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Representation of aversive prediction errors in the human periaqueductal gray
Open accessAbstract
Pain is a primary driver of learning and motivated action. It is also a target of learning, as nociceptive brain responses are shaped by learning processes. We combined an instrumental pain avoidance task with an axiomatic approach to assessing fMRI signals related to prediction errors (PEs), which drive reinforcement-based learning. We found that pain PEs were encoded in the periaqueductal gray (PAG), a structure important for pain control and learning in animal models. Axiomatic tests combined with dynamic causal modeling suggested that ventromedial prefrontal cortex, supported by putamen, provides an expected value–related input to the PAG, which then conveys PE signals to prefrontal regions important for behavioral regulation, including orbitofrontal, anterior mid-cingulate and dorsomedial prefrontal cortices. Thus, pain-related learning involves distinct neural circuitry, with implications for behavior and pain dynamics.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Negative correlations with PE (greater activity for better-than-expected outcomes) were found in the entorhinal/parahippocampal cortices, right inferior frontal gyrus, right temporal pole and right lateral thalamus (Fig. 1d and Supplementary Table 1).”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Aversive prediction error signals
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The signal-to-noise (SNR) ratio in the ventral striatum (171.13 ± 9.68) and PAG (163.20 ± 5.57) were not significantly different (p >0.23).”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Studies 2 and 3: Monetary rewards and varying pain levels
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In the paper
“In accordance with Axiom #2, activity was higher during pain for low vs. high pain conditioned cues (F(1,49) = 4.39, p < 0.05)”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Studies 2 and 3: Monetary rewards and varying pain levels
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“As expected, in contradistinction to the main study, appetitive PEs to monetary rewards were tracked by activity in the VS. (t(20) = 5.77, p < 0.001), but not the PAG (PAG–appetitive: t(20) = 1.54, p = 0.14; see Supplementary Fig. 2).”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Studies 2 and 3: Monetary rewards and varying pain levels
What the sources say
- Not checked yetcites [23] Wimmer, G.E., Daw, N.D. & Shohamy, D. Generalization of value in reinforcement learning by humans. Eur. J. Neurosci. 35, 1092–1104 (2012). source
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In the paper
“Finally, follow-up ROI analyses of response patterns within these regions revealed that the midbrain shows a significant correlation with expected value on No-Stimulus trials (t(22)=–1.82, p<0.05, one-tailed) that did not meet the whole-brain threshold (blue in Fig. 3b).”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Expectancies and other learning-related variables
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In the paper
“It showed reduced responses to outcomes with greater pain expectancy, for both Pain and No-Stimulus trials (Axiom #2; Pain trials: t(22)=–2.05, p < 0.05; No-Stimulus trials: t(22)=–1.98, p < 0.05)”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Aversive prediction error signals
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In the paper
“Conversely, negative activations were observed in the aMCC, lateral frontal pole, parietal operculum, cerebellum and visual cortex.”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Expectancies and other learning-related variables
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The PAG responded more strongly to Pain than No-Stimulus trials, holding pain expectancy constant (Axiom #1; t(22) = 3.67, p <0.05).”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Aversive prediction error signals
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In the paper
“Positive effects (i.e., greater activity with high avoidance value or low pain expectancy) were observed in the ventromedial prefrontal cortex (vmPFC), and in particular in the medial OFC and perigenual anterior cingulate cortex (pgACC).”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Expectancies and other learning-related variables
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As expected, participants switched options more frequently after receiving pain than no stimulus (40.5±4.2% vs. 6±1.1% of trials, p < .0001).”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Behavioral results
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- It may state two separate claims as one. 26
- Probably not a substantial claim. 11
In the paper
“The analysis revealed learning rates (α=0.63±0.26), softmax inverse temperatures (β=4.74±2.74), and model fits (negative log likelihood = 65 ± 21) comparable to those found in similar studies of reinforcement learning20.”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Behavioral results
What the sources say
- Not checked yetcites [20] Schönberg, T., Daw, N.D., Joel, D. & O'Doherty, J.P. Reinforcement learning signals in the human striatum distinguish learners from nonlearners during reward-based decision making. J. Neurosci. 27, 12860–12867 (2007). source
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In the paper
“The effects of pain on switching also decayed exponentially with time, as evidenced by the results of logistic regressions assessing the effects of reinforcement history (pain delivered 1 to 6 trials back) on switches (p < 0.05 for 1 to 2 trials back; see Fig. 1c).”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Behavioral results
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Activity correlating with model-based aversive PEs (greater activity for worse-than-expected outcomes) was found in several areas, as shown in Figure 1d. These included the left anterior insula, anterior and midcingulate cortices (ACC and MCC), the right pre- and post- central gyrii, the right dorsolateral prefrontal cortex (dlPFC), and a large cluster in the midbrain encompassing the periaqueduct”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Aversive prediction error signals
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Several regions identified in the conjunction analysis correlated with PEs only on pain trials (blue in Fig. 3a), including the left OFC, anterior MCC (aMCC), dorsomedial prefrontal cortex (dmPFC) and a larger dorsal midbrain cluster comprising the PAG, tectum, DRN, NCF and red nucleus (RN).”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Expectancies and other learning-related variables
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was no activity difference between Pain and No-Stimulus trials when outcomes were highly predicted (t(22): 0.56, p > 0.4, odds in favor of the null: 5.13), thereby confirming Axiom #3.”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Aversive prediction error signals
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We identified clusters in the left putamen, vmPFC, and right hippocampus in which activity fit this profile, consistent with expectancy effects. These regions displayed increased activity when pain was expected to be avoided (low pain expectancy), but didn't respond differentially to pain vs. No-stimulus outcomes (green clusters in Fig. 3a).”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Expectancies and other learning-related variables
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In the paper
“This was caused by complete reliance on a win-stay loose-shift strategy (1 subject), frequent switches in choice following absence of pain, which was caused by use of an irrelevant strategy (1 subject), or numerous missing responses (20% missing; 1 subject).”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > Reinforcement model-based analysis
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this model, vmPFC projects most directly to PAG, and avoidance value is most closely related to the putamen, which transmits value information to vmPFC.”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > fMRI data analyses
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: Primary nociceptive afferents project directly to the PAG.
- The authors state this as an assumption: Expected avoidance value reaches the PAG through at least one of the three expected-value structures (vmPFC, putamen, hippocampus).
- The authors state this as an assumption: Prediction error signals can be sent directly to the OFC and aMCC, and indirectly to the dmPFC via either aMCC or OFC.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The best model overall is shown in Figure 4, and included a) direct connections from both putamen and midbrain to OFC and aMCC, with dmPFC effects mediated by OFC, and b) modulatory effects of noxious input to putamen → OFC, putamen → aMCC, and midbrain → aMCC connections.”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > fMRI data analyses
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: Primary nociceptive afferents project directly to the PAG.
- The authors state this as an assumption: Expected avoidance value reaches the PAG through at least one of the three expected-value structures (vmPFC, putamen, hippocampus).
- The authors state this as an assumption: Prediction error signals can be sent directly to the OFC and aMCC, and indirectly to the dmPFC via either aMCC or OFC.
In the paper
“Our data and connectivity models identify the PAG as a primary site for aversive PEs, in contrast to previous neuroimaging findings and theories that a single system drives appetitive and aversive PEs29.”
§ Representation of aversive prediction errors in the human periaqueductal gray > DISCUSSION > Towards a neural systems model for aversive PEs
What the sources say
- Not checked yetcites [29] Brooks, A.M. & Berns, G.S. Aversive stimuli and loss in the mesocorticolimbic dopamine system. Trends Cogn. Sci. 17, 281–286 (2013). source
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In the paper
“All participants provided informed consent. The study was approved by the Columbia University Institutional Review Board.”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > Participants
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, results from this Supplementary experiment replicate and extend the findings of pain-related aversive prediction errors in the PAG, demonstrating sensitivity to the level of painful stimulus intensity and sensitivity to verbal instructions as well as predictive cues.”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Studies 2 and 3: Monetary rewards and varying pain levels
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hence, our results seem to indicate both a convergence between appetitive and aversive systems in value representations in the vmPFC, and a segregation between the two systems when these expected values signals are integrated with ascending aversive unconditioned stimuli (US) inputs in the PAG to generate PE signals.”
§ Representation of aversive prediction errors in the human periaqueductal gray > DISCUSSION > Overlap in systems for reward and aversive PEs
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Results were cluster-corrected (p<0.05, FWE, two-tailed) with cluster-defining thresholds of p <0.001, p<0.01 and p<0.05 using AFNI's alphasim.”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > fMRI data analyses
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Then, PE and expected value signals from the midbrain and putamen are transmitted to OFC and aMCC, with effects on dmPFC mediated by OFC.”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Network dynamics underlying aversive PE signals
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The PAG a priori ROI was constructed by aligning three overlapping 6-mm spheres along the central aqueduct ([0 –24 –4; 0 –26 –6; 0 –29 –8]), and closely matched the findings of a recent meta-analysis on pain-processing in the PAG (Linnman, Moulton, Barmettler, Becerra, & Borsook, 2012a).”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > fMRI data analyses
What the sources say
- Not checked yetcites Linnman, Moulton, Barmettler, Becerra, & Borsook, 2012a
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, findings in this larger midbrain cluster are consistent with aversive PE signals, though the dorsal PAG region was the only portion to survive whole-brain correction in all three contrasts.”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Expectancies and other learning-related variables
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In the paper
“PAG neurons respond more strongly to unexpected vs. expected electric shocks18, consistent with our fMRI findings here.”
§ Representation of aversive prediction errors in the human periaqueductal gray > DISCUSSION > Towards a neural systems model for aversive PEs
What the sources say
- Not checked yetcites [18] Johansen, J.P., Tarpley, J.W., LeDoux, J.E. & Blair, H.T. Neural substrates for expectation-modulated fear learning in the amygdala and periaqueductal gray. Nat. Neurosci. 13, 979–986 (2010). source
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In order to minimize the effects of peripheral sensitization/habituation, the thermode was moved to a new skin spot after each run.”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > Thermal stimulation
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The aMCC in particular is critical for pain avoidance18 and is heavily connected to motor and premotor centers (aMCC).”
§ Representation of aversive prediction errors in the human periaqueductal gray > DISCUSSION > Towards a neural systems model for aversive PEs
What the sources say
- Not checked yetcites [18] Johansen, J.P., Tarpley, J.W., LeDoux, J.E. & Blair, H.T. Neural substrates for expectation-modulated fear learning in the amygdala and periaqueductal gray. Nat. Neurosci. 13, 979–986 (2010). source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“This is consistent with recent findings that the vmPFC may act as a “hub” or “convergence point” for different types of expected value signals, such as experienced-based expected value signals computed in the putamen and model-based value signals computed in the caudate48.”
§ Representation of aversive prediction errors in the human periaqueductal gray > DISCUSSION > Overlap in systems for reward and aversive PEs
What the sources say
- Not checked yetcites [48] Wunderlich, K., Dayan, P. & Dolan, R.J. Mapping value based planning and extensively trained choice in the human brain. Nat. Neurosci. 15, 786–791 (2012). source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results are consistent with the vmPFC as the most direct representation of value as related to choice and learning (Fig. 3 and Supplementary Fig. 4), and most closely connected to the PAG in the retained DCM model.”
§ Representation of aversive prediction errors in the human periaqueductal gray > DISCUSSION > Overlap in systems for reward and aversive PEs
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In the paper
“Three participants were excluded from the analysis because of their poor performance on task (see section on reinforcement model-based analysis below).”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > Participants
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Noxious input had direct effects on PAG, in keeping with the known anatomy of the ascending spinomesencephalic nociceptive pathway28, and modulatory effects on ascending putamen-to-OFC, putamen-to-aMCC, and midbrain-to-aMCC connections.”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Network dynamics underlying aversive PE signals
What the sources say
- Not checked yetcites [28] Millan, M.J. The induction of pain: an integrative review. Prog. Neurobiol. 57, 1–164 (1999). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Temperatures were individually calibrated to be at a level 7 on a continuous scale ranging from 0 to 8 (0, no sensation; 1, nonpainful warmth; 2, low pain; 5, moderate pain; 8, maximum tolerable pain), during a practice session performed on a separate day prior to the imaging session. This procedure ensured that participants received the most painful level of the temperature within tolerance”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > Thermal stimulation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The PAG receives monosynaptic inputs from both nociceptive spinal projection neurons28 and top-down projections from the vmPFC30, positioning it as a potential comparator of ‘bottom up’ aversive sensations with expectations.”
§ Representation of aversive prediction errors in the human periaqueductal gray > DISCUSSION > Towards a neural systems model for aversive PEs
What the sources say
- Not checked yetcites [28] Millan, M.J. The induction of pain: an integrative review. Prog. Neurobiol. 57, 1–164 (1999). source
- Not checked yetcites [30] Price, J.L. Definition of the orbital cortex in relation to specific connections with limbic and visceral structures and other cortical regions. Ann. NY Acad. Sci. 1121, 54–71 (2007). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The other three regions showed little evidence for expectancy effects on No-Stimulus trials (Bayes factors in favour of the null all > 2.24), and thus are more likely to reflect avoidance value updating or other motivational processes.”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Expectancies and other learning-related variables
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In order to maximize signal in the vmPFC, slices were tilted by 30° from AC-PC axis, resulting in a loss of coverage in dorso-posterior parietal areas, including S1 in the arm area. We were therefore unable to assess the contribution of S1 in pain avoidance learning.”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > fMRI data acquisition and preprocessing
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the final, most likely model (Fig. 4), vmPFC projects most directly to PAG among value-encoding regions, and avoidance value is most closely related to the putamen, which transmits value information to vmPFC.”
§ Representation of aversive prediction errors in the human periaqueductal gray > RESULTS > Network dynamics underlying aversive PE signals
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The VS ROI was based on Rutledge et al. (2010)9 nucleus accumbens ROI and was comprised of three 5 mm spheres for each hemisphere ([8 13 –3; 12 13 –8; 9 13 –7; –8 13 –3; –12 13 –8; –9 13 –7 ]).”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > fMRI data analyses
What the sources say
- Not checked yetcites Rutledge et al. (2010) source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Though this procedure cannot definitively isolate causal relationships among regions, this model provides a plausible working model considering the direct anatomical projections from vmPFC to PAG30.”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > fMRI data analyses
What the sources say
- Not checked yetcites [30] Price, J.L. Definition of the orbital cortex in relation to specific connections with limbic and visceral structures and other cortical regions. Ann. NY Acad. Sci. 1121, 54–71 (2007). source
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: Primary nociceptive afferents project directly to the PAG.
- The authors state this as an assumption: Expected avoidance value reaches the PAG through at least one of the three expected-value structures (vmPFC, putamen, hippocampus).
- The authors state this as an assumption: Prediction error signals can be sent directly to the OFC and aMCC, and indirectly to the dmPFC via either aMCC or OFC.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Based on the principles governing RL models (Fig. 2a), regions that encode aversive PEs (PAG) should receive converging input from those that encode expectancies (vmPFC, putamen, hippocampus) and primary reinforcement (nociceptive) signals. Regions important for action value and decision-making (aMCC, OFC, and dmPFC) may receive converging PE and primary reinforcement signals.”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > fMRI data analyses
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Based on existent animal models of fear conditioning1,18, we posited that these regions receive the PE signals generated in PAG.”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > fMRI data analyses
What the sources say
- Not checked yetcites [1] McNally, G.P., Johansen, J.P. & Blair, H.T. Placing prediction into the fear circuit. Trends Neurosci. 34, 283–292 (2011). source
- Not checked yetcites [18] Johansen, J.P., Tarpley, J.W., LeDoux, J.E. & Blair, H.T. Neural substrates for expectation-modulated fear learning in the amygdala and periaqueductal gray. Nat. Neurosci. 13, 979–986 (2010). source
Tests✗ Asserted: fails✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. The authors may not put it forward as true.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Unfortunately, this axiom cannot be fully tested here because the outcome is never fully predicted by the cue (50%–50%), and the non-linear relationship between temperature and pain makes it difficult to precisely estimate expectations.”
§ Representation of aversive prediction errors in the human periaqueductal gray > Online Methods > Study 3 – Comparison of different pain levels
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The authors state this as an assumption.
Primary nociceptive afferents project directly to the PAG.
“1) primary nociceptive afferents directly project to PAG28”
The authors state this as an assumption.
Expected avoidance value reaches the PAG through at least one of the three expected-value structures (vmPFC, putamen, hippocampus).
“2) expected avoidance value is conveyed to the PAG through one or more of the three expected value structures (green in Fig. 3).”
The authors state this as an assumption.
Prediction error signals can be sent directly to the OFC and aMCC, and indirectly to the dmPFC via either aMCC or OFC.
“we constrained the space of possible models by assuming that PE signals could be directly conveyed to the OFC and aMCC32, and indirectly to the dmPFC through either aMCC or OFC.”
The authors state this as an assumption.
Higher pain is always more aversive than lower pain (monotonicity in pain intensity).
“namely, that higher pain is always more aversive than lower pain (monotonicity in pain intensity)”
The authors state this as an assumption.
High versus low expectancies are similarly monotonic.
“and that high vs. low expectancies are similarly monotonic.”
The authors state this as an assumption.
More intense noxious stimulus intensities are more aversive (monotonicity of aversiveness with stimulus intensity).
“we adapted study 1 axioms by making the additional assumption that more intense noxious stimulus intensities should be more aversive (i.e., monotonicity of aversiveness with stimulus intensity).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“However, three decision-making studies (Seymour et al., 2012; Roy et al., 2014; Eldar et al., 2016) that involved avoiding pain or shock examined prediction errors to successful and unsuccessful avoidance, and two found evidence for striatal prediction errors to successful avoidance of shock.”
From Active avoidance: Neural mechanisms and attenuation of pavlovian conditioned responding (2017) · cites this paper as Roy et al., 2014
In the citing paper
“The vmPFC, rather than regions included in the NPS, correlates with spontaneous, clinical pain [52], and encodes the learned, behavioral avoidance value associated with painful stimulation [85],[86].”
From Distinct Brain Systems Mediate the Effects of Nociceptive Input and Self-Regulation on Pain (2015) · cites this paper as [86]
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- Not confirmedt(22) = -2.05reported p < .05 · recomputed p = .052
“t(22)=-2.05, p < .05”
- Not confirmedt(22) = -1.98reported p < .05 · recomputed p = .060
“t(22)=-1.98, p < .05”
- Consistentt(22) = 3.67reported p < .05 · recomputed p = .001
“t(22) = 3.67, p < .05”
- Consistentt(20) = 5.77reported p < .001 · recomputed p < .001
“t(20) = 5.77, p < .001”
- Consistentt(20) = 1.54reported p = .14 · recomputed p = .139
“t(20) = 1.54, p = .14”
- ConsistentF(1, 49) = 4.39reported p < .05 · recomputed p = .041
“F(1,49) = 4.39, p < .05”
- ConsistentF(1, 49) = 16.03reported p < .001 · recomputed p < .001
“F(1,49) =16.03, p < .001”
- Consistentt(22) = -1.82reported p < .05 · recomputed p = .082
“t(22)=-1.82, p < .05”
The paper states a one-tailed test
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Self-check results appear here once an independent check has confirmed them.
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Research works printed but not linked: 1
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Metadata
- Authors
- Roy, M., Shohamy, D., Daw, N., Jepma, M., Wimmer, G. E., & Wager, T. D.
- Affiliations
- University of Colorado Boulder (US)
- New York University (US)
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Wager, Tor D
- Venue
- Nature Neuroscience
- Published
- 2014-10-05
- Volume
- 17
- Issue
- 11
- Pages
- 1607-1612
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4213247
- OpenAlex
- W1995906064
- Semantic Scholar
- 3b5deee843f5e9ff6e35df44aee33bc777a01def
- Cited by
- 246
- References
- 52
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 20 · 2023: 19 · 2022: 24 · 2021: 20 · 2020: 24 · 2019: 16 · 2018: 24 · 2017: 27 · 2016: 18 · 2015: 18 · 2014: 2
- FWCI
- 12.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Canadian Institutes of Health Research
- National Institute of Mental Health (R01MH076136)
- National Institute on Drug Abuse (R01DA027794, R01DA035484)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- periaqueductal gray, pain, pain avoidance, reinforcement learning, expected value, ventromedial prefrontal cortex, putamen, midbrain, dynamic causal modeling, axiomatic analysis, nociception, pain management, orbitofrontal cortex, anterior midcingulate cortex, dorsomedial prefrontal cortex
- MeSH terms
- Adolescent, Adult, Behavior, Brain Mapping, Female, Gyrus Cinguli, Humans, Learning, Magnetic Resonance Imaging, Male, Pain, Periaqueductal Gray, Reinforcement, Psychology, Prefrontal Cortex, Young Adult, Pain Management
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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