Quick Summary

• UC Davis researchers are exploring new ways  to help diagnose and fight debilitating conditions like schizophrenia, dementia and Parkinson's
• A key to understanding our visual processes is the brain’s capability to anticipate a change in sensory information due to self-movement
• This guidance system allows you to distinguish the source of environmental changes that occur and likely contributes to performing rapid motor activities

Making sense of your perceptions

When you step into Wilsaan Joiner's lab, the foosball table in the corner might seem a bit out of place. But for Joiner’s research on perception and eye movement, playing a simple game can tell you a lot about how your visual system works.

Your eyes are amazing sensors. Visual information sweeps across the retinas so fast that what you perceive should be a blur. However, your visual system smooths the action like an image stabilization tool for shaky camera shots. Your brain constantly applies corrections, providing a seamless picture of your world.

In the brains of people who have schizophrenia, bipolar disorder and other mental illnesses, these unconscious functions are in disarray, blurring the lines between internal and external sensations.

“Your central nervous system is making constant predictions about your body all the time,” says Joiner, an assistant professor of neurobiology, physiology and behavior. “It’s always going on in the background and you’re not typically aware of it. But when you can’t do it, it has pronounced consequences that are fairly devastating. You can’t make sense of many of the common things we experience in the world.”

UC Davis College of Biological Sciences neuroscientists like Joiner and his colleague Jochen Ditterich are exploring new ways to understand how our brains make sense of our perceptions, in hopes to help diagnose and fight these debilitating conditions.

To fool the eye—or brain?

A key to understanding our visual processes is the concept of “corollary discharge,” a term that describes the brain’s capability to anticipate a change in sensory information due to self-movement. This guidance system allows you to distinguish the source of changes that occur in our environment and likely contributes to performing rapid activities, like hitting a baseball. 

Another way to think about this internal, unconscious signal is to consider how it’s impossible to tickle yourself. Somehow, your brain recognizes your self-initiated movement and betrays the physical stimulation you’re trying to induce.

In healthy brains, the thalamus likely conveys this information with great fidelity. But schizophrenic patients have perceptual difficulty with tasks that rely on corollary discharge, including identification of visual changes in the environment.

It’s unclear whether this difficulty is related to the transmission or actual utilization of the signal. Without it, test subjects will make a perceptual decision solely based on visual information rather than some combination of internal knowledge of our movements and the experienced visual information.

With a simple visual test, Joiner can evaluate corollary discharge in both non-human primates and humans with schizophrenia. In the experiments, which involve eye movements and perceptual decisions, Joiner found subjects relying solely on visual information consistently make the wrong choices.

“It’s only when you have this kind of deficit that you have more pronounced perceptual symptoms,” says Joiner. “So what this is showing is a somewhat simple visual perception task that correlates very well to the extent that you have delusions and hallucinations.”

While the absence of these internal signal cues reveals a larger void in our understanding of the origins of psychosis, it provides clues about how individuals with mental illness perceive themselves and the origins of their thoughts and ideas.

Joiner’s research suggests that deficits in corollary discharge may be an accurate and objective tool for diagnosing mental health conditions with psychotic symptoms.

Joiner discovered that as an individual’s deficit in corollary discharge increases, their sense of agency (e.g., ownership over thoughts or actions) decreases. This behavior can lead to trouble recognizing self-caused vs. externally caused sensations, which may lead to confusion, hearing voices and other psychoses.

Joiner’s long-term hope is that the absence of corollary discharge may help provide a simple, but objective litmus test that clinicians can use to accurately identify and develop treatments for these neurological diseases.

“If you have deficits in transmitting or utilizing corollary discharge signals, it speaks to higher mental disorders that are very pronounced, but we don’t quite understand,” says Joiner.

The power of decision-making

If you hear an unfamiliar sound in the woods, your survival could depend on making a rapid decision with very limited information.

Ditterich, an associate professor of neurobiology, physiology and behavior, wants to better understand how our brains make such quick decisions. He evaluates this process through a “decisional threshold,” which describes the amount of information you want to collect before you commit to a particular choice. For any scenario, the goal is to find a tradeoff between maximizing the accuracy of the decision and minimizing the time it takes to do so.

With the clear and precise diction of his German accent, combined with a system engineer’s analytical perspective, Ditterich methodically outlines his plan to transform the way we treat neurological and psychiatric diseases that involve cognitive deficits.

“Implanting a technical device called a deep brain stimulator (DBS), has become a viable treatment option for patients with motor disorders, like Parkinson’s, that do not respond well to drug therapy,” says Ditterich. “Using a more intelligent version of stimulation, we might at some point be able to treat cognitive deficits resulting from neurological or mental disorders that are also difficult to treat with medications.”

His approach is ambitious, but if successful, it could one day improve cognitive functioning related to decision-making, attention, memory and more. The basic idea is to design an intelligent, implantable device that directly communicates with the brain and steers it in an attempt to restore healthy neural signaling. In concept, such an advanced device would monitor and decode a patient’s neural activity and dynamically stimulate the brain to achieve a desired state. But first, Ditterich needs to understand precisely how cognitive functions are implemented within a healthy brain.

While this scenario may sound like science fiction, implants are already being used on a regular basis to treat patients with Parkinson’s. They are also being tested to treat conditions like depression and obsessive-compulsive disorder. But these devices aren’t particularly intelligent. Instead of responding to dynamic brain states, the current generation of stimulators provides only constant and steady stimulation.

Parkinson’s is generally thought of as a motor disorder, but it turns out patients experience cognitive deficits as well, including decision-making deficits, which are not typically addressed through current treatment options.

Ditterich’s research suggests that these patients experience problems using previous knowledge when making decisions. It’s not a learning problem but an implementation problem, and the patients’ decision thresholds cannot adjust appropriately.

Lifting the neural veil

By compiling neural activity from healthy brains during different decision-making situations, Ditterich can use machine learning to plot an optimal decision path for any scenario. It’s like coming up with enough evidence for a choice before the exact moment of committing to it. And amazingly, the data shows that in healthy brains the decision process is an approximation of a statistically optimal algorithm.

Your healthy brain operates across a vast distributed network involving the frontal cortex, parietal cortex, basal ganglia and other subcortical areas that collectively compute different outcomes simultaneously. You can take pride that the final results of your “organic computing” are on par with even the most advanced supercomputers.

This staggering concept is what first drew Ditterich to neuroscience. An electrical engineer by training, he began investigating how the eye recalibrates during movement, similar to Joiner’s research on visual perception.

For Ditterich, who sees the central nervous system as the ultimate information processor, “there are some things that are just very, very hard to do with machines that the brain can accomplish with ease. We have to figure out how, ” he says.

“As engineers, we know a lot about how machines process information. You can use all the mathematics and the engineering tools behind that to analyze what’s going on biologically, to reverse-engineer the brain,” he adds.

While such advanced implantable devices are still a ways off, Ditterich is already in talks with control engineers at UC Davis to explore machine guidance. “They know very well how to steer airplanes and navigate other complex technical systems,” says Ditterich. “Could we use this understanding to steer the brain into a particular desired state?”

Now Ditterich is collaborating with UC Davis Health clinicians to monitor brain activity in patients receiving a DBS implant. He conducts research performing the same perceptual decision tests in both humans and rhesus monkeys.“

We use identical tasks to understand how cognitive functions work in humans and can be validated in non-human primates,” Ditterich says. “Behaviorally, in visual decision-making tasks, we find very, very similar results.”

Reframing your world

Your eye movement and decision-making processes are things you probably take for granted. Your identity is intimately connected to your ability and independence to make decisions.

But imagine if you couldn’t answer, “Who’s in control?” How would this impact your routine decisions, like “What will I eat for lunch? What do I do next in my day?” These are the very real challenges that people with cognitive deficits face every day.

Fortunately, building the foundations to diagnose and treat these conditions is a driving force for Joiner and Ditterich and many other faculty and student researchers at UC Davis.

They’re pushing the boundaries of knowledge to make sense of our world, and to help us make sense of our place in it.