Involvement of Inferior Parietal Lobules in Prospective Memory Impairment During Acute MDMA (Ecstasy) Intoxication: An Event-Related fMRI Study

Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology (Impact Factor: 7.05). 06/2009; 34(7):1641-8. DOI: 10.1038/npp.2008.219
Source: PubMed


Prospective memory refers to the realization of delayed intentions. Several studies have shown that 3,4-methylenedioxy-methamphetamine (MDMA) users perform worse on measures of prospective memory as compared to nondrug users. Interpretation of these data may be limited because of polydrug use, psychosocial stressors, and increased psychopathology that have been reported in MDMA users. This study was designed to directly assess the pharmacological effect of MDMA on prospective memory and brain activity in a double-blind, placebo-controlled, cross-over study. Twelve recreational MDMA users received MDMA 75 mg and placebo and performed an objective prospective memory task during functional imaging. During prospective memory task performance subjects were engaged in a foreground task that consisted of a simple reaction time to visual stimuli (Go trials) and a prospective task of withholding a response during trials that were part of a dynamic memory set (No go trials). Behavioral data showed that a single dose of MDMA increased prospective memory failures in the No go trials, and that number of prospective memory failures was positively correlated to MDMA concentration in plasma. Functional imaging showed that MDMA decreased BOLD activation during Go trials in the thalamus (left), putamen (left), precuneus (left), and the inferior parietal lobules (bilateral), as compared to placebo. During No go trials, MDMA reduced BOLD deactivation in the inferior parietal lobules (bilateral), as compared to placebo. It is concluded that the loss of deactivation in inferior parietal lobules may account for increments in memory failures observed during MDMA intoxication.

Download full-text


Available from: Kim P. C. Kuypers, Jan 16, 2015
  • Source
    • "Prospective memory task ( PMT ) The PMT was developed to examine prospective memory performance ( Ramaekers et al . 2009b ) . The subjects were shown the letter A or B in the middle of a computer screen . Subjects were required to re - spond to each letter as quickly as possible by pressing one of two response buttons ( go trials ) . Letters were displayed for 3 s and the interval before displaying the following letter was 0 . 5 s . The test consisted of 2"
    [Show abstract] [Hide abstract]
    ABSTRACT: One of the most often reported cognitive deficits of acute cannabis administration is an impaired recall of previously learned information. The aim of the present study was to determine whether cannabis-induced memory impairment in humans is mediated via glutamatergic or cholinergic pathways. Fifteen occasional cannabis users participated in a double-blind, placebo-controlled, six-way cross-over study. On separate test days, subjects received combinations of pretreatment (placebo, vardenafil 20 mg or rivastigmine 3 mg) and treatment (placebo or 1,376 mg cannabis/kg body weight). Cognitive tests were administered immediately after inhalation of treatment was finished and included measures of memory (visual verbal learning task, prospective memory test, Sternberg memory test), perceptual-motor control (critical tracking task), attention (divided attention task) and motor impulsivity (stop signal task). The results of this study demonstrate that subjects under the influence of cannabis were impaired in all memory tasks, in critical tracking, divided attention and the stop signal task. Pretreatment with rivastigmine attenuated the effect of cannabis on delayed recall and showed a trend towards significance on immediate recall. When cannabis was given in combination with vardenafil, there were no significant interaction effects in any of the tasks. The present data therefore suggest that acetylcholine plays an important role in cannabis-induced memory impairment, whereas similar results for glutamate have not been demonstrated in this study.
    Psychopharmacology 07/2014; 232(2). DOI:10.1007/s00213-014-3667-2 · 3.88 Impact Factor
  • Source
    • "Four different lists of words are used for the different test days, which had been matched for abstraction. The Prospective Memory Task (PMT) is a newly developed paradigm (Ramaekers et al., 2009) to examine prospective memory performance in an event-based memory task. The foreground task consists of 240 successive presentations of a letter (A or B) in the centre of a computer screen. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have shown that single doses of MDMA can affect mood and impair memory in humans. The neuropharmacological mechanisms involved in MDMA-induced memory impairment are not clear. Memantine, an NMDA and alpha 7 nicotinic acetylcholine (ACh) receptor antagonist, was able to reverse MDMA-induced memory impairment in rats. This study investigated whether treatment with memantine can prevent MDMA-induced memory impairment in humans. 15 subjects participated in a double-blind, placebo controlled, within-subject design. Subjects received both pre-treatment (placebo/memantine 20 mg) (T1) and treatment (placebo/MDMA 75 mg) (T2) on separate test days. T1 preceded T2 by 120 minutes. Memory function was assessed 90 minutes after T2 by means of a visual verbal learning task, a prospective memory task, the Sternberg memory test and the abstract visual pattern learning task. Profile of Mood State (POMS) and psychomotor performance were also assessed to control whether MDMA and memantine interactions would selectively pertain to memory or transfer to other domains as well. MDMA significantly impaired performance in the visual verbal learning task and abstract visual pattern learning task. Pre-treatment with memantine did not prevent MDMA-induced memory impairment in these two tasks. Both positive (vigor, arousal, elation) and negative effects (anxiety) were increased by MDMA. The responses were not altered by pretreatment with memantine which had no effect on memory or mood when given alone. These preliminary results suggest that memantine does not reverse MDMA-induced memory impairment and mood in humans.
    Neuropharmacology 03/2014; 87. DOI:10.1016/j.neuropharm.2014.03.008 · 5.11 Impact Factor
  • Source
    • "The neurobiological mechanisms underlying these putative effects are, however, poorly understood. There have been a limited number of small-scale functional magnetic resonance imaging (fMRI) studies on the acute effects of MDMA (Bedi et al., 2009; Ramaekers et al., 2009; Kuypers et al., 2011) and only one that has overt implications for its therapeutic use: reduced amygdala responses to angry faces was observed under MDMA (Bedi et al., 2009), broadly consistent with reduced fear. The positive mood effects of MDMA appear to be mediated by stimulation of the "
    [Show abstract] [Hide abstract]
    ABSTRACT: 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine-releaser that is widely used as a recreational drug. Preliminary work has supported the potential of MDMA in psychotherapy for post-traumatic stress disorder (PTSD). The neurobiological mechanisms underlying its putative efficacy are, however, poorly understood. Psychotherapy for PTSD usually requires that patients revisit traumatic memories, and it has been argued that this is easier to do under MDMA. Functional magnetic resonance imaging (fMRI) was used to investigate the effect of MDMA on recollection of favourite and worst autobiographical memories (AMs). Nineteen participants (five females) with previous experience with MDMA performed a blocked AM recollection (AMR) paradigm after ingestion of 100 mg of MDMA-HCl or ascorbic acid (placebo) in a double-blind, repeated-measures design. Memory cues describing participants' AMs were read by them in the scanner. Favourite memories were rated as significantly more vivid, emotionally intense and positive after MDMA than placebo and worst memories were rated as less negative. Functional MRI data from 17 participants showed robust activations to AMs in regions known to be involved in AMR. There was also a significant effect of memory valence: hippocampal regions showed preferential activations to favourite memories and executive regions to worst memories. MDMA augmented activations to favourite memories in the bilateral fusiform gyrus and somatosensory cortex and attenuated activations to worst memories in the left anterior temporal cortex. These findings are consistent with a positive emotional-bias likely mediated by MDMA's pro-monoaminergic pharmacology.
    The International Journal of Neuropsychopharmacology 12/2013; 17(04):1-14. DOI:10.1017/S1461145713001405 · 4.01 Impact Factor
Show more