Low-intensity repetitive transcranial magnetic stimulation requires concurrent visual system activity to modulate visual evoked potentials in adult mice

Kalina Makowiecki,Jennifer Rodger,Andrew Garrett,Alan R. Harvey

doi:10.1038/s41598-018-23979-y

Abstract

Repetitive transcranial stimulation (rTMS) is an increasingly popular method to non-invasively modulate cortical excitability in research and clinical settings. During rTMS, low-intensity magnetic fields reach areas perifocal to the target brain region, however, effects of these low-intensity (LI-) fields and how they interact with ongoing neural activity remains poorly defined. We evaluated whether coordinated neural activity during electromagnetic stimulation alters LI-rTMS effects on cortical excitability by comparing visually evoked potentials (VEP) and densities of parvalbumin-expressing (PV+) GABAergic interneurons in adult mouse visual cortex after LI-rTMS under different conditions: LI-rTMS applied during visually evoked (strong, coordinated) activity or in darkness (weak, spontaneous activity).We also compared response to LI-rTMS in wildtype and ephrin-A2A5−/− mice, which have visuotopic anomalies thought to disrupt coherence of visually-evoked cortical activity. Demonstrating that LI-rTMS effects in V1 require concurrent sensory-evoked activity, LI-rTMS delivered during visually-evoked activity increased PV+ immunoreactivity in both genotypes; however, VEP peak amplitudes changed only in wildtypes, consistent with intracortical disinhibition. We show, for the first time, that neural activity and the degree of coordination in cortical population activity interact with LI-rTMS to alter excitability in a context-dependent manner.

Highlights

Cortical processing of sensory-motor stimuli is important in many aspects of cognition and behaviour[1]
Comparisons between wildtype and ephrin-A2A5−/− mice revealed that electrophysiological effects of LI-repetitive transcranial magnetic stimulation (rTMS) on visually evoked potentials (VEP) responses were dissociable from its effects on parvalbumin immunoreactivity
When spontaneous firing was likely equivalent between genotypes, the genotype-specific effects of low-intensity rTMS (LI-rTMS) were absent. These findings suggest that coherence of brain activity may play a role in differential effects of LI-rTMS between normal and abnormal systems previously shown in mice[21,22,50] and in healthy compared to clinical populations in humans receiving higher intensity rTMS51

Summary

Introduction

Cortical processing of sensory-motor stimuli is important in many aspects of cognition and behaviour[1]. Intracortical inhibitory-excitatory circuits are critically important, because of their roles in processing stimulus characteristics and regulating activity-dependent plasticity of stimulus-specific responses[3]. In these recurrent intracortical circuits, inhibitory interneurons play a vital role by controlling individual pyramidal neuron response properties and regulating principal neuron output and signal propagation of sensory stimuli[4,5]. Because low-intensity stimulation alters membrane electrophysiological properties and firing probabilities, without directly evoking action-potentials[17], functional effects may be determined by interactions with evoked and/or stochastic neural activity during stimulation[26,27]. We hypothesized that the type of activity during LI-rTMS would modulate its effects on intracortical inhibition-excitation balance, reflected in late VEP response components which are sensitive to cortical state and changes in GABAergic inhibition

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Discussion

Conclusion