Functional Spectroscopy Mapping of Pain Processing Cortical Areas During Non-painful Peripheral Electrical Stimulation of the Accessory Spinal Nerve

Abstract

Peripheral electrical stimulation (PES), which encompasses several techniques with heterogeneous physiological responses, has shown in some cases remarkable outcomes for pain treatment and clinical rehabilitation. However, results are still mixed, mainly because there is a lack of understanding regarding its neural mechanisms of action. In this study, we aimed to assess its effects by measuring cortical activation as indexed by functional near infrared spectroscopy (fNIRS). fNIRS is a functional optical imaging method to evaluate hemodynamic changes in oxygenated (HbO) and de-oxygenated (HbR) blood hemoglobin concentrations in cortical capillary networks that can be related to cortical activity. We hypothesized that non-painful PES of accessory spinal nerve (ASN) can promote cortical activation of sensorimotor cortex (SMC) and dorsolateral prefrontal cortex (DLPFC) pain processing cortical areas. Fifteen healthy volunteers received both active and sham ASN electrical stimulation in a crossover study. The hemodynamic cortical response to unilateral right ASN burst electrical stimulation with 10 Hz was measured by a 40-channel fNIRS system. The effect of ASN electrical stimulation over HbO concentration in cortical areas of interest (CAI) was observed through the activation of right-DLPFC (p = 0.025) and left-SMC (p = 0.042) in the active group but not in sham group. Regarding left-DLPFC (p = 0.610) and right-SMC (p = 0.174) there was no statistical difference between groups. As in non-invasive brain stimulation (NIBS) top-down modulation, bottom-up electrical stimulation to the ASN seems to activate the same critical cortical areas on pain pathways related to sensory-discriminative and affective-motivational pain dimensions. These results provide additional mechanistic evidence to develop and optimize the use of peripheral nerve electrical stimulation as a neuromodulatory tool (NCT03295370- www.clinicaltrials.gov).

Keywords: accessory spinal nerve; cortical activation; electrical nerve stimulation; electroacupuncture; near infrared spectroscopy; peripheral nerve stimulation.

Figure 1

Flow diagram.

Figure 2

Cap montage. Sources (red), detectors (blue), in correspondence with 10/10 electroencephalography (EEG) system. Channels formed are in yellow bar. Dorsolateral prefrontal cortex (DLPFC) and sensorimotor cortex (SMC) areas are shown separately.

Figure 3

Experiment layout. Sequence of events: (A) 10 min of data acquisition in resting state, followed by needling right accessory spinal nerve (ASN); (B) randomization in active or sham intervention; (C) 10 min of data acquisition in resting state. In caption, representation of the subcutaneous location of the ASN (yellow trace) between trapezius muscle (a) and sternocleidomastoid muscle (b).

Figure 4

Comparison of DLPFC activation between active and sham groups (n = 15). The figure shows a representation of the mean oxygenated hemoglobin (HbO) concentration changes, measured in millimoles per liter (mmol/l) with correspondent p-value, indicating the difference of right DLPFC activation during accessory spinal nerve-peripheral electrical stimulation (ASN-PES).

Figure 5

Comparison of SMC activation between active and sham groups (n = 15). The figure shows a representation of the mean HbO concentration changes, measured in millimoles per liter (mmol/l) with correspondent p-value, indicating the difference of left SMC activation during accessory spinal nerve-peripheral electrical stimulation (ASN-PES).

Figure 6

HbO concentration changes in each channel between active and sham groups (n = 40). The figure shows a representation of the mean HbO concentration changes, measured in millimoles per liter (mmol/l), in each channel, demonstrating subtle changes in oxy-hemoglobin between active and sham groups in almost all of 40 channels.

Figure 7

HbO mean curves for each cortical area of interest between groups. Channels were gathered to display the oxy-hemoglobin changes for active (Gr1) and sham (Gr2) groups, from 5 s before (baseline) to 20 s after stimulation onset.

Figure 8

Graphic representation frames on a 3D brain surface model in two subjects, showing oxy-hemoglobin changes in time sequence. Color bars represent activation (red) or deactivation (blue) response. The first frame represents oxy-hemoglobin before the electrical stimulus, followed by frames in time sequence.