Dr. Parikh is Fellow in Pediatric Neurology, Weill Cornell Medical College. Dr. Kosofsky is Professor of Pediatrics and Neurology, and Chief, Division of Pediatric Neurology, Weill Cornell Medical College and New York Presbyterian Hospital.

Dr. Parikh reports no financial relationships relevant to this field of study. Dr. Kosofsky reports he is the founder and president of ANSwers Neuroscience.

SYNOPSIS: These investigators prospectively studied auditory event-related potentials (ERPs) in junior competitive male ice hockey players and identified a pattern of ERPs that distinguishes acutely concussed from non-concussed players, establishing this noninvasive, easy-to-administer test as a biomarker to assist trainers, coaches, and clinicians with making the diagnosis of concussion.

SOURCE: Fickling SD, Smith AM, Pawlowski G, et al. Brain vital signs detect concussion-related neurophysiological impairments in ice hockey. Brain 2019;142:255-262.

Concussion from sports continues to be an ongoing growing public health concern, particularly as it relates to the cumulative effects on cognition and long-term brain health. Recently, the emphasis has focused on augmenting the clinical diagnosis of concussion based on self-report, with objective biomarkers reflective of functional brain injury. Such physiologic metrics can be followed over time and enable objective recommendations informing decisions regarding return to learn, as well as return to play. One such potential biomarker is auditory event-related potentials (ERPs). ERPs are derived from EEGs and represent the brain’s evoked neural response to auditory input as reflected by the amplitude and latency of three easily identified and well-studied waveforms, which can be collected using a portable device requiring five minutes of testing. Specifically, the N100, the P300, and the N400 waves induced by auditory stimulation are known to be reflective of auditory sensation, basic attention, and cognitive processing, respectively. In prior work, Ghosh Hajra et al established an analytic framework, normative values, and graphic depiction for the amplitude and latency of each of these waveforms, which they refer to as six unique “brain vital signs.”

In the study by Fickling et al, 47 tier III junior-A competitive male ice hockey players were recruited over two seasons, more than half of whom had one to five prior concussions. Forty-three players participated in baseline testing. Twelve players sustained concussions following baseline testing and then completed assessments within 24 hours of injury, as well as when they passed the protocol for return to play. Twenty-three players were not diagnosed with a concussion during the season and completed both baseline and post-season testing.

The ERP for each player was generated with a task that involved a five-minute auditory stimulus sequence with interlaced tones and spoken word pair primes. The auditory tones were randomized to produced specific frequency-related ERPs, and the word primes were created to be both semantically congruent or incongruent. The results were generated on radar plots that showed group mean changes across test points and on plots that compared individual brain vital signs components test points for each participant.

There was a statistically significant difference between baseline and concussion in all six brain vital signs. This included increased amplitude and increased latency in all three waveforms when analyzed acutely in concussed athletes compared with their individual baselines, which then normalized. Of note, the amplitude of the P300 wave remained increased from its baseline at the time of return to play in concussed athletes, suggesting there were measurable physiological effects still persistent even though each athlete’s symptoms had resolved.

Additionally, the authors also looked at the hockey players pre- and post-season who did not sustain a concussion to see if there were changes in their baseline (i.e., suggestive of subconcussive effects). This study showed a significant increase in the latency of the P300 wave, which is hypothesized to reflect impaired cognitive processing. This suggests that subconcussive impacts may result in cumulative effects, which, although clinically silent, may be reflective of significant changes in brain function.

COMMENTARY

The novelty of this study rests on the claim that this simple, rapid, and objective test can be used as a sensitive biomarker for concussion. In addition, Fickling et al proposed that this test also is sensitive to functional brain injury resulting from subconcussive brain injury. As the authors noted, the study was small and needs to be replicated in larger populations with the addition of relevant control groups.

Although this approach appears to help clinicians discern within-group differences between baseline and acutely concussed subjects, as well as between pre- and post-season for non-concussed subjects, the test is unable to identify such differences in individual subjects consistently. As such, more sensitive metrics will be required to enable athletes to be diagnosed definitively with functional deficits following concussive or subconcussive blows sustained during the hockey season.

When used in combination with other noninvasive biomarkers of brain function, such as eye tracking, balance, and autonomic function, there may be an opportunity to develop an integrated suite of objective tests that will assist coaches, trainers, and physicians in making decisions regarding when athletes should be removed from play following concussion, when they are ready to return to play following concussion, and when they should cease play as a result of cumulative subconcussive brain injury. Such tools are urgently needed to inform the return-to-play protocols now required for athletes participating in collision and helmet sports.

REFERENCE

1. Ghosh Hajra S, Liu CC, Song X, et al. Developing brain vital signs: Initial framework for monitoring brain function changes over time. Front Neurosci 2016;10:211.