Woman lost in her own house

The study of age-related disorders may reveal new secrets of the brain.

They call him Dr. WAI, short for Where Am I [Where I Am]. A well-educated man, 29 years old, without any serious illness or injury, was able to draw a more or less accurate map of the house, where he had been living for 15 years only from the fourth attempt [Bianchini, F., et al. Where am i A new case of developmental topographical disorientation. Journal of Neuropsychology 8, 107-124 (2014)]. Another patient, Jennifer from San Francisco, all the time seems to be facing north, regardless of the direction in which she is looking. Judy Bentley once, when she was in high school, suddenly lost the memory of everything that surrounds her. She lost all idea of ​​what is behind the door of the class.

These are just a few examples to study, opened by a new field of medicine, which began with a girl who can be called "zero patient". Call her Alice [Iaria, G., Bogod, N., Fox, CJ, & Barton, JJ. Developed topographical disorientation: Case one. Neuropsychologia 47, 30-40 (2009)]. In 2007, Alice addressed a neurobiologist, Giuseppe Yaria, with a strange and annoying problem: it was very difficult for her to navigate the terrain. Sometimes she was even lost in her own house. She had to rely on standard routes, door-to-door hikes along a carefully hewn path. To get to work, she remembered where she needed to get off the bus, and how to go from one learned reference point to another, until you reach the office building where she works.

But if Alice deviated from the route, she was immediately lost, and she could only call her father to pick her up. She had no vision problems — she could recognize landmarks and other objects as well as others. Her intellect was fine, and she was an avid book lover. And although she developed a strategy for herself that helps her in life, she was afraid that she would refuse: her company decided to transfer it to another place, and she was terrified of the prospect of learning a new route in a new area.
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On the left is a map of the house drawn by a person with a deviation. On the right is the real map of his house.

Yaria from the University of Calgary was fascinated by this incident. For years, he studied the way people navigate the terrain and the associated brain systems, and he knew many people with orientation problems. But all of them had brain damage, most often the result of a stroke. Alice was the first person he met who had serious problems with orientation without any visible brain damage.

Yaria tested Alice, and found that she coped normally with a wide range of cognitive tasks. The brain had no structural abnormalities, and no obvious problems with education, which could be related to the fact that it is unable to navigate. She absolutely could not draw a meaningful map or present it. The only possible explanation, apparently, was some kind of genetic problem. Yaria coined the term “age-related topographical disorientation” (ATD) [Developmental Topographic Disorientation, DTD] for Alice and other similar cases that were soon revealed in sufficient quantities.

Suddenly, a new and fairly common problem emerged, with the potential of demonstrating new knowledge about how we know that we are where we are.

Suppose you walk in a mountainous area. You have a map (paper) and a compass (magnetic). You are trying to reach the mountain of Opportunities. You have several options:

1. If you see a mountain from your place, and also see the ground between you, you can build a path based on what you see. This is a visual navigation.
2. If you are on a trail, and you see the “Mount of Possibilities, 500 m” sign, you can simply follow the trail further, without turning to the map. This is the route navigation.
3. Otherwise, you need to find yourself on the map, use the compass to deploy it correctly, find on it a mountain of possibilities, and using the map, build a route leading you from your current location to the mountain. This is a map navigation.

People like Alice usually have no problems with visual or route navigation. Their difficulties are associated with navigating the map. But navigating the map is quite complicated, and there are several options why it can go wrong. Among them: the inability to form a good environment map; inability to find oneself on the map; the inability to understand their orientation relative to the map; inability to use a map to build a route between two points. Each of these options is probably associated with different problems and different parts of the brain.

If the problem is to build a map, then it is most likely related to the hippocampus . Hippocampal neurons are activated when an animal passes certain areas of the environment. This “response to the terrain” combines information from the senses and from other parts of the brain, in particular, from the entorhial area of ​​the cortex , located near the hippocampus and responsible for the spatial coordinate system.

If the problem is related to orientation, then it may lie in the region of the “head direction” system — an inertial compass located in the brain. The set of brain structures on which this system is based works closely with the hippocampus and the entorhial cortex. Unlike a magnetic compass, the head orientation orientation system does not store any north direction; it is more like a gyrocompass, and uses inertial properties to maintain a constant sense of direction in the process of movements and orientation changes.

But most often with the topographic orientation resulting from damage to the brain, the retrosplenial cortex is associated. This area is located near the center of the brain and is strongly associated with the hippocampus and other areas that work with navigation. The retrosplenial crust is not involved in building an accurate map or sense of direction, but it somehow, while it is not clear how, is crucial for being able to correctly use the map and compass to build a route to your goal.



Among the causes of VTD, perhaps there are the above. Some people, including Alice, appear to form highly distorted cognitive maps. This suggests dysfunction of the entorhial cortex or parietal cortex , areas associated with the construction of spatial relationships. Others have difficulties with orientation, which suggests a dysfunction of the head-guidance system. Judy Bentley, one of Yaria's patients, discovers that her sense of direction suddenly switches between four options, and each time she has to learn a new set of relationships. Sharon Roseman, too, often loses her sense of direction, but she discovered that if she closes her eyes and twists in place, then the feeling usually returns. And Jennifer, a patient from San Francisco, always seems to be looking in the same direction, even if she turns.

Conducted systematic studies of VTD pointed to some structures and functions of the brain, but the findings are not yet decisive. Two years ago, Yaria and colleagues found in nine women suffering from ITD a reduced interaction between the hippocampus and the prefrontal cortex , compared with the control group. This is interesting, but there is a suspicion that this fact may be a consequence of the ITD, and not the cause. Roughly speaking, the hippocampus maps, and the prefrontal cortex plans. Reducing the interaction suggests that the resulting maps have less impact on the plans. This may simply be the result of people learning the unreliability of their cards.

In 2014, a group of researchers from Princeton and Carnegie-Mallon studied in detail the brain activity in women with VTD, who were asked only to observe spatial scenes unfolding on a computer screen, rather than focus on real terrain [Kim, JG, Aminoff, EM, Kastner, S., & Behrmann, M. A neural basis for developmental topographic disorientation. The Journal of Neuroscience 35, 12954-12969 (2015)]. When their brain activity was compared to a control group, no differences were found in the hippocampus. Clear differences appeared in the retrosplenial cortex - in the same area of ​​the brain, due to injuries of which topographic disorientation most often occurs. In the subjects, a decrease in the response to familiar places and a decrease in the functional connection between the retrosplenial cortex and the area surrounding the hippocampus, which is responsible for putting the surrounding environment in memory, was observed. It is possible that the retrosplenial cortex will be just as important for an ATD as it is for topographic disorientation due to injury — at least in some cases.

Over time, the most likely important information that VTD research will give us will be an improved understanding of the genes associated with spatial recognition. There is evidence that VTD is inherited. Yyara promises to publish soon the work confirming this observation. If it becomes possible to identify a small number of genetic mutations that distinguish people with ITD from the rest, this will be an excellent starting point. This may not work: the number of genes subject to expression in the brain is enormous, and it is impossible to predict in advance how many of them are related to spatial recognition. If only a few people with VTD have mutations in the same genes, it will be rather difficult to move on. But it's worth a try. The results will not only come in handy for studying ITDs, but are also likely to be useful for understanding the normal spectrum of spatial possibilities. Large mutations cause great difficulties, and small differences in gene expression are likely to lead to less significant differences in behavior.

In connection with the genetics of ITD, it is particularly interesting that this condition appears much more often in women than in men. In the initial group of Yyar, 120 people included 102 women and 18 men [Iaria, G., & Barton, JJ. Experimental Brain Research 206, 189-196 (2010)]. This cannot be considered evidence, since most of the members of the Yyara group came independently, and women may simply be more open in such cases. To establish a clear connection, you will need to make a random sample of people. But still, the difference turns out to be quite large, and it can be expected that it will continue even after sampling - given that some studies have shown that men, on average, do a little better than women on map orientation [Andersen, NE, Dahmani, L., Konishi, K., & Bohbot, VD Eye tracking, strategies, and sex differences in virtual navigation. Neurobiology of Learning and Memory 97, 81-89 (2012)]. Therefore, at least the expression of some of these genes may be sex-related.

Over the past five years, several hundred cases of ITD have been detected. It may be that this problem is not so rare. An informational survey among students, conducted by Yiara at the University of Calgary, showed that at least 2% of them may fall under the criteria for ITL. There are chances that any of the readers of this article also suffers from this condition without knowing it. Yyara prepared an online test [English] - perhaps it is worth passing. As for Alice, as a result, they decided not to transfer her place of work, and she continues to find her work on landmarks.

William Skaggs - neurobiologist, author of popular science articles, explores the role of the hippocampus in spatial recognition and memory.