A nociresponsive specific area of human somatosensory cortex within BA3a: BA3c?

Rosa M Sanchez Panchuelo,Sally Eldeghaidy,Andrew Marshall,Francis Mcglone,Susan T Francis,Oleg Favorov

doi:10.1016/j.neuroimage.2020.117187

Abstract

It is well recognized that in primates, including humans, noxious body stimulation evokes a neural response in the posterior bank of the central sulcus, in Brodmann cytoarchitectonic subdivisions 3b and 1 of the primary somatosensory cortex. This response is associated with the 1st/sharp pain and contributes to sensory discriminative aspects of pain perception and spatial localization of the noxious stimulus. However, neurophysiological studies in New World monkeys predict that in humans noxious stimulation also evokes a separate neural response—mediated by C-afferent drive and associated with the 2nd/burning pain—in the depth of the central sulcus in Brodmann area 3a (BA3a) at the transition between the somatosensory and motor cortices. To evoke such a response, it is necessary to use multi-second duration noxious stimulation, rather than brief laser pulses. Given the limited human pain-imaging literature on cortical responses induced by C-nociceptive input specifically within BA3a, here we used high spatial resolution 7T fMRI to study the response to thermonoxious skin stimulation. We observed the predicted response of BA3a in the depth of the central sulcus in five human volunteers. Review of the available evidence suggests that the nociresponsive region in the depth of the central sulcus is a structurally and functionally distinct cortical area that should not be confused with proprioceptive BA3a. It is most likely engaged in interoception and control of the autonomic nervous system, and contributes to the sympathetic response to noxious stimulation, arguably the most intolerable aspect of pain experience. Ablation of this region has been shown to reduce pain sensibility and might offer an effective means of ameliorating some pathological pain conditions.

Highlights

In primates, noxious body stimulation evokes neural activity in a distributed network of cortical regions, including primary and secondary somatosensory areas, insula, anterior cingulate cortex (ACC), and prefrontal cortex, each region making its own contribution to discriminative, cognitive, or affective/motivational aspects of the evoked pain (Apkarian et al, 2005; Iannetti and Mouraux, 2010)
Due to RF interference inside the 7T scanner, the Galvanic skin responses (GSR) recording often stopped during the actual fMRI experiment, though the subject reported the sensation as being perceived painful throughout the fMRI run
Our results show that BOLD responses evoked by the thermonoxious stimulation were distributed throughout the depth of the central sulcus, overlapping primarily with FreeSurfer-demarcated Brodmann area 3a (BA3a) and BA3b

Summary

Introduction

Noxious body stimulation evokes neural activity in a distributed network of cortical regions, including primary and secondary somatosensory areas, insula, anterior cingulate cortex (ACC), and prefrontal cortex, each region making its own contribution to discriminative, cognitive, or affective/motivational aspects of the evoked pain (Apkarian et al, 2005; Iannetti and Mouraux, 2010). Neurons with functional properties indicative of their involvement in discriminative representation of nociceptive stimuli are found in BA1 and BA3b (Chudler et al, 1990; Kenshalo et al, 2000; Ploner et al, 2000) These nociresponsive neurons are dominated by Aδ nociceptive afferent drive and respond with stimulus-response characteristics fully consistent with their mediation of the early, sharp, and well-localized percept designated as “fast/discriminative pain” (Kenshalo and Willis, 1991). These neurons do not form nociceptionpure cortical columns, but are interspersed among other neurons that are innervated exclusively by Aβ mechanoreceptors and are responsible for the discriminative touch

Objectives

Methods

Results

Discussion

Conclusion