**4. Discussion**

The electrophysiological paradigm implemented in the present study allowed us to measure several visuoperceptual and cognitive functions in a single session, resulting in a detailed examination and in original findings regarding the possible functional consequences of mTBI.

First, this study agrees with previous results by showing that, after a mTBI, earlier visual potentials are comparable to data from uninjured control participants [22]. It is, however, worth mentioning that there was a strong tendency for P2 amplitude reduction in mTBI compared to controls. This could sugges<sup>t</sup> early attentional modulation difficulties in the form of less efficient visual search following mTBI [44].

Neuropsychological testing is recognized as an important part of the evaluation and follow-up of possible sequalae caused by mTBI [45]. It is now well known that, while symptoms sometimes recover within the few days after an injury, cognitive deficits may persist for longer [46]. The results obtained in this study are in accordance with the literature demonstrating that neuropsychological measures can be sensitive after a mTBI, at least in the subacute phase. Participants tested in the first three months post-mTBI showed slower processing speed in a visual attention task. While their basic selective visual attention abilities (TEA Map search, DKEFS Trail 1) appeared intact, they were negatively affected on a condition requiring rapid visuospatial processing (DKEFS: Trails 2 and 3), as well as in a condition known to target attentional and cognitive flexibility (DKEFS: Trail 4).

The chronic mTBI participants in this study did not show significant neuropsychological deficits. This result is in accordance with the literature, which often failed to demonstrate long-term effects on clinical neuropsychological testing after a single mTBI [47]. However, studies using more sensitive

neurocognitive tasks measuring information processing speed and working memory have been able to show persisting cognitive impacts following mTBI [17,48]. Also, some studies have shown some neuropsychological deficits after two or more mTBIs [49,50].

In this study, the electrophysiological paradigm used revealed several statistically significant impacts, with large e ffect sizes, on neurocognition following a single mTBI. Previous work has found decreased amplitudes and increased latencies of the P3b component after mTBI [20,22,49,51]. Our results replicate such a pattern, where participants who sustained a mTBI showed significantly decreased amplitudes and increased latencies on the P3b component. Animal models have suggested that these impacts could be explained by the fragility of the hippocampic cells and of their related brain circuits, which are involved in updating the stimulus representation within working memory during an oddball paradigm and are thus reflected in the P3b component [52].

Neurometabolic and microstructural changes taking place after a mTBI were thus evidenced using the present ERP paradigm and can explain the decrease in e fficiency and speed of associated cognitive processes. Indeed, participants who sustained a mTBI and were tested during the subacute phase (less than three months post-trauma) did have slower response times than uninjured controls and individuals with chronic mTBI during the ERP task, as well as on the neuropsychological tests requiring deployment of visuospatial attentional and executive processes. Another indicator that these cognitive processes were impacted by mTBI and were not as e fficient as those of uninjured control participants is the fact that, while neuropsychological measures in the chronic mTBI group were comparable to those of the control group, P3b results showed persisting amplitude attenuation, even six months postinjury. This finding is in accordance with studies reporting the longer-term impact of mTBI on the P3b [21]. While the study of de Beaumont and al. [21] showed this type of result after multiple concussions, the present study demonstrates that such impairments can occur after a single mTBI.

Based on a study published by Halterman et al. [12], we assumed that orienting visuospatial attention would be a ffected in the subacute phase after mTBI. Indeed, they showed that individuals with mTBI were slower than controls in an orientation task, especially on the executive components of the task. In our ERP task, the N2pc component reflects these mechanisms, more precisely the attentional filter that allows the orientation of attention toward the target. Results obtained in this study did not show a significant impact of mTBI on the N2pc, although, as shown in Figure 3, visual inspection of the component appears to indicate an amplitude reduction in mTBI compared to controls at a more acute stage. This result is consistent with a previous study by de Beaumont et al. [49], who found no significant e ffect on that component at nine months post-trauma in athletes who sustained multiple concussions. The N2pc is a component of relatively small amplitude (often less than 3 μV) obtained from a subtraction (contralateral minus ipsilateral), and thus the di fference score has the combined variance of the contralateral and ipsilateral waves. It is possible that more participants could have allowed a significant di fference to emerge. Indeed, even a small decrease in the amplitude of the N2pc could be clinically significant without being statistically significant. The same pattern of results was obtained with the SPCN, which represents the coding of visual information in visual short-term memory. As the N2pc, the SPCN is of very small amplitude, so at this point, it is not possible to exclude the possibility that this component could be a ffected by a mTBI in larger groups of participants.

Further observation of the results allows the identification of the latency shift between the N2pc and the following positivity Ptc peak, which significantly di ffers between the control and subacute mTBI groups. The Ptc component is thought to reflect the process used to isolate the target once it is identified among distractors [29]. The shorter N2pc-Ptc peak-to-peak amplitude shift in the subacute mTBI group is another aspect that points to a disruption in the spatiotemporal dynamics of attentional processes following mTBI. This mechanism appears to be a ffected in the subacute phase but seems to recover among chronic mTBI participants. Such a fluctuation in these spatiotemporal processes could have important implications, especially when clinicians contribute to return to play decisions for athletes. Indeed, contact sports rely heavily on visual–attentional abilities and require one to be alert and respond rapidly in order to avoid re-injury. Knowing that another mTBI within a short time frame

could ultimately result in a second impact syndrome, causing massive brain swelling and sometimes death [53], returning an athlete to play before the recovery of such neurophysiological alterations could have major impacts on the health of the player.

While these mechanisms appear to recover within a few months after mTBI, the results of the P3b di ffer in the way that the amplitude decrease and latency increase shown for this component, as well as postconcussion symptoms, remain significantly present in the chronic stage of mTBI. The results obtained for the P3a also show a long-term impact on the orientation of attention. Indeed, it appears that the mTBI participants (both subacute and chronic) had di fficulties in disengaging their attention (as reflected in a much larger and sustained amplitude) once it had been directed toward the target. Such a result was also obtained for the subacute mTBI group on the neuropsychological task tapping into this process (D-KEFS: trail 4). Indeed, it measures cognitive flexibility, a process that allows one to disengage attention to be able to switch between di fferent stimuli. While this task was a ffected in mTBI in the subacute phase, P3a results show that this disengaging process was still impaired after more than six months postinjury. These original results, which are along the same line as others obtained with di fferent methodologies [13,14,17], underscore the importance of carefully monitoring, with appropriate tools, individuals with mTBI who need to go back to activities that require maintaining high attentional levels or multitasking (e.g., operation of heavy machinery, contact sports, driving).

The main limitation of this study is the small number of participants in each group and the cross-sectional design. Indeed, we were confronted with di fferent recruitment and participation retention issues because of the nature of this clinical population. Also, some of the participants had to be removed from the analyses because they showed too many artefacts on their EEG. Performance accuracy rates were, however, very high in all groups. Among the participants included in the analyses, we noticed a relatively high degree of inter- and intra-individual variability. Nonetheless, e ffect sizes for significant results were large.

Future studies with a greater number of subjects will help to determine the optimal conditions for clinical use of this paradigm. This is especially relevant as this new task allowed us to track the deployment of visuospatial attention as reflected in several ERP components, ultimately providing a rich possible set of biomarkers for mTBI. For example, in some individuals with mTBI, we were able to observe a clear decrease of the N2pc, with a normal P3b and SPCN. For other participants, the P3b was decreased, while the N2pc and the SPCN were normal. These specific patterns were lost in the averaging process required for ERP analyses. It appears that the clinical interest of this ERP task lies in the gathering of normative data that could bring to light these di fferent individual clinical neurocognitive patterns of visual–attentional processing after a mTBI.
