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Cited by 176Neural and Behavioral Psychology StudiesStress Responses and CortisolNeurotransmitter Receptor Influence on Behavior

Prefrontal cortex executive processes affected by stress in health and disease

Open access
Girotti, Milena, Adler, Samantha M., Bulin, Sarah E., Fucich, Elizabeth A., Paredes, Denisse, Morilak, David A.·2018·Progress in Neuro-Psychopharmacology and Biological Psychiatry
DOI 10.1016/j.pnpbp.2017.07.004PMC PMC5756532
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Abstract

Prefrontal cortical executive functions comprise a number of cognitive capabilities necessary for goal directed behavior and adaptation to a changing environment. Executive dysfunction that leads to maladaptive behavior and is a symptom of psychiatric pathology can be instigated or exacerbated by stress. In this review we survey research addressing the impact of stress on executive function, with specific focus on working memory, attention, response inhibition, and cognitive flexibility. We then consider the neurochemical pathways underlying these cognitive capabilities and, where known, how stress alters them. Finally, we review work exploring potential pharmacological and non-pharmacological approaches that can ameliorate deficits in executive function. Both preclinical and clinical literature indicates that chronic stress negatively affects executive function. Although some of the circuitry and neurochemical processes underlying executive function have been characterized, a great deal is still unknown regarding how stress affects these processes. Additional work focusing on this question is needed in order to make progress on developing interventions that ameliorate executive dysfunction.

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Crossref · 10.1016/j.pnpbp.2017.07.004

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  • Interpretationnone given

    Executive dysfunction that produces maladaptive behavior and is a symptom of psychiatric pathology can be triggered or worsened by stress.

    “Executive dysfunction that leads to maladaptive behavior and is a symptom of psychiatric pathology can be instigated or exacerbated by stress.”
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  • Interpretationnone given

    Both preclinical and clinical literature indicates that chronic stress negatively affects executive function.

    “Both preclinical and clinical literature indicates that chronic stress negatively affects executive function.”
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    In non-clinical human cohorts, chronic stress levels that elicited subjective cognitive complaints were associated with poor performance in attentional shifting and working memory tests.

    “chronic stress levels which elicited subjective cognitive complaint, i.e., perceived difficulties with concentration, memory and decision making, were associated with poor performance in tests of attentional shifting and working memory (Stenfors et al 2013).”
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    Several prefrontal cortex regions including anterior cingulate, orbital cortex, and ventrolateral PFC have decreased grey matter volume in individuals with major depression and bipolar disorder.

    “several prefrontal cortex regions including the anterior cingulate, the orbital cortex and the ventrolateral PFC have decreased grey matter volume in individuals with major depression and bipolar disorder (Drevets et al 2008, Lyoo et al 2004).”
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    These structural changes in rats were accompanied by increased biases toward habit behaviors.

    “These structural changes in rats were also accompanied by increased biases toward habit behaviors.”
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    • cites Dias-Ferreira et al 2009 source

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    The stress response is highly conserved and essential for survival under environmental challenge.

    “The stress response is a highly conserved process essential for survival under conditions of environmental challenge (McEwen et al 2015, McKlveen et al 2015).”
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    Interpretationnone given

    In some cases, executive impairment may be a direct consequence of an underlying disease process independent of stress.

    “in some cases, executive impairment may be a direct consequence of an underlying disease process independent of stress.”
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    Human fMRI studies identified the central executive network as one of three core neurocognitive networks.

    “human fMRI studies of large-scale interconnectivity networks identified the central executive network (CEN) as one of three core neurocognitive networks.”
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    Major depression shows anomalies in recruitment of prefrontal circuitry and activation patterns, with decreases in dorsolateral PFC activation and hyperactivation of OFC.

    “Anomalies in the recruitment of prefrontal circuitry and patterns of activation in major depression have also been shown (Johnstone et al 2007), with decreases in activation of the dorsolateral PFC (DLPFC) (Drevets 1998) and hyperactivation of the OFC (Biver et al 1994, Drevets et al 1992).”
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    Rats exposed to chronic stress display atrophy of the associative network and hypertrophy of the sensorimotor network responsible for automated responses.

    “rats exposed to chronic stress displayed atrophy of the associative network (dorsomedial striatum-prefrontal circuitry) and hypertrophy of the sensorimotor network responsible for automated responses (dorsolateral striatal-prefrontal circuitry).”
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    Interpretationreasoning

    Stress produces structural and functional changes in fronto-striatal circuitry that reduce the ability to shift from automated behavior to goal-directed behavior and may be maladaptive in situations of change.

    “this work demonstrates stress produces structural and functinoal changes in fronto-striatal circuitry that reduces the ability of an individual to shift from automated behavior to goal-directed behavior and may be maladaptive in situations of change.”
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    Acute stressful life events and chronic stressors are strong risk factors for mood disorders, anxiety disorders, and addictive disorders.

    “both acute stressful life events and chronic stressors are strong risk factors for the development of mental illnesses such as mood disorders (Beck 2008, Kessler 1997), anxiety disorders and addictive disorders (Kessler et al 1997).”
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    Working memory, problem solving, and cognitive flexibility are negatively affected by acute stress.

    “processes underlying working memory, problem solving and cognitive flexibility are negatively affected by acute stress (Oei et al 2006, Plessow et al 2011, Plessow et al 2012, Schoofs et al 2008, Schoofs et al 2009, Steinhauser et al 2007).”
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    In the aftermath of acute stress, executive processes improve, and these effects correlate with genomic corticosteroid actions.

    “In the aftermath of an acute stress exposure, executive processes improve and these effects have been shown to correlate with genomic corticosteroid actions (Henckens et al 2011, Het & Wolf 2007, Maheu et al 2005, Oei et al 2009, Putman et al 2007).”
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    Individuals with major depressive disorder show impairments in working memory and cognitive flexibility on the Wisconsin Card Sorting Test.

    “individuals with major depressive disorder show impairments in working memory (Landro et al 2001, Rose & Ebmeier 2006) and cognitive flexibility on the Wisconsin card sorting test (Merriam et al 1999).”
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    Acute stress in humans activates saliency networks and enhances sensory gain and environmental scanning, resulting in better performance.

    “Acute stress in humans has been shown to activate saliency networks centered around the amygdala, cingulate cortex, hypothalamus, insula, striatum, and locus coeruleus, and is responsible for enhancing sensory gain and environmental scanning, resulting in better performance (Cousijn et al 2010, Oei et al 2012, van Marle et al 2009, van Marle et al 2010).”
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    About one hour after a stressful stimulus, when catecholamine levels are low but glucocorticoids remain elevated, salience network processes weaken while working memory and cognitive task performance improve and anxiety behavior decreases.

    “about 1 hour after exposure to a stressful stimulus, when catecholamine levels are low but glucocorticoid levels are still elevated, the neurocognitive processes associated with the salience network weaken (Henckens et al 2012, Henckens et al 2010), while working memory and the ability to perform cognitive tasks improve, along with reduced anxiety behavior.”
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    In amygdala, orbitofrontal cortex, and putamen, chronic stress increases dendritic elaboration and produces structural hypertrophy.

    “in other brain regions, such as amygdala, orbitofrontal cortex (OFC), and putamen, chronic stress increases dendritic elaboration and produces structural hypertrophy (Dias-Ferreira et al 2009, Liston et al 2006).”
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    GABA-related overinhibition may underlie working memory impairment in schizophrenia, and targeting this system may offer a treatment strategy.

    “These data suggest that GABA-related “overinhibition” may underlie working memory impairment in schizophrenia, and that targeting this system may offer a strategy for treating such impairments.”
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    Lorazepam impaired working memory in healthy controls, with even more impairment in schizophrenia patients.

    “lorazepam, a positive modulator at the GABAA receptor benzodiazepine site, impaired working memory in healthy controls, with even more impairment in the patient group.”
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    Low doses of stimulants administered to stably medicated schizophrenia patients can improve working memory performance, likely via prefrontal D1 receptor activation.

    “low doses administered to stably medicated patients can improve cognitive performance in working memory tasks, likely via prefrontal D1 receptor activation (Barch & Carter 2005, Goldberg et al 1991)”
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    Flumazenil significantly improved working memory in schizophrenia patients but impaired working memory in healthy controls.

    “the GABAA receptor antagonist flumazenil significantly improved working memory in the patient group but impaired working memory in healthy controls (Menzies et al 2007).”
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    FG7142 mimics increased norepinephrine release in the PFC that accompanies stress, implicating a role for norepinephrine in detrimental effects on PFC-mediated working memory.

    “FG7142 also mimics the increased norepinephrine release in the PFC that accompanies stress, implicating a role for norepinephrine in the detrimental effects on PFC-mediated working memory.”
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    Working memory deficits are present in PTSD, depression, substance dependence, schizophrenia, and ADHD.

    “working memory deficits are present in a wide range of stress-related psychiatric illnesses, such as PTSD (Veltmeyer et al 2006), depression (Rose & Ebmeier 2006), substance dependence (Bechara & Martin 2004), schizophrenia (Stone et al 1998), and ADHD (Martinussen et al 2005).”
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    Premisenone given

    Stress-induced working memory impairments are accompanied by increased prefrontal dopamine turnover and release, similar to prefrontal dopamine dysfunction in schizophrenia.

    “stress-induced working memory impairments are accompanied by increased prefrontal dopamine turnover and release, similar to the prefrontal dopamine dysfunction seen in schizophrenia.”
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    Study design and conductnone given

    The review excluded articles where deficits in executive functions were confounded by neurological conditions or physical trauma.

    “We excluded articles where the deficits in executive functions were confounded by neurological conditions or physical trauma.”
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    Administration of stimulants to unmedicated schizophrenic patients can enhance positive symptoms, likely due to subcortical D2 receptor activation.

    “Administration of stimulants to unmedicated schizophrenic patients can enhance positive symptoms (Angrist et al 1980, van Kammen et al 1982), which is likely due to subcortical D2 receptor activation.”
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    Vortioxetine reverses working memory impairments caused by serotonin depletion, effects attributed to 5HT1A agonism.

    “vortioxetine reverses working memory impairments caused by serotonin depletion, effects attributed to its 5HT1A agonism (du Jardin et al 2014)”
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    Lesions of the mPFC, as well as compromised connectivity of the inferior PFC to striatal, cerebellar, and parietal regions, result in deficits in attention in rats and humans.

    “Lesions of the mPFC, as well as compromised connectivity of the inferior PFC to striatal, cerebellar, and parietal regions, result in deficits in attention in rats and humans (Maddux & Holland 2011, Muir et al 1996), (Arnsten 2009, Arnsten & Rubia 2012, Aron & Poldrack 2005).”
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    Attention is an executive function of the PFC that is affected by emotional and motivational state and is often impaired by stress in humans and animal models.

    “Attention is another executive function of the PFC that is affected by an individual’s emotional and motivational state (Goetz et al 2008) and is often impaired by stress in both humans and in animal models.”
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    Modafinil enhances working memory in healthy individuals and individuals with a wide range of psychiatric illnesses, likely due to catecholaminergic actions.

    “modafinil enhances working memory in healthy individuals as well as individuals with a wide range of psychiatric illnesses, and this improvement is likely due to modafinil’s catecholaminergic actions (Kalechstein et al 2010, Kalechstein et al 2013, Minzenberg & Carter 2008).”
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    In college students, those in the negative stressor condition were quicker to switch attention from negative words to positive or neutral words, and participants with higher Beck Depression Inventory scores were slower to redirect attention from negative to positive words.

    “students in the negative stressor condition (where stress was induced by engaging in a competitive computer task) were quicker to switch their attention from negative words to positive or neutral words, and participants who had higher scores on the Beck Depression Inventory were slower to redirect their attention from negative to positive words (Ellenbogen et al 2002).”
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    Modafinil reverses chronic stress-induced impairments in a spontaneous alternation task in mice and improves working memory in non-stressed animals.

    “modafinil, an atypical dopamine transporter inhibitor, reverses chronic stress-induced impairments in a spontaneous alternation task in mice and improves working memory in non-stressed animals (Pierard et al 2006).”
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    Military personnel with high practice time of mindfulness training during high-stress pre-deployment demonstrated increases in working memory capacity, while those in control or low practice demonstrated decreases.

    “Military personnel with a high practice time of mindfulness training during the high-stress pre-deployment period demonstrated increases in working memory capacity, while those in the military control group or those with low practice time demonstrated decreases in working memory.”
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    Systemic fluoxetine reversed a predator stress-induced deficit in working memory, while diazepam was not effective.

    “systemic administration of fluoxetine did reverse a predator stress-induced deficit in working memory, while the benzodiazepine diazepam was not effective (Hage et al 2004).”
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    Expressive writing about a negative stressful experience produced higher increases in working memory capacity in college freshmen compared to writing about a trivial topic; gains were associated with decreases in intrusive and avoidant thinking.

    “expressive writing, in particular about a negative stressful experience, produced higher increases in working memory capacity in college freshmen compared to those writing about a trivial topic; these gains were associated with decreases in intrusive and avoidant thinking (Klein & Boals 2001).”
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    The effects of stress on attention may depend on the amount of time one is subjected to stress and the emotional valence of stimuli presented during the task.

    “Taken together, these studies suggest that the effects of stress on attention may depend on the amount of time one is subjected to stress (i.e. chronic, acute, and experimentally-induced brief stress) and the emotional valence of the stimuli presented during the task.”
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    MBSR improves the ability to direct attention and detect changes in stimuli.

    “Another form of behavioral therapy, mindfulness-based stress reduction (MBSR), improves subjects’ ability to direct attention and detect changes in stimuli through mindfulness training (Jha et al 2007).”
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    OFC and infralimbic mPFC mediate response inhibition, as lesions produce premature responding in the 5-CSRTT and SSRT.

    “OFC and infralimbic (IL) mPFC have been shown to mediate response inhibition, as lesions of these areas produce premature responding in the 5-CSRTT and SSRT (Chudasama et al 2003, Eagle et al 2008a, Eagle & Robbins 2003).”
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    Prazosin and propranolol produce attentional deficits.

    “The α1-adrenoceptor antagonist prazosin and the αβ1/β/α2 adrenergic receptor antagonist propranolol produced deficits in attention, the α2-adrenoceptor antagonist atipamezole improved continued attention (Bari & Robbins 2013b).”
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    Activation of α2 autoreceptors improved attention in some studies but not in others.

    “Activation of α2 autoreceptors improved attention in some studies (Smith & Nutt 1996), but not in others (Fernando et al 2012).”
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    Methylphenidate increases extracellular dopamine by inhibiting DAT and is routinely used to target attention deficits, with context-dependent effects.

    “drugs such as methylphenidate that function by increasing extracellular dopamine through DAT inhibition are routinely used to target attention deficits, and these effects are context-dependent (Volkow et al 2005).”
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    In depressed patients, one session of TMS to the left DLPFC increased activity in that region and increased attention in an affective go-no-go task.

    “Within depressed patients, one session of TMS targeted to the left DLPFC increased activity within the region and increased attention in an affective go-no-go task (Bermpohl et al 2006).”
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    Striatal D2 receptors have been linked to impulsivity and addictive behavior.

    “Additionally, the role of striatal D2 receptors have been linked to impulsivity and addictive behavior (Volkow et al 2007).”
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    Both NMDA-R antagonism and 5-HT2A receptor activation increase glutamate release.

    “Additionally, both NMDA-R antagonism and 5-HT2A receptor activation result in increased glutamate release (Aghajanian & Marek 2000, Moghaddam et al 1997).”
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    Interpretationcitation

    SSRIs within the PFC directly affect animals already exhibiting a deficit but do not enhance response inhibition in normal animals.

    “Microinjections of fluoxetine into the OFC increase response inhibition in rats already showing impulsive tendencies, but have no effect in low impulsivity rats. This finding indicates direct effects of SSRIs within the PFC of animals already exhibiting a deficit, but do not enhance response inhibition in normal animals (Darna et al 2015).”
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    The serotonergic system has long been implicated in regulating behavioral inhibition.

    “The serotonergic system has long been implicated in the regulation of behavioral inhibition (Evenden 1999, Linnoila et al 1983).”
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    VNS may increase 5-HT and norepinephrine levels, leading to increased NMDA-R function in the mPFC and beneficial effects on response inhibition.

    “which may increase levels of 5-HT and norepinephrine leading to increased NMDA-R function within the mPFC, and subsequent beneficial effects on response inhibition measures (Carli et al 2011, Carli & Invernizzi 2014, Darna et al 2015, Mirjana et al 2004).”
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    VNS significantly improved response inhibition and other cognitive symptoms after 10 weeks.

    “In comparing patients before and after 10 weeks of VNS, the treatment significantly improved response inhibition, as well as other cognitive symptoms (Sackeim et al 2001).”
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    Reversal learning is mediated by the OFC, evidenced by impairments after OFC lesions in humans, monkeys, mice, and rats.

    “This form of learning is mediated by the orbitofrontal cortex (OFC), as evidenced by impairments in reversal learning following lesions of this region in humans (Fellows & Farah 2003, Hornak et al 2004), monkeys (Dias et al 1996), mice (Bissonette et al 2008) and rats (McAlonan & Brown 2003).”
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    PCP at schizophrenia-like doses impaired reversal in some cases, had no effect in others, or improved reversal learning.

    “Similarly, phencyclidine (PCP), when used at doses to mimic schizophrenia-like symptoms in rats, impaired reversal in some cases (Abdul-Monim et al 2007), but in other studies it was found to have no effect (Brigman et al 2010, Janhunen et al 2015), or to even improve reversal learning (Dix et al 2010, Fellini et al 2014, McAllister et al 2015).”
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    The striatum, amygdala, and hippocampus are important for reversal learning.

    “Other brain regions important for reversal learning are the striatum (Cools et al 2002, Rogers et al 2000), amygdala (Izquierdo et al 2013, Schoenbaum et al 2003, Wassum & Izquierdo 2015) and the hippocampus (Mala et al 2015).”
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    Blockade of IL-6 signaling or JAK2 inhibition produces reversal learning deficits.

    “other activators of the JAK2/STAT3 pathway, such as interleukin 6 (IL-6), have been shown to correct the reversal learning deficits induced by cold stress, and blockade of IL-6 signaling or JAK2 inhibition produce deficits in reversal learning (Donegan et al 2014).”
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    Ketamine correction of stress-induced reversal learning deficits is accompanied by decreased OFC field potentials evoked by mediodorsothalamic afferent activation, and both effects require JAK2/STAT3 signaling in the OFC.

    “In a recent study, the ability of ketamine to correct stress-induced reversal learning deficits was accompanied by decreased field potentials in the OFC evoked by activation of mediodorsothalamic afferents, and both effects required activation of the JAK2/STAT3 signaling pathway in the OFC (Patton et al 2016).”
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    Administration of a GluN2B selective antagonist or blockade of GluA-R internalization prevents hippocampal LTD and disrupts spatial reversal learning in the Morris water maze.

    “Indeed, LTD is required for optimal reversal learning: administration of a ionotropic glutamate receptor NMDA subunit 2B (GluN2B) selective antagonist or blockade of GluA-R internalization prevents LTD in the hippocampus, and produces a disruption of spatial reversal learning in the Morris water maze (Dong et al 2013, Duffy et al 2008, Mills et al 2014).”
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    • cites Duffy et al 2008 source

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    • cites Mills et al 2014 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Ketamine's beneficial effects on reversal learning may be due to regulation of AMPA-R transmission.

    “Thus, it is possible that ketamine’s beneficial effects on reversal learning are due to regulation of AMPA-R transmission.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Vortioxetine's effects are not solely due to serotonin reuptake inhibition, because it corrected reversal learning deficits induced by PCPA serotonin depletion.

    “The effects of vortioxetine are not due solely to its ability to inhibit serotonin reuptake, since the drug was effective in correcting reversal learning deficits induced by serotonin depletion with PCPA (Wallace et al 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wallace et al 2014 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    In animal models, outcomes of acute stress experiments on set-shifting are mixed, possibly due to varying stress intensity.

    “In animal models, the outcomes of experiments with acute stressors have been mixed, possibly due to varying intensity of the stress used.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In monkeys, prefrontal serotonin depletion with 5,7-dihydroxytryptamine causes reversal learning deficits but not set-shifting deficits.

    “In monkeys, serotonin depletion within the prefrontal cortex using 5,7-dihydroxytryptamine caused reversal learning deficits, but not set-shifting deficits (Clarke et al 2004, Clarke et al 2005).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Clarke et al 2004 source

      Not checked in the free run.

    • cites Clarke et al 2005 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    After 8-12 weeks of CBT, OCD patients improve their YBOCS and reversal task scores.

    “After 8–12 weeks of CBT, these individuals improved both their YBOCS and reversal task scores”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Freyer et al 2011 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tryptophan depletion in healthy human volunteers homozygous for the long allele of 5-HTT reduces their capacity to use negative feedback from punishment and impairs reversal learning.

    “depletion of tryptophan in healthy human volunteers homozygous for the long allele of 5-HTT reduced the capacity of the individuals to utilize negative feedback information from punishment and impaired performance on reversal learning.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Finger et al 2007 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Serotonin depletion impairs reversal learning but not set-shifting.

    “Although serotonin depletion has been shown to impair reversal learning but not set-shifting (Clarke et al 2005, Lapiz-Bluhm et al 2009)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Clarke et al 2005 source

      Not checked in the free run.

    • cites Lapiz-Bluhm et al 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Available therapies are only partially effective at ameliorating cognitive symptoms.

    “available therapies are only partially effective at ameliorating cognitive symptoms.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The impact of stress on executive function is well documented in humans and animal models.

    “The impact of stress on executive function is well documented both in humans and in animal models.”
    Quote in the paperNot a substantial claim
59 of 59

  • The paper relies on this without support.

    Findings from animal models of stress and executive function can be generalized to humans.

    “Paralleling human studies, chronic stress impairs working memory (Arnsten et al 2012, Barsegyan et al 2010, Mizoguchi et al 2000) as well as cognitive flexibility”

  • The paper relies on this without support.

    The stress manipulations used in the cited animal and human studies are valid models of chronic stress as it occurs in humans.

    “conditions that are the hallmarks of chronic stress”

  • The paper relies on this without support.

    Orbitofrontal cortex damage does not impair extradimensional shifting.

    “OFC damage does not impair ED shifting, and lateral or medial PFC damage does not impair reversal learning, suggesting a functional dissociation between those regions.”

  • The paper relies on this without support.

    Lateral or medial prefrontal cortex damage does not impair reversal learning.

    “OFC damage does not impair ED shifting, and lateral or medial PFC damage does not impair reversal learning, suggesting a functional dissociation between those regions.”
4 of 4

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?

  • As part of the frontoparietal network, the parietal cortex interacts with core PFC regions to support attention and integration; hypoactivation due to PFC dysconnectivity may exacerbate cognitive inflexibility by impairing spatial attention and working memory updating, indirectly amplifying DMN rumination in OCD.

    “As part of the frontoparietal network (188), the parietal cortex interacts with core PFC regions to support attention and integration (189); hypoactivation due to PFC dysconnectivity (175) may exacerbate cognitive inflexibility by impairing spatial attention and working memory updating (190), indirectly amplifying DMN rumination in OCD (191).”

    From Neural mechanisms underlying cognitive inflexibility in obsessive-compulsive disorder: a review (2026) · cites this paper as [189]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

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.

  • The cited serotonin-transporter study used rats, not mice

    Minor

    The review identifies the knockout animals as mice, while the cited reference identifies them as rats.

  • The cited amantadine study used rats, not mice

    Minor

    The review attributes the spatial reversal-learning result to mice, but the cited reference describes a rat model.

  • A cited stimulation study used tDCS, not TMS

    Minor

    The described working-memory study is presented as a TMS session, but the cited reference identifies the intervention as tDCS.

  • The cited attention study names a different drug

    Minor

    The review names citalopram, but the cited study's title names escitalopram.

  • VNS is called noninvasive despite the described electrode placement

    Minor

    The treatment is described as noninvasive, although the review's own description places an electrode around the vagus nerve.

  • 8-OH-DPAT is assigned opposite receptor actions

    Minor

    The review first identifies 8-OH-DPAT as a 5-HT1A agonist, then calls its action 5-HT1A antagonism.

  • Reversal-learning effect conflicts with the cited reference

    Minor

    The review says genetic inactivation of the serotonin transporter causes reversal-learning deficits, but the cited reference says it improves reversal learning.

  • D2/D3 drug effect is reversed in the cited reference

    Minor

    The review describes the rat study as testing D2/D3 antagonists, whereas its cited reference identifies the drug as a D2/D3 agonist. That distinction affects the review's interpretation of receptor down-regulation.

8 of 8

Cites

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Related

Authors
Girotti, M., Adler, S. M., Bulin, S. E., Fucich, E. A., Paredes, D., & Morilak, D. A.
Affiliations
The University of Texas at San Antonio Health Science Center (US)
Corresponding author
Girotti, Milena
ORCID
Venue
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Publisher
Elsevier BV
Published
2018-07
Volume
85
Pages
161-179
ISSN
0278-5846 (ISSN-L)
DOI
10.1016/j.pnpbp.2017.07.004
PMC
PMC5756532
OpenAlex
W2725639589
Cited by
176
References
422
Citations by year
2026: 29 · 2025: 35 · 2024: 21 · 2023: 21 · 2022: 18 · 2021: 17 · 2020: 19 · 2019: 11 · 2018: 5
FWCI
1.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Progress in Neuro-Psychopharmacology and Biological Psychiatry (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH (MH072672, MH053851, MH100652)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
prefrontal cortex, executive function, chronic stress, executive dysfunction, working memory, attention, response inhibition, cognitive flexibility, neurochemical pathways, stress-related psychiatric disorders, pharmacological interventions, non-pharmacological treatment
MeSH terms
Animals, Humans, Stress, Psychological, Prefrontal Cortex, Executive Function

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.

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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