Manganese-enhanced magnetic resonance imaging of mossy fiber plasticity in vivo

Mn(2+)-enhanced magnetic resonance imaging (MEMRI) was used to characterize activity-dependent plasticity in the mossy fiber pathway after intraperitoneal kainic acid (KA) injection. Enhancement of the MEMRI signal in the dentate gyrus and the CA3 subregion of the hippocampus was evident 3 to 5 days after injection of MnCl(2) into the entorhinal cortex both in control and KA-injected rats. In volume-rendered three-dimensional reconstructions, Mn(2+)-induced signal enhancement revealed the extent of the mossy fiber pathway throughout the septotemporal axis of the dentate gyrus. An increase in the number of Mn(2+)-enhanced pixels in the dentate gyrus and CA3 subfield of rats with KA injection correlated (P < 0.05) with histologically verified mossy fiber sprouting. These data demonstrate that MEMRI can be used to detect specific changes at the cellular level during activity-dependent plasticity in vivo. The present findings also suggest that MEMRI signal changes can serve as an imaging marker of epileptogenesis.     

In vivo detection of neuroarchitecture in the rodent brain using manganese-enhanced MRI

Visualizing brain anatomy in vivo could provide insight into normal and pathophysiology. Here it is demonstrated that neuroarchitecture can be detected in the rodent brain using MRI after systemic MnCl2. Administration of MnCl2 leads to rapid T1 enhancement in the choroid plexus and circumventricular organs, which spreads to the CSF space in ventricles and periventricular tissue. After 1 day, there was MRI enhancement throughout the brain with high intensity in the pituitary, olfactory bulb, cortex, basal forebrain, hippocampus, basal ganglia, hypothalamus, amygdala, and cerebellum. Contrast obtained enabled visualization of specific features of neuroarchitecture. The arrowhead structure of the dentate gyrus as well as the CA1-CA3 region of the hippocampus and layers in cortex, cerebellum, as well as the olfactory bulb could be readily observed. Preliminary assignments of olfactory bulb layers, cortical layers in frontal and somatosensory cortex, and cerebellum were made. Systemic MnCl2 leads to MRI visualization of neuroarchitecture nondestructively.     

Global and regional differences in cerebral blood flow after asphyxial versus ventricular fibrillation cardiac arrest in rats using ASL-MRI

Both ventricular fibrillation cardiac arrest (VFCA) and asphyxial cardiac arrest (ACA) are frequent causes of CA. However, only isolated reports compared cerebral blood flow (CBF) reperfusion patterns after different types of CA, and even fewer reports used methods that allow serial and regional assessment of CBF. We hypothesized that the reperfusion patterns of CBF will differ between individual types of experimental CA. In a prospective block-randomized study, fentanyl-anesthetized adult rats were subjected to 8 min VFCA or ACA. Rats were then resuscitated with epinephrine, bicarbonate, manual chest compressions and mechanical ventilation. After the return of spontaneous circulation, CBF was then serially assessed via arterial spin-labeling magnetic resonance imaging (ASL-MRI) in cortex, thalamus, hippocampus and amygdala/piriform complex over 1 h resuscitation time (RT). Both ACA and VFCA produced significant temporal and regional differences in CBF. All regions in both models showed significant changes over time (p < 0.01), with early hyperperfusion and delayed hypoperfusion. ACA resulted in early hyperperfusion in cortex and thalamus (both p < 0.05 vs. amygdala/piriform complex). In contrast, VFCA induced early hyperperfusion only in cortex (p < 0.05 vs. other regions). Hyperperfusion was prolonged after ACA, peaking at 7 min RT (RT7; 199% vs. BL, Baseline, in cortex and 201% in thalamus, p < 0.05), then returning close to BL at ∼RT15. In contrast, VFCA model induced mild hyperemia, peaking at RT7 (141% vs. BL in cortex). Both ACA and VFCA showed delayed hypoperfusion (ACA, ∼30% below BL in hippocampus and amygdala/piriform complex, p < 0.05; VFCA, 34–41% below BL in hippocampus and amygdala/piriform complex, p < 0.05). In conclusion, both ACA and VFCA in adult rats produced significant regional and temporal differences in CBF. In ACA, hyperperfusion was most pronounced in cortex and thalamus. In VFCA, the changes were more modest, with hyperperfusion seen only in cortex. Both insults resulted in delayed hypoperfusion in all regions. Both early hyperperfusion and delayed hypoperfusion may be important therapeutic targets.     

The GluK1 (GluR5) Kainate/{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist LY293558 reduces soman-induced seizures and neuropathology

The possibility of mass exposure to nerve agents by a terrorist attack necessitates the availability of antidotes that can be effective against nerve agent toxicity even when administered at a relatively long latency after exposure, because medical assistance may not be immediately available. Nerve agents induce status epilepticus (SE), which can cause brain damage or death. Antagonists of kainate receptors that contain the GluK1 (formerly known as GluR5) subunit (GluK1Rs) are emerging as a new potential treatment for SE and epilepsy from animal research, whereas clinical trials to treat pain have shown that the GluK1/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist LY293558 [(3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid] is safe and well tolerated. Therefore, we tested whether LY293558 is effective against soman-induced seizures and neuropathology, when administered 1 h after soman exposure, in rats. LY293558 stopped seizures induced by soman and reduced the total duration of SE, monitored by electroencephalographic recordings within a 24 h-period after exposure. In addition, LY293558 prevented neuronal loss in the basolateral amygdala (BLA) and the CA1 hippocampal area on both days 1 and 7 after soman exposure and reduced neuronal degeneration in the CA1, CA3, and hilar hippocampal regions, entorhinal cortex, amygdala, and neocortex on day 1 after exposure and in the CA1, CA3, amygdala, and neocortex on day 7 after exposure. It also prevented the delayed loss of glutamic acid decarboxylase-67 immuno-stained BLA interneurons on day 7 after exposure. LY293558 is a potential new emergency treatment for nerve agent exposure that can be expected to be effective against seizures and brain damage even with late administration.     

In vivo tracing of major rat brain pathways using manganese-enhanced magnetic resonance imaging and three-dimensional digital atlasing

The magnetic resonance imaging (MRI)-detectable T1 contrast agent manganese (Mn2+) has recently been introduced as a neural tracer in rodents, birds, and monkeys. We have tested to what extent this in vivo method is useful for three-dimensional (3-D) survey of connectivity patterns in the rat somatosensory system. A commonly available 3 T human clinical MRI scanner was used to trace neural pathways following focal injection of manganese chloride (MnCl2) in the somatosensory cortex. Six to 10 h after MnCl2 injection, we found significant signal enhancement in major projection systems, including corticocortical, corticostriatal, corticothalamic, corticotectal, corticopontine, and corticospinal pathways. To facilitate the assignment of anatomic localization to the observed Mn2+ signal enhancement, we registered the MRI data with a 3-D digital reconstruction of a stereotaxic rat brain atlas. Across-animal comparison using the digital model allowed demonstration of a corticothalamic 3-D topographic organization in agreement with previously published two-dimensional topographic schemes based on classical neural tracing data. We conclude that anterograde MnCl2/MRI tracing allows rapid analysis of topographic organization across multiple brain regions. The method allows a higher data throughput for 3-D studies of large-scale brain connectivity than conventional methods based on tissue sectioning.     

Basal functional connectivity within the anterior temporal network is associated with performance on declarative memory tasks

Spontaneous fluctuations in the blood oxygenation level-dependent (BOLD) signal, as measured by functional magnetic resonance imaging (fMRI) at rest, exhibit a temporally coherent activity thought to reflect functionally relevant networks. Antero-mesial temporal structures are the site of early pathological changes in Alzheimer's disease and have been shown to be critical for declarative memory. Our study aimed at exploring the functional impact of basal connectivity of an anterior temporal network (ATN) on declarative memory. A heterogeneous group of subjects with varying performance on tasks assessing memory was therefore selected, including healthy subjects and patients with isolated memory complaint, amnestic Mild Cognitive Impairment (aMCI) and mild Alzheimer's disease (AD). Using Independent Component Analysis on resting-state fMRI, we extracted a relevant anterior temporal network (ATN) composed of the perirhinal and entorhinal cortex, the hippocampal head, the amygdala and the lateral temporal cortex extending to the temporal pole. A default mode network and an executive-control network were also selected to serve as control networks. We first compared basal functional connectivity of the ATN between patients and control subjects. Relative to controls, patients exhibited significantly increased functional connectivity in the ATN during rest. Specifically, voxel-based analysis revealed an increase within the inferior and superior temporal gyrus and the uncus. In the patient group, positive correlations between averaged connectivity values of ATN and performance on anterograde and retrograde object-based memory tasks were observed, while no correlation was found with other evaluated cognitive measures. These correlations were specific to the ATN, as no correlation between performance on memory tasks and the other selected networks was found. Taken together, these findings provide evidence that basal connectivity inside the ATN network has a functional role in object-related, context-free memory. They also suggest that increased connectivity at rest within the ATN could reflect compensatory mechanisms that occur in response to early pathological insult.     

Neuroprotective properties of topiramate in the lithium-pilocarpine model of epilepsy

The lithium-pilocarpine model reproduces the main characteristics of human temporal lobe epilepsy. After status epilepticus (SE), rats exhibit a latent seizure-free phase characterized by development of extensive damage in limbic areas and occurrence of spontaneous recurrent seizures. Neuroprotective and antiepileptogenic effects of topiramate were investigated in this model. SE was induced in adult male rats by LiCl (3 mEq/kg) followed 20 h later by pilocarpine (25 mg/kg). Topiramate (10, 30, or 60 mg/kg) was injected at 1 and 10 h of SE. Injections were repeated twice a day for six additional days. Another group received two injections of diazepam on the day of SE and of vehicle for 6 days. Neuronal damage was assessed at 14 days after SE by cell counting on thionin-stained sections. Occurrence of spontaneous recurrent seizures (SRS) was videorecorded for 10 h per day in other groups of rats. In diazepam-treated rats, the number of neurons was dramatically reduced after SE in all subregions of hippocampus and layers II-IV of ventral cortices. At all doses, topiramate induced a 24 to 30% neuroprotection in layer CA1 of hippocampus (p < 0.05). In CA3b, the 30-mg/kg dose prevented neuronal death. All rats subjected to SE became epileptic. The latency (14-17 days) to and frequency of SRS were similar in topiramate- and diazepam-treated rats. The high mortality in the 30 mg/kg topiramate group (84%) was possibly the result of interaction between lithium and topiramate. In conclusion, topiramate displayed neuroprotective properties only in CA1 and CA3 that were not sufficient to prevent epileptogenesis.     

Functional networks underlying latent inhibition learning in the mouse brain

The present study reports the first comprehensive map of brain networks underlying latent inhibition learning and the first application of structural equation modeling to cytochrome oxidase data. In latent inhibition, repeated exposure to a stimulus results in a latent form of learning that inhibits subsequent associations with that stimulus. As neuronal energy demands to form learned associations changes, so does the induction of the respiratory enzyme cytochrome oxidase. Therefore, cytochrome oxidase can be used as an endpoint metabolic marker of the effects of experience on regional brain metabolic capacity. Quantitative cytochrome oxidase histochemistry was used to map brain regions in mice trained on a tone-footshock fear conditioning paradigm with either tone preexposure (latent inhibition), conditioning only (acquisition), conditioning followed by tone alone (extinction), or no handling or conditioning (naive). The ventral cochlear nucleus, medial geniculate, CA1 hippocampus, and perirhinal cortex showed modified metabolic capacity due to latent inhibition. Structural equation modeling was used to determine the causal influences in an anatomical network of these regions and others thought to mediate latent inhibition, including the accumbens and entorhinal cortex. An uncoupling of ascending influences between auditory regions was observed in latent inhibition. There was also a reduced influence on the accumbens from the perirhinal cortex in both latent inhibition and extinction. The results suggest a specific network with a neural mechanism of latent inhibition that appears to involve sensory gating, as evidenced by modifications in metabolic capacity and effective connectivity between auditory regions and reduced perirhinal cortex influence on the accumbens.     

Reduced cortical thickness in hippocampal subregions among cognitively normal apolipoprotein E e4 carriers

Our objective was to investigate whether asymptomatic carriers of apolipoprotein E epsilon4 [APOE-4] demonstrate pathological differences and atrophy in medial temporal lobe (MTL) subregions. We measured cortical thickness and volume in MTL subregions (hippocampal CA fields 1, 2 and 3; dentate gyrus; entorhinal cortex; subiculum; perirhinal cortex; parahippocampal cortex; and fusiform gyrus) using a high-resolution in-plane (0.4x0.4 mm) MRI sequence in 30 cognitively normal volunteers (14 APOE-4 carriers, 16 non-carriers, mean age 57 years). A cortical unfolding procedure maximized the visibility of this convoluted cortex, providing cortical ribbon thickness measures throughout individual subregions of the hippocampus and surrounding cortex. APOE-4 carriers had reduced cortical thickness compared with non-carriers in entorhinal cortex (ERC) and the subiculum (Sub), but not in the main hippocampal body or perirhinal cortex. Average cortical thickness was 14.8% lower (p=1.0e(- 6)) for ERC and 12.6% lower (p=6.8e(- 5)) for Sub in APOE-4 carriers. Standard volumetric measures of the same regions showed similar, but non-significant trends. Cognitively intact carriers of APOE-4 show regionally specific thinning of the cortical ribbon compared to APOE-3 carriers; cortical thickness may be a more sensitive measure of pathological differences in genetic risk subjects than standard volumetry.     

Statistical mapping of functional olfactory connections of the rat brain in vivo

The olfactory pathway is a unique route into the brain. To better characterize this system in vivo, rat olfactory functional connections were mapped using magnetic resonance (MR) imaging and manganese ion (Mn2+) as a transport-mediated tracer combined with newly developed statistical brain image analysis. Six rats underwent imaging on a 1.5-T MR scanner at pre-administration, and 6, 12, 24, 36, 48, and 72 h and 5.5, 7.5, 10.5, and 13.5 days post-administration of manganese chloride (MnCl2) into the right nasal cavity. Images were coregistered, pixel-intensity normalized, and stereotactically transformed to the Paxinos and Watson rat brain atlas, then averaged across subjects using automated image analysis software (NEUROSTAT). Images at each time point were compared to pre-administration using a one-sample t statistic on a pixel-by-pixel basis in 3-D and converted to Z statistic maps. Statistical mapping and group averaging improved signal to noise ratios and signal detection sensitivity. Significant transport of Mn2+ was observed in olfactory structures ipsilateral to site of Mn2+ administration including the bulb, lateral olfactory tract (lo) by 12 h and in the tubercle, piriform cortex, ventral pallidum, amygdala, and in smaller structures such as the anterior commissure after 24 h post-administration. MR imaging with group-wise statistical analysis clearly demonstrated bilateral transsynaptic Mn2+ transport to secondary and tertiary neurons of the olfactory system. The method permits in vivo investigations of functional neuronal connections within the brain.     

颞叶癫痫模型和失神癫痫模型的行为学、组织学对比研究

目的比较匹罗卡品癫痫模型及戊四唑点燃癫痫模型的行为学特征及组织学特征.方法制作两种不同的癫痫模型,应用Vedio观察行为学特征,不同时点Nissl染色及Neo-timms＇染色,对比研究神经元丢失及苔藓出芽的变化.结果戊四唑点燃模型无持续性癫痫自发发作,癫痫产生过程中无神经元丢失及苔藓出芽现象;匹罗卡品癫痫持续状态模型在海马的CA1、CA3及齿状回的门区出现神经元丢失,在大鼠出现反复自发发作的同时出现苔藓纤维出芽现象.结论戊四唑点燃模型类似人类失神癫痫特征,匹罗卡品癫痫持续状态模型类似人类慢性颞叶癫痫特征,神经元丢失和苔藓纤维出芽可能是癫痫发生的原因,是一理想的颞叶癫痫动物模型.     

The responsive amygdala: Treatment-induced alterations in functional connectivity in pediatric complex regional pain syndrome

The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear, and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-sex matched control subjects before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared with control subjects, with differences predominantly in the left amygdala in the pretreated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy control subjects from time 1 to time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores; and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity after an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response.     

Sequence of information processing for emotions through pathways linking temporal and insular cortices with the amygdala

The amygdala has a pivotal role in deciphering the emotional significance of sensory stimuli enabling emotional memory formation. We have previously shown that prefrontal cortices in rhesus monkeys project to the amygdala mainly from their deep layers, suggesting feedback communication. If sensory areas convey signals pertinent to the state of the environment, they should issue feedforward projections to the amygdala, arising mainly from the upper layers, consistent with the flow of information from earlier- to later-processing sensory cortices. Here we addressed this hypothesis in cases with injection of tracers in sites of the amygdala known to have robust connections with prefrontal cortices and mapped connections in insular and temporal cortices associated with sensory processing and memory. The medial temporal pole, the entorhinal and perirhinal areas, and the agranular and dysgranular insula had the densest connections with the amygdala, and the lateral temporal pole, the parahippocampal region, and the granular insula had sparser connections. Most areas projected to the amygdala predominantly from the upper layers, suggesting feedforward communication, and received reciprocal amygdalar innervation primarily in their superficial layers, suggesting feedback communication. In contrast, the entorhinal cortex issued projections to the amygdala from its deep layers, suggesting feedback communication, and received reciprocal amygdalar projections most densely in layers II-III, which project to the hippocampus. These findings may help explain how the amygdala can attach emotional value to environmental stimuli, participate in the sequence of information processing of emotions, and modulate the formation of emotional memories.     

Effects of entorhinal cortex lesions on sensory integration and spatial learning

BACKGROUND: The entorhinal cortex provides sensory information to the hippocampus for memory and learning. Damage to the entorhinal cortex is common in patients who experience traumatic brain injury, stroke, and Alzheimer's disease. Entorhinal damage is assumed to interfere with sensory integration; however, substantive knowledge of behavioral patterns is lacking. OBJECTIVES: To describe specific behavioral deficits associated with entorhinal cortex injury related to special senses identification, sensory integration, and spatial learning. METHOD: Adult male rats received bilateral entorhinal cortex damage (n = 19) or sham surgery (n = 11) with a subset randomized to participate in special senses identification, exploration, and sensory integration testing. Spatial learning was examined using a water maze. RESULTS: Lesion and control animals were similar in special senses identification testing. Sensory integration was markedly impaired in lesion animals over 3 days for all integration tasks; however, travel deficit persisted for 4 days. By day 5 sensory integration ability was equal. Lesion animals were significantly impaired across all days of spatial learning for swim time (p = .0001) and directional heading error (p = .03). Control animals exposed to sensory testing demonstrated significantly more efficient learning (p = .005) on swim days 2 and 3 versus control animals not exposed to sensory testing. CONCLUSIONS: Early and prolonged behavioral changes are evident following entorhinal cortex damage including sensory integration deficits and persistent spatial learning impairment.     

年龄相关性记忆缺损者内颞叶结构MR体积测量研究

目的观察年龄相关性记忆缺损(AAMI)者与认知功能正常老年人和轻度认知障碍(MCI)者内颞叶结构体积测量值,评价AAMI者内颞叶结构体积指标与正常对照者和MCI者的差别.方法对45名研究对象(正常老年人22例,AAMI者10例,MCI者 13例)行颅脑磁共振成像检查,在不知晓临床资料的情况下测量海马结构、内嗅皮层、杏仁核和侧脑室颞角等结构的体积,应用社会科学统计程序(SPSS)对所获数据进行统计学处理.结果三组间比较,右侧海马结构体积测量值有显著性差异(P=0.011),其他内颞叶结构体积测量值未见显著性差异.各组间两两比较,AAMI组与MCI组之间右侧海马结构体积测量值有显著差异(P=0.003);AAMI组与正常对照组之间各脑结构体积测量值无显著差异;MCI组与正常对照组比较,左侧内嗅皮层显著性萎缩(P=0.032).结论 AAMI者与正常对照者比较,内颞叶脑结构体积测量值无明显差异;而MCI者右侧海马结构和左侧内嗅皮层体积测量值明显减小.     

Examining the gateway to the limbic system with diffusion tensor imaging: the perforant pathway in dementia

Current treatments for Alzheimer's disease (AD) are only able to slow the progression of mental deterioration, making early and reliable diagnosis an essential part of any promising therapeutic strategy. In the initial stages of AD, the first neuropathological alterations occur in the perforant pathway (PP), a large neuronal fiber tract located at the entrance to the limbic system. However, to date, there is no sensitive diagnostic tool for performing in vivo assessments of this structure. In the present bimodal magnetic resonance imaging (MRI) study, we examined 10 elderly controls, 10 subjects suffering from mild cognitive impairment (MCI), and 10 AD patients in order to evaluate the sensitivity of diffusion tensor imaging (DTI), a new MRI technique, for detecting changes in the PP. Furthermore, the diagnostic explanatory power of DTI data of the PP should be compared to high-resolution MRI volumetry and intervoxel coherences (COH) of the hippocampus and the entorhinal cortex, two limbic regions also involved in the pathophysiology of early AD. DTI revealed a marked decrease in COH values in the PP region of MCI (right side: 26%, left side: 29%, as compared to controls) and AD patients (right side: 37%, left side: 43%, as compared to controls). Reductions in COH values of the PP region were significantly correlated with cognitive impairment. DTI data of the PP zone were the only parameter differing significantly between control subjects and MCI patients, while the volumetric measures and the COH values of the hippocampus and the entorhinal cortex did not. DTI of medial temporal brain regions is a promising non-invasive tool for the in vivo diagnosis of the early/preclinical stages of AD.     

Strengthened functional connectivity in the brain during muscle fatigue

By combining language functional magnetic resonance imaging and voxel-based morphometry in patients with left-sided mesial temporal lobe epilepsy and hippocampal sclerosis, we studied whether atypical language dominance is associated with temporal and/or extratemporal cortical changes. Using verbal fluency functional magnetic resonance imaging for language lateralisation, we identified 20 patients with left-sided mesial temporal lobe epilepsy with hippocampal sclerosis and atypical language lateralisation. These patients were compared with a group of 20 matched left-sided mesial temporal lobe epilepsy patients who had typical language lateralisation. Using T1-weighted 3D images of all patients and voxel-based morphometry, we compared grey matter volumes between the groups of patients. We also correlated grey matter volumes with the degree of atypical language activation. Patients with atypical language lateralisation had increases of grey matter volumes, mainly within right-sided temporo-lateral cortex (x = 59, y = − 16, z = − 1, T = 6.36, p < .001 corrected), and less significantly within frontal brain regions compared to patients with typical language lateralisation. The degree of atypical fronto-temporal language activation (measured by lateralisation indices and relative functional magnetic resonance imaging activity) was correlated with right-sided temporal and frontal grey matter volumes. Patients with atypical language lateralisation did not differ in terms of language performance from patients with typical language dominance. Atypical language lateralisation in patients with left-sided mesial temporal lobe epilepsy was associated with increased grey matter volume within the non-epileptic right temporal and frontal lobe. Grey matter increases associated with atypical language might represent morphological changes underlying functional reorganisation of the language network. This hard-wired reorganised atypical language network seems to be suitable to support language functions.     

Spatiotemporal dynamics of epileptiform propagations: imaging of human brain slices

Seizure activities often originate from a localized region of the cerebral cortex and spread across large areas of the brain. The properties of these spreading abnormal discharges may account for clinical phenotypes in epilepsy patients, although the manner of their propagation and the underlying mechanisms are not well understood. In the present study we performed flavoprotein fluorescence imaging of cortical brain slices surgically resected from patients with partial epilepsy caused by various symptomatic lesions. Elicited neural activities in the epileptogenic tissue spread horizontally over the cortex momentarily, but those in control tissue taken from patients with brain tumors who had no history of epilepsy demonstrated only localized responses. Characteristically, the epileptiform propagation comprised early and late phases. When the stimulus intensity was changed gradually, the early phase showed an all-or-none behavior, whereas the late phase showed a gradual increase in the response. Moreover, the two phases were propagated through different cortical layers, suggesting that they are derived from distinct neural circuits. Morphological investigation revealed the presence of hypertrophic neurons and loss of dendritic spines, which might participate in the aberrant activities observed by flavoprotein fluorescence imaging. These findings indicate that synchronized activities of the early phase may play a key role in spreading abnormal discharges in human cortical epilepsies.     

1例偏瘫患者康复训练前后视觉指令食指伸屈运动脑磁图分析

目的观察偏瘫患者恢复期康复训练前后双手食指伸屈运动过程中脑磁图（MEG）变化。方法对1例偏瘫患者应用MEG记录双手食指伸屈运动时的脑电磁波并与MRI叠加形成磁源性影像（MSI）,对比康复训练前后MEG变化。结果两次MEG检测右侧半球皮质均无运动诱发出脑磁反应,左侧半球均有运动诱发反应;第1次和第2次潜伏期分别为-34.2ms和-61.7ms,部位向内前下移位,MSI显示兴奋的皮质位于中央前回,第2次激活的脑皮质体积（9569.6m3）明显大于第1次（2309.7m3）;第1次食指运动未诱发右半球体感反应;第2次食指运动诱发了右半球的体感反应,潜伏期为91.1ms,MSI显示兴奋的皮质位于中央后回。结论脑卒中患者皮质感觉功能先于运动功能恢复,未损半球经康复训练后功能明显增强。     

Hippocampal CA1 apical neuropil atrophy and memory performance in Alzheimer's disease

Memory loss is often the first and most prominent symptom of Alzheimer's disease (AD), coinciding with the spread of neurofibrillary pathology from the entorhinal cortex (ERC) to the hippocampus. The apical dendrites of hippocampal CA1 pyramidal neurons, in the stratum radiatum/stratum lacunosum-moleculare (SRLM), are among the earliest targets of this pathology, and atrophy of the CA1-SRLM is apparent in postmortem tissue from patients with mild AD. We previously demonstrated that CA1-SRLM thinning is also apparent in vivo, using ultra-high field 7-Tesla (7T) MRI to obtain high-resolution hippocampal microstructural imaging. Here, we hypothesized that CA1-SRLM thickness would correlate with episodic memory performance among patients with mild AD. We scanned nine patients, using an oblique coronal T2-weighted sequence through the hippocampal body with an in-plane resolution of 220μm, allowing direct visual identification of subfields - dentate gyrus (DG)/CA3, CA2, CA1, and ERC - and hippocampal strata - SRLM and stratum pyramidale (SP). We present a novel semi-automated method of measuring stratal width that correlated well with manual measurements. We performed multi-domain neuropsychological evaluations that included three tests of episodic memory, yielding composite scores for immediate recall, delayed recall, and delayed recognition memory. Strong correlations occurred between delayed recall performance and the widths of CA1-SRLM (r(2)=0.69; p=0.005), CA1-SP (r(2)=0.5; p=0.034), and ERC (r(2)=0.62; p=0.012). The correlation between CA1-SRLM width and delayed recall lateralized to the left hemisphere. DG/CA3 size did not correlate significantly with any aspect of memory performance. These findings highlight a role for 7T hippocampal microstructural imaging in revealing focal structural pathology that correlates with the central cognitive feature of AD.