Overnight memory consolidation and neurocognition in ecstasy users

2017-02-16T04:13:51Z (GMT) by Smithies, Vanessa Gwendoline
A wide body of animal and human research suggests that MDMA/ecstasy use is associated with lasting serotonergic neurotoxicity, particularly in mediotemporal and frontostriatal brain regions (Benningfield, 2013; Green, Mechan, Elliott, O'Shea, & Colado, 2003). Serotonin is important for a wide range of neurocognitive and psychobiological processes, and therefore neurotoxicity in these regions may have significant functional implications for ecstasy users. The objective of this thesis was to examine the neurocognitive and psychobiological effects of ecstasy that may be associated with serotonergic damage to mediotemporal and frontostriatal regions. Specifically, we examined this using an overnight memory consolidation paradigm. Overnight memory consolidation refers to the process of memory enhancement and increased resistance to interference that occurs across an episode of sleep, relative to a similar time-frame of wakefulness (Stickgold & Walker, 2013). The consolidation of declarative material in healthy participants is associated with prefrontal slow wave activity normally observed during deep sleep (Mander et al., 2013). The findings outlined above of serotonergic dysfunction in frontostriatal regions, coupled with evidence that ecstasy users have disrupted sleep architecture (Ogeil, Rajaratnam, & Broadbear, 2012) led us to hypothesise that ecstasy users will show impairments in the overnight consolidation of memory. We examined this hypothesis in two overnight consolidation studies. The first explored the overnight consolidation of emotional material using a visual recognition task delivered in an online environment. We found that compared to drug-naïve controls (N=16), ecstasy users (N=15) tested after a period of sleep had stronger memory for negative visual images relative to neutral visual images. We suggest that this is due to a negative attribution bias, whereby material with negative content is preferentially consolidated and better recalled relative to material with neutral or positive content. The second overnight consolidation study utilised a verbal memory task to explore overnight memory consolidation in a laboratory setting. The task assessed whether sleep protects against interference from similar material, a phenomenon that has been confirmed in several studies among drug-naïve controls (e.g. Ellenbogen, Hulbert, Jiang, & Stickgold, 2009). The results indicated that ecstasy users (N=12) did not show the same resistance to interference that was conferred to control participants (N=13) by overnight consolidation processes. Furthermore, our objective measurement of sleep architecture indicated that ecstasy users spent less time in deep sleep relative to controls, indicating that less time was spent in sleep stages that are known to be important for overnight memory consolidation. Together, this data suggests that ecstasy users experience dysfunctional sleep leading to impaired overnight memory consolidation. Finally, additional functional implications of disrupted mediotemporal and frontostriatal circuitry were examined using neurocognitive tasks that recruit these regions. Consistent with past research, we found reduced performance in a (same day) declarative long term memory task in ecstasy users. We also found that ecstasy users were selectively impaired on tasks of encoding, proactive interference memory, updating of working memory and complex planning, and therefore propose that executive functioning tasks engaging a higher cognitive load might reveal more subtle neurocognitive impairments experienced by ecstasy users. This thesis highlights the presence of selective neurocognitive executive dysfunction among ecstasy users. Furthermore, this thesis provides a unique contribution to the literature by demonstrating the key role of disrupted overnight consolidation processes in subsequent dysfunctional memory recall.