The DOI matches its Crossref record; 136 of the 139 references it cites were found in a registry or an index; 5 of the 185 sources its claims cite were checked for support.
Localization of Dysfunction in Major Depressive Disorder: Prefrontal Cortex and Amygdala
Open accessAbstract
Despite considerable effort, the localization of dysfunction in major depressive disorder (MDD) remains poorly understood. We present a hypothesis about its localization that builds on recent findings from primate neuropsychology. The hypothesis has four key components: a deficit in the valuation of "self" underlies the core disorder in MDD; the medial frontal cortex represents "self"; interactions between the amygdala and cortical representations update their valuation; and inefficiency in using positive feedback by orbital prefrontal cortex contributes to MDD.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
The paper proposes that major depressive disorder involves dysfunction in medial and orbital frontal cortex and their interactions with the amygdala, especially in valuing the self, objects, rules, and actions. It argues that inefficient use of positive feedback by orbital prefrontal cortex, together with altered amygdala updating, can produce negative bias and low self-esteem.
Key findings
- The authors advance a four-part hypothesis: impaired valuation of the self is central to MDD; medial frontal cortex carries a self representation; amygdala–cortical interactions update valuations; and orbital prefrontal cortex contributes through inefficient use of positive feedback.
- Human evidence cited implicates medial and orbital frontal cortex plus amygdala: altered activation during emotional and reward tasks, frontal lesions in depression after cerebrovascular disease, altered metabolism in depressed Parkinson’s patients, and volume/thickness reductions in PFo area 11, sulcal area 47, and subgenual cortex (areas 24, 32, 25). Subgenual volume reduction is reported before symptom onset in high familial risk, early in illness, persistent across episodes, and most consistent in severe cases.
- In macaque devaluation tasks, bilateral amygdala lesions, bilateral PFo lesions, or crossed amygdala–PFo disconnection attenuate the devaluation effect, while lesions of ventral/dorsolateral prefrontal cortex, entorhinal cortex, perirhinal cortex, or hippocampus do not. In serial object reversal, PFo lesions slow learning, amygdala lesions do not; trial-by-trial analysis shows PFo lesions impair use of positive feedback, whereas amygdala lesions improve performance one trial after an error followed by a correct response. Buckley et al. reported EC+1 accuracy falling from 77% preoperatively to 50% after PFo lesions.
- Treatment-related findings include increased activation in medial/orbital frontal and temporal/amygdala regions during depression versus remission; sertraline restored a normal happy-face bias and PFo activation to happy faces in a 26 ms masked-face paradigm. Deep brain stimulation is noted to improve about one-half of cases and produce remission in about one-third.
Methods
- This is a theoretical review and hypothesis paper, not a primary empirical study; it synthesizes human clinical and neuroimaging findings with nonhuman primate neuropsychology, lesion, and physiology research.
- The main analysis is a narrative integration of evidence from devaluation tasks, serial object-reversal learning, probabilistic learning, Pavlovian conditioning, and self-representation studies.
- Cited data include MDD patients, healthy controls, remitted patients, patients with Parkinson’s or cerebrovascular disease, and nonhuman primates including macaques and marmosets, with some rodent findings.
Limitations
- The paper states that animal conditioning tasks are blunt tools for human conscious emotion; that rodent frontal cortex is not homologous to primate granular prefrontal cortex; that cause versus effect in MDD remains unclear; that some arguments, such as the aversive analogue prediction, are indirect; and that gray matter reductions can produce partial volume effects that complicate activation–severity relationships.
- Evident from the text: as a review/hypothesis, it does not directly test the proposed mechanism, relies heavily on cross-species inference, and draws on separate studies with varied methods rather than a systematic meta-analysis.
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Claims the paper makes
110 Not checked yet · 46 Own interpretation · 2 Supported so far · 2 Own result · 2 No basis given · 1 Supported · 1 Mixed support · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“These patients had less activation in response to gains in the left nucleus accumbens and the caudate nucleus in both hemispheres (130)”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Brain activation in MDD before and after treatment
What the sources say
- Supportedcites [130] Pizzagalli, 2009, Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder, Am J Psychiatry source
The Results (Functional MRI Data) report significantly weaker responses to gains in the left nucleus accumbens and bilateral dorsal caudate in the MDD group than in comparison subjects. The paper notes that the nucleus accumbens difference should be considered preliminary because it did not survive correction for multiple comparisons. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
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- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“in recovered MDD patients who relapse when challenged with serotonin or catecholamine depletion, metabolism increases in these regions as the depressive symptoms return (125, 129).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Brain activation in MDD before and after treatment
What the sources say
- Supportedcites [125] Hasler, 2008, Neural response to catecholamine depletion in unmedicated subjects with major depressive disorder in remission and healthy subjects, Arch Gen Psychiatry source
The Results report that catecholamine depletion increased metabolism in several regions in remitted MDD subjects, with metabolic changes correlated with depressive responses. The same section reports that depressive relapse under tryptophan depletion, used to reduce serotonergic function, was associated with increased metabolism in overlapping regions. Page numbers are not provided in our copy. (LLM, conf=0.91)
- Not checked yetcites [129] Neumeister, 2004, Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls, Arch Gen Psychiatry source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
In the paper
“and deficits in verbal memory (33).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Major depression
What the sources say
- Not checked yetcites [33] MacQueen, 2002, Recollection memory deficits in patients with major depressive disorder predicted by past depressions but not current mood state or treatment status, Psychol Med source
plaincorrelational- 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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None of the sources cited for this claim have been checked yet.
In the paper
“altered attentional set-shifting after the presentation of negative (sad) stimuli (30–32);”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Major depression
What the sources say
- Not checked yetcites [30] Mogg, 2006, Interpretation of ambiguous information in clinical depression, Behav Res Ther source
- Not checked yetcites [31] Erickson, 2005, Mood-congruent bias in affective go/no-go performance of unmedicated patients with major depressive disorder, Am J Psychiatry source
- Not checked yetcites [32] Gotlib, 2004, Attentional biases for negative interpersonal stimuli in clinical depression, J Abnorm Psychol source
plaincorrelational- 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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None of the sources cited for this claim have been checked yet.
In the paper
“When cognitively challenged, depressed patients show less change than controls in heart-rate variability (HRV) in response to mildly stressful tasks (37, 38).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Major depression
What the sources say
- Not checked yetcites [37] Shinba, 2008, Decrease in heart rate variability response to task is related to anxiety and depressiveness in normal subjects, Psychiatry Clin Neurosci source
- Not checked yetcites [38] Nugent AC, Bain EE, Thayer JF, Sollers J, Drevets WC (in press): Heart rate variability during motor and cognitive tasks in female subjects with and without major depressive disorder. Psychiatry Res Neuroimaging.
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.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Visceral, neuroendocrine, and autonomic disturbances also characterize MDD, and they often lead to altered weight, appetite, and sleep (34).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Major depression
What the sources say
- Not checked yetcites [34] Gold, 2002, New insights into the role of cortisol and the glucocorticoid receptor in severe depression, Biol Psychiatry 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.
None of the sources cited for this claim have been checked yet.
In the paper
“mood-dependent deficits in the integration of sensory and social information (25–28);”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Major depression
What the sources say
- Not checked yetcites [25] Gotlib, 2004, Coherence and specificity of information-processing biases in depression and social phobia, J Abnorm Psychol source
- Not checked yetcites [26] Murphy, 1999, Emotional bias and inhibitory control processes in mania and depression, Psychol Med source
- Not checked yetcites [27] Bhagwagar, 2004, Normalization of enhanced fear recognition by acute SSRI treatment in subjects with a previous history of depression, Am J Psychiatry source
- Not checked yetcites [28] Victor TA, Furey ML, Fromm SJ, Ohman A, Drevets WC (in press): Relationship of emotional processing to masked faces in the amgydala to mood state and treatment in major depressive disorder. Arch Gen Psychiatry.
plaincorrelational- 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.
- Based: passes — The paper gives a reason why it holds.
In the paper
“These findings could account for the increased risk of sudden death and ventricular arrhythmia among MDD patients who develop cardiovascular disease (35).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Major depression
What the sources say
- Not checked yetcites [35] Carney, 2005, Depression, the autonomic nervous system, and coronary heart disease, Psychosom Med source
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.
In the paper
“They also show oversensitivity to negative feedback under certain circumstances (21);”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Major depression
What the sources say
- Not checked yetcites [21] Elliott, 1996, Neuropsychological impairments in unipolar depression: The influence of perceived failure on subsequent performance, Psychol Med 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.
None of the sources cited for this claim have been checked yet.
In the paper
“inflexibility in the face of changing reinforcement contingencies, as assessed in choice-reversal tasks (22–24);”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Major depression
What the sources say
- Not checked yetcites [22] Pizzagalli, 2008, Reduced hedonic capacity in major depressive disorder: Evidence from a probabilistic reward task, J Psychiatr Res source
- Not checked yetcites [23] Dombrovski, 2010, Reward/punishment reversal learning in older suicide attempters, Am J Psychiatry source
- Not checked yetcites [24] Murphy, 2001, Decision-making cognition in mania and depression, Psychol Med source
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. 45
- Probably not a substantial claim. 7
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“These findings indicate that PFo lesions cause a deficit in using positive feedback, but not in the use of negative feedback (91, but cf. 94).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in reversal tasks
What the sources say
- Partly supportedcites [91] Rudebeck, 2008, Amygdala and orbitofrontal cortex lesions differentially influence choices during object reversal learning, J Neurosci sourceExperimental — accuracy not yet measured
The Discussion reports that monkeys with OFC lesions benefited less from rewarded trials after a reversal, supporting the positive-feedback part of the claim. But it also says they were impaired, to a lesser extent, at using error information; the claim that negative-feedback use was unaffected is therefore not supported. No page number is available in our copy. (LLM, conf=0.90)
- Disputedcites [94] Clarke, 2008, Lesions of the medial striatum in monkeys produce perseverative impairments during reversal learning similar to those produced by lesions of the orbitofrontal cortex, J Neurosci sourceExperimental — accuracy not yet measured
The Discussion (‘The striatum, amygdala, and behavioral switching’; page not provided) supports a positive-feedback deficit after OFC lesions, but explicitly says OFC-lesioned monkeys were also insensitive to negative outcomes. The claim’s exclusion of a negative-feedback deficit contradicts that passage. (LLM, conf=0.91)
Checked by a reasoning model — may be wrong.
hedgeddirect- 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.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“MFa shows activation when people consider personality characteristics about themselves or receive social feedback about themselves from others (104, 105).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Role of prefrontal cortex in self-representation
What the sources say
- Supportedcites [104] Somerville, 2010, Self-esteem modulates medial prefrontal cortical responses to evaluative social feedback, Cereb Cortex source
The section on differential fMRI responses (p. 6) says the mPFC is more active when people report on their personality traits. The Discussion (p. 5) reports vACC/mPFC activity while participants received social feedback from purported peers, with a greater response to positive than negative feedback. (LLM, conf=0.90)
- Not checked yetcites [105] Moran, 2006, Neuroanatomical evidence for distinct cognitive and affective components of self, J Cogn Neurosci source
plaindirect- 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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
None of the sources cited for this claim have been checked yet.
In the paper
“MDD patients show altered incentive and reward processing, leading to a lack of motivation, including abulia, as well as apathy and anhedonia (18, 19).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Major depression
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Several studies have reported evidence for abnormally elevated sympathetic function in MDD, coupled with reduced parasympathetic tone on heart rate under resting conditions (35, 36).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Major depression
What the sources say
- Not checked yetcites [35] Carney, 2005, Depression, the autonomic nervous system, and coronary heart disease, Psychosom Med source
- Not checked yetcites [36] Udupa, 2007, Modulation of cardiac autonomic functions in patients with major depression treated with repetitive transcranial magnetic stimulation, J Affect Disord 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.
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It may state two separate claims as one.
In the paper
“These patients manifest markedly lowered self-esteem and ruminate endlessly on the aversive aspects of events in their lives, their hopelessness about a better future, and their helplessness to do anything about it (20).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Major depression
What the sources say
- Not checked yetcites [20] 1994
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
“According to our hypothesis, the amygdala updates the valuation of representations in the medial and orbital frontal cortex, among which is a representation of ‘self’.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Major depression
hedgeddirect- Asserted: fails — The authors may not 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. The authors may not put it forward as true. The paper may give no reason why it holds.
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
“Taken together, the findings cited so far implicate both granular and agranular parts of frontal cortex, as well as both its medial and orbital networks.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Neuroanatomical correlates
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 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
“These patients thus seem to show a bias toward negative emotions, with excessive amygdala activation for negative stimuli and blunted activation for positive ones.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Neuroanatomical correlates
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.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In these key parts of the MFa, the reduction in cortical volume arises prior to the onset of symptoms in subjects at high familial risk for depression, appears early in the course of the illness, persists across depressive episodes, and occurs consistently in the most severe cases (48, 49, 51–53).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Neuroanatomical correlates
What the sources say
- Not checked yetcites [48] Coryell, 2005, Subgenual prefrontal cortex volumes in major depressive disorder and schizophrenia: Diagnostic specificity and prognostic implications, Am J Psychiatry source
- Not checked yetcites [49] Hirayasu, 1999, Subgenual cingulate cortex volume in first-episode psychosis, Am J Psychiatry source
- Not checked yetcites [51] Botteron, 2002, Volumetric reduction in left subgenual prefrontal cortex in early onset depression, Biol Psychiatry source
- Not checked yetcites [52] Boes, 2008, Rostral anterior cingulate cortex volume correlates with depressed mood in normal healthy children, Biol Psychiatry source
- Not checked yetcites [53] McDonald, 2004, Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes, Arch Gen Psychiatry source
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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, several findings implicate the orbital frontal cortex, the medial frontal cortex, and the amygdala in MDD. And several correlates have been found with its affective and autonomic symptoms.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Neuroanatomical correlates
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.
In the paper
“In both MDD patients and healthy controls, HRV regulation correlated with activation levels in the ventromedial part of area 10p (a part of PFm), but the sign of the correlation differed between the groups.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Neuroanatomical correlates
What the sources say
- Not checked yetcites [38] Nugent AC, Bain EE, Thayer JF, Sollers J, Drevets WC (in press): Heart rate variability during motor and cognitive tasks in female subjects with and without major depressive disorder. Psychiatry Res Neuroimaging.
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, reductions of cortical volume and thickness occur in several parts of the frontal cortex in depressed patients, with the most reliable and best characterized of these abnormalities occurring in PFo area 11 (44), the sulcal part of area 47 (45, 46), and the subgenual frontal cortex (47–50).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Neuroanatomical correlates
What the sources say
- Not checked yetcites [44] Rajkowska, 1997, Morphometric methods for studying the prefrontal cortex in suicide victims and psychiatric patients, Ann N Y Acad Sci source
- Not checked yetcites [45] Nugent, 2006, Cortical abnormalities in bipolar disorder investigated with MRI and voxel-based morphometry, Neuroimage source
- Not checked yetcites [46] Lyoo, 2004, Frontal lobe gray matter density decreases in bipolar I disorder, Biol Psychiatry source
- Not checked yetcites [47] Drevets, 1997, Subgenual prefrontal cortex abnormalities in mood disorders, Nature source
- Not checked yetcites [48] Coryell, 2005, Subgenual prefrontal cortex volumes in major depressive disorder and schizophrenia: Diagnostic specificity and prognostic implications, Am J Psychiatry source
- Not checked yetcites [49] Hirayasu, 1999, Subgenual cingulate cortex volume in first-episode psychosis, Am J Psychiatry source
- Not checked yetcites [50] Koo, 2008, A cross-sectional and longitudinal magnetic resonance imaging study of cingulate gyrus gray matter volume abnormalities in first-episode schizophrenia and first-episode affective psychosis, Arch Gen Psychiatry source
boostedcorrelational- 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 corollary of that hypothesis is that the representation of self is an emergent property arising from the interaction of the phylogenetically older areas of frontal cortex, MFa and OFa, with those that evolved in advanced primates, PFm and PFo, and underwent further modification during human evolution.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Major depression
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. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Electrical stimulation of the amygdala can produce fear, anxiety, dysphoria, sympathetic autonomic arousal, social withdrawal, and cortisol release (61, 62).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Neuroanatomical correlates
What the sources say
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.
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
“As a result, the devaluation effect does not depend on learning about the objects and the now-devalued food. Instead, the updating of valuations occurs automatically; the monkeys predict the value of the food before they make a choice between the two objects.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in devaluation tasks
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.
In the paper
“Patients with cerebrovascular disease who develop depression have lesions in the orbital and medial frontal cortex, but other cerebrovascular patients—those without depression—do not (41).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Neuroanatomical correlates
What the sources say
- Not checked yetcites [41] MacFall, 2001, Medial orbital frontal lesions in late-onset depression, Biol Psychiatry 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.
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
“Thus, the amygdala updates the value of the food as monkeys consume it, and this change in value is registered elsewhere in the brain, presumably including but not restricted to PFo.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in devaluation tasks
hedgeddirect- 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
“A more detailed, trial-by-trial analysis indicates that both PFo and amygdala lesions influence the use of positive feedback. As Figure 4B shows, however, they do so in opposite directions.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in reversal tasks
What the sources say
- Not checked yetcites [91] Rudebeck, 2008, Amygdala and orbitofrontal cortex lesions differentially influence choices during object reversal learning, J Neurosci source
hedgeddirect- 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
“Whereas preoperatively their monkeys scored 77% correct on the EC+1 trial type, postoperatively the monkeys with PFo lesions scored only 50% correct.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in reversal tasks
What the sources say
- Not checked yetcites [95] Buckley, 2009, Dissociable components of rule-guided behavior depend on distinct medial and prefrontal regions, Science source
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Like the monkeys studied by Rudebeck and Murray (91), the PFo lesion group studied by Buckley et al. was inefficient in using positive feedback after rule changes, suggesting that PFo plays an important role in the valuation of rule representations as well as object representations.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in reversal tasks
What the sources say
- Not checked yetcites [91] Rudebeck, 2008, Amygdala and orbitofrontal cortex lesions differentially influence choices during object reversal learning, J Neurosci source
- Not checked yetcites [95] Buckley, 2009, Dissociable components of rule-guided behavior depend on distinct medial and prefrontal regions, Science source
hedgeddirect- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Some monkeys received bilateral PFo ablations (blue) and others received a crossed surgical disconnection (green) of the amygdala and PFo (a unilateral amygdala lesion in one hemisphere along with unilateral PFo lesion in the other hemisphere, combined with section of the forebrain commissures). In all lesion groups, the devaluation effect was markedly attenuated.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in devaluation tasks
What the sources say
- Not checked yetcites [74] Malkova, 1997, Excitotoxic lesions of the amygdala fail to produce impairment in visual learning for auditory secondary reinforcement but interfere with reinforcer devaluation effects in rhesus monkeys, J Neurosci source
- Not checked yetcites [75] Izquierdo, 2007, Selective bilateral amygdala lesions in rhesus monkeys fail to disrupt object reversal learning, J Neurosci source
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.
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
“Instead, results from this test show that the monkeys could not update valuations based on current biological needs and use those updated valuations to make adaptive choices.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in devaluation tasks
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.
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
“(With more consecutive correct choices, this effect disappears, perhaps because the scores approach the maximum.)”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in reversal tasks
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.
None of the sources cited for this claim have been checked yet.
In the paper
“The same groups of operated monkeys showed little or no change in food preferences and worked for food like control monkeys.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in devaluation tasks
What the sources say
- Not checked yetcites [74] Malkova, 1997, Excitotoxic lesions of the amygdala fail to produce impairment in visual learning for auditory secondary reinforcement but interfere with reinforcer devaluation effects in rhesus monkeys, J Neurosci source
- Not checked yetcites [75] Izquierdo, 2007, Selective bilateral amygdala lesions in rhesus monkeys fail to disrupt object reversal learning, J Neurosci source
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 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
“Importantly, monkeys do not need to experience receiving the food in its devalued state. This updating occurs automatically, and the monkeys predict the food’s value before they make a choice.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in devaluation tasks
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.
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
“Taken together with the results from the devaluation task, these results show that PFo contributes to updating valuations in two ways: (1) by registering the changes in outcome value as they occur, a function mediated via interaction with the amygdala, and (2) by registering changes in object-reward mappings.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in reversal tasks
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.
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 finding indicates that amygdala activity is critical during the selective satiation procedure, while the food value changes, but not after the updating process has run its course.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in devaluation tasks
hedgeddirect- 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
“Several lines of evidence point to medial frontal areas as playing a key role in linking actions with outcomes, in parallel with the results just mentioned on linking object or rule representation with outcomes.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in reversal tasks
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.
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
“Perseveration occurs to a small extent, but it appears to be a minor aspect of the “PFo syndrome”.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in reversal tasks
hedged- 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.
In the paper
“After watching a videotape of their own interview, they changed their assessment. The patients then downgraded their behavior, based on how socially embarrassing their behavior had been, but they did not change their ratings of other (nonsocial) factors.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Role of prefrontal cortex in self-representation
What the sources say
- Not checked yetcites [109] Beer, 2006, Orbitofrontal cortex and social behavior: Integrating self-monitoring and emotion-cognition interactions, J Cogn Neurosci source
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.
None of the sources cited for this claim have been checked yet.
In the paper
“This updating needs to occur in order to make good choices in the serial object-reversal task (91) and when making object choices that optimize the probability of reward (90).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in reversal tasks
What the sources say
- Not checked yetcites [91] Rudebeck, 2008, Amygdala and orbitofrontal cortex lesions differentially influence choices during object reversal learning, J Neurosci source
- Not checked yetcites [90] Rudebeck, 2008, Frontal cortex subregions play distinct roles in choices between actions and stimuli, J Neurosci source
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
“They found that PFo lesions produced a deficit in stimulus-based, but not action-based learning, whereas anterior cingulate cortex lesions had the opposite effect.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Prefrontal cortex and amygdala function in reversal tasks
What the sources say
- Not checked yetcites [90] Rudebeck, 2008, Frontal cortex subregions play distinct roles in choices between actions and stimuli, J Neurosci 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.
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
“These findings support the idea that PFo and OFa contribute to valuations of ‘self’, or at least of one’s own actions.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Role of prefrontal cortex in self-representation
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.
In the paper
“Neuroimaging studies in humans confirm that activations in anterior cingulate cortex are related to the learning of action-outcome associations, but not to learning stimulus-outcome associations (100).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Role of prefrontal cortex in self-representation
What the sources say
- Not checked yetcites [100] Glascher, 2009, Determining a role for ventromedial prefrontal cortex in encoding action-based value signals during reward-related decision making, Cereb Cortex source
boostedcorrelational- 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.
In the paper
“When an aversive event becomes linked to a context, that context serves as a constant reminder of the US, putting the subject in “a sustained state of fearful apprehension” (118).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Hyper-emotionality in the absence of an expected event
What the sources say
- Not checked yetcites [118] Davis, 2010, Phasic vs sustained fear in rats and humans: Role of the extended amygdala in fear vs anxiety, Neuropsychopharmacology source
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.
Probably not a substantial claim.
In the paper
“In the absence of immediate reward, i.e., when they needed to predict an outcome, MDD patients were impaired at integrating reinforcement history over time and in expressing a response bias toward a more frequently rewarded cue.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Brain activation in MDD before and after treatment
What the sources say
- Not checked yetcites Pizzagalli et al. (22) Pizzagalli, 2008, Reduced hedonic capacity in major depressive disorder: Evidence from a probabilistic reward task, J Psychiatr Res source
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Activation decreases in these regions during both antidepressant treatment and deep brain stimulation of the subgenual MFa or the anterior capsule (4, 126–128).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Brain activation in MDD before and after treatment
What the sources say
- Not checked yetcites [4] Mayberg, 2005, Deep brain stimulation for treatment-resistant depression, Neuron source
- Not checked yetcites [126] Mayberg, 1999, Reciprocal limbic-cortical function and negative mood: Converging PET findings in depression and normal sadness, Am J Psychiatry source
- Not checked yetcites [127] Drevets, 2002, Glucose metabolism in the amygdala in depression: Relationship to diagnostic subtype and plasma cortisol levels, Pharmacol Biochem Behav source
- Not checked yetcites [128] Van Laere, 2006, Metabolic imaging of anterior capsular stimulation in refractory obsessive-compulsive disorder: A key role for the subgenual anterior cingulate and ventral striatum, J Nucl Med
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
“Healthy controls showed greater amygdala activation and faster behavioral responses to happy faces, compared to sad or neutral faces.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Brain activation in MDD before and after treatment
What the sources say
- Not checked yetcites Victor et al. (28) Victor TA, Furey ML, Fromm SJ, Ohman A, Drevets WC (in press): Relationship of emotional processing to masked faces in the amgydala to mood state and treatment in major depressive disorder. Arch Gen Psychiatry.
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.
In the paper
“This effect is associated with an attenuation of the normal activation of ventral PF cortex (areas 12/47 and 45) and a failure of the normal deactivation of the amygdala as they perform this task (117).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Hyper-emotionality in the absence of an expected event
What the sources say
- Not checked yetcites [117] Taylor Tavares, 2008, Neural basis of abnormal response to negative feedback in unmedicated mood disorders, Neuroimage 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.
It may state two separate claims as one.
In the paper
“both depressed and remitted MDD patients—when off medication—showed greater amygdala activation and faster behavioral responses to sad faces, compared to happy faces.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Brain activation in MDD before and after treatment
What the sources say
- Not checked yetcites Victor et al. (28) Victor TA, Furey ML, Fromm SJ, Ohman A, Drevets WC (in press): Relationship of emotional processing to masked faces in the amgydala to mood state and treatment in major depressive disorder. Arch Gen Psychiatry.
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 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 monkeys, these valuations involve either objects, rules, or actions, but humans have in addition a representation of self.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Summary and conclusions
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: 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.
- Rests on an assumption: Findings from nonhuman primates about frontal-amygdala function can be extended to humans and to MDD.
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
“PFo lesions lead to an abnormally persistent autonomic and emotional response and CSs become more associable.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Summary and conclusions
plaindirectn = 2- 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.
- The authors state this as an assumption: Negative affective responses would be affected by PFo and amygdala lesions in the same way as positive affective responses.
In the paper
“GAD and other anxiety disorders are frequent antecedents of MDD and increase the risk of developing “secondary” major depressive episodes (119).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Hyper-emotionality in the absence of an expected event
What the sources say
- Not checked yetcites [119] Wittchen, 2000, Why do people with anxiety disorders become depressed?, Acta Psychiatr Scand Suppl 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.
In the paper
“During successful treatment, MDD patients exhibited the normal bias toward happy faces, and this behavioral improvement correlated with neuroimaging results from PFo; before treatment, PFo showed no activation in response to happy faces, whereas during successful treatment a robust activation occurred in response to such stimuli.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Brain activation in MDD before and after treatment
What the sources say
- Not checked yetcites Victor et al. (28) Victor TA, Furey ML, Fromm SJ, Ohman A, Drevets WC (in press): Relationship of emotional processing to masked faces in the amgydala to mood state and treatment in major depressive disorder. Arch Gen Psychiatry.
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.
In the paper
“Corticostriatal projections from the agranular areas target the nucleus accumbens, and those from the granular prefrontal areas terminate in the caudate nucleus.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Brain activation in MDD before and after treatment
What the sources say
- Not checked yetcites [131] Haber, 2003, The primate basal ganglia: Parallel and integrative networks, J Chem Neuroanat 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.
None of the sources cited for this claim have been checked yet.
In the paper
“metabolic activation appears elevated in depressed samples of mild-to-moderate severity, but reduced in more severe, treatment-refractory cases (1, 121)”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Brain activation in MDD before and after treatment
What the sources say
hedgedcorrelational- 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 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
“neuroimaging and clinical studies have repeatedly implicated PFo, PFm, OFa, MFa, and the amygdala in MDD.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Summary and conclusions
boostedcorrelational- 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.
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
“studies of nonhuman primates have pointed to the homologues of these brain structures as fundamental to affective responses and processing reward feedback.”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Summary and conclusions
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“depressed individuals fail to sustain nucleus accumbens activation over time compared with controls, which correlates with individual differences in self-reported positive affect (133).”
§ Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala > Brain activation in MDD before and after treatment
What the sources say
- Not checked yetcites [133] Heller, 2009, Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation, Proc Natl Acad Sci U S A 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.
It may state two separate claims as one.
The paper relies on this without support.
The neural mechanisms revealed by macaque devaluation and reversal tasks are relevant to the pathophysiology of major depressive disorder in humans.
“Despite this limitation, recent advances in primate neuropsychology can contribute to understanding MDD, and the largest part of this article considers some of these findings.”
“In the next two sections, we explore recent neuropsychological results from nonhuman primates in order to gain insight into this problem.”
The paper relies on this without support.
PFo receives relatively direct inputs from olfactory, gustatory, and visceral receptors via OFa.
“PFo also receives relatively direct inputs from olfactory, gustatory and visceral receptors via the OFa (which includes the agranular insular cortex).”
The authors state this as an assumption.
Negative affective responses would be affected by PFo and amygdala lesions in the same way as positive affective responses.
“We will assume, however, that negative affective responses would be similarly affected by PFo and amygdala lesions.”
The paper relies on this without support.
Findings from nonhuman primates about frontal-amygdala function can be extended to humans and to MDD.
“using insights gained mainly from the study of nonhuman primates, we suggest how dysfunction in amygdala–frontal interactions could produce certain key symptoms of MDD.”
The paper relies on this without support.
The same valuation mechanisms that operate on object, rule, and action representations in nonhuman primates also operate on the representation of self in humans.
“Understanding how the frontal lobe functions in the valuation of object-, rule-, and action representations in nonhuman primates will illuminate how homologous areas function in the valuation of self in humans.”
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
“For example, anxiety disorders and mood disorders share hyperactive amygdala responses to negatively valenced stimuli [2,3]”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [3]
Citations
Cites
Kessler, R. C., Chiu, W. T., Demler, O., & Walters, E. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.6.617 · Cited by 12,052
Deep Brain Stimulation for Treatment-Resistant Depression
Mayberg, H. S., Lozano, A. M., Voon, V., McNeely, H. E., Seminowicz, D., Hamani, C., Schwalb, J. M., & Kennedy, S. H. (2005) · Neuron · doi:10.1016/j.neuron.2005.02.014 · Cited by 4,059
Meeting of minds: the medial frontal cortex and social cognition
Amodio, D. M., & Frith, C. D. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1884 · Cited by 3,782 · cited 1×
“Fourth, PFm and Fa show activations when humans reflect on the thoughts and ntentions of others (107,108).”
BackgroundNeural systems supporting interoceptive awareness
Critchley, H. D., Wiens, S., Rotshtein, P., Öhman, A., & Dolan, R. J. (2004) · Nature Neuroscience · doi:10.1038/nn1176 · Cited by 3,406 · cited 1×
“” First, reflecting on one’s internal state (101,102) r on whether particular trait words apply to oneself (103) increases ctivation in the dorsal anterior cingulate cortex (area 24 of the Fa).”
BackgroundSubgenual prefrontal cortex abnormalities in mood disorders
Drevets, W. C., Price, J. L., Simpson, J. R., Todd, R. D., Reich, T., Vannier, M., & Raichle, M. E. (1997) · Nature · doi:10.1038/386824a0 · Cited by 2,693
Self-citationMayberg, H. S., Liotti, M., Brannan, S. K., McGinnis, S., Mahurin, R. K., Jerabek, P. A., Silva, J. A., Tekell, J. L., Martin, C. C., Lancaster, J. L., et al. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.5.675 · Cited by 2,416
Drevets, W. C., Price, J. L., & Furey, M. L. (2008) · Brain Structure and Function · doi:10.1007/s00429-008-0189-x · Cited by 2,241 · cited 2×
“Compared with healthy control subjects, patients with MDD show altered activation in the orbital and medial frontal cortex during exposure to emotionally charged stimuli and during performance of rewardprocessing tasks (39,40).”
BackgroundSelf-citationThe mesolimbic dopamine reward circuit in depression
Nestler, E. J., & Carlezon, W. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.09.018 · Cited by 2,059
Neurobiology of emotion perception II: implications for major psychiatric disorders
Phillips, M. L., Drevets, W. C., Rauch, S. L., & Lane, R. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00171-9 · Cited by 1,736
Self-citationNeurocircuitry of Mood Disorders
Price, J. L., & Drevets, W. C. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.104 · Cited by 1,606 · cited 3×
“Additional structures include he mid- and posterior cingulate cortex, ventromedial striatum (inluding the nucleus accumbens), and the medial thalamus, among thers (8).”
BackgroundSelf-citation
Research works printed but not linked: 2
- Drevets, 1997, Subgenual prefrontal cortex abnormalities in mood disorders, Nature, 386, 824, 10.1038/386824a0 · DOI · Paper page
- Martin-Soelch, 2006, Dysfunctional learning and neurophysiological activation during appetitive and aversive conditioning in major depression: An fMRI study, Neuroimage
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Depressive rumination, the default-mode network, and the dark matter of clinical neuroscience
Hamilton, J. P., Farmer, M., Fogelman, P., & Gotlib, I. H. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.02.020 · Cited by 952
Resting-state functional connectivity in major depressive disorder: A review
Mulders, P. C., van Eijndhoven, P. F., Schene, A. H., Beckmann, C. F., & Tendolkar, I. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.07.014 · Cited by 884
Neural circuits underlying the pathophysiology of mood disorders
Price, J. L., & Drevets, W. C. (2012) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.12.011 · Cited by 788
Self-citationThe Sertraline vs Electrical Current Therapy for Treating Depression Clinical Study
Brunoni, A. R., Valiengo, L. D. C. L., Baccaro, A., Zanao, T. A., de Oliveira, J. F., Goulart, A. C., Boggio, P. S., Lotufo, P. A., Benseñor, I. M., & Fregni, F. (2013) · JAMA Psychiatry · doi:10.1001/2013.jamapsychiatry.32 · Cited by 617
Metadata
- Authors
- Murray, E. A., Wise, S. P., & Drevets, W. C.
- Affiliations
- National Institutes of Health (US)
- Laureate Institute for Brain Research (US)
- Corresponding author
- Murray, Elisabeth A.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 69
- Issue
- 12
- Pages
- e43-e54
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3058124
- OpenAlex
- W2078617766
- Cited by
- 208
- References
- 139
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 11 · 2023: 10 · 2022: 13 · 2021: 13 · 2020: 15 · 2019: 16 · 2018: 12 · 2017: 12 · 2016: 21 · 2015: 16 · 2014: 13 · 2013: 22 · 2012: 15
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (ZIAMH002886, ZIAMH002887)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- major depressive disorder, prefrontal cortex, amygdala, self-representation, self-valuation, medial frontal cortex, orbitofrontal cortex, positive feedback
- MeSH terms
- Amygdala, Animals, Choice Behavior, Major Depressive Disorder, Ego, Emotions, Frontal Lobe, Humans, Psychomotor Performance, Reversal Learning, Self Concept, Prefrontal Cortex
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.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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