2009). The CRS-R motor subscore was significantly and inversely correlated with a general absence/presence of brain activation in the pain network and with the number of activated regions. At first sight, this result is surprising, as one might have expected a positive correlation between brain activation in the pain matrix and the clinical reaction to noxious stimuli. However, absent motor reaction to

pain stimulation does not necessarily mean the absence Inhibitors,research,lifescience,medical of pain perception. Perception of pain, more precisely the sensory afference, and the visible motor reaction, thus the motor efference, are two different and independent pathways and can be impaired separately from each other. In fact, our findings emphasize that the clinical examination of UWS patients is difficult and might miss some patients who are actually more conscious than they seem (Childs et al. 1993; Andrews et al. 1996; Schnakers et al. 2009). This fact stresses the necessity Inhibitors,research,lifescience,medical for new methods, like functional imaging, to examine patients with disorders of consciousness objectively. Of course, diagnosis of consciousness remains a philosophical problem, not just a neurological one. An increase of brain activity in some brain areas Inhibitors,research,lifescience,medical cannot strongly prove the presence of subjective experience. However, given pain-related changes in such brain structures as anterior check details insula and ACC, which are related to emotional awareness and autonomic

regulation of pain (Vogt 2005), we find it risky to still argue that the respective patients are unable to feel pain. Note that among these were also chronic patients (several years after the incident) Inhibitors,research,lifescience,medical with a very severe hypoxic brain injury. Limitations By definition, subjective threshold of pain perception and pain tolerance cannot be obtained in UWS patients. Therefore, and primarily for ethical reasons, rather moderate noxious stimuli were applied in the present experiment. Inhibitors,research,lifescience,medical We cannot rule out that they were weaker than in the comparable PET studies, which would partially explain the differences in results. Moreover, to avoid long, uncomfortable, and exhausting transportation, the patients were examined at

two different imaging centers with different scanners. Although the results obtained with the 1.5 T and the 3 T scanners are not substantially different, a replication study in which all patients are measured with the same scanner is desirable. Furthermore, Boyle et al. (2006) either demonstrated that MRI scanner noise significantly reduces unpleasantness ratings of pain stimulation. Although healthy individuals evaluated the presented stimuli as highly arousing and rather unpleasant, it should be taken into account that the evaluations were done immediately outside MRI scan (i.e., without noise). The difference in the physical environment should, therefore, also be considered when discussing neuroimaging studies on human pain perception.