Analysis of Brainstem Auditory Evoked Potential Characteristics in Patients with Chronic Disorders of Consciousness: A Cross-Sectional Study

Analysis of Brainstem Auditory Evoked Potential Characteristics in Patients with Chronic Disorders of Consciousness: A Cross-Sectional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Analysis of Brainstem Auditory Evoked Potential Characteristics in Patients with Chronic Disorders of Consciousness: A Cross-Sectional Study Dan Wang¹, Tao Feng, Xu Dong This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8113139/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Background Brainstem auditory evoked potentials (BAEP) provide an objective assessment of brainstem functional integrity. However, their characteristic profiles and clinical significance in patients with prolonged disorders of consciousness (pDOC) remain to be fully elucidated, especially in small, well-characterized cohorts. Objective This study aimed to preliminarily characterize BAEP parameters in a small sample of pDOC patients and explore their relationship with consciousness levels. Methods In this cross-sectional study, 29 patients with pDOC (16 with unresponsive wakefulness syndrome [UWS] and 13 in a minimally conscious state [MCS]) were enrolled. BAEP recordings, neurological assessments using the Coma Recovery Scale-Revised (CRS-R), and medical record reviews were performed. BAEP parameters (wave latencies, interpeak latencies [IPLs]) were compared between UWS and MCS groups using Mann-Whitney U tests. Effect sizes (r) were calculated to quantify the magnitude of observed differences. Spearman correlation was used to assess the relationship between BAEP parameters and CRS-R scores. Results No significant differences were observed in the latencies of wave I, wave III, the I–III interpeak interval (IPL), the III–V IPL, or the I–V IPL between the unresponsive wakefulness syndrome (UWS) group and the minimally conscious state (MCS) group (all P > 0.05). However, the study revealed a trend toward prolongation in the latency of wave V and the I–V IPL in the UWS group. Both wave V latency (r = − 0.342) and I–V IPL (r = − 0.354) demonstrated moderate effect sizes, suggesting the presence of substantive differences in these measures between the two groups. Additionally, a moderate negative correlation was observed between the I–V IPL and the total score of the Coma Recovery Scale–Revised (CRS-R) (Spearman’s ρ = − 0.447, p < 0.001). Conclusion Although no significant differences were observed in the brainstem auditory evoked potential (BAEP) parameters between the two patient groups, the trend of prolonged I–V interpeak interval (IPL) in the unresponsive wakefulness syndrome (UWS) group, along with its moderate correlation with the Coma Recovery Scale–Revised (CRS-R) score, suggests that UWS patients may have more severe brainstem dysfunction. Therefore, BAEP remains a promising electrophysiological marker for assessing brainstem impairment in patients with prolonged disorders of consciousness (pDOC). Although these preliminary findings did not reach statistical significance in intergroup comparisons, they highlight the need for larger sample sizes in future studies to clarify the role of BAEP in the evaluation of consciousness disorders. Health sciences/Medical research Health sciences/Neurology Biological sciences/Neuroscience Prolonged Disorders of Consciousness Brainstem Auditory Evoked Potentials Coma Recovery Scale-Revised Unresponsive Wakefulness Syndrome Minimally Conscious State Small Sample Study Figures Figure 1 1. Introduction Prolonged disorders of consciousness (pDOC), encompassing unresponsive wakefulness syndrome (UWS, formerly vegetative state) and minimally conscious state (MCS), represent profound challenges in neurorehabilitation following severe brain injury [1] . The accurate diagnosis and prognosis of pDOC heavily rely on standardized behavioral scales like the Coma Recovery Scale-Revised (CRS-R) [2] . However, behavioral assessments can be confounded by motor deficits, fluctuations in arousal, and examiner experience, underscoring the need for complementary objective biomarkers [3] . Brainstem auditory evoked potentials (BAEP) are short-latency electrophysiological responses that objectively evaluates the functional integrity of the auditory pathway from the eighth cranial nerve to the midbrain, without requiring patient cooperation [4] . The I-V interpeak latency (IPL) is a key parameter, reflecting central conduction time within the brainstem. BAEP has well-established utility in acute coma prognosis [5] and diagnosing brainstem pathologies like multiple sclerosis [6] . Its application in the chronic phase of DOC, however, is less standardized, and studies often involve heterogeneous cohorts with large sample sizes [7] . While large-sample studies are ideal, focused preliminary investigations in small, well-defined populations are crucial for generating hypotheses and characterizing specific electrophysiological phenotypes. Brainstem auditory evoked potentials (BAEP) are short-latency electrophysiological responses.There is a paucity of detailed BAEP profiles focusing specifically on the pDOC population in the Chinese context. Furthermore, the relationship between BAEP parameters and clinically assessed consciousness levels (UWS vs. MCS) in small cohorts needs further exploration with appropriate statistical methodology. This preliminary, cross-sectional study therefore sought to characterize BAEP parameters in a carefully selected pDOC cohort and investigate their association with behavioral consciousness levels, employing statistical methods appropriate for the limited sample size. 2. Methods 2.1. Participants Twenty-nine patients with disorders of consciousness (pDOC), including 16 with unresponsive wakefulness syndrome (UWS) and 13 with minimally conscious state (MCS), were all recruited as study participants from the Department of Critical Care Rehabilitation of Ningxia Hui Autonomous Region Hospital of Integrated Traditional Chinese and Western Medicine between January 2025 to June 2025.This study was approved by the Ethics Committee of Ningxia Hui Autonomous Region Hospital of Integrated Traditional Chinese and Western Medicine (Approval No. XJSLL-2025-005).We confirm that all methods were performed in accordance with the relevant guidelines and regulations. Informed consent has been obtained from the legal surrogates of all participants in this study, and all of them have signed the informed consent form. Inclusion criteria were (1) meeting diagnostic criteria for UWS or MCS according to international guidelines [ 1 , 2 ], with a condition duration > 28 days; (2) age between 18 and 75 years; (3) availability of complete BAEP data. Exclusion criteria included (1) premorbid hearing impairment or peripheral auditory pathway lesion; (2) primary brainstem hemorrhage or infarction; (3) administration of high-dose sedative medications within 24 hours prior to testing. 2.2. Clinical Assessment Consciousness was diagnosed and classified based on at least two standardized CRS-R assessments performed by trained physicians within 24 hours before or after the BAEP test. The highest total score obtained was used for analysis. Patients were categorized into UWS or MCS groups based on these assessments. 2.3. BAEP Recording and Analysis BAEPs were recorded using a Nicolet Endeavor CR system (Viasys Healthcare, USA) according to a standardized protocol. Click stimuli of 100 µs duration were presented monaurally at 80 dB nHL at a rate of 11.1 Hz, with white noise masking (40 dB) applied to the contralateral ear. Recording electrodes were placed at the Cz (active), A1/A2 (reference), and Fpz (ground) positions according to the international 10–20 system. The analysis time was 10 ms, and the filter bandpass was set at 100–3000 Hz. A minimum of 1000 repetitions were averaged for each trial, and two reproducible traces were obtained to ensure waveform reliability. The absolute latencies of Waves I, III, and V, and the I-III, III-V, and I-V IPLs were measured for both ears. The data from the side with better waveform morphology were used for statistical analysis. 2.4. Statistical Analysis Non-parametric tests were employed due to the small sample size and non-normal distribution of the data, as assessed by the Shapiro-Wilk test. All analyses were performed using SPSS software (version 26.0; IBM Corp., USA). Descriptive statistics are presented as medians with interquartile ranges (IQR) for continuous variables and as counts with percentages for categorical variables.Intergroup comparisons of BAEP parameters between the UWS and MCS groups were analyzed using the Mann-Whitney U test. The magnitude of the observed differences was quantified by calculating the effect size (r), where r = Z / √N. Effect sizes of 0.1, 0.3, and 0.5 were interpreted as small, medium, and large, respectively.Correlation analysis between BAEP parameters and the CRS-R total score was assessed using Spearman's rank correlation coefficient (ρ). A two-tailed p-value < 0.05 was considered statistically significant. 3. Results 3.1. Patient Characteristics The demographic and clinical characteristics of the 29 patients are summarized in Table 1 . The two groups (UWS vs. MCS) were comparable in terms of age, gender, and etiology of brain injury (all P > 0.05), minimizing potential confounding effects. Time since injury showed no significant difference between groups ( P = 0.112). As expected, the CRS-R total score was significantly lower in the UWS group than in the MCS group ( P < 0.0001). Table 1 Demographic and Clinical Characteristics of pDOC Patients Characteristic Total (n = 29) UWS (n = 16) MCS (n = 13) P-value Age, years, Med (IQR) 52.0 (45.0, 60.0) 51.5 (43.5, 59.8) 54.0 (47.0, 61.0) 0.418a Male, n (%) 20 (69.0%) 11 (68.8%) 9 (69.2%) 0.978b Etiology, n (%) 0.295b Traumatic Brain Injury 15 (51.7%) 9 (56.3%) 6 (46.2%) Stroke 11 (37.9%) 6 (37.5%) 5 (38.5%) Hypoxic-Ischemic Enceph. 3 (10.3%) 1 (6.3%) 2 (15.4%) Time since injury, mon, Med (IQR) 2.2 (1.8, 2.8) 2.4 (1.9, 3.0) 1.9 (1.6, 2.3) 0.112a CRS-R Total Score, Med (IQR) 6.0 (4.0, 10.0) 4.0 (3.0, 5.0) 10.0 (9.0, 12.0) < 0.0001a a:Mann-Whitney U test; b:Fisher's exact test. 3.2. BAEP Parameters BAEP parameters are summarized in Table 2 . No significant differences were observed in the latencies of wave I, wave III, the I–III interpeak interval (IPL), the III–V IPL, or the I–V IPL between the unresponsive wakefulness syndrome (UWS) group and the minimally conscious state (MCS) group (all P > 0.05). Although prolonged wave V latency and I–V IPL were noted in the UWS group, these differences did not reach statistical significance (wave V latency: P = 0.069; I–V IPL: P = 0.059). Table 2 Comparison of BAEP Parameters between UWS and MCS Patients BAEP Parameter (ms) UWS (n = 16) MCS (n = 13) P-valuea Effect Size (r) Wave I latency 1.280(1.280,1.342) 1.290(1.280,1.350) 0.893 -0.028 Wave III latency 3.835(3.650,4.178) 3.690(3.540,3.950) 0.303 -0.195 Wave V latency 6.535(6.430,6.700) 6.370(6.220,6.570) 0.069 -0.342 I-III IPL 2.570(2.270,2.898) 2.370(2.230,2.580) 0.283 -0.204 III-V IPL 2.750(2.392,2.880) 2.590(2.220,2.890) 0.497 -0.130 I-V IPL 5.265(5.052,5.435) 5.010(4.610,5.260) 0.059 -0.354 a:Mann-Whitney U test. Data are presented as median (interquartile range). P-values were derived from the Mann-Whitney U test. In the UWS group, the I-V interpeak interval (IPL) (P = 0.059) and wave V latency (P = 0.069) showed a trend toward prolongation with moderate effect sizes (r = -0.354 and r = -0.342, respectively). Additionally, the I-V IPL demonstrated a moderate negative correlation with the total score of the Coma Recovery Scale–Revised (CRS-R) (ρ = -0.447, P < 0.001). 3.3. Correlation between BAEP and CRS-R Spearman correlation analysis revealed a moderate negative correlation between the I–V interpeak interval (IPL) and the Coma Recovery Scale–Revised (CRS-R) total score (ρ = -0.447, P < 0.001). A significant negative correlation was also observed for wave V latency (ρ = -0.441, P < 0.05), whereas no other brainstem auditory evoked potential (BAEP) parameters showed significant correlations with the CRS-R score(in Table 3 ). Table 3 Correlation between BAEP Parameters and CRS-R Total Scores BAEP Parameter Spearman Correlation (rs) P-value Wave I latency 0.111 0.336 Wave III latency 0.229 0.906 Wave V latency -0.441 < 0.05 I-III IPL -0.326 0.333 III-V IPL -0.046 0.721 I-V IPL -0.447 < 0.001 The correlation between I-V IPL and CRS-R total score is visually presented in Fig. 1 . 4. Discussion This preliminary study found no statistically significant differences in brainstem auditory evoked potential (BAEP) parameters between patients with unresponsive wakefulness syndrome (UWS) and those in a minimally conscious state (MCS). However, a trend towards prolongation of the I-V interpeak interval (IPL) was observed in the UWS group. Furthermore, the I-V IPL demonstrated a moderate negative correlation with the behavioral evaluation score, as assessed by the Coma Recovery Scale-Revised (CRS-R). These results suggest that, although no significant differences in BAEP parameters were found between groups with differing consciousness levels in this small sample, the moderate correlation between the I-V IPL and the CRS-R score (ρ = -0.447) supports the potential utility of BAEP as an objective adjunct to behavioral assessment. This finding also reinforces the concept that "brainstem integrity is a core foundation of conscious behavior" [ 8 , 9 ]. Our conclusions are consistent with numerous studies indicating that electrophysiological markers, including electroencephalography (EEG) and evoked potentials, play a significant role in evaluating patients with severe brain injury [ 10 ]. The present findings align with the established neurophysiological basis of BAEP, suggesting a potential link between brainstem conduction time and clinical outcomes. Specifically, wave V latency and the I-V IPL reflect neural conduction within the upper pons and midbrain—key components of the ascending reticular activating system (ARAS), which is crucial for regulating wakefulness and awareness [ 8 ]. The observed trend of prolonged I-V IPL in UWS patients implies more severe functional-structural impairment within the brainstem compared to MCS patients. The absence of significant intergroup differences in wave I latency, wave III latency, and the I-III IPL indicates that the functional impairment is likely localized to the upper brainstem, rather than involving the peripheral auditory pathway or the lower pons [ 4 , 6 ]. The lack of statistically significant differences in group comparisons may be attributable to the limited sample size and consequent reduction in statistical power. Nonetheless, the effect sizes and correlation patterns observed in this study provide valuable reference points for future research, underscoring that effect size estimation can offer critical supplementary information beyond null hypothesis significance testing [ 11 ]. 4.1. Limitations and Future Directions This study has several limitations. The primary limitation is its small sample size, which constrains statistical power and limits the generalizability of the findings. Secondly, the cross-sectional design precludes any causal inferences or assessment of BAEP's prognostic value. Thirdly, the absence of a control group of healthy individuals or conscious patients with severe brain injury makes it difficult to definitively ascertain the specificity of the observed BAEP abnormalities to disorders of consciousness. However, the primary aim was to compare electrophysiological profiles between different states of disordered consciousness, for which the MCS group served as a critical internal reference, a methodology consistent with other studies in this field [7, 12] . Finally, we acknowledge the risk of Type I error due to multiple comparisons without statistical correction, though the consistency of the findings for the III-V IPL and the observed effect sizes provide some reassurance. Future studies should involve larger, prospective, multi-center cohorts to validate these findings and establish the clinical utility of BAEP in pDOC assessment. Particular attention should be paid to determining clinically meaningful cutoff values for BAEP parameters and evaluating their diagnostic and prognostic accuracy alongside established multimodal biomarkers. 5. Conclusion This preliminary study found no significant differences in brainstem auditory evoked potential (BAEP) parameters between patients with unresponsive wakefulness syndrome (UWS) and those in a minimally conscious state (MCS). However, the correlation observed between the I–V interpeak interval (IPL) and Coma Recovery Scale–Revised (CRS-R) scores provides compelling preliminary evidence for an association between impaired brainstem conduction and consciousness deficits. Therefore, BAEP holds promise as a reliable tool for assessing brainstem function in patients with prolonged disorders of consciousness (pDOC) in future studies. Given the limitation of the small sample size in this study, further research with larger cohorts is warranted to verify these trends and explore the potential utility of BAEP in the multimodal assessment of consciousness disorders. Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of Ningxia Hui Autonomous Region Hospital of Integrated Traditional Chinese and Western Medicine (Approval No. XJSLL-2025-005). Informed consent was obtained from the legal surrogates of all participants. Consent for publication The legal surrogates of all participants have provided consent for the results of this study to be published. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests-Funding The authors declare that they have no competing interests. Funding This study did not receive any specific funding. Authors' contributions D.W.: Research design, data collection, manuscript writing. X.D.: Data analysis, statistical processing, manuscript revision. T.F.: Research supervision, funding acquisition, final review. All authors read and approved the final manuscript. Acknowledgements We thank the Department of Critical Care Rehabilitation and the Department of Critical Care Medicine of Ningxia Hui Autonomous Region Hospital of Integrated Traditional Chinese and Western Medicine for their support in this research. References Giacino, J. T. et al. Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Neurology 91 (10), 450–460 (2018). Kalmar, K. & Giacino, J. T. The JFK Coma Recovery Scale-Revised. Neuropsychol. Rehabil . 15 (3–4), 454–460 (2005). Schnakers, C. Update on diagnosis in disorders of consciousness. Expert Rev. Neurother. 20 (10), 997–1004 (2020). Chiappa, K. H. & Hill, R. A. Short-latency somatosensory evoked potentials: interpretation. In: (ed Chiappa, K. H.) Evoked Potentials in Clinical Medicine. 3rd ed. Lippincott-Raven; :311–338. (1997). Fischer, C., Luaute, J., Adeleine, P. & Morlet, D. Predictive value of sensory and cognitive evoked potentials for awakening from coma. Neurology 63 (4), 669–673 (2004). Stockard, J. J., Stockard, J. E. & Sharbrough, F. W. Brainstem auditory evoked potentials in neurology: methodology, interpretation, clinical application. In: (ed Aminoff, M. J.) Electrodiagnosis in clinical neurology. 6th ed. Elsevier; :519–552. (2012). Zhou, G. P. et al. Prognostic Value of Brainstem Auditory Evoked Potentials in Patients with Severe Traumatic Brain Injury. Biomed. Res. Int. 2021 , 6615876 (2021). Edlow, B. L., Claassen, J., Schiff, N. D. & Greer, D. M. Recovery from disorders of consciousness: mechanisms, prognosis and emerging therapies. Nat. Rev. Neurol. 17 (3), 135–156 (2021). Kondziella, D. et al. European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness. Eur. J. Neurol. 27 (5), 741–756 (2020). Bagnato, S. et al. Prognostic value of standard EEG in traumatic and non-traumatic disorders of consciousness following coma. Clin. Neurophysiol. 131 (8), 1926–1934 (2020). Sullivan, G. M. & Feinn, R. Using Effect Size-or Why the P Value Is Not Enough. J. Grad Med. Educ. 4 (3), 279–282 (2012). Bodien, Y. G. et al. Diagnosing level of consciousness: the limits of the Glasgow Coma Scale total score. J. Neurotrauma . 38 (23), 3295–3305 (2021). Additional Declarations No competing interests reported. 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07:09:21","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":57430,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8113139/v1/2b820a3ecf20cbcac5f77a73.html"},{"id":97655958,"identity":"53bba775-9e44-4ca9-a5df-a1b3f4105dd8","added_by":"auto","created_at":"2025-12-08 07:09:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":29534,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScatter plot showing the correlation between I-V interpeak latency (IPL) and CRS-R total score.\u003c/strong\u003e The solid line represents the Spearman correlation fit (ρ = -0.447, P \u0026lt; 0.001). Each point represents one patient (MCS: redcircles; UWS:bluesquares).\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8113139/v1/d6698a94a57a639270b0654e.png"},{"id":97673175,"identity":"467f49cf-6e8c-4a73-86e1-964f01dff79f","added_by":"auto","created_at":"2025-12-08 09:39:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":737456,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8113139/v1/f97f270e-80f9-4f8a-8c2c-2ec7b57e5b98.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analysis of Brainstem Auditory Evoked Potential Characteristics in Patients with Chronic Disorders of Consciousness: A Cross-Sectional Study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eProlonged disorders of consciousness (pDOC), encompassing unresponsive wakefulness syndrome (UWS, formerly vegetative state) and minimally conscious state (MCS), represent profound challenges in neurorehabilitation following severe brain injury \u003csup\u003e[1]\u003c/sup\u003e. The accurate diagnosis and prognosis of pDOC heavily rely on standardized behavioral scales like the Coma Recovery Scale-Revised (CRS-R) \u003csup\u003e[2]\u003c/sup\u003e. However, behavioral assessments can be confounded by motor deficits, fluctuations in arousal, and examiner experience, underscoring the need for complementary objective biomarkers \u003csup\u003e[3]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eBrainstem auditory evoked potentials (BAEP) are short-latency electrophysiological responses that objectively evaluates the functional integrity of the auditory pathway from the eighth cranial nerve to the midbrain, without requiring patient cooperation \u003csup\u003e[4]\u003c/sup\u003e. The I-V interpeak latency (IPL) is a key parameter, reflecting central conduction time within the brainstem. BAEP has well-established utility in acute coma prognosis \u003csup\u003e[5]\u003c/sup\u003e and diagnosing brainstem pathologies like multiple sclerosis \u003csup\u003e[6]\u003c/sup\u003e. Its application in the chronic phase of DOC, however, is less standardized, and studies often involve heterogeneous cohorts with large sample sizes \u003csup\u003e[7]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eWhile large-sample studies are ideal, focused preliminary investigations in small, well-defined populations are crucial for generating hypotheses and characterizing specific electrophysiological phenotypes. Brainstem auditory evoked potentials (BAEP) are short-latency electrophysiological responses.There is a paucity of detailed BAEP profiles focusing specifically on the pDOC population in the Chinese context. Furthermore, the relationship between BAEP parameters and clinically assessed consciousness levels (UWS vs. MCS) in small cohorts needs further exploration with appropriate statistical methodology.\u003c/p\u003e\u003cp\u003eThis preliminary, cross-sectional study therefore sought to characterize BAEP parameters in a carefully selected pDOC cohort and investigate their association with behavioral consciousness levels, employing statistical methods appropriate for the limited sample size.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Participants\u003c/h2\u003e\u003cp\u003e Twenty-nine patients with disorders of consciousness (pDOC), including 16 with unresponsive wakefulness syndrome (UWS) and 13 with minimally conscious state (MCS), were all recruited as study participants from the Department of Critical Care Rehabilitation of Ningxia Hui Autonomous Region Hospital of Integrated Traditional Chinese and Western Medicine between January 2025 to June 2025.This study was approved by the Ethics Committee of Ningxia Hui Autonomous Region Hospital of Integrated Traditional Chinese and Western Medicine (Approval No. XJSLL-2025-005).We confirm that all methods were performed in accordance with the relevant guidelines and regulations. Informed consent has been obtained from the legal surrogates of all participants in this study, and all of them have signed the informed consent form.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eInclusion criteria were\u003c/strong\u003e\u003cp\u003e(1) meeting diagnostic criteria for UWS or MCS according to international guidelines [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], with a condition duration\u0026thinsp;\u0026gt;\u0026thinsp;28 days; (2) age between 18 and 75 years; (3) availability of complete BAEP data.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eExclusion criteria included\u003c/strong\u003e\u003cp\u003e(1) premorbid hearing impairment or peripheral auditory pathway lesion; (2) primary brainstem hemorrhage or infarction; (3) administration of high-dose sedative medications within 24 hours prior to testing.\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Clinical Assessment\u003c/h2\u003e\u003cp\u003eConsciousness was diagnosed and classified based on at least two standardized CRS-R assessments performed by trained physicians within 24 hours before or after the BAEP test. The highest total score obtained was used for analysis. Patients were categorized into UWS or MCS groups based on these assessments.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. BAEP Recording and Analysis\u003c/h2\u003e\u003cp\u003eBAEPs were recorded using a Nicolet Endeavor CR system (Viasys Healthcare, USA) according to a standardized protocol. Click stimuli of 100 \u0026micro;s duration were presented monaurally at 80 dB nHL at a rate of 11.1 Hz, with white noise masking (40 dB) applied to the contralateral ear. Recording electrodes were placed at the Cz (active), A1/A2 (reference), and Fpz (ground) positions according to the international 10\u0026ndash;20 system. The analysis time was 10 ms, and the filter bandpass was set at 100\u0026ndash;3000 Hz. A minimum of 1000 repetitions were averaged for each trial, and two reproducible traces were obtained to ensure waveform reliability. The absolute latencies of Waves I, III, and V, and the I-III, III-V, and I-V IPLs were measured for both ears. The data from the side with better waveform morphology were used for statistical analysis.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4. Statistical Analysis\u003c/h2\u003e\u003cp\u003eNon-parametric tests were employed due to the small sample size and non-normal distribution of the data, as assessed by the Shapiro-Wilk test. All analyses were performed using SPSS software (version 26.0; IBM Corp., USA).\u003c/p\u003e\u003cp\u003eDescriptive statistics are presented as medians with interquartile ranges (IQR) for continuous variables and as counts with percentages for categorical variables.Intergroup comparisons of BAEP parameters between the UWS and MCS groups were analyzed using the Mann-Whitney U test. The magnitude of the observed differences was quantified by calculating the effect size (r), where r\u0026thinsp;=\u0026thinsp;Z / \u0026radic;N. Effect sizes of 0.1, 0.3, and 0.5 were interpreted as small, medium, and large, respectively.Correlation analysis between BAEP parameters and the CRS-R total score was assessed using Spearman's rank correlation coefficient (ρ). A two-tailed p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.1. Patient Characteristics\u003c/h2\u003e\u003cp\u003eThe demographic and clinical characteristics of the 29 patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The two groups (UWS vs. MCS) were comparable in terms of age, gender, and etiology of brain injury (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), minimizing potential confounding effects. Time since injury showed no significant difference between groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.112). As expected, the CRS-R total score was significantly lower in the UWS group than in the MCS group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic and Clinical Characteristics of pDOC Patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUWS (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMCS (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years, Med (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e52.0 (45.0, 60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e51.5 (43.5, 59.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e54.0 (47.0, 61.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.418a\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20 (69.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11 (68.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9 (69.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.978b\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEtiology, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.295b\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTraumatic Brain Injury\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e15 (51.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9 (56.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6 (46.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStroke\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11 (37.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6 (37.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5 (38.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypoxic-Ischemic Enceph.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (10.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (6.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2 (15.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime since injury, mon, Med (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.2 (1.8, 2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.4 (1.9, 3.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.9 (1.6, 2.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.112a\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCRS-R Total Score, Med (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6.0 (4.0, 10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.0 (3.0, 5.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10.0 (9.0, 12.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001a\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003ea:Mann-Whitney U test; b:Fisher's exact test.\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.2. BAEP Parameters\u003c/h2\u003e\u003cp\u003eBAEP parameters are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. No significant differences were observed in the latencies of wave I, wave III, the I\u0026ndash;III interpeak interval (IPL), the III\u0026ndash;V IPL, or the I\u0026ndash;V IPL between the unresponsive wakefulness syndrome (UWS) group and the minimally conscious state (MCS) group (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Although prolonged wave V latency and I\u0026ndash;V IPL were noted in the UWS group, these differences did not reach statistical significance (wave V latency: P\u0026thinsp;=\u0026thinsp;0.069; I\u0026ndash;V IPL: P\u0026thinsp;=\u0026thinsp;0.059).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of BAEP Parameters between UWS and MCS Patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBAEP Parameter (ms)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUWS (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMCS (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP-valuea\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eEffect Size (r)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWave I latency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.280(1.280,1.342)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.290(1.280,1.350)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.893\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.028\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWave III latency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.835(3.650,4.178)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.690(3.540,3.950)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.303\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.195\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWave V latency\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6.535(6.430,6.700)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6.370(6.220,6.570)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.069\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e-0.342\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI-III IPL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.570(2.270,2.898)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.370(2.230,2.580)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.283\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.204\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIII-V IPL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.750(2.392,2.880)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.590(2.220,2.890)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.497\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.130\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eI-V IPL\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5.265(5.052,5.435)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5.010(4.610,5.260)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.059\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e-0.354\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003ea:Mann-Whitney U test.\u003c/em\u003e\u003c/p\u003e\u003cp\u003eData are presented as median (interquartile range). P-values were derived from the Mann-Whitney U test. In the UWS group, the I-V interpeak interval (IPL) (P\u0026thinsp;=\u0026thinsp;0.059) and wave V latency (P\u0026thinsp;=\u0026thinsp;0.069) showed a trend toward prolongation with moderate effect sizes (r = -0.354 and r = -0.342, respectively). Additionally, the I-V IPL demonstrated a moderate negative correlation with the total score of the Coma Recovery Scale\u0026ndash;Revised (CRS-R) (ρ = -0.447, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.3. Correlation between BAEP and CRS-R\u003c/h2\u003e\u003cp\u003eSpearman correlation analysis revealed a moderate negative correlation between the I\u0026ndash;V interpeak interval (IPL) and the Coma Recovery Scale\u0026ndash;Revised (CRS-R) total score (ρ = -0.447, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). A significant negative correlation was also observed for wave V latency (ρ = -0.441, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), whereas no other brainstem auditory evoked potential (BAEP) parameters showed significant correlations with the CRS-R score(in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCorrelation between BAEP Parameters and CRS-R Total Scores\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBAEP Parameter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSpearman Correlation (rs)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWave I latency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.111\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.336\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWave III latency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.229\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.906\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWave V latency\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e-0.441\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.05\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI-III IPL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.326\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.333\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIII-V IPL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.046\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.721\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eI-V IPL\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e-0.447\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe correlation between I-V IPL and CRS-R total score is visually presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis preliminary study found no statistically significant differences in brainstem auditory evoked potential (BAEP) parameters between patients with unresponsive wakefulness syndrome (UWS) and those in a minimally conscious state (MCS). However, a trend towards prolongation of the I-V interpeak interval (IPL) was observed in the UWS group. Furthermore, the I-V IPL demonstrated a moderate negative correlation with the behavioral evaluation score, as assessed by the Coma Recovery Scale-Revised (CRS-R).\u003c/p\u003e\u003cp\u003eThese results suggest that, although no significant differences in BAEP parameters were found between groups with differing consciousness levels in this small sample, the moderate correlation between the I-V IPL and the CRS-R score (ρ = -0.447) supports the potential utility of BAEP as an objective adjunct to behavioral assessment. This finding also reinforces the concept that \"brainstem integrity is a core foundation of conscious behavior\" [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Our conclusions are consistent with numerous studies indicating that electrophysiological markers, including electroencephalography (EEG) and evoked potentials, play a significant role in evaluating patients with severe brain injury [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe present findings align with the established neurophysiological basis of BAEP, suggesting a potential link between brainstem conduction time and clinical outcomes. Specifically, wave V latency and the I-V IPL reflect neural conduction within the upper pons and midbrain\u0026mdash;key components of the ascending reticular activating system (ARAS), which is crucial for regulating wakefulness and awareness [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The observed trend of prolonged I-V IPL in UWS patients implies more severe functional-structural impairment within the brainstem compared to MCS patients.\u003c/p\u003e\u003cp\u003eThe absence of significant intergroup differences in wave I latency, wave III latency, and the I-III IPL indicates that the functional impairment is likely localized to the upper brainstem, rather than involving the peripheral auditory pathway or the lower pons [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe lack of statistically significant differences in group comparisons may be attributable to the limited sample size and consequent reduction in statistical power. Nonetheless, the effect sizes and correlation patterns observed in this study provide valuable reference points for future research, underscoring that effect size estimation can offer critical supplementary information beyond null hypothesis significance testing [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e4.1. Limitations and Future Directions\u003c/h2\u003e\u003cp\u003eThis study has several limitations. The primary limitation is its small sample size, which constrains statistical power and limits the generalizability of the findings. Secondly, the cross-sectional design precludes any causal inferences or assessment of BAEP's prognostic value. Thirdly, the absence of a control group of healthy individuals or conscious patients with severe brain injury makes it difficult to definitively ascertain the specificity of the observed BAEP abnormalities to disorders of consciousness. However, the primary aim was to compare electrophysiological profiles between different states of disordered consciousness, for which the MCS group served as a critical internal reference, a methodology consistent with other studies in this field \u003csup\u003e[7, 12]\u003c/sup\u003e. Finally, we acknowledge the risk of Type I error due to multiple comparisons without statistical correction, though the consistency of the findings for the III-V IPL and the observed effect sizes provide some reassurance.\u003c/p\u003e\u003cp\u003eFuture studies should involve larger, prospective, multi-center cohorts to validate these findings and establish the clinical utility of BAEP in pDOC assessment. Particular attention should be paid to determining clinically meaningful cutoff values for BAEP parameters and evaluating their diagnostic and prognostic accuracy alongside established multimodal biomarkers.\u003c/p\u003e\u003c/div\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThis preliminary study found no significant differences in brainstem auditory evoked potential (BAEP) parameters between patients with unresponsive wakefulness syndrome (UWS) and those in a minimally conscious state (MCS). However, the correlation observed between the I\u0026ndash;V interpeak interval (IPL) and Coma Recovery Scale\u0026ndash;Revised (CRS-R) scores provides compelling preliminary evidence for an association between impaired brainstem conduction and consciousness deficits. Therefore, BAEP holds promise as a reliable tool for assessing brainstem function in patients with prolonged disorders of consciousness (pDOC) in future studies. Given the limitation of the small sample size in this study, further research with larger cohorts is warranted to verify these trends and explore the potential utility of BAEP in the multimodal assessment of consciousness disorders.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;This study was approved by the Ethics Committee of Ningxia Hui Autonomous Region Hospital of Integrated Traditional Chinese and Western Medicine (Approval No. XJSLL-2025-005). Informed consent was obtained from the legal surrogates of all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The legal surrogates of all participants have provided consent for the results of this study to be published.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests-Funding\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;This study did not receive any specific funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;D.W.: Research design, data collection, manuscript writing. X.D.: Data analysis, statistical processing, manuscript revision. T.F.: Research supervision, funding acquisition, final review. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;We thank the Department of Critical Care Rehabilitation and the Department of Critical Care Medicine of Ningxia Hui Autonomous Region Hospital of Integrated Traditional Chinese and Western Medicine for their support in this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGiacino, J. T. et al. Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. \u003cem\u003eNeurology\u003c/em\u003e \u003cb\u003e91\u003c/b\u003e (10), 450\u0026ndash;460 (2018).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKalmar, K. \u0026amp; Giacino, J. T. The JFK Coma Recovery Scale-Revised. \u003cem\u003eNeuropsychol. Rehabil\u003c/em\u003e. \u003cb\u003e15\u003c/b\u003e (3\u0026ndash;4), 454\u0026ndash;460 (2005).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchnakers, C. Update on diagnosis in disorders of consciousness. \u003cem\u003eExpert Rev. Neurother.\u003c/em\u003e \u003cb\u003e20\u003c/b\u003e (10), 997\u0026ndash;1004 (2020).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChiappa, K. H. \u0026amp; Hill, R. A. Short-latency somatosensory evoked potentials: interpretation. In: (ed Chiappa, K. H.) Evoked Potentials in Clinical Medicine. 3rd ed. Lippincott-Raven; :311\u0026ndash;338. (1997).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFischer, C., Luaute, J., Adeleine, P. \u0026amp; Morlet, D. Predictive value of sensory and cognitive evoked potentials for awakening from coma. \u003cem\u003eNeurology\u003c/em\u003e \u003cb\u003e63\u003c/b\u003e (4), 669\u0026ndash;673 (2004).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStockard, J. J., Stockard, J. E. \u0026amp; Sharbrough, F. W. Brainstem auditory evoked potentials in neurology: methodology, interpretation, clinical application. In: (ed Aminoff, M. J.) Electrodiagnosis in clinical neurology. 6th ed. Elsevier; :519\u0026ndash;552. (2012).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhou, G. P. et al. Prognostic Value of Brainstem Auditory Evoked Potentials in Patients with Severe Traumatic Brain Injury. \u003cem\u003eBiomed. Res. Int.\u003c/em\u003e \u003cb\u003e2021\u003c/b\u003e, 6615876 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEdlow, B. L., Claassen, J., Schiff, N. D. \u0026amp; Greer, D. M. Recovery from disorders of consciousness: mechanisms, prognosis and emerging therapies. \u003cem\u003eNat. Rev. Neurol.\u003c/em\u003e \u003cb\u003e17\u003c/b\u003e (3), 135\u0026ndash;156 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKondziella, D. et al. European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness. \u003cem\u003eEur. J. Neurol.\u003c/em\u003e \u003cb\u003e27\u003c/b\u003e (5), 741\u0026ndash;756 (2020).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBagnato, S. et al. Prognostic value of standard EEG in traumatic and non-traumatic disorders of consciousness following coma. \u003cem\u003eClin. Neurophysiol.\u003c/em\u003e \u003cb\u003e131\u003c/b\u003e (8), 1926\u0026ndash;1934 (2020).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSullivan, G. M. \u0026amp; Feinn, R. Using Effect Size-or Why the P Value Is Not Enough. \u003cem\u003eJ. Grad Med. Educ.\u003c/em\u003e \u003cb\u003e4\u003c/b\u003e (3), 279\u0026ndash;282 (2012).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBodien, Y. G. et al. Diagnosing level of consciousness: the limits of the Glasgow Coma Scale total score. \u003cem\u003eJ. Neurotrauma\u003c/em\u003e. \u003cb\u003e38\u003c/b\u003e (23), 3295\u0026ndash;3305 (2021).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Prolonged Disorders of Consciousness, Brainstem Auditory Evoked Potentials, Coma Recovery Scale-Revised, Unresponsive Wakefulness Syndrome, Minimally Conscious State, Small Sample Study","lastPublishedDoi":"10.21203/rs.3.rs-8113139/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8113139/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eBrainstem auditory evoked potentials (BAEP) provide an objective assessment of brainstem functional integrity. However, their characteristic profiles and clinical significance in patients with prolonged disorders of consciousness (pDOC) remain to be fully elucidated, especially in small, well-characterized cohorts.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThis study aimed to preliminarily characterize BAEP parameters in a small sample of pDOC patients and explore their relationship with consciousness levels.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eIn this cross-sectional study, 29 patients with pDOC (16 with unresponsive wakefulness syndrome [UWS] and 13 in a minimally conscious state [MCS]) were enrolled. BAEP recordings, neurological assessments using the Coma Recovery Scale-Revised (CRS-R), and medical record reviews were performed. BAEP parameters (wave latencies, interpeak latencies [IPLs]) were compared between UWS and MCS groups using Mann-Whitney U tests. Effect sizes (r) were calculated to quantify the magnitude of observed differences. Spearman correlation was used to assess the relationship between BAEP parameters and CRS-R scores.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eNo significant differences were observed in the latencies of wave I, wave III, the I\u0026ndash;III interpeak interval (IPL), the III\u0026ndash;V IPL, or the I\u0026ndash;V IPL between the unresponsive wakefulness syndrome (UWS) group and the minimally conscious state (MCS) group (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, the study revealed a trend toward prolongation in the latency of wave V and the I\u0026ndash;V IPL in the UWS group. Both wave V latency (r = \u0026minus;\u0026thinsp;0.342) and I\u0026ndash;V IPL (r = \u0026minus;\u0026thinsp;0.354) demonstrated moderate effect sizes, suggesting the presence of substantive differences in these measures between the two groups. Additionally, a moderate negative correlation was observed between the I\u0026ndash;V IPL and the total score of the Coma Recovery Scale\u0026ndash;Revised (CRS-R) (Spearman\u0026rsquo;s ρ = \u0026minus;\u0026thinsp;0.447, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eAlthough no significant differences were observed in the brainstem auditory evoked potential (BAEP) parameters between the two patient groups, the trend of prolonged I\u0026ndash;V interpeak interval (IPL) in the unresponsive wakefulness syndrome (UWS) group, along with its moderate correlation with the Coma Recovery Scale\u0026ndash;Revised (CRS-R) score, suggests that UWS patients may have more severe brainstem dysfunction. Therefore, BAEP remains a promising electrophysiological marker for assessing brainstem impairment in patients with prolonged disorders of consciousness (pDOC). Although these preliminary findings did not reach statistical significance in intergroup comparisons, they highlight the need for larger sample sizes in future studies to clarify the role of BAEP in the evaluation of consciousness disorders.\u003c/p\u003e","manuscriptTitle":"Analysis of Brainstem Auditory Evoked Potential Characteristics in Patients with Chronic Disorders of Consciousness: A Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-08 07:08:20","doi":"10.21203/rs.3.rs-8113139/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-29T12:02:11+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"270171949330694338508107031291200863835","date":"2026-01-21T18:13:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-21T01:20:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"329060170353668052519880169267816075096","date":"2026-01-18T00:05:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-10T19:58:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"223976076209076811806978298905285615226","date":"2025-12-08T20:37:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"294377578902835080508796978142299856737","date":"2025-12-02T19:55:17+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-02T19:24:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-02T19:12:44+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-19T17:33:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-18T09:37:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-11-18T09:30:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e666fa9d-4fea-4344-adad-a95742379b61","owner":[],"postedDate":"December 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":59008441,"name":"Health sciences/Medical research"},{"id":59008442,"name":"Health sciences/Neurology"},{"id":59008443,"name":"Biological sciences/Neuroscience"}],"tags":[],"updatedAt":"2026-04-19T17:23:30+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-08 07:08:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8113139","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8113139","identity":"rs-8113139","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}