Paired Associative Stimulation of the Auditory System: A Proof-Of-Principle Study

Martin Schecklmann,Gabriele Frank,Gregor Volberg,Joseph Classen,Michael Landgrebe,Berthold Langguth,Göran Hajak,Nathan Weisz,Mark Greenlee,Julia Hadersdorfer,Thomas Steffens

doi:10.1371/journal.pone.0027088

Abstract

BackgroundPaired associative stimulation (PAS) consisting of repeated application of transcranial magnetic stimulation (TMS) pulses and contingent exteroceptive stimuli has been shown to induce neuroplastic effects in the motor and somatosensory system. The objective was to investigate whether the auditory system can be modulated by PAS.MethodsAcoustic stimuli (4 kHz) were paired with TMS of the auditory cortex with intervals of either 45 ms (PAS(45 ms)) or 10 ms (PAS(10 ms)). Two-hundred paired stimuli were applied at 0.1 Hz and effects were compared with low frequency repetitive TMS (rTMS) at 0.1 Hz (200 stimuli) and 1 Hz (1000 stimuli) in eleven healthy students. Auditory cortex excitability was measured before and after the interventions by long latency auditory evoked potentials (AEPs) for the tone (4 kHz) used in the pairing, and a control tone (1 kHz) in a within subjects design.ResultsAmplitudes of the N1-P2 complex were reduced for the 4 kHz tone after both PAS(45 ms) and PAS(10 ms), but not after the 0.1 Hz and 1 Hz rTMS protocols with more pronounced effects for PAS(45 ms). Similar, but less pronounced effects were observed for the 1 kHz control tone.ConclusionThese findings indicate that paired associative stimulation may induce tonotopically specific and also tone unspecific human auditory cortex plasticity.

Highlights

Transcranial magnetic stimulation (TMS) is a noninvasive method for focal stimulation of superficial cortical areas
Most information about the effects of repetitive TMS (rTMS) is obtained from studies of the motor cortex, as it is easy to assess the excitability of the cortico-spinal system by recording motor-evoked potentials from the target muscles [2]
All subjects rated the tones during auditory evoked potentials (AEPs) recordings correctly as low or high tones in more than 98% of the trials

Summary

Introduction

Transcranial magnetic stimulation (TMS) is a noninvasive method for focal stimulation of superficial cortical areas. Stimulation with low frequency rTMS (1 Hz and below) over the motor cortex has been shown to induce LTD-like effects [5]. Based on its ability to induce effects on neuronal excitability that outlast the stimulation period, low frequency rTMS has been investigated as a treatment for many neuropsychiatric disorders characterized by focal hyper-excitability [5]. It has been shown that low frequency rTMS over temporal and temporo-parietal cortex can reduce tinnitus [7,8] and auditory hallucinations [9]. Paired associative stimulation (PAS) consisting of repeated application of transcranial magnetic stimulation (TMS) pulses and contingent exteroceptive stimuli has been shown to induce neuroplastic effects in the motor and somatosensory system. The objective was to investigate whether the auditory system can be modulated by PAS

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Results

Conclusion