Paired Associative Stimulation of the Temporal Cortex: Effects on the Auditory Steady-State Response

Abstract

BackgroundPaired associative stimulation (PAS) is the repeated combination of a sensory stimulus with transcranial magnetic stimulation (TMS) in close temporal association. Recently, a study demonstrated that PAS of an auditory stimulus together with TMS of the temporal cortex is capable of changing the amplitude of auditory evoked potentials (AEP).ObjectiveThis study examined the influence of tone duration and habituation in temporal cortex PAS as elicited by 40 and 20 Hz amplitude modulated auditory steady-state responses (aSSR).MethodsEighteen subjects participated in two experiments, including two PAS protocols each, which consisted of 200 auditory stimuli (4 kHz) paired with temporal cortex TMS with an interstimulus interval (ISI) of 45 ms between tone onset and TMS pulse, delivered at 0.1 Hz. Experiment 1 compared auditory stimuli with different lengths [PAS (23 ms) vs. PAS (400 ms)]. Experiment 2 investigated verum vs. sham PAS. aSSR for the paired tone (4 kHz) and a control tone (1 kHz) were measured pre- and post-interventional—using 40 Hz aSSR in experiment 1 and both 20 and 40 Hz aSSR in experiment 2.ResultsA statistically significant, sham-controlled decrease in amplitude was observed for the 20 Hz aSSR using the 4 kHz PAS carrier frequency in experiment 2.ConclusionFrequency-specific effects for the 20 Hz aSSR confirm the feasibility of auditory PAS and highlight the secondary auditory cortex as its target site, introducing new possible treatment protocols for patients suffering from tinnitus. The amplitude decrease can be explained by principles of spike timing-dependent plasticity and the superposition model of aSSR.

Effects of Acoustic Paired Associative Stimulation on Late Auditory Evoked Potentials

“…In sum, Engel and colleagues found a significant sham-controlled decrease specifically in the amplitude of the 20 Hz ASSR after PAS with a paired tone of 400 ms duration (Engel et al 2017 ). This was interpreted as a carrier-frequency specific inhibitory effect of auditory PAS taking place in the secondary auditory cortex.…”

“…Based on the abovementioned conclusions, auditory PAS should induce the same sham-controlled tone specific effects for LAEP (comparable to the effects of the 20 Hz ASSR). Aim of the present work is the re-analysis of the work of Engel and colleagues (Engel et al 2017 ) analyzing LAEP which were the dependent variable in the study by Schecklmann et al According to the published LAEP and ASSR findings, we hypothesize sham-controlled reductions of LAEP induced by the PAS. Longer stimulus duration is associated with increased perception of and therefore attention to the stimulus (Debner and Jacoby 1994 ; Overgaard et al 2006 ; Sandberg et al 2010 ).…”

“…Besides the extensively investigated motor and somatosensory system, two PAS pilot studies of the auditory cortex were conducted so far by our workgroup (Engel et al 2017 ; Schecklmann et al 2011 ). In the first study by Schecklmann et al it could be shown that inhibitory effects of PAS were associated with a close timing between the cortical arrival of a sine tone and the application of a TMS pulse as indicated by a decrease in the amplitude of the long-latency auditory evoked potentials (LAEP) N1 and P2.…”

“…Among several open questions, three were investigated by the subsequent work of Engel and colleagues in two experiments (Engel et al 2017 ). One open question was whether the effects of auditory PAS take place on the level of the primary or secondary auditory cortex.…”

“…No effects of the PAS intervention were found for the amplitudes of the 40 Hz ASSR. This was explained by a possible lack of appropriate stimulation of the main generators of the 40 Hz ASSR due to the specifics of their anatomical origin and properties of the TMS stimulation (Engel et al 2017 ). However, since only 40 Hz ASSR were used to measure the effects of the duration of the paired tone in this study, the influence of paired tone duration on PAS effects remains unclear.…”