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Biomedical subjects

E E Smith

Publications and source records attributed to E E Smith.

At least 55 records · Page 3Linked to original sources

Toxicological evaluations of cyclopiazonic acid and ochratoxin A in broilers.

The individual and combined effects of ochratoxin A (OA) and cyclopiazonic acid (CPA) were evaluated in Petersen x Hubbard broiler chickens from 1 d to 3 wk of age. The experimental design was a 2 x 2 factorial with treatments of 0 and 2.5 mg OA/kg feed and 0 and 34 mg CPA/kg feed. Production performance, serum biochemistry, and gross pathological observations were evaluated. Body weight gain was reduced (P < 0.05) by OA, CPA, and OA-CPA in combination at the end of 3 wk. Ochratoxin A significantly increased the relative weight of the kidney and serum concentrations of uric acid and triglycerides and decreased total protein, albumin, and cholesterol. The toxicity of CPA was expressed primarily through increased relative weights of the proventriculus and increased activity of creatine kinase. Exposure to OA-CPA was characterized by increased relative weights of the liver, kidney, pancreas, and proventriculus; decreased concentrations of serum albumin, total protein, and cholesterol; increased activity of creatine kinase; and increased concentrations of triglycerides and uric acid. Postmortem examination revealed that the chickens fed CPA or OA-CPA had thickened mucosa and dilated proventricular lumen. Data from this study demonstrate that OA, CPA, and the OA-CPA combination can limit broiler performance and adversely affect broiler health. The interaction of the compounds was primarily additive or less than additive in the parameter in which the interaction occurred.

Animal Feed↗

Neuroimaging analyses of human working memory.

We review a program of research that uses neuroimaging techniques to determine the functional and neural architecture of human working memory. A first set of studies indicates that verbal working memory includes a storage component, which is implemented neurally by areas in the left-hemisphere posterior parietal cortex, and a subvocal rehearsal component, which is implemented by left-hemisphere speech areas, including Broca's area as well as the premotor and supplementary motor areas. We provide a number of neuroimaging dissociations between the storage and rehearsal areas. A second set of studies focuses on spatial working memory and indicates that it is mediated by a network of predominantly right-hemisphere regions that include areas in posterior parietal, occipital, and frontal cortex. We provide some suggestive evidence that these areas, too, divide into storage and rehearsal regions, with right-hemisphere posterior parietal and premotor regions subserving spatial rehearsal. In a final set of studies, we turn to "executive processes," metaprocesses that regulate the processing of working-memory contents. We focus on the executive process of inhibition as it is used in verbal working memory. We provide evidence that such inhibition is mediated by the left-hemisphere prefrontal region and that it can be dissociated from verbal storage and rehearsal processes.

Brain↗

Inhibition in verbal working memory revealed by brain activation.

There are many occasions in which humans and other animals must inhibit the production of some behavior or inhibit the processing of some internal representation. Success in inhibitory processing under normal circumstances can be revealed by the fact that certain brain pathologies render inhibitory processing ineffective. These pathologies often have been associated with damage to frontal cortex, including lateral and inferior aspects. We provide behavioral evidence of a verbal working memory task that, by hypothesis, engaged inhibitory processing, and we show (by using positron emission tomograpny) that the inhibitory processing is associated with a lateral portion of the left prefrontal cortex. The task in which subjects engaged was item-recognition: Four target letters were presented for storage followed, after a brief interval, by a probe letter that could match a target letter or not. On some trials, when the probe did not match a target letter and therefore required a "no" response, the probe had matched a target letter of the previous trial, so on these trials a "yes" response was prepotent and had to be inhibited, by hypothesis. Compared with a condition in which no prepotent response was created, this condition yielded brain activation in left inferior frontal gyrus, in the region of Brodmann's area 45.

Adult↗

The role of parietal cortex in verbal working memory.

Neuroimaging studies of normal subjects and studies of patients with focal lesions implicate regions of parietal cortex in verbal working memory (VWM), yet the precise role of parietal cortex in VWM remains unclear. Some evidence (; ) suggests that the parietal cortex mediates the storage of verbal information, but these studies and most previous ones included encoding and retrieval processes as well as storage and rehearsal of verbal information. A recent positron emission tomography (PET) study by isolated storage and rehearsal from other VWM processes and did not find reliable activation in parietal cortex. This result suggests that parietal cortex may not be involved in VWM storage, contrary to previous proposals. However, we report two behavioral studies indicating that some of the verbal material used by may not have required phonological representations in VWM. In addition, we report a PET study that isolated VWM encoding, retrieval, and storage and rehearsal processes in different PET scans and used material likely to require phonological codes in VWM. After subtraction of appropriate controls, the encoding condition revealed no reliable activations; the retrieval condition revealed reliable activations in dorsolateral prefrontal, anterior cingulate, posterior parietal, and extrastriate cortices, and the storage condition revealed reliable activations in dorsolateral prefrontal, inferior frontal, premotor, and posterior parietal cortices, as well as cerebellum. These results suggest that parietal regions are part of a network of brain areas that mediate the short-term storage and retrieval of phonologically coded verbal material.

Cerebellum↗

Components of verbal working memory: evidence from neuroimaging.

We review research on the neural bases of verbal working memory, focusing on human neuroimaging studies. We first consider experiments that indicate that verbal working memory is composed of multiple components. One component involves the subvocal rehearsal of phonological information and is neurally implemented by left-hemisphere speech areas, including Broca's area, the premotor area, and the supplementary motor area. Other components of verbal working memory may be devoted to pure storage and to executive processing of the contents of memory. These studies rest on a subtraction logic, in which two tasks are imaged, differing only in that one task presumably has an extra process, and the difference image is taken to reflect that process. We then review studies that show that the previous results can be obtained with experimental methods other than subtraction. We focus on the method of parametric variation, in which a parameter that presumably reflects a single process is varied. In the last section, we consider the distinction between working memory tasks that require only storage of information vs. those that require that the stored items be processed in some way. These experiments provide some support for the hypothesis that, when a task requires processing the contents of working memory, the dorsolateral prefrontal cortex is disproportionately activated.

Brain↗

Cardiopulmonary bypass with danaparoid sodium and ancrod in heparin-induced thrombocytopenia.

Heparin is the standard anticoagulant for patients undergoing cardiopulmonary bypass. There are some patients for whom heparin is unsuitable and ancrod (a defibrinogenating enzyme) has been used as an alternative. We present a patient with heparin-induced thrombocytopenia in whom treatment ancrod was ineffective. The addition of danaparoid sodium (a heparinoid) allowed safe cardiopulmonary bypass. We discuss the reasons for this and suggest that the combination of ancrod and danaparoid sodium is a logical one in such cases.

Ancrod↗

Alternative strategies of categorization.

Psychological studies of categorization often assume that all concepts are of the same general kind, and are operated on by the same kind of categorization process. In this paper, we argue against this unitary view, and for the existence of qualitatively different categorization processes. In particular, we focus on the distinction between categorizing an item by: (a) applying a category-defining rule to the item vs. (b) determining the similarity of that item to remembered exemplars of a category. We begin by characterizing rule application and similarity computations as strategies of categorization. Next, we review experimental studies that have used artificial categories and shown that differences in instructions or time pressure can lead to either rule-based categorization or similarity-based categorization. Then we consider studies that have used natural concepts and again demonstrated that categorization can be done by either rule application or similarity calculations. Lastly, we take up evidence from cognitive neuroscience relevant to the rule vs. similarity issue. There is some indirect evidence from brain-damaged patients for neurological differences between categorization based on rules vs. that based on similarity (with the former involving frontal regions, and the latter relying more on posterior areas). For more direct evidence, we present the results of a recent neuroimaging experiment, which indicates that different neural circuits are involved when people categorize items on the basis of a rule as compared with when they categorize the same items on the basis of similarity.

Adult↗

Temporal dynamics of brain activation during a working memory task.

Working memory is responsible for the short-term storage and online manipulation of information necessary for higher cognitive functions, such as language, planning and problem-solving. Traditionally, working memory has been divided into two types of processes: executive control (governing the encoding manipulation and retrieval of information in working memory) and active maintenance (keeping information available 'online'). It has also been proposed that these two types of processes may be subserved by distinct cortical structures, with the prefrontal cortex housing the executive control processes, and more posterior regions housing the content-specific buffers (for example verbal versus visuospatial) responsible for active maintenance. However, studies in non-human primates suggest that dorsolateral regions of the prefrontal cortex may also be involved in active maintenance. We have used functional magnetic resonance imaging to examine brain activation in human subjects during performance of a working memory task. We used the temporal resolution of this technique to examine the dynamics of regional activation, and to show that prefrontal cortex along with parietal cortex appears to play a role in active maintenance.

Adult↗

Working memory: a view from neuroimaging.

We have used neuroimaging techniques, mainly positron emission tomography (PET), to study cognitively driven issues about working memory. Two kinds of experiments are described. In the first kind, we employ standard subtraction logic to uncover the basic components of working memory. These studies indicate that: (a) there are different working-memory systems for spatial, object, and verbal information (with the spatial system localized more in the right hemisphere, and the verbal system more in the left hemisphere); (b) within at least the spatial and verbal systems, separable components seem to be responsible for the passive storage of information and the active maintenance of information (with the storage component being localized more in the back of the brain, and the maintenance component in the front); and (c) there may be separate components responsible for processing the contents of working memory (localized in prefrontal cortex). In our second kind of experiment we have focused on verbal working memory and incrementally varied one task parameter-memory load-in an effort to obtain a more fine-grained analysis of the system's operations. The results indicate that all relevant components of the system show some increase in activity with increasing memory load (e.g., the frontal regions responsible for verbal rehearsal show incremental increases in activation with increasing memory load). In contrast, brain regions that are not part of the working-memory system show no effect of memory load. Furthermore, the time courses of activation may differ for regions that are sensitive to load versus those that are not. Taken together, our results provide support for certain cognitive models of working memory (e.g., Baddeley, 1992) and also suggest some distinctions that these models have not emphasized. And more fundamentally, the results provide a neural base for cognitive models of working memory.

Brain↗

A parametric study of prefrontal cortex involvement in human working memory.

Although recent neuroimaging studies suggest that prefrontal cortex (PFC) is involved in working memory (WM), the relationship between PFC activity and memory load has not yet been well-described in humans. Here we use functional magnetic resonance imaging (fMRI) to probe PFC activity during a sequential letter task in which memory load was varied in an incremental fashion. In all nine subjects studied, dorsolateral and left inferior regions of PFC were identified that exhibited a linear relationship between activity and WM load. Furthermore, these same regions were independently identified through direct correlations of the fMRI signal with a behavioral measure that indexes WM function during task performance. A second experiment, using whole-brain imaging techniques, both replicated these findings and identified additional brain regions showing a linear relationship with load, suggesting a distributed circuit that participates with PFC in subserving WM. Taken together, these results provide a "dose-response curve" describing the involvement of both PFC and related brain regions in WM function, and highlight the benefits of using graded, parametric designs in neuroimaging research.

Adolescent↗

Culture, category salience, and inductive reasoning.

The role of category salience in category-based induction was demonstrated in two ways: (i) temporarily increasing category salience facilitated category-based induction, and (ii) this effect was moderated by cultural differences that we predicted would be related to chronic category salience. Subjects for whom categories were presumed to be more accessible (Americans) were not as much influenced by manipulations to increase category salience as subjects who were presumed to have lower chronic accessibility of categories (Koreans). However, as anticipated, this pattern was reversed for inferences about behavioral properties of social categories. Due to the 'interdependent' nature of their culture, Koreans presumably have relatively higher chronic accessibility for social categories than do relatively 'independent' Americans, and hence were not influenced as much by increasing category salience.

Cross-Cultural Comparison↗

Spatial, but not object, delayed response is impaired in early Parkinson's disease.

The authors hypothesized that the pathophysiology of early Parkinson's disease (PD) may selectively target structures that support visual working memory for spatial relations but leave structures that support working memory for featural characteristics of objects relatively intact. Fifteen PD and 15 normal control participants took a visual delayed-response test with a spatial condition and a (nonspatial) object condition, equating the perceptual difficulty of the tests for each participant. The stimuli were irregular polygons presented at different locations on a computer screen. Results revealed a selective impairment of spatial delayed response in PD, indicating a disruption of spatial working memory unconfounded by sensory processing difficulties. The selectivity of this deficit may reflect the circumscribed nature of pathophysiological change affecting the caudate nucleus in early PD.

Aged↗

PET evidence for an amodal verbal working memory system.

Current models of verbal working memory assume that modality-specific representations are translated into phonological representations before entering the working memory system. We report an experiment that tests this assumption. Positron emission tomography measures were taken while subjects performed a verbal working memory task. Stimuli were presented either visually or aurally, and a visual or auditory search tasks, respectively, was used as a control. Results revealed an almost complete overlap between the active memory areas regardless of input modality. These areas included dorsolateral frontal, Broca's area, SMA, and premotor cortex in the left hemisphere; bilateral superior and posterior parietal cortices and anterior cingulate; and right cerebellum. These results correspond well with previous research and suggest that verbal working memory is modality independent and is mediated by a circuit involving frontal, parietal, and cerebellar mechanisms.

Adult↗