背景 运动不耐受（motion sickness，MS）/运动病（motion sickness disorder，MSD）一直是研究人员关注的热点问题。2021年，Bárány协会分类委员会首次定义了MSD的概念，对于大多数临床医师而言，这是一种全新的临床疾病概念。随着最新诊断标准的颁布，此类疾病也亟待我们进一步的深入研究。目前，国内外对基于Bárány协会诊断标准纳入MSD患者进行的相关研究颇少，在此背景下，本研究拟通过对MSD患者临床症状学、前庭功能、神经影像学及其相关性的多维度评价，探讨可能的发病机制，以期为MSD的精准诊治提供科学的依据。 目的 多维度探讨MSD患者症状学特征、外周前庭功能情况，并进一步分析神经影像学特征及其与临床的相关性，初步探讨MSD发病的可能神经机制。 方法 基于国际Bárány协会诊断标准，本研究纳入20例MSD患者及20例性别年龄相匹配、无MS病史的健康对照（HC）。（1）临床症状学及外周前庭功能评估：应用MS易感性问卷简版（MSSQ-short）、MS评估问卷（MSAQ）、视觉诱发运动不耐受问卷（VIMSSQ）、恐高量表（AQ）进行症状学评价；完善外周前庭功能评价，包括双温试验及双温刺激诱发症状评估（MSAQ-CI）、视频头脉冲试验（vHIT）、前庭诱发肌源性电位（VEMP）、主观视觉垂直/水平（SVV/SVH），对比分析两组受试者前庭功能差异。（2）神经影像学评估：应用低频振幅（ALFF）、局部一致性（ReHo）进行静息态局部脑功能活动分析，应用基于体素的形态学测量分析（VBM）精确识别脑结构变化，对MSD患者异常脑区进行定位，将异常脑区作为种子点，进行基于种子点的功能连接分析（FC）。（3）症状学与影像学相关分析：提取异常脑区灰质体积（GMV）与MSSQ-short、MSAQ、VIMSSQ、AQ问卷进行相关分析。 结果 （1）症状学特征及外周前庭功能分析：与HC组相比，（a）MSD组MSSQ-short，MSAQ，VIMSSQ，AQ得分均显著增高。（b）MSD患者对双温刺激敏感，双温不耐受发生率、症状严重程度和持续时间均显著增加，MSAQ-CI与MSAQ、MSSQ-short存在较强正相关关系。（c）前庭检查中，MSD组oVEMP异常率增加，P波潜伏期延长，P波潜伏期与MSSQ-short、MSAQ、双温不耐受症状持续时间均呈正相关。双温试验、vHIT、SVV/SVH异常率无明显差异。 （2）静息态脑功能和结构改变分析：与HC组相比，（a）MSD患者局部脑功能活动的ALFF、ReHo指标无明显差异。（b）MSD患者左侧海马、岛叶、杏仁核、颞上回和广泛额叶皮层，包括两侧背外侧前额叶（DLPFC）、额叶眼动区（FEF）、辅助运动区（SMA）的GMV增加。（c）MSD组左侧岛叶与左侧扣带回功能连接增强。 （3）MSD临床症状学与影像学相关分析：VBM和MSAQ相关分析发现，左侧额上回与胃肠道症状得分、两侧SMA与MSAQ总分及头晕症状得分、右侧内侧额上回与头晕症状得分、左侧颞上回与外周症状得分均呈中度正相关。针对双温不耐受的MSAQ-CI相关分析中，左侧额上回与MSAQ-CI总分及胃肠道症状得分、右侧SMA与头晕症状得分呈中度正相关。与视觉诱发MS的相关分析中，左侧额中回与VIMSSQ得分呈中度正相关。与恐高的相关分析中，左侧杏仁核、海马与AQ-回避得分呈中度正相关。 结论 （1）MSD患者视觉诱发MS、恐高及双温刺激不耐受现象亦较为常见；MSD患者存在半规管和耳石器功能的“分离”现象，推测可能参与MSD的多感觉整合异常、影响“内部模型”的更新机制。 （2）MSD患者静息态脑功能（正常）与脑灰质结构增厚/功能连接增强的“分离现象”，提示MSD可能存在中枢可塑性代偿（敏化）机制，推测：（a）海马GMV增加可能是由感觉传入与预期“内部模型”的失匹配引起的海马灰质可塑性变化。（b）以岛叶为核心的广泛内感受神经网络出现皮质可塑性变化，介导MSD相关剧烈胃肠道症状；杏仁核可能参与预期焦虑和回避行为的发生。（c）广泛额叶皮层灰质体积的增厚与MSD的胃肠道、头晕/眩晕、视觉诱发MS等症状密切相关。

Background: Motion sickness (MS) and motion sickness disorder (MSD) is a widespread public health problems. In 2021, the Bárány Society defined the diagnostic criteria of MSD for the first time, which is a new clinical entity that deserves attention. Currently, there are rare clinical studies that include subjects with MSD according to diagnostic criteria. Also, there is a lack of domestic and international studies on the symptomatology, vestibular function, and neuroimaging of MSD, which deserve further attention. Objective: The study aimed to investigate clinical presentation and comprehensive assessment of vestibular function in patients with MSD, and to further analyze the neuroimaging changes and their correlation with clinical features to explore the underlying neurological mechanisms of MSD, with a view to providing ideas for future treatment directions. Methods: Based on the Bárány Society diagnostic criteria, 20 patients with MSD and 20 gender-age matched healthy controls (HC) without a history of MS were included. (1) Clinical presentation and peripheral vestibular assessments: The motion sickness susceptibility questionnaire-short (MSSQ-short), motion sickness assessment questionnaire (MSAQ), visually induced motion sickness disorder (VIMSSQ), and acrophobia questionnaire (AQ) were assessed, and correlation analysis was performed. A series of vestibular function tests, including the caloric test and caloric evoked symptoms assessment (MSAQ-CI), video head impulse test (vHIT), vestibular evoked myogenic potential (VEMP), and subjective visual vertical/horizontal (SVV/SVH), were conducted to compare the differences in vestibular function between MSD and HC group. (2) Neuroimaging assessments: The amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were applied to detect resting-state regional brain functional activity. Voxel-based morphometry (VBM) was applied to accurately reveal brain structural changes and to localize abnormal brain regions in MSD patients. Abnormal brain regions in VBM were selected as seeds for resting-state seed-based functional connectivity (FC) analysis. (3) The correlation between grey matter volume (GMV) of abnormal brain regions and clinical questionnaires was analyzed. Results: (1) Clinical presentation and comprehensive assessment of vestibular function: (a) MSSQ-short, MSAQ, VIMSSQ, and AQ scores were significantly higher in the MSD group than in the HC group. (b) MSD group was more sensitive to caloric stimulation, and the incidence of caloric intolerance, the severity of caloric evoked symptoms and duration of symptoms were significantly higher than those in the HC group. The MSAQ-CI showed a positive correlation with MSAQ and MSSQ-short. (c) In vestibular tests, the abnormal rate of oVEMP was significantly higher in the MSD group than HC group, and the latency of the P-wave was delayed. P-wave latency in oVEMP was positively correlated with MSSQ-short, MSAQ scores, and duration of caloric intolerance. There were no significant differences in the results of caloric test, vHIT, and SVV/SVH results between the two groups. (2) Resting-state functional and structural brain changes studies: (a) There were no significant changes in regional brain activity between two groups. (b) Compared with HC group, MSD group had increased GMV in the left temporal lobe (temporal pole: superior temporal gyrus), left insula, left amygdala, left hippocampus, and extensive frontal cortex like bilateral dorsolateral prefrontal cortex (DLPFC), frontal eye field (FEF) and supplementary motor area (SMA). (c) Compared with HC group, MSD group showed increased functional connectivity between left insula and left anterior cingulate gyrus. (3) Correlation analysis of clinical characteristics and neuroimaging: For patients with MSD, the SMA showed a moderate positive correlation with MSAQ-Total and MSAQ-Central scores, the left superior frontal gyrus showed a moderate positive correlation with MSAQ-Gastric, the right medial superior frontal gyrus showed a moderate positive correlation with MSAQ-Central, and the left superior temporal gyrus showed a moderate positive correlation with MSAQ-Peripheral. For MSAQ-CI symptom assessment after caloric test, the left superior frontal gyrus was moderately positively correlated with MSAQ-CI-Total, and the right SMA was moderately positively correlated with MSAQ-CI-Central. The left middle frontal gyrus was moderately positively correlated with VIMSSQ scores. The left amygdala and hippocampus were moderately positively correlated with AQ-avoidance scores. Conclusion (1) Visually induced MS, agoraphobic symptoms and caloric intolerance are also common in patients with MSD. The presence of a "separation" between the canal and otolith function in patients with MSD may be related to the abnormal multisensory integration and the updating mechanism of the internal model. (2) The "separation phenomenon" of normal resting-state regional brain function and abnormal thickened grey matter structures with increased functional connectivity in MSD patients suggests the compensatory mechanisms and cortex plasticity in MSD, we hypothesized that, (a) Changes in hippocampal grey matter plasticity in MSD patients, which may be an adaptive mechanism for the mismatch between multisensory afferents and the expected "internal model" during motor stimulation. (b) Thickened interoceptive neural networks with the insula as the core might mediate the onset of severe nausea. The amygdala may be involved in anticipatory anxiety and avoidance behaviors for motion stimulus. (c) The thickening of GMV in the extensive frontal cortex is closely related to the gastrointestinal symptoms, dizziness/vertigo, and visually induced MS of MSD.

第一章 文献综述 1
1.1 MSD假说理论 1
1.2 病理生理学机制 5
1.3 症状学/问卷研究 6
1.4 外周前庭功能评价 7
1.5 神经影像学评价 8
1.6 诊断和治疗策略 10
第二章 引言 12
2.1 选题背景及意义 12
2.2 科学问题的构建及研究目的 12
2.3 研究方法 13
2.4 论文结构安排 15
第三章 MSD症状学特征及外周前庭功能分析 16
3.1 研究对象与方法 16
3.1.1 研究对象 16
3.1.2 问卷评估 17
3.1.3 前庭检查 17
3.1.4 统计分析 19
3.2 结果 19
3.2.1 基线资料 19
3.2.2 症状学特征 20
3.2.3 前庭功能评价结果 22
3.3 讨论 26
3.3.1 VIMS易感性和恐高相关性分析 26
3.3.2 MSD患者双温不耐受易感性分析 26
3.3.3 MSD半规管和耳石器的功能“分离” 28
3.4 小结 29
第四章 静息态脑功能及脑灰质结构改变研究 30
4.1 研究方法 30
4.1.1 研究对象 30
4.1.2 MRI数据采集 30
4.1.3 静息态局部脑功能数据处理及分析 31
4.1.4 基于体素的形态学数据处理及分析 32
4.1.5 静息态脑功能连接数据处理及分析 33
4.2 研究结果 34
4.2.1 静息态局部脑功能活动结果 34
4.2.2 基于体素的形态学分析结果 34
4.2.3 静息态功能连接分析结果 36
4.2.4 异常脑区与临床评分的相关分析 36
4.3 讨论 39
4.3.1 海马“比较器”在感觉失匹配的重要作用 39
4.3.2 内感受与MS恶心相关皮质可塑性改变 40
4.3.3 MSD临床症状学与影像学相关性分析 42
4.3.4 外周前庭评价与影像学改变相关性探讨 44
4.3.5 GMV改变的意义 45
4.4 小结 46
第五章 结论及展望 47
5.1 研究结论 47
5.2 研究局限性及展望 48
参考文献 49
致谢 58
北京大学学位论文原创性声明和使用授权说明 59
个人简历、在学期间发表的学术论文与研究成果 60
学位论文答辩委员会名单 61
学位论文答辩委员会决议书 62

[1] CHA Y H, GOLDING J F, KESHAVARZ B, et al. Motion sickness diagnostic criteria: Consensus Document of the Classification Committee of the Barany Society [J]. J Vestib Res, 2021, 31(5): 327-344.

[2] CASERMAN P, GARCIA-AGUNDEZ A, GáMEZ ZERBAN A, et al. Cybersickness in current-generation virtual reality head-mounted displays: systematic review and outlook [J]. Virtual Reality, 2021, 25(4): 1153-1170.

[3] GOLDING J F. Motion sickness [J]. Handb Clin Neurol, 2016, 137: 371-390.

[4] 宋宁译, 邢玥译, 李康之译, 等. 运动不耐受诊断标准:Bárány协会分类委员会共识文件 [J]. 神经损伤与功能重建, 2022, 17(12):9.

[5] KOCH A, CASCORBI I, WESTHOFEN M, et al. The Neurophysiology and Treatment of Motion Sickness [J]. Dtsch Arztebl Int, 2018, 115(41): 687-696.

[6] TAL D, WIENER G, SHUPAK A. Mal de debarquement, motion sickness and the effect of an artificial horizon [J]. J Vestib Res, 2014, 24(1): 17-23.

[7] OMAN C M. Are evolutionary hypotheses for motion sickness "just-so" stories? [J]. J Vestib Res, 2012, 22(2): 117-127.

[8] WADA T. Computational Model of Motion Sickness Describing the Effects of Learning Exogenous Motion Dynamics [J]. Frontiers in systems neuroscience, 2021, 15: 634604.

[9] BLES W, BOS J E, DE GRAAF B, et al. Motion sickness: only one provocative conflict? [J]. Brain research bulletin, 1998, 47(5): 481-487.

[10] DOBIE T. Physiological Mechanisms Underlying Motion Sickness [M]. 2019: 93-111.

[11] ZHANG L L, WANG J Q, QI R R, et al. Motion Sickness: Current Knowledge and Recent Advance [J]. CNS Neurosci Ther, 2016, 22(1): 15-24.

[12] CARRIOT J, BROOKS J X, CULLEN K E. Multimodal integration of self-motion cues in the vestibular system: active versus passive translations [J]. J Neurosci, 2013, 33(50): 19555-19566.

[13] ROLLS E T. The cingulate cortex and limbic systems for emotion, action, and memory [J]. Brain Struct Funct, 2019, 224(9): 3001-3018.

[14] ZOU D, NISHIMARU H, MATSUMOTO J, et al. Experience-Related Changes in Place Cell Responses to New Sensory Configuration That Does Not Occur in the Natural Environment in the Rat Hippocampus [J]. Front Pharmacol, 2017, 8: 581.

[15] WOOD C D, STEWART J J, WOOD M J, et al. Habituation and motion sickness [J]. Journal of clinical pharmacology, 1994, 34(6): 628-634.

[16] WANG J, LIU J, PAN L, et al. Storage of passive motion pattern in hippocampal CA1 region depends on CaMKII/CREB signaling pathway in a motion sickness rodent model [J]. Sci Rep, 2017, 7: 43385.

[17] LAWSON B. Motion Sickness Symptomatology and Origins [M]. 2014: 531-600.

[18] MORROW G R. The effect of a susceptibility to motion sickness on the side effects of cancer chemotherapy [J]. Cancer, 1985, 55(12): 2766-2770.

[19] TAKEDA N, MORITA M, HORII A, et al. Neural mechanisms of motion sickness [J]. J Med Invest, 2001, 48(1-2): 44-59.

[20] YATES B J, CATANZARO M F, MILLER D J, et al. Integration of vestibular and emetic gastrointestinal signals that produce nausea and vomiting: potential contributions to motion sickness [J]. Exp Brain Res, 2014, 232(8): 2455-2469.

[21] YATES B J, BOLTON P S, MACEFIELD V G. Vestibulo-sympathetic responses [J]. Compr Physiol, 2014, 4(2): 851-887.

[22] NGAMPRAMUAN S, CERRI M, DEL VECCHIO F, et al. Thermoregulatory correlates of nausea in rats and musk shrews [J]. Oncotarget, 2014, 5(6): 1565-1575.

[23] NALIVAIKO E, RUDD J A, SO R H. Motion sickness, nausea and thermoregulation: The "toxic" hypothesis [J]. Temperature (Austin), 2014, 1(3): 164-171.

[24] FULLER P M, JONES T A, JONES S M, et al. Neurovestibular modulation of circadian and homeostatic regulation: vestibulohypothalamic connection? [J]. Proc Natl Acad Sci U S A, 2002, 99(24): 15723-15728.

[25] GOLDING J F. Predicting individual differences in motion sickness susceptibility by questionnaire [J]. Personality and Individual Differences, 2006, 41(2): 237-248.

[26] BALABAN C D, JACOB R G. Background and history of the interface between anxiety and vertigo [J]. J Anxiety Disord, 2001, 15(1-2): 27-51.

[27] BRIZZEE K R, IGARASHI M. Effect of macular ablation on frequency and latency of motion-induced emesis in the squirrel monkey [J]. Aviat Space Environ Med, 1986, 57(11): 1066-1070.

[28] CHEUNG B S, HOWARD I P, MONEY K E. Visually-induced sickness in normal and bilaterally labyrinthine-defective subjects [J]. Aviat Space Environ Med, 1991, 62(6): 527-531.

[29] SHAHAL B, NACHUM Z, SPITZER O, et al. Computerized dynamic posturography and seasickness susceptibility [J]. The Laryngoscope, 1999, 109(12): 1996-2000.

[30] BROWNLEE W J, SWANTON J K, ALTMANN D R, et al. Earlier and more frequent diagnosis of multiple sclerosis using the McDonald criteria [J]. J Neurol Neurosurg Psychiatry, 2015, 86(5): 584-5.

[31] PAILLARD A C, QUARCK G, PAOLINO F, et al. Motion sickness susceptibility in healthy subjects and vestibular patients: effects of gender, age and trait-anxiety [J]. J Vestib Res, 2013, 23(4-5): 203-209.

[32] BUYUKLU F, TARHAN E, OZLUOGLU L. Vestibular functions in motion sickness susceptible individuals [J]. Eur Arch Otorhinolaryngol, 2009, 266(9): 1365-1371.

[33] FOWLER C G, DALLAPIAZZA M, HADSELL K T. Vestibular Function and Motion Sickness Susceptibility: Videonystagmographic Evidence From Oculomotor and Caloric Tests [J]. American journal of audiology, 2020, 29(2): 188-198.

[34] GEDIK-SOYUYUCE O, YALINAY-DIKMEN P, KORKUT N. The effect of migraine and motion sickness on symptoms evoked by the caloric vestibular test [J]. J Vestib Res, 2022, 32(2): 135-144.

[35] NEUPANE A K, GURURAJ K, SINHA S K. Higher Asymmetry Ratio and Refixation Saccades in Individuals with Motion Sickness [J]. J Am Acad Audiol, 2018, 29(2): 175-186.

[36] KUMAR R T, SINHA S K. Head Impulse Test Paradigm and Suppression Head Impulse Test Paradigm in Individuals With and Without Motion Sickness [J]. American journal of audiology, 2021, 30(3): 518-523.

[37] CLéMENT G, RESCHKE M F. Relationship between motion sickness susceptibility and vestibulo-ocular reflex gain and phase [J]. J Vestib Res, 2018, 28(3-4): 295-304.

[38] XIE S J, CHEN W, JIA H B, et al. Ocular vestibular evoked myogenic potentials and motion sickness susceptibility [J]. Aviat Space Environ Med, 2012, 83(1): 14-18.

[39] FOWLER C G, SWEET A, STEFFEL E. Effects of motion sickness severity on the vestibular-evoked myogenic potentials [J]. J Am Acad Audiol, 2014, 25(9): 814-822.

[40] SINGH N K, PANDEY P, MAHESH S. Assessment of otolith function using cervical and ocular vestibular evoked myogenic potentials in individuals with motion sickness [J]. Ergonomics, 2014, 57(12): 1907-1918.

[41] TAL D, SHEMY S, KAMINSKI-GRAIF G, et al. Vestibular evoked myogenic potentials and motion sickness medications [J]. Clin Neurophysiol, 2016, 127(6): 2350-2354.

[42] DESSAI T, KRANTHI K, R M. Subjective vestibular test findings in individuals with motion sickness [J]. International Journal of Scientific Research, 2021: 63-65.

[43] WENZEL R, BARTENSTEIN P, DIETERICH M, et al. Deactivation of human visual cortex during involuntary ocular oscillations. A PET activation study [J]. Brain, 1996, 119 ( Pt 1): 101-110.

[44] BRANDT T, BARTENSTEIN P, JANEK A, et al. Reciprocal inhibitory visual-vestibular interaction. Visual motion stimulation deactivates the parieto-insular vestibular cortex [J]. Brain, 1998, 121 ( Pt 9): 1749-1758.

[45] BRANDT T, DIETERICH M. The vestibular cortex. Its locations, functions, and disorders [J]. Ann N Y Acad Sci, 1999, 871: 293-312.

[46] FRANK S M, BAUMANN O, MATTINGLEY J B, et al. Vestibular and visual responses in human posterior insular cortex [J]. J Neurophysiol, 2014, 112(10): 2481-2491.

[47] FRANK S M, WIRTH A M, GREENLEE M W. Visual-vestibular processing in the human Sylvian fissure [J]. J Neurophysiol, 2016, 116(2): 263-271.

[48] INDOVINA I, BOSCO G, RICCELLI R, et al. Structural connectome and connectivity lateralization of the multimodal vestibular cortical network [J]. Neuroimage, 2020, 222: 117247.

[49] SAKAI H, HARADA T, LARROQUE S K, et al. Left parietal involvement in motion sickness susceptibility revealed by multimodal magnetic resonance imaging [J]. Hum Brain Mapp, 2022, 43(3): 1103-1111.

[50] ARSHAD Q, CERCHIAI N, GOGA U, et al. Electrocortical therapy for motion sickness [J]. Neurology, 2015, 85(14): 1257-1259.

[51] NAPADOW V, SHEEHAN J D, KIM J, et al. The brain circuitry underlying the temporal evolution of nausea in humans [J]. Cereb Cortex, 2013, 23(4): 806-813.

[52] CRAIG A D. How do you feel? Interoception: the sense of the physiological condition of the body [J]. Nat Rev Neurosci, 2002, 3(8): 655-666.

[53] WIENS S. Interoception in emotional experience [J]. Curr Opin Neurol, 2005, 18(4): 442-447.

[54] CRITCHLEY H D, WIENS S, ROTSHTEIN P, et al. Neural systems supporting interoceptive awareness [J]. Nat Neurosci, 2004, 7(2): 189-195.

[55] BEISSNER F, MEISSNER K, BAR K J, et al. The autonomic brain: an activation likelihood estimation meta-analysis for central processing of autonomic function [J]. J Neurosci, 2013, 33(25): 10503-10511.

[56] LACOUNT L T, BARBIERI R, PARK K, et al. Static and dynamic autonomic response with increasing nausea perception [J]. Aviat Space Environ Med, 2011, 82(4): 424-433.

[57] MUTH E R. Motion and space sickness: intestinal and autonomic correlates [J]. Auton Neurosci, 2006, 129(1-2): 58-66.

[58] SCLOCCO R, KIM J, GARCIA R G, et al. Brain Circuitry Supporting Multi-Organ Autonomic Outflow in Response to Nausea [J]. Cereb Cortex, 2016, 26(2): 485-497.

[59] TOSCHI N, KIM J, SCLOCCO R, et al. Motion sickness increases functional connectivity between visual motion and nausea-associated brain regions [J]. Auton Neurosci, 2017, 202: 108-113.

[60] BRONSTEIN A M, GOLDING J F, GRESTY M A. Visual Vertigo, Motion Sickness, and Disorientation in Vehicles [J]. Semin Neurol, 2020, 40(1): 116-129.

[61] WIBBLE T, ENGSTROM J, VERRECCHIA L, et al. The effects of meclizine on motion sickness revisited [J]. Br J Clin Pharmacol, 2020, 86(8): 1510-1518.

[62] HOUSTON B T, CHOWDHURY Y S. Meclizine [M]. StatPearls. Treasure Island (FL). 2022.

[63] DORON O, SAMUEL O, KARFUNKEL-DORON D, et al. Scopolamine Treatment and Adaptation to Airsickness [J]. Aerosp Med Hum Perform, 2020, 91(4): 313-317.

[64] RIAD M, HITHE C C. Scopolamine [M]. StatPearls. Treasure Island (FL). 2022.

[65] POLYMEROPOULOS V M, CZEISLER M E, GIBSON M M, et al. Tradipitant in the Treatment of Motion Sickness: A Randomized, Double-Blind, Placebo-Controlled Study [J]. Front Neurol, 2020, 11: 563373.

[66] WEECH S, WALL T, BARNETT-COWAN M. Reduction of cybersickness during and immediately following noisy galvanic vestibular stimulation [J]. Exp Brain Res, 2020, 238(2): 427-437.

[67] GALVEZ-GARCIA G, ALDUNATE N, BASCOUR-SANDOVAL C, et al. Decreasing motion sickness by mixing different techniques [J]. Appl Ergon, 2020, 82: 102931.

[68] GRIFFIN M J, NEWMAN M M. Visual field effects on motion sickness in cars [J]. Aviat Space Environ Med, 2004, 75(9): 739-748.

[69] YEN PIK SANG F D, BILLAR J P, GOLDING J F, et al. Behavioral methods of alleviating motion sickness: effectiveness of controlled breathing and a music audiotape [J]. J Travel Med, 2003, 10(2): 108-111.

[70] KUIPER O X, BOS J E, DIELS C, et al. Knowing what's coming: Anticipatory audio cues can mitigate motion sickness [J]. Appl Ergon, 2020, 85: 103068.

[71] GIANAROS P J, MUTH E R, MORDKOFF J T, et al. A questionnaire for the assessment of the multiple dimensions of motion sickness [J]. Aviat Space Environ Med, 2001, 72(2): 115-119.

[72] KESHAVARZ B, MUROVEC B, MOHANATHAS N, et al. The Visually Induced Motion Sickness Susceptibility Questionnaire (VIMSSQ): Estimating Individual Susceptibility to Motion Sickness-Like Symptoms When Using Visual Devices [J]. Human factors, 2023, 65(1): 107-24.

[73] COHEN D C. Comparison of self-report and overt-behavioral procedures for assessing acrophobia [J]. Behavior therapy, 1977, 8(1): 17-23.

[74] 孔净雅. 虚拟现实暴露治疗对恐高症的作用与脑机制研究 [硕士学位论文].南京：南京师范大学心理学院 ,2020.

[75] SHEPARD N T, JACOBSON G P. The caloric irrigation test [J]. Handb Clin Neurol, 2016, 137: 119-131.

[76] LI Z Y, SHEN B, SI L H, et al. Clinical characteristics of definite vestibular migraine diagnosed according to criteria jointly formulated by the Barany Society and the International Headache Society [J]. Braz J Otorhinolaryngol, 2022, 88: 147-154.

[77] 赵媛, 陈太生, 王巍, 等. 主观视觉重力线在前庭代偿评定中的应用初探 [J]. 中华耳鼻咽喉头颈外科杂志, 2016, (5): 6.

[78] KANDEL E R, KOESTER J D, MACK S H, et al. The Vestibular System [M]. Principles of Neural Science, 6e. New York, NY; McGraw Hill. 2021.

[79] BARMACK N H. Central vestibular system: vestibular nuclei and posterior cerebellum [J]. Brain Res Bull, 2003, 60(5-6): 511-541.

[80] COELHO C, SILVA J, PEREIRA A, et al. Visual-vestibular and postural analysis of motion sickness, panic, and Acrophobia [J]. Acta Neuropsychologica, 2017, 15: 21-33.

[81] TEGGI R, COMACCHIO F, FORNASARI F, et al. Height intolerance between physiological mechanisms and psychological distress: a review of literature and our experience [J]. Acta Otorhinolaryngol Ital, 2019, 39(4): 263-268.

[82] COELHO C M, WALLIS G. Deconstructing acrophobia: physiological and psychological precursors to developing a fear of heights [J]. Depress Anxiety, 2010, 27(9): 864-870.

[83] COELHO C M, BALABAN C D. Visuo-vestibular contributions to anxiety and fear [J]. Neurosci Biobehav Rev, 2015, 48: 148-159.

[84] BRANDT T, ARNOLD F, BLES W, et al. The mechanism of physiological height vertigo. I. Theoretical approach and psychophysics [J]. Acta oto-laryngologica, 1980, 89(5-6): 513-523.

[85] British Society of Audiology (BSA). Recommended Procedure: The Caloric Test. Berkshire. UK: British Society of Audiology; 2010.

[86] JEONG S H, OH S Y, KIM H J, et al. Vestibular dysfunction in migraine: effects of associated vertigo and motion sickness [J]. J Neurol, 2010, 257(6): 905-912.

[87] GOLDING J F, MUELLER A G, GRESTY M A. A motion sickness maximum around the 0.2 Hz frequency range of horizontal translational oscillation [J]. Aviat Space Environ Med, 2001, 72(3): 188-192.

[88] UCHINO Y, SASAKI M, SATO H, et al. Otolith and canal integration on single vestibular neurons in cats [J]. Experimental brain research, 2005, 164(3): 271-285.

[89] YAKUSHIN S B, RAPHAN T, COHEN B. Spatial properties of central vestibular neurons [J]. Journal of neurophysiology, 2006, 95(1): 464-478.

[90] MACNEILAGE P R, TURNER A H, ANGELAKI D E. Canal-otolith interactions and detection thresholds of linear and angular components during curved-path self-motion [J]. Journal of neurophysiology, 2010, 104(2): 765-773.

[91] ASHBURNER J, FRISTON K J. Voxel-based morphometry-the methods [J]. Neuroimage, 2000, 11(6 Pt 1): 805-821.

[92] CHAO-GAN Y, YU-FENG Z. DPARSF: A MATLAB Toolbox for "Pipeline" Data Analysis of Resting-State fMRI [J]. Front Syst Neurosci, 2010, 4: 13.

[93] LOPEZ C, BLANKE O. The thalamocortical vestibular system in animals and humans [J]. Brain Res Rev, 2011, 67(1-2): 119-146.

[94] CULLEN K E. Physiology of central pathways [J]. Handbook of clinical neurology, 2016, 137: 17-40.

[95] MARCELLI V, ESPOSITO F, ARAGRI A, et al. Spatio-temporal pattern of vestibular information processing after brief caloric stimulation [J]. Eur J Radiol, 2009, 70(2): 312-316.

[96] DIETERICH M, BENSE S, LUTZ S, et al. Dominance for vestibular cortical function in the non-dominant hemisphere [J]. Cereb Cortex, 2003, 13(9): 994-1007.

[97] SAH P, FABER E S, LOPEZ DE ARMENTIA M, et al. The amygdaloid complex: anatomy and physiology [J]. Physiol Rev, 2003, 83(3): 803-834.

[98] BRANDT T, SCHAUTZER F, HAMILTON D A, et al. Vestibular loss causes hippocampal atrophy and impaired spatial memory in humans [J]. Brain, 2005, 128(Pt 11): 2732-2741.

[99] BADRE D, NEE D E. Frontal Cortex and the Hierarchical Control of Behavior [J]. Trends in cognitive sciences, 2018, 22(2): 170-188.

[100] MILNER A D, GOODALE M A. Two visual systems re-viewed [J]. Neuropsychologia, 2008, 46(3): 774-785.

[101] MIHARA M, MIYAI I, HATAKENAKA M, et al. Role of the prefrontal cortex in human balance control [J]. Neuroimage, 2008, 43(2): 329-336.

[102] SLOBOUNOV S, HALLETT M, STANHOPE S, et al. Role of cerebral cortex in human postural control: an EEG study [J]. Clin Neurophysiol, 2005, 116(2): 315-323.

[103] HUFNER K, STRUPP M, SMITH P, et al. Spatial separation of visual and vestibular processing in the human hippocampal formation [J]. Ann N Y Acad Sci, 2011;1233:177-186.

[104] VAN BUREN J M. The abdominal aura. A study of abdominal sensations occurring in epilepsy and produced by depth stimulation [J]. Electroencephalogr Clin Neurophysiol, 1963, 15: 1-19.

[105] PEDEMONTE M, GOLDSTEIN-DARUECH N, VELLUTI R A. Temporal correlations between heart rate, medullary units and hippocampal theta rhythm in anesthetized, sleeping and awake guinea pigs [J]. Auton Neurosci, 2003, 107(2): 99-104.

[106] PETROVICH G D, CANTERAS N S, SWANSON L W. Combinatorial amygdalar inputs to hippocampal domains and hypothalamic behavior systems [J]. Brain Res Brain Res Rev, 2001, 38(1-2): 247-289.

[107] AITAKE M, HORI E, MATSUMOTO J, et al. Sensory mismatch induces autonomic responses associated with hippocampal theta waves in rats [J]. Behav Brain Res, 2011, 220(1): 244-253.

[108] CRAIG A D. Interoception: the sense of the physiological condition of the body [J]. Curr Opin Neurobiol, 2003, 13(4): 500-505.

[109] MAYER E A, AZIZ Q, COEN S, et al. Brain imaging approaches to the study of functional GI disorders: a Rome working team report [J]. Neurogastroenterol Motil, 2009, 21(6): 579-596.

[110] CRAIG A D. How do you feel-now? The anterior insula and human awareness [J]. Nat Rev Neurosci, 2009, 10(1): 59-70.

[111] CAMERON O G. Interoception: the inside story-a model for psychosomatic processes [J]. Psychosom Med, 2001, 63(5): 697-710.

[112] MORROW G R, ANDREWS P L, HICKOK J T, et al. Vagal changes following cancer chemotherapy: implications for the development of nausea [J]. Psychophysiology, 2000, 37(3): 378-84.

[113] UDDIN L Q. Salience processing and insular cortical function and dysfunction [J]. Nature Reviews Neuroscience, 2015, 16(1): 55-61.

[114] DOWNAR J, CRAWLEY A P, MIKULIS D J, et al. A cortical network sensitive to stimulus salience in a neutral behavioral context across multiple sensory modalities [J]. J Neurophysiol, 2002, 87(1): 615-620.

[115] SEELEY W W, MENON V, SCHATZBERG A F, et al. Dissociable intrinsic connectivity networks for salience processing and executive control [J]. J Neurosci, 2007, 27(9): 2349-2356.

[116] GRAY M A, CRITCHLEY H D. Interoceptive basis to craving [J]. Neuron, 2007, 54(2): 183-186.

[117] CRITCHLEY H D. The human cortex responds to an interoceptive challenge [J]. Proc Natl Acad Sci U S A, 2004, 101(17): 6333-6334.

[118] HARRISON N A, GRAY M A, GIANAROS P J, et al. The embodiment of emotional feelings in the brain [J]. J Neurosci, 2010, 30(38): 12878-12884.

[119] LEDOUX J. The emotional brain, fear, and the amygdala [J]. Cell Mol Neurobiol, 2003, 23(4-5): 727-738.

[120] DAVIS M. The role of the amygdala in fear and anxiety [J]. Annu Rev Neurosci, 1992, 15: 353-375.

[121] HERMAN J P, CULLINAN W E. Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis [J]. Trends Neurosci, 1997, 20(2): 78-84.

[122] OTTO B, RIEPL R L, KLOSTERHALFEN S, et al. Endocrine correlates of acute nausea and vomiting [J]. Autonomic Neuroscience, 2006, 129(1): 17-21.

[123] 杨天使. 基于MRI的晕动敏感个体差异与脑结构及功能连接的相关性研究 [硕士学术论文].西安： 西安电子科技大学生命科学技术学院, 2017.

[124] NALIBOFF B D, BERMAN S, CHANG L, et al. Sex-related differences in IBS patients: central processing of visceral stimuli [J]. Gastroenterology, 2003, 124(7): 1738-1747.

[125] AIZAWA Y, MORISHITA J, KANO M, et al. Effect of repetitive transcranial magnetic stimulation on rectal function and emotion in humans [J]. J Gastroenterol, 2011, 46(9): 1071-1080.

[126] PAWLIK R J, PETRAKOVA L, CUEILLETTE A, et al. Inflammation shapes neural processing of interoceptive fear predictors during extinction learning in healthy humans [J]. Brain Behav Immun, 2023, 108: 328-339.

[127] NACHEV P, KENNARD C, HUSAIN M. Functional role of the supplementary and pre-supplementary motor areas [J]. Nat Rev Neurosci, 2008, 9(11): 856-869.

[128] FUKUSHIMA K, AKAO T, KURKIN S, et al. Role of vestibular signals in the caudal part of the frontal eye fields in pursuit eye movements in three-dimensional space [J]. Ann N Y Acad Sci, 2005, 1039: 272-282.

[129] CAMPANA G, COWEY A, CASCO C, et al. Left frontal eye field remembers "where" but not "what" [J]. Neuropsychologia, 2007, 45(10): 2340-2345.

[130] JENSEN O, BONNEFOND M, VANRULLEN R. An oscillatory mechanism for prioritizing salient unattended stimuli [J]. Trends in cognitive sciences, 2012, 16(4): 200-206.

[131] MARSHALL T R, O'SHEA J, JENSEN O, et al. Frontal eye fields control attentional modulation of alpha and gamma oscillations in contralateral occipitoparietal cortex [J]. J Neurosci, 2015, 35(4): 1638-1647.

[132] GU Y, CHENG Z, YANG L, et al. Multisensory Convergence of Visual and Vestibular Heading Cues in the Pursuit Area of the Frontal Eye Field [J]. Cereb Cortex, 2016, 26(9): 3785-3801.

[133] GU Y, ANGELAKI D E, DEANGELIS G C. Neural correlates of multisensory cue integration in macaque MSTd [J]. Nat Neurosci, 2008, 11(10): 1201-1210.

[134] BUTLER J S, SMITH S T, CAMPOS J L, et al. Bayesian integration of visual and vestibular signals for heading [J]. J Vis, 2010, 10(11): 23.

[135] FETSCH C R, POUGET A, DEANGELIS G C, et al. Neural correlates of reliability-based cue weighting during multisensory integration [J]. Nat Neurosci, 2011, 15(1): 146-154.

[136] ZHOU L, GU Y. Cortical Mechanisms of Multisensory Linear Self-motion Perception [J]. Neurosci Bull, 2023, 39(1): 125-137.

[137] EBATA S, SUGIUCHI Y, IZAWA Y, et al. Vestibular projection to the periarcuate cortex in the monkey [J]. Neurosci Res, 2004, 49(1): 55-68.

[138] LYNCH J C, TIAN J R. Cortico-cortical networks and cortico-subcortical loops for the higher control of eye movements [J]. Prog Brain Res, 2006, 151: 461-501.

[139] SUZUKI M, KITANO H, ITO R, et al. Cortical and subcortical vestibular response to caloric stimulation detected by functional magnetic resonance imaging [J]. Brain Res Cogn Brain Res, 2001, 12(3): 441-449.

[140] HELMCHEN C, KLINKENSTEIN J, MACHNER B, et al. Structural changes in the human brain following vestibular neuritis indicate central vestibular compensation [J]. Ann N Y Acad Sci, 2009, 1164: 104-115.

[141] ZU EULENBURG P, STOETER P, DIETERICH M. Voxel-based morphometry depicts central compensation after vestibular neuritis [J]. Ann Neurol, 2010, 68(2): 241-249.

[142] FASOLD O, VON BREVERN M, KUHBERG M, et al. Human Vestibular Cortex as Identified with Caloric Stimulation in Functional Magnetic Resonance Imaging [J]. NeuroImage, 2002, 17(3): 1384-1393.

[143] VITTE E, DEROSIER C, CARITU Y, et al. Activation of the hippocampal formation by vestibular stimulation: a functional magnetic resonance imaging study [J]. Exp Brain Res, 1996, 112(3): 523-526.

[144] DIETERICH M, BRANDT T. Functional brain imaging of peripheral and central vestibular disorders [J]. Brain, 2008, 131(10): 2538-2552.

[145] MIYAMOTO T, FUKUSHIMA K, TAKADA T, et al. Saccular stimulation of the human cortex: A functional magnetic resonance imaging study [J]. Neuroscience Letters, 2007, 423(1): 68-72.

[146] VIDAL P P, DE WAELE C, BAUDONNIERE P M, et al. Vestibular projections in the human cortex [J]. Ann N Y Acad Sci, 1999, 871: 455-457.

[147] DRAGANSKI B, GASER C, BUSCH V, et al. Neuroplasticity: changes in grey matter induced by training [J]. Nature, 2004, 427(6972): 311-312.

[148] TEUTSCH S, HERKEN W, BINGEL U, et al. Changes in brain gray matter due to repetitive painful stimulation [J]. Neuroimage, 2008, 42(2): 845-849.