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Biomedical subjects

J Currie

Publications and source records attributed to J Currie.

At least 19 recordsLinked to original sources

Attentional modulation of implicit processing of information in spatial neglect.

Patients with parietal lesions often fail to identify stimuli in the contralesional field (i.e. neglect) but may nevertheless demonstrate implicit processing of neglected stimuli. Explanations of implicit processing in neglect range from intact preattentive mechanisms, to intact higher level categorical processing. Such theories assume implicit processing in neglect is passive and not subject to attentional modulation. We investigated implicit processing in a neglect patient US) using a flanker task in which targets differed on two dimensions simultaneously (i.e. coloured letters). Controls demonstrated interference effects only from goal-relevant dimensions of flankers. JS showed a similar pattern of results even when flankers appeared in his neglected field, suggesting that implicit processing of neglected stimuli can be modulated by behavioural goals.

Aged

Asymmetries between dominant and non-dominant hands in real and imagined motor task performance.

Motor imagery is a dynamic state in which an individual mentally simulates the performance of a specific motor action or motor task. Recent behavioural and neuroimaging evidence suggests that the same neurocognitive networks control real and imagined movements. This hypothesis was tested by investigating whether motor asymmetries related to cerebral dominance also occurred for imagined movements. Fifty subjects performed the visually guided pointing task of Sirigu et al. [Sirigu, A., Duhamel, J., Cohen, L., Pillon, B., Dubois, B. and Agid, Y., The mental representation of hand movements after parietal cortex damage. Science, 1996, 273, 1564-1567.] using their dominant and non-dominant hands. Analysis of group data indicated that both real and imagined movement conformed to Fitts' law. Analysis of individual data indicated that asymmetries arising from motor dominance in real movements also occurred for imagined movements. However, the relative slowing and error associated with the non-dominant hand was greater for imagined movements than for real movements. These asymmetries support the hypothesis that real and imagined movements are represented within the same neurocognitive networks but suggest that asymmetries in performance related to handedness are greater for imagined movements. In addition, while the visually guided pointing task provides a useful test of the ability to make imagined movements, asymmetries in the speed and reliability of imagined performance are significantly greater than those for real performance.

Adolescent

Facilitation and inhibition arising from the exogenous orienting of covert attention depends on the temporal properties of spatial cues and targets.

On the covert orienting of visual attention task (COVAT), responses to targets appearing at the location indicated by a non-predictive spatial cue are faster than responses to targets appearing at uncued locations when stimulus onset asynchrony (SOA) is less than approximately 200 ms. For longer SOAs, this pattern reverses and RTs to targets appearing at uncued locations become faster than RTs to targets appearing at the cued location. This facilitation followed by inhibition has been termed the biphasic effect of non-predictive peripheral spatial cues. Currently, there is debate about whether these two processes are independent. This issue was addressed in a series of experiments where the temporal overlap between the peripheral cue and target was manipulated at both short and long SOAs. Results showed that facilitation was present only when the SOA was short and there was temporal overlap between cue and target. Conversely, inhibition occurred only when the SOA was long and there was no temporal overlap between cue and target. The biphasic effect, with an early facilitation followed by a later inhibition, occurred only when the cue duration was fixed such that there was temporal overlap between the cue and target at short but not long SOAs. In a final experiment, the duration of targets the temporal overlap between cue and target and the SOA were manipulated factorially. The results showed that facilitation occurred only when the SOA was short, there was temporal overlap between cue and target and the target remained visible until the subject responded. These results suggest that the facilitation and inhibition found on COVATs which use non-informative peripheral cues are independent processes and their presence and magnitude is related to the temporal properties of cues and targets.

Adult

Investigating form and colour perception in blindsight using an interference task.

Patients with striate cortical damage causing a hemianopic field defect can nevertheless demonstrate residual visual capacities in their blind field. Previous research investigating blindsight required patients to respond explicitly to stimuli appearing in the blind field by making forced choice judgements. We present data from a patient with a left occipital lesion resulting in a homonymous hemianopia, using the flanker task. This patient displayed a significant flanker congruency effect (FCE) for colour and letter stimuli even when they appeared in the blind field. A control patient with a lesion of the right thalamus showed no FCE in the blind field. This suggests that thalamo-extrastriate neural pathways are necessary for residual functioning in blindsight.

Aged

The gap effect and express saccades in the auditory modality.

Latencies of eye movements to peripheral targets are reduced when there is a short delay (typically 200 ms) between the offset of a central visual fixation point and the target onset. This has been termed the gap effect. In addition, some subjects, usually with practice, exhibit a separate population of very short latency saccades, called express saccades. Both these phenomena have been attributed to disengagement of visual attention when the fixation point is extinguished. A competing theory of the gap effect attributes it to disengagement of oculomotor fixation during the temporal gap. It is known that auditory targets are effective in eliciting saccadic eye movements, and also that covert attention operates in the auditory modality. If the gap effect and express saccades are due to disengagement of spatial attention, both should persist in the auditory modality. However, fixation of gaze is largely under visual control. If the gap effect results from disengagement of fixation, then at least a reduced effect should be seen in the auditory modality. Human subjects performed the gap task and a control task in the dark, using auditory fixation points and saccadic targets, on five successive days. Despite this practice, express saccades were not observed. There was a reliable gap effect, but the reduction in saccadic latency was only 17 ms, compared with 32 ms for the same subjects in the visual modality. This suggests that about half the gap effect is due to disengagement of visual fixation. The remainder was not due to non-specific warning effects and could be attributed to offset of the auditory fixation stimulus.

Acoustic Stimulation

Saccadic and attentional abnormalities in patients with schizophrenia.

BACKGROUND: Abnormal performance on the antisaccade task suggests that patients with schizophrenia have difficulty with the inhibition of reflexive attentional shifts. The aim of the study was to investigate whether deficits in the inhibition of reflexive attentional shifts were specific to the oculomotor modality or whether they could also occur when attentional shifts were made without eye movements (e.g. covert attentional shifts). METHODS: Fifteen medicated patients with chronic schizophrenia and 15 matched controls performed the antisaccade task and the covert orientating task (COVAT) where the probability of targets appearing at the same location of a peripheral cue was varied so that voluntary and reflexive orientating systems had the same goal (80% probability of target and cued condition) or opposite goals (20% probability of target at cued location). A condition where only reflexive orientating was initiated was also included (50% probability of target at cued location). For each of these conditions the stimulus onset asynchrony (SOA) varied between 150 and 350 ms. RESULTS: Patients with schizophrenia showed normal latency and accuracy for visually guided saccades but increased error rates and latency on the antisaccade task. For the COVAT, patients with schizophrenia were unable to use voluntary orientating strategies to inhibit reflexive shifts of covert attention. On conditions where only reflexive orientating was required or when the goals of the reflexive and voluntary orientating systems were the same, patients with schizophrenia showed normal performance. CONCLUSIONS: These results suggest the reflexive orientating mode is normal in patients with chronic schizophrenia. However, these patients have a reduced ability to utilize the voluntary orientating mode to control or inhibit reflexive orientating. This impairment of voluntary control is evident for both overt and covert attentional shifts.

Adult

Inhibitory processes in covert orienting in patients with Alzheimer's disease.

Previous studies of covert orienting in Alzheimer's disease (AD) have investigated exogenous and endogenous processes separately. We aimed to investigate how the 2 modes of orienting interact to control attention in healthy older participants and patients with AD. The covert orienting of visual attention task (COVAT) with abrupt onset cues was used in all experiments. In Experiments 1 and 2, predictive information was added to cues to initiate an endogenous orienting response. Results showed that healthy older participants were able to use endogenous processes to inhibit exogenous orienting. In contrast, patients with AD were unable to inhibit exogenous orienting to cues even when targets rarely appeared there. Experiment 3 investigated inhibition of return (IOR) in patients with AD. Both healthy older controls and patients with AD showed a normal IOR, suggesting that exogenous orienting processes are relatively unaffected by the normal aging process or in patients with AD. A model of covert orienting in which exogenous and endogenous orienting processes interact to control attentional behaviors is discussed.

Aged

Neurological and cognitive abnormalities associated with chronic petrol sniffing.

Substance abuse through the deliberate inhalation of petrol (petrol sniffing or gasoline sniffing) is prevalent in inner-urban and remote rural communities. Although acute toxic encephalopathy is a well-documented consequence of petrol sniffing, the neurological and cognitive effects of chronic petrol sniffing are unknown. A structured neurological examination and the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess neurological and cognitive function in 33 current-sniffers (individuals who had sniffed petrol for >6 months), 30 ex-sniffers (individuals who had sniffed petrol in the past but had abstained for 6 months) and 34 matched non-sniffers (individuals who had never sniffed petrol). No subject was, or had been, encephalopathic from petrol sniffing and all were residing in their community. Blood lead and hydrocarbon levels and information about petrol sniffing behaviour were obtained from each subject. When compared with non-sniffers, current-sniffers showed higher rates of abnormal tandem gait, rapid alternating hand movements, finger to nose movements, postural tremor, bilateral palmomental reflexes and brisk deep reflexes. Cognitive deficits occurred in the areas of visual attention, visual recognition memory and visual paired associate learning. Ex-petrol sniffers showed higher rates of abnormal tandem gait and bilateral palmomental reflexes and cognitive deficits in the areas of visual recognition memory and pattern-location paired associate learning. Blood lead levels and length of time of petrol sniffing correlated significantly with the magnitude of neurological and cognitive deficits. Blood hydrocarbon levels were not related to neurocognitive deficits, although this may have been due to methodological difficulties in obtaining hydrocarbon levels. These results suggest that subtle neurological and cognitive abnormalities do occur in individuals who abuse petrol but who do not have acute toxic encephalopathy and that the severity of these abnormalities is reduced with abstinence.

Adolescent

Prevalence and vascular associations with migraine in older Australians.

BACKGROUND: Migraine is a common disorder with recently described vascular associations, yet there are few Australian population-based data describing migraine prevalence. AIMS: To assess the prevalence and vascular associations with lifetime past history of typical migraine headache in a representative sample of older Australians. METHODS: The Blue Mountains Eye Study examined 3654 permanent residents aged 49 or older living in two postcode areas, west of Sydney (82.4% participation) during 1992-4. A structured interview was administered, including questions about past or present history of typical migraine. The diagnosis was consistent with International Headache Society criteria. RESULTS: A lifetime past history of typical migraine was given by 17% of participants, including 22% of women and 10% of men, a female:male ratio of 2.3:1. A marked trend for declining lifetime migraine frequency with increasing age was found for both sexes. Modest statistically significant associations were found with vascular disease history, after multivariate adjustment, which included vascular risk factors. These associations were stronger in men than in women. Among men, typical migraine was significantly associated with history of angina, odds ratio (OR) 2.0, acute myocardial infarction (OR 1.9) and stroke (OR 2.2). Among women, statistically significant associations were present only with history of myocardial infarct (OR 1.8). CONCLUSIONS: These data indicate similar prevalence rates for lifetime typical migraine history in a representative sample of older Australians, compared to recent US and Canadian populations. Modest, statistically significant associations between typical migraine and past history of vascular disease were found, with the strongest associations found in men.

Aged

Collection and normal levels of the amyloid precursor protein in plasma.

The amyloid precursor protein is contained in platelet alpha granules and released with degranulation. Methods are described to control for amyloid precursor protein release from platelets during blood collection and processing. In normal subjects (n = 97; age range, 44-84 years), the average plasma level of amyloid precursor protein was 6.5 +/- 1.8 ng/ml.

Adult

Inv(10)(p11.2q21.2), a variant chromosome.

We present 33 families in which a pericentric inversion of chromosome 10 is segregating. In addition, we summarise the data on 32 families in which an apparently identical inv(10) has been reported in the literature. Ascertainment was through prenatal diagnosis or with a normal phenotype in 21/33 families. In the other 12 families, probands were ascertained through a wide variety of referral reasons but in all but one case (a stillbirth), studies of the family showed that the reason for referral was unrelated to the chromosome abnormality. There has been, to our knowledge, no recorded instance of a recombinant chromosome 10 arising from this inversion and no excess of infertility or spontaneous abortion among carriers of either sex. We propose that inv(10)(p11.2q21.2) can be regarded as a variant analogous to the pericentric inversion of chromosome 2(p11q13). We conclude that prenatal chromosome analysis is not justified for inv(10) carriers. In addition, family investigation of carrier status is not warranted in view of the unnecessary concern this may cause parents and other family members.

Abortion, Spontaneous

Object-based visual attention in luminance increment detection?

A cued reaction time task was used to test the hypothesis that there is an 'object-based' component to shifts of attention mediating the detection of luminance increment targets. The test stimulus consisted of two intersecting triangles forming a 'Star of David'. In two experiments, the cue was a brief brightening of one triangle. The target (a bright green dot) appeared on one of the triangles after a delay of 100, 200 or 500 msec. In one experiment, the target was more likely to appear on the cued triangle. In a second experiment, there was no contingency between cue and target. In both cases, reaction times to targets which appeared outside (but not inside) the cued triangle were more than 10 msec longer than other targets, but only at the shorter cue-target delays. This indicates that the attentional system which regulates luminance increment detection cannot select the cued triangle. It appears that the attentional spotlight can be briefly deformed into a triangular shape, and that it is the rapid, fast-decaying and reflexive exogenous system, rather than the slower acting, persistent and voluntary endogenous system, that mediates this effect. A third experiment using a central, symbolic cue showed no significant cue-validity effects, indicating no contribution from the endogenous system. It is concluded that tasks requiring only stimulus detection cannot unequivocally discriminate between spatial and object-based components of attention.

Adolescent

Cognitive deficits in Machado-Joseph disease.

Cognitive function was examined in 6 patients with genetically confirmed Machado-Joseph disease (MJD) and 15 age- and ethnically matched controls using a series of subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB), a touch screen-based testing system previously validated in a number of movement and neurodegenerative disorders. The MJD patients had deficits in visual attentional function that were characterized by a slowing of the processing of visual information when task demands were high and an inability to shift attention to previously irrelevant stimulus dimensions to discriminate between complex stimuli. Tests of learning and visual memory were normal. These results demonstrate that specific cognitive deficits occur in patients with MJD, independent of motor dysfunction, and these deficits may reflect disruption to frontosubcortical pathways.

Adult

Combination chemotherapy with hydroxyurea, dacarbazine (DTIC), and etoposide in the treatment of uterine leiomyosarcoma: a Gynecologic Oncology Group study.

Advanced or recurrent uterine leiomyosarcomas have traditionally been resistant to most chemotherapeutic regimens. Preliminary reports suggested the combination of hydroxyurea, dacarbazine (DTIC), and etoposide (VP-16) was sufficiently effective to warrant larger trials. In a Phase II trial undertaken by the Gynecologic Oncology Group, 39 patients with advanced or recurrent leiomyosarcoma were treated with 2 g of hydroxyurea, 700 mg/m2 of DTIC, and 300 mg/m2 of VP-16 in divided doses every 4 weeks. Thirty-eight patients were evaluable for response. Two patients experienced complete responses and five had partial responses for a total objective response rate of 18.4% (95% confidence interval: 7.7-34.3%). In general, therapy was well tolerated with moderate toxicity. Six of the seven responders had disease outside the pelvis. The combination of hydroxyurea, DTIC, and VP-16 exhibits moderate activity against uterine leiomyosarcoma.

Adult

Deficits in the endogenous redirection of covert visual attention in chronic schizophrenia.

In patients with schizophrenia, abnormal performance on the antisaccade task suggests that for overt attentional shifts, there is difficulty with the endogenous modes have opposite goals. We examined whether patients with schizophrenia also have difficulty with the endogenous control of exogenous orienting when endogenous and exogenous control of exogenous orienting for covert shifts of attention. Fifteen medicated patients with chronic schizophrenia and 15 matched controls performed two versions of the covert orienting of attention task (COVAT). On one COVAT, targets appeared at the cued location (TAC) on all trials. On the second COVAT, targets appeared at the contralateral location to the cue (TCC) on all trials. Reaction time (RT) for TAC and TCC trials was equal in the control group. However, for the schizophrenia group, RT for TCC trials was significantly slower than RT for TAC trials. This indicates that patients with schizophrenia were unable to inhibit the orienting of attention to peripheral cues even when they knew that targets would never appear at the same location as the cue. These results suggest that patients with chronic schizophrenia have difficulty utilizing the endogenous strategies to inhibit exogenous covert attentional shifts.

Adult

Naive human alpha beta T cells respond to membrane-associated components of malaria-infected erythrocytes by proliferation and production of interferon-gamma.

Crude extracts of Plasmodium falciparum schizont-infected erythrocytes (PfSE) induce polyclonal activation of peripheral blood T lymphocytes from naive (malaria unexposed) humans. We demonstrate that the active component of PfSE is membrane bound, soluble in sodium dodecyl sulphate (SDS) and partially heat stable, but distinct from the tumour necrosis factor (TNF)-inducing, exoantigen-like activity of schizont extracts. Malaria pigment induces little or no T-cell activation. The responding cells are predominately CD4+, CD45RO+, T-cell receptor (TCR) alpha beta+. Contrary to previous reports, expansion of the TCR gamma delta+ subset was observed in cells from only one of eight donors. Proliferating cells secrete interferon-gamma (IFN-gamma) and release large amounts of soluble interleukin-2R (sIL-2R) into the culture supernatant but produce no detectable interleukin-4 (IL-4), a phenotype typical of the T-helper (Th)1 subset of CD4+ T cells. We propose that these activated T cells may initiate the inflammatory response to malaria infection in non-immunes and may contribute to the pathology of the disease.

Animals