The apolipoprotein E (APOE) ε2 allele has been associated with both Parkinson's disease (PD) and lower low density lipoprotein cholesterol (LDL-C). The study is to test the hypothesis that lower LDL-C may be associated with PD. This case-control study used fasting lipid profiles obtained from 124 PD cases and 110 controls, the PD cases recruited from consecutive cases presenting at our tertiary Movement Disorder Clinic, and controls recruited from the spouse populations of the same clinic. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were calculated from unconditional logistic regressions, adjusting for age, gender, smoking status, and use of cholesterollowering agents. Lower LDL-C concentrations were associated with a higher prevalence of PD. Compared with participants with the highest LDL-C (≥139 mg/dL), the OR was 2.2 (95% CI 0.9-5.1) for participants with LDL-C of 115-138, 3.5 (95% CI 1.6-8.1) for LDL-C of 93-114, and 2.6 (95% CI 1.1 -5.9) for LDL-C ≤ 92. Interestingly, use of cholesterol lowering drugs or just statins was related to lower PD prevalence. Our data provide preliminary evidence that low LDL-C may be associated with higher occurrence of PD, and/or that statin use may lower PD occurrence; either of which findings warrant further investigations. KeywordsParkinson's disease; LDL cholesterol; apolipoprotein E; statin; case control study Parkinson's disease (PD) is an age-related progressive neurodegenerative disorder affecting 1-2% of the population over the age of 60 years. The lifetime risk for PD is higher in men than in women. 1 Although a few PD cases are due to several known genetic mutations, the disorder is largely idiopathic, and likely involves interactions of the genome and the environment 2 .The role of apolipoprotein (APOE) in Alzheimer's disease (AD), another age-related neurodegenerative disease, has been elucidated in the past decade. It is generally believed that the ε4 allele is a major susceptibility gene, whereas the ε2 allele is protective for AD and possibly other neurological disorders see review 3 . A recent systematic review, however, Previous epidemiological evidence on dietary fats/cholesterol and PD risk has not been consistent. 10;11 Further, these studies are not directly relevant to the potential role of cholesterol in PD etiology, as non-dietary factors may play more important roles in regulating serum lipid levels. For example, the APOE ε4 allele has been associated with higher low density lipid cholesterol (LDL-C), whereas the ε2 allele has been consistently associated with lower plasma LDL-C. 12;13 Interestingly, there has been one published abstract reporting lower plasma cholesterol concentrations in PD patients than in controls. 14 Further, Musanti et al. 15 reported dramatically lower cholesterol biosynthesis in PD patients than in controls, although there has been no subsequent follow up on this association. The above evidence, coupled with the association between ε2 and PD, led us to test hypothesis that lower serum LDL-C may be ass...
We report a patient with a clinical syndrome indistinguishable from Parkinson's disease in which postmortem examination revealed extensive lacunar infarction of the basal ganglia without evidence of coexistent Parkinson's disease. This case provides pathologic confirmation of the concept of vascular parkinsonism.
The role of higher-order thalamic structures in sensory processing remains poorly understood. Here, we used the ferret (Mustela putorius furo) as a novel model species for the study of the lateral posterior-pulvinar complex (LP/pulvinar) and its structural and functional connectivity with area 17 (primary visual cortex, V1). We found reciprocal anatomical connections between the lateral part of the Lateral Posterior Nucleus of the LP/pulvinar (LPl) and V1. In order to investigate the role of this feedback loop between LPl and V1 in shaping network activity, we determined the functional interactions between LPl and supragranular, granular, and infragranular layers of V1 by recording multiunit activity (MUA) and local field potential (LFP). Coherence was strongest between LPl and supragranular V1 with the most distinct peaks in the delta and alpha frequency bands. Inter-area interaction measured by spike-phase coupling identified the delta frequency band dominated by infragranular V1 and multiple frequency bands that were most pronounced in supragranular V1. This inter-area coupling was differentially modulated by full-field synthetic and naturalistic visual stimulation. We also found that visual responses in LPl were distinct from the ones in V1 in terms of their reliability. Together, our data support a model of multiple communication channels between the LPl and layers of V1 that are enabled by oscillations in different frequency bands. This demonstration of anatomical and functional connectivity between LPl and V1 in ferrets provides a roadmap for studying the interaction dynamics during behavior and a template for identifying activity dynamics of other thalamic feedback loops.
Context: Despite its widespread use, the precise mechanism of action of Deep Brain Stimulation (DBS) therapy remains unknown. The modern urgency to publish more and new data can obscure previously learned lessons by the giants who have preceded us and whose shoulders we now stand upon. Wilder Penfield extensively studied the effects of artificial electrical brain stimulation and his comments on the subject are still very relevant today. In particular, he noted two very different (and seemingly opposite) effects of stimulation within the human brain. In some structures, artificial electrical stimulation has an effect, which mimics ablation, while, in other structures, it produces a stimulatory effect on that tissue.Hypothesis: The hypothesis of this paper is fourfold. First, it proposes that some neural circuits are widely synchronized with other neural circuits, while some neural circuits are unsynchronized and operate independently. Second, it proposes that artificial high-frequency electrical stimulation of a synchronized neural circuit results in an ablative effect, but artificial high-frequency electrical stimulation of an unsynchronized neural circuit results in a stimulatory effect. Third, it suggests a part of the mechanism by which large-scale physiologic synchronization of widely distributed independently processed information streams may occur. This may be the neural mechanism underlying Penfield’s “centrencephalic system,” which he emphasized so many years ago. Fourth, it outlines the specific anatomic distribution of this physiologic synchronization, which Penfield has already clearly delineated as the distribution of his centrencephalic system.Evidence: This paper draws on a brief overview of previous theory regarding the mechanism of action of DBS and on historical, as well as widely known modern clinical data regarding the observed effects of stimulation delivered to various targets within the brain. Basic science investigations, which support the hypothesis are also cited.Conclusion: This paper proposes a novel hypothesis for the mechanism of action of DBS, which was conceptually foreshadowed by Wilder Penfield decades ago.
Dehumanization is anecdotally and historically associated with reduced empathy for the pain of dehumanized individuals and groups and with psychological and legal denial of their human rights and extreme violence against them. We hypothesize that ‘empathy’ for the pain and suffering of dehumanized social groups is automatically reduced because, as the research we review suggests, an individual's neural mechanisms of pain empathy best respond to (or produce empathy for) the pain of people whom the individual automatically or implicitly associates with her or his own species. This theory has implications for the philosophical conception of ‘human’ and of ‘legal personhood’ in human rights jurisprudence. It further has implications for First Amendment free speech jurisprudence, including the doctrine of ‘corporate personhood’ and consideration of the potential harm caused by dehumanizing hate speech. We suggest that the new, social neuroscience of empathy provides evidence that both the vagaries of the legal definition or legal fiction of ‘personhood’ and hate speech that explicitly and implicitly dehumanizes may (in their respective capacities to artificially humanize or dehumanize) manipulate the neural mechanisms of pain empathy in ways that could pose more of a true threat to human rights and rights-based democracy than previously appreciated.
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