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Biomedical subjects

S E Petersen

Publications and source records attributed to S E Petersen.

At least 19 recordsLinked to original sources

Activation of the hippocampus in normal humans: a functional anatomical study of memory.

We studied regional cerebral blood flow using the H2(15)O method while normal subjects performed four similar tasks involving three-letter word beginnings (stems). Prior to each task, subjects studied a list of words. Local blood flow was then monitored during a 40-sec period while subjects (i) silently viewed word stems, (ii) completed stems to form the first words to come to mind, but the stems were not the beginnings of any study words (baseline), (iii) completed stems and half of them could form study words (priming), or (iv) tried to recall study words, and half of the stems could form these words (memory). There were three major findings. (i) The memory task engaged the right hippocampal region when the memory task was compared to either the baseline or the priming condition. The right hemispheric locus suggests that performance is driven by the visual characteristics of the words rather than by semantic or phonetic analysis. (ii) In the priming-minus-baseline comparison, there was reduction in blood flow in the right posterior cortex. (iii) Right prefrontal cortex was activated in the memory-minus-baseline condition. The results provide evidence for selective activation of the human hippocampal region in association with memory function. The results also lead to a suggestion about the neural basis of repetition priming: following presentation of a stimulus, less neural activity is required to process the same stimulus.

Adult

The pulvinar and visual salience.

One of the major problems of living in a rich visual environment is deciding which particular object or location should be chosen for complete processing or attention; that is, deciding which object is most salient at any particular time. The pulvinar has enlarged substantially during evolution, although little has previously been known about its function. Recent studies suggest that the pulvinar contains neurons that generate signals related to the salience of visual objects. This evidence includes: (1) anatomical and physiological observations of visual function; (2) augmented responses in the pulvinar for visual stimuli presented in important contexts; (3) suppression of activity for stimuli presented in irrelevant conditions; (4) thalamic modulation producing behavioral changes in cued attention paradigms; and (5) similar changes with visual distracter tasks.

Animals

Neuroimaging.

Recent advances in neuroimaging have led to an increase in the types of studies possible in the field of cognitive neuroscience. Researchers are now using neuroimaging to enhance classic approaches, such as lesion-behavior studies, as well as provide information about normal functions at levels that were previously difficult to assess.

Animals

Impaired non-motor learning and error detection associated with cerebellar damage. A single case study.

A previously conducted positron emission tomography (PET) study of normal humans suggested that the cerebellum makes important non-motor contributions to language processing. Beginning with the task which produced right cerebellar PET activation, we studied a 49-yr-old male (RC1) with right cerebellar damage on a variety of tasks involving complex non-motor processing. Whereas RC1's performance on standard tests of memory, intelligence, 'frontal function' and language skills was excellent, he had profound deficits in two areas: (1) practice-related learning; (2) detection of errors. Considered in relation to cerebellar contributions to motor tasks, the results suggest some functions performed by the cerebellum may be generalized beyond a purely motor domain.

Cerebellar Diseases

Selective attention modulates extrastriate visual regions in humans during visual feature discrimination and recognition.

Positron emission tomography (PET) was used to identify regions of the human visual system which were selectively modulated by attention during feature discrimination and recognition tasks. In a first experiment, subjects were cued to the shape, colour or speed of visual stimulus arrays during a same-different match-to-sample paradigm. The psychophysical sensitivity for discriminating subtle attribute variations was enhanced by selective attention. Correspondingly, the neural activity (as measured by blood flow changes) in different visual associative regions was enhanced when subjects attended to different attributes of the same stimulus (intraparietal sulcus for speed; collateral sulcus and dorsolateral occipital cortex for colour; collateral sulcus, fusiform and parahippocampal gyri, superior temporal sulcus for shape). These regions appeared to be specialized for processing the selected attribute. Attention to a visual feature, therefore, enhances the psychophysical sensitivity as well as the neural activity of specialized processing regions of the human visual system. In a second experiment the effect of target probability (which biases attentional selection) was studied during visual search tasks involving the recognition of a single-feature (i.e. colour) or a feature-conjunction (i.e. colour x orientation) target. Target probability positively modulated neural activity of extrastriate visual regions, which were related to the single-feature or feature-conjunction processing level. These results suggest that selective attention can influence different processing levels in the visual system, possibly reflecting a facilitatory effect on different visual computations or task components.

Attention

Chromosome number distribution and cellular DNA content in colorectal adenomas from polyposis and nonpolyposis patients.

Ploidy analyses of colorectal adenomas were performed by combined flow cytometric DNA analysis of unfixed isolated nuclei and direct chromosome preparation after Colcemid incubation for 9-20 hours. Ten of 18 adenomas from nonpolyposis patients and 4 of 13 adenomas from patients with familial adenomatous polyposis yielded a mean of 25 countable metaphases (range 7-44) per tumor. Of 343 metaphases, only 38% had 46 chromosomes, and 62% were nondiploid. All but one adenoma had diploid or peridiploid modes in the range of 46-50 chromosomes. One adenoma was hyperploid, with a mode of 74 chromosomes and a correspondingly increased nuclear DNA content. In another two adenomas, the DNA analyses showed small hyperploid populations constituting 6% and 2% of the cells. The most striking difference between the DNA analyses and chromosome number distributions was that 13% of all metaphases were hyperploid with chromosome numbers outside the perimodal range but, except in one adenoma, without indication in the DNA histogram of corresponding hyperploid cell populations. We propose that these aberrant metaphases indicate an early acquired genetic instability of the neoplastic epithelium, which may be instrumental in generation of hyperploid, invasive clones, which constitute most colorectal carcinomas.

Adenoma

Visual responses of pulvinar and collicular neurons during eye movements of awake, trained macaques.

1. We recorded from single neurons in awake, trained rhesus monkeys in a lighted environment and compared responses to stimulus movement during periods of fixation with those to motion caused by saccadic or pursuit eye movements. Neurons in the inferior pulvinar (PI), lateral pulvinar (PL), and superior colliculus were tested. 2. Cells in PI and PL respond to stimulus movement over a wide range of speeds. Some of these cells do not respond to comparable stimulus motion, or discharge only weakly, when it is generated by saccadic or pursuit eye movements. Other neurons respond equivalently to both types of motion. Cells in the superficial layers of the superior colliculus have similar properties to those in PI and PL. 3. When tested in the dark to reduce visual stimulation from the background, cells in PI and PL still do not respond to motion generated by eye movements. Some of these cells have a suppression of activity after saccadic eye movements made in total darkness. These data suggest that an extraretinal signal suppresses responses to visual stimuli during eye movements. 4. The suppression of responses to stimuli during eye movements is not an absolute effect. Images brighter than 2.0 log units above background illumination evoke responses from cells in PI and PL. The suppression appears stronger in the superior colliculus than in PI and PL. 5. These experiments demonstrate that many cells in PI and PL have a suppression of their responses to stimuli that cross their receptive fields during eye movements. These cells are probably suppressed by an extraretinal signal. Comparable effects are present in the superficial layers of the superior colliculus. These properties in PI and PL may reflect the function of the ascending tectopulvinar system.

Animals

Selective and divided attention during visual discriminations of shape, color, and speed: functional anatomy by positron emission tomography.

Positron emission tomography (PET) was used to identify the neural systems involved in discriminating the shape, color, and speed of a visual stimulus under conditions of selective and divided attention. Psychophysical evidence indicated that the sensitivity for discriminating subtle stimulus changes in a same-different matching task was higher when subjects selectively attended to one attribute than when they divided attention among the attributes. PET measurements of brain activity indicated that modulations of extrastriate visual activity were primarily produced by task conditions of selective attention. Attention to speed activated a region in the left inferior parietal lobule. Attention to color activated a region in the collateral sulcus and dorsolateral occipital cortex, while attention to shape activated collateral sulcus (similarly to color), fusiform and parahippocampal gyri, and temporal cortex along the superior temporal sulcus. Outside the visual system, selective and divided attention activated nonoverlapping sets of brain regions. Selective conditions activated globus pallidus, caudate nucleus, lateral orbitofrontal cortex, posterior thalamus/colliculus, and insular-premotor regions, while the divided condition activated the anterior cingulate and dorsolateral prefrontal cortex. The results in the visual system demonstrate that selective attention to different features modulates activity in distinct regions of extrastriate cortex that appear to be specialized for processing the selected feature. The disjoint pattern of activations in extravisual brain regions during selective- and divided-attention conditions also suggests that preceptual judgements involve different neural systems, depending on attentional strategies.

Adult

Activation of extrastriate and frontal cortical areas by visual words and word-like stimuli.

Visual presentation of words activates extrastriate regions of the occipital lobes of the brain. When analyzed by positron emission tomography (PET), certain areas in the left, medial extrastriate visual cortex were activated by visually presented pseudowords that obey English spelling rules, as well as by actual words. These areas were not activated by nonsense strings of letters or letter-like forms. Thus visual word form computations are based on learned distinctions between words and nonwords. In addition, during passive presentation of words, but not pseudowords, activation occurred in a left frontal area that is related to semantic processing. These findings support distinctions made in cognitive psychology and computational modeling between high-level visual and semantic computations on single words and describe the anatomy that may underlie these distinctions.

Adult

Attentional modulation of neural processing of shape, color, and velocity in humans.

Positron emission tomography (PET) was used to measure changes in regional cerebral blood flow of normal subjects, while they were discriminating different attributes (shape, color, and velocity) of the same set of visual stimuli. Psychophysical evidence indicated that the sensitivity for discriminating subtle stimulus changes was higher when subjects focused attention on one attribute than when they divided attention among several attributes. Correspondingly, attention enhanced the activity of different regions of extrastriate visual cortex that appear to be specialized for processing information related to the selected attribute.

Adult

Secondary treatment of advanced cancer of the prostate with Zoladex.

Twelve patients with advanced prostatic carcinoma and relapse following previous hormone manipulation therapy were treated with Zoladex-depot every 4 weeks. The treatment was well tolerated and the endocrine response was satisfactory. However, no clinically important improvement was obtained.

Aged

Influences of lesions of parietal cortex on visual spatial attention in humans.

Several brain areas have been identified with attention, because damage to these regions leads to neglect and extinction. We have tested elements of visual attentional processing in patients with parietal, frontal, or temporal lesions and compared their responses to control subjects. Normal humans respond faster in a reaction time task when the spatial location of a target is correctly predicted by an antecedent stimulus (valid cue) than when the location is incorrectly predicted (invalid cue). The cue is hypothesized to shift attention towards its location and thereby facilitate or impede response latencies. The reaction times of individuals with damage to the parietal lobe are somewhat slowed for targets ipsilateral or contralateral to the side of the lesion if the targets are preceded by valid cues. These same patients are extremely slow in responding to targets in the visual field contralateral to the lesion when the cue has just appeared in the unaffected (ipsilateral) visual field. In addition, these individuals are especially slow in responding to targets in either visual field when the lights are preceded by weak, diffuse illumination of the entire visual field. Patients with lesions of the frontal lobe have very slow reaction times in general and, as is the case for patients with lesions of the temporal lobe, are slow in all conditions for targets in the field contralateral to the lesion. These patterns are probably not associated with attentional defects. For patients with parietal lesions, these studies demonstrate a further deficit in a cued reaction-time task suggesting abnormal visual attention. Since different sites of brain damage yield different patterns of responses, tests such as these could be of analytic and diagnostic value.

Adolescent

Identification of hemoglobin and two serine proteases in acid extracts of calcium containing kidney stones.

By stepwise extraction of kidney stones, first with 10% acetic acid then 0.1 M EDTA, three pools of protein material have been obtained. The soluble material from the acid extract showed well defined bands when analyzed by sodium dodecyl sulfate (SDS) gel electrophoresis, and amino acid sequence analysis of peptides identified hemoglobin as a common constituent. From one stone neutrophil elastase has been identified along with another serine protease of unknown origin. The second pool of material which was soluble in EDTA showed a smear on SDS gel electrophoresis while the third pool consisted of the insoluble matrix. The finding of proteolytic enzymes opens up the possibility that limited proteolysis might be involved in the stone forming process.

Amino Acid Sequence

A comparison between stereological estimates of mean nuclear volume and DNA flow cytometry in bladder tumours.

The correlation between stereological estimate of mean nuclear volume and DNA-content was studied in 55 human urinary bladder tumours. The DNA-content was determined by flow cytometry on isolated nuclei stained with ethidium bromide. Trout erythrocytes were used as a biological internal standard providing an accurate determination of the DNA-histogram. An unbiased estimate of the mean nuclear volume (vv) was obtained after standard formaline fixation, paraffin-embedding, sectioning and hematoxylin-eosin staining using the equation vv = pi/3.l3(0). Here l0 is the length of an intercept measured in a random direction through a test point, which hit a nucleus. A highly significant correlation was found between vv and mean DNA-content of nuclei (2p = 0.0004). A highly significant correlation was also found between vv and the highest DNA-content present in tumours having cell populations with different DNA content (2p = 0.0016). The mean nuclear volume and the DNA-content also correlated well with the pathologic grade. Although significant the correlations were far from perfect, which indicates that DNA content and mean nuclear volume may provide partly independent biological information. The methods provide objective, unbiased and reproducible data which may improve the possibility of grading and predicting the disease course of human urinary bladder tumours.

Cell Nucleus

Urinary cytology in the detection of bladder tumours. Influence of concomitant urothelial atypia.

The role of urinary cytology in detection and follow-up of urinary bladder tumours is still evolving. However, considerable variations in the accuracy of detecting bladder tumours exist in published work on the subject. In this study the influence of concomitant urothelial atypia on urinary cytology was investigated. Further, the correlation of grading between cytology and tumour histology was examined, and finally the role of urinary cytology as a prognostic factor was investigated. 102 comparative studies of simultaneously achieved precystoscopic voided urine samples, tumour histology and 8 pre-selected site biopsies were available from patients having a Ta, T1 or T2 bladder tumour. The overall numbers of positive cytology were found to be 64%, but correcting for false positives caused by concomitant urothelial atypia the numbers were reduced to 55% (p less than 0.01). A considerable higher ability to detect high-grade than low-grade tumours was found. Correlation between grading of tumour histology and cytology was found to be only 50%. Patients were followed for 3 years. From the results of pre-cystoscopic cytology it was possible to define a low-risk group and a high-risk group. Patients with negative cytology had very low risk of future invasive tumour recurrence whereas all patients with grade III-IV cytologic changes were found to harbour either a grade III tumour or carcinoma in situ, both conditions predictive of aggressive tumour course.

Carcinoma in Situ

Transabdominal ultrasonography plus urine cytology in control of benign bladder tumours.

Transabdominal ultrasonography can detect bladder tumours down to 5 mm in diameter, and in combination with urine cytology it is a potential alternative to cystoscopy for control of bladder tumour patients. This modality was compared with cystoscopy in 260 investigations on patients with previous non-invasive tumours. Of 153 negative ultrasonographies 55 (21%) were false negative, overlooking 15 tumours above 5 mm (including 5 flat papillomatous areas), 30 tumours 5 mm or less and 10 flat dysplastic lesions (diagnostic sensitivity 64%). In 14 of the false negative ultrasonographies urine cytology was abnormal, increasing the combined diagnostic sensitivity to 73%. Most overlooked tumours above 5 mm were in bladder neck, anterior wall and dome. Of 89 positive ultrasonographies 15 were false positive (diagnostic specificity 83%). Two patients developed invasive tumours in the study period. One was detected by ultrasound and urine cytology, the other - a flat muscle invasive tumour - was not. Ultrasonography plus urine cytology is only acceptable for control of patients with very little risk of invasive and few non-invasive recurrences, i.e. patients with previous Ta, grade I or II transitional cell tumours and no recurrences after 1 or 2 control cystoscopies.

Abdomen

Localization of cognitive operations in the human brain.

The human brain localizes mental operations of the kind posited by cognitive theories. These local computations are integrated in the performance of cognitive tasks such as reading. To support this general hypothesis, new data from neural imaging studies of word reading are related to results of studies on normal subjects and patients with lesions. Further support comes from studies in mental imagery, timing, and memory.

Attention