Widespread nociceptive maps in the human neonatal somatosensory cortex
- University College London, United Kingdom
- University College London Hospitals NHS Foundation Trust, United Kingdom
Abstract
Topographic cortical maps are essential for spatial localisation of sensory stimulation and generation of appropriate task-related motor responses. Somatosensation and nociception are finely mapped and aligned in the adult somatosensory (S1) cortex, but in infancy, when pain behaviour is disorganised and poorly directed, nociceptive maps may be less refined. We compared the topographic pattern of S1 activation following noxious (clinically required heel lance) and innocuous (touch) mechanical stimulation of the same skin region in newborn infants (n=32) using multi-optode functional near-infrared spectroscopy (fNIRS). Within S1 cortex, touch and lance of the heel elicit localised, partially overlapping increases in oxygenated haemoglobin concentration (D[HbO]), but while touch activation was restricted to the heel area, lance activation extended into cortical hand regions. The data reveals a widespread cortical nociceptive map in infant S1, consistent with their poorly directed pain behaviour.
Data availability
All raw data files are open access and are available to download from Figshare (https://doi.org/10.6084/m9.figshare.13252388.v2).
Article and author information
Author details
Madeleine Verriotis
Funding
Medical Research Council (MR/M006468/1)
- Judith Meek
- Lorenzo Fabrizi
- Maria Fitzgerald
Medical Research Council (MR/L019248/1)
- Lorenzo Fabrizi
Engineering and Physical Sciences Research Council (EP/N025946/1)
- Robert J Cooper
Medical Research Council (MR/S003207/1)
- Judith Meek
- Lorenzo Fabrizi
- Maria Fitzgerald
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Ethical approval for this study was given by the NHS Health Research Authority (London - Surrey Borders) and the study conformed to the standards set by the Declaration of Helsinki. Informed written parental consent was obtained before each study (REC no: 11/LO/0350; NIHR Portfolio Study ID: 12036). Separate media consent was obtained from the parent to use a photo of their child in academic publications (Figure 4a).
Copyright
© 2022, Jones et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 250
- downloads
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Widespread nociceptive maps in the human neonatal somatosensory cortex
eLife 11:e71655.
https://doi.org/10.7554/eLife.71655
Further reading
-
- Neuroscience
Historically, the creation of the parasympathetic division of the autonomic nervous system of the vertebrates is inextricably linked to the unification of the cranial and sacral autonomic outflows. There is an intriguing disproportion between the entrenchment of the notion of a ‘cranio-sacral’ pathway, which informs every textbook schematic of the autonomic nervous system since the early XXth century, and the wobbliness of its two roots: an anatomical detail overinterpreted by Walter Holbrook Gaskell (the ‘gap’ between the lumbar and sacral outflows), on which John Newport Langley grafted a piece of physiology (a supposed antagonism of these two outflows on external genitals), repeatedly questioned since, to little avail. I retrace the birth of a flawed scientific concept (the cranio-sacral outflow) and the way in which it ossified instead of dissipated. Then, I suggest that the critique of the ‘cranio-sacral outflow’ invites, in turn, a radical deconstruction of the very notion of a ‘parasympathetic’ outflow, and a more realistic description of the autonomic nervous system.
-
- Immunology and Inflammation
- Neuroscience
Somatic genetic heterogeneity resulting from post-zygotic DNA mutations is widespread in human tissues and can cause diseases, however, few studies have investigated its role in neurodegenerative processes such as Alzheimer’s disease (AD). Here, we report the selective enrichment of microglia clones carrying pathogenic variants, that are not present in neuronal, glia/stromal cells, or blood, from patients with AD in comparison to age-matched controls. Notably, microglia-specific AD-associated variants preferentially target the MAPK pathway, including recurrent CBL ring-domain mutations. These variants activate ERK and drive a microglia transcriptional program characterized by a strong neuro-inflammatory response, both in vitro and in patients. Although the natural history of AD-associated microglial clones is difficult to establish in humans, microglial expression of a MAPK pathway activating variant was previously shown to cause neurodegeneration in mice, suggesting that AD-associated neuroinflammatory microglial clones may contribute to the neurodegenerative process in patients.
