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Background and objective: Repetitive transcranial magnetic stimulation (rTMS) is a first-line treatment for treatment-resistant depression (TRD). The mechanisms of action of rTMS are not fully understood, and no biomarkers are available to assist in clinical practice to predict response to rTMS. This study aimed to demonstrate that after-rTMS clinical improvement is associated with functional connectivity (FC) changes of the subgenual cingulate cortex (sgACC) and rostral anterior cingulate (rACC), and FC of sgACC and rACC might serve as potential predictors for treatment response. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected within 1 week before rTMS initiation in 50 TRD patients to predict subsequent response to rTMS on the left dorsolateral prefrontal cortex (DLPFC). Follow-up rs-fMRI was obtained 12 weeks after completion of rTMS and neural correlates of rTMS in sgACC-and rACC-related FC patterns were compared to before rTMS data and with rs-fMRI from healthy participants. Results: Treatment response was associated with lower FC of sgACC to right DLPFC and higher FC of rACC to left lateral parietal cortex (IPL) measured at baseline. Using sgACC-DLPFC and rACC-IPL connectivity as features, responder-nonresponder classification accuracies of 84% and 76% (end-of-treatment), 88% and 81% (3-month follow-up), respectively were achieved. Longitudinal rs-fMRI data analyses revealed that the hyperconnectivity between sgACC and visual cortex was normalized to a level which was comparable to that of healthy participants. Conclusions: Brain activity patterns in depression are predictive of treatment response to rTMS, and longitudinal change of brain activity in relevant brain circuits after rTMS is associated with treatment response in depression. Target engagement paradigms may offer opportunities to increase the efficacy of rTMS in TRD by optimal selection of patients for treatment. Trial registration: ClinicalTrials.gov Identifiers: NCT01887782 and NCT02800226.

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BackgroundLearning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning.Methodology/Principal FindingsWe performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN.Conclusions/SignificanceThese results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning.

Numerous studies provide evidences that motor skill learning changes the activity of some brain regions during task as well as some resting networks during rest. However, it is still unclear how motor learning affects the resting-state default-mode network (DMN). Using functional magnetic resonance imaging, this study investigated the alteration of the DMN after motor skill learning with mental imagery practice. Fourteen participants in the experimental group learned to imagine a sequential finger movement over a two-week period while twelve control participants did not undergo motor imagery learning. For the experimental group, interregional connectivity, estimated by the graph theory method, between the medial temporal lobe, lateral temporal, and lateral parietal cortex within the DMN was increased after learning, whereas activity of the DMN network, estimated by the independent component analysis method, remained stable. Moreover, the experimental group showed significant improvement in motor performance after learning and a negative correlation between the alteration of the execution rate and changes in activity in the lateral parietal cortex. These results indicate that the DMN could be sculpted by motor learning in a manner of altering interregional connectivity and may imply that the DMN plays a role in improving behavioral performance.