The hippocampus holds a model of the environment that can be mentally traversed during recall or simulation. It is unknown whether animals can intentionally control their hippocampal activity according to their model of the world. By combining virtual reality and a real-time brain‐machine interface, Dr. Chongxi Lai of Beth Israel Deaconess Medical Center and colleagues discovered that rats directly controlled their hippocampal neuronal firing in a goal-directed manner. The rodents first formed a hippocampal map of a virtual environment; then, in brain‐machine interface mode, they demonstrated the ability to activate representations from this map corresponding to specific remote locations, which then brought either them or an object to spatial goals; they could sustain a hippocampal representation of a remote location for tens of seconds, reminiscent of human imagination or mental time travel.
Lai et al. developed a novel system combining virtual reality and a brain-machine interface to probe the rat’s inner thoughts.
“The rat can indeed activate the representation of places in the environment without going there,” said Dr. Lai, first author of a paper published in the journal Science.
“Even if his physical body is fixed, his spatial thoughts can go to a very remote location.”
“To imagine is one of the remarkable things that humans can do,” said Dr. Albert Lee, also from Beth Israel Deaconess Medical Center.
“Now we have found that animals can do it too, and we found a way to study it.”
The researchers worked to develop a system to understand what animals are thinking — a real-time ‘thought detector’ that could measure neural activity and translate what it meant.
The system uses a brain-machine interface (BMI), which provides a direct connection between brain activity and an external device.
In the team’s system, the BMI produces a connection between the electrical activity in the rat’s hippocampus and its position in a 360-degree virtual reality arena.
The hippocampus stores mental maps of the world involved in recalling past events and imagining future scenarios.
Memory recall involves the generation of specific hippocampal activity patterns related to places and events. But no one knew whether animals could voluntarily control this activity.
The BMI allows the scientists to test whether a rat can activate hippocampal activity to just think about a location in the arena without physically going there — essentially, detecting if the animal is able to imagine going to the location.
Once they developed their system, the authors had to create the ‘thought dictionary’ that would allow them to decode the rat’s brain signals.
This dictionary compiles what activity patterns look like when the rat experiences something — in this case, places in the VR arena.
The rat is harnessed in the VR system. As the rodent walks on a spherical treadmill, its movements are translated on the 360-degree screen. The rat is rewarded when it navigates to its goal.
At the same time, the BMI system records the rat’s hippocampal activity.
The researchers can see which neurons are activated when the rat navigates the arena to reach each goal. These signals provide the basis for a real-time hippocampal BMI, with the brain’s hippocampal activity translated into actions on the screen.
Next, the researchers disconnect the treadmill and reward the rat for reproducing the hippocampal activity pattern associated with a goal location.
In this task, the BMI translates the animal’s brain activity into motion on the virtual reality screen.
Essentially, the animal uses its thoughts to navigate to the reward by first thinking about where they need to go to get the reward.
This thought process is something humans experience regularly. For example, when we’re asked to pick up groceries at a familiar store, we might imagine the locations we will pass along the way before we ever leave the house.
In the second task, the rat moves an object to a location by thoughts alone. The rat is fixed in a virtual place but ‘moves’ an object to a goal in the VR space by controlling its hippocampal activity, like how a person sitting in their office might imagine taking a cup next to the coffee machine and filling it with coffee.
The scientists then changed the location of the goal, requiring the animal to produce activity patterns associated with the new location.
They found that rats can precisely and flexibly control their hippocampal activity, in the same way humans likely do.
The animals are also able to sustain this hippocampal activity, holding their thoughts on a given location for many seconds — a timeframe similar to the one at which humans relive past events or imagine new scenarios.
“The stunning thing is how rats learn to think about that place, and no other place, for a very long period of time, based on our, perhaps naïve, notion of the attention span of a rat,” said Dr. Tim Harris, a researcher at Howard Hughes Medical Institute.
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Chongxi Lai et al. 2023. Volitional activation of remote place representations with a hippocampal brain-machine interface. Science 382 (6670): 566-573; doi: 10.1126/science.adh5206
