Human ecstasy (MDMA) polydrug users have altered brain activation during semantic processing

Abstract

Rationale Ecstasy (MDMA) polydrug users have verbal memory performance that is statistically significantly lower than comparison 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 23 abstinent ecstasy polydrug users (age=24.57) and 11 controls (age=22.36) performed a two-part 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<0.05). Results During the encoding phase, ecstasy polydrug users had greater activation during semantic encoding bilaterally in language processing regions, including Brodmann Areas 7, 39, and 40. Of this bilateral activation, signal intensity with a peak T in the right superior parietal lobe was correlated with lifetime ecstasy use (rs=0.43, p=0.042). Behavioral performance did not differ between groups. Conclusions These findings demonstrate that ecstasy polydrug users have increased brain activation during semantic processing. This increase in brain activation in the absence of behavioral deficits suggests that ecstasy polydrug users have reduced cortical efficiency during semantic encoding, possibly secondary to MDMA-induced 5-HT neurotoxicity. Although pre-existing differences cannot be ruled out, this suggests the possibility of a compensatory mechanism allowing ecstasy polydrug users to perform equivalently to controls, providing additional support for an association of altered cerebral neurophysiology with MDMA exposure.

Polysubstance use

“…Other studies have shown dose-dependent associations between MDMA and brain activity in the parahippocampal gyrus and superior parietal lobule during memory encoding but not retrieval [54,55]. However, these studies, and other recent investigations of inhibitory control [56] and decision-making [57], find no difference in behavioural performance between polysubstance abusers and controls.…”

“…reflecting the engagement of compensatory processes to achieve equivalent performance [56,55]. It is also possible that neuropsychological tasks adapted and simplified for the scanner lack sensitivity or that neuroimaging studies lack sufficient sample sizes for adequate statistical power [60].…”

Verbal Memory Impairment in Polydrug Ecstasy Users: A Clinical Perspective

“…Furthermore, inclusion of tasks of different complexity and brain imaging measures could provide a more detailed picture on the potential impairing effect of chronic Ecstasy use. It has been shown that behavioral measures can be less sensitive than imaging measures in that aberrant functional patterns are shown in the absence of behavioral effects (e.g., [ 20 , 21 ]). However, with regard to the behavioral measure (verbal memory) used in the present study it is interesting to note that at least in healthy older adults, performance in immediate verbal memory was the best predictor for activities of daily living [ 38 ].…”

The functional connectome of 3,4‐methyldioxymethamphetamine‐related declarative memory impairments

“…Semantic encoding was associated with greater activity in somatosensory areas, the supramarginal gyrus, and the angular gyrus (Watkins et al, 2013) (see (Roberts et al, 2018) for recent review). To date, however, resting-state functional connectivity (FC) has not been examined in chronic MDMA users before.…”