Changes in motor cortex excitability associated with temporal repetitive transcranial magnetic stimulation in tinnitus: hints for cross-modal plasticity?

Abstract

BackgroundMotor cortex excitability was found to be changed after repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex highlighting the occurrence of cross-modal plasticity in non-invasive brain stimulation. Here, we investigated the effects of temporal low-frequency rTMS on motor cortex plasticity in a large sample of tinnitus patients. In 116 patients with chronic tinnitus different parameters of cortical excitability were assessed before and after ten rTMS treatment sessions. Patients received one of three different protocols all including 1 Hz rTMS over the left temporal cortex. Treatment response was defined as improvement by at least five points in the tinnitus questionnaire (TQ). Variables of interest were resting motor threshold (RMT), short-interval intra-cortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP).ResultsAfter rTMS treatment RMT was decreased by about 1% of stimulator output near-significantly in the whole group of patients. SICI was associated with significant changes with respect to treatment response. The group of treatment responders showed a decrease of SICI over the course of treatment, the group of non-responders the reverse pattern.ConclusionsMinor RMT changes during rTMS treatment do not necessarily suggest the need for systematic re-examination of the RMT for safety and efficacy issues. Treatment response to rTMS was shown to be related to changes in SICI that might reflect modulation of GABAergic mechanisms directly or indirectly related to rTMS treatment effects.

A systematic review of non-motor rTMS induced motor cortex plasticity

“…Furthermore, a clinical study with tinnitus patients correlated rTMS-induced (5 treatment days, 2000 pulses, 1 Hz stimulation frequency) increases in SICI with reduction in tinnitus questionnaire scores (Langguth et al, 2007 ). The same authors reported inverse effects in a later retrospective analysis of a larger sample, i.e., decrease in SICI in responding tinnitus patients over the course of the trial (Schecklmann et al, 2014 ). Three studies with major depressive patients and healthy controls report no effects of rTMS on SICI values (Eichhammer et al, 2007 ; Lee et al, 2013 ; Spampinato et al, 2013 ).…”

“…Also, although established, the parameters investigated here are not free from controversy: recently, a study systematically investigated the reliability of MEPs and found out that at least 30 repetitions are necessary for stable MEPs (Cuypers et al, 2014 ). This is in contrast with common practice, as can be seen in well referenced articles (Gerschlager et al, 2002 ; Schecklmann et al, 2014 ) and as suggested by textbooks (Siebner and Ziemann, 2007 ). In addition, further measurement methods (e.g., conditioning TMS pulse intensity and inter-stimulus intervals in the paired-pulse paradigms), for which we abstained from reporting them due to shortage of space, might also contribute to the high variability.…”

“…In the patient studies, an increase of the CSP was only detected in clinically responding patients. Association of CSP and treatment response could not be replicated in a later retrospective analysis of a larger sample of tinnitus patients (Schecklmann et al, 2014 ). Reduction of CSP duration was reported only in one study in major depression patients who responded to 3 or 10 Hz with 450 or 500 daily pulses over 10 days (Chistyakov et al, 2005 ).…”

“…Over the course of the 10-day treatment with 500 daily pulses over the DLPFC, they found an increase in RMT during the first 7 days followed by a decrease in the following 4 days. In contrast, three studies (two stimulating the DLPFC using 10/20 Hz in patients with major depression; one stimulating both the DLPFC with 20 Hz and the TC with 1 Hz in tinnitus patients) using at least 2000 pulses over at least 2 weeks described a decrease of RMT (Triggs et al, 1999 ; Croarkin et al, 2012 ; Schecklmann et al, 2014 ). However, in one of these studies the effect of a mean decrease of 1% stimulator output was small and only near significant due to the large sample size (Schecklmann et al, 2014 ).…”

“…In contrast, three studies (two stimulating the DLPFC using 10/20 Hz in patients with major depression; one stimulating both the DLPFC with 20 Hz and the TC with 1 Hz in tinnitus patients) using at least 2000 pulses over at least 2 weeks described a decrease of RMT (Triggs et al, 1999 ; Croarkin et al, 2012 ; Schecklmann et al, 2014 ). However, in one of these studies the effect of a mean decrease of 1% stimulator output was small and only near significant due to the large sample size (Schecklmann et al, 2014 ). Additionally, RMT decreases after DLPFC stimulation were found in patients with affective disorders (1 Hz, 15 days, 420 daily pulses) and were associated with clinical response (Pallanti et al, 2012 ).…”