V34. Paired associative stimulation of the temporal cortex

Abstract

Background Paired associative stimulation (PAS) is a specific repetitive transcranial magnetic stimulation (rTMS) protocol where every pulse is combined with an external stimulus. Based on a close timing between the TMS induced action potential and the cortical arrival of the external stimulus in the stimulated area neural plasticity is induced by mechanisms of spike-timing dependent plasticity. After a first proof-of-principle study of PAS of the auditory cortex by our group, we here extend these findings by investigating the effects of stimulus duration and of sham stimulation on primary and secondary auditory cortical activity. Methods The left temporal cortex of 18 healthy controls with normal hearing was stimulated in two experimental parts. One PAS session consisted of 200 stimulations with an interstimulus interval of 45 ms between tone onset (400 ms length, 4 kHz frequency) and the TMS pulse proven to be effective in the pilot study. Part 1 contrasted effects of a short (23 ms) and a long (400 ms) PAS-tone on secondary auditory cortex activity (short vs. long condition); part 2 contrasted effects of verum and sham stimulation (6-fold reduced intensity, not targeting the cortex) on primary and secondary auditory cortex activity (verum vs. sham condition). Primary auditory cortex activity was measured with auditory steady state responses (ASSR) as elicited by 40 Hz amplitude-modulated (AM) sine tones. Secondary auditory cortex activity was elicited with ASSRs using a 20 Hz AM tone and late auditory evoked potentials (AEPs) for the 40 Hz and 20 Hz AM tone. Evoked activity was done for the PAS tone (4 kHz carrier frequency) and a control tone (1 kHz carrier frequency) - each tone presented 70 times (60 dB SL, 800 ms length). As STDP is based on close timing of pre- and post-synaptic activity we concentrated on evoked activity by using analyses time-locked to the tone onset. Results For part 1, the short PAS condition showed an increase in AEP amplitude accompanied by a decrease for the long PAS condition specific for the PAS carrier frequency. Verum and sham stimulation showed comparable decreases in AEP amplitude independent from the PAS protocol. Part 2 showed no effects for the contrast short vs. long condition. 20 Hz ASSR amplitude showed sham-controlled decreases for the PAS-specific carrier frequency. ASSR amplitudes of the control tone or of the 40 Hz AM tone showed no significant effects. Discussion PAS of the auditory cortex seem to be restricted to the secondary auditory cortex as effects could only be found for the AEPs and the 20 Hz ASSRs which have neural generators rather in secondary than in primary auditory cortex. AEPs findings raise the importance of habituation effects and of duration of the PAS tone and challenge the validity of the transfer of PAS using sine tones to evoked potentials using AM tones.