Background and aims FMRI-Neurofeedback (NF) has shown to be a promising technique to characterize and modify brain-behavior interactions in both healthy individuals and various clinical conditions. In the field of pain research, it can be seen as an excellent tool to up- and downregulate both individual brain activation hotspots as well as connectivity patterns related to pain-relevant mechanisms to delineate important brain circuits in pain chronicity. The aim of this study is to integrate dynamic functional connectivity (dFC)-informed neurofeedback of emotion-related brain pathways to modulate pain and evaluate its feasibility and efficiency, also determining potential individual characteristics, that might significantly contribute to neurofeedback performance and related outcomes. Method Healthy participants as well as participant with chronic low-back pain undergo a NF training of up- and down-regulation of amygdala-dlPFC connectivity (4 consecutive days, each with six alternating blocks including 6 trials of 50s NF intermitted by 2-back tasks of 25s). During NF acute pain was continually evoked using individually pre-set electric stimulation. Brain regions of interest were individualized using a combined machine learning and dFC-GLM approach based on metanalytic results. Two transfer-blocks are applied after the last NF-session. Prior to the first NF-session subjects answered pain and mood related as well as general psychological questionnaires and conducted cognitive tests and quantitative sensory testing which were repeated three weeks after last NF-session. Results First results show significant individual variations with relation to NF-regulation success of DLPFC-Amygdala dFC, both across individuals and along the training course. DFC and regulation signal is significantly correlated with DLPFC-activation but not with Amygdala-activation. Individual psychological and pain-related factors like locus of pain control, mental comorbidities and mood-states vary and may define subgroups that will be investigated for association with NF-regulation. Conclusion The results highlight the complexity of connectivity-informed neurofeedback and enhance on the one hand the importance of methodological as well as theoretical advances for the implementation of this method, and on the other hand also demonstrate potential key modulatory factors, which are important to increase the mechanistic understanding and specifically gain importance when bringing findings into clinical application.
Pain conditions are a major health problem. While brain correlates of (chronic) pain in adulthood has been described, epidemiological studies spanning adolescence to adulthood and thus the transition of pain are rare.The aim of this study was to examine the link of functional brain (re)organization to pain complaints from late adolescence into early adulthood. We used individual resting-state fMRI-data (age: 19 and 23) from the IMAGEN project to build individual functional connectomes of cortical nodes and basal ganglia structures known to be involved in pain processing for each timepoint. Brain reorganization was operationalized as the difference between functional connectomes at age 23 and 19. The Children's Somatization Inventory was used as measure of pain complaints. We then calculated the association of every connectivity of the functional connectomes on pain complaints. At age 19 we did not find significant associations of functional connectomes with pain complaints. However, we found multiple significant associations at age 23, most prominent negative associations of connectivities of the subthalamic nucleus to cortical networks, and positive associations for connectivities between multiple cortical nodes. These associations were even more pronounced for the difference between functional connectomes at age 19 and 23. These data indicate a significant transition in brain-pain associations from late adolescence into early adulthood, with cortico-basal loops as the main brain correlates, and underscores adolescence as a sensitive period not only for the development of mental, but also somatic disorders.
