By: Stephanie A. Waryasz, Au.D., CCC-A, F-AAA
Sport-related concussion is a type of injury that tends to produce subtle anatomical abnormalities on the microscopic level within the brain (Gaetz & Weinberg, 2000; Gaetz, Goodman, & Weinberg, 2000; Barth, Freeman, Broshek, & Verney, 2001). These types of injuries may be asymptomatic and remain unidentified through standard clinical neuropsychological testing, consequently putting the athlete at further risk if he were to return to play (Gosselin, Thériault, Leclerc, Montplaisir, & Lassonde, 2006; Thériault, Beaumont, Gosselin, Filipinni, & Lassonde, 2009). Prior research has shown that the P300 may be sensitive to such subtle damage from sport-related concussions and has potential clinical utility for future post-concussion evaluations (Pratap-Chand, Sinniah, & Salem, 1988; Gaetz & Weinberg, 2000; Gaetz, et al., 2000; Gosselin et al., 2006; De Beaumont, Brisson, Lassonde, & Jolicoeur, 2007; Thériault et al., 2009).
The P300 or “P3” evoked response was first reported by Squires, Squires, and Hillyard in 1975 based on work by Sutton, Braren, Tueting, Zubin, and John from the late 1960s (Sutton et al., 1965; Sutton et al., 1967; Squires et al., 1975). Although the P300 has earned its name by Squires et al. (1975) from its appearance at a latency of 300 milliseconds and being the third major positive-voltage component in the late auditory evoked response series, subsequent research by Hall III (1992) has demonstrated that the P300 could normally occur anywhere between 250-400 milliseconds post-stimulus onset. With the use of auditory stimuli, research by Knight et al. (1989) supports that the tempro-parietal junction contributes to the auditory P300 response; however, multiple generator sites are likely. Generator sites may vary based on the stimuli and task (Hall III, 1992).
P300 is typically considered to be an endogenous response as it is highly dependent on the stimulus context and subject state (Hall III, 1992). However, recent research has shown that an intensity effect exists in regards to amplitude and latency of the P300 response (Roth et al. 1982; Backs, 1987; Polich et al., 1996; Musiek et al. 2005). Given the fact that external acoustic stimulus characteristics impact these waveforms, an exogenous component to the P300 is also likely (McCullagh et al., 2009). The P300 response is typically elicited using a rare or infrequent “target” or “oddball” stimuli among a set of predictable, frequent “non-target” stimuli (Squires et al., 1975; Hall III, 1992). The P300 complex consists of a negative-voltage N2b component and the notable positive-voltage P3a/P3b. The amplitude of the P3a /P3b can be affected by attention or inattention to a given stimulus. Specifically, P3a has a smaller amplitude occurring subconsciously when a change in the stimulus is passively noticed. Conversely, P3b yields a larger amplitude due to the conscious recognition of stimulus deviation and identification of that stimulus as the “target” (Hall III, 1992). P300 latency increases and amplitude decreases as the differences between the rare and frequent stimuli become less obvious and as the rare stimuli become more frequently occurring (Hall III, 1992). P300 latency is also directly related to the time it takes for cognitive processing of the signal; therefore, shorter P300 latencies are associated with superior cognitive performance (Hall III, 1992). Consequently, the P300 is widely accepted as a useful measure of cognitive function, with the caveat that there is an exogenous component to this evoked potential.
At the 2nd International Conference on Concussion in Sports in 2004, McCrory et al. (2005) defined sport-related concussion as a “complex pathophysiologic process affecting the brain that can be caused by a direct blow to the head, face, neck, or elsewhere on the body with an ‘impulsive’ force transmitted to the head.” Common symptoms of concussion include headache, dizziness, nausea, loss of balance, and/or poor concentration (McCrory et al., 2005). Concussion accounts for approximately 5% of all injuries across a variety of sports (Daneshvar, Nowinski, McKee, & Cantu, 2011) and approximately 1.6 to 3.8 million are affected by sport-related concussion annually in the United States (Giza et al., 2013). There are several physical factors that influence the severity of a concussion that have been well defined through research by Barth et al. (2001).
Firstly, the trauma of concussion results from the rapid change in velocity of the head over time, which is known as acceleration or deceleration. One of the damaging factors of concussions is the gravitational force or “g-force” associated with these sports injuries. So the faster a person is moving and the smaller the distance they have before they come to a stop will yield a greater g-force due to a shorter time and distance for acceleration/deceleration to occur. This could consequently yield a more harmful concussion that typically produces microscopic diffuse damage to the brain (Barth et al., 2001).
An additional factor when considering damaging effects of concussions is the type of impact. For example, head-on, helmet-to-helmet type hits would yield a quick deceleration over a short distance and period of time, which would cause a greater g-force that could cause more damage. Conversely, a head-on collision where one athlete’s helmet hits a defender’s chest or waist would yield a longer deceleration over a longer distance and time, which would cause a smaller g-force. This is generally a safer type of hit with less damaging consequences (Barth et al., 2001).
It is important to understand that the brain does not always move as a whole unit during these impacts. For example, if an athlete were to get hit in his head while he is turning, one hemisphere could decelerate anteriorly, while the contralateral hemisphere decelerates posteriorly creating a torsional effect, which stretches and displaces many neural fibers throughout the cerebrum and the brainstem. This same torque is also seen in whiplash type forces during which the head is being rotated out of its original plane. An example of this would be when an athlete is “clotheslined,” or his forward progress is stopped so rapidly, that he is thrown backwards. In this scenario, the head would decelerate rapidly in the initial direction of movement, then accelerate quickly in the opposite direction and down towards the ground as the athlete falls. This would cause the brain to rebound from its initial direction of deceleration within the skull and strike the opposite wall of the cranium creating a “contrecoup injury,” which could yield damaging effects. It is because of such physical factors that no two concussions are the same when assessing damage.
Assessing the Effects of Sport-Related Concussion with P300
Concussions, especially multiple concussions, can create persisting damage that is often not identified through self-reported post-concussion symptoms or through clinical neuropsychological test scores (Pratap-Chand et al., 1988; Gaetz & Weinberg, 2000; Gaetz, et al., 2000; Gosselin et al., 2006; De Beaumont et al., 2007; Thériault et al., 2009). Therefore, it is critical to assess such athletes with a measurement that is sensitive to such damage to accurately monitor their neuro-cognitive status. As a measurement of cognitive function, P300 has proved to be a valuable tool in prior research for assessing subtle cortical abnormalities in symptomatic and asymptomatic athletes that have sustained concussions, which can be evidenced through the subsequent literature review.
Gaetz and Weinberg (2000) conducted a comprehensive electrophysiological study of athletes who had sustained concussions one to 53 months post-injury with post-concussion symptoms compared to control subjects who had not sustained any head injuries and did not report post-concussion symptoms for at least two years since testing. The P3 latency indicated the largest difference between the post-concussion symptom group and the control group for this study. Latency abnormalities were consistent between different age groups, while amplitude ratios were inconsistent. This suggests that latency may be a more reliable indicator of abnormalities or changes within the brain since amplitude can vary between subjects due to factors other than brain injury (Gaetz & Weinberg, 2000).
A subsequent study by Gaetz et al. (2000) assessed post-concussion syndrome self-reports and P300 evoked potentials in multi-concussed athletes to single-concussed and non-concussed athletes. All single- and multi-concussed athletes were at least six months post-injury at the time of testing. Results demonstrated significant differences in self-reported post-concussion syndrome symptoms, in addition to P3 latency compared to controls. These results support the validity and clinical utility of P300 evoked responses as an assessment tool of cumulative damage associated with multiple concussions (Gaetz et al., 2000).
Gosselin et al. (2006) examined P300 differences between symptomatic and asymptomatic athletes who had sustained concussions with control athletes. Amplitude reduction and increased latency of the P3 component was found between the symptomatic and asymptomatic groups when compared to the control group. The similar P3 abnormalities evident in the symptomatic and asymptomatic groups suggest the presence of subtle cognitive deficits at the neuronal level despite self-reported symptoms, which could “challenge the validity of return-to-play guidelines for which the absence of symptoms is a major issue” (Gosselin et al., 2006). Ultimately, this research supports the call for a more sensitive test battery to accurately assess cognitive function and readiness to continue athletic involvement post-concussion.
Research by De Beaumont et al. (2007) compared P3 amplitudes in multi-concussed athletes to single-concussed and non-concussed athletes, which showed significant decreases in P3 amplitude with an intact N2b component for the multi-concussed group compared to others although post-concussion symptom self-reports and neuropsychological test scores were equivalent across groups. These findings suggest that P300 may be more sensitive to subtle, persistent damage of concussions than traditional neuropsychological evaluations, as all of the concussed athletes were at least nine months post-injury. Furthermore, since attenuation was only noticed in the P3 component and N2b amplitude was unaffected, Brisson et al. (2007) believe that future research may allow one to pinpoint the specific cognitive system impacted by multiple concussions.
An experiment by Thériault et al. (2009) examined P300 evoked responses in multiple concussed athletes with a negative history for post-concussion symptoms compared to controls. Results demonstrated significantly decreased P3a and P3b amplitudes in athletes that have sustained concussions five to twelve months prior to testing compared to control subjects. However, P3a and P3b amplitudes of asymptomatic athletes who sustained their concussions more than two years prior to testing compared to controls were equivalent. Such results suggest that although no functional deficits are present in daily living for these athletes, subtle processing abnormalities are present at the neuronal level that suggests sub-optimal cognitive compensation that could yield increased vulnerability to subsequent concussions (Thériault et al., 2009).
Research by Gaetz and Weinberg (2000), Gaetz et al. (2000), Gosselin et al., (2006), De Beaumont et al. (2007), and Thériault et al. (2009) support the call for a more sensitive assessment measure for sport-related concussion even after post-concussion symptoms have subsided. Based on their research, latency and amplitude abnormalities are present for the P3 evoked response at various post-injury intervals, including months and even years after the onset of the most recent concussion. This research also demonstrates the accumulative nature of concussions yielding greater neuronal damage and, in some cases, greater functional deficits. As similar findings have been replicated between research studies, one can make an argument for the validity and clinical utility of P300 in cognitive assessment post-concussion. This seems to be a promising measure for identifying subtle persistent anatomical damage from these injuries, which may prove to be a useful clinical measurement of post-concussion status in the future.
Stephanie Waryasz is a clinical audiologist at Boston Medical Center, where she is afforded the opportunity of working with an extremely diverse patient population in a large teaching hospital setting. Her clinical interests include diagnostic testing for all ages, electrophysiological testing, vestibular evaluation, auditory processing disorders, and hearing aids. She is a recent graduate of the University of Connecticut Doctor of Audiology (AuD) program. Her current research interests include traumatic brain injury (TBI) and sport-related concussion effects on the auditory and vestibular systems. Stephanie also enjoys volunteering annually for the Healthy Hearing screenings at the Connecticut Special Olympics, held at her undergraduate alma mater, Southern Connecticut State University.
- Backs, R. (1987). Stimulus intensity and task complexity effects on late components of the event-related potential. In: Johnson, R., Jr., Rohrbaugh, J., Parasuraman, R., eds. Current Trends in Event-Related Potential Research. New York: Elsevier Science Publishers, Biomedical Division, 163-169.
- Barth, J. T., Freeman, J. R., Broshek, D. K., & Varney, R. N. (2001). Acceleration-deceleration sport-related concussion: The gravity of it all. Journal of Athletic Training, 36(3), 253–256.
- Daneshvar, D. H., Nowinski, C. J., McKee, A., & Cantu, R. C. (2011). The epidemiology of sport-related concussion. Clinical Sports Medicine, 30(1), 1–17. doi:10.1016/j.biotechadv.2011.08.021.Secreted
- De Beaumont, L., Brisson, B., Lassonde, M., & Jolicoeur, P. (2007). Long-term electrophysiological changes in athletes with a history of multiple concussions. Brain Injury, 21(6), 631–644. doi:10.1080/02699050701426931
- Gaetz, M., Goodman, D., & Weinberg, H. (2000). Electrophysiological evidence for the cumulative effects of concussion. Brain Injury, 14(12), 1077–1088. doi:10.1080/02699050050203577
- Gaetz, M., & Weinberg, H. (2000). Electrophysiological indices of persistent post-concussion symptoms. Brain Injury, 14(9), 815–832. doi:10.1080/026990500421921
- Giza, C. C., Kutcher, J. S., Ashwal, S., Barth, J., Getchius, T. S., Gioia, G. A., … Zafonte, R. (2013). Summary of evidence-based guideline update: Evaluation and management of concussion in sports. American Academy of Neurology, 80, 2250–2257.
- Gosselin, N., Thériault, M., Leclerc, S., Montplaisir, J., & Lassonde, M. (2006). Neurophysiological anomalies in symptomatic and asymptomatic concussed athletes. Neurosurgery, 58(6), 1151–1160. doi:10.1227/01.NEU.0000215953.44097.FA
- Hall III, J. W. (1992). Handbook of Auditory Evoked Responses (1st ed.). Needham Heights: Allyn & Bacon.
- Knight, R. T., Scabini, D., Woods, D. L., & Clayworth, C. C. (1989). Contributions of temporal-parietal junction to the human auditory P3. Brain Research, 502, 109-116.
- McCrory, P., K, J., Meeuwisse, W., Aubry, M., Cantu, R., Dvorak, J., … Schamasch, P. (2005). Summary and agreement statement of the 2nd International Conference on Concussion in Sport, Prague 2004. Br J Sports Med, 39, 196–204. doi:10.1136/bjsm.2005.018614
- McCullagh, J., Weihing, J., & Musiek, F. (2009). Comparisons of P300 from standard oddball and omitted paradigms: Implications to exogenous/endogenous contributions. Journal of the American Academy of Audiology, 20, 187-195. doi:10.3766/jaaa.20.3.5
- Musiek, F., Froke, R., Weihing, J. (2005). The auditory P300 at or near threshold. Journal of the American Academy of Audiology, 16, 699-708.
- Pratap-Chand, R., Sinniah, M., & Salem, F. A. (1988). Cognitive evoked potential (P300): A metric for cerebral concussion. Acta Neurol Scand, 78, 185–189. doi:10.4319/lo.2013.58.2.0489
- Polich, J., Ellerson, P., & Cohen, J. (1996). P300 stimulus intensity, modality, and probability. International Journal of Psychophysiology, 23, 55-62.
- Roth, W., Blowers, T., Doyle, C., & Koppell, B. (1982). Auditory stimulus intensity effects on components of the late positive complex. EEG Clinical Neurophysiology, 54, 132-146
- Squires, N. K., Squires, K. C., & Hillyard, S. A. (1975). Two varieties of long-latency positive waves evoked by unpredictable auditory stimuli in man. Electroencephalography and Clinical Neurophysiology, 38, 387–401.
- Sutton, S., Braren, M., Zubin, J., & John, E. R. (1965). Evoked-potential correlates of stimulus uncertainty. Science, 150, 1187–1188.
- Sutton, S., Tueting, P., Zubin, J., & John, E. R. (1967). Information delivery and the sensory evoked potential. Science, 155, 1437–1439.
- Thériault, M., De Beaumont, L., Gosselin, N., Filipinni, M., & Lassonde, M. (2009). Electrophysiological abnormalities in well functioning multiple concussed athletes. Brain Injury : [BI], 23(11), 899–906. doi:10.1080/02699050903283189