EEG functional connectivity is a weak predictor of causal brain interactions

In recent years there has been an explosion of research evaluating resting-state brain functional connectivity (FC) using different modalities. However, the relationship between such measures of FC and the underlying causal brain interactions has not been well characterized. To further characterize this relationship, we assessed the relationship between electroencephalography (EEG) resting state FC and propagation of transcranial magnetic stimulation (TMS) evoked potentials (TEPs) at the sensor and source level in healthy participants. TMS was applied to six different cortical regions in ten healthy individuals (9 male; 1 female), and effects on brain activity were measured using simultaneous EEG. Pre-stimulus FC was assessed using five different FC measures (Pearson’s correlation, mutual information, weighted phase lag index, coherence and phase locking value). Propagation of the TEPs was quantified as the root mean square (RMS) of the TEP voltage and current source density (CSD) at the sensor and source level, respectively. The relationship between pre-stimulus FC and the spatial distribution of TEP activity was determined using a generalized linear model (GLM) analysis. On the group level, all FC measures correlated significantly with TEP activity over the early (15–75 ms) and full range (15–400 ms) of the TEP at the sensor and source level. However, the predictive value of all FC measures is quite limited, accounting for less than 10% of the variance of TEP activity, and varies substantially across participants and stimulation sites. Taken together, these results suggest that EEG functional connectivity studies in sensor and source space should be interpreted with caution

Indirect frontocingulate structural connectivity predicts clinical response to accelerated rTMS in major depressive disorder

Background: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD), but its clinical efficacy remains rather modest. One reason for this could be that the propagation of rTMS effects via structural connections from the stimulated area to deeper brain structures (such as the cingulate cortices) is suboptimal. Methods: We investigated whether structural connectivity - derived from diffusion MRI data - could serve as a biomarker to predict treatment response. We hypothesized that stronger structural connections between the patient-specific stimulation position in the left dorsolateral prefrontal cortex (dlPFC) and the cingulate cortices would predict better clinical outcomes. We applied accelerated intermittent theta burst stimulation (aiTBS) to the left dlPFC in 40 patients with MDD. We correlated baseline structural connectivity, quantified using various metrics (fractional anisotropy, mean diffusivity, tract density, tract volume and number of tracts), with changes in depression severity scores after aiTBS. Results: Exploratory results (p < 0.05) showed that structural connectivity between the patient-specific stimulation site and the caudal and posterior parts of the cingulate cortex had predictive potential for clinical response to aiTBS. Limitations: We used the diffusion tensor to perform tractography. A main limitation was that multiple fibre directions within voxels could not be resolved, which might have led to missing connections in some patients. Conclusion: Stronger structural frontocingular connections may be of essence to optimally benefit from left dlPFC rTMS treatment in MDD. Even though the results are promising, further investigation with larger numbers of patients, more advanced tractography algorithms and classic daily rTMS treatment paradigms is warranted

Neural and behavioral effects of theta burst stimulation priming on processing of affective and neutral information in working memory

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