9 research outputs found
The role of the mammalian prion protein in the control of sleep
Sleep disruption is a prevalent clinical feature in many neurodegenerative disorders, including human prion diseases where it can be the defining dysfunction, as in the case of the âeponymousâ fatal familial insomnia, or an early-stage symptom as in certain types of Creutzfeldt-Jakob disease. It is important to establish the role of the cellular prion protein (PrPC), the key molecule involved in prion pathogenesis, within the sleep-wake system in order to understand fully the mechanisms underlying its contribution to both healthy circadian rhythmicity and sleep dysfunction during disease. Although severe disruption to the circadian rhythm and melatonin release is evident during the pathogenic phases of some prion diseases, untangling whether PrPC plays a role in circadian rhythmicity, as suggested in mice deficient for PrPC expression, is challenging given the lack of basic experimental research. We provide a short review of the small amount of direct literature focused on the role of PrPC in melatonin and circadian rhythm regulation, as well as suggesting mechanisms by which PrPC might exert influence upon noradrenergic and dopaminergic signaling and melatonin synthesis. Future research in this area should focus upon isolating the points of dysfunction within the retino-pineal pathway and further investigate PrPC mediation of pinealocyte GPCR activity
A Time Series Approach to Parkinson's Disease Classification from EEG
Firstly, we present a novel representation for EEG data, a 7-variate series
of band power coefficients, which enables the use of (previously inaccessible)
time series classification methods. Specifically, we implement the
multi-resolution representation-based time series classification method MrSQL.
This is deployed on a challenging early-stage Parkinson's dataset that includes
wakeful and sleep EEG. Initial results are promising with over 90% accuracy
achieved on all EEG data types used. Secondly, we present a framework that
enables high-importance data types and brain regions for classification to be
identified. Using our framework, we find that, across different EEG data types,
it is the Prefrontal brain region that has the most predictive power for the
presence of Parkinson's Disease. This outperformance was statistically
significant versus ten of the twelve other brain regions (not significant
versus adjacent Left Frontal and Right Frontal regions). The Prefrontal region
of the brain is important for higher-order cognitive processes and our results
align with studies that have shown neural dysfunction in the prefrontal cortex
in Parkinson's Disease
Inaccurate self-report of olfactory dysfunction in REM Sleep Behaviour Disorder and implications for prognosis
Introduction: The earliest stages of alpha-synucleinopathies are accompanied by non-specific prodromal symptoms such as diminished sense of smell, constipation and depression, as well as more specific prodromal conditions including REM Sleep Behaviour Disorder (RBD). While the majority of RBD patients will develop an alpha-synucleinopathy, one of the greatest clinical challenges is determining whether and when individual patients will phenoconvert. Clinical evaluation of a patient presenting with RBD should therefore include robust and objective assessments of known alpha-synucleinopathy prodromes. Methods: This study compared olfactory function self-report measures with psychophysical âSniffinâ Stick 16-item Identificationâ test scores in Control (n = 19), RBD (n = 16) and PD (n = 17) participants. Results: We confirm that olfactory test scores are significantly diminished in RBD and PD groups compared to Controls (p < 0.001, One-Way ANOVA with Tukey-Kramer Post-Hoc, effect size = 0.401). However, RBD participants were only 56 % accurate when self-reporting olfactory dysfunction, hence markedly less likely to perceive or acknowledge their own hyposmia compared to Controls (p = 0.045, Fisherâs Exact Test, effect-size = 0.35). Conclusion: When isolated RBD presents with hyposmia, there is an increased likelihood of phenoconversion to Parkinsonâs Disease (PD) or Dementia with Lewy Bodies (DLB); unawareness of olfactory dysfunction in an individual with isolated RBD may therefore confound differential diagnosis and prognosis. Our results evidence the fallibility of olfactory function self-report in the context of RBD prognosis, indicating that clinical assessments of RBD patients should include more reliable measures of olfactory status