Omega-3 supplementation improves cognition and modifies brain activation in young adults Isabelle Bauer 1 , Matthew Hughes 2 , Renee Rowsell 1 , Robyn Cockerell 1 , Andrew Pipingas 1 , Sheila Crewther 3 and David Crewther 1 * 1 Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, Australia 2 Brain and Psychological Sciences Research Centre, Swinburne University of Technology, Hawthorn, Australia 3 School of Psychological Sciences, La Trobe University, Bundoora, Australia Objective The current study aimed to investigate the effects of eicosapentaenoic acid (EPA)-rich and docosahexaenoic acid (DHA)-rich supplementations on cognitive performance and functional brain activation. Design A double-blind, counterbalanced, crossover design, with a 30-day washout period between two supplementation periods (EPA-rich and DHA-rich) was employed. Functional magnetic resonance imaging scans were obtained during performance of Stroop and Spatial Working Memory tasks prior to supplementation and after each 30-day supplementation period. Results Both supplementations resulted in reduced ratio of arachidonic acid to EPA levels. Following the EPA-rich supplementation, there was a reduction in functional activation in the left anterior cingulate cortex and an increase in activation in the right precentral gyrus coupled with a reduction in reaction times on the colour–word Stroop task. By contrast, the DHA-rich supplementation led to a significant increase in functional activation in the right precentral gyrus during the Stroop and Spatial Working Memory tasks, but there was no change in behavioural performance. Conclusions By extending the theory of neural efficiency to the within-subject neurocognitive effects of supplementation, we concluded that following the EPA-rich supplementation, participants’ brains worked ‘less hard’ and achieved a better cognitive performance than prior to supplementation. Conversely, the increase in functional activation and lack of improvement in time or accuracy of cognitive performance following DHA-rich supplementation may indicate that DHA-rich supplementation is less effective than EPA-rich supplementation in enhancing neurocognitive functioning after a 30-day supplementation period in the same group of individuals. Copyright © 2014 John Wiley & Sons, Ltd. key words—omega-3 fatty acid; fMRI; eicosapentaenoic acid; docosahexaenoic acid; arachidonic acid; Stroop task INTRODUCTION Although the beneficial effects of eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) on cardiovascular health (Psota et al., 2006), mood (Hibbeln, 2009) and neuroinflammation (Pascoe et al., 2011; Gillies et al., 2012) have often been reported in the literature, it is still unclear whether omega-3 fatty acids alter the cognitive functionality of the brain and whether the benefits, if any, are specific to a particular omega-3 fatty acid. This is particularly interesting as although both EPA and DHA cross brain membranes with equal ease, both brain and retinal DHA levels exceed EPA by several hundredfold (Arterburn et al., 2006). Chen has suggested that this extreme difference in brain concentrations may be be- cause EPA is more vulnerable than DHA to β-oxidation and degradation and hence less likely to be incorporated into membranes (as EPA) in the long term (Chen et al., 2009; Chen et al., 2011). The first functional magnetic resonance imaging (fMRI) study in the omega-3 fatty acid research field (Mcnamara et al., 2010b) revealed that an 8-week DHA supplementation led to an increase in functional activation in the dorsolateral prefrontal brain regions during a sustained visual attention task (a simple continuous performance task) compared with pre- supplementation in healthy children aged 8 to 10years. However, these cortical activation changes were not accompanied by a corresponding change in either accu- racy or reaction times comparing pre-supplementation and post-supplementation testing sessions, a finding supported by other DHA intervention studies using near-infrared spectroscopy (Dullemeijer et al., 2007; *Correspondence to: D. Crewther, Brain Sciences Institute, Centre for Human Psychopharmacology, Hawthorn 3122, Australia. Tel.: +613 9214 5877; Fax: +613 9214 5525 E-mail: dcrewther@swin.edu.au Revised 26 September 2013 Accepted 11 November 2013 Copyright © 2014 John Wiley & Sons, Ltd. human psychopharmacology Hum. Psychopharmacol Clin Exp (2014) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/hup.2379