On Neuro-Immunity and Excitability: Innovative Brain Biomarkers of Pain and Response to Therapy

Session Title: On Neuro-Immunity and Excitability: Innovative Brain Biomarkers of Pain and Response to Therapy

Topic: CLINICAL SCIENCE

Description of Workshop: The search for reliable biomarkers is a key quest in pain research, and brain-based markers are among the hottest candidates. However, no actionable biomarkers are available yet, and new candidates may help advance the field. This workshop will present some of the latest and most promising candidates, including measures of cortical excitability:connectivity and neuroinflammation. Excitability can be captured by TMS-EEG as well as the aperiodic 1/f component of EEG, both of which provide insights into the excitation:inhibition balance, a mechanism implicated in the pathology of various neuropsychiatric disorders. Emerging evidence suggests that neuroinflammatory processes may drive such excitability changes, providing a mechanistic link between immune activation and altered neuronal network dynamics. The workshop will be chaired by DCA, who will contextualize its content and start with a recorded lived-experience testimonial from a patient, in whose case the existence of a biomarker of response to therapy could have been useful. ML will focus on neuroimmune changes as biomarker of pain. Using PET imaging of neuroinflammation, his work provides direct evidence of immune system involvement in chronic pain and its relationship to brain network alterations. This lecture will discuss the most recent developments in the field, highlighting how neuroinflammatory processes can serve as mechanistic and translational biomarkers and discuss their potential to guide patient stratification and therapy development. MP will present novel EEG-based measures of cortical excitability. In addition to traditional oscillatory markers, his work emphasizes the aperiodic 1/f component of resting-state EEG, providing a non-invasive, scalable indicator of excitation:inhibition balance in the cortex. This approach allows researchers to probe mechanistic aspects of pain-related brain dysfunction and may complement neuroinflammatory markers to improve biomarker precision. DCA will extend this focus by presenting how TMS-EEG measures of excitability and connectivity are qualitatively affected by experimental pain models and by different clinical pain syndromes. TMS-EEG measures of cortical excitability balance and potential to generate complexity has shown inspiring results in other fields of neuroscience and has recently been introduced in the pain field by his team. His research demonstrates how pain reshapes cortical excitability and connectivity and how these measures can guide precision medicine approaches by non-pharmacological therapy by non-invasive neuromodulation. Together with EEG aperiodic markers, TMS–EEG provides complementary windows into excitation: inhibition balance at both spontaneous and perturbed states of brain activity. MMB will close presenting this approach in action: results from the first large clinical trials using pre-treatment measures of cortical excitability/connectivity by TMS-EEG to predict response therapy. The concluding discussion will address key questions: which markers hold the greatest translational potential, how multimodal approaches can be integrated to increase predictive power, and whether specificity is truly necessary for clinical utility. Specificity remains hotly debated, but both specific and unspecific biomarkers, including excitability/connectivity and neuroinflammation, can provide clinical value and advance precision pain medicine.

Speakers