Altered White Matter Pain Pathway Connectivity in Congenital Pain Insensitivity Cohort
Poster No:
2047
Submission Type:
Abstract Submission
Authors:
ARNAS TAMASAUSKAS1, Irene Perini2, India Morrison2, Andrew Marshall1
Institutions:
1University of Liverpool, Liverpool, Merseyside, 2Linköping University, Linköping, Linköping
First Author:
Co-Author(s):
Introduction:
Research into congenital pain insensitivity provides important insights into human pain pathway physiology. Currently, there is a gap in literature of structural central nervous system analysis of congenital pain insensitivity, as previously researchers have only looked in to the peripheral C-nociceptor afferent fibres. This investigation of R221W Nerve Growth Factor (NGF) mutation carriers provides an opportunity to understand white matter changes due to the R221W mutation. This research aims to identify both macro and micro differences in the pain pathways between 11 of these individuals and 11 gender-, age-, and education-matched healthy controls.
Methods:
DTI scans were acquired using single phase encoding. For preprocessing, Synb0, was utilised to synthesize reverse phase encoding from T1 scans. FreeSurfer was used to construct a pain atlas for this cohort with included areas being: bilateral Sensory Cortex, Anterior Cingulate Cortex (ACC), Anterior Insula (AI), Thalamus, and Brainstem. Region Of Interest (ROI) masks were then generated from this atlas, and anatomically constrained tractography (ACT) was applied within these ROIs to perform Fixel-based ROI analysis using Probabilistic Second-order Integration over Fibre Orientation Distributions (iFOD2). Fibre density (FD) and fibre density and cross-section (FDC) metrics were compared between groups. Connectome matrices and centroid nodes generated from each participants ACT Fixel analyses were additionally used in Network-based statistics (NBS) analysis. Proportional thresholding of 10% strongest edges was applied to all matrices, and NBS t-test threshold was 3.1
Results:
ROI-specific Fixel tractography showed significant FD and FDC reductions in the brainstem of R221W carriers compared to controls (p < 0.05). These reductions suggest localized microstructural impairments in pathways going through the brainstem. Conversely, connections to the brainstem, were not found to be significantly different in NBS structural networks between the two groups. However, there were significant differences in the structural network connecting left and right ACCs to the left Insula (p = 0.0026).
·Figure 1: Significantly Different FDC Fixel plots (left) and streamlines passing through them (right)
·Figure 2: NBS Identified Altered Network Connections Between Left ACC, Right ACC, and Left Insula
Conclusions:
These findings provide evidence that the structural impacts of R221W mutations are not restricted to peripheral C-nociceptor afferent fibres but extend to specific pain relay and modulation pathways, particularly within the brainstem, ACC and AI. This targeted ROI approach integrates both micro-structural fibre differences, and macro-structural pain networks in identifying potential central nervous system areas implicated in pain insensitivity in NGF mutations. Further research is needed to understand why some important pain-related brain structures, such as the Thalamus or Sensory Cortex seem to be un-altered while primarily pain relay structures are impacted.
Genetics:
Neurogenetic Syndromes
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity
Novel Imaging Acquisition Methods:
Diffusion MRI
Perception, Attention and Motor Behavior:
Perception: Pain and Visceral 1
Keywords:
Data analysis
Pain
Tractography
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
Abstract Information
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Provide references using APA citation style.
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