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.

Non-Contact Hand Movement Analysis for Optimal Configuration of Smart Sensors to Capture Parkinson's Disease Hand Tremor.

Parkinson's disease affects millions worldwide with a large rise in expected burden over the coming decades. More easily accessible tools and techniques to diagnose and monitor Parkinson's disease can improve the quality of life of patients. With the advent of new wearable technologies such as smart rings and watches, this is within reach. However, it is unclear what method for these new technologies may provide the best opportunity to capture the patient-specific severity. This study investigates which locations on the hand can be used to capture and monitor maximal movement/tremor severity. Using a Leap Motion device and custom-made software the volume, velocity, acceleration, and frequency of Parkinson's (n = 55, all right-handed, majority right-sided onset) patients' hand locations (25 joints inclusive of all fingers/thumb and the wrist) were captured simultaneously. Distal locations of the right hand, i.e., the ends of fingers and the wrist showed significant trends (p < 0.05) towards having the largest movement velocities and accelerations. The right hand, compared with the left hand, showed significantly greater volumes, velocities, and accelerations (p < 0.01). Supplementary analysis showed that the volumes, acceleration, and velocities had significant correlations (p < 0.001) with clinical MDS-UPDRS scores, indicating the potential suitability of using these metrics for monitoring disease progression. Maximal movements at the distal hand and wrist area indicate that these locations are best suited to capture hand tremor movements and monitor Parkinson's disease.

Childbirth and Delayed Parkinson's Onset: A Reproducible Nonbiological Artifact of Societal Change.

BACKGROUND: Uncontrolled studies have reported associations between later Parkinson's disease onset in women and a history of giving birth, with age at onset delayed by nearly 3 years per child. We tested this association in two independent data sets, but, as a control to test for nonbiological explanations, also included men with PD. METHODS: We analyzed valid cases from the Parkinson's Progressive Markers Initiative incident sample (145 women, 276 men) and a prevalent sample surveyed by the New Zealand Brain Research Institute (210 women, 394 men). RESULTS: The association was present in both women and men in the Parkinson's Progressive Markers Initiative study, and absent in both in the New Zealand Brain Research Institute study. This is consistent with generational differences common to men and women, which confound with age at onset in incident-dominant samples. CONCLUSIONS: Despite being replicable in certain circumstances, associations between childbirth and later PD onset are an artifact of generational cohort differences. © 2020 International Parkinson and Movement Disorder Society.

Parkinson's disease across ethnicities: A nationwide study in New Zealand.

BACKGROUND: New Zealand is an ethnically diverse country with a unified national prescribing system. This provides a good framework to use drug-tracing methodology to establish the prevalence and incidence of Parkinson's disease across different ethnic groups. The objective of this study was to determine the prevalence and incidence of Parkinson's disease in the major ethnic groups in New Zealand. METHODS: Information on Parkinson's disease-related medications was extracted from the national Pharmaceutical Collection of community-dispensed medications for the period January 1, 2005, to December 31, 2014. Diagnoses for a large subset of individuals were independently determined through national mortality and hospital admissions data sets. We used a Bayesian model, accommodating uncertainty and bias, to estimate the number of people with Parkinson's disease. RESULTS: We found the highest rate of Parkinson's disease in the European ethnic group and the lowest rate in the indigenous Maori. The 2006-2013 age-standardized incidence (per 100,000 population per year) was European, 33; Asian, 28; Pasifika, 27; Maori, 20. The 2013 age-standardized prevalence (per 100,000 population) was European, 223; Asian, 174; Pasifika, 160; Maori, 114. CONCLUSIONS: There is a differential occurrence of Parkinson's disease across the major ethnic groups within the New Zealand population, with indigenous Maori showing the lowest incidence. Varying susceptibility profiles, gene-environment interactions, and inequalities in accessing health care may play a role in the variation in rates of Parkinson's disease in New Zealand. © 2018 International Parkinson and Movement Disorder Society.

Response to "Parkinson's disease mild cognitive impairment classifications and neurobehavioral symptoms".

A recent paper, "Parkinson's disease mild cognitive impairment classifications and neurobehavioral symptoms" (McDermott et al., 2017), provides an interesting comparison of the influence of different criteria for Parkinson's disease with mild cognitive impairment (PD-MCI) on progression to dementia (PDD). Unfortunately, McDermott et al. (2017) incorrectly stated that "only 21% of PD-MCI participants (identified with a 1.5 SD cut-off) converted to PDD within four years" (p.6) in our study (Wood et al., 2016). However, the important point made by Wood et al. (2016) was that the proportion of conversions to PDD was 51% when the PD-MCI diagnosis required a minimum of two 1.5 SD impairments within any single cognitive domain, whereas additional PD-MCI patients classified with one impairment at 1.5 SD in each of the two domains (but never two impairments in the same domain) had a non-significant risk of dementia relative to non-MCI patients (11% vs. 6% converted, respectively). Our PDD conversion rate was 38% when combining both 1.5 SD criteria (21/56 PD-MCI patients vs. 4/65 non-MCI patients converted); McDermott et al. (2017) found a 42% conversion rate over three years for similarly described PD-MCI patients (10/24 PD-MCI patients vs. 0/27 non-MCI patients converted). Our study was also part of a multinational study (n = 467) showing that PD-MCI has predictive validity beyond known demographic and PD-specific factors of influence (Hoogland et al., 2017). All three studies found that multiple cognitive domain impairments are common in PD-MCI. Nonetheless, the research community needs to clarify the association between PD-MCI subtypes and, especially, the optimal cognitive markers for dementia risk in PD patients.

Eye movements in neurodegenerative diseases.

PURPOSE OF REVIEW: Abnormalities of oculomotor control accompany the pathological changes underlying many neurodegenerative diseases. Clinical examination of eye movements can contribute to differential diagnosis, whereas quantitative laboratory measures can provide detailed insight into the disease process. In this review of eye movements in neurodegenerative disease, we summarise recent empirical findings and conceptual advances. RECENT FINDINGS: Oculomotor researchers continue to be particularly prolific in studying Parkinson's disease but there is also substantial activity in Alzheimer's disease and spinocerebellar ataxia. Interesting findings have been reported in Huntington's, motor neuron disease, and glaucoma. Most studies report laboratory-based investigations but useful progress in clinical description continues to be made. SUMMARY: Eye movements remain an active field of investigation across a variety of neurodegenerative conditions. Progress continues to be made at the clinical level as well by using laboratory techniques.

A Randomized Controlled Feasibility Trial of a Specific Cueing Program for Falls Management in Persons With Parkinson Disease and Freezing of Gait.

BACKGROUND AND PURPOSE: Freezing of gait (FOG) increases fall risk in persons with Parkinson disease (PD). Cueing improves gait parameters associated with freezing, but it is unclear whether a cueing program can address falling. METHODS: We used a parallel-groups delayed- (n = 12) or immediate-start (n = 9) randomized controlled trial design to evaluate a cueing exercise program for FOG and falls in participants with PD. Each group received preintervention falls monitoring, followed by a 6-month standardized, home-based, cueing exercise and education program. Participant questionnaires rated program value and compliance. Freezing was measured with the New Freezing of Gait Questionnaire (NFOGQ). Falls were recorded by weekly diaries. RESULTS: Self-reported adherence was high; 83% of participants reported exercising after 6 months. Participants reported that the program was beneficial (89%), walking improved (78%), falls were fewer (73%), and self-management of freezing improved (61%). Mean (standard deviation) NFOGQ scores were 14.8 (5.0), for the immediate (n = 10), and 16.0 (7.7) for the delayed group (n = 9), after 6 months (difference -1.0 [95% confidence interval, -7.9 to 6.0; P = 0.78]). With baseline NFOGQ scores as a covariate, the estimate of difference was -0.7 (95% confidence interval, -6.1 to 4.7; P = 0.79). The relative rate of falls for immediate compared with delayed groups was 1.22 (95% confidence interval, 0.45 to 3.26). CONCLUSIONS: The cueing program intervention is acceptable and participants feel they improve; however, this small feasibility study lacks statistical power to detect important changes in falls rates or FOG severity. A larger study is warranted to further investigate the potential to influence FOG and falls.Video Abstract available for more insights from the authors (Supplemental Digital Content 1, http://links.lww.com/JNPT/A105).

Fixational saccades alter the gap effect.

The reaction times of saccadic eye movements have been studied extensively as a probe for cognitive behavior controlled by large-scale cortical and subcortical neural networks. Recent studies have shown that the reaction times of targeting saccades toward peripheral visual stimuli are prolonged by fixational saccades, the largest miniature eye movements including microsaccades. We have shown previously that the frequency of fixational saccades is decreased by volitional action preparation controlled internally during the antisaccade paradigm (look away from a stimulus). Instead, here we examined whether fixational saccade modulation induced externally by sensory events could also account for targeting saccade facilitation by the same sensory events. When targeting saccades were facilitated by prior fixation stimulus disappearance (gap effect), fixational saccade occurrence was reduced, which could theoretically facilitate targeting saccades. However, such reduction was followed immediately by the rebound of fixational saccade occurrence in some subjects, which could eliminate potential benefits from the previous fixational saccade reduction. These results do not mean that fixational saccades were unrelated to the gap effect because they indeed altered that effect by delaying targeting saccade initiation on trials without the fixation gap more strongly than trials with it. Such changes might be attributed to the disruption of volitional saccade preparation because the frequency of fixational saccades observed in this study was associated with the ability of volitional control over antisaccade behavior. These results suggest that fixational saccades alter the gap effect on targeting saccade reaction times, presumably by disrupting volitional saccade commands.

Cross-Sectional and Longitudinal Association of Clinical and Neurocognitive Factors With Apathy in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: A robust understanding of the natural history of apathy in Parkinson disease (PD) is foundational for developing effective clinical management tools. However, large longitudinal studies are lacking while the literature is inconsistent about even cross-sectional associations. We aimed to determine the longitudinal predictors of apathy development in a large cohort of people with PD and its cross-sectional associations and trajectories over time, using sophisticated Bayesian modeling techniques. METHODS: People with PD followed up in the longitudinal New Zealand Parkinson's progression project were included. Apathy was defined using the neuropsychiatric inventory subscale ≥4, and analyses were also repeated using a less stringent cutoff of ≥1. Both MoCA and comprehensive neuropsychological testing were used as appropriate to the model. Depression was assessed using the hospital anxiety and depression scale. Cross-sectional Bayesian regressions were conducted, and a multistate predictive model was used to identify factors that predict the initial onset of apathy in nonapathetic PD, while also accounting for the competing risk of death. The relationship between apathy presence and mortality was also investigated. RESULTS: Three hundred forty-six people with PD followed up for up to 14 years across a total of 1,392 sessions were included. Apathy occurrence did not vary significantly across the disease course (disease duration odds ratio [OR] = 0.55, [95% CI 0.28-1.12], affecting approximately 11% or 22% of people at any time depending on the NPI cutoff used. Its presence was associated with a significantly higher risk of death after controlling for all other factors (hazard ratio [HR] = 2.92 [1.50-5.66]). Lower cognition, higher depression levels, and greater motor severity predicted apathy development in those without motivational deficits (HR [cognition] = 0.66 [0.48-0.90], HR [depression] = 1.45 [1.04-2.02], HR [motor severity] = 1.37 [1.01-1.86]). Cognition and depression were also associated with apathy cross-sectionally, along with male sex and possibly lower dopaminergic therapy level, but apathy still occurred across the full spectrum of each variable (OR [cognition] = 0.58 [0.44-0.76], OR [depression] = 1.43 [1.04-1.97], OR [female sex] = 0.45 [0.22-0.92], and OR [levodopa equivalent dose] = 0.78 [0.59-1.04]. DISCUSSION: Apathy occurs across the PD time course and is associated with higher mortality. Depressive symptoms and cognitive impairment in particular predict its future development in those with normal motivation.

A perceptual discrimination task results in greater facilitation of voluntary saccades in Parkinson's disease patients.

Many studies have shown that Parkinson's disease (PD) affects not only the ability to generate voluntary saccades but also the ability to suppress reflexive saccades (hyper-reflexivity). To further investigate these apparently contradictory effects of PD on the saccade system we adapted a well-known dual-task paradigm (Deubel, 2008) to measure saccades with and without a peripheral discrimination task. Previously we reported that the concurrent performance of a perceptual discrimination task abnormally reduced the latencies of reflexive saccades in PD. Here we report the effects of the concurrent discrimination task on the generation of voluntary saccades in a PD and a control group. As expected, when saccades were performed without the discrimination task the PD group made voluntary saccades with longer latencies and smaller gain than the control group. The concurrent performance of the perceptual discrimination task facilitated the initiation of voluntary saccades in both groups, but, surprisingly, this facilitatory effect was stronger in the PD group than in the control group. In addition, in the PD group voluntary saccades were abnormally facilitated by the peripheral symbol-changes that occur during saccade planning in this paradigm. The results of this study may help to clarify apparently contradictory oculomotor abnormalities observed in PD.

Grey matter atrophy in cognitively impaired Parkinson's disease.

OBJECTIVE: Mild cognitive impairment and dementia are common non-motor features of Parkinson's disease (PD). The aim of this study was to characterise grey matter changes associated with clearly defined stages of cognitive impairment in PD using structural MRI. METHODS: 96 PD subjects were classified using detailed cognitive testing as PD with normal cognition (PD-N, n=57), PD with mild cognitive impairment (PD-MCI, n=23) or PD with dementia (PD-D, n=16); 34 controls matched for mean age and sex ratio also participated. Grey matter volume differences were evaluated using voxel based morphometry of grey matter segments derived from T1 weighted 3 T MRI, and multiple linear regression assessed the relationship between cognitive and motor impairments and grey matter concentration. RESULTS: Compared with controls, no grey matter differences were found in PD-N. PD-MCI showed limited grey matter atrophy in the temporal, parietal and frontal cortex as well as the bilateral caudal hippocampus, amygdala and right putamen. PD-D subjects exhibited far more extensive atrophy in regions involved in PD-MCI but also had reduced grey matter volume in other large areas of the temporal lobe (including the parahippocampi), the intracalcarine and lingual gyri, posterior cingulate gyrus, frontal regions and bilateral caudate. Grey matter loss in PD correlated with global cognitive score but not motor impairment in most of these regions. INTERPRETATION: Marked grey matter atrophy occurs in PD with dementia but far less extensive changes are evident in PD-MCI. Some grey matter atrophy precedes the development of dementia but may be accelerated once frank dementia begins.

Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease.

There is a need for objective imaging markers of Parkinson's disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinson's disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinson's disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinson's disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinson's disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinson's disease.

A perceptual discrimination task abnormally facilitates reflexive saccades in Parkinson's disease.

Numerous studies have shown that Parkinson's disease (PD) affects the ability to generate voluntary saccades and the ability to suppress reflexive saccades. The effects of PD on the generation of reflexive saccades, however, are not clear. Some studies report impairments, but there are also reports of abnormal facilitation or hyper-reflexivity of the saccade system in PD. Meanwhile, it has been reported that the concurrent performance of a perceptual discrimination task facilitates saccade initiation and reduces saccade latencies in healthy subjects [A. Montagnini & L. Chelazzi (2005)Vis. Res., 45, 3391-3401; L. Trottier & J. Pratt (2005)Vis. Res., 45, 1349-1354]. To investigate the circumstances under which the saccade system may appear hyper-reflexive in PD, we compared reflexive saccades with and without a concurrent perceptual discrimination task in 20 PD patients and 20 controls. Without the discrimination task, the PD group produced reflexive saccades at normal latencies. The discrimination task reduced saccade latencies more in the PD group than in the control group, resulting in abnormally short mean reflexive saccade latencies in the PD group. The discrimination task increased saccade gain in both groups, but saccades in the PD group remained hypometric as compared with saccades in the control group. We conclude that the attentional demands of this paradigm revealed a hypersensitivity to visual inputs in the PD group.

Characterizing mild cognitive impairment in Parkinson's disease.

There is growing interest in identifying Parkinson's disease (PD) patients with mild cognitive impairment (PD-MCI), but widely disparate criteria have been used. We assessed 143 PD patients and 50 matched controls on 20 measures across 4 cognitive domains (executive function, attention and working memory, learning and memory, visuoperception). Twenty-four patients met criteria for dementia (PD-D); nondementia patients were classified as either with normal cognition or MCI for 12 neuropsychological criteria. We compared the influence of these criteria on the distribution of global cognitive performance in the resulting PD-MCI groups relative to the control and PD-D groups. Different criteria produced substantial variation in the proportion of PD-MCI cases identified. Fourteen percent PD-MCI was found when using 2 scores in 1 domain at 2 standard deviations (SD) below normative scores, with no controls identified as MCI, through to 89% PD-MCI with 1 score in 1 domain at 1 SD below normative scores, when 70% of controls were identified as MCI. The balance of cases with impaired cognition but not those with generally intact cognition was better served by using criteria that required 2 specific deficit scores or deficits across 2 domains. As comparisons with external normative data may have greater applicability across centers, we suggest that 2 scores at -1.5 SD within any single domain (30% PD-MCI) or 1 score at -1.5 SD in each of 2 domains (37% PD-MCI) provide suitable criteria to minimize the inclusion of cognitively well patients. Clinical dementia rating did not improve the relative identification of cognitively impaired and unimpaired nondementia PD patients.

Bottom-up effects modulate saccadic latencies in well-known eye movement paradigm.

A well-known eye movement paradigm combines saccades (fast eye movements) with a perceptual discrimination task. At a variable time after the onset of a central arrow cue indicating the target direction [the stimulus onset asynchrony (SOA)], discrimination symbols appear briefly at saccade target and non-target locations. A previous study revealed an unexpected effect of SOA on saccadic latencies: latencies were longer in trials with longer SOAs. It was suggested that this effect reflects a top-down process as observers may wait for the discrimination symbol to appear before executing saccades. However, symbol onsets may also modulate saccade latencies from the bottom-up. To clarify the origin of the SOA effect on latencies in this paradigm, we used a simplified version of the original task plus two new symbol onset conditions for comparison. The results indicate that the modulation of saccadic latencies was not due to a top-down strategy, but to a combination of two opposing bottom-up effects: the symbol onsets at the target location shortened saccade latencies, while symbol onsets at non-target locations lengthened saccade latencies.

Neuropsychiatric Symptoms Are Associated with Dementia in Parkinson's Disease but Not Predictive of it.

BACKGROUND: Neuropsychiatric symptoms in Parkinson's disease (PD) may increase dementia (PDD) risk. The predictive value of these symptoms, however, has not been compared to clinical and demographic predictors of future PDD. OBJECTIVES: Determine if neuropsychiatric symptoms are useful markers of PDD risk. METHODS: 328 PD participants completed baseline neuropsychiatric and MDS-Task Force-Level II assessments. Of these, 202 non-demented individuals were followed-up over a four-years period to detect conversion to PDD; 51 developed PDD. ROC analysis tested associations between baseline neuropsychiatric symptoms and future PDD. The probability of developing PDD was also modeled as a function of neuropsychiatric inventory (NPI)-total score, PD Questionnaire (PDQ)-hallucinations, PDQ-anxiety, and contrasted to cognitive ability, age, and motor function. Leave-one-out information criterion was used to evaluate which models provided useful information when predicting future PDD. RESULTS: The PDD group experienced greater levels of neuropsychiatric symptoms compared to the non-PDD groups at baseline. Few differences were found between the PD-MCI and PD-N groups. Six neuropsychiatric measures were significantly, but weakly, associated with future PDD. The strongest was NPI-total score: AUC = 0.66 [0.57-0.75]. There was, however, no evidence it contained useful out-of-sample predictive information of future PDD (delta ELPD = 1.8 (SD 2.5)); Similar results held for PDQ-hallucinations and PDQ-anxiety. In contrast, cognitive ability (delta ELPD = 36 (SD 8)) and age (delta ELPD = 11 (SD 5)) provided useful predictive information of future PDD. CONCLUSIONS: Cognitive ability and age strongly out-performed neuropsychiatric measures as markers of developing PDD within 4 years. Therefore, neuropsychiatric symptoms do not appear to be useful markers of PDD risk.

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.

The timing mega-study: comparing a range of experiment generators, both lab-based and online.

Many researchers in the behavioral sciences depend on research software that presents stimuli, and records response times, with sub-millisecond precision. There are a large number of software packages with which to conduct these behavioral experiments and measure response times and performance of participants. Very little information is available, however, on what timing performance they achieve in practice. Here we report a wide-ranging study looking at the precision and accuracy of visual and auditory stimulus timing and response times, measured with a Black Box Toolkit. We compared a range of popular packages: PsychoPy, E-Prime®, NBS Presentation®, Psychophysics Toolbox, OpenSesame, Expyriment, Gorilla, jsPsych, Lab.js and Testable. Where possible, the packages were tested on Windows, macOS, and Ubuntu, and in a range of browsers for the online studies, to try to identify common patterns in performance. Among the lab-based experiments, Psychtoolbox, PsychoPy, Presentation and E-Prime provided the best timing, all with mean precision under 1 millisecond across the visual, audio and response measures. OpenSesame had slightly less precision across the board, but most notably in audio stimuli and Expyriment had rather poor precision. Across operating systems, the pattern was that precision was generally very slightly better under Ubuntu than Windows, and that macOS was the worst, at least for visual stimuli, for all packages. Online studies did not deliver the same level of precision as lab-based systems, with slightly more variability in all measurements. That said, PsychoPy and Gorilla, broadly the best performers, were achieving very close to millisecond precision on several browser/operating system combinations. For response times (measured using a high-performance button box), most of the packages achieved precision at least under 10 ms in all browsers, with PsychoPy achieving a precision under 3.5 ms in all. There was considerable variability between OS/browser combinations, especially in audio-visual synchrony which is the least precise aspect of the browser-based experiments. Nonetheless, the data indicate that online methods can be suitable for a wide range of studies, with due thought about the sources of variability that result. The results, from over 110,000 trials, highlight the wide range of timing qualities that can occur even in these dedicated software packages for the task. We stress the importance of scientists making their own timing validation measurements for their own stimuli and computer configuration.

Volitional Suppression of Parkinsonian Resting Tremor.

BACKGROUND: We have observed in the clinic that a number of patients with Parkinson's disease (PD) can suppress their tremor at will for brief periods, by conscious mental processes. To our knowledge, the ability to consciously diminish one's resting tremor has not yet been reported nor assessed quantitatively. OBJECTIVE: To provide the first detailed systematic investigation of the phenomenon of voluntary tremor suppression in PD. METHODS: We examined changes in tremor characteristics during voluntary tremor suppression in 37 PD patients (on medication) presenting with rest tremor in their upper limb. We measured tremor oscillations with a triaxis accelerometer on the index finger of the most-affected hand (n = 27). With surface electromyography (EMG), we measured changes in neuromuscular activity of the forearm flexor digitorum superficialis and extensor digitorum muscles (n = 15). Participants completed four 1-minute trials, consisting of alternating consecutive 30-second periods of resting tremor and 30-second periods of attempted tremor suppression. RESULTS: Bayesian multilevel modeling revealed that attempted voluntary tremor suppression did indeed reduce tremor amplitude (peak power) of the acceleration signal and increased tremor frequency of the acceleration and EMG signals. Relative EMG power in the 3- to 8-Hz tremor band was also smaller. Tremor suppression was not by enhanced voluntary contraction of the relevant muscle pairs. CONCLUSIONS: We present novel empirical evidence that PD resting tremor can be suppressed by an act of will, as evidenced by significant modulation of key neurophysiological tremor characteristics. These data highlight that it is possible to exert significant conscious control over parkinsonian resting tremor.