Few people possess a perfect sense of direction. Some need a GPS just to find their wits. Then there's Patient 1.

Patient 1, as Giuseppe Iaria and his colleagues refer to her in an online article in Neuropsychologia(doi:10.1016/
.2008.08.021), doesn't even try to drive because she gets turned around in her own neighborhood. Family and friends accompany her almost everywhere, and she only ventures out alone when heading by bus to her job in downtown Vancouver. Even the short walk from the bus stop to her office has been painstakingly memorized; the slightest deviation leaves her hopelessly lost. Now 43, she has suffered this impairment since childhood. Yet in every other regard, she is normal and healthy. "She's smart," says Iaria, a University of British Columbia neuroscientist who spent a year assessing her cognitive functions. "She just doesn't get oriented."

Since 1876, when English neurologist John Hughlings Jackson described a glioma sufferer who couldn't find the entrance to a familiar park, researchers have documented a similar phenomenon shared by patients with problems including traumatic brain injury, dementia and epilepsy. But there had never been a case of a person exhibiting such topographical disorientation—the clinical name for losing your bearings—in the absence of other abnormalities. Never, that is, until Patient 1.

Patient 1 can get lost on her way home; she rarely goes out alone.

Two years ago, when Patient 1 finally sought medical help for her condition, Iaria and his colleagues performed a magnetic resonance imaging (MRI) scan on her brain to look for lesions or other telltale problems. Her MRI showed no structural abnormalities.

Intrigued, the scientists put Patient 1 through a series of navigation tests. To their surprise, she performed perfectly in some, such as retracing a six-block walking route that had just been demonstrated to her.

When asked to draw the floor plan of her home, however, she situated the rooms correctly but in wildly flawed dimensions. Her deepest dysfunction emerged when the researchers had her venture through a three-dimensional virtual city while sitting at a computer. She took 32 minutes, nearly three times longer than control subjects, to gauge the positions of four landmarks in relation to each other. Again and again in a Sisyphean struggle, she would find a landmark only after losing the other three.

Topographical orientation is the last cognitive ability children develop, says Iaria, because it synergizes other faculties such as attention, perception, and memory. Learning a new route turn-by-turn, which Patient 1 did with ease, is known as procedural memory and uses (among other regions) the caudate nucleus, which sits near the center of the brain and is involved in learning and memory.

Conversely, grasping the spatial relationships between elements to get the lay of the land, which gave Patient 1 the biggest headache, taps a far wispier talent called cognitive mapping and draws heavily on the hippocampus, which also participates in memory. Indeed, an fMRI scan performed on Patient 1 as she struggled through the virtual environment revealed that her caudate nucleus showed normal activity, but her hippocampus lay dormant.

Iaria and his co-authors consider Patient 1's case the first instance of developmental topographical disorientation. None of her family members share the condition, and Iaria is unsure whether it's hereditary or not.

Patient 1 is the first, but she's not alone. To find others with the same problem, Iaria set up an informational website (www.gettinglost.ca) and received approximately 80 similar-sounding inquiries in just a month.

Wondering if Patient 1's lethargic hippocampus could benefit from some exercise, Iaria and his team invited her to return for weekly one-hour visits to the virtual city. After just six sessions, she needed only five minutes to map the landmarks, less than half the time required by the initial control group and a six-fold improvement upon her own first attempt. Iaria is now helping her apply her new skills, very gingerly, to venture beyond her tiny, memorized comfort zone in downtown Vancouver. "She has three landmarks and now she's integrating the fourth one," he says.

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