Article Figures & Data
Figures
- Figure 1.
Alternating warm/pain task. In this task, subjects received 20 warm (40°C) and 20 painfully hot (3 s plateau) stimuli in an alternating manner separated by a 4 s ISI in which the temperature was 38°C. Three areas of the inner calf were used for the presentation of the heat stimuli. The thermode was moved from one area to the next after each warm and painful heat pair. Puffs of unscented air were delivered with each thermal stimulus. Subjects had to attend to the heat and were asked for their ratings at the end of the trial (see Materials and Methods for details). Because the baseline temperature and the rise/fall time were constants (38 and 10°C/s, respectively), the total duration of the task varied according to the temperatures used (higher painful temperatures resulted in longer duration). The shadowed boxes represent the time periods analyzed for brain activations. Periods of baseline heat when the thermode was not moved (pale gray boxes) were subtracted from painful heat periods (dark gray boxes).
- Figure 2.
Intensity discrimination task. For this task, both painful heat and odorants (pleasant or unpleasant) were delivered simultaneously. The thermode was moved after each pair of stimuli to another of the three regions of the inner calf. In the example shown here, the subjects attended the painful heat and performed the heat intensity discrimination task, evaluating whether the second stimulus of the pair was stronger or the same intensity as the first after each pair. Twelve discriminations were performed in each of the following four conditions: (1) attending heat in the presence of a good odor (AHGO); (2) attending heat in the presence of a bad odor (AHBO); (3) attending to a good odor in the presence of painful heat (AOGO); and (4) attending to a bad odor in the presence of painful heat (AOBO). The order was counterbalanced between subjects. At the end of the trial, subjects gave their ratings of pain intensity and unpleasantness, odor intensity and hedonics, mood, and anxiety (see Materials and Methods for details). Because the baseline temperature and the rise/fall time were constants (38 and 10°C/s, respectively), the total duration of the task varied according to the temperatures used (higher temperatures resulted in longer duration). The shadowed boxes represent the time periods analyzed for brain activations reported in this study. Periods of baseline with a touch component (pale gray boxes) were subtracted from periods of painful heat (dark gray boxes).
- Figure 3.
Thalamic and cortical activity evoked by heat pain in the alternating warm/pain task. The pain network activated by the painful heat stimuli when no attentional or emotional modulations are used is shown. Ipsi, Ipsilateral; Contra, contralateral. All figures depict neurological orientation (left is left).
- Figure 4.
Attentional modulation network. Attentional effects within the previously identified pain network are observed in the aIC. All figures depict neurological orientation (left is left).
- Figure 5.
Emotional modulation network. Emotional effects within the previously identified pain network are observed in ACC, thalamus, S2, and S1. All figures depict neurological orientation (left is left).
- Figure 6.
Possible pain modulating regions. A, Attentional condition weighted (w) with pain intensity scores for AHw and AOw conditions and with the difference in pain intensity ratings between attentional conditions (NRS score in AH minus NRS score in AO) for the subtraction AH − AOw. Activity within the SPP (BA7) and the ERC (BA28) correlated with both the pain intensity ratings and the change in pain intensity ratings between attentional conditions. Activity within aIC (the key perceptual region modulated by attention direction) covaried with superior parietal activity and, to a lesser degree (not statistically significant), with entorhinal activity in the AH condition. B, Emotional condition weighted with pain unpleasantness scores for BOw and GOw conditions and with the difference in pain unpleasantness ratings between emotional conditions (NRS score in BO minus NRS score in GO) for the subtraction BO − GOw. Activity within the LinfF, triangular and orbital parts (BA45/47), correlated with both the pain unpleasantness ratings and the change in pain unpleasantness ratings between emotional conditions. Activity within ACC (the key perceptual region modulated by mood) covaried with both the inferior frontal cortex and PAG activity in the BO condition. All figures depict neurological orientation (left is left).
Tables
Brain area Total volume (mm3) Threshold t for peak Threshold volume (mm3) for cluster with t > 2.5 Thresholds for pain processing-related areas S1 leg area 4229 3.2622 177 S2 9177 3.4989 324 aIC 6968 3.4171 268 Entire IC 14,509 3.6369 424 ACC 6647 3.4030 259 Perigenual cingulate 4840 3.3061 201 Thalamus 6892 3.3144 266 Thresholds for pain modulator areas ERC 2439 3.0855 93 PAG 385 2.4350 n.a. Superior parietal 12,906 3.6017 397 Inferior frontal cortex including lateral OFC 9000 3.4947 320 -
n.a., Not applicable.
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- Table 2.
Pain processing-related areas in the absence of attentional or emotional modulations
Region (BA) MNI coordinates t score Cluster size Contralateral ACC 8, 14, 34 3.466 368 Ipsilateral ACC −8, 12, 34 3.568 216 Contralateral insula 32, 16, 8 3.737 13,128 42, 6, −10 4.773 42, −4, −2 4.246 Contralateral S2 56, −14, 14 5.138 62, −18, 22 4.111 Ipsilateral insula −44, 2, 2 3.958 7112 −34, 2, 6 3.438 −34, −2, 10 3.446 −42, −8, 0 4.806 −42, −10, 2 4.820 −42, −14, 8 4.394 −38, −16, 18 3.648 Ipsilateral S2 −50, −24, 22 3.541 1632 Contralateral medialTH 6, −24, 0 5.532 1376 2, −18, 0 4.839 Contralateral S1 10, −42, 64 4.102 896 14, −44, 62 3.916 -
Thalamic and cortical regions show increased BOLD response during the alternating warm/pain condition for the painful stimuli compared with warm nonpainful baseline. Cluster size refers to the size of the cluster in cubed millimeters with t values superior to 2.5. t scores significant in global search are bolded and underlined. t scores and cluster sizes significant in the directed search are indicated in bold.
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Region (BA) Condition MNI coordinates t score Cluster size Attentional modulation Anterior insula AH −28, 16, 6 4.310 1160* AO −28, 16, 6 1.105 0 AH − AO −28, 14, 6 1.898 0 AH −34, 20, 16 3.579 1160* AO −34, 20, 16 0.792 0 AH − AO −34, 18, 16 1.898 0 Emotional modulation Contralateral ACC (BA24) BO 6, 4, 34 3.536 1800* GO 6, 4, 34 −0.493 0 BO − GO 6, 6, 30 3.195 760* BO 4, −4, 32 4.042 1800* GO 4, −4, 32 0.090 0 BO − GO 6, 0, 32 3.434 760* medialTH BO 2, −8, 0 3.871 208 GO 2, –8, 0 −0.881 0 BO − GO −2, −8, 0 3.501 456 Contralateral S2 BO 52, −38, 24 3.754 432 GO 52, −38, 24 −0.260 0 BO − GO 52, −40, 22 3.242 96 Contralateral S1 BO 22, −38, 62 3.934 816 GO 20, −32, 62 2.677 32 BO − GO 24, −38, 58 2.978 536 -
Cluster size refers to the size of the cluster in cubed millimeters with t values superior to 2.5. t scores and cluster sizes significant in the directed search are indicated in bold.
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↵*Same cluster with more than one peak.
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- Table 4.
Potential pain modulators associated with the attentional and emotional conditions
Region (BA) Condition MNI coordinates t score Cluster size Attentional modulation SPP (BA7) AHw −18, −50, 70 4.362 208 AOw −18, −50, 70 −1.375 0 AH − AOw −18, −50, 70 3.400 184 ERC (BA28) AHw 18, −4, −38 3.335 80 AOw 18, −4, −38 0.70 0 AH − AOw 14, −4, −34 3.171 104 Emotional modulation Inferior frontal gyrus—triangular part (BA45/47) BOw 46, 32, 10 3.464** 192 GOw 46, 32, 10 −0.507 0 BO − GOw 48, 32, 12 3.633 376 Inferior frontal gyrus—orbital part (BA47) BOw 50, 32, −4 5.364 1336 GOw 50, 32, −4 −1.364 0 BO − GOw 48, 32, −6 3.653 1344 -
The AH and AO conditions were weighted (w) with pain intensity scores, whereas the BO and GO conditions were weighted with pain unpleasantness scores. The subtractions were weighted with the change in pain intensity or unpleasantness ratings for the attention and emotion conditions, respectively. Cluster size refers to the size of the cluster in cubed millimeters with t values superior to 2.5. t scores significant in the directed search are indicated in bold. t scores significant in global search are bolded and underlined.
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↵**Approaching significance.
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- Table 5.
Covariation between the main pain processing-related areas modulated by attention (aIC) or emotion (ACC) and potential pain modulators
Region (BA) Condition MNI coordinates (x, y, z) t score Cluster size Attentional condition (areas that covary with aIC) aIC AH −28, 16, 6 5.623 5336 SPP (BA7) AH −18, −50, 70 4.333 224 ERC (BA28) AH 16, −4, −38 2.761 40 Emotional condition (areas that covary with ACC) ACC (BA24) BO −2, 10, 32 3.774 4672* BO 4, −2, 32 5.981 4672* Inferior frontal—triangular part (BA45/47) BO 46, 32, 10 4.158 752* Inferior frontal—orbital part (BA47) BO 48, 30, −4 3.706 752* PAG BO 6, −32, −16 3.184 480 -
Cluster size refers to the size of the cluster in cubed millimeters with t values superior to 2.5. t scores and cluster sizes significant in the directed search are indicated in bold. t scores significant in global search are bolded and underlined.
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↵*Same cluster with more than one peak.
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