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Behavioral and endocrine interactions between thyrotropin-releasing hormone and ethanol in normal human subjects.

Thyrotropin-releasing hormone (TRH) has been shown to antagonize the depressant effects of ethanol in animals, but conflicting findings have been reported in humans. To test whether TRH counteracts any of a variety of ethanol-sensitive behavioral measures in normal human subjects and for an effect of ethanol on TRH-induced thyrotropin (TSH) and prolactin (PRL) response, we administered TRH (500 micrograms) or placebo over 1 min intravenously, 30 min after subjects had ingested 0.8 g/kg of ethanol or a placebo drink. Blood samples for TSH and PRL were drawn prior to and 15 and 30 min after injection. Eight male subjects were studied in a balanced, crossover design with each subject receiving placebo-placebo, TRH-placebo, placebo-ethanol, and TRH-ethanol. Whereas ethanol had significant and expected effects on subjective measures, memory, disinhibition, reaction time and time perception, TRH failed to counteract any ethanol effect, except for a small effect in one memory task. Similarly, no effect of ethanol on TRH-induced TSH or PRL response was found. Though the behavioral findings could be interpreted to indicate that TRH does not alter ethanol sensitive behaviors in humans it will be necessary to utilize higher dosages of TRH and/or TRH analogues before firmly drawing this conclusion.

Adult↗

Neostigmine-induced postprandial phasic contractility in the proximal stomach and dyspepsia-like symptoms in healthy volunteers.

BACKGROUND AND AIMS: In a subset of functional dyspepsia patients, we have recently described the association between unsuppressed postprandial phasic contractions of the proximal stomach and a specific symptom pattern. To better elucidate the role of phasic contractility of the proximal stomach in symptom generation, we aimed at inducing this motility pattern in healthy volunteers and we carefully monitored symptom onset. PATIENTS AND METHODS: Eleven healthy volunteers underwent gastric barostat on two separate days. Gastric tone and phasic contractility were evaluated for a 90-minute period. In particular, after 30 min of basal recording, a caloric liquid meal and neostigmine 0.5 mg IV or saline in a double-blind, randomized, crossover protocol were administered. During the measurement, severity of 9 dyspeptic symptoms was evaluated on a visual analog scale. Computer-aided baseline reconstruction allowed us to quantify phasic contractions as a motility index (MI), reflecting the area between signal and baseline normalized over time. Perception of contractions after placebo or neostigmine was evaluated. Moreover, we tested for influence of gastric tone and phasic contractility on symptoms. RESULTS: After neostigmine, gastric accommodation was not different than after placebo (225 +/- 36 vs 206 +/- 76 mL, P= NS). During the first 30-min postprandial period, the MI was significantly higher after neostigmine than after placebo (26.4 +/- 3 vs 21.4 +/- 3, P < 0.001), confirming the induction of unsuppressed postprandial phasic contractions. The postprandial total symptom score was significantly higher after neostigmine compared to saline; several individual postprandial symptom scores were also significantly higher after neostigmine-compared placebo. After neostigmine, a higher percentage of postprandial contractions was perceived compared to placebo. CONCLUSIONS: Unsuppressed postprandial phasic contractility of the proximal stomach is a mechanism potentially involved in the pathogenesis of dyspeptic symptoms.

Adult↗

Apolipoprotein epsilon4 advances appearance of psychosis in patients with Parkinson's disease.

BACKGROUND: Psychosis is one of the most serious complications of advanced parkinsonism, but many patients are spared. The genetic factors predisposing to psychosis are unclear. OBJECTIVES: To assess the association between apolipoprotein E (APOE) polymorphism and the development of psychosis in patients with Parkinson's disease (PD). METHODS: Eighty-seven patients with advanced PD were assessed. Psychosis was diagnosed in 50 patients who manifested paranoid delusions, hallucinations without insight, or disorders of perception. Time of onset of psychosis was retrieved from the medical records and caregivers' recall. APOE genotype was determined by restriction enzyme digests of amplified alleles. Cox models of logistic regression and Kaplan-Meier survival curves were used to assess factors determining early development of psychosis. RESULTS: APOE epsilon3/epsilon4 allele was carried by 20 patients (14 with psychosis), epsilon2/epsilon3 by 11 patients (10 with psychosis), epsilon3/epsilon3 by 55 patients (25 with psychosis) and epsilon2/epsilon4 by one patient who had psychosis. The mean age of onset of PD symptoms was 60.0 +/- 12.5 years. The mean duration of motor symptoms at the onset of psychosis was 7.3 +/- 4.3 years for the 15 patients harboring an APOE epsilon4 allele and 10.1 +/- 6.2 years among those who did not carry APOE epsilon4 (n = 35). The APOE epsilon4 allele was significantly associated with earlier onset of psychosis (P < 0.05) when the age of onset of motor symptoms and presence of dementia were included in the Cox regression model. Carrying the APOE epsilon4 allele was a significant risk factor for earlier appearance of psychosis with a hazard ratio of 3.24 (95% CI 1.62-6.46) while dementia by itself did not increase the risk. CONCLUSION: Parkinson's disease patients who carry the APOE epsilon4 allele develop psychosis earlier.

Age of Onset↗

The neural processing of complex sounds.

This paper considers the temporal processing of complex sounds relevant to musical analysis. Functional imaging studies, using positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG), and the psychophysical assessment of patients with lesions allow two different approaches to this. Functional imaging allows the determination of structures normally involved in temporal analysis, while patient studies allow inference about the necessary structures for temporal analysis. Both approaches suggest a hierarchal organization in the brain corresponding to the processing of music. The features of individual notes are analyzed in the pathway up to and including the auditory cortices, while higher-order patterns formed by those features are analyzed by distributed networks in the temporal lobe and frontal lobes distinct from the auditory cortices.

Auditory Perception↗

Spatial and temporal properties of cat geniculate neurones after prolonged deprivation.

1. Extracellular recordings were made from the dorsal lateral geniculate nucleus of monocularly deprived, dark-reared and normal cats. The spatial and temporal properties of the neurones were studied. 2. The mean acuity of X-cells with receptive fields 3 degrees of the area centralis was 3.9 c/degree for deprived eye cells from monocularly deprived cats, compared was 3.8 c/degree for normal cells. 3. The mean activity of X-cells with receptive fields within 4 degrees of the area centralis was 4.3 c/degree for a dark-reared cat compared with 4.0 c/degree for a normal cat. 4. The peak response rates of X-cells to their best spatial frequency were determined. The mean values for the normal, monocularly deprived and dark-reared populations were all similar. 5 Measurement of the temporal frequency tuning of a number of cells was made. The mean peak temporal frequency for the dark-reared X-cells was lower than for monocularly deprived or normal X-cells. 6. The results are discussed with reference to the location of the primary neural deficit induced by visual deprivation.

Action Potentials↗

Functional differences between vowel onsets and offsets in temporal perception of speech: local-change detection and speaking-rate discrimination.

To provide a perceptual framework for the objective evaluation of durational rules in speech synthesis, two experiments were conducted to investigate the differences between vowel (V) onsets and V-offsets in their functions of marking the perceived temporal structure of speech. The first experiment measured the detectability of temporal modifications given in four-mora (CVCVCVCV) Japanese words. In the V-onset condition, the inter-onset intervals of vowels were uniformly changed (either expanded or reduced) while their inter-offset intervals were preserved. In the V-offset condition, this was reversed. These manipulations did not change the duration of the entire word. Each of the modified words was paired with its unmodified counterpart, and the pair was given to listeners, who were asked to rate the difference between the paired words. The results show that there were no significant differences in the listeners' abilities to detect the temporal modification between the V-onset and V-offset conditions. In the second experiment, the listeners were asked to estimate the differences they perceived in speaking rates for the same stimulus set as that of the first experiment. Interestingly, the results show a clear difference in the listeners' performance between the V-onset and V-offset conditions. Specifically, changing the V-onset intervals changed the perceived speaking rates, which showed a linear relation (r = -0.9) despite the fact that the duration of the entire word remained unchanged. In contrast, modifying the V-offset intervals produced no clear relation with the perceived speaking rates. The second experiment also showed that the listeners performed well in speaking rate discrimination (3.5%-5% in the change ratio). These results are discussed in relation to the differences in the listeners' temporal processing range (local or global) between the two experiments.

Adult↗

Human temporal auditory acuity as assessed by envelope following responses.

Temporal auditory acuity, the ability to discriminate rapid changes in the envelope of a sound, is essential for speech comprehension. Human envelope following responses (EFRs) recorded from scalp electrodes were evaluated as an objective measurement of temporal processing in the auditory nervous system. The temporal auditory acuity of older and younger participants was measured behaviorally using both gap and modulation detection tasks. These findings were then related to EFRs evoked by white noise that was amplitude modulated (25% modulation depth) with a sweep of modulation frequencies from 20 to 600 Hz. The frequency at which the EFR was no longer detectable was significantly correlated with behavioral measurements of gap detection (r = -0.43), and with the maximum perceptible modulation frequency (r = 0.72). The EFR techniques investigated here might be developed into a clinically useful objective estimate of temporal auditory acuity for subjects who cannot provide reliable behavioral responses.

Acoustic Stimulation↗

The temporal representation of speech in a nonlinear model of the guinea pig cochlea.

The temporal representation of speechlike stimuli in the auditory-nerve output of a guinea pig cochlea model is described. The model consists of a bank of dual resonance nonlinear filters that simulate the vibratory response of the basilar membrane followed by a model of the inner hair cell/auditory nerve complex. The model is evaluated by comparing its output with published physiological auditory nerve data in response to single and double vowels. The evaluation includes analyses of individual fibers, as well as ensemble responses over a wide range of best frequencies. In all cases the model response closely follows the patterns in the physiological data, particularly the tendency for the temporal firing pattern of each fiber to represent the frequency of a nearby formant of the speech sound. In the model this behavior is largely a consequence of filter shapes; nonlinear filtering has only a small contribution at low frequencies. The guinea pig cochlear model produces a useful simulation of the measured physiological response to simple speech sounds and is therefore suitable for use in more advanced applications including attempts to generalize these principles to the response of human auditory system, both normal and impaired.

Animals↗

Relative contributions of temporal and place pitch cues to fundamental frequency discrimination in cochlear implantees.

The effect of the filter bank on fundamental frequency (F0) discrimination was examined in four Nucleus CI24 cochlear implant subjects for synthetic stylized vowel-like stimuli. The four tested filter banks differed in cutoff frequencies, amount of overlap between filters, and shape of the filters. To assess the effects of temporal pitch cues on F0 discrimination, temporal fluctuations were removed above 10 Hz in one condition and above 200 Hz in another. Results indicate that F0 discrimination based upon place pitch cues is possible, but just-noticeable differences exceed 1 octave or more depending on the filter bank used. Increasing the frequency resolution in the F0 range improves the F0 discrimination based upon place pitch cues. The results of F0 discrimination based upon place pitch agree with a model that compares the centroids of the electrical excitation pattern. The addition of temporal fluctuations up to 200 Hz significantly improves F0 discrimination. Just-noticeable differences using both place and temporal pitch cues range from 6% to 60%. Filter banks that do not resolve the higher harmonics provided the best temporal pitch cues, because temporal pitch cues are clearest when the fluctuation on all channels is at F0 and preferably in phase.

Adult↗

Relative contributions of spectral and temporal cues for phoneme recognition.

Cochlear implants provide users with limited spectral and temporal information. In this study, the amount of spectral and temporal information was systematically varied through simulations of cochlear implant processors using a noise-excited vocoder. Spectral information was controlled by varying the number of channels between 1 and 16, and temporal information was controlled by varying the lowpass cutoff frequencies of the envelope extractors from 1 to 512 Hz. Consonants and vowels processed using those conditions were presented to seven normal-hearing native-English-speaking listeners for identification. The results demonstrated that both spectral and temporal cues were important for consonant and vowel recognition with the spectral cues having a greater effect than the temporal cues for the ranges of numbers of channels and lowpass cutoff frequencies tested. The lowpass cutoff for asymptotic performance in consonant and vowel recognition was 16 and 4 Hz, respectively. The number of channels at which performance plateaued for consonants and vowels was 8 and 12, respectively. Within the above-mentioned ranges of lowpass cutoff frequency and number of channels, the temporal and spectral cues showed a tradeoff for phoneme recognition. Information transfer analyses showed different relative contributions of spectral and temporal cues in the perception of various phonetic/acoustic features.

Adult↗

Enhancement of temporal periodicity cues in cochlear implants: effects on prosodic perception and vowel identification.

Standard continuous interleaved sampling processing, and a modified processing strategy designed to enhance temporal cues to voice pitch, were compared on tests of intonation perception, and vowel perception, both in implant users and in acoustic simulations. In standard processing, 400 Hz low-pass envelopes modulated either pulse trains (implant users) or noise carriers (simulations). In the modified strategy, slow-rate envelope modulations, which convey dynamic spectral variation crucial for speech understanding, were extracted by low-pass filtering (32 Hz). In addition, during voiced speech, higher-rate temporal modulation in each channel was provided by 100% amplitude-modulation by a sawtooth-like wave form whose periodicity followed the fundamental frequency (F0) of the input. Channel levels were determined by the product of the lower- and higher-rate modulation components. Both in acoustic simulations and in implant users, the ability to use intonation information to identify sentences as question or statement was significantly better with modified processing. However, while there was no difference in vowel recognition in the acoustic simulation, implant users performed worse with modified processing both in vowel recognition and in formant frequency discrimination. It appears that, while enhancing pitch perception, modified processing harmed the transmission of spectral information.

Adult↗

Autocorrelation in meter induction: the role of accent structure.

The performance of autocorrelation-based meter induction was tested with two large collections of folk melodies, consisting of approximately 13 000 melodies for which the correct meters were available. The performance was measured by the proportion of melodies whose meter was correctly classified by a discriminant function. Furthermore, it was examined whether including different melodic accent types would improve the classification performance. By determining the components of the autocorrelation functions that were significant in the classification it was found that periodicity in note onset locations was the most important cue for the determination of meter. Of the melodic accents included, Thomassen's melodic accent was found to provide the most reliable cues for the determination of meter. The discriminant function analyses suggested that periodicities longer than one measure may provide cues for meter determination that are more reliable than shorter periodicities. Overall, the method predicted notated meter with an accuracy reaching 96% for binary classification and 75% for classification into nine categories of meter.

Auditory Perception↗