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PubMed2000

[EEG synchronization index spectrum: definition, calculation and the changes related to visual selective response].

OBJECTIVE: EEG synchronization is usually estimated in terms of coherence amplitude, but the estimation is with apparent uncertainty because of the poor resolution both in time and frequency. The purpose of this work is to surmount this problem. METHOD: A new definition of EEG synchronization index spectrum [SynI(f)] was developed basing on the distribution characteristics of EEG coherence phase which was calculated by a tested algorithm with 1 s and 1 Hz resolution. The basic feature and its changes during visual selective responses were calculated in 25 normal subjects. EEG signals were recorded from 9 locations in two conditions: looking at the central LED only(VC) and making switch response to the target LED flash signals (T) differentially (DR): switch to left or right for Ts from left (LVF) or right (RVF) visual field, repectively but making no response to the non-target ones (NT). RESULT: (1) The frequency dependency of SynI varied with brain location, e.g., SynI was higher in alpha range than others at frontal locations but the situation reversed at posterior locations. (2) The SynIs between midline and right brain locations were higher than that between mid line and left ones. (3) As compared with VC, SynI was increased in DR condition at central and posterior brain locations but not frontal ones, it happened mainly in 7-23 Hz at central locations but in 1-4 Hz at posterior ones. (4) The augmentation of SynI in DR was greater for T than for NT signals. CONCLUSION: The results indicated that the SynI(f) was meaningful for studying the frequency-spatial feature of EEG synchronization change among brain locations related to cognitive activities.

Aerospace Medicine↗
PubMed2002

Potentiation of radioimmunotherapy with response-selective peptide agonist of human C5a.

UNLABELLED: Physiologic barriers to the delivery of macromolecules to solid tumors are a major obstacle to the clinical success of radioimmunotherapy (RIT). Only a small fraction of the injected dose of the radiolabeled monoclonal antibody (mAb) localizes at the tumor site. This situation worsens as the tumor burden increases. It is hypothesized that improvements to RIT of adenocarcinoma can be realized by inclusion of vasoactive agents, in particular agents able to increase the vascular permeability of tumor capillaries. In these studies, a response-selective peptide agonist of human C5a, GCGYSFKPMPLaR (AP), was used to transiently increase tumor vascular permeability in an effort to improve RIT of solid tumors. METHODS: Athymic mice xenografted with human colorectal adenocarcinoma LS174T were treated intravenously with low doses (9.25 MBq) of 131I-labeled mAb B72.3 in combination with various intravenous doses of AP. The progression of the disease or the loss of >20% body weight was taken as the endpoint. Biodistribution and tumor uptake kinetics were studied in the same tumor-antibody system. RESULTS: The uptake of 125I-B72.3 in LS174T xenografts increased in a dose-dependent manner with an apparent maximal effect between 3 and 6 h after intravenous administration of AP. Augmenting the dose of 9.25 MBq 131I-B72.3 with a single administration of 0.1 mg AP delayed tumor growth nearly 2-fold; the tumor quadrupling time (T(q)) was 14.2 +/- 3.3 d for 131I-B72.3 alone versus 26.0 +/- 3.6 d for 131I-B72.3 plus 0.1 mg AP (P < 0.001). An additional dose of 0.1 mg AP 24 h after 131I-B72.3 further improved the therapeutic outcome (T(q) = 48.5 +/- 7.9 d; P < 0.001) and resulted in several cases of tumor regression. CONCLUSION: The inclusion of agonist peptides of human C5a in the RIT scheme results in improved tumor responses without any manifest side effects.

Adenocarcinoma↗
PubMed2004

Neurocognitive mechanisms of cognitive control: the role of prefrontal cortex in action selection, response inhibition, performance monitoring, and reward-based learning.

Convergent evidence highlights the differential contributions of various regions of the prefrontal cortex in the service of cognitive control, but little is understood about how the brain determines and communicates the need to recruit cognitive control, and how such signals instigate the implementation of appropriate performance adjustments. Here we review recent progress from cognitive neuroscience in examining some of the main constituent processes of cognitive control as involved in dynamic decision making: goal-directed action selection, response activation and inhibition, performance monitoring, and reward-based learning. Medial frontal cortex is found to be involved in performance monitoring: evaluating outcome vis-a-vis expectancy, and detecting performance errors or conflicting response tendencies. Lateral and orbitofrontal divisions of prefrontal cortex are involved in subsequently implementing appropriate adjustments.

Animals↗
PubMed1984

Neurons in the cortex of the temporal lobe and in the amygdala of the monkey with responses selective for faces.

There are populations of neurons in the temporal lobe of the macaque which appear to be specialised to respond to faces. These neurons are relatively rare in the inferior temporal visual cortex, area TE, but are more common in the cortex in the middle and anterior parts of the superior temporal sulcus. In some cases these neurons can respond to parts of faces such as the eyes, and in other cases a fuller complement of the features present in faces, with even the correct configuration of these features, appears to be necessary for these neurons to respond. In experiments to investigate whether the responses of these neurons would be useful for recognition of an individual, it has been shown that in many cases (77% of one sample), these neurons are sensitive to differences between faces. In experiments designed to investigate the information required for these neurons to respond, it has been shown that these neurons can respond to blurred images of faces, and to faces with only the high spatial frequencies included. A population of neurons with face-selective responses has also been found in the amygdala, which receives inputs from the temporal lobe visual cortex. In many cases these neurons respond differently to different faces. It is suggested that the importance of this type of neuron may be in the different emotional and social responses which occur to different faces, and which are disrupted by damage to the amygdala.

Amygdala↗
PubMed2005

Postcentral neurons with covert receptive fields in conscious macaque monkeys: their selective responsiveness to simultaneous two-point stimuli applied to discrete oral portions.

The representation of the oral structures in the postcentral somatosensory cortex was studied in conscious macaque monkeys by recording the activity of single neurons. A total of 2,807 neurons were isolated in the oral regions of three hemispheres in two animals. Of these, 375 neurons (area 3a, 3; area 3b, 123; area 1, 99; area 2, 150) lacked an apparent receptive field (RF), and their relative frequency was significantly higher in area 2 (19%) than in more rostral areas (area 3a, 8%; area 3b, 10%; area 1, 12%). We tested the responsiveness of these neurons to stimuli applied simultaneously to two discrete, but functionally related, oral structures (interstructural two-point stimuli: iTPS). Neurons in areas 3a, 3b, and 1 that lacked an apparent RF were not responsive to iTPS. However, 35 neurons in area 2 responded stably to iTPS applied to either of the following sets of oral structures: the tongue and incisors (n=18), incisors and lip (n=9), lip and tongue (n=12), or upper and lower lips (n=8). Of them, 19 neurons were activated during self-movements such as tongue protrusion, lip licking, and food manipulation. The neurons selectively responsive to iTPS might detect converging inputs from different oral structures and play a pivotal role in detecting objects straddling different oral structures and the mutual contact of oral structures.

Action Potentials↗
PubMed2002

Transgenic overexpression of amphiregulin induces a mitogenic response selectively in pancreatic duct cells.

BACKGROUND & AIMS: The epidermal growth factor (EGF) receptor family and the corresponding ligands are frequently overexpressed in pancreatic cancer. To compare the biological effects of transforming growth factor (TGF)-alpha and amphiregulin (AR) on growth and differentiation of the exocrine pancreas, we have generated transgenic mice overexpressing AR under control of the elastase promoter. METHODS: Two independently generated transgenic mouse lines overexpress 50-, 43-, 28-, 26-, and 16-kilodalton AR forms in the pancreas. RESULTS: Morphologic and immunohistochemical examinations suggest that small intralobular duct and centro-acinar cells proliferate in response to AR in these mice. AR transgenic mice display increased Ras, Erk1/2, cyclin D/CDK4, and cyclin E/CDK2 activity and G1/S progression in pancreatic duct cells. In contrast to TGF-alpha transgenic mice, AR neither induced tubular complex formation nor elicited a strong fibrogenic response. AR induced a slight induction of ErbB2 on duct cells, whereas TGF-alpha resulted in overexpression of the EGF receptor in cells within tubular complexes. Furthermore, AR and TGF-alpha displayed different effects on differentiation of isolated acini in vitro comparable to the situation in vivo. CONCLUSIONS: These data suggest that AR induces a mitogenic response selectively in small duct cells through activation of Ras, CDK2, and CDK4, respectively. The closely related EGF receptor ligands, AR and TGF-alpha, display different biological effects when overexpressed in the exocrine pancreas in vivo.

Amphiregulin↗
PubMed1988

Developmental changes in attentional skills: the effect of irrelevant variations on encoding and response selection.

The present experiments examine how irrelevant variations within a stimulus set interfere with performance in a selective attention task. Second graders, fifth graders, and adults were administered a discrete trial version of a selective attention task in which they were required to search for an object that matched the prime on the targeted dimension. The stimuli in the first experiment were constructed from spatially integrated dimensions whereas the second experiment used spatially separated dimensions. The results indicated that while the spatially separated dimensions were perceived independently by all age groups, developmental differences in perceived structure were evident with the spatially integrated dimensions. Problems associated with response selection were a major source of interference with both types of stimuli, but the severity of the interference varied with the age of the perceiver and the nature of the stimuli. The developmental implications of these findings were considered.

Adult↗
PubMed2003

Neural coding of "attention for action" and "response selection" in primate anterior cingulate cortex.

Noninvasive imaging techniques showed that the anterior cingulate cortex is related to higher-order cognitive and motor-related functions in humans. To elucidate the cellular mechanism of such cingulate functions, single-unit activity was recorded from three cingulate motor areas of macaque monkeys performing delayed conditional Go/No-go discrimination tasks using spatial (location) and nonspatial (color) visual cues. Unlike prefrontal neurons, only a few neurons coded the visual information on individual features (e.g., "left" or "red") in all of the rostral (CMAr), dorsal (CMAd), and ventral (CMAv) cingulate motor areas. Instead, many neurons in the CMAr exhibited the attention-like activity anticipating the second (conditioned) visual cues, with the specificity to visual category ("location" or "color"). In addition, there were a number of CMAr neurons specific to motor response (Go or No-go) in relation to the second visual cues. Some of the visual category-specific neurons in the CMAr further displayed the motor response-specific activity. On the other hand, many of the task-related CMAd and CMAv neurons seemed to be implicated directly in motor functions, such as preparation and execution of movements in Go trials. The present results suggest that the CMAr neurons may participate in cognitive and motor functions of "attention for action" and "response selection" for an appropriate action according to an intention, whereas the CMAd and CMAv neurons may be involved in "motor preparation and execution".

Animals↗
PubMed1995

Nicotinic and muscarinic receptors in the rat prefrontal cortex: differential roles in working memory, response selection and effortful processing.

The aim of the present study was to evaluate the effects of cholinergic receptor blockade in the rat prefrontal cortex on cognitive processes. The nicotinic antagonists neuronal bungarotoxin and dihydro-beta-erythroidine and the muscarinic antagonist scopolamine were injected into the prelimbic area of the prefrontal cortex. Their behavioural effects were assessed in a T-maze to test reference memory (visual discrimination task) and working memory in delayed matching (MTS) and non-matching to sample (NMTS) tasks. Neuronal bungarotoxin produced a significant decrease in working memory performance in the MTS task but not in the NMTS task. In contrast, scopolamine impaired working memory in both MTS and NMTS tasks. Reference memory was not altered by any of the cholinergic antagonists. These results demonstrate a differential role of nicotinic and muscarinic receptors in the rat prefrontal cortex. Nicotinic transmission appears to be important in delayed response tasks requiring effortful processing for response selection, while the muscarinic system is involved in general working memory processes.

Acetylcholine↗
PubMed1994

Working memory, response selection, and effortful processing in rats with medial prefrontal lesions.

This study examined the effects of lesions of the prelimbic area of the rat prefrontal cortex on acquisition and retention of nonmatching (NMTS) and matching-to-sample (MTS) tasks. Both tasks involved a reference and a working memory component, but only working memory was impaired by the lesions. A comparison of the 2 tasks revealed quantitatively similar deficits in postoperatively trained rats. In preoperatively trained rats, however, the deficits were more important in the MTS task than in the NMTS task. In addition, an effect of interference between successive trials was observed in the NMTS task but not in the MTS task. Perseverative tendencies were observed in the MTS task only. These results suggest that prefrontal lesions induce working memory deficits as a result of poor temporal encoding and increased susceptibility to interference and impair effortful processing, such as that engaged in response selection mechanisms.

Animals↗
PubMed2002

Bimanual cross-talk during reaching movements is primarily related to response selection, not the specification of motor parameters.

Simultaneous reaching movements made with the two hands can show a considerable increase in reaction time (RT) when they differ in terms of direction or extent, compared to when the movements involve the same direction and extent. This cost has been attributed to cross-talk in the specification of the motor parameters for the two hands. However, a recent study [Diedrichsen, Hazeltine, Kennerley, & Ivry, (2001). Psychological Science, 12, 493-498] indicates that when reaching movements are cued by the onset of the target endpoint, no compatibility effects are observed. To determine why directly cued movements are immune from interference, we varied the stimulus onset asynchrony for the two movements and used different combinations of directly cued and symbolically cued movements. In two experiments, compatibility effects were only observed when both movements were symbolically cued. No difference was found between compatible and incompatible movements when both movements were directly cued or when one was directly cued and the other was symbolically cued. These results indicate that interference is not related to the specification of movement parameters but instead emerges from processes associated with response selection. Moreover, the data suggest that cross-talk, when present, primarily shortens the RT of the second movement on compatible trials rather than lengthening this RT on incompatible trials.

Analysis of Variance↗
PubMed2005

The Corridor Task: a simple test of lateralised response selection sensitive to unilateral dopamine deafferentation and graft-derived dopamine replacement in the striatum.

In this experiment, we report a novel drug-free behavioural test of lateralised neglect which is sensitive to unilateral dopamine-denervating lesions and subsequent graft-derived striatal dopamine replacement. For the task, white plastic lids containing sugar pellets were placed along the left and right sides of the floor of a long narrow corridor at regular intervals. Hungry female Sprague-Dawley rats were placed individually into the corridor where they were allowed to make up to 20 pellet retrievals. The number of retrievals each rat made from its left and right sides was counted. Complete mesencephalic or partial nigrostriatal lesions were induced by injection of 6-hydroxydopamine into the medial forebrain bundle or striatum, respectively. Both lesions induced a pronounced ipsilateral retrieval bias in the task. Five weeks after lesion surgery, half of the rats from each lesion group were given E14 ventral mesencephalic cell suspension transplants into the denervated striatum, and were then re-tested in the Corridor Task 5 and 10 weeks later. There was no amelioration of the side bias in rats with medial forebrain bundle lesions. In contrast, in nigrostriatal-lesioned rats, the graft significantly reduced the lesion-induced ipsilateral bias. We conclude that the Corridor Task is a sensitive test of lateralised sensorimotor response selection, and is suitable for assessing deficits and recovery associated with lesions and grafts within the nigrostriatal system.

Animals↗
PubMed2005

Selective responsiveness to common gamma chain cytokines in peripheral blood-derived cytotoxic T lymphocytes induced by Melan-A/MART-1(27-35)targeted active specific immunotherapy.

We have comparatively evaluated the proliferative response of CTL induced in metastatic melanoma patients upon immunization against Melan-A/MART-1(27-35) tumor associated antigen (TAA) to IL-2, IL-7 or IL-15 cytokines, sharing a receptor common gamma-chain (c gamma-c cytokines). Twenty-eight CTL clones were generated from CD8+ T cells obtained from 3 patients during the contraction phase of immune response following a successful vaccine mediated expansion of specific effectors. All clones were able to kill tumor cell lines expressing HLA-A0201 and Melan-A/MART-1, and displayed phenotypic characteristics of effector/memory (CD45RA-/CCR7-) or CD45RA+/CCR7- effector cells in intermediate to late developmental stage (CD28-/CD276+/-) CTL. Proliferative responses could be elicited or enhanced by IL-2 and IL-15, but not IL-7, in the absence or in the presence of T-cell receptor (TCR) triggering, respectively. Accordingly, only IL-2 and IL-15 were able to promote the survival of the CTL clones under investigation. While all clones expressed high amounts of receptor c gamma-c (CD132), lower, but detectable, expression of IL-7 receptor alpha chain was also observed. CD8+ cells from one of the patients treated were obtained 6 months after the last vaccine boost and were cultured in the presence of Melan-A/MART-1(27-35) and each of the 3 cytokines under investigation. Consistent with data from CTL clones, expansion of Melan-A/MART-1(27-35) tetramer positive cells was only observed in the presence of IL-2 or IL-15 but not IL-7. Instead, when CD8+ cells from the same patient were sampled shortly (14 days) after an additional vaccination only IL-2 was able to promote the expansion of Melan-A/MART-1(27-35) tetramer positive cells. Taken together these data suggest a selective responsiveness of TAA-specific CTL to different c gamma-c cytokines.

Antigens, Neoplasm↗
PubMed2003

Genetic architecture of a selection response in Arabidopsis thaliana.

Quantitative trait locus (QTL) mapping has become an established and effective method for studying the genetic architecture of complex traits. In this report, we use a QTL mapping approach in combination with data from a large selection experiment in Arabidopsis thaliana to explore a response to selection of experimental populations with differentiated genetic backgrounds. Experimental populations with genetic backgrounds derived from ecotypes Landsberg and Niederzenz were exposed to multiple generations of fertility and viability selection. This selection resulted in phenotypic shifts in a number of life-history and fitness-related characters including early development time, flowering time, dry biomass, longevity, and fruit production. Quantitative trait loci were mapped for these traits and their positions were compared to previously characterized allele frequency changes in the experimental populations (Ungerer et al. 2003). Quantitative trait locus positions largely colocalized with genomic regions under strong and consistent selection in populations with differentiated genetic backgrounds, suggesting that alleles for these traits were selected similarly in differentiated genetic backgrounds. However, one QTL region exhibited a more variable response; being positively selected on one genetic background but apparently neutral in another. This study demonstrates how QTL mapping approaches can be combined with map-based population genetic data to study how selection acts on standing genetic variation in populations.

Analysis of Variance↗
PubMed1984

Tissue response selectivity of calcium antagonists is not due to heterogeneity of [3H]-nitrendipine binding sites.

[3H]-nitrendipine binding data and isolated tissue response for five calcium antagonists were evaluated in rabbit myocardium and aorta. The [3H]-nitrendipine binding site was qualitatively identical in myocardium and aorta, as the [3H]-nitrendipine KD, KIS for nicardipine and nifedipine and interactions with verapamil, D600 and diltiazem were not different in aortic and cardiac membranes prepared by similar means. In contrast, the inhibition of the Ca2+-induced contractile response in right ventricular myocardium and aortic ring segments indicated a greater than 10,000 fold selectivity of nicardipine for antagonism of vascular responses. This resulted in a different order of potency for calcium antagonist interaction with the [3H]-nitrendipine binding site in cardiac membranes (nicardipine greater than nifedipine greater than D600 greater than verapamil greater than diltiazem) as compared to antagonism of myocardial tissue response (D600 greater than verapamil greater than or equal to nifedipine greater than nicardipine greater than or equal to diltiazem). In heart the difference between the potency of nicardipine in binding experiments and tissue response approached 4 orders of magnitude. We conclude that tissue response selectivity of calcium antagonists is not explained by heterogeneity of [3H]-nitrendipine binding sites.

Animals↗
PubMed1992

Prediction of selection response for threshold dichotomous traits.

This paper presents a formula to predict expected response to one generation of truncation selection for a dichotomous trait under polygenic additive inheritance. The derivation relies on the threshold liability concept and on the normality assumption of the joint distribution of additive genetic values and their predictors used as selection criteria. This formula accounts for asymmetry of response when both the prevalence of the trait and the selection rate differ from 1/2 via a bivariate normal integral term. The relationship with the classical formula R = iota rho sigma G is explained with a Taylor expansion about a zero value of the correlation factor. Properties are illustrated with an example of sire selection based on progeny test performance which shows a departure from usual predictions up to 15-20% at low (0.05) or high (0.95) selection rates. Univariate approximations and extensions to several paths of genetic change are also discussed.

Animals↗
PubMed1972

Long-term selection response for 12-day litter weight in mice.

Long-term selection for increased 12-day litter weight in two replicate lines (W(2), W(3)) of mice resulted in an apparent selection limit at about 17 generations. Quadratic polynomial and exponential models were fitted to the data in order to estimate the plateaued response and half-life of the selection process. Using the polynomial results, the half-life estimates were 4.5 and 8.6 generations for W(2) and W(3), respectively. The plateaued responses were 5.1 and 5.8 g which, when expressed in phenotypic standard deviation units, became 1.1 and 1.3. The exponential model provides similar estimates. A negative association between 12-day litter weight and fitness was not considered to be an adequate explanation for the plateau since there was no decrease in fertility of the selected lines. Evidence that exhaustion of genetic variability was not the cause of the plateau came from the immediate response to reverse selection. It was proposed that the plateau may be due to a negative genetic correlation between direct and maternal genetic effects, which would be expected to occur after many generations of selection. There were positive correlated responses in both replicates for adult body weight, which was in agreement with the positive genetic correlation between preweaning and postweaning body weight. The expected positive correlated response for number born was realized in only one of the replicates.

Animals↗
PubMed1998

Necessity of acetylcholine for retinal directionally selective responses to drifting gratings in rabbit.

1. A model for retinal directional selectivity postulates that GABAergic inhibition of responses to motions in the null (anti-preferred) direction underlies this selectivity. An alternative model postulates that besides this inhibition, there exists an asymmetric, nicotinic acetylcholine (ACh) input from starburst amacrine cells. It is possible for the latter but not the former model that stimuli could exist such that nicotinic blockade eliminates directional selectivity. Such stimuli would drive the cholinergic but not the GABAergic system well. 2. So far, attempts to eliminate directional selectivity with nicotinic blockade have failed, but they always used isolated, moving bars as the stimulus. We confirmed this failure for On-Off directionally selective (DS) ganglion cells in our preparation of the rabbit's retina. 3. However, while recording from these cells, we discovered that nicotinic blockade eliminated directional selectivity to drifting, low spatial frequency sine- and square-wave gratings. 4. This effect was not just due to the smallness of the responses under nicotinic blockade. NMDA blockade caused even smaller responses, but no loss of directional selectivity. 5. This result is consistent with a two-asymmetric-pathways model of directional selectivity, but inconsistent with an asymmetric-GABA-only model. 6. We conclude that asymmetric nicotinic inputs extend the range of stimuli that can elicit directional selectivity to include moving textures, that is, those with multiple peaks in their spatial luminance profile.

Acetylcholine↗