All Is Relative—A Call for Considering “Physiologically Informed” Control Conditions to Improve the Mechanistic Understanding of the Effects of Physical Exercise on Cognition

There is a growing interest in elucidating the mechanisms that drive the benefits of physical exercise on cognitive performance. A key element for a better understanding of a particular phenomenon (e.g., the mediators of the exercise-cognition interaction) is the selection of an appropriate control condition/group as the basis for causal inference. In contemporary practice, control conditions/groups used in exercise-cognition research can be broadly categorized as related to (i) study design, (ii) level of energy expenditure, and (iii) level of cognitive engagement. Although such control conditions are valuable for reducing the effects of specific sources of bias (e.g., time or placebo effects), their potential to advance our mechanistic understanding is limited. To address this research gap, the present article proposes and discusses the application of "physiologically informed" control conditions by narratively summarizing the current evidence concerning "physiologically informed" control conditions in acute exercise-cognition studies, wherein specific physical exercise-induced physiological responses (e.g., increases in cerebral blood flow or peripheral blood lactate concentration) are mimicked by nonexercise experimental manipulations (e.g., through inhaling hypercapnic gas mixture or infusion of lactate at rest). Based on our narrative evidence synthesis, we discuss how "physiologically informed" control conditions can serve as a valuable approach to strengthen causal interferences by allowing for a better isolation of cognitive benefits that can be "solely" attributed to specific physical exercise-induced physiological changes. As applying "physiologically informed" control conditions can advance knowledge generation on the physiological mechanisms that drive the positive effects of physical exercise on cognition, we advocate for a more widespread use of these control conditions in future research practice.