Early TMS—EEG responses predict symptom severity in major depressive disorder

The diagnosis and treatment of major depressive disorder (MDD) heavily rely on subjective self-reports, which inadequately reflect underlying neurobiological changes.We lack reliable measures to predict the disorder trajectory or a response to a particular therapeutic intervention.Transcranial magnetic stimulation (TMS) combined with simultaneous acquisition of electroencephalography (TMSeEEG) allows investigation of cortical excitability, TMS-evoked potentials (TEPs) reflecting both glutamatergic and GABAergic activity.In this study, we investigated the association between the properties of the early TEPs (10 to 50 ms poststimulus) and the MDD symptom severity.Single-pulse TMS was delivered to the left dorsolateral prefrontal cortex of 20 MDD patients and 7 healthy controls with concurrent EEG recording.The stimulation target and intensity were personalized for each subject to minimize artifacts and to ensure the presence of observable TMS responses.We calculated the ratio between peak-to-peak amplitudes of the first two TEP components between 10e50 ms.We observed a larger peakto-peak amplitude of the second component in 14 out of 20 MDD patients, but not in healthy controls.The peak-to-peak amplitude ratio of the second to the first component was significantly different between groups (p<0.001) and correlated with the Patient Health Questionnaire (PHQ-9) and the Quick Inventory of Depressive Symptomatology (QIDS) symptom scores with correlation coefficients of 0.58 and 0.56, respectively (p<0.05).The observed alteration of the relative size of the waveform complexes and its connection to the symptom severity might offer new insights into the neurophysiological basis of MDD.Further investigation on how the early TMSeEEG ratio is affected by different pharmacological treatments and whether this finding can be utilized to differentiate non-responders is needed.