Intracranial electrophysiology reveals distinct neural representations of nociception and salience in the human brain

Neuroimaging studies have shown close overlap between neural representations of nociceptive stimuli and non-nociceptive, salient stimuli (such as low-probability sounds), leading to the proposal that nociception and salience share a common neural substrate in the human brain. Here we use high-resolution intracranial recordings from 13 neurosurgical patients (2,018 total electrodes) to show that neural representations of nociception and salience are anatomically and functionally distinct in the human brain. 77% of 107 electrodes that encoded nociceptive stimuli did not encode low-probability sounds ("nociceptive representations"), whereas 23% encoded both nociceptive and low-probability sounds ("salience representations"). Nociceptive representations were distinct from salience representations in terms of anatomical prevalence (posterior insula, inferior parietal, and perirolandic cortex vs. anterior insula, thalamus, and inferior frontal gyrus), timing (nociception preceded salience by 120 ms on a trial-by-trial basis), and function (intracranial electrical stimulation was more likely to cause sensory experience when applied near nociceptive representations, as compared to salience representations). These results provide strong evidence that nociception and salience have distinct neural substrates in the human brain, and that selective measurement of these distinct processes may help understand patient-to-patient variability in chronic pain and develop personalized brain stimulation treatments.