PubMed Health⌕ Search

Biomedical subjects

R J Wise

Publications and source records attributed to R J Wise.

At least 19 recordsLinked to original sources
PubMed2001

Separate neural subsystems within 'Wernicke's area'.

Over time, both the functional and anatomical boundaries of 'Wernicke's area' have become so broad as to be meaningless. We have re-analysed four functional neuroimaging (PET) studies, three previously published and one unpublished, to identify anatomically separable, functional subsystems in the left superior temporal cortex posterior to primary auditory cortex. From the results we identified a posterior stream of auditory processing. One part, directed along the supratemporal cortical plane, responded to both non-speech and speech sounds, including the sound of the speaker's own voice. Activity in its most posterior and medial part, at the junction with the inferior parietal lobe, was linked to speech production rather than perception. The second, more lateral and ventral part lay in the posterior left superior temporal sulcus, a region that responded to an external source of speech. In addition, this region was activated by the recall of lists of words during verbal fluency tasks. The results are compatible with an hypothesis that the posterior superior temporal cortex is specialized for processes involved in the mimicry of sounds, including repetition, the specific role of the posterior left superior temporal sulcus being to transiently represent phonetic sequences, whether heard or internally generated and rehearsed. These processes are central to the acquisition of long- term lexical memories of novel words.

Acoustic Stimulation↗
PubMed2001

The functional anatomy of single-word reading in patients with hemianopic and pure alexia.

We investigated single-word reading in normal subjects and patients with alexia following a left occipital infarct, using PET. The most posterior brain region to show a lateralized response was at the left occipitotemporal junction, in the inferior temporal gyrus. This region was activated when normal subjects, patients with hemianopic alexia and patients with an incomplete right homonymous hemianopia, but no reading deficit, viewed single words presented at increasing rates. This same area was damaged in a patient with pure alexia ("alexia without agraphia") and no hemianopia, who read words slowly using a letter-by-letter strategy. Although the exact level of the functional deficit is controversial, pure alexia is the result of an inability to map a percept of all the letters in a familiar letter string on to the mental representation of the whole word form. However, the commonest deficit associated with "pure" alexia is a right homonymous field defect; an impairment that may, by itself, interfere with single-word reading because of inability to see the letters towards the end of a word. The relative contributions of pure and hemianopic alexia in individual patients needs to be assessed, as the latter has been shown to respond well to specific rehabilitation programmes.

Adult↗
PubMed2001

The planning and guiding of reading saccades: a repetitive transcranial magnetic stimulation study.

A previous positron emission tomography study that investigated the cortical areas involved in directing eye movements during text reading showed two areas of extra-occipital asymmetry: left > right posterior parietal cortex (PPC), and right > left frontal eye-field (FEF). We used the temporal resolution of repetitive TMS (rTMS) to isolate the contributions of the left and right PPC and FEF to the planning and execution of rightward reading saccades. We present eye-movement data collected during text reading, which involves the initiation and maintenance of a series of saccades (scanpath). rTMS over the left but not right PPC slowed reading speeds for the whole array of words, indicating that this area is involved throughout the scanpath. rTMS over the right but not the left FEF slowed the time to make the first saccade, but only when triggered before the stimuli appeared, demonstrating that the role of this region is in the preparation of the scanpath. Our results are compatible with the hypotheses that the left PPC maintains reading saccades along a line of text while the right FEF is involved in the preparation of the motor plan for the scanpath at the start of each new line of text.

Adult↗
PubMed2000

Breathlessness in humans activates insular cortex.

Dyspnea (shortness of breath, breathlessness) is a major and disabling symptom of heart and lung disease. The representation of dyspnea in the cerebral cortex is unknown. In the first study designed to explore the central neural structures underlying perception of dyspnea, we evoked the perception of severe 'air hunger' in healthy subjects by restraining ventilation below spontaneous levels while holding arterial oxygen and carbon dioxide levels constant. PET revealed that air hunger activated the insular cortex. The insula is a limbic structure also activated by visceral stimuli, temperature, taste, nausea and pain. Like dyspnea, such perceptions underlie behaviors essential to homeostasis and survival.

Adult↗
PubMed2000

A thalamo-prefrontal system for representation in executive response choice.

This study demonstrates the neural system potentially involved in the representation of, and choice between, stimulus classifications in an ambiguous, novel, decision-making task. This difficult choice behaviour is taken as an example of a basic executive processing task. Subjects heard sounds that were consonant-vowel combinations that had been distorted and were required to categorize each stimulus as speech-like or not-speech-like. Cerebral activity was measured with positron emission tomography. A neural system (thalamic and medial prefrontal cortical regions) was demonstrated; there was greater activity involved in assigning the sound to the larger class of not-speech-like sounds than to the more restricted category of speech-like sounds. We interpret this activity as reflecting process and representation in a simple central executive task.

Acoustic Stimulation↗
PubMed2000

Noun imageability and the temporal lobes.

We used positron emission tomography to investigate brain activity in response to hearing or reading nouns of varying imageability. Three experiments were performed. Activity increased with noun imageability in the left mid-fusiform gyrus, the lateral parahippocampal area in humans, and in the rostral medial temporal lobes close to or within perirhinal cortex. The left mid-fusiform activation has been observed in previous imaging studies of single word processing. Its functional significance was variously attributed to semantic processing, visual imagery, encoding episodic memories, or the integration of lexical inputs from different sensory modalities. These hypotheses are not mutually exclusive. The more rostral medial lobe response to noun imageability has not been observed previously. However, lesions in perirhinal cortex impair knowledge about objects in non-human primates, and bilateral rostral ventromedial temporal lobe potentials in response to object nouns were observed with human intracranial recordings. Imageable (object) nouns are learnt with reference to sensory experiences of living and non-living objects, whereas acquisition of the meaning of low imageable (abstract) nouns is more dependent on their context within sentences. Parahippocampal and perirhinal cortices are reciprocally connected with, respectively, second and third order sensory association cortices. We conclude that access to the representations of word meaning is dependent on heteromodal temporal lobe cortex, and that during the acquisition of object nouns one route is established through ventromedial temporal cortical regions that have reciprocal connections with all sensory association cortices.

Adult↗
PubMed2000

First report of an intravenous and oral glycoprotein IIb/IIIa inhibitor (RPR 109891) in patients with recent acute coronary syndromes: results of the TIMI 15A and 15B trials.

BACKGROUND: RPR 109891 is a modified tetrapeptide glycoprotein IIb/IIIa inhibitor available in intravenous and oral formulations. Two phase II dose-ranging studies were performed to investigate pharmacodynamics and safety in acute coronary syndromes. METHODS: The Thrombolysis In Myocardial Infarction (TIMI) 15A trial was a randomized, open-label, study of RPR 109891 administered intravenously for 24 to 96 hours in 91 patients. TIMI 15B was a randomized, double-blind comparison of intravenous RPR 109891 plus 4 weeks of oral RPR 109891 (n = 142) compared with placebo (n = 50). RESULTS: Intravenous RPR 109891 exhibited a dose-response inhibition of platelet aggregation; mean inhibition after a bolus ranged from 53% to 92%, and at steady state 49% to 98%. Oral RPR 109891 demonstrated less platelet inhibition (peaks, range 48% to 59%; troughs, range 18% to 39%). Mean glycoprotein IIb/IIIa receptor occupancy and platelet inhibition were highly correlated (r = 0.82, 95% confidence interval 0.74-0.88). There were trends for increased major hemorrhage (10% vs 6%, P =.57), thrombocytopenia <90,000 cells/mm(3) (13% vs 4%, P =.11), and profound thrombocytopenia <20, 000 (3.5% vs 0%, P =.33) with intravenous plus oral RPR 109891 compared with placebo. In 3 of 5 cases of profound thrombocytopenia, RPR 109891 had been interrupted because of bypass surgery, and a precipitous fall in platelet count occurred after the first postoperative oral dose. CONCLUSIONS: Intravenous RPR 109891 is a potent, predictable, dose-related platelet inhibitor. Oral RPR 109891 (</=600 mg/d) achieves moderate platelet inhibition. Interrupted glycoprotein IIb/IIIa blockade may be associated with a higher risk of profound thrombocytopenia and deserves closer examination in future studies.

Administration, Oral↗
PubMed2000

Identification of a pathway for intelligible speech in the left temporal lobe.

It has been proposed that the identification of sounds, including species-specific vocalizations, by primates depends on anterior projections from the primary auditory cortex, an auditory pathway analogous to the ventral route proposed for the visual identification of objects. We have identified a similar route in the human for understanding intelligible speech. Using PET imaging to identify separable neural subsystems within the human auditory cortex, we used a variety of speech and speech-like stimuli with equivalent acoustic complexity but varying intelligibility. We have demonstrated that the left superior temporal sulcus responds to the presence of phonetic information, but its anterior part only responds if the stimulus is also intelligible. This novel observation demonstrates a left anterior temporal pathway for speech comprehension.

Acoustic Stimulation↗
PubMed2000

Statistical modeling of positron emission tomography images in wavelet space.

A new method is introduced for the analysis of multiple studies measured with emission tomography. Traditional models of statistical analysis (ANOVA, ANCOVA and other linear models) are applied not directly on images but on their correspondent wavelet transforms. Maps of model effects estimated from these models are filtered using a thresholding procedure based on a simple Bonferroni correction and then reconstructed. This procedure inherently represents a complete modeling approach and therefore obtains estimates of the effects of interest (condition effect, difference between conditions, covariate of interest, and so on) under the specified statistical risk. By performing the statistical modeling step in wavelet space. the procedure allows the direct estimation of the error for each wavelet coefficient; hence, the local noise characteristics are accounted for in the subsequent filtering. The method was validated by use of a null dataset and then applied to typical examples of neuroimaging studies to highlight conceptual and practical differences from existing statistical parametric mapping approaches.

Artifacts↗
PubMed2000

Impaired reading in patients with right hemianopia.

A left occipital stroke may result in alexia for two reasons, which may coexist depending on the distribution of the lesion. A lesion of the left lateroventral prestriate cortex or its afferents impairs word recognition ("pure" alexia). If the left primary visual cortex or its afferents are destroyed, resulting in a complete right homonymous hemianopia, rightward saccades during text reading are disrupted ("hemianopic" alexia). By using functional imaging, we showed two separate but interdependent systems involved in reading. The first, subserving word recognition, involved the representation of foveal vision in the left and right primary visual cortex and the ventral prestriate cortex. The second system, responsible for the planning and execution of reading saccades, consisted of the representation of right parafoveal vision in the left visual cortex, the bilateral posterior parietal cortex (left > right), and the frontal eye fields (right > left). Disruption of this distributed neural system was demonstrated in patients with severe right homonymous hemianopia, commensurate with their inability to perform normal reading eye movements. Text reading, before processes involved in comprehension, requires the integration of perceptual and motor processes. We have demonstrated these distributed neural systems in normal readers and have shown how a right homonymous hemianopia disrupts the motor preparation of reading saccades during text reading.

Adult↗
PubMed1999

Collagen-bound von Willebrand factor has reduced affinity for factor VIII.

von Willebrand factor (vWf) is a multimeric adhesive glycoprotein that serves as a carrier for factor VIII in plasma. Although each vWf subunit displays a high affinity binding site for factor VIII in vitro, in plasma, only 2% of the vWf sites for factor VIII are occupied. We investigated whether interaction of plasma proteins with vWf or adhesion of vWf to collagen may alter the affinity or availability of factor VIII-binding sites on vWf. When vWf was immobilized on agarose-linked monoclonal antibody, factor VIII bound to vWf with high affinity, and neither the affinity nor binding site availability was influenced by the presence of 50% plasma. Therefore, plasma proteins do not alter the affinity or availability of factor VIII-binding sites. In contrast, when vWf was immobilized on agarose-linked collagen, its affinity for factor VIII was reduced 4-fold, with KD increasing from 0.9 to 3.8 nM. However, one factor VIII-binding site remained available on each vWf subunit. A comparable reduction in affinity for factor VIII was observed when vWf was a constituent of the subendothelial cell matrix and when it was bound to purified type VI collagen. In parallel with the decreased affinity for factor VIII, collagen-bound vWf displayed a 6-fold lower affinity for monoclonal antibody W5-6A, with an epitope composed of residues 78-96 within the factor VIII-binding motif of vWf. We conclude that collagen induces a conformational change within the factor VIII-binding motif of vWf that lowers the affinity for factor VIII.

Animals↗
PubMed1999

Brain regions involved in articulation.

BACKGROUND: The left inferior frontal gyrus (Broca's area) is generally believed to be critical for the motor act of speech. A lesion-based analysis has, however, shown that the left anterior insula is necessary for accurate articulation. We used functional imaging in normal people to show the neural systems involved in speech during different speech tasks. METHODS: 12 normal people underwent positron emission tomography with oxygen-15-labelled water as tracer. We measured cerebral activity while participants performed three different tasks: repetition of heard nouns at different rates; listening to single nouns at different rates; and anticipation of listening or repetition. We analysed the data with imaging software. FINDINGS: Repetition of single words did not activate Broca's area but activity in three left-lateralised regions was seen: the anterior insula, a localised region in the lateral premotor cortex, and the posterior pallidum. The left anterior insula and lateral premotor cortex showed a conjunction of activity for hearing and articulation. In addition, articulation modulated the response to hearing words in the left dorsolateral temporal cortex, the physiological expression of the speaker's auditory attention being directed towards the stimuli and not his or her articulated responses. INTERPRETATION: The formulation of an articulatory plan is a function of the left anterior insula and lateral premotor cortex and not of Broca's area. The left basal ganglia seem to be dominant for speech, although the axial muscles involved receive their motor output from both cerebral hemispheres.

Adult↗
PubMed1999

Long-term cure of the photosensitivity of murine erythropoietic protoporphyria by preselective gene therapy.

Definitive cure of an animal model of a human disease by gene transfer into hematopoietic stem cells has not yet been accomplished in the absence of spontaneous in vivo selection for transduced cells. Erythropoietic protoporphyria is a genetic disease in which ferrochelatase is defective. Protoporphyrin accumulates in erythrocytes, leaks into the plasma and results in severe skin photosensitivity. Using a mouse model of erythropoietic protoporphyria, we demonstrate here that ex vivo preselection of hematopoietic stem cells transduced with a polycistronic retrovirus expressing both human ferrochelatase and green fluorescent protein results in complete and long-term correction of skin photosensitivity in all transplanted mice.

Animals↗
PubMed1999

Disrupted temporal lobe connections in semantic dementia.

Semantic dementia refers to the variant of frontotemporal dementia in which there is progressive semantic deterioration and anomia in the face of relative preservation of other language and cognitive functions. Structural imaging and SPECT studies of such patients have suggested that the site of damage, and by inference the region critical to semantic processing, is the anterolateral temporal lobe, especially on the left. Recent functional imaging studies of normal participants have revealed a network of areas involved in semantic tasks. The present study used PET to examine the consequences of focal damage to the anterolateral temporal cortex for the operation of this semantic network. We measured PET activation associated with a semantic decision task relative to a visual decision task in four patients with semantic dementia compared with six age-matched normal controls. Normals activated a network of regions consistent with previous studies. The patients activated some areas consistently with the normals, including some regions of significant atrophy, but showed substantially reduced activity particularly in the left posterior inferior temporal gyrus (iTG) (Brodmann area 37/19). Voxel-based morphometry, used to identify the regions of structural deficit, revealed significant anterolateral temporal atrophy (especially on the left), but no significant structural damage to the posterior inferior temporal lobe. Other evidence suggests that the left posterior iTG is critically involved in lexical-phonological retrieval: the lack of activation here is consistent with the observation that these patients are all anomic. We conclude that changes in activity in regions distant from the patients' structural damage support the argument that their prominent anomia is due to disrupted temporal lobe connections.

Anomia↗
PubMed1999

Functional neuroimaging of speech perception in six normal and two aphasic subjects.

This positron emission tomography study used a correlational design to investigate neural activity during speech perception in six normal subjects and two aphasic patients. The normal subjects listened either to speech or to signal-correlated noise equivalents; the latter were nonspeech stimuli, similar to speech in complexity but not perceived as speechlike. Regions common to the auditory processing of both types of stimuli were dissociated from those specific to spoken words. Increasing rates of presentation of both speech and nonspeech correlated with cerebral activity in bilateral transverse gyri and adjacent superior temporal cortex. Correlations specific to speech stimuli were located more anteriorly in both superior temporal sulci. The only asymmetry in normal subjects was a left lateralized response to speech in the posterior superior temporal sulcus, corresponding closely to structural asymmetry on the subjects' magnetic resonance images. Two patients, who had left temporal infarction but performed well on single word comprehension tasks, were also scanned while listening to speech. These cases showed right superior temporal activity correlating with increasing rates of hearing speech, but no significant left temporal activation. These findings together suggest that the dorsolateral temporal cortex of both hemispheres can be involved in prelexical processing of speech.

Adult↗
PubMed1999

Mechanisms of recovery from aphasia: evidence from positron emission tomography studies.

OBJECTIVES: Language functions comprise a distributed neural system, largely lateralised to the left cerebral hemisphere. Late recovery from aphasia after a focal lesion, other than by behavioural strategies, has been attributed to one of two changes at a systems level: a laterality shift, with mirror region cortex in the contralateral cortex assuming the function(s) of the damaged region; or a partial lesion effect, with recovery of perilesional tissue to support impaired language functions. Functional neuroimaging with PET allows direct observations of brain functions at systems level. This study used PET to compare regional brain activations in response to a word retrieval task in normal subjects and in aphasic patients who had shown at least some recovery and were able to attempt the task. Emphasis has been placed on single subject analysis of the results as there is no reason to assume that the mechanisms of recovery are necessarily uniform among aphasic patients. METHODS: Six right handed aphasic patients, each with a left cerebral hemispheric lesion (five strokes and one glioma), were studied. Criteria for inclusion were symptomatic or formal test evidence of at least some recovery and an ability to attempt word retrieval in response to heard word cues. Each patient underwent 12 PET scans using oxygen-15 labelled water (H2(15)O) as tracer to index regional cerebral blood flow (rCBF). The task, repeated six times, required the patient to think of verbs appropriate to different lists of heard noun cues. The six scans obtained during word retrieval were contrasted with six made while the subject was "at rest". The patients' individual results were compared with those of nine right handed normal volunteers undergoing the same activation study. The data were analysed using statistical parametric mapping (SPM96, Wellcome Department of Cognitive Neurology, London, UK). RESULTS: Perception of the noun cues would be expected to result in bilateral dorsolateral temporal cortical activations, but as the rate of presentation was only four per minute the auditory perceptual activations were not evident in all people. Anterior cingulate, medial premotor (supplementary speech area) and dorsolateral frontal activations were evident in all normal subjects and patients. There were limited right dorsolateral frontal activations in three of the six patients, but a similar pattern was also found in four of the nine normal subjects. In the left inferolateral temporal cortex, activation was found for the normal subjects and five of the six patients, including two of the three subjects with lesions involving the left temporal lobe. The only patient who showed subthreshold activation in the left inferolateral temporal activation had a very high error rate when performing the verb retrieval task. CONCLUSIONS: The normal subjects showed a left lateralised inferolateral temporal activation, reflecting retrieval of words appropriate in meaning to the cue from the semantic system. Lateralisation of frontal activations to the left was only relative, with right prefrontal involvement in half of the normal subjects. Frontal activations are associated with parallel psychological processes involved in word retrieval, including task initiation, short term (working) memory for the cue and responses, and prearticulatory processes (even though no overt articulation was required). There was little evidence of a laterality shift of word retrieval functions to the right temporal lobe after a left hemispheric lesion. In particular, left inferolateral temporal activation was seen in all patients except one, and he proved to be very inefficient at the task. The results provide indirect evidence that even limited salvage of peri-infarct tissue with acute stroke treatments will have an important impact on the rehabilitation of cognitive functions.

Adult↗
PubMed1998

Binding of factor VIII to von willebrand factor is enabled by cleavage of the von Willebrand factor propeptide and enhanced by formation of disulfide-linked multimers.

von Willebrand factor (vWF) is a multimeric adhesive glycoprotein with one factor VIII binding site/subunit. Prior reports suggest that posttranslational modifications of vWF, including formation of N-terminal intersubunit disulfide bonds and subsequent cleavage of the propeptide, influence availability and/or affinity of factor VIII binding sites. We found that deletion of the vWF propeptide produced a dimeric vWF molecule lacking N-terminal intersubunit disulfide bonds. This molecule bound fluorescein-labeled factor VIII with sixfold lower affinity than multimeric vWF in an equilibrium flow cytometry assay (approximate KDs, 5 nmol/L v 0.9 nmol/L). Coexpression of propeptide-deleted vWF with the vWF propeptide in trans yielded multimeric vWF that displayed increased affinity for factor VIII. Insertion of an alanine residue at the N-terminus of the mature vWF subunit destroyed binding to factor VIII, indicating that the native mature N-terminus is required for factor VIII binding. The requirement for vWF propeptide cleavage was shown by (1) a point mutation of the vWF propeptide cleavage site yielding pro-vWF that was defective in factor VIII binding and (2) correlation between efficiency of intracellular propeptide cleavage and factor VIII binding. Furthermore, in a cell-free system, addition of the propeptide-cleaving enzyme PACE/furin enabled factor VIII binding in parallel with propeptide cleavage. Our results indicate that high-affinity factor VIII binding sites are located on N-terminal disulfide-linked vWF subunits from which the propeptide has been cleaved.

Binding Sites↗