Pain, the Triple Network, and Infraslow sLORETA Neurofeedback

Pain for most is experienced as a unitary sensory phenomenon. But in fact, pain is more complex. It is both an unpleasant sensory and emotional experience related to actual or potential tissue damage. It consists of two components: physical pain (painfulness) and psychological pain (suffering). It is processed in cortex by three distinct but interconnected pathways, a lateral “painfulness” pathway embedded in the somatosensory network. A medial “suffering” pathway situated in the Salience Network and a descending brain inhibition circuit that begins in the Pregenual Anterior Cingulate. Physical pain is linked to the lateral pathway, and psychological pain is linked to the medial pathway. Suffering arises from the emotional unpleasantness and cognitive catastrophizing associated with pain when activity in the Salience Network, the suffering area, exceeds the capabilities of the descending inhibitory circuit (De Ridder, Vanneste, Smith, & Adhia, 2022).

Pain catastrophizing, characterized by magnification, helplessness, and rumination, can amplify unpleasantness and pain intensity, especially in individuals with deficient cognitive coping strategies. Pain catastrophizing is associated with activity in the cognitive component of the insula and negatively correlated to the medial component of the default mode network (DMN). Suffering can manifest in various behaviors, including anger, fear, frustration, anxiety, and depression, as well as functional disability.

If pain lasts longer than the time it takes to heal it becomes chronic. This in turn makes it more likely that the pain will become a part of the self-percept. That is, chronicity is more likely to develop when the pain associated somatosensory cortex activity becomes functionally connected to the Default mode network, the network of a sense of self. Most likely this adaptation takes place to reduce energy consumption by separating the pain from the high energy consuming sympathoexcitory drive (fight, flight, and freeze) to the more energy efficient Default Mode Network of rest and digest. Chronic pain can lead to suffering, decreased quality of life, and development of pain-associated disability. Network science principles suggest that each aspect of pain is the result of connectivity changes between the lateral pathway (somatosensory network) and other resting- state networks, such as the salience network (suffering), DMN (embodiment), central executive network (cognitive disability), and motor network (physical disability).

In chronic pain, the anti-correlation between the DMN and the salience network (which overlaps with the medial pathway and stress network) is lost. Chronic pain is characterized by hyperconnectivity of the primary somatosensory cortex to the DMN and executive control network. We continue to explore the concept that chronic pain is linked to the progressive engagement of multiple resting-state networks that connects specific clinical characteristics of pain to activity and connectivity metrics.

The authors hypothesize that painfulness below a certain threshold (e.g., NRS of 4- 5) only results in painfulness without suffering, showing limited network activation in functional imaging. When pain level rises to 6/10, functional connections between the lateral and medial circuits may begin to cause suffering. Increased connectivity to the central executive network may result in functional incapacity once the pain reaches a higher value, such as 7/10.

It is this concept that has led us to develop more customized neurofeedback for pain. The therapeutic implications of targeting the medial, lateral, and descending pathways has been described and extended to the model of the triple network in research by Drs Mathew and Adhia (Adhia et al., 2023; Mathew, Adhia, Smith, De Ridder, & Mani, 2022). Infraslow frequency sLORETA (ISF) neurofeedback is currently being used to modulate the triple network in clinical practice with success in reducing acute and chronic pain. This neuromodulatory technique, if adopted more widely, could help reduce the opioid crisis.



Adhia, D. B., Mani, R., Mathew, J., O’Leary, F., Smith, M., Vanneste, S., & De Ridder, D. (2023). Exploring electroencephalographic infraslow neurofeedback treatment for chronic low back pain: a double-blinded safety and feasibility randomized placebo-controlled trial. Scientific Reports, 13(1), 1177. doi:10.1038/s41598-023-28344-2

De Ridder, D., Vanneste, S., Smith, M., & Adhia, D. (2022). Pain and the Triple Network Model. Frontiers in Neurology, 13. doi:10.3389/fneur.2022.757241

Mathew, J., Adhia, D. B., Smith, M. L., De Ridder, D., & Mani, R. (2022). Source localized infraslow neurofeedback training in people with chronic painful knee osteoarthritis: A randomized, double-blind, sham-controlled feasibility clinical trial. Frontiers in Neuroscience, 16. doi:10.3389/fnins.2022.899772

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