Australian Parkinson's Genetics Study (APGS): pilot (n=1532).

PURPOSE: Parkinson's disease (PD) is a neurodegenerative disorder associated with progressive disability. While the precise aetiology is unknown, there is evidence of significant genetic and environmental influences on individual risk. The Australian Parkinson's Genetics Study seeks to study genetic and patient-reported data from a large cohort of individuals with PD in Australia to understand the sociodemographic, genetic and environmental basis of PD susceptibility, symptoms and progression. PARTICIPANTS: In the pilot phase reported here, 1819 participants were recruited through assisted mailouts facilitated by Services Australia based on having three or more prescriptions for anti-PD medications in their Pharmaceutical Benefits Scheme records. The average age at the time of the questionnaire was 64±6 years. We collected patient-reported information and sociodemographic variables via an online (93% of the cohort) or paper-based (7%) questionnaire. One thousand five hundred and thirty-two participants (84.2%) met all inclusion criteria, and 1499 provided a DNA sample via traditional post. FINDINGS TO DATE: 65% of participants were men, and 92% identified as being of European descent. A previous traumatic brain injury was reported by 16% of participants and was correlated with a younger age of symptom onset. At the time of the questionnaire, constipation (36% of participants), depression (34%), anxiety (17%), melanoma (16%) and diabetes (10%) were the most reported comorbid conditions. FUTURE PLANS: We plan to recruit sex-matched and age-matched unaffected controls, genotype all participants and collect non-motor symptoms and cognitive function data. Future work will explore the role of genetic and environmental factors in the aetiology of PD susceptibility, onset, symptoms, and progression, including as part of international PD research consortia.

Non-uniform Effects of Nociceptive Stimulation to Motoneurones during Experimental Muscle Pain.

Nociceptive stimulation is predicted to uniformly inhibit motoneurone pools of painful muscles and those producing painful movements. Although reduced motoneurone discharge rate during pain provides some evidence, recent data show evidence of increased excitability of some motoneurones. These observations suggest non-uniform effects of nociception on motoneurone excitability. More direct measures are required, but this is difficult to assess as few measures enable in vivo evaluation of motoneurone excitability in humans. We investigated changes in motoneurone excitability during experimental pain using two methods in separate experiments: (i) estimation of the time-course of motoneurone afterhyperpolarization (AHP) from interval death rate analysis of interspike intervals of single motor unit discharge; and (ii) probability of early motoneurone discharge to a descending volley excited using transcranial magnetic stimulation (TMS). Tibialis anterior motor units were recorded with fine-wire electrodes before, during and after painful infusion of 5% hypertonic saline into the muscle. Activation of 17 units (16 participants) could be used for AHP analysis. Data show shortened (n = 11) and lengthened (n = 6) AHP time-course. Increased (n = 6) and decreased (n = 6) probability of early motoneurone discharge were observed in the TMS experiment. These convergent observations suggest non-uniform effects of nociceptive stimulation on motoneurone pools. This does not support the hypothesis that nociceptive input induces uniform inhibition of painful muscle. Instead, interpretation of results implies redistribution of activity between motor units, with possible benefit for unloading painful tissues. This finding supports an interpretation that differs from the generally accepted view in pain physiology regarding adaptation to motor function in pain.

The Queensland Parkinson's Project: An Overview of 20 Years of Mortality from Parkinson's Disease.

OBJECTIVE: The consensus is that life expectancy for individuals with Parkinson's disease (PD) is reduced, but estimations vary. We aimed to provide an overview of 20 years of mortality and risk factor data from the Queensland Parkinson's Project. METHODS: The analysis included 1,334 PD and 1,127 control participants. Preliminary analysis of baseline characteristics (sex, age at onset, family history, smoking status, pesticide exposure, depression and neurosurgery) was conducted, and Kaplan-Meier curves were generated for each potential risk factor. Standardized mortality ratios (SMRs) were calculated comparing this cohort to the general Australian population. Cox proportional hazards regression modeling was used to analyze potential predictors of mortality. RESULTS: In total, 625 (46.8%) PD and 237 (21.0%) control participants were deceased. Mean disease duration until death was 15.3 ± 7.84 years. Average ages at death were 78.0 ± 7.4 years and 80.4 ± 8.4 years for the deceased PD and control participants, respectively. Mortality was significantly increased for PD in general {SMR = 2.75 [95% confidence interval (CI): 2.53-2.96]; p = 0.001}. SMRs were slightly higher for women and those with an age of onset before 60 years. Multivariate analysis showed that deep brain stimulation (DBS) treatment was associated with lower mortality [hazard ratio (HR) = 0.76; 95% CI: 0.59-0.98], while occasional pesticide exposure increased mortality risk (HR = 1.48; 95% CI: 1.17-1.88). Family history of PD, smoking and depression were not independent predictors of mortality. CONCLUSION: Mortality in PD is increased. Sex, age at onset and occasional pesticide exposure were independent determinants of increased mortality, while DBS treatment was associated with reduced mortality.

Perspective: Current Pitfalls in the Search for Future Treatments and Prevention of Parkinson's Disease.

We are gradually becoming aware that there is more to Parkinson's disease (PD) than meets the eye. Accumulating evidence has unveiled a disease complexity that has not (yet) been incorporated into ongoing efforts aimed at slowing, halting or reversing the course of PD, likely underlying their lack of success. There is a substantial latency between the actual onset of PD pathology and our ability to confirm diagnosis, during which accumulating structural and functional damage might be too advanced for effective modification or protection. Identification at the earliest stages of the disease course in the absence of Parkinsonism is crucial if we are to intervene when it matters most. Prognostic and therapeutic inferences can only be successful if we are able to accurately predict who is at risk for developing PD and if we can differentiate amongst the considerable clinicopathologic diversity. Biomarkers can greatly improve our identification and differentiation abilities if we are able to disentangle cause and effect.

Experimental Pain Decreases Corticomuscular Coherence in a Force- But Not a Position-Control Task.

Differences in neural drive could explain variation in adaptation to acute pain between postural and voluntary motor actions. We investigated whether cortical contributions, quantified by corticomuscular coherence, are affected differently by acute experimental pain in more posturally focused position-control tasks and voluntary focused force-control tasks. Seventeen participants performed position- and force-control contractions with matched loads (10% maximum voluntary contraction) before and during pain (injection of hypertonic saline into the infrapatellar fat pad of the knee). Surface electromyography (EMG) of right knee extensor and flexor muscles was recorded. Electroencephalography (EEG) was recorded using a 128-channel sensor net. Corticomuscular coherence was calculated between 4 EEG electrodes that approximated the contralateral motor cortical area, and EMG. Coherence, EEG, EMG, and target performance accuracy were compared between task types and pain states. Before pain, coherence EEG and EMG did not differ between tasks. During pain, EMG increased in both tasks, but the force-control task showed greater pain interference (decreased coherence, higher EEG frequencies, and increased force fluctuations). Neural substrates of motor performance of postural functions are changed uniquely by experimental pain, which might be explained by differences in cortical demands. Our results provide new insights into the mechanisms of motor adaptations during acute pain. PERSPECTIVE: Understanding of the mechanisms underlying adaptations to motor function in acute pain is incomplete. Experimental work almost exclusively focuses on voluntary motor actions, but these adaptations may be inappropriate for postural actions. Our results show less pain-related interference in brain activity and its relationship to muscle activation during position-control tasks.

Cerebellar transcranial direct current stimulation improves adaptive postural control.

OBJECTIVE: Rehabilitation interventions contribute to recovery of impaired postural control, but it remains a priority to optimize their effectiveness. A promising strategy may involve transcranial direct current stimulation (tDCS) of brain areas involved in fine-tuning of motor adaptation. This study explored the effects of cerebellar tDCS (ctDCS) on postural recovery from disturbance by Achilles tendon vibration. METHODS: Twenty-eight healthy volunteers participated in this sham-ctDCS controlled study. Standing blindfolded on a force platform, four trials were completed: 60 s quiet standing followed by 20 min active (anodal-tDCS, 1 mA, 20 min, N = 14) or sham-ctDCS (40 s, N = 14) tDCS; three quiet standing trials with 15 s of Achilles tendon vibration and 25 s of postural recovery. Postural steadiness was quantified as displacement, standard deviation and path derived from the center of pressure (COP). RESULTS: Baseline demographics and quiet standing postural steadiness, and backwards displacement during vibration were comparable between groups. However, active-tDCS significantly improved postural steadiness during vibration and reduced forward displacement and variability in COP derivatives during recovery. CONCLUSIONS: We demonstrate that ctDCS results in short-term improvement of postural adaptation in healthy individuals. SIGNIFICANCE: Future studies need to investigate if multisession ctDCS combined with training or rehabilitation interventions can induce prolonged improvement of postural balance.

Cortical activity differs between position- and force-control knee extension tasks.

Neural control differs between position- and force-control tasks as evident from divergent effects of fatigue and pain. Unlike force-control tasks, position-control tasks focus on a postural goal to maintain a joint angle. Cortical involvement is suggested to be less during postural control, but whether this differs between position- and force-control paradigms remains unclear. Coherence estimates the functional communication between spatially distinct active regions within the cortex (cortico-cortical coherence; CCC) and between the cortex and muscles (corticomuscular coherence; CMC). We investigated whether cortical involvement differed between force-control and more posturally focused, position-control tasks. Seventeen adults performed position- and force-control knee extensor efforts at a submaximal load (10 % maximum voluntary contraction). Surface electromyography was recorded from the right knee extensor and flexor muscles and brain activity using electroencephalography (EEG). CCC and CMC in the beta (13-30 Hz) and gamma (30-45 Hz) frequency bands were calculated between combinations of intra- and inter-hemispheric pairs of electrodes, and between four EEG electrodes that approximated the left motor cortical area, and right knee extensor EMG, respectively. Differences in EEG power and muscle activity were also calculated. CCC was greater across distributed regions in the force-control task. Beta EEG power in the left hemisphere was higher for the position-control task. Although averaged CMC data differed between tasks, there was no task difference for individual CMC data. Muscle activity and force did not differ between tasks. The results demonstrate differential cortical contributions to control force- versus position-control tasks. This might contribute to differences in performance outcomes of these tasks that have been shown previously.

Experimental pain has a greater effect on single motor unit discharge during force-control than position-control tasks.

OBJECTIVE: When matching target force during pain, single motor unit (SMU) discharge is modified in a manner thought to redistribute load in painful tissue. This adaptation might not be appropriate when maintaining joint posture against an external load. We compared changes in SMU discharge rate of knee extensor muscles in a force-control and a position-control task during pain. METHODS: Thirteen healthy adults (31±6years) performed position- and force-control contractions using matched loads in non-pain and pain states. Pain was induced by injection of hypertonic saline into the infrapatellar fat pad. Intramuscular and surface electromyography of knee extensor and flexor muscles was recorded. RESULTS: When considering the discharge of a select population of SMUs that were recorded across all conditions performed on the same day, there was a decrease in mean discharge rate, and this was smaller in the position- than force-control task for the same SMUs. A similar tendency was observed for SMUs recorded on different days. However, gross agonist muscle activity (which incorporates SMUs that are not included in the discharge rate analysis because they were not present in all conditions) increased in both tasks during pain. Gross antagonist muscle EMG only increased in the force-control task. CONCLUSION: The effect of pain on muscle activity appears unique to the contraction type, with less influence during position- than force-control tasks. SIGNIFICANCE: Simplistic theories of pain adaptation of movement during voluntary efforts cannot be extrapolated to more postural functions. This has implications for understanding movement changes that may underpin persistence/recurrence of pain and the management of musculoskeletal pain.

Changes in constraint of proximal segments effects time to task failure and activity of proximal muscles in knee position-control tasks.

OBJECTIVE: Maintenance of a limb position against external load (position-control) fails earlier (time to task failure: TTF) than maintenance of identical force against rigid restraint (force-control). Although possibly explained by physiological differences between contractions, we investigated whether less constraint of movements in other planes and proximal segments (commonly less in position-control tasks) shortens TTF. METHODS: Seventeen adults (32±7 years) contracted knee extensor muscles to task failure in a position-control task, with and without constraint of motion in other planes and proximal segments, and a force-control task with constraints. Electromyography of knee extensors, their antagonist and hip muscles was recorded with force/position. RESULTS: TTF was shorter for position-control without (161±55 s) than with constraint (184±51 s). Despite identical constraint, TTF was shorter in position- than force-control (216±56 s). Muscle activity and position variability at failure was greater without constraint. CONCLUSION: Constraint of motion of proximal segments and other planes increases position-control TTF with less muscle activity and variability. As TTF differed between force- and position-control, despite equivalent constraint, other factors contribute to shorter position-control TTF. SIGNIFICANCE: Results clarify that differences in the TTF between position- and force-control tasks are partly explained by unmatched restriction of motion in other planes and proximal segments.

Effects of a healthy meal course on spontaneous energy intake, satiety and palatability.

Many food components can influence satiety or energy intake. Combined together, these food components could represent an interesting dietary strategy in the prevention and treatment of obesity. The aims of this study were: 1) to determine the effect of a functional food in the form of a healthy meal course on subsequent energy intake and satiety; 2) to verify if it is possible to maintain palatability while preserving the satiating effects of the test meal. Thirteen subjects were invited to eat two lunch sessions: healthy and control meal courses (2090 kJ/meal). Anthropometric and ad libitum food intake measurements, and visual analogue scales (VAS) were performed during the two lunch sessions. The healthy main course acutely decreased energy intake during the rest of the meal (-744 kJ, P