Modulation of motor cortex excitability predicts antidepressant response to prefrontal cortex repetitive transcranial magnetic stimulation

Abstract

Background Repetitive transcranial magnetic stimulation (RTMS) targeting the left dorsolateral prefrontal cortex (DLPFC) is a treatment option for patients with medication-resistant major depressive disorder (MDD). However, antidepressant response is variable and there are currently no response predictors with sufficient accuracy for clinical use. Objective We report on results of an observational open-label study to determine whether the modulatory effect of 10 Hz motor cortex (MC) rTMS is predictive of the antidepressant effect of 10 Hz DLPFC rTMS. Methods Fifty-one medication-resistant MDD patients were enrolled for a 10-day treatment course of DLPFC rTMS and antidepressant response was assessed according to post-treatment reduction of the 17-item Hamilton Rating Scale for Depression score. Prior to treatment, we assessed the modulation of motor evoked potential (MEP) amplitude by MC rTMS. MEP’s were induced with single TMS pulses and measured using surface electromyography. MEP modulation was calculated as the change of mean MEP amplitude after MC rTMS. Results MEP modulation proved to be a robust predictor of reduction of clinician-rated depression severity following the course of DLPFC rTMS: larger MC rTMS-induced increase of corticospinal excitability anticipated a better antidepressant response. This was found both in univariate analyses (Spearman regression: rho=0.43, p<0.005) and a multivariable linear regression model (β=0.25, p<0.0001) controlling for baseline depression severity, age and resting motor threshold. Conclusions These findings suggest that MC rTMS-induced modulation of corticospinal excitability warrants further evaluation as a potential predictive biomarker of antidepressant response to left DLPFC 10 Hz rTMS.

Corticomotor Plasticity Predicts Clinical Efficacy of Combined Neuromodulation and Cognitive Training in Alzheimer’s Disease

“…A neuroimaging study has shown that memory training can drive non-motor brain activation patterns of patients with mild cognitive impairment toward normalization (Belleville et al, 2011). Changes in motor cortical measures after stimulation of non-motor areas have been reported previously (Pallanti et al, 2012), as has prediction of non-motor effects of prefrontal stimulation by motor cortical measures (Oliveira-Maia et al, 2017). These effects could arise through changes in overlapping subcortical glutamatergic and dopaminergic pathways (Wang et al, 2012), which in turn could be driven via cortico-subcortical projections from stimulated non-motor areas.…”

Identification of clinical features and biomarkers that may inform a personalized approach to rTMS for depression

“…The question of whether properties of motor cortex excitability may relate to rTMS response has also garnered some interest. While baseline motor threshold has not been found to be related to treatment response [7], recent work by Oliviera-Maia and colleagues [19] has suggested a potential relationship between modulation of motor cortex excitability prior to rTMS treatment and outcome with DLPFC stimulation. This finding (n = 51) must be considered preliminary due to the small sample size, as well as and the small number of motor evoked potentials used to assess excitability.…”

“…A number of rTMS studies have found support for the notion that rTMS may be less effective for depression in older individuals (e.g., [5,[14][15][16]), while others have not found age to be a significant predictor of rTMS outcomes (e.g., [6,7,17,18]). At least one group has found the relationship between age and rTMS outcome to be curvilinear [19]. Greater cortical atrophy has been linked to diminished response to rTMS [20] and strategies have been described to compensate for distance between scalp and cortex in older depressed patients (e.g., [21]).…”

Precision non-implantable neuromodulation therapies: a perspective for the depressed brain

“…Motor cortical excitability (MCE) measures were the first neurophysiological biomarkers investigated in MDD, as the motor cortex can be easily probed using single- and paired-pulse TMS, which are associated with GABA and glutamate activity in this structure. 181 , 182 Studies have shown that baseline measures of cortical inhibition and facilitation were associated with antidepressant response to tDCS, rTMS, and ECT, 31 , 183 , 184 although effect sizes were small. In addition, EEG-based neurophysiological parameters are associated with antidepressant response to rTMS.…”