UNM professor reveals critical discovery in traumatic brain injury research

With about 214,110 traumatic brain injuries (TBIs) and over 69,000 TBI-related deaths in2021 according to the Centers for Disease Control and Prevention (CDC), understanding the physical and mental consequences of TBI is critical for study.

That's what UNM Department of Psychology Assistant Professor Jeremy Hogeveen is analyzing in a new Stage 2 Registered Report published in Brain Communications. The study- reported in a manuscript titled Neural response to monetary incentives in acquired adolescent depression after mild traumatic brain injury-is structured differently than a regular study. As a Registered Report, Hogeveen and his team had already received acceptance on the topic and study design for this project no matter the outcome.

"Registered reports like this are a nice option where the whole peer review team and the editor know it is an important question and a rigorous study design ahead of time. No matter what happens with it, by accepting the initial Stage 1 Registered Report they agree it will be worth publishing the results in Stage 2 whether or not there is a big effect. That's what we did here. In this study, the specific question that we were going after is related to traumatic brain injury, and consequences related to psychiatric symptoms, in particular, depression," Hogeveen said.

The results his team found are quite imperative to how minor TBIs are approached in youth.

"With TBI, you can sometimes have changes in depression or mood- which can often linger well after the brain injury event. One thing that we've noticed in that field is most of the time when there's a finding relating some brain injury to some psychiatric symptom, it's depression. This is well-documented in adults after a TBI, but there is less data available on whether or not depression occurs after a TBI in childhood or adolescence," Hogeveen said.

As a cognitive neuroscientist and father, Hogeveen understands the concern parents have for the possibility of irreversible damage to the brain as kids turn into teens and teens turn into adults.

"Generally speaking, the reporting of these findings in the field is scary. There are NFL players who played football for much of their lifespan and then had their brains donated to science because their families knew something was not quite right after their injuries. There is plenty to see in these samples for potential post-injury depression, and a high number of these cases find evidence for CTE (chronic traumatic encephalopathy) post-mortem." - Assistant Professor Jeremy Hogeveen

In this new Report, Hogeveen and colleagues took advantage of an ongoing NIH-funded study called the Adolescent Brain Cognitive Development (ABCD) study. This large-scale study began between 2016 and 2018, enrolling over 10,000 children aged 9-10 for initial brain scans and neuropsychological assessments. These participants will continue to undergo follow-up assessments and brain scans every two years until they are 18-19 years old, with data collection concluding in 2027.

The nature of the ABCD study allows researchers like Hogeveen to track participants over time. They identified individuals who had not experienced a traumatic brain injury (TBI) at their initial assessment but suffered a TBI between subsequent study visits. By comparing depression scores before and after the injury, researchers could determine if the TBI led to increased depression. Additionally, the large participant pool ensures the ability to find a well-matched comparison group of individuals who did not experience a TBI, strengthening the study's conclusions about the impact

of brain injuries on depression.

"In most of the highly-reported TBI findings in the field, the study samples may be enriched to include a higher percentage of people that had significant consequences of their injuries. In other words, individuals who are experiencing post-concussion symptoms-or their families-might be more likely to sign up for a TBI study than individuals who hit their head and went about their life and didn't notice it again, so there might be a sampling difference between the two," Hogeveen said.

In contrast, in this pre-registered prospective analysis, Hogeveen and colleagues identified 43 ABCDstudy participants that had no brain injury history at baseline, but experienced a mild TBI (mTBI; typically involving a loss of consciousness lasting <30 minutes) 3-24 months prior to their follow-up ABCDstudy visit. They then identified a group of 43 "control" participants that were demographically-matched to the mTBI group, and had levels of cognitive functioning and depression that were identical to mTBI group at baseline. The key question was whether the mTBI group or control group demonstrated differences in the brain and behavioral data collected by the ABCDstudy team-with a special focus on depression-between the baseline and follow-up visits. To be clear, their hypothesis was that depression scores would increase between visits in mTBI but not control.

Surprisingly, neither the mTBI nor the control group demonstrated any changes in depression between the baseline and follow-up study visits. The study therefore found a clear lackof evidence for post-injury depression in adolescents after a mildTBI event. The groups also did not differ in terms of general cognitive functioning on a set of tasks that probed things like attention, memory, and cognitive flexibility. However, cognitive functioning scores were slightly lower in individuals that had experienced a more recent brain injury.

At this stage, Hogeveen is careful to point out that this study does not say anything about the potential consequences of more severe TBI in youth, or mild TBI in adults-either of which may be more likely to cause depression than what the team found in the current study.

"In TBI studies of adults or folks in old age, it's possible there would be more of a predisposition to having a bad outcome from TBI because your brain's a little bit less plastic as you age. This may make the brain less resilient than an adolescent brain or a child's brain. Based on what we're seeing, it suggests that if there's a single TBI event in early adolescence, it has a lot of resources and neuroplasticity to recover and not have any lingering depression symptoms after," he said.

Remarkably, these scans and reporting helped Hogeveen figure out that depression levels stayed the same; that's what makes the Stage 2 Registered Report format so perfect for this type of study. In any other clinical trial, a null effect could result in a lack of publication, or be considered a failure.

"This is one of the biggest null effects I've observed in my career as a researcher, when it comes to cognitive or depression differences across groups. A lot of parents are equating major findings in the TBI field with actions like notregistering their kid for any sort of sport," he said. "I don't think we necessarily need to go that far, but I thought this could help reduce some anxiety about this among the parent community. This is not to say 'don't wear a helmet' or 'don't be worried about brain injury' though."

This reveals, however, that a mild TBI in youth does not in fact generate or exasperate depression.

"We did find some evidence of subtle functional MRI changes in the brains of these kids, but it was pretty clearly notrelated to depression. That's the exciting and encouraging part of it, because it suggests that when we bring in adolescents without a brain injury history, and then we look at their scores pre to post injury, we shouldn't expect any changes in depression," Hogeveen said.

That's a huge deal, with prior researchindicating there to be a connection. Hogeveen says that's further proof there's more work to be done here.

"That's the major public health finding: yes, wear a helmet. Yes, avoid getting your brain injured. but having a single, mild TBI doesn't necessarily have the same changes in mood and depression that we might have thought it could," he said.