The effect of Modafinil on behavioural and ERP measures of attention and associated sex differences

Modafinil is a wakefulness-promoting drug that is becoming more commonly used for off-label for attentional enhancement in healthy individuals despite conflicting evidence to support this. The aim of the current study was to investigate the effects of modafinil on behavioural (reaction time & accuracy) and ERP (N1 amplitude) measures of the attentional alerting and orienting networks and also investigate any sex differences associated with these effects. The final sample consisted of 14 females and 22 males who were all healthy and met the screening criteria. Each participant completed two sessions differing by drug condition (200mg modafinil or placebo). The Attentional Network Task was used to assess the effects on both the alerting and orienting network and this task was completed at baseline and at 2.5 hours post-ingestion. As expected, reaction time decreased and N1 amplitude increased as cues became more informative. There was a small enhancement of the alerting network demonstrated by a significant decrease in reaction time from baseline to post-ingestion for central cues in the modafinil condition but not placebo. There was a small significant decrease in reaction time from baseline to post-ingestion for spatial cues but this is likely due to alerting enhancement rather than orienting as the effects were of similar size. Inconsistent to the hypotheses, males had a faster reaction time to all cue types when compared to females. Males also showed greater N1 amplitude after modafinil ingestion than placebo, indicating some sex differences in the effect of modafinil may be present. These results suggest that modafinil may have an enhancing effect on the alerting network but not the orienting network. The effects of modafinil on the orienting network has not been well studied so future research is required to confirm this finding. There also appears to be differential effects of modafinil on males and females, which also requires future investigation as this is the first study to look at these effects. Modafinil is a schedule IV drug labelled as a psychostimulant for its wakefulness promoting properties (Minzenburg & Carter, 2008). It is most commonly used to treat excessive daytime sleepiness in narcolepsy, shift work disorder and obstructive sleep apnoea. However, it is becoming more commonly used off-label for a variety of other conditions including attention-deficit/hyperactivity disorder (ADHD) and depression. Modafinil has also been evaluated for cognitive enhancement (including attention) in healthy individuals. Petersen and Posner (2012) suggest three main networks of attention, alerting, orienting and executive control. Findings into the effects of modafinil on these networks have been inconsistent. When methodological issues are accounted for (task complexity), there are consistent findings of alerting network enhancement after modafinil ingestion, but only for complex task paradigms (Battleday & Brem, 2015). The orienting network has not been extensively studied, with only one study using a task that could analyse orienting (Ikeda, Funayama, Tateno, Fukayama, Okubo, & Suzuki, 2017). This study did not find any orienting enhancement after modafinil ingestion, but further research is required into the effect of modafinil on this network. Similarly to the alerting network, research suggests that more complex task paradigms (including inhibitory control processes) are required to detect enhancement after modafinil in executive control components of attention (Battleday & Brem, 2015). There is evidence that males and females differ in the attentional networks. Specifically, females appear to be better at orienting their attention (orienting network) and responding to valid cues while males show less costs to invalid cues (Liu, Hu, Fan, Wang, 2013; Merritt, Hirshman, Wharton, Stangl, Devlin & Lenz, 2007. With regards to Event-Related Potential (ERP) indices of attentional processes, females have shown greater N1 amplitude while completing orienting based tasks than males. However, no study is yet to investigate the differing effects of modafinil on males and females attentional processing. Most studies examining the effects of modafinil have recruited exclusively male participants, while studies that do incorporate females have failed to analyse for any sex differences. Therefore, this study aims to investigate the effects of modafinil on both males and females attention, by using an attentional network task to specifically assess Petersen and Posner (2012)’s alerting and orienting networks.