Unusual neural tract between injured fornix and pedunculopontine nucleus in a patient with traumatic brain injury

It has been known that four cholinergic nuclei are located in the septal region and basal forebrain （Ch 1： medial septal nucleus, Ch 2： vertical nucleus of the diagonal band, Ch 3： horizontal limb of the diagonal band and Ch 4： nucleus basalis of Meynert） and two are located in the brainstem （Ch 5： pedunculopontine nucleus and Ch 6： laterodorsal tegmental nucleus） （Selden et al., 1998; Lucas-Meunier et al., 2003; Mesulam, 2004; Nieuwenhuys et al., 2007）. The fornix transfers information on episodic mem- ory between the medial diencephalon and the medial temporal lobe （Afifi and Bergman, 2005; Wolk and Budson, 2010）. The fornix is known to obtain cholinergic innervation from Ch 1 and Ch 2, and to project to the hippocampal formation （Selden et al., 1998; Lucas-Meunier et al., 2003; Mesulam, 2004; Nieu- wenhuys et al., 2007; Dere et al., 2008; Naidich and Duvernoy, 2009; Isaacson and Pribram, 2013）.

Biotinylated dextran amine as a neural tracer in the rat corticospinal tract

BACKGROUND： The corticospinal tract is the core structure of cerebral control of extremity movement and plasticity, which are prerequisites for movement rehabilitation after brain injury. The measurement and assessment of plasticity changes within the corticospinal tract has become one of the key goals in this field. OBJECTIVE： To explore the effects of biotinylated dextran amine （BDA） as a neural tracer in the rat corticospinal tract and the possibilities of assessing plasticity within the corticospinal tract. DESIGN： An observational experiment. SETTING： Department of Acupuncture of Chinese Medical College, Chongqing Medical University, Department of Neurology, the Second Affiliated Hospital, Chongqing Medical University. MATERIALS： Eighteen male adult Sprague Dawley （SD） rats of clean grade, weighing 200-250 g, were provided by the experimental animal center of Chongqing Medical University. The animal procedures in this study were in accordance with the animal ethics standards. BDA was provided by Vector Laboratories Company （USA, catalogue Sp- 1140; serial number R0721 ）. METHODS. This experiment was performed in the Laboratory of Chongqing Medical University between September and December 2006. Adult SD rats were used in the experiment and 15% BDA was injected slowly with a mini-syringe through two round （3 mm diameter） holes into the left sensory and motor cortex. The center of one hole was located 3 mm anterior from the anterior fontanel and 1.5 mm left of the midline; the second hole was located 1.5 mm posterior from the anterior fontanel and 4 mm left of the midline. Three injections were made at each hole at three different levels： 1.4, 1.2, and 1 mm ventral from the surface of the flat skull. After 14 days, the brains and spinal cords were removed and frozen. Sections were cut on a cryostat and BDA transportation absorbed by axons was observed under a fluorescence microscope. MAIN OUTCOME MEASURES： Axonal absorption and transportation of BDA was observed under fluorescence microscope. RESULTS： Eighteen SD rats were enrolled in this experiment; 12 rats were included in the final analysis and six were eliminated, resulting in a dropout rate of 33% （6/18）. BDA injected into the left cortex was absorbed in the axons, and fluorescence was observed throughout the pyramidal neurons and axons of the left cerebral cortex. At 14 days after rejection, BDA was detected in the midbrain and cervical enlargement along the CST, and axonal structures and Ranvier nodes were clearly observed with 200x magnification. CONCLUSION： BDA injected into the cerebral cortex effectively traces the corticospinal tract and is biologically stable over long distance transportation. In addition, the method of BDA tracing is fairly simple to perform.

Biotinylated dextran amine tracing of nerve tracts determines regeneration of corticospinal tracts after neural stem cell transplantation

We investigated regeneration of the corticospinal tract and rearrangement of corticospinal nerves after spinal cord injury by biotinylated dextran amine （BDA） nerve tract tracing after neural stem cell transplantation. Neural stem cell transplantation increased motor function scores of rats at 3 weeks after spinal cord transection injury at the thoracic 10 segment. A proportion of BDA-labeled corticospinal tract regenerated through the spinal cord injury site at 12 weeks after transplantation. Electron microscopy revealed that the regenerated BDA-labeled nerve terminals formed new synaptic connections with neurons at the distal end of the injured site. These findings indicate that BDA nerve tract tracing effectively provides anatomic and morphological evidence of recovery after spinal cord injury.

Neural tracer for visualization of the corticospinal tract

Fluoro-ruby was injected into the posterior funiculus of the spinal cord in the cervical （C5 -I-2） and lumbar （L3a） segments of adult guinea pigs. The spinal cord was cut into serial frozen sections. The Fluoro-ruby labeling was clearly delineated from the surrounding structure. The labeling traversed the cervical, thoracic and lumbar segments, and was located on the ventral portion of the posterior funiculus on the injected side, proximal to the intermediate zone of the dorsal gray matter. The fluorescence area narrowed rostro-caudally. The spinal cord, spinal cord gray matter and corticospinal tract were reconstructed using 3D-DOCTOR 4.0 software, resulting in a robust three-dimensional profile. Using functionality provided by the reconstruction software, free multi-angle observation and sectioning could be conducted on the spinal cord and corticospinal tract. Our experimental findings indicate that the Fluoro-ruby retrograde fluorescent tracing technique can accurately display the anatomical location of corticospinal tract in the guinea pig and that three-dimensional reconstruction software can be used to provide a three-dimensional image of the corticospinal tract.

Diffusion tensor tractography characteristics of axonal injury in concussion/mild traumatic brain injury

The main advantage of diffusion tensor tractography is that it allows the entire neural tract to be evaluated.In addition,configurational analysis of reconstructed neural tracts can indicate abnormalities such as tearing,narrowing,or discontinuations,which have been used to identify axonal injury of neural tracts in concussion patients.This review focuses on the characteristic features of axonal injury in concussion or mild traumatic brain injury(m TBI)patients through the use of diffusion tensor tractography.Axonal injury in concussion(m TBI)patients is characterized by their occurrence in long neural tracts and multiple injuries,and these characteristics are common in patients with diffuse axonal injury and in concussion(m TBI)patients with axonal injury.However,the discontinuation of the corticospinal tract is mostly observed in diffuse axonal injury,and partial tearing and narrowing in the subcortical white matter are frequently observed in concussion(m TBI)patients with axonal injury.This difference appears to be attributed to the observation that axonal injury in concussion(m TBI)patients is the result of weaker forces than those producing diffuse axonal injuries.In addition,regarding the fornix,in diffuse axonal injury,discontinuation of the fornical crus has been frequently reported,but in concussion(m TBI)patients,many collateral branches form in the fornix in addition to these findings in many case studies.It is presumed that the impact on the brain in TBI is relatively weaker than that in diffuse axonal injury,and that the formation of collateral branches occurs during the fornix recovery process.Although the occurrence of axonal injury in multiple areas of the brain is an important feature of diffuse axonal injury,case studies in concussion(m TBI)have shown that axonal injury occurs in multiple neural tracts.Because axonal injury lesions in m TBI patients may persist for approximately 10 years after injury onset,the characteristics of axonal injury in concussion(m TBI)patients,which are reviewed and categorized in this review,are expected to serve as useful supplementary information in the diagnosis of axonal injury in concussion(m TBI)patients.

磁共振弥散张量成像评估针刺治疗儿童孤独症的疗效价值研究

目的 采用磁共振弥散张量成像(diffusion tensor imaging, DTI)观察针刺治疗前后孤独症谱系障碍(autism spectrum disorder, ASD)患儿脑白质微观结构的变化,以探索针刺在ASD中应用价值及DTI在评估针刺效果中作用。材料与方法 前瞻性纳入2021年11月至2022年10月在我院确诊的ASD患儿,按照随机数字表法分为针刺组和假针刺组,进行12周的干预治疗,于治疗前(第0周)及治疗后(第12周)行儿童孤独症评定量表(Child Autism Rating Scale, CARS)、孤独症儿童行为量表(Autism Behavior Checklist, ABC)、孤独症疗效评价量表(Autism Treatment Evaluation Checklist, ATEC)及DTI检查。比较两组间各项量表评分变化,采用基于纤维束示踪的空间统计方法(tract-based spatial statistics, TBSS)分析两组间脑白质各向异性分数(fractional anisotropy, FA)的差异,继而比较FA有差异脑区的平均弥散率(mean diffusivity, MD)、径向弥散系数(radial diffusivity, RD)和轴向弥散系数(axial diffusivity, AD)的不同及量表评分与DTI参数相关性。结果 与假针刺组相比,治疗后针刺组各项量表评分较治疗前显著降低,差异具有统计学意义(P<0.05)。治疗后两组间FA值差异具有统计学意义(P<0.05),RD值差异无统计学意义(P>0.05),AD值两组间在左下纵束差异有统计学意义(P<0.05)。相关性分析发现:ASD患儿ATEC评分与右扣带回的FA值呈负相关,与右额枕下束、右下纵束、右扣带回的RD值呈正相关,与右扣带回的AD值呈正相关;CARS评分与右扣带回的AD值呈正相关(P<0.05)。右下纵束的FA值与ASD患儿的语言问题、感知觉异常呈负相关,RD值与社交障碍、感知觉异常呈正相关;右扣带回的FA值与语言问题、社交障碍、感知觉异常呈负相关,而RD值与上述临床症状呈正相关,AD值与社交障碍、健康问题呈正相关;双侧额枕下束FA值与感知觉异常存在负相关,右额枕下束RD值与其社交障碍、感知觉异常呈正相关;右上纵束的RD值与感知觉异常呈正相关;左丘脑前辐射束的AD值与感知觉异常呈正相关(P<0.05)。结论 针刺可能通过促进脑白质纤维束完整性增强,从而改善ASD患儿临床症状,尤其在言语、社交、感知觉、健康问题等方面,进而说明DTI在评估针刺治疗效果中具有重要价值。

Fine motor skill training enhances functional plasticity of the corticospinal tract after spinal cord injury

Following central nervous system injury, axonal sprouts form distal to the injury site and extend into the denervated area, reconstructing neural circuits through neural plasticity. How to facilitate this plasticity has become the key to the success of central nervous system repair. It remains controversial whether fine motor skill training contributes to the recovery of neurological function after spinal cord injury. Therefore, we established a rat model of unilateral corticospinal tract injury using a pyramidal tract cutting method. Horizontal ladder crawling and food ball grasping training procedures were conducted 2 weeks before injury and 3 days after injury. The neurological function of rat forelimbs was assessed at 1, 2, 3, 4, and 6 weeks after injury. Axon growth was observed with biotinylated dextran amine anterograde tracing in the healthy corticospinal tract of the denervated area at different time periods. Our results demonstrate that compared with untrained rats, functional recovery was better in the forelimbs and forepaws of trained rats. The number of axons and the expression of growth associated protein 43 were increased at the injury site 3 weeks after corticospinal tract injury. These findings confirm that fine motor skill training promotes central nervous system plasticity in spinal cord injury rats.

Pathological verification of corticospinal tract Wallerian degeneration in a rat model of brain ischemia

Although neuroimaging is commonly utilized to study Wallerian degeneration, it cannot display Wallerian degeneration early after brain injury. In the present study, we attempted to examine pathologically the process of Wallerian degeneration early after brain injury. Cerebral peduncle demyelination was observed at 3 weeks post brain ischemia, followed by demyelination in the cervical enlargement at 6 weeks. Anterograde tracing of the corticospinal tract with biotinylated dextran amine showed that following serious neurologic deficit, the tracing of the corticospinal tract of the intemal capsule, cerebral peduncle, and cervical enlargement indicated serious Wallerian degeneration.

Central post-stroke pain due to injury of the spinothalamic tract in patients with cerebral infarction： a diffusion tensor tractography imaging study

Many studies using diffusion tensor tractography（DTT） have demonstrated that injury of the spinothalamic tract（STT） is the pathogenetic mechanism of central post-stroke pain（CPSP） in intracerebral hemorrhage; however, there is no DTT study reporting the pathogenetic mechanism of CPSP in cerebral infarction. In this study, we investigated injury of the STT in patients with CPSP following cerebral infarction, using DTT. Five patients with CPSP following cerebral infarction and eight age-and sex-matched healthy control subjects were recruited for this study. STT was examined using DTT. Among DTT parameters of the affected STT, fractional anisotropy and tract volume were decreased by more than two standard deviations in two patients（patients 1 and 2） and three patients（patients 3, 4, and 5）, respectively, compared with those of the control subjects, while mean diffusivity value was increased by more than two standard deviations in one patient（patient 2）. Regarding DTT configuration, all affected STTs passed through adjacent part of the infarct and three STTs showed narrowing. These findings suggest that injury of the STT might be a pathogenetic etiology of CPSP in patients with cerebral infarction.

Right lower limb apraxia in a patient with left supplementary motor area infarction: intactness of the corticospinal tract confirmed by transcranial magnetic stimulation

We reported a 50-year-old female patient with left supplementary motor area infarction who presented right lower limb apraxia and investigated the possible causes using transcranial magnetic stimulation. The patient was able to walk and climb stairs spontaneously without any assistance at 3 weeks after onset. However, she was unable to intentionally move her right lower limb although she understood what she supposed to do. The motor evoked potential evoked by transcranial magnetic stimulation from the right lower limb was within the normal range, indicating that the corticospinal tract innervating the right lower limb was uninjured. Thus, we thought that her motor dysfunction was not induced by motor weakness, and confirmed her symptoms as aprax- ia. In addition, these results also suggest that transcranial magnetic stimulation is helpful for diagnosing apraxia.

A new computational approach for modeling diffusion tractography in the brain

Computational models provide additional tools for studying the brain,however,many techniques are currently disconnected from each other.There is a need for new computational approaches that span the range of physics operating in the brain.In this review paper,we offer some new perspectives on how the embedded element method can fill this gap and has the potential to connect a myriad of modeling genre.The embedded element method is a mesh superposition technique used within finite element analysis.This method allows for the incorporation of axonal fiber tracts to be explicitly represented.Here,we explore the use of the approach beyond its original goal of predicting axonal strain in brain injury.We explore the potential application of the embedded element method in areas of electrophysiology,neurodegeneration,neuropharmacology and mechanobiology.We conclude that this method has the potential to provide us with an integrated computational framework that can assist in developing improved diagnostic tools and regeneration technologies.

Activation of less affected corticospinal tract and poor motor outcome in hemiplegic pediatric patients:a diffusion tensor tractography imaging study

The less affected hemisphere is important in motor recovery in mature brains.However,in terms of motor outcome in immature brains,no study has been reported on the less affected corticospinal tract in hemiplegic pediatric patients.Therefore,we examined the relationship between the condition of the less affected corticospinal tract and motor function in hemiplegic pediatric patients.Forty patients with hemiplegia due to perinatal or prenatal injury（13.7±3.0 months）and 40 age-matched typically developing controls were recruited.These patients were divided into two age-matched groups,the high functioning group（20 patients）and the low functioning group（20 patients）using functional level of hemiplegia scale.Diffusion tensor tractography images showed that compared with the control group,the patient group of the less affected corticospinal tract showed significantly increased fiber number and significantly decreased fractional anisotropy value.Significantly increased fiber number and significantly decreased fractional anisotropy value in the low functioning group were observed than in the high functioning group.These findings suggest that activation of the less affected hemisphere presenting as increased fiber number and decreased fractional anisotropy value is related to poor motor function in pediatric hemiplegic patients.

Diffusion tensor imaging detects Wallerian degeneration of the corticospinal tract early after cerebral infarction

To investigate the feasibility and time window of early detection of Wallerian degeneration in the corticospinal tract after middle cerebral artery infarction, 23 patients were assessed using magnetic resonance diffusion tensor imaging at 3.0T within 14 days after the infarction. The fractional anisotropy values of the affected corticospinal tract began to decrease at 3 days after onset and decreased in all cases at 7 days. The diffusion coefficient remained unchanged. Experimental findings indicate that diffusion tensor imaging can detect the changes associated with Wallerian degeneration of the corticospinal tract as early as 3 days after cerebral infarction.

Effects of Fujian tablet on Nogo-A mRNA expression and plasticity of the corticospinal tract in a rat model of focal cerebral ischemia

The present study investigated the effects of Fujian tablet, a Chinese medicine compound that can nourish liver and kidney, on corticospinal tract plasticity and cervical cord microenvironment in rats with focal cerebral ischemia. Results showed that motor function of rats with right proximal middle cerebral artery occlusion was significantly improved following treatment with Fujian tablet, 9 g crude drug/kg. Anterograde tracing revealed significantly increased biotinylated dextran amine expression in the denervated （left） side of the cervical cord （C4-6） following Fujian tablet treatment, and significantly decreased Nogo-A mRNA expression was detected in the denervated side of the cervical cord （C4-6） using in situ hybridization. Pearson＇s correlation analysis showed a negative correlation between biotinylated dextran amine and Nogo-A mRNA expression （r = -0.943, P 〈 0.01）. Results demonstrated that Fujian tablet can promote corticospinal tract plasticity possibly through the inhibitory effect on Nogo-A mRNA expression in the cervical spinal cord, thereby improving motor dysfunction.

Change in connection between corticospinal tract and Broca's area during motor recovery in a patient with an intracerebral hemorrhage

The present study reported a 42-year-old male patient who underwent conservative management for a spontaneous intracerebral hemorrhage in the left corona radiata and the basal ganglia. The patient presented with complete weakness of the right upper and lower extremities at the onset of intracerebral hemorrhage; however, he showed progressive motor recovery to the level that he was able to extent the affected extremities against some resistance at 5 weeks after onset. The corticospinal tract of the affected （left） hemisphere connected to the left Broca＇s area at 3 weeks after onset as shown by diffusion tensor tractography. By contrast, this connection had disappeared at 5 weeks after onset as shown by diffusion tensor tractogaphy. Transcranial magnetic stimulation study showed that no motor evoked potential was elicited from the affected （left） hemisphere at 3 weeks after onset, but motor evoked potentials were elicited at 5 weeks after onset. These findings suggest that the connection between the injured corticospinal tract and Broca＇s area in this patient appears to be a compensation for severe motor weakness; consequently, the connection seems to disappear with motor recovery.

Fractional anisotropy of the corticospinal tract in normal adults: Preliminary study using a diffusion tensor imaging technique

BACKGROUND： The corticospinal tract is an important tract for conducting motor function. The majority of studies focus on lesions of the corticospinal tract on appearance and function, whereas observation of normal corticospinal pathways can also improve understanding of lesion outcomes. OBJECTIVE： To observe the normal adult corticospinal tract using a diffusion tensor imaging technique to analyze fractional anisotropy （FA） in different levels of the brain. DESIGN, TIME AND SETTING： Neuroimaging observation was performed in the MRI Department, First Affiliated Hospital of Kunming Medical College in China, from October 2005 to October 2008. PARTICIPANTS： A total of 30 healthy adults were selected from the Department of MRI, First Affiliated Hospital of Kunming Medical College in China, from October 2005 to October 2008, and people with nervous system symptoms and signs were excluded. METHODS： Participants with normal conventional MRI results underwent diffusion tensor imaging examination in a 1.5 T GE MRI （slice thickness 4-5 mm, slice gap 0） for gradient data acquisition from 15 directions. The scanning involved the entire brain from the inferior medulla oblongata to the inferior cranial plate. Imaging post-processing was performed to obtain FA values; a paired t-test was applied for statistical analysis. MAIN OUTCOME MEASURES： FA values of the bilateral corticospinal tract in the medulla oblongata, pons, cerebral peduncle, basal ganglia, corona radiata, and centrum semiovale. RESULTS： FA values in the medulla oblongata and centrum semiovale were similar （P 〉 0.01）. FA values of left corticospinal tract were significantly greater than the right side in the pons, cerebral peduncle, basal ganglia and corona radiata （P 〈 0.01）. CONCLUSION： FA values vary by brain levels, including pons, cerebral peduncle, basal ganglia, and corona radiata. Moreover, FA values of the left corticospinal tract pathway were greater than the right side, which may relate to right handedness.

Peri-infarct reorganization at the centrum semiovale and corona radiata A diffusion tensor tractography and functional MRI study

Peri-infarct reorganization has been reported in stroke patients with a lesion at the cerebral cortex, corona radiata, or pons, separately. However, there have been no reports describing the patients with peri-infarct reorganization at multiple levels. The present study reported a patient with a middle cerebral artery infarct who showed complete paralysis of the right extremities at stroke onset. Results showed that at 3 years after stroke onset, patient＇s motor function of the affected hand appeared to have been recovered by the motor tract, which reorganized into the anterior areas of the infarcted centrum semiovale and corona radiata, as demonstrated by diffusion tensor tractography study analyzed using functional MRI activation results. This result indicates that the human brain can show extensive brain plasticity and that saving the adjacent area or penumbra around the infarct even though the lesion from multiple levels is important for functional recovery after stroke.

人工神经网络算法在消化道恶性肿瘤病理诊断及患者预后预测中的应用

消化道恶性肿瘤相关的人工神经网络诊断研究成为人工智能研究热点领域。研究工具主要集中在基于卷积神经网络的模型开发上,少部分采用卷积神经网络与循环神经网络联用的方式;研究内容方面则聚焦于基于人工神经网络实现经典组织病理学诊断、利用人工神经网络进行肿瘤分子分型诊断以及预测患者预后情况。本文综述了消化道恶性肿瘤病理诊断及预后预测中人工神经网络算法的相关研究。

基于深度卷积神经网络的上消化道内镜解剖分类模型构建

目的:利用深度卷积神经网络构建上消化道内镜解剖分类模型。方法:收集苏州大学附属第一医院消化内镜中心4183张胃镜图片,按照8:2的比例随机分为训练集和验证集;同时收集江苏大学附属金坛医院270张胃镜图片作为测试集。以上图片标注上消化道解剖位置(包括食管、贲门、胃底、胃体、胃角、胃窦、幽门、十二指肠球部及降部)。选择ImageNet数据库中预训练的Xception、NASNet Large(NASNet)和ResNet50V2(ResNet)3个深度卷积神经网络,在训练集及验证集中训练,构建上消化道图片解剖部位分类模型。使用梯度加权分类激活映射对模型的分类结果进行可视化解释。在验证集和测试集中评价模型分类能力。结果:成功构建了基于深度卷积神经网络的上消化道内镜解剖分类的3个模型,各模型均具备较高的分类能力。在验证集中,平均分类准确性为0.980,平均分类召回率为0.894,平均分类精确度为0.920;其中,ResNet模型表现最优,其分类准确性(0.982)、分类召回率(0.905)和分类精确度(0.933)最高。在测试集中,平均分类准确性为0.988,平均分类召回率为0.942,平均分类精确度为0.950;其中,NASNet模型表现最优,其分类准确性(0.992)、分类召回率(0.959)和分类精确度(0.970)最高。梯度加权分类激活映射以热力图形式对模型分类结果提供可视化解释。结论:利用深度卷积神经网络,构建的上消化道内镜解剖分类模型具有较好的分类能力。

大鼠前庭核向脑干呕吐区的间接投射

前庭信息调节内脏活动的神经通路是产生运动病的结构基础,但至今尚未明了。本研究旨在探讨接受初级前庭传入信息的前庭核到脑干呕吐中枢的神经通路。向大鼠前庭内侧核和前庭下核内注入顺行追踪剂生物素化葡聚糖胺(BDA),向脑干呕吐区注入逆行追踪剂荧光金(FG),用荧光组织化学方法显示BDA顺行标记纤维和终末,在荧光显微镜下观察BDA顺行标记纤维和终末与荧光金逆行标记细胞的重叠区域。结果发现在延髓背侧巨细胞旁核(DPGi)、巨细胞网状核(Gi)和小细胞网状核(PCRt)有顺行标记纤维与逆行标记细胞的重叠。表明前庭核可能经DPGi、Gi和PCRt向呕吐区有间接投射,此结果为进一步揭示前庭信号引发恶心、呕吐的神经机制提供了形态学依据。