Pathological responses to single‐pulse electrical stimuli in epilepsy: The role of feedforward inhibition

Delineation of epileptogenic cortex in focal epilepsy patients may profit from single‐pulse electrical stimulation during intracranial EEG recordings. Single‐pulse electrical stimulation evokes early and delayed responses. Early responses represent connectivity. Delayed responses are a biomarker for epileptogenic cortex, but up till now, the precise mechanism generating delayed responses remains elusive. We used a data‐driven modelling approach to study early and delayed responses. We hypothesized that delayed responses represent indirect responses triggered by early response activity and investigated this for 11 patients. Using two coupled neural masses, we modelled early and delayed responses by combining simulations and bifurcation analysis. An important feature of the model is the inclusion of feedforward inhibitory connections. The waveform of early responses can be explained by feedforward inhibition. Delayed responses can be viewed as second‐order responses in the early response network which appear when input to a neural mass falls below a threshold forcing it temporarily to a spiking state. The combination of the threshold with noisy background input explains the typical stochastic appearance of delayed responses. The intrinsic excitability of a neural mass and the strength of its input influence the probability at which delayed responses to occur. Our work gives a theoretical basis for the use of delayed responses as a biomarker for the epileptogenic zone, confirming earlier clinical observations. The combination of early responses revealing effective connectivity, and delayed responses showing intrinsic excitability, makes single‐pulse electrical stimulation an interesting tool to obtain data for computational models of epilepsy surgery.     

Dectin-1 mediates the biological effects of beta-glucans

The ability of fungal-derived beta-glucan particles to induce leukocyte activation and the production of inflammatory mediators, such as tumor necrosis factor (TNF)-alpha, is a well characterized phenomenon. Although efforts have been made to understand how these carbohydrate polymers exert their immunomodulatory effects, the receptors involved in generating these responses are unknown. Here we show that Dectin-1 mediates the production of TNF-alpha in response to zymosan and live fungal pathogens, an activity that occurs at the cell surface and requires the cytoplasmic tail and immunoreceptor tyrosine activation motif of Dectin-1 as well as Toll-like receptor (TLR)-2 and Myd88. This is the first demonstration that the inflammatory response to pathogens requires recognition by a specific receptor in addition to the TLRs. Furthermore, these studies implicate Dectin-1 in the production of TNF-alpha in response to fungi, a critical step required for the successful control of these pathogens.     

Assessment of Needle Guidance Devices for Their Potential to Reduce Fluoroscopy Time and Operator Hand Dose during C-Arm Cone-Beam Computed Tomography–guided Needle Interventions

PurposeTo assess whether the use of needle guidance devices can reduce fluoroscopy time and operator hand dose during cone-beam computed tomography–guided needle interventions.Materials and MethodsThe freehand technique was compared with techniques employing two distinct needle holders and a ceiling-mounted laser guidance technique. Laser guidance was used either alone or in combination with needle holders. Four interventional radiologists were instructed to reach predetermined targets in an abdominal phantom using these techniques. Each operator used all six techniques three times. Fluoroscopy time, procedure time, operator hand dose, and needle tip deviation were obtained for all simulated needle interventions. All data are presented as median (ranges).ResultsAll procedures were successfully completed within 2–4 minutes, resulting in a deviation from target of 0.8 mm (0–4.7). In freehand procedures, the fluoroscopy time to reach the target was 50 seconds (31–98 s). Laser guidance, used alone or in combination with needle holders, reduced fluoroscopy time to 31 seconds (14–68 s) (P<.02). The operator hand dose in freehand procedures was 275 μSv (20–603 μSv). Laser guidance alone or in combination with needle holders resulted in a reduction of the hand dose to<36 μSv (5–82 μSv) per procedure (P<.001). There were no statistically significant effects on hand dose levels or fluoroscopy time when the needle holders were employed alone.ConclusionsCompared with the freehand technique, all three tested needle guidance devices performed with equivalent efficiency in terms of accuracy and procedure time. Only the addition of laser guidance was found to reduce both fluoroscopy time and operator hand dose.     

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