In the past 15 years, thanks to studies in brain damaged patients and the most recent neuroimaging techniques, we have acquired a great deal of knowledge about the neural mechanisms involved in the cognitive functions underlying our orientation skills. For instance, by using functional Magnetic Resonance Imaging (fMRI), we found that the participants’ spontaneous use of the procedural memory system mainly involved the striatum (i.e. the caudate nucleus), a subcortical region that guides most of our automatic behaviours; whereas, the spontaneous use of landmarks while orienting in the environment, that is the spatial memory system, mainly relied on the hippocampus,  a structure located within the medial region of the temporal lobe (Figure 1).

In a recent study, we made use of a 3D virtual environment combined with fMRI to assess the neural mechanisms involved specifically in the formation and use of a cognitive map. We asked participants to navigate their way around a small virtual town and to create a mental representation of the environment, i.e. a cognitive map. After the cognitive map was successfully formed, we asked participants to make use of the cognitive map to reach different target locations by starting from different places within the environment. We named this test “The Cognitive Map Test” (CMT). We looked at the brain activity of participants while they were performing the tasks, and found that the test involved several frontal and parietal brain regions most likely involved in the attentional and perceptual mechanisms required while navigating. However, both the formation and use of the cognitive map involved the hippocampus. These findings confirmed previous pioneer studies in rodents showing that the hippocampus is, indeed, a critical brain region for both the formation and the use of an environmental cognitive map in humans as well (Figure 2).  

It is commonly known that people have different orientation skills, mainly due to the spontaneous bias in using different orientation strategies. However, we wanted to assess whether or not the same individuals’ variability is present when participants are asked to perform the same tasks and use the same orientation strategy, namely the formation and use of a cognitive map. Again, we asked a group of participants to perform the CMT. As expected, we found a great variability in the individuals’ performance in solving the test. Some subjects were able to form a cognitive map of the environment in just a couple of minutes; some others needed over ten minutes to form the same cognitive map. A similar variability was found while using the cognitive map for the purpose of orientation. Some subjects were able to reach target locations very quickly, while some others required more time. In order to explain this variability in terms of neural mechanisms, we used a very recent neuroimaging technique, namely the Diffusion Tensor Imaging (DTI), to look at the molecular structural organization of the hippocampus of those subjects described above who showed a great variability in solving the tasks. We found that the better the structural organization of the hippocampus, the better the individuals’ performance at both the formation and use of the cognitive map. These findings tell us that the variability observed in orientation by forming and using a cognitive map of the environment is strongly related to the structural organization of the hippocampus. We are not sure how and why the structural organization of the hippocampus may vary at a molecular level, but this may be a relevant index to consider when assessing orientation skills, and most likely is responsible for impaired orientation skills in healthy individuals (Figure 3).

In 2009 we published the first case in scientific literature of a 43-year old person affected by developmental topographical orientation. Despite a normal cognitive development, this person has never been able to orient in her environment. From about the age of 6 years onwards she recalls panicking at the grocery store each time her mother disappeared from sight. Her sisters or parents accompanied her to school and she never left home by herself because she got lost each time she tried. As a teenager, she relied on friends to accompany her when she left her parents’ house. Neither she nor her parents know of similar navigational difficulties in their family members. She follows strict stereotyped directions to get to the office where she has worked for five years. She knows which bus to take downtown, recognizes a large distinctive square at which she must exit the bus, and then follows a straight route of about 30 meters to locate the tall building where her office is situated. She follows the same path in reverse fashion to get home, although sometimes she gets lost in her neighbourhood and needs to phone her father to ask him to come and get her. Aside from this specific path, she cannot find her way to other locations, such as stores or theatres, and gets lost each time she tries. After extensive testing, we found that this person has a selective impairment in forming a cognitive map of the environment. fMRI confirmed activity in several brain regions while forming a cognitive map, except for the hippocampus, which, instead was active when she attempted to make use of a previously formed cognitive map after a very long training. These behavioural and neuroimaging findings suggest that her lack of orientation skills is mainly related to the inability to create cognitive maps.

In early 2010 we replicated the findings described in our original case report and documented 120 new cases of people affected by DTD. To date, our databse consists of about 700 individuals who are affected by this newly discovered cogntive disorder. This number is increasing daily, confirming that DTD is indeed a condition that affects a significant number of individuals.