Cortical Excitability

This paper introduces a new method for measuring cortical excitability using an electrical probing stimulus via intracranial electroencephalography (iEEG). Stimuli consisted of 100 single bi-phasic pulses, delivered every 10 minutes. Neural excitability is estimated by extracting a feature from the iEEG responses to the stimuli, which we dub the mean phase variance (PV). We show that the mean PV increases with the rate of inter-ictal discharges in one patient. In another patient, we show that the mean PV changes with sleep and an epileptic seizure. The results demonstrate a proof-of-principal for the method to be applied in a seizure anticipation framework.

Transcranial magnetic (TMS) and direct current (tDCS) stimulation are non-invasive brain stimulation techniques that allow researchers to purposefully modulate cortical excitability in focal areas of the brain. Recent work has provided preclinical evidence indicating that TMS and tDCS can facilitate motor performance, motor memory formation, and motor skill learning in healthy subjects and possibly in patients with brain lesions. Although the optimal stimulation parameters to accomplish these goals remain to be determined, and controlled multicentre clinical studies are lacking, these findings suggest that cortical stimulation techniques could become in the future adjuvant strategies in the rehabilitation of motor deficits. The aim of this article is to critically review these findings and to discuss future directions regarding the possibility of combining these techniques with other interventions in neurorehabilitation.

Transcranial alternating current stimulation (tACS) seems likely to open a new era of the field of noninvasive electrical stimulation of the human brain by directly interfering with cortical rhythms. It is expected to synchronize (by one single resonance frequency) or desynchronize (e.g., by the application of several frequencies) cortical oscillations. If applied long enough it may cause neuroplastic effects. In the theta range it may improve cognition when applied in phase. Alpha rhythms could improve motor performance, whereas beta intrusion may deteriorate them. TACS with both alpha and beta frequencies has a high likelihood to induce retinal phosphenes. Gamma intrusion can possibly interfere with attention. Stimulation in the "ripple" range induces intensity dependent inhibition or excitation in the motor cortex (M1) most likely by entrainment of neuronal networks, whereas stimulation in the low kHz range induces excitation by neuronal membrane interference. TACS in t...

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that activates neurons via generation of brief pulses of high-intensity magnetic field. If these pulses are applied in a repetitive fashion (rTMS), persistent modulation of neural excitability can be achieved. The technique has proved beneficial in the treatment of a number of neurological and psychiatric conditions. However, the effect of rTMS on excitability and the other performance indicators shows a considerable degree of variability across different sessions and subjects. The frequency of stimulation has always been considered as the main determinant of the direction of excitability modulation. However, interactions exist between frequency and several other stimulation parameters that also influence the degree of modulation. In addition, the spatial interaction of the transient electric field induced by the TMS pulse with the cortical neurons is another contributor to variability. Considerati...

Chronic pain resulting from injury of the peripheral or central nervous system may be associated with a significant dysfunction of extensive neural networks. Noninvasive stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) may be suitable to treat chronic pain as they can act on these networks by modulating neural activities not only in the stimulated area, but also in remote regions that are interconnected to the site of stimulation. Motor cortex was the first cortical target that was proved to be efficacious in chronic pain treatment. At present, significant analgesic effects were also shown to occur after the stimulation of other cortical targets (including prefrontal and parietal areas) in acute provoked pain, chronic neuropathic pain, fibromyalgia, or visceral pain. Therapeutic applications of rTMS in pain syndromes are limited by the short duration of the induced effects, but prolonged pain relief can be obtained by repeating rTMS sessions every day for several weeks. Recent tDCS studies also showed some effects on various types of chronic pain. We review the evidence to date of these two techniques of noninvasive brain stimulation for the treatment of pain.

The effects of sleep deprivation on neural activity underlying stimulus change detection are still debated. The aim of this study was to investigate the effects of sleep deprivation on the relationship between N1 refractoriness and Mismatch Negativity (MMN) as indexes of different stages of change detection. Respectively, N1 represents the sensory feature trace creation with stimulus repetition and MMN represents the memory-based detection of deviance in a new incoming stimulus. Event-related potentials (ERPs) were recorded from 22 healthy participants during a passive auditory oddball task after a night of normal sleep and after a night of total sleep deprivation (TSD). Importantly, stimulus presentation was organized as a train of 10 stimuli, so that N1 refractoriness could be measured as amplitude decrease with stimulus repetition within each train. Results showed that N1 refractoriness and MMN were not affected by TSD suggesting that the change detection process was preserved in our paradigm. However, the overall N1 amplitude increased after TSD, an effect that may be related to an enhancement of cortical excitability.► We investigated the effect of total sleep deprivation on auditory change detection. ► We adapted a roving-standard oddball task to measure N1, N1 refractoriness and MMN. ► N1 refractoriness and MMN were not affected by total sleep deprivation. ► Regardless N1 refractoriness, N1 amplitude increased after total sleep deprivation. ► The increment of N1 may suggest a possible enhancement in cortical excitability.

Despite their abundance, the molecular functions of long non-coding RNAs in mammalian nervous systems remain poorly understood. Here we show that the long non-coding RNA, NEAT1, directly modulates neuronal excitability and is associated with pathological seizure states. Specifically, NEAT1 is dynamically regulated by neuronal activity in vitro and in vivo, binds epilepsy-associated potassium channel-interacting proteins including KCNAB2 and KCNIP1, and induces a neuronal hyper-potentiation phenotype in iPSC-derived human cortical neurons following antisense oligonucleotide knockdown. Next generation sequencing reveals a strong association of NEAT1 with increased ion channel gene expression upon activation of iPSC-derived neurons following NEAT1 knockdown. Furthermore, we show that while NEAT1 is acutely down-regulated in response to neuronal activity, repeated stimulation results in NEAT1 becoming chronically unresponsive in independent in vivo rat model systems relevant to temporal...