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Biomedical subjects

John Duncan

Publications and source records attributed to John Duncan.

At least 19 recordsLinked to original sources
PubMed2006

Frontoparietal activity with minimal decision and control.

In the human brain, a well known frontoparietal circuit, including lateral prefrontal cortex (LPFC), presupplementary motor area/anterior cingulate cortex (pre-SMA/ACC), and both the superior and inferior parietal cortex, is involved in cognitive control. One proposal is that the frontoparietal cortex holds a flexible description of attended or task-relevant information, biasing processing in favor of this information in many different parts of the brain. Here, we separate frontoparietal coding of attended information from its active use in behavior. In two experiments, subjects watch a stream of visual stimuli in a fixed location. In the first experiment, there is no task to perform; in the second, decisions are orthogonal to the occurrence of new stimulus events. Even in these simple circumstances, we find that attended stimulus changes give extensive activation of LPFC, pre-SMA/ACC and parietal cortex, whereas unattended changes do not. Even without behavior to control, these classical "control" regions are active in simple update of attended information.

Adult↗
PubMed2006

Modulation of spatial bias in the dual task paradigm: evidence from patients with unilateral parietal lesions and controls.

Lateral attentional bias is common after unilateral brain damage. It has sometimes been proposed that lateral bias is increased by concurrent cognitive demands, perhaps because of lost top-down compensation. However, an important limitation of previous studies is the sole use of right hemisphere patients. Here we employed a dual task paradigm to measure spatial bias on a visual task while manipulating demands of a concurrent auditory task. Bias was examined in patients with left or right parietal lesions and controls. In Experiment 1 the addition of either a non-spatial or spatial auditory task led to a rightward shift in visual bias. This same rightward shift occurred in controls, left parietals and right parietals. Experiment 2 examined whether the participant's response hand affected their bias. In addition, it attempted to distinguish between the hypothesis that modulatory effects are strongly dependent on lateralization of the concurrent task, and the hypothesis that dual tasks cause a general rightward shift. Response hand was found to have no effect on spatial bias. In addition, bias did not differ between left hemisphere (verbal) and right hemisphere (pitch) concurrent tasks, though the trend was for a smaller rightward shift with the verbal task. Our results show that dual tasks do not exacerbate patients' underlying deficits; instead they cause a global shift in attention to the right. This shift may resemble general rightward shifts that have previously been linked to reduced arousal.

Acoustic Stimulation↗
PubMed2006

EPS Mid-Career Award 2004: brain mechanisms of attention.

There are many varieties of "attention", to some extent separate yet working together to produce coherent perception, thought, and behaviour. Using data from human behaviour, functional neuroimaging, and single-cell recording in the behaving monkey, I consider different levels of attention and their basis in physiological mechanisms of biased competition. Beginning with visual attention, I suggest that processing is competitive in many brain systems that code visual input. Competition is biased towards stimuli that match task requirements and is integrated between systems coding different object properties. The result is flexible, object-based attentional selection. In the second part of the paper, I describe recent experiments on attentional competition within and between sensory modalities. Though competition is often modality specific, more global levels of interference are also easy to demonstrate. In the third part of the paper, I move to frontoparietal cortex and to a pattern of similar brain regions recruited by many different cognitive demands. This multiple-demand (MD) pattern, I suggest, reflects neurons with highly flexible response properties, adapting to represent the information and events of many different tasks. Biased competition in MD regions may play a central role in broad attentional capacity limits and attentional focusing. More generally, I suggest that biased competition is characteristic of many different cognitive domains and brain systems. Coherent "attention" develops as different systems converge to work on related cognitive content.

Attention↗
PubMed2006

Detection of anti-pertussis toxin IgG in oral fluids for use in diagnosis and surveillance of Bordetella pertussis infection in children and young adults.

Bordetella pertussis infection is being increasingly recognized as a cause of prolonged, distressing cough (without whooping symptoms) in children and young adults. Diagnosis of infection in this population is important for treatment and surveillance purposes, and may also prove useful in reducing transmission to unvaccinated babies, for whom disease can be fatal. Serum IgG titres against pertussis toxin (PT) are routinely used as a marker of recent or persisting B. pertussis infection. However, collection of serum from young children is difficult, and compliance amongst these subjects to give samples is low. To circumvent these problems, an IgG-capture ELISA capable of detecting anti-PT IgG in oral fluid was devised. The assay was evaluated by comparison to a serum ELISA, using 187 matched serum and oral fluid samples from children (aged 5-16 years) with a history of prolonged coughing, whose serum anti-PT titre had already been determined (69 seropositive, 118 seronegative). The results showed that, using a cutoff of 70 arbitrary units (AU), the oral fluid assay detected seropositive subjects with a sensitivity of 79.7% [95% confidence interval (CI) 68.3-88.4] and a specificity of 96.6% (95% CI 91.5-99.1). Thus, oral fluid titres of >or=70 AU would possess a positive predictive value of 76.2-93.2% for pertussis amongst children with chronic coughs when used as a surrogate for the serum ELISA (assuming disease prevalence of 12-37%). This oral fluid ELISA will greatly assist in the convenience of B. pertussis disease diagnosis and surveillance.

Adolescent↗
PubMed2006

Selective representation of task-relevant objects and locations in the monkey prefrontal cortex.

In the monkey prefrontal cortex (PFC), task context exerts a strong influence on neural activity. We examined different aspects of task context in a temporal search task. On each trial, the monkey (Macaca mulatta) watched a stream of pictures presented to left or right of fixation. The task was to hold fixation until seeing a particular target, and then to make an immediate saccade to it. Sometimes (unilateral task), the attended pictures appeared alone, with a cue at trial onset indicating whether they would be presented to left or right. Sometimes (bilateral task), the attended picture stream (cued side) was accompanied by an irrelevant stream on the opposite side. In two macaques, we recorded responses from a total of 161 cells in the lateral PFC. Many cells (75/161) showed visual responses. Object-selective responses were strongly shaped by task relevance - with stronger responses to targets than to nontargets, failure to discriminate one nontarget from another, and filtering out of information from an irrelevant stimulus stream. Location selectivity occurred rather independently of object selectivity, and independently in visual responses and delay periods between one stimulus and the next. On error trials, PFC activity followed the correct rules of the task, rather than the incorrect overt behaviour. Together, these results suggest a highly programmable system, with responses strongly determined by the rules and requirements of the task performed.

Action Potentials↗
PubMed2006

Predicting memory decline following epilepsy surgery: a multivariate approach.

BACKGROUND: While some patients experience a decline in memory function following an anterior temporal lobe resection, there is considerable individual variation in the extent, nature, and direction of postoperative memory change. Patients with surgically remediable temporal lobe epilepsy differ in etiology, the extent and type of underlying pathology, and on demographic and epilepsy-related variables, all of which may have an impact on their pre- and postoperative neuropsychological functioning. This study examined the relationship between these variables and postoperative memory decline. METHODS: Logistic regression was used to examine the effects of age, laterality of surgery, age of onset of epilepsy, underlying pathology and preoperative level of memory function on postoperative verbal learning in 288 patients who had undergone an anterior temporal lobe resection. One hundred twenty-five patients underwent a right temporal lobe resection (RTL), 163 patients underwent a left temporal lobe resection (LTL). RESULTS: In the group as a whole, 25% of the patients demonstrated a significant postoperative deterioration in verbal learning. Postoperative deterioration in verbal learning was significantly associated with higher levels of preoperative function in both the RTL and LTL groups. Older age at the time of the operation and a lower verbal IQ were additional significant predictors for the RTL group. The presence of cortical dysgenesis was a significant predictor of postoperative decline in the LTL group. The logistic regression models accurately identified 3/4 of those who experienced a postoperative decline in memory, using a cutoff of 0.25 or above to identify high risk. CONCLUSIONS: Our analyses suggest that the majority of patients with a high risk of significant postoperative memory decline can be reliably identified preoperatively. These models are valuable tools helping patients make an informed decision regarding surgery.

Epilepsy↗
PubMed2006

Within-modality and cross-modality attentional blinks in a simple discrimination task.

Following up on studies of the "attentional blink," we studied interference between successive target stimuli in visual and auditory modalities. In each experiment, stimuli were two tones and four dots, simultaneously presented for 1,800 msec. Targets were brief intensity changes in either a tone or a dot. Subjects gave unspeeded responses. In four experiments, our results showed interference between targets in the same modality, but not across modalities. We conclude that, under our experimental conditions, restrictions in concurrent target identification are largely modality specific.

Adult↗
PubMed2005

Haemoglobin at time of referral prior to dialysis predicts survival: an association of haemoglobin with long-term outcomes.

Haemoglobin (Hgb) levels are known to be associated with numerous adverse outcomes in both chronic kidney disease (CKD) and non-CKD patients. This analysis evaluates the association of baseline haemoglobin levels on survival in CKD patients, who are followed by nephrologists, irrespective of glomerular filtration rate (GFR), prior to initiation of renal replacement therapy (RRT) and erythropoietin hormone replacement therapy. Analysis of data from the provincial database (PROMIS, Patient Registration and Outcome Management Information System) in British Columbia, Canada, was undertaken. Records used for the analysis included all CKD patients at first registration: GFR <60 ml/min/1.73 m(2), not yet on dialysis, starting from May 1998 to October 2002, and who had complete data (defined as age and gender, diabetic status, eGFR and Hgb levels). The primary objective of this study was to determine the association of Hgb and survival controlling for eGFR at first registration value, age, gender and diabetic status. Multivariate Cox proportional hazards analysis with time to death as outcome variable was performed. The cohort included 3028 patients: the mean age was 65 years, 28% were diabetic, and the mean eGFR in the cohort was 21 ml/min/1.73 m(2). The cohort is representative of the BC CKD and dialysis population regarding ethnicity: 64% Caucasian, 32% Asian. Median follow-up was 27 months, 1 year survival was 0.92, 2 year survival was 0.85. Hgb at initial registration is a statistically independent predictor of survival (RR = 0.875 for every 10 g/l, 95% CI: 0.835-0.917, P = 0.0001), after adjusting for age, gender, diabetic status and baseline eGFR. Further analysis, controlling for RRT, demonstrated a similar association between Hgb and survival (RR = 0.853 for every 10 g/l, 95% CI: 0.799-0.910, P = 0.0001), after adjusting for above variables. Substantial variation in Hgb values exists at all GFR levels. These findings underscore the importance of evaluating Hgb at all GFR levels, and the need to study the impact of modification of Hgb at different GFR levels on survival.

Aged↗
PubMed2005

The development of DMA for the detection of amorphous content in pharmaceutical powdered materials.

The aim of this short study was to develop a novel method of sample presentation that will allow currently available DMA apparatus designed for the testing of self-supporting materials to detect amorphous content in controlled mixtures of amorphous and crystalline powders. The preparation of amorphous lactose was carried out by spraying drying, using a Büchi mini spray drier. Controlled mixtures of amorphous and crystalline lactose were produced to give eight samples ranging between 2% and 75% (w/w) amorphous content. These powdered mixtures were loaded into the DMA using a novel powder-pocket device, which consisted of folded sheet of stainless steel. The pocket was clamped directly into the DMA using a single cantilever configuration, and subjected to oscillating displacement, forcing horizontal shearing of the powder between the two plates of the pocket. Typical experimental parameters were a dynamic displacement of 0.05 mm with a frequency of 1 Hz and a heating rate of 5 degrees C/min, from 25 degrees C to 250 degrees C. Over the glass transition region of amorphous lactose, the storage modulus decreased rapidly and a peak was observed in the tandelta signal, which are typical DMA responses for self-supporting glassy materials over their glass transition region. In both the storage modulus and tandelta signals, contributions from both plasticized and non-plasticized amorphous lactose were demonstrated. Such an observation was caused by the powder pocket restricting the loss of the 2.5% (w/w) water present in the spray-dried lactose within the time scale of the first heating cycle. The tandelta peak for the non-plasticized amorphous lactose showed Arrhenius behaviour as function of oscillation frequency. The relationship between the increase in the tandelta peak with increasing frequency allowed the determination of an activation energy that was comparable to the literature values for similar compounds. The height of the tandelta peak for the non-plasticized material was directly proportional to the amount of amorphous lactose present in the mixtures. The glass transition response was still detectable in mixtures containing as little as 2% (w/w) amorphous content, however the theoretical limit of detection was higher than that determined for the same mixtures using solution calorimetry. The results demonstrate that the novel powder pocket allows the use of conventional DMA instruments for the analysis of pharmaceutical powders, however the technique requires more development to further reduce its theoretical limit of detection.

Algorithms↗
PubMed2005

Frontal lobe involvement in spatial span: converging studies of normal and impaired function.

Although monkey lesion studies involving the prefrontal cortex commonly report working memory deficits, and neuroimaging studies consistently show prefrontal involvement in such tasks, patients with damage to this region commonly fail to show any working memory impairment. Such a discrepancy may be due to insensitive testing measures for patients, as well as small, yet critical differences between working memory tasks in imaging and patient studies. The current study utilised a more sensitive measure of spatial working memory spans, based either on structured or unstructured spatial arrays. A PET study in normal subjects confirmed that both variants did indeed activate prefrontal cortex. The same tasks were given to frontal lobe patients and closely matched controls. Patients with large frontal lesions were significantly impaired on this task, with those patients with damage to the right dorsolateral prefrontal cortex appearing particularly impaired. This result demonstrates that prefrontal cortex is necessary for normal working memory, even in simple tasks, such as spatial span. It is suggested, however, that the patient deficit reflects strategic or goal-based dysfunction, rather than storage limitations.

Adult↗
PubMed2005

Attentional functions of parietal and frontal cortex.

A model of normal attentional function, based on the concept of competitive parallel processing, is used to compare attentional deficits following parietal and frontal lobe lesions. Measurements are obtained for visual processing speed, capacity of visual short-term memory (VSTM), spatial bias (bias to left or right hemifield) and top-down control (selective attention based on task relevance). The results show important differences, but also surprising similarities, in parietal and frontal lobe patients. For processing speed and VSTM, deficits are selectively associated with parietal lesions, in particular lesions of the temporoparietal junction. We discuss explanations based on either grey matter or white matter lesions. In striking contrast, measures of attentional weighting (spatial bias and top-down control) are predicted by simple lesion volume. We suggest that attentional weights reflect competition between broadly distributed object representations. Parietal and frontal mechanisms work together, both in weighting by location and weighting by task context.

Acoustic Stimulation↗
PubMed2005

Effect of template complexity on visual search and dual-task performance.

Even dissimilar tasks interfere with one another when done together. We used visual search to examine the underlying cause of such interference. In many models, visual search is a process of biased competition controlled by a template describing the target to be sought. When the display is processed, matching against this template guides attention to the target. We show that increasing template complexity increased interference with a dissimilar concurrent task, story memory. This result was independent of reaction time: Increases in template complexity were associated with no increase in search time in Experiment 1 and with a decrease in search time in Experiment 2. The results show that the dual-task demands of visual search reflect the complexity of the template used in task control, and that this factor can be isolated from other sources of difficulty.

Adolescent↗
PubMed2005

Bordetella petrii clinical isolate.

We describe the first clinical isolate of Bordetella petrii from a patient with mandibular osteomyelitis. The only previously documented isolation of B. petrii occurred after the initial culture of a single strain from an environmental source.

Aged↗
PubMed2005

Nonconvulsive status epilepticus: Epilepsy Research Foundation workshop reports.

In April 2004, a group of physicians with an interest in nonconvulsive status epilepticus representing a spectrum of opinion met in Oxford, sponsored by the Epilepsy Research Foundation (a charitable organization), to discuss and debate the definition, diagnosis and treatment of nonconvulsive status epilepticus. We felt that such a meeting would be useful, as nonconvulsive status epilepticus is a subject that provokes strong reactions, perhaps largely due to the relative lack of evidence and the surfeit of opinion. The meeting was arranged such that there were formal talks followed by a discussion led by one of the attendees. We present here the extended abstracts of the main talks with the points raised by the discussants. Despite disagreements on certain issues there was much in the way of consensus. First, it was agreed that nonconvulsive status epilepticus is a term that covers a range of disparate conditions with varying prognoses and treatments. The agreed definition was thus suitably vague, A< >. Secondly, it was agreed that even within a specific condition (e.g. complex partial status epilepticus), the prognosis and treatment depends upon the context in which the condition occurs (e.g. in the critically ill, in coma, in the A< > and in people with prior epilepsy). Perhaps, most importantly it was agreed that we lacked good clinical data, and the challenge was to design good studies for a condition that is underrecognised and often difficult to diagnose.

Brain Damage, Chronic↗
PubMed2004

Homeostatic capabilities of the choroid plexus epithelium in Alzheimer's disease.

As the secretory source of vitamins, peptides and hormones for neurons, the choroid plexus (CP) epithelium critically provides substances for brain homeostasis. This distributive process of cerebrospinal fluid (CSF) volume transmission reaches many cellular targets in the CNS. In ageing and ageing-related dementias, the CP-CSF system is less able to regulate brain interstitial fluid. CP primarily generates CSF bulk flow, and so its malfunctioning exacerbates Alzheimers disease (AD). Considerable attention has been devoted to the blood-brain barrier in AD, but more insight is needed on regulatory systems at the human blood-CSF barrier in order to improve epithelial function in severe disease. Using autopsied CP specimens from AD patients, we immunocytochemically examined expression of heat shock proteins (HSP90 and GRP94), fibroblast growth factor receptors (FGFr) and a fluid-regulatory protein (NaK2Cl cotransporter isoform 1 or NKCC1). CP upregulated HSP90, FGFr and NKCC1, even in end-stage AD. These CP adjustments involve growth factors and neuropeptides that help to buffer perturbations in CNS water balance and metabolism. They shed light on CP-CSF system responses to ventriculomegaly and the altered intracranial pressure that occurs in AD and normal pressure hydrocephalus. The ability of injured CP to express key regulatory proteins even at Braak stage V/VI, points to plasticity and function that may be boosted by drug treatment to expedite CSF dynamics. The enhanced expression of human CP 'homeostatic proteins' in AD dementia is discussed in relation to brain deficits and pharmacology.

Journal Article↗
PubMed2004

State anxiety modulation of the amygdala response to unattended threat-related stimuli.

Findings from fear-conditioning studies in rats and functional neuroimaging with human volunteers have led to the suggestion that the amygdala is involved in the preattentive detection of threat-related stimuli. However, some neuroimaging findings point to attentional modulation of the amygdala response. The clinical-cognitive literature suggests that the extent to which the processing of threat-related stimuli is modulated by attention is crucially dependent on participants' anxiety levels. Here, we conducted a functional magnetic resonance imaging study with 27 healthy volunteers to examine whether amygdala responsivity to unattended threat-related stimuli varies with individual differences in state anxiety. Pairs of houses and faces (both fearful or neutral in expression) were presented, and participants attended to either the faces or the houses and matched these stimuli on identity. "Low-anxious" participants showed a reduced amygdala response to unattended versus attended fearful faces, but "high-anxious" participants showed no such reduction, having an increased amygdala response to fearful versus neutral faces regardless of attentional focus. These findings suggest that anxiety may interact with attentional focus to determine the magnitude of the amygdala response to threat-related stimuli.

Adolescent↗
PubMed2004

Prefrontal cortical function and anxiety: controlling attention to threat-related stimuli.

Threat-related stimuli are strong competitors for attention, particularly in anxious individuals. We used functional magnetic resonance imaging (fMRI) with healthy human volunteers to study how the processing of threat-related distractors is controlled and whether this alters as anxiety levels increase. Our work builds upon prior analyses of the cognitive control functions of lateral prefrontal cortex (lateral PFC) and anterior cingulate cortex (ACC). We found that rostral ACC was strongly activated by infrequent threat-related distractors, consistent with a role for this area in responding to unexpected processing conflict caused by salient emotional stimuli. Participants with higher anxiety levels showed both less rostral ACC activity overall and reduced recruitment of lateral PFC as expectancy of threat-related distractors was established. This supports the proposal that anxiety is associated with reduced top-down control over threat-related distractors. Our results suggest distinct roles for rostral ACC and lateral PFC in governing the processing of task-irrelevant, threat-related stimuli, and indicate reduced recruitment of this circuitry in anxiety.

Adolescent↗