INTEGRATING PAIN · Cortical integration and interaction of nociceptive inputs

Final Activity Report Summary - INTEGRATING PAIN (Cortical integration and interaction of nociceptive inputs)

Functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) are the most widely-used non-invasive techniques to sample brain activity, and consequently explore brain function in humans. fMRI measures neural activity indirectly, by detecting local changes in cerebral blood flow that are known to follow neural activity. EEG measures neural activity directly, by detecting transient changes in scalp electrical potentials resulting from synchronous electro-cortical activity. fMRI has a low temporal resolution (it integrates changes in neural activity over several seconds), but allows to explore brain function with a high spatial resolution (in the range of millimetres). On the contrary, EEG has a high temporal resolution (in the order of milliseconds), but a low spatial resolution (in the range of centimetres). For this reason, both techniques provide complementary information. The objective of the Marie Curie fellowship was to use EEG and fMRI to better understand how, in humans, the perception of pain may emerge from nociception (i.e. the neural input generated by noxious or potentially noxious sensory stimuli). In a first set of studies, we compared the brain responses elicited by noxious stimulation to the brain responses elicited by innocuous somatosensory, auditory and visual stimulation, in order to investigate the widely-accepted notion that the brain responses elicited by a noxious stimulus constitute a cortical network specifically involved in the perception of pain. We found that not a single component of the brain responses to noxious stimulation reflect brain processes that are specific for the nociceptive system. The finding has far-reaching consequences because it questions the appropriateness of relying on these responses to build models of how noxious input is processed in the human brain. Using an original experimental paradigm to modulate stimulus saliency (i.e. the ability of the stimulus to attract attention) independently of stimulus intensity, we investigated another widely-accepted notion: that the brain responses elicited by a noxious stimulus reflect neural mechanisms coding for pain intensity. We showed that this notion is unfounded and that these brain responses are largely related to non-specific mechanisms of arousal and attention-al reorientation. In another study, we aimed to investigate the cortical activity related to the emergence of a conscious painful experience, using a novel adaptive stimulation paradigm to compare the brain responses elicited by physically identical noxious stimuli that are either perceived or not perceived. We found that early-latency responses reflect cortical processing that occurs regardless of whether the noxious stimulus reaches consciousness, while later-latency responses reflect cortical processing that is triggered only if the nociceptive input reaches consciousness. Furthermore, we developed and implemented a number of novel signal-processing techniques for the analysis of EEG signals, as well as for the analysis of combined EEG-fMRI recordings.The results obtained during the fellowship are not only relevant for basic science in the field of pain neuroscience. They are also relevant for the recent efforts to introduce functional neuroimaging as a tool to understand the central mechanisms underlying certain states of chronic pain (clinical applications), and to optimize and accelerate the development of novel pain-relieving compounds targeting the central nervous system (applications for the pharmaceutical industry).

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