More than two million Americans have served in the Iraq and Afghanistan wars. Of those that return, thousands carry invisible trauma that impact their daily lives. The effects of mild traumatic brain injury (mTBI) from explosive blasts are especially commonplace for these veterans, afflicting hundreds of thousands of service members.

New research explores how the number of explosions experienced by a veteran relates to lasting changes in the activity of specific brain cells in the cerebellum, an area traditionally associated with motor coordination. It is possible these changes contribute to some of the mood changes and cognitive complaints, such as memory loss, that service members report even years after exposure to combat.

In the new study a team based at the VA Puget Sound Health Care System and University of Washington—including clinical psychiatrist Elaine Peskind and molecular biologist David Cook of U.W. and VA Puget Sound molecular neurophysiologist James Meabon—worked with 33 participants who had been exposed to explosive blasts. The research team used functional imaging to observe brain activity and found that the more blast injuries former soldiers had sustained, the less activity occurred in their cerebellums. To look closer at the changes, the team assessed the cerebellums of mice that were also exposed to a blast and observed some breakdown in the blood–brain barrier as well as a loss of neurons called Purkinje cells, associated with the cerebellum. Further, structural imaging of some of the veterans found that blast injury had changed their brains’ pathways, although precisely what those findings mean remains harder to interpret.

The study appeared yesterday in Science Translational Medicine and study authors Peskind, Cook and Meabon spoke with Scientific American about the research.

[An edited transcript of the interview follows.]

In this study, you looked at traumatic brain injury (TBI) induced by an explosive blast. Can you describe what distinguishes a blast-induced injury like the ones these combat veterans sustain from more commonplace causes of concussion?

Cook: Blast-induced TBI is in many ways is more complex than, say, what happens if you get in an automobile accident and bang your head. When explosives detonate, they send out this incredibly intense shock wave that moves at supersonic speeds and is essentially a shell of highly pressurized air—that’s the so-called primary blast overpressure. That’s different from the secondary effects like the shrapnel and getting hit by flying objects and tertiary events that involve the person himself being hurled against the side of a vehicle or the ground, for example. The blast exposure can be very intense but doesn’t necessarily knock you over. But if the primary blast overpressure is intense enough, it is capable all by itself of killing you.

TBI is considered the signature injury of the wars in Iraq and Afghanistan. It’s estimated that of the 2.6 million service members deployed to Iraq and Afghanistan, 10 to 20 percent return with post-concussive symptoms. Why is that the case?

Cook: The soldiers in Iraq and Afghanistan are having a very unique experience both because they have very good body armor now and because of the way in which insurgents use a lot of explosives. The soldiers are exposed to a lot of explosions, so they get hit over and over again, but they’re protected from all but the worst cases of secondary and tertiary effects. Whereas had it been the Vietnam War, for example, they [the soldiers] would have been much more grievously injured and would have been evacuated.

Peskind: Probably the only war that is comparable to the wars in Iraq and Afghanistan is World War I, the trench and artillery warfare. The term “shell shock” came from that war and that really refers to the effects of these post-concussive symptoms.

In the group of veteran participants in this study, the average number of blast exposures that were severe enough to cause acute symptoms consistent with the diagnosis of mild traumatic brain injury was 20. It was more common to have been exposed to between 50 to 100 blasts than to have a single one.

Are there long-term consequences to these injuries?

Peskind: We’ve heard a lot about the effects of repetitive-impact mild TBI in professional athletes like boxers and football, soccer and hockey players. And we became very concerned that our young service members and veterans might similarly be at risk for chronic traumatic encephalopathy, a midlife neurodegenerative disorder, and also Alzheimer’s because head trauma is really the only environmental risk factor for Alzheimer’s.

Cook: TBI and Alzheimer’s disease share some common genetic similarities. If you’re familiar with the APOE [Apolipoprotein E] gene that’s associated with Alzheimer’s, you know that if you inherit the associated E4 allele gene, your risk for getting Alzheimer’s as you get old is significantly increased. Similarly if you have TBI and you harbor one of these E4 alleles, your likelihood of having a poor outcome is significantly increased.

Your findings in each part of this study pinpointed the cerebellum as especially vulnerable to damage. What does that finding tell us?

Peskind: The cerebellum has classically been thought of as an integrative center for sensory input and motor output. But now it’s thought to have a much broader set of functions. Damage to the cerebellum and cerebellar dysfunction may play a role in the behavioral and cognitive problems these veterans have with respect to mood, irritability, impulsivity and also cognitive complaints, which include the ability to multitask and problems with memory.

Meabon: The cerebellum is starting to be understood as a multisystem integrator. So what it does is it takes all parts of the brain and it gets them talking to one another at the right time. [Our study suggests that blasts can] throw those different systems out of whack, so that they can’t coordinate to perform efficiently.

Cook: Bear in mind that what we’re not saying is that the cerebellum is the only place or the major place. We know—from our work and excellent research from other groups—that this is not the only brain region involved and sensitive to repetitive blast exposure.

Within the cerebellum of blast-injured mice, you found a loss of a specialized neuron called a Purkinje cells. What’s their role?

Cook: One of the things that’s interesting about the Purkinje cells of any species is that [these cells] are the primary output of the cerebellum [for the integration of sensorimotor function, affect and cognition]. Any time you talk about messing with them, you’re talking about messing with connectivity between brain regions. That’s why we started looking at these pathways in and out of the cerebellum [with structural imaging].

How do you see your findings informing future research and efforts to help veterans with TBI?

Peskind: We feel that this study is a piece of a larger puzzle. There’s much more work to be done but we’re not waiting for that work to be done to try to find treatments to improve symptoms now and prevent neurodegeneration. So we’re doing a number of other studies to treat post-traumatic stress disorders linked to TBI and blast concussion, and to treat comorbid symptoms [that is, ones occurring simultaneously, but independently] like alcohol abuse and dependence as well as prophylaxis for post-concussive migraine. In the longer term we have two studies going on to prevent neurodegeneration.

Meabon: [Our findings] give you a sense of the magnitude of the issue. These guys are going out there and coming back home and they’re carrying with them this huge cumulative burden that continues to affect their daily lives. That’s really the question that the study wants to ultimately spawn other studies to start looking at.