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


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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    ABSTRACT: Ecstasy is a widely used recreational drug that usually consists primarily of 3,4-methylenedioxymethamphetamine (MDMA). Most ecstasy users consume other substances as well, which complicates the interpretation of research in this field. The positively rated effects of MDMA consumption include euphoria, arousal, enhanced mood, increased sociability, and heightened perceptions; some common adverse reactions are nausea, headache, tachycardia, bruxism, and trismus. Lowering of mood is an aftereffect that is sometimes reported from 2 to 5 days after a session of ecstasy use. The acute effects of MDMA in ecstasy users have been attributed primarily to increased release and inhibited reuptake of serotonin (5-HT) and norepinephrine, along with possible release of the neuropeptide oxytocin. Repeated or high-dose MDMA/ecstasy use has been associated with tolerance, depressive symptomatology, and persisting cognitive deficits, particularly in memory tests. Animal studies have demonstrated that high doses of MDMA can lead to long-term decreases in forebrain 5-HT concentrations, tryptophan hydroxylase activity, serotonin transporter (SERT) expression, and visualization of axons immunoreactive for 5-HT or SERT. These neurotoxic effects may reflect either a drug-induced degeneration of serotonergic fibers or a long-lasting downregulation in 5-HT and SERT biosynthesis. Possible neurotoxicity in heavy ecstasy users has been revealed by neuroimaging studies showing reduced SERT binding and increased 5-HT2A receptor binding in several cortical and/or subcortical areas. MDMA overdose or use with certain other drugs can also cause severe morbidity and even death. Repeated use of MDMA may lead to dose escalation and the development of dependence, although such dependence is usually not as profound as is seen with many other drugs of abuse. MDMA/ecstasy-dependent patients are treated with standard addiction programs, since there are no specific programs for this substance and no proven medications. Finally, even though MDMA is listed as a Schedule I compound by the Drug Enforcement Agency, MDMA-assisted psychotherapy for patients with chronic, treatment-resistant posttraumatic stress disorder is currently under investigation. Initial results show efficacy for this treatment approach, although considerably more research must be performed to confirm such efficacy and to ensure that the benefits of MDMA-assisted therapy outweigh the risks to the patients.
    11/2013; 4:83-99. DOI:10.2147/SAR.S37258
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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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    ABSTRACT: Rationale Ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) polydrug users have verbal memory performance that is statistically significantly lower than that of control subjects. Studies have correlated long-term MDMA use with altered brain activation in regions that play a role in verbal memory. Objectives The aim of our study was to examine the association of lifetime ecstasy use with semantic memory performance and brain activation in ecstasy polydrug users. Methods A total of 23 abstinent ecstasy polydrug users (age = 24.57 years) and 11 controls (age = 22.36 years) performed a two-part functional magnetic resonance imaging (fMRI) semantic encoding and recognition task. To isolate brain regions activated during each semantic task, we created statistical activation maps in which brain activation was greater for word stimuli than for non-word stimuli (corrected p
    Psychopharmacology 12/2012; 227(1). DOI:10.1007/s00213-012-2936-1 · 3.88 Impact Factor
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    • "However, this issue of brain interconnectivity is relatively novel in the addiction literature. Only one recent fMRI study has examined brain functional connectivity during a finger tapping task in MDMA abusers [100] whereas in another fMRI study brain effective connectivity was examined while the healthy subjects were under the influence of pure compounds of cannabis sativa. Furthermore, only one previous PET study of opiate craving [61] and only one previous resting state fMRI study involving opioid dependent patients [101] have investigated this important issue of brain interconnectivity. "
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    07/2012; 2012(Suppl 7):003. DOI:10.4172/2161-0495.S7-003
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