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PubMed2003

A simple simultaneous geometric and intensity correction method for echo-planar imaging by EPI-based phase modulation.

A technique, based on Echo planar imaging (EPI)-based phase modulation factor maps, is described for correction of EPI distortions resulting from field inhomogeneity. In this paper, a phase modulation factor was employed to remove the distortions. The phase modulation factor was obtained experimentally by collecting EPI images with a spin-echo (TE) spacing, deltaTE, equal to the inter-echo time interval, T(i). Then, the distortions resulting from the field inhomogeneity were removed by modulating the kappa-space data with the phase modulation factor. One of the advantages of this method is that it requires only a few extra scans to collect the information on field inhomogeneity. The proposed method does not require a phase unwrapping procedure for field inhomogeneity correction and, hence, is easier to implement, compared to other techniques. In addition, it corrects geometric distortion as well as intensity distortions simultaneously, which is robust to external noise or estimation error in severely distorted images. In this work, we also compared the proposed technique with others including, a) interpolation method with EPI-based displacement maps, and b) modulation method with phase modulation factor maps generated from spin-echo images. The results suggest the proposed technique is superior in correcting severely distorted images.

Algorithms↗
PubMed1995

The combined epidermal growth factor-like modules of Plasmodium yoelii Merozoite Surface Protein-1 are required for a protective immune response to the parasite.

We have reported previously that immunization with a bacterial recombinant protein containing the two epidermal growth factor (EGF)-like modules of Plasmodium yoelii Merozoite Surface Protein-1 (MSP-1) protected mice against challenge with this malaria parasite. Bacterial plasmids containing sequences coding for the individual modules fused to glutathione S-transferase (GST) have now been made. The fusion protein containing the combined EGF-like modules was recognized by anti-parasite antibodies and was immunogenic, producing high titre anti-parasite and anti-GST antibodies. In contrast, fusion proteins containing the two individual EGF-like modules reacted poorly with the natural antibodies and their proteins, as well as a simple mixture of them, induced low levels of anti-parasite antibodies despite producing high levels of anti-GST antibody. Antibodies raised to the recombinant proteins recognized the 230 kDa MSP-1. Groups of mice immunized with the different recombinant proteins were challenged with parasites: protection was observed in the group which had received the recombinant protein containing both modules but not in those groups immunized with the individual modules, either alone or as a mixture. These results suggest that there are important structural determinants formed by the two modules together, which are not present in either of the individual domains alone, and which are responsible for the immunogenicity of the protein or are the target of protective antibodies.

Animals↗
PubMed2001

Neural control of rhythmic, cyclical human arm movement: task dependency, nerve specificity and phase modulation of cutaneous reflexes.

1. The organization and pattern of cutaneous reflex modulation during rhythmic cyclical movements of the human upper limbs has received much less attention than that afforded the lower limb. Our working hypothesis is that control mechanisms underlying the modulation of cutaneous reflex amplitude during rhythmic arm movement are similar to those that control reflex modulation in the leg. Thus, we hypothesized that cutaneous reflexes would show task dependency and nerve specificity in the upper limb during rhythmic cyclical arm movement as has been demonstrated in the human lower limb. 2. EMG was recorded from 10 muscles crossing the human shoulder, elbow and wrist joints while bilateral whole arm rhythmic cyclical movements were performed on a custom-made, hydraulic apparatus. 3. Cutaneous reflexes were evoked with trains (5 x 1.0 ms pulses at 300 Hz) of electrical stimulation delivered at non-noxious intensities (approximately 2 x threshold for radiating parasthesia) to the superficial radial, median and ulnar nerves innervating the hand. 4. Cutaneous reflexes were typically modulated with the movement cycle (i.e. phase dependency was observed). There was evidence for nerve specificity of cutaneous reflexes during rhythmic movement of the upper limbs. Task-dependent modulation was also seen as cutaneous reflexes were of larger amplitude or inhibitory (reflex reversal) during arm cycling as compared to static contraction. 5. While there are some differences in the patterns of cutaneous reflex modulation seen between the arms and legs, it is concluded that cutaneous reflexes are modulated similarly in the upper and lower limbs implicating similar motor control mechanisms.

Adult↗
PubMed2006

An interactive computer kiosk module for the treatment of recurrent uncomplicated cystitis in women.

OBJECTIVE: To validate and implement a computer module for the management of uncomplicated urinary tract infections (UTI). PARTICIPANTS: Women age 18 to 64 years, with a previous UTI, voiding symptoms, and absence of complicating features (comorbidities, vaginal discharge, back pain, emesis, and fever/chills). MEASUREMENTS: The computer module was validated against clinician diagnosis and urine culture. Following validation, the module was implemented in the urgent care clinic as a management option for women with suspected UTI; computer-directed therapy (CDT)-eligible women received antibiotic treatment without a clinician examination. Patient satisfaction with the module and return visits for UTI-related complaints were assessed. RESULTS: In the validation study, 18 of 68 women (26%) were CDT-eligible. Clinicians diagnosed 17/18 CDT-eligible women with uncomplicated UTI. Sixty-seven percent of CDT-eligible women had a positive urine culture. Since implementation, 162 women have accessed the module, and 35% have received CDT. Ninety-eight percent (95% confidence interval: 95% to 100%) found the program easy to use and 95% (89% to 100%) would recommend it to friends/family. Two (4%) CDT-treated women had a return visit to our institution for a UTI-related illness within 2 weeks. CONCLUSIONS: A computer module accurately identifies women with culture-confirmed, uncomplicated UTIs. Patients are highly satisfied with the module.

Adolescent↗
PubMed1995

H-reflex modulation during gait in multiple sclerosis patients with spasticity.

The aim of the present study was to quantitate the Hoffmann (H-) reflex modulation in the soleus muscle of spastic multiple sclerosis patients during walking at different stimulus strengths, and to quantitate the influence of the excitation level of the soleus muscle on the H-reflex. The H-reflex modulation was quantified by the minimum H-reflex in the swing phase and the modulation index introduced by Yang et al. (1). Stimulus strengths were matched between subjects, and only stimuli intensities, which reflect modulation in the H-reflex with true neurophysiological origin, were used. Based on this approach, we found that the reflex modulation is impaired in moderate spastic patients at both a strong and a weak afferent input to the motoneuron pool in consistency with studies on severe spastic patients. This study concludes that the H-reflex modulation in the spastic patients is only related to the excitation level of the muscles, whereas both the excitation level and other factors than the excitation level are known to influence the H-reflex modulation in healthy subjects.

Adult↗
PubMed1987

Clinical correlations of antibodies that bind, block, or modulate human acetylcholine receptors in myasthenia gravis.

Acetylcholine receptor (AChR) binding and AChR modulating antibodies were found with approximately the same frequency (86%) in 349 patients with myasthenia gravis (MG). However, the total yield of positive serological results was significantly improved (90%) by assaying AChR modulating antibodies when AChR binding antibodies were not detected, because in 27 patients (8%) only one of the two tests was positive. The immunoprecipitation test for AChR blocking antibodies yielded fewer positive results (52%), but there was a significant correlation between the degree of AChR blockade and generalization of muscle weakness. In no patient was this the only positive test, because the test for AChR modulating antibodies in this study detected both AChR blocking and modulating antibodies. Human muscle AChR was used as antigen in all tests. False positive results were rare and were attributed to unexplained antibodies to 125I-alpha-Bgt (AChR binding antibody assay) and recent general anesthesia using muscle relaxants (AChR blocking and AChR modulating antibody assays). Unexplained positive results, documented previously in 5% of patients with the Lambert-Eaton myasthenic syndrome and amyotrophic lateral sclerosis (ALS), were found in this study in two of 22 patients with ALS, but in none of 427 patients with miscellaneous neurological diseases. Patients with severe generalized MG and/or thymoma tended to have higher titers of AChR binding antibodies and greater AChR modulating antibody activity. However, some patients with severe muscle weakness had low titers of antibodies, and some patients in remission or with only ocular manifestations had high titers. These seemingly paradoxical results reflect heterogeneity in the specificities, affinities, and isotypes of anti-AChR antibodies. To effect pathogenicity, antibodies must have access in vivo to extracellular antigenic sites on the AChR. One would anticipate that antibodies with greatest pathophysiological potential would be of an IgG with greatest pathophysiological potential would be of an IgG subclass that activates complement, or of a specificity that competes for acetylcholine's binding site on the receptor or readily cross-links two AChR molecules to trigger receptor modulation (e.g., by binding to sites on the duplicated alpha-subunit). In patients with suspected MG who lack serological evidence of anti-AChR antibodies, motor endplate biopsy is required for microelectrophysiological, immunochemical, and ultrastructural studies to establish with certainty whether or not the condition is acquired MG.

Autoantibodies↗
PubMed1993

Membrane potential modulates inositol 1,4,5-trisphosphate-mediated Ca2+ transients in guinea-pig coronary myocytes.

1. Vascular smooth muscle cells were isolated from the coronary artery of the guinea-pig. At 2.5 mM [Ca2+]o and 36 degrees C, whole cell membrane currents were recorded under voltage-clamp and the concentration of ionized calcium in the cytoplasm ([Ca2+]i) was monitored by indo-1 fluorescence. 2. At -60 mV, [Ca2+]i was 143 +/- 36 mM (mean +/- S.D.) and was insensitive to clamp steps to +100 mV. During 1 min application of acetylcholine (ACh, 10 microM) [Ca2+]i increased within approximately 2 s to 1480 +/- 250 nM. During the subsequent slow decay, [Ca2+]i was transiently increased by depolarizing clamp steps and decreased during hyperpolarizing steps. [Ca2+]i transients in response to caffeine (10 mM) could not be modulated by voltage steps. The results suggest that modulation of [Ca2+]i by membrane potential involves inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-induced Ca2+ release (IICR). 3. Modulation of IICR by membrane potential did not depend on sarcolemmal Ca2+ fluxes; it persisted after block of sarcolemmal Ca2+ fluxes with 3 mM lanthanum or after a change to nominally Ca(2+)-free bathing solutions. 4. Modulation of [Ca2+]i by membrane potential was recorded during cell dialysis of 50 microM GTP-gamma-S in the absence of ACh. Cell dialysis of exogenous Ins(1,4,5)P3 (50 or 100 microM) did not mimic the effects. The sensitivity of [Ca2+]i to depolarizing clamp steps was also induced by cell dialysis of lithium ions which, presumably, inhibited the breakdown of Ins(1,4,5)P3. The results are compatible with the idea that the membrane potential modulates the liberation of Ins(1,4,5)P3. 5. Modulation of IICR by membrane potential is discussed as a new mechanism that contributes to the regulation of activator calcium and to the modulation of contraction in vascular smooth muscle cells.

Acetylcholine↗
PubMed2002

Spectral integration in bands of modulated or unmodulated noise.

Spectral integration was measured for pure-tone signals masked by unmodulated or modulated noise bands centered at the signal frequencies. The bands were typically 100 Hz wide, and when modulated, they were sinusoidally amplitude modulated at a rate of 8 Hz and a depth of 100%. In experiment 1, thresholds were first measured for each individual pure tone of a triplet in the presence of its respective masker band, and then for those three tones added together at their respective threshold levels, masked by their respective masker bands. Four sets of triplets were used: 250, 1000, 4000 Hz; 354, 1000, 2828 Hz; 500, 1000, 2000 Hz; and 800, 1000, 1200 Hz. When the masker bands were unmodulated, the amount of spectral integration was about 2.4 dB for all triplets, consistent with the integration expected based on the multiband energy detector model. When the bands were modulated, the amount of integration depended upon the spacing between masker bands; for the two widest spacings, the integration was between about 0 and 3 dB, whereas for the two closest spacings, the integration was approximately 5 dB. Experiments 2 and 3 addressed the cause of this greater spectral integration in the presence of the modulated masker bands with closer spacing. The second experiment demonstrated that sensitivity (d') was proportional to signal power regardless of whether the background noise was modulated or not, and thus the greater integration in dB in the presence of the modulated noise bands could not be accounted for by shallower psychometric functions in those conditions. Instead, the third experiment showed that the greater integration was likely due to the fact that the masker bands were comodulated. In other words, it was probably due to cues related to comodulation masking release when all three bands (and signals) were present.

Adult↗
PubMed2005

Noise improves modulation detection by cochlear implant listeners at moderate carrier levels.

Envelope detection and processing are very important for cochlear implant (CI) listeners, who must rely on obtaining significant amounts of acoustic information from the time-varying envelopes of stimuli. In previous work, Chatterjee and Robert [JARO 2(2), 159-171 (2001)] reported on a stochastic-resonance-type effect in modulation detection by CI listeners: optimum levels of noise in the envelope enhanced modulation detection under certain conditions, particularly when the carrier level was low. The results of that study suggested that a low carrier level was sufficient to evoke the observed stochastic resonance effect, but did not clarify whether a low carrier level was necessary to evoke the effect. Modulation thresholds in CI listeners generally decrease with increasing carrier level. The experiments in this study were designed to investigate whether the observed noise-induced enhancement is related to the low carrier level per se, or to the poor modulation sensitivity that accompanies it. This was done by keeping the carrier amplitude fixed at a moderate level and increasing modulation frequency so that modulation sensitivity could be reduced without lowering carrier level. The results suggest that modulation sensitivity, not carrier level, is the primary factor determining the effect of the noise.

Acoustic Stimulation↗
PubMed2006

Amplitude modulation of turbulence noise by voicing in fricatives.

The two principal sources of sound in speech, voicing and frication, occur simultaneously in voiced fricatives as well as at the vowel-fricative boundary in phonologically voiceless fricatives. Instead of simply overlapping, the two sources interact. This paper is an acoustic study of one such interaction effect: the amplitude modulation of the frication component when voicing is present. Corpora of sustained and fluent-speech English fricatives were recorded and analyzed using a signal-processing technique designed to extract estimates of modulation depth. Results reveal a pattern, consistent across speaking style, speaker, and place of articulation, for modulation at fo to rise at low voicing strengths and subsequently saturate. Voicing strength needed to produce saturation varied 60-66 dB across subjects and experimental conditions. Modulation depths at saturation varied little across speakers but significantly for place of articulation (with [z] showing particularly strong modulation) clustering at approximately 0.4-0.5 (a 40%-50% fluctuation above and below unmodulated amplitude); spectral analysis of modulating signals revealed weak but detectable modulation at the second and third harmonics (i.e., 2fo and 3fo).

Humans↗
PubMed1989

Comodulation masking release (CMR) as a function of masker bandwidth, modulator bandwidth, and signal duration.

These experiments examine how comodulation masking release (CMR) varies with masker bandwidth, modulator bandwidth, and signal duration. In experiment 1, thresholds were measured for a 400-ms, 2000-Hz signal masked by continuous noise varying in bandwidth from 50-3200 Hz in 1-oct steps. In one condition, using random noise maskers, thresholds increased with increasing bandwidth up to 400 Hz and then remained approximately constant. In another set of conditions, the masker was multiplied (amplitude modulated) by a low-pass noise (bandwidth varied from 12.5-400 Hz in 1-oct steps). This produced correlated envelope fluctuations across frequency. Thresholds were generally lower than for random noise maskers with the same bandwidth. For maskers less than one critical band wide, the release from masking was largest (about 5 dB) for maskers with low rates of modulation (12.5-Hz-wide low-pass modulator). It is argued that this release from masking is not a "true" CMR but results from a within-channel cue. For broadband maskers (greater than 400 Hz), the release from masking increased with increasing masker bandwidth and decreasing modulator bandwidth, reaching an asymptote of 12 dB for a masker bandwidth of 800 Hz and a modulator bandwidth of 50 Hz. Most of this release from masking can be attributed to a CMR. In experiment 2, the modulator bandwidth was fixed at 12.5 Hz and the signal duration was varied. For masker bandwidths greater than 400 Hz, the CMR decreased from 12 to 5 dB as the signal duration was decreased from 400 to 25 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1989

Detection and discrimination of frequency modulation of complex signals.

Detection and discrimination of frequency modulation were studied for harmonic signals with triangular spectral envelopes. The center frequency of the stimuli was near 2 kHz; the fundamental frequency was near 100 Hz. To prevent the possibility that the discrimination was based on differences of initial or final frequencies, these frequencies were equal within and across modulations in each individual experiment. Differences between modulations consisted of differences in the trajectories between the initial and final frequencies. Performance worsened as the slopes of the spectral envelopes decreased. Addition of noise also impaired modulation discrimination. The dependence on the signal-to-noise ratio was similar to what is found for stationary stimuli: Discrimination of frequency modulation deteriorated more rapidly with decreasing signal-to-noise ratio when stimuli had shallow spectral slopes than when they had steep spectral slopes. In spite of the precautions taken (i.e., initial and final frequency the same), the discrimination of these stimuli was more likely based on quasistationary frequency discrimination than on discrimination of modulation rate. This conclusion is consistent with previous findings for pure tones presented in quiet that frequency discrimination is more acute than modulation-rate discrimination.

Acoustic Stimulation↗
PubMed1990

Temporal integration in amplitude modulation detection.

Thresholds for detecting sinusoidal amplitude modulation (AM) of a wideband noise carrier were measured as a function of the duration of the modulating signal. The carrier was either; (a) gated with a duration that exceeded the duration of modulation by the combined stimulus rise and fall times; (b) presented with a fixed duration that included a 500-ms carrier fringe preceding the onset of modulation; or (c) on continuously. In condition (a), the gated-carrier temporal modulation transfer functions (TMTFs) exhibited a bandpass characteristic. For AM frequencies above the individual subject's TMTF high-pass segment, the mean slope of the integration functions was - 7.46 dB per log unit duration. For the fringe and continuous-carrier conditions [(b) and (c)], the mean slopes of the integration functions were, respectively, - 9.30 and - 9.36 dB per log unit duration. Simulations based on integration of the output of an envelope detector approximate the results from the gated-carrier conditions. The more rapid rates of integration obtained in the fringe and continuous-carrier conditions may be due to "overintegration" where, at brief modulation durations, portions of the unmodulated carrier envelope are included in the integration of modulating signal energy.

Adult↗
PubMed1993

The perception of temporal modulations by cochlear implant patients.

The perception of temporal modulations of pulsatile electric stimuli was measured in seven cochlear implant patients using the Cochlear Pty. Limited prosthesis. Four patients were postlingually deafened adults and three patients were young adults who were deafened very early in life. The first study measured detection thresholds for modulated pulse duration for a series of modulation frequencies and pulse rates. The shape of the detection thresholds as a function of modulation frequency, the temporal modulation transfer function, often resembled a low-pass filter with a 50-100-Hz cut-off frequency. Thresholds did not markedly vary across the different pulse rates for most patients. Thresholds were less than 10%-20% of the range of usable hearing for most patients. The second study compared detection thresholds for modulated pulse durations around different reference pulse durations: 50, 100, and 300 microseconds. Detection thresholds were generally proportional to the different reference pulse durations. The third study measured difference limens for the discrimination of modulation depth. The difference limens were similar to the detection thresholds for the same reference pulse duration and pulse rate. The three patients deafened very early in life showed more within-group variation in performance, and their overall levels of performance were poorer than those of the postlingually deafened adults.

Acoustic Stimulation↗
PubMed1994

Modulation detection and discrimination with three-component signals.

In an attempt to study the processing of amplitude and frequency modulation (AM and FM), detection and discrimination tasks using mixed modulation (MM) signals were performed. Modulation detection thresholds were obtained for three-component signals that span the parameter space between AM and quasi-FM. A single-cue modulation detection model predicts the thresholds with reasonable accuracy. If one assumes that the AM and FM components are extracted separately, thresholds are also well predicted if the d' of the MM signals is equal to the sum of the separate d's of the AM and FM components (two-cue summation model). This could arise from common internal noise that puts the AM and FM information along a single decision axis. A modulation discrimination task was then examined in which the subjects discriminate between signals with both different modulation depths and different modulation types. The single-cue model predicts performance well. In order for the two-cue model to predict the results, the AM and FM cues must be combined into a single statistic before a decision can be made; the listener cannot process the cues separately.

Adult↗
PubMed1994

Stroboscopic hearing as a mechanism for prey discrimination in frequency-modulated bats?

A hypothesis was proposed that bats employing frequency-modulated (FM) echolocation pulses could utilize dynamic information of a flying insect to discriminate prey on the basis of "stroboscopic hearing." To test this hypothesis, single unit recordings were made from the inferior colliculus (IC) of the little brown bat, Myotis lucifugus. Response characteristics of IC units to trains of modulated and unmodulated sound pulses were analyzed at various pulse repetition rates that corresponded to a bat's pulse emission rates during the different stages of its target directed flight. The results show that amplitude modulation (AM) across a train of sound pulses was faithfully encoded in the units' discharge pattern when the pulse repetition rate was different from the AM frequency. When the AM frequency was integer multiples of the pulse repetition rate, the stimulus amplitude was reduced drastically under these conditions. Consequently, the discharge of an IC unit diminished precipitously, or if there was a phase delay between the pulse onset and the modulating sinusoidal waveform the unit fired to each modulation cycle with more or less the same vigor as if the modulation was absent. These data indicate that the across-pulse amplitude modulation becomes undetectable when the AM frequency is integer multiples of the pulse repetition rate. It is interpreted that FM bats can potentially employ a "stroboscopic hearing" strategy for discriminating insects on the basis of the wing-beat frequency of the prey.

Acoustic Stimulation↗
PubMed1994

Low-pass filtering in amplitude modulation detection associated with vowel and consonant identification in subjects with cochlear implants.

Temporal auditory analysis of acoustic events in various frequency channels is influenced by the ability to detect amplitude modulations which for normal hearing involves low-pass filtering with a cutoff frequency around 100 Hz and a rejection slope of about 10 dB per decade. These characteristics were established in previous studies measuring modulation transfer functions. For cochlear implant subjects, the delivery of detailed amplitude modulation information has been recently shown to result in very significant improvements in speech understanding. Several previous studies on cochlear implant subjects have reported capacities for temporal resolution rather equivalent to those of normally hearing subjects but with some notable individual differences. Recently two studies on some cochlear implant subjects indicated modulation transfer functions often quite similar to those of normal hearing but exhibiting marked individual differences in shape and absolute sensitivity. The present study compared amplitude modulation detection and phonetic recognition in a group of cochlear implant subjects to determine the extent to which the two tasks are correlated. Nine individuals who had been implanted with an Ineraid device and who demonstrated open speech understanding ranging from excellent to poor were chosen and tested in the present study. For each subject modulation transfer functions were measured at the most apical electrode and phonetic recognition of isolated vowels and intervocalic consonants was assessed. Results showed a strong correlation between the depth of high-frequency rejection in modulation transfer functions and success in vowel and consonant intelligibility. These results emphasize the importance of temporal speech features and offer perspectives for customizing signal processing in cochlear implants.

Adult↗
PubMed1994

Development of temporal resolution in children as measured by the temporal modulation transfer function.

Temporal modulation transfer functions (TMTFs) were measured in listeners aged 4 years to adult in order to characterize the development of temporal resolution in children. Four age groups were tested, 4-5 years of age, 6-7 years of age, 9-10 years of age, and adult. Sensitivity to sinuosoidal modulation of a noise carrier (a bandpass noise from 200-1200 Hz) was determined for modulation frequencies of 5, 20, 100, 150, and 200 Hz. The data from all listeners indicated decreasing sensitivity to modulation as a function of increasing frequency of modulation. Time constants were derived from the 3-dB down points of functions that were fitted to the data. No age effects were observed for the derived time constants. However, sensitivity to modulation was found to be reduced in the children 4-5 and 6-7 years of age, as compared to adults, and in the children 4-5 years of age as compared to children 9-10 years of age. The agreement of time constant across all age groups was interpreted as indicating that the peripheral encoding of the temporal envelope is probably adultlike in children aged 4 years and above; however, young children appear to be relatively inefficient in processing the information underlying modulation detection.

Acoustic Stimulation↗