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  • Fractionating the Neurocognitive Mechanisms Underlying Working Memory: Independent Effects of Dopamine and Parkinson's Disease.

    20 November 2017

    Deficits in working memory (WM) in Parkinson's disease (PD) are often considered to be secondary to dopaminergic depletion. However, the neurocognitive mechanisms by which dopamine causes these deficits remain highly contested, and PD is now also known to be associated with nondopaminergic pathology. Here, we examined how PD and dopaminergic medication modulate three components of WM: maintenance over time, updating contents with new information and making memories distracter-resistant. Compared with controls, patients were disproportionately impaired when retaining information for longer durations. By applying a probabilistic model, we were able to reveal that the source of this error was selectively due to precision of memory representations degrading over time. By contrast, replenishing dopamine levels in PD improved executive control over both the ability to ignore and update, but did not affect maintenance of information across time. This was due to a decrease in guess responses, consistent with the view that dopamine serves to prevent WM representations being corrupted by irrelevant information, but has no impact on information decay. Cumulatively, these results reveal a dissociation in the neural mechanisms underlying poor WM: whereas dopamine reduces interference, nondopaminergic systems in PD appear to modulate processes that prevent information decaying more quickly over time.

  • Apathy in rapid eye movement sleep behaviour disorder is common and under-recognised.

    20 November 2017

    BACKGROUND: Apathy is an important neuropsychiatric feature of Parkinson's disease (PD), which often emerges before the onset of motor symptoms. Patients with rapid eye movement sleep behaviour disorder (RBD) have a high probability of developing Parkinson's disease in future. Neuropsychiatric problems are common in RBD, but apathy has not previously been detailed in this key prodromal population. METHODS: 88 patients with polysomnographically proven RBD, 65 patients with PD and 33 controls were assessed for apathy using the Lille Apathy Rating Scale (LARS). Cognition and depression were also quantified. The sensitivity of the Unified Parkinson's Disease Rating Scale screening questions for apathy and depression was calculated. RESULTS: 46% of Patients with RBD were apathetic, compared with 31% of Parkinson's patients in our sample. Most RBD patients with depression were apathetic but more than half of apathetic patients were not depressed. The sensitivity of the single UPDRS screening question was only 33% for mild apathy and 50% for severe apathy. CONCLUSIONS: Apathy is common in RBD and is underestimated by a single self-report question. Recognition of apathy as a distinct neuropsychiatric feature in RBD could aid targeted treatment interventions and might contribute to understanding of prodromal Parkinson's disease. This article is protected by copyright. All rights reserved.

  • Fundamental bound on the persistence and capacity of short-term memory stored as graded persistent activity.

    17 November 2017

    It is widely believed that persistent neural activity underlies short-term memory. Yet, as we show, the degradation of information stored directly in such networks behaves differently from human short-term memory performance. We build a more general framework where memory is viewed as a problem of passing information through noisy channels whose degradation characteristics resemble those of persistent activity networks. If the brain first encoded the information appropriately before passing the information into such networks, the information can be stored substantially more faithfully. Within this framework, we derive a fundamental lower-bound on recall precision, which declines with storage duration and number of stored items. We show that human performance, though inconsistent with models involving direct (uncoded) storage in persistent activity networks, can be well-fit by the theoretical bound. This finding is consistent with the view that if the brain stores information in patterns of persistent activity, it might use codes that minimize the effects of noise, motivating the search for such codes in the brain.

  • Amiloride does not protect retinal nerve fibre layer thickness in optic neuritis in a phase 2 randomised controlled trial.

    20 November 2017

    Background: Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel. Objective: To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON). Methods: 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial with scanning laser polarimetry (GDx) at 6 month as a primary outcome measure, optical coherence tomography (OCT), visual and electrophysiological secondary outcome measures. Participants aged 18­55 years, ≤ 28 days of onset of first episode unilateral ON, were randomised to amiloride (10mg daily for 5 months) or placebo. (clinicaltrials.gov, NCT 01802489) Results: ITT cohort consisted of 43 patients; 23 placebo, and 20 amiloride. No significant drug related adverse events occurred. No significant differences were found in GDx (p=0.840). Visual evoked potentials were significantly prolonged in the amiloride group compared to placebo (p=0.004). All other secondary outcome measures showed no significant difference. Baseline analysis of OCT data demonstrated a significant pre-randomisation thinning of ganglion cell layer. Conclusion: Amiloride has not demonstrated any neuroprotective benefit within this trial paradigm but future neuroprotective trials in ON should target the window of opportunity to maximize potential neuroprotective benefit.