Altered nucleus accumbens functional connectivity precedes apathy in Parkinson's disease.

Work in animal and human neuroscience has identified neural regions forming a network involved in the production of motivated, goal-directed behaviour. In particular, the nucleus accumbens and anterior cingulate cortex are recognized as key network nodes underlying decisions of whether to exert effort for reward, to drive behaviour. Previous work has convincingly shown that this cognitive mechanism, known as effort-based decision making, is altered in people with Parkinson's disease with a syndrome of reduced goal-directed behaviour-apathy. Building on this work, we investigated whether the neural regions implementing effort-based decision-making were associated with apathy in Parkinson's disease, and more importantly, whether changes to these regions were evident prior to apathy development. We performed a large, multimodal neuroimaging analysis in a cohort of people with Parkinson's disease (n = 199) with and without apathy at baseline. All participants had ∼2-year follow-up apathy scores, enabling examination of brain structure and function specifically in those with normal motivation who converted to apathy by ∼2-year follow-up. In addition, of the people with normal motivation, a subset (n = 56) had follow-up neuroimaging data, allowing for examination of the 'rate of change' in key nodes over time in those who did, and did not, convert to apathy. Healthy control (n = 54) data were also included to aid interpretation of findings. Functional connectivity between the nucleus accumbens and dorsal anterior cingulate cortex was higher in people with normal motivation who later converted to apathy compared to those who did not, whereas no structural differences were evident between these groups. In contrast, grey matter volume in these regions was reduced in the group with existing apathy. Furthermore, of those with normal motivation who had undergone longitudinal neuroimaging, converters to apathy showed a higher rate of change in grey matter volume within the nucleus accumbens. Overall, we show that changes in functional connectivity between nucleus accumbens and anterior cingulate cortex precedes apathy in people with Parkinson's disease, with conversion to apathy associated with higher rate of grey matter volume loss in nucleus accumbens, despite no baseline differences. These findings significantly add to an accumulating body of transdiagnostic evidence that apathy arises from disruption to key nodes within a network in which normal goal-directed behaviour is instantiated, and raise the possibility of identifying those at risk for developing apathy before overt motivational deficits have arisen.

Higher perceived stress and exacerbated motor symptoms in Parkinson's disease during the COVID-19 lockdown in New Zealand.

AIMS: Stress plays a key role in Parkinson's disease (PD) by acting on the dopaminergic system and worsening patients' motor function. The impact of New Zealand's strict lockdown measures to contain COVID-19 on perceived stress and PD motor symptoms remains unknown. Here we examined the relationship between perceived levels of stress, changes in physical activity levels and PD motor symptoms during lockdown. METHODS: During lockdown, 134 participants with PD and 49 controls completed a survey assessing perceived stress, self-reported changes in PD motor symptoms and physical activity duration and intensity prior to and during lockdown. RESULTS: Perceived stress was higher in PD than controls, and in those reporting a worsening of tremor, balance/gait, dyskinesia and bradykinesia compared to those indicating no change during the COVID-19 lockdown. These effects were not modulated by physical activity. CONCLUSIONS: Reducing stressors may be an important adjunct treatment strategy to improve motor function in PD.

Comparing cerebral perfusion in Alzheimer's disease and Parkinson's disease dementia: an ASL-MRI study.

Emerging evidence suggests that Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) share neurodegenerative mechanisms. We sought to directly compare cerebral perfusion in these two conditions using arterial spin labeling magnetic resonance imaging (ASL-MRI). In total, 17 AD, 20 PDD, and 37 matched healthy controls completed ASL and structural MRI, and comprehensive neuropsychological testing. Alzheimer's disease and PDD perfusion was analyzed by whole-brain voxel-based analysis (to assess absolute blood flow), a priori specified region of interest analysis, and principal component analysis (to generate a network differentiating the two groups). Corrections were made for cerebral atrophy, age, sex, education, and MRI scanner software version. Analysis of absolute blood flow showed no significant differences between AD and PDD. Comparing each group with controls revealed an overlapping, posterior pattern of hypoperfusion, including posterior cingulate gyrus, precuneus, and occipital regions. The perfusion network that differentiated AD and PDD groups identified relative differences in medial temporal lobes (AD

Memory-guided saccades in Parkinson's disease: long delays can improve performance.

A recent study in control subjects suggested the existence of separate pathways for oculomotor spatial working memory tasks depending on whether the delay before movement execution is either short or long (>20 s). The long delay pathway might bypass brain areas commonly affected by Parkinson's disease (PD). This study aimed to assess spatial working memory in Parkinson's disease using short (3 s) and long (30 s) delays in a memory-guided saccade task. Fifteen mild-moderately affected PD subjects off-medication, and 15 age and sex-matched controls were tested (PD mean age 65.3; control 65.9). Subjects were tested in a darkened room using a horizontal LED bar to generate eye movements which were recorded using an infrared limbus tracker. Percentage error in amplitude of the primary saccade was analysed by repeated measures ANOVA. There was a significant interaction between the groups and their response to the short and long delay periods (P<0.02). PD subjects were more strongly impaired in the short delay than the long delay trials when compared with controls. Analysis of the percentage error in amplitude of the final eye position showed the same pattern but only in female subjects. This study provides the first evidence that the proposed parallel spatial memory pathway utilised in longer delay periods is relatively unimpaired in PD. In a broader sense, our results suggest there might be other alternative pathways to overcome deficits in functions impaired by PD.

ECG score predicts those with the greatest percentage of perfusion defects due to acute pulmonary thromboembolic disease.

BACKGROUND: More aggressive management may be warranted for patients with acute pulmonary embolism (PE) and the greatest pulmonary vascular obstruction. We hypothesized that a scoring system based on the ECG might identify such patients. METHODS: Consecutive patients investigated for PE at Christchurch Hospital between 1997 and 2002 with high-probability ventilation/perfusion (V/Q) scan findings were studied. The ECG obtained closest to and within 48 h of the scan was scored by two independent observers, and the mean ECG score was calculated. V/Q scan findings were categorized into those with < 30%, 30 to 50%, and > 50% perfusion defect by two independent observers experienced in V/Q interpretation. A consensus score was taken when disagreement occurred. RESULTS: Two hundred twenty-nine patients were included in the study. The interobserver agreement for ECG score was 0.96 (Cronbach alpha) and V/Q score was 0.55 (kappa). The ECG predicted those with the greatest amount of perfusion defects. Mean ECG score was 2.6 (SD 2.8) in patients with < 30% perfusion defect, 3.2 (SD 2.9) in patients with 30 to 50% perfusion defect, and 5.3 (SD 3.7) in patients with > 50% perfusion defect. The area under the receiver operating characteristic curve for ECG score and those with > 50% perfusion defect was 0.71 (SE 0.04). An ECG score of > or = 3 predicted those with > 50% perfusion defect with a sensitivity of 70% (95% confidence interval [CI], 59 to 81%), and a specificity of 59% (95% CI, 51 to 67%). CONCLUSION: An ECG score, simple to derive, predicts those with the greatest percentage of perfusion defect. Using the ECG for management warrants prospective evaluation.