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PubMed2000

The effects of selective response preparation on corticospinal excitability.

OBJECTIVE: Both motor imagery and selective motor cues enhance performance. Motor cortex is activated during motor imagery. We wanted to learn if selective motor cueing also activates motor cortex. METHODS: We gave normal right-handed subjects information about which hand to use to respond to an imperative stimulus (selective intention) or where in space an imperative stimulus would occur (selective attention). To minimize anticipatory responses, warning stimulus validity was 80%. During this choice reaction time task, we recorded magnetic motor evoked potentials. Imperative stimuli and transcranial magnetic stimulation were presented randomly to assess the effect of warning cues on reaction times and corticospinal excitability. RESULTS: Selective intentional and attentional warning cues reduced reaction times, but neither stimulus altered motor evoked potentials. CONCLUSIONS: These results suggest that unlike motor imagery, selective intention to respond to an imperative stimulus and shifting spatial attention to an imperative stimulus do not alter corticospinal excitability.

Adult↗
PubMed1975

Population size and selection intensity effects on long-term selection response in mice.

Long-term response to within full-sib family selection for increased postweaning gain was evaluated in lines having different effective population sized (Ne) and selection intensities (i). Line designations were I4(4), I8(2), I16(2), M4(4), M8(2) and M16(2), where I and M indicate selection of the top 50% and 25%, respectively; 4, 8 and 16 represent the number of parental pairs per replicate and number of replicates is given in parentheses. Realized within full-sib family heritabilities (hR-2) in the first phase of selection (0-14 generations) were larger in 16-pair lines than in 4- and 8-pair lines. In the second phase of selection (greater than 14 generations), hR-2 declined significantly (P smaller than .01) in all lines, and only the I16 and M16 lines had hR-2 values significantly (P smaller than .01) greater than zero. Realized genetic correlations involving number born, 12-day litter weight, weaning weight and six-week weight tended to decline in the second phase of selection. The I16, M16 and control (C16) replicates were crossed in all combinations at generation 14. Crosses were then selected within litters for high postweaning gain. The hR-2 values in the crossbred lines were all larger than those in the second selection phase for M16-1. M16-2 and I16-1, but not for I16-2. Within each Ne level, total response was significantly (P smaller than .01) less for I lines compared with M lines. Total response increased as Ne increased, within each level of i. Relatively small differences in realized i values among Ne lines could not account for this result. The difference in total response among the Ne lines at a given selection intensity may be due to inbreeding depression and a combination of interactions involving "drift" and selection. By crossing replicates of the M lines with the C16 control, the effects of inbreeding depression were removed. Inbreeding depression and genetic drift, as defined herein, were equally important in accounting for differences among Ne lines in total response.

Animals↗
PubMed2001

Effects of STN lesions on simple vs choice reaction time tasks in the rat: preserved motor readiness, but impaired response selection.

The subthalamic nucleus (STN) is a key structure within the basal ganglia, inactivation of which is a current strategy for treating parkinsonism. We have previously shown that bilateral lesions of the STN or pharmacological inactivation of this structure in the rat induce multiple deficits in serial reaction time tasks. The aim of the present study was to investigate further a possible role for the STN in response preparatory processes by using simple (SRT) and choice (CRT) reaction time tasks. In contrast to the CRT procedure, the information related to the location of where the response had to be made was given in advance in the SRT procedure. Accurate performance on these tasks requires not only the selection of the correct response (i.e. which response), but also preparation in order to perform when required. A comparison between the two tasks allows assessment of whether STN lesions affect which response ("which") or when to perform it ("when"). As previously observed in these procedures, the responses were faster as a function of the variable foreperiod preceding the trigger stimulus. This well-known effect, termed "motor readiness, was maintained after STN lesions, suggesting that STN lesions did not affect the "when" phase of action preparation. However, while performance on the SRT was faster than on the CRT task preoperatively, STN lesions slowed RTs and abolished the beneficial effect of advance information, suggesting a deficit in the selection ("which") phase of response preparation. This deficit in the selection phase was further supported by deficits in accuracy of responding after STN lesions, as well as increases in mislocated premature responding in the SRT condition. Together, these results suggest that the STN plays an important role in response preparatory processes, including response selection and inhibitory control processes.

Animals↗
PubMed1991

Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors.

We report here the identification of thyroid hormone response elements (TREs) that consist of a direct repeat, not a palindrome, of the half-sites. Unlike palindromic TREs, direct repeat TREs do not confer a retinoic acid response. The tandem TRE can be converted into a retinoic acid response element by increasing the spacing between the half-sites by 1 nucleotide, and the resulting retinoic acid response element is no longer a TRE. Decreasing the half-site spacing by 1 nucleotide converts the TRE to a vitamin D3 response element, while eliminating response to T3. These results correlate well with DNA-binding affinities of the thyroid hormone, retinoic acid, and vitamin D3 receptors. This study points to the general importance of tandem repeat hormone response elements and suggests a simple physiologic code exists in which half-site spacing plays a critical role in achieving selective hormonal response.

Animals↗
PubMed2004

Response selection deficits in melancholic but not nonmelancholic unipolar major depression.

One consistent functional imaging finding from patients with major depression has been abnormality of the anterior cingulate cortex (ACC). Hypoperfusion has been most commonly reported, but some studies suggest relative hyperperfusion is associated with response to somatic treatments. Despite these indications of the possible importance of the ACC in depression there have been relatively few cognitive studies ACC function in patients with major depression. The present study employed a series of reaction time (RT) tasks involving selection with melancholic and nonmelancholic depressed patients, as well as age-matched controls. Fifteen patients with unipolar major depression (7 melancholic, 8 nonmelancholic) and 8 healthy age-matched controls performed a series of response selection tasks (choice RT, spatial Stroop, spatial stimulus-response compatibility (SRC), and a combined Stroop + SRC condition). Reaction time and error data were collected. Melancholic patients were significantly slower than controls on all tasks but were slower than nonmelancholic patients only on the Stroop and Stroop + SRC conditions. Nonmelancholic patients did not differ from the control group on any task. The Stroop task seems crucial in differentiating the two depressive groups, they did not differ on the choice RT or SRC tasks. This may reflect differential task demands, the SRC involved symbolic manipulation that might engage the dorsal ACC and dorsolateral prefrontal cortex (DLPFC) to a greater extent than the, primarily inhibitory, Stroop task which may engage the ventral ACC and orbitofrontal cortex (OFC). This might suggest the melancholic group showed a greater ventral ACC-OFC deficit than the nonmelancholic group, while both groups showed similar dorsal ACC-DLPFC deficit.

Adult↗
PubMed2005

Development of spectral and temporal response selectivity in the auditory cortex.

The mechanisms by which hearing selectivity is elaborated and refined in early development are very incompletely determined. In this study, we documented contributions of progressively maturing inhibitory influences on the refinement of spectral and temporal response properties in the primary auditory cortex. Inhibitory receptive fields (IRFs) of infant rat auditory cortical neurons were spectrally far broader and had extended over far longer duration than did those of adults. The selective refinement of IRFs was delayed relative to that of excitatory receptive fields by an approximately 2-week period that corresponded to the critical period for plasticity. Local application of a GABA(A) receptor antagonist revealed that intracortical inhibition contributes to this progressive receptive field maturation for response selectivity in frequency. Conversely, it had no effect on the duration of IRFs or successive-signal cortical response recovery times. The importance of exposure to patterned acoustic inputs was suggested when both spectral and temporal IRF maturation were disrupted in rat pups reared in continuous, moderate-intensity noise. They were subsequently renormalized when animals were returned to standard housing conditions as adults.

Animals↗
PubMed2004

Genotype-assisted optimum contribution selection to maximize selection response over a specified time period.

Genotype-assisted selection (GAS), i.e. selection for an identified quantitative trait locus (QTL) and polygenic background genes, has been shown to increase short-term genetic gain but may reduce long-term genetic gains. In order to avoid this reduction of long-term gain, multi-generation optimization of truncation selection schemes is needed. This paper presents a multi-generation optimization of optimum contribution (OC) selection with selection on an identified QTL. This genotype-assisted optimum contribution (GAOC) selection method assumes that the optimum selection differential at the QTL is constant over the time horizon, and achieves this by controlling the increase of the frequency of the positive QTL allele. Implementation was straightforward by an additional linear restriction in the OC algorithm. GAOC achieved 35.2%, 2.3% and 1.1%, respectively, more cumulative genetic gain than OC selection (ignoring the QTL) using time horizons of 5, 10 and 15 generations. When one-generation optimization of GAS was used instead of multi-generation optimization, these figures were 2.8%, 3.1% and 3.2%, respectively. Simulated annealing was used to optimize the increases of the frequency of the positive QTL allele in order to test the optimality of GAOC. This latter resulted in genetic gains that were always within 0.4% of those of GAOC. In practice, short-term genetic gains are also important, which makes one-generation optimization of genetic gain closer to optimal.

Data Interpretation, Statistical↗
PubMed2002

Heritability, reliability of genetic evaluations and response to selection in proportional hazard models.

The purposes of this study were 1) to investigate the heritability, reliability, and selection response for survival traits following a Weibull frailty proportional hazard model; and 2) to examine the relationship between genetic parameters from a Weibull model, a discrete proportional hazard model, and a binary data analysis using a linear model. Both analytical methods and Monte Carlo simulations were used to achieve these aims. Data were simulated using the Weibull frailty model with two different shapes of the Weibull distribution. Breeding values of 100 unrelated sires with 50 to 100 progeny (with different levels of censoring) were generated from a normal distribution and two different sire variances. For analysis of longevity data on the discrete scale, simulated data were transformed to a discrete scale using arbitrary ends of discrete intervals of 400, 800, or 1200 d. For binary data analysis, an individual's longevity was either 0 (when longevity was less than the end of interval) or 1 (when longevity was equal or greater than the end of interval). Three different statistical models were investigated in this study: a Weibull model, a discrete-time model (a proportional hazard model assuming that the survival data are measured on a discrete scale with few classes), and a linear model based upon binary data. An alternative derivation using basic expressions of reliabilities in sire models suggests a simple equation for the heritability on the original scale (effective heritability) that is not dependent on the Weibull parameters. The predictions of reliabilities using the proposed formulae in this study are in very good agreement with reliabilities observed from simulations. In general, the estimates of reliability from either the discrete model or the binary data analysis were close to estimates from the Weibull model for a given number of uncensored records in this simplified case of a balanced design. Although selection response from the binary data analysis depends on the end of interval point, there is a relatively good agreement between selection responses in the Weibull model and the binary data analysis. In general, when the underlying survival data is from a Weibull distribution, it appears that the method of analyzing data does not greatly affect the results in terms of sire ranking or response to selection, at least for the simplified context considered in this study.

Animals↗
PubMedDate not supplied

Neuromodulation of decision and response selection.

We present a model for the attentional neuromodulation of decision and selection processes. The model assumes that phasic responses in the brain nucleus Locus Coeruleus modulate, via the transmission of norepinephrine, the synaptic efficiency of neural circuits, at specific (stimulus and task dependent) time intervals. The model is applied first, to a task of perceptual choice, simulating attentional fluctuations and accounting for a series of behavioral and neurophysiological data. Second, the flexibility of information processing, whereby the parameters of the local circuits are modified online, is illustrated in the application of the model to a task of selection from short-term memory.

Animals↗
PubMed2002

Object-selective responses in the human motion area MT/MST.

The perception of moving objects and our successful interaction with them entail that the visual system integrates shape and motion information about objects. However, neuroimaging studies have implicated different human brain regions in the analysis of visual motion (medial temporal cortex; MT/MST) and shape (lateral occipital complex; LOC), consistent with traditional approaches in visual processing that attribute shape and motion processing to anatomically and functionally separable neural mechanisms. Here we demonstrate object-selective fMRI responses (higher responses for intact than for scrambled images of objects) in MT/MST, and especially in a ventral subregion of MT/MST, suggesting that human brain regions involved mainly in the processing of visual motion are also engaged in the analysis of object shape.

Brain Mapping↗
PubMed2005

Inhibitory control and response selection in problem solving: how cotton-top tamarins (Saguinus oedipus) overcome a bias for selecting the larger quantity of food.

When presented with a choice between 1 and 3 pieces of food in a type of reversed contingency task, 4 cotton-top tamarins (Saguinus oedipus) consistently chose the 3 pieces of food and received nothing, even though the choice of 1 piece would have yielded 3. However, in a task in which the tamarins received the 1 piece of food when they chose it, all subjects learned to select 1 over 3. Thus, the tamarins' prior failure on the reversed contingency task did not result entirely from an inherent inability to suppress the prepotent response of reaching to the larger of 2 quantities of food. After the experience of selecting the smaller quantity and receiving it, all of the tamarins solved the version of the reversed contingency task that they failed initially. These results suggest that the tamarins' initial failure may have reflected a difficulty with selecting an alternative response option.

Animals↗
PubMedDate not supplied

Potassium-evoked directionally selective responses from rabbit retinal ganglion cells.

Previous studies have shown that directionally selective (DS) retinal ganglion cells cannot only discriminate the direction of a moving object but they can also discriminate the sequence of two flashes of light at neighboring locations in the visual field: that is, the cells elicit a DS response to both real and apparent motion. This study examines whether a DS response can be elicited in DS ganglion cells by simply stimulating two neighboring areas of the retina with high external K+. Extracellular recordings were made from ON-OFF DS ganglion cells in superfused rabbit retinas, and the responses of these cells to focal applications of 100 mM KCl to the vitreal surface of the retina were measured. All cells produced a burst of spikes (typically lasting 50-200 ms) when a short pulse (10-50 ms duration) of KCl was ejected from the tip of a micropipette that was placed within the cell's receptive field. When KCl was ejected successively from the tips of two micropipettes that were aligned along the preferred-null axis of a cell, sequence-dependent responses were observed. The response to the second micropipette was suppressed when mimicking motion in the cell's null direction, whereas an enhancement during apparent motion in the opposite direction frequently occurred. Sequence discrimination in these cells was eliminated by the GABA antagonist picrotoxin and by the Ca(2+)-channel blocker omega-conotoxin MVIIC, two drugs that are known to abolish directional selectivity in these ganglion cells. The spatiotemporal properties of the K(+)-evoked sequence-dependent responses are described and compared with previous findings on apparent motion responses of ON-OFF DS ganglion cells.

Animals↗
PubMed1984

Response selectivity of neocortical neurons to specific odors in the rabbit.

Odor responses of neocortical neurons in rabbits under light pentobarbital anesthesia were studied in a restricted area in the lateral half of the prefrontal cortex close to the frontal pole. A preevent cumulative sum chart provided a visual display of the change in unit discharge rate following each odor stimulation, and critical levels on each chart provided a visual display of statistical significance. The neocortical neurons studied were activated predominantly by biologically significant odors, such as feces, urine, and dry food. Of those same neurons, 90% failed to respond to pure-chemical odors, and no neurons were found that responded to pure-chemical odors alone. Some neurons responded exclusively to one of the animal-product odors. Some odor-sensitive neurons were affected by electrical stimulation of the mediodorsal thalamic nucleus. Responses to the animal-product odors were observed after ablation of the trigeminal and/or vomeronasal inputs. The responses to these pheromone-like substances are discussed in the context of a central role for odor-sensitive neocortical neurons in cognitive aspects of discrimination of specific odor patterns in the mammals.

Animals↗
PubMed2001

Pre-B cell receptor signaling mediates selective response to IL-7 at the pro-B to pre-B cell transition via an ERK/MAP kinase-dependent pathway.

B lymphocyte development is regulated at multiple checkpoints, mediated by signals originating both inside and outside the cell. Two signaling pathways known to be essential in this process are interleukin-7 (IL-7) and the pre-B cell receptor (pBCR). We have shown previously that these signaling pathways intersect functionally. Specifically, response to low concentrations of IL-7 requires pBCR expression. In this report, we identify the ERK/MAP kinase pathway as a key regulatory component of this response. We propose a molecular mechanism for the selective expansion of pBCR(+) precursors and for the culling of inappropriately rearranged pro-B cells.

Animals↗
PubMed2001

Inspection times, the change task, and the rapid-response selection task.

Three experiments are reported, which are based upon the Wason four-card selection task inspection time paradigm, in which subjects solve computer-presented trials while using a mouse to indicate the card currently under consideration. Evans (1996) had shown that selected cards were inspected for longer than non-selected cards, and this was taken as support for the existence of pre-conscious heuristic processes that direct attention towards relevant aspects of a problem. However, Roberts (1998b) suggested that this inspection time effect is artefactual, due to task format induced biases. Experiment 1 utilized a "change" task: Cards were presented either as selected or not selected, and subjects changed these where necessary. This demonstrated an association between card selection and inspection time independently of one between the act of response and inspection time. Experiment 2 utilized a standard selection task, but subjects either responded within 2 s of each card presentation, or made selections with no time pressure. The curtailment of thinking time increased matching behaviour--more cards matching the terms in the rules were selected--and was replicated in Experiment 3 using a within-subjects design. Overall, the data support Evans' heuristic-analytic framework albeit with some caveats.

Adolescent↗
PubMed1984

Phenothiazines cause a shift in the cAMP dose-response: selection of resistant variants in a murine thymoma line.

Cyclic AMP and glucocorticoid hormones each promote a cytolytic response in the murine lymphoid cell line WEHI-7.1 (W7). The sensitivity to dibutyryl cyclic AMP (dbcAMP), but not dexamethasone, can be enhanced by several psychotropic drugs that have the capacity to interfere with a variety of calcium-regulated functions. We have characterized the response of W7 cells to the phenothiazine trifluoperazine (TFP) and found that TFP concentrations, which decreased the growth rate by twofold, shifted the dose response to dbcAMP approximately tenfold. A similar but smaller shift was seen with the phosphodiesterase inhibitor methylisobutylxanthine (MIX). The effects of TFP and MIX on the dbcAMP response were additive, suggesting that TFP may act to increase the sensitivity of W7 cells to the action of cAMP-dependent protein kinase, and that the increased sensitivity may be due to altered lytic functions coregulated by both cAMP and calcium. The change in the dose response to dbcAMP caused by TFP provided a means of selection to obtain variants that were altered in their capacity to respond to dbcAMP, TFP, or the combination of the two drugs. Eight (out of 36) of the lines that were obtained after a mutagenesis and combined drug selection have been partially characterized. This has revealed the existence of several new phenotypes. Most have an altered response to dbcAMP in the presence of TFP and are likely to represent variants that have not been observed before.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Selective responsiveness of polymodal nociceptors of the rabbit ear to capsaicin, bradykinin and ultra-violet irradiation.

1. The activity of single C- and A-fibre cutaneous sensory units was recorded from the great auricular nerve of anaesthetized rabbits to compare the effects of chemical with other forms of stimulation under several experimental conditions. Chemical agents were delivered by close arterial injection. 2. Small intra-arterial injections of bradykinin (0.2 microgram) and a substantial range of capsaicin doses (2-200 micrograms) consistently activated C polymodal nociceptors without exciting other types of C- or A-fibre cutaneous sense organs. 3. Topical application of xylene to the receptive field of polymodal nociceptors evoked a strong excitation which lasted several minutes. 4. The responses of polymodal nociceptors to mechanical, chemical (bradykinin, xylene) and noxious thermal stimuli were suppressed or abolished after large intra-arterial doses of capsaicin. Capsaicin desensitization of polymodal nociceptors to one kind of stimulation often was not paralleled by similar changes in responsiveness to other stimuli. However, on the average, capsaicin desensitization altered responses to thermal, chemical and mechanical stimuli without afferent selectivity. 5. Background discharge developed in C polymodal nociceptors of the rabbit ear following ultra-violet irradiation sufficient to produce evidence of delayed inflammation. Noxious heat and bradykinin injection (0.2 micrograms) evoked more activity from C polymodal nociceptors in the irradiated ears than from control units.

Action Potentials↗