The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index; 1 of the 24 sources its claims cite were checked for support.
A human brain network derived from coma-causing brainstem lesions
Open accessAbstract
OBJECTIVE: To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. METHODS: We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. RESULTS: A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. CONCLUSIONS: Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
A case-control lesion analysis identified a 2-mm³ coma-specific region in the left rostral dorsolateral pontine tegmentum, near the medial parabrachial nucleus. In healthy adults this brainstem site was functionally connected to the anterior insula (AI) and pregenual anterior cingulate cortex (pACC), and AI–pACC connectivity was disrupted in patients with disorders of consciousness.
Key findings
- Coma-causing lesions maximally overlapped in the pontine tegmentum (10 of 12 cases), whereas control lesions primarily involved the pontine base (11 of 24); voxel-based lesion-symptom mapping identified a 2-mm³ coma-specific region in the left pontine tegmentum, with 10 of 12 coma lesions but only the periphery of 1 of 24 control lesions involving it.
- In 98 healthy right-handed participants (48 men, ages 22 ± 3.2 years), the coma-specific brainstem region was functionally connected to the left ventral AI and pACC; these nodes were more connected to coma lesions than control lesions (p < 0.05).
- Partial correlations were stronger between brainstem and AI (r = 0.15) and between AI and pACC (r = 0.26) than between brainstem and pACC (r = 0.06).
- In patients with disorders of consciousness (26 MCS, 19 VS/UWS, 6 coma, 21 controls), connectivity was reduced in all networks (p < 0.001), but only AI–pACC connectivity was absent in MCS/VS/UWS; this reduction exceeded that of other networks, including the default mode network (p < 0.05).
Methods
- Case-control lesion study: 12 coma-causing brainstem lesions (7 local, 5 literature; mean age 57.3 ± 16.5 years; mean lesion volume 3,540 ± 2,988 mm³) compared with 24 control brainstem lesions (8 local, 16 literature; mean age 58.1 ± 12.8 years; mean lesion volume 2,364 ± 2,644 mm³), using subtraction and voxel-based lesion-symptom mapping.
- Resting-state functional connectivity MRI in a normative dataset of 98 right-handed healthy participants to identify regions connected to the coma-specific brainstem site, with comparison to previously defined resting-state networks and von Economo neuron distribution.
- Independent rs-fcMRI dataset from patients with disorders of consciousness and age-matched controls to compare AI–pACC connectivity with default mode and motor network connectivity.
Limitations
- The paper states that rarity of focal coma-causing brainstem lesions limited new cases, so additional cases came from retrospective literature review, creating potential selection and reporting bias; prospective validation in a larger independent cohort is needed.
- The paper states that rs-fcMRI has limited spatial resolution, especially in the brainstem, and cannot determine mono- vs polysynaptic mediation or directionality; absence of rs-fcMRI connectivity does not imply absence of anatomical connectivity.
- The paper states that left-lateralized findings are uncertain because handedness was difficult to ascertain in some comatose patients and the healthy rs-fcMRI cohort was right-handed; AI–pACC connectivity did not differentiate MCS from VS/UWS, and heart rate variability could confound connectivity differences.
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Claims the paper makes
20 Own result · 8 Check pending · 5 Own method · 4 Not checked yet · 4 Own interpretation · 2 Sources not found · 2 No full text of the sources · 1 Supported · 1 No basis given
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 contrast, control lesions primarily involved the pontine base (11 of 24; figure 1B).”
plainn = 24- Asserted: passes — The authors put it forward as true.
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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
“A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions.”
- Also stated in: § GLOSSARY · plain
“revealed a 2-mm 3 ' coma-specific region ' significantly more involved by coma lesions compared to control lesions, located in the left pontine tegmentum, near the medial parabrachial nucleus”
- Also stated in: § GLOSSARY · plain
“a small region of the left rostral dorsolateral pontine tegmentum is significantly more associated with coma-causing compared to control lesions”
plaincorrelationaln = 12- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The control brainstem lesions did not impair conscious wakefulness.
- Also stated in: § GLOSSARY · plain
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 2 coma lesions that spared this region involved the midbrain immediately rostral to it (figures e-2, B and C, and e-3A).”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“However, unlike connectivity to the AI and pACC, none of these connections were specific to coma lesions over control lesions.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“Microscopic plotting of VENs in a human brain revealed that the AI and pACC nodes identified here correspond more closely to the VEN distribution than to any major resting-state network (figures 3 and e-7).”
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The distribution of von Economo neurons is a meaningful marker of cortical regions involved in consciousness.
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
“At a lower statistical threshold, the coma-specific region showed connectivity to midline and lateral thalamus, posterior hypothalamus, and basal forebrain (figure e-6).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“located in the left pontine tegmentum, near the medial parabrachial nucleus”
- Also stated in: § GLOSSARY · plain
“a small region of the left rostral dorsolateral pontine tegmentum”
plainn = 12- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § GLOSSARY · plain
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
“Coma-causing lesions maximally overlapped in the pontine tegmentum (10 of 12 cases; figure 1A).”
plainn = 12- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Fifth, in disorders of consciousness, AI-pACC connectivity did not differentiate between MCS and VS/UWS.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 comatose patients, connectivity was absent (not significantly different from zero) across all 3 networks.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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- It may state two separate claims as one. 15
- The quote only partly states this claim. 1
- Probably not a substantial claim. 12
Every source the paper cites for this claim was checked and supports it.
In the paper
“Here, we show that connectivity between the AI and pACC is disrupted in these patients, and to a greater extent than connectivity within the default mode network, a network previously implicated in disorders of consciousness. 20”
What the sources say
- Supportedcites [20] 20. Vanhaudenhuyse A, Noirhomme Q, Tshibanda LJF, et al. Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. Brain 2010;133:161 -171. source
The citation supports the statement that the default mode network was previously implicated in disorders of consciousness, not the citing authors’ own finding about AI–pACC connectivity. The Discussion (p. 167) reports that default mode network connectivity varies with patients’ level of consciousness. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
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
“Stronger partial correlations were observed between the brainstem node and AI ( r 5 0.15) and between the AI and pACC ( r 5 0.26), than between the brainstem node and pACC ( r 5 0.06).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
“In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Together, the AI and pACC do not match any cortical network previously defined by rs-fcMRI analysis 10,11 : the AI node straddles the salience network, limbic network, and default mode network, while the pACC node falls mostly within the default mode network.”
What the sources say
- Not matchedcites [10] 10. Yeo BTT, Krienen FM, Sepulcre J, et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol 2011;106:1125 -1165.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked yetcites [11] 11. Seeley WW, Menon V, Schatzberg AF, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 2007;27:2349 -2356. source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Not matched
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
“Ten of 12 coma lesions, but only the periphery of 1 of 24 control lesions, involved this region (figure e-2A).”
plaincorrelationaln = 24- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
“The AI node exhibited connectivity to the original brainstem node, and less so to a symmetric region of the contralateral pontine tegmentum (figure 4A).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
“Voxels within both nodes were functionally connected to all 12 coma lesions (figure 2C), and were significantly more connected to coma lesions than to control lesions ( p , 0.05; figure 2D).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, both regions do correspond to the distribution of VENs. 36”
What the sources say
- Check pendingcites [36] 36. Allman JM, Tetreault NA, Hakeem AY, et al. The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans. Brain Struct Funct 2010; 214:495 -517. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The distribution of von Economo neurons is a meaningful marker of cortical regions involved in consciousness.
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 patients with disrupted awareness (MCS or VS/UWS), connectivity was reduced in all networks ( p , 0.001), but only absent between the AI and pACC (figure 5).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
“Splitting MCS and VS/UWS into separate groups, only AI-pACC connectivity was absent in both groups. Motor network connectivity was present in both groups, and default mode network connectivity was present in MCS and absent in VS/ UWS (figure e-9).”
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“These spindle-shaped neurons are found in the AI and ACC of particular mammals, such as humans, other great apes, whales, dolphins, and elephants. 28,36”
What the sources say
- Not matchedcites [28] 28. Craig ADB. How do you feel -now? The anterior insula and human awareness. Nat Rev Neurosci 2009;10:59 -70.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Check pendingcites [36] 36. Allman JM, Tetreault NA, Hakeem AY, et al. The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans. Brain Struct Funct 2010; 214:495 -517. source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
None of the sources cited for this claim have been checked yet.
In the paper
“These functional connectivity results are consistent with known axonal projections between the parabrachial region and AI 24 and from the AI to ACC 25 in rodents and monkeys.”
What the sources say
- Not matchedcites [24] 24. Saper CB. Reciprocal parabrachial-cortical connections in the rat. Brain Res 1982;242:33 -40.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [25] 25. Saleem K, Kondo H, Price J. Complementary circuits connecting the orbital and medial prefrontal networks with the temporal, insular, and opercular cortex in the macaque monkey. J Comp Neurol 2008;506:659 -693. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Not matched
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
“Third, rsfcMRI cannot determine whether functional associations are mediated by mono- or polysynaptic connections, or the directionality of these connections, and the absence of rs-fcMRI connectivity does not imply absence of anatomical connectivity.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It 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
“To assess connectivity of the identified network in disorders of consciousness, we used an independent rs-fcMRI dataset acquired from 26 patients in a minimally conscious state (MCS), 19 patients in a vegetative state/unresponsive wakefulness syndrome (VS/UWS), 6 patients in coma, and 21 age-matched healthy controls.”
plainn = 26- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
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
“First, the rarity of focal brainstem lesions causing coma limited the number of new lesions we could include, so additional cases were acquired from a retrospective literature review, creating potential for selection and reporting bias.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, the AI and ACC become jointly active during awareness of visual, somatosensory, interoceptive, and other sensory stimuli. 27,28”
What the sources say
- Not checked yetcites [27] 27. Medford N, Critchley HD. Conjoint activity of anterior insular and anterior cingulate cortex: awareness and response. Brain Struct Funct 2010;214:535 -549. source
- Not matchedcites [28] 28. Craig ADB. How do you feel -now? The anterior insula and human awareness. Nat Rev Neurosci 2009;10:59 -70.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Moreover, selective degeneration of VENs has been observed in behavioral variant frontotemporal dementia, a condition in which cognition and self-regulation are impaired. 37”
What the sources say
- Not checked — no full text of the sourcecites [37] 37. Seeley WW, Carlin DA, Allman JM, et al. Early frontotemporal dementia targets neurons unique to apes and humans. Ann Neurol 2006;60:660 -667. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Second, rs-fcMRI has limited spatial resolution, a factor particularly relevant in the brainstem; better resolution and larger cohorts may refine functional brainstem anatomy further.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Disrupting neurons bilaterally in or near the medial parabrachial nucleus impairs arousal in rodents. 2,21”
What the sources say
- Not matchedcites [2] 2. Fuller P, Sherman D, Pedersen NP, Saper CB, Lu J. Reassessment of the structural basis of the ascending arousal system. J Comp Neurol 2011;519:933 -956.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [21] 21. Benarroch EE. Parabrachial nuclear complex: multiple functions and potential clinical implications. Neurology 2016;86:676 -683.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
- Not matched
None of the sources cited for this claim have been checked yet.
In the paper
“The 2 regions that did show selective connectivity to coma-causing brainstem lesions, the AI and pACC, were previously implicated in arousal and awareness (i.e., the content of experience).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
“Our results suggest that the left AI, and secondarily the pACC, may be important targets of this system.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“These findings were similar with or without regression of the global signal (figure e-4) 17 and were not driven by CSF signal (figure e-5).”
What the sources say
- Check pendingcites [17] 17. Wong CW, Olafsson V, Tal O, Liu TT. The amplitude of the resting-state fMRI global signal is related to EEG vigilance measures. Neuroimage 2013;83:983 -990. source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Species with VENs in the AI and ACC are generally capable of more complex cognition, such as self-recognition in a mirror. 28”
What the sources say
- Not matchedcites [28] 28. Craig ADB. How do you feel -now? The anterior insula and human awareness. Nat Rev Neurosci 2009;10:59 -70.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Sixth, given a correlation between insula-ACC connectivity and heart rate variability, 38 we cannot exclude the possibility that connectivity differences between healthy individuals and individuals with disorders of consciousness may be confounded by unanticipated differences in heart rate variability.”
What the sources say
- Check pendingcites [38] 38. Chang C, Metzger CD, Glover GH, Duyn JH, Heinze HJ, Walter M. Association between heart rate variability and fluctuations in resting-state functional connectivity. Neuroimage 2013;68:93 -104. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Both regions are more active during wakefulness 22,26 and autonomic arousal. 27”
What the sources say
- Check pendingcites [22] 22. Jakobson AJ, Laird AR, Maller JJ, Conduit RD, Fitzgerald PB. Brain activity in sleep compared to wakefulness: a metaanalysis. J Behav Brain Sci 2012;2:249 -257. source
- Not checked — no full text of the sourcecites [26] 26. Braun AR, Balkin TJ, Wesenten NJ, et al. Regional cerebral blood flow throughout the sleep-wake cycle: an H2 (15)O PET study. Brain 1997;120:1173 -1197. source
- Not checked yetcites [27] 27. Medford N, Critchley HD. Conjoint activity of anterior insular and anterior cingulate cortex: awareness and response. Brain Struct Funct 2010;214:535 -549. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Based on their large size and dendrites that span all cortical layers, VENs have been proposed to rapidly integrate and transmit information across large brains. 36”
What the sources say
- Check pendingcites [36] 36. Allman JM, Tetreault NA, Hakeem AY, et al. The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans. Brain Struct Funct 2010; 214:495 -517. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The functional connectivity network identified in healthy adults from the coma-specific brainstem region is functionally relevant to the maintenance of human consciousness.
“This network may therefore serve as a neuroanatomical interface between arousal and awareness, the 2 fundamental components of human consciousness.”
“This network of brain regions may have a role in the maintenance of human consciousness.”
The paper relies on this without support.
The distribution of von Economo neurons is a meaningful marker of cortical regions involved in consciousness.
“However, both regions do correspond to the distribution of VENs. 36”
“Although the precise function of these neurons remains unknown, it has been speculated that they have a role in some form of self-awareness. 28,37”
The paper relies on this without support.
The control brainstem lesions did not impair conscious wakefulness.
“which either caused coma or were ' controls ' (i.e., did not impair conscious wakefulness)”
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?
In the citing paper
“Early models of an ascending reticular activating system (ARAS) originating from diffuse neurons in the brainstem reticular formation have been revised to include discrete brainstem regions and individual nuclei that are preferentially involved in maintaining a state of wakefulness.1–5”
From Thalamic strokes that severely impair arousal extend into the brainstem (2018) · cites this paper as [1]
In the citing paper
“this is not consistent with past evidence that ischemic strokes and other lesions limited to the brainstem cause coma.1,4”
From Thalamic strokes that severely impair arousal extend into the brainstem (2018) · cites this paper as [1]
In the citing paper
“Similarly, our findings are consistent with previous work linking dorsolateral pontine tegmentum lesions to coma in humans1,4 and coma-like outcomes in animals.9”
From Thalamic strokes that severely impair arousal extend into the brainstem (2018) · cites this paper as [1]
In the citing paper
“These findings are consistent with previous research highlighting the role of the brainstem and posterior hypothalamus as critical regions in the arousal pathway,1–4”
From Thalamic strokes that severely impair arousal extend into the brainstem (2018) · cites this paper as [1]
Citations
Cites
The organization of the human cerebral cortex estimated by intrinsic functional connectivity
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Self-citationDissociable intrinsic connectivity networks for salience processing and executive control
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The organization of the human cerebellum estimated by intrinsic functional connectivity
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Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging
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“These spindle-shaped neurons are found in the AI and ACC of particular mammals, such as humans, other great apes, whales, dolphins, and elephants.(28,36) Based on their large size and dendrites that span all cortical layers, VENs have been proposed to rapidly integrate and transmit information across large brains.”
BackgroundInfluentialHypothalamic regulation of sleep and circadian rhythms
Saper, C. B., Scammell, T. E., & Lu, J. (2005) · Nature · doi:10.1038/nature04284 · Cited by 2,804
Self-citationImproving Lesion-Symptom Mapping
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Spatial Neglect and Attention Networks
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Efferent connections of the parabrachial nucleus in the rat
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Self-citationVanhaudenhuyse, A., Noirhomme, Q., Tshibanda, L. J.-F., Bruno, M.-A., Boveroux, P., Schnakers, C., Soddu, A., Perlbarg, V., Ledoux, D., Brichant, J.-F., et al. (2010) · Brain · doi:10.1093/brain/awp313 · Cited by 911 · cited 2×
“05) including the default mode network, a network previously implicated in disorders of consciousness.(20) Splitting MCS and VS/UWS into separate groups, only AI-pACC connectivity was absent in both groups.”
BackgroundSelf-citationWhat is the function of the claustrum?
Crick, F. C., & Koch, C. (2005) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2005.1661 · Cited by 742
Conjoint activity of anterior insular and anterior cingulate cortex: awareness and response
Medford, N., & Critchley, H. D. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0265-x · Cited by 627
Network localization of neurological symptoms from focal brain lesions
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Self-citationPartial correlation for functional brain interactivity investigation in functional MRI
Marrelec, G., Krainik, A., Duffau, H., Pélégrini-Issac, M., Lehéricy, S., Doyon, J., & Benali, H. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.12.057 · Cited by 488
Reassessment of the structural basis of the ascending arousal system
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Self-citationNeuroanatomical correlates of brainstem coma
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“These findings replicate and extend those of Parvizi and Damasio (2003),3 refining the localization of this region by incorporating more coma-causing lesions and statistical comparisons to control lesions.”
ResultIntrinsic functional connectivity differentiates minimally conscious from unresponsive patients
Athena Demertzi, A., Antonopoulos, G., Heine, L., Voss, H. U., Crone, J. S., Angeles, C. D. L., Bahri, M. A., Perri, C. D., Vanhaudenhuyse, A., Charland‐Verville, V., et al. (2015) · Brain · doi:10.1093/brain/awv169 · Cited by 398
Self-citationPlum and Posner's Diagnosis of Stupor and Coma
Posner, J. B., Saper, C. B., Schiff, N. D., & Plum, F. (2008) · Oxford University Press eBooks · doi:10.1093/med/9780195321319.001.0001 · Cited by 393
Self-citationAssociation between heart rate variability and fluctuations in resting-state functional connectivity
Chang, C., Metzger, C. D., Glover, G. H., Duyn, J. H., Heinze, H.-J., & Walter, M. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2012.11.038 · Cited by 367
Early frontotemporal dementia targets neurons unique to apes and humans
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The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans
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The amplitude of the resting-state fMRI global signal is related to EEG vigilance measures
Wong, C. W., Olafsson, V., Tal, O., & Liu, T. T. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.07.057 · Cited by 318
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AN ASCENDING RETICULAR ACTIVATING SYSTEM IN THE BRAIN STEM
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Plum and Posner’s Diagnosis of Stupor and Coma
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Reciprocal parabrachial-cortical connections in the rat
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Self-citationImpaired consciousness in temporal lobe seizures: role of cortical slow activity
Englot, D. J., Yang, L., Altalib, H. H., Danielson, N., Bai, X., Marfeo, A., Yu, L., Gordon, A. S., Purcaro, M. J., Motelow, J. E., et al. (2010) · Brain · doi:10.1093/brain/awq316 · Cited by 229
Electrical stimulation of a small brain area reversibly disrupts consciousness.
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Self-citationA mesencephalic locked-in syndrome
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Hemispheric asymmetries in arousal affect outcome of the intracarotid amobarbital test
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Brain Activity in Sleep Compared to Wakefulness: A Meta-Analysis
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The Salience Network: A Neural System for Perceiving and Responding to Homeostatic Demands
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Self-citation
Metadata
- Authors
- Fischer, D. B., Boes, A. D., Demertzi, A., Evrard, H. C., Laureys, S., Edlow, B. L., Liu, H., Saper, C. B., Pascual-Leone, A., Fox, M. D., & Geerling, J. C.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- From the Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology (D.B.F., A.D.B., A.P.-L., M.D.F.), and Department of Neurology (C.B.S., A.P.-L., M.D.F., J.C.G.), Harvard Medical School and Beth Israel Deaconess Medical Center, Boston; Harvard Medical School (D.B.F.), Boston; Departments of Pediatric Neurology (A.D.B.) and Neurology (B.L.E.), Harvard Medical School and Massachusetts General Hospital, Boston, MA; Brain and Spine Institute ...
- ORCID
- Venue
- Neurology
- Published
- 2016-12-06
- Volume
- 87
- Issue
- 23
- Pages
- 2427-2434
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC5177681
- OpenAlex
- W2547120907
- Semantic Scholar
- 7b647efb2ec2d19f8929428b8e083c682375d553
- Cited by
- 283
- References
- 42
- Citations by year
- 2026: 25 · 2025: 34 · 2024: 26 · 2023: 29 · 2022: 27 · 2021: 40 · 2020: 26 · 2019: 31 · 2018: 26 · 2017: 16 · 2016: 2
- FWCI
- 12.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Institutes of Health (S10RR023043)
- National Heart, Lung, and Blood Institute (P01HL095491, T32HL007901)
- National Institute of Mental Health (R21MH099196)
- National Institute of Neurological Disorders and Stroke (K23NS083741, R01NS073601, R25NS070682, R21NS082870, R01NS085477, R01NS091604, R21NS085491, R25NS065743)
- National Center for Research Resources (S10-RR-023043)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD069776)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- coma, brainstem lesions, functional connectivity, resting-state networks, anterior insula, pregenual anterior cingulate cortex, von Economo neurons, disorders of consciousness, consciousness, voxel-based lesion-symptom mapping
- MeSH terms
- Brain Mapping, Brain Stem, Coma, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Rest, Cohort Studies, Case-Control Studies, Young Adult
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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