Electrical neurostimulation for chronic pain: on selective relay of sensory neural activities in myelinated nerve fibers

Chronic pain affects about 100 million adults in the US. Despite their great need, neuropharmacology and neurostimulation therapies for chronic pain have been associated with suboptimal efficacy and limited long-term success, as their mechanisms of action are unclear. Yet current computational models of pain transmission suffer from several limitations. In particular, dorsal column models do not include the fundamental underlying sensory activity traveling in these nerve fibers. We developed a (simple) simulation test bed of electrical neurostimulation of myelinated nerve fibers with underlying sensory activity. This paper reports our findings so far. Interactions between stimulation-evoked and underlying activities are mainly due to collisions of action potentials and losses of excitability due to the refractory period following an action potential. In addition, intuitively, the reliability of sensory activity decreases as the stimulation frequency increases. This first step opens the door to a better understanding of pain transmission and its modulation by neurostimulation therapies

A role for recurrent processing in object completion: neurophysiological, psychophysical and computational"evidence

Recognition of objects from partial information presents a significant challenge for theories of vision because it requires spatial integration and extrapolation from prior knowledge. We combined neurophysiological recordings in human cortex with psychophysical measurements and computational modeling to investigate the mechanisms involved in object completion. We recorded intracranial field potentials from 1,699 electrodes in 18 epilepsy patients to measure the timing and selectivity of responses along human visual cortex to whole and partial objects. Responses along the ventral visual stream remained selective despite showing only 9-25% of the object. However, these visually selective signals emerged ~100 ms later for partial versus whole objects. The processing delays were particularly pronounced in higher visual areas within the ventral stream, suggesting the involvement of additional recurrent processing. In separate psychophysics experiments, disrupting this recurrent computation with a backward mask at ~75ms significantly impaired recognition of partial, but not whole, objects. Additionally, computational modeling shows that the performance of a purely bottom-up architecture is impaired by heavy occlusion and that this effect can be partially rescued via the incorporation of top-down connections. These results provide spatiotemporal constraints on theories of object recognition that involve recurrent processing to recognize objects from partial information

Sensitivity to Timing and Order in Human Visual Cortex

Visual recognition takes a small fraction of a second and relies on the cascade of signals along the ventral visual stream. Given the rapid path through multiple processing steps between photoreceptors and higher visual areas, information must progress from stage to stage very quickly. This rapid progression of information suggests that fine temporal details of the neural response may be important to the how the brain encodes visual signals. We investigated how changes in the relative timing of incoming visual stimulation affect the representation of object information by recording intracranial field potentials along the human ventral visual stream while subjects recognized objects whose parts were presented with varying asynchrony. Visual responses along the ventral stream were sensitive to timing differences between parts as small as 17 ms. In particular, there was a strong dependency on the temporal order of stimulus presentation, even at short asynchronies. This sensitivity to the order of stimulus presentation provides evidence that the brain may use differences in relative timing as a means of representing information.Comment: 10 figures, 1 tabl

Optimization of diarylazines as anti-HIV agents with dramatically

Non-nucleoside inhibitors of HIV-1 reverse transcriptase are reported that have ca. 100-fold greater solubility than the structurally related drugs etravirine and rilpivirine, while retaining high anti-viral activity. The solubility enhancements come from strategic placement of a morpholinylalkoxy substituent in the entrance channel of the NNRTI binding site. Compound 4d shows low-nanomolar activity similar to etravirine towards wild-type HIV-1 and key viral variants.Fil: Bollini, Mariela. University of Yale; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cisneros, José A.. University of Yale; Estados UnidosFil: Spasov, Krasimir A.. University of Yale; Estados UnidosFil: Anderson, Karen S.. University of Yale; Estados UnidosFil: Jorgensen, William L.. University of Yale; Estados Unido

A study on vortex flow control on inlet distortion in the re-engined 727-100 center inlet duct using computational fluid dynamics

Computational fluid dynamics was used to investigate the management of inlet distortion by the introduction of discrete vorticity sources at selected locations in the inlet for the purpose of controlling secondary flow. These sources of vorticity were introduced by means of vortex generators. A series of design observations were made concerning the importance of various vortex generator design parameters in minimizing engine face circumferential distortion. The study showed that vortex strength, generator scale, and secondary flow field structure have a complicated and interrelated influence on the engine face distortion, over and above the initial geometry and arrangement of the generators. The installed vortex generator performance was found to be a function of three categories of variables: the inflow conditions, the aerodynamic characteristics associated with the inlet duct, and the design parameters related to the geometry, arrangement, and placement of the vortex generators within the outlet duct itself