Voltage-sensitive dye imaging of transcranial magnetic stimulation-induced intracortical dynamics

Abstract

Transcranial magnetic stimulation (TMS) is widely used in clinical interventions and basic neuroscience. Additionally, it has become a powerful tool to drive plastic changes in neuronal networks. However, highly resolved recordings of the immediate TMS effects have remained scarce, because existing recording techniques are limited in spatial or temporal resolution or are interfered with by the strong TMS-induced electric field. To circumvent these constraints, we performed optical imaging with voltage-sensitive dye (VSD) in an animal experimental setting using anaesthetized cats. The dye signals reflect gradual changes in the cells' membrane potential across several square millimeters of cortical tissue, thus enabling direct visualization of TMS-induced neuronal population dynamics. After application of a single TMS pulse across visual cortex, brief focal activation was immediately followed by synchronous suppression of a large pool of neurons. With consecutive magnetic pulses (10 Hz), widespread activity within this "basin of suppression" increased stepwise to suprathreshold levels and spontaneous activity was enhanced. Visual stimulation after repetitive TMS revealed long-term potentiation of evoked activity. Furthermore, loss of the "deceleration-acceleration" notch during the rising phase of the response, as a signature of fast intracortical inhibition detectable with VSD imaging, indicated weakened inhibition as an important driving force of increasing cortical excitability. In summary, our data show that high-frequency TMS changes the balance between excitation and inhibition in favor of an excitatory cortical state. VSD imaging may thus be a promising technique to trace TMS-induced changes in excitability and resulting plastic processes across cortical maps with high spatial and temporal resolutions. (1) (TMS) has become a frequently used method for noninvasive diagnostics, therapeutic treatment, and intervention for neurorehabilitation of neurological disorders (2-8). Additionally, TMS has proved a valuable tool in basic brain research as its perturbative effects allow area-selective manipulation of immediate cortical function (9-11), as well as its long-lasting alteration through plasticity and learning protocols (12, 13). However, direct measurements of the TMS-induced cortical dynamics at highly resolved spatiotemporal scales are missing because "online approaches" (14), using modern neuroimaging techniques such as functional MRI (fMRI) (15-18), magnetoencephalography (19), EEG (20), and near-infrared (21) or intrinsic optical imaging (22), are limited in either spatial or temporal resolutions or in both.Here we overcame these limitations, using optical imaging with voltage-sensitive dyes (VSD), which exploits the dye's property to transduce gradual changes in voltage across neuronal membranes into fluorescent light signals. In contrast to imaging methods applicable in humans, this method is invasive but allows avoiding the commonly experienced contamination of signals by artifacts due to the strong ...

Assessment and modulation of cortical inhibition using transcranial magnetic stimulation

“…Meanwhile 'contact-free' functional microscopy techniques, e.g. via calcium-or voltagesensitive dyes (Kozyrev et al, 2014;Murphy et al, 2016), indicate that a low stimulation intensity mainly activates inhibitory interneurons, whereas projection neurons will be recruited with higher intensities [see (Pashut et al, 2014)]. Hence, these studies convey a plausible explanation for the already described SICI double-pulse protocol, where the subthreshold conditioning TMS pulse results in a GABA A receptor-dependent inhibition of the test MEP response.…”

Catching the voltage gradient—asymmetric boost of cortical spread generates motion signals across visual cortex: a brief review with special thanks to Amiram Grinvald

“…112 Recently, we used VSDI to explore the effects of transcranial magnetic stimulation (TMS) on V1 activity and its induced plastic changes. 113 In these settings (i.e., using light as a measure), VSDI has the advantage of being able to avoid interference with the strong TMS-induced electric field.…”

Untersuchung und Modulation kortikaler Inhibition mittels transkranieller Magnetstimulation

“…Der Einsatz "kontaktfreier" funktioneller Mikroskopieverfahren, z. B. mittels kalzium-oder spannungssensitiver Farbstoffe (Kozyrev et al 2014;Murphy et al 2016), deutet darauf hin, dass bei geringer Stimulationsintensität vornehmlich inhibitorische Interneurone aktiviert werden, während Projektionsneurone erst bei höheren Intensitä-ten rekrutiert werden (siehe auch Pashut et al 2014). Somit bieten diese Studien einen plausiblen Erklärungsansatz für das bereits beschriebene SICI-Doppelpulsprotokoll, bei dem der unterschwellige konditionierende TMS-Puls zu einer GABA A -abhängigen Inhibition der durch den TMS Test-Puls induzierten MEP-Antwort führt.…”