Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in diabetic neuropathic pain

Abstract

Background: In this paper we explored thalamocortical functional connectivity in a group of eight patients suffering from peripheral neuropathic pain (diabetic pain), and compared it with that of a group of healthy subjects. We hypothesized that functional interconnections between the thalamus and cortex can be altered after years of ongoing chronic neuropathic pain.

Results: Functional connectivity was studied through a resting state functional magnetic resonance imaging (fMRI) paradigm: temporal correlations between predefined regions of interest (primary somatosensory cortex, ventral posterior lateral thalamic nucleus, medial dorsal thalamic nucleus) and the rest of the brain were systematically investigated. The patient group showed decreased resting state functional connectivity between the thalamus and the cortex.

Conclusion: This supports the idea that chronic pain can alter thalamocortical connections causing a disruption of thalamic feedback, and the view of chronic pain as a thalamocortical dysrhythmia.

Figure 1

S1 resting state connectivity analysis. A: Probabilistic maps of the S1 rsFC thalamic projection relative to pain subjects. B: Probabilistic maps of the S1 rsFC thalamic projection relative to healthy subjects. C: Group comparison of the S1 rsFC thalamic projection (Two sample t-test q<0.05 FDR-corrected, minimum cluster dimension K>5 voxels in the native resolution). D: Example of the time course of a healthy subject. E: Group comparison of the S1 rsFC brain projection (Two sample t-test q<0.05 FDR-corrected, minimum cluster dimension K>5 voxels in the native resolution). Right middle panel represents the Seed ROI. Colors from green to white indicate an increasing spatial overlapping probability (%) (single subject correlation maps before probabilistic map creation thresholded at q<0.05 FDR-corrected, minimum cluster dimension K>5 voxels in the native resolution). Colors from red to yellow indicate an increased connectivity in the pain group; colors from blue to green indicate a reduced connectivity in the pain group. All rsFC maps were projected on 3D representations of the brain using BrainVoyager QX.

Figure 2

VPL resting state connectivity analysis. Group comparison of the VPL rsFC brain projection (Two sample t-test q<0.05 FDR-corrected, minimum cluster dimension K>5 voxels in the native resolution). Middle panel represents the Seed ROI. Colors from red to yellow indicate an increased connectivity in the pain group; colors from blue to green indicate a reduced connectivity in the pain group. All rsFC maps were projected on 3D representations of the brain using BrainVoyager QX.

Figure 3

MDN resting state connectivity analysis. A: Probabilistic maps of the MDN rsFC Amygdale projection relative to healthy subjects. B: Probabilistic maps of the MDN rsFC Amygdale projection relative to pain subjects. C: Group comparison of the MDN rsFC Amygdale projection. D: Group comparison of the MDN rsFC Subgenual ACC projection. E: Group comparison of the MDN rsFC S1 projection. Colors from green to white indicate an increasing spatial overlapping probability (%) (single subject correlation maps before probability map creation thresholded at q<0.05 FDR-corrected, minimum cluster dimension K>5 voxels in the native resolution). Group comparison with two sample t-test, q<0.05 FDR-corrected, minimum cluster dimension K>5 voxels in the native resolution; colors from red to yellow indicate an increased connectivity in the pain group; colors from blue to green indicate a reduced connectivity in the pain group. All rsFC maps were projected on 3D representation of the brain using BrainVoyager QX.

Figure 4

Pairwise correlations. Mean correlations and standard deviations for each pair of investigated ROIs in the patient and control groups. Red lines indicate statistically relevant differences in rsFC between the two groups, blue dotted lines indicate no statistically relevant differences.