Mismatch negativity as a marker for evaluating overall neurocognitive impairment following postconcussion syndrome

Abstract

BACKGROUND

Mismatch negativity (MMN) is used to assess psychiatric and neurological disorders. Currently, methods for evaluating neurocognitive dysfunction following traumatic brain injury, particularly postconcussion syndrome (PCS), are limited.

AIM

To investigate the correlation between MMN and social function, personality changes, and daily living abilities in patients with PCS.

METHODS

Overall, 63 patients with PCS and 56 age- and sex-matched healthy controls were included. Intelligence quotient (IQ) was measured using the Chinese Revised Wechsler Adult Intelligence Scale. Social and daily living functions were assessed using the Social Disability Screening Schedule, functional activities questionnaire, and Activity of Daily Living Scale. Personality changes were evaluated using the post-traumatic brain injury personality change scale. MMN data were collected using the classical auditory oddball paradigm.

RESULTS

There were no significant differences in age and sex between the groups. Social dysfunction was significantly higher in the PCS than in the control group (P < 0.001). Daily living ability impairment scores were higher, and IQ levels were lower in patients in the PCS compared with control group; patients in the PCS group did not reach mild intellectual impairment. In the PCS group, negative amplitudes at Fz (r = 0.255, P_FDR = 0.048), F1 (r = 0.465, P_FDR = 0.003), and F2 (r = 0.281, P_FDR = 0.028) were significantly correlated with the degree of social dysfunction and personality change after controlling for age, IQ, and education level using partial correlation analysis.

CONCLUSION

MMN amplitude was significantly reduced in PCS; lower amplitudes were associated with more severe social function impairments and personality changes. MMN amplitude reduction may reflect neurocognitive dysfunction in PCS and could serve as a potential electrophysiological marker.

Key Words: Postconcussion syndrome; Mismatch negativity; Event-related potentials; Cognitive impairment; Traumatic brain injury

Core Tip: Postconcussion syndrome (PCS) can result in long-term cognitive impairment, impacting daily function and social interactions. Despite its prevalence, effective evaluation methods for PCS-related neurocognitive dysfunction remain limited. Patients with PCS experience social dysfunction and personality changes. Mismatch negativity amplitude in the prefrontal region correlates with social dysfunction and personality changes, with smaller amplitudes indicating more severe social dysfunction and personality changes. Mismatch negativity may therefore serve as a potential indicator for assessing the symptoms of PCS.

INTRODUCTION

Traumatic brain injury (TBI) has become a significant public health concern and is one of the leading causes of disability and death from trauma[1]. Over 50 million people worldwide experience TBI annually, with approximately 75% classified as mild TBI (mTBI)[2], commonly known as a concussion. A concussion involves a mild head injury, which causes a brief loss of consciousness. mTBI can also lead to various symptoms, notably headache, depression, anxiety, and irritability, collectively termed postconcussion syndrome (PCS)[3]. Research has shown that approximately 15% of patients with cerebral concussion will experience persistent PCS, which affects their daily functions[4,5]. Chinese forensic psychiatrists believe that sleep problems and anxiety in patients with PCS are mostly subjective descriptions and lack objective evidence. They conclude that these patients should not receive disability compensation as they do not have obvious brain parenchymal injuries, such as brain contusion and intracerebral hematoma. However, some scholars believe that although the intelligence of patients with PCS is mostly within the normal range, their neurocognition is still impaired. Among the various symptoms of PCS, cognitive impairment is a primary factor contributing to long-term social dysfunction, particularly affecting executive function, attention, and processing speed. However, in clinical practice, patients with PCS often focus on easily noticeable symptoms, such as sleep problems and anxiety, while overlooking cognitive impairment issues, leading to a decline in functional abilities[6].

The etiology of neurocognitive dysfunction in PCS remains unclear. Research has shown that PCS may result in physiological changes in the brain, such as modifications in white matter composition, marked by variations in neurotransmitter function and adjustments in brain excitability[7,8]. However, effective approaches for evaluating neurocognitive dysfunction after PCS are limited. In patients with severe brain injury, conventional computed tomography and magnetic resonance imaging can be used to identify structural damage in the brain. In animal experiments, approximately 67% of rats with mTBI do not display significant alterations in brain structure upon examination[9]; however, some demonstrate abnormal behavior and cognitive dysfunction.

Event-related potentials (ERPs) are a specialized form of brain-evoked potentials that showcase the neurophysiological changes in the brain during cognitive processes[10], serving as indicators of cognitive functions, including memory and attention[11-14]. Mismatch negativity (MMN) represents one component of ERPs, computed as the difference wave between the ERPs elicited by frequent standard and rare deviant sounds[15]. MMN is characterized by a negative wave emerging approximately 100-250 milliseconds poststimulus, reflecting the unconscious processing of brain responses to varied stimuli[15]. The presence of MMN signifies the brain’s ability to automatically generate different responses to stimuli under nonattention conditions and automatically process information[16]. MMN reflects the sensory memory mechanism of auditory information, where the repeated presentation of standard stimuli creates memory traces in specific brain areas. After each presentation of auditory information, the brain automatically compares it with the formed memory traces. If the auditory input corresponds to the memory trace (i.e., standard stimulus), no MMN is generated; if the auditory input diverges from the memory trace (i.e., deviant stimulus), MMN is generated[17]. Its primary advantage is its independence from an individual’s subjective consciousness. It offers excellent applicability, even for patients with limited cooperation, and extends to comatose patients, making it extensively utilized in clinical settings[18,19]. MMN plays a specific role in aiding the diagnosis of mental disorders. Research has shown that MMN demonstrates prolonged latency and decreased amplitude in psychiatric conditions, such as depression, bipolar disorder, schizophrenia, and personality disorders[20-22].

Additionally, studies have indicated that a decrease in MMN amplitude is more pronounced in patients with schizophrenia than in those with bipolar disorder[23]. Abnormalities in MMN have been reported in patients with organic mental disorders, noticeable anomalies in MMN in patients with frontotemporal dementia, and a decrease in the MMN curve area as the stimulus interval increases in patients with Alzheimer’s disease[24]. MMN has significant value in TBI research as it can predict the arousal state of patients in a coma[25]. Research conducted by Sun et al[26] has shown that MMN reflects the recovery of social function in patients with TBI. However, to the best of our knowledge, there is currently no relevant research on social function, MMN, and recovery status in patients with PCS.

The assessment of TBI emphasizes the crucial need to evaluate daily functioning and social interactions. As patients with PCS typically have less severe injuries, the likelihood of significant impairment in daily activities is reduced, making the evaluation of social interaction important. The Chinese “Classification of the Degree of Disability Caused by Bodily Injury” includes relevant provisions. In addition to the scales for evaluating daily functioning, scales are available to assess social interaction deficits, including the Social Disability Screening Schedule (SDSS) and the functional activities questionnaire (FAQ)[27].

In this study, we aimed to investigate the difference in MMN between patients with PCS and healthy individuals, and to seek the correlation between MMN and the levels of social function and daily living ability in patients with PCS to confirm whether MMN can be a potential marker to predict the symptoms of PCS.

MATERIALS AND METHODS

Overall, 63 patients with persistent PCS after mTBI, diagnosed according to the International Classification of Diseases Tenth Revision criteria by two experienced neurologists, were enrolled between July 14, 2021 and March 21, 2022 at the Affiliated Mental Health Center, Zhejiang University School of Medicine (Figure 1). The inclusion criteria were: (1) An age between 18 and 65 years; (2) A diagnosis of PCS according to the International Classification of Diseases Tenth Revision F07.2 criteria; (3) TBI for ≥ 6 months; (4) No abnormal manifestations, such as softening lesions; (5) Found on brain imaging examination; and (6) Right-handedness. The exclusion criteria were: (1) The use of psychiatric and antiepileptic drugs in the past 3 months; (2) A diagnosis of mental or neurological disorders before trauma, alcohol or substance dependence or the use of psychotropic drugs; (3) Hearing impairment, and hearing impairment before and after brain injury; and (4) No history of TBI or organic brain disease prior to the current trauma.

Figure 1 Cohort diagram of enrolled patients. TBI: Traumatic brain injury.

The control group comprised 56 healthy volunteers of appropriate age and sex. All control participants met the following inclusion criteria: (1) Aged between 18 and 65 years; (2) Right-handed; (3) No observed mental or neurological disorders; (4) No family history of mental disorders; (5) No history of brain trauma; (6) No use of psychotropic or antiepileptic drugs; (7) No hearing impairment; and (8) No history of TBI or organic brain disease prior to the current trauma.

The study was approved by the Ethics Committee of Hangzhou Seventh People’s Hospital, No. 2021-047. All experimental procedures complied with the provisions of the Declaration of Helsinki and the relevant national and international requirements for human research. All participants were informed of the study process and possible adverse effects, and provided written informed consent before inclusion.

Demographic information and scales assessment

Self-reported research forms were used to collect demographic information about the participants, including sex, age, education level, illness, and drug use. The Wechsler Intelligence Test (Chinese version) was used to collect the intelligence quotient (IQ) levels of the subjects. Social function and daily living abilities were evaluated using the Activity of Daily Living (ADL) scale, SDSS, and FAQ, respectively. The degree of personality change following TBI was assessed using the scale of personality change.

The ADL scale, developed by Lawton in the United States, is divided into the physical self-maintenance scale and instrumental ADL scale[28]; it involves a total of 14 items, with each item scoring 0-4 points. Scoring > 16 points indicates impaired daily living ability, and the higher the score, the more severe the impairment.

The SDSS was derived from the disability assessment schedule developed by the World Health Organization and is mainly used to assess the degree of social dysfunction in patients with mental illness. It comprises 10 evaluation items scored from 0-2 points, where 0 indicates normal or very slightly abnormal function, 1 indicates a functional defect, and 2 indicates a severe functional defect. A score of ≥ 2 indicates a social functional deficit. The SDSS has good reliability and validity, and higher scores indicate greater impairment in social functioning[29].

The FAQ effectively detects and evaluates patients with mild dysfunctions. It consists of 10 items, each graded 0-2 on three levels. A score of 0 indicates no difficulty and independent completion, 1 signifies the need for guidance and help from others, and 2 indicates an inability to finish the task. A total score of ≥ 5 points indicates the existence of social functional defects. The scale of personality change following a TBI includes 19 items, each scored 0-3[30,31]. A score of > 14 points indicates personality change; a score of > 22 points signifies severe personality change.

The experimental process of auditory MMN

MMN was induced through pure tone auditory stimulation. Using the classic auditory oddball paradigm, we randomly generated the order of the standard and deviant stimuli, with standard stimuli at 1000 Hz, 200 milliseconds, 70 dB, and an occurrence frequency of 80%. The deviation stimulus was a low-pitched, short, pure tone with the following parameters: 120 Hz, 200 milliseconds, and 70 dB. A total of 1000 stimuli were administered.

Electroencephalography (EEG) data were recorded using a Neuroscan device (SynAmps 2 8050; Compumedics, Melbourne, Australia), with the international 10-20 system as the reference coordinate, CZ, FZ, and PZ electrodes as positioning points to place electrodes, and the earlobe as the reference electrode. The scalp resistance was reduced to below 5 kΩ by washing the hair and using saline solution. The experiments were conducted in a quiet room with soft lighting and a temperature of 23 °C. The participant was placed in a sitting position, fully relaxed, and their head remained stationary. Four electrodes (Fz, FCz, Cz, and Pz) situated over the midline were selected for EEG recording. To explore regions potentially associated with the prefrontal region, electrodes F1 and F2, which are adjacent to the Fz electrode, were included. The sound stimuli were played through audio equipment while recording the EEG data.

All EEG data were collected and processed by Curry Neuroimaging Suite (version 7.0; Compumedics Neuroscan). The EEG data collected were preprocessed using a high-pass filter (0.5 Hz) and a low-pass filter (40 Hz) to eliminate undesirable frequency components. Subsequently, independent component analysis was employed to remove artifacts attributable to eye movements. Raw EEG signals with amplitudes exceeding ± 200 microvolts were classified as outliers and excluded from further analysis. At least 100 trials per participant were included. The deviant and standard stimuli of each electrode were subjected to ensemble averaging separately, and the resulting ERP waveform from the standard stimuli was then subtracted from that of the deviant stimuli to generate the difference wave. The maximum negative peak occurring within 100 to 250 milliseconds poststimulus onset was defined as the MMN.

Statistical analysis

The results are expressed as the mean ± SD. Categorical data were assessed using the χ² test. Comparisons of variables between patients and healthy controls were conducted using the Student’s t-test. Partial correlation analysis (Spearman’s rho) controlling for age, years of education, and IQ was used to determine the relationships between the parameters. To control the false positive rate in multiple hypothesis testing, the false discovery rate (FDR) correction method (Benjamini-Hochberg procedure) was applied to adjust the P values, with an FDR threshold set at 0.05, aiming to limit the proportion of incorrect rejections of the null hypothesis. FDR correction was applied separately to: (1) Amplitude comparisons across electrodes; (2) Latency comparisons across electrodes; (3) Amplitude correlations with each scale score; and (4) Latency correlations with each scale score. The data were processed using IBM Statistical Product and Service Solutions (version 22.0; IBM Corp., Armonk, NY, United States). Statistical significance was defined as P < 0.05. Post-hoc power analysis (G*Power 3.1.9.7) indicated that our sample size (n = 119) provided sufficient power (0.91) to detect the primary group difference in MMN amplitude. However, power was limited for non-significant secondary analyses (MMN latency), which should be interpreted with caution.

RESULTS

A total of 63 patients and 56 healthy volunteers completed all tests, with two patients withdrawing due to physical discomfort, making it impossible to complete the study. Table 1 shows the comparison of demographic characteristics and scale assessment results between the patient and control groups. No statistically significant differences were found between the two groups regarding age, sex, or years of education (P > 0.05). The average time of the patient’s injury was 14.95 ± 4.93 months. In the IQ test, the intelligence score of the PCS group was significantly lower than that of the control group (P < 0.001). The patient group scored higher than the control group on the ADL, FAQ, SDSS, and scale of personality changes; all comparisons were statistically significant (P < 0.001).

Table 1 Demographic and clinical characteristics of patients with postconcussion syndrome and controls, mean ± SD.

Parameter	Controls (n = 56)	Patients (n = 63)	P value
Age (years)	42.27 ± 12.04	42.30 ± 12.98	0.993
Sex			0.9831
Male (n)	25	28
Female (n)	31	35
Years of education	9.35 ± 4.10	9.40 ± 3.38	0.962
Injury time (months)		14.95 ± 4.93
IQ	86.03 ± 9.37	72.45 ± 6.00	< 0.001a
ADL scale score	14.54 ± 0.58	16.05 ± 1.31	< 0.001a
FAQ scale score	1.35 ± 1.16	3.35 ± 0.99	< 0.001a
SDSS scale score	0.15 ± 0.37	2.30 ± 0.87	< 0.001a
Scale of personality change following TBI score	3.08 ± 1.57	6.80 ± 2.29	< 0.001a

¹χ² test, other statistics: Student’s t-test.

^aP < 0.05.

IQ: Intelligence quotient; ADL: Activity of daily living; FAQ: Functional activities questionnaire; SDSS: Social disability screening schedule; TBI: Traumatic brain injury.

As shown in Table 2, the amplitudes of F1, F2, FZ and FCZ were significantly lower in the patient than control group (all P_FDR < 0.05; Figure 2). Conversely, no statistically significant differences were found between the two groups regarding the amplitudes of CZ and PZ (P_FDR = 0.284 and P_FDR = 0.500, respectively). Similarly, no statistically significant differences were observed in latencies between the two groups at all electrode sites (P_FDR > 0.05).

Figure 2 The results and difference wave between postconcussion syndrome and control group. A: Results; B: Difference wave. PCS: Postconcussion syndrome.

Table 2 The results of mismatch negativity between controls and patients with postconcussion syndrome, mean ± SD.

Parameter	Controls (n = 56)	Patients (n = 63)	P value	PFDR value
Amplitude (μV)
FZ	-3.89 ± 1.79	-2.98 ± 0.99	< 0.001a	0.0014
F1	-3.97 ± 1.71	-2.94 ± 1.12	< 0.001a	0.0008
F2	-4.01 ± 1.84	-2.82 ± 1.04	< 0.001a	0.0002
FCZ	-3.32 ± 1.53	-2.50 ± 0.95	< 0.001a	0.0014
CZ	-2.42 ± 1.16	-2.15 ± 1.06	0.189	0.2843
PZ	-1.65 ± 0.92	-1.52 ± 0.94	0.459	0.5002
Latency (milliseconds)
FZ	207.17 ± 37.46	216.40 ± 35.06	0.168	0.2841
F1	208.20 ± 35.46	214.95 ± 35.03	0.299	0.3583
F2	206.86 ± 33.45	216.15 ± 35.69	0.146	0.2841
FCZ	208.55 ± 36.56	217.05 ± 33.11	0.186	0.2943
CZ	206.70 ± 39.70	215.75 ± 39.21	0.214	0.2854
PZ	203.46 ± 42.10	208.37 ± 38.97	0.511	0.5112

Data were calculated by Student’s t-test.

^aP < 0.05.

FDR: False discovery rate.

As shown in Table 3, in the patient group, the amplitudes of FZ, F1, and F2 were positively and significantly correlated with the SDSS (P_FDR = 0.048, P_FDR = 0.003, and P_FDR = 0.028, respectively; Figure 3), FAQ scale (P_FDR = 0.046, P_FDR = 0.043, and P_FDR = 0.028, respectively), and scale of personality change following TBI (P_FDR = 0.033 and P_FDR = 0.041, respectively), but not with the ADL score (P_FDR > 0.05). However, the amplitudes of CZ and PZ showed no statistically significant correlation with any of the scale scores (P_FDR > 0.05). Further, no statistically significant correlation was found between the latencies of F1, FZ, F2, FCZ, CZ, and PZ, and the SDSS, ADL, and FAQ scores or personality changes following TBI (P_FDR > 0.05).

Figure 3 Correlations between amplitude (F1) and social disability screening schedule scores. SDSS: Social disability screening schedule.

Table 3 Partial correlations between mismatch negativity and scale scores in patients with postconcussion syndrome, controlling for age, years of education, and intelligence quotient.

Parameter	SDSS scale		ADL scale		FAQ scale		Scale of personality change following TBI
	PFDR value	r-value	PFDR value	r-value	PFDR value	r-value	PFDR value	r-value
Amplitude (μV)
FZ	0.048a	0.255	0.278	-0.141	0.046a	0.258	0.033a	0.273
F1	0.003a	0.465	0.321	-0.129	0.043a	0.260	0.041a	0.267
F2	0.028a	0.281	0.753	-0.041	0.028a	0.281	0.722	-0.046
FCZ	0.103	0.151	0.984	-0.003	0.889	0.018	0.130	0.196
CZ	0.360	0.119	0.322	-0.129	0.360	0.119	0.758	0.040
PZ	0.682	-0.054	0.285	-0.139	0.682	-0.054	0.380	0.114
Latency (milliseconds)
FZ	0.478	0.093	0.071	-0.233	0.886	-0.019	0.805	0.032
F1	0.819	0.030	0.245	-0.151	0.521	-0.084	0.260	0.147
F2	0.197	-0.167	0.865	-0.022	0.433	-0.102	0.994	0.001
FCZ	0.866	0.022	0.210	-0.163	0.428	0.103	0.349	0.122
CZ	0.246	0.151	0.373	-0.116	0.922	0.013	0.523	-0.083
PZ	0.215	0.161	0.588	-0.071	0.416	-0.106	0.740	-0.043

All correlations reported are partial correlations controlling for age, years of education, and intelligence quotient.

^aP_FDR < 0.05.

ADL: Activity of daily living; SDSS: Social disability screening schedule; FAQ: Functional activities questionnaire; TBI: Traumatic brain injury; FDR: False discovery rate.

DISCUSSION

Neurocognitive disorders and the difficulties in evaluating them after PCS are multifaceted. In this study, MMN was used to assess the severity of mental disorders caused by mTBI. TBI can result in reduced cognitive function and impaired ADL; however, current studies have indicated that while individuals with PCS have lower IQ levels than healthy controls, those levels do not reach those of mild intellectual impairment. This may be related to the recruited participants, some of whom were patients with concussion. Prior to recruitment, they underwent disability level assessment to obtain disability compensation. Some patients may have been uncooperative, resulting in lower scores. Additionally, although the ADL scale scores of patients with PCS are higher than those of the healthy population, they did not demonstrate impaired daily living abilities. the mean ADL score of the PCS group was very close to the clinical threshold for dysfunction. This nearthreshold finding suggests that the ADL impairments in our PCS sample were likely mild. In addition, the widely used ADL scale may exhibit a ceiling effect when applied to functionally preserved or mildly impaired populations such as chronic PCS patients, as has been noted in other mTBI studies.

This research employed two scales to assess the social functioning of two distinct cohorts. The findings indicated that the social functioning of patients with PCS was notably poorer than that of the healthy controls, as evidenced by the higher scores. Consequently, solely evaluating the functional level of patients with PCS based on cognition and ADL is insufficient, highlighting the need to prioritize the social functional deficits of patients with PCS.

MMN has been extensively studied in various medical conditions and is considered an ideal marker for assessing cognitive function in brain disorders[22,32,33]. Evaluation of MMN amplitude and latency can offer valuable insights into patients with impaired brain function, where reduced MMN amplitude aligns with lower prefrontal lobe amplitudes observed in patients compared to healthy controls[26,34]. MMN amplitude levels have been linked to attention, memory, and information-processing abilities at the auditory cortex level in disease studies[35,36]. Therefore, a decreased amplitude may indicate compromised information-processing capacity and executive function impairment. Our findings indicate that patients with PCS have reduced amplitude in the prefrontal region (F1, F2, FZ); this may indicate defects in attention and information processing, which may further affect their social function.

Although this study found no difference in MMN latency between patients with PCS and healthy individuals, previous research has indicated that MMN latency serves as an indicator of cognitive function and disease severity[37]. A shorter latency is associated with youth, high intelligence, and musical experience[38,39]. However, the relationship between intellectual impairment and MMN latency remains inconclusive based on some studies[40]. The lack of difference in MMN latency between patients with PCS and healthy individuals observed in this study may be attributed to the minor degree of injury among the enrolled patients, despite most experiencing a decline in intelligence within the normal range.

Additionally, this study revealed an association between MMN amplitude and social function and other functions in patients with PCS, further demonstrating the significance of MMN in patient assessment. The study found that the MMN amplitude in the prefrontal region inversely correlated with the degree of social function impairment. Lower MMN amplitude was associated with more severe social function impairment, possibly due to cerebral cortex dysfunction and impaired interaction between cortical pyramidal neurons and local circuit SST-type GABAergic interneurons[35]. Personality changes are a manifestation of mTBI, as supported by the results of this study. Emotional instability often follows trauma; however, the specific cause of personality change resulting from PCS remains unclear. Some studies have suggested that it may be related to frontal lobe dysfunction[41].

This study explored the relationship between personality changes and MMN. The MMN amplitude in the prefrontal region correlated with the degree of personality change. Previous reports have indicated that MMN amplitude differs between individuals with schizoid or antisocial personality disorder compared to those without such disorders[42,43], suggesting that MMN can predict personality disorders to some extent. Therefore, MMN has the potential to serve as an indicator of personality changes after mTBI.

From the perspective of forensic psychiatry, the subjective nature of PCS symptoms and the lack of objective imaging evidence have long posed challenges for forensic psychiatrists conducting disability evaluations in patients with PCS[44]. Our study found that the amplitude of MMN correlates with the degree of social dysfunction and personality changes in PCS patients, thereby offering a potential electrophysiological tool to support clinical judgment. Furthermore, forensic psychiatric evaluations may be compromised by patients exaggerating symptoms for secondary gain, whereas MMN is largely unaffected by the patient’s level of active cooperation, as it does not require an active response. These features make MMN suited for application in forensic psychiatric assessments. Although the use of MMN in forensic psychiatry is still in its early stages, our findings suggest that it can serve as a supportive objective marker, helping to bridge subjective symptoms and objective evidence, thereby enhancing the consistency and credibility of disability evaluations for PCS.

This study has some limitations; first, no a priori sample size calculation was performed. Although post hoc power analysis indicated adequate power 0.91 for the primary MMN amplitude comparison, the power for nonsignificant findings (MMN latency comparisons) was limited. Therefore, the absence of significant correlations in these secondary analyses may be attributable to insufficient statistical power rather than a true lack of association. Future studies with larger sample sizes are warranted to further explore these relationships. Second, we solely focused on patients with PCS. Thus, the findings may not be generalizable to wider patient populations. Exploring the relationship between MMN and neurocognitive dysfunction after TBI in future research should involve a larger number of patients with varying injury levels and detailed studies on different injury areas. Third, we note that the relatively large frequency deviance (880 Hz) used in our MMN paradigm may enhance physical mismatch contributions and affect the specificity of the findings. Future studies employing moderate frequency deviances are warranted to cross validate our results. Additionally, more refined electrophysiological and neuropsychological studies combining various injury locations and model biomarkers are necessary to predict the functional recovery of patients after TBI.

CONCLUSION

Patients with PCS experience social dysfunction and personality changes. MMN amplitude in the prefrontal region correlates with social dysfunction and personality changes, with smaller amplitudes indicating more severe social dysfunction and personality changes. Therefore, MMN may serve as a potential indicator for assessing the symptoms of PCS.

ACKNOWLEDGEMENTS

We thank all participants of Hangzhou Seventh People’s Hospital and the Academy of Forensic Science, who provided help in this study.