Faculty Bibliography

Although there is an increasing agreement that hypertension is associated with cerebrovascular compromise, relationships between blood pressure (BP) and cerebral blood flow are not fully understood. It is not known what BP level, and consequently what therapeutic goal, is optimal for brain perfusion. Moreover, there is limited data on how BP affects hippocampal perfusion, a structure critically involved in memory. We conducted a cross-sectional (n=445) and longitudinal (n=185) study of adults and elderly without dementia or clinically apparent stroke, who underwent clinical examination and brain perfusion assessment (age 69.2±7.5 years, 62% women, 45% hypertensive). Linear models were used to test baseline BP-blood flow relationship and to examine how changes in BP influence changes in perfusion. In the entire group, systolic BP (SBP) was negatively related to cortical (β=-0.13, P=0.005) and hippocampal blood flow (β=-0.12, P=0.01). Notably, this negative relationship was apparent already in subjects without hypertension. Hypertensive subjects showed a quadratic relationship between SBP and hippocampal blood flow (β=-1.55, P=0.03): Perfusion was the highest in subjects with mid-range SBP around 125 mm Hg. Longitudinally, in hypertensive subjects perfusion increased with increased SBP at low baseline SBP but increased with decreased SBP at high baseline SBP. Cortical and hippocampal perfusion decrease with increasing SBP across the entire BP spectrum. However, in hypertension, there seems to be a window of mid-range SBP which maximizes perfusion.

During movement, modulation of beta power occurs over the sensorimotor areas, with a decrease just before its start (event-related desynchronization, ERD) and a rebound after its end (event-related synchronization, ERS). We have recently found that the depth of ERD-to-ERS modulation increases during practice in a reaching task and the following day decreases to baseline levels. Importantly, the magnitude of the beta modulation increase during practice is highly correlated with the retention of motor skill tested the following day. Together with other evidence, this suggests that the increase of practice-related modulation depth may be the expression of sensorimotor cortex's plasticity. Here, we determine whether the practice-related increase of beta modulation depth is equally present in a group of younger and a group of older subjects during the performance of a 30-minute block of reaching movements. We focused our analyses on two regions of interest (ROIs): the left sensorimotor and the frontal region. Performance indices were significantly different in the two groups, with the movements of older subjects being slower and less accurate. Importantly, both groups presented a similar increase of the practice-related beta modulation depth in both ROIs in the course of the task. Peak latency analysis revealed a progressive delay of the ERS peak that correlated with the total movement time. Altogether, these findings support the notion that the depth of beta modulation in a reaching movement task does not depend on age and confirm previous findings that only ERS peak latency but not ERS magnitude is related to performance indices.

Background/UNASSIGNED:Progressive multifocal leukoencephalopathy (PML), a potentially fatal demyelinating disease caused by the John Cunningham virus (JCV), can occur as a complication of treatment with rituximab, fingolimod, and dimethyl fumarate. The primary objective of this study was to determine changes in anti-JCV antibody index values in multiple sclerosis (MS) patients treated with these three medications. Second, we explored the relationship between absolute lymphocyte count (ALC), anti-JCV antibody index values, and various patient characteristics. Methods/UNASSIGNED:In this retrospective chart review, we evaluated changes in JCV serology and ALC in 172 MS patients treated with fingolimod, rituximab, or dimethyl fumarate (2013-2016). Only those with known anti-JCV antibody and ALC values before starting the study medications were included. Subsequent values were obtained on an ad hoc basis throughout the study. Results/UNASSIGNED:= 0.014, respectively). A non-significant decreasing trend in anti-JCV antibody index values occurred in patients treated with dimethyl fumarate. Notably, there was no relationship between ALC and anti-JCV antibody index values for patients treated with rituximab, fingolimod, or dimethyl fumarate. Conclusions/UNASSIGNED:Anti-JCV antibody index values significantly decreased in MS patients treated with fingolimod and rituximab; however, this did not occur with dimethyl fumarate. Fingolimod and rituximab may impair the humoral response to the JCV. Nevertheless, a declining anti-JCV antibody index in MS patients treated with fingolimod or rituximab should not necessarily be interpreted as correlating with a decreased risk for PML.

Gradient-based approaches to brain function have recently unmasked fundamental properties of brain organization. Diffusion map embedding analysis of resting-state fMRI data revealed a primary-to-transmodal axis of cerebral cortical macroscale functional organization. The same method was recently used to analyze resting-state data within the cerebellum, revealing for the first time a sensorimotor-fugal macroscale organization principle of cerebellar function. Cerebellar gradient 1 extended from motor to non-motor task-unfocused (default-mode network) areas, and cerebellar gradient 2 isolated task-focused processing regions. Here we present a freely available and easily accessible tool that applies this new knowledge to the topographical interpretation of cerebellar neuroimaging findings. LittleBrain illustrates the relationship between cerebellar data (e.g., volumetric patient study clusters, task activation maps, etc.) and cerebellar gradients 1 and 2. Specifically, LittleBrain plots all voxels of the cerebellum in a two-dimensional scatterplot, with each axis corresponding to one of the two principal functional gradients of the cerebellum, and indicates the position of cerebellar neuroimaging data within these two dimensions. This novel method of data mapping provides alternative, gradual visualizations that complement discrete parcellation maps of cerebellar functional neuroanatomy. We present application examples to show that LittleBrain can also capture subtle, progressive aspects of cerebellar functional neuroanatomy that would be difficult to visualize using conventional mapping techniques. Download and use instructions can be found at https://xaviergp.github.io/littlebrain.

Background/UNASSIGNED:Left atrial (LA) enlargement is a reliable predictor of adverse cardiovascular events, and reduced atrial function is an independent risk factor for mortality in patients with amyloidosis. The objective of this study was to characterize the LA function in Mexican patients with a confirmed diagnosis of hereditary transthyretin amyloidosis (amyloid transthyretin [ATTR]). Methods/UNASSIGNED:All consecutive patients with diagnosis of hereditary ATTR who underwent a cardiac magnetic resonance study in the period from March 2016 to June 2017 were included in the study; the volumes and function of the left atrium were evaluated. Results/UNASSIGNED:Patients were divided into two groups, one with and one without cardiac amyloidosis. Statistically significant differences were observed between both groups in terms of indexed maximal LA volume, 26 mL versus 35.9mL, p = 0.03; indexed minimal LA volume, 10.7 mL versus 13.6mL, p = 0.03; and indexed LA pre-contraction volume, 17 mL versus 22.4mL, p = 0.03. No statistically significant differences were observed between both groups when comparing neither different ejection volumes nor the different ejection fractions. Conclusions/UNASSIGNED:Patients with hereditary ATTR with cardiac involvement have remodeling of the left atrium, with increased atrial volumes, without diminishing its function.