Rats’ (Rattus norvegicus) temporal discrimination of brief auditory stimuli: How does it compare with that of humans (Homo sapiens) and zebra finches (Taeniopygia guttata)?

The present study with rats replicated an experiment on the ability of zebra finches and humans to discriminate among brief auditory stimuli (see Weisman et al., 1999, Experiment 2). We trained rats with 27 3-kHz tones that varied in duration from 10 ms to 1420 ms. Reinforcement was contingent on responding (approaching the food well) to the nine medium-durations range tones (56-255 ms) but not to the nine short-durations range (10-46 ms) or long-durations range tones (309-1420 ms). Rats also received post-discrimination transfer tests with 2 kHz and 4 kHz tones that varied over the same durations as the 3 kHz tones. Rats acquired the temporal discrimination to a slightly lower level of accuracy than seen in finches or humans by Weisman et al. (1999). We tested for transfer of the temporal discrimination to find that rats, similar to humans (data from Weisman et al., 1999), transferred to untrained 2-kHz and 4-kHz tones at levels approaching accuracy to that achieved to the trained 3-kHz tone. By contrast, zebra finches (data from Weisman et al., 1999) failed to transfer their discrimination to the trained tone. We conclude that (a) rats discriminate among tone durations at least as well as they do among auditory frequencies and (b) rats like humans, but unlike finches, are insensitive to absolute pitch in their temporal discrimination.     

Prediction of time to exhaustion in competitive cyclists from a perceptually based scale

Prediction of time to exhaustion in competitive cyclists from a perceptually based scale. We have tested the validity of the estimated time limit (ETL) scale to predict an exhaustion time (T(lim)) from values stemming from incremental and randomized constant workloads tests on a cycle ergometer. Twenty-five cyclists performed 1 continuous incremental test, 1 discontinuous test with randomized workloads, and 1 constant power output test at 90% of maximal aerobic power (MAP) to exhaustion. Estimated time limits at 90% MAP during the incremental test and the test with randomized workloads were calculated from exponential relationships between power and ETL using the same 4 workloads. Real measured T(lim) during the constant power output test was converted into ETL values (called measured ETL). The differences between the calculated and measured ETLs were examined. Estimated time limits calculated at 90% MAP during the incremental and randomized tests corresponded to 14 minutes 56 seconds and 10 minutes 14 seconds, whereas measured ETL was equal to 11 minutes 19 seconds ± 3 minutes 40 seconds. The results showed a nonsignificant difference between calculated and measured ETLs. However, the mean differences between the measured ETL values during the constant test performed at the same intensity were -1.3 ± 2.9 and 0.3 ± 3.0 for the incremental and the randomized constant workloads tests, respectively. Consequently, the use of ETL calculated at 90% MAP during the test with randomized constant workloads may be preferable to predict the accurate T(lim). Moreover, it would seem that high-level cyclists, who were more consciously attuned to their bodies and their own effort sense, were more accurate in their prediction than low-level cyclists. It is concluded that the randomized constant workloads test that is both shorter and less strenuous would be more convenient for high-level athletes.     

The human circadian pacemaker can see by the dawn's early light

The authors' previous experiments have shown that dawn simulation at low light intensities can phase advance the circadian rhythm of melatonin in humans. The aim of this study was to compare the effect of repeated dawn signals on the phase position of circadian rhythms in healthy participants kept under controlled light conditions. Nine men participated in two 9-day laboratory sessions under an LD cycle 17.5:6.5 h, < 30:0 lux, receiving 6 consecutive daily dawn (average illuminance 155 lux) or control light (0.1 lux) signals from 0600 to 0730 h (crossover, random-order design). Two modified constant routine protocols before and after the light stimuli measured salivary melatonin (dim light melatonin onset DLMOn and offset DLMOff) and rectal temperature rhythms (midrange crossing time [MRCT]). Compared with initial values, participants significantly phase delayed after 6 days under control light conditions (at least -42 min DLMOn, -54 min DLMOff, -41 min MRCT) in spite of constant bedtimes. This delay was not observed with dawn signals (+10 min DLMOn, +2 min DLMOff, 0 min MRCT). Given that the endogenous circadian period of the human circadian pacemaker is slightly longer than 24 h, the findings suggest that a naturalistic dawn signal is sufficient to forestall this natural delay drift. Zeitgeber transduction and circadian system response are hypothesized to be tuned to the time-rate-of-change of naturalistic twilight signals.     

Temporal Expectation and Attention Jointly Modulate Auditory Oscillatory Activity in the Beta Band

The neural response to a stimulus is influenced by endogenous factors such as expectation and attention. Current research suggests that expectation and attention exert their effects in opposite directions, where expectation decreases neural activity in sensory areas, while attention increases it. However, expectation and attention are usually studied either in isolation or confounded with each other. A recent study suggests that expectation and attention may act jointly on sensory processing, by increasing the neural response to expected events when they are attended, but decreasing it when they are unattended. Here we test this hypothesis in an auditory temporal cueing paradigm using magnetoencephalography in humans. In our study participants attended to, or away from, tones that could arrive at expected or unexpected moments. We found a decrease in auditory beta band synchrony to expected (versus unexpected) tones if they were unattended, but no difference if they were attended. Modulations in beta power were already evident prior to the expected onset times of the tones. These findings suggest that expectation and attention jointly modulate sensory processing.     

Comparison of auditory functions in the chimpanzee and human

Absolute thresholds for pure tones, loudness, frequency and intensity difference thresholds and the resonance of the external auditory meatus were measured in chimpanzees and compared with those in humans. Chimpanzees were more sensitive than humans to frequencies higher than 8 kHz but less sensitive to frequencies lower than 250 Hz and 2- to 4-kHz tones. Difference thresholds for frequency and intensity were greater in chimpanzees than in humans. The resonance of the external ear was about the same in the two species. The effects of differences in hearing between species upon speech perception are discussed.     

Exercise elicits phase shifts and acute alterations of melatonin that vary with circadian phase

To examine the immediate phase-shifting effects of high-intensity exercise of a practical duration (1 h) on human circadian phase, five groups of healthy men 20-30 yr of age participated in studies involving no exercise or exposure to morning, afternoon, evening, or nocturnal exercise. Except during scheduled sleep/dark and exercise periods, subjects remained under modified constant routine conditions allowing a sleep period and including constant posture, knowledge of clock time, and exposure to dim light intensities averaging (+/-SD) 42 +/- 19 lx. The nocturnal onset of plasma melatonin secretion was used as a marker of circadian phase. A phase response curve was used to summarize the phase-shifting effects of exercise as a function of the timing of exercise. A significant effect of time of day on circadian phase shifts was observed (P < 0.004). Over the interval from the melatonin onset before exercise to the first onset after exercise, circadian phase was significantly advanced in the evening exercise group by 30 +/- 15 min (SE) compared with the phase delays observed in the no-exercise group (-25 +/- 14 min, P < 0.05). Phase shifts in response to evening exercise exposure were attenuated on the second day after exercise exposure and no longer significantly different from phase shifts observed in the absence of exercise. Unanticipated transient elevations of melatonin levels were observed in response to nocturnal exercise and in some evening exercise subjects. Taken together with the results from previous studies in humans and diurnal rodents, the current results suggest that 1) a longer duration of exercise exposure and/or repeated daily exposure to exercise may be necessary for reliable phase-shifting of the human circadian system and that 2) early evening exercise of high intensity may induce phase advances relevant for nonphotic entrainment of the human circadian system.     

Discrimination task reveals differences in neural bases of tinnitus and hearing impairment

We investigated auditory perception and cognitive processing in individuals with chronic tinnitus or hearing loss using functional magnetic resonance imaging (fMRI). Our participants belonged to one of three groups: bilateral hearing loss and tinnitus (TIN), bilateral hearing loss without tinnitus (HL), and normal hearing without tinnitus (NH). We employed pure tones and frequency-modulated sweeps as stimuli in two tasks: passive listening and active discrimination. All subjects had normal hearing through 2 kHz and all stimuli were low-pass filtered at 2 kHz so that all participants could hear them equally well. Performance was similar among all three groups for the discrimination task. In all participants, a distributed set of brain regions including the primary and non-primary auditory cortices showed greater response for both tasks compared to rest. Comparing the groups directly, we found decreased activation in the parietal and frontal lobes in the participants with tinnitus compared to the HL group and decreased response in the frontal lobes relative to the NH group. Additionally, the HL subjects exhibited increased response in the anterior cingulate relative to the NH group. Our results suggest that a differential engagement of a putative auditory attention and short-term memory network, comprising regions in the frontal, parietal and temporal cortices and the anterior cingulate, may represent a key difference in the neural bases of chronic tinnitus accompanied by hearing loss relative to hearing loss alone.     

Dynamics of skate horizontal cells

The all-rod retina of the skate (Raja erinacea or R. oscellata) is known to have the remarkable capability of responding to incremental flashes superimposed on background intensities that initially block all light-evoked responses and are well above the level at which rods saturate in mixed rod/cone retinas. To examine further the unusual properties of the skate visual system, we have analyzed responses of their horizontal cells to intensity-modulated step, sinusoidal, and white-noise stimuli. We found that during exposures to mean intensities bright enough to block responses to incremental stimuli, decremental stimuli were also initially blocked. Thereafter, the horizontal cells underwent a slow recovery phase during which there was marked nonlinearity in their response properties. The cell first (within 2-3 min) responded to decrements in intensity and later (after greater than 10 min) became responsive to incremental stimuli. After adaptation to a steady state, however, the responses to intensity modulation were nearly linear over a broad range of modulation depths even at the brightest mean levels of illumination. Indeed, examination of the steady-state responses over a 5-log-unit range of mean intensities revealed that the amplitude of the white noise-evoked responses depended solely on contrast, and was independent of the retinal irradiance as the latter was increased from 0.02 to 20 muW/cm2; i.e., contrast sensitivity remained unchanged over this 1,000-fold increase in mean irradiance. A decrement from the mean as brief as 2 s, however, disturbed the steady state. Another unexpected finding in this all-rod retina concerns surround-enhancement, a phenomenon observed previously for cone-mediated responses of horizontal cells in the retinas of turtle and catfish. While exposure to annular illumination induced response compression and a pronounced sensitivity loss in response to incremental light flashes delivered to the dark central region, the cell's sensitivity showed a significant increase when tested with a white noise or sinusoidally modulated central spot. Unlike horizontal cells in other retinas studied thus far, however, response dynamics remained unchanged. Responses evoked either by a small spot (0.25-mm diam) or by a large field light covering the entire retina were almost identical in time course. This is in contrast with past findings from cone-driven horizontal cells whose response waveform (dynamics) was dependent upon the size of the retinal area stimulated.     

Avian dependence on sound pressure level as an auditory distance cue

Sound pressure level (SPL) has received little attention as a distance cue or signal for communication because of the methodological difficulty of determining source SPL from free-ranging signallers and because SPL is presumed to be unreliable as a distance cue. Eastern towhees, Pipilo erythrophthalmus (Emberizidae, Passeriformes), in south-central Florida give a simple call during territorial interactions. I obtained measurements of call-source SPL with a calibrated microphone positioned 100+/-10 cm from caged male eastern towhees. Measurements of source SPL were highly variable, but much of this variation can be predicted from measurements of call duration or call frequency variables (spectrotemporal variables). Male towhees accurately perceived the distance of a speaker after it played synthetic calls that matched the amplitude and structure of natural 84-dB and 78-dB call types. Subjects flew further in response to an attenuated (-6 or -12 dB) version of an otherwise identical 84-dB call and flew shorter in response to an amplified (+6 dB) version of this same call. Towhees misjudged speaker distance in approximately half of the trials that included a discrepancy (-6, -12 or +6 dB SPL) between playback source SPL and predicted spectrotemporal variables. These distance errors suggest that towhees assess auditory distance partly from the difference between perceived SPL and source SPL, determined from spectrotemporal variables. Copyright 2000 The Association for the Study of Animal Behaviour.     

Comparison of incremental and steady state tests of endurance training

To compare the results obtained by incremental or constant work load exercises in the evaluation of endurance conditioning, a 20-week training programme was performed by 9 healthy human subjects on the bicycle ergometer for 1 h a day, 4 days a week, at 70-80% VO2max. Before and at the end of the training programme, (1) the blood lactate response to a progressive incremental exercise (18 W increments every 2nd min until exhaustion) was used to determine the aerobic and anaerobic thresholds (AeT and AnT respectively). On a different day, (2) blood lactate concentrations were measured during two sessions of constant work load exercises of 20 min duration corresponding to the relative intensities of AeT (1st session) and AnT (2nd session) levels obtained before training. A muscle biopsy was obtained from vastus lateralis at the end of these sessions to determine muscle lactate. AeT and AnT, when expressed as % VO2max, increased with training by 17% (p less than 0.01) and 9% (p less than 0.05) respectively. Constant workload exercise performed at AeT intensity was linked before training (60% VO2max) to a blood lactate steady state (4.8 +/- 1.4 mmol.l-1) whereas, after training, AeT intensity (73% VO2max) led to a blood lactate accumulation of up to 6.6 +/- 1.7 mmol.l-1 without significant modification of muscle lactate (7.6 +/- 3.1 and 8.2 +/- 2.8 mmol.kg-1 wet weight respectively). It is concluded that increase in AeT with training may reflect transient changes linked to lower early blood lactate accumulation during incremental exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of electromyographic feedback training on suppression of the oral-lingual movements associated with tardive dyskinesia.

The efficacy of electromyographic feedback training in reducing the magnitude and frequency of the oral-lingual movements associated with tardive dyskinesia (TD) was investigated in a groups design. Twenty adult male inpatients diagnosed as having TD using the Abnormal Involuntary Movements Scale (AIMS) were randomly assigned to one of two treatment conditions. Following identification, all participants were initially reduced to the lowest effective dosage of neuroleptics, and then discontinued from anticholinergics. Following one month on this regimen, they were given a course of feedback training consisting of ten 14-minute sessions. Group one participants were provided with a tone contingent upon oral-lingual movements above a yoked threshold. Group two participants were given noncontingent feedback tones generated randomly. Weekly AIMS were administered as well as an initial baseline during each session to determine current level of oral-lingual activity. An analysis of session effects indicated significantly more suppression of oral-lingual activity in the contingent group versus the noncontingent feedback group. Jaw and forehead activity also measured showed reductions of similar magnitudes for both groups.     

Voltage responses to tones of outer hair cells in the basal turn of the guinea-pig cochlea: significance for electromotility and desensitization.

Voltage responses were recorded from outer hair cells (OHCS) in the basal coil of the guinea-pig cochlea in response to tones at frequencies above the characteristic frequency (CF) presented together with a 100 Hz tone at 80 dB or 85 dB sound pressure level (SPL). The amplitude and polarity of voltage responses to a 100 Hz, 85 dB SPL tone were altered when presented together with tones at frequencies above CF according to the frequency and level of the high-frequency tone, OHC phasic (ac) (greater than 500 microV) but not tonic (dc) voltage responses were elicited by the high-frequency tone. Thus the responses of OHCS to low-frequency tones can be altered when presented together with a high-frequency tone without an apparent dc change in membrane potential. Recordings were made from an OHC during cochlear desensitization through exposure to an intense tone. The maximum voltage response to high-level low-frequency tones remained unchanged, although the OHC response to high-frequency tones became less sensitive to low-level stimuli and more linear as a function of level. It is suggested that desensitization is associated with a change in the mechanical properties of the cochlea, possibly associated with the OHCS themselves, and not with inactivation of the transducer channels. The amplitude of the OHC ac voltage response was measured at neural threshold, and the consequences of these measurements on hair cell electromotility are considered.     

Left ventricular mechanical limitations to stroke volume in healthy humans during incremental exercise

During incremental exercise, stroke volume (SV) plateaus at 40-50% of maximal exercise capacity. In healthy individuals, left ventricular (LV) twist and untwisting ("LV twist mechanics") contribute to the generation of SV at rest, but whether the plateau in SV during incremental exercise is related to a blunting in LV twist mechanics remains unknown. To test this hypothesis, nine healthy young males performed continuous and discontinuous incremental supine cycling exercise up to 90% peak power in a randomized order. During both exercise protocols, end-diastolic volume (EDV), end-systolic volume (ESV), and SV reached a plateau at submaximal exercise intensities while heart rate increased continuously. Similar to LV volumes, two-dimensional speckle tracking-derived LV twist and untwisting velocity increased gradually from rest (all P < 0.001) and then leveled off at submaximal intensities. During continuous exercise, LV twist mechanics were linearly related to ESV, SV, heart rate, and cardiac output (all P < 0.01) while the relationship with EDV was exponential. In diastole, the increase in apical untwisting was significantly larger than that of basal untwisting (P < 0.01), emphasizing the importance of dynamic apical function. In conclusion, during incremental exercise, the plateau in LV twist mechanics and their close relationship with SV and cardiac output indicate a mechanical limitation in maximizing LV output during high exercise intensities. However, LV twist mechanics do not appear to be the sole factor limiting LV output, since EDV reaches its maximum before the plateau in LV twist mechanics, suggesting additional limitations in diastolic filling to the heart.     

A chimpanzee recognizes synthetic speech with significantly reduced acoustic cues to phonetic content

A long-standing debate concerns whether humans are specialized for speech perception, which some researchers argue is demonstrated by the ability to understand synthetic speech with significantly reduced acoustic cues to phonetic content. We tested a chimpanzee (Pan troglodytes) that recognizes 128 spoken words, asking whether she could understand such speech. Three experiments presented 48 individual words, with the animal selecting a corresponding visuographic symbol from among four alternatives. Experiment 1 tested spectrally reduced, noise-vocoded (NV) synthesis, originally developed to simulate input received by human cochlear-implant users. Experiment 2 tested "impossibly unspeechlike" sine-wave (SW) synthesis, which reduces speech to just three moving tones. Although receiving only intermittent and noncontingent reward, the chimpanzee performed well above chance level, including when hearing synthetic versions for the first time. Recognition of SW words was least accurate but improved in experiment 3 when natural words in the same session were rewarded. The chimpanzee was more accurate with NV than SW versions, as were 32 human participants hearing these items. The chimpanzee's ability to spontaneously recognize acoustically reduced synthetic words suggests that experience rather than specialization is critical for speech-perception capabilities that some have suggested are uniquely human.     

The effect of resistance-training intensity on strength-gain response in the older adult

This study examined how training intensity affects strength gains in older adults over an 18-week training period using nonperiodized, progressive resistance-training protocols. Untrained men and women participants were separated into 4 groups: group A (n = 17, 71.4 +/- 4.6 years) performed 2 sets of 15 repetitions maximum (RM), group B (n = 13, 71.5 +/- 5.2 years) performed 3 sets of 9 RM, group C (n = 17, 69.4 +/- 4.4 years) performed 4 sets of 6 RM, group D (n = 14, 72.3 +/- 5.9 years) served as controls. Training groups exercised 2 days/week performing 8 resistance exercises. Except for training intensity, the acute program variables were equated between groups. A 1RM for 8 exercises was obtained every 6 weeks. The total of 1RM for the 8 exercises served as the dependent variable. Results: repeated measures analysis of variance (ANOVA) and Scheffe post hoc revealed that, at 6 weeks, only groups B and C were significantly stronger than group D (p < 0.01). By weeks 12 and 18, all training groups were significantly stronger than controls (p < 0.01). However, no difference existed between groups A, B, and C at any time. The data suggests that, for protocols with equated acute program variables, strength gain is similar over 18 weeks for training intensities ranging from 6 to 15 RM in previously untrained older adults. When programming nonperiodized, progressive resistance exercise for novice senior lifters, in the initial phases of the program, a wide range of intensities may be employed with similar strength gain.     

Spectral and temporal gating mechanisms enhance the clutter rejection in the echolocating bat,Rhinolophus rouxi

Summary Doppler shift compensation behaviour in horseshoe bats, Rhinolophus rouxi, was used to test the interference of pure tones and narrow band noise with compensation performance. The distortions in Doppler shift compensation to sinusoidally frequency shifted echoes (modulation frequency: 0.1 Hz, maximum frequency shift: 3 kHz) consisted of a reduced compensation amplitude and/or a shift of the emitted frequency to lower frequencies (Fig. 1).Pure tones at frequencies between 200 and 900 Hz above the bat's resting frequency (RF) disturbed the Doppler shift compensation, with a maximum of intererence between 400 and 550 Hz (Fig. 2). Minimum duration of pure tones for interference was 20 ms and durations above 40 ms were most effective (Fig. 3). Interfering pure tones arriving later than about 10 ms after the onset of the echolocation call showed markedly reduced interference (Fig. 4). Doppler shift compensation was affected by pure tones at the optimum interfering frequency with sound pressure levels down to –48 dB rel the intensity level of the emitted call (Figs. 5, 6).Narrow bandwidth noise (bandwidth from ± 100 Hz to ± 800 Hz) disturbed Doppler shift compensation at carrier frequencies between –250 Hz below and 800 Hz above RF with a maximum of interference between 250 and 500 Hz above resting frequency (Fig. 7). The duration and delay of the noise had similar influences on interference with Doppler shift compensation as did pure tones (Figs. 8, 9). Intensity dependence for noise interference was more variable than for pure tones (-32 dB to -45 dB rel emitted sound pressure level, Fig. 10).The temporal and spectral gating in Doppler shift compensation behaviour is discussed as an effective mechanism for clutter rejection by improving the processing of frequency and amplitude transients in the echoes of horseshoe bats.Abbreviations CF constant frequency - FM frequency modulation - RF resting frequency - SPL sound pressure level     

The startle response during whiplash: a protective or harmful response?

Whiplash injuries are common following rear-end collisions. During such collisions, initially relaxed occupants exhibit brisk, stereotypical muscle responses consisting of postural and startle responses that may contribute to the injury. Using prestimulus inhibition, we sought to determine if the startle response elicited during a rear-end collision contributes to head stabilization or represents a potentially harmful overreaction of the body. Three experiments were performed. In the first two experiments, two groups of 14 subjects were exposed to loud tones (124 dB) preceded by prestimulus tones at either four interstimulus intervals (100-1,000 ms) or five prestimulus intensities (80-124 dB). On the basis of the results of the first two experiments, 20 subjects were exposed to a simulated rear-end collision (peak sled acceleration = 2 g; speed change = 0.75 m/s) preceded by one of the following: no prestimulus tone, a weak tone (85 dB), or a loud tone (105 dB). The prestimulus tones were presented 250 ms before sled acceleration onset. The loud prestimulus tone decreased the amplitude of the sternocleidomastoid (16%) and cervical paraspinal (29%) muscles, and key peak kinematics: head retraction (17%), horizontal head acceleration (23%), and head angular acceleration in extension (23%). No changes in muscle amplitude or kinematics occurred for the weak prestimulus. The reduced muscle and kinematic responses observed with loud tones suggest that the startle response represents an overreaction that increases the kinematics in a way that potentially increases the forces and strains in the neck tissues. We propose that minimizing this overreaction during a car collision may decrease the risk of whiplash injuries.     

The effects of electromyographic feedback training on suppression of the oral-lingual movements associated with tardive dyskinesia

The efficacy of electromyographic feedback training in reducing the magnitude and frequency of the oral-lingual movements associated with tardive dyskinesia (TD) was investigated in a groups design. Twenty adult male inpatients diagnosed as having TD using the Abnormal Involuntary Movements Scale (AIMS) were randomly assigned to one of two treatment conditions. Following identification, all participants were initially reduced to the lowest effective dosage of neuroleptics, and then discontinued from anticholinergics. Following one month on this regimen, they were given a course of feedback training consisting of ten 14-minute sessions. Group one participants were provided with a tone contingent upon oral-lingual movements above a yoked threshold. Group two participants were given noncontingent feedback tones generated randomly. Weekly AIMS were administered as well as an initial baseline during each session to determine current level of oral-lingual activity. An analysis of session effects indicated significantly more suppression of oral-lingual activity in the contingent group versus the noncontingent feedback group. Jaw and forehead activity also measured showed reductions of similar magnitudes for both groups.This work was sponsored in part by a Research Advisory Grant from the Department of Veterans Affairs awarded to Joanne Intrator. We gratefully acknowledge the valuable contributions of K. Duvvi, S. Kemble, and L. Kolman.     

Influence of central dopaminergic activity on thyrotropin responsiveness to thyrotropin-releasing hormone in normal and thyrotoxic subjects

To study whether central dopaminergic activity influences TSH responsiveness to TRH in normal individuals and in patients with hyperthyroidism, three experiments (A, B and C) were carried out in 8 normal subjects, and two experiments (A and B) in 8 patients with untreated thyrotoxicosis. In experiment A oral placebo (PBO) preceded iv administration of 200 micrograms TRH by 90 min. In experiment B dopamine receptor blockade with 15 mg oral metoclopramide (MET) was given 90 min before iv administration of 200 micrograms TRH. In experiment C two oral doses (each dose 2.5 mg) of bromocriptine (BCT), known for dopamine agonistic properties, were given 9 and 1 hour before ingestion of 15 mg MET which, in turn, preceded iv injection of 200 micrograms TRH by 90 min. In the healthy subjects experiment A revealed a TSH responsiveness, as reflected by the TSH incremental area, which was 430 +/- 74. The corresponding TSH responsiveness was significantly larger in experiment B (661 +/- 138; P less than 0.02). In experiment C the TSH incremental area (332 +/- 102) did not differ significantly from the one obtained in experiment A. The thyrotrophs responded quite different to TRH in the group of thyrotoxic patients, where the TSH incremental area was zero regardless of whether PBO or MET were given as oral pretreatments. These results imply that central dopaminergic activity inhibits the pituitary thyrotrophs and modulates the TSH response to TRH in healthy subjects, but does not contribute significantly to the blocked TSH responsiveness in patients with untreated hyperthyroidism.