In vivo functional neurochemistry of human cortical cholinergic function during visuospatial attention

Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dysfunction in the cholinergic system has been described in a number of neuropsychiatric disorders. Levels of brain acetylcholine can be pharmacologically manipulated, but it is not possible to directly measure it in vivo in humans. However, key parts of its biochemical cascade in neural tissue, such as choline, can be measured using magnetic resonance spectroscopy (MRS). There is evidence that levels of choline may be an indirect but proportional measure of acetylcholine availability in brain tissue. In this study, we measured relative choline levels in the parietal cortex using functional (event-related) MRS (fMRS) during performance of a visuospatial attention task, with a modelling approach verified using simulated data. We describe a task-driven interaction effect on choline concentration, specifically driven by contralateral attention shifts. Our results suggest that choline MRS has the potential to serve as a proxy of brain acetylcholine function in humans

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Retinal ganglion cell loss is associated with future disability worsening in early relapsing remitting multiple sclerosis

BACKGROUND: Thinning of the retinal combined ganglion cell and inner plexiform layer (GCIP) as measured by optical coherence tomography (OCT) is a common finding in patients with multiple sclerosis. This study aimed to investigate whether a single retinal OCT analysis allows prediction of future disease activity after a first demyelinating event. METHODS: Observational cohort study including 201 patients with recently diagnosed clinically isolated syndrome or relapsing remitting multiple sclerosis from two German tertiary referral centers. Individuals underwent neurological examination, MRI and OCT at baseline and at yearly follow-up visits. RESULTS: Patients were included at a median disease duration of 2.0 months. During a median follow-up of 59 (interquartile range 43 - 71) months, 82% of patients had ongoing disease activity as demonstrated by failing the no evidence of disease activity (NEDA)-3 criteria and 19% presented with confirmed disability worsening. A GCIP threshold ≤ 77 μm at baseline identified patients with a high risk for NEDA-3 failure (hazard ratio 1.7 [95% CI 1.1 - 2.8], p=0.04) and GCIP measures ≤ 69 μm predicted disability worsening (hazard ratio 2.2 (95% CI, 1.2 - 4.3); p=0.01). Higher rates of annualized GCIP loss increased the risk for disability worsening (hazard ratio 2.5 per 1 μm/year increase of GCIP loss, p=0.03). CONCLUSIONS: Ganglion cell thickness as measured by OCT after the initial manifestation of multiple sclerosis may allow early risk stratification as to future disease activity and progression