I'm just asking the question - I don't have an answer Most studies purporting to study PEM use various forms of physical exercise yet we know that mental exertion can also cause PEM. Whether its the same PEM is debateable but I know that I get the same painful and heavy limbs following mental exertion and conversely physical exertion causes cognitive problems as well as the expected physical ones. To provoke a reaction (PEM) physical and mental exertion must be producing a signal of some description (an effector?) but which signal would they have in common? Vigorous exercise causes microlesions in muscle tissue prompting the production of heat shock proteins that chaperone cellular repair mechanisms. The Lights' work shows increased expression of pathways signalling fatigue and pain following physical exercise. With mental exertion we can easily rule out microlesions and its unlikely that pain signalling would be involved (even if subjectively thinking makes your head ache). 'Fatigue signals' are a possibility but its not clear that the same pathways might signal muscle fatigue and neural fatigue. Both activities of course require energy but as the interesting Scientific American article below discusses, the brain actually consumes a large amount of energy in its 'resting' state and difficult tasks don't really significantly affect that : http://www.scientificamerican.com/article/thinking-hard-calories/ Both activities may also be perceived as stressful but again from personal experience an enjoyable non physical activity can wipe me out as easily as an unpleasant one. As I said I don't have the answer but I think its a question worth asking.