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Neuroanatomical correlates of brainstem coma
Abstract
The brainstem tegmentum, including the reticular formation, contains distinct nuclei, each of which has a set of chemical, physiological and anatomical features. Damage to the brainstem tegmentum is known to cause coma, the most radical disturbance of consciousness. However, it has remained unclear which nuclei within the tegmentum are crucial for the maintenance of consciousness in humans. Accordingly, we initiated a retrospective study of MRIs obtained from 47 patients with brainstem stroke. The lesion boundaries were charted on patient MRIs and transferred onto a corresponding series of 4.7 T MRIs obtained from a control brainstem specimen that later was cut on a freezing microtome and analysed histologically. In addition, medical charts and available post-mortem materials were used to obtain relevant clinical and anatomical data to verify the MRI readings in each case. We found that in the 38 patients who did not have coma, brainstem damage either was located outside the tegmentum (n = 29) or produced a very small and unilateral compromise of the tegmentum (n = 9). In contrast, in patients who had coma (n = 9), the lesions in the tegmentum were mostly bilateral (n = 7) and were located either in the pons alone (n = 4) or in the upper pons and the midbrain (n = 5). The maximum overlap territory of the lesions coincided with the location of the rostral raphe complex, locus coeruleus, laterodorsal tegmental nucleus, nucleus pontis oralis, parabrachial nucleus and the white matter in between these nuclei. We also found that four coma subjects developed hyperthermia and died in the absence of any infections. In these cases, the maximum lesion overlap was centred in the core of pontine tegmentum. Our findings suggest that lesions confined to the upper pons can cause coma in humans even in the absence of damage to the midbrain. The findings also point to the brainstem nuclei whose lesions are likely to be associated with loss of consciousness and fatal hyperthermia in humans.
Overview
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Written from the paper’s full text.
TL;DR
In a retrospective MRI study of 47 patients with brainstem stroke, coma was associated with lesions clustered in the pontomesencephalic tegmentum, especially the upper pontine tegmentum, whereas non-coma lesions mostly spared the tegmentum or produced small unilateral tegmental damage. The maximum lesion overlap in coma cases coincided with the rostral raphe complex, locus coeruleus, laterodorsal tegmental nucleus, nucleus pontis oralis, parabrachial nucleus, and the white matter between these nuclei.
Key findings
- Of 47 patients, 38 did not have coma: 29 had brainstem damage outside the tegmentum and 9 had very small unilateral tegmental compromise. Of the 9 coma patients, 7 had mostly bilateral tegmental lesions; lesions were in the pons alone in 4 and in the upper pons plus midbrain in 5. The upper pons was always damaged in coma cases, and no coma case had lesions confined to the medulla or midbrain only.
- The maximum overlap territory in coma patients coincided with the rostral raphe complex, locus coeruleus, laterodorsal tegmental nucleus, nucleus pontis oralis, parabrachial nucleus, and intervening white matter; local connections between these nuclei and the ascending central tegmental tract were also severed.
- Four coma patients died in a hyperthermic state (temperature >40°C) without any explainable source of fever; their lesions overlapped in the core of the upper pontine tegmentum, and they had signs of pontine compromise such as Cheyne–Stokes respiration.
- Longer coma duration was associated with bilateral lesions and shorter duration with unilateral lesions; the longest coma was 7 days in patient M.M., who died without gaining consciousness, and none of the cases had persistent vegetative state or loss of consciousness beyond 1 week.
Methods
- Retrospective study: from 236 subjects admitted with stroke and MRI studies, exclusion criteria reduced the sample to 47 patients (19.9%) with brainstem lesions. Lesion boundaries were traced on patient MRIs and transferred onto a 4.7 T MRI template from a control brainstem specimen, which was also cut and analysed histologically; clinical charts and available post-mortem material were used to verify MRI readings.
- Coma was defined as a state of deep sleep with and without stimulations, whereas hypersomnolence was defined as a tendency to sleep when unstimulated but arousable when stimulated. Identification of damaged nuclei was qualitative, based on whether a nucleus location coincided with the lesion territory; no quantification of the degree of nuclear damage was attempted.
Limitations
- The paper states that the records did not include behavioural or cognitive measurements regarding the degree of impaired consciousness, and that no quantification of nuclear damage was attempted because it is beyond current technology. It also notes the limited spatial resolution of the imaging techniques and that the aim was not to identify brainstem nuclei directly with imaging.
- The paper states that exclusion criteria may have selected somewhat “pure” brainstem cases, possibly explaining the absence of coma lasting longer than 7 days; it also states that diffuse CNS inflammation following stroke could not be ruled out as a cause of hyperthermia.
- Evident from the text: the coma group was small (n = 9), the design was retrospective, and the anatomical inference relies on lesion overlap rather than direct causal testing.
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Claims the paper makes
37 Own result · 17 Own interpretation · 15 No full text of the sources · 5 Own method · 4 No basis given · 3 Sources not found · 3 Not checked yet · 1 Check pending
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, regardless of their rostrocaudal level, lesions in the majority of these cases (n = 29) were clustered in the anterior portion of the brainstem, sparing the tegmentum but involving structures such as the cerebral peduncles, the pontine nuclei of the basis pontis or the pyramidal tracts.”
§ Neuroanatomical correlates of brainstem coma > Results
plaincorrelationaln = 29- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition to patient M.M., patients P.H., V.S. and V.R. also died without gaining consciousness (Tables 1 and 3).”
§ Neuroanatomical correlates of brainstem coma > Results
plainn = 4- 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
“These lesions involved the posterior aspect of the tegmentum (Fig. 4).”
§ Neuroanatomical correlates of brainstem coma > Results
plaincorrelationaln = 9- 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
“In cases with coma, the maximum overlap of lesion territories was centred in the core of the upper pontine tegmentum involving the raphe complex (NR), locus coeruleus (LC), laterodorsal tegmental nucleus (LDT), pedunculopontine tegmental nucleus (PPTg), nucleus pontis oralis (PnO) and the parabrachial nucleus (PBN).”
§ Neuroanatomical correlates of brainstem coma > Results
plaincorrelationaln = 9- 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
“Accordingly, patients who died of hyperthermia had signs of pontine compromise such as pinpoint pupils and Cheyne±Stoke respiration.”
§ Neuroanatomical correlates of brainstem coma > Brainstem stroke and fatal hyperthermia
plaincorrelationaln = 4- 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
“We also found that four coma subjects developed hyperthermia and died in the absence of any infections.”
- Also stated in: § Results · plain
“To our surprise, we found that all four cases died in a state of hyperthermia (temperature >40°C) in the absence of any explainable source of fever.”
§ Neuroanatomical correlates of brainstem coma > Abstract
plainn = 4- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Results · 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
“We found that the shortest duration of coma was associated with unilateral lesions, especially when the lesions were non-haemorrhagic (patients T.G. and I.P. compared with patient H.R.).”
§ Neuroanatomical correlates of brainstem coma > Duration of coma in patients with brainstem stroke
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.
- Rests on an assumption: The brainstem lesions observed in the patients are the cause of their coma.
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 these cases, the maximum lesion overlap was centred in the core of pontine tegmentum.”
§ Neuroanatomical correlates of brainstem coma > Abstract
plaincorrelationaln = 4- Asserted: passes — The authors put it forward as true.
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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
“In summary, none of the 47 cases included in the study had lesions in the hypothalamus, basal forebrain or bilateral cerebral cortex.”
§ Neuroanatomical correlates of brainstem coma > Results
plainn = 47- 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
“Among the cases included in the study, 38 had brainstem stroke without loss of consciousness.”
§ Neuroanatomical correlates of brainstem coma > Results
plain- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 28
- Probably not a substantial claim. 15
- The quote only partly states this claim. 1
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
“Patients T.G. and I.P. were the only coma patients who had acquired unilateral lesions of the tegmentum, and both had the shortest duration of coma (Table 1).”
§ Neuroanatomical correlates of brainstem coma > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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 only ®ve cases, a small portion of the tegmentum was affected unilaterally, but the lesions were always in the most anterior portion of the tegmentum affecting structures such as the substantia nigra or the red nucleus.”
§ Neuroanatomical correlates of brainstem coma > Results
plainn = 5- Asserted: passes — The authors put it forward as true.
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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 contrast, in patients who had coma (n = 9), the lesions in the tegmentum were mostly bilateral (n = 7) and were located either in the pons alone (n = 4) or in the upper pons and the midbrain (n = 5).”
§ Neuroanatomical correlates of brainstem coma > Abstract
plaincorrelationaln = 9- Asserted: passes — The authors put it forward as true.
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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
“Post-mortem analysis con®rmed the MRI readings and indicated a thrombotic basilar artery with an infarct area in the upper pons that affected the lateral tegmental regions including the corticospinal tracts bilaterally.”
§ Neuroanatomical correlates of brainstem coma > Results
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
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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
“None of our cases had persistent vegetative state or loss of consciousness beyond 1 week.”
§ Neuroanatomical correlates of brainstem coma > Duration of coma in patients with brainstem stroke
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
“In these four cases, brainstem lesions were either in the pons alone (n = 2) or in the pons and the midbrain (n = 2).”
§ Neuroanatomical correlates of brainstem coma > Results
plainn = 4- 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
“We found that in the 38 patients who did not have coma, brainstem damage either was located outside the tegmentum (n = 29) or produced a very small and unilateral compromise of the tegmentum (n = 9).”
§ Neuroanatomical correlates of brainstem coma > Abstract
plaincorrelationaln = 38- Asserted: passes — The authors put it forward as true.
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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
“Comparing the unilateral lesions in non-coma patients with the unilateral lesions in coma patients revealed the following: lesions in comatose patients with unilateral lesions were close to the midline and the posterior tegmentum, while the lesions in non-comatose patients were centred in the lateral and anterior tegmentum.”
§ Neuroanatomical correlates of brainstem coma > Duration of coma in patients with brainstem stroke
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.
- Rests on an assumption: The brainstem lesions observed in the patients are the cause of their coma.
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 our study, we found that four cases had died without recovering consciousness and that they all had died in a hyperthermic state in the absence of any obvious cause for their fever.”
§ Neuroanatomical correlates of brainstem coma > Brainstem stroke and fatal hyperthermia
plaincorrelationaln = 4- 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.
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
“Patients P.H., V.S. and V.R. had 2, 5 and 5 days of coma, respectively.”
§ Neuroanatomical correlates of brainstem coma > Results
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. 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
“Only patient P.H. had haemorrhagic stroke, whereas the other three had non-haemorrhagic infarcts.”
§ Neuroanatomical correlates of brainstem coma > Results
plainn = 4- Asserted: passes — The authors put it forward as true.
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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 duration of coma in our cases varied signi®cantly: longer duration of coma was associated with bilateral lesions, and shorter duration was associated with unilateral lesions (Tables 1 and 3).”
§ Neuroanatomical correlates of brainstem coma > Results
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.
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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
“None of the cases with coma had lesions in the medulla, and no cases contained lesions con®ned to the midbrain only.”
§ Neuroanatomical correlates of brainstem coma > Results
plainn = 9- 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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The quote only partly states this claim.
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
“Lesions in coma cases affected either the midbrain and pontine tegmentum together (n = 5), or only the upper pontine tegmentum without involving the midbrain (n = 4).”
§ Neuroanatomical correlates of brainstem coma > Results
plaincorrelationaln = 9- 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.
In the paper
“Although hyperthermia can be caused by hydrocephalus (Talman et al., 1988) or lesions anywhere between the upper pons and the hypothalamus (Simpson et al., 1993), there is evidence suggesting a strong correlation between fatal hyperthermia and pontine compromise (Wijdicks and St Louis, 1997).”
§ Neuroanatomical correlates of brainstem coma > Brainstem stroke and fatal hyperthermia
What the sources say
- Not checked — no full text of the sourcecites Simpson et al., 1993 source
plaindirect- 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.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In a recent study, it was found that the dopaminergic cells in the ventral PAG and NR are active during wakefulness, and their lesion causes 20% more sleep (Lu et al., 2002).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
- Not matchedcites Lu et al., 2002
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
- Not matched
In the paper
“Of note is that these patients developed Cheyne±Stoke respiration and one had pathological sneezing, all suggesting a pontine compromise (Miller et al., 1994).”
§ Neuroanatomical correlates of brainstem coma > Results
What the sources say
- Not checked — no full text of the sourcecites Miller et al., 1994 source
hedgedcorrelationaln = 4- 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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It may state two separate claims as one.
In the paper
“They also project to the basal forebrain where widespread projections to the cerebral cortex originate (Smiley et al., 1999).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
- Not checked — no full text of the sourcecites Smiley et al., 1999 source
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.
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 other words, we were con®dent that coma in our subjects was due exclusively to the compromise of the brainstem and not the other brain structures.”
§ Neuroanatomical correlates of brainstem coma > Results
boosteddirectn = 47- 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 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
“A third possibility is that a lesion in the midbrain disrupts the pathways that descend from the rostral structures and target the upper pons.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
hedgedconditional- Asserted: fails — The authors may not put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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
“We did not have behavioural and cognitive measurements regarding the quality of consciousness in patients who had not become comatose or had gained consciousness after being in a coma.”
§ Neuroanatomical correlates of brainstem coma > Exclusion criteria were: (i) absence of lesions in the brainstem; (ii) presence of extensive damage to other brain structures; (iii) unavailable MRIs; (iv) poor quality MRIs; or (v) presence of con¯icting
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.
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
“It could be due to, for instance, the disruption of pathways passing through the midbrain such as those that originate in the upper pons and target the rostral structures, or those that descend from the rostral structures and target the pontine structures.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
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. 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 summary, it is conceivable that brainstem lesions compromise the function of the PnO, LC, NR, LDT and PBN and impair their in¯uence on rostral structures, thus halting their orchestrated modulation of the global activity of the brain.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
hedgedconditional- 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.
- Rests on an assumption: The anatomical and physiological findings from non-human mammals about brainstem nuclei apply to humans.
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 addition, medical charts and available post-mortem materials were used to obtain relevant clinical and anatomical data to verify the MRI readings in each case.”
§ Neuroanatomical correlates of brainstem coma > Abstract
plainn = 47- 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
“However, our study complements that notion by ®nding that the maximum overlap of coma-causing lesions is centred in the upper pons, and that lesions con®ned to the pons alone can cause coma even in the absence of midbrain damage.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
plaindirect- 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.
In the paper
“Although hyperthermia can be caused by hydrocephalus (Talman et al., 1988) or lesions anywhere between the upper pons and the hypothalamus (Simpson et al., 1993), there is evidence suggesting a strong correlation between fatal hyperthermia and pontine compromise (Wijdicks and St Louis, 1997).”
§ Neuroanatomical correlates of brainstem coma > Brainstem stroke and fatal hyperthermia
What the sources say
- Not checked — no full text of the sourcecites Talman et al., 1988 source
plaindirect- 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.
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
“This impairment could be due to a direct lesion centred in the upper pons from where these nuclei operate, or to a lesion in the midbrain through which the ascending pathways from these nuclei must travel.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
hedgedconditional- 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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no 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
“The PnO sends presumably glutamatergic projections to the intralaminar nuclei of the thalamus, which in turn project to various cortical regions (Brodal, 1957;Steriade et al., 1988;Newman and Ginsberg, 1994).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
- Not matchedcites Brodal, 1957
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites Steriade et al., 1988 source
- Not matchedcites Newman and Ginsberg, 1994
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedcorrelational- 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.
- 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
“The application of these criteria reduced the number of suitable subjects to 47 (19.9%).”
§ Neuroanatomical correlates of brainstem coma > Exclusion criteria were: (i) absence of lesions in the brainstem; (ii) presence of extensive damage to other brain structures; (iii) unavailable MRIs; (iv) poor quality MRIs; or (v) presence of con¯icting
plaindirect- 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
“It is noteworthy that anatomical studies in the early 1950s showed that the PnO is also a major recipient of cortical projections to the `reticular formation' (Brodal, 1957).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
- Not matchedcites Brodal, 1957
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
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The LDT contains cholinergic neurons (Mesulam et al., 1989), which project to several thalamic nuclei including the reticular nucleus of the thalamus (Steriade et al., 1988) and to basal forebrain regions such as the substantia innominata (Muller et al., 1993).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
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.
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
“The identi®cation of damaged nuclei was qualitative, i.e. ®nding whether a nucleus location coincided with the lesion territory.No quanti®cation of the degree of nuclear damage was attempted because this is a task beyond the reach of current state of the art technology.”
§ Neuroanatomical correlates of brainstem coma > Exclusion criteria were: (i) absence of lesions in the brainstem; (ii) presence of extensive damage to other brain structures; (iii) unavailable MRIs; (iv) poor quality MRIs; or (v) presence of con¯icting
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.
Probably not a substantial claim. 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
“It is possible that they could have had longer duration of coma had they survived.”
§ Neuroanatomical correlates of brainstem coma > Duration of coma in patients with brainstem stroke
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check 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. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The reticular nucleus of the thalamus, in turn, sends inhibitory projections to other thalamic nuclei (Scheibel et al., 1966;Steriade and Deschenes, 1984;Barth and MacDonald, 1996), thereby functioning as a pacemaker for the thalamic oscillations, which hallmark non-rapid eye movement sleep.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
plaindirect- 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
“The PBN is known as an afferent integration site that is involved in many aspects of homeostasis, including thermal, ¯uid, electrolyte and energy balance (Caille et al., 1981;Dick et al., 1994;Saper and Breder, 1994;Menani et al., 1995;Mizusawa et al., 1995;Buritova et al., 1998).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
boostedcorrelational- 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.
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
“Thirdly, our study suggests a neuroanatomical correlate for hyperthermia following brainstem stroke, and raises the possibility that some brainstem lesions are fatal perhaps due to the compromise of the components of the brainstem involved in temperature regulation.”
§ Neuroanatomical correlates of brainstem coma > Discussion
hedgedconditional- 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.
- Rests on an assumption: The absence of an explainable source of fever in the four hyperthermic coma patients indicates that the hyperthermia is due to the brainstem lesion rather than an undetected infection or other cause.
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 brief, our ®nding is in agreement with the classical notion of brainstem coma, but it narrows down the crucial brainstem territory and points to the possibility that, compared with the midbrain, the human upper pons may play a more crucial role in the maintenance of consciousness than the classical notion implies.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
hedgedconditional- 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 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
“It is possible that the lack of cases with long duration of coma among our subjects had to do with the fact that our cases were somewhat `pure' brainstem cases.”
§ Neuroanatomical correlates of brainstem coma > Duration of coma in patients with brainstem stroke
hedgedconditionaln = 236- 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
“The LC and the NR, respectively, are the source of direct noradrenergic and serotonergic projections to most of the cortical mantle (Moore and Bloom, 1979).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
- Not checked — no full text of the sourcecites Moore and Bloom, 1979 source
plaindirect- 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.
The paper relies on this without support.
The normal brainstem specimen used as a template is representative of the brainstem anatomy of the patients with brainstem stroke.
“First, a normal brainstem specimen was selected randomly from a collection of 610 brains from the University of Iowa brain collections at Dr Gary Van Hoesen's laboratory.The donor had died of stomach cancer without any neurological or psychiatric history.”
The paper relies on this without support.
The anatomical and physiological findings from non-human mammals about brainstem nuclei apply to humans.
“As shown in Fig. 1, studies in non-human mammals have shown that these nuclei have the anatomical and physiological means to induce global changes in the electrophysiological activity of the brain.”
The paper relies on this without support.
The absence of an explainable source of fever in the four hyperthermic coma patients indicates that the hyperthermia is due to the brainstem lesion rather than an undetected infection or other cause.
“To our surprise, we found that all four cases died in a state of hyperthermia (temperature >40°C) in the absence of any explainable source of fever.”
The paper relies on this without support.
The brainstem lesions observed in the patients are the cause of their coma.
“This design made it possible for us to compare brainstem lesions that cause short lapses of consciousness with those that cause longer duration of coma.”
The paper relies on this without support.
The control brainstem specimen used for charting nuclei is representative of normal human brainstem anatomy.
“The control brainstem specimen used in our study was cut on a freezing microtome into 50 mm thick sections.”
The paper relies on this without support.
The MRI chartings transferred to the template brainstem MRI atlas accurately represent the lesion boundaries in each patient.
“Once the MRI chartings were transferred to the template brainstem MRI atlas, the overlapping regions were coded with different colours.”
The paper relies on this without support.
The absence of an obvious cause for fever in the four patients means their hyperthermia was not due to infection or other systemic causes.
“they all had died in a hyperthermic state in the absence of any obvious cause for their fever.”
The paper relies on this without support.
The patients included in the study are representative of patients with brainstem coma generally.
“As noted, from a pool of 236 subjects, we included only 19.9% of the cases.”
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Similarly, in patients with brainstem stroke, Parvizi and Damasio found that acute coma was associated with magnetic resonance imaging (MRI) lesions in the pontine tegmentum extending from the upper pons into the midbrain.7”
From Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury (2016) · cites this paper as [7]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Still, it remains unknown whether TBI injures these specific arousalpromoting neurons.”
From Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury (2016) · cites this paper as [7]
Experimental — accuracy not yet measuredIn the citing paper
“Evidence that the AAn is essential for consciousness comes from experimentally induced lesions in rodents3 and cats4 and mapping of brainstem infarctions in humans.5”
From Disruption of the ascending arousal network in acute traumatic disorders of consciousness (2019) · cites this paper as [5]
In the citing paper
“In addition, several brainstem nuclei (locus coeruleus, dorsal raphe, median raphe, pedunculopontine nucleus, parabrachial nucleus), non-specific thalamic nuclei, hypothalamus, and basal forebrain are also included in the ARAS system (Aston-Jones et al., 2001; Parvizi and Damasio, 2003; Fuller et al., 2011).”
From The Ascending Reticular Activating System from Pontine Reticular Formation to the Thalamus in the Human Brain (2013) · cites this paper as Parvizi and Damasio, 2003
In the citing paper
“Conventional brain MRI, functional neuroimaging techniques, electrophysiological methods, and MR spectroscopy have been used in studies of the ARAS in the human brain (Parvizi and Damasio, 2003; Schiff, 2006; Tshibanda et al., 2009, 2010; Gawryluk et al., 2010).”
From The Ascending Reticular Activating System from Pontine Reticular Formation to the Thalamus in the Human Brain (2013) · cites this paper as Parvizi and Damasio, 2003
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 [4]
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 [4]
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 [4]
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 [4]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Neuroanatomical correlates of brainstem coma > Abstract
“four coma subjects developed hyperthermia and died in the absence of any infections”
§ Neuroanatomical correlates of brainstem coma > Table 3. Short summary of clinical data regarding the patients with brainstem coma
“VR Admitted in the early morning for bacterial endocarditis.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Neuroanatomical correlates of brainstem coma > Abstract
“a very small and unilateral compromise of the tegmentum (n = 9)”
§ Neuroanatomical correlates of brainstem coma > Results
“In only ®ve cases, a small portion of the tegmentum was affected unilaterally”
Citations
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Cited by
Sorted by citations
Items 101–200 of 400
Boukrina, O. V., & Barrett, A. M. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.09.024 · Cited by 36
“…through the reticular formation carry neurotransmitter-specific projections from brainstem source nuclei to the thalamus, hypothalamus, basal forebrain, and the cerebral cortex (Edlow et al., 2012; Heilman et al., 2012; Mesulam, 2000; Parvizi and Damasio, 2003; Paus et al., 1997; Yeo et al., 2013).”
BackgroundZimmerman, K. A., Cournoyer, J., Lai, H., Snider, S. B., Fischer, D. B., Kemp, S. P. T., Karton, C., Hoshizaki, T. B., Ghajari, M., & Sharp, D. J. (2022) · Brain · doi:10.1093/brain/awac485 · Cited by 39
The Neuropsychology of Emotion and Emotion Regulation: The Role of Laterality and Hierarchy
Turnbull, O. H., & Salas, C. E. (2021) · Brain Sciences · doi:10.3390/brainsci11081075 · Cited by 35
“Only deep subcortical lesions, especially to the upper brain stem, appear to completely abolish emotional experience, but in this case due to a complete loss of consciousness [55].”
BackgroundWu, X., Zhang, J., Cui, Z., Tang, W., Shao, C., Hu, J., Zhu, J., Zhao, Y., Lu, L., Chen, G., et al. (2018) · Neuroscience Bulletin · doi:10.1007/s12264-018-0253-3 · Cited by 35
Brainstem Diffuse Axonal Injury and Consciousness
Sandhu, S. J. S., Soule, E., Fiester, P. J., Natter, P., Tavanaiepour, D., Rahmathulla, G., & Rao, D. (2019) · Journal of Clinical Imaging Science · doi:10.25259/jcis-11-2019 · Cited by 35
A Century Searching for the Neurons Necessary for Wakefulness
Grady, F. S., Boes, A. D., & Geerling, J. C. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.930514 · Cited by 40
Long COVID: Complications, Underlying Mechanisms, and Treatment Strategies
Zadeh, F. H. (2023) · Archives of Microbiology & Immunology · doi:10.26502/ami.93650103 · Cited by 35
Towards an integrative theory of consciousness: Part 1 (Neurobiological and cognitive models)
De Sousa, A. (2013) · Mens Sana Monographs · doi:10.4103/0973-1229.109335 · Cited by 33
“MSM : www.msmonographs.org Direct injuries to the central thalamus can alone produce global disturbances of consciousness (Parvizi and Damasio, 2003[161]).”
BackgroundManagement Strategy of a Transorbital Penetrating Pontine Injury by a Wooden Chopstick
Sun, G., Yağmurlu, K., Belykh, E. G., Lei, T., & Preul, M. C. (2016) · World Neurosurgery · doi:10.1016/j.wneu.2016.07.104 · Cited by 33
Multimodal assessment of recovery from coma in a rat model of diffuse brainstem tegmentum injury
Pais‐Roldán, P., Edlow, B. L., Jiang, Y., Stelzer, J., Zou, M., & Yu, X. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.01.060 · Cited by 33
“Using the ET-1 approach to disrupt the brainstem vasculature, we found that the neuroanatomic localization of the coma-causing lesion in our rat model was consistent with that of coma-causing brainstem lesions in prior animal and human studies, which have consistently highlighted the critical role of the brainstem teg…”
BackgroundMethodResultInfluentialWhat are neural correlates neural correlates of?
Abend, G. (2017) · BioSocieties · doi:10.1057/s41292-016-0019-y · Cited by 51
Vadakkan, K. I. (2015) · SpringerPlus · doi:10.1186/s40064-015-1283-1 · Cited by 31
“In addition to the brain stem nuclei including the locus coeruleus, dorsal raphe, median raphe, pedunculopontine nucleus, and parabrachial nucleus, the ARAS also includes non-specific thalamic nuclei, the hypothalamus and the basal forebrain (Aston-Jones et al. 2001; Parvizi and Damasio 2003).”
BackgroundThe claustrum and consciousness: An update
Liaw, Y. S., & Augustine, G. J. (2023) · International Journal of Clinical and Health Psychology · doi:10.1016/j.ijchp.2023.100405 · Cited by 35
Bianciardi, M., Izzy, S., Rosen, B. R., Wald, L. L., & Edlow, B. L. (2021) · Neurology · doi:10.1212/wnl.0000000000012192 · Cited by 26
Frontal Networks Associated With Command Following After Hemorrhagic Stroke
Mikell, C. B., Banks, G. P., Frey, H., Youngerman, B. E., Nelp, T. B., Karas, P. J., Chan, A. K.-H., Voss, H. U., Connolly, E. S., & Claassen, J. (2014) · Stroke · doi:10.1161/strokeaha.114.007645 · Cited by 31
“We first assessed whether structural injury to the pons, midbrain, and thalamus accounted for unresponsiveness in our population, as these structures are known to be critical for arousal.(27,28) Second, we used resting-state fMRI to identify from a screen of multiple standard networks those that were disrupted in unre…”
Rohaut, B., Doyle, K. W., Reynolds, A. S., Igwe, K. C., Couch, C., Matory, A., Rizvi, B. M., Roh, D. J., Velazquez, A. G., Megjhani, M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-41042-2 · Cited by 30
Psychoanalysis, representation, and neuroscience: The Freudian unconscious and the Bayesian brain
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“But the central role of input seems established by a simple contrast put forward by Damasio (1999) and elaborated in more detail elsewhere (Parvizi and Damasio, 2001, 2003).”
BackgroundMicrotubules in the Cerebral Cortex: Role in Memory and Consciousness
Woolf, N. J. (2006) · Springer eBooks · doi:10.1007/3-540-36723-3_3 · Cited by 29
Consciousness, Coma, and Brain Death—2009
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Mind, brain and altered states of consciousness
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Taran, S., Gros, P., Gofton, T. E., Boyd, G., Briard, J. N., Chassé, M., & Singh, J. M. (2023) · Canadian Journal of Anesthesia/Journal canadien d anesthésie · doi:10.1007/s12630-023-02421-6 · Cited by 28
“which the sleep-wake cycle is lost, the eyes remain closed, and there is no speech or purposeful movement.(14) Cortical metabolism and activity may be virtually undisturbed by such lesions and yet the clinical syndrome is one of profound unresponsiveness.”
BackgroundBenarroch, E. E. (2016) · Neurology · doi:10.1212/wnl.0000000000002393 · Cited by 29
Andrews, J. P., Yue, Z., Ryu, J. H., Neske, G. T., McCormick, D. A., & Blumenfeld, H. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.11.008 · Cited by 27
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“It is important to note the disparity between the final infarct and the symmetric clinical improvement. This highlights the importance of infarct location even within the brainstem. Nevertheless, it is somewhat surprising that given the location of the infarct in the left paramedian basis pontis that there was no arm…”
BackgroundAscending Reticular Activating System of the Brain
Kovalzon, V. M. (2016) · Translational Neuroscience and Clinics · doi:10.18679/cn11-6030_r.2016.034 · Cited by 34
Homeostatic Feelings and the Emergence of Consciousness
Damasio, A., & Damasio, H. (2024) · Journal of Cognitive Neuroscience · doi:10.1162/jocn_a_02119 · Cited by 26
“On the other hand, damage to upper and posterior brain stem nuclei, such as periaque-ductal gray area, parabrachial nucleus, and nucleus tractus solitarius, do abolish feelings and consciousness (Parvizi & Damasio, 2001, 2003).”
BackgroundChen, S., Wu, X., Wang, L., Wang, Y., Wu, B., Ge, M., Xu, Z., Ward, B. D., Li, S., Liu, X., et al. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.04.039 · Cited by 25
Magnetic resonance imaging in ischemic stroke
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Immediate, Irreversible, Posttraumatic Coma
Rosenblum, W. I. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000170 · Cited by 24
Injury patterns associated with cognitive motor dissociation
Franzova, E., Shen, Q., Doyle, K. W., Chen, J. M., Egbebike, J. A., Vrosgou, A., Carmona, J. C., Grobois, L., Heinonen, G., Velazquez, A. G., et al. (2023) · Brain · doi:10.1093/brain/awad197 · Cited by 23
Framework of Consciousness from Semblance of Activity at Functionally LINKed Postsynaptic Membranes
Vadakkan, K. I. (2010) · Frontiers in Psychology · doi:10.3389/fpsyg.2010.00168 · Cited by 24
“Acute injuries that damage the brain stem may cause sensory deficits that can evoke an unconscious state (Parvizi and Damasio, 2003).”
BackgroundAltered States of Consciousness after Brain Injury
Stender, J., Laureys, S., & Gosseries, O. (2017) · Wiley eBooks · doi:10.1002/9781119132363.ch47 · Cited by 23
Howard, R. (2008) · Handbook of clinical neurology · doi:10.1016/s0072-9752(07)01704-6 · Cited by 22
Deafferentation in thalamic and pontine areas in severe traumatic brain injury
Laouchedi, M., Damien Galanaud, E., Delmaire, C., Fernández-Vidal, S., Messé, A., Mesmoudi, S., Boumghar, F. O., Pélégrini‐Issac, M., Puybasset, L., Benali, H., et al. (2014) · Journal of Neuroradiology · doi:10.1016/j.neurad.2014.03.001 · Cited by 22
Silencing The Brain May Be Better Than Stimulating it. The GABA Effect
Pistoia, F., Sarà, M., Sacco, S., Franceschini, M., & Carolei, A. (2013) · Current Pharmaceutical Design · doi:10.2174/13816128113196660649 · Cited by 22
“On the other hand, lesions clustered in the anterior portion of the brainstem, regardless of their rostrocaudal level, do not cause loss of consciousness: these lesions spare the tegmentum but involve structures such as the cerebral peduncles, the pontine nuclei of the basis pontis or the pyramidal tracts, causing sev…”
BackgroundMemory and Learning as Key Competences of Living Organisms
Witzany, G. (2018) · Signaling and communication in plants · doi:10.1007/978-3-319-75596-0_1 · Cited by 24
“If some of the communication brain parts are deformed or damaged, consciousness looks rather strange, and the de fi cits in the different concepts of consciousness become obvious (Parvizi and Damasio 2001, 2003).”
BackgroundDynamic sodium imaging at ultra-high field reveals progression in a preclinical migraine model
Abad, N., Rosenberg, J. T., Hike, D., Harrington, M. G., & Grant, S. C. (2018) · Pain · doi:10.1097/j.pain.0000000000001307 · Cited by 20
Prefrontal neural dynamics in consciousness
León-Domínguez, U., & León‐Carrión, J. (2019) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2019.05.018 · Cited by 23
Inactivation of Prefrontal Cortex Delays Emergence From Sevoflurane Anesthesia
Huels, E. R., Groenhout, T., Fields, C. W., Liu, T., Mashour, G. A., & Pal, D. (2021) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2021.690717 · Cited by 19
Persistent Vegetative and Minimally Conscious States
Machado, C., & Korein, J. (2009) · Reviews in the Neurosciences · doi:10.1515/revneuro.2009.20.3-4.203 · Cited by 18
Wiegand, K., Heiland, S., Uhlig, C. H., Dykstra, A. R., & Gutschalk, A. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.11.036 · Cited by 19
“The locus coeruleus is one of the nuclei whose projections are required for human states of consciousness (Parvizi and Damasio, 2003), and the activation-level of this system has been shown to interact with the detection of peri-threshold sounds at the level of auditory cortex (McGinley et al.,…”
The role of plasticity in the recovery of consciousness
Bagnato, S. (2022) · Handbook of clinical neurology · doi:10.1016/b978-0-12-819410-2.00020-5 · Cited by 17
Applications of Advanced MRI to Disorders of Consciousness
Fischer, D. B., Newcombe, V., Fernández‐Espejo, D., & Snider, S. B. (2022) · Seminars in Neurology · doi:10.1055/a-1892-1894 · Cited by 18
Edlow, B. L., Boerwinkle, V. L., Annen, J., Boly, M., Gosseries, O., Laureys, S., Mukherjee, P., Puybasset, L., Stevens, R. D., Threlkeld, Z. D., et al. (2023) · Neurocritical Care · doi:10.1007/s12028-023-01794-2 · Cited by 18
“Volumetry and lesion mapping studies have identified neuroanatomic regions, such as the brainstem tegmentum [8–13], thalamus [14–17], posterior cingulate cortex [17, 18], medial prefrontal cortex [17], and occipital cortex [19], where lesions are associated with reduced levels of consciousness.”
BackgroundReduced Brainstem Volume After Mild Traumatic Brain Injury
Kim, E., Seo, H. G., Lee, H. H., Lee, S. H., Choi, S. H., Yoo, R., Cho, W., Yun, S. J., Kang, M., & Oh, B. (2020) · American Journal of Physical Medicine & Rehabilitation · doi:10.1097/phm.0000000000001580 · Cited by 18
“In addition, loss of consciousness—a cardinal sign of mTBI—is believed to be related to the transient disruption of brainstem function.(30) It has been reported that the Glasgow Coma Scale, which measures the state of consciousness, is associated with the location of traumatic axonal injury lesions in the brainstem (i.”
BackgroundTang, H., Zhu, Q., Li, W., Qin, S., Gong, Y., Wang, H., Shioda, S., Li, S., Huang, J., Liu, B., et al. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191029101830 · Cited by 17
Jahi McMath: a new state of disorder of consciousness
Machado, C. (2021) · Journal of Neurosurgical Sciences · doi:10.23736/s0390-5616.20.04939-5 · Cited by 17
Improvement in Pisa Syndrome and Tardive Dyskinesia Following Aripiprazole Treatment
Shan, J., & Tseng, M. M. (2009) · Journal of Neuropsychiatry · doi:10.1176/appi.neuropsych.21.3.350 · Cited by 17
Deep brain stimulation of hypothalamus for narcolepsy-cataplexy in mice
Rogers, A., Aiani, L. M., Blanpain, L. T., Sun, Y., Moore, R. H., & Willie, J. T. (2020) · Brain stimulation · doi:10.1016/j.brs.2020.04.006 · Cited by 21
Acetylcholine, Cognition, and Consciousness
Woolf, N. J. (2006) · Journal of Molecular Neuroscience · doi:10.1385/jmn:30:1:219 · Cited by 17
“It is well-known that cholinergic and monoaminergic systems control the level of consciousness ( Parvizi and Damasio, 2003 ).”
BackgroundMethodological aspects of studying the mechanisms of consciousness
Tsytsarev, V. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113684 · Cited by 17
Mao, R., Cavelli, M., Findlay, G., Driessen, K., Peterson, M. J., Marshall, W., Tononi, G., & Cirelli, C. (2024) · iScience · doi:10.1016/j.isci.2024.109919 · Cited by 19
“18,19 This isbecause patientswithwidefrontoparietal corticalnetwork dysfunctiontypicallyremainunresponsive, in vegetative state,evenwhenthe functionof the brainstem reticular formation is preserved.”
BackgroundHow Brain Arousal Mechanisms Work
Pfaff, D. W. (2018) · Cambridge University Press eBooks · doi:10.1017/9781108377485 · Cited by 22
Vascular diseases of the central nervous system
Itabashi, H. H., Andrews, J. M., Tomiyasu, U., Erlich, S. S., & Sathyavagiswaran, L. (2007) · Elsevier eBooks · doi:10.1016/b978-012058527-4/50013-4 · Cited by 15
Kvello, P., & Gericke, N. (2021) · PLoS ONE · doi:10.1371/journal.pone.0260752 · Cited by 30
Persistent Akinetic Mutism After Bilateral Paramedian Thalamic Infarction
Cavanna, A. E., Bertero, L., Cavanna, S., Servo, S., Strigaro, G., & Monaco, F. L. (2009) · Journal of Neuropsychiatry · doi:10.1176/appi.neuropsych.21.3.351 · Cited by 14
Nir, T., Or‐Borichev, A., Izraitel, E., Hendler, T., Lerner, Y., & Matot, I. (2019) · British Journal of Anaesthesia · doi:10.1016/j.bja.2019.05.038 · Cited by 13
Tang, H., Qin, S., Li, W., Chen, X., Ulloa, L., Zhu, Q., Liu, B., Gong, Y., Zhao, Y., Wang, S., et al. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.598198 · Cited by 14
“Richmond, VA, USA) (Romine et al., 2014).”
Overlap of Encephalopathies and Epileptic Seizures
Drislane, F. W. (2013) · Journal of Clinical Neurophysiology · doi:10.1097/wnp.0b013e3182a73bfa · Cited by 14
“Indeed, deep coma without intrinsic neocortical damage or dysfunction can be caused by lesions such as strokes in the dorsal pontine tegmentum (Parvizi and Damasio, 2003).”
Background[Seasonal changes in the course of atopic eczema].
Imai, S., Takeuchi, S., & Mashiko, T. (1987) · PubMed · Cited by 14
A review of the sufficient conditions for consciousnessPreprint
Coppola, P. (2023) · PsyArXiv (OSF Preprints) · doi:10.31234/osf.io/2xvc4 · Cited by 14
Global Disorders of Consciousness
Schiff, N. (2007) · Blackwell Publishing Ltd eBooks · doi:10.1002/9780470751466.ch47 · Cited by 5
Prognostic Value of Hemorrhagic Brainstem Injury on Early Computed Tomography: A TRACK-TBI Study
Williams, J. R., Nieblas‐Bedolla, E., Feroze, A. H., Young, C. C., Temkin, N. R., Giacino, J. T., Okonkwo, D. O., Manley, G. T., Barber, J. K., Durfy, S. J., et al. (2021) · Neurocritical Care · doi:10.1007/s12028-021-01263-8 · Cited by 13
Gibson, R. M., Ray, L. B., Laforge, G., Owen, A. M., & Fogel, S. M. (2020) · Journal of Neurology · doi:10.1007/s00415-020-10076-2 · Cited by 14
Fiber Pathway Pathology, Synapse Loss and Decline of Cortical Function in Schizophrenia
Bennett, M. R., Farnell, L., & Gibson, W. G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060518 · Cited by 12
Bulbospinal neurons implicated in mesopontine‐induced anesthesia are substantially collateralized
Reiner, K., Sukhotinsky, I., & Devor, M. G. (2008) · The Journal of Comparative Neurology · doi:10.1002/cne.21689 · Cited by 12
“© 2008 WILEY-LISS, INC. lesions, or manipulations such as concussion or explosive head rotation, that produce widespread and diffuse whitematter injury (Nauta, 1946; Hayes et al., 1984; Katayama et al., 1988; Smith et al., 2000; Finnie and Blumbergs, 2002; Parvizi and Damasio, 2003).”
BackgroundDiscriminating cognitive motor dissociation from disorders of consciousness using structural MRI
Pozeg, P., Jöhr, J., Pincherle, A., Marie, G., Ryvlin, P., Meuli, R. A., Hagmann, P., Diserens, K., & Dunet, V. (2021) · NeuroImage Clinical · doi:10.1016/j.nicl.2021.102651 · Cited by 13
The Reticular Formation and Some Related Nuclei
ten Donkelaar, H. J. (2011) · Springer eBooks · doi:10.1007/978-3-642-19134-3_5 · Cited by 12
Subcortical Hubs of Brain Networks Sustaining Human Consciousness
Cambareri, M. K., Horn, A., Lewis, L. D., Li, J., & Edlow, B. L. (2025) · Human Brain Mapping · doi:10.1002/hbm.70352 · Cited by 12
Ascending reticular activating system of the brain
Kovalzon, V. M. (2016) · Translational Neuroscience and Clinics · doi:10.18679/cn11-6030/r.2016.034 · Cited by 11
Lesions in deep gray nuclei after severe traumatic brain injury predict neurologic outcome
Clarençon, F., Bardinet, É., Martinerie, J. M., Pelbarg, V., de Champfleur, N. M., Gupta, R., Tollard, É., Ares, G. S., Ibarrola, D., Schmitt, E., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0186641 · Cited by 11
Groß, M., & Hennig, B. (2023) · Springer eBooks · doi:10.1007/978-3-662-64118-7_29 · Cited by 11
Lu, K., Wang, Z., Bai, N., Zhao, Z., Zhao, X., & He, Y. (2023) · BMC Anesthesiology · doi:10.1186/s12871-023-02294-8 · Cited by 10
Injury of the lower ascending reticular activating system in patients with pontine hemorrhage
Jang, S. H., & Yeo, S. S. (2016) · Medicine · doi:10.1097/md.0000000000005527 · Cited by 10
Sustaining wakefulness: Brainstem connectivity in human consciousnessPreprint
Edlow, B. L., Olchanyi, M., Freeman, H. J., Li, J., Maffei, C., Snider, S. B., Zöllei, L., Iglesias, J. E., Augustinack, J. C., Bodien, Y. G., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.13.548265 · Cited by 10
Eliason, M. C., Kalbande, P. P., & Saleem, G. T. (2024) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2024.1341707 · Cited by 9
A Paradox of Studying Dream Alteration in Patients with Pontine Lesions
Yu, C. K.-C. (2005) · Neuropsychoanalysis · doi:10.1080/15294145.2005.10773496 · Cited by 9
“Indeed, the core consciousness can be conceived as a general conscious background, constituted, at least partly, by the body state at the lower level, and perhaps by the body schema at the higher level (Parvizi & Damasio, 2003).”
BackgroundInfluentialLevels of Consciousness and Attention
Bleck, T. P. (2007) · Elsevier eBooks · doi:10.1016/b978-141603618-0.10001-3 · Cited by 9
Pontine parabrachial nucleus-basal forebrain circuitry regulating cortical and hippocampal arousal
Lv, Y., Wen, Y., Vetrivelan, R., & Lu, J. (2023) · Sleep Medicine · doi:10.1016/j.sleep.2023.10.032 · Cited by 8
Arousal-promoting effect of the parabrachial nucleus and the underlying mechanisms: Recent advances
Li, Y.-A., Yao, J., Li, X., & Hu, K.-H. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.111226 · Cited by 9
Parabrachial Foxp2-expressing neurons are necessary for sustaining core body temperature in the cold
Grady, F. S., Graff, S. A., Warnock, M. M., Gasparini, S., Tish, M. M., Li, Y., Buchanan, G. F., Resch, J. M., & Geerling, J. C. (2025) · iScience · doi:10.1016/j.isci.2025.112764 · Cited by 7
“Our experimental mice had grossly normal behavior, but damage in this part of the brain has been re-ported to reduce wakefulness 49 or even cause coma, 37,39,40,50,51 which would reduce thermogenic activity.”
Automated MRI Segmentation of Brainstem Nuclei Critical to Consciousness
Olchanyi, M., Augustinack, J. C., Haynes, R. L., Lewis, L. D., Cicero, N. G., Li, J., Destrieux, C., Folkerth, R. D., Kinney, H. C., Fischl, B. R., et al. (2025) · Human Brain Mapping · doi:10.1002/hbm.70357 · Cited by 12
“…segmentation method to SWI scans and replicated prior observations that structural injury to AAN nuclei correlates with levels of consciousness and functional measures of recovery (Bianciardi et al. 2021; Edlow et al. 2013; Parvizi and Damasio 2003; Snider et al. 2019; Snider, Bodien, et al. 2020).”
Resolving the role of the paramedian thalamus in forebrain arousal mechanisms
Schiff, N. D. (2018) · Annals of Neurology · doi:10.1002/ana.25378 · Cited by 8
Kognitive Störungen: Koma, Delir, Demenz
Förstl, H. (2006) · Springer eBooks · doi:10.1007/3-540-30887-3_5 · Cited by 8
Khalaf, A. F., Lopez, E., Li, J., Horn, A., Edlow, B. L., & Blumenfeld, H. (2025) · NeuroImage · doi:10.1016/j.neuroimage.2025.121224 · Cited by 8
“This is further supported by lesion studies in the brainstem and thalamus identifying a key role of these regions in conscious perception and attention modulation (Parvizi and Damasio, 2003; Bogen, 1995).”
The Reticular Formation and the Neuromodulatory Systems
Horn, A. K. E., Němcová, V., ten Donkelaar, H. J., & Overeem, S. (2020) · Springer eBooks · doi:10.1007/978-3-030-41878-6_5 · Cited by 7
Neuroimaging in Disorders of Consciousness and Recovery
Xu, L. B., Hampton, S. E., & Fischer, D. B. (2023) · Physical Medicine and Rehabilitation Clinics of North America · doi:10.1016/j.pmr.2023.06.017 · Cited by 7
Chapter 6 Neuropsychological testing: bedside approaches
Schnider, A. (2008) · Handbook of clinical neurology · doi:10.1016/s0072-9752(07)88006-7 · Cited by 7
“This system with its projections through the basal forebrain and the thalamus to wide areas of the hemispheres constitutes the ascending reticular activating system (Brodal, 1981; Parvizi and Damasio, 2003).”
Consciousness and Subcortical Arousal Systems
Motelow, J. E., & Blumenfeld, H. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-415804-7.00021-6 · Cited by 6
Are the irreversibly comatose still here? The destruction of brains and the persistence of persons
Meier, L. J. (2019) · Journal of Medical Ethics · doi:10.1136/medethics-2019-105618 · Cited by 7
MAGNETIC RESONANCE IMAGING IN PREDICTING OUTCOMES OF SEVERE TRAUMATIC BRAIN INJURY IN CHILDREN
Ahadov, T. A., Semenova, N. A., Akhlebina, M. I., Manzhurtsev, A. V., Bozhko, O. V., Melnikov, I. A., & Ublinskiy, M. V. (2019) · Russian Journal of Pediatric Surgery · doi:10.18821/1560-9510-2019-23-6-321-328 · Cited by 7
Stone, J. L., Bailes, J. E., Hassan, A. N. E.-D., Sindelar, B., Patel, V. A., & Fino, J. J. (2016) · Neurocritical Care · doi:10.1007/s12028-016-0298-y · Cited by 7
How Brain Arousal Mechanisms Work: Paths Toward Consciousness
Pfaff, D. W. (2018) · Cited by 9
A new look to coma from the viewpoint of nonlinear dynamics
Kamali, S., Gharibzadeh, S., & Jafari, S. (2018) · Nonlinear Dynamics · doi:10.1007/s11071-018-4184-3 · Cited by 6
Wei, Y.-Y., Oldroyd, J., Haste, P., Jayamohan, J., Jones, M., Casey, N., Peña, J.-M., Baylis, S., Gilmour, S., & Jérusalem, A. (2025) · Communications Engineer · doi:10.1038/s44172-025-00352-2 · Cited by 8
A review of the sufficient conditions for consciousness
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“In fact, Damasio and Carvalho propose 116 that the first feelings emerged even before the phylogenic advent of the cerebral cortex.”
Animal minds: The case for emotion, based on neuroscience
Turnbull, O. H., & Bär, A. (2020) · Neuropsychoanalysis · doi:10.1080/15294145.2020.1848611 · Cited by 7
Neuropsychological Assessment in a Case of Adult-Onset Hemophagocytic Lymphohistiocytosis (HLH)
Ruppert, P. D., Edmonds, E. C., Brook, M. A., Musil, S., & Han, S. D. (2012) · The Clinical Neuropsychologist · doi:10.1080/13854046.2012.702788 · Cited by 6
“For example, the patient's early neurological presentation was characterized by coma, and acute MRI conducted during this time revealed extensive subcortical abnormalities including brainstem structures which are known to be important for maintaining alertness (Parvizi & Damasio, 2003 ).”
BackgroundThe Circuit, Cellular, and Synaptic Bases of Sleep-Wake Regulation
Arrigoni, E., & Fuller, P. M. (2019) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-12-813743-7.00005-0 · Cited by 6
Wu, Y., Yu, L., Chen, P., Hu, G., Lin, B., Zhang, C., Wu, X., & Wang, L. (2023) · Journal of Neuroscience Research · doi:10.1002/jnr.25182 · Cited by 6
Metadata
- Authors
- Parvizi, J.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Parvizi, J.
- ORCID
- Parvizi, J.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-04-22
- Volume
- 126
- Issue
- 7
- Pages
- 1524-1536
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2045226019
- Semantic Scholar
- ed5a0f5772d8594a017b9bd04a0e5a297dd75efe
- Cited by
- 400
- References
- 74
- Citations by year
- 2026: 17 · 2025: 27 · 2024: 27 · 2023: 23 · 2022: 16 · 2021: 19 · 2020: 18 · 2019: 20 · 2018: 36 · 2017: 13 · 2016: 20 · 2015: 14 · 2014: 14 · 2013: 30 · 2012: 15
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- G. Harold and Leila Y. Mathers Foundation
- University of Illinois at Urbana-Champaign
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- brainstem infarction, reticular formation, consciousness, pontine tegmentum, locus coeruleus, laterodorsal tegmental nucleus, parabrachial nucleus, hyperthermia, lesion localization, midbrain
- MeSH terms
- Adult, Aged, Brain Stem, Coma, Female, Fever, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Pons, Reticular Formation, Retrospective Studies, Stroke
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