Article

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

Psychiatric Neuroimaging Program, Vanderbilt University School of Medicine, Nashville, TN 37212, USA.
Drug and alcohol dependence (Impact Factor: 3.42). 07/2011; 120(1-3):41-7. DOI: 10.1016/j.drugalcdep.2011.06.022
Source: PubMed

ABSTRACT

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.
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.
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.
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.

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    • "The use of structural and functional MRI, DTI, and MRS has revealed additional differences between ecstasy users and control subjects under some conditions. Although the results of this work cannot be detailed here due to space limitations, interested readers are referred to the appropriate references.106,107,109,110,114–117 "
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    • "The MDMA users had already shown greater activations in motor pathway regions during finger tapping, possibly due to loss of 5HT- mediated cortical inhibition. In the reanalysis, prior MDMA-use was associated with diminished intra-thalamic coherence, and also with diminished thalamo-cortical functional connectivity (Salomon et al., 2012b). Clinically, this may be important since abnormal thalamo-cortical connectivity in BOLD fMRI has been previously demonstrated in a variety of psychiatric pathologies, including autism (Mizuno et al. 2006, Villalobos et al 2005). "
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    • "We have previously reported stronger MDMA-associated effects observed in the right hemisphere as compared to the left hemisphere (Di Iorio et al. 2011), suggesting that if MDMA is responsible for lasting neurophysiological effects, the right hemisphere may be more susceptible. The current results are consistent with our earlier cross-sectional findings that lifetime ecstasy use is associated with greater task-evoked activation during simple motor (Karageorgiou et al. 2009) and visual tasks (Bauernfeind et al. 2011; Cowan et al. 2006), and with altered functional connectivity (Salomon et al. 2012). However, given the cross-sectional nature of the current study, the potential for both pre-existing differences in the control and ecstasy polydrug user groups, and the unknown effects of higher polydrug use levels in the ecstasy cohort, considerations of the potential links between our findings and altered 5-HT function are speculative. "
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