David Abernethy

Is implicit sequence learning impaired in Parkinson's disease? A meta-analysis

The aim of the present study was to examine impairment of implicit learning in Parkinsons disease (PD) by means of a meta-analysis of studies that used the serial reaction time (SRT) task. The authors performed a systematic review and meta-analysis of published journal articles (1987-2005) that used the SRT task with patients with PD. The principal outcome measures used to compare studies were (a) the difference in reaction time between the last block of ordered sequence trials and the randomized block for PD and control participants and (b) fixed and random effects pooled estimates by the inverse weighting method. Six studies, including 67 patients with PD, met the inclusion criteria. The meta-analysis showed that implicit learning was impaired in PD, relative to healthy controls, with a standardized mean difference of 0.73 (95% confidence interval = 0.38, 1.07). Implicit sequence learning appears to be impaired in patients with PD. Some common methodological weaknesses and limitations in the reporting of statistical data are discussed.

Preserved implicit learning on both the serial reaction time task and artificial grammar in patients with Parkinson's disease.

Thirteen nondemented patients with Parkinsons disease (PD) were compared with age-matched controls on two standard tests of implicit learning. A verbal version of the Serial Reaction Time (SRT) task was used to assess sequence learning and an artificial grammar (AG) task assessed perceptual learning. It was predicted that PD patients would show implicit learning on the AG task but not the SRT task, as motor sequence learning is thought to be reliant on the basal ganglia, which is damaged in PD. Patients with PD demonstrated implicit learning on both tasks. In light of these unexpected results the research on SRT learning in PD is reconsidered, and some possible explanations for the sometimes conflicting results of PD patient samples on the SRT task are considered. Four factors which merit further study in this regard are the degree to which the SRT task relies on overt motor responses, the effects of frontal lobe dysfunction upon implicit sequence learning, the effects of cerebellar degeneration, and the degree to which the illness itself has advanced.

The effect of Parkinson’s disease on time estimation as a function of stimulus duration range and modality

The present research sought to investigate the role of the basal ganglia in timing of sub- and supra-second intervals via an examination of the ability of people with Parkinsons disease (PD) to make temporal judgments in two ranges, 100-500 ms, and 1-5 s. Eighteen non-demented medicated patients with PD were compared with 14 matched controls on a duration-bisection task in which participants were required to discriminate auditory and visual signal durations within each time range. Results showed that patients with PD exhibited more variable duration judgments across both signal modality and duration range than controls, although closer analyses confirmed a timing deficit in the longer duration range only. The findings presented here suggest the bisection procedure may be a useful tool in identifying timing impairments in PD and, more generally, reaffirm the hypothesised role of the basal ganglia in temporal perception at the level of the attentionally mediated internal clock as well as memory retrieval and/or decision-making processes.

MS prevalence in New Zealand, an ethnically and latitudinally diverse country

Background: The prevalence of multiple sclerosis (MS) is not uniform, with a latitudinal gradient of prevalence present in most studies. Understanding the drivers of this gradient may allow a better understanding of the environmental factors involved in MS pathogenesis. Method: The New Zealand national MS prevalence study (NZMSPS) is a cross-sectional study of people with definite MS (DMS) (McDonald criteria 2005) resident in New Zealand on census night, 7 March 2006, utilizing multiple sources of notification. Capture—recapture analysis (CRA) was used to estimate missing cases. Results: Of 2917 people with DMS identified, the crude prevalence was 72.4 per 100,000 population, and 73.1 per 100,000 when age-standardized to the European population. CRA estimated that 96.7% of cases were identified. A latitudinal gradient was seen with MS prevalence increasing three-fold from the North (35°S) to the South (48°S). The gradient was non-uniform; females with relapsing—remitting/secondary-progressive (RRMS/SPMS) disease have a gradient 11 times greater than males with primary-progressive MS (p < 1 × 10-7). DMS was significantly less common among those of Māori ethnicity. Conclusions: This study confirms the presence of a robust latitudinal gradient of MS prevalence in New Zealand. This gradient is largely driven by European females with the RRMS/SPMS phenotype. These results indicate that the environmental factors that underlie the latitudinal gradient act differentially by gender, ethnicity and MS phenotype. A better understanding of these factors may allow more targeted MS therapies aimed at modifiable environmental triggers at the population level.

Self-initiated versus externally cued reaction times in Parkinson's disease.

It has long been observed that patients with Parkinsons disease (PD) can sometimes react and move quickly in response to an external stimulus in a way that they cannot when required to initiate the movement themselves. This curious phenomenon has sometimes been called ‘paradoxical kinesis’. The present study was an attempt to demonstrate this phenomenon in patients with PD using an objective and quantifiable experimental procedure. A reaction time task was used in which participants had to press one of two computer keys, either left or right, to save a cartoon person on a computer screen from being run over by a motor car. In one condition, trials started after a traffic light appeared on the computer screen and then changed from red to green. In a second condition, the participants had to first press a third response key which resulted in the traffic light appearing on screen and changing from red to green. Participants also received both these conditions with the addition of a visual cue, an arrow, which told them in advance which direction to respond in (i.e., left or right key) on each trial. The purpose of the visual cue was to separate the effects of motor planning from motor activation. Healthy controls reacted quickest when they initiated trials themselves whereas the PD group were quicker to respond when trials were externally generated. Both groups were quicker under the visual cue condition. The results are discussed in terms of recent research which has suggested that two separate neural systems may be involved in externally generated or stereotyped actions and motor responses which require self-generated or nonroutine decision making.

A meta-analysis of performance on simple span and more complex working memory tasks in Parkinson's disease

The working memory (WM) concept has stimulated substantial research since Baddeley and Hitch advanced their model in 1974. There has also been growing interest in WM in Parkinsons disease (PD) where the brain structures considered important for WM are often compromised. However, it remains unclear how and to what degree WM is affected in PD. The authors used meta-analysis to clarify the research findings on WM in PD. The results confirmed that people with PD are impaired on tests of WM. This impairment is small for verbal span but moderate on complex verbal and both simple and complex visuospatial tasks. These data do not support the belief that WM impairment in PD is solely at the level of the central executive. However, our findings support the notion that impairment is more pronounced for visuospatial than verbal WM. A number of different interpretations of these results are discussed. It remains to be established what these statistically significant differences mean in terms of clinically significant levels of impairment in WM. Another important methodological issue that demands greater consideration in this area is that of sampling and the generalizability of results.

Assessing possible selection bias in a national voluntary MS longitudinal study in Australia

Background: Surveying volunteer members of a multiple sclerosis registry is a very cost-effective way of assessing the impact of the disease on life outcomes. However, whether the data from such a study can be generalised to the whole population of persons living with MS in a country or region is unclear. Methods: Here we compare the demographic and disease characteristics of participants in one such study, the Australian Multiple Sclerosis Longitudinal Study (AMSLS), with two well-characterised MS prevalence studies with near-complete ascertainment of MS in their study regions. Results: Although some differences were found, these largely represented the effects of geography (sex ratios) and local factors (national immunomodulatory therapy prescribing requirements), and the cohorts were otherwise comparable. Overall, despite comprising only 12–16% of MS cases in Australia, the AMSLS is highly representative of the MS population. Conclusions: Therefore with some minor caveats, the AMSLS data can be generalised to the whole Australasian MS population. Volunteer disease registries such as this can be highly representative and provide an excellent convenience sample when studying rare conditions such as MS.

Incidence and prevalence of NMOSD in Australia and New Zealand

Objectives We have undertaken a clinic-based survey of neuromyelitis optica spectrum disorders (NMOSDs) in Australia and New Zealand to establish incidence and prevalence across the region and in populations of differing ancestry. Background NMOSD is a recently defined demyelinating disease of the central nervous system (CNS). The incidence and prevalence of NMOSD in Australia and New Zealand has not been established. Methods Centres managing patients with demyelinating disease of the CNS across Australia and New Zealand reported patients with clinical and laboratory features that were suspicious for NMOSD. Testing for aquaporin 4 antibodies was undertaken in all suspected cases. From this group, cases were identified who fulfilled the 2015 Wingerchuk diagnostic criteria for NMOSD. A capture–recapture methodology was used to estimate incidence and prevalence, based on additional laboratory identified cases. Results NMOSD was confirmed in 81/170 (48%) cases referred. Capture–recapture analysis gave an adjusted incidence estimate of 0.37 (95% CI 0.35 to 0.39) per million per year and a prevalence estimate for NMOSD of 0.70 (95% CI 0.61 to 0.78) per 100 000. NMOSD was three times more common in the Asian population (1.57 (95% CI 1.15 to 1.98) per 100 000) compared with the remainder of the population (0.57 (95% CI 0.50 to 0.65) per 100 000). The latitudinal gradient evident in multiple sclerosis was not seen in NMOSD. Conclusions NMOSD incidence and prevalence in Australia and New Zealand are comparable with figures from other populations of largely European ancestry. We found NMOSD to be more common in the population with Asian ancestry.

16. Prevalence of multiple sclerosis in New Zealand

Multiple sclerosis (MS) is thought to result from a complex interplay of genetic and environmental factors. The degree to which genetic factors contribute and the existence of a latitudinal gradient in the prevalence of multiple sclerosis remain controversial. The studies that have shown geographical differences in prevalence have varied widely in terms of the size and ethnicity of the populations surveyed; the way in which MS was diagnosed: and in the completeness of case ascertainment. Knowledge of MS prevalence across a whole country therefore, could provide valuable information about the presence of a latitudinal gradient and about the genetic factors which contribute to the risk of developing MS. New Zealand is ideally suited to an observational study examining these factors as it has a geographically well defined population of manageable size (4,027,938) with a national healthcare system and geographical extent over 13 degrees of latitude (34-47 degrees south).

Multiple Sclerosis impact on employment and income in New Zealand

We investigated the demographic, social and clinical characteristics associated with employment status and income for people with multiple sclerosis (MS) in New Zealand (NZ).