Impact of Theory of Mind Training on Brain-to-Brain Patient-Clinician Concordance

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Abstract The patient-clinician interaction is central to most therapies and is supported by key interpersonal mechanisms of action such as clinician empathy, therapeutic alliance, and trust. However, the neural underpinnings of this effect are mostly unknown. Our recently published study applied functional MRI (fMRI) hyperscanning (i.e. simultaneously neuroimaging chronic pain patients and clinicians in synchronized MRI scanners) demonstrated that brain-to-brain concordance in the temporoparietal junction (TPJ) is up-regulated following a clinical interaction and associated with patient analgesia. Our study also found that greater facial expression mirroring is associated with higher therapeutic alliance and greater evoked pain analgesia. Interestingly, the TPJ is known to be a key region for theory-of-mind processing (ToM, i.e. mentalizing, perspective-taking), defined as the ability to infer and understand others’ mental states - a cognitive function critical for social communication, empathy, and social mirroring. Furthermore, ToM training protocols have been found to improve mentalizing ability, which can generalize to other cognitive / quality of life functions. We propose that patient/clinician TPJ concordance, linked with ToM processing, is a key aspect of therapeutic alliance, and thus ToM training for fibromyalgia patients will increase alliance, facial expression mirroring, and TPJ concordance, with the latter mediating improvements in pain outcomes following acupuncture therapy, an established non-pharmacological therapy for chronic pain. Fibromyalgia is a nociplastic chronic pain disorder showing a deficit in ToM processing, potentially contributing to the difficulties in social functioning characterizing this condition, and in great need of novel therapies. Our study will evaluate the impact of a novel multimodal therapy, a type of approach known to improve pain outcomes and recommended by the Institute of Medicine report for chronic pain management. Our study design will also allow us to evaluate a neural model supporting therapeutic alliance for pain outcomes for fibromyalgia wherein combined ToM training and acupuncture will synergistically target a critical therapeutic pathway - i.e., patient-provider alliance, instantiated by TPJ concordance. Our Aims will: (1) Determine behavioral and neurophysiological effects of ToM training, (2) Evaluate the impact of ToM training on brain-to-brain concordance with fMRI hyperscanning, and (3) Assess if brain/behavioral markers mediate the effect of ToM training on longitudinal acupuncture outcomes.