title: Human ecstasy (MDMA) polydrug users have altered brain activation during semantic processing.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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 < 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 (r s = 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.
authors.affiliation: Vanderbilt Addiction Center, Vanderbilt University School of Medicine, Nashville, TN 37212, USA. tristan.j.watkins@vanderbilt.edu
authors.forename: Tristan J
authors.initials: TJ
authors.lastname: Watkins
authors.forename: Vidya
authors.initials: V
authors.lastname: Raj
authors.forename: Junghee
authors.initials: J
authors.lastname: Lee
authors.forename: Mary S
authors.initials: MS
authors.lastname: Dietrich
authors.forename: Aize
authors.initials: A
authors.lastname: Cao
authors.forename: Jennifer U
authors.initials: JU
authors.lastname: Blackford
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Salomon
authors.forename: Sohee
authors.initials: S
authors.lastname: Park
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Benningfield
authors.forename: Christina R
authors.initials: CR
authors.lastname: Di Iorio
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Cowan
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D013287:Illicit Drugs / Q000009:adverse effects*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000009:adverse effects*; D011446:Prospective Studies; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D012660:Semantics; D055815:Young Adult
chemical_list: D013287:Illicit Drugs; D018817:N-Methyl-3,4-methylenedioxyamphetamine