Neurophysiological effects of low and high frequency rTMS on long latency auditory evoked potentials

Abstract

Objectives Long latency auditory evoked potentials (LLAEP; N1a, N1b, N1c and P2) involving local and global auditory processes were investigated in order to examine the impact of low-(LF) and high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) on the cortical excitability of the temporal cortex. We hypothesized that both stimulation frequencies have the same modulation effect, in accordance with clinical data showing a reduction of auditory verbal hallucinations (AVH) after LF- and HF-temporal rTMS in patients with schizophrenia. Methods In 30 right-handed healthy volunteer subjects enrolled in a crossover trial, we studied the changes of LLAEP before and after neuronavigated LF- and HF-rTMS protocols over the left temporal cortex. The target was defined using fMRI (comprehensive versus listening contrasted auditory task). We studied changes in latencies, amplitudes, surface potential maps and cortical generators (swLORETA). N1a generators are mainly located in the temporal cortex while N1b, N1c and P2 generators are located mainly in the frontal cortex. Results While no effect on N1a was observed, similar inhibitory effect of both rTMS frequencies on LLAEP amplitudes was obtained for N1b, N1c and P2. The study of surface potential maps and cortical generators noticed some differences regarding the auditory processes: HF-rTMS produced earlier, more diffused and more right-lateralized effects than LF-rTMS. Conclusions While N1a may only reflect auditory processes, later cortical responses such as N1c and P2 may reflect more integrative, cognitive, attentional processing, in addition to auditory processes. Thus, beyond local inhibitory effects, rTMS, and particularly HF-rTMS, exerted a remote modulation effect on the frontal cortex that might be involved in the attentional processes. This could be an explanation for the therapeutic effect of temporal HF-rTMS on AVHs in patients with schizophrenia.