bioRxiv ScienceSearch

Biology subjects

Golan, T.

Publications and source records attributed to Golan, T..

4 recordsLinked to original sources

Specific detection of cell-free DNA derived from intestinal epithelial cells using methylation patterns

Epithelial cells of the intestine undergo rapid turnover and are thought to be cleared via stool. Disruption of tissue architecture, as occurs in colorectal cancer (CRC), results in the release of material from dying intestinal epithelial cells to blood. This phenomenon could be utilized for diagnosis and monitoring of intestinal diseases, if circulating cell-free DNA (cfDNA) derived from intestinal cells could be specifically identified. Here we describe two genomic loci that are unmethylated specifically in intestinal epithelial cells, allowing for sensitive and specific detection of DNA derived from such cells. As expected, intestinal DNA is found in stool, but not in plasma, of healthy individuals. Patients with inflammatory bowel disease (IBD) have minimal amounts of intestinal cfDNA in the plasma, whereas patients with advanced CRC show a strong signal. The intestinal markers are not elevated in plasma samples from patients with pancreatic ductal adenocarcinoma (PDAC), and a combination of intestine- and pancreas-specific markers allowed for robust differentiation between plasma cfDNA derived from CRC and PDAC patients. Intestinal DNA markers provide a mutation-independent tool for monitoring intestinal dynamics in health and disease.

developmental biology

Repeated performance in problem-solving tasks attenuates human cortical responses

A ubiquitous characteristic of human cortical networks is their tendency to rapidly change their response properties upon repetition. While this phenomenon has been amply documented using simple sensory-motor tasks, it is still unclear to what extent brain activations change on a short time scale when we are engaged in high level, complex tasks. Here, we examined this question using three types of high-level visual problems. We analyzed data from intracranial recordings performed in eight patients, focusing on the location and type of changes and on their relationship to overt behavior. Our results show significant repetition effects, manifested as signal decrease with repetition, in three different groups of electrodes: Visual sites, which increased their activity during stimuli presentation; Processing Positive sites, which demonstrated increased activity throughout the experimental trial; and Processing Negative sites, which demonstrated suppression of activity during the trial as compared to baseline. Interestingly, despite these significant repetition effects, response time remained unchanged with repetition. These findings bear directly upon our ability to interpret results aggregated across multiple repetitions of the same complex task.

neuroscience

Increasing Suppression Of Saccade-Related Transients Along The Human Visual Hierarchy

A key hallmark of visual perceptual awareness is robustness to instabilities arising from unnoticeable eye and eyelid movements. In previous human intracranial (iEEG) work (Golan et al., 2016) we found that excitatory broadband high-frequency activity transients, driven by eye blinks, are suppressed in higher-level but not early visual cortex. Here, we utilized the broad anatomical coverage of iEEG recordings in 12 eye-tracked neurosurgical patients to test whether a similar stabilizing mechanism operates following small saccades. We compared saccades (1.3{degrees}-3.7{degrees}) initiated during inspection of large individual visual objects with similarly-sized external stimulus displacements. Early visual cortex sites responded with positive transients to both conditions. In contrast, in both dorsal and ventral higher-level sites the response to saccades (but not to external displacements) was suppressed. These findings indicate that early visual cortex is highly unstable compared to higher-level visual regions which apparently constitute the main target of stabilizing extra-retinal oculomotor influences.

neuroscience

Persistent neural activity encoding real-time presence of visual stimuli decays along the ventral stream

Neural populations that encode sensory experience should be persistently active for as long as the experience persists. However, research into visual neural activity has focused almost exclusively on onset-driven responses that cannot account for sustained perception. We used intracranial recordings in humans to determine the degree to which the presence of a visual stimulus is persistently encoded by neural activity. The correspondence between stimulus duration and response duration was strongest in early visual cortex and gradually diminished along the visual hierarchy, such that is was weakest in inferior-temporal category-selective regions. A similar posterior-anterior gradient was found within inferior temporal face-selective regions, with posterior but not anterior sites showing persistent face-selective activity. The results suggest that regions that appear uniform in terms of their category selectivity are dissociated by how they temporally represent a stimulus in support of real-time experience, and delineate a large-scale organizing principle of the ventral visual stream.

neuroscience