Large-scale EEG neural network changes in response to therapeutic TMS.

BACKGROUND: Transcranial magnetic stimulation (TMS) is an effective therapy for patients with treatment-resistant depression. TMS likely induces functional connectivity changes in aberrant circuits implicated in depression. Electroencephalography (EEG) "microstates" are topographies hypothesized to represent large-scale resting networks. Canonical microstates have recently been proposed as markers for major depressive disorder (MDD), but it is not known if or how they change following TMS. METHODS: Resting EEG was obtained from 49 MDD patients at baseline and following six weeks of daily TMS. Polarity-insensitive modified k-means clustering was used to segment EEGs into constituent microstates. Microstates were localized via sLORETA. Repeated-measures mixed models tested for within-subject differences over time and t-tests compared microstate features between TMS responder and non-responder groups. RESULTS: Six microstates (MS-1 - MS-6) were identified from all available EEG data. Clinical response to TMS was associated with increases in features of MS-2, along with decreased metrics of MS-3. Nonresponders showed no significant changes in any microstate. Change in occurrence and coverage of both MS-2 (increased) and MS-3 (decreased) correlated with symptom change magnitude over the course of TMS treatment. CONCLUSIONS: We identified EEG microstates associated with clinical improvement following a course of TMS therapy. Results suggest selective modulation of resting networks observable by EEG, which is inexpensive and easily acquired in the clinic setting.

Audio-Guided Mindfulness Meditation During Transcranial Magnetic Stimulation Sessions for the Treatment of Major Depressive Disorder: A Pilot Feasibility Study.

Background: Mindfulness-Based Cognitive Therapy (MBCT) has been shown to enhance the long-term treatment outcomes for major depressive disorder (MDD), and engagement of specific brain activities during brain stimulation may produce synergistic effects. Audio-guided meditation exercises are a component of MBCT that might be combined with standard transcranial magnetic stimulation (TMS) therapy sessions. We developed and pilot-tested a modified MBCT protocol for patients undergoing a standard course of TMS for MDD. Methods: Four MBCT audiotracks with differing durations and types of mental focus were selected. Patients listened to the audiotapes through headphones during daily TMS sessions for 5 consecutive weeks. The primary goal was to evaluate the feasibility and acceptability of the meditation intervention with TMS. Changes in self-rated measures of symptom severity, stress, life satisfaction, and mindfulness were also assessed. Results: Seventeen depressed subjects completed the study and 12 terminated early. Reasons for discontinuation included an inability to meditate in the treatment setting and induction of negative mood states. TMS percussive sensations and clicking sounds hindered the ability of patients to fully concentrate on or hear the voice of the audiotape narrator. Some became overwhelmed or felt increased pressure, anxiety, or aggravation trying to do meditation exercises while receiving TMS. Conclusion: There is a growing interest in combining TMS with other concurrent psychotherapeutic interventions to optimize treatment outcomes. The results highlight numerous feasibility issues with MBCT via guided audiotapes during TMS treatment. Future work should draw on these shortcomings to evaluate the appropriateness of MBCT for depressed patients undergoing neuromodulation.