Biology subjects

Levine, S. M.

Publications and source records attributed to Levine, S. M..

3 recordsLinked to original sources

bioRxiv2022

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation

ME/CFS is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we used single-cell RNA-seq (scRNA-seq) to examine immune cells in cohorts of patients and controls. Post-exertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. Thus, to detect changes coincident with PEM, we also performed scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients displayed dysregulation of classical monocytes suggestive of inappropriate differentiation and migration to tissue. We were able to identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlated with metrics of disease severity. Comparing the transcriptome at baseline and post-exercise challenge, we discovered patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation following exercise. HighlightsME/CFS is a debilitating disease with unknown causes. Here, we provide, for the first time, an extensive single cell resolution dataset detailing the gene expression programs of circulating immune cells of ME/CFS cases at baseline and after symptom provocation. We were able to detect robust dysregulation in certain immune cells from patients, with dysregulation of classical monocytes manifesting the strongest signal. Indeed, the fraction of aberrant monocytes in ME/CFS patients correlated with the degree of disease severity. Surprisingly, platelet transcriptomes were also altered in ME/CFS, and they were the only component of the immune system that showed large-scale changes following symptom provocation.

immunology↗

bioRxiv2020

Supracategorical fear information revealed by aversively conditioning multiple categories

Fear-generalization is a critical function for survival, in which an organism extracts information from a specific instantiation of a threat (e.g., the western diamondback rattlesnake in my front yard on Sunday) and learns to fear--and accordingly respond to--pertinent higher-order information (e.g., snakes live in my yard). Previous work investigating fear-conditioning in humans has used functional magnetic resonance imaging (fMRI) to demonstrate that activity-patterns of stimuli from an aversively-conditioned category (CS+) are more similar to each other than those of a neutral category (CS-). Here we designed a three-phase (i.e., baseline, conditioned, extinction) experiment using fMRI and multiple aversively-conditioned categories to ask whether we would find only similarity increases within the CS+ categories or also an increase in similarity between the CS+ categories. Using representational similarity analysis, we correlated a set of models to activity-patterns underlying several regions of interest and found that, following fear-conditioning, between-category and within-category similarity increased for the CS+ categories in the superior frontal gyrus (SFG) and the right temporal pole (rTP). Activity patterns in the object-selective lateral occipital cortex tended to prefer the semantic model, regardless of the experimental phase. These results advance prior pattern-based neuroimaging work by exploring the effect of aversively-conditioning multiple categories and indicate an extended role for the SFG and rTP in potentially linking discrete information or abstractly representing supracategorical information during fear-learning for the purpose of proper generalization.

neuroscience↗

bioRxiv2019

Temporal signal-to-noise changes in combined multiband- and slice-accelerated echo-planar imaging with a 20- and 64-channel coil

Echo planar imaging (EPI) is the most common method of functional magnetic resonance imaging for acquiring the blood oxygenation level-dependent (BOLD) contrast. One of the primary benefits of using EPI is that an entire volume of the brain can be acquired on the order of two seconds. However, this speed benefit comes with a cost. Because imaging protocols are limited by hardware (e.g., fast gradient switching), researchers are forced to compromise between spatial resolution, temporal resolution, or whole-brain coverage. Earlier attempts to circumvent this problem included developing protocols in which slices of a volume were acquired faster (i.e., slice (S) acceleration), while more recent protocols allow for multiple slices to be acquired simultaneously (i.e., multiband (MB) acceleration). However, applying such acceleration methods can lead to a reduction in the temporal signal-to-noise ratio (tSNR), which is a critical measure of the stability of the signal over time. Here we show, in five healthy subjects, using a 20- and 64-channel receiver coil, that enabling S-acceleration consistently yielded, as expected, a substantial decrease in tSNR, regardless of the receiver coil employed, whereas tSNR decrease resulting from MB acceleration was less pronounced. Specifically, with the 20-channel coil, tSNR of upto 4-fold MB-acceleration is comparable to that of no acceleration, while up to 6-fold MB-acceleration with the 64-channel coil yields comparable tSNR to that of no acceleration. Moreover, observed tSNR losses tended to be localized to temporal, insular, and medial brain regions and were more noticeable in the 20-than in the 64-channel coil. Conversely, with the 64-channel coil, the tSNR in lateral frontoparietal regions remained relatively stable with increasing MB factors. Such methodological explorations can inform researchers and clinicians as to how they can optimize imaging protocols depending on the available hardware and the brain regions they want to investigate.

neuroscience↗