Research Sheds New Light on the Brain’s Internal Compass

March 22, 2023 

A new study by Dr. Mark Brandon, researcher at the Douglas Research Centre and Associate Professor at McGill University, and published in the journal Nature, explores how the brain’s internal compass aligns with its surroundings. These results already represent a significant step forward in the fundamental understanding of how the brain orients itself in space, which has been linked to various cognitive functions and disorders, such as Alzheimer’s disease. 

“One of the first self-reported cognitive symptoms of Alzheimer’s Disease is that people become disoriented and lost, even in familiar settings.”
Dr. Mark Brandon, corresponding author 

The researchers expect that a mechanistic understanding of how the brain’s internal compass and navigation system works will lead to earlier detection and better assessment of treatments for Alzheimer’s disease.  

“We are very excited by the important discovery made by Mark Brandon and colleagues. Gaining a better understanding of how the brain processes information to orient the organism in space and give it a sense of direction represents a major breakthrough.”
— Dr. Gustavo Turecki, Scientific Director, Douglas Research Centre

Uncovering how head-direction cells orient our brain’s sense of direction 

Our sense of direction is attributed to a specialized group of brain cells called ‘Head-Direction’ (HD) cells, which serve as the brain’s internal compass. Maintaining a stable internal HD representation is crucial for an animal’s survival and for that, finding a reliable reference frame, in the environment, is arguably a problem that the brain is constantly trying to solve. Until now, technical barriers have limited scientists’ ability to understand how this internal compass functions.  

“Neuroscience research has witnessed a technology revolution in the last decade – the latest methods in neuronal recordings and analysis allow us to ask and answer questions that could only be dreamed of just years ago.”
— Dr. Mark Brandon, corresponding author 

Dr. Brandon’s study was conducted in close collaboration with Dr. Zaki Ajabi, a postdoctoral research fellow at Harvard University and former PhD graduate student in Dr. Brandon’s laboratory, as well as with Dr. Xue-Xin Wei, a computational neuroscientist and an Assistant Professor at The University of Texas at Austin. The paper is the first time that neuroscientists have been able to record from hundreds of neurons simultaneously by adapting state-of-the-art technology – an order of magnitude increase in comparison with prior studies. This enabled them to discover unexpected population dynamics of the HD system and revealed new insights into the interactions between the internal compass and the visual environment. Using cutting edge technology and statistical modelling, the researchers discovered that the amplitude of global fluctuations in neural activity, referred to as ‘network gain’, determined how quickly the brain’s internal compass could re-orient itself.  

The authors hypothesize that these fluctuations reflect a general mechanism used in brain systems to gate the transitions between states. As such, the reported findings have significant implications for understanding the neural basis of the sense of orientation and how the brain’s internal compass is stabilized within changing visual surroundings.  

In addition to being relevant to the cognitive changes associated with Alzheimer’s disease, the authors argue that their findings also apply to healthy individuals who, like the animals in this study, may find themselves in unnatural situations of visual experience, especially with the rapid spread of virtual reality technology.  

“These findings may eventually explain how virtual reality systems can easily take control over our sense of orientation.”
 Dr. Zaki Ajabi, first author of the study. 

Identifying a “reset” button for rapid reorientation of the brain’s head direction system  

Together, the authors showed that calcium imaging of the collective activity of thalamic head direction neurons could be used to decode the actual head direction of a mouse accurately.  

Dr. Wei has been developing computational and statistical modelling approaches to understand the function of neural circuits. The team applied a statistical technique recently developed by Wei and colleagues for analyzing calcium imaging data and found that they were able to accurately decode the internal head direction with an error of only a few degrees.  

“By integrating large-scale neural recording and advanced data analysis tools, we can read out the animal’s head direction from neural activity with such high precision.”
— Dr. Xue-Xin Wei, co-author

The ability to accurately decode the animal’s internal head direction enabled the researcher to examine how the HD system supports re-orientation in ambiguous environments. The researchers discovered that the amplitude of global fluctuations in neural activity, referred to as ‘network gain’, determined how quickly the brain’s internal compass could re-orient itself. The researchers also discovered that the activity of HD neurons was informative of the location of a previously presented visual cue even after its display on the circular screen surrounding the animal was turned off (i.e., darkness condition). Indeed, the HD cells that fired preferentially when the animal was facing a prior visual cue kept high levels of activity in darkness, while the rest of the neurons underwent a significant reduction in activity.  

This memory trace of visual landmarks indicated that the internal compass was more complex than a 1-dimensional construct to track an animal’s current head direction and that the network gain, as a secondary dimension in the representational space of the HD system, carries additional information about the past visual experience. The authors speculate that these memory traces may help stabilize the internal HD representation even when reliable visual cues become temporarily missing.  

Disrupting internal spatial representation to identify key networks 

To understand to what extent visual information impacts the HD system, the researchers exposed mice to a continuously rotating (instead of a discretely shifting) visual cue. In this situation of constant conflict between self-motion and visual information, they found that the rotating cue exerted total control over the HD neurons inducing a continuous rotation of the internal HD representation. Unexpectedly, the HD network continued rotating at a similar angular velocity to that of the visual cue even after it was removed. This indicates that the HD system readapts to the artificially imposed changes in the relationship between self-motion and optical flow, possibly through a mechanism that allows experience-dependent recalibration of the integration of vestibular input.  

These results inspired the research team to develop new computational models to better understand the underlying mechanisms. They found that their key experimental observations could be explained by generalizing a class of network models (called ring attractor models) to incorporate gain fluctuations and synaptic plasticity that associates the HD neurons and the visual scene. In doing so, the modeling also generates new predictions that will need to be tested in future experiments.  

“This work is a beautiful demonstration of how tight integrations of experimental and computational approaches can advance our understanding of neural circuit mechanisms that support behaviour. One interesting open question is whether the particular type of gain modulation observed in fact represents an optimal strategy for the system to control the re-orienting behaviour.”
— Dr. Xue-Xin Wei, co-author

The new research was supported by the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research.  

For media inquiries, contact Dr. Mark Brandon.

For McGill’s Press Release

For University of Texas at Austin Press Release