(SS#III) William H. Sweet Young Investigators Award (2023 Award Winner): Brain Connectivity Analysis of Chronic Pain States Using Single Pulse Intracranial Network Mapping

Introduction: Network mapping of the brain with single pulse electrical stimulation is widely used in functional mapping for tumor or epileptic foci resection, but has never before been conducted in humans with chronic pain. Here, we compare electrophysiological features from intracranial recordings during a systematic single pulse network mapping protocol taken during spontaneous high and low chronic pain states using a graph theory-based modeling approach.

Methods: Five patients undergoing stereoelectroencephalography (sEEG) for chronic pain had 10 or more temporary grid and/or depth electrodes targeting the anterior cingulate cortex, medial thalamus, insula, prefrontal cortex, and motor/sensory cortices during a 10-day inpatient therapeutic trial period. We systematically stimulated up to 30 unique brain regions using 6mA bipolar pulses (0.5Hz with 25 pulse epochs) per region during both high and low chronic pain states. Evoked response potentials were averaged over a 1 second window locked to each pulse. Amplitudes and latencies were calculated using a prominence-based algorithm. Binarized connectivity matrices with a z-score threshold of 6 were used to determine directional functional connectivity of widespread pain-related brain circuits.

Results: Significantly connected regions corroborate with known nodes of the ‘pain matrix’ and revealed important edges that correlated with chronic pain perception. Broad connectivity matrix patterns from a given pain state are stable within patients across days. Brain regions that display high degrees of connectivity such as the caudate nucleus and anterior cingulate cortex are attenuated in high pain states across patients. Our preliminary results also illustrate overlap between significantly connected brain regions and stimulation targets with acute analgesic effects.

Conclusion : Graph-based network interrogation with single pulse electrical stimulation may offer unique insights on brain circuit dynamics and may help identify optimal stimulation targets for chronic pain.