Background & Aims

The anterior Mid-Cingulate Cortex (aMCC), sometimes referred to as dorsal Anterior Cingulate Cortex (dACC), has been identified as a key region involved in pain processing (Vogt, 2016). Conversely, recent integrationist theories suggest that aMCC may act as a co-localized functional hub for pain as well as other processes from distinct psychological domains, including negative emotion and cognitive control (Shackman et al., 2011). While task-based functional Magnetic Resonance Imaging (fMRI) studies have demonstrated considerable evidence of aMCC’s involvement during pain and non-pain manipulations (Kragel et al., 2018), how the region is involved in carrying out distinct functions in synchrony with the whole brain has not been investigated. Using task-based functional connectivity analysis, the current study aims to explore the functional connectivity differences between the whole brain and the aMCC during pain, negative emotion and cognitive control tasks.

Methods

23 healthy adults (12 males) with no pain underwent fMRI scans while completing tasks that induced pain, negative emotions and cognitive control using thermal stimulation, the threat-of-shock paradigm and the Multi-Source Inference Task, respectively, presented in counterbalanced order. The co-activated region in the aMCC during all three tasks was constructed as the seed for connectivity analysis. Using the Statistical Parametric Mapping (SPM, https://www.fil.ion.ucl.ac.uk/spm/)-based functional connectivity package CONN-toolbox (22a, Whitfield-Gabrieli & Nieto-Castanon, 2012), Pearson’s correlation scores were computed between each voxel and the seed for each task at first level and normalized using Fisher’s r to z transformation. Normalized seed-based connectivity maps for each participant per task were entered into a repeated-measure ANOVA, specified through the second-level analysis function in SPM.

Results

Cluster-level Family Wise Error thresholding was used to correct for multiple comparisons in all results. Repeated-measure ANOVA revealed differences in functional connectivity during pain, negative emotion and cognitive control tasks between aMCC and right Posterior Insula (pIns), right Postcentral Gyrus (S1) and dorsomedial prefrontal cortex (DMPFC). Post-hoc paired-sample t-test identified stronger functional connectivity of aMCC with right pIns and right S1 during both negative emotion and pain compared to cognitive control. Stronger functional connectivity between aMCC and DMPFC was identified in pain compared to cognitive control. No functional connectivity difference was identified between the threat and pain tasks.

Conclusions

Taken together, the present study identified differences in whole brain connectivity patterns in relation to the aMCC under distinct psychological paradigms. While activations in the aMCC during pain, cognitive control and negative emotion tasks have been observed in the literature and this study, the present findings suggest that aMCC connectivity to sensory and prefrontal areas is distinguishable based on the cognitive load of the task, as compared to pain or negative emotion. Results warrant future research to investigate (1) how the aMCC is incorporated into executing cognitive functions and (2) to what extent pain and negative emotion processing have shared mechanisms of functioning in the brain.

References

Kragel, P. A., Kano, M., Van Oudenhove, L., Ly, H. G., Dupont, P., Rubio, A., Delon?Martin, C., Bonaz, B., Manuck, S. B., Gianaros, P. J., ?eko, M., Losin, E. a. R., Woo, C., Nichols, T. E., & Wager, T. D. (2018). Generalizable representations of pain, cognitive control, and negative emotion in medial frontal cortex. Nature Neuroscience, 21(2), 283–289. https://doi.org/10.1038/s41593-017-0051-7

Shackman, A. J., Salomons, T. V., Slagter, H. A., Fox, A. S., Winter, J., & Davidson, R. J. (2011). The integration of negative affect, pain and cognitive control in the cingulate cortex. Nature Reviews Neuroscience, 12(3), 154–167. https://doi.org/10.1038/nrn2994

Vogt, B. A. (2016). Midcingulate cortex: Structure, connections, homologies, functions and diseases. Journal of Chemical Neuroanatomy, 74, 28–46. https://doi.org/10.1016/j.jchemneu.2016.01.010

Whitfield?Gabrieli, S., & Nieto-Castañón, A. (2012). CONN: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connectivity, 2(3), 125–141. https://doi.org/10.1089/brain.2012.0073

Presenting Author

Yuan Yao

Poster Authors

Yuan Yao

BSc(Hons)

University of Western Ontario

Lead Author

Topics

  • Pain Imaging