Detecting cortical circuits resonant to high-frequency oscillations in the human primary motor cortex: a TMS-tACS study

Abstract

Corticospinal volleys evoked by transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) consist of high-frequency bursts (≈667 and ≈333 Hz). However, intracortical circuits producing such corticospinal high-frequency bursts are unknown. We here investigated whether neurons activated by single TMS pulses over M1 are resonant to high-frequency oscillations, using a combined transcranial alternating current stimulation (tACS)-TMS approach. We applied 667, 333 Hz or sham-tACS and, concurrently, we delivered six single-pulse TMS protocols using monophasic or biphasic pulses, different stimulation intensities, muscular states, types and orientations of coils. We recorded motor evoked potentials (MEPs) before, during and after tACS. 333 Hz tACS facilitated MEPs evoked by biphasic TMS through a figure-of-eight coil at active motor threshold (AMT), and by monophasic TMS with anteriorto-posterior-induced current in the brain. 333 Hz tACS also facilitated MEPs evoked by monophasic TMS through a circular coil at AMT, an effect that weakly persisted after the stimulation. 667 Hz tACS had no effects. 333 Hz, but not 667 Hz, tACS may have reinforced the synchronization of specific neurons to high-frequency oscillations enhancing this activity, and facilitating MEPs. Our findings suggest that different bursting modes of corticospinal neurons are produced by separate circuits with different oscillatory properties. Corticospinal neurons (CSNs) of the mammalian brain show a high frequency (≈667 Hz) burst of activity in response to transcranial electric (TES) and magnetic (TMS) stimulation. These stereotyped bursts of activity can be recorded from the surface of the high cervical cord and reflect the spiking of a large number of corticospinal axons 1-5. Recently, Maier et al. 6 recorded the responses of single corticospinal axons together with volleys from the surface of the cervical cord after intracortical stimulation in monkey and showed that individual axons fire repetitively at the high frequency revealed by surface recordings, thus demonstrating that bursts originate from the repetitive synchronous discharge of CSNs. They also found that while most of the corticospinal axons discharged at around 600 Hz, there were other axons responding at lower frequencies 6. In humans, bursts of corticospinal activity with different frequencies can be recorded by cervical epidural electrodes after TMS over the motor cortex 5. This descending bursting activity is influenced by the direction of the current flowing across the central sulcus. The more commonly used posterior-to-anterior (PA)-induced current in the brain (perpendicular to the central sulcus) preferentially evokes the 667 Hz repetitive discharge. However, when the orientation of the induced current is reversed (anterior-to-posterior in the brain; AP) or when stimulation is performed using a biphasic TMS that combines sequentially both directions of stimulation (a PA induced current followed by an AP induced current), the output changes with less synchronized vol...

Neurobiological After-Effects of Low Intensity Transcranial Electric Stimulation of the Human Nervous System: From Basic Mechanisms to Metaplasticity

“…TDCS acts in a polarity-dependent fashion, with anodal stimulation increasing and cathodal stimulation decreasing neuronal excitability, whereas tACS consists in the application of a sinusoidal waveform current that alternates between the anode and the cathode ( switching polarity ) and modulates the power of oscillatory rhythms in a frequency-dependent manner by synchronizing or desynchronizing neuronal networks ( 30 ). For example, in studies that coupled transcranial magnetic stimulation (TMS) with ES, tACS was found to synchronize cortical networks bursting at frequencies higher than 300 Hz ( 31 ).…”

Online and offline effects of transcranial alternating current stimulation of the primary motor cortex

“…For instance, it was shown that when the stimulation is combined with a simultaneous active motor task, physiological and behavioral effects outlast the stimulation period 42 . Other evidence showed that tACS induced offline effects on MEPs size when delivered at ripple frequencies 43 with 140 Hz 44 – 46 , 250 Hz 45 , 333 Hz 47 or even higher frequencies such as 1, 2 and 5 kHz 48 . In summary, the dynamics of online and offline tACS effects are still a matter of debate.…”

After-Effects of Intermittent Theta-Burst Stimulation Are Differentially and Phase-Dependently Suppressed by α- and β-Frequency Transcranial Alternating Current Stimulation

“…Although our current results could be derived from an interaction between tACS and iTBS, another explanation involves additive tACS after-effects. tACS after-effects have been consistently reported in studies using much higher stimulation frequencies (140 Hz and 250 Hz tACS; Moliadze et al, 2010Moliadze et al, , 2012Inukai et al, 2016;Guerra et al, 2020b). αand β-tACS also induce after-effects on visual (Zaehle et al, 2010;Neuling et al, 2013;Vossen et al, 2015;Kasten et al, 2016;Nakazono et al, 2020) and auditory (Ahn et al, 2019;Wang et al, 2020) neurophysiological functions.…”