基于Granger因果性的功能磁共振成像对内侧颞叶癫痫活动的研究

在内侧颞叶癫痫(mTLE)中,内侧颞叶与皮层及皮层下结构参与了癫痫活动的起源与传播.基于Granger因果性(GC)检验方法,对脑电联合功能磁共振(EEG-fMRI)数据进行分析,研究内侧颞叶在mTLE中的作用.以内侧颞叶激活区域为参考区域,计算参考区域与大脑其余每个体素点之间的Granger因果关系,并映射到全脑,形成Granger因果图(GCM).结果表明,内侧颞叶将癫痫活动传播到外侧颞叶、额叶、顶叶及丘脑等区域,同时受到脑岛、壳核以及丘脑等区域脑活动的影响,提示内侧颞叶在mTLE痫样发放的传播环路中具有关键作用.     

应用因果分析方法对癫痫发作间期头皮脑电信号进行致痫灶定侧

目的利用因果分析方法对癫痫发作间期的头皮脑电信号进行致痫灶定侧。方法在频域因果分析方法——自适应直接传递函数（ADTF）的基础上提出功率谱加权ADTF（psADTF）法,以给定频段内信号的功率谱对ADTF的标准化做加权,以适应不同癫痫波频域信息不同的特点。利用该方法对2组共30例患者的头皮脑电信号进行分析,含组1癫痫手术患者15例,组2门诊癫痫患者15例。其中组1患者共截取癫痫波样本数104个,组2患者共截取癫痫波样本数98个。结果组1患者通过psADTF分析对致痫灶定侧与手术侧一致的有96个,平均单个癫痫波致痫灶定侧准确率可达92％;组2患者通过psADTF分析对致痫灶定侧与专家判读结果一致的有94个,平均单个癫痫波致痫灶定侧准确率达96％。结论发作间期头皮脑电癫痫波信号的psADTF分析能够很好地辅助临床致痫灶定侧。     

以癫痫起病的颞叶胶质瘤的显微外科治疗

目的探讨以癫痫起病的颞叶胶质瘤的临床特征、显微治疗方式及效果。方法选择22例以癫痫起病的颞叶胶质瘤患者,其中男性16例,女性6例;年龄5~52岁,平均年龄31.1岁。术前进行MRI、24 h视频脑电图(VEEG)和发作间期正电子发射断层摄影术(PET)等检查,综合评估制定手术方案,同时结合术中皮层电极描记(ECo G)探查异常放电确定致痫灶切除范围,对患者临床资料、病理结果、手术方式和手术效果进行回顾性分析。结果 22例患者均行显微手术肿瘤全切,其中7例行单纯病变切除;15例存在额外异常放电区域加行致痫灶切除。病理组织检查提示病变以低级别胶质瘤为主,部分病例合并颞叶内侧结构硬化改变。术后随访1~2年,患者癫痫缓解率满意,未见肿瘤复发。结论对颞叶胶质瘤继发癫痫患者,术前积极评估,采取个体化手术方案,争取肿瘤显微全切,同时恰当处理致痫灶,是抑制肿瘤复发和控制癫痫发作的有效手段。     

难治性枕叶癫痫的外科治疗及病因分析

目的：总结难治性枕叶癫痫的外科治疗经验，分析该类病例的致痫病因。方法：本组19例经临床评估确诊为难治性枕叶癫痫者，其中13例行病灶周围扩大切除术，3例将病灶和颞叶后部、颞叶内侧结构一并切除，3例切除病灶后联合低功率电凝热灼术。结果：手术后病理诊断为脑组织软化坏死7例、局灶性皮质发育不良4例、低级别胶质瘤4例、海绵状血管瘤3例、颜面血管瘤病（Sturge-Weber综合征）1例。经过1年3个月至2年4个月的随访，Engel-Ⅰ级17例，Engel-Ⅱ级2例。手术后3例患者并发视野缺损。结论：难治性枕叶癫痫的致痫病变多为静止性病变或缓慢生长的低级别肿瘤，将病变和致痫灶一并切除可以有效控制癫痫发作。     

奥卡西平对癫痫患者运动皮质兴奋性的影响

目的：利用经颅磁刺激（transcranial magnetic stimulation, TMS）技术来研究奥卡西平（oxcarbazepine, OXC）对部分性癫痫患者运动皮质兴奋性的影响，并与卡马西平(carbamazepine, CBZ)的作用相比较。方法：对38例头颅MRI正常的部分性癫痫患者和20例正常对照进行磁刺激，并记录双侧大脑的静息期运动皮质阈值(rest motor threshold, rMT)、运动诱发电位波幅（motor evoked potential amplitude，MEP amplitude）、皮质潜伏期(cortical latency, CL)和中枢传导时间（central motor conduction time, CMCT）。癫痫组中18例给予OXC治疗，20例给予CBZ治疗，在治疗后第2周末、第4周末分别给予TMS。结果： 癫痫组38例治疗前可能致痫灶同侧大脑rMT高于对侧大脑，但差异无显著(P>0.05)。奥卡西平组可能致痫灶同侧大脑rMT在第2周末和第4周末均明显高于治疗前(P<0.05)，卡马西平组可能致痫灶同侧大脑rMT仅在第4周末时高于治疗前(P<0.05)。癫痫组治疗前后同侧大脑MEP amplitude、CL和CMCT差别均无显著，两侧大脑半球间比较差别也无显著。结论： 头颅MRI正常的部分性癫痫患者可能致痫灶所在半球和对侧半球的大脑皮质兴奋性可能存在差异，OXC和CBZ均能降低运动皮质兴奋性，可能机制为细胞膜钠离子通道阻滞。 TMS是从电生理角度研究大脑皮质兴奋性的可靠辅助工具。     

颅内电极V-EEG对难治性颞叶癫痫致痫灶的定位价值

目的：探讨颅内埋藏电极同步录像脑电图监测（V-EEG）对难治性颞叶癫痫致痫灶的定位作用。方法：对临床、影像学检查及头皮电极脑电图（EEG）不能明确癫痫致痫灶的3例难治性颞叶癫痫患者,采用颅骨钻孔方法埋置硬膜下电极和深部电极,经长程颅内电极V—EEG监测进一步定位致痫灶。结果：3例难治性颡叶癫痫患者通过颅内电极V-EEG监测,并依据发作初始期的EEG异常放电特征确定了致痫灶,并进行病灶切除。结论：依据发作初始期颅内电极EEG痫样放电的部位和范围,能够为难治性癫痫外科手术治疗提供更可靠的定位指标。     

基于Granger因果分析的癫痫发作间歇期EEG在δ频段的功能连接模式

目的 应用频域Granger因果分析方法,研究颞叶癫痫发作间歇期16导脑电图(EEG)在与癫痫发作相关的δ频段的过度放电功能连接特性.方法 实验数据来自颞叶癫痫9例患者(6例左颞叶癫痫,3例右颞叶癫痫),9例正常对照受试者.记录每例颞叶癫痫受试者在发作间歇期的痫样放电、非痫样放电以及正常对照组的共3个状态的16导EEG;每个状态下各记录10个EEG数据段,每个数据段长度为20s,采样频率为200 Hz;应用带通滤波提取EEG的δ分量(1～4 Hz).应用频域Granger因果分析方法,分别计算痫样放电组、非痫样放电组和正常组10次记录的16通道EEGδ频段分量之间的频域因果度量平均值Iδ;分析以上3个组颞叶区(左颞叶癫痫:T3、T5,右颞叶癫痫:T4、T6)与额区(Fp1、Fp2、F3、F4)和顶区(C3、C4)之间EEG在δ频段的功能连接模式.结果 痫样放电组:下颞叶区(左下颞叶区T5,右下颞叶区T6)与额区、顶区之间Iδ在0.1323±0.0329～0.1670±0.0289;非痫样放电组:下颞叶区与额区、顶区之间的Iδ在0.0300±0.0130～0.0420±0.0072;正常对照组:下颞叶区与额区、顶区之间的Iδ在0.0153±0.0028～0.0193±0.0057.统计结果表明:痫样放电组下颞叶区与额区、顶区之间的Iδ值与非痫样放电组相比差异有统计学意义(P＜0.05),与正常对照组相比差异有统计学意义(P＜0.01);非痫样放电组下颞叶区与额叶、顶叶之间的Iδ值和正常对照组相比差异无统计学意义(P＞0.05).结论 颞叶癫痫发作间歇期在痫样放电状态下,EEGδ频段在下颞叶区与额区、顶区之间存在较强连接,过度放电从下颞叶区传递到额区和顶区.非痫样放电组和正常组的EEGδ频段,下颞叶区与额叶、顶叶之间连接弱,下颞叶区不是EEG信号传导的起始区.     

颞叶癫痫患者全脑皮层厚度分析

观察并探讨颞叶癫痫(TLE)患者脑皮层厚度变化。 对71例颞叶癫痫患者(左侧癫痫组40例、右侧癫痫组31例)及17名健康对照组进行三维扰相梯度回波序列(3D-SPGR)扫描,采集数据通过Freesurfer软件进行大脑模型重建;再利用Brainstorm软件配准、平滑,以双样本独立t检验分别比较癫痫组与对照组,和癫痫组间皮层厚度的差异,并将具有统计学意义(P<0.01)的区域在标准脑模板上标注显示。 结果显示,与正常组比较,癫痫组均出现部分颞叶及颞叶意外脑区皮层厚度增大的现象,但异常脑区存在不同(左侧27个,右侧11个);癫痫组间比较,左侧癫痫组患者在左侧额下回眶部皮层增厚现象更为明显。 颞叶癫痫患者的情感及认知等障碍可能与多个脑区皮层增厚的问题有关。     

视频脑电图对颞叶内侧癫癎致癎灶定侧价值探讨

目的：探讨视频脑电图（V—EEG）对颞叶内侧癫癎（MTLE）致痼灶定侧的价值。方法：回顾性分析34例MTLE患者的发作间期及发作期V—EEG提供的致癎灶的侧别信息,并与术中深部电极检测到颞叶内侧部位的痫样放电的侧别进行比较。结果：发作间期、发作期V-EEG能定侧的分别是23例（68％）,29例（85％）。与术中深部电极检查定侧符合的分别是20例（87％）,26例（90％）,两者的定侧符合率比较差异无统计学意义（P〉0．05）。结论：MTLE患者发作间期痫样放电呈单侧分布或分布有绝对的侧别优势时,定侧意义较大,与发作期EEG对致癎灶定侧意义相当。     

基于立体定向脑电图的颞叶致痫网络独立有效相干分析

临床上,立体定向脑电图(SEEG)广泛应用于记录患者颅内的电活动,其中基于SEEG构建的致痫网络能更好地描述癫痫发作的起源与传播过程,是神经外科确定致痫区的重要手段。本文以5例难治性颞叶癫痫和1例颞叶外癫痫患者的SEEG数据为基础,结合手术切除区域,分析了致痫网络中信息流出(出度值)、流入(入度值)节点与致痫区的相对关系。本文首先在对SEEG数据进行双极导联变换的基础上,对发作初期、中期和后期的SEEG以替代数据法和独立有效相干方法(iCoh)建立致痫网络,然后在δ、θ、α、β和γ频段上分别计算了网络节点的出度值和入度值。最后对患者致痫区内外节点的网络特征进行K-均值(K-means)聚类算法分析,将均值高的分类与致痫区通道进行比较,计算分类准确率。最终结果表明,出度值在δ、α和β频段下对颞叶癫痫的平均分类准确率分别为0.90、0.88和0.89,而网络节点的入度值无区分性。与之相比,颞叶外癫痫患者出度值在颞叶外区域高于颞叶区域。本文研究结果体现出颞叶癫痫患者的低频致痫网络出度值具有很高的分类准确率,今后或可为临床判断患者是否为颞叶癫痫提供一种量化参考指标。     

Fetal cortical transplants reduce the thalamic atrophy induced by frontal cortical lesions in newborn rats

Fetal neocortical tissue was grafted into frontal cortex lesion cavities made in newborn rats. After survival periods extending up to 14 months, volumetric measurements of the total thalamus and of the lateral, medial and anterior thalamic compartments showed an amelioration of the thalamic atrophy that normally is found after cortical lesions. These results correspond to previous findings demonstrating interconnections between fetal cortical transplants and the host thalamus.     

Spinocerebellar ataxia type 3 (SCA3): thalamic neurodegeneration occurs independently from thalamic ataxin-3 immunopositive neuronal intranuclear inclusions

In the last years progress has been made regarding the involvement of the thalamus during the course of the currently known polyglutamine diseases. Although recent studies have shown that the thalamus consistently undergoes neurodegeneration in Huntington's disease (HD) and spinocerebellar ataxia type 2 (SCA2) it is still unclear whether it is also a consistent target of the pathological process of spinocerebellar ataxia type 3 (SCA3). Accordingly we studied the thalamic pathoanatomy and distribution pattern of ataxin-3 immunopositive neuronal intranuclear inclusions (NI) in nine clinically diagnosed and genetically confirmed SCA3 patients and carried out a detailed statistical analysis of our findings. During our pathoanatomical study we disclosed (i) a consistent degeneration of the ventral anterior, ventral lateral and reticular thalamic nuclei; (ii) a degeneration of the ventral posterior lateral nucleus and inferior and lateral subnuclei of the pulvinar in the majority of these SCA3 patients; and (iii) a degeneration of the ventral posterior medial and lateral posterior thalamic nuclei, the lateral geniculate body and some of the limbic thalamic nuclei in some of them. Upon immunocytochemical analysis we detected NI in all of the thalamic nuclei of all of our SCA3 patients. According to our statistical analysis (i) thalamic neurodegeneration and the occurrence of ataxin-3 immunopositive thalamic NI was not associated with the individual length of the CAG-repeats in the mutated SCA3 allele, the patients age at disease onset and the duration of SCA3 and (ii) thalamic neurodegeneration was not correlated with the occurrence of ataxin-3 immunopositive thalamic NI. This lack of correlation may suggest that ataxin-3 immunopositive NI are not immediately decisive for the fate of affected nerve cells but rather represent unspecific and pathognomonic morphological markers of SCA3.     

Unusual manifestations of thalamic strokes

Four patients of thalamic strokes with different symptoms are reported. The first had thalamic haemorrhage and developed delayed blepharospasm. The second patient had occlusion of posterior cerebral artery causing infarction of lateral thalamus and occipital lobes. The remaining two patients exhibited ipsilateral hemisensory loss and hemiataxia in absence of hemiparesis (thalamic ataxia). Both had circumscribed lesions in lateral thalamus. 'Thalamic ataxia' has a distinct localizing value. Thalamic strokes produce heterogenous clinical manifestations attributed to the involvement of different nuclei.     

Synaptic physiology of the flow of information in the cat's visual cortex in vivo

Each stage of the striate cortical circuit extracts novel information about the visual environment. We asked if this analytic process reflected laminar variations in synaptic physiology by making whole-cell recording with dye-filled electrodes from the cat's visual cortex and thalamus; the stimuli were flashed spots. Thalamic afferents terminate in layer 4, which contains two types of cell, simple and complex, distinguished by the spatial structure of the receptive field. Previously, we had found that the postsynaptic and spike responses of simple cells reliably followed the time course of flash-evoked thalamic activity. Here we report that complex cells in layer 4 (or cells intermediate between simple and complex) similarly reprised thalamic activity (response/trial, 99 ± 1.9 %; response duration 159 ± 57 ms; latency 25 ± 4 ms; average ± standard deviation;   n = 7  ). Thus, all cells in layer 4 share a common synaptic physiology that allows secure integration of thalamic input. By contrast, at the second cortical stage (layer 2+3), where layer 4 directs its output, postsynaptic responses did not track simple patterns of antecedent activity. Typical responses to the static stimulus were intermittent and brief (response/trial, 31 ± 40 %; response duration 72 ± 60 ms, latency 39 ± 7 ms;   n = 11  ). Only richer stimuli like those including motion evoked reliable responses. All told, the second level of cortical processing differs markedly from the first. At that later stage, ascending information seems strongly gated by connections between cortical neurons. Inputs must be combined in newly specified patterns to influence intracortical stages of processing.     

Cyto- and chemoarchitecture of the dorsal thalamus of the monotreme Tachyglossus aculeatus, the short beaked echidna

We have examined the cyto- and chemoarchitecture of the dorsal thalamus of the short beaked echidna (Tachyglossus aculeatus), using Nissl and myelin staining, immunoreactivity for parvalbumin, calbindin, calretinin and non-phosphorylated neurofilament protein (SMI-32 antibody), and histochemistry for acetylcholinesterase and NADPH diaphorase. Immunohistochemical methods revealed many nuclear boundaries, which were difficult to discern with Nissl staining. Parvalbumin immunoreactive somata were concentrated in the ventral posterior, reticular, posterior, lateral and medial geniculate nuclei, while parvalbumin immunoreactivity of the neuropil was present throughout all but the midline nuclei. Large numbers of calbindin immunoreactive somata were also found within the midline thalamic nuclei, and thalamic sensory relay nuclei. Immunoreactivity for calretinin was found in many small somata within the lateral geniculate “a” nucleus, with other labelled somata found in the lateral geniculate “b” nucleus, ventral posterior medial and ventral posterior lateral nuclei. Immunoreactivity with the SMI-32 antibody was largely confined to somata and neuropil within the thalamocortical relay nuclei (ventral posterior medial and lateral nuclei, lateral and medial geniculate nuclei and the posterior thalamic nucleus). In broad terms there were many similarities between the thalamus of this monotreme and that of eutheria (e.g. disposition of somatosensory thalamus, complementarity of parvalbumin and calbindin immunoreactive structures), but there were some unique features of the thalamus of the echidna. These include the relatively small size of the thalamic reticular nucleus and the preponderance of calbindin immunoreactive neurons over parvalbumin immunoreactive neurons in the ventral posterior nucleus.     

Cyto- and chemoarchitecture of the dorsal thalamus of the monotreme Tachyglossus aculeatus,the short beaked echidna

We have examined the cyto- and chemoarchitecture of the dorsal thalamus of the short beaked echidna (Tachyglossus aculeatus), using Nissl and myelin staining, immunoreactivity for parvalbumin, calbindin, calretinin and non-phosphorylated neurofilament protein (SMI-32 antibody), and histochemistry for acetylcholinesterase and NADPH diaphorase. Immunohistochemical methods revealed many nuclear boundaries, which were difficult to discern with Nissl staining. Parvalbumin immunoreactive somata were concentrated in the ventral posterior, reticular, posterior, lateral and medial geniculate nuclei, while parvalbumin immunoreactivity of the neuropil was present throughout all but the midline nuclei. Large numbers of calbindin immunoreactive somata were also found within the midline thalamic nuclei, and thalamic sensory relay nuclei. Immunoreactivity for calretinin was found in many small somata within the lateral geniculate “a” nucleus, with other labelled somata found in the lateral geniculate “b” nucleus, ventral posterior medial and ventral posterior lateral nuclei. Immunoreactivity with the SMI-32 antibody was largely confined to somata and neuropil within the thalamocortical relay nuclei (ventral posterior medial and lateral nuclei, lateral and medial geniculate nuclei and the posterior thalamic nucleus). In broad terms there were many similarities between the thalamus of this monotreme and that of eutheria (e.g. disposition of somatosensory thalamus, complementarity of parvalbumin and calbindin immunoreactive structures), but there were some unique features of the thalamus of the echidna. These include the relatively small size of the thalamic reticular nucleus and the preponderance of calbindin immunoreactive neurons over parvalbumin immunoreactive neurons in the ventral posterior nucleus.     

The visceral sector of the thalamic reticular nucleus in the rat.

Visceral sensory perception is subjected to modulation by attention or distraction, like other sensory systems. The thalamic reticular nucleus is a key region in selective attention, effecting a change in the mode of thalamocortical transmission. Each major thalamocortical system is connected with a particular sector of the thalamic reticular nucleus. No connections from the thalamic reticular nucleus have been described to the visceral sensory thalamus. We used axonal tracing techniques to study the possible existence of reciprocal connections between the visceral sensory relay in the lateral ventroposterior parvicellular thalamic nucleus, and the reticular nucleus of the thalamus. We also studied the projections from the visceral sensory cortex, located in the granular insular cortex in the rat, to the reticular nucleus of the thalamus. We found a convergent input from both thalamic and cortical sensory visceral regions to the same sector of the reticular nucleus of the thalamus. This visceral sector in turn sent GABAergic feedback connections to the lateral ventroposterior parvicellular thalamic nucleus. In addition, the visceral thalamus received histaminergic projections from the tuberomammillary nucleus, and noradrenergic projections from the locus coeruleus; both nuclei belong to the ascending activating system.Our findings indicate that the visceral sensory thalamocortical pathway is connected to the same subcortical structures that provide attention mechanisms for other thalamocortical systems.     

Comparison of oculomotor neuronal activity in paralaminar and mediodorsal thalamus in the rhesus monkey

We previously reported that neurons in the mediodorsal thalamic nucleus (MD) are topographically organized and express spatial and nonspatial coding properties similar to those of the prefrontal areas with which they are connected. In the course of mapping the dorsal thalamus, we also studied neurons in a subset of thalamic nuclei (the caudal part of the ventral lateral nucleus (VLc), the oral part of the ventral posterior lateral nucleus (VPLo), the parvocellular part of the ventral anterior nucleus (VApc)) lateral to the MD and just across the internal medullary lamina. We compared these "paralaminar" neurons to MD neurons by having monkeys perform the same spatial and nonspatial cognitive tasks as those used to investigate the MD; these included two saccadic tasks-one requiring delayed and the other immediate responses-and one picture fixation task. Of the paralaminar thalamic neurons modulated by the saccadic tasks, a majority had saccade-related activity, and this was nearly always spatially tuned. Also, for about half of these neurons, the saccade-related activity occurred exclusively during the delayed-response task. No neurons with event-related activity in the saccadic tasks were preferentially modulated by specific picture stimuli, although other neurons were. All of these results were similar to what we had found for MD neurons. However, in contrast to the high proportion of presaccadic responses observed in the MD, the majority of saccade-related neurons in paralaminar thalamus exhibited mid- or postsaccadic activity, i.e., that started during or after the saccade. Our findings suggest that neurons in the paralaminar thalamus may be possible conduits of oculomotor feedback signals, especially during memory-guided saccades.     

Cross-modal plasticity in the human thalamus: evidence from intraoperative macrostimulations

During stereotactic functional neurosurgery, stimulation procedure to control for proper target localization provides a unique opportunity to investigate pathophysiological phenomena that cannot be addressed in experimental setups. Here we report on the distribution of response modalities to 487 intraoperative thalamic stimulations performed in 24 neurogenic pain (NP), 17 parkinsonian (PD) and 10 neuropsychiatric (Npsy) patients. Threshold responses were subdivided into somatosensory, motor and affective, and compared between medial (central lateral nucleus) and lateral (ventral anterior, ventral lateral and ventral medial) thalamic nuclei and between patients groups. Major findings were as follows: in the medial thalamus, evoked responses were for a large majority (95%) somatosensory in NP patients, 47% were motor in PD patients, and 54% affective in Npsy patients. In the lateral thalamus, a much higher proportion of somatosensory (83%) than motor responses (5%) was evoked in NP patients, while the proportion was reversed in PD patients (69% motor vs. 21% somatosensory). These results provide the first evidence for functional cross-modal changes in lateral and medial thalamic nuclei in response to intraoperative stimulations in different functional disorders. This extensive functional reorganization sheds new light on wide-range plasticity in the adult human thalamocortical system.     

Mapping of somatostatin-28 (1-12) in the alpaca diencephalon

Using an immunocytochemical technique, we report for the first time the distribution of immunoreactive cell bodies and fibers containing somatostatin-28 (1-12) in the alpaca diencephalon. Somatostatin-28 (1-12)-immunoreactive cell bodies were only observed in the hypothalamus (lateral hypothalamic area, arcuate nucleus and ventromedial hypothalamic nucleus). However, immunoreactive fibers were widely distributed throughout the thalamus and hypothalamus. A high density of such fibers was observed in the central medial thalamic nucleus, laterodorsal thalamic nucleus, lateral habenular nucleus, mediodorsal thalamic nucleus, paraventricular thalamic nucleus, reuniens thalamic nucleus, rhomboid thalamic nucleus, subparafascicular thalamic nucleus, anterior hypothalamic area, arcuate nucleus, dorsal hypothalamic area, around the fornix, lateral hypothalamic area, lateral mammilary nucleus, posterior hypothalamic nucleus, paraventricular hypothalamic nucleus, suprachiasmatic nucleus, supraoptic hypothalamic nucleus, and in the ventromedial hypothalamic nucleus. The widespread distribution of somatostatin-28 (1-12) in the thalamus and hypothalamus of the alpaca suggests that the neuropeptide could be involved in many physiological actions.