ReviewNeurocircuitry Models of Posttraumatic Stress Disorder and Extinction: Human Neuroimaging Research—Past, Present, and Future
Section snippets
Neurocircuitry Model of PTSD
We have previously presented a neurocircuitry model of PTSD that emphasizes the role of the amygdala, as well as its interactions with the ventral/medial prefrontal cortex (vmPFC) and hippocampus (Rauch et al 1998). Briefly, this model hypothesizes hyperresponsivity within the amygdala to threat-related stimuli, with inadequate top-down governance over the amygdala by vmPFC (encompassing the rostral anterior cingulate cortex [rACC], medial prefrontal cortex [mPFC], subcallosal cortex [SC,
Functional Neuroimaging Findings in PTSD
An initial positron emission tomography (PET) symptom provocation study of PTSD (Rauch et al 1996) used a script-driven imagery method for inducing symptoms. For the provoked versus control conditions, increased regional cerebral blood flow (rCBF) was found within the right amygdala and rACC, as well as other anterior paralimbic regions; decreases in rCBF were observed within the left inferior frontal region (Broca’s area). Interpretations of this initial study, with regard to the
Structural and Neurochemical Imaging Findings in PTSD
To date, morphometric magnetic resonance imaging (MRI) studies of PTSD have focused on subtle between-group differences with respect to hippocampal volume. The possibility of reduced hippocampal volume and function is scientifically appealing, given that studies of chronic stress in animals have shown degenerative changes within the hippocampus associated with chronic exposure to glucocorticoids (Sapolsky et al 1990). In fact, an initial series of four studies showed smaller hippocampal volumes
Summary of PTSD Neuroimaging Research to Date
Taken together, imaging data support the current neurocircuitry model of PTSD that emphasizes the functional relationship between a triad of brain structures: the amygdala, vmPFC, and hippocampus. When exposed to reminders of traumatic events, subjects appear to recruit anterior paralimbic regions and the amygdala, while exhibiting decreased activity within other heteromodal cortical areas. In comparison with control subjects, patients with PTSD exhibit vmPFC activation of diminished magnitude
The Future of Neuroimaging Research in PTSD
Although current neurocircuitry models of PTSD are steeped in references to fear conditioning, thus far, neuroimaging studies of PTSD have yet to employ a full range of fear conditioning and extinction paradigms (Bremner et al 2005). Rather, as outlined above, neuroimaging of amygdala function in PTSD has involved reminders of the traumatic event or emotionally expressive face stimuli, rather than conditioned fear acquisition protocols. Similarly, neuroimaging studies of the vmPFC have utilized
Fear Conditioning and the Amygdala
Consistent with animal research (e.g., LeDoux 1996), several neuroimaging experiments of fear conditioning in healthy humans have likewise implicated the amygdala. Such studies have found significant correlation between rCBF changes in the right amygdala and electrodermal activity changes (Fredrikson et al 1995, Furmark et al 1997), as well as interregional correlations between amygdala and thalamus (Morris et al 1997). Several fMRI studies have also demonstrated amygdala activation during fear
Implications for Cognitive and Behavioral Therapies
The implications of extinction research for behavior therapies are detailed in other articles within this special issue (see Davis et al 2006, Hermans et al 2006, in this issue). Here, however, we wish to emphasize two points that are of particular relevance to neuroimaging. First, it remains to be determined to what degree cognitive therapies, which depend on conscious reappraisal of threatening stimuli or contexts, rely on the same neurocircuitry as behavior therapies that involve extinction
Summary and Conclusions
Animal studies of fear conditioning and extinction have provided a foundation for neurocurcuitry models of anxiety disorders in humans. Specifically, it has been hypothesized that PTSD is characterized by exaggerated amygdala responsivity and deficient top-down governance of the amygdala by vmPFC and hippocampus. Moreover, we have proposed that this regional pathophysiology in PTSD corresponds to exuberant acquisition of conditioned fear and exaggerated fear responses, as well as deficient
References (83)
- et al.
Contextual and temporal modulation of extinctionBehavioral and biological mechanisms
Biol Psychiatry
(2006) - et al.
Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse–a preliminary report
Biol Psychiatry
(1997) - et al.
Neural correlates of exposure to traumatic pictures and sound in vietnam combat veterans with and without posttraumatic stress disorderA positron emission tomography study
Biol Psychiatry
(1999) - et al.
Neural correlates of the classic color and emotional Stroop in women with abuse-related posttraumatic stress disorder
Biol Psychiatry
(2004) - et al.
Neural correlates of declarative memory for emotionally valenced words in women with posttraumatic stress disorder related to early childhood sexual abuse
Biol Psychiatry
(2003) - et al.
FDG-PET predictors of response to behavioral therapy versus pharmacotherapy in obsessive-compulsive disorder
Psychiatry Res
(1998) - et al.
Brain systems mediating aversive conditioningAn event-related fMRI study
Neuron
(1998) - et al.
Attenuation of frontal asymmetry in pediatric posttraumatic stress disorder
Biol Psychiatry
(2001) - et al.
Size versus shape differencesContrasting voxel-based and volumetric analyses of the anterior cingulate cortex in individuals with acute posttraumatic stress disorder
Biol Psychiatry
(2005) - et al.
Effects of D-cycloserine on extinctionTranslation from preclinical to clinical work
Biol Psychiatry
(2006)
A pilot longitudinal study of hippocampal volumes in pediatric maltreatment-realted posttraumatic stress disorder
Biol Psychiatry
Developmental traumatology. Part II: Brain development
Biol Psychiatry
Central type benzodiazepine receptors in Gulf War veterans with posttraumatic stress disorder
Biol Psychiatry
Functional connectivity of the prefrontal cortex and the amygdala in posttraumatic stress disorder
Biol Psychiatry
Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder
Biol Psychiatry
Sensing the invisibleDifferential sensitivity of visual cortex and amygdala to traumatic context
Neuroimage
Extinction in human fear conditioning
Biol Psychiatry
Human amygdala activation during conditioned fear acquisition and extinctionA mixed-trial fMRI study
Neuron
Brain activation in PTSD in response to trauma-related stimuli
Biol Psychiatry
Cerebral blood flow changes during script-driven imagery in police officers with posttraumatic stress disorder
Biol Psychiatry
Smaller hippocampal volume in Dutch police officers with posttraumatic stress disorder
Biol Psychiatry
Fear extinction in ratsImplications for human brain imaging and anxiety disorders
Biol Psychol
Single-voxel proton MR spectroscopy of right versus left hippocampi in PTSD
Psychiatry Res
Extinction of emotional learningContribution of medial prefrontal cortex
Neurosci Lett
Dissociable amygdala and orbitofrontal responses during reversal fear conditioning
Neuroimage
Behavioral and neural analysis of extinction
Neuron
Extinction learning in humansRole of the amygdala and vmPFC
Neuron
Methods for developmental studies of fear conditioning circuitry
Biol Psychiatry
Exaggerated amygdala responses to masked facial stimuli in posttraumatic stress disorderA functional MRI study
Biol Psychiatry
Understanding contextual fear conditioningInsights from a two-process model
Neurosci Biobehav Rev
The place of the hippocampus in fear conditioning
Eur J Pharmacol
Decreased hippocampal N-acetyl aspartate in the absence of atrophy in posttraumatic stress disorder
Biol Psychiatry
An fMRI study of anterior cingulate function in posttraumatic stress disorder
Biol Psychiatry
Brain mechanisms of fear extinctionHistorical perspectives on the contribution of prefrontal cortex
Biol Psychiatry
Return of fear in human differential conditioning paradigm caused by a return to the original acquisition context
Behav Res Ther
Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder
Biol Psychiatry
The Emotional Counting Stroop paradigmA functional magnetic resonance imaging probe of the anterior cingulate affective division
Biol Psychiatry
Diagnostic and Statistical Manual of Mental Disorders
Amygdala response in patients with acute PTSD to masked and unmasked emotional facial expressions
Am J Psychiatry
Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD
Am J Psychiatry
Context and behavioral processes in extinction
Learn Mem
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