Biomedical subjects

P Chua

Publications and source records attributed to P Chua.

7 recordsLinked to original sources

PubMed2006

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↗

PubMed2006

Depression and neurocognitive performance in individuals with HIV/AIDS: 2-year follow-up.

OBJECTIVES: The aims of this study were to follow a cohort of HIV-infected individuals for 2 years to assess changes in depression and neuropsychological performance over time, to explore the relationship between depression, HIV illness and neuropsychological performance, and to examine the natural history of the effect of highly active antiretroviral therapy (HAART) on depression and neurocognitive performance. METHODS: HIV-seropositive out-patients were assessed at baseline and at 2-year follow-up. At each assessment, patients were assessed for depression [using the Beck Depression Inventory (BDI) and Structured Clinical Interview (SCID-CV)] and completed a battery of neuropsychological tests including the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Hopkins HIV Dementia Scale (HDS). RESULTS: At baseline, 34.8% scored > or =14 on the BDI [> or =14 suggests depressive symptoms (DS)]. The SCID-CV revealed that 27% of participants met the criteria for current mood disorder. Seven per cent of the participants' scores on the HDS indicated HIV-associated cognitive changes. Eighty participants were re-tested at 2-year follow-up and were split into two groups based on BDI scores at baseline. CANTAB results revealed that the cohort were significantly impaired on nine of 10 measures compared with age-matched normative data. Neurocognitive performance significantly improved for participants with no DS at baseline, whereas participants with DS at baseline did not show as much improvement. Multivariate analysis revealed that 40% of the change in cognitive performance was attributable to the variables age, AIDS and HAART regimen. CONCLUSION: These results suggest a significant decline in depression scores and an improvement in several neurocognitive domains over time, with a relationship between HIV illness, HAART, symptoms of depression and neurocognitive performance.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Dissociable temporal lobe activations during emotional episodic memory retrieval.

The richness of human recollective experience is, in part, related to evocation of previously experienced emotions. An extensive functional neuroimaging literature has provided a description of brain regions involved in retrieving emotionally neutral episodic memories. Whether similar or distinct systems are involved in retrieving emotional memories is unresolved. This question motivated the present functional neuroimaging study, using 0-15 positron emission tomography (PET), where we compared patterns of brain activation associated with retrieving previously studied emotional and neutral pictorial material. By varying task requirements and item density we characterized two distinct neural response patterns during emotional memory retrieval. First, we identified an anterior temporal pole activation that reflected the psychological set associated with emotional memory retrieval. Second, we identified a left amygdala response sensitive to actual retrieval of emotional items. These data suggest distinct functional roles for temporal lobe regions during emotional memory retrieval involving context-related tonic anterior temporal pole activation and a phasic item-related amygdala response. We conclude that brain regions involved in episodic memory retrieval reflect not only physical attributes of stimulus material, for example, their verbal or visual qualities, but also their affective significance.

Amygdala↗

PubMed1999

A functional anatomy of anticipatory anxiety.

Anticipatory anxiety is a complex combination of a future-oriented cognitive state, negative affect, and autonomic arousal. A dual-task paradigm of anticipation of electric shocks and a motor-learning task was used to examine the changes in neural patterns of activation associated with modulation of the cognitive state in anxiety by a distracting motor task. We used positron emission tomography (PET) and 15O-water to measure regional cerebral blood flow (rcbf) in 10 healthy male volunteers. A 2x2 factorial design-(shock vs no shock) x (low vs high distraction) was used with three scans per condition. Twelve PET scans were performed on each subject. In six of these scans, subjects were given electric shocks. In all scans, subjects also simultaneously performed a motor repetition (low distraction) or learning (high distraction) task. Galvanic skin conductance (GSR), Spielberger State and Trait Anxiety Inventory (STAI), and self-report data were also collected. In comparisons between the shock and no-shock conditions, the main finding was of increased rcbf in the left insula (-38,8,8) (z = 4.85, P<0.05 corrected) and a homologous area in the right insula at a lower threshold (z =3.20, P = 0.001 uncorrected). Other areas activated were the right superior temporal sulcus, left fusiform, and left anterior cingulate. Using the STAI-state scores as a covariate of interest, significant correlations with rCBF were seen in the left orbitofrontal cortex, left insula, and left anterior cingulate cortex. There was no significant distraction effect as measured by the STAI, self-report, GSR response or interactional analysis of the PET data. These findings support the role of paralimbic structures as neural substrates of anticipatory anxiety. The failure to demonstrate behavioral and neurophysiological changes with the distractor task may reflect the modest increases in anxiety with the shock, the relatively simple distractor task, and small sample size.

Adult↗

PubMed1995

Bdf1, a yeast chromosomal protein required for sporulation.

The BDF1 gene of Saccharomyces cerevisiae is required for sporulation. Under starvation conditions, most cells from the bdf1 null mutant fail to undergo one or both meiotic divisions, and there is an absolute defect in spore formation. The Bdf1 protein localizes to the nucleus throughout all stages of the mitotic and meiotic cell cycles. Analysis of spread meiotic nuclei reveals that the Bdf1 protein is localized fairly uniformly along chromosomes, except that it is excluded specifically from the nucleolus. A bdf1 null mutant displays a reduced rate of vegetative growth and sensitivity to a DNA-damaging agent. The BDF1 gene encodes a 77-kDa protein that contains two bromodomains, sequence motifs of unknown function. Separation-of-function alleles suggest that only one of the two bromodomains is required for sporulation, whereas both are required for Bdf1 function in vegetative cells. We propose that the Bdf1 protein is a component of chromatin and that the mitotic and meiotic defects of the bdf1 null mutant result from alterations in chromatin structure.

Alleles↗

PubMed1991

Segregation of recombinant chromatids following mitotic crossing over in yeast.

It has long been assumed that chromatid segregation following mitotic crossing over in yeast is random, with the recombinant chromatids segregating to opposite poles of the cell (x-segregation) or to the same pole of the cell (z-segregation) with equal frequency. X-segregation events can be readily identified because heterozygous markers distal to the point of the exchange are reduced to homozygosity. Z-segregation events yield daughter cells which are identical phenotypically to nonrecombinant cells and thus can only be identified by the altered linkage relationships of genetic markers on opposite sides of the exchange. We have systematically examined the segregation patterns of chromatids with a spontaneous mitotic exchange in the CEN5-CAN1 interval on chromosome V. We find that the number of x-segregation events is equal to the number of z-segregations, thus demonstrating that chromatid segregation is indeed random. In addition, we have found that at least 5% of the cells selected for a recombination event on chromosome V are trisomic for this chromosome, indicating a strong association between mitotic recombination and chromosome nondisjunction.

Alleles↗

PubMed1991

Fenfluramine augmentation of clomipramine treatment of obsessive compulsive disorder.

Recently, much research interest has been directed to demonstrating a possible biological basis to obsessive compulsive disorder. In particular, dysregulation in brain serotonin is suggested to be important. Two cases are described in which fenfluramine, a presynaptic 5 HT-releasing agent and 5HT-reuptake inhibitor was used to augment clomipramine treatment for OCD.

Adult↗