Reduction of Trace but Not Delay Eyeblink Conditioning in Panic Disorder

Grillon, Christian; Lissek, Shmuel; McDowell, B.A. Dana; Levenson, B.A. Jessica; Pine, Daniel S.

doi:10.1176/ajp.2007.164.2.283

Cited by 11 publications

(3 citation statements)

References 35 publications

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“…Following contemporary learning theories of panic disorder (32,76), propensity for interoceptive and exteroceptive fear conditioning may initially result in heightened, overgeneralization of defensive responding. Grillon and colleagues have demonstrated that panic disorder in the absence of significant comorbid broad distress is characterized by fear-conditioned overgeneralization indexed by both subjective report and startle potentiation (29–32). Notably, in these samples the comorbidity rates and symptom measures (e.g., mean BDI range 6.9–11.3) were markedly lower than the comorbidly depressed panic patients in the Melzig et al (28) sample and even the no agoraphobia group in the current study, suggesting that these hyper-reactive samples are predominantly a purer panic disorder.…”

Section: Discussionmentioning

confidence: 99%

Aversive Imagery in Panic Disorder: Agoraphobia Severity, Comorbidity, and Defensive Physiology

McTeague

Lang

Laplante

et al. 2011

Biological Psychiatry

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Background Panic is characterized as a disorder of interoceptive physiological hyperarousal, secondary to persistent anticipation of panic attacks. The novel aim of the present research was to investigate whether severity of agoraphobia within panic disorder covaries with the intensity of physiological reactions to imagery of panic attacks and other aversive scenarios. Methods A community sample of principal panic disorder (n=112; 41 without agoraphobia, 71 with agoraphobia) and control (n=76) participants imagined threatening and neutral events while acoustic startle probes were presented and the eye-blink response (orbicularis oculi) recorded. Changes in heart rate, skin conductance level, and facial expressivity were also measured. Results Overall panic disorder patients exceeded controls in startle reflex and heart rate during imagery of standard panic attack scenarios, concordant with more extreme ratings of aversion and emotional arousal. Accounting for the presence of agoraphobia revealed that both panic disorder with and without situational apprehension showed the pronounced heart rate increases during standard panic attack imagery observed for the sample as a whole. In contrast, startle potentiation to aversive imagery was more robust in those without versus with agoraphobia. Reflex diminution was most dramatic in those with the most pervasive agoraphobia, coincident with the most extreme levels of comorbid broad negative affectivity, disorder chronicity, and functional impairment. Conclusions Principal panic disorder may represent initial, heightened interoceptive fearfulness and concomitant defensive hyperactivity, which through progressive generalization of anticipatory anxiety, ultimately transitions to a disorder of pervasive agoraphobic apprehension and avoidance, broad dysphoria and compromised mobilization for defensive action.

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Section: Discussionmentioning

confidence: 99%

Aversive Imagery in Panic Disorder: Agoraphobia Severity, Comorbidity, and Defensive Physiology

McTeague

Lang

Laplante

et al. 2011

Biological Psychiatry

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“…While these results do not allow for differentiation of cerebellar and hippocampal dysfunction, comparison of the delay and trace paradigms has been used in other disorders to differentiate functional regions. Grillon et al ( 45 ) compared performance on both the delay and trace EBC paradigms in patients suffering from panic disorder. There was no difference in performance between patients and control subjects on the delay task; however, patients performed significantly worse on the trace paradigm, showing a delayed acquisition rate.…”

Section: Eyeblink Classical Conditioningmentioning

confidence: 99%

Hippocampal Non-Theta-Contingent Eyeblink Classical Conditioning: A Model System for Neurobiological Dysfunction

Cicchese

Berry

2016

Front. Psychiatry

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Typical information processing is thought to depend on the integrity of neurobiological oscillations that may underlie coordination and timing of cells and assemblies within and between structures. The 3–7 Hz bandwidth of hippocampal theta rhythm is associated with cognitive processes essential to learning and depends on the integrity of cholinergic, GABAergic, and glutamatergic forebrain systems. Since several significant psychiatric disorders appear to result from dysfunction of medial temporal lobe (MTL) neurochemical systems, preclinical studies on animal models may be an important step in defining and treating such syndromes. Many studies have shown that the amount of hippocampal theta in the rabbit strongly predicts the acquisition rate of classical eyeblink conditioning and that impairment of this system substantially slows the rate of learning and attainment of asymptotic performance. Our lab has developed a brain–computer interface that makes eyeblink training trials contingent upon the explicit presence or absence of hippocampal theta. The behavioral benefit of theta-contingent training has been demonstrated in both delay and trace forms of the paradigm with a two- to fourfold increase in learning speed over non-theta states. The non-theta behavioral impairment is accompanied by disruption of the amplitude and synchrony of hippocampal local field potentials, multiple-unit excitation, and single-unit response patterns dependent on theta state. Our findings indicate a significant electrophysiological and behavioral impact of the pretrial state of the hippocampus that suggests an important role for this MTL system in associative learning and a significant deleterious impact in the absence of theta. Here, we focus on the impairments in the non-theta state, integrate them into current models of psychiatric disorders, and suggest how improvement in our understanding of neurobiological oscillations is critical for theories and treatment of psychiatric pathology.

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“…ACC and medial PFC (mPFC) are both involved in aspects of negative-emotion processing, such as appraisal, expression, and regulation of emotion [Etkin et al, 2011]. Hyperactivation in (dorsal) ACC has been reported across anxiety disorders, and interestingly, is also observed in fear conditioning [for a review see Shin and Liberzon, 2009], a mechanism that plays a pivotal role in the etiology of PD [Bouton et al, 2001;Grillon et al, 2007;Lissek et al, 2005Lissek et al, , 2009. Moreover, in their review of neurobiological findings in PD, Graeff and Del-Ben [2008] propose ACC and insula to be involved in the detection of interoceptive cues.…”

Section: Introductionmentioning

confidence: 99%

Brain responses to disorder‐related visual threat in panic disorder

Feldker

Heitmann

Neumeister

et al. 2016

Human Brain Mapping

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Panic disorder (PD) patients show aberrant neural responses to threatening stimuli in an extended fear network, but results are only partially comparable, and studies implementing disorder-related visual scenes are lacking as stimuli. The neural responses and functional connectivity to a newly developed set of disorder-related, ecologically valid scenes as compared with matched neutral visual scenes, using event-related functional magnetic resonance imaging (fMRI) in 26 PD patients and 26 healthy controls (HC) were investigated. PD patients versus HC showed hyperactivation in an extended fear network comprising brainstem, insula, thalamus, anterior, and mid-cingulate cortex and (dorso-)medial prefrontal cortex for disorder-related versus neutral scenes. Amygdala differences between groups failed significance. Subjective levels of anxiety significantly correlated with brainstem activation in PD patients. Analysis of functional connectivity by means of beta series correlation revealed no emotion-specific alterations in connectivity in PD patients versus HC. The results suggest that subjective anxiety evoked by external stimuli is directly related to altered activation in the homeostatic alarm system in PD. With novel disorder-related stimuli, the study sheds new light on the neural underpinnings of pathological threat processing in PD. Hum Brain Mapp 37:4439-4453, 2016. © 2016 Wiley Periodicals, Inc.

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Reduction of Trace but Not Delay Eyeblink Conditioning in Panic Disorder

Abstract: These results suggest that individuals with panic disorder suffer from a deficit in declarative associative learning. Such a deficit points to impaired hippocampal function that may disrupt cognitive processing of internal and external cues predictive of a panic attack.

Cited by 11 publications

References 35 publications

Aversive Imagery in Panic Disorder: Agoraphobia Severity, Comorbidity, and Defensive Physiology

Aversive Imagery in Panic Disorder: Agoraphobia Severity, Comorbidity, and Defensive Physiology

Hippocampal Non-Theta-Contingent Eyeblink Classical Conditioning: A Model System for Neurobiological Dysfunction

Brain responses to disorder‐related visual threat in panic disorder

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