Functional integration within the human pain system as revealed by Granger causality

Abstract

Pain is a complex experience subserved by an extended network of brain areas. However, the functional integration among these brain areas, i.e., how they interact and communicate to generate a coherent pain percept and an adequate behavioral response is largely unknown. Here, we used magnetoencephalography to investigate functional integration among pain-related cortical activations in terms of Granger causality and compared it with tactile-related activations. The results show causal influences of primary somatosensory cortex on secondary somatosensory cortex for tactile-related but not for pain-related activations, which supports the proposition of a partially parallel organization of pain processing in the human brain. Furthermore, during a simple reaction time task, the strength of causal influences between somatosensory areas but not the latencies between activations correlated significantly with the speed of reaction times. These findings show how the analysis of functional integration complements traditional analyses of electrophysiological data and provides novel and behaviorally relevant information about the organization of the human pain system.

Mismatch responses evoked by nociceptive stimuli

“…Importantly, two spatiotemporal features could be appreciated when comparing the significant modulation of sMMN and nMMN (see Figures and , left panel, first two graphs from top): (1) The amplitude modulation of the sMMN had an earlier onset than the nMMN both at the contralateral temporal region (SEP‐M‐tROI a: 110 ms vs. NEP‐M‐tROI a: 182 ms) and ipsilateral temporal region (SEP‐M‐tROI d: 162 ms vs. NEP‐M‐tROI c: 186 ms)—a finding that is fully compatible with the conduction velocity of somatosensory Aβ and nociceptive Aδ fibers (Ploner, Schmitz, Freund, & Schnitzler, , ), respectively. (2) The difference of latency between the contralateral and the ipsilateral onset of activity was larger for the sMMN than for the nMMN (52 ms vs. 4 ms), thus supporting the notion that nociceptive processing is faster than tactile processing in the human brain; that is, somatosensory inputs are processed in a serial fashion (e.g., Hu, Zhang, & Hu, ) whereas the nociceptive inputs are processed in a parallel manner (Liang, Mouraux, & Iannetti, ; Ploner, Gross, Timmermann, & Schnitzler, ; Ploner, Schoffelen, Schnitzler, & Gross, ). Crucially, as the topographies of these responses largely overlapped, latency discrepancies are the main salient differences between sMMN and nMMN.…”

Attention to painful cutaneous laser stimuli evokes directed functional connectivity between activity recorded directly from human pain-related cortical structures

“…Contrary to this study, an earlier study has reported the significant GRC between S1 and SII (part of PS) in response to a tactile but not a painful laser stimulus in healthy subjects carrying out a reaction time task [81]. In that study, responses were magnetic signals that were projected upon maps derived from source analysis of activity recorded during sensory and motor tasks.…”

The primary somatosensory cortex and the insula contribute differently to the processing of transient and sustained nociceptive and non‐nociceptive somatosensory inputs

“…This leads to an interesting possibility: that S1 could be specifically involved in the detection of changes in non-nociceptive somatosensory input, whereas the anterior insula could be specifically involved in the detection of changes in nociceptive somatosensory input. This difference in the cortical processing of nociceptive and non-nociceptive sensory inputs could be related to the results of previous studies suggesting that ascending non-nociceptive somatosensory thalamocortical input projects primarily to the contralateral S1 [Gardner and Kandel, 2000;Hu et al, 2012;Iwamura, 1998], whereas ascending nociceptive somatosensory thalamocortical input predominantly projects to other brain structures such as insular and cingulate cortices [Frot et al, 2008;Inui et al, 2004;Ploner et al, 2009]. Importantly, our observation does not rule out other possible functions of the anterior insula in nociceptive processing [e.g., representation of prediction error; Seymour et al, 2005].…”