Low-intensity repetitive paired associative stimulation targeting the motor hand area at theta frequency causes a lasting reduction in corticospinal excitability

V Rizzo; C Mastroeni; R Maggio; C Terranova; P Girlanda; H R Siebner; A Quartarone

doi:10.1016/j.clinph.2020.06.033

Low-intensity repetitive paired associative stimulation targeting the motor hand area at theta frequency causes a lasting reduction in corticospinal excitability

Clin Neurophysiol. 2020 Oct;131(10):2402-2409. doi: 10.1016/j.clinph.2020.06.033. Epub 2020 Aug 6.

Authors

V Rizzo¹, C Mastroeni², R Maggio³, C Terranova², P Girlanda², H R Siebner⁴, A Quartarone⁵

Affiliations

¹ Department of Clinical and Experimental Medicine, University of Messina, Italy. Electronic address: enzo.rizzo@gmail.com.
² Department of Clinical and Experimental Medicine, University of Messina, Italy.
³ Department of Neurology, Humanitas Research Hospital, Rozzano, Milan, Italy.
⁴ Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark; Institute for Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁵ Department of Biomedical Science and Morphological and Functional Images, University of Messina, Italy; IRCCS Centro "Bonino Pulejo", Messina, Italy.

PMID: 32828043
DOI: 10.1016/j.clinph.2020.06.033

Abstract

Objective: Sub-motor threshold 5 Hz repetitive paired associative stimulation (5 Hz-rPAS_25ms) produces a long-lasting increase in corticospinal excitability. Assuming a spike-timing dependent plasticity-like (STDP-like) mechanism, we hypothesized that 5 Hz-rPAS at a shorter inter-stimulus interval (ISI) of 15 ms (5 Hz-rPAS_15ms) would exert a lasting inhibitory effect on corticospinal excitability.

Methods: 20 healthy volunteers received two minutes of 5 Hz-rPAS_15ms. Transcranial magnetic stimulation (TMS) was applied over the motor hotspot of the right abductor pollicis brevis muscle at 90% active motor threshold. Sub-motor threshold peripheral electrical stimulation was given to the left median nerve 15 ms before each TMS pulse. We assessed changes in mean amplitude of the unconditioned motor evoked potential (MEP), short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), long-latency afferent inhibition (LAI), and cortical silent period (CSP) before and for 60 minutes after 5-Hz rPAS_15ms.

Results: Subthreshold 5-Hz rPAS_15ms produced a 20-40% decrease in mean MEP amplitude along with an attenuation in SAI, lasting at least 60 minutes. A follow-up experiment revealed that MEP facilitation was spatially restricted to the target muscle.

Conclusions: Subthreshold 5-Hz rPAS_15ms effectively suppresses corticospinal excitability. Together with the facilitatory effects of subthreshold 5-Hz rPAS_25ms (Quartarone et al., J Physiol 2006;575:657-670), the results show that sub-motor threshold 5-Hz rPAS induces STDP-like bidirectional plasticity in the motor cortex.

Significance: The results of the present study provide a new short-time paradigm of long term depression (LTD) induction in human sensory-motor cortex.

Keywords: Associative plasticity; Paired associative stimulation; Transcranial magnetic stimulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Electromyography
Evoked Potentials, Motor / physiology*
Female
Humans
Male
Motor Cortex / physiology*
Muscle, Skeletal / physiology
Neural Inhibition / physiology*
Neuronal Plasticity / physiology*
Theta Rhythm / physiology*
Transcranial Magnetic Stimulation
Young Adult