Short-latency afferent inhibition and somato-sensory evoked potentials during the migraine cycle: surrogate markers of a cycling cholinergic thalamo-cortical drive?

Gianluca Coppola,Maurizio Evangelista,Mariano Serrao,Gabriele Sebastianelli,Francesco Pierelli,Jean Schoenen,Davide Di Lenola,Francesco Casillo,Chiara Abagnale,Fabio Ferrandes,Cherubino Di Lorenzo

doi:10.1186/s10194-020-01104-7

Abstract

BackgroundShort-latency afferent inhibition (SAI) consists of motor cortex inhibition induced by sensory afferents and depends on the excitatory effect of cholinergic thalamocortical projections on inhibitory GABAergic cortical networks. Given the electrophysiological evidence for thalamo-cortical dysrhythmia in migraine, we studied SAI in migraineurs during and between attacks and searched for correlations with somatosensory habituation, thalamocortical activation, and clinical features.MethodsSAI was obtained by conditioning the transcranial magnetic stimulation-induced motor evoked potential (MEP) with an electric stimulus on the median nerve at the wrist with random stimulus intervals corresponding to the latency of individual somatosensory evoked potentials (SSEP) N20 plus 2, 4, 6, or 8 ms. We recruited 30 migraine without aura patients, 16 between (MO), 14 during an attack (MI), and 16 healthy volunteers (HV). We calculated the slope of the linear regression between the unconditioned MEP amplitude and the 4-conditioned MEPs as a measure of SAI. We also measured SSEP amplitude habituation, and high-frequency oscillations (HFO) as an index of thalamo-cortical activation.ResultsCompared to HV, SAI, SSEP habituation and early SSEP HFOs were significantly reduced in MO patients between attacks, but enhanced during an attack. There was a positive correlation between degree of SAI and amplitude of early HFOs in HV, but not in MO or MI.ConclusionsThe migraine cycle-dependent variations of SAI and SSEP HFOs are further evidence that facilitatory thalamocortical activation (of GABAergic networks in the motor cortex for SAI), likely to be cholinergic, is reduced in migraine between attacks, but increased ictally.

Highlights

Short-latency afferent inhibition (SAI) consists of motor cortex inhibition induced by sensory afferents and depends on the excitatory effect of cholinergic thalamocortical projections on inhibitory GABAergic cortical networks
The clinical features did not differ between the 2 groups of migraineurs, except for a significantly longer duration of disease in patients recorded during an attack (F1,29 = 5.833, p = 0.023, Table 1)
In both healthy volunteers (HV) and patients during an attack, the linear regression slope of somatosensory evoked potentials (SSEP) N20-P25 amplitudes over the 3 blocks showed a negative value, i.e. habituated, while it was positive in patients between attacks, indicating a habituation deficit (+ 0.49, p < 0.001 Migraine without aura between attacks (MO) vs. HV)

Summary

Introduction

Short-latency afferent inhibition (SAI) consists of motor cortex inhibition induced by sensory afferents and depends on the excitatory effect of cholinergic thalamocortical projections on inhibitory GABAergic cortical networks. Given the electrophysiological evidence for thalamo-cortical dysrhythmia in migraine, we studied SAI in migraineurs during and between attacks and searched for correlations with somatosensory habituation, thalamocortical activation, and clinical features. Part of the evidence comes from a study of the phenomenon of short-latency afferent inhibition (SAI) by which a peripheral sensory afferent volley inhibits the homotopic muscle response obtained by stimulation of the motor cortex [11]. SAI depends on the excitatory effect exerted by cholinergic thalamocortical afferents on inhibitory GABAergic cortical networks [11]. Previous studies have shown that migraineurs are characterized by ictal and interictal dysfunctions of both thalamic and cortical somatosensory nodes [2, 12,13,14], and of the cortical synaptic plasticity partially depending on GABAergic mechanisms [15,16,17]

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Conclusion