Jon Currie

Asymmetries in the covert orienting of visual spatial attention in schizophrenia

The presence of attentional asymmetries in patients with schizophrenia was investigated with particular emphasis on the effects of stage of disease, medication status and clinical symptom severity. A modified version of Posners covert orienting of visual attention task (COVAT) which included both spatial and non-spatial cues was administered to six volunteer samples of subjects which consisted of (i) 15 unmedicated and acutely psychotic male subjects with schizophrenia, (ii) 15 male subjects with schizophrenia who had been receiving medication for 14-21 days, (iii) 10 chronic male schizophrenic subjects who had been receiving medication for at least two years, (iv) 10 acutely psychotic male subjects with non-schizophrenic psychoses, (v) 15 subjects with unilateral brain frontal lobe (n = 6) or parietal lobe (n = 9) lesions, (vi) and 15 male control subjects. Measures of saccadic and pursuit eye movements were also obtained from unmedicated and recently medicated subjects with schizophrenia. COVAT attentional asymmetries were present in unmedicated subjects with schizophrenia for the 150 msec stimulus onset asynchrony (SOA). These asymmetries arose because reaction times (RTs) to right visual field targets were significantly slower than RTs to left visual field targets when targets followed invalid spatial or non-spatial cues. These asymmetries were qualitatively similar to those found in the patients with unilateral parietal lobe lesions. Attentional asymmetries partially resolved with brief periods of medication and completely resolved with long periods of medication. No asymmetries were found in controls nor in unmedicated subjects without schizophrenia. No asymmetries of ocular motor function were found. In schizophrenia, attentional asymmetries may reflect a deficit in the disengagement of visual attention from the right visual field and appear to be a stage marker for the disease. However this attentional deficit is dynamic and may reflect disruption to the neurocognitive network controlling attention at the level of the anterior cingulate cortex.

Frontal atrophy correlates with behavioural changes in progressive supranuclear palsy

Regional brain volumes were measured in 21 patients with progressive supranuclear palsy (PSP), 17 patients with Parkinsons disease and 23 controls using 3D MRI-based volumetry. Cortical, subcortical and ventricular volume measures were correlated with global indices of motor disability and cognitive disturbance. All MRI measures, including hippocampal volume, were preserved in Parkinsons disease. Patients with PSP could be distinguished from both Parkinsons disease and controls by whole brain volume loss, ventricular dilatation and disproportionate atrophy of the frontal cortex. Caudate nucleus volume loss additionally differentiated PSP from controls, but was modest in severity and proportionate to whole brain volume loss. The present study identifies disease-specific differences in the topography of brain atrophy between PSP and Parkinsons disease, and has potential implications for the in vivo radiological differentiation of these two disorders. In PSP, the variance in frontal grey matter volume related to measures of behavioural disturbance, confirming the use of behavioural tests for ante-mortem case differentiation and suggesting that intrinsic cortical deficits contribute to these clinical disturbances.

Abnormalities of imagined motor sequences in children with developmental coordination disorder

Abstract The chronometry of real and imagined movements was investigated in a group of children with developmental coordination disorder (DCD) and a group of matched controls. The visually-guided pointing task was used to investigate the speed for accuracy trade-offs that occur as target size is varied for both real and imagined performance. In the control group, the speed for accuracy trade-off for both real and imagined performance conformed to Fitts’ law. In the DCD group only real movements conformed to Fitts’ law. This pattern of performance suggests that children with DCD have an impairment in the ability to generate internal representations of volitional movements. This may reflect part of a general impairment in the processing of efference copy in DCD.

Spatiotemporal distribution of facilitation and inhibition of return arising from the reflexive orienting of covert attention

Currently, there is debate regarding both the spatial and temporal relationship between facilitation and inhibition of return (IOR) components of attention, as observed on the covert orienting of visual attention task (COVAT). These issues were addressed in a series of experiments where the spatial and temporal relationships between cue and target were manipulated. Facilitation occurred only when the stimulus onset asynchrony (SOA) was short and there was temporal overlap between cue and target. IOR occurred only when SOA was long and there was no temporal overlap between cue and target. Facilitation encompassed the cued location and all locations between the cue and fixation, whereas IOR arose for the entire cued hemifield. These findings suggest that the facilitation and IOR found on COVATs that use noninformative peripheral cues are separable and stimulus-driven processes.

Memory decline in healthy older people Implications for identifying mild cognitive impairment

Background: Criteria for mild cognitive impairment require objective evidence of a memory deficit but do not require objective evidence of memory decline. Application of these criteria may therefore result in the misclassification of older patients with memory decline as normal because their neuropsychological test performance at a single point in time may be within normal limits. This study aimed to identify and characterize older people with memory decline. Method: Word list delayed recall (WLDR) test performance was assessed on five occasions during a 2-year period in a cohort of healthy older individuals. Older people with declining (n = 35) and nondeclining (n = 66) WLDR scores were identified. Both subgroups were then compared on apoE genotype, Clinical Dementia Rating, and neuropsychological test performance at the fifth assessment. Results: Thirty-four percent of the group with declining memory recorded a Clinical Dementia Rating of 0.5, compared with 5% of the nondeclining memory group. No between-group differences were observed in cognitive domains other than memory, self-reported cognitive failures, or the proportion of each group carrying the apoE epsilon 4 allele. Conclusions: A large proportion of healthy older individuals show memory decline, which may represent the early stages of a potentially more severe cognitive impairment. Further investigation is necessary to determine the relationship between apoE genotype, self-reported cognitive impairment, and memory decline in older people.

Norms and the effects of demographic variables on a neuropsychological battery for use in healthy ageing Australian populations

Objective: The current study examined the performance of a healthy ageing population on the Consortium to Establish a Registry for Alzheimers Disease (CERAD) neuropsychological test battery in order to determine norms for use in an Australian setting. The effects of age, education, gender and mood on cognitive performance in healthy older individuals were also explored. Method: The CERAD neuropsychological battery was administered to a sample of healthy elderly subjects (n = 243). Subjects also completed an anxiety inventory and a depression scale. Means and standard deviations of different age, gender and education groups are reported as normative data. A Principal Components Analysis (PCA) was also calculated. Linear regression was applied to the five factors extracted from the PCA using age, education, gender and mood as independent variables. Results: All recorded means were within 1 SD of those reported in the original CERAD normative study. Five factors that loaded on measures of memory and learning, language, praxis and executive function were extracted. The independent variables age, education and gender all had significant effects on cognitive performance. However, mood had no such effect. Conclusions: Risk factors for cognitive decline indicated by the CERAD battery include age, education and gender. Anxiety and depression are not associated with CERAD cognitive performance. The CERAD battery is a valid and reliable neuropsychological tool that may assist in the detection and diagnosis of Alzheimers disease in Australian populations.

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.

Behavioral Characterization of Mild Cognitive Impairment

Results from recent investigations of behavioral and genetic outcomes in older people with mild cognitive impairment (MCI) have been inconsistent. These conflicting results may be attributed to between-study differences in the diagnostic systems employed, as well as the use of unreliable neuropsychological measures. We investigated behavioral and genetic outcomes in older people classified as having MCI according to novel criterion that required evidence of cognitive impairment on three consecutive neurological/neuropsychological assessments. One hundred and seventy four healthy older people were evaluated semi-annually for 12 months. Of these, 23 subjects were rated as having MCI on three consecutive assessments and were compared to 23 matched control subjects. Subjects rated as impaired on one or two of the three semi-annual assessments were also identified. MCI and matched control groups were compared on a range of behavioral measures. The prevalence of the Apolipoprotein E4 (ApoE4) allele was determined in all groups, and estimates of anxiety and depressive symptomatology were obtained. Subjective cognitive complaints were also assessed. Many subjects were classified as impaired on one or two assessments, however relatively few (n = 23) recorded consistent cognitive deficits. The most severe impairment observed in MCI subjects was on a test of pattern-location associative learning, however MCI subjects did not have insight into this impairment. The prevalence of the ApoE4 allele was not different between matched control and MCI groups. These results indicate that individuals with MCI can be differentiated from healthy older people and older people with transient cognitive impairments, but that such differentiation requires serial assessment of cognitive function.

Appearance modeling of 11C PiB PET images : Characterizing amyloid deposition in Alzheimer's disease, mild cognitive impairment and healthy aging

Beta-amyloid (Abeta) deposition is one of the neuropathological hallmarks of Alzheimers disease (AD), Abeta burden can be quantified using (11)C PiB PET. Neuropathological studies have shown that the initial plaques are located in the temporal and orbitofrontal cortices, extending later to the cingulate, frontal and parietal cortices (Braak and Braak, 1997). Previous studies have shown an overlap in (11)C PiB PET retention between AD, mild cognitive impairment (MCI) patients and normal elderly control (NC) participants. It has also been shown that there is a relationship between Abeta deposition and memory impairment in MCI patients. In this paper we explored the variability seen in 15 AD, 15 MCI and 18 NC by modeling the voxel data from spatially and uptake normalized PiB images using principal component analysis. The first two principal components accounted for 80% of the variability seen in the data, providing a clear separation between AD and NC, and allowing subsequent classification. The MCI cases were distributed along an apparent axis between the AD and NC group, closely aligned with the first principal component axis. The NC cases that were PiB(+) formed a distinct cluster that was between, but separated from the AD and PiB(-) NC clusters. The PiB(+) MCI were found to cluster with the AD cases, and exhibited a similar deposition pattern. The primary principal component score was found to correlate with episodic memory scores and mini mental status examination and it was observed that by varying the first principal component, a change in amyloid deposition could be derived that is similar to the expected progression of amyloid deposition observed from post mortem studies.

Subtle Memory Decline over 12 Months in Mild Cognitive Impairment

Objective: Screening of normal older persons for progressive memory decline is a worthwhile strategy in the pursuit of the earliest possible stages of pre-clinical Alzheimer’s disease (AD) or mild cognitive impairment (MCI). Reliable tests are needed to both detect MCI and measure the natural history of decline over months rather than years. We aimed to detect memory decline over 1 year in a group of older individuals with well-characterised amnestic MCI. Methods: The continuous learning task (CLT) from the CogState test battery was administered 8 times in 12 months to 15 individuals with MCI and 35 controls matched for age, education, IQ and gender. All subjects were recruited from an ongoing aging study. The rate of change in CLT performance over the year was compared between groups and also compared to that detected with a word list learning task and a computerised paired associate learning task. Results: At baseline, memory performance in the amnestic MCI group was significantly worse than controls on all memory tests. However, at 12 months the magnitude of the difference between the groups had increased significantly on the CLT due to decline in memory accuracy in the MCI group. No decline over 12 months was detectable on the routine memory tests. Conclusions: Subtle memory decline is detectable in amnestic MCI using reliable and sensitive tests of memory. Such measures may assist in the early identification of AD and also in trials of putative disease-modifying therapies to be conducted over as little as 12 months.