نتایج ناهمگن در یادگیری مکانی در بین بیماران مبتلا به اختلال پانیک با موقعیت هراسی

Patients affected by panic disorder with agoraphobia (PDA) often suffer from visuo-spatial disturbances. In the present study, we tested the place-learning abilities in a sample of 31 PDA patients compared to 31 healthy controls (CTR) using the computer-generated arena (C-G Arena), a desktop-based computer program developed at the University of Arizona (Jacobs et al 1997, for further detail about the program, see http://web.arizona.edu/~arg/data.html). Subjects were asked to search the computer-generated space, over several trials, for the location of a hidden target. Results showed that control subjects rapidly learned to locate the invisible target and consistently returned to it, while PDA patients were divided in two subgroups: some of them (PDA-A) were as good as controls in place learning, while some others (PDA-B) were unable to learn the correct strategies to find the target. Further analyses revealed that PDA-A patients were significantly younger and affected by panic disorder from less time than PDA-B, indicating that age and duration of illness can be critical factors that influence the place-learning abilities. The existence of two different subgroups of PDA patients who differ in their spatial orientation abilities could provide new insight into the mechanisms of panic and open new perspectives in the cognitive–behavioral treatment of this diffuse and disabling disorder.

Anxiety disorders are often characterized by automatic attentional biases for selective processing of information or stimulation related to cues perceived as threatening in the anxious people's environment (Keogh and French, 1999 and Wittchen and Hoyer, 2001). In particular, visuo-spatial cognition biases are common in patients affected by panic disorder with agoraphobia (PDA), who are often so worried about their own physical reactions that they become unable to be attentive to changes occurring in the surrounding environment (Kallai et al., 1995). These observations are supported by different experimental studies showing that patients with PDA have scarce abilities in orientating in a maze and in performing blind orientation tasks as compared with patients affected by other anxiety disorders and healthy controls (Kallai et al., 1995 and Kallai et al., 1996). Recent data obtained by Kallai et al. (2007a) have also shown a correlation between altered physiological parameters and the PDA patients' inability to detect the navigation signals indicating the right route to exit from a labyrinth. Disorders of visuo-spatial attention have been found in PDA patients during a computerized visual target discrimination task (Dupont et al., 2000) and in a distance estimation task, indicating the presence of a possible distortion in the patients' representational mechanisms of the extrapersonal space (Iavarone et al., 2005). PDA patients also present deficit in spatial memory and learning, as shown by Boldrini et al. (2005). Moreover, the positive effects of attentional fixation training in reducing panic-related symptoms (Kallai et al., 1999) strengthen the hypothesis that spatial disturbances are often associated with PDA. Besides these experimental data supporting the hypothesis that PDA should at least partially depend on the ways in which the cognitive structures interact with the situational variables (Taylor et al., 1986), there are a series of neuropsychological studies that have failed to find any spatial deficit in PDA patients compared to control subjects (Gladsjo et al., 1998 and Purcell et al., 1998). These discordant results make the role of visuo-spatial abilities in PDA still unclear. However, as shown by Kallai et al. (1999), understanding the role of orientation abilities in PDA is crucial to gain new insight into the mechanisms of panic disorder and to find an efficient therapeutic approach. In the present study, we propose to test spatial orientation and place-learning abilities in a sample of severe PDA patients using the computer-generated arena (C-G Arena), a desktop-based computer program developed at the University of Arizona ((Jacobs et al., 1997 and Jacobs et al., 1998); for further detail about the program, see http://web.arizona.edu/~arg/data.html) representing a virtual adaptation of the original water maze task (Morris, 1981). The main advantage of using a virtual space instead of a real one is the possibility to test patients in a safe and controlled environment reducing the risk, usually associated with in vivo exposure, of inducing panic-related symptoms and altering their physiological, emotional, and cognitive functioning during the experimental session. Moreover, compared to the traditional neuropsychological tests, a virtual space has the advantage of enhancing the ecological validity of the test, increasing predictions about the patient's functioning in the real world ( Parsons et al., 2008). Up to date, several researches using such technology have been conducted ( Gillner and Mallot, 1998, Jacobs et al., 1997, Jacobs et al., 1998, May et al., 1995, Nadel et al., 1998 and Ruddle et al., 1997). The main findings emerged from these studies are that (a) subjects can make accurate judgments about metrics in real space after learning in a virtual environment ( Péruch et al., 1995), (b) there is good transfer of spatial information from virtual to real environments ( Wilson et al., 1997), (c) different spatial performances in the virtual spaces are predicted by different search strategies that reproduce the strategies used in real spaces ( Kallai et al., 2005 and Kallai et al., 2007b), (d) virtual environments are suitable to explore the neural substrate of place learning and spatial navigation in humans ( Thomas et al., 2001), and (e) virtual environments, and virtual reality technology, in general, show promise in aiding neuropsychological evaluation and rehabilitation ( Rizzo et al., 1998, Rose et al., 1996 and Thomas et al., 2001). Additionally, thanks to their programmable flexibility, data-handling capabilities, and their psychometric properties, virtual environments reproducing classical navigation tasks have been also used to explore the issue of gender ( Astur et al., 1998 and Astur et al., 2004) and age-related ( Thomas et al., 1999) differences showing robust sex differences in virtual place learning, as well as the presence of age-related changes in the human cognitive mapping system. The C-G Arena consists in a computer-generated three-dimensional virtual space in which subjects are asked to find a hidden platform using a number of distal cues on the walls. This kind of place-learning task requires distal spatial orientation abilities (Morris, 1981): to complete it, subjects use only localized distal cues coming from fixed places at some distance from the target objects, learning and remembering location of the target relative to them. In order to successfully perform the task, organisms use a spatial map consisting of information about specific objects and relations among them, formed when they enter and observe a new environment for the first time (Jacobs et al., 1997). As demonstrated by Jacobs et al. (1998), the place learning in C-G space is comparable to both rat and human place learning in real space. Using the C-G Arena we wanted to investigate if place learning based on distal cues occurs in PDA patients as it occurs in healthy subjects and if it generalizes from familiar to novel start locations. To answer these questions, we used a version of the C-G Arena in which only distal cues existed and trained participants to find an invisible target entering in the virtual space from different start locations. Our hypothesis is that the ecological characteristics of the C-G Arena could be useful to discriminate the spatial abilities of subjects, eventually indicating difference between PDA patients and healthy controls, or within the PDA group itself, allowing the therapist to decide to integrate the traditional therapeutic approach with spatial orientation training.