Research On Mismatch Negativity Of Nociceptive System And Its Extraction

Ever since mismatch negativity had been found in selective-attention research, it has been hotpots through these decades. Auditory mismatch negativity that has been applied in clinical use as a predictor of consciousness showed its superiority. This suggests that mismatch negativity would be a useful tool in clinics. By using robust and reliable nociceptive mismatch negativity as an objective detector serves clinical pain measurement, the problems, like cognitive, the expression of pain perception, emotion, which affect the accuracy of measurement, will possibly be avoided. The research of this objective tool will have profound implication in future pain diagnoses and assessment.Except for auditory mismatch negativity, this phenomenon has also been found in other sensory modalities (i.e. visual and somatosensory). However, no study to date has reported the existence of a mismatch phenomenon exerted through the selective stimulation of Aδ nociceptive fibers. This discrepancy between sensory modalities may be related to the inherent low signal-to-noise ratio of mismatch negativity. Even when elicited by auditory stimuli, the MMN is normally no more than5μV on average across several individuals. This fact makes it therefore difficult to detect mismatch negativity activity in non-nociceptive somatosensory and nociceptive systems, where the signal-to-noise ratio is even lower and a clear mismatch negativity peak may be absent at single-subject level.In present study, we planned to get reliable nociceptive mismatch negativity through two experiments. First experiment was to explore the plausible existence of nociceptive mismatch negativity. In the second experiment, we improved the experiment design, and developed new approach to analyze mismatch negativity data, in the hope of obtaining robust and reliable mismatch negativity.The first experiment used within subject design. There were two experiment conditions:data collected either while the participants were attending to (Active condition), or were distracted from (Passive condition), the sensory stimulation. Non-nociceptive somatosensory stimuli and nociceptive stimuli were delivered in separately blocks. Non-nociceptive somatosensory MMN and nociceptive MMN were evoked by trains of non-nociceptive somatosensory stimuli and nociceptive stimuli, which were administered according to a roving paradigm, and delivered to the lateral (L), median (M), or wrist (W) section of the participants’ left and right hands, respectively. In other words, the first stimulus in each train was a deviant that started from one of the three different hand’s sections, then the next train of stimuli would from the other section of the same hand. In each train,4-8repeated identical stimuli (the number of stimuli in each train was pseudorandomly distributed across trains), were delivered to the same hand’s section with an interstimulus interval of1000ms.We observed three main findings in experiment one. First, the factor mismatch (standard vs. deviant) significantly modulated three distinct spatial regions of interest (sROIs) for both non-nociceptive evoked potentials and nociceptive evoked potentials (bilateral temporal and central regions). Similarly, the factor attention (active vs. passive) significantly modulated three distinct sROIs (bilateral temporal-parietal and frontal-central regions) for both non-nociceptive evoked potentials and nociceptive evoked potentials. Second, we disclosed the time course of the amplitude modulation exerted by the factors mismatch and attention on each significant sROI. This analysis revealed that both mismatch and attention significantly modulated early and late poststimulus activity elicited by both non-nociceptive TES and nociceptive IES, thus suggesting a high sensitivity of both non-nociceptive evoked potentials and nociceptive evoked potentials to the break of regularities, despite the manipulation of the attentional focus. Third, within mismatch modulated sROIs, some temporal region of interest (tROIs) in the expected MMN latency range were modulated by the factor mismatch without being concurrently affected by the factor attention (Figure8). Altogether, these findings brought about evidence that (1) mismatch brain responses can be elicited by nociceptive stimuli as much as those elicited by non-nociceptive somatosensory stimuli, provided that the effect of attention is accounted for; and (2) these responses are topographically similar but crucially different in their contralateral and ipsilateral onset of activation.The second experiment used within subject design. There were two experiment conditions:data collected either while the participants were attending to (Active condition), or were distracted from (Passive condition), the sensory stimulation. Trains of auditory, non-nociceptive somatosensory, and nociceptive stimuli were also administered according to roving paradigm. In other words, the first stimulus in each train was a deviant that started from one of the three sensory modalities (auditory, non-nociceptive somatosensory, and nociceptive), then the next train of stimuli would from the other modality. In each train,11-15repeated identical stimuli from same modality (the number of stimuli in each train was pseudorandomly distributed across trains) were delivered with the interstimulus interval of1000ms.Experiment two has introduced an effective and reliable approach to extract mismatch negativity in different sensory modalities, and suggested that sensory memory trace formation and deviance detection may be, at least partly, modality dependent. In summary, we obtained four main findings. First, the MMN elicited by stimuli of different sensory modalities could be effectively identified using a topographical segmentation analysis by means of quasi-stable landscape, that is electroencephalography (EEG) activity functionally associated to MMN could be detected even when no clear peak amplitude was present in the event-related potentials (ERPs) responses (Figs.2-3). Second, regardless of the preceding sensory modality, a standard sensory event in a train of stimuli belonging to the same modality was mainly identified following at least two repetitions (i.e., after the3rd position in a train) across sensory modalities and attentional conditions. Third, we found that once a robust standard could be identified in the preceding train, the modality deviant activity was influenced by the kind of preceding sensory modality. Fourth, amplitudes of MMN co-varied significantly between Active and Passive conditions within the same sensory modality but not between different sensory modalities (Fig.8, Table4), thus hinting to the existence of modality dependence in the process of sensory memory trace formation and deviance detection.In this study, we have proved the existence of nociceptive mismatch negativity, detailed the latency, time course, topography of nociceptive MMN, and developed a reliable and effeicent approach to extract mismatch responses.The confirmation of existence of nociceptive mismatch negativity has filled the blank in pain MMN research, which will be the complement of multi-modality MMN research. In addition, as the objective nerual physiological marker nociceptive MMN will offer a way to observe the chronic pain processing without patients’ attention, which will have profound implication.