Functional MRI of Pain- and Attention-Related Activations in the Human Cingulate Cortex

Abstract

The aims of the study were to use functional magnetic resonance imaging (fMRI) to 1) locate pain-related regions in the anterior cingulate cortex (ACC) of normal human subjects and 2) determine whether each subject's pain-related activation is congruent with ACC regions involved in attention-demanding cognitive processes. Ten normal subjects underwent fMRI with a 1.5-T standard commercial MRI scanner. A conventional gradient echo technique was used to obtain data from a single 4-mm sagittal slice of the left ACC, approximately 3.5 mm from midline. For each subject, interleaved sets of 6 images were obtained during a pain task, an attention-demanding task, and at rest, for a total of 36 images per task. Pain of different intensities was evoked via electrical stimulation of the right median nerve. The attention-demanding task consisted of silent word generation (verbal fluency). Additional experiments obtained data from the right ACC. A pixel-by-pixel statistical analysis of task versus rest images was used to determine task-related activated regions. The pain task resulted in a 1.6-4.0% increase in mean signal intensity within a small region of the ACC. The exact location of this activation varied from subject to subject, but was typically in the posterior part of area 24. The signal intensity changes within this region correlated with pain intensity reported by the subject. The attention-demanding tasks increased the mean signal intensity by 1.3-3.3% in a region anterior and/or superior to the pain-related activation in each subject. The activated region was typically larger than the pain-related activation. In some cases this activation was at or superior to the ACC border, near the supplementary motor area. These regions did not show any pain-intensity-related activation. In one subject both right and left ACC were imaged, revealing bilateral ACC activation during the attention task but only contralateral pain-related activation. These findings shed light on pain- and attention-related cognitive processes. The results provide evidence for a region in the posterior part of the ACC that is involved in pain and a more anterior region involved in other attention-demanding cognitive tasks.

A PET activation study of dynamic mechanical allodynia in patients with mononeuropathy

“…Acute phasic noxious stimulation has been used in most of these studies. Apart from some inconsistencies, there is a general consensus that such stimuli activate the anterior cingulate cortex (ACC) and the mid-/anterior insula of the medial pain system as well as the primary-and secondary somatosensory cortices (S1 and S2) of the lateral pain system Talbot et al, 1991;Casey et al, 1994Casey et al, , 1996Coghill et al, 1994;Apkarian, 1995;Davis et al, 1995Davis et al, , 1997Hsieh, 1995;Vogt et al, 1996). These ®ndings support the hypothesis that the experience of pain is processed in a parallel interactive and distributed fashion.…”

“…Also, when the rCBF was regressed on the rated pain intensity across conditions a signi®cant correlation was observed in the ACC (Davis et al, 1997;Derbyshire et al, 1997;Silverman et al, 1997). Thus, subjectively perceived pain intensity/ unpleasentness may be more important for the level of activity in the ACC than the type of pain.…”

“…A continuous activation of the medial pain system has been demonstrated in ongoing spontaneous pain (Hsieh et al, 1995a) and the ACC response shows correlation with the subjectively perceived pain intensity and unpleasantness (Davis et al, 1997;Derbyshire et al, 1997;Rainville et al, 1997). The variability of the perceived pain intensity may have been paralleled by a variable response in the medial pain system during both the allodynic and the rest states which may explain the lack of signi®cant activation in these structures when directly comparing the rCBF in the allodynic with the non-allodynic states.…”

Pain and functional imaging

“…The rostral section (perigenual part) has shown activation in almost all studies where the level of attention was unbalanced between the di¡erent states, which is analogous to the ACC activation in studies of executive attention (Bench et al 1992;Ghatan et al 1995;Pardo et al 1990). In contrasts that are balanced for components of attention, the pain-elicited activation in the ACC is generally more caudal and more con¢ned to the Brodmann area (BA) 24 0 (Davis et al 1997;Hsieh et al 1995). Thus, it seems that the general strati¢cation of the ACC into sub-regions of visceromotor, skeletomotor control cortex and nociceptive cortex, that was developed from animal studies and sparse human lesion data (Devinsky et al 1995), has been con¢rmed by functional imaging in man.…”

Cognitive interference is associated with neuronal marker N-acetyl aspartate in the anterior cingulate cortex: an in vivo 1H-MRS study of the Stroop Color-Word task

“…22,[63][64][65][66] Thus, it seems that the ACC does not play a specific role in cognitive interference, but rather is engaged in more general non-specific attentional states that are involved in the execution of the Stroop task (contributing to multiple cognitive functions during the Stroop performance, which become impossible without engagement of divided attention, errors detection, interference conflict, inhibition, affect). Our analysis of connectivity pattern in high vs low interference states suggests involvement of the prefrontal cortex as well, which is not surprising since this area has extensive reciprocal connections with ACC.…”