【作者】 刘子龙；

【导师】 刘良；

【作者基本信息】 华中科技大学 ， 法医学， 2009， 博士

【摘要】 【背景】重型颅脑损伤（severe traumatic brain injury，sTBI）患者临床治疗终结后往往遗留广泛的认知功能损害，如注意缺陷、记忆减退、失语、计算不能等。智能障碍作为认知功能损害的最终表现可能长期持续存在。法医学鉴定时，准确有效地评估智能损害程度与伤残鉴定结论密切相关。中国修订韦氏成人智力量表（WAIS-RC）是使用最多的神经心理学测评工具，但该量表依赖伤者的言语和行为反应能力，对一些存在言语功能障碍、运动功能障碍或不完全配合的伤者采用标准化WAIS-RC测试常极为困难甚至无法施测，有时测验获得的WAIS-RC结果与鉴定所见临床表现明显不符。事件相关电位（Event-related potentials，ERP）作为评估大脑神经电生理活动的客观指标不仅可以实时检测大脑的认知功能，而且较少受被试主观动机的影响。文献报道一些特异性ERP成分可以反映信息加工速度、注意力和工作记忆更新，并与神经心理学测评量表存在显著相关性。因此，探讨使用多范式ERP技术评定智能损害严重程度的具体方法及其应用于法医学领域的可行性具有重要意义。【目的】参考WAIS-RC的测试内容，编制符合ERP检测要求的视/听觉Oddball任务、图片再认、图片命名和数字计算共五个刺激范式，选择健康志愿者和重型颅脑损伤志愿者为研究对象，观察各刺激范式所引出的ERP波形特征及其与WAIS-RC的相关性，并建立利用多个ERP指标推断智商的多元回归模型。【方法】采用Neuroscan ERP仪对29名重型颅脑损伤患者（外伤组，其中男性22人，女性7人）和46名健康志愿者（对照组，其中男性和女性各23人）进行视觉和听觉Oddball任务、图片再认、图片命名和数字计算五个刺激范式的实时检测及离线分析，并以WAIS-RC测定被试的智力水平；比较各刺激范式引出的ERP成分特征及其与WAIS-RC的相关性并筛选合适的ERP自变量建立多元回归方程。【结果】（1）外伤组被试的WAIS-RC各分测验量表分、IQ及MQ均值均显著低于对照组，下降约两个标准差（P＜0．01）。（2）Oddball范式引出的视觉P₃₀₀包括P2、N2和P3成分，听觉P₃₀₀包括N1、P2、N2和P3成分，视觉P3潜伏期长于听觉P3；外伤组P₃₀₀波形分化不良，波幅和潜伏期较对照组明显降低和延长（P＜0．01）；视、听觉P3潜伏期与FIQ呈负相关（r≈-0．30～-0．42，P＜0．05）。（3）图片再认范式的靶与非靶刺激呈现后可记录到潜伏期无显著性差异的二个正向波(P₁₇₀和P₅₀₀)，靶刺激的P₅₀₀波幅明显高于非靶（P＜0．01）；外伤组各成分的波幅、潜伏期均明显降低和延长（P＜0．01）。对照组和外伤组的P₅₀₀潜伏期与FIQ呈显著负相关（r=-0．62～-0．68，P＜0．01）。（4）图片命名Go/Nogo范式引出的ERP波形包括N1_pn、P2_pn、N2_pn和P3_pn成分，靶刺激P3_pn潜伏期较非靶刺激延长；外伤组分化欠佳，潜伏期延长，波幅下降；靶刺激P3_pn潜伏期与FIQ存在显著负相关（r=-0．68～-0．76，P＜0．01）。（5）数字计算的算式与正确/错误答案图片间隔呈现引出的ERP波形包括N_1c、P_2c、N_2c和P_3c，正确答案的P_3c波幅最高，错误答案的P_3c潜伏期最长；外伤组波幅降低、潜伏期延长；错误答案的P_3c潜伏期与FIQ呈中度负相关（r=-0．45～-0．60，P＜0．01）。（6）纳入智商推断回归分析的自变量为AP₃₀₀、VP₃₀₀、P₅₀₀、P_3c和P_3pn的潜伏期，对照组可建立5个推断模型，AP₃₀₀Lat、P₅₀₀Lat、P_3cLat和P_3pnLat联合可解释58％的FIQ方差变异；外伤组可建立8个模型，P₅₀₀Lat、P_3cLat、P_3pnLat和VP₃₀₀Lat联合可解释73％的FIQ方差变异；各推断模型无明显共线性；多范式ERP推断的FIQ与实测FIQ无显著统计学差异（差值小于1个标准差）。【结论】重型颅脑外伤患者临床治疗终结后IQ仍显著低于对照组（2个标准差以上）；视觉和听觉Oddball任务、图片再认、图片命名和数字计算范式的靶刺激均可引出特征性ERP波形——AP₃₀₀、VP₃₀₀、P₅₀₀、P_3pn和P_3c，其潜伏期与WAIS-RC智商呈显著负相关；外伤组波形分化不良，潜伏期延长，波幅降低；采用AP₃₀₀、VP₃₀₀、P₅₀₀、P_3c和P_3pn多个指标建立的模型推断的FIQ非常接近实测值，具有一定的法医学应用价值。更多还原

【Abstract】 【Background】After recovery from the acute phase of severe traumatic brain injury（sTBI）,patients usually have extensive cognitive impairments,including attention deficit,hypomnesia,aphasia and anarithmia,and so on.Intelligence disorder is commonlyimpaired in a TBI patient,and it may persist for several years.In forensic practice,accurateassessment of a patient’s intellectual ability is essential in the determination of handicapdegree.Wechsler Adult Intelligence Scale （WAIS） is the most frequently administeredneuropsychological test,but this test entails verbal or behavioral responses from the patient.Unfortunately,following neurological trauma,patients tend to suffer from speech and/ormotor disabilities,which render the assessment of cognitive functioning with standardneuropsychological tests difficult or impossible.Especially,forensic assessment of braininjury is likely invalid if the subject involved is not 100% honest,or refuses to cooperate.Marked discrepancy could be found between the test performance or claimed disability andthe objective findings.Event-related potentials （ERP） is of value in the neuropsychologicalevaluation by providing a neurophysiologic index of patients’ on-line cognitive functioning,and it is less affected by motivational factors than behavioral measurement.Somecomponents of ERP were reported to be able to reflect the information processing speeds,attention capacity,and the updating of working memory,and were significantly correlatedwith the intelligence as assessed by standardized neuropsychological tests.Some forensicresearchers have recognized the value to evaluate the severity of intelligence disorder in theevaluation of neuropsychological functions by ERP.【Objectives】According to the contents of WAIS-RC and the theory of ERP,five ERPstimulus paradigms were developed,including visual and auditory Oddball,picture-recognition,pictures naming and digital calculation.These studies was to investigate thefeatures of ERP elicited by these paradigms in healthy persons and patients with sTBI,and evaluate the correlations between intelligence quotient and the components of ERP,anddevelop some regression models for estimating intellectual status by using some ERPindexes of these paradigms in forensic expertise.【Methods】EEG were recorded on-line in 29 patients with intelligence impairmentinduced by sTBI （sTBI group） and 46 healthy volunteers （the controls） by Neuroscan’s ERP,while they were asked to performance on the 5 paradigms （compare target and non-targetpictures and judge whether it was target stimulus）,including visual and auditory Oddballtask,picture-recognition,pictures naming and digital calculation,and the character of ERPcomponents were analyzed off-line for these paradigms effects.Intelligence quotient （IQ）was measured using the Wechsler Adult Intelligence Scale-Revised in China （WAIS-RC）.【Results】（1） The sTBI patients’ scores of all sub-tests and mean intelligence quotientin WAIS-RC were significantly lower than those of the controls （P＜0.01）.（2） Thecomponents of visual P₃₀₀ elicited by Oddball paradigm included P2,N2 and P3,andauditory P₃₀₀ included N1,P2,N2 and P3.P3 from auditory stimuli was shorter in latencythan that from the visual stimuli.When compared to the control group,the mean latencyand amplitude of P₃₀₀ in sTBI patients were significantly longer and smaller （P＜0.01）.Thelatency of visual and auditory P3 was significantly negatively correlated with FIQ incontrols and sTBI patients （r≈-0.30～-0.42,P＜0.05）.（3） In the control group,P₁₇₀ andP₅₀₀ were two positive-going waves in the 170-ms and 500-ms post-stimulus range fortarget and non-target stimuli of picture recognition paradigm.There had no difference onthe latency of P₁₇₀ and P₅₀₀ between target and non-target stimuli,but P₅₀₀ amplitude oftarget stimulus was significantly higher than that of non-target stimulus （P＜0.01）.Compared to controls,the mean amplitude and latency of P₁₇₀ and P₅₀₀ of sTBI patients wassignificantly lower and prolonged （P＜0.01）.In control group and sTBI group,the latencyof P₅₀₀ was significant negatively correlated with IQ （r=-0.62～-0.68,P＜0.01）.（4） Thecomponents of ERP elicited by pictures naming paradigm included N1_pn,P2_pn,N2_pn andP3_pn,and the P3_pn latency of target stimulus was significantly prolonged than that ofnon-target stimulus （P＜0.01）.The mean amplitude and latency of P3_pn of sTBI patientswere significantly lower and prolonged than those of controls （P＜0.01）.The latency of P3_pn of target stimulus was negatively correlated with IQ （r=-0.68～-0.76,P＜0.01）.（5）The components of ERP elicited by digital calculation paradigm included N1_c,P2_c,N2_c andP3_c.The P3_c amplitude of correct answer stimulus was highest,while the P3_c latency oferror answer stimulus was longest （P＜0.01）.The mean amplitude and latency of P3_c ofsTBI patients were significantly lower and prolonged than those of controls （P＜0.01）.Thelatency of P3_c of error answer was negatively correlated with VIQ and FIQ （r=-0.45～-0.60,P＜0.01）.（6） The independent variables of regression equation for evaluating IQincluded the latency of AP₃₀₀、VP₃₀₀、P₅₀₀、P_3c and P_3pn.There had five models in controlgroup and eight models in sTBI group,and these regression equations had no significantcolinearity.When combined AP₃₀₀Lat、P₅₀₀Lat、P_3cLat and P_3pnLat in controls,the modelcould predict FIQ accounted for 58% of the variance,and when combined P₅₀₀Lat、P_3cLat、P_3pnLat and VP₃₀₀Lat in sTBI group,the model could predict FIQ accounted for 73% of thevariance.There was no significant difference between the FIQ evaluated by multi-paradigmERP and WAIS-RC.【Conclusion】The patients of sTBI had significant intelligence impairment.Thelatency and amplitude of components of ERP elicited by the paradigms of visual andauditory Oddball task,picture-recognition,pictures naming and digital calculation weresensitive to the cognitive deficits,and the latency of AP₃₀₀,VP₃₀₀,P₅₀₀,P_3c and P_3pn weresignificantly correlated with IQ.Multi-paradigm ERP may be an objective method forassessing the severity of intelligence impairment by in forensic practice.更多还原