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Biomedical subjects

G F Egan

Publications and source records attributed to G F Egan.

At least 19 recordsLinked to original sources

Emotional prosodic processing in auditory hallucinations.

Deficits in emotional prosodic processing, the expression of emotions in voice, have been widely reported in patients with schizophrenia, not only in comprehending emotional prosody but also expressing it. Given that prosodic cues are important in memory for voice and speaker identity, Cutting has proposed that prosodic deficits may contribute to the misattribution that appears to occur in auditory hallucinations in psychosis. The present study compared hallucinating patients with schizophrenia, non-hallucinating patients and normal controls on an emotional prosodic processing task. It was hypothesised that hallucinators would demonstrate greater deficits in emotional prosodic processing than non-hallucinators and normal controls. Participants were 67 patients with a diagnosis of schizophrenia or schizoaffective disorder (hallucinating=38, non-hallucinating=29) and 31 normal controls. The prosodic processing task used in this study comprised a series of semantically neutral sentences expressed in happy, sad and neutral voices which were rated on a 7-point Likert scale from sad (-3) through neutral (0) to happy (+3). Significant deficits in the prosodic processing tasks were found in hallucinating patients compared to non-hallucinating patients and normal controls. No significant differences were observed between non-hallucinating patients and normal controls. In the present study, patients experiencing auditory hallucinations were not as successful in recognising and using prosodic cues as the non-hallucinating patients. These results are consistent with Cutting's hypothesis, that prosodic dysfunction may mediate the misattribution of auditory hallucinations.

Adult↗

Functional connectivity of the prefrontal cortex in Huntington's disease.

BACKGROUND: Huntington's disease is a progressive neurodegenerative disorder that results in deterioration and atrophy of various brain regions. AIM: To assess the functional connectivity between prefrontal brain regions in patients with Huntington's disease, compared with normal controls, using functional magnetic resonance imaging. PATIENTS AND METHODS: 20 patients with Huntington's disease and 17 matched controls performed a Simon task that is known to activate lateral prefrontal and anterior cingulate cortical regions. The functional connectivity was hypothesised to be impaired in patients with Huntington's disease between prefrontal regions of interest, selected from both hemispheres, in the anterior cingulate and dorsal lateral prefrontal cortex. RESULTS: Controls showed a dynamic increase in interhemispheric functional connectivity during task performance, compared with the baseline state; patients with Huntington's disease, however, showed no such increase in prefrontal connectivity. Overall, patients with Huntington's disease showed significantly impaired functional connectivity between anterior cingulate and lateral prefrontal regions in both hemispheres compared with controls. Furthermore, poor task performance was predicted by reduced connectivity in patients with Huntington's disease between the left anterior cingulate and prefrontal regions. CONCLUSIONS: This finding represents a loss of synchrony in activity between prefrontal regions in patients with Huntington's disease when engaged in the task, which predicted poor task performance. Results show that functional interactions between critical prefrontal regions, necessary for cognitive performance, are compromised in Huntington's disease. It is speculated whether significantly greater levels of activation in patients with Huntington's disease (compared with controls) observed in several brain regions partially compensate for the otherwise compromised interactions between cortical regions.

Adult↗

Motor imagery in Parkinson's disease: a PET study.

We used positron emission tomography (PET) with 15O-labelled water to record patterns of cerebral activation in six patients with Parkinson's disease (PD), studied when clinically "off" and after turning "on" as a result of dopaminergic stimulation. They were asked to imagine a finger opposition movement performed with their right hand, externally paced at a rate of 1 Hz. Trials alternating between motor imagery and rest were measured. A pilot study of three age-matched controls was also performed. We chose the task as a robust method of activating the supplementary motor area (SMA), defects of which have been reported in PD. The PD patients showed normal degrees of activation of the SMA (proper) when both "off" and "on." Significant activation with imagining movement also occurred in the ipsilateral inferior parietal cortex (both "off" and when "on") and ipsilateral premotor cortex (when "off" only). The patients showed significantly greater activation of the rostral anterior cingulate and significantly less activation of the left lingual gyrus and precuneus when performing the task "on" compared with their performance when "off." PD patients when imagining movement and "off" showed less activation of several sites including the right dorsolateral prefrontal cortex (DLPFC) when compared to the controls performing the same task. No significant differences from controls were present when the patients imagined when "on." Our results are consistent with other studies showing deficits of pre-SMA function in PD with preserved function of the SMA proper. In addition to the areas of reduced activation (anterior cingulate, DLPFC), there were also sites of activation (ipsilateral premotor and inferior parietal cortex) previously reported as locations of compensatory overactivity for PD patients performing similar tasks. Both failure of activation and compensatory changes are likely to contribute to the motor deficit in PD.

Aged↗

Updating working memory for words: a PET activation study.

A PET study of 10 normal individuals was carried out to investigate the cerebral regions involved in the controlled updating of verbal working memory. Subjects viewed single concrete words on a computer monitor and detected occasional target words in an attended color. In the activating condition, a target was defined as a word that was identical to the previous word presented in the attended color. In the control condition, the target was a predesignated word. The same word lists, target probabilities, and target response demands were used for both conditions, with interword intervals constrained to ensure equivalence in the demand for target rehearsal. A comparison of the conditions found bilateral activation of dorsolateral prefrontal (middle frontal gyrus; MFG) and inferior parietal (supramarginal gyrus; SMG) cortical regions. Activation of the MFG is taken to reflect executive control by prefrontal regions over the working memory updating process linking posterior representations of the anticipated target stimulus to anterior representations of the planned response. It is proposed that the updating of the stimulus link is mediated via connections between the MFG and SMG. The role of the SMG as an amodal region binding the various modal representations in posterior association cortex of the word being retained in working memory is considered and reviewed. It is suggested that the combined activation of these regions is related to the executive control of goal-setting in planned behavior.

Blood Flow Velocity↗

The functional neuroanatomy and long-term reproducibility of brain activation associated with a simple finger tapping task in older healthy volunteers: a serial PET study.

We examined long-term reproducibility of the functional organization of the brain associated with a simple finger tapping movement using positron emission tomography (PET). Repeat measurements of regional cerebral blood flow were obtained in 10 individuals, ages 35 to 82 years (mean 52 years), at scanning sessions separated by 6 months. Although the functional neuroanatomy of hand movements has previously been investigated with PET by a number of groups, none has reported systematic investigation of the consistency of brain activation over an extended time. As expected, we found significant activation in the left precentral gyrus [Talairach coordinate (-32, -34, 52)], postcentral gyrus (-22, -48, 56), and supplementary motor area (SMA) (-2, -18, 52) at the initial study, consistent with previous studies in younger subjects. For the follow-up study we also found significant activation in the left precentral (-36, -28, 52) and postcentral (-28, -36, 52) gyri and in the SMA (2, -16, 56). Our group results demonstrate consistent anatomical location and extent of motor activation over time. More importantly, analysis of individuals confirmed the presence of consistent sites of activation in primary sensorimotor cortex and SMA over the 6-month interval in most subjects. A high degree of consistency in location of activation in the group, and within individuals, over time suggests that changes in loci of activation may be confidently monitored using the PET method. Evidence of individual differences in extent of activation over time highlights the need for caution when interpreting similar changes in patient studies.

Adult↗

The functional neuroanatomy of simple calculation and number repetition: A parametric PET activation study.

We examined cerebral activation patterns with positron emission tomography (PET) in 12 right-handed normal volunteers while they were completing simple calculation tasks or merely repeating numbers. Using a parametric experimental design, during calculation we found activation in the medial frontal/cingulate gyri, left dorsolateral prefrontal cortex, left anterior insular cortex and right anterior insular cortex/putamen, left lateral parietal cortex, and the medial thalamus. Number repetition engaged bilateral inferior sensorimotor cortex, bilateral temporal areas, and left inferior frontal cortex. These results suggest a functional anatomical network for simple calculation, which includes aspects of attention, auditory, and motor processing and the phonological store and articulatory loop components of working memory; they add some support for a special role of the parietal cortex in calculation tasks.

Adult↗

Selective right parietal lobe activation during mental rotation: a parametric PET study.

Regional cerebral blood flow (rCBF) was measured with PET in seven healthy subjects while they carried out a mental rotation task in which they decided whether alphanumeric characters presented in different orientations were in their canonical form or mirror-reversed. Consistent with previous findings, subjects took proportionally longer to respond as characters were rotated further from the upright, indicating that they were mentally rotating the characters to the upright position before making a decision. We used a parametric design in which we varied the mental rotation demands in an incremental fashion while keeping all other aspects of the task constant. In four different scanning conditions, 10, 40, 70 or 100% of the stimuli presented during the scan required mental rotation while the rest were upright. The statistical parametric mapping technique was used to identify areas where changes in rCBF were correlated with the rotational demands of the task. Significant activation was found in only one area located in the right posterior parietal lobe, centred on the intraparietal sulcus (Brodmann area 7). The experimental literature on monkeys and humans suggests that this area is involved in a variety of spatial transformations. Our results contribute evidence that such transformations are recruited during mental rotation and add to a body of evidence which suggests that the right posterior parietal lobe is important for carrying out visuospatial transformations.

Adult↗

The fate of hypoxic tissue on 18F-fluoromisonidazole positron emission tomography after ischemic stroke.

We studied 24 patients up to 51 hours after ischemic stroke using 18F-fluoromisonidazole positron emission tomography to determine the fate of hypoxic tissue likely to represent the ischemic penumbra. Areas of hypoxic tissue were detected on positron emission tomography in 15 patients, and computed tomography was available in 12 patients, allowing comparison with the infarct volume to determine the proportions of the hypoxic tissue volume that infarcted and survived. The proportion of patients with hypoxic tissue and the amount of hypoxic tissue detected declined with time. On average, 45% of the total hypoxic tissue volume survived and 55% infarcted. Up to 68% (mean, 17.5%) of the infarct volume was initially hypoxic. Most of the tissue "initially affected" proceeded to infarction. We correlated hypoxic tissue volumes with neurological and functional outcome assessed using the National Institutes of Health Stroke Scale, Barthel Index, and Rankin Score. Initial stroke severity correlated significantly with the "initially affected" volume, neurological deterioration during the first week after stroke with the proportion of the "initially affected" volume that infarcted, and functional outcome with the infarct volume. Significant reductions in the size of the infarct and improved clinical outcomes might be achieved if hypoxic tissue can be rescued.

Adult↗

No evidence of hypoxic tissue on 18F-fluoromisonidazole PET after intracerebral hemorrhage.

We studied six patients after intracerebral hemorrhage (ICH) and eight controls using positron emission tomography (PET) with to determine whether a zone of tissue hypoxia, possibly representing "penumbral" tissue, exists surrounding an intracerebral hemorrhage. None of the stroke patients, studied 24 to 43 hours after symptom onset, nor any of the controls exhibited areas of tissue hypoxia on 18F-fluoromisonidazole PET images. These findings may have implications for the treatment of intracerebral hemorrhage with neuroprotective strategies.

Aged↗

Second order components of moving plaids activate extrastriate cortex: a positron emission tomography study.

A moving plaid is a composite pattern produced by superimposing two sinusoidal gratings which differ in orientation and motion direction. The perceived drift direction of a plaid appears to be determined partly by a binocular mechanism, which follows intersection of constraint rules (Burke and Wenderoth, 1993b), and partly by a monocular mechanism, which tracks the dark and bright intersects of the plaid, the contrast envelopes. The first neurones that respond to plaids as patterns rather than component gratings are found in area V5, also known as MT, which is exclusively binocular. Therefore, the psychophysical evidence suggesting that the contrast envelope tracking mechanism is monocular is surprising but has been obtained consistently. We aimed to localize the contrast envelope tracking mechanism by undertaking a positron emission tomography (PET) activation experiment in which the subjects were presented with alternating plaid components during the control scan and with the moving plaid resulting from the superposition of these components as the activation scan. The results showed differential activation in area V3. Recent results from macaque single cell recordings have also demonstrated increased sensitivity to moving plaid stimuli compared to the plaid component gratings in V3 neurones.

Adult↗

Positron emission tomography: radioisotope and radiopharmaceutical production.

A Centre for Positron Emission Tomography (PET) has been operational within the Department of Nuclear Medicine at the Austin & Repatriation Medical Centre (A&RMC) in Melbourne for seven years. PET is a non-invasive imaging technique based on the use of biologically relevant compounds labelled with short-lived positron-emitting radionuclides such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18. The basic facility consists of a medical cyclotron (10 MeV proton & 5 MeV deuteron), six lead-shielded hotcells with associated radiochemistry facilities, radiopharmacy and a whole body PET scanner. A strong radiolabelling development program, including the production of 15O-oxygen, 15O-carbon monoxide, 15O-carbon dioxide, 15O-water, 13N-ammonia, 18F-FDG, 18F-FMISO, 11C-SCH23390 and 11C-flumazenil has been pursued to support an ambitious clinical and research program in neurology, oncology, cardiology and psychiatry.

Drug Design↗

Identifying hypoxic tissue after acute ischemic stroke using PET and 18F-fluoromisonidazole.

OBJECTIVE: To show that PET with 18F-fluoromisonidazole (18F-FMISO) can detect peri-infarct hypoxic tissue in patients after ischemic stroke. BACKGROUND: PET with (15)O-labeled oxygen and water is the only established method for identifying the ischemic penumbra in humans. We used PET with 18F-FMISO in patients after ischemic stroke to identify hypoxic but viable peri-infarct tissue likely to represent the ischemic penumbra, and to determine how long hypoxic tissues persist after stroke. METHODS: Patients with acute hemispheric ischemic stroke were studied using PET with 18F-FMISO either within 48 hours or 6 to 11 days after stroke onset. The final infarct was defined by CT performed 6 to 11 days after stroke. Tracer uptake was assessed objectively by calculating the mean activity in the contralateral (normal) hemisphere, then identifying pixels with activity greater than 3 SDs above the mean in both hemispheres. Positive studies were those with high-activity pixels ipsilateral to the infarct. RESULTS: Fifteen patients were studied; 13 within 48 hours of stroke, 8 at 6 to 11 days, and 6 during both time periods. Hypoxic tissue was detected in 9 of the 13 patients studied within 48 hours of stroke, generally distributed in the peripheries of the infarct and adjacent peri-infarct tissues. None of the 8 patients studied 6 to 11 days after stroke exhibited increased 18F-FMISO activity. All 6 patients studied both early and late exhibited areas of increased activity during the early but not the late study. CONCLUSIONS: PET with 18F-FMISO can detect peri-infarct hypoxic tissue after acute ischemic stroke. The distribution of hypoxic tissue suggests that it may represent the ischemic penumbra. Hypoxic tissues do not persist to the subacute phase of stroke (6 to 11 days).

Acute Disease↗

Comparison of ictal SPECT and interictal PET in the presurgical evaluation of temporal lobe epilepsy.

We retrospectively compared ictal technetium 99m hexamethylpropyleneamineoxime single-photon emission computed tomography (SPECT) and interictal 18F-fluorodeoxyglucose positron emission tomography (PET) in 35 patients with well-lateralized temporal lobe epilepsy (TLE). Based on SPECT scans the two observers correctly lateralized seizure foci with certainty in 89% of patients; interobserver agreement was excellent. Both observers incorrectly lateralized the seizure focus on two SPECT scans; one error was explained by rapid electroencephalographic spread to the contralateral side and for the other patient, isotope was injected during a brief aura. Based on PET scans, observers correctly lateralized the foci with certainty in 63% and with lesser confidence in 83%; four incorrect lateralizations were made by one observer and none by the other. PET interobserver disagreement was explained by differences between observers in weighting the relative hypometabolism in medial and lateral temporal regions. The detection rate for PET was lower in the absence of structural imaging abnormalities (60 vs 87%). PET yielded correct lateralizations in the 2 patients for whom SPECT interpretation was difficult. We conclude that both ictal SPECT and interictal PET are sensitive methods for the lateralization of TLE, but SPECT can be interpreted with greater certainty and is more sensitive when magnetic resonance imaging findings are negative. False lateralization is rare with ictal SPECT and can be explained when interpreted in conjunction with electroclinical data. Both investigations have complementary roles when localization is difficult.

Adolescent↗

Is planar thallium-201/fluorine-18 fluorodeoxyglucose imaging a reasonable clinical alternative to positron emission tomographic myocardial viability scanning?

This comparative study was performed to determine whether a conventional planar gamma camera optimised for 511-keV imaging can reliably assess myocardial viability using the fluorine-18 fluorodeoxyglucose (FDG) metabolic tracer previously developed for positron emission tomography (PET). Twenty-seven patients with severe ischaemic cardiomyopathy (mean left ventricular ejection fraction: 20% +/- 9%) having clinically indicated nitrogen-13 ammonia/FDG PET myocardial viability studies consented to resting, four-view, planar myocardial thallium-201 perfusion and FDG metabolism imaging. The resultant PET and planar perfusion/metabolism images (PPI) were independently assessed for FDG defect size and perfusion/metabolism mismatch, using a four-point scale, in each of four vascular regions: apex, circumflex, left anterior and posterior descending coronary artery territories. Of 108 regions, 106 were evaluable (two not assessed by PET). There was complete agreement in 70% of coronary vascular territories, giving an unweighted kappa score of 0.56. Moreover, in 94% of segments agreement was within one grade. Interestingly, six of the seven differences of more than one grade occurred in the circumflex coronary territory, which was also the only region for which planar positron imaging underestimated FDG defect size. Three of four moderate areas of perfusion/metabolism mismatch seen with PET were also seen on PPI. PPI showed three small regions of mismatch not seen on PET, whilst the reverse occurred with one other small region of mismatch. Thus, for this PET protocol, PPI provides very similar information on the extent of regional FDG uptake and occurrence of mismatch.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Computers and networks in medical and healthcare systems.

Information technology has an important and expanding role in the delivery of high quality healthcare services. Until recently health informatics systems have generally been developed as independent centralized databases. With computing communications technologies now being introduced into major hospitals, many new information services can now be provided to enhance the patient-care provider interaction. This paper firstly reviews (existing and currently evolving) information technologies related to text and image-based patient related data. A case study of the introduction of network services at the Austin Hospital, Melbourne, then describes the advantages of computing communication technologies in the healthcare environment, and outlines the strategy adopted to implement these services in a clinically advantageous cost-effective manner.

Computer Communication Networks↗

Status of the Positron Emission Tomography Centre at the Austin Hospital.

A Positron Emission Tomography (PET) Centre is currently being established at the Austin Hospital, Melbourne. The Centre has recently purchased a Siemens Model 951/31 PET scanner and an Ion Beam Applications (IBA) Model 10/5 cyclotron with associated targetry and automated radiochemistry modules. The initial areas of clinical investigation at the Austin Hospital will be heart and brain studies using 18Fluorodeoxyglucose (FDG) and 13Nitrogen-ammonia (13NH3). The heart studies will concentrate on determining myocardial viability in patients following infarction whilst studies of epileptic patients will involve determination of the epileptic focus in the brain. A description of the major technical instrumentation is given together with an overview of the radiopharmaceutical production processes and the initial program of clinical investigations to be undertaken.

Australia↗

Evaluation of the teratogenic potential of octyl acetate in rats.

Octyl acetate (CAS RN 108419-32-5) was administered via oral gavage to pregnant Sprague-Dawley rats on Gestation Days 6 through 15 at dose levels of 0, 0.1, 0.5, and 1.0 g/kg. The dams were weighed and observed for clinical signs of toxicity during pregnancy, and food consumption was measured. On Gestation Day 20 the dams were sacrificed and the fetuses were examined for external, visceral, and skeletal malformations and variations. The mid- and high-dose levels resulted in maternal toxicity as evidenced by reductions in body weight gain and food consumption. There were no statistically significant effects on embryo-fetal lethality or fetal growth for any treatment group. The number of litters with at least one malformed fetus and the mean percentage of the litter malformed were significantly (p less than 0.05) elevated in the high-dose group only. The results of the present study demonstrate that octyl acetate produced some evidence of developmental toxicity at a dose (1.0 g/kg) that was maternally toxic. Developmental toxicity was not observed at the maternally toxic 0.5 g/kg dose level or the maternally nontoxic dose level (0.1 g/kg). Therefore, these data indicate that octyl acetate is not a selective developmental toxicant in the rat.

Acetates↗