Neuroscientists Decipher Brain’s Response to Unexpected Sensory Stimuli

Scientists have discovered how two brain regions, the neocortex and the thalamus, work together to detect discrepancies between what animals expect from their environment and what actually happens. These prediction errors are implemented by selectively amplifying unexpected sensory information. These findings augment our understanding of predictive processing in the brain and could provide insight into how brain circuits are altered in autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SSD).

Research published today in Nature, describes how scientists at the Sainsbury Wellcome Centre at UCL studied mice in a virtual reality environment, bringing us closer to understanding both the nature of prediction error signals in the brain and the mechanisms by which they arise.

Our brains constantly predict what we can expect from the world around us and what the consequences of our actions will be. When these predictions turn out to be wrong, it causes sturdy activation of different brain regions, and such prediction error signals are vital because they lend a hand us learn from our mistakes and update our predictions. Yet despite their importance, surprisingly little is known about the neural circuitry mechanisms responsible for implementing them in the brain.

Professor Sonja Hofer, group leader at SWC and corresponding author of the article

To investigate how the brain processes expected and unexpected events, the researchers placed mice in a virtual reality environment where they could navigate a familiar hallway to reach a reward. The virtual environment allowed the team to precisely control the visual stimuli and introduce unexpected images onto the walls. Using a technique called two-photon calcium imaging, the researchers were able to record the neural activity of many individual neurons in the primary visual cortex, the first region in our neocortex that receives visual information from the eyes.

“Previous theories have assumed that prediction error signals encode how the actual visual stimulus differs from expectations, but surprisingly we found no experimental evidence for this. Instead, we found that the brain amplifies the responses of neurons that have the strongest preference for the unexpected visual stimulus. The error signal we observed is a consequence of this selective amplification of visual information. This means that our brain detects discrepancies between predictions and actual stimuli to make unexpected events more salient,” explained Dr. Shohei Furutachi, a senior researcher in the Hofer and Mrsic-Flogel laboratories at SWC and the first author of the study.

To understand how the brain generates this amplification of unexpected sensory input in the visual cortex, the team used a technique called optogenetics to deactivate or activate different groups of neurons. They found two groups of neurons that were vital for triggering the prediction error signal in the visual cortex: inhibitory interneurons expressing vasoactive intestinal polypeptide (VIP) in V1, and a thalamic region of the brain called the peduncle, which integrates information from multiple neocortical and subcortical areas and is highly connected to V1. But the researchers found that these two groups of neurons interacted in surprising ways.

“In neuroscience, we often focus on studying one brain region or pathway at a time. However, having a background in molecular biology, I was fascinated by how different molecular pathways work synergistically together, enabling elastic and contextual regulation. I decided to test the possibility that this cooperation might occur at the level of the neuronal circuitry, between VIP neurons and the eyelid pad,” Dr. Furutachi explained.

Indeed, Dr. Furutachi’s work has shown that VIP and pulvinar neurons work synergistically. VIP neurons act like a switchboard: when they are off, the pulvinar suppresses activity in the neocortex, but when VIP neurons are on, the pulvinar can strongly and selectively amplify sensory responses in the neocortex. The joint interaction of these two pathways thus mediates sensory prediction error signals in the visual cortex.

The next steps for the team are to investigate how and where in the brain the animals’ predictions are compared with actual sensory data to calculate sensory prediction errors, and how prediction error signals drive learning. They are also investigating how their findings could lend a hand us understand ASD and SSD.

“It has been proposed that both ASD and SSD can be explained by an imbalance in the prediction error system. We are currently trying to apply our findings to animal models of ASD and SSD to investigate the mechanistic basis of the neural circuits of these disorders,” Dr. Furutachi explained.

This research was supported by a Sainsbury Wellcome Centre Core Grant from the Gatsby Charity Foundation and Wellcome (219627/Z/19/Z and 090843/F/09/Z); a Wellcome Investigator Award (219561/Z/19/Z); the Gatsby Charitable Foundation (GAT3212 and GAT3361); the Wellcome Trust (090843/E/09/Z and 217211/Z/19/Z); the European Research Council (HigherVision 337797; NeuroV1sion 616509); the SNSF (31003A 169525); and Biozentrum Core Funds (University of Basel).