Efficacy and safety of selective serotonin reuptake inhibitors for diabetes mellitus with depression: a systematic review and meta-analysis.

It is standard practice, in both sleep and anesthesia research as well as in the clinical anesthetic setting,, to assess the depth of sleep or anesthesia by presenting a sensory stimulus and observing the behavioral response. In humans, this may go from verbally asking the patient to open their eyes or calling their name, through gentle shaking, all the way to applying a painful surgery-like stimulus (eg, skin pinch pre-incision). In rodents, it often involves turning them on their back to assess for righting reflex,,, through to more painful tail/paw pinches. Furthermore, even technologies used to assess consciousness without stimulation and observing responses, eg exhaled gas analysis, EEG, entropy, SEF-95% and BIS, typically calibrate these against gold-standard behavioral tests. However, an implicit assumption is often made when performing these tests, that the behavioral response observed after testing reflects the state prior to the test, when it is possible, and even likely, that the test itself changes the state of the subject. In a loose analogy to quantum physics, we coined the term “Schrödinger’s Rat” to describe this effect. This effect extends beyond rats; non-invasive evidence in humans has shown that scalp EEGs resemble a more awake state following painful stimuli. Furthermore, it is acknowledged that more active tasks during behavioral testing may mask reduced levels of consciousness/sleepiness owing to their stimulating effect. In this manuscript, we test the extent to which cortical neurons modulate their spiking activity due to behavioral testing employing external sensory stimuli, which may or may not occur simultaneously with behavioral awakening of the rat itself.