Functional Brain Network Mechanism of Hypersensitivity in Chronic Pain

Abstract

Fibromyalgia (FM) is a chronic widespread pain condition characterized by augmented multi-modal sensory sensitivity. Although the mechanisms underlying this sensitivity are thought to involve an imbalance in excitatory and inhibitory activity throughout the brain, the underlying neural network properties associated with hypersensitivity to pain stimuli are largely unknown. In network science, explosive synchronization (ES) was introduced as a mechanism of hypersensitivity in diverse biological and physical systems that display explosive and global propagations with small perturbations. We hypothesized that ES may also be a mechanism of the hypersensitivity in FM brains. To test this hypothesis, we analyzed resting state electroencephalogram (EEG) of 10 FM patients. First, we examined theoretically well-known ES conditions within functional brain networks reconstructed from EEG, then tested whether a brain network model with ES conditions identified in the EEG data is sensitive to an external perturbation. We demonstrate for the first time that the FM brain displays characteristics of ES conditions, and that these factors significantly correlate with chronic pain intensity. The simulation data support the conclusion that networks with ES conditions are more sensitive to perturbation compared to non-ES network. The model and empirical data analysis provide convergent evidence that ES may be a network mechanism of FM hypersensitivity.

Delay regulated explosive synchronization in multiplex networks

“…We have also shown analytically that the average frequency of each layer depends on the inter-layer coupling strength and the average connectivity of all the layers along with the time-delay. Lately, the evidence of ES is reported in the brains of patients suffering from fibromyalgia (FM), a condition described as an omnipresent, chronic pain [10]. The patients with FM have brain networks predisposed towards abrupt, global responses or abnormal hypersensitivity (ES) to minor changes.…”

“…In recent years, a novel synchronization process exhibiting hypersensitivity or explosiveness in the natural physical and biological systems, called explosive synchronization (ES), has drawn much attention in the scientific community [1][2][3][4][5][6][7][8]. The epileptic seizures in the brain [9], chronic pain in the Fibromyalgia brain [10], the cascading failure of power grids [11], and the jamming of the internet [12] have shown ES transitions with small initial perturbations. Furthermore, needless to say, the presence of time-delay is innate in a variety of communication systems and seems to have enhanced synchronization in such systems [13][14][15][16][17][18].…”

Multifractal Analysis Reveals Decreased Non-linearity and Stronger Anticorrelations in Heart Period Fluctuations of Fibromyalgia Patients

“…From a functional point of view, the interaction between brain areas of FM patients has been assessed through network sensitivity analysis of electroencephalogram data. Two properties of such networks (node degree and frequency) showed significant correlation with chronic intensity pain, suggesting that the central nervous system of these patients has an altered network configuration that may increase hypersensitivity to pain (Lee et al, 2018 ). However, it remains uncertain if such changes of the central nervous system participate in functional alterations of other regulatory systems, and if this participation modifies effector variables such as the heart rate period.…”

Oscillations, criticality and responsiveness in complex brain networks

“…The = 2 and is an initial angular natural frequency of each ℎ oscillator. We used a Gaussian distribution for natural frequency with a mean frequency of 10 Hz and standard deviation of 0.5 Hz to simulate the alpha bandwidth of human EEG activity [20][21][22]24,51]. We also used the homogeneous coupling term = between the ℎ and ℎ oscillators from 0 to 0.4 with = 0.002, which determines the global connection strength among brain regions.…”