late pregnancy has been related to increased responsiveness of the adrenal to ACTH. Most reports have suggested that plasma ACTH concentrations rise coincident with or after the prepartum increase in cortisol. To reexamine the relationship of cortisol with basal immunoreactive ACTH (IR-ACTH) throughout the last 40 days of pregnancy and to determine changes in fetal pituitary responsiveness during this time, we measured basal and synthetic ovine corticotrophin-releasing factor (oCRF) (10 ng-10 micrograms) induced rises in ACTH and cortisol in fetal sheep at days 110-115, 125-130, and 135-140 of pregnancy. The fetuses were catheterized on day 105-120 and entered spontaneous labour at greater than 140 days. Basal IR-ACTH (picograms per millilitre +/- SEM) rose from 16.7 +/- 2.9 pg/mL at day 110-115 to 34.8 +/- 8.7 pg/mL at day 141-145. There was a significant effect of time on basal ACTH concentrations with a mean increase of approximately 5 pg ACTH per millilitre of plasma per 5-day sampling interval. Plasma cortisol changed gradually between day 110 and 125 of gestation and then more rapidly to term. At day 110-115 of gestation there was no significant change in plasma ACTH after 10 or 100 ng oCRF, but there was a significant increase in ACTH after 1 microgram of oCRF. Plasma cortisol did not change after any CRF injection. The change in IR-ACTH after oCRF at day 125-130 of gestation was significantly greater than that at day 110-115. Plasma cortisol concentrations were elevated following 1- and 10-micrograms injections of oCRF.(ABSTRACT TRUNCATED AT 250 WORDS)