Post Traumatic Stress Disorder (PTSD) is characterised by recurrent and intrusive memories, avoidance, and hyperarousal. PTSD is also associated with impairment in attention, and some studies have shown deficits in learning and memory  It has been suggested that disturbed processing of new environmental information in PTSD is due to continuous background re-processing of traumatic events, resulting in modifications of neural circuits [2, 3]. The resources required to maintain these autonomous loops may therefore not be available for general attention and memory function. The capacity of working memory has been shown to be directly related to the severity of intrusive memories , providing empirical support for this theory.
The hippocampus (HC), located within the ventral medial temporal lobe, is central to the encoding and reconstruction of episodic memories . The hippocampus is part of a large extended network involving the learning of material available within working memory. Plasticity in the physical connections between the HC and the neocortex is crucial for integrating multi-modal sensory information and modifying memory dynamics over time . In addition the HC has a significant role in executive processing systems [7, 8]. The HC also contributes to regulation of the hypothalamic-pituitary-adrenocortical system, which is crucial in both acute and chronic responses to stress .
The hippocampus, located within the ventral medial temporal lobe, has long been known to be central to explicit long-term recognition memory. Olsen et al. (2012) , reviewed recent research showing that the hippocampus is also involved in short-delay recognition and perception. Olsen et al. (2012)  concluded that the hippocampus rapidly and continuously forms associations between disparate environmental inputs, including comparing current perceptual input with internal representations. The hippocampus is therefore part of a large extended network involving the recognition and learning of material available within working memory. This network incorporates multiple brain regions, including the prefrontal cortex. Failure in a significant part of this extended network will compromise the functioning of the network as a whole. The hippocampus also contributes to regulation of the hypothalamic-pituitary-adrenocortical system, which is crucial in both acute and chronic responses to stress .
Psychological trauma has been found to have damaging effects on the HC [11–14], and animal studies have shown that stress induces changes in hippocampal morphology and function [15, 16]. In normal subjects the volume of the right hippocampus is larger than the left hippocampus [17, 18]. Numerous studies have shown that hippocampal volume (HCV) is smaller in people with PTSD compared to controls [19–21]. A recent meta-analysis of 39 studies reporting hippocampal volume in PTSD  found that people with PTSD and trauma-exposed people without PTSD had smaller left, right and total hippocampal volumes than people never exposed to trauma. This suggests that trauma has an impact on the hippocampus bilaterally. In addition, people with PTSD had smaller volumes of the right, but not the left, hippocampus compared to people who had been exposed to trauma but did not have PTSD. The reduction in right hippocampal volume in PTSD reported by Woon et al.  is consistent with an MRI study showing reduced neuronal density in the right medial temporal cortex in people with PTSD, compared to trauma-exposed people without PTSD . These findings suggest that the right hippocampus is differentially reduced in volume in people who develop PTSD.
Disruption of the normal pattern of hippocampal asymmetry has been found in people with schizophrenia [24, 25] and in young people meeting criteria for an at-risk mental state for psychosis . Studies in mild cognitive impairment and dementia suggest that there may be changes in hippocampal asymmetry as memory deteriorates . Taken together, these findings demonstrate that abnormal hippocampal asymmetry is found in people subject to pathological processes that affect brain function and manifest as disorders affecting mental state and cognitive function.
Our participants consisted of male Vietnam combat veterans with and without PTSD, and their non-combat exposed monozygotic twins. The contributions of familial vulnerability and trauma exposure to biological abnormalities in this study population have been investigated by Pitman and colleagues . Gilbertson et al.  demonstrated that total hippocampal volumes were about 10% smaller in men with severe PTSD, compared to men who did not have PTSD. Consistent with this finding, there was a significant correlation between total hippocampal volume and PTSD symptom severity in the PTSD group. However, these investigators also found that there was no difference in hippocampal volume between participants with severe PTSD, and their combat-unexposed identical twins, suggesting that smaller hippocampal volume might be a biological risk factor, rather than a consequence of trauma exposure and the pathophysiological processes associated with PTSD.
In the present study, we investigated the relationship between hippocampal asymmetry and the capacity to process information about the immediate environment in a sample of identical twins discordant for Vietnam combat exposure. We utilised the amplitude of the event related potential (ERP) P300 component as a measure of the controlled allocation of attentional resources to an anticipated stimulus. The P300 reflects processing of information about a significant stimulus, including context updating, context disclosure, event-categorisation and memory updating [30, 31]. The P300 is most commonly elicited by asking participants to identify target tones in an auditory oddball task. The P300 has generators in a number of brain regions, including the temporo-parietal cortex, the cingulate cortex, the thalamus and the inferior and middle frontal cortex . There are two separate generators in the hippocampus, located in the anterior subiculum and the posterior hippocampal body .
Numerous studies [34–39] including a meta-analysis by Karl et al.  have indicated that the amplitude of the P300 at midline electrodes in relation to trauma-neutral target tones is generally reduced in patients with PTSD. In a study involving the same monozygotic twin population as the present study, Metzger et al.  found smaller P300 amplitude in non-medicated, non-smoking twins with PTSD, compared to their combat-unexposed co-twins. In the full sample, there was no difference in reaction time or P300 amplitude between any of the groups (combat veterans with and without PTSD, and their combat-unexposed co-twins respectively). A recent study  found that P300 current source density was significantly reduced in people with PTSD in the inferior frontal gyrus, insula, and anterior cingulate.
The aim of the present study was to investigate the relationship between P300 amplitude and hippocampal asymmetry in the twin sample described above. As noted above, it has been established that hippocampal volume has a role in predisposing to PTSD, and there may be further changes related to both trauma exposure and to the development of PTSD. The amplitude of the P300 to trauma-neutral stimuli is generally reduced in PTSD, indicating that the information processing abnormalities characteristic of PTSD are reflected in changes in the P300. In addition, hippocampal generators contribute to P300 amplitude.
Given that both reduced P300 amplitude and greater hippocampal asymmetry (with relatively great volume reduction of the right hippocampus) are likely to reflect pathological changes related to PTSD, we hypothesised that there would be a negative correlation between P300 amplitude to trauma-neutral target tones and the magnitude of hippocampal asymmetry in people with combat-related PTSD (such that smaller P300 amplitude would be found in participants with greater hippocampal asymmetry).