精神分裂症幻听患者汉语听觉语言皮质定位的脑磁图研究

目的 采用脑磁图(MEG)技术探讨男性精神分裂症幻听患者汉语听觉语言皮质的定位.方法 给予13例精神分裂症幻听患者和14名正常对照组双耳男、女声各100对词义相关及不相关的二个字汉语词汇刺激,并由MEG设备记录刺激后产生的听觉诱发磁场,将MEG采集数据叠加到核磁共振上获得磁源性影像.结果 ①患者组10例汉语听觉语言皮质定位在大脑半球双侧颞中、上回后部、额下回后部,2例在右侧额下回后部,1例在左侧颞上回后部.对照组10名定位于左侧颞中、上回后部,即Wernicke区,2名定位于右侧颞中回后部,2名定位在双侧颞上回后部.患者组定位在双侧比例明显高于对照组(76.92% vs 14.29%,x2=2.88,P＜0.05).②无论男声或女声刺激,患者组与对照组的中枢三维坐标在X轴上差异均有统计学意义(P＜0.05).结论 精神分裂症幻听患者的汉语语言皮质定位与正常人的位置不同,更靠近颞中、上回外侧部,这一改变可能是其听觉性语言认知功能障碍的神经病理学基础之一.     

急性脑梗死听觉皮层中枢脑磁图特征

目的 研究急性脑梗死患者听觉皮层中枢脑磁图(MEG)变化特征。方法 对15例急性脑梗死患者于发病后3-4周进行听觉诱发磁场(AEFs)检测,同时检测9名健康志愿者作为对照。采用双耳纯音刺激,诱发双侧听觉皮层兴奋。纯音频率2 kHz,声音强度90 dB,刺激间隔1s,纯音持续时间8ms。脑磁图检查后进行MRI超薄扫描。AEFs波峰由等价电流偶极子(ECD)评估。结果两组AEFs的最主要波峰为M100,其ECD位于两侧颞横回。患者组多个AEFs参数均存在异常,即:(1)健康对照组两侧M100 ECD空间位置差值为(14.9±10.6)mm;患者组为(18.6±3.3)mm,患者组不对称性增大(P<0.05);(2)健康对照组M100潜伏期为(89.3±27.9)ms;患者组(97.0±6.0)ms.患者组潜伏期明显延迟(P<0.05);(3)患者患侧ECD强度为(17.2±4.8)nA,健侧ECD强度为(30.5±5.9)nA,患侧ECD强度减小(P<0.01)。结论 MEG可灵敏地检测出急性脑梗死患者听觉皮层中枢功能损伤,并能够客观地评价该病听觉皮层中枢的功能状态。     

急性脑梗死脑磁图脑诱发磁场发生源空间位置特征研究

目的:研究急性脑梗死患者体感皮层中枢和听觉皮层中枢脑磁图(MEG)变化特征。方法:对15例急性脑梗死患者于发病后3-4周进行体感诱发磁场(SEFs)和听觉诱发磁场(AEFs)检测,同时检测健康志愿者作为对照。SEFs电刺激部位为腕部正中神经处,电流脉冲宽度0.3ms,刺激间隔0.5s。AEFs采用双耳纯音刺激,频率2KHz,声音强度90dB,刺激间隔ls,持续时间8ms,脑磁图检查后进行MRI超薄扫描。结果:SEFs的最主要波峰为M20,其ECD均位于体感皮层中枢,AEFs为M100,位于两侧颞横回。两侧ECD位置三维不对称性由(△X2+△Y2+△Z2)1-2表示,SEFs和AEFs测定患者组均较正常对照组不对称性增大。结论:MEG可灵敏地检测出急性脑梗死患者皮层中枢功能损伤。     

重复经颅磁刺激治疗精神分裂症顽固性幻听对照研究

目的研究重复经颅磁刺激治疗精神分裂症幻听的临床疗效和安全性。方法伴顽固性幻听的精神分裂症患者随机分为研究组(n=60)和对照组(n=60)。在维持原抗精神病药物治疗基础上,研究组给予6周左侧颞顶叶的rTMS治疗,对照组给予伪刺激治疗。采用幻听量表(AHRS)、阳性症状和阴性症状量表(PANSS)、幻听量表(AHRS)评定临床疗效,采用不良反应量表(TESS)评估不良反应。结果 6周治疗后,研究组治疗幻听的有效率高于对照组(P<0.01),研究组AHRS、PANSS的总分和分量表评分均低于对照组,差异有统计学意义(P<0.05或0.01)。治疗中未见明显不良反应。结论左侧颞顶叶rTMS治疗能减轻精神分裂症患者的顽固性幻听。     

男性精神分裂症患者脑侧化与幻听的功能磁共振成像研究

目的利用事件相关功能磁共振成像（fMRI）在体研究精神分裂症伴有幻听的男性患者左右侧化声音激活脑区的差异，以验证幻听是由脑侧化异常产生的假说。方法男性健康志愿者13名（正常对照组），幻听和非幻听偏执型精神分裂症男性患者各13例，接受预先编制的左右侧化声音刺激，进行功能磁共振扫描。结果（1）组内比较：与右侧化声音刺激相比，正常对照组在辨别左侧化声音刺激时显著激活了左楔前叶和右旁中央小叶（FDR校正，P〈0．01，体素值〉10）；两个患者组组内左右侧化声音显著激活脑区比较，差异均无统计学意义。（2）组间比较：与幻听组相比，正常对照组在辨别左侧化声音刺激时右旁中央小叶显著激活；与非幻听组相比，正常对照组在辨别左侧化声音刺激时显著激活两侧颞上回、左楔前叶、两侧扣带回和左缘上回，而在辨别右侧化声音刺激时两侧颞上回、右颞中回和左脑岛显著激活；与非幻听组相比，幻听组无论在辨别左或右侧化声音刺激时均引起左侧颞横回激活（P〈0．001，未校正，体素值〉50）。结论精神分裂症患者正常的语言侧化减弱，而幻听的产生可能与左脑尤其是左颞横回的功能障碍有关。     

低频重复经颅磁刺激治疗精神分裂症慢性幻听的疗效及随访研究

目的研究低频重复经颅磁刺激（rTMS）对精神分裂症难治性慢性幻听症状的疗效。方法将46例精神分裂症伴慢性幻听患者随机分为研究组（23例）和对照组（23例）。研究组在原有抗精神病药物种类及剂量不变的同时给予经左侧颞顶叶的2周共10次低频（1Hz）rTMS刺激,对照组采用假rTMS刺激。治疗前后对两组分别进行AHRS听幻觉量表及临床疗效总评量表（CGI）评定幻听症状的变化,并对治疗有效者于3个月后随访。结果研究组治疗前、后AHRS评分分别为（8．1±2．5）和（3．5±1．5）;对照组为（7．8±2．6）和（6．5±2．1）,研究组疗效明显优于对照组（F=20．3,P〈0．05）。所有患者均完成试验,未见有严重的副反应出现。结论低频rTMS治疗精神分裂症难治性慢性幻听症状,疗效肯定且安全性好。     

低频重复经颅磁刺激治疗精神分裂症顽固性幻听的临床研究

目的：研究左侧颞顶区低频（1Hz）重复经颅磁刺激（rTMS）治疗伴有顽固性言语性幻听的精神分裂症的疗效。方法：将35例伴有顽固言语性幻听的精神分裂症患者随机分为研究组18例和对照组17例。在原有抗精神病药种类及剂量不变的基础上,研究组给予左侧颞顶区频率为1Hz的真性rTMS刺激2周共10次,对照组给予相应的假性刺激。两组治疗前后均采用阳性与阴性症状量表（PANSS）评定其总体临床症状及幻听的变化,并进行威斯康星卡片分类测验（WCST）及听觉注意力测验（CPT）。结果：35例患者均完成治疗,研究组治疗前后幻听评分分别为（4．89±1．18）分和（3．00±1．75）分,对照组治疗前后幻听评分分别为（4．88±1．11）分和（4．24±1．20）分（F=7．72,P=0．009）。研究组有效率77．8％显著优于对照组41．2％（P=0．041）。治疗后两组问PANSS评分除阴性症状外其他各项评分改善差异均有显著性（P〈0．05）。WCST和CFF评分治疗后两组间差异无显著性（P〉0．05）。结论：左侧颞顶区rTMS对于幻听具有较肯定的治疗作用,并且能够改善精神分裂症患者的总体精神病性症状。在一定程度上能够改善患者的认知功能,但尚无确切疗效。     

精神分裂症患者情绪图片刺激脑磁图比较

目的:比较精神分裂症患者不同情绪图片刺激脑磁图的差异。方法:精神分裂症患者和正常对照者均给予相同的情绪图片刺激,记录每次给图片刺激前150ms至刺激后750ms所诱发脑磁场的位置及频数。结果:与正常对照组相比,不同情绪图片刺激时精神分裂症患者所激活视觉皮质位置无明显偏移,顶叶、额叶、颞叶及枕叶所诱发的磁场频数均无明显差异;当抑郁情绪图片刺激时,精神分裂症患者扣带回和颞上回(尤其右颞上回)所诱发的磁场频数比正常对照组增多,而颞顶交界处所诱发的磁场频数减少;当愉快情绪图片刺激时,精神分裂症患者额极所诱发的磁场频数比正常对照组增多。结论:本研究证实精神分裂症患者情绪视觉信息加工过程存在异常。     

不同部位低频重复经颅磁刺激治疗顽固性幻听起效时间和安全性的双盲对照研究

目的 初步探讨背外侧前额叶和左侧颞顶叶低频重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)治疗精神分裂症顽固性幻听的疗效(起效时间)和安全性.方法 36例伴有顽固性幻听的精神分裂症患者随机分为三组,分别为背外侧前额叶rTMS治疗组(n1 =12)、左侧颞顶叶rTMS治疗组(n2=14)及对照组(假性刺激)(n3=10),背外侧前额叶rTMS治疗组、左侧颞顶叶rTMS治疗组分别给予10次1 Hz rTMS真性刺激,对照组给予假刺激,治疗期间维持原有抗精神病药种类及剂量不变.采用阳性和阴性症状量表(Positive and Negative Syndrome Scale,PANSS)评定临床症状,不良反应症状量表(Treatment Emergent Symptom Scale,TESS)、纯音听力测试评估副反应.结果 两个真性治疗组疗效均明显优于假性治疗组,与基线比较,背外侧前额叶组第4次评估、左侧颞顶叶组第7次评估出现统计学差异,两个治疗组比较差异无统计学意义.无论治疗组、对照组均未观察到明显的副反应.结论 1 Hz背外侧前额叶、左侧颞顶叶低频重复经颅磁刺激治疗精神分裂症顽固性幻听均有效,且安全性高.     

男性精神分裂症患者视觉诱发磁场的初步研究

目的:以脑磁图(MEG)研究精神分裂症患者视觉诱发磁场(VEFs)的特点. 方法:20例男性精神分裂症患者(患者组)和13名正常人(对照组),给予右眼左半垂直视野黑白翻转格图形视觉刺激,记录受试者VEFs的M100波形、潜伏期、振幅及激活脑区的等电流偶极(ECD)的磁源性影像(MSI)的XYZ值. 结果:所有受试者VEFs的最基本波形为M100,位于距状裂两侧的皮质.与对照组比较,患者组VEFs的M100波形存在异常,潜伏期明显延长,振幅显著降低(P均<0.05);且ECD的XYZ值显示其M100反应的ECD位置在X轴上分布偏移. 结论:MEG可检测出精神分裂症患者VEFs存在异常,其视觉皮质中枢功能亦存在异常.     

Ear of stimulation determines schizophrenia-normal brain activity differences in an auditory paired-stimuli paradigm

Schizophrenia patients have abnormalities of auditory information processing, theoretically associated with dysfunction of neuronal excitation. Auditory paired-stimuli (S1-S2) paradigms are used to evaluate the nature of these abnormalities. It is unknown whether patients' abnormalities during S1-S2 paradigms are attributable to specific hemispheric differences in cortical processing. The present studies used whole head magnetoencephalography and monaural or binaural versions of the paired-stimuli paradigm to evaluate auditory processing among 38 schizophrenia and 38 normal subjects. The strengths of auditory-evoked brain responses over time were quantified using distributed source reconstructions with L2 minimum norm constraint and realistic head models. For left ear stimuli, schizophrenia and normal groups did not differ on either left or right hemisphere activity over auditory cortex. For right ear and binaural stimuli, schizophrenia patients had less activity over left auditory cortex from 80 to 120 ms post-stimulus but did not differ from normal on activity over right auditory cortex. Additionally, in response to monaural stimulation, schizophrenia patients had significantly less activity than normal over right temporal parietal junction from 60 to 120 ms post-stimulus. These data are consistent with four propositions about schizophrenia: (i). right auditory cortex is functioning normally; (ii). processing of simple auditory stimuli is abnormal in left auditory cortex, probably specifically in supra-granular layers; (iii). auditory localization abilities are deficient; and (iv). auditory cortex abnormalities are not a function of deficient hemispheric communication because they are evident early in processing as long as stimuli are delivered directly to left hemisphere.     

The functional anatomy of auditory hallucinations in schizophrenia

We used continuous whole brain functional magnetic resonance imaging (fMRI) with a 3-T magnet to map the cerebral activation associated with auditory hallucinations in four subjects with schizophrenia. The subjects experienced episodes of hallucination whilst in the scanner so that periods of hallucination could be compared with periods of rest in the same individuals. Group analysis demonstrated shared areas of activation in right and left superior temporal gyri, left inferior parietal cortex and left middle frontal gyrus. When the data were examined on an individual basis, the temporal cortex and prefrontal cortex areas were activated during episodes of hallucination in all four subjects. These findings support the theory that auditory hallucination reflects abnormal activation of normal auditory pathways.     

MEG auditory evoked fields suggest altered structural/functional asymmetry in primary but not secondary auditory cortex in bipolar disorder

Objectives: Objective physiological indices independently characterizing affective and schizophreniform psychoses would contribute to our understanding of the nature of their relationships. Magnetoencephalography (MEG)‐based metrics of altered structural/functional asymmetry in the superior temporal gyrus have previously been found to characterize schizophrenia at the level of both the primary auditory (AI) and the secondary auditory (AII) cortex. This study examines these markers in patients with bipolar disorder, with the goal of improved understanding of the patterns of brain asymmetry that may independently characterize affective and schizophreniform psychosis. Methods: We studied 17 euthymic bipolar subjects and 17 matched controls. Auditory evoked fields were generated by both 40 Hz auditory stimuli eliciting steady state gamma band (SSR), activating the AI cortex, and discrete 1 kHz tone pips, activating the AII cortex. MEG was recorded from the hemisphere contralateral to the ear stimulated using a 37‐channel MEG system. Source location estimates were calculated in both left and right hemispheres. Neuroanatomical location estimates for medial Heschl’s gyri were determined from magnetic resonance images for correlation with MEG source locations. Results: Bipolar subjects failed to demonstrate normal laterality of SSR AI responses, indicating altered patterns of asymmetry at the level of AI cortex, but demonstrated normal asymmetry of AII responses (right anterior to left). Medial Heschl’s gyri centroids were similarly lateralized in both groups, however (right anterior to left), dissociating function from structure in the AI cortex in the bipolar group. Conclusions: The findings are compatible with altered functional/structural relationships, including diminished left‐right hemisphere asymmetry of the AI, but not the AII cortex in bipolar disorder. In schizophrenia, both the AI and AII cortices exhibit such derangements; thus, the findings support both shared and nonshared features of auditory cortical disruption between the two disorders. This functional disorganization may help explain previously reported decreases in amplitude and phase synchrony of SSR gamma band responses in bipolar subjects, suggesting impaired neocortical synchrony in AI, possibly at a cortico‐thalamic level, but perhaps not extending to heteromodal association cortex, and may relate to the cognitive impairments found in bipolar disorder.     

Impaired temporal lobe processing of preattentive auditory discrimination in schizophrenia

Feature-specific stimulus discrimination related to short-term auditory sensory memory can be studied electrophysiologically using a specific event-related potential (ERP) component termed mismatch negativity (MMN), which is generated in the auditory cortex, indexing automatic comparison of the existing memory trace to incoming novel stimuli. Previous results with electroencephalography (EEG) and magnetoencephalography (MEG) suggest that schizophrenia patients have attenuated MMN response and that preattentive auditory processing preceding MMN appears to be functionally asymmetric in schizophrenia. Here we studied parallel MMN activity of the hemispheres using a whole-head MEG by presenting stimulus blocks consisting of frequent standard and infrequent deviant tones to 15 schizophrenia patients and 19 healthy control subjects. Auditory evoked fields (AEFs) were recorded simultaneously over both auditory cortices. The equivalent current dipole (ECD) modeling revealed that patients had significant MMNm reduction (magnetic counterpart of MMN) in both temporal lobes. In addition, patients had significantly delayed MMNm in the left but not in the right hemisphere to ipsilateral auditory stimuli. These results suggest that patients with schizophrenia have impaired auditory processing in the temporal lobes underlying preattentive stimulus discrimination that is also selectively delayed in the left hemisphere.     

EEG coherence measures during auditory hallucinations in schizophrenia

We studied the change in EEG alpha-band average coherence between auditory hallucination (AH) and non-auditory hallucination (non-AH) states in seven auditory hallucinating schizophrenia patients. Four cortical regions were considered based on the existing dominant models for auditory hallucinations, the inner speech model and the central auditory processing deficit (CAPD) model. Coherences between electrodes located over Broca's area (BA 44/45) and Wernicke's area (BA 22/42) and between electrodes located over left-right temporal cortices were examined. There was no significant change observed in the coherence between Broca's and Wernicke's areas, but a significant increase was observed in coherence between the left and right superior temporal cortices during AHs compared with non-AHs, suggesting increased bilateral coherence between auditory cortical areas. Since coherence is a pairwise measure of functional correlation between regions, our findings suggest abnormally increased synchrony between the left and right auditory cortices during AHs in schizophrenia. Further, a significant increase in relative power was observed in the left, but not in the right auditory cortex during AHs. Thus our findings support the CAPD model and are consistent with that which postulate reduced prosodic processing during AHs.     

Left superior temporal blood flow increases in schizophrenic and schizophreniform patients with auditory hallucination: A longitudinal case study using123I-IMP SPECT

Summary Serial assessments of regional cerebral blood flow were performed using¹²³I-IMP SPECT in two schizophrenic and three schizophreniform patients with persistent auditory hallucination. The initial SPECT study in the period with prominent auditory hallucination revealed an increased accumulation of¹²³I-IMP in the left superior temporal area which corresponded to the auditory association cortex. In the follow-up SPECT study performed after clinical improvement, the distribution of¹²³I-IMP had normalized. One of the case with schizophrenia showed a similar increased uptake of¹²³I-IMP in the left superior temporal area in the third SPECT scan performed when a psychotic relapse with auditory hallucination occurred. MRI scans in two of the five patients demonstrated reduced volume of the temporal lobes. These findings suggest that the auditory hallucinations in schizophrenia may be involved in functional hyperactivity in the left superior temporal cortex which might be based partly on structural abnormalities in the temporal lobes.     

Mismatch negativity responses in schizophrenia: a combined fMRI and whole-head MEG study

OBJECTIVE: Mismatch negativity is an event-related brain response sensitive to deviations within a sequence of repetitive auditory stimuli. It is thought to reflect short-term sensory memory and is independent of higher-level cognitive processes. Mismatch negativity response is diminished in patients with schizophrenia. Little is known about the mechanisms of this decreased response, the contribution of the different hemispheres, and its locus of generation. METHOD: Patients with schizophrenia (N=12) and matched comparison subjects (N=12) were studied. A novel design to measure mismatch negativity responses to deviant auditory stimuli was generated by using the switching noises from the functional magnetic resonance imaging (fMRI) scanner, thus avoiding any interfering background sound. Stimuli included deviants of amplitude (9 dB lower) and duration (76 msec shorter) presented in a random sequence. The scanner noise was recorded and applied to the same subjects in a whole-head magnetoencephalography (MEG) device. Neuromagnetic and hemodynamic responses to the identical stimuli were compared between the patients and comparison subjects. RESULTS: As expected, neuromagnetic mismatch fields were smaller in the patient group. More specifically, a lateralization to the right for duration deviance was only found in comparison subjects. For the relative amplitude of the blood-oxygen-level-dependent signal (measured with fMRI), differences emerged in the secondary (planum temporale), but not primary (Heschl's gyrus), auditory cortex. Duration deviants achieved a right hemispheric advantage only in the comparison group. A significantly stronger lateralization to the left was found for the deviant amplitude stimuli in the patients. CONCLUSIONS: The data support the view of altered hemispheric interactions in the formation of the short-term memory traces necessary for the integration of auditory stimuli. This process is predominantly mediated by the planum temporale (secondary auditory cortex). Altered interaction of regions within the superior temporal plane and across hemispheres could be in part responsible for language-mediated cognitive (e.g., verbal memory) and psychopathological (hallucinations, formal thought disorder) symptoms in schizophrenia.     

Auditory evoked neuromagnetic response in cerebrovascular diseases: a preliminary study

OBJECTIVES—Magnetoencephalography (MEG) measuresaspects of the function of the auditory cortex of the human brain withhigh spatial resolution. The objective was to determine whether MEGalso accurately identifies the auditory cortex of the brain in patientswith ischaemic stroke.
METHODS—The auditory evoked magnetic field (AEF)was examined after stimuli of 1 kHz tone bursts in 24 stroke patientswithout apparent infarcts in the auditory cortex, and compared thetopography of sources of 50 ms (P50m) and 100 ms latency deflections(N100m), the most prominent components of middle and long latency AEFs, with that of 12 normal subjects. Cerebral haemodynamics in and aroundthe auditory cortex were evaluated using PET.
RESULTS—In nine of 24 stroke patients, theaccurate magnetic sources of P50m or N100m were not identified. Thedistribution of P50m sources varied more widely than N100m. Eight ofthese nine patients had severe stenotic lesions in the carotid ormiddle cerebral arterial trunks. Patients with abnormal P50m responseshad decreased supratemporal and hemispheric blood flow compared withpatients with normal P50m responses.
CONCLUSIONS—These findings suggest that largevessel disease with disturbed cerebral haemodynamics in and near theauditory cortex tend to affect AEFs, especially the middle latencycomponents. This is the first combined study of MEG and PET to show asignificant correlation between AEF responses in stroke patients andtheir PET indices.

     

Left superior temporal gyrus activation during sentence perception negatively correlates with auditory hallucination severity in schizophrenia patients

The left superior temporal cortex, which supports linguistic functions, has consistently been reported to activate during auditory-verbal hallucinations in schizophrenia patients. It has been suggested that auditory hallucinations and the processing of normal external speech compete for common neurophysiological resources. We tested the hypothesis of a negative relationship between the clinical severity of hallucinations and local brain activity in posterior linguistic regions while patients were listening to external speech. Fifteen right-handed patients with schizophrenia and daily auditory hallucinations for at least 3 months were studied with event-related fMRI while listening to sentences in French or to silence. Severity of hallucinations, assessed using the auditory hallucination subscales of the Psychotic Symptom Rating Scales (PSYRATS) and of the Scale for the Assessment of Positive Symptoms (SAPS-AH), negatively correlated with activation in the left temporal superior region in the French minus silence condition. This finding supports the hypothesis that auditory hallucinations compete with normal external speech for processing sites within the temporal cortex in schizophrenia.     

Altered hemispheric asymmetry and positive symptoms in schizophrenia: equivalent current dipole of auditory mismatch negativity

The abnormality of mismatch negativity (MMN) in schizophrenia is thought to be associated with perceptional disturbance and cognitive dysfunction. The purpose of the present study was to investigate the change of the normal functional hemispheric lateralization in schizophrenia by employing the equivalent current dipole (ECD) model of auditory MMN with individual MRI and high-density electroencephalography (EEG). The MMNs resulting from auditory stimuli with passive oddball paradigm in a group of schizophrenics (n = 15), and also a group of age-, sex-, and handedness-matched normal controls, were recorded by 128 channel EEG. The location and power of ECD sources at the peak point were calculated. Individual 3-D brain magnetic resonance images (MRI) were used for realistic head modeling and for source localization. For both groups, the MMN source was determined to be located in the superior temporal gyrus (STG). However, the normal functional hemispheric asymmetry of ECD power was significantly altered in the schizophrenics (chi(2) test = 16.13, p < 0.001). Left MMN ECD power and the asymmetry coefficient (AC) were negatively correlated with the positive scores from Positive and Negative Syndrome Scale (PANSS) (r = -0.673, p = 0.008), especially with the hallucinatory behavior subscale (r = -0.677, p = 0.008). These findings support the deficits in preattentive automatic processing of auditory stimuli, especially in the left hemisphere, and indicate the correlation between positive symptoms, especially auditory hallucination, and left temporal lobe dysfunction in schizophrenia.