Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “modulators”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed1998

The European Organization for Research and Treatment of Cancer approach to developing questionnaire modules: an update and overview. EORTC Quality of Life Study Group.

The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Study Group has adopted a modular approach to quality of life (QoL) assessment in cancer clinical trials. The core instrument (the EORTC QLQ-C30) covers a range of QoL issues relevant to a broad spectrum of patients with cancer. The QLQ-C30 is designed to be supplemented by more specific subscales ('modules') to assess aspects of QoL of particular importance to specific subgroups of patients. Since individual members of the study group were to be involved in module development, guidelines were established. The primary aim of these guidelines was to standardize the module development process in order to ensure uniformly high quality across modules. This paper gives an update of the work completed to date. First, while the guidelines proved practical for module development, producing modules that exhibit adequate levels of psychometric and cross-cultural validity, experience pointed to three areas where the guidelines required more precision. These amendments will be provided and include (1) stricter monitoring of the developmental process from within the study group, (2) the explicit requirement of involvement of the study group and (3) a more precise definition of the criteria to be fulfilled before modules are allowed to be called 'EORTC modules'. Second, an overview of the modules currently under development or available for general use is provided. These modules include those for body image, high-dose chemotherapy, leukaemia, myeloma, palliative care and the following cancers: bladder, brain, breast, colorectal, head and neck, lung, oesophageal, ophthalmic, ovarian, pancreas and prostate. Finally, the need for the coordination of efforts in module development, both from within and outside the EORTC, is discussed.

Algorithms↗
PubMed2003

Small-molecule cyclin-dependent kinase modulators.

Aberrations in cell cycle progression occur in the majority of human malignancies. The main pathway affected is the retinoblastoma (Rb) pathway. The tumor suppressor gene Rb is an important component in the G(1)/S transition and its function is abnormal in most human neoplasms. Loss in Rb function occurs by the hyperactivation of the cyclin-dependent kinases (cdk's). Therefore, modulation of cdk's may have an important use for the therapy and prevention of human neoplasms. Efforts to obtain small-molecule cdk modulators yielded two classes of modulators: direct and indirect modulators. Direct cdk modulators are small molecules that specifically target the ATP binding site of cdk's. Examples for this group include flavopiridol, roscovitine and BMS-387032. In contrast, indirect cdk modulators affect cdk function due to modulation of upstream pathways required for cdk activation. Some examples include perifosine, lovastatin, and UCN-01. The first example of a direct small-molecule cdk modulator tested in the clinic, flavopiridol, is a pan-cdk inhibitor that not only promotes cell cycle arrest but also halts transcriptional elongation, promotes apoptosis, induces differentiation, and has antiangiogenic properties. Clinical trials with this agent were performed with at least three different schedules of administration: 1-, 24- and 72-h infusions. The main toxicities for infusions >/=24-h are secretory diarrhea and proinflammatory syndrome. In addition, patients receiving shorter infusions have nausea/vomiting and neutropenia. A phase II trial of patients with advanced non-small-cell lung carcinoma using the 72-h infusion every 2 weeks was recently completed. The median overall survival for the 20 patients who received treatment was 7.5 months, a survival similar to that obtained in a randomized trial of four chemotherapy regimens containing platinum analogues in combination with taxanes or gemcitabine, or with gefitinib, a recently approved EGFR inhibitor for the treatment of advanced lung cancer. Based on these encouraging results, a phase III trial comparing standard combination chemotherapy versus combination chemotherapy plus flavopiridol is currently under investigation. The second example of direct small-molecule cdk modulator tested in clinical trials is UCN-01 (7-hydroxystaurosporine). UCN-01 has interesting preclinical features: it inhibits Ca(2+)-dependent PKCs, promotes apoptosis, arrests cell cycle progression at G(1)/S, and abrogates checkpoints upon DNA damage. The first phase I trial of UCN-01 demonstrated a very prolonged half-life. Based on this novel feature, UCN-01 is administered as a 72-h continuous infusion every 4 weeks (in second and subsequent cycles UCN-01 is administered as a 36-h infusion). Other shorter schedules (i.e. 3 h) are being tested. Dose-limiting toxicities include nausea/vomiting, hypoxemia, and insulin-resistant hyperglycemia. Combination trials with cisplatin and other DNA-damaging agents are being tested. Recently, phase I trials with two novel small-molecule cdk modulators, BMS 387032 and R-Roscovitine (CYC202), have commenced with good tolerability. In summary, novel small-molecule cdk modulators are being tested in the clinic with interesting results. Although these small molecules are directed towards a very prevalent cause of carcinogenesis, we need to test them in advanced clinical trials to determine the future of this class of agents for the prevention and therapy of human malignancies.

Cell Cycle↗
PubMed1988

Evidence that the modulator of the glucocorticoid-receptor complex is the endogenous molybdate factor.

We have recently purified the modulator of the glucocorticoid-receptor complex from rat liver. Purified modulator inhibits glucocorticoid-receptor complex activation and stabilizes the steroid-binding ability of the unoccupied glucocorticoid receptor. Since these activities are shared by exogenous sodium molybdate, modulator appears to be the endogenous factor that sodium molybdate mimics. In this report, we present additional evidence for the mechanism of action of purified modulator. (i) Molybdate and modulator inhibit receptor activation as measured by DNA-cellulose binding, DEAE-cellulose chromatography, and Sepharose 4B gel filtration. (ii) The ability of molybdate and modulator to inhibit receptor activation and stabilize the unoccupied receptor appears to be additive. (iii) Scatchard analysis of heat-destabilized unoccupied receptors indicates that the number of steroid-binding sites is reduced during destabilization, whereas the steroid dissociation constant remains unchanged. Molybdate and modulator stabilize the receptor by maintaining the number of steroid-binding sites. (iv) Molybdate and modulator do not inhibit alkaline phosphatase-induced destabilization of the unoccupied receptor. However, alkaline phosphatase-induced destabilization is reversed by the addition of dithiothreitol in the presence, but not in the absence, of molybdate or modulator. These results suggest that the mechanism of action for modulator is identical to that of sodium molybdate, and we propose that modulator is the endogenous molybdate factor for the glucocorticoid receptor.

DNA↗
PubMed1997

The high affinity calcium-binding sites in the epidermal growth factor module region of vitamin K-dependent protein S.

Vitamin K-dependent protein S, a cofactor of the anticoagulant enzyme-activated protein C, has four epidermal growth factor (EGF)-like modules, all of which have one partially hydroxylated Asp (EGF 1; beta-hydroxyaspartic acid) or Asn (EGF 2, 3, and 4; beta-hydroxyasparagine) residue. The three C-terminal modules have a typical Ca2+ binding sequence motif that is usually present in EGF modules with hydroxylated Asp/Asn residues. Using the chromophoric Ca2+ chelators Quin 2 and 5,5'-Br2BAPTA, we have now determined the Ca2+ affinity of recombinant fragments containing EGF modules 1-3, 1-4, 2-3, and 2-4. EGF modules 1-4 and 2-4 each contains two very high affinity Ca2+-binding sites, i.e. with dissociation constants ranging from 10(-10) to 10(-8) M in the absence of salt and from 10(-8) to 10(-6) M in the presence of 0.15 M NaCl. In contrast, in EGF 1-3 and EGF 2-3, the Ca2+ affinity is 2-4 orders of magnitude lower. EGF 4 thus appears to have the highest Ca2+ affinity, and furthermore it seems to influence the Ca2+ affinity of its immediate N-terminal neighbor EGF 3 by a factor of approximately 230. In addition, EGF 4 seems to influence the Ca2+ affinity of EGF 2 by a factor of approximately 25. The Ca2+ affinity of the binding sites in EGF modules 3 and 4 in fragments EGF 1-4 and EGF 2-4 is 10(3)-10(5)-fold higher than in the corresponding isolated modules, implying important contributions to the Ca2+ affinity of each module from interactions with neighboring modules. This difference is much higher than the approximately 10-fold difference previously found in similar comparisons of EGF modules from fibrillin. However, the modules studied in protein S and fibrillin appear to have the similar Ca2+ ligands. The structural basis for the difference in Ca2+ affinity is not yet understood.

Amino Acid Sequence↗
PubMed2004

Demonstration of the effectiveness and acceptability of self-study module use in residency education.

Educators face increasing challenges to promote lifelong learning skills, to include new content areas in an already full curriculum and to maximize limited resources for curriculum implementation. Self-study modules (hereafter modules) offer potential solutions. Three modules on preventive medicine topics were evaluated in Family Medicine residencies. A retrospective pre-/post-test of a resident's ability to meet the module's objectives was used for evaluation. Additionally, residents rated the appropriateness and acceptability of the modules, their preference for 13 methods of learning, and completed a multiple-choice knowledge test. This study demonstrates the effectiveness of modules at multiple levels of evaluation in accordance with a modified version of Kirkpatrick's hierarchy of levels of evaluation. Residents found the modules to be acceptable and useful. Significant gains were seen in residents' abilities to meet objectives. The multiple-choice knowledge test was used to demonstrate mastery of the module materials at an appropriate performance level for future practitioners. Module use was in the top five choices of preferred learning methods. No correlation was seen between residents' preference for learning using modules and educational outcomes. Modules are an effective and acceptable learning method for residents. Even those who prefer other learning methods show improved educational outcomes.

Humans↗
PubMed2004

Effects of amplitude compression on first- and second-order modulation detection thresholds in cochlear implant listeners.

The aim of this study was to examine the effects of instantaneous non-linear amplitude mapping on the detection of single-component and multicomponent temporal envelopes. To address this issue, first- and second-order amplitude modulation detection thresholds were measured in four cochlear implant users with the intervention of the compression device of the implant processor. The compression device is set to produce either a strongly or a weakly logarithmic mapping of stimulus amplitude to electrical amplitude. 'First-order' modulation detection thresholds indicate the ability of listeners to detect sinusoidal amplitude modulation (SAM) applied to a white noise carrier; they are measured as a function of the rate of that modulation, fm. 'Second-order' modulation detection thresholds indicate the ability to detect sinusoidal modulation applied to the depth of a sinusoidally amplitude-modulated signal (here, a 16-Hz sinusoidally amplitude-modulated white noise); they are measured as a function of the rate of the modulation applied to the modulation depth (referred to as fm'). In each task, stimuli are transformed by the implant processor and are presented through one electrode at approximately the same level. The results show that, in cochlear implant listeners, both first- and second-order modulation detection thresholds measured at the lower rates (< or =7 Hz) decrease slightly by about 3-6dB when the stronger compression is used. No effect of compression is observed at higher rates. These results suggest that instantaneous logarithmic amplitude mapping has beneficial- but limited-effects on the detection of single-component and multicomponent temporal envelopes. These results are discussed in light of current models of temporal envelope processing.

Auditory Threshold↗
PubMed2002

Working with interpreters: an interactive Web-based learning module.

OBJECTIVE: Medical students are presented with unique challenges when they care for patients with limited English proficiency. Students must learn a complex set of skills needed to care for patients across cultural and language barriers and to understand the impact of their own attitudes and beliefs about caring for these patients. We developed and piloted a multimedia interactive Web-based module aimed at teaching students effective strategies for working with interpreters and diverse patient populations, and at raising their awareness of important legal, ethical, and cultural issues. DESCRIPTION: First the learner completes a 37-multiple-choice-question (MCQ) pre-test that assesses attitudes, factual knowledge, and ability to analyze written clinical scenarios relevant to the module's content. Learners are then shown a series of professionally produced video vignettes, which reflect diverse patient populations, interpreters, and effectiveness of interpretation strategies (e.g., a Russian-speaking woman with chest pain whose daughter interprets, a medical student interpreting for a Chinese-speaking man using herbal medication, a Haitian woman told of an abnormal mammogram through a trained simultaneous interpreter). In each case, learners submit short answers to on-screen questions analyzing the effectiveness of the interpretation strategies demonstrated. Immediate feedback is given comparing student responses with those of experts. At any time during the module, the learners may view video commentary by legal, ethics, and cultural experts, or access a glossary and Web site links. Students conclude the module by again taking the MCQ test. A final screen compares their pre- and post-MCQ test responses and shows best answers, allowing them to assess their learning. The learners also complete a survey, providing personal cultural information and feedback on the module. DISCUSSION: All 160 first-year medical students completed the module and evaluated its effectiveness this year. On average, students improved by 20% on the MCQ post-test and 86% of the students were satisfied with the learning experience and acquired new knowledge. As a result of their participation in the module, students examined their own cultural and linguistic backgrounds and made the following comments: "I am interested in exploring the way my own culture and cultural biases could impact my working with patients from other cultures"; "This module has opened my eyes to the fears and concerns of immigrants who do not speak English." Therefore, this pilot of the module effectively imparted guidelines for, and raised awareness of, medical interpreting. The most common critique of the module was that as a result of technical difficulties, it was time-consuming. A more rigorous evaluation is planned for the next academic year. We are also working to enrich and enhance the module for more experienced clinicians (GME and CME). As a complementary educational tool, the Internet has the advantages of allowing students to work at their own paces, view engaging video clips, and participate in interactive learning with immediate feedback and self-assessment.

Communication Barriers↗
PubMed2002

Nonribosomal biosynthesis of vancomycin-type antibiotics: a heptapeptide backbone and eight peptide synthetase modules.

During analysis of the recently identified gene cluster for the glycopeptide antibiotic balhimycin, produced by Amycolatopsis mediterranei DSM 5908, novel genes were identified and characterized in detail. The gene products of four of the identified genes (bpsA, bpsB, bpsC and bpsD) are nonribosomal peptide synthetases (NRPSs); one (Orf1-protein) shows similarities to small proteins associated with several NRPSs without an assigned function. BpsA and BpsB are composed of three modules each (modules 1-6), BpsC of one module (module 7) and BpsD of a minimal module (module 8). Thus, the balhimycin gene cluster encodes eight modules, whereas its biosynthetic product is a heptapeptide. Non-producing mutants were created by a gene disruption of bpsB, an in-frame deletion of bpsC and a gene replacement of bpsD. After establishment of a gene complementation system for Amycolatopsis strains, the replacement mutant of bpsD was complemented, demonstrating for the first time that BpsD, encoding the eighth module, is indeed involved in balhimycin biosynthesis. After feeding with beta-hydroxytyrosine the capability of the bpsD mutant to produce balhimycin was restored, demonstrating the participation of BpsD in the biosynthesis of this amino acid. The specificity of four of the eight adenylation domains was determined by ATP/PP(i) exchange assays: modules 4 and 5 activated L-4-hydroxyphenylglycine, module 6 activated beta-hydroxytyrosine and module 7 activated L-3,5-dihydroxyphenylglycine, which is in accordance with the sequence of the non-proteogenic amino acids 4 to 7 of the balhimycin backbone.

Actinomycetales↗
PubMed2006

Elucidation of the mechanism of the regulatory function of the Ig1 module of the fibroblast growth factor receptor 1.

The extracellular part of the fibroblast growth factor (FGF) receptor (FGFR) consists of up to three Ig modules (Ig1-Ig3), in which the Ig2 and Ig3 modules determine affinity and specificity for FGF and heparin. The FGFR isoforms lacking the Ig1 module have higher affinity for FGF and heparin than the triple Ig-module isoforms, suggesting that the Ig1 module is involved in the regulation of the FGFR-ligand interaction. We show here by surface plasmon resonance and NMR analyses that the Ig1 module binds to the Ig2 module, and identify by NMR the binding sites involved in the Ig1-Ig2 interaction. The identified binding site in the Ig2 module was found to be in the area of the FGF-Ig2 and Ig2-heparin contact sites, thus providing direct structural evidence that the Ig1 module functions as a competitive autoinhibitor of the FGFR-ligand interaction. Furthermore, the Ig1 binding site of the Ig2 module overlaps the Ig2-Ig2 contact site. This suggests that the function of the Ig1 module is not only regulation of the FGFR-ligand binding affinity but also prevention of spontaneous FGFR dimerization (through a direct Ig2-Ig2 interaction) in the absence of FGF.

Animals↗
PubMed1999

Dental students' evaluation of 2 community-oriented PBL modules.

OBJECTIVES: To evaluate dental students' perception of 2 problem-based learning (PBL) modules in Dental Public Health implemented within the context of a traditional formal curriculum. METHODS: 2 dental community modules were implemented with an 8-month interval between them on the same group of dental undergraduates; the first in Term 2 and the second in Term 4 of a 5-year 15-term dental course. At the end of each module, a semi-structured questionnaire was administered to evaluate the introductory lecture, the fieldwork activity and the organisation of the modules. RESULTS: In both modules, students reported gaining insight into the subject matter, skills in teamwork, making presentations and collecting data. Some students in the 1st module needed more time to fulfil their learning objectives and had difficulty in collecting data. In the 2nd module, students reported that they lacked motivation because of the place of the module within their timetable. Opinions differed about groupwork. The content of and interest generated by fieldwork activity was rated more positively in the 2nd module than the 1st. Less positively rated in the 2nd module was the introductory lecture and module organisation. CONCLUSIONS: Implementing PBL within a traditional curriculum does not offer uniform outcomes for students. Optimum group size and adequate time are necessary if students are to benefit from PBL. A consistent and continuous PBL approach should be adopted rather than a sporadic one. Further research should establish the optimum balance between PBL and traditional approaches that would allow students to maximise the benefits of both and to identify those students best equipped to benefit from a 'mixed economy' of learning.

Community Dentistry↗
PubMed2003

Understanding speech in modulated interference: cochlear implant users and normal-hearing listeners.

Many competing noises in real environments are modulated or fluctuating in level. Listeners with normal hearing are able to take advantage of temporal gaps in fluctuating maskers. Listeners with sensorineural hearing loss show less benefit from modulated maskers. Cochlear implant users may be more adversely affected by modulated maskers because of their limited spectral resolution and by their reliance on envelope-based signal-processing strategies of implant processors. The current study evaluated cochlear implant users' ability to understand sentences in the presence of modulated speech-shaped noise. Normal-hearing listeners served as a comparison group. Listeners repeated IEEE sentences in quiet, steady noise, and modulated noise maskers. Maskers were presented at varying signal-to-noise ratios (SNRs) at six modulation rates varying from 1 to 32 Hz. Results suggested that normal-hearing listeners obtain significant release from masking from modulated maskers, especially at 8-Hz masker modulation frequency. In contrast, cochlear implant users experience very little release from masking from modulated maskers. The data suggest, in fact, that they may show negative effects of modulated maskers at syllabic modulation rates (2-4 Hz). Similar patterns of results were obtained from implant listeners using three different devices with different speech-processor strategies. The lack of release from masking occurs in implant listeners independent of their device characteristics, and may be attributable to the nature of implant processing strategies and/or the lack of spectral detail in processed stimuli.

Adult↗
PubMed1986

Critical modulation frequency based on detection of AM versus FM tones.

The ratios between the modulation index (eta) for just noticeable FM of a sinusoidally modulated pure tone and the degree of modulation (m) for just noticeable AM at the same carrier and the same modulation frequency were measured at carrier frequencies of 0.125, 0.25, 0.5, 1, 2, 4, and 8 kHz. Signal levels were 20 dB SL and 50 dB SPL or 80 dB SPL. At low modulation frequencies, for example, 8 Hz, AM and FM elicit very different auditory sensations (i.e., a fluctuation in loudness or pitch, respectively). In this case, eta and m show different values for just noticeable modulation. Since both stimuli have almost equal amplitude spectra if eta equals m (m less than 0.3), the difference in detection thresholds reflects differences in the phase relation between carrier and sidebands in AM and FM. With increasing modulation frequency, the eta-m ratio decreases and reaches unity at a modulation frequency called the "critical modulation frequency" (CMF). At modulation frequencies above the CMF, the same modulation thresholds are obtained for AM and FM. Therefore, it can be concluded that the difference in phase between the two types of stimuli is not perceived in this range. At center frequencies below 1 kHz, where phase errors caused by headphones and ear canal presumably are small, the CMF is useful in estimating critical bandwidth.

Adult↗
PubMed1992

Temporal modulation transfer functions in patients with cochlear implants.

Thresholds for the detection of amplitude modulation were measured in cochlear implant patients as a function of modulation frequency. Three types of threshold measures were taken: detection of amplitude modulation, detection of low-frequency sinusoidal current waveforms, and detection of beats in two-tone complexes. The temporal modulation transfer function (TMTF), defined as the plot of modulation detection thresholds as a function of modulation frequency, show low-pass filter characteristics with similar cutoff frequencies for all three tasks. The similarity of these three measures suggests a common temporal mechanism. While modulation detection differs somewhat in normal-hearing and implanted listeners, both exhibit the same general characteristics. The TMTFs are low pass with a cutoff frequency near 70 Hz for normal-hearing listeners and near 140 Hz for implanted listeners. Patients with cochlear implants can best detect temporal modulation at modulation frequencies below 300 Hz, and are most sensitive to 80- to 100-Hz modulation. At high carrier levels many implant patients could detect smaller modulation amplitudes than normal-hearing listeners, a finding that is consistent with the smaller intensity DLs for some implanted listeners at high levels. These results demonstrate that, while implant listeners cannot discriminate steady-state, high-frequency stimuli, speech information might be conveyed by the envelope of the high-frequency components of speech.

Auditory Threshold↗
PubMed1996

The effects on comodulation masking release of systemic variations in on- and off-frequency masker modulation patterns.

Detection thresholds were obtained for a 500-Hz tone added to a masker comprised of an amplitude-modulated tone centered at the signal frequency (on-frequency masker) and an array of amplitude modulated tones centered at 300, 700, 800, 900, 1000, and 1100 Hz (off-frequency maskers). The shapes of the amplitude modulation patterns of the on- and off-frequency maskers were either matched or mismatched. In the shape-matched conditions the on- and off-frequency masker modulation patterns were the same, either sinusoidally or square-wave amplitude modulated. In the shape-mismatched conditions, the on-frequency masker was sinusoidally amplitude modulated and the off-frequency maskers were square-wave amplitude modulated. The rate of modulation was either 10 or 20 Hz, and the duty cycle of square-wave modulation was systemically varied. The relative phases of the on- and off-frequency modulators were either in-phase, out-of-phase, or random-phase. Comodulation masking release (CMR) was defined as the difference between thresholds in the in-phase and random-phase conditions. CMRs as large as 12 dB were obtained for the shape-matched as well as the shape-mismatched conditions. Thresholds in the out-of-phase condition were on average 2.6 dB higher than those in the random-phase condition. Results are consistent with a cued listening model where off-frequency modulation minima trigger sampling at the output of the auditory filter centered on the signal frequency.

Adult↗
PubMed1997

Effect of reducing temporal intensity modulations on sentence intelligibility.

Modulations in the temporal intensity envelope of 24 1/4-octave bands were reduced by proportionally raising the troughs and lowering the peaks relative to the mean intensity in each band. The effect on intelligibility of various degrees of modulation reduction was investigated by measuring the speech-reception threshold (SRT) in noise. For conditions of severe modulation reduction, the number of correctly received sentences in quiet was scored. The effect of this deterministic modulation reduction was compared to the effect of stochastic modulation reduction obtained with addition of noise. Results for 12 normal-hearing subjects show that in the case of deterministic modulation reduction, intelligibility is reduced to 50% when the modulation-transfer factor equals 0.10, whereas in the case of modulation reduction by addition of noise, this intelligibility is reached already at a modulation-transfer factor of 0.27. This confirms that the effect of additive noise on intelligibility cannot be understood completely as a result of only modulation reduction. As suggested by Drullman [J. Acoust. Soc. Am. 97, 585-592 (1995)] two other factors associated with the addition of noise have to be taken into account: (1) the introduction of nonrelevant modulations, and (2) the corruption of the fine structure.

Adult↗
PubMed1997

Modeling auditory processing of amplitude modulation. I. Detection and masking with narrow-band carriers.

This paper presents a quantitative model for describing data from modulation-detection and modulation-masking experiments, which extends the model of the "effective" signal processing of the auditory system described in Dau et al. [J. Acoust. Soc. Am. 99, 3615-3622 (1996)]. The new element in the present model is a modulation filterbank, which exhibits two domains with different scaling. In the range 0-10 Hz, the modulation filters have a constant bandwidth of 5 Hz. Between 10 Hz and 1000 Hz a logarithmic scaling with a constant Q value of 2 was assumed. To preclude spectral effects in temporal processing, measurements and corresponding simulations were performed with stochastic narrow-band noise carriers at a high center frequency (5 kHz). For conditions in which the modulation rate (fmod) was smaller than half the bandwidth of the carrier (delta f), the model accounts for the low-pass characteristic in the threshold functions [e.g., Viemeister, J. Acoust. Soc. Am. 66, 1364-1380 (1979)]. In conditions with fmod > delta f/2, the model can account for the high-pass characteristic in the threshold function. In a further experiment, a classical masking paradigm for investigating frequency selectivity was adopted and translated to the modulation-frequency domain. Masked thresholds for sinusoidal test modulation in the presence of a competing modulation masker were measured and simulated as a function of the test modulation rate. In all cases, the model describes the experimental data to within a few dB. It is proposed that the typical low-pass characteristic of the temporal modulation transfer function observed with wide-band noise carriers is not due to "sluggishness" in the auditory system, but can instead be understood in terms of the interaction between modulation filters and the inherent fluctuations in the carrier.

Acoustics↗
PubMed2000

Detection of quasitrapezoidal frequency and amplitude modulation.

It has been proposed that the detection of frequency modulation (FM) of sinusoidal carriers can be mediated by two mechanisms; a place mechanism based on FM-induced amplitude modulation (AM) in the excitation pattern, and a temporal mechanism based on phase locking in the auditory nerve. The temporal mechanism appears to be "sluggish" and does not play a role for FM rates above about 10 Hz. It also does not play a role for high carrier frequencies (above about 5 kHz). This experiment provided a further test of the hypothesis that the effectiveness of the temporal mechanism depends upon the time spent close to frequency extremes during the modulation cycle. Psychometric functions for the detection of AM and FM were measured for two carrier frequencies, 1 and 6 kHz. The modulation waveform was quasitrapezoidal. Within each modulation period, P, a time Tss was spent at each extreme of frequency or amplitude. The transitions between the extremes, with duration Ttrans had the form of a half-cycle of a cosine function. The modulation rate was 2, 5, 10, or 20 Hz, giving values of P of 500, 200, 100, and 50 ms. TSS varied from 0 ms (sinusoidal modulation) up to 160, 80, 40, or 20 ms, for rates of 2, 5, 10, and 20 Hz, respectively. The detectability of AM was not greatly affected by modulation rate or by the value of TSS, except for a slight improvement with increasing TSS for the lowest modulation rates; this was true for both carrier frequencies. For FM of the 6-kHz carrier, the pattern of results was similar to that found for AM, which is consistent with an excitation-pattern model of FM detection. For FM of the 1-kHz carrier, performance improved markedly with increasing TSS, especially for the lower FM rates; there was no change in performance with TSS for the 20-Hz modulation rate. The results are consistent with the idea that detection of FM of a 1-kHz carrier is partly mediated by a sluggish temporal mechanism. That mechanism benefits from greater time spent at frequency extremes of the modulation cycle for rates up to 10 Hz.

Auditory Perception↗
PubMed2000

Outputs of radula mechanoafferent neurons in Aplysia are modulated by motor neurons, interneurons, and sensory neurons.

The gain of sensory inputs into the nervous system can be modulated so that the nature and intensity of afferent input is variable. Sometimes the variability is a function of other sensory inputs or of the state of motor systems that generate behavior. A form of sensory modulation was investigated in the Aplysia feeding system at the level of a radula mechanoafferent neuron (B21) that provides chemical synaptic input to a group of motor neurons (B8a/b, B15) that control closure and retraction movements of the radula, a food grasping structure. B21 has been shown to receive both excitatory and inhibitory synaptic inputs from a variety of neuron types. The current study investigated the morphological basis of these heterosynaptic inputs, whether the inputs could serve to modulate the chemical synaptic outputs of B21, and whether the neurons producing the heterosynaptic inputs were periodically active during feeding motor programs that might modulate B21 outputs in a phase-specific manner. Four cell types making monosynaptic connections to B21 were found capable of heterosynaptically modulating the chemical synaptic output of B21 to motor neurons B8a and B15. These included the following: 1) other sensory neurons, e.g. , B22; 2) interneurons, e.g., B19; 3) motor neurons, e.g., B82; and 4) multifunction neurons that have sensory, motor, and interneuronal functions, e.g., B4/5. Each cell type was phasically active in one or more feeding motor programs driven by command-like interneurons, including an egestive motor program driven by CBI-1 and an ingestive motor program driven by CBI-2. Moreover, the phase of activity differed for each of the modulator cells. During the motor programs, shifts in B21 membrane potential were related to the activity patterns of some of the modulator cells. Inhibitory chemical synapses mediated the modulation produced by B4/5, whereas excitatory and/or electrical synapses were involved in the other instances. The data indicate that modulation is due to block of action potential invasion into synaptic release regions or to alterations of transmitter release as a function of the presynaptic membrane potential. The results indicate that just as the motor system of Aplysia can be modulated by intrinsic mechanisms that can enhance its efficiency, the properties of primary sensory cells can be modified by diverse inputs from mediating circuitry. Such modulation could serve to optimize sensory cells for the different roles they might play.

Animals↗