MDMA (Ecstasy) association with impaired fMRI BOLD thalamic coherence and functional connectivity

Background: MDMA exposure is associated with chronic serotonergic dysfunction in preclinical and clinical studies. A recent functional magnetic resonance imaging (fMRI) comparison of past MDMA users to non-MDMA-using controls revealed increased spatial extent and amplitude of activation in the supplementary motor area during motor tasks (Karageorgiou et al., 2009). Blood oxygenation level dependent (BOLD) data from that study were reanalyzed for intraregional coherence and for inter-regional temporal correlations between time series, as functional connectivity. Methods: Fourteen MDMA users and ten controls reporting similar non-MDMA abuse performed finger taps during fMRI. Fourteen motor pathway regions plus a pontine raphé region were examined. Coherence was expressed as percent of voxels positively correlated with an intraregional index voxel. Functional connectivity was determined using wavelet correlations. Results: Intraregional thalamic coherence was significantly diminished at low frequencies in MDMA users compared to controls (p = 0.009). Inter-regional functional connectivity was significantly weaker for right thalamo - left caudate (p = 0.002), right thalamo - left thalamus (p = 0.007), right caudate - right postcentral (p = 0.007) and right supplementary motor area - right precentral gyrus (p = 0.011) region pairs compared to controls. When stratified by lifetime exposure, significant negative associations were observed between cumulative MDMA use and functional connectivity in seven other region-pairs, while only one region-pair showed a positive association. Conclusions: Reported prior MDMA use was associated with deficits in BOLD intraregional coherence and inter-regional functional connectivity, even among functionally robust pathways involving motor regions. This suggests that MDMA use is associated with long-lasting effects on brain neurophysiology beyond the cognitive domain.