Assessment of the visual thalamic circuitry in hallucinations in dementia with Lewy bodies

PhD ThesisBackground Visual hallucinations occur in 70-90% of patients with dementia with Lewy bodies (DLB) and are related to decreased quality of life for patients. However, the underlying neuropathological changes that promote the manifestation of visual hallucinations in DLB are not known. Several hypotheses of visual hallucinations in DLB have either directly implicated the lateral geniculate nucleus (LGN), pulvinar and superior colliculus or suggested impairments in their putative functions. Methods Post-mortem LGN, pulvinar and superior colliculus tissue was obtained from DLB cases with a clinical history of visual hallucinations and compared to cognitively normal control and Alzheimer’s disease (AD) cases without visual hallucinations. Neuropathological lesions were quantified in individual cases using densitometry and neuronal and glial cell populations were quantified with stereology. RNA sequencing and subsequent bioinformatics analysis of biological pathway alterations was performed by a collaborator on pulvinar tissue from DLB and non-hallucinating control cases. The bioinformatics data was used to identify protein targets based on pathway alterations, which were then investigated using western blot analysis. Results Lewy body pathology and neuronal loss was specifically found in the pulvinar and superior colliculus of DLB cases, particularly in regions implicated in visual attention and target selection. In contrast, AD cases had more widespread degenerative changes. Molecular analysis of the pulvinar demonstrated reduced expression of several synaptic markers, concomitant with elevated expression of several astrocytic markers in DLB. Conclusion ii The relative specificity of changes in visual thalamic regions may contribute to the occurrence of visual hallucinations in DLB. Synaptic degeneration in the pulvinar likely further impedes visual attentional function in DLB. The present results may indicate DLB patients have impairments in directing visual attention to external stimuli, thus facilitating visual hallucinations by an over-reliance upon expectations and experience rather than stimulus-driven perception.Yvonne Emily Mairy, whose generous donation to the National Institute for Health Research Biomedical Research Unit in Lewy body dementia at Newcastle University funded this project. I a

The Trial of Queen Caroline and the Impeachment of President Clinton: Law As a Weapon for Political Reform

This Article addresses the trial of Queen Caroline in the English House of Lords in 1820, and the impeachment in 1998 and trial in 1999 of President Clinton

An Analysis of the Legality of Television Cameras Broadcasting Juror Deliberations in a Criminal Case

This work sets out the constitutional, statutory, and common law applicable to television’s intrusion into the jury room. The first section addresses federal constitutional considerations focusing on Article III Section 2, the Sixth Amendment, and the First Amendment. The second section analyzes certain federal rules and particular statutes applicable to televising federal judicial proceedings, as well as the rationale behind their enactment. Finally, the third section discusses comparative approaches addressing television’s intrusion into the courtroom, particularly focusing on recent jurisprudence from the European Court of Human Rights and the Scottish Court of Session

Neurodegenerative brain changes are associated with area deprivation in the United Kingdom: findings from the Brains for Dementia Research study

Socioeconomic disadvantage is associated with greater risk of dementia. This has been theorised to reflect inequalities in cognitive reserve, healthcare access, lifestyle, and other health factors which may contribute to the clinical manifestation of dementia. We aimed to assess whether area deprivation in the United Kingdom was associated with greater risk or severity of the specific neurodegenerative diseases which lead to dementia in a multi-centre cohort with autopsy assessment. Participants underwent clinical assessment prior to brain tissue donation post-mortem. Each then underwent detailed, standardised neuropathological assessment. National area deprivation statistics were derived for each participant’s neighbourhood, for use as a predictor in binary and ordinal logistic models assessing the respective presence and severity of staging of key neuropathological changes, adjusting for theorised confounders. Individuals from among the 20% most deprived neighbourhoods in the United Kingdom had significantly higher neurofibrillary tangle and neuritic plaque staging, and increased risk of cerebral amyloid angiopathy. These findings were not explained by a greater risk of diabetes or hypertension, APOE genotype, alcohol misuse or tobacco smoking, sex, or age differences. A sensitivity analysis conditioning on baseline cognitive impairment did not meaningfully change the observed association. Socioeconomic disadvantage may contribute to dementia incidence through a greater severity of specific neuropathological changes (neurofibrillary tangles, neuritic plaques, and cerebral amyloid angiopathy), independent of other indirect influences. Mechanisms through which deprivation is associated with these require further exploration

Precise Stellar Radial Velocities of an M Dwarf with a Michelson Interferometer and a Medium-resolution Near-infrared Spectrograph

Precise near-infrared radial velocimetry enables efficient detection and transit verification of low-mass extrasolar planets orbiting M dwarf hosts, which are faint for visible-wavelength radial velocity surveys. The TripleSpec Exoplanet Discovery Instrument, or TEDI, is the combination of a variable-delay Michelson interferometer and a medium-resolution (R=2700) near-infrared spectrograph on the Palomar 200" Hale Telescope. We used TEDI to monitor GJ 699, a nearby mid-M dwarf, over 11 nights spread across 3 months. Analysis of 106 independent observations reveals a root-mean-square precision of less than 37 m/s for 5 minutes of integration time. This performance is within a factor of 2 of our expected photon-limited precision. We further decompose the residuals into a 33 m/s white noise component, and a 15 m/s systematic noise component, which we identify as likely due to contamination by telluric absorption lines. With further development this technique holds promise for broad implementation on medium-resolution near-infrared spectrographs to search for low-mass exoplanets orbiting M dwarfs, and to verify low-mass transit candidates.Comment: 55 pages and 13 figures in aastex format. Accepted by PAS