The effects of methylphenidate and propranolol on the interplay between induced-anxiety and working memory

Abstract

Rationale Research documents a reciprocal impact of anxiety on working memory (WM), although its strength and direction depend on factors like task difficulty. A better understanding of these factors may generate insights into cognitive mechanisms of action involved in anxiety, culminating into treatment implications. By blocking the physiological effects of anxiety, propranolol might also block anxiety interference on WM. Conversely, by improving task-directed attention, methylphenidate might reduce anxiety, or, alternatively, by improving cognitive efficiency and free up processing resources to compute anxiety. Objectives To investigate the interplay between induced anxiety and WM, we pharmacologically manipulated either anxiety or cognition, using single doses of 40 mg propranolol (PRO), 20 mg methylphenidate (MPH), or placebo (PLA). In this double-blind parallel-group design study, 60 healthy volunteers (20/drug group) performed a verbal WM task under three loads, 1-, 2- and 3-back, and in two conditions, threat of shock and safety. Startle electromyography (EMG) was used to measure anxiety. Results Findings were twofold: (1) MPH blocked anxiety interference only on the 3-back WM performance, while PRO or PLA had no effects on anxiety-WM interference, and (2) drugs had no effects on anxiety, but, after controlling for baseline anxiety, MPH enhanced anxiety-potentiated startle during the 3-back task. Conclusions These findings support that MPH-related improvement of cognitive efficiency permits anxiety to be processed and expressed. In conclusion, MPH may be a useful tool to investigate the mechanisms of interaction between anxiety and WM, particularly those under catecholaminergic control.

Exercise modulates the interaction between cognition and anxiety in humans

“…Finally, this study design did not include a noactivity control. For example, contrary to expectations (Ernst et al, 2016; Shackman et al, 2006; Vytal et al, 2012), the threat did not impair WM (accuracy or RT) in the control-activity. This result may be due to effects of light intensity activity, but without a no-activity control, this hypothesis cannot be tested.…”

“…Prior data from our lab (Ernst et al, 2016; Vytal et al, 2012) indicated an expected moderate effect size for startle potentiation (Cohen’s d = 0.45). A priori calculations indicated that testing of 36 participants at an alpha of 0.05 would provide the power of 0.95 to detect a significant 2 (Activity) × 2 (Load) interaction on startle.…”

“…This interpretation is reminiscent of the effects of methylphenidate on the same experimental design (Ernst et al, 2016). In this study, researchers used methylphenidate, a cognitive enhancer (Husain & Mehta, 2011), to probe the relationship between cognition and anxiety.…”

“…Second, exercise can improve attention control. Regarding the former, the relationship between cognition and anxiety has been studied extensively (Ernst, Lago, Davis, & Grillon, 2016; Shackman et al, 2006; Vytal, Cornwell, Arkin, & Grillon, 2012). Several studies show that increase in WM-load decreases anxiety (Clarke & Johnstone, 2013; Patel, Stoodley, Pine, Grillon, & Ernst, 2017; Vytal et al, 2012).…”

Patients with anxiety disorders rely on bilateral dlPFC activation during verbal working memory

“…This suggests that threat impairs WM manipulation processes in the dlPFC. Indeed, there have been a number of studies investigating the effect of threat on WM, primarily using the n -back WM task ( Vytal et al , 2012 2013 ; Clarke and Johnstone, 2013 ; Patel et al , 2016 ; Ernst et al , 2016 ). The major findings from these studies are that (i) threat reduces accuracy, especially on low-load WM trials ( Vytal et al , 2012 2013 ; Patel et al , 2016 ) and (ii) threat reduces overall dlPFC processing ( Clarke and Johnstone, 2013 ).…”