Measuring Latency Variations in Evoked Potential Components Using a Simple Autocorrelation Technique

Interpretation of averaged evoked potentials is difficult when the time relationship between stimulus and response is not constant. Later components are more prone to latency jitter, making them insufficiently reliable for routine clinical use even though they could contribute to greater understanding of the functioning of polysynaptic components of the afferent nervous system. This study is aimed at providing a simple but effective method of identifying and quantifying latency jitter in averaged evoked potentials. Autocorrelation techniques were applied within defined time windows on simulated jittered signals embedded within the noise component of recorded evoked potentials and on real examples of somatosensory evoked potentials. We demonstrated that the technique accurately identifies the distribution and maximum levels of jitter of the simulated components and clearly identifies the jitter properties of real evoked potential recording components. This method is designed to complement the conventional analytical methods used in neurophysiological practice to provide valuable additional information about the distribution of latency jitter within an averaged evoked potential. It will be useful for the assessment of the reliability of averaged components and will aid the interpretation of longer-latency, polysynaptic components such as those found in nociceptive evoked potentials.

An organic transistor matrix for multipoint intracellular action potential recording

Electrode arrays are widely used for multipoint recording of electrophysiological activities, and organic electronics have been utilized to achieve both high performance and biocompatibility. However, extracellular electrode arrays record the field potential instead of the membrane potential itself, resulting in the loss of information and signal amplitude. Although much effort has been dedicated to developing intracellular access methods, their three-dimensional structures and advanced protocols prohibited implementation with organic electronics. Here, we show an organic electrochemical transistor (OECT) matrix for the intracellular action potential recording. The driving voltage of sensor matrix simultaneously causes electroporation so that intracellular action potentials are recorded with simple equipment. The amplitude of the recorded peaks was larger than that of an extracellular field potential recording, and it was further enhanced by tuning the driving voltage and geometry of OECTs. The capability of miniaturization and multiplexed recording was demonstrated through a 4 × 4 action potential mapping using a matrix of 5- × 5-μm2 OECTs. Those features are realized using a mild fabrication process and a simple circuit without limiting the potential applications of functional organic electronics.

Amphetamine Promotes Cortical Up State in Part Via Dopamine Receptors

Cortical neurons oscillate between Up and Down states during slow wave sleep and general anesthesia. Recent studies show that Up/Down oscillations also occur during quiet wakefulness. Arousal eliminates Down states and transforms Up/Down oscillations to a persistent Up state. Further evidence suggests that Up/Down oscillations are crucial to memory consolidation, whereas their transition to a persistent Up state is essential for arousal and attention. We have shown that D-amphetamine promotes cortical Up state, and the effect depends on activation of central α1A adrenergic receptors. Here, we report that dopamine also plays a role in D-amphetamine’s effect. Thus, using local-field-potential recording in the prefrontal cortex in chloral hydrate-anesthetized rats, we showed that the Up-state promoting effect of D-amphetamine was attenuated by antagonists at either D1 or D2-like dopamine receptors. The effect was also partially mimicked by co-activation of D1 and D2-like receptors. These results are consistent with the fact that D-amphetamine increases the release of both norepinephrine and dopamine. They are also in agreement with studies showing that dopamine promotes wakefulness and mediates D-amphetamine-induced emergence from general anesthesia. The effect of D-amphetamine was not mimicked, however, by activation of either D1 or D2-like receptors alone, indicating an interdependence between D1 and D2-like receptors. The dopamine/norepinephrine precursor L-DOPA also failed to promote the Up state. While more studies are needed to understand the difference between L-DOPA and D-amphetamine, our finding may provide an explanation for why L-DOPA lacks significant psychostimulant properties and is ineffective in treating attention-deficit/hyperactivity disorder.

Impaired Binding to Junctophilin2 and Nanostructural Alteration in CPVT Mutation

Rationale: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare disease, manifested by syncope or sudden death in children or young adults under stress conditions. Mutations in the Ca 2+ release channel/ryanodine receptor (RyR2) gene account for about 60% of the identified mutations. Recently, we found and described a mutation in RyR2 N-terminal domain, RyR2 R420Q . Objective: To determine the arrhythmogenic mechanisms of this mutation. Methods and Results: Ventricular tachycardias under stress conditions were observed in both CPVT patients and KI mice. During action potential recording (by patch-clamp in KI mouse cardiomyocytes and by microelectrodes in mutant hiPSC-CM) we observed an increased occurrence of delayed after-depolarizations (DADs) under isoproterenol stimulation, associated with increased Ca 2+ waves during confocal Ca 2+ recording in both mouse and human RyR2 R420Q cardiomyocytes. In addition, Ca 2+ -induced Ca 2+ -release, as well as a rough indicator of fractional Ca 2+ release, were higher and Ca 2+ sparks longer in the RyR2 R420Q expressing cells. At the ultrastructural nanodomain level, we observed smaller RyR2 clusters and widened junctional sarcoplasmic reticulum (jSR) measured by g-STED super-resolution and electronic microscopy, respectively. The increase in jSR width might be due to the impairment of RyR2 R420Q binding to junctophilin-2, as there were less junctophilin-2 co-immunoprecipitated with RyR2 R420Q . At the single current level, the RyR2R420Q channel dwells longer in the open state at low [Ca 2+ ] i , but there is predominance of a subconductance state. The latter might be correlated with an enhanced interaction between the N-terminus and the core solenoid, a RyR2 inter-domain association that has not been previously implicated in the pathogenesis of arrhythmias and sudden cardiac death. Conclusions: The RyR2 R420Q CPVT mutation modifies the interdomain interaction of the channel and weaken its association with junctophillin-2. These defects may underlie both nanoscale disarrangement of the dyad and channel dysfunction.

Relation Between Event-Related Potential Latency and Saccade Latency in Overt Shifts of Attention

Controlled shifts of attention between competing stimuli are crucial for effective everyday visual behaviour. While these typically involve overt shifts of fixation, many past studies used covert attention shifts in which fixation is unchanged, meaning that some response components may result from the inhibition of eye movements. In this study, the neural events in the human brain when making overt shifts of attention are studied through the combination of event-related potential recording with simultaneous eye tracking. Fixation shifts under competition (central target remains visible when a peripheral target appears) were compared with noncompetition (central target disappears). A longer latency for competition compared with noncompetition, which is found in the saccadic response, is already present in the early occipital positivity when a single target is presented for the fixation shift. These results indicate that the requirement to disengage from a current target affects the time course of neural processing at an early level. However, the relation is more complex when the participant is required to choose which of two targets to fixate.