Modulations of cortical oscillatory activities by nociceptive pain

Abstract

Nociception is the encoding and processing of noxious stimuli that is important as a protective mechanism to avoid potential or actual tissue damage. Previously, the neural basis of nociceptive processing was investigated by various neuroimaging techniques that measured neural activities in response to the experimental noxious stimuli. Such noxious stimuli can elicit sudden and short-lasting changes (event related potentials [ERPs], time-locked and phase-locked to the stimuli), and can trigger transient modulations of the ongoing oscillatory brain activity (appearing as event related desynchronization [ERD]/event related synchronization [ERS], time-locked but non-phase-locked to the stimuli). Most investigated pain-related ERPs have been shown to be correlated with subjective pain perception, reflecting the involuntary mechanism of attentional reorientation to a novel stimulus. In addition, pain induced α-ERD/ERS has been repeatedly associated with the administration of noxious stimuli, but their neural functions are still not fully understood. For a better understanding of the neural mechanism of α-ERD in pain perception, we comprehensively investigated changes in alpha oscillatory activities induced by transient and tonic experimental noxious stimuli. First, by applying oddball paradigms composed of auditory, visual, somatosensory, and pain modalities, we evaluated the characteristics of α-ERD and assessed the effective connectivity between P300 and α-ERD across the different sensory modalities. Second, we evaluated the specific neural functions of α-ERD in pain perception by comparing the temporal, spectral and spatial characteristics in response to frequent and infrequent painful stimuli. Third, we investigated changes in oscillatory activities induced by tonic heat by comparing the resting-state, innoxious-distracted, noxious-distracted, and noxious-attended conditions. We demonstrated that regardless of the sensory modalities, P300 and α-ERD were mainly generated from the posterior cingulate cortex and occipital lobe, respectively. The cortical information was consistently found to flow from α-ERD sources to P300 sources. This indicates that both α-ERD and the effective connectivity between the neural generators of P300 and α-ERD induced by the target stimuli were modality-independent, and that P300 was modulated by changes in α-ERD. These findings are useful for exploring the neural mechanism of cognitive information processing in the human brain. Moreover, α-ERD induced by painful stimuli reflected the summary effects of stimulus-related and task-related cortical processing, and could be greatly influenced by variations in the subject’s mental state. Our findings add to the understanding of the multiple neural functions of α-ERD, and could potentially help us more accurately interpret the possible modulation of physiological and/or psychological factors on α-ERD. Furthermore, the change of oscillatory activity in tonic heat pain perception was characterized by a stable and persistent decrease of contralateral-central alpha oscillation power and widespread increase of gamma oscillation power, which were significantly correlated with subjective pain intensity. The observed alpha suppression primarily reflected a top-down attention cognitive process, whereas the widespread gamma enhancement reflected the summary effects of bottom-up stimulus-related and top-down subject-driven cognitive processes. Finally, a theory model comprised of sensory, affective and cognitive modulations was proposed to explain the determinants of modulations of alpha oscillatory activity by pain.