CoChat
Sign Up
Cited by 288Memory and Neural MechanismsAnxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesNeural and Behavioral Psychology Studies

TOWARD AN ACCOUNT OF CLINICAL ANXIETY PREDICATED ON BASIC, NEURALLY MAPPED MECHANISMS OF PAVLOVIAN FEAR-LEARNING: THE CASE FOR CONDITIONED OVERGENERALIZATION: Special Article: The Case for Conditioned Overgeneralization

Open access
Lissek, Shmuel·2012·Depression and Anxiety
DOI 10.1002/da.21922PMC PMC4194209
Open this paper in CoChat — free accountOpen PDF

Abstract

The past two decades have brought dramatic progress in the neuroscience of anxiety due, in no small part, to animal findings specifying the neurobiology of Pavlovian fear-conditioning. Fortuitously, this neurally mapped process of fear learning is widely expressed in humans, and has been centrally implicated in the etiology of clinical anxiety. Fear-conditioning experiments in anxiety patients thus represent a unique opportunity to bring recent advances in animal neuroscience to bear on working, brain-based models of clinical anxiety. The current presentation details the neural basis and clinical relevance of fear conditioning, and highlights generalization of conditioned fear to stimuli resembling the conditioned danger cue as one of the more robust conditioning markers of clinical anxiety. Studies testing such generalization across a variety of anxiety disorders (panic, generalized anxiety disorder, and social anxiety disorder) with systematic methods developed in animals will next be presented. Finally, neural accounts of overgeneralization deriving from animal and human data will be described with emphasis given to implications for the neurobiology and treatment of clinical anxiety.

Integrity signals

Registry

Crossref · 10.1002/da.21922

Cites

32 of 32 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 37 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Amygdala and anterior insula activations fell in a curve-linear way as generalization stimuli became less similar to the CS+.

    “Inversely, amygdala (and anterior insula) activations decreased curve-linearly as the match between GS and CS+ decreased.”
    Quote in the paperSubstantial claim
  • Findingcitation

    Preliminary fMRI results from a generalization gradient task show human generalization engaging brain regions that overlap with animal findings, including hippocampus, medial prefrontal cortex, and amygdala.

    “Preliminary findings from an fMRI version of the generalization gradient paradigm displayed in Figure 2 reveal brain areas engaged by human generalization, that overlap with animal findings, including the hippocampus, medial prefrontal cortex, and amygdala21.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Lissek, 2011

      Not checked in the free run.

  • Findingown data

    In healthy controls, the data show a continuous decline in conditioned fear generalization, with the strongest fear-potentiated startle to the CS+ and weaker responses to less similar stimuli.

    “Data in Figure 2A demonstrate continuous decreases in generalization of conditioned fear in healthy controls, with the highest level of fear-potentiated startle to the CS+, and gradually subsiding levels to stimuli of decreasing similarity to the CS+.”
    Quote in the paperSubstantial claim
  • Findingown data

    In those fMRI data, hippocampus and ventromedial prefrontal cortex activations were lowest for generalization stimuli that best matched the CS+ and rose in a curve-linear way as the match fell.

    “activations in the hippocampus and ventro-medial prefrontal-cortex (vmPFC) were weakest to generalization stimuli (GS) with the best “schematic match” to the CS+ (i.e., stimuli most similar to the CS+) and strengthened in a curve-linear manner as the schematic match decreased.”
    Quote in the paperSubstantial claim
  • Premisecitation

    The amygdala plays a central role in handling fear-related stimuli.

    “Evidence from animal studies demonstrates the centrality of the amygdala for processing fear-relevant stimuli.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Blair, 2001, Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning, Learn Mem source

      Not checked in the free run.

  • May combine two claims. 22
  • Classified as probably not a substantial claim. 5

  • May combine two claims.

    Findingcitation

    A meta-analysis of psychophysiological conditioning scores from 453 anxiety patients and 455 healthy comparisons did not find the expected greater differential responding (CS+ > CS−) in anxiety patients, but instead pointed to stronger fear responding to the CS− as a robust correlate of clinical anxiety.

    “A meta-analysis of such studies reflecting psychophysiologically indexed conditioning scores across 453 anxiety patients and 455 healthy comparisons failed to show the expected elevation in differential responding (i.e., CS+ > CS−) among those with, versus without, an anxiety disorder, but rather implicated enhanced fear-responding to the CS− as one of the more robust conditioning correlates of”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Lissek, 2005, Classical fear-conditioning in the anxiety disorders: a meta-analysis, Behav Res Ther source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The predictions were mostly confirmed: conditioned fear-potentiated startle over-generalization similar to panic disorder appeared in generalized anxiety disorder but not social anxiety disorder.

    “Predictions were largely confirmed with evidence of over-generalization in conditioned fear-potentiated startle, akin to that found in panic disorder, among those with GAD but not SAD21.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Lissek, 2011

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Follow-up contrasts showed that panic patients generalized conditioned fear to stimuli up to three units different from the CS+, while healthy comparisons generalized only to one unit.

    “Such analyses revealed generalization of conditioned fear to stimuli with up to three units of CS+ differentiation in panic patients, but only one unit of differentiation in healthy comparisons.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Panic patients and healthy comparisons differed in gradient shape: patients showed shallower linear declines and healthy comparisons steeper quadratic declines, indicating more generalization in panic disorder.

    “Group differences in the shape of gradients emerged with more shallow linear decreases in patients and steeper quadratic decreases in healthy comparisons, indicating more generalization among those with panic disorder.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Other learning processes have been connected to brain mechanisms in animal Pavlovian conditioning experiments.

    “a variety of other learning processes (e.g., extinction retention, consolidation, reconsolidation, contextual conditioning, reversal, discrimination/generalization) have been linked to brain mechanisms with lab-based Pavlovian conditioning experiments in animals (for a review see9,10).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [9] Pape, 2010, Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear, Physiol Rev source

      Not checked in the free run.

    • cites [10] Davis, 2010, Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety, Neuropsychopharmacology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In extinction, repeated CS+ presentations without the unconditioned stimulus cause the thalamus to activate the medial prefrontal cortex more, which excites intercalated amygdala cells that suppress the central nucleus; extinction occurs when this suppression outweighs excitatory lateral-to-central nucleus signaling.

    “with repeated presentations of the CS+ in the absence of the US, the thalamus increasingly activates the medial prefrontal cortex which relays excitation to intercalated cells of the amygdala, a group of GABAergic amygdaloid neurons that inhibit activation of the Ce and its fear-related projections. Extinction, or neutralization, of fear to the CS+ results when the inhibitory influence of medial”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Quirk, 2006, Prefrontal mechanisms in extinction of conditioned fear, Biol Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Before conditioning, CS+ presentations do not activate the amygdala's lateral or central nuclei, but they do cause thalamus-mediated glutamate release in the lateral nucleus.

    “pre-conditioning exposures to the CS+ do not lead to activation of the input (La) or output (Ce) nodes of the amygdala, but do—by way of the thalamus—evoke the release of glutamate in the La which then binds to glutamate receptors of La neurons7.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7] Rodrigues, 2004, Molecular mechanisms underlying emotional learning and memory in the lateral amygdala, Neuron source

      Not checked in the free run.

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

    Premisereasoning

    Conditioning is believed to add anxiogenic value to conditioned cues and similar cues across these disorders, allowing them to evoke and sustain anxiety after the brief unconditioned event ends.

    “Conditioning processes are similarly thought to contribute to all these disorders by conferring anxiogenic valence to CSs, and stimuli resembling the CSs, that are then capable of eliciting and maintaining (conditioned) anxiety responses well after the termination of the time-limited US.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisereasoning

    Whether brain circuits for these conditioning processes matter clinically depends on human experiments that identify conditioning abnormalities linked to anxiety disorders.

    “the clinical relevance of brain circuits subserving these different conditioning processes depends on human data, from comparable experiments, specifying conditioning aberrancies associated with anxiety disorders.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    Animal results inform understanding of human fear conditioning and of the neural bases of conditioning abnormalities in clinical anxiety.

    “Such animal data provide important insights on human fear-conditioning, generally, as well as neural substrates of conditioning aberrancies in clinical anxiety, specifically.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    During acquisition, if the unconditioned stimulus closely follows the CS+, lateral amygdala neurons are activated by the unconditioned stimulus while CS+-evoked glutamate is present, setting off intracellular events that yield new proteins and raise amygdala sensitivity to the CS+.

    “During acquisition of conditioned fear, when the US follows the CS+ closely in time, activation of La neurons by the US occurs in the presence of CS+ provoked glutamate, triggering a cascade of intracellular processes (e.g., release of Ca2+ which binds to NMDA receptors → excitation of protein kinases [e.g., MAPK] → activation of transcription factors [CREB] → synthesis of RNA and protein)—the end”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7] Rodrigues, 2004, Molecular mechanisms underlying emotional learning and memory in the lateral amygdala, Neuron source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    For social anxiety disorder, panic disorder, and PTSD, the unconditioned events are respectively brief embarrassing episodes, panic attacks, and traumatic encounters; the conditioned cues are the related people, places, and objects.

    “in social anxiety disorder, panic disorder, and PTSD the respective USs are “time limited” embarrassing events, panic attacks, and traumatic encounters that elicit unconditioned anxiety, and the CSs are those people, places, and things associated with the relevant US.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    In generalized anxiety disorder, many situations provoke anxiety, and some of this breadth may come from overgeneralizing fear to similar situations.

    “In GAD, a multiplicity of situations lead to anxiety and part of this multiplicity may well stem from the overgeneralization of fear to resembling situations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Animal findings show that D-cycloserine improves conditioning acquisition in a dose-dependent way and reduces generalization to stimuli resembling the CS+.

    “animal findings demonstrating that DCS dose dependently improves acquisition of conditioning and results in less generalization to stimuli resembling the CS+34.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Thompson, 1997, Age- and dose-dependent facilitation of associative eyeblink conditioning by D-cycloserine in rabbits, Behav Neurosc source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    The authors created and psychophysiologically validated a new paradigm using animal-derived systematic generalization tests called generalization gradients.

    “we designed and psychophysiologically validated a novel paradigm13 employing systematic tests of generalization developed in animals referred to as generalization gradients”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Lissek, 2008, Generalization of conditioned fear-potentiated startle in humans: experimental validation and clinical relevance, Behav Res Ther source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Earlier clinical anxiety conditioning studies did not aim to assess generalization, and CS− reactions served only as controls for CS+ reactivity.

    “past conditioning studies in clinical anxiety were not explicitly interested in assessing generalization, and reactions to CS− were included only as control conditions with which to contrast levels of CS+ reactivity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Because the CS+ activity pattern includes fear-related regions, completing it during CS− exposure activates the amygdala and anterior insula and produces the amygdala-mediated fear response, i.e., fear generalization to the CS−.

    “Because part of the pattern of brain activity subserving the CS+ includes fear related brain areas, completion of this pattern, via CS− exposure, will result in activation of such structures as the amygdala and anterior insula culminating in the amygdala-mediated fear response (i.e., fear generalization to the CS−).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Generalization is a failure to tell CS+ from CS−, so hippocampal lesion deficits can also be seen as impaired discriminative conditioning.

    “generalization constitutes a failure to discriminate CS+ from CS− and, as such, previously reported deficits evoked by hippocampal lesions can also be interpreted as impairments in discriminative conditioning.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    Conditioning is thought to help start and maintain panic disorder by giving panicogenic value to conditioned cues, which can then trigger anticipatory anxiety or further attacks.

    “Conditioning is thought to contribute to the onset and maintenance of PD by conferring panicogenic valence to the CSs that are then capable of eliciting anticipatory anxiety for, or actual occurrence of, additional attacks.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In mammalian fear conditioning, the amygdala activates the nucleus basalis of Meynert, which sends projections to visual, auditory, and somatosensory cortex and supplies acetylcholine to the cortical CS+ representation.

    “During mammalian fear-conditioning, the amygdala activates the nucleus basalis of Meynert27 which then projects to the visual, auditory, and somatosensory cortices—providing acetylcholine to the representation of the CS+ in sensory cortex28.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [27] Kapp, 1992

      Not checked in the free run.

    • cites [28] Weinberger, 1998, Physiological memory in primary auditory cortex: characteristics and mechanisms, Neurobiol Learn Mem source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    This fMRI pattern suggests that generalization stimuli with less schematic match to the CS+ produced more hippocampally mediated pattern separation, leading to stronger vmPFC activation and stronger inhibition of fear-related regions such as amygdala and anterior insula.

    “This pattern of results, informed by inferences from animal findings, suggests that GSs with decreasing schematic match to the CS+ elicited increasing, hippocampally-mediated, pattern separation of GS from CS+ representations, resulting in increasingly strong vmPFC activations and a correspondingly strong inhibition of such fear-related areas as the amygdala and anterior insula.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    One process is hippocampally mediated pattern separation of CS+ from CS−, which may activate fear-inhibiting vmPFC and deactivate fear-exciting amygdala and anterior insula, yielding good discrimination and little generalization.

    “One such process involves hippocampally-mediated pattern separation of CS+ from CS− that may both activate brain areas associated with fear inhibition (vmPFC) and deactivate areas associated with fear excitation (amygdala, anterior insula) resulting in both successful discrimination of CS+ from CS− and little generalization.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    Social anxiety disorder involves circumscribed anxiety tied to fear of social scrutiny and humiliation.

    “SAD is characterized by circumscribed anxiety responses associated with the fear of social scrutiny and humiliation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    The scientific value of fear conditioning here comes from its cross-species conservation and demonstrated link to clinical anxiety.

    “The scientific traction of fear-conditioning, in this context, is fueled by its conservation across species and demonstrated relevance to clinical anxiety.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    In panic disorder, the panic attack itself is the unconditioned stimulus, and the conditioned cues are the people, places, and sensations that occur with it.

    “In the context of PD, the US is the panic attack itself and the CSs are the people, places, and sensations that co-occur with the attack.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Because clinical anxiety is associated with greater amygdala activity during fear conditioning, anxiety patients may have larger acetylcholine influx into sensory cortex, more neural overlap between CS+ and approximation representations, and a greater chance of activating the CS+ representation and linked fear circuitry when encountering similar stimuli.

    “Given findings of increased amygdala activity during fear conditioning in clinical anxiety31, it logically follows that anxiety patients undergoing fear-conditioning may incur greater influx of acetylcholine into sensory cortex, increased neural overlap between the memorial representations of the CS+ and its approximations, and a heightened likelihood of activating the CS+ representation—and the”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Bremner, 2005, Positron emission tomographic imaging of neural correlates of a fear acquisition and extinction paradigm in women with childhood sexual-abuse-related post-traumatic stress disorder, Psychol Med source

      Not checked in the free run.

26 of 26

  • The paper relies on this without support.

    The CS+ and CS− used in the conditioning literature share many stimulus features.

    “Given that CS+ and CS− employed by this literature, invariably share many stimulus properties (e.g., size, shape, duration)”

  • The paper relies on this without support.

    The generalization stimuli in the paradigm are intermediate-sized rings that represent a more uncertain and ambiguous threat.

    “Because generalization stimuli in this paradigm are intermediary sized rings constituting threat of a more uncertain and ambiguous nature”

  • The paper relies on this without support.

    The electric shock threat used in this work is a physical threat outside the circumscribed content of social anxiety disorder phobic fear.

    “Threat of electric shock used in this program of work is a more physical threat that falls outside the circumscribed content of their phobic fear”

  • The paper relies on this without support.

    D-cycloserine has a favorable neurotoxicity profile in humans.

    “given the favorable neurotoxicity profile of DCS in human beings.”
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?

  • People with emotional disorders often show impaired reward and threat learning, producing narrow and rigid behavioral repertoires.

    “individuals with emotional disorders often exhibit deficiencies in reward (e.g., Bogdan & Pizzagalli, 2006) and threat learning (e.g., Lissek, 2012; Whitmer et al., 2012) that result in impoverished and inflexible repertoires of behavior in response to the situations that typically function to promote escape, avoidance, or inactivity as a means of attempting to manage emotional/motivational”

    From What, me worry and ruminate about dsm-5 and rdoc? The importance of targeting negative self-referential processing (2013) · cites this paper as Lissek, 2012

    The Introduction and Section III link anxiety disorders to abnormalities in fear conditioning and overgeneralization of learned threat. The paper does not establish that these abnormalities produce impoverished, inflexible behavioral repertoires, and its findings do not cover emotional disorders broadly. The citing sentence attributes reward learning to a different source. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Worry results in increased threat conditionability, greater stimulus generalization, and diminished ability to discriminate stimuli and learning contingencies, and GAD is associated with restrictions in valued actions and goals.

    “worry results in increased threat conditionability, greater stimulus generalization, and diminished ability to discriminate stimuli and learning contingencies37–39 and GAD is associated with restrictions in valued actions and goals40.”

    From AN OPEN TRIAL OF EMOTION REGULATION THERAPY FOR GENERALIZED ANXIETY DISORDER AND COOCCURRING DEPRESSION. (2015) · cites this paper as [38]

    Section IV, “GAD, SAD, and generalization” (page unavailable), reports greater conditioned-fear generalization in people with GAD; Section III discusses fear responding to safety cues in clinical anxiety. The paper does not establish that worry causes increased threat conditionability or diminished discrimination of learning contingencies. The valued-actions clause has a separate citation (40), so it is not attributed to this source. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Elevated NSRP is linked to poorer cognitive and behavioral performance, worse treatment response, and more relapse.

    “High levels of NSRP are associated with considerable deficits in cognitive and behavioral responding (e.g., Lissek, 2012; Whitmer, Frank, & Gotlib, 2012) as well as an inferior treatment response and greater relapse (e.g., Jones, Siegle, & Thase, 2008).”

    From What, me worry and ruminate about dsm-5 and rdoc? The importance of targeting negative self-referential processing (2013) · cites this paper as Lissek, 2012

    The sections on clinical testing and neural mechanisms discuss conditioned-fear overgeneralization in anxiety, not NSRP or a link between NSRP and cognitive or behavioral deficits. Searches for NSRP and the claimed deficits found no relevant passage in our copy. The treatment-response and relapse clause is cited to Jones et al., not Lissek. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

  • Individuals prone to anxiety disorders are less successful in discriminating properties of stimuli that share characteristics with a training CS, resulting in stimulus overgeneralization and fear elicitation to a broader array of stimuli.

    “In particular, individuals prone to anxiety disorders are less successful in discriminating the properties of stimuli that share characteristics with a training CS, thereby resulting in stimulus overgeneralization and experiencing fear elicitation to a broader array of stimuli.”

    From Emotion Regulation Therapy: A Mechanism-Targeted Treatment for Disorders of Distress (2017) · cites this paper as Lissek, 2012

  • Negative self-referentiality is associated with habitually inflexible dysfunctional behavioral responses, deficits in reward sensitivity, and aversive stimulus generalization.

    “which is associated with habitually inflexible and dysfunctional behavioral responses [20] deficits in reward sensitivity [21, 22], and aversive stimulus generalization [23].”

    From All together now: utilizing common functional change principles to unify cognitive behavioral and mindfulness-based therapies (2019) · cites this paper as [23]

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.

  • Pattern completion targets different stored stimuli

    Minor

    One passage says exposure to a similar cue completes the stored pattern for the currently experienced CS−. A later passage says the same process activates the stored CS+ representation.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Mineka, 1996, Nebraska Symposium on Motivation: Vol. 43. Perspectives on Anxiety, Panic, and Fear
  2. Lissek, 2012, The Oxford Handbook of Traumatic Disorders
  3. Bouton, 2001, A modern learning theory perspective on the etiology of panic disorder, Psychol Rev, 108, 4, 10.1037/0033-295X.108.1.4 · DOI · Paper page
  4. Lissek, 2011, Dimensions of Psychopathology: Implications for Treatment and Research in Anxiety Disorders

Cited by

Sorted by citations

Related

Authors
Lissek, S.
Affiliations
University of Minnesota (US)
Corresponding author
Lissek, Shmuel
ORCID
Lissek, Shmuel
Venue
Depression and Anxiety
Publisher
Wiley
Published
2012-03-23
Volume
29
Issue
4
Pages
257-263
ISSN
1091-4269 (ISSN-L)
DOI
10.1002/da.21922
PMC
PMC4194209
OpenAlex
W1569165477
Semantic Scholar
68194d93a56b08fe1cc377990d94d0f71c6dfa81
Cited by
288
References
32
Citations by year
2026: 11 · 2025: 12 · 2024: 21 · 2023: 13 · 2022: 24 · 2021: 18 · 2020: 27 · 2019: 23 · 2018: 23 · 2017: 21 · 2016: 23 · 2015: 26 · 2014: 25 · 2013: 20 · 2012: 1
FWCI
1.82
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1257 d)
Locations
  • Depression and Anxiety (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (R00MH080130)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
clinical anxiety, fear conditioning, overgeneralization, anxiety disorders, panic disorder, generalized anxiety disorder, social anxiety disorder, neurobiology of anxiety, anxiety treatment
MeSH terms
Anxiety Disorders, Brain Mapping, Conditioning, Classical, Fear, Generalization, Stimulus, Humans, Magnetic Resonance Imaging, Neurons, Predictive Value of Tests, Biomarkers

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 2026-10-04.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-04.

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 ›

Are you an author, or do you see a problem with this page? Request a review