Human neuroimaging tasks

• Current fMRI resolution and techniques does not easily permit the identification of specific brainstem nuclei

• Tasks that activate regions may not activate the pathways of interest within regions. Therefore, the use of “probe tasks” chosen simply because they activate regions may not reveal meaningful signals.

Recent advances that may help include the following:

• High-field imaging (7T) e.g., Wald et al.
• Rapid imaging (multiband sequence) for physio noise reduction (Feinberg et al. 2010)
• Brainstem-specific normalization across participants (Eippert et al. 2009), or individual localizers/ROIs (Topolovec et al. 2004)
• Simultaneous physio recording for noise reduction and as predictors of autonomic signal (e.g., Chang and Glover 2009; Birn et al.; Wager et al. 2009)
• Multiple localizers to identify known nuclei if possible (e.g., Topolovec 2004)
• Pattern classification to identify patterns related to specific peripheral measures (e.g., Mitchell 2008; Kamitani and Tong 2004)
• Functional connectivity/pathway analysis to identify multiple elements of relevant circuits (e.g., Wager et al. 2009)
• T2-weighted images to identify some brainstem regions (e.g., STN; e.g., Aron et al. 2004)
• Cardiac-gated imaging (e.g., Beissner et al. 2011)
• Variable-TR and flip angle imaging (e.g., Sprenger et al. 2012)

• Activated by many task types: Pain, stressors, emotional words/faces, cognitive errors, complex cognitive tasks, trauma scripts, correlations with some peripheral cytokines and cortisol (e.g., O'Connor et al., Eisenberger, Liberzon, Pruessner), self-related evaluations (e.g., Denny et al. meta-analysis; Northoff meta-analysis).
• Emotion meta-analysis: happy and sad emotions, food, odors and personal events
• Specific evidence on rdACC connections with PAG and heart rate in social evaluative threat task (speech preparation; Wager et al. 2009)

• Activated by many task types: Neuroeconomic value (e.g. Rangel), long-term memory recall and prospection (e.g., Schacter, McDermott meta-analysis), fear extinction recall (e.g., Milad),
• Deactivated by pain, stressors, negative correlations with cortisol (e.g., Eisenberger 2009) and heart rate (e.g., Wager 2009)
• Emotion meta-analysis: happy and fear emotions, food, personal events
• Specific evidence on negative VMPFC connections with PAG and heart rate in social evaluative threat task (speech preparation; Wager et al. 2009) and positive correlations with heart-rate variability (Gianaros et al. 2004)

• Activated by pain and aversive images (IAPS; e.g., Buhle et al. 2012), and likely fear conditioning. Pain is the most reliable and well-demonstrated (e.g., Tracey 2008; Fairhurst et al.), but PAG has multiple functional columns that serve different functions.
• Emotion meta-analysis: affect (mixed events), sad, music, personal events, sentences
• Specific evidence on negative VMPFC connections with PAG and heart rate in social evaluative threat task (speech preparation; Wager et al. 2009)

• Activated by fear faces and other faces, IAPS images (stronger for faces; e.g., Phan et al. 2004, Wager et al. 2008), aversive sounds. No reliable response to pain or social evaluative threat. Activated by brief, salient sensory stimuli (e.g., conditioned fear cues; Phelps 2004), even if unconsciously presented (e.g., Whalen et al. 2004).
• Emotion meta-analysis: negative, fear, odors, sounds

• Activated by food cues/consumption, pain (though not well documented), other emotion tasks (but not studied systematically).
• Emotion meta-analysis: slight positive bias, contempt, humor, film, odor, food, sentences

• Activated reliably by pain (but not studied systematically), modulation with expectation and placebo (e.g., Petrovic 2002, Eippert 2009, Atlas 2010).
• Emotion meta-analysis: negative, anger, sad, odors, personal events
• Likely tasks involve primary reinforcers and drive states, somatic stimulation, correlations with autonomic outcomes across time.
• Topolovec et al. 2004 studied several tasks that activated different regions of pons and medulla:

general visceral (the isometric hand-grip, maximal inspiration, Valsalva maneuver) or special visceral sensory systems (sucrose administration to the tongue). Activation of the nucleus of the solitary tract and parabrachial nucleus was observed with all general visceral tasks. Raphe activation was reported in response to isometric hand-grip and maximal inspiration tasks.

• Activated reliably by pain (but not studied systematically), some reports of modulation with placebo (e.g., Eippert 2009). Activated by basic, primary sensory stimuli (e.g., taste, swallowing; Topolovec 2004).
• Emotion meta-analysis: Not enough reported contrasts to analyze.
• Very little reliable data on any tasks. Often not in coverage area in neuroimaging studies.
• Likely tasks: pain, somatic stimulation, correlation with specific autonomic outcomes across time.

Aron, A. R., & Poldrack, R. A. (2006). Cortical and subcortical contributions to Stop signal response inhibition: role of the subthalamic nucleus. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 26(9), 2424–2433. doi:10.1523/JNEUROSCI.4682-05.2006 Beissner, F., Deichmann, R., & Baudrexel, S. (2011). fMRI of the brainstem using dual-echo EPI. NeuroImage, 55(4), 1593–1599. doi:10.1016/j.neuroimage.2011.01.042 Birn, R. M., Murphy, K., Handwerker, D. A., & Bandettini, P. A. (2009). fMRI in the presence of task-correlated breathing variations. NeuroImage, 47(3), 1092–1104. doi:10.1016/j.neuroimage.2009.05.030 Chang, C., Cunningham, J. P., & Glover, G. C. (2009). Influence of heart rate on the BOLD signal: the cardiac response function. NeuroImage, 44(3), 857–869. doi:10.1016/j.neuroimage.2008.09.029 Fairhurst, M., Wiech, K., Dunckley, P., & Tracey, I. (2007). Anticipatory brainstem activity predicts neural processing of pain in humans. Pain. Feinberg, D. A., Moeller, S., Smith, S. M., Auerbach, E., Ramanna, S., Glasser, M. F., et al. (2010). Multiplexed Echo Planar Imaging for Sub-Second Whole Brain FMRI and Fast Diffusion Imaging. PLoS ONE, 5(12), e15710. doi:10.1371/journal.pone.0015710.g006 Polimeni, J. R., Fischl, B., Greve, D. N., & Wald, L. L. (2010). Laminar analysis of 7T BOLD using an imposed spatial activation pattern in human V1. NeuroImage, 52(4), 1334–1346. doi:10.1016/j.neuroimage.2010.05.005 Sprenger, C., Eippert, F., Finsterbusch, J., Bingel, U., Rose, M., & Buchel, C. (2012). Attention Modulates Spinal Cord Responses to Pain. Current Biology. doi:10.1016/j.cub.2012.04.006 Wager, T. D., Waugh, C. E., Lindquist, M. A., Noll, D. C., Fredrickson, B. L., & Taylor, S. F. (2009). Brain mediators of cardiovascular responses to social threat: part I: Reciprocal dorsal and ventral sub-regions of the medial prefrontal cortex and heart-rate reactivity. NeuroImage, 47(3), 821–835. doi:10.1016/j.neuroimage.2009.05.043