Differential activity of subgenual cingulate and brainstem in panic disorder and PTSD. J Anxiety Disord

Functional Neuroimaging Laboratory, Department of Psychiatry, Weill Medical College of Cornell University, United States.
Journal of anxiety disorders (Impact Factor: 2.68). 11/2010; 25(2):251-7. DOI: 10.1016/j.janxdis.2010.09.010
Source: PubMed


Most functional neuroimaging studies of panic disorder (PD) have focused on the resting state, and have explored PD in relation to healthy controls rather than in relation to other anxiety disorders. Here, PD patients, posttraumatic stress disorder (PTSD) patients, and healthy control subjects were studied with functional magnetic resonance imaging utilizing an instructed fear conditioning paradigm incorporating both Threat and Safe conditions. Relative to PTSD and control subjects, PD patients demonstrated significantly less activation to the Threat condition and increased activity to the Safe condition in the subgenual cingulate, ventral striatum and extended amygdala, as well as in midbrain periaquaeductal grey, suggesting abnormal reactivity in this key region for fear expression. PTSD subjects failed to show the temporal pattern of activity decrease found in control subjects.

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Available from: Hong Pan, Jul 17, 2014
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    • "This two-task approach enabled the investigation of convergent and stimuli/modality specific neural activations associated with persecutory delusion severity. Our laboratory has previously implemented instructed-fear/safety paradigms to probe frontolimbic and subcortical emotional processing in healthy subjects (Butler et al., 2005, 2007b) and anxiety disorders (Tuescher et al., 2011). Emotional word fMRI paradigms have also been designed by our group to investigate emotionallinguistic processing in healthy subjects (Isenberg et al., 1999; Protopopescu et al., 2005a) and neuropsychiatric populations (Protopopescu et al., 2005b; Epstein et al., 2006, 2011; Silbersweig et al., 2007). "
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    ABSTRACT: Persecutory delusions are a clinically important symptom in schizophrenia associated with social avoidance and increased violence. Few studies have investigated the neurobiology of persecutory delusions, which is a prerequisite for developing novel treatments. The aim of this two-paradigm functional magnetic resonance imaging (fMRI) study is to characterize social "real world" and linguistic threat brain activations linked to persecutory delusions in schizophrenia (n=26) using instructed-fear/safety and emotional word paradigms. Instructed-fear/safety activations correlated to persecutory delusion severity demonstrated significant increased lateral orbitofrontal cortex and visual association cortex activations for the instructed-fear vs. safety and instructed-fear vs. baseline contrasts; decreased lateral orbitofrontal cortex and ventral occipital-temporal cortex activations were observed for the instructed-safety stimuli vs. baseline contrast. The salience network also showed divergent fear and safety cued activations correlated to persecutory delusions. Emotional word paradigm analyses showed positive correlations between persecutory delusion severity and left-lateralized linguistic and hippocampal-parahippocampal activations for the threat vs. neutral word contrast. Visual word form area activations correlated positively with persecutory delusions for both threat and neutral word vs. baseline contrasts. This study links persecutory delusions to enhanced neural processing of threatening stimuli and decreased processing of safety cues, and helps elucidate systems-level activations associated with persecutory delusions in schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research: Neuroimaging 06/2015; 233(3). DOI:10.1016/j.pscychresns.2015.06.002 · 2.42 Impact Factor
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    • "Specifically, PD patients show increased anterior cingulate cortex activation in response to happy faces, but reduced activation in response to fearful faces (Pillay et al., 2006, 2007). Moreover, in an instructed fear-conditioning paradigm, reduced activation to the " threat " and increased sensitivity to the " safe " conditions were found in the subgenual cingulate in PD patients, as compared to control subjects (Tuescher et al., 2011). These results suggest that PD patients have a cognitive bias, meaning that they will attribute neutral/safe stimuli stronger than normal emotional valence. "
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    ABSTRACT: Fear is an ancestral emotion, an intrinsic defensive response present in every organism. Although fear is an evolutionarily advantageous emotion, under certain pathologies such as panic disorder it might become exaggerated and non-adaptive. Clinical and preclinical work pinpoints that changes in cognitive processes, such as perception and interpretation of environmental stimuli that rely on brain regions responsible for high-level function, are essential for the development of fear-related disorders. This review focuses on the involvement of cognitive function to fear circuitry disorders. Moreover, we address how animal models are contributing to understand the involvement of human candidate genes to pathological fear and helping achieve progress in this field. Multidisciplinary approaches that integrate human genetic findings with state of the art genetic mouse models will allow to elucidate the mechanisms underlying pathology and to develop new strategies for therapeutic targeting. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmacology 03/2015; 759. DOI:10.1016/j.ejphar.2015.03.039 · 2.53 Impact Factor
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    • "Corbett & Glidden, 2000) reporting impaired fear recognition for facial fear cues. The finding of increased amygdala response to CS− stimuli in the ADHD group resembles earlier findings with the same paradigm in patients with panic disorder (Tuescher et al. 2011). Furthermore, Plessen et al. (2006) reported altered amygdala shape in ADHD. "
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    ABSTRACT: Background: Emotional dysregulation is becoming increasingly recognized as an important feature of attention deficit hyperactivity disorder (ADHD). In this study, two experiments were conducted investigating the neural response to either verbally instructed fear (IF) or uninstructed (classically conditioned) fear (UF) using the skin conductance response (SCR) and functional magnetic resonance imaging (fMRI). Method: In the conditioning phase of the UF experiment (17 ADHD and 17 healthy controls), subjects experienced an unconditioned stimulus (UCS, unpleasant electrodermal stimulation) paired with a former neutral conditioned stimulus (CS+), whereas a control stimulus (CS-) was never paired with the UCS. In the subsequent test phase, only the CS+ and the CS- were presented. In the IF experiment (13 ADHD and 17 healthy controls), subjects were only told that an independently experienced UCS might occur together with the CS+ but not the CS- during testing. No UCS was presented. Results: Groups did not detectably differ in SCR or neural responses to UF. In IF, ADHD patients showed a trend-line decreased SCR and significantly decreased activation of the dorsal anterior cingulate cortex (dACC), a region prominently involved in fear responding, to the CS+. This was accompanied by higher amygdala activation to the CS-. Conclusions: During IF, ADHD patients showed deficits in regions centrally involved in fear learning and expression in terms of diminished CS+-related dACC and increased CS--related amygdala signals. This suggests an impaired processing of verbally transmitted aversive information, which is central for conveying fear information in social contexts. This result extends the growing literature on emotional alterations in ADHD.
    Psychological Medicine 03/2013; 44(1):1-14. DOI:10.1017/S0033291713000469 · 5.94 Impact Factor
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