Availability and safety assessment of infrared neural stimulation at high repetition rate through an implantable optrode

An implantable optrode with micro-thermal detectors was designed to investigate the availability and safety of INS using high repetition rates. Optical auditory brainstem responses (oABRs) were recorded in normal-hearing guinea pigs, and the energy thresholds, pulse durations, and amplitudes evoked by the varied stimulus repetitions were analyzed. Stable oABRs could be evoked through INS even as the repetition rate of stimulation reached 19[Formula: see text]kHz. The energy threshold of oABRs was elevated, the amplitudes decreased as pulse durations increased and repetition rates were higher, and the latencies were delayed as the pulse durations increased. The temperature variation curves on the site of stimulation significantly increased as the pulse duration increased to 400 [Formula: see text]s. INS elevated the temperature around the stimulus site area via thermal accumulation during radiation, especially when higher repetition stimuli were used. Our results demonstrate that high repetition infrared stimulations can safely evoke stable and available oABRs in normal-hearing guinea pigs.

Species-Specific and Distance-Dependent Dispersive Behaviour of Forisomes in Different Legume Species

Forisomes are giant fusiform protein complexes composed of sieve element occlusion (SEO) protein monomers, exclusively found in sieve elements (SEs) of legumes. Forisomes block the phloem mass flow by a Ca2+-induced conformational change (swelling and rounding). We studied the forisome reactivity in four different legume species—Medicago sativa, Pisum sativum, Trifolium pratense and Vicia faba. Depending on the species, we found direct relationships between SE diameter, forisome surface area and distance from the leaf tip, all indicative of a developmentally tuned regulation of SE diameter and forisome size. Heat-induced forisome dispersion occurred later with increasing distance from the stimulus site. T. pratense and V. faba dispersion occurred faster for forisomes with a smaller surface area. Near the stimulus site, electro potential waves (EPWs)—overlapping action (APs), and variation potentials (VPs)—were linked with high full-dispersion rates of forisomes. Distance-associated reduction of forisome reactivity was assigned to the disintegration of EPWs into APs, VPs and system potentials (SPs). Overall, APs and SPs alone were unable to induce forisome dispersion and only VPs above a critical threshold were capable of inducing forisome reactions.

Cardiac intramural electrical mapping reveals focal delays but no conduction velocity slowing in the peri-infarct region

Altered electrical behavior alongside healed myocardial infarcts (MIs) is associated with increased risk of sudden cardiac death. However, the multidimensional mechanisms are poorly understood and described. This study characterizes, for the first time, the intramural spread of electrical activation in the peri-infarct region of chronic reperfusion MIs. Four sheep were studied 13 wk after antero-apical reperfusion infarction. Extracellular potentials (ECPs) were recorded in a ~20 × 20-mm2 region adjacent to the infarct boundary (25 plunge needles <0.5-mm diameter with 15 electrodes at 1-mm centers) during multisite stimulation. Infarct geometry and electrode locations were reconstructed from magnetic resonance images. Three-dimensional activation spread was characterized by local activation times and interpolated ECP fields ( n = 191 records). Control data were acquired in 4 non-infarcted sheep ( n = 96 records). Electrodes were distributed uniformly around 15 ± 5% of the intramural infarct boundary. There were marked changes in pacing success and ECP morphology across a functional border zone (BZ) ±2 mm from the boundary. Stimulation adjacent to the infarct boundary was associated with low-amplitude electrical activity within the BZ and delayed activation of surrounding myocardium. Bulk tissue depolarization occurred 3.5–14.6 mm from the pacing site for 39% of stimuli with delays of 4–37 ms, both significantly greater than control ( P < 0.0001). Conduction velocity (CV) adjacent to the infarct was not reduced compared with control, consistent with structure-only computer model results. Insignificant CV slowing, irregular stimulus-site specific activation delays, and obvious indirect activation pathways strongly suggest that the substrate for conduction abnormalities in chronic MI is predominantly structural in nature. NEW & NOTEWORTHY Intramural in vivo measurements of peri-infarct electrical activity were not available before this study. We use pace-mapping in a three-dimensional electrode array to show that a subset of stimuli in the peri-infarct region initiates coordinated myocardial activation some distance from the stimulus site with substantial associated time delays. This is site dependent and heterogeneous and occurs for <50% of ectopic stimuli in the border zone. Furthermore, once coordinated activation is initiated, conduction velocity adjacent to the infarct boundary is not significantly different from control. These results give new insights to peri-infarct electrical activity and do not support the widespread view of uniform electrical remodeling in the border zone of chronic myocardial infarcts, with depressed conduction velocity throughout.

Ventricular stimulus site influences dynamic dispersion of repolarization in the intact human heart

The spatial variation in restitution properties in relation to varying stimulus site is poorly defined. This study aimed to investigate the effect of varying stimulus site on apicobasal and transmural activation time (AT), action potential duration (APD) and repolarization time (RT) during restitution studies in the intact human heart. Ten patients with structurally normal hearts, undergoing clinical electrophysiology studies, were enrolled. Decapolar catheters were placed apex to base in the endocardial right ventricle (RVendo) and left ventricle (LVendo), and an LV branch of the coronary sinus (LVepi) for transmural recording. S1–S2 restitution protocols were performed pacing RVendo apex, LVendo base, and LVepi base. Overall, 725 restitution curves were analyzed, 74% of slopes had a maximum slope of activation recovery interval (ARI) restitution ( Smax) > 1 ( P < 0.001); mean Smax = 1.76. APD was shorter in the LVepi compared with LVendo, regardless of pacing site (30-ms difference during RVendo pacing, 25-ms during LVendo, and 48-ms during LVepi; 50th quantile, P < 0.01). Basal LVepi pacing resulted in a significant transmural gradient of RT (77 ms, 50th quantile: P < 0.01), due to loss of negative transmural AT-APD coupling (mean slope 0.63 ± 0.3). No significant transmural gradient in RT was demonstrated during endocardial RV or LV pacing, with preserved negative transmural AT-APD coupling (mean slope −1.36 ± 1.9 and −0.71 ± 0.4, respectively). Steep ARI restitution slopes predominate in the normal ventricle and dynamic ARI; RT gradients exist that are modulated by the site of activation. Epicardial stimulation to initiate ventricular activation promotes significant transmural gradients of repolarization that could be proarrhythmic.

Mucosal stimulation activates secretomotor neurons via long myenteric pathways in guinea pig ileum

This study examined whether mucosal stimulation activates long secretomotor neural reflexes and, if so, how they are organized. The submucosa of in vitro full thickness guinea pig ileal preparations was exposed in the distal portion and intracellular recordings were obtained from electrophysiologically identified secretomotor neurons. Axons in the intact mucosa of the oral segment were stimulated by a large bipolar stimulating electrode. In control preparations, a single stimulus pulse evoked a fast excitatory postsynaptic potential (EPSP) in 86% of neurons located 0.7–1.0 cm anal to the stimulus site. A stimulus train evoked multiple fast EPSPs, but slow EPSPs were not observed. To examine whether mucosal stimulation specifically activated mucosal sensory nerve terminals, the mucosa/submucosa was severed from the underlying layers and repositioned. In these preparations, fast EPSPs could not be elicited in 89% of cells. Superfusion with phorbol dibutyrate enhanced excitability of sensory neurons and pressure-pulse application of serotonin to the mucosa increased the fast EPSPs evoked by mucosal stimulation, providing further evidence that sensory neurons were involved. To determine whether these reflexes projected through the myenteric plexus, this plexus was surgically lesioned between the stimulus site and the impaled neuron. No fast EPSPs were recorded in these preparations following mucosal stimulation whereas lesioning the submucosal plexus had no effect. These results demonstrate that mucosal stimulation triggers a long myenteric pathway that activates submucosal secretomotor neurons. This pathway projects in parallel with motor and vasodilator reflexes, and this common pathway may enable coordination of intestinal secretion, blood flow, and motility.

Functional Connections Between Auditory Cortex on Heschl's Gyrus and on the Lateral Superior Temporal Gyrus in Humans

Functional connections between auditory fields on Heschl's gyrus (HG) and the acoustically responsive posterior lateral superior temporal gyrus (field PLST) were studied using electrical stimulation and recording methods in patients undergoing diagnosis and treatment of intractable epilepsy. Averaged auditory (click-train) evoked potentials were recorded from multicontact subdural recording arrays chronically implanted over the lateral surface of the superior temporal gyrus (STG) and from modified depth electrodes inserted into HG. Biphasic electrical pulses (bipolar, constant current, 0.2 ms) were delivered to HG sites while recording from the electrode array over acoustically responsive STG cortex. Stimulation of sites along the mediolateral extent of HG resulted in complex waveforms distributed over posterolateral STG. These areas overlapped each other and field PLST. For any given HG stimulus site, the morphology of the electrically evoked waveform varied across the STG map. A characteristic waveform was recorded at the site of maximal amplitude of response to stimulation of mesial HG [presumed primary auditory field (AI)]. Latency measurements suggest that the earliest evoked wave resulted from activation of connections within the cortex. Waveforms changed with changes in rate of electrical HG stimulation or with shifts in the HG stimulus site. Data suggest widespread convergence and divergence of input from HG to posterior STG. Evidence is presented for a reciprocal functional projection, from posterolateral STG to HG. Results indicate that in humans there is a processing stream from AI on mesial HG to an associational auditory field (PLST) on the lateral surface of the superior temporal gyrus.