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Biomedical subjects

John Bradshaw

Publications and source records attributed to John Bradshaw.

10 recordsLinked to original sources

Age-related differences in cognitive function using a global local hierarchical paradigm.

While research suggests that normal ageing is associated with compromised divided attentional processing abilities, such studies are comparatively few in comparison to other areas of attention (e.g. selective attention). The current study sought to examine age-related effects in divided attention using a global/local paradigm in three normal healthy age groups: younger adults (20-40 years), middle-aged (40-60 years), and older adults (61-80 years). In three experiments we sought to examine the ability to process local/global stimuli, ability to divide and switch attention, as well as the influence of a cue on target performance. Experiment 1 revealed global precedence and interference for all age groups; older adults were overall significantly slower in their response times. Experiments 2 and 3 suggest an age-related impairment in dividing and switching attention, which may begin as early as middle age. The findings are considered to reflect reduced inhibitory mechanisms, as well as possible neurobiological changes in the normal ageing process.

Adult↗

Accelerated time-course of inhibition of return in Huntington's disease.

A non-predictive peripheral cueing paradigm was used to evaluate visuospatial attentional deficits in symptomatic HD patients, employing spatially valid and invalid visual cues over a range of stimulus onset asynchronies (SOA) to elicit a saccadic response. Although both patients and controls demonstrated initial facilitation for valid versus invalid cues following the shortest SOA, and a performance decrement (inhibition of return), at the longest SOA, a clear differentiation between these groups was found for the intermediate SOAs. Unlike controls, where IOR manifested between 350 and 1000 ms, IOR was evident as early as 150 ms for HD patients. Further, the benefit of valid cueing correlated significantly with the level of impairment. Although patients exhibited poor fixation, principally attributable to saccadic intrusions, they were capable of appropriately suppressing a purely stimulus-driven response to the cue. A similar proportion of erroneous saccades to the cue were generated by both groups prior to stimulus onset, also correlating significantly with level of impairment. These results are discussed with respect to neural processes implicated in spatial cueing and within the context of reduced inhibitory activity of the BG in HD.

Adult↗

No sequence dependent modulation of the Simon effect in Parkinson's disease.

This study sought to evaluate impaired response tendencies and modulation of automatic processes in Parkinson's disease (PD), utilising a saccadic Simon task with stimulus-response (S-R) compatibility determined on the basis of cue shape. The appearance of either a circle or a square in one of two boxes presented peripherally required the generation of a leftward or rightward horizontal saccade, respectively. These goal-directed responses were considered behaviourally relevant to an examination of visuospatial performance. Although response times are typically faster when stimulus and response are spatially compatible than when they are not, sequence-dependent modulation of this effect results in large differences between S-R compatible and S-R incompatible trials when stimulus and response are spatially compatible in the preceding trial, and reduced or absent differences when stimulus and response are spatially incompatible in the preceding trial. Unlike control subjects, PD patients demonstrated significantly shorter saccadic latencies overall, compared to a baseline condition involving endogenously-driven saccades. Patients also responded erroneously to cue stimuli with greater frequency. Analyses of both saccadic latency and errors to cue demonstrated a Simon effect (relatively faster response for S-R compatible trials), irrespective of the preceding trial. This suggests impaired modulation of the Simon effect in PD, consistent with predictions of inhibitory dysfunction, or impaired episodic memory. These results demonstrate the pivotal role of the basal ganglia in the regulation of context-dependent neural activity.

Adult↗

Impaired modulation of the vestibulo-ocular reflex in Huntington's disease.

The vestibulo-ocular reflex (VOR) stabilizes gaze during movement, in conjunction with other afferent information: visual, proprioceptive, and somaesthetic. The reflex can either be augmented or suppressed, depending on visual requirements, and undergoes long-term adaptation to compensate for physical changes in the subject. Importantly, over relatively short periods of time, the VOR should function consistently under the same circumstances. This study examines VOR function in patients with Huntington's disease (HD), with a view to investigating cortical influences on the reflex. Horizontal eye movements were recorded in 9 patients with HD and 7 normal subjects, using the scleral search coil technique, in response to high frequency, unpredictable head rotations imposed manually. To establish base VOR function, recordings were made in darkness, without instruction, before and after wearing x2 magnifying lenses for a period of 2 hours to adapt the reflex. Recordings were also made before adaptation, while fixating a stationary visual target (VOR augmentation), and while fixating a target moving with the head (VOR suppression). Although results suggest that the VOR is preserved in HD, with relatively normal gain values and appropriate augmentation and suppression of the reflex with visual input, patients were unable to adapt the VOR to altered visual conditions. This represents a novel finding in HD and suggests that cortical structures compromised in HD exert influences on the long-term adaptation of the VOR.

Adult↗

Inhibition of return in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is characterized by repetitive obsessions and/or compulsions that interfere with daily functioning. Neuropsychological studies have suggested that such perseverative behaviors may be due to underlying attentional deficits. Inhibition of return (IOR) is an adaptive mechanism that is thought to assist visual search by biasing attention after a critical, short interval to novel, previously unattended areas. Therefore, this study aimed to examine whether deficient IOR mechanisms could underlie some of the attentional, and perhaps behavioral, problems, reported in OCD patients. Using a computerized IOR paradigm, participants were required to respond to a target that appeared at either the same or different location to a precue that was presented either 100 ms or 700 ms earlier. Results indicate that patients had a reduced IOR for targets presented in the left visual field, suggesting lateralized anomalies in shifting attention. Results are consistent with lateralization anomalies previously reported in OCD.

Adult↗

Drug rings database with web interface. A tool for identifying alternative chemical rings in lead discovery programs.

This paper describes the development of a drug rings database and Web-based search tools. The database contains ring structures from both corporate and commercial databases, along with characteristic descriptors including frequency of occurrence as an indicator of synthetic accessibility and calculated property and geometric parameters. Analysis of the rings in several major databases is described, with illustrations of applications of the database in lead discovery programs where bioisosteres and geometric isosteres are sought.

Databases, Factual↗

Orienting attention in obsessive-compulsive disorder.

OBJECTIVES AND BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by recurrent obsessions and/or compulsions that affect daily functioning. This study aimed to ascertain whether OCD patients have problems in orienting attention, via the use of a vibrotactile choice reaction time task. METHODS: Participants were required to depress a button in response to a vibration delivered to the index finger of either the right or left hand. Prior to the stimulus, one of three precues was administered: valid (precue delivered to the same hand as stimulus), invalid (precue delivered to opposite hand to stimulus), or neutral (precue delivered simultaneously to both hands). RESULTS: Obsessive-compulsive disorder participants were overall slower and less accurate than controls. Contrary to our predictions, OCD participants did not show increased costs or benefits. However, unlike controls, patients did not show the normal pattern of faster reaction times on neutral compared with invalid precues, which may reflect a problem in inhibiting irrelevant information. CONCLUSIONS: Both patients and controls may benefit from the provision of directed attention in tactile tasks when difficulty levels are maximal. OCD patients may have problems with inhibitory control.

Adult↗

Cold-adapted influenza vaccines.

Because of the health impact of complicated disease from influenza in children, the role played by children in spreading influenza, and the limitations of inactivated influenza vaccine in this population, there has been ongoing effort to identify a more effective and acceptable vaccine. This review will focus on the development, limitations, and potential of a leading candidate vaccine studied in children. This is a live, attenuated, intranasally administered cold-adapted influenza vaccine.

Administration, Intranasal↗

The ability to orient attention in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome is characterised by tics, although patients also commonly present with attentional problems. This experiment aimed to ascertain whether TS patients have problems in orienting attention, via the use of a vibrotactile choice reaction time task. Participants were required to push a button in response to a faint vibration delivered to the index finger. Prior to each stimulus vibration, a pre-cue (valid, neutral or invalid) was administered to the finger. The performance benefits and costs participants gained from valid and invalid precues were calculated. Contrary to our prediction TS patients did not show significantly different costs or benefits. Furthermore, both patients and controls showed an equal and increased benefit in the crossed arm posture, compared to the uncrossed. These results suggest TS patients do not generally have problems in orienting attention. In addition, in the tactile modality, both patients and controls may benefit from directed attention when difficulty levels are maximal.

Journal Article↗

Similarity searching using reduced graphs.

Reduced graphs provide summary representations of chemical structures. In this work, the effectiveness of reduced graphs for similarity searching is investigated. Different types of reduced graphs are introduced that aim to summarize features of structures that have the potential to form interactions with receptors while retaining the topology between the features. Similarity searches have been carried out across a variety of different activity classes. The effectiveness of the reduced graphs at retrieving compounds with the same activity as known target compounds is compared with searching using Daylight fingerprints. The reduced graphs are shown to be effective for similarity searching and to retrieve more diverse active compounds than those found using Daylight fingerprints; they thus represent a complementary similarity searching tool.

Journal Article↗