Abstract

The objective of this study was to compare the functional connectivity of the lateral and medial thalamocortical pain pathways by investigating the blood oxygen level-dependent (BOLD) activation patterns in the forebrain elicited by direct electrical stimulation of the ventroposterior (VP) and medial (MT) thalamus. An MRI-compatible stimulation electrode was implanted in the VP or MT of α-chloralose-anesthetized rats. Electrical stimulation was applied to the VP or MT at various intensities (50 µA to 300 µA) and frequencies (1 Hz to 12 Hz). BOLD responses were analyzed in the ipsilateral forelimb region of the primary somatosensory cortex (iS1FL) after VP stimulation and in the ipsilateral cingulate cortex (iCC) after MT stimulation. When stimulating the VP, the strongest activation occurred at 3 Hz. The stimulation intensity threshold was 50 µA and the response rapidly peaked at 100 µA. When stimulating the MT, The optimal frequency for stimulation was 9 Hz or 12 Hz, the stimulation intensity threshold was 100 µA and we observed a graded increase in the BOLD response following the application of higher intensity stimuli. We also evaluated c-Fos expression following the application of a 200-µA stimulus. Ventroposterior thalamic stimulation elicited c-Fos-positivity in few cells in the iS1FL and caudate putamen (iCPu). Medial thalamic stimulation, however, produced numerous c-Fos-positive cells in the iCC and iCPu. The differential BOLD responses and c-Fos expressions elicited by VP and MT stimulation indicate differences in stimulus-response properties of the medial and lateral thalamic pain pathways.

Highlights

  • Nociceptive sensory processing within the thalamus involves 2 distinct and parallel systems: the lateral and medial systems [1]

  • Mid-top and top locations of stimulation induced robust activation in the iS1FL and iS1BF. These results indicated that the responses evoked by VP stimulation were in accordance with the VP sensory map

  • In the cCC areas (Figure 4E), We found a similar patterns in increased blood oxygen level-dependent (BOLD) amplitude with increasing stimulus intensity below 200-mA stimulation as in the ipsilateral cingulate cortex (iCC)

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Summary

Introduction

Nociceptive sensory processing within the thalamus involves 2 distinct and parallel systems: the lateral and medial systems [1]. Lateral regions of the thalamus project to the primary (S1) and secondary (S2) somatosensory cortices, which are considered important in the sensory-discriminative aspects of pain. Medial regions of the thalamus transmit processed nociceptive signals to the anterior cingulate cortex, insular cortex, and other limbic brain areas, which might be involved in the affective-motivational aspects of pain [2,3,4,5]. Most primary studies of these 2 systems used recording and tracing methods to investigate the anatomical and electrophysiological interconnections of these brain regions. It remains unclear if fundamental differences in signal processing exist between the medial and lateral thalamic pathways. A global comparison using direct stimulation and functional brain imaging is, needed

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