Cortical gamma band oscillations during Somatic and Visceral Pain Paul L. Furlong1, Sian F. Worthen1, Adam Farmer2, Caroline Witton1, Stephen D. Hall3, Qasim Aziz2, Holly E. Rossiter4

1.Wellcome Laboratory for MEG studies, Aston University, Birmingham, UK, 2.Wingate Institute for Neurogastroenterology, London, UK 3.Psychology, Plymouth University, UK .4.Institute of Neurology, UCL, London UK

IntroductionBiomarkers that could allow some objective evaluation of pain perception would have important physiological and clinical implications. Recently, several studies have implicated gamma band oscillations (GBO) within the somatosensory system as a correlate of pain perception (Gross et al 2007, Zhang et al (2012) and Tiemann et al 2010), whilst others have characterised GBO arising from SI following non-painful stimuli (Tecchio et al 2003; Fukuda et al 2008; 2010).The reported differences between these studies may in partbe explained by the differences in stimuli (Laser v Electrical).

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Rationale for studyThe distal oesophagus is mediated by vagal afferents of the Aδ and C-fibre class, thus providing an alternative approach to exploring pain mediated GBOs to these afferent projections alone.The purpose of this study therefore was to evaluate the nature of gamma band oscillatory activity following both somatic and visceral pain stimuli both within and between subjects.

MethodParticipants:12 healthy participants (6 female; age range= 21-36 years) Experimental procedure:2 datasets were collected for each participant; visceral pain and somatic pain. Stimuli:Electrical pulses of 200μs with a frequency of 0.2Hz. Somatic stimulations:Two disk electrodes on the pads of the right index finger of each participant, approximately 1cm apart.Visceral stimulations:Intubated with a naso-oesophageal tube with a pair of platinum bipolar ring electrodes sited 5cm from the tip of the intraluminal catheter.Distal Oesophageal stimulation excites Vagal afferents which are largely unmyelinated C-fibres and A-delta fibres

Figure 1 Region of Interest boundaries were estimated from functional data across multiple modalities (Peyron et al. 2002; Ferrettiet al. 2004; Garcia-Larrea et al. 2003) together with invasive neurophysiological measures for SII (Frot et al 2001) opercular-insular cortex (Frot & Mauguière 2003) and SI (Mayka et al 2006). Range (mm) of the operculo-insular ROI’s in Talairach co-ordinate space in the x, y and z axes (left to right respectively) shown on MRI’s (lower left).Opercular-insular cortex shown in violet and blue, SI in yellow.

Analysis

Peak latencies of evoked responses were used to perform an Event-Related Beamformer analysis on the data to determine the sources contributing to the evoked fields at specific latencies (Cheyne et al 2007).To compare activations within and between individuals, a Region of Interest (ROI) analysis was undertaken. Talairach co-ordinates were determined for each individual and ROI boundaries determined from previous literature (Figure 1).

Normalised bootstrap time frequency plots were then created from the combined data of participants within each respective ROI to visualise the average oscillatory activity across the group (Graimann et al. 2002) (Figure 3).

Somatic painContralateralSI

Somatic pain Contralateral OpercularInsular

Visceral pain SI (RT)

Visceral pain OpercularInsular (RT)

Figure 3. Group Mean BootstrapTime-Frequency plots derived from SI and Opercular-Insular ROI following painful somatic and painful visceral stimulation. Notable features of painful somatic plots are early gamma band activity in SI (20-50ms; 30-40Hz and 60-80Hz ) followed by simultaneous gamma activity in both SI and opercular-insular cortex between 80-180ms; 50-80Hz and 90-150Hz). Painful visceral stimulation produced significant gamma band activation (40-60Hz; >10% from baseline) in the group bootstrap time-frequency plots, most notably in the Right Opercular-insula cortex, occurring between 80 and 180ms following painful electrical stimulation. A coincidental burst of gamma band activity (150ms; 80-120Hz) was observed in SI. As with somatic pain, high beta/ low gamma band changes (20-40Hz) are also seen in SI with a decrease in power between 150 – 400ms (>5%) and a marked increase between 400-700ms (>20%).

Results

Conclusion

• Painful stimulation of the oesophagus activating A-delta / C-fibres does yield gamma band activity in both SI and Opercular-insular cortex.

• Latencies of gamma band co-activation supports the notion of ‘binding’ of cortical sites within the matrix.

• Gamma within the pain network is more complex than previously interpreted.

ReferencesCheyne, D. et al., 2007. Event-related beamforming: a robust method for presurgical functional mapping using MEG. Clinical Neurophysiology, 118: 1691–1704Ferretti, A. et al., 2004. Functional topography of the secondary somatosensory cortex for non-painful and painful stimulation of median and tibial nerve: an fMRI study. NeuroImage, 23(3): 1217–25.Frot, M. et al., 2001. Responses of the supra-sylvian (SII) cortex in humans to painful and innocuous stimuli. A study using intra-cerebral recordings. Pain, 94(1): 65–73. Frot, M. & Mauguière, F., 2003. Dual representation of pain in the operculo-insular cortex in humans. Brain, pp.438–450Fukuda, M. et al., 2008. Short-latency median-nerve somatosensory-evoked potentials and induced gamma-oscillations in humans. Brain : a journal of neurology, 131(Pt 7), pp.1793–805.Fukuda, M., Juhász, C. & Hoechstetter, K., 2010. Somatosensory-related gamma-, beta-and alpha-augmentation precedes alpha-and beta-attenuation in humans. Clinical Neurophysiology, 121(3):1–20.Garcia-Larrea, L., Frot, M. & Valeriani, M., 2003. Brain generators of laser-evoked potentials: from dipoles to functional significance. Clinical Neurophysiology, 33: 279–292.Graimann, B. et al., 2002. Visualization of significant ERD/ERS patterns in multichannel EEG and ECoG data. Clinical neurophysiology :113(1): 43–7.Gross, J. et al., 2007. Gamma oscillations in human primary somatosensory cortex reflect pain perception. PLoS biology, 5(5), p.e133.Mayka, M. et al., 2006. Three-dimensional locations and boundaries of motor and premotor cortices as defined by functional brain imaging: a meta-analysis. Neuroimage, 31(4): 1453–1474.Peyron, R. et al., 2002. Role of Operculoinsular Cortices in Human Pain Processing: Converging Evidence from PET, fMRI, Dipole Modeling, and Intracerebral Recordings of Evoked Potentials. NeuroImage, 17(3): 1336–1346Tecchio, F., Babiloni, C. & Zappasodi, F., 2003. Gamma synchronization in human primary somatosensory cortex as revealed by somatosensory evoked neuromagnetic fields. Brain research, 986: 63–70.Tiemann, L. et al., 2010. Gamma oscillations as a neuronal correlate of the attentional effects of pain. Pain, 150(2): 302–8. Zhang, Z.G. et al., 2012. Gamma-band oscillations in the primary somatosensory cortex--a direct and obligatory correlate of subjective pain intensity. The Journal of neuroscience, 32(22): 7429–38.

Figure 2 Group mean Talairachco-ordinates in SI following painful somatic (hand) [ red ] and painful visceral (distal oesophagus) electrical stimulation [white]

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