Table 1.

Delineation of learning based theories of PTSD, clinical illustrations, and empirical evidence.

Theory	Thesis	Clinical Vignette	Lab-Based Evidence
		A USA combat veteran with PTSD acquired Pavlovian fear to a roadside object (CS+) used to encase an improvised explosive device (US) by which he was injured while on street patrol in Iraq.
I. Associative
1. Resistance to Extinction	The persistence of conditioned fear to CS+ that are no longer indicative of environmental danger (i.e., CS+ no longer paired with the US), contributes to PTSD symptomatology.	Though, upon return to civilian life in the USA, this veteran’s initial display of conditioned fear to roadside objects (CS+) would be considered normative, if this veteran fails to extinguish fear through repeated exposures to benign roadside objects (trash, debris, fire hydrants), conditioned fear would pathogenically contribute to his post-deployment functioning.	• Inconsistent evidence for impaired acquisition of extinction learning in PTSD. • Accumulating support for impaired recall of extinction learning over time in PTSD.
1a. Increased fear excitation (hyper-conditionability)	Individuals with, or at risk for PTSD have a heightened tendency to form aversive associations reflected by abnormally strong excitatory fear-conditioning to the CS+, resulting in resistance to extinguish fear to the CS+.	If this soldier forms overly strong associations between roadside objects (CS+) and the explosion (US), upon return to the USA the roadside objects will be particularly salient trauma cues that will resist extinction via exposures to roadside objects in the absence of the US, and thereby maintain traumatic fear over time.	• Little support from empirical literature as most lab-based studies do not show heightened fear conditioning to the CS+ in PTSD.
1b. Incubation	Heightened excitatory fear-conditioning in those with, or at risk for PTSD results in a CR (fear) that is aversive enough to serve as a US-substitute. In turn, the CR continues to reinforce the CS+ in the absence of US pairings, blocking extinction, and perhaps even ‘incubating’, or enhancing, the conditioned fear response with repeated, unpaired CS+ exposures.	Upon return to the USA, the veteran’s conditioned fear response to roadside objects is sufficiently acute and aversive to serve as a ‘US substitute’ that continues to aversively reinforce the CS+ (roadside objects) in the absence of the US (explosions). This prevents the veteran from extinguishing fear to the CS+ and may result in enhanced conditioned fear responses over time.	• No evidence.
1c. Two-stage learning	Heightened Pavlovian fear in those with, or at risk for PTSD (Stage 1) is proposed to act as a drive that motivates and reinforces avoidance of the CS+ (Stage 2). Such avoidance prevents extinction by denying the individual future opportunities to experience the CS+ in the absence of the US.	Strong Pavlovian fear to roadside objects motivates the returning veteran to avoid driving or walking on streets to avert conditioned fear elicited by roadside objects. By so doing, the veteran is denied the opportunity to extinguish this conditioned response, in their now safe post-deployment environment, through exposure to roadside objects in the absence of dangerous outcomes.	• No evidence.
1d. Reduced fear inhibition	Individuals with, or at risk for PTSD have an impaired ability to inhibit fear to CSs previously, but no longer, paired with an aversive US, blocking or retarding extinction of conditioned fear.	The veteran’s memories of post-deployment exposures to roadside objects, in the absence of any aversive outcomes, are insufficiently strong to inhibit the excitatory fear memory of the CS-US association acquired in Iraq, resulting in a failure to extinguish fear.	• Theory supported by fMRI data linking poor retention of extinction in PTSD to under-functioning mPFC: a brain region contributing to fear reduction through inhibition of amygdaloid neurons.
2. Associative learning deficits & Sustained contextual anxiety	The impaired ability to learn environmental cues (CS+) of danger (US) denies those with, or at risk for PTSD the awareness of safety periods, resulting in chronic anxiety. Further, the unawareness of danger cues leads the individual to more generally associate the unpleasant US with the environment in which the US is experienced, resulting in heightened contextual anxiety.	While still in Iraq, the veteran fails to distinguish between danger and safety due to insufficient learning of danger cues. This leads to chronic anxiety during deployment and heightened contextual anxiety to the deployment environment, which are both risk factors for PTSD.	• Mixed evidence for associative learning deficits in PTSD. • Substantial lab-based evidence of heightened contextual anxiety in PTSD.
3. Over-generalization	A heightened tendency among those with, or at risk for PTSD, to transfer conditioned fear from the CS+ to stimuli resembling the CS+. Such overgeneralization results in the undue spreading of conditioned fear to stimuli that resemble features of the traumatic encounter.	Though conditioned-fear was acquired to a particular encasement of a roadside explosive device, upon return to the USA the veteran’s fears may generalize to such ‘benign’ roadside objects as trash cans, fire hydrants, or other roadside debris. This may promote frequent trauma-related anxiety in his benign posttraumatic environment because these roadside objects are ubiquitous in his neighborhood and town.	• Preliminary support derives from differential conditioning studies in PTSD evidencing heightened fear reactivity to CS-sharing multiple stimulus features (e.g., shape, size, duration, spatial location) with the conditioned danger-cue. • Recent support from ‘generalization gradient’ studies identifying less steep gradients of generalization in PTSD.
4. Failure to inhibit fear in the presence of safety cues	A compromised capacity for fear inhibition results in the failure to suppress fear in the presence of safety cues, and maintains fear responding during periods of safety among those with, or at risk for PTSD.	Upon return to the USA, the veteran encounters roadside objects (CS+) coincident with many potential environmental cues of safety including neighborhood people, shops, parks, and houses. These safety cues are however unable to exert inhibitory control over the conditioned response to roadside objects leading to a continuation of the traumatic response in the benign, civilian context.	• Support derives from ‘conditional discrimination’ findings of impaired inhibition of fear to a conditioned danger-cue when presented in tandem with a conditioned safety-cue among PTSD patients. • Additional support is provided by neuroimaging studies documenting reduced activation in brain areas associated with fear inhibition (mPFC) among those with, versus without, PTSD during exposure to traumatic pictures and sounds, script driven traumatic imagery, and fearful faces.
II. Non-Associative
1. Failure-to-habituate	Trauma induces an impaired ability to autonomically adapt, or habituate, to intense, novel, or fear-relevant environmental stimuli (whether or not they resemble aspects of the trauma) among those with, or at risk for PTSD. The failure of this type of habituation is proposed as a central contributor to the hyper-arousal cluster of PTSD symptoms.	Upon return to the USA, this veteran may display persistent autonomic responding to reoccurring, and more or less irrelevant, sensory stimuli (sounds, sights, touches), as displayed by exaggerated startle responses and hypervigilance. Additionally, the inability to filter out these reoccurring sensory stimuli compromises concentration by exhausting attentional resources otherwise available for processing more consequential stimulus events.	• Supported by the well replicated finding of less steep habituation slopes, measured via SCR (but not HR or startle EMG) to intense acoustic tones.
2. Stress sensitization	Trauma induces autonomic hyper-excitability (i.e., stress sensitization) to intense, novel, or fear related stimuli (whether or not they resemble aspects of the trauma) among those with, or at risk for PTSD. This hyper-excitability is proposed as an underlying mechanism for the hyper-arousal cluster of PTSD symptoms.	Upon return to the USA, this veteran may display increasing autonomic responding to reoccurring, and more or less irrelevant, sensory stimuli (sounds, sights, touches), resulting in the same hyper-arousal symptoms described above for habituation failure (exaggerated startle, hypervigilance, poor concentration).	• Supported by replicated findings of increased HR (and SCR and startle EMG to some degree) responses to repeatedly presented, high intensity noises in those with vs. without PTSD.
2a. Amygdala kindling	A variant of stress sensitization theory in which the traumatic experience is proposed to stimulate, or kindle, the amygdala-based fear circuit rendering the fear system hyper-excitable to either future trauma or fear-relevant stimuli.	Because of trauma-related kindling of this veteran’s fear circuit, upon return to the US, he displays heightened anxiety to fear-relevant stimuli contributing to the maintenance of PTSD symptomatology.	• Supported by replicated neuroimaging findings of stronger amygdala activation to fearful and neutral faces in those with vs. without PTSD. • Epileptic discharges in the human temporal lobe (the cerebral structure encasing the amygdala) are associated with marked increases in reported fear and anxiety.

CS+ = conditioned danger-cue; CS− = conditioned safety-cue; US=unconditioned stimulus; CR=conditioned response; EMG=electromyography; HR=heart-rate; SCR=skin conductance response; fMRI=functional magnetic resonance imaging; mPFC=medial prefrontal cortex.