Biology subjects

McKeown, M. J.

Publications and source records attributed to McKeown, M. J..

3 recordsLinked to original sources

bioRxiv2021

Preservation of eye movements in Parkinson's disease is stimulus and task specific

Parkinsons disease (PD) is a neurodegenerative disease that includes motor impairments such as tremor, bradykinesia, and postural instability. Although eye movement deficits are commonly found in saccade and pursuit tasks, preservation of oculomotor function has also been reported. Here we investigate specific task and stimulus conditions under which oculomotor function in PD is preserved. Sixteen PD patients and eighteen healthy, age-matched controls completed a battery of movement tasks that included stationary or moving targets eliciting reactive or deliberate eye movements: pro-saccades, anti-saccades, visually-guided pursuit, and rapid go/no-go manual interception. Compared to controls, patients demonstrated systematic impairments in tasks with stationary targets: pro-saccades were hypometric and anti-saccades were incorrectly initiated toward the cued target in about 35% of trials compared to 14% errors in controls. In patients, task errors were linked to short latency saccades, indicating abnormalities in inhibitory control. However, patients eye movements in response to dynamic targets were relatively preserved. PD patients were able to track and predict a disappearing moving target and make quick go/no-go decisions as accurately as controls. Patients interceptive hand movements were slower on average but initiated earlier, indicating adaptive processes to compensate for motor slowing. We conclude that PD patients demonstrate stimulus- and task-dependency of oculomotor impairments and propose that preservation of eye and hand movement function in PD is linked to a separate functional pathway through the SC-brainstem loop that bypasses the fronto-basal ganglia network. Significance StatementEye movements are a promising clinical tool to aid in the diagnosis of movement disorders and to monitor disease progression. Although Parkinsons disease (PD) patients show some oculomotor abnormalities, it is not clear whether previously-described eye movement impairments are task specific. We assessed eye movements in PD under different visual (stationary vs. moving targets) and movement (reactive vs. deliberate) conditions. We demonstrate that PD patients are able to accurately track moving objects but make inaccurate eye movements towards stationary targets. The preservation of eye movements towards dynamic stimuli might enable patients to accurately act upon the predicted motion path of the moving target. These results can inform the development of tools for the rehabilitation or maintenance of functional performance.

neuroscience↗

bioRxiv2019

Dopamine deficiency is associated with risk aversion but not loss aversion in Parkinson’s disease

IntroductionClinical evidence suggests that Parkinsons Disease (PD) patients are risk averse. Dopaminergic therapy has been reported to increase risk tolerance, but the underlying mechanisms are unclear. Some studies have suggested an amplification of subjective reward value, consistent with the role of dopamine in reward value coding. Others have reported value-independent risk enhancement. We evaluated the value-dependence of the effects of PD and its therapy on risk using tasks designed to sensitively measure risk over a wide range of expected values.\n\nMethod36 patients with idiopathic PD receiving levodopa monotherapy and 36 healthy matched controls performed two behavioural economic tasks aimed at quantifying 1) risk tolerance/ aversion in the gain frame and 2) valuation of potential gains relative to losses. PD patients performed the tasks on and off their usual dose of levodopa in randomized order; controls performed the same tasks twice.\n\nResultsRelative to the controls, unmedicated PD patients showed significant value-independent risk aversion in the gain frame, which was normalized by levodopa. PD patients did not differ from controls in their valuation of gains relative to losses. However, across both tasks and regardless of medication, choices of the patients were more determined by expected values of the prospects than those of controls.\n\nConclusionDopamine deficiency in PD was associated with risk aversion, and levodopa promoted riskier choice in a value-independent manner. PD patients also showed an increased sensitivity to expected value, which was independent of levodopa and does not appear to result directly from dopamine deficiency.

neuroscience↗

bioRxiv2018

Small effect size leads to reproducibility failure in resting-state fMRI studies

Thousands of papers using resting-state functional magnetic resonance imaging (RS-fMRI) have been published on brain disorders. Results in each paper may have survived correction for multiple comparison. However, since there have been no robust results from large scale meta-analysis, we do not know how many of published results are truly positives. The present meta-analytic work included 60 original studies, with 57 studies (4 datasets, 2266 participants) that used a between-group design and 3 studies (1 dataset, 107 participants) that employed a within-group design. To evaluate the effect size of brain disorders, a very large neuroimaging dataset ranging from neurological to psychiatric isorders together with healthy individuals have been analyzed. Parkinsons disease off levodopa (PD-off) included 687 participants from 15 studies. PD on levodopa (PD-on) included 261 participants from 9 studies. Autism spectrum disorder (ASD) included 958 participants from 27 studies. The meta-analyses of a metric named amplitude of low frequency fluctuation (ALFF) showed that the effect size (Hedges g) was 0.19 - 0.39 for the 4 datasets using between-group design and 0.46 for the dataset using within-group design. The effect size of PD-off, PD-on and ASD were 0.23, 0.39, and 0.19, respectively. Using the meta-analysis results as the robust results, the between-group design results of each study showed high false negative rates (median 99%), high false discovery rates (median 86%), and low accuracy (median 1%), regardless of whether stringent or liberal multiple comparison correction was used. The findings were similar for 4 RS-fMRI metrics including ALFF, regional homogeneity, and degree centrality, as well as for another widely used RS-fMRI metric namely seed-based functional connectivity. These observations suggest that multiple comparison correction does not control for false discoveries across multiple studies when the effect sizes are relatively small. Meta-analysis on un-thresholded t-maps is critical for the recovery of ground truth. We recommend that to achieve high reproducibility through meta-analysis, the neuroimaging research field should share raw data or, at minimum, provide un-thresholded statistical images.

neuroscience↗