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Intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex is effective for treatment-resistant depression, but the effects of iTBS on neurophysiological markers remain unclear. Here, we indexed transcranial magnetic stimulation–electroencephalography (TMS-EEG) markers, specifically, the N45 and N100 amplitudes, at baseline and post-iTBS, comparing separated and contiguous iTBS schedules. TMS-EEG markers were also compared between iTBS responders and nonresponders. TMS-EEG was analyzed from a triple-blind 1:1 randomized trial for treatment-resistant depression, comparing a separated (54-minute interval) and contiguous (0-minute interval) schedule of 2 × 600-pulse iTBS for 30 treatments. Participants underwent TMS-EEG over the left dorsolateral prefrontal cortex at baseline and posttreatment. One hundred fourteen participants had usable TMS-EEG at baseline, and 98 at posttreatment. TMS-evoked potential components (N45, N100) were examined via global mean field analysis. The N100 amplitude decreased from baseline to posttreatment, regardless of the treatment group (F 1,106 = 5.20, p =.02). There were no changes in N45 amplitude in either treatment group. In responders, the N100 amplitude decreased after iTBS (F 1,102 = 11.30, p =.001, p corrected =.0004). Responders showed higher posttreatment N45 amplitude than nonresponders (F 1,94 = 4.11, p =.045, p corrected =.016). Higher baseline N100 amplitude predicted lower post-iTBS depression scores (F 4,106 = 6.28, p =.00014). These results provide further evidence for an association between the neurophysiological effects of iTBS and treatment efficacy in treatment-resistant depression. Future studies are needed to test the predictive potential for clinical applications of TMS-EEG markers. [ABSTRACT FROM AUTHOR]

Background: Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) is emerging as a powerful technique for interrogating neural circuit dysfunction in psychiatric disorders. Here, we utilized time-frequency analyses to characterize differences in neural oscillatory dynamics between subjects with major depressive disorder (MDD) and healthy controls (HC). We further examined changes in TMS-related oscillatory power following convulsive therapy.Methods: Oscillatory power was examined following TMS over the dorsolateral prefrontal and motor cortices (DLPFC and M1) in 38 MDD subjects, and 22 HCs. We further investigated how these responses changed in the MDD group following an acute course of convulsive therapy (either magnetic seizure therapy [MST, n = 24] or electroconvulsive therapy [ECT, n = 14]).Results: Prior to treatment, MDD subjects exhibited increased oscillatory power within delta, theta, and alpha frequency bands with TMS-EEG over the DLPFC, but showed no differences to HCs with stimulation over M1. Following MST, DLPFC stimulation revealed attenuated baseline-normalized power in the delta and theta bands, with reductions in the delta, theta, and alpha power following ECT. TMS over M1 revealed reduced delta and theta power following ECT, with no changes observed following MST. An association was also observed between the treatment- induced change in alpha power and depression severity score.Limitations: Limitations include the modest sample size, open-label MST and ECT treatment designs, and lack of a placebo condition.Conclusions: These results provide evidence of alterations in TMS-related oscillatory activity in MDD, and further suggest modulation of oscillatory power following ECT and MST. [ABSTRACT FROM AUTHOR]

An overly negative self-schema is a proposed cognitive mechanism of major depressive disorder (MDD). Self-schema − one’s core conception of self, including how strongly one believes one possesses various characteristics − is part of semantic memory (SM), our knowledge about concepts and their relationships. We used the N400 event-related potential (ERP) − elicited by meaningful stimuli, and reduced by greater association of the stimulus with preceding context − to measure association strength between self-concept and positive, negative, and neutral characteristics in SM. ERPs were recorded from MDD patients ( n = 16) and controls ( n = 16) who viewed trials comprising a self-referential phrase followed by a positive, negative, or neutral adjective. Participants’ task was to indicate via button-press whether or not they felt each adjective described themselves. Controls endorsed more positive adjectives than did MDD patients, but the opposite was true for negative adjectives. Patients had smaller N400s than controls specifically for negative adjectives, suggesting that MDD is associated with stronger than normal functional neural links between self-concept and negative characteristics in SM. [ABSTRACT FROM AUTHOR]

Magnetic seizure therapy (MST) is emerging as a safe and well-tolerated experimental intervention for major depressive disorder (MDD), with very minimal cognitive side-effects. However, the underlying mechanism of action of MST remains uncertain. Here, we used resting-state electroencephalography (RS-EEG) to characterise the physiological effects of MST for treatment resistant MDD. We recorded RS-EEG in 21 patients before and after an open label trial of MST applied over the prefrontal cortex using a bilateral twin coil. RS-EEG was analysed for changes in functional connectivity, network topology, and spectral power. We also ran further baseline comparisons between the MDD patients and a cohort of healthy controls (n = 22). Network-based connectivity analysis revealed a functional subnetwork of significantly increased theta connectivity spanning frontal and parieto-occipital channels following MST. The change in theta connectivity was further found to predict clinical response to treatment. An additional widespread subnetwork of reduced beta connectivity was also elucidated. Graph-based topological analyses showed an increase in functional network segregation and reduction in integration in the theta band, with a decline in segregation in the beta band. Finally, delta and theta power were significantly elevated following treatment, while gamma power declined. No baseline differences between MDD patients and healthy subjects were observed. These results highlight widespread changes in resting-state brain dynamics following a course of MST in MDD patients, with changes in theta connectivity providing a potential physiological marker of treatment response. Future prospective studies are required to confirm these initial findings. • We utilised rest EEG to characterise physiological changes following MST in MDD. • MST significantly altered functional connectivity, network topology, and spectral power. • Changes in theta connectivity predicted clinical response to MST. • Rest EEG is a sensitive marker of neural response to MST. [ABSTRACT FROM AUTHOR]