The neurobiology of the patient-clinician interaction, and its impact on treatment outcome

When meeting a clinician, we are often nervous, uneasy, and distressed about the situation. Many of us are anxious about what the doctor is about to tell us, and hope she/he will be reassuring and show genuine engagement in attempting to treat the illness or discomfort. Multiple studies have documented a substantial effect of the quality of the patient-clinician relationship on treatment outcome. A widespread understanding in the field is that a good patient-clinician relationship, characterized by trust, safety, and where the patient feels genuinely cared for, account for a large part of the unspecific effects, or placebo effects, which are prominent in health care and medical treatment across various conditions, and in particular pain, anxiety and depression. However, we know very little about how a good patient-provider relationship can lead to clinical improvement for the patient. This project aims to elucidate the neurobiological mechanisms, in the patient and the clinician, whereby a good relationship can improve the outcome of pain treatment. To investigate this, we conducted an experiment where clinicians performed pain treatment on patients suffering from chronic pain, during 2 different contexts. In half of the sessions, the clinician did a clinical intake of the patient prior to treatment, thereby establishing a clinical relationship (social interaction condition). In the other half, they did not do an intake and consequently did not establish a clinical relationship prior to treatment (no interaction condition). During treatment, we recorded the clinicians' and patients' brain activity using dual functional magnetic resonance imaging (fMRI), stress responses and (patients´) pain relief. Live audio-video transmission during fMRI scanning allowed clinicians and patients to communicate as if face-to-face. This setup enabled us to assess the impact of the clinical relationship on autonomic responses, brain-to-brain communication, and exchange of facial expression between clinicians and patients and in turn, pain outcomes, during live pain treatment. The results suggest that concordant activation (simultaneously in both patients and clinicians who interact) in brain circuitry involved in empathy and social mirroring (understanding the actions, feelings, and intentions of other people), underpins the patients´ placebo analgesia. The larger the patient-clinician concordance in this brain circuitry during pain treatment, the larger the patient´s pain relief (placebo analgesia). These preliminary findings have been presented orally at the research conferences Neuroscience 2018 (Society for Neuroscience), Association for Psychological Science (2019, APS), and The Society for Interdisciplinary Placebo Studies (2019, SIPS). Data collection for this first study is completed, and one manuscript has been submitted, while several others are being prepared for journal submissions. In a secondary experiment, we will assess a potential role of the hormone oxytocin, which is important for social bonding, in these relationship effects on pain. To investigate this, participants will self-administer a nasal spray containing either oxytocin or saline prior to the experiment. The project is a collaboration between Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, and the Department of Psychology, University of Oslo.

During my stay at the MGH/Harvard Medical School, I received training in cutting-edge neuroimaging techniques at one of the world's leading imaging centers, and gained extensive experience in managing clinical imaging studies, as well as valuable experience in supervision and project management. The FRIPRO funding enabled me to establish a lasting collaboration with MGH/Harvard that may be mutually beneficial for my career and future research projects at Oslo/Boston. Building on the FRIPRO-funded project, my mentors and I have started two follow-up studies - one longitudinal fMRI hyperscanning study (funded by a 5-year NIH R61/R33 grant) and one pseudonaturalistic EEG/fNIRS hyperscanning study. In the long term this research program may, by contributing knowledge about the neurobiological mechanisms of the patient-clinician relationship and how it affects clinical outcomes, help transform this art-of-medicine into a science of the clinical encounter and lead to improved clinical care.

The interaction between a patient and a clinician can significantly influence the treatment outcome - for better or for worse. This represents a resource that may be harnessed to improve clinical practice. The neurobiological mechanisms, through which the patient-clinician interaction influences treatment outcome, are not well-understood. Here, we employ an innovative translational approach to inspect the underlying behavioral, autonomic, and brain activity in both the patient and the clinician, during interactions characterized by either a "warm-empathetic" (augmented) treatment style or a cold "business-like" (limited) style. We expect patient-reported analgesia to be strongest in the augmented condition. We hypothesize that this analgesic effect will be mediated by mutual recruitment of pain modulatory brain systems, increased eye-contact, and synchronization of autonomic functioning between the patient and the clinician. Further, we expect that intranasal oxytocin, through its effects on social bond formation, will potentiate these effects specifically in the augmented interaction. In close collaboration with internationally leading experts in neuroscientific and behavioral studies of placebo effects and the clinical encounter at Harvard Medical School, the project manager will be trained in state-of-the-art methods for assessment and analysis of simultaneous recordings of brain and autonomic activity, and will be trained in organizing studies with clinical pain patients. Upon the reintegration to the Norwegian host institution, the project manager will set up a related experimental setup at the Univ. of Oslo, in collaboration with Dr. Laeng and Dr. Endestad, and implement pre-treatment of intranasal oxytocin and the unique on-site combination of fMRI and eye-tracking. This project provides unique training that will considerably benefit the project manager's academic career and promises a high potential for future collaborations between Harvard and Oslo.