Presence and acquired origin of reduced recall for fear extinction in PTSD: Results of a twin study

Milad, Mohammed R.; Orr, Scott P.; Lasko, Natasha B.; Chang, Yuchiao; Rauch, Scott L.; Pitman, Roger K.

doi:10.1016/j.jpsychires.2008.01.017

Cited by 457 publications

(430 citation statements)

References 36 publications

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“…Some design aspects are worth noting; in our experimental paradigm, extinction training was initiated within approximately 10 min after fear conditioning, which was done in order to allow comparison to previous studies (McLaughlin et al., 2015; Milad et al., 2005, 2005, 2007, 2008; van ‘t Wout et al., 2013). Prior research supports the presence of differences in extinction processes depending on their temporal relationship with fear conditioning (Myers, Ressler, & Davis, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…The experimental protocol utilized a standardized 2‐day Pavlovian fear‐conditioning–extinction‐recall paradigm (Milad, Orr, Pitman, & Rauch, 2005; Milad et al., 2005, 2007, 2008; van ‘t Wout et al., 2013) using E‐Prime 2.0 software (Psychology Software Tools, Pittsburgh, PA). Participants were presented with photographs of two different rooms, one serving as the fear acquisition context (CX+; picture of an office) and one as the fear extinction context (CX−; picture of a bookcase) in which two conditioned stimuli (CS+; red and blue light) and one never‐to‐be conditioned stimulus (CS−; yellow light) were presented.…”

Section: Methodsmentioning

confidence: 99%

“…Two CS+ were included to allow comparison of results to previous studies on PTSD (Milad et al., 2009) and the effects of tDCS during fear extinction in healthy volunteers (van ‘t Wout et al., 2013), and lay the foundation for future sham‐controlled studies. For this same reason, we followed prior studies in the timing of habituation, conditioning, and extinction to occur on Day 1, and extinction recall on Day 2 approximately 24 hr later (McLaughlin et al., 2015; Milad et al., 2005, 2005, 2007, 2008; van ‘t Wout et al., 2013). …”

Section: Methodsmentioning

confidence: 99%

“…More specifically, vmPFC engagement during extinction learning predicts extinction success and is associated with “top‐down” modulation of amygdala‐driven fear expression (Do‐Monte, Manzano‐Nieves, Quiñones‐Laracuente, Ramos‐Medina, & Quirk, 2015; Lebrón, Milad, & Quirk, 2004; Milad et al., 2005, 2007; Phelps, Delgado, Nearing, & LeDoux, 2004; Quirk, Likhtik, Pelletier, & Paré, 2003; Rosenkranz, Moore, & Grace, 2003). Results from studies with PTSD patients revealed deficits in extinction recall (Milad et al., 2008), reduced vmPFC volume, and activation during fear extinction compared to controls (Bremner et al., 2005; Milad et al., 2009; Rauch et al., 2003; Rougemont‐Bücking et al., 2011; Shin, Rauch, & Pitman, 2006). Therefore, facilitating endogenous vmPFC activity using brain stimulation techniques, in the context of extinction learning, may be one method to improve fear extinction and retention (i.e., recall of safety memories; Milad & Quirk, 2002; Milad, Vidal‐Gonzalez, & Quirk, 2004) in those suffering from PTSD.…”

Section: Introductionmentioning

confidence: 99%

“…We conducted this pilot study to test the following hypotheses: (1) whether active tDCS during extinction learning compared to sham stimulation would augment late extinction learning, and (2) whether the effects of tDCS during extinction learning vs. during extinction consolidation, that is, immediately after extinction learning, on early extinction recall tested 24 hr later would differ. This idea of stimulating immediately after extinction learning, during consolidation, was based on reports that PTSD is associated with impairments in extinction recall (Garfinkel et al., 2014; Milad et al., 2008, 2009; Norrholm et al., 2011), even though extinction can be acquired. Therefore, testing the effects of tDCS during consolidation of fear extinction provides a first step to examining various possibly important time points in which noninvasive brain stimulation could be used to enhance components of extinction learning and memory (Marin & Milad, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Transcranial direct current stimulation may modulate extinction memory in posttraumatic stress disorder

et al. 2017

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BackgroundAbnormalities in fear extinction and recall are core components of posttraumatic stress disorder (PTSD). Data from animal and human studies point to a role of the ventromedial prefrontal cortex (vmPFC) in extinction learning and subsequent retention of extinction memories. Given the increasing interest in developing noninvasive brain stimulation protocols for psychopathology treatment, we piloted whether transcranial direct current stimulation (tDCS) during extinction learning, vs. during consolidation of extinction learning, might improve extinction recall in veterans with warzone‐related PTSD.MethodsTwenty‐eight veterans with PTSD completed a 2‐day Pavlovian fear conditioning, extinction, and recall paradigm. Participants received one 10‐min session of 2 mA anodal tDCS over AF3, intended to target the vmPFC. Fourteen received tDCS that started simultaneously with extinction learning onset, and the remaining 14 participants received tDCS during extinction consolidation. Normalized skin conductance reactivity (SCR) was the primary outcome measure. Linear mixed effects models were used to test for effects of tDCS on late extinction and early extinction recall 24 hr later.ResultsDuring early recall, veterans who received tDCS during extinction consolidation showed slightly lower SCR in response to previously extinguished stimuli as compared to veterans who received tDCS simultaneous with extinction learning (p = .08), generating a medium effect size (Cohen's d = .38). There was no significant effect of tDCS on SCR during late extinction.ConclusionsThese preliminary findings suggest that testing the effects of tDCS during consolidation of fear extinction may have promise as a way of enhancing extinction recall.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transcranial direct current stimulation may modulate extinction memory in posttraumatic stress disorder

et al. 2017

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Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders

et al. 2017

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IMPORTANCEThe fear conditioning and extinction neurocircuitry has been extensively studied in healthy and clinical populations, with a particular focus on posttraumatic stress disorder. Despite significant overlap of symptoms between posttraumatic stress disorder and anxiety disorders, the latter has received less attention. Given that dysregulated fear levels characterize anxiety disorders, examining the neural correlates of fear and extinction learning may shed light on the pathogenesis of underlying anxiety disorders.OBJECTIVES To investigate the psychophysiological and neural correlates of fear conditioning and extinction recall in anxiety disorders and to document how these features differ as a function of multiple diagnoses or anxiety severity. DESIGN, SETTING, AND PARTICIPANTSThis investigation was a cross-sectional, case-control, functional magnetic resonance imaging study at an academic medical center. Participants were healthy controls and individuals with at least 1 of the following anxiety disorders: generalized anxiety disorder, social anxiety disorder, specific phobia, and panic disorder. The study dates were between March 2013 and May 2015.EXPOSURES Two-day fear conditioning and extinction paradigm. CONCLUSIONS AND RELEVANCE Despite no skin conductance response group differences during extinction recall, brain activation patterns between anxious and healthy individuals differed. These findings encourage future studies to examine the conditions longitudinally and in the context of treatment trials to improve and guide therapeutics via advanced neurobiological understanding of each disorder.

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Multimodal Categorical and Dimensional Approaches to Understanding Threat Conditioning and Its Extinction in Individuals With Anxiety Disorders

et al. 2020

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to guide neuropsychiatry toward precision medicine. Its inception was partly in response to the overlap of clinical manifestations between different DSM-IV diagnoses within a category. For example, anxiety disorders comprise a DSM-IV category that includes diagnoses that differ from each other but are all characterized by dysregulated fear levels. Whether DSM-IV-based and Research Domain Criteria-based analytic approaches provide distinct or similar information with regard to the fear circuitry of individuals with anxiety disorders has not been directly tested. OBJECTIVE To use a threat conditioning and extinction protocol to conduct categorical (DSM-IV-based) and dimensional (Research Domain Criteria-based) assessments of psychophysiological, neural, and psychometric responses in individuals with and without anxiety disorders. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study was conducted at the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital in Boston between March 2013 and May 2015. Functional magnetic resonance imaging was used to assess psychophysiological, neural, and psychometric responses among adults aged 18 to 65 years with specific phobia, generalized anxiety disorder, social anxiety disorder, and panic disorder as well as a control group of adults without anxiety disorders. Data were analyzed between May 2018 and April 2019. EXPOSURES A 2-day threat conditioning and extinction protocol.MAIN OUTCOMES AND MEASURES Skin conductance responses and blood oxygenated level-dependent responses were measured during the threat and extinction protocol. The categorical analysis was performed by grouping participants based on their primary DSM-IV diagnosis. The dimensional analysis was performed by regrouping participants, irrespective of their diagnoses, based on their skin conductance responses to shock delivery during threat conditioning. RESULTSThis cross-sectional study of 114 adults aged 18 to 65 years included 93 participants (34 men and 59 women; mean [SD] age, 29.7 [11.1] years) with at least 1 anxiety disorder (specific phobia, generalized anxiety disorder, social anxiety disorder, or panic disorder) and 21 participants (11 men and 10 women) without an anxiety disorder. The categorical DSM-IV-based approach indicated that all anxiety disorder groups exhibited hypoactivation in the ventromedial prefrontal cortex during extinction recall (η p 2 = 0.15; P = .004). The Research Domain Criteria-based approach revealed that higher arousal to the unconditioned stimulus was associated with higher threat responses during extinction recall (for skin conductance responses, η p 2 = 0.21; P = .01 and in functional magnetic resonance imaging results, η p 2 = 0.12; P = .02). The direct comparison of DSM-IV-based vs Research Domain Criteria-based results did not yield significant findings (η p 2 values ranged from 0.02 to 0.078; P values ranged from .09 to .98), suggesting no overlap between the approaches. CONCLUSIONS AND RELEVANCEThe data obtained from both approaches ...

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Presence and acquired origin of reduced recall for fear extinction in PTSD: Results of a twin study

Cited by 457 publications

References 36 publications

Transcranial direct current stimulation may modulate extinction memory in posttraumatic stress disorder

Transcranial direct current stimulation may modulate extinction memory in posttraumatic stress disorder

Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders

Multimodal Categorical and Dimensional Approaches to Understanding Threat Conditioning and Its Extinction in Individuals With Anxiety Disorders

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