Magnetic Seizure Therapy Produces Neuroplasticity in Treatment-Resistant Depression

Abstract

Therapeutic seizures may work for treatment-resistant depression (TRD) by producing neuroplasticity. We evaluated whether magnetic seizure therapy (MST) produces neuroplasticity as indexed through transcranial magnetic stimulation and electroencephalography (TMS-EEG) of the dorsolateral prefrontal cortex (DLPFC). Twenty-three patients with TRD were treated with MST. Before and after the treatment course, neuroplasticity in excitatory and inhibitory circuits was assessed with TMS-EEG measures of cortical evoked activity (CEA) and long interval cortical inhibition (LICI) from the left DLPFC, and the left motor cortex as a control condition. As in our previous report, the relationship between TMS-EEG measures and suicidal ideation was examined with the SSI. Based on DLPFC assessment, MST produced significant CEA increase over the frontal central electrodes (cluster p<0.05), but did not change LICI on a group level. MST also reduced the SSI scores (p<0.005) and the amount of reduction correlated with the decrease in LICI over the right frontal central electrodes (cluster p<0.05; rho=0.73 for Cz). LICI change identified patients who were resolved of suicidal ideation with 90% sensitivity and 88% specificity (AUC=0.9, p=0.004). There was no significant finding with motor cortex assessment. Overall, MST produced neuroplasticity in the frontal cortex, likely through long-term potentiation (LTP)-like mechanisms. The largest reduction in suicidal ideation was demonstrated in patients showing concomitant decreases in cortical inhibition – a mechanism linked to enhanced LTP-like plasticity. These findings provide insights into the mechanisms through which patients experience resolution of suicidal ideation following seizure treatments in depression. Additional neurophysiological mechanisms of potential MST efficacy will also be discussed.