Dissociation of Motor Task-Induced Cortical Excitability and Pain Perception Changes in Healthy Volunteers

Background: There is evidence that interventions aiming at modulation of the motor cortex activity lead to pain reduction. In order to understand further the role of the motor cortex on pain modulation, we aimed to compare the behavioral (pressure pain threshold) and neurophysiological effects (transcranial magnetic stimulation (TMS) induced cortical excitability) across three different motor tasks. Methodology/Principal Findings Fifteen healthy male subjects were enrolled in this randomized, controlled, blinded, cross-over designed study. Three different tasks were tested including motor learning with and without visual feedback, and simple hand movements. Cortical excitability was assessed using single and paired-pulse TMS measures such as resting motor threshold (RMT), motor-evoked potential (MEP), intracortical facilitation (ICF), short intracortical inhibition (SICI), and cortical silent period (CSP). All tasks showed significant reduction in pain perception represented by an increase in pressure pain threshold compared to the control condition (untrained hand). ANOVA indicated a difference among the three tasks regarding motor cortex excitability change. There was a significant increase in motor cortex excitability (as indexed by MEP increase and CSP shortening) for the simple hand movements. Conclusions/Significance: Although different motor tasks involving motor learning with and without visual feedback and simple hand movements appear to change pain perception similarly, it is likely that the neural mechanisms might not be the same as evidenced by differential effects in motor cortex excitability induced by these tasks. In addition, TMS-indexed motor excitability measures are not likely good markers to index the effects of motor-based tasks on pain perception in healthy subjects as other neural networks besides primary motor cortex might be involved with pain modulation during motor training

The number of full-sine cycles per pulse influences the efficacy of multicycle transcranial magnetic stimulation

Background Previous studies have shown that the efficacy of transcranial magnetic stimulation (TMS) to excite corticospinal neurons depends on pulse waveform. Objective/Hypotheses In this study, we examined whether the effectiveness of polyphasic TMS can be increased by using a pulse profile that consists of multiple sine cycles. Methods In eight subjects, single-pulse TMS was applied to the left primary motor hand area through a round coil attached to a stimulator device that generated polyphasic pulses consisting of one to six full-sine cycles with a cycle length of 86 μs. In different blocks, we varied the number of sine cycles per pulse and recorded the motor-evoked potential (MEP) from the right first dorsal interosseus muscle. For each stimulus type, we determined resting motor threshold (RMT), stimulus-response curve (SRC), and mean MEP amplitude evoked at maximal stimulator output to assess the efficacy of stimulation. Results Multicycle pulses were more effective than a single full-sine cycle in exciting corticospinal neurons. TMS with multicycle pulses resulted in lower RMT, larger MEP amplitudes at maximal stimulator output and a steeper slope of the SRC relative to a TMS pulse consisting of a single-sine cycle. The increase in efficacy was already evident when two full-sine cycles were used and did not increase further by adding more cycles to the TMS pulse. Conclusions Increasing the number of full-sine cycles per pulse can improve the efficacy of TMS to excite corticospinal neurons, but there is no simple linear relationship between the number of cycles and TMS efficacy

Ultrafast action potentials mediate Kilohertz signaling at a central synapse

SummaryFast synaptic transmission is important for rapid information processing. To explore the maximal rate of neuronal signaling and to analyze the presynaptic mechanisms, we focused on the input layer of the cerebellar cortex, where exceptionally high action potential (AP) frequencies have been reported in vivo. With paired recordings between presynaptic cerebellar mossy fiber boutons and postsynaptic granule cells, we demonstrate reliable neurotransmission up to ∼1 kHz. Presynaptic APs are ultrafast, with ∼100 μs half-duration. Both Kv1 and Kv3 potassium channels mediate the fast repolarization, rapidly inactivating sodium channels ensure metabolic efficiency, and little AP broadening occurs during bursts of up to 1.5 kHz. Presynaptic Cav2.1 (P/Q-type) calcium channels open efficiently during ultrafast APs. Furthermore, a subset of synaptic vesicles is tightly coupled to Ca2+ channels, and vesicles are rapidly recruited to the release site. These data reveal mechanisms of presynaptic AP generation and transmitter release underlying neuronal kHz signaling

Network Models to Organize a Dispersed Literature: The Case of Misunderstanding Analysis of Covariance

We outline a network method to synthesize a literature overview from search results obtained by multiple team members. Several network statistics are used to create a single representativeness ranking. We illustrate the method with the dispersed literature on a common misinterpretation of analysis of covariance (ANCOVA). The network method yields a top ten list of the most relevant articles that students and researchers can take as a point of departure for a more detailed study on this topic. The proposed methodology is implemented in Shiny, an open-source R package