Ocular emotion discrimination disorders in self‐limited epilepsy patients with centrotemporal spikes complicated with electrical status epilepticus during sleep: A pediatric neuropsychological study

ABSTRACT Objective We investigated the characteristics and factors influencing eye emotion recognition in self‐limited epilepsy patients with centrotemporal spikes (SeLECTS) complicated with electrical status epilepticus during sleep (ESES). Methods We selected SeLECTS (n = 160) patients treated in the outpatient and inpatient departments of Anhui Children's Hospital from September 2020 to January 2022. According to the video electroencephalogram monitoring slow‐wave index (SWI), SeLECTS patients with SWI < 50% were assigned into the typical SeLECTS group (n = 79), and patients with SWI ≥ 50% were assigned into the ESES group (n = 81). Patients in the two groups were assessed by The Eye Basic Emotion Discrimination Task (EBEDT) and The Eye Complex Emotion Discrimination Task (ECEDT), respectively. Comparisons were made with age‐, sex‐ and education level‐matched healthy control participants. The correlation between the characteristics of emotional discrimination disorder in the eye area and the clinical influencing factors was analyzed in ESES group, and p ≤ .050 was the threshold for significance. Results Relative to the healthy control group, scores of sadness and fear in the typical SeLECTS group were markedly lower (p = .018, p = .023), while differences in scores of disgust, happiness, surprise, and anger were not significantly different between the groups (p = .072, p = .162, p = .395, p = .380, respectively). Compared with the healthy control group, the ESES group had significantly low scores in recognition of sadness, fear, disgust, and surprise (p = .006, p = .016, p = .043 and p = .038, respectively). However, differences in recognition of happiness and anger between the groups were not significant (p = .665 and p = .272). Univariate logistic analysis showed that the score of eye recognition for sadness in the ESES group was affected by age of onset, SWI, ESES duration and number of seizures. The score of eye recognition for fear was mainly affected by SWI, while the score of eye recognition for disgust was affected by SWI and number of seizures. The surprised eye emotion recognition score was mainly affected by the number of seizures. Variables with p < .1 were considered to be independent variables of multivariable ordered logistic regression. Multivariate logistic analysis showed that sadness emotion recognition was mainly affected by SWI and ESES duration, while disgust was mainly affected by SWI. Conclusion The typical SeLECTS group showed impaired emotion (sadness and fear) recognition function in the eye area. The ESES group was associated with more intense emotional (sadness, fear, disgust, and surprise) recognition impairment in the eye region. The higher the SWI, the younger the onset age and the longer the duration of ESES, while the more the number of seizures, the more serious the impairment of emotional recognition function in the affected eye area.


INTRODUCTION
Self-limited epilepsy with centrotemporal spikes (SeLECTS) is the most common childhood idiopathic focal epilepsy syndrome, with a prevalence of about 10/210,000. It accounts for approximately 15%−24% of all epilepsy cases among children. The age of onset is majorly around 3-13 years old, the peak age of onset is around 5-8 years old, while spontaneous remission is about 2-4 years after onset (Lee et al., 2017). Electrical status epilepticus in sleep (ESES) is a special electroencephalogram (EEG) phenomenon, which refers to the continuous or nearly continuous epileptiform discharges of 1.5-2.5 Hz spike and slow waves during non-rapid eye movement sleep (Yan & Xiaoming, 2018). This abnormal EEG phenomenon was first proposed by Patry et al. in 1971, and named as electrical status epileptiform during sleep in children by Tassinari et al. (1992). Its hallmark features are age dependence and self-limitation. In clinical practice, ESES patients manifest diverse symptoms such as, neuropsychological impairment, including language, behavior, learning, memory, attention, social interaction, motor skills, and cognitive. Even if EEG paradoxical discharge and seizures are controlled in children with ESES, neurocognitive and behavioral deterioration may be permanent (Loddenkemper et al., 2011).
Spike-wave index (SWI) in sleep stage is an EEG index for describing the severity of ESES, which refers to the percentage of the duration of all abnormal spines during the first non-rapid eye movement (NREM) stage (Tarokh et al., 2014). It can utilized as part of the diagnostic criteria of ESES, but the corresponding quantification criteria are not given in all of the current studies. Tassinari et al. (2009) suggested that SWI of ESES should reach 85%−100%, and most clinicians use SWI ≥ 50% as the diagnostic criteria for ESES. The ESES defined in this article are SWI ≥ 50%. Eye area emotion recognition is used to infer the inner view, purpose and attitude of others via various clues in the eye area, which plays an important role in development of social emotions among children. However, it has not been established whether SeLECTS patients develop ocular emotional discrimination disorders during seizures, and whether SeLECTS patients with ESES (SWI ≥ 50%) have more severe ocular emotional discrimination disorders than SeLECTS patients (SW < 50%). Therefore, we conducted a study on emotional discrimination in eye regions of patients with SeLECTS complicated with ESES to establish the clinical factors and characteristics of potential emotional recognition disorders.

Study participants
A total of 79 children (46 males and 33 females, with a median age of 8 (7, 9) years) diagnosed with the typical SeLECTS (SWI < 50%) at Anhui Provincial Children's Hospital from September 2020 to January 2022 were enrolled in this study. A total of 81 patients (44 males and 37 females, with a median age of 8 (7, 9) years) diagnosed with SeLECTS combined with ESES (SWI ≥ 50%) (ESES group) in our hospital during the same period were also enrolled. A total of 71 healthy children (49 boys and 22 girls, median age 8 (7, 9) years) who underwent physical examination in our hospital and found not to have hearing disorders or mental or nervous system diseases were enrolled as the healthy control group. Differences in gender, age, and years of education among the three groups were not significant (p > .050).

Inclusion criteria for the typical SeLECTS group
The inclusion criteria for this group were as follows: (i) patients who met the SeLECTS diagnostic criteria per the International Anti-Epileptic Alliance (ILAE) in 2022; (ii) the spike-wave and spike-slow wave in the Rolandic area were detected by 24-h VEEG, and the SWI in the first NREM period was less than 50%; (iii) patients who had no history of asphyxia at birth or a previous history of mental disorders or congenital diseases; (iv) patients who had no abnormalities in vision, hearing and color recognition.

Inclusion criteria for the ESES group
The inclusion criteria for this group were as follows: (i)

Inclusion criteria for the healthy control group
The inclusion criteria for the healthy control group were as follows: (i) Individuals whose Minimum Mental State Examination (MMSE) scores were between 17 and 30 points and (ii) Individuals who had no family history of epilepsy or a history of convulsions.

Exclusion criteria
The exclusion criteria for this study were as follows: (i) Individuals

Clinical data collection
We collected relevant clinical data by questionnaire. We recorded the

Scoring criteria for The Eye Basic Emotion Discrimination Task
Eye emotion discrimination analyses for the ESES group, the typical SeLECTS group and the healthy control participants were respectively performed using The Eye Basic Emotion Discrimination Task (EBEDT) (Adolphs et al., 2002). The test involves 120 eye expressions, including six basic eye expressions: anger, happiness, fear, sadness, disgust, and surprise. During the test, pictures were presented in random form on a computer, each containing an image of the eye, and two basic emotional words (Figure 1). Participants were asked to select the emotion they thought the person in the picture was experiencing, and a correct choice was 1 point. The highest score of each eye area emotion was 20 points, and the total score of the six basic emotions was 120 points. The number of correct choices for each emotion and the total number of correct emotions were calculated separately.

Scoring criteria for The Eye Complex Emotion Discrimination Task
Eye emotion discrimination analyses for the ESES group, typical SeLECTS group and healthy control participants were respectively performed and analyzed using The Eye Complex Emotion Discrimination Task (ECEDT) (Adolphs et al., 2002). This test involved 34 black and white photos of Chinese faces (17 men and 17 women), showing emotions such as worry, sadness, satisfaction, and expectation. Participants were asked to select the emotion they thought the person in the picture was experiencing, and to assess the gender of the subjects in the images ( Figure 2). When both emotion and sex were correctly identified, the score was 1, with a potential maximum score of 34.

Statistical analysis
Statistical analyses were performed using the SPSS25.0 software.
The normality for data distribution were tested by a histogram and Shapiro-Wilk test. Normally distributed data are expressed as

F I G U R E 2 Pictures of The Eye Complex Emotion Discrimination
Task.
mean ± standard deviation, while data that did not conform to normal distribution are expressed as medians or quartiles [M (Q25, Q75)].
The Mann-Whitney U t-test was used to compare data between groups. Enumeration data are expressed as the number of cases. All variables were initially analyzed by univariate ordered logistic regression analysis, and variables with p < .1 were used as covariates in multivariate ordered logistic regression. Factors that were related to emotion recognition disorders were analyzed by multiple-ordered logistic regression.

Clinical characteristics of patients in the typical SeLECTS group and the ESES group
The SeLECTS group consisted of a total of 79 children, including 46 males and 33 females, SWI less than 50% in the Rolandic area, with a median age of onset 6 (5, 8) years, a median age of enrollment 8 (7,9) years, and a median of 3 (2, 4) years of education. The median number of seizures was 3 (3, 3.5), 17 cases were abnormal in the left Rolandic area, 22 cases were abnormal in the right Rolandic area, 40 cases were bilateral Rolandic area, 45 patients were focal seizures, and 34 patients were generalized seizures. Of these, 11 patients had a previous history of febrile convulsions, 4 patients had a family history of SeLECTS, and 6 patients had a family history of febrile convulsions. All patients had normal cranial imaging.
There were 16 cases of abnormal discharge in the left Rolandic area, 19 cases in the right Rolandic area, and 46 cases in the bilateral Rolandic area. Among them, 20 patients had a previous history of febrile convulsions, 2 patients had a family history of SeLECTS, 8 patients had a F I G U R E 3 Comparison of basic eye area emotion recognition scores between the typical SeLECTS and healthy control groups.
family history of febrile convulsions, and 2 patients had a family history of psychiatric disorders. The cranial imaging of 81 patients was normal.
Clinical data are summarized in Table 1.

4.2
Results of eye emotion discrimination task in patient groups

4.2.1
Results of eye region discrimination task in typical SeLECTS group Scores of patients in the typical SeLECTS group on recognition of sadness and fear were lower than those of the healthy control group (p = .018, p = .023). Differences between the two groups in the recognition scores of happiness, anger, disgust, and surprise were insignificant (p = .162, p = .380, p = .072, p = .395). Differences in EBEDT score and ECEDT between the SeLECTS group and the healthy control group were not significant (p = .061) and (p = .922) ( Figure 3 and Table 2).

4.2.2
Results of eye emotion discrimination task in ESES group Scores of sadness, fear, disgust, and surprise in ESES group were significantly lower than those of the healthy control group (p = .006, p = .016, p = .043 and p = .038). Differences in scores of happiness and anger discrimination between the groups were not significant (p = .665, p = .272). The score for EBEDT in the ESES group was significantly lower than those of the healthy control group (p = .041). Differences in ECEDT between the two groups were insignificant (p = .697). These results are presented in Table 3 and

Clinical factors related to eye emotion discrimination for patients in the ESES group
Univariate analysis showed that age of onset (p = .025), duration of ESES (p = .004), SWI index (p = .003), and number of seizures (p = .042) TA B L E 1 Clinical characteristics of patients in typical SeLECTS group and the ESES group.

F I G U R E 4
Comparison of basic eye area emotion recognition scores between the ESES and healthy control groups.
were associated with sadness discrimination scores. Scores for fear recognition were correlated with the SWI index (p = .003), while scores for disgust recognition were correlated with the SWI index (p = .003) The number of seizures (p = .030). The score for surprise was associated with the number of seizures (p = .010) ( Table 4). In univariate analysis, the factors found to be associated with eye emotion recognition and discrimination were selected as independent variables for multiple-ordered regression, while scores for sadness, fear, disgust, and surprise were the dependent variables. Multiple-ordered regression analysis showed that the longer the duration of ESES (p = .043), the higher the SWI index (p = .031) and the lower the sadness recog-nition score; the higher the SWI index (p = .014), the lower the disgust recognition score (Table 5).

DISCUSSION
Sleep activation of epileptiform discharges is very common in SeLECTS.
In SeLECTS children, learning and behavioral disorders may also occur, but generally, there is no serious intellectual regression (Vinayan et al., 2005). Currently, it has not been conclusively determined whether  a special eye area emotion discrimination disorder, which was mainly related to sadness and fear, but there were no significant differences in recognition of happiness, disgust, surprise, and anger. Emotional differences in emotion recognition in the eyes of ESES patients is not extensive but is associated with specific emotion recognition of sadness, fear, disgust, and surprise. Differences in emotion recognition of joy and anger between patients with ESES and healthy controls were insignificant. Consistent with our findings, it has been reported that the most common cognitive impairment of focal epilepsy is cognitive impairment of fear, followed by cognitive impairment of sadness and disgust, while cognitive impairment of anger and surprise is relatively small (Monti & Meletti, 2015). The amygdala plays an important role in facial expression recognition of emotional content (Gordon, 2000). The amygdala and ventromedial prefrontal cortex exert strong bidirectional projection functions via the uncinate fasciculus muscle.
These areas are two important nodes in emotion recognition network.
During emotion recognition, the amygdala plays an important role in guiding people to focus on facial emotion prominent areas, especially the eyes, which play an important role in controlling visual attention, while the thalamus is associated with impairment of negative emotion recognition. Liza (2022) found that mSTN-CRH neurons are the key pivot of the common loop regulating fear and sleep. The corticotropin releasing hormone in the medial subthalamic nucleus is produced by neurons under the control of acute fear responses, and it mediates the REM sleep state caused by continuous pressure. Xiaoting et al. (2018) found that the thalamus is involved in emotion recognition and regulates emotional memory processing. The emotional memory of thalamic patients is impaired, mainly in terms of neutral and negative emotion recognition. With advances in neuroimaging, it has been confirmed that children with SeLECTS have abnormal developments in the frontal, temporal, amygdala, hypothalamus, and other brain regions. Sanchez et al. (2017) found that the relative thalamus volume of ESES patients with normal MRI was smaller and was associated with age and total brain volume. After correcting for age and brain volume, the dif- Our logistic analysis showed that the higher the SWI, the lower the scores for sadness, fear, and disgust recognition. Recently, Huber et al. (2004) reported that an increase in local slow-wave activity (SWA) in sleep after learning results in improvement of learning tasks. Based on these findings, we postulated that ESES interferes with local SWA of the epileptic focus, impairs the neural transmission process, and may damage the local cognitive functions that are related to learning and other processes. In their study on SeleCTS, Massa et al. (2001) showed that the disorder of higher cortical functions is related to the continuous existence of a large number of spikes during sleep. We also found that the age of patients was negatively correlated with scores of sad emotion recognition, and the younger the age of onset, the more impaired the sad emotion recognition ability. The recognition ability of negative emotions is seriously damaged in the early stages of epileptic seizures, and the younger the age of onset, the more serious the damage to negative emotion recognition. Ciumas et al. (2017) postulated that delayed development of neural networks may affect the cognitive functions of patients. Bora and Meletti (2016) found that epileptic patients have obvious defects in the theory of mind and facial emotion recognition. Earlier onset was associated with mental theory impairment, and the rightside attack was mainly associated with cognitive impairment of fear, sadness, and disgust. Meletti et al. (2003) found that the severity of emotion recognition disorders was associated with age at the time of first seizure, and the right temporal lobe discharge of early seizure was a key factor in the serious defect of fear recognition. However, in our study, we found no significant correlation between epileptic discharge areas and eye emotion recognition scores.
High SWI and long-term ESES are the main predictors of poor prognosis of epilepsy (Veggiotti et al., 2002). Scholtes et al. (2005) reported that cognitive decline is associated with long-term ESES and early epileptic activities. We found that the longer the patient's ESES lasted, the more severe the impairment of sadness emotion recognition. Therefore, we believe that the duration of ESES may be associated with cognitive and behavioral deterioration. The longer the duration of ESES, the severer the impairment of eye area emotion recognition abilities.
In addition, we found that the number of seizures is associated with specific emotional disorders. The more seizures, the more significant the impairment of sadness, disgust, and surprise emotion recognition abilities, consistent with findings from previous studies. Fuerst et al. (2003) identified a negative correlation between sad emotion recognition scores and the number of seizures, with patients with more epileptic seizures having more severely impaired synaptic connections between brain microstructure and adjacent neurons, which may lead to more frequent seizures and more impaired sad emotion recognition. According to the research conducted by van den Munckhof et al. ity. However, in this study, we did not find a significant relationship between seizure patterns and ocular emotion recognition scores.
In this study, ECEDT scores for patients in the affected group were not significantly different from those of healthy controls, which may be due to the younger age of the affected group and control group, the incomplete maturity of the complex emotion recognition system in the eye region, and the inability of both groups to accurately identify complex emotions. person an image of someone crying does not invariably mean that the person in the image is sad. According to Adolphs et al. (2019), the perceiver's brain makes sense of data meaningful by categorizing it, and in doing so imposes a socially agreed-upon emotional function. In a given moment, my brain might categorize my sense data as an instance of sadness and your brain might categorize the sense data coming from me-my movements, my vocal acoustics, in the same context-as an instance of anger. We can compare our inferences to one another, or what is normative in that particular situation, but there are no objective criteria to say who is right. In addition, this study is completely psychological and behavioral. Future studies should assess the mechanisms of emotion recognition disorders by combining neuroimaging and electrophysiological technologies.

CONCLUSION
In the typical SeLECTS group, eye area emotion recognition function was impaired, mainly sadness and fear emotion recognitions. The emotion recognition function of eyes for patients with SeLECTS complicated with ESES was severely damaged, particularly in terms of emotional recognition of sadness, fear, disgust, and surprise. The higher the SWI, the younger the age of onset, the longer the duration of ESES, and higher the number of attacks, the severer is the impairment of eye area emotion recognition function.

AUTHOR CONTRIBUTIONS
Bin Yang designed the study. Chunmei Yang wrote the manuscript. Kaili Zhang and Xiaocui Wang analyzed the EEG data. Lulu Wu, Nan Jiang revised the manuscript and directed the research. All authors agreed to the publication of the final version of the manuscript.

ACKNOWLEDGMENTS
Thanks to Dr. Bin for his suggestions on the experimental design and the guidance for the later revision of the article.

FUNDING
This research did not receive any specific grant from funding agencies in public, commercial, or not-for-profit sectors.

CONFLICT OF INTEREST STATEMENT
The author declares that there is no potential conflict of interest with the research, authorship, and publication of this article.

DATA AVAILABILITY STATEMENT
The data sets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.