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Biomedical subjects

J M Clarke

Publications and source records attributed to J M Clarke.

At least 37 records · Page 2Linked to original sources

Auditory and visual sensory representations in human prefrontal cortex as revealed by stimulus-evoked spike-wave complexes.

Multimodal sensory properties of the prefrontal cortex have been extensively studied in monkeys, while little is known of such functions in humans. We report electrophysiological evidence for auditory and visual representations in the dorsolateral prefrontal cortex, as inferred from intracerebral 'depth' recordings of focal, sensory-evoked spike-wave complexes (SWC) in an epileptic patient. In addition to clinical monitoring, the patient participated in behavioural evoked potential studies involving auditory and visual discrimination tasks. Inspection of evoked potential recordings from different medial-to-lateral prefrontal sites revealed overlapping, but non-identical topographies of evoked SWC for the two sensory modalities. The maximal activity of sensory-evoked SWC was located 7 mm more medially for visual than for auditory stimuli, and occurred later for visual presentations (mean = 117 ms following stimulus onset) than for auditory ones (mean = 87 ms). Effects of sensory habituation were seen. Evoked SWC were less likely to occur following repeated presentations of an unchanging tone than when tones alternated in pitch, or when a tone followed an omission in stimulus presentation. Visual hemifield effects were found, with greater prefrontal responsiveness to presentations in the contralateral visual hemifield. These results are consistent with electrophysiological findings in animals indicating overlapping auditory and visual representations in the dorsolateral prefrontal cortex.

Adult↗

Anatomical-behavioral relationships: corpus callosum morphometry and hemispheric specialization.

We obtained midsagittal measures of the corpus callosum in 60 healthy young adults (right-handed and left-handed males and females), and examined whether individual differences in anatomical measures of callosal connectivity are related to behavioral laterality measures in the same subjects. In an attempt to tap functionally-distinct callosal "channels", four behavioral laterality tasks were used that differed in sensory modality (visual, auditory, tactile) and/or level of cognitive processing (sensory versus semantic). In addition, the tasks had both intrahemispheric and interhemispheric conditions. Sex differences were found for measures of the posterior body (i.e. isthmus) of the corpus callosum, which, in turn, interacted with handedness. In contrast, only handedness effects were found for the behavioral laterality measures. Anatomical-behavioral correlations did not disclose relationships between callosal size and performance on task conditions requiring sensory interhemispheric integration or transfer. Instead, the correlational findings are consistent with the view that the corpus callosum participates in such higher order "control" functions as the support of bilateral representation of language, functional interhemispheric inhibition, and the maintenance of hemispheric differences in arousal. This is consistent with the finding that regional callosal size is related to the number of small diameter fibers, which are presumed to interconnect homologous association cortices in the two hemispheres.

Adult↗

Spatio-temporal stages in face and word processing. I. Depth-recorded potentials in the human occipital, temporal and parietal lobes [corrected].

Evoked potentials (EPs) were used to help identify the timing, location, and intensity of the information-processing stages applied to faces and words in humans. EP generators were localized using intracranial recordings in 33 patients with depth electrodes implanted in order to direct surgical treatment of drug-resistant epilepsy. While awaiting spontaneous seizure onset, the patients gave their fully informed consent to perform cognitive tasks. Depth recordings were obtained from 1198 sites in the occipital, temporal and parietal cortices, and in the limbic system (amygdala, hippocampal formation and posterior cingulate gyrus). Twenty-three patients received a declarative memory recognition task in which faces of previously unfamiliar young adults without verbalizable distinguishing features were exposed for 300 ms every 3 s; 25 patients received an analogous task using words. For component identification, some patients also received simple auditory (21 patients) or visual (12 patients) discrimination tasks. Eight successive EP stages preceding the behavioral response (at about 600 ms) could be distinguished by latency, and each of 14 anatomical structures was found to participate in 2-8 of these stages. The earliest response, an N75-P105, focal in the most medial and posterior of the leads implanted in the occipital lobe (lingual g), was probably generated in visual cortical areas 17 and 18. These components were not visible in response to words, presumably because words were presented foveally. A focal evoked alpha rhythm to both words and faces was also noted in the lingual g. This was followed by an N130-P180-N240 focal and polarity-inverting in the basal occipitotemporal cortex (fusiform g, probably areas 19 and 37). In most cases, the P180 was evoked only by faces, and not by words, letters or symbols. Although largest in the fusiform g this sequence of potentials (especially the N240) was also observed in the supramarginal g, posterior superior and middle temporal g, posterior cingulate g, and posterior hippocampal formation. The N130, but not later components of this complex, was observed in the anterior hippocampus and amygdala. Faces only also evoked longer-latency potentials up to 600 ms in the right fusiform g. Words only evoked a series of potentials beginning at 190 ms and extending to 600 ms in the fusiform g and near the angular g (especially left). Both words and faces evoked a N150-P200-PN260 in the lingual g, and posterior inferior and middle temporal g.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Spatio-temporal stages in face and word processing. 2. Depth-recorded potentials in the human frontal and Rolandic cortices.

Evoked potentials (EPs) were recorded directly from 650 frontal and peri-Rolandic sites in 26 subjects during face and/or word recognition, as well as during control tasks (simple auditory and visual discrimination). Electrodes were implanted in order to localize epileptogenic foci resistant to medication, and thus direct their surgical removal. While awaiting spontaneous seizure onset, the patients gave informed consent to perform cognitive tasks during intracerebral EEG recording. The earliest potentials appeared to be related to sensory stimulation, were prominent in lateral prefrontal cortex, and occurred at peak latencies of about 150 and 190 ms. A small triphasic complex beginning slightly later (peak latencies about 200-285-350 ms) appeared to correspond to the scalp N2-P3a-slow wave, associated with non-specific orienting. Multiple components peaking from 280 to 900 ms, and apparently specific to words were occasionally recorded in the left inferior frontal g, pars triangularis (Broca's area). Components peaking at about 430 and 600 ms were recorded in all parts of the prefrontal cortex, but were largest (up to 180 microV) and frequently polarity-inverted in the ventro-lateral prefrontal cortex. These components appeared to represent the N4-P3b, which have been associated with contextual integration and cognitive closure. Finally, a late negativity (650-900 ms) was recorded in precentral and premotor cortices, probably corresponding to a peri-movement readiness potential. In summary, EP components related to early sensory processing were most prominent in lateral prefrontal, to orienting in medial limbic, to word-specific processing in Broca's area, to cognitive integration in ventro-lateral prefrontal, and to response organization in premotor cortices.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Corpus callosum morphometry and dichotic listening performance: individual differences in functional interhemispheric inhibition?

We examined the relationship between midsagittal corpus callosum area, as seen by magnetic resonance imaging, and behavioral laterality effects from a dichotic listening task requiring cross-callosal relay of an auditory signal, in 60 healthy young adults. Four patients with complete forebrain commissurotomy were also given the dichotic listening task, confirming that in this task, the report of left ear items is dependent on callosal pathways. Contrary to our predictions, callosum measures were unrelated to either a laterality measure or to inferior (typically left) ear performance. Surprisingly, superior (typically right) ear accuracies, which do not depend on cross-callosal sensory transfer, were significantly and negatively correlated with callosum size. These findings show that normal variations in callosum size do not appear to contribute significantly to individual differences in hemispheric specialization. Callosum size may, instead, be associated with degree of functional interhemispheric inhibition.

Acoustic Stimulation↗

Plasma lipids and large bowel volatile fatty acids in pigs fed on white rice, brown rice and rice bran.

Adult male pigs were fed on a diet containing (% of energy) fat 25 starch 55 from white rice and providing 20 g fibre/pig d (diet WR). In two other groups rice bran was added to the diet to provide 43 g fibre/d. One group received the diet unmodified (diet RB), but in another (diet RO) heat-stabilized unrefined rice oil replaced the palm oil. In a further group brown rice replaced white rice and provided 37 g fibre/pig per d (diet BR). Plasma cholesterol concentrations were similar with diets WR, RB and BR. With diet RO the concentration was significantly lower than with diets WR and BR but was not different from diet RB. Plasma high-density-lipoprotein-cholesterol and plasma triacylglycerols were unaffected by diet. In all groups, digesta mass rose from the caecum to the proximal colon but fell in the distal colon. Diet WR gave the lowest digesta mass while diet BR gave a significantly higher mass along the large bowel length. RB- and RO-fed pigs had equal masses of digesta which were intermediate between BR- and WR-fed pigs at all sampling sites. Pools of individual and total volatile fatty acids (VFA) in the proximal large bowel were unaffected by diet. Pools of total and individual VFA in the median and distal colon were lowest with diets WR and RB and significantly higher with diet BR. In these regions of the colon pools of acetate in RO-fed pigs did not differ from those in the BR-fed group but were higher than in other groups. However, pools of propionate and butyrate with the RO diet were significantly lower than with diet BR and the same as with diets WR and RB. Portal venous VFA concentrations were unaffected by diet. The higher large bowel digesta masses and VFA with diet BR may reflect the escape of starch from the small intestine.

Animals↗

Dietary fat and fiber alter large bowel and portal venous volatile fatty acids and plasma cholesterol but not biliary steroids in pigs.

Male pigs were fed a low fiber beef diet (control) or that diet with additional fiber either as wheat bran, oat bran or baked beans. Total large bowel digesta and volatile fatty acid (VFA) pools were highest in pigs fed the diet with baked beans, intermediate in those fed the diets with oat bran and wheat bran and lowest in those fed the control diet. In all groups digesta mass and total VFA pools rose from the cecum and then fell to the distal colon, and incremental effects of diet were the same at all sampling sites. For acetate and propionate pools there was a significant interaction between diet and anatomical site, but data conversion to logarithms abolished this interaction, indicating that all dietary effects were proportionately the same across sections. Consumption of the diets with wheat bran, oat bran and baked beans increased the total large bowel butyrate pool compared with consumption of the control diet. Digesta H+ concentrations fell along the large bowel and correlated positively with VFA concentrations in the median colon. Portal venous VFA concentrations correlated with VFA in the proximal colon only. Plasma cholesterol and biliary steroids were unrelated to portal venous propionate concentrations.

Animals↗

Non-steroidal anti-inflammatory drug-induced jejunal and colonic diaphragm disease: a report of two cases.

Two patients with intestinal submucosal diaphragm disease associated with non-steroidal anti-inflammatory drugs are presented. The jejunum was affected in one, and in the other the ascending colon. Most previously reported cases have shown ileal disease and no case to date has shown involvement of the colon. The reasons for the localisation of these diaphragms remain unclear.

Aged↗

A phase II study of ifosfamide and cisplatin chemotherapy for metastatic or relapsed carcinoma of the cervix.

A total of 44 women received a combination of ifosfamide (1.5 g/m2 daily x5) and cisplatin (50 mg/m2 on day 1 only) as first-line chemotherapy for recurrent or metastatic carcinoma of the cervix. In all, 12/42 (38%) evaluable patients responded, with the median duration of response being 7 months. Bone marrow and gastrointestinal toxicity were frequently severe. There were 3 septic deaths. Although cisplatin plus ifosfamide is an active combination against this disease, these results suggest that it is no more so than either drug used alone.

Adult↗

Molecular genetic evidence for common pathogenesis of childhood and adult Wilms' tumor.

A case of Wilms' tumor in an adult is reported, showing, by restriction fragment length polymorphism analysis of somatic and tumor DNA, the loss of alleles from the short arm of chromosome 11. Loss of alleles in this region has previously been reported in childhood Wilms' tumor. The findings of this study indicate that adult Wilms' tumor and childhood Wilms' tumor may share a common pathogenic pathway. These results may also be useful in differentiating between Wilms' tumor and renal cell carcinoma or sarcoma in adults when the histologic findings are unclear.

Adult↗

Simple reaction times to lateralized light flashes. Varieties of interhemispheric communication routes.

Simple unimanual reaction times to lateralized light flashes were measured in 40 normal subjects, 4 commissurotomized patients, and a boy with callosal agenesis. In all subjects, reaction times tended to be shorter when the stimuli were presented on the same side as the response hand (uncrossed condition) than on the opposite side (crossed condition). In 2 experiments, the magnitude of the crossed-uncrossed difference (CUD) was greatest in the commissurotimized patients (ranging from 35 to 96 ms), the acallosal boy showed an intermediate CUD (20 and 12 ms for the first and second experiment, respectively), and normal subjects exhibited the smallest CUD (an insignificant 1 ms difference and a significant 3 ms difference in the first and second experiment, respectively). For all subjects, reaction times increased when the stimulus light intensity was decreased (Experiment 1) or when stimulus eccentricity was increased (Experiment 2). However, the effects of these visual parameters on the CUD revealed group and individual differences. Neither stimulus light intensity nor eccentricity affected the CUD in the normals, in 1 of the commissurotomized patients, and in the acallosal boy. The CUDs in these subjects are attributed to the transfer of nonsensory information via the corpus callosum, via ipsilateral corticospinal tracts, and via the anterior commissure or ipsilateral motor pathways, respectively. The CUDs of 2 commissurotomized patients varied with stimulus eccentricity but not intensity. Subcallosal interhemispheric visual transfer is thus apparently more sensitive to stimulus eccentricity than to intensity. The final commissurotomized patient, R.Y., had slower and less accurate responses to stimuli presented in the right visual hemifield during left, but not right, hand responses. An asymmetry in subcortical visual interhemispheric communication is suspected in this patient. The disparate results amongst these subjects are discussed and contrasted with previous findings. Finally, an information processing model of cortical and subcortical interhemispheric communication is presented.

Agenesis of Corpus Callosum↗

Effects of autologous mesothelial cell seeding on prostacyclin production within Dacron arterial prostheses.

Canine abdominal aortas have been replaced with Dacron arterial prostheses to assess the effects of mesothelial cell seeding on graft prostacyclin and thromboxane A2 release. At both 2 weeks and 6 weeks after surgery, three seeded and two unseeded control grafts were examined for prostacyclin release. In addition, thromboxane release was assessed in one seeded and one unseeded graft. Sections of aorta and graft were removed and incubated in PBS containing either 10 microM calcium ionophore A23187 or 20 microM arachidonic acid. The incubation mixture was sub-sampled at 5 min intervals over a 20 min period to assess the progressive release of prostacyclin and thromboxane A2 using a radioimmunoassay for 6-keto-prostaglandin F1 alpha and thromboxane B2 respectively. In seeded grafts, 6-keto-prostaglandin F1 alpha release averaged 15 per cent compared with aorta at 2 weeks and 45 per cent compared with aorta at 6 weeks. By contrast, release from unseeded grafts was undetectable at 2 weeks; however, by 6 weeks there was some release amounting to 15 per cent compared with aorta. There was a statistically significant increase in the release of 6-keto-prostaglandin F1 alpha from mesothelial cell seeded grafts at 6 weeks compared with unseeded grafts (P less than 0.01). Thromboxane release from the graft sections was variable and unrelated to whether the grafts had been seeded or not. These preliminary results, showing that grafts seeded with autologous peritoneal mesothelial cells release more prostacyclin than unseeded grafts, further highlight the role of the mesothelial cell as an alternative to the endothelial cell for improving the patency of arterial Dacron prostheses in the early postoperative days.

Animals↗