Studying Your Best Friend’s Brain – Dog’s unique role in the study of evolution, speech processing, and brain diseases

05Sep16

Step aside, Cesar Millan—these days when you want to know what the dog really saw, ask a scientist, not a Dog Whisperer.

While studies of domestic dogs (Canis familiaris) have long been fundamental to neuroscience—it was Pavlov’s dog after all that drooled when it heard that bell—dog research is undergoing a renaissance due to advances in genetic and brain-scanning techniques. And dogs themselves are emerging as unique research subjects due to their evolutionary history, their close relationship with humans, their high intelligence, and—most importantly—their ability to sit. (Sit still while their brain is being scanned, that is.)

In this blog post I’ll discuss recent dog research: evolutionary studies comparing dogs to wolves, studies probing whether dogs understand what we say and how their brains process speech, and finally how millennia of selectively breeding dogs is now helping in the search for genetic markers of mental illness and has even lead to the development of a new drug to treat insomnia.

The Origin of Man’s Best Friend

Pop quiz: which animal is more closely related to humans—a mouse or a dog?

It may come as a shock, but genetically we’re closer to mice than dogs. Despite this, while our kindred mice were stealing our food during the night, we were developing a companion-like relationship with dogs.

It’s unclear how the relationship between humans and dogs began, and what led dogs to diverge from wolves. For example, did humans actively seek out and domesticate wolves? Or did wolves seek out man: flocking to early farms and eating human food scraps, and then the domestication occurred incidentally as the less-aggressive, cuter wolves were more likely to be allowed to stick around?

We do know that dogs have evolved with us. At the time of the agricultural revolution 10,000 years ago, humans and dog genomes both evolved, modifying enzymes to allow for better processing of the carbohydrates found in the grains we cultivated. (If you want to hear more, check out this interview with the study’s author.)

A study published just last week suggests that this change from hunter to scavenger may have also affected dog’s appetite for risk. Although C.M. Coolidge immortalized dogs as gamblers for a series of cigar advertisements, the domestication of dogs may have actually rendered them risk-averse. Given a choice between receiving a reward of guaranteed but inferior food, or a 50-50 chance at getting either a tastier treat or nothing, 80% of wolves chose the risky option, whereas dogs did so only 58% of the time[1].

Note that the dogs and wolves used in this study all grew up in the same conditions at the Wolf Science Center in Dorfes, Austria, so differences observed are likely to stem from genes not different developmental experiences.

The authors of this study argue that these results are constant with other cross-species comparisons that show that species with unstable food sources tend to be risk-takers, possibly because these species need to explore to find food, and because exploration is inherently risky, these species tend to be greater risk-takers.

What do dogs understand?

Dogs were the first species that humans domesticated, and as such have acquired the ability to understand and communicate with humans. But how much do they really understand and how do they do it?

Gregory Burns wondered that same question. He was using fMRI to scan brain activity in humans, and he wondered if it could be applied to dogs. fMRI brain scans depend on the research subject staying completely still. We can tell humans to stay still, but the few previous fMRI studies of animals had used anesthesia or immobilization.

Watching a TV program about military dogs, Berns had a hunch. If dogs could be trained to stay calm and jump out of a noisy helicopter, they could also be train to stay still and calm through the loud racket generated by an fMRI machine. By scanning the brains of dogs, we could apply the techniques of modern cognitive science to study how dogs had adapted to understand us and become integrated into our families. His hunch was right. He trained his own dog Callie, to sit inside the fMRI machine and made history, generating the first fMRI scan of an unrestrained thinking dog’s brain—showing how the dog’s brain responded when it saw a hand signal that indicated it would get a reward. Berns outlines the story of his pioneering research and findings in his book, How Dogs Love Us.

Since Berns’ pioneering work, a number of groups have begun using fMRI to study dogs’ brain activity during a variety of tasks:

From Thompkins et al., 2016 Early days of dog MRI studies show upward trend.

Just last week, a new study published in Science, Hungarian researcher Attila Andics and his group showed that with dogs, it’s not just ‘what you say’ but ‘what you say, how you say it, and the combination of the two’ (gotta workshop that one).

Inside the scanner, they played the dogs recordings of either praising words, like ‘clever’—actually, they used the Hungarian equivalent ‘ügyes’—or separate words they thought would have no meaning to the dogs like ‘olyan,’ which means ‘such.’ These words were said both in neutral tones and in tones consistent with praise. Dogs showed three distinct patterns of neural activity: a set of responses sensitive to the words themselves, another sensitive to the intonation of words, and a final pattern when the praise words were combined with the congratulatory intonation.

Here, researcher Attila Andics explains his research:

Interestingly consistent with what has been observed in humans, the left hemisphere appeared more involved in the dogs’ processing of words themselves, possibly due to the left hemisphere’s preferential ability to process rapidly changing acoustic signals, as has been observed in humans and gerbils. Also, like humans, the dogs preferentially processed intonation using their right hemisphere. Perhaps most interestingly, only one sound combination activated the dogs’ reward systems: the combination of both praise words and praise intonation, indicating that the dogs may be combining information from these lexical and tonal processing systems to inform their decisions, and that, when training a dog, using a consistent tone and word may work best.

From Information is Beautiful  – How does your dog stack up?

Dog Breeds and Brain Disease

The history of selectively breeding of dogs has also created interesting avenues for research. The process of creating inbred or ‘purebred’ lines of dogs selected over generations for certain traits, also led some breeds to become enriched for genetic disorders. For example, many Dobermann pinschers suffer from narcolepsy, a disease that disrupts the sleep-wake cycle and leads to excessive daytime sleepiness and often uncontrollable episodes of falling asleep in the daytime.The fact that many Dobermanns suffer from narcolepsy indicates that through selective breeding of the traits that define pinschers, a gene that causes narcolepsy was also inadvertently enriched within the breed.

One of the greatest success stories in modern neuroscience has come from studying these pinchers. It begins with Emmanuel Mignot of Stanford University, who had the insight that narcoleptic dogs could teach us something about human narcolepsy. He first tackled the problem by searching for and trying to discover (pinsch-point?) the gene that made them narcoleptic.

In 1999, Mignot found a mutation to the dog’s hypocretin receptor 2 (also known as the orexin receptor 2), was found to be the culprit. While the exact same mutation does not often cause narcolepsy in humans, Mignot’s studies showed that the effect of the mutation, disruption of the hypocretin pathway, results in the difficulties regulating sleep in narcoleptic patients. Based on these findings, in 2000, doctors realized that a majority of patients with narcolepsy show undetectable levels of hypocretin in their cerebral spinal fluid, while it was detectable in every control.

Additionally, this research led to the discovery that hypocretin signaling is important for the sleep-wake cycle in healthy people, and that blocking hypocretin signaling can induce sleep. These discoveries led to pharmaceutical research into an hypocretin blocker suvorexant, which the FDA approved it in 2014 as the first in a new class of sleeping pill to help treat insomnia, and it theoretically shouldn’t have the same risks for abuse as many traditional sleeping pills.

The reason this story is so remarkable is that, throughout history, most drugs that target the brain have been discovered serendipitously. This is one of the few success stories in neuroscience of a basic science finding informing drug synthesis and clinical trials, and finally resulting in an FDA-approved product.

So far research into dog narcolepsy has only resulted in suvorexant, a drug for human insomnia that blocks the hypocretin receptor, and therefore helps people sleep by functionally mimics the narcolepsy seen in dogs. However, treatments for narcolepsy are being investigated, and may be on the way. For example promising drug that stimulates the hypocretin receptor was reported last year. (But keep in mind only a small percentage of promising drugs make their way through clinical trials, and when they do it still takes years.)

Conclusion

You can learn a lot about a person by meeting their best friend. As we learn more about dogs we’ll learn more about ourselves—our history, our language, and our idiosyncrasies. In addition to being loving and devoted pets and disciplined service animals, dogs can act as valuable research subjects. I think research can be ethically and thoughtfully performed on dogs, the same way it is ethically and thoughtfully performed on humans, and I hope dogs’ contribution to science, will further elevate our respect for them and treatment of them—I mean, when’s the last time a cat contributed to science? (Actually there’s an interesting story about that, but I’ll leave it for another day.)

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[1] Authors did earlier tests to calibrate the tasty food given, to ensure that wolves and dogs showed equal preference for the food, and therefore the authors were only measuring preference for risk.

 

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