阿尔茨海默病脑区葡萄糖代谢研究

目的:探讨阿尔茨海默病(AD)患者部分脑区葡萄糖代谢增强的原因及意义. 方法:符合美国精神障碍诊断和统计手册第4版(DSM-4)诊断标准的AD患者33例(AD组),其中17例伴有痴呆精神行为症状(BPSD),16例不伴有BPSD;以20名健康人作对照(对照组).两组均进行一般资料、简易智能状态(MMSE)、日常生活能力及Hachinski缺血指数量表测定,并进行脑正电子发射断层成像(PET)检查;应用SPM2000软件对两组PET图像进行基于像素的比较. 结果:与对照组相比,AD患者左侧额叶内侧回皮质下白质,左侧枕叶楔回灰质(Brodmann 17区)及皮质下白质,右侧小脑扁桃体等脑区葡萄糖代谢显著增强(P<0.001);与不伴有BPSD的AD患者相比,伴有BPSD的AD患者额叶、顶枕叶及颞叶下部等脑区的葡萄糖代谢显著减低(P<0.001),而枕叶、小脑等脑区的代谢显著增强(P<0.001). 结论:无论是否伴有BPSD的AD患者,其脑葡萄糖代谢均有弥漫性减低,但部分脑区呈代谢增强,增强区域主要位于旧皮质,次级运动及感知觉中枢,局部皮质下白质等.AD患者大脑新皮质代谢及高级功能容易受损,而旧皮质及皮质下结构的代谢及功能出现代偿性增强,与BPSD相一致.     

脑网络模块化分析用于阿尔茨海默病、路易体痴呆和帕金森病性痴呆脑葡萄糖代谢特点研究

目的本研究探究脑功能成像的脑网络模块化分析在阿尔茨海默病(AD),路易体痴呆(DLB),帕金森病性痴呆(PDD)脑网络模块参数特点和异同点,寻找疾病相关特异性脑葡萄糖代谢网络模块参数。方法回顾性分析复旦大学附属华山医院AD、DLB、PDD组和正常对照组的静息状态18F-FDG PET显像,采用网络模块化分析分别获得4组受试者的脑葡萄糖代谢网络模块化参数,并应用种子点相关分析得到葡萄糖代谢网络连接改变的脑区,比较4组受试者脑代谢网络连接的异同点。结果在稀疏阈值15%时,正常对照组和AD组的网络由4个模块组成,PDD组由6个模块组成,DLB组由10个模块组成。以右侧丘脑为种子点,AD组的颞叶和皮质下脑区连接增强,枕叶和左侧额叶连接减弱。PDD组的额叶、皮质下脑区连接增强,枕叶、颞叶、左侧顶叶的连接减弱。DLB组的左侧额叶和皮质下脑区连接增强,右侧枕叶和顶叶连接减弱。结论 3种不同类型痴呆患者的脑葡萄糖代谢网络具有不同的模块化特性,提示发病机制的差异,为进一步探究其神经机制提供新思路。     

阿尔茨海默病正电子发射计算机断层扫描和神经心理测定的初步研究

目的 探讨阿尔茨海默病(Alzheimer’s disease,AD)的脑葡萄糖代谢、神经心理学特点及AD的正电子发射计算机断层扫描(positron emission photography,PET)诊断。方法 对13例AD患者和11例年龄、性别和文化程度相匹配的健康对照者(HC)进行PET检查、简易智能状态检查(mini-mental state examination,MMSE)、韦克斯勒记忆量表测定(wechsler memory scale,WMS)和日常生活能力量表(activity of daily living,ADL)测定。结果 ①AD组MMSE、WMS分值明显低于HC组(P<0.01)。②肉眼读片,AD组存在脑萎缩,尤其是颞叶萎缩;大脑皮层放射性分布不均匀;健康老人可出现顶叶局部脑葡萄糖代谢率(regional cerebral metabolism rate of glucose,rCMRglc)的减低,但程度较轻;AD组全脑rGMRglc减低,以顶叶为最明显,其次为颞叶,再次为额叶。③AD组在双侧额叶上、中、下回、眶回、直回、颞叶中下回、顶上小叶、缘上回、前扣带回、尾状核、岛叶、丘脑,左侧角回、左侧杏仁核等脑区rCMRglc半定量指标降低较明显,与健康对照组相比,差异具有显著性或高度显著性((P<0.05-P<0.001);AD组病人额叶上中下回葡萄糖代谢半定量指标降低最为明显,其次为丘脑和尾状核。④相关分析表明,MMSE评分与性别呈负相关(P=0.025);右侧顶上小叶和右侧丘脑的rCMRg     

轻度认知障碍及阿尔茨海默病脑葡萄糖代谢改变的统计参数图的PET研究

目的应用氟脱氧葡萄糖正电子发射计算机断层扫描(18F-FDG PET)探讨阿尔茨海默病(AD)、遗忘型轻度认知障碍(aMCI)患者脑部葡萄糖代谢改变的特点。方法对27例轻度AD患者(AD组)、10例aMCI患者(aMCI组)和21例年龄匹配正常老年志愿者(对照组)行18F-FDG PET成像,对扫描获得的18F-FDG PET图像进行预处理后应用统计参数图(SPM8)对脑葡萄糖代谢进行基于体素水平的组间t检验的统计学分析。结果①与对照组比较,AD组脑葡萄糖代谢减低的脑区包括后扣带回(BA23、31)及楔前叶(BA19)、双侧顶叶(BA40)、双侧颞叶(BA20、21、22、37)、双侧额叶(BA6、9、10)等(P<0.001,未校正,K≥50像素);②AD组与aMCI组比较,脑葡萄糖代谢相对减低的脑区包括后扣带回(BA23、31)及楔前叶(BA19)、颞顶叶(BA40、20、21、22、39)及额叶(BA6、8、9)等(P<0.001,未校正,K≥50体素);③AD组和aMCI组葡萄糖减低的体素数目(12 413个)要少于AD组和对照组的体素数目(17 592个);④aMCI组葡萄糖代谢与对照组比较,仅右侧枕叶的舌回(BA17)减低(P<0.05,未校正)。结论 SPM8可用于诊断和区分AD患者的脑葡萄糖代谢模式。     

不同类型痴呆脑代谢改变图型:~(18)F-FDG PET显像

目的探讨不同类型痴呆患者基于像素水平的脑代谢图型特点。方法对最终临床诊断为阿尔茨海默病(20例)、额颞叶痴呆(20例)、路易体痴呆(10例)、进行性核上性麻痹(7例)、原发性进行性失语(3例)、皮质基底节变性(1例)和多系统萎缩(1例)等认知功能障碍患者的18F-FDG PET显像资料进行回顾分析,描述各种神经变性疾病脑代谢降低区域和程度。结果 SPM分析表明,各种神经变性疾病引起的痴呆18F-FDG PET显像均表现为皮质代谢降低,但其代谢图型变化明显不同:阿尔茨海默病组以双侧颞顶叶和额叶皮质代谢降低为主,基本感觉运动皮质、枕叶、基底节和丘脑活性保留;额颞叶痴呆组额叶和颞叶皮质不对称性代谢降低,伴部分顶叶皮质和基底节、丘脑等皮质下核团不同程度代谢降低;路易体痴呆组枕叶、视皮质和双侧颞上回前部代谢降低;进行性核上性麻痹组双侧前额叶背外侧、颞叶前外侧、中脑和双侧尾状核代谢降低;原发性进行性失语组左侧额叶Broca区、左侧颞叶皮质(除左侧颞上回后部)和右侧颞叶内侧皮质代谢降低;皮质基底节变性组双侧中央沟周围额顶叶皮质(右侧显著)、右侧基底节代谢降低;多系统萎缩组双侧小脑背外侧皮质和左侧壳核代谢降低。结论神经变性疾病所致痴呆在18F-FDG PET显像中表现出各自特征性脑代谢降低图型,18F-FDG PET显像有可能成为痴呆鉴别诊断的一种辅助手段。     

伴行为和精神症状痴呆患者的脑葡萄糖代谢研究

目的:研究有、无痴呆的行为和精神症状(BPSD)的阿尔茨海默病(AD)患者脑葡萄糖代谢的不同特点,以探讨AD患者BPSD的病理生理及其与大脑神经病理之间的关系。方法:对13例符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断标准的AD患者,其中6例有BPSD(BPSD组),7例无BPSD(NBPSD组),并进行PET检查,对各脑区局部脑葡萄糖代谢率(rCMRglc)及多个核团进行测定,并用统计参数图(SPM)对两组脑PET图像进行像素间比较。结果:①BPSD组的AD患者额叶放射性减低者多于NBPSD组(4/6∶2/7);②应用感兴趣区(ROI)方法进行比较,BPSD组和NBPSD组在所选脑区中的rCMRglc差异无显著性(P>0.05);③应用SPM方法进行比较发现,BPSD组和NBPSD组rCMRglc显著减低的脑区主要分布在前额叶、顶枕交界处和颞下回。BPSD组比NBPSD组rCMRglc减低面积大,左侧额叶上回、右侧颞叶前内部、右侧岛叶前下部葡萄糖代谢减低。结论:AD患者,不管有无BPSD,rCMRglc减低区主要位于前额叶、顶枕叶交界处和颞叶下回;有BPSD的AD患者比无BPSD的患者rCMRglc的减低区面积大,分布广,程度重,提示BPSD可能是AD病程中的一个症状,而并非是另一种AD类型;额叶rCMRglc减低可能与BPSD的发生有关。     

~(18)F-FDG PET显像观察特发性快眼动睡眠期行为障碍患者脑葡萄糖代谢特点的研究

目的探讨~(18)F-FDG PET显像观察特发性快眼动睡眠期行为障碍(iRBD)患者脑葡萄糖代谢改变和iRBD脑葡萄糖代谢改变与病程间的相关性。方法纳入多导睡眠监测(PSG)确诊的iRBD患者20例(iRBD组)和年龄、性别匹配的健康对照者19例(对照组)。两组均行~(18)F-FDG PET脑显像。基于自动解剖标记模板将大脑划分为90个左右对称的脑区,计算各脑区葡萄糖代谢半定量值。对iRBD组和对照组各脑区葡萄糖代谢半定量值进行独立样本t检验;并对iRBD组脑葡萄糖代谢改变与病程行Pearson相关分析。结果 (1)与对照组比较,iRBD组的双侧背外侧额上回、双侧眶部额上回、双侧眶部额中回、双侧海马、双侧海马旁回、双侧杏仁核、左侧眶部额下回、左侧岛叶、左侧内侧与旁扣带脑回、左侧中央旁小叶、左侧苍白球的葡萄糖代谢半定量值均增高(P0.05);双侧距状裂周围皮质、双侧楔叶、双侧舌回、双侧枕上回、双侧枕中回、双侧枕下回、双侧角回、双侧颞上回、双侧颞中回、右侧颞横回的葡萄糖代谢半定量值均降低(P0.05)。Pearson相关分析结果,iRBD组双侧杏仁核、双侧颞上回、右侧楔叶、右侧枕上回、右侧颞横回、左侧海马、左侧颞中回的葡萄糖代谢半定量值与病程呈正相关(P0.05);而双侧眶部额上回、双侧眶部额中回、左侧中央旁小叶、左侧眶部额下回、左侧内侧和旁扣带回、右侧背外侧额上回、右侧海马旁回的葡萄糖代谢半定量值与病程呈负相关(P0.05)。结论 iRBD患者脑内存在疾病相关的葡萄糖代谢水平改变,有助于客观评估iRBD病情的变化。     

弥散张量成像对阿尔茨海默病脑白质改变的评价

目的分析阿尔茨海默病(Alzheimer's disease,AD)脑白质结构改变及与认知功能的关系。方法对37例AD组和32例对照组行简易精神状态量表(mini-mental State examinationn,MMSE)评估和DTI扫描。采用基于全脑体素分析法对两组全脑白质各向异性(fractional anisotropy,FA)图进行比较,采用t检验分析FA值差异,并评估AD组MMSE评分与FA值相关性。结果 AD患者出现FA值下降区域广泛分布在右侧额叶、颞叶、枕叶、丘脑及双侧扣带回、胼胝体、楔前叶、顶叶下回、顶下小叶、缘上回及海马旁回(其中P0.001,未经校正的P值);当使用经FWE校正的P0.05后,AD患者右侧扣带回、左侧胼胝体、颞叶下回及双侧顶叶下回、额叶下回、楔前叶区域FA值较对照组显著下降。AD患者FA值下降与MMSE量表评分呈正相关,(P0.001,未经校正)。结论 AD患者存在特定脑区白质结构改变,并与认知功能损害程度呈正相关。     

早发性与迟发性阿尔茨海默病患者大脑葡萄糖代谢的差异

目的初步探讨早发性阿尔茨海默病（AD）与迟发性AD患者大脑葡萄糖代谢的差异。方法对9例早发性AD、14例迟发性AD患者及分别与其年龄相匹配的29名年轻健康对照者和11名老年健康对照者进行^18F-氟脱氧葡萄糖（^18F-FDG）PET脑显像。应用统计参数图对PET数据进行基于体素水平的图像分析。结果早发性AD组葡萄糖代谢相对于年轻对照组减低的脑区及其在Brodmann分区图（BA）的定位分别为双侧额上回（BA6，8）、额中回（BA6），左侧顶下小叶（BA39），右侧缘上回（BA40）、扣带回（BA31）等部位（P〈0．01）；迟发性AD组葡萄糖代谢相对于老年对照组葡萄糖代谢减低的脑区及其定位分别为双侧额上回（BA8）、额中回（BA6，8）、楔前叶（BA19）、右侧角回（BA39）等部位（P〈0．01）。结论尽管严重程度、病程及受教育水平相当，但是早发性AD患者大脑葡萄糖代谢减低的范围比迟发性AD更广泛，程度也更严重。不同发病年龄AD患者大脑葡萄糖代谢的差异可能是由于二者的认知储备能力不同所致。     

轻度认知功能障碍患者正电子发射计算机体层摄影术和神经心理学测定的初步研究

目的　探讨轻度认知功能障碍患者脑葡萄糖代谢与神经心理学特点及其相互关系。方法　采用正电子发射体层摄影术 (PET)、简易智能状态测定 (MMSE)、韦克斯勒记忆量表测定 (WMS)和总体衰退量表 (GDS)测定 10例轻度认知功能障碍 (MCI)患者和 10名健康志愿者 (HC)。结果 (1)MCI组MMSE[(2 4.6± 2 2 )分 ]、WMS[(6 9.4± 10 .4)分 ]分值低于HC组 [分别为 (2 8.9± 1.1)分和 (93.1± 9.0 )分 ;P〈0 .0 1];(2 )MCI组左侧眶回、右侧颞叶中回和右侧壳核的局部脑葡萄糖代谢率 (rCMRglc)较HC组低 (P〈0 .0 5～ 0 .0 1) ;(3)将年龄、受教育年限、MMSE、WMS与不同脑区用18F标记的脱氧葡萄糖放射性比值进行相关分析显示 ,与年龄呈负相关 (P〈0 .0 5或P〈0 .0 1)的脑区有 :眶回、左侧额上回、左侧额下回、颞叶中回、颞叶下回、左侧顶叶、左侧中央前回、右侧中央后回、左颞叶内侧皮质、左侧海马回、左侧海马旁回、右侧前扣带回、后扣带回、左侧杏仁核等。与文化程度呈正相关 (P〈0 .0 5或P〈0 .0 1)的脑区有 :左侧颞叶下回、中央前回、左侧中央后回等 ;而右侧壳核则呈负相关。与MMSE呈正相关 (P〈0 .0 5或P〈0 .0 1)的脑区有 :额下回、左侧颞叶上回、颞叶中回、颞叶下回、左侧顶叶、左侧中央前回、中央后回、颞叶内侧皮     

Age, sex and laterality effects on cerebral glucose metabolism in healthy adults

Normal cerebral glucose metabolism (CMRglc) was assessed with positron emission tomography in 66 healthy adults (28 women, 38 men; mean age 39, range 20--69 years) to determine effects of age, sex and laterality on CMRglc using statistical parametric mapping. Significant age-related decreases in global metabolism (gCMRglc) were noted in the entire sample and in both sexes, as well as widespread and bilateral decreases in cortical absolute regional metabolism (rCMRglc) and more focal anterior paralimbic normalized rCMRglc. However, significant positive correlations of age with normalized rCMRglc were observed in cerebellum, thalamus and occipital areas. Although the declines in gCMRglc and rCMRglc with age did not significantly differ between sexes, men compared with women had significantly lower gCMRglc and widespread decreased cortical and subcortical absolute rCMRglc. In the entire sample, and similarly in both sexes, left greater than right asymmetry was observed in medial frontal gyrus, posterior thalamus, lingual gyrus, cuneus and superior cingulate. The opposite laterality appeared in mesio-anterior cerebellum, and lateral frontal and temporal regions. Few regions showed significant interactions of metabolic laterality with either age or sex. These findings contribute toward a convergence in the literature, and the regression models of CMRglc vs. age serve as a normative database to which patients may be compared.     

健康成人脑葡萄糖代谢的PET研究

目的：探求健康成人脑葡萄糖代谢的变化,及其与性别、年龄的关系。方法：对11例年龄60岁以上（SS）和17例在60岁以下（LS）的两组健康成年人进行正电子发射断层扫描（pstitron emission photography,PET),对各脑区及多个核团进行半定量测定。结果：SS组双侧额叶、眶回、前后扣带回、海马、海马旁回、尾状核、壳核、颞叶、丘脑、岛叶、枕颞外侧回、中央后回、顶叶、颞－顶枕交界区（temorparieto-occiptial,TPO）、杏仁核及左侧枕颞内侧回、左侧中央前回等大脑各部局部脑葡萄糖代谢率（regiona cerebral metabolism rate of glucose,rCMRglc) 较LS组低,其差异具有显著性（P＜0．05或P＜0．01）。相关分析发现,左侧颞叶下加双侧中央前回rCMRglc的变化与增龄无关,提示该部位CMRblc相对稳定,其余脑区均与增龄呈负相关（P＜0．05或P＜0．01）;另外,所有脑区CMRglc的改变均与性别无关（P＞0．05）。结论：健康成年人的大脑代谢和功能随着年龄的增长而减弱,对健康成年人的变化有所了解,方能更好地对异常情况作出正确的判断。     

反社会人格障碍男性青年大脑白质异常改变： 证据来自于基于体素脑形态测量学的DARTEL分析

SPM8 DARTEL工具包对3D脑结构成像数据对男性青年反社会人格障碍者和正常组的大脑白质结构进行基于体素的形态学分析（VBM）。结果显示,与正常对照者比较,反社会人格障碍者主要表现为双侧前额叶、右岛叶、中央前回,左右颞上回、右中央后回、右侧顶下小叶、右侧楔前叶、右枕中叶、右海马旁回及双侧扣带回等多个脑区白质体积密度增加,左颞中叶、右小脑的白质体积密度减小。相关分析显示,额内侧回的白质体积密度增加与反社会行为的评分(PDQ)有正相关。提示反社会人格障碍者存在多个脑区的白质形态学明显异常,这些异常可能与其反社会行为有关。     

PET study of human voluntary saccadic eye movements in darkness: effect of task repetition on the activation pattern

Using H₂¹⁵O 3D Positron Emission Tomography (PET), regional cerebral blood flow (rCBF) was measured in six human subjects under two different conditions: at rest and while performing self-paced horizontal saccadic eye movements in darkness. These two conditions were repeated four times each. First, the comparison between the four saccadic and four resting conditions was investigated in a group and a single subject analysis. Saccades elicited bilateral rCBF increases in the medial part of the superior frontal gyrus (supplementary eye field), precentral gyrus (frontal eye field), superior parietal lobule, anterior medial part of the occipital lobe involving striate and extrastriate cortex (lingual gyrus and cuneus), and in the right inferior parietal lobule. At the subcortical level, activations were found in the left putamen. These results mainly replicate previous PET findings on saccadic control. Second, the interaction between the experimental conditions and their repetition was examined. When activations throughout repetition of the same saccadic task are compared, the supplementary eye fields show a progressive increase of activation. On the contrary, the activation in the cerebellum, left superior parietal lobule and left occipital cortex progressively decreases during the scanning session. Given the existence of such an interaction, the pattern of activations must be interpreted as a function of task repetition. This may be a factor explaining some apparent mismatch between different studies.     

正常人安静和催眠状态下脑葡萄糖代谢的自身对照研究

目的 研究健康正常人催眠静息状态和清醒安静状态下脑内葡萄糖代谢的差异,初步探索催眠状态的神经生理基础。方法 正常人在清醒安静状态下行^18F—FDG PET扫描。隔日后,采用凝视法将受试者诱导进入催眠状态,再次行^18F—FDG PET扫描。两种状态皆应采用3D模式进行PET脑显像,应用SPM分析对催眠静息状态和清醒安静状态^18F—FDG PET图像进行组间体元统计,统计所得到的一系列数值构成了统计参数地图（SPM）。比较催眠静息状态和清醒安静状态脑局部糖代谢的变化,根据变化差异显著（P〈0．001）区域的Talariach坐标值确定其部位。结果 SPM分析显示催眠静息状态较清醒安静状态右侧枕叶（BA17,18）、左侧枕叶（BA17,18）、左侧顶叶（BA40,）、左侧颞上回（BA22）、右侧尾状核、右侧小脑后叶、右侧额叶（BA6）、左侧额中回（BA8,9）和右侧丘脑葡萄糖代谢明显降低（P〈0．001）。结论 催眠静息状态脑葡萄糖代谢不同于清醒安静状态,催眠静息状态存在神经生理基础。     

Relations between neuropsychological and cerebral metabolic asymmetries in early Alzheimer's disease

Regional CMRglc (rCMRglc) values were determined with positron emission tomography (PET) in 10 patients with mild to moderate clinically diagnosed Alzheimer's disease (AD) and in 26 healthy controls. rCMRglc in frontal, parietal, and temporal association cortices were significantly more laterally asymmetrical in AD patients than in controls (p less than 0.05). Furthermore, lateral asymmetry of rCMRglc in AD patients but not in the control subjects correlated significantly with asymmetry of language and visuospatial functions such that lower left than right rCMRglc was associated with relatively greater impairment of language and vice versa. The results demonstrate that discrepancies between language and visuospatial deficits in patients with early AD are related to asymmetrical reductions in cerebral cortical glucose metabolism.     

基于体素的形态测量法分析高功能孤独性障碍患儿的脑组织密度

目的 分析学龄孤独性障碍患儿脑组织密度.方法 对17例智能正常的孤独性障碍患儿(病例组)以及15名年龄、性别、智商与之相匹配的健康儿童(对照组)进行T1加权三维磁共振成像扫描,应用基于体素的形态测量法(VBM)比较两组脑灰质及脑白质密度的差异.结果 与对照组相比,孤独性障碍患儿右侧小脑前叶的脑灰质密度低.右前扣带回、右额中回区域的脑白质密度低,双侧顶下小叶、右缘上回、右中央后回、右颞上回、右小脑后叶、左楔前叶、左楔叶的脑灰质密度高(P<0.001).结论 智力正常的学龄孤独性障碍患儿脑组织密度异常明显,且部位广泛.     

Cortical cerebral metabolism correlates with MRI lesion load and cognitive dysfunction in MS

OBJECTIVE: To study the association between the cortical cerebral metabolic rate of glucose (CMRglc), MRI T2-weighted total lesion area (TLA), cognitive dysfunction, and neurologic disability in MS. BACKGROUND: MRI lesion load is widely used in the clinical evaluation of the MS patient but little is known about the associated changes in cortical activation. METHODS: Twenty-three patients with clinically definite MS underwent measurements of CMRglc, TLA, motor evoked potentials (MEPs), and cognitive and neurologic disability. CMRglc was calculated using PET and 18-F-deoxyglucose and compared with nine normal control subjects. RESULTS: Reductions in CMRglc (p < 0.01) were found in the cortical global and regional lobar measurements. Furthermore, regional CMRglc (rCMRglc) was reduced in the dorsolateral prefrontal cortex, orbitofrontal cortex, caudate, putamen, thalamus, and hippocampus. Global cortical CMRglc correlated with TLA (Spearman rank correlation coefficient [SRCC] = -0.66, p = 0.001), and rCMRglc correlated with regional lesion load in all cerebral lobes (p < or = 0.05). Global cortical CMRglc and cognitive disability also correlated (SRCC = 0.58, p = 0.015), and stepwise regression analysis showed a significant association between rCMRglc of the right thalamus and cognitive performance as well as TLA. There was no correlation between CMRglc and neurologic disability (Expanded Disability Status Scale) or MEP. CONCLUSION: Global and regional cortical CMRglc is reduced significantly in MS patients compared with normal control subjects. Furthermore, the CMRglc reductions correlate with TLA as well as with cognitive dysfunction, which indicates that MRI white matter lesion burden has a deteriorating effect on cortical cerebral neural function.