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The duration of response inhibition in the stop-signal paradigm varies with response force.

In a previous study, we have found that the speed of stopping a response is delayed when response readiness is reduced by cuing the probability of no-go trials [Acta Psychol. 111 (2002) 155]. Other investigators observed that responses are more forceful when the probability to respond is low than when it is high (e.g. [Quart. J. Exp. Psychol. A 50 (1997) 405]). In this study, the hypothesis was tested that low probability responses are more forceful than high probability responses and that these responses are more difficult to stop. Subjects performed on a choice reaction task and on three tasks with respectively 100%, 80%, and 50% response probabilities. Stop signals were presented on 30% of the trials, instructing subjects to withhold their response. Response force on non-signal (go) trials and the duration of response inhibition on signal (stop) trials increased as response probability decreased. This pattern of findings was interpreted to support the hypothesis predicting that stopping is more difficult when response readiness is low than when it is high.

Adult↗

Specific immune response to Parietaria judaica plant profilin: a low T cell proliferative response supports high IgE and skin prick test.

BACKGROUND: allergic disease caused by Parietaria judaica (Pj) has been widely documented in Mediterranean area. Profilins have been identified as widely distributed allergenic proteins. The role of Pj profilin in specific immune response in Pj-sensitized patients is unknown. METHODS: skin prick test and determination of specific and total IgE levels in serum were performed in all patients (n = 28) and non-allergic controls (n = 18). Peripheral blood mononuclear cells (PBMC) were isolated from both groups and stimulated with crude extract or highly purified Pj profilin. The production of type I and type II cytokines was determined by specific and polyclonal stimuli in patients and controls. T-cell lines specific to Pj profilin were established and cross-reactivity with another highly purified profilin from Phleum pratense (Phl p) was evaluated. RESULTS: Pj profilin-sensitized patients showed a small but significantly increased in T-cell proliferative response to this profilin compared with non-atopic controls. The production of interleukin (IL)-4 and interferon (IFN)-γ in response to the specific stimulus was undetectable. However, the production of IL-4 in response to a polyclonal stimulus [phytohemagglutinin (PHA)] was significantly higher in atopic patients than in controls. The T-cell response did not correlate with the magnitude of response to skin prick tests with Pj profilin or with Pj-specific serum IgE levels. In addition, the production of IL-4 in response to a polyclonal stimulus (PHA) did not correlate with the individual skin prick tests to Pj profilin or with Pj-specific IgE levels in serum. The T-cell lines tested showed no cross-reactivity with Phl p profilin. CONCLUSIONS: our results suggest that Pj profilin is partly responsible for the T-cell-mediated response in patients allergic to Pj. The high skin reactivity to Pj profilin is these patients was accompanied by a small increase in the T-cell response to this profilin. The response was highly specific since Pj profilin specific T-cell lines showed no cross-reactivity with a highly homologous profilin from Phl p. The lack of correlation between the proliferative T-cell response and polyclonal IL-4 production with allergen-specific serum IgE and skin reactivity probably indicates that some of the responding T-cells may be involved in immune reactions other than those supporting IgE production.

Adult↗

Differences in responses to 70 dB clicks of cerebellar units with simple versus complex spike activity: (i) in medial and lateral ansiform lobes and flocculus; and (ii) before and after conditioning blink conditioned responses with clicks as conditioned stimuli.

Activity was recorded from 554 cerebellar units in eleven conscious cats to determine if responses to 70 dB clicks differed in units with simple and complex spike discharges. Effects of region of recording and behavioral state (with click used as a conditioned stimulus for conditioning) were also assessed. Cells with only simple spikes were distinguished from cells that had the following types of complex spike events: Type I-simple or initial spike followed > 1 ms by multiple spikes with baseline displacement (classical complex spikes), Type II--followed < or = 1 ms by spikes with or without baseline displacement (spikes in the absolute refractory period should arise from a separate site of initiation), and Type III-followed by spikes and displacement too close to the baseline noise to distinguish as Type I or II. Among the groups mean baseline activity was greatest in cells with Type I complex spikes, least in cells with Type III complex spikes, and greater in Type II cells than simple cells. Significant increases in activity within 32 ms of presenting clicks were found in the groups of Type II cells and simple cells. These appear to be the main auditory responsive cells of the cerebellar regions studied. Activity of Type II cells best reflected the temporal properties of the click; responses of simple cells had slower onsets (except in flocculus) and longer durations. Responses to click in Type II and simple cells differed in recordings from: (i) lateral ansiform lobe (lateral crus I and portions of crus II), (ii) medial ansiform lobe (medial crus I), and (iii) flocculus. The largest mean responses above baseline in the first 32 ms after click were found in Type II cells of the lateral ansiform lobe with onsets of 8-16 ms. Magnitudes of response differed before and after conditioning and backward conditioning. In the lateral ansiform lobe, the < 32 ms response to click was greater in Type II than simple cells in each state, but showed a greater increase above baseline after backward conditioning when conditioned responses were not produced than after conditioning. The onset of increased activity to click conditioned stimuli in Type II cells of the lateral ansiform region preceded the onset of the blink conditioned response after conditioning, consisted almost entirely of simple spikes, and reflected an increase in magnitude of response as opposed to an increased number of responsive units. After conditioning, an increased number of units in the flocculus responded to click conditioned stimuli in the 16-24 ms post stimulus period. Of the 16 cells with an onset of increased activity at this time, eight showed only simple spike activity. Seven of the remaining eight cells (all Type II) showed a significant increase in conditioned stimulus-evoked complex spiking above the low (usually < 1/s) baseline level of complex spike discharges. The findings support the conclusions that cerebellar units can respond rapidly enough to acoustic stimuli to play a role in auditory as well as motor processing and that the responses to 70 dB clicks differ among cells with simple and complex spike discharges. The differences are influenced substantially by the region of cerebellar recording and the behavioral state. The findings in cells of the flocculus offer the first evidence that complex as well as simple spike activity can contribute to an increased probability of discharge to click as a conditioned stimulus after conditioning.

Acoustic Stimulation↗

Differential responsivity of the hypothalamic-pituitary-adrenal axis to glucocorticoid negative-feedback and corticotropin releasing hormone in rats undergoing morphine withdrawal: possible mechanisms involved in facilitated and attenuated stress responses.

Chronic morphine treatment produces profound and long-lasting changes in the pituitary-adrenal responses to stressful stimuli. The purpose of the present study was to explore the mechanisms involved in these altered stress responses. Chronic morphine administration increased basal plasma concentrations of corticosterone and adrenocorticotropic hormone (ACTH), which peaked at 36 h after the final morphine injection and returned to normal levels within 84-h. Whole brain glucocorticoid receptor protein expression was reduced (approximately 70%) in morphine-treated rats 4-h after the final morphine injection and these levels recovered within 16-h. Twelve hours following morphine withdrawal, rats displayed normal ACTH, but potentiated and prolonged corticosterone responses to restraint stress. Both the ACTH and corticosterone responses to restraint in acutely withdrawn rats were insensitive to dexamethasone. Furthermore, acutely withdrawn rats displayed reduced ACTH but prolonged corticosterone responses to peripheral corticotropin releasing hormone (CRH) administration. These findings suggest that the normal ACTH and enhanced corticosterone responses to stress in acutely withdrawn rats involved decreased sensitivity of negative-feedback systems to glucocorticoids, reduced pituitary responsivity to CRH, and enhanced sensitivity of the adrenals to ACTH. Eight days following morphine withdrawal, rats displayed dramatically reduced ACTH, but normal corticosterone responses to restraint stress. These rats displayed enhanced sensitivity to dexamethasone and normal pituitary-adrenal responses to CRH. These data suggest that the reduced ACTH responses to stress in 8-day withdrawal rats involved increased sensitivity of negative-feedback systems to glucocorticoids as well as reduced CRH and/or AVP function in response to stress. Taken together, the results of this study illustrate some of the mechanisms mediating altered stress responsivity in rats that have received chronic morphine treatment.

Adrenocorticotropic Hormone↗

Functional regulatory immune responses against human cartilage glycoprotein-39 in health vs. proinflammatory responses in rheumatoid arthritis.

The class of immune response against autoantigens could profoundly influence the onset and/or outcome of autoimmune diseases. Until now, there is only limited information on the antigen-specific balance between proinflammatory and regulatory responses in humans. Here we analyzed the natural immune response against a candidate autoantigen in rheumatoid arthritis, human cartilage glycoprotein-39 (HC gp-39). Peripheral blood mononuclear cells from healthy individuals reacted against HC gp-39 with the production of IL-10 but not IFN-gamma. Ex vivo assays indicated that the naturally occurring HC gp-39-specific immune response in bulk is powerful enough to suppress antigen-specific recall responses, demonstrating that rather than being unresponsive, the HC gp-39-directed immune response in healthy individuals shows a strong bias toward a regulatory phenotype. Moreover, CD4(+) T cell lines directed against HC gp-39 expressed CD25, glucocorticoid-induced tumor necrosis factor receptor, and Foxp3 molecules and were capable of suppressing antigen-specific T cell responses. Cell-cell contact was required for this suppression. As opposed to healthy individuals, the HC gp-39-directed immune response in 50% of patients with rheumatoid arthritis exhibits polarization toward a proinflammatory T helper 1 phenotype and is significantly less powerful in suppressing antigen-specific recall responses. Together these findings indicate that the presence of HC gp-39-specific immune responses in healthy individuals may have an inhibitory effect on inflammatory responses in areas where HC gp-39 is present. Furthermore, these data indicate that the class of HC gp-39-directed immune response in rheumatoid arthritis patients has shifted from an antiinflammatory toward a proinflammatory phenotype.

Adipokines↗

Mutational analysis of the CYP2B2 phenobarbital response unit and inhibitory effect of the constitutive androstane receptor on phenobarbital responsiveness.

A 163-base pair enhancer in the CYP2B2 5' flank confers phenobarbital (PB) inducibility and constitutes a PB response unit (PBRU). By transfection of primary hepatocytes, we analyzed the function of elements comprising the PBRU and evaluated the role of the constitutive androstane receptor (CAR) in PB responsiveness. A 51-base pair PB-responsive enhancer module (PBREM) within the PBRU confers near-maximal PB response when fused to a tk promoter. However, replacing the PBRU with the PBREM in the CYP2B2 5' flank in the natural sequence context reduced PB responsiveness by approximately 4-fold. Mutational analysis also demonstrated that PBRU sequence elements outside the PBREM are essential for maximal PB responsiveness. The PBRU contains two putative nuclear receptor binding sites, NR1 and NR2. CAR binds to retinoic acid beta2 response elements (betaRARE) and to the NR1 and NR2 sites of the PBRU and activates transcription of reporter genes in cell lines. However, conversion of NR1 into betaRARE was the equivalent of an inactivating mutation, indicating that CAR does not activate PB-dependent transcription via NR1 in the natural sequence context. A betaRAREx2-tk reporter construct was inducible by all-trans-retinoic acid (at-RA) as expected and also responded to PB. The latter can be attributed to nuclear accumulation of CAR after PB exposure. Exogenous CAR increased both the basal and PB-induced response of betaRAREx2-tk but reduced PBRU-dependent PB response. Furthermore, exogenous CAR also reduced the at-RA response of the betaRAREx2-tk construct. Thus, CAR acts negatively on PB responsiveness mediated by the CYP2B2 PBRU just as it prevents maximal at-RA responsiveness mediated by betaRARE.

Amino Acid Sequence↗

Immune responses in vitro. 3. Development of primary gamma-M, gamma-G, and gamma-A plaque-forming cell responses in mouse spleen cell cultures stimulated with heterologous erythrocytes.

We have demonstrated for the first time that mouse spleen cells stimulated in vitro with heterologous erythrocytes developed immunoglobulin class-specific gammaM, gamma(1), gamma(2a+2b), and gammaA plaque-forming cell (PFC) responses. A modification of the hemolytic plaque technique, the addition of goat anti-mouse micro-chain antibody to the assay preparation, specifically prevented development of all gammaM PFC and enabled accurate and reproducible enumeration of immunoglobulin class-specific PFC after treatment with appropriate monospecific anti-globulins and complement. Culture conditions, with regard to medium, atmosphere, agitation, and spleen cell densities, were similar to those previously shown to support only gammaM PFC responses. Evaluation of the kinetics of appearance of PFC showed that gammaM PFC reached maximum numbers on days 4-5; the magnitude of this response was 3-10 times greater than gamma(1) gamma(2a+2b), or gammaA PFC which reached maximum numbers on days 5-6. Optimal erythrocyte antigen dose for gammaM PFC responses was 10(7)/culture, whereas a dose of 10(6) erythrocytes/culture consistently stimulated optimal gamma(1) gamma(2a+2b), or gammaA PFC responses. Investigations of the effects of anti-erythrocyte antibody on gammaM and gammaG PFC responses indicated that antibody suppressed these responses by neutralizing the effective antigenic stimulus at the macrophage-dependent phase of the response. At the same antibody concentration, gammaG PFC responses were more effectively suppressed than gammaM PFC responses. Further, gammaG responses could be almost completely suppressed by antibody as long as 48 hr after initiation of cultures, whereas gammaM PFC responses could only be completely suppressed during the first 24 hr. These results were discusssed in terms of the role of antigen in the stimulation gammaM and gammaG antibody.

Animals↗

Differential expression of genes for response regulators in response to cytokinins and nitrate in Arabidopsis thaliana.

In Arabidopsis thaliana, a number of response regulators are presumably involved in His-Asp phosphorelay signal transduction in response to environmental stimuli, such as phytohormones. Previously, it was shown that expression of a certain set of genes for response regulators are cytokinin- and nitrate-responsive in their mRNA accumulation, under certain growth conditions [Taniguchi et al. (1998) FEBS Lett. 429: 259, Brandstatter and Kieber (1998) Plant Cell 10: 1009]. To answer the critical question of whether or not other response regulator genes, so far identified in Arabidopsis thaliana, are also cytokinin-inducible, here an extended comparative examination was carried out. It was demonstrated that not all of response regulator genes are necessarily cytokinin-responsive in their transcription. Rather, the members of a certain subfamily (type-A) are cytokinin-responsive, but those belonging to the other (type-B) are not. The presumed nitrate-responsiveness was also assessed for the same set of response regulators, and the analogous view was supported. These results suggest that the two subtypes of response regulators differ from each other, as judged from not only their structural designs, but also the expression profiles of their transcripts in response to plant stimuli.

Arabidopsis↗

The auditory evoked "off" response: sources and comparison with the "on" and the "sustained" responses.

OBJECTIVE: It is well known that tone bursts elicit a prominent N1/P2 complex in the auditory evoked potential (the on-response), but less is known about a morphologically similar complex (the off-response) that can be recorded under suitable stimulus conditions. The interaction between the two responses indicated that the responses were not physiologically independent. The present experiment employed neuromagnetic methods to determine the cortical sources of N1 and P2 on- and off-responses and their relation to other events observed in the auditory evoked field. DESIGN: Five female and five male subjects with no history of otologic or neurological disorders and with normal audiological status participated in this study. Tone bursts of 2 sec duration (10 msec rise and decay time, cosine function), carrier frequency of 1 kHz, and intensity of 60 dB nHL (normative hearing level) were presented 512 times to the subject's right ear (contralateral to the investigated hemisphere) with an interstimulus interval randomized between 5 and 7 sec. RESULTS: The present study is unique in that several components of the complex auditory evoked response (P1, N1on, P2on, sustained-field, N1off, P2off) were recorded and localized in the same subjects and in the same experiment. The source coordinates obtained for N1 and P2 on- and off-responses indicated that the two responses are generated by overlapping cortical regions. Sources for the P2 components were situated anterior and medial to sources for the N1 components and were indistinguishable from sources for the auditory sustained-field. An early P1on event preceded the N1on (but not the N1off) response and was spatially indistinguishable from the N1on. The equivalent source strength was greater for N1on and P2on sources compared with N1off and P2off sources. CONCLUSIONS: The recoding process signaled by on-and off-responses may be a dynamic form of plasticity in the auditory cortex with a time constant on the order of hundreds of milliseconds, corresponding to the duration of sustained-responses released by acoustic changes and to the duration of the acoustic foreperiod that is necessary before on-and off-responses to acoustic changes can be observed.

Adult↗

Molecular analysis of the immune response to human cytomegalovirus glycoprotein B (gB). II. Low gB-specific T and B cell responses are associated with expression of certain HLA-DR alleles.

Human cytomegalovirus (HCMV) is a common cause of congenital infection leading to birth defects and a leading cause of serious illness in patients with immunodeficiencies. Studies in this laboratory have focused on a molecular analysis of the immune response to glycoprotein B (gB) of HCMV. This protein has been shown to elicit B cell, helper T cell (Th), and cytotoxic T cell responses, suggesting that it may be useful as a subunit HCMV vaccine. However, previous studies showed that although peripheral blood mononuclear cells (PBMC) from all HCMV-seropositive donors proliferate in response to stimulation with whole HCMV, not all donors respond to purified recombinant gB. In the present study, PBMC from HCMV-seropositive donors homozygous for HLA-DR were tested for proliferative responses to whole HCMV and to purified gB expressed in vaccinia virus. PBMC from all donors proliferated in response to HCMV, but those from multiple donors expressing the HLA-DR3Dw3 and -DR4Dw4 specificities, and single donors expressing the -DR15Dw2, -DR13Dw19 and -DR14Dw9 specificities, failed to respond to gB. These results suggested a possible HLA-DR association with low proliferative responses to gB. In further studies, PBMC from donors expressing both putative gB-high responder and low responder HLA-DR alleles were stimulated multiple times with gB to generate gB-specific T cell lines. These cells were then tested for proliferative responses to gB presented by irradiated PBMC sharing only one DR allele with the responder cells. Cells from the gB-specific lines proliferated only when antigen was presented in the context of a responder DR allele but not when presented in the context of a low responder DR allele. Analysis of immune sera revealed that those from donors with PBMC proliferative responses always contained antibodies reactive with B cell epitopes on both the N-terminal gp93 and C-terminal gp55 portions of gB. In contrast, many of the sera from donors with low gB-specific proliferative responses had gp55-specific antibodies but lacked antibodies to gp93. These results suggest that immunogenetic differences in Th responsiveness to gB may lead to lack of antigen-specific help for antibody responses to gp93 in some cases. The prevalence of these low responder HLA alleles in the population, and the central importance of the T cell response to the generation of antibodies suggest that native gB alone may not be an attractive candidate for an HCMV subunit vaccine.

Adult↗

Predictors of sustained response, relapse and no response in patients with chronic hepatitis C treated with interferon-alpha.

Three main patterns of response are seen when interferon-alpha (IFN-alpha) is used for the treatment of chronic hepatitis C: 1 sustained response with alanine-aminotransferase (ALT) normalization that is maintained after cessation of therapy, with or without clearance of serum hepatitis C virus (HCV) RNA; 2 transient response with ALT normalization during therapy followed by relapse after its withdrawal, and 3 no response with no or only partial reduction in ALT levels. In order to define variables that could predict each of these three types of response we studied 321 cases of chronic hepatitis C treated with IFN-alpha in two consecutive trials conducted in our Unit. By univariate analysis, age < 45 years (P < 0.01), known disease duration < 60 months (P < 0.01), normal gamma-glutamyl-transpeptidase (gamma GT) levels (P < 0.01) and infection by HCV genotype 2 or HCV genotype 3 (P < 0.01) were found to be statistically associated with sustained response while age > 45 years (P < 0.01), body weight (P = 0.05), cirrhosis (P < 0.01) and elevated gamma GT levels (P < 0.01) were associated with no response. By multivariate analysis sustained response was predicted by HCV genotype 2 (P < 0.01) and HCV genotype 3 (P < 0.01), known disease duration (P < 0.01), patient's age (P < 0.05) and associated with the use of a more aggressive treatment schedule (P < 0.05). Transient response with relapse was predicted by known duration of disease (P < 0.05), HCV genotype 1 (P < 0.05) and female sex (P < 0.05). No response was statistically associated with elevated gamma GT levels (P < 0.01), higher body weight (P < 0.05) and with the less aggressive regimen of 3 MU of natural IFN-alpha given three times weekly for 6 months (P < 0.05). These results indicate that the HCV genotype as well as the schedule of treatment greatly affect the pattern of response to IFN in chronic hepatitis C and allow us to define criteria to predict which type of response is more likely in individual patients.

Adult↗

Improving response rates to primary and supplementary questionnaires by changing response and instruction burden: cluster randomised trial.

OBJECTIVE: Supplementary questionnaires provide additional information from subgroups, but may have an attritional effect on response rates. We examined the effects of different instruction methods on response rates to a two-part questionnaire. METHODS: The ACT Kindergarten Health Survey comprises a health questionnaire for all school-entry children. A supplementary questionnaire targets children with respiratory symptoms. We cluster-randomised 109 schools in the ACT (4,494 children) to two instruction groups. Group 1 (instruction burden) had instructions to complete the supplementary questionnaire if certain questions in the primary questionnaire were answered. Group 2 (response burden) had instructions to complete both questionnaires irrespective of answers to the primary questionnaire. RESULTS: Instructing all respondents to complete both questionnaires regardless of eligibility resulted in a statistically significantly lower primary questionnaire response rate (82% vs. 87%), but a statistically significantly higher response rate to the supplementary questionnaire (99% vs. 91%). The net effect was a small overall gain (82% vs. 79%) for the response burden group. CONCLUSION: Increasing the response burden had a minor impact on response rate to the primary questionnaire, but increased the response rate for most items to the supplementary questionnaire. IMPLICATIONS: Large surveys may be broken into primary and supplementary questionnaires, if strategies to maximise response rates are used. Questionnaires may need to be modified to take into account the likely attrition on response to either questionnaire resulting from instruction and response burdens.

Child↗

Extended concentration-response curves used to reflect full agonist efficacies and receptor occupancy-response coupling ranges.

1. An approach is described for generating extended agonist concentration-response curves where the responses are unconstrained by the normal tissue maximum response. Functional antagonism is employed to hold the tissue state in the range where any change in stimulus can be translated into a measurable response. 2. The maximum response of these extended concentration-response curves provides an index of intrinsic activity reflecting the agonist efficacy and the receptor occupancy-response coupling range. 3. The use of this approach is illustrated with extended concentration-response curves for noradrenaline (NA), vasopressin, acetylcholine (ACh), and 5-methylfurmethide in the small mesenteric and tail arteries of the rat. Both NA and vasopressin can maximally activate the arteries, but the new protocol shows that NA can produce more cellular activation than vasopressin in the tail artery. Both ACh and 5-methylfurmethide are full agonists but ACh has a higher intrinsic activity than 5-methylfurmethide. The ACh muscarinic receptors in the mesenteric artery have a larger occupancy-response range than the ACh muscarinic-receptors in the tail artery, and the alpha-adrenoceptors in the tail artery appear to have a larger occupancy-response coupling range than those in the mesenteric artery. 4. This approach extends our ability to compare the efficacies of full agonists, and to compare the occupancy-response coupling ranges of receptors that can normally maximally activate the assay tissue. This is achieved without the use of an irreversible antagonist and should be applicable to many receptors and pharmacological assay systems where responses are stable and functional antagonists are available.

Acetylcholine↗

Dynamic response of immature bovine articular cartilage in tension and compression, and nonlinear viscoelastic modeling of the tensile response.

Very limited information is currently available on the constitutive modeling of the tensile response of articular cartilage and its dynamic modulus at various loading frequencies. The objectives of this study were to (1) formulate and experimentally validate a constitutive model for the intrinsic viscoelasticity of cartilage in tension, (2) confirm the hypothesis that energy dissipation in tension is less than in compression at various loading frequencies, and (3) test the hypothesis that the dynamic modulus of cartilage in unconfined compression is dependent upon the dynamic tensile modulus. Experiment 1: Immature bovine articular cartilage samples were tested in tensile stress relaxation and cyclical loading. A proposed reduced relaxation function was fitted to the stress-relaxation response and the resulting material coefficients were used to predict the response to cyclical loading. Adjoining tissue samples were tested in unconfined compression stress relaxation and cyclical loading. Experiment 2: Tensile stress relaxation experiments were performed at varying strains to explore the strain-dependence of the viscoelastic response. The proposed relaxation function successfully fit the experimental tensile stress-relaxation response, with R2 = 0.970+/-0.019 at 1% strain and R2 = 0.992+/-0.007 at 2% strain. The predicted cyclical response agreed well with experimental measurements, particularly for the dynamic modulus at various frequencies. The relaxation function, measured from 2% to 10% strain, was found to be strain dependent, indicating that cartilage is nonlinearly viscoelastic in tension. Under dynamic loading, the tensile modulus at 10 Hz was approximately 2.3 times the value of the equilibrium modulus. In contrast, the dynamic stiffening ratio in unconfined compression was approximately 24. The energy dissipation in tension was found to be significantly smaller than in compression (dynamic phase angle of 16.7+/-7.4 deg versus 53.5+/-12.8 deg at 10(-3) Hz). A very strong linear correlation was observed between the dynamic tensile and dynamic compressive moduli at various frequencies (R2 = 0.908+/-0.100). The tensile response of cartilage is nonlinearly viscoelastic, with the relaxation response varying with strain. A proposed constitutive relation for the tensile response was successfully validated. The frequency response of the tensile modulus of cartilage was reported for the first time. Results emphasize that fluid-flow dependent viscoelasticity dominates the compressive response of cartilage, whereas intrinsic solid matrix viscoelasticity dominates the tensile response. Yet the dynamic compressive modulus of cartilage is critically dependent upon elevated values of the dynamic tensile modulus.

Animals↗

Response characteristics of amygdaloid neurons provoked by emotionally significant environmental stimuli in cats, with special reference to response durations.

Extracellular single or multiple neuronal activities were recorded from the basolateral portion of the amygdala of wild adult cats under an unanesthetized, freely moving condition, and neuronal responsiveness to neutral, aversive, and appetitive stimuli was studied. Of 71 units, 47 (66%) responded to some of the stimuli. The patterns of neuronal responses were classified into three types on the basis of response duration. Of the responses sampled, 9% rapidly attenuated and disappeared before termination of stimulus presentation (pattern A), 58% of responses were maintained during the period of the stimulus presentation but disappeared abruptly after termination (pattern B), and 33% of responses markedly outlasted the stimulus presentation period (pattern C). Pattern A responses habituated readily and were most prominent when neutral stimuli were presented, so this type of response was considered to underlie altering or orienting responses. Pattern B responses were observed equally for the three kinds of stimuli, and were suggested to be predominantly involved in perception of the environmental stimuli. Pattern C responses habituated least and tended to be elicited more frequently by aversive stimuli. This type of response was interpreted to reflect emotional arousal. These findings were considered to be compatible with the hypothesis that the amygdala plays an important role in converting environmental stimuli into emotions such as rage or fear.

Amygdala↗

Analysis of response properties of deefferented mammalian spindle receptors based on frequency response.

Sinusoidal responses of primary and secondary endings in deefferented spindles of anesthetized cats were studied over the low-frequency range 0.001-0.1 Hz. Stretch amplitudes were chosen conservatively small (25-100 mum peak-to-peak) so as to lie within the linear region. 1. At 0.1 Hz average sensitivity was 350 pps/mm for primary endings and 80 pps/mm for secondary endings. Sensitivity fell to lower values at lower frequencies, but even at 0.001 Hz, corresponding to 17 min/cycle, sensitivity remained elevated above static values determined with large stretches. Phase lead varied from 5 to 50 degrees and, in the case of primary endings, tended to be greater at lower frequencies. 2. Except for the different scaling factors, the only apparent difference between the frequency responses of primary and secondary endings was a tendency for primary endings to show a greater phase lead over the range 0.001-0.01 Hz. 3. Dynamic responsiveness was assessed theoretically from frequency-response data by calculating responses to ramps at various velocities. Over most of the velocity range dynamic responses were not proportional to velocity. The greater dynamic responsiveness of primary endings during large (6 mm) ramp stretches might be related to frequency response below 0.01 Hz. 4. Certain aspects of dynamic responsiveness to large ramps (6 mm) were accounted for by assuming all phases of responses were attenuated by 25 dB in the case of primary endings and 20 dB in the case of secondary endings. The nonlinearity responsible for attenuation appears to occur at an early stage in the sensory process. 5. Comparison of individual responses to slow ramps with predictions based on linear theory indicated the presence of abrupt departures from linearity for both primary and secondary endings.

Animals↗

Excitatory/inhibitory response types in the cochlear nucleus: relationships to discharge patterns and responses to electrical stimulation of the auditory nerve.

We have studied the response properties of single units in the cochlear nucleus of unanesthetized decerebrate cats. The purpose of the study was to compare the properties of cochlear nucleus units as described in two commonly used classification schemes. Units were first classified according to their receptive-field properties based on the relative prominence of excitatory and inhibitory responses to tones and noise. Units were then classified on the basis of their discharge patterns to short tone bursts at their best frequencies (BFs). Our results show that systematic relationships exist between the receptive-field properties and discharge patterns of cochlear nucleus units. Type I units give only excitatory responses to tones and noise. They are characterized by primary-like and chopper discharge patterns. Some units in the anteroventral cochlear nucleus have prepotentials in their spike waveforms. Prepotential units most often show primary-like discharge patterns, but prepotential units characterized by nonprimary-like discharge patterns are also found. Most prepotential units lack detectable inhibitory sidebands (type I), but two of the nonprimary-like prepotential units encountered in this study had inhibitory sidebands (type III). Type III units also give excitatory responses to BF tones, but they have inhibitory sidebands. Most type III units give chopper discharge patterns, and these units can be recorded throughout the cochlear nucleus. Some type III units in the dorsal cochlear nucleus give complex discharge patterns that can be described as a composite of the pauser pattern and other patterns. The complexity of these responses seems to increase as the amount of inhibition at BF increases. Type I/III units give excitatory responses to tones and noise, but have little or no spontaneous activity so they cannot be tested directly for inhibitory responses. Type I/III units typically show chopper discharge patterns. One group of type I/III units have rate-level functions with sloping saturation, suggesting that these may receive a predominance of input from low spontaneous rate auditory nerve fibers. Type II units are nonspontaneous and give excitatory responses to tones, but give weak or no responses to noise. While type II units are homogeneous as a group in terms of their response maps. BF rate-level functions, and responses to noise, they show a variety of discharge patterns in response to short tone bursts at BF.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The neurophysiology of response competition: motor cortex activation and inhibition following subliminal response priming.

Some widely used tasks in cognitive neuroscience depend on the induction of a response conflict between choice alternatives, involving partial activation of the incorrect response before the correct response is emitted. Although such ''conflict tasks'' are often used to investigate frontal-lobe-based conflict-monitoring processes, it is not known how response competition evolves in the motor cortex. To investigate the dynamics of motor cortex activation during response competition, we used a subliminal priming task that induced response competition while bypassing pre-response stage processing conflict. Analyses of movement-related EEG potentials supported an interaction between competing responses characterized by reciprocal inhibition. Inhibitory interactions between response channels contribute to the resolution of response conflict. However, the reciprocal inhibition at motor cortex level seemed to operate independent of higher level conflict-monitoring processes, which were relatively insensitive to response conflict induced by subliminal priming. These results elucidate how response conflict causes interference as well as the conditions under which frontal-lobe-based interference control processes are engaged.

Adult↗