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Biomedical subjects

D G Thompson

Publications and source records attributed to D G Thompson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Laterality effects of human pudendal nerve stimulation on corticoanal pathways: evidence for functional asymmetry.

BACKGROUND: Although motor and sensory pathways to the human external anal sphincter are bilateral, a unilateral pudendal neuropathy may still disrupt anal continence. Anal continence can, however, be preserved despite unilateral pudendal damage, and so to explain those differing observations, we postulated that pudendal innervation might be asymmetric. AIMS: To explore the individual effects of right and left pudendal nerve stimulation on the corticofugal pathways to the human external anal sphincter and thus assess evidence for functional asymmetric pelvic innervation. METHODS: In eight healthy subjects, anal sphincter electromyographic responses, evoked to transcranial magnetic stimulation of the motor cortex, were recorded 5-500 msec after digital transrectal electrical conditioning stimuli applied to each pudendal nerve. RESULTS: Right or left pudendal nerve stimulation evoked anal responses of similar latencies but asymmetric amplitudes in six subjects: dominant responses (>50% contralateral side) from the right pudendal in four subjects and from the left in two. Cortical stimulation also evoked anal responses with amplitude 448 (121) microV and latency 20.9 (1.1) msec. When cortical stimulation was preceded by pudendal nerve stimulation, the cortical responses were facilitated at interstimulus intervals of 5-20 msec. Dominant pudendal nerve stimulation induced greater facilitation of the cortically evoked responses than the non-dominant nerve. CONCLUSIONS: Cortical pathways to the external anal sphincter are facilitated by pudendal nerve conditioning, in an asymmetric manner. This functional asymmetry may explain the presence and absence of anal incontinence after unilateral pudendal nerve injury.

Adult↗
PubMed1999

Principles of applied neurogastroenterology: physiology/motility-sensation.

Many of the symptoms characteristic of the functional gastrointestinal disorders (FGID) are consistent with dysfunction of the motor and/or sensory apparatus of the digestive tract. Those aspects of sensorimotor dysfunction most relevant to the FGID include alterations in: gut contractile activity; myoelectrical activity; tone and compliance; and transit, as well as an enhanced sensitivity to distension, in each region of the gastrointestinal tract. Assessment of these phenomena involves a number of techniques, some well established and others requiring further validation. Using such techniques, researchers have reported a wide range of alterations in sensory and in motor function in the FGID. Importantly, however, relationships between such dysfunction and symptoms have been relatively weak, and so the clinical relevance of the former remains unclear. Moreover, the proportions of patients in the various symptom subgroups who display dysfunction, and the extent and severity of their symptoms, require better characterization. On a positive note, progress is occurring on several fronts, especially in relation to functional dyspepsia and irritable bowel syndrome, and based on the data gathered to date, a number of areas where further advances are required can be highlighted.

Colonic Diseases, Functional↗
PubMed1999

Identification of the cerebral loci processing human swallowing with H2(15)O PET activation.

Lesional and electrophysiological data implicate a role for the cerebral cortex in the initiation and modulation of human swallowing, and yet its functional neuroanatomy remains undefined. We therefore conducted a functional study of the cerebral loci processing human volitional swallowing with 15O-labeled water positron emission tomography (PET) activation imaging. Regional cerebral activation was investigated in 8 healthy right handed male volunteers with a randomized 12-scan paradigm of rest and water swallows (5 ml/bolus, continuous infusion) at increasing frequencies of 0.1, 0.2, and 0.3 Hz, which were visually cued and monitored with submental electromyogram (EMG). Group and individual linear covariate analyses were performed with SPM96. In five of eight subjects, the cortical motor representation of pharynx was subsequently mapped with transcranial magnetic stimulation (TMS) in a posthoc manner to substantiate findings of hemispheric differences in sensorimotor cortex activation seen with PET. During swallowing, group PET analysis identified increased regional cerebral blood flow (rCBF) (P < 0.001) within bilateral caudolateral sensorimotor cortex [Brodmann's area (BA) 3, 4, and 6], right anterior insula (BA 16), right orbitofrontal and temporopolar cortex (BA 11 and 38), left mesial premotor cortex (BA 6 and 24), left temporopolar cortex and amygdala (BA 38 and 34), left superiomedial cerebellum, and dorsal brain stem. Decreased rCBF (P < 0.001) was also observed within bilateral posterior parietal cortex (BA 7), right anterior occipital cortex (BA 19), left superior frontal cortex (BA 8), right prefrontal cortex (BA 9), and bilateral superiomedial temporal cortex (BA 41 and 42). Individual PET analysis revealed asymmetric representation within sensorimotor cortex in six of eight subjects, four lateralizing to right hemisphere and two to left hemisphere. TMS mapping in the five subjects identified condordant interhemisphere asymmetries in the motor representation for pharynx, consistent with the PET findings. We conclude that volitional swallowing recruits multiple cerebral regions, in particular sensorimotor cortex, insula, temporopolar cortex, cerebellum, and brain stem, the sensorimotor cortex displaying strong degrees of interhemispheric asymmetry, further substantiated with TMS. Such findings may help explain the variable nature of swallowing disorders after stroke and other focal lesions to the cerebral cortex.

Adult↗
PubMed1998

Fatty acids stimulate cholecystokinin secretion via an acyl chain length-specific, Ca2+-dependent mechanism in the enteroendocrine cell line STC-1.

1. The present study has investigated whether fatty acids directly influence peptide release from enteroendocrine cells using STC-1, a mouse intestinal endocrine tumour cell line, previously shown to release cholecystokinin (CCK) in response to other physiological stimuli. 2. Fatty acids elicited a chain length- and dose-dependent stimulation of CCK secretion. Dodecanoic acid (C12) was most effective, producing up to a 5-fold increase in CCK secretion. Fatty acids with less than ten carbon atoms did not increase secretion. The chain length dependence of these effects mimics closely fatty acid-induced CCK secretion previously observed in humans in vivo. 3. Esterification of C12 abolished CCK secretion, indicating a critical role for a free carboxyl group in eliciting secretion. In contrast, modification of the methyl terminus had no effect on C12-induced secretion. The non-metabolizable C12 analogue 2-bromododecanoic acid was equally effective. 4. C12 elicited a marked increase in intracellular calcium levels (200-300 nM) in STC-1 cells which was abolished by the L-type Ca2+ channel antagonist nicardipine. In contrast, C8 produced a smaller and more transient Ca2+ response. C12-induced CCK secretion was also blocked by nicardipine. 5. These data suggest that fatty acids can interact directly with enteroendocrine cells to stimulate CCK secretion via increases in intracellular calcium mediated primarily by L-type Ca2+ channels.

Animals↗
PubMed1998

Sensorimotor modulation of human cortical swallowing pathways.

1. Transcranial magnetic stimulation over motor areas of cerebral cortex in man can activate short latency bilateral cortical projections to the pharynx and oesophagus. In the present paper we investigate the interaction between pathways from each hemisphere and explore how activity in these pathways is modulated by afferent feedback from the face, pharynx and oesophagus. 2. Comparison of unilateral and bilateral stimulation (using interstimulus intervals (ISIs) of 1, 5 or 10 ms between shocks) showed spatial summation of responses from each hemisphere at an ISI of 1 ms, indicating that cortical efferents project onto a shared population of target neurones. Such summation was not evident at ISIs of 5 or 10 ms. There was little evidence for transcallosal inhibition of responses from each hemisphere, as described for limb muscles. 3. Single stimuli applied to the vagus nerve in the neck or the supraorbital nerve, which alone produce intermediate (onset 20-30 ms) and long (50-70 ms) latency reflex responses in the pharynx and oesophagus, were used to condition the cortical responses. Compared with rest, responses evoked by cortical stimulation were facilitated when they were timed to coincide with the late part of the reflex. The onset latency was reduced during both parts of the reflex response. No facilitation was observed with subthreshold reflex stimuli. 4. Single electrical stimuli applied to the pharynx or oesophagus had no effect on the response to cortical stimulation. However, trains of stimuli at frequencies varying from 0.2 to 10 Hz decreased the latency of the cortically evoked responses without consistently influencing their amplitudes. The effect was site specific: pharyngeal stimulation shortened both pharyngeal and oesophageal response latencies, whereas oesophageal stimulation shortened only the oesophageal response latencies. 5. Cortical swallowing motor pathways from each hemisphere interact and their excitability is modulated in a site-specific manner by sensory input. The latter may produce a mixture of excitation and inhibition at both brainstem and cortical levels.

Adult↗
PubMed1998

Recovery of swallowing after dysphagic stroke relates to functional reorganization in the intact motor cortex.

BACKGROUND & AIMS: The aim of this study was to determine the mechanism for recovery of swallowing after dysphagic stroke. METHODS: Twenty-eight patients who had a unilateral hemispheric stroke were studied 1 week and 1 and 3 months after the stroke by videofluoroscopy. Pharyngeal and thenar electromyographic responses to magnetic stimulation of multiple sites over both hemispheres were recorded, and motor representations were correlated with swallowing recovery. RESULTS: Dysphagia was initially present in 71% of patients and in 46% and 41% of the patients at 1 and 3 months, respectively. Cortical representation of the pharynx was smaller in the affected hemisphere (5 +/- 1 sites) than the unaffected hemisphere (13 +/- 1 sites; P </= 0.001). Nondysphagic and persistently dysphagic patients showed little change in pharyngeal representation in either hemisphere at 1 and 3 months compared with presentation, but dysphagic patients who recovered had an increased pharyngeal representation in the unaffected hemisphere at 1 and 3 months (15 +/- 2 and 17 +/- 3 vs. 9 +/- 2 sites; P </= 0.02) without change in the affected hemisphere. In contrast, thenar representation increased in the affected hemisphere but not the unaffected hemisphere at 1 and 3 months (P </= 0.01). CONCLUSIONS: Return of swallowing after dysphagic stroke is associated with increased pharyngeal representation in the unaffected hemisphere, suggesting a role for intact hemisphere reorganization in recovery.

Aged↗
PubMed1998

Octreotide suppression test predicts beneficial outcome from antrectomy in a patient with gastric carcinoid tumor.

Multiple gastric carcinoids are a well-recognized complication of hypergastrinemia associated with chronic atrophic gastritis. However, the management of large tumors (>2 cm in diameter) remains uncertain, with the decision between antrectomy or total gastrectomy being empirical. This report describes the investigation of a patient with chronic atrophic gastritis and multiple large gastric carcinoid tumors. Before surgery, octreotide was infused for 72 hours to suppress enterochromaffin-like (ECL) cell and gastrin cell function. The infusion decreased plasma gastrin and gastrin synthesis; moreover, there were marked reductions in markers of ECL cell function, e.g., histidine decarboxylase and chromogranin A messenger RNA abundance, in carcinoid tumor tissue and macroscopically normal corpus mucosa. An antrectomy was performed, after which the patient made an uneventful recovery. Six months after surgery, a single residual polyp, enriched with smooth muscle cells but not ECL cells, was removed. One year after antrectomy, the remaining stomach was normal. The response of ECL cell markers in carcinoid tissue to octreotide suggested that these cells were under neuroendocrine control and, therefore, predicted a beneficial outcome for antrectomy. It is suggested that an octreotide supression test coupled with assay of histidine decarboxylase or chromogranin A gene expression is useful in the assessment of gastric carcinoid tumors.

Adult↗
PubMed1998

Cortical localisation of magnetic fields evoked by oesophageal distension.

Magnetoencephalographic source localisation techniques were used to measure oesophageal evoked magnetic fields from the cerebral cortex in 3 subjects. By using rapid balloon distension as a stimulus, a comparison of proximal and distal oesophageal cortical representation was made. The distal oesophagus was represented bilaterally in the insular cortex and SII as well as the inferior aspect of SI. The proximal oesophagus was represented unilaterally in superior and inferior SI, insular cortex and SII. Significantly, the superior portion of SI was consistently activated in subjects following stimulation of the proximal oesophagus, but similar activation was not found in response to distal stimulation. This may reflect the contribution from somatic afferent fibres in the striate muscle of the proximal segment. In conclusion, vagal afferents appear to contribute more to cortical activation following stimulation of the distal rather than the proximal oesophagus, while spinal afferents appear to be activated by both proximal and distal oesophageal stimulation.

Adult↗
PubMed1998

Long-term reorganization of human motor cortex driven by short-term sensory stimulation.

Removal of sensory input can induce changes in cortical motor representation that reverse when sensation is restored. Here we ask whether manipulation of sensory input can induce long-term reorganization in human motor cortex that outlasts the initial conditioning. We report that for at least 30 minutes after pharyngeal stimulation, motor cortex excitability and area of representation for the pharynx increased, while esophagus representation decreased, without parallel changes in the excitability of brainstem-mediated reflexes. Therefore increased sensory input can drive long-term cross-system changes in motor areas of the cerebral cortex, which suggests that sensory stimulation might rehabilitate dysphagia, a frequent consequence of cerebral injury.

Adult↗
PubMed1998

Identification of the optimal parameters for recording cortical evoked potentials to human oesophageal electrical stimulation.

Cortical evoked potentials in response to stimulation of the oesophagus may prove to be a powerful technique for assessing the oesophageal afferent pathway in health and disease. However, in order to maximize the potential of this technique it is essential that the optimal parameters for recording oesophageal CEP are established. The aim was to determine the optimal parameters required to record reproducible CEP. CEP were recorded from the vertex in eight subjects (age range 23-44 years). Electrical stimulation was performed 5 cm above the lower oesophageal sphincter using a bipolar ring electrode at 0.2 Hz. Protocol 1: to determine the stimulation intensity which generates the largest amplitude and shortest latency, two runs of 50 stimuli were applied at increasing intensities. Protocol 2: to determine the number of stimuli for optimal signal to noise ratio, 10 runs of 50 stimuli were recorded. Individual runs were averaged. Protocol 3: to determine the optimal inter-run interval, CEP evoked by 200 stimuli were averaged using randomly chosen inter-run intervals. Protocol 4: CEP reproducibility using parameters determined from Protocols 1-3 was assessed in three subjects on three separate occasions. The results were as follows: Protocol 1; P1 latency was shortest and P1-N1 amplitude largest at an intensity of 75% above threshold. Protocol 2; optimal signal-to-noise was achieved by averaging four runs of 50 stimuli. Protocol 3; the optimal interstudy interval was 10 min. Protocol 4; highly reproducible CEP were obtained in all individuals. Using these optimal parameters, it is possible to obtain highly reproducible oesophageal CEP to ES which can now be used for clinical study.

Adult↗
PubMed1998

Evidence for a lipid specific effect in nutrient induced human proximal gastric relaxation.

BACKGROUND/AIM: The presence of lipid in the upper gut is able to modify gastrointestinal motor performance, but its influence on the relaxation of the human stomach, which is known to modify gastric emptying, remains incompletely understood. The relaxation of the proximal stomach in response to various lipid concentrations was therefore studied in healthy volunteers. Since the observed effects could be mediated through osmolality or energy sensitive pathways, the effects of equicaloric and equiosmolar non-lipid solutions were also determined. METHODS: The tone of the proximal stomach was measured during stepwise inflation of a non-compliant bag sited in the proximal stomach, both before and after a test meal was delivered intragastrically. Iso-osmolar lipid emulsions were diluted in iso-osmolar saline at concentrations of 1.25, 2.5, 5, 10, and 20%. NaCl solutions at osmolalities of 300, 600, 1200 and 2400 mmol/kg and glucose solutions of 836 and 3344 kJ/l were also given. RESULTS: All lipid meals of 2.5% or greater concentration induced a reduction in gastric tone in a non-dose-dependent manner, responses to 5% lipid (median (range) 74 (62-92)%) being similar to those to 20% lipid (80 (55-83)%; p > 0.05). No relaxation was elicited by isocaloric glucose. NaCl only consistently caused relaxation at 2400 mmol/kg. CONCLUSION: Lipid meals reduce human proximal gastric tone by a lipid specific mechanism, independently of their energy content or osmolality.

Adult↗
PubMed1998

Spinal and pudendal nerve modulation of human corticoanal motor pathways.

We investigated the effects of lumbosacral and pudendal nerve stimulation on the corticofugal pathways to the human external anal sphincter. In 11 healthy subjects, anal sphincter electromyographic responses, evoked to transcranial magnetic stimulation of the motor cortex, were recorded 5-500 ms after lumbosacral root or pudendal nerve stimulation. Lumbosacral and pudendal nerve stimulation alone evoked responses with amplitudes of 293 +/- 73 and 401 +/- 153 microV and latencies of 3.2 +/- 0.2 and 2.2 +/- 0.2 ms, respectively. Cortical stimulation also evoked responses with amplitudes of 351 +/- 104 microV and latencies of 20.9 +/- 1.1 ms. When lumbosacral or pudendal nerve stimulation preceded cortical stimulation, the cortically evoked responses were facilitated (P < 0.01), with the effect appearing greatest at 5-20 ms after both lumbosacral and pudendal excitation and at 50-100 ms after lumbosacral excitation alone. Our results demonstrate that cortical pathways to the external anal sphincter are facilitated by prior lumbosacral and pudendal nerve stimulation, indicating that sensorimotor interactions are important in the central neural control of sphincter function.

Adult↗
PubMed1998

Experiences with functional magnetic resonance imaging at 1 tesla.

Functional magnetic resonance imaging (fMRI) has been performed on a standard 1 T system using a pulse sequence developed to utilize blood oxygen level dependent (BOLD) contrast and an off-line analysis routine using correlation techniques. The sequence and the data analysis routine have been validated by reproducing the conventional hand movement paradigm studies reported by numerous other workers. Our work has then been extended to investigate cerebral foci for a tonic pain stimulus and the cortical representation of oesophageal stimulation. Both these studies relate to paradigms where the expected BOLD signal is significantly less than that encountered for motor or visual cortex paradigms. The results show good agreement with other modalities (positron emission tomography, magnetoencephalography and cortical evoked potentials). Performing fMRI at 1 T is slightly controversial. However, our successful study of demanding paradigms, using a standard clinical 1 T imaging system, has important implications for many other users operating at this field strength.

Brain↗
PubMed1997

Explaining oropharyngeal dysphagia after unilateral hemispheric stroke.

BACKGROUND: Oropharyngeal dysphagia occurs in up to a third of patients presenting with a unilateral hemiplegic stroke, yet its neurophysiological basis remains unknown. To explore the relation between cortical motor function of swallowing and oropharyngeal dysphagia, mylohyoid, pharyngeal, and thenar electromyographic responses to stimulation of affected and unaffected hemispheres were recorded in dysphagic and non-dysphagic patients. METHODS: The 20 patients studied had unilateral hemispheric stroke confirmed by computed tomography. Eight of them had associated swallowing difficulties. Electromyographic responses were recorded after suprathreshold transcranial magneto-electric stimulation of affected and unaffected hemispheres with a figure-of-eight coil. FINDINGS: Stimulation of the unaffected hemisphere evoked smaller pharyngeal responses in dysphagic patients than in non-dysphagic patients (mean 64 microV, median 48, interquartile range 44-86 vs 118 microV, 81, 73-150) (p < 0.02). With stimulation of the affected hemisphere, the pharyngeal responses were smaller than for the unaffected hemisphere but similar between the two patient groups (26 microV, 0, 0-48 vs 54 microV, 0, 0-80). Dysphagic and non-dysphagic patients showed similar mylohyoid and thenar responses to stimulation of the unaffected hemisphere as well as to stimulation of the affected hemisphere-unaffected mylohyoid (269 microV, 239, 89-372 vs 239 microV, 163, 133-307), thenar (572 microV, 463, 175-638 vs 638 microV, 485, 381-764); affected mylohyoid (60 microV, 41, 0-129 vs 96 microV, 0, 0-195); thenar (259 microV, 258, 0-538 vs 451 microV, 206, 8-717). INTERPRETATION: The findings indicate that dysphagia after unilateral hemispheric stroke is related to the magnitude of pharyngeal motor representation in the unaffected hemisphere.

Adult↗
PubMed1997

Increased sensitivity of gastrin cells to gastric distension following antral denervation in the rat.

1. Secretion of the antral hormone gastrin is increased by protein in the gastric lumen and by nervous reflexes. We have examined the relative importance of luminal and neuronal mechanisms, by lesioning the antral innervation using benzalkonium chloride. 2. Benzalkonium chloride was applied to the serosa of the antrum in anaesthetized rats. In some animals, a stainless-steel cannula was also implanted in the corpus. Animals were allowed 10 days to recover. Plasma gastrin was measured by radioimmunoassay and mRNAs encoding gastrin, somatostatin and histidine decarboxylase were measured by Northern blot. 3. Antral denervation was associated with gastric retention after fasting, and elevated plasma gastrin (28.4 +/- 7 pM compared with 7.6 +/- 1.0 pM in controls). When fasted control or denervated rats were refed, plasma gastrin increased 3-fold in both cases. A gastrin-releasing peptide antagonist inhibited the post-prandial rise in plasma gastrin in control rats, but had no effect in antrally denervated rats. 4. In fasted, antrally denervated rats with a gastric fistula, basal gastric acid secretion was depressed 3-fold, and plasma gastrin concentrations were similar to controls. 5. Distension of the stomach with peptone via a barostat attached to the gastric cannula (5 cm H2O, 30 min), produced 3-fold increases in plasma gastrin in both control and denervated rats. However, distension with a non-nutrient solution at pH 6.0 had no effect in controls, but increased gastrin to a similar extent to peptone in denervated rats; distension with 50 mM HCl had no effect in either control or denervated rats. 6. Somatostatin and gastrin mRNA abundances in the antrum were depressed by about 35% by antral denervation, but somatostatin mRNA in the corpus was unchanged; GAPDH mRNA abundance was unaffected by antral denervation. 7. The data suggest that luminal nutrient releases gastrin in the rat, in vivo, via activation of antral neurons secreting gastrin-releasing peptide, and that the antral innervation normally inhibits G-cell responses to non-nutrient distension of the stomach. After antral denervation, gastric distension with a non-nutrient solution is an adequate stimulus for gastrin release.

Animals↗
PubMed1997

Identification of human brain loci processing esophageal sensation using positron emission tomography.

BACKGROUND & AIMS: Brain loci that process human esophageal sensation remain unidentified. The aim of this study was to identify the brain loci that process nonpainful and painful human esophageal sensation. METHODS: In 8 healthy subjects (7 men; age range, 24-47 years), distal esophageal stimulation was performed by repeatedly inflating a balloon at volumes that produced either no sensation, definite sensation, or pain. Two positron emission tomography scans were performed for each sensation using H2(15)O. Magnetic resonance brain scans were also performed in each subject, and the positron emission tomography data were coregistered with magnetic resonance scans. Analysis of covariance-corrected t images showing the contrasts definite sensation-baseline, pain-baseline, and pain-definite sensation were created. RESULTS: Nonpainful stimulation elicited bilateral activations along the central sulcus, insular cortex, and frontal/parietal operculum (P < 0.01). Painful stimulation produced more intense activations of the same areas and additional activation of the right anterior insular cortex and the anterior cingulate gyrus. Multiple areas of decreased activation were also observed; prominent among these was the right prefrontal cortex, which was inhibited during both nonpainful and painful stimulation. CONCLUSIONS: Esophageal sensation activates bilaterally the insula, primary somatosensory cortex, and operculum. The right anterior insular cortex and anterior cingulate gyrus process esophageal pain.

Adult↗