Microsleep is associated with brain activity patterns unperturbed by auditory inputs.

Microsleeps are brief episodes of arousal level decrease manifested through behavioral signs. Brain activity during microsleep in the presence of external stimulus remains poorly understood. In this study, we sought to understand neural responses to auditory stimulation during microsleep. We gave participants the simple task of listening to audios of different pitches and amplitude modulation frequencies during early afternoon functional MRI scans. We found the following: 1) microsleep was associated with cortical activations in broad motor and sensory regions and deactivations in thalamus, irrespective of auditory stimulation; 2) high and low pitch audios elicited different activity patterns in the auditory cortex during awake but not microsleep state; and 3) during microsleep, spatial activity patterns in broad brain regions were similar regardless of the presence or types of auditory stimulus (i.e., stimulus invariant). These findings show that the brain is highly active during microsleep but the activity patterns across broad regions are unperturbed by auditory inputs.NEW & NOTEWORTHY During deep drowsy states, auditory inputs could induce activations in the auditory cortex, but the activation patterns lose differentiation to high/low pitch stimuli. Instead of random activations, activity patterns across the brain during microsleep appear to be structured and may reflect underlying neurophysiological processes that remain unclear.

Cerebral neural correlates of differential melanopic photic stimulation in humans.

Photic stimulation of rods, cones and intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGCs) mediates non-visual light responses, including entrainment of circadian rhythms and pupillary light reflex. Unlike visual responses to photic stimulation, the cerebral correlates of non-visual light responses in humans remains elusive. In this study, we used functional magnetic resonance imaging (fMRI) in 14 healthy young participants, to localize cerebral regions which are differentially activated by metameric light that gave rise to different levels of melanopic excitation. Mean blood oxygen-level dependent (BOLD) responses disclosed bilateral activation of the frontal eye fields during exposure to light geared towards melanopsin. Furthermore, multivariate pattern analyses showed distinct bilateral pattern activity in the inferior temporal gyri and the caudate nuclei. Taken together, our findings suggest that melanopsin-based photoreception activates a cerebral network including frontal regions, classically involved in attention and ocular motor responses.

Eye-specific information biases perceived direction of bistable motion.

While eye-of origin information is normally not accessible to observers, processing of visual information within a monocular channel does contribute to our final percept. Here we investigate if visual information is processed more efficiently when it is contained within a monocular channel or across two eyes and how it affects visual perception. Specifically, we used a bistable apparent motion display, a motion quartet, to investigate the role of eye-specific information in determining perceived motion direction. To an observer, this ambiguous display leads to the perception of either horizontal or vertical motion. We attempted to bias perceived direction by presenting separate spatial halves of the motion quartet to each eye. Our results show that observers were more likely to see horizontal motion when top and bottom halves of the quartet was presented to separate eyes. Similarly, when left and right halves were presented dichoptically, observers reported viewing more vertical motion. This change in proportion of observed motion direction indicates that eye specific information is processed more efficiently and can bias overall perception.

The study of muscle remodeling in Drosophila metamorphosis using in vivo microscopy and bioimage informatics.

BACKGROUND: Metamorphosis in insects transforms the larval into an adult body plan and comprises the destruction and remodeling of larval and the generation of adult tissues. The remodeling of larval into adult muscles promises to be a genetic model for human atrophy since it is associated with dramatic alteration in cell size. Furthermore, muscle development is amenable to 3D in vivo microscopy at high cellular resolution. However, multi-dimensional image acquisition leads to sizeable amounts of data that demand novel approaches in image processing and analysis. RESULTS: To handle, visualize and quantify time-lapse datasets recorded in multiple locations, we designed a workflow comprising three major modules. First, the previously introduced TLM-converter concatenates stacks of single time-points. The second module, TLM-2D-Explorer, creates maximum intensity projections for rapid inspection and allows the temporal alignment of multiple datasets. The transition between prepupal and pupal stage serves as reference point to compare datasets of different genotypes or treatments. We demonstrate how the temporal alignment can reveal novel insights into the east gene which is involved in muscle remodeling. The third module, TLM-3D-Segmenter, performs semi-automated segmentation of selected muscle fibers over multiple frames. 3D image segmentation consists of 3 stages. First, the user places a seed into a muscle of a key frame and performs surface detection based on level-set evolution. Second, the surface is propagated to subsequent frames. Third, automated segmentation detects nuclei inside the muscle fiber. The detected surfaces can be used to visualize and quantify the dynamics of cellular remodeling. To estimate the accuracy of our segmentation method, we performed a comparison with a manually created ground truth. Key and predicted frames achieved a performance of 84% and 80%, respectively. CONCLUSIONS: We describe an analysis pipeline for the efficient handling and analysis of time-series microscopy data that enhances productivity and facilitates the phenotypic characterization of genetic perturbations. Our methodology can easily be scaled up for genome-wide genetic screens using readily available resources for RNAi based gene silencing in Drosophila and other animal models.

Characterization of tumor necrosis factor-α block haplotypes associated with susceptibility to chronic venous leg ulcers in Caucasian patients.

Polymorphisms in the central major histocompatibility complex (MHC) are associated with several immunopathologic and inflammatory diseases, including chronic venous leg ulcers (CVLU). Because of strong linkage disequilibrium, identification of loci affecting disease susceptibility must be based on comparisons between haplotypes. Here we examine the association of conserved tumor necrosis factor (TNF) block haplotypes with CVLU susceptibility. A total of 171 Caucasian patients with CVLU were compared with 173 age-/gender-matched controls, excluding individuals with type 1 diabetes or rheumatoid arthritis. A total of 194 healthy subjects formed a separate population-based control group. Samples were typed for 38 tumor necrosis factor (TNF) block single nucleotide polymorphisms (SNP), human leukocyte antigen (HLA)-B and HLA-DRB1 alleles. TNF haplotypes were derived using the PHASE algorithm and assigned numbers (FVx) defined previously. The patients and matched controls shared 16 TNF block haplotypes. The patients had increased carriage of FV16 and alleles of the 8.1 and 60.3 MHC ancestral haplotypes (AH). CVLU risk is modulated by alleles within FV16 (e.g., TNF-308A and BAT1intron10 C insertion) or near FV16 in the 8.1AH. CVLU risk may also be mediated by unidentified alleles (not in FV22) marked by HLA-B40 and HLA-DR13. FV16 appears to be the best MHC and TNF block marker of susceptibility. After disease onset, an individual's TNF block haplotype does not modulate CVLU severity.