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Biomedical subjects

R M Klein

Publications and source records attributed to R M Klein.

At least 19 recordsLinked to original sources

A model of saccade initiation based on the competitive integration of exogenous and endogenous signals in the superior colliculus.

Significant advances in cognitive neuroscience can be achieved by combining techniques used to measure behavior and brain activity with neural modeling. Here we apply this approach to the initiation of rapid eye movements (saccades), which are used to redirect the visual axis to targets of interest. It is well known that the superior colliculus (SC) in the midbrain plays a major role in generating saccadic eye movements, and physiological studies have provided important knowledge of the activity pattern of neurons in this structure. Based on the observation that the SC receives localized sensory (exogenous) and voluntary (endogenous) inputs, our model assumes that this information is integrated by dynamic competition across local collicular interactions. The model accounts well for the effects upon saccadic reaction time (SRT) due to removal of fixation, the presence of distractors, execution of pro- versus antisaccades, and variation in target probability, and suggests a possible mechanism for the generation of express saccades. In each of these cases, the activity patterns of "neurons" within the model closely resemble actual cell behavior in the intermediate layer of the SC. The interaction structure we employ is instrumental for producing a physiologically faithful model and results in new insights and hypotheses regarding the neural mechanisms underlying saccade initiation.

Humans↗

Increased chemokine gene expression during aging in the murine brain.

Normal aging results in changes in the brain that contribute to the decline of various functions, including learning and memory. Mechanisms causing this decline have not been clearly established. Activation of microglia is associated with the normal aging process in rodents and primates. Microglial activation is regulated by chemokine gene expression, and activated microglia produce substances that can be detrimental to surrounding cells. In this study we determined whether changes in chemokine expression occur during normal aging in the mouse brain. RNA samples taken from the cortex, midbrain, hippocampus, and cerebellum of 4-, 10-, 21- and 30-month-old C57BL6/DBA2 mice were analyzed for changes in gene expression. RNase protection assays were used to examine a panel of chemokines. Increased expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES occurred in all four regions of the brains in the oldest mice. These increases were first detectable at 21 months of age. Increases in MIP-1alpha, MIP-1beta, and RANTES protein levels were also detected in the brains of old mice, as measured by ELISA. Increased microglial activation in the brains of 30-month-old mice, as detected by immunohistochemistry using F4/80 antibodies, correlated with increases in chemokine expression. The observed increases in chemokine gene expression that occur in conjunction with increased microglial activation suggest that chemokines may contribute to the decreased brain function that occurs during normal aging.

Aging↗

Histomorphological studies of the distal internal thoracic artery which support its use for coronary artery bypass grafting.

The use of the internal thoracic artery (ITA) for myocardial revascularization in coronary artery disease increased because of its relative immunity to atherosclerotic obstruction. This study investigated the distal part of the vessel, the region of anastomosis by means of histology to focus the visualization of this region of interest. The histological examination of arterial segments showed minor intimal thickening in 48 out of 100 patients. Twelve patients demonstrated a severe intimal thickening, the residual patients were without any changes. In 52% the elastic type dominated in the distal part. Hybrid and muscular patterns were found in 22 and 26%, respectively. The media could be classified into three different types: muscular, hybrid and elastic type. There was no correlation concerning the different histological type and the incidence of intimal thickening. No evidence whatsoever of atherosclerotic lesion was encountered in any of the investigated vessels. There is no limitation in the use of the distal part of the ITA for coronary artery revascularization.

Arteriosclerosis↗

A review of the evidence for a disengage deficit following parietal lobe damage.

We review the literature on response times to ipsilesional and contralesional targets following spatial precues in patients with damage involving the left- and right-parietal lobes with the aim of appraising the 'disengage deficit' reported initially by Posner and colleagues (Posner MI, Cohen A, Rafal RD. Neural systems control of spatial orienting. Proceedings of the Royal Society of London, B 1982;298:187-98). The data of individual subjects from a sub-sample of studies were submitted to analyses of variance, and data from all studies meeting our selection criteria were submitted to meta-analytic procedures (Hunter JE, Schmidt FL. Methods of meta-analysis: correcting error and bias in research. Newberg Park: Sagge Publications, 1990). Findings from both types of analysis conducted on data from patients with right-hemisphere lesions indicate that: (1) the disengage deficit phenomenon is robust following peripheral cues, but not following central cues; (2) the disengage deficit is large at shorter cue-target stimulus onset asynchronies (SOAs), and decreases as SOA increases; (3) the disengage deficit is larger in patients with a diagnosis of hemispatial neglect; and (4) although the magnitude of the disengage deficit appears to increase with increases in lesion size, multilobar vs unilobar involvement did not significantly alter the pattern of the disengage deficit. We also show that responses to validly cued targets in the contralesional hemispace were significantly slower than for validly cued targets in ipsilesional hemispace. Similar, but usually smaller, effects were observed in patients with homologous left-hemisphere damage. The implications of these results for current models of the role of the parietal lobes in attentional orienting are discussed.

Animals↗

Morphological differences of the internal thoracic artery in patients with and without coronary artery disease--evaluation by duplex-scanning.

OBJECTIVE: The internal thoracic artery is an established arterial graft for myocardial revascularisation, especially of the left anterior descending artery because of a higher patency rate compared to venous grafts. It has never been investigated, whether there are morphological differences in this vessel between patients with or without coronary artery disease or if they are comparable to morphological changes in the common carotid artery. METHODS: We investigated the internal thoracic artery and the common carotid artery of 24 patients (12 with coronary artery disease, 12 without coronary artery disease) with an ultrasonic system on both sides. The intima-media thickness and the diameter of both vessels were estimated. RESULTS: The intima-media-thickness of the internal thoracic artery was comparable in all patients, independent of the presence of a coronary artery disease (0.51+/-0.11 mm with coronary artery disease, 0.50+/-0.17 mm without coronary artery disease, P>0.05). Compared with this the intima-media-thickness of the common carotid artery was thicker in patients with coronary artery disease (0.84+/-0.13 mm with coronary artery disease, 0.73+/-0.07 mm without coronary artery disease, P< or or =0.014). There was no correlation between the thickness of the internal thoracic artery and the common carotid artery (r=0.018, P>0.05). CONCLUSIONS: It could be demonstrated for the first with non-invasive ultrasound, that the intima-media-complex of the internal thoracic artery is protected of the influence of arteriosclerosis. There are no morphological differences like the intima-media-thickness of the common carotid artery. The proven protective mechanism underlines the widespread use of the internal thoracic artery as a coronary artery bypass graft.

Aged↗

Manipulations of the features of standard video lottery terminal (VLT) games: effects in pathological and non-pathological gamblers.

The present study was conducted to identify game parameters that would reduce the risk of abuse of video lottery terminals (VLTs) by pathological gamblers, while exerting minimal effects on the behavior of non-pathological gamblers. Three manipulations of standard VLT game features were explored. Participants were exposed to: a counter which displayed a running total of money spent; a VLT spinning reels game where participants could no longer "stop" the reels by touching the screen; and sensory feature manipulations. In control conditions, participants were exposed to standard settings for either a spinning reels or a video poker game. Dependent variables were self-ratings of reactions to each set of parameters. A set of 2(3) x 2 x 2 (game manipulation [experimental condition(s) vs. control condition] x game [spinning reels vs. video poker] x gambler status [pathological vs. non-pathological]) repeated measures ANOVAs were conducted on all dependent variables. The findings suggest that the sensory manipulations (i.e., fast speed/sound or slow speed/no sound manipulations) produced the most robust reaction differences. Before advocating harm reduction policies such as lowering sensory features of VLT games to reduce potential harm to pathological gamblers, it is important to replicate findings in a more naturalistic setting, such as a real bar.

Adult↗

Influence of parafoveal processing on the missing-letter effect.

According to the parafoveal-processing hypothesis, letters are more often missed in function words than in content words because the former are more likely to be identified in the parafovea, where letter processing is not available. Contrary to previous demonstrations, more omissions occurred in function words than in content words when parafoveal processing was not available because words were displayed in column format, text was read through a 5-letter window, or words were presented 1 at a time on a computer screen. In all experiments, impeding parafoveal processing decreased omission rates for function but not for content words. In the last experiment, direct monitoring of eye movements revealed that, for both fixated and skipped words, letters in function words are missed more often than content words. These results are best interpreted within a model including the structural precedence hypothesis and stressing the importance of visual factors.

Analysis of Variance↗

Multisensory prior entry.

Despite 2 centuries of research, the question of whether attending to a sensory modality speeds the perception of stimuli in that modality has yet to be resolved. The authors highlight weaknesses inherent in this previous research and report the results of 4 experiments in which a novel methodology was used to investigate the effects on temporal order judgments (TOJs) of attending to a particular sensory modality or spatial location. Participants were presented with pairs of visual and tactile stimuli from the left and/or right at varying stimulus onset asynchronies and were required to make unspeeded TOJs regarding which stimulus appeared first. The results provide the strongest evidence to date for the existence of multisensory prior entry and support previous claims for attentional biases toward the visual modality and toward the right side of space. These findings have important implications for studies in many areas of human and animal cognition.

Adolescent↗

Negative priming for spatial location?

The term negative priming has been used to describe the deleterious consequences for performance when the current target shares properties with an ignored distractor from the previous trial. Location-based negative priming was first reported by Tipper, Brehaut, and Driver (1990) who used a prime-probe procedure wherein the task was to localize targets defined by their identity (shape). Design imbalances in this seminal study, and others, are illustrated and it is indicated how these might have contaminated the reported effects. The findings, from three experiments using an unbiased design, suggest that negative priming in the spatial location procedure may be more closely related to inhibition of return (IOR), or to the automatic attraction of attention by new objects, than to the concepts of distractor inhibition, episodic retrieval, and feature mismatch, which have traditionally been used to explain negative priming for spatial location.

Adult↗

Modulation of the attentional blink by differential resource allocation.

When one masked target (T2) follows another (T1) in close temporal proximity, identification accuracy of the second target is reduced for a period referred to as the attentional blink. Analysis of the attentional blink literature suggests that increasing the difficulty of T1 processing increases the magnitude of the blink. In a previous study that eliminated several untoward features of the typical attentional blink design (e.g., task switching, location switching, and stream contribution), we found no effect on blink magnitude when three levels of T1 difficulty (manipulated in a data-limited manner) were randomly intermixed. Here, when we repeated the previous study using a blocked manipulation of T1 difficulty, which is characteristic of the literature, a significant positive relation between T1 difficulty and blink magnitude was found. Resource allocation put in place to encode T1 in advance of a dual-target trial thus seems to be the critical factor in mediating this relation.

Attention↗

The attentional blink is immune to masking-induced data limits.

The attentional blink is the robust finding that processing a masked item (T1) hinders the subsequent identification of a backwards masked second item (T2), which follows soon after the first one. There has been some debate about the theoretically important relation between the difficulty of T1 processing and the ensuing blink. In Experiment 1 we manipulated the difficulty of T1 in such a way as to affect the quality of data without altering the amount of resources allocated to its identification. We found no relation between the accuracy of T1 identification and the blink. In Experiment 2, the same difficulty manipulation was applied to T2, and we observed an additive pattern with the blink. Together, this pattern of results indicates that a data-limited difficulty manipulation does not affect the blink, whether applied to T1 or T2. In Experiment 3 we used an individual differences methodology to show that performance in the traditional "stream"-like presentation (rapid serial visual presentation) was highly correlated with performance in our modified "target mask, target mask" paradigm, thus allowing for comparisons beyond the present methodology to much of the previous literature that has used the stream paradigm.

Adult↗

Visual prior entry.

It has long been claimed that attended stimuli are perceived prior to unattended stimuli--doctrine of prior entry. Most, if not all, studies on which such claims have been based, however, are open to a nonattentional interpretation involving response bias, leading some researchers to assert that prior entry may not exist. Given this controversy, we introduce a novel methodology to minimize the effect of response bias by manipulating attention and response demands in orthogonal dimensions. Attention was oriented to the left or right (ie., spatially), but instead of reporting on the basis of location, observers reported the order (first or second) of vertical versus horizontal line segments. Although second-order response biases were demonstrated, effects of attention in accordance with the law of prior entry were clearly obtained following both exogenous and endogenous attentional cuing.

Adult↗

Atrial natriuretic peptide-like immunoreactivity in neurons and astrocytes of human cerebellum and inferior olivary complex.

Atrial natriuretic peptide (ANP) has previously been localized in areas of mammalian brain associated with olfaction, cardiovascular function, and fluid/electrolyte homeostasis. Despite the presence of several types of natriuretic peptide receptors in mammalian cerebellum, neither intrinsic nor extrinsic sources of the natriuretic peptides have been described. In this report we describe the immunohistochemical localization of both intrinsic and extrinsic sources for ANP in human cerebellum. ANP-like immunoreactivity (ANP-LIR) was observed in climbing fibers in the cerebellar molecular layer that probably originated from isolated immunopositive neurons of the inferior olivary complex. Intrinsic sources of ANP-LIR included small subpopulations of protoplasmic and fibrous astrocytes and Bergmann glia, as well as Golgi and Lugaro neurons of the granule cell layer. These results suggest that, in addition to its presumptive roles in local vasoregulation, ANP may serve as a modulator of the activity of Purkinje neurons.

Astrocytes↗

Estrogen and tamoxifen interplay with T(3) in male rats: pharmacologically distinct classes of estrogen responses affecting growth, bone, and lipid metabolism, and their relation to serum GH and IGF-I.

Estrogen (E) and T(3) regulate gene expression by receptor mechanisms that may enable hormonal interplay affecting growth and metabolism. Prior studies of E and tamoxifen (TM) interplay with T(3) in female rats identified a subset of E responses that required T(3) for expression and exhibited large agonist responses to TM. In contrast, TM acted more like an antagonist in most T(3)-independent E responses. This study used male rats to further explore the role of T(3) in E effects on growth and metabolism, and the relation of such effects to changes in serum GH and IGF-I. Orchidectomized, hypothyroid rats were treated 6 wk with vehicle, E2 benzoate (E2B), or TM with or without T(3). The following parameters were measured: body weight change; tibia length and bone mineral density; heart and kidney weight; food intake and body temperature; serum levels of glucose, cholesterol, triglycerides, GH, and IGF-I; seminal vesicle weight; and anterior pituitary levels of GH, PRL, glandular kallikrein, and total protein. Interplay with T(3) contributed to multiple E effects on growth and metabolism, and some E responses involved both T(3)-dependent and T(3)-independent components. Both E2B and TM increased serum GH, but the increases were poorly coupled to IGF-I. Correlation/regression analysis of individual rat data sets suggested distinct roles for GH and IGF-I in specific E effects. E2B and TM effects on somatic growth exhibited positive correlations with IGF-I and negative correlations with GH; effects on bone mineral density and triglycerides exhibited positive correlations with GH and negative correlations with IGF-I. Three pharmacologically distinct classes of in vivo E responses were identified in this study, and TM displayed a profile of biological activity that may be useful for men undergoing androgen-deprivation therapy.

Animals↗

The presence of a nonresponding effector increases inhibition of return.

Inhibition of return (IOR) refers to the performance disadvantage for targets presented at an exogenously cued location, relative to an uncued location, at relatively long cue-target onset asynchronies. In this experiment, we investigated the influence on IOR of a nonresponding effector (i.e., the index finger of the nonresponding hand) placed on a response key in a simple-RT task. With peripheral cues and targets, IOR and spatial stimulus-response compatibility effects were larger when the nonresponding hand was placed on a response key. IOR--the slowed responding to go signals at the cued location--was accompanied by a lower false alarm rate when no-go signals were presented there. These findings provide direct evidence for a motoric component to IOR wherein some portion of the inhibition is observed as a criterion shift against responding to the cued location.

Adult↗

Combined expectancies: event-related potentials reveal the early benefits of spatial attention that are obscured by reaction time measures.

Visual spatial attention has been likened to a "spotlight" that selectively facilitates the perceptual processing of events at covertly attended locations. However, if participants have advance knowledge of the likely location of an impending target and the likely response it will require, facilitation in response performance does not occur for targets at the expected (or attended) location that require an unexpected response. Event-related potentials (ERPs) were recorded during a discrimination task in which the most likely target location and target response were simultaneously cued prior to target onset. The ERPs showed evidence of enhanced perceptual-level processing for all targets at attended locations. These results suggest that the lack of response facilitation for unexpected targets at attended locations is likely due to postperceptual processes that are activated by the inclusion of nonspatial stimulus expectancies, response expectancies, or both.

Adult↗