PART 2

Following on from the role of memory system in PTSD and simialr psychopathologies (and disorders with which PTSD is also co-occurring)

“We propose a similar mechanism may underlie the development and persistence of some PTSD symptoms  The traumatic memories of PTSD patients can be deficient in hippocampus-dependent contextual or autobiographical aspects, and enhanced in responding to trauma-related cues, which we suggest may reflect increased involvement of the dorsal striatum.

We briefly consider the potential role of a stress/anxiety induced habit bias with regard to other psychopathologies, including obsessive-compulsive disorder and drug addiction.

…neurobiological theories suggest, in part, that the concomitant impairment and enhancement of traumatic memory observed in PTSD may be explained through differential involvement of the hippocampus and amygdala. For example, Layton and Krikorian (2002) propose that as a situation increases in emotional intensity the amygdala becomes progressively more involved in the encoding process. At moderate levels of arousal, the amygdala enhances hippocampal function, thus strengthening the consolidation of aspects of the event dependent on the hippocampus (e.g., contextual aspects, integration of the event into autobiographical memory, etc.). However, at extreme levels of emotional intensity (such as those experienced under trauma) the amygdala inhibits hippocampal function, thus leading to impairments in the consolidation of hippocampal-dependent features of the event.

Evidence the amygdala has a role in PTSD

Using various neuroimaging techniques, studies have consistently revealed increased activation of the amygdala in PTSD subjects (Hughes and Shin, 2011). For example, amygdala activation is increased in combat veterans with PTSD in response to both combat-related noises (Liberzon et al., 1999) and odors (Vermetten et al., 2007), suggesting that the amygdala may be involved in the discrete-cued recall of the traumatic event. In another study, Vietnam veterans with PTSD listened to a script describing a traumatic event that the subject had actually experienced during the war (Shin et al., 2004). Positron emission tomography scans revealed that the regional cerebral blood flow in the right amygdala maintained a positive correlation with the severity of PTSD symptoms. Using similar techniques, several other studies have established positive correlations between amygdala activation and PTSD symptom severity (Rauch et al., 2000; Pissiota et al., 2002; Armony et al., 2005; Bryant et al., 2005; Protopopescu et al., 2005; Dickie et al., 2008; Brunetti et al., 2010). Conversely, there is evidence that in subjects exposed to trauma, decreased amygdala activation may actually be associated with a failure to develop PTSD (Britton et al., 2005; Osuch et al., 2008). Taken together, the evidence suggests that the amygdala is likely to be involved in the development, and potentially the expression, of PTSD symptoms.

Evidence the hippocampus has a role in PTSD

PTSD patients tend to perform poorly on declarative memory tasks (for a brief review, see Bremner, 2006). Considering their characteristics, these memory impairments may reflect a functional decline of hippocampal-dependent cognitive memory processes in PTSD (Bremner, 2006). There are several lines of research in support of this idea that indicate abnormalities of the hippocampus in PTSD patients. For example, several neuroimaging studies suggest that patients with PTSD have a reduced hippocampal volume (for a review, see Bremner, 2007; and also Bonne et al., 2001; Carrion et al., 2001; De Bellis et al., 2001; Fennema-Notestine et al., 2002; Pederson et al., 2004; Golier et al., 2005). Moreover, neuroimaging studies have established a negative correlation between hippocampal volume and the severity of PTSD symptoms (Gilbertson et al., 2002; Villarreal et al., 2002; Bremner et al., 2003). In view of extensive evidence that behavioral stressors and stress hormones can be detrimental to hippocampal structure and morphology (Watanabe et   al., 1992; Gould et al., 1998; Kim and Diamond, 2002), it is possible that the traumatic event and the distress it may engender reduces the volume of the hippocampus.

However, there is also evidence that a prior reduction in hippocampal volume may serve as a risk factor for developing PTSD (e.g., Pitman et al., 2006). Indeed, whether the reduction in hippocampal volume precedes or follows the traumatic event and the development of PTSD symptoms remains debatable (Bremner, 2001; Pitman, 2001). Results in favor of the latter view (i.e., that traumatic stress reduces hippocampal volume) came from one study that measured hippocampal gray matter volume in healthy human subjects at two different time points, separated by a three-month interval (Papagni et al., 2011). The number of stressful life events that a participant experienced during the three-month interval was positively correlated with a reduction in gray matter volume of the right hippocampus, suggesting that the stressful life events preceded and contributed to the reduction in hippocampal volume.

In addition to reduced hippocampal volume, neuroimaging studies reveal decreased activation of the hippocampus in patients with PTSD (for reviews, see Francati et al., 2007; Hughes and Shin, 2011). Typically, these experiments measure hippocampal activation while the subject performs a hippocampal-dependent memory task.

Evidence the dorsal striatum has a role in PTSD

…there is extensive evidence from studies in… humans indicating that the dorsal striatum has a selective role in stimulus response ( S – R)/habit learning and memory. In PTSD, the learning of behavioral responses to trauma-related cues may be a form of S – R learning.

…recent neuroimaging studies indicate that the dorsal striatum has a role in PTSD symptomatology. For example, researchers played personalized auditory scripts to traumatized train drivers and asked them to re-imagine the traumatic event as if it were actually recurring (Nardo et al., 2011). Subsequent single-photon emission computed tomography analyses revealed increased regional cerebral blood flow in the caudate and putamen of train drivers with PTSD, relative to train drivers without PTSD. An additional study using script-driven imagery established a positive correlation between regional cerebral blood flow in the right putamen and self-reported intensity of the flashback (Osuch et al., 2001). Script-driven activations of the caudate head and putamen have also been correlated positively with the severity of PTSD symptoms (Mickleborough et al., 2011).

Evidence the noradrenergic system has a role in PTSD

Consistent with the hypothesis that this anxiety-mediated habit bias may underlie some PTSD symptoms, converging evidence indicates that PTSD patients have increased basal norepinephrine levels and show exaggerated noradrenergic responses to trauma-related stimuli (for reviews, see Pitman and Delahanty, 2005; Strawn and Geracioti, 2008). Pitman (1989) advanced a pathophysiological model of PTSD suggesting that stress hormones released during and after a traumatic event may lead to an ‘ overconsolidation ’ of the traumatic memory, precipitating the intrusive recollections and conditioned emotional responses observed in PTSD. Aside from the consolidation of traumatic experiences, it has also been suggested that the retrieval of traumatic memories may depend on noradrenergic mechanisms (Pitman, 1989; Pitman and Delahanty, 2005).

Considering the effects of norepinephrine on the relative use of memory systems (Packard, 2009), it is tempting to speculate that exaggerated norepinephrine release during and after a traumatic event may increase amygdala activation, thus mobilizing a shift from a hippocampal-dependent memory system towards a dorsal striatal-dependent system.

The stress-induced habit bias: implications for PTSD

…we suggest that during a traumatic event the amygdala becomes highly active and modulates memory of the experience by impairing modulatory influence on the hippocampus, essentially allowing the dorsal striatum to play a prominent role in encoding and consolidating trauma-related cues.

The stress-induced habit bias: implications for other psychopathologies

In addition to PTSD, other human psychopathologies may similarly reflect a stress-induced facilitation of the dorsal striatal-dependent habit memory system. Considering both the role of anxiety and the habit-like nature of compulsions in obsessive-compulsive disorder (American Psychiatric Association, 2000), the stress-mediated habit bias may also underlie at least some symptoms of the disorder (McDonald et al., 2004).

More specifically, the anxiety arising from obsessions or stressful/traumatic life events may lead to the compulsive behavior observed in obsessive-compulsive disorder patients, and this process may depend on an interaction between the amygdala, hippocampus and dorsal striatum. When exposed to distressing life events or obsessions, the amygdala may become highly active and, through its inputs to different learning and memory structures, modulate which behavioral strategy becomes employed to relieve the anxiety. In this situation, a highly active amygdala may favor the use of a habit learning strategy mediated by the dorsal striatum, as opposed to a more cognitive strategy, which would be mediated in part by the hippocampus.

In a recent study, researchers trained obsessive-compulsive disorder patients on a set of instrumental learning tasks and found that relative to healthy individuals they demonstrated deficient knowledge of action – outcome relationships and were more likely to rely on habit like responses to the stimuli (Gillan et al., 2011). These results may represent the impairment of a cognitive, goal directed learning system and consequent reliance on the habit memory system in obsessive-compulsive disorder.

In addition, a number of studies report that environmental factors contributing to the development and persistence of obsessive-compulsive disorder symptoms may include stressful or traumatic life events (Happle, 2005; Sasson et al., 2005; Cromer et al., 2007a,b; Tolin et al., 2010; Landau et al., 2011). Lastly, several neuroimaging studies have provided evidence of abnormal structure and function of the amygdala, hippocampus and regions of the dorsal striatum in obsessive-compulsive disorder patients (for recent reviews, see Del Casale et al., 2011; Milad and Rauch, 2012).

In drug abuse, the acquisition and subsequent relapse of drug-seeking behaviors may be attributed to aberrant or maladaptive functioning of different memory systems (White, 1996; Di Chiara, 1999; Everitt and Robbins, 2005; Schwabe et al., 2011). Whereas the initial acquisition of drug taking behavior may depend on a hippocampal-dependent memory system, extended drug use may shift the control of drug-taking behavior to a dorsal striatal-dependent system, increasing the rigid and habit-like nature of these behaviors (White, 1996).

In a similar hypothesis, initial drug-taking behavior may depend on a goal-directed learning system mediated by the dorsomedial region of the striatum and gradually shift to a habit-learning system mediated by the dorsolateral striatum (Everitt and Robbins, 2005; Schwabe et al., 2011).

In humans, major stressful life events have been associated with increased drug abuse (Newcomb and Bentler, 1988; Kaplan and Johnson, 1992; Harrison et al., 1997; Chilcoat and Breslau, 1998). Acute stressors can also increase alcohol consumption (Higgins and Marlatt, 1975). Drug abusers often report that stress and negative affective states are common factors contributing to their relapse (Marlatt and Gordon, 1980; Wallace, 1989), and successfully coping with stress is associated with the prevention of relapse in abstinent drug-users (Marlatt and Gordon, 1980; Shiffman, 1982). Thus, although the present review has focused on emotional modulation of multiple memory systems in PTSD, a stress-induced bias towards the use of habit memory may have implications for the neurobiology of several psychopathologies.

References

1. Goodman, J., Leong, K. C., & Packard, M. G. (2012). Emotional modulation of multiple memory systems: implications for the neurobiology of post-traumatic stress disorder.