ESTIMATION OF GLYCOLIPIDS IN FOUR SELECTED LOBES OF HUMAN BRAIN IN NEUROLOGICAL DISEASES1

Glycolipid (ganglioside, cerebroside and cerebroside sulphate) and cholesterol concentrations for cerebral grey matter from frontal, occipital, temporal and hippocampal lobes of patients with neurological diseases (Alzheimer's disease, senile dementia, cerebrocortical atrophy, schizophrenia and chronic alcoholism) and controls are reported. The results indicate that the concentrations of these lipids are not uniform in the different lobes of both diseased and control brains. The concentrations of the cerebrosides and cerebroside sulphates were generally highest in the occipital lobe and lowest in the frontal lobe; ganglioside N-acetymeuraminic acid (NANA) concentrations on the other hand were lowest in the occipital lobe and highest in the frontal lobe. About one-half of the total NANA was found in the lipid-free residues. There was a general decrease in the concentrations of the glycolipids in the grey matter from the frontal, temporal and hippocampal lobes of brain obtained from patients with neurological diseases (the chronic alcoholic being excluded) below the control values from patients with no known neurological diseases. The cholesterol concentrations in the schizophrenic and alcoholic brains were reduced slightly in all the lobes studied. The general decrease in the glycolipid concentration in the diseased brain may indicate the extent of cortical degeneration.     

Hemodynamic response of the frontal cortex elicited by intravenous thiamine propyldisulphide administration

The intravenous olfaction (IVO) test is a unique type of clinical olfactometry and is widely used in Japan. However, it is difficult to distinguish actual olfactory disturbance from feigned disturbance because the IVO test is a psychophysical test. To resolve this problem, we investigated the possibility of an objective IVO test assisted with near infrared spectroscopy (NIRS). IVO testing was performed according to the usual protocol with thiamine propyldisulphide (alinamin) administration. The relative oxy- and deoxyhemoglobin levels of the orbitofrontal area during olfactory stimulation by IVO test were measured by NIRS. Pairs of NIRS emitters and detectors were positioned on the bilateral frontal scalp. After administration of alinamin, oxyhemoglobin levels increased, though deoxyhemoglobin levels did not change. An increase in oxyhemoglobin levels was observed bilaterally. Administration of saline did not elicit any change in the oxy- or deoxyhemoglobin levels and concentration of the administered alinamin related increasing of the oxyhemoglobin level was observed. Oxyhemoglobin remained unchanged in anosmic subjects despite administration of alinamin. The latency of oxyhemoglobin increase on each side and smelling latency showed significant correlation. Latencies of oxyhemoglobin increases between the right and left sides also showed significant correlation. Oxyhemoglobin response appears to be linked to olfactory related response. NIRS is a useful technique for the development of an objective form of IVO testing.     

Development, set-up and first results for a one-channel near-infrared spectroscopy system.

Abstract Near-infrared spectroscopy (NIRS) is a non-invasive optical technique that can be used to assess functional activity in the human brain. This work describes the set-up of a one-channel NIRS system designed for use as an optical brain-computer interface (BCI) and reports on first measurements of deoxyhemoglobin (Hb) and oxyhemoglobin (HbO(2)) changes during mental arithmetic tasks. We found relatively stable and reproducible hemodynamic responses in a group of 13 healthy subjects. Unexpected observations of a decrease in HbO(2) and increase in Hb concentrations measured over the prefrontal cortex were in contrast to the typical hemodynamic responses (increase in HbO(2), decrease in Hb) during cortical activation previously reported.     

Analysis for Distinctive Activation Patterns of Pain and Itchy in the Human Brain Cortex Measured Using Near Infrared Spectroscopy (NIRS)

Pain and itch are closely related sensations, yet qualitatively quite distinct. Despite recent advances in brain imaging techniques, identifying the differences between pain and itch signals in the brain cortex is difficult due to continuous temporal and spatial changes in the signals. The high spatial resolution of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) has substantially advanced research of pain and itch, but these are uncomfortable because of expensiveness, importability and the limited operation in the shielded room. Here, we used near infrared spectroscopy (NIRS), which has more conventional usability. NIRS can be used to visualize dynamic changes in oxygenated hemoglobin and deoxyhemoglobin concentrations in the capillary networks near activated neural circuits in real-time as well as fMRI. We observed distinct activation patterns in the frontal cortex for acute pain and histamine-induced itch. The prefrontal cortex exhibited a pain-related and itch-related activation pattern of blood flow in each subject. Although it looked as though that activation pattern for pain and itching was different in each subject, further cross correlation analysis of NIRS signals between each channels showed an overall agreement with regard to prefrontal area involvement. As a result, pain-related and itch-related blood flow responses (delayed responses in prefrontal area) were found to be clearly different between pain (τ = +18.7 sec) and itch (τ = +0.63 sec) stimulation. This is the first pilot study to demonstrate the temporal and spatial separation of a pain-induced blood flow and an itch-induced blood flow in human cortex during information processing.     

Corticosteroid receptor mRNA expression in the brains of patients with epilepsy

The effects of corticosteroids in the brain are mediated through the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). We used a sensitive competitive RT-PCR assay to quantify the amounts of GR and MR mRNA in human brain tissue specimens from patients with focal epilepsies. GR and MR mRNAs were expressed at approximately the same levels in the temporal lobe, frontal lobe, and hippocampus as compared to tissues with high glucocorticoid/mineralocorticoid receptor expression (liver/kidney). GR and MR mRNA concentrations in the temporal lobe increased markedly during childhood and reached adult levels at puberty. GR and MR mRNA expression was significantly higher in the temporal lobe and frontal lobe cortex of women than in those of men. In women, MR and GR mRNA concentrations were markedly lower in hippocampal tissue than in frontal and temporal lobe cortex tissue. In conclusion, our data demonstrate sex- and site-dependent expression of corticosteroid receptor mRNA in the human brain.     

Frontal White Matter Volume Is Associated with Brain Enlargement and Higher Structural Connectivity in Anthropoid Primates

Previous research has indicated the importance of the frontal lobe and its ‘executive’ connections to other brain structures as crucial in explaining primate neocortical adaptations. However, a representative sample of volumetric measurements of frontal connective tissue (white matter) has not been available. In this study, we present new volumetric measurements of white and grey matter in the frontal and non-frontal neocortical lobes from 18 anthropoid species. We analyze this data in the context of existing theories of neocortex, frontal lobe and white versus grey matter hyperscaling. Results indicate that the ‘universal scaling law’ of neocortical white to grey matter applies separately for frontal and non-frontal lobes; that hyperscaling of both neocortex and frontal lobe to rest of brain is mainly due to frontal white matter; and that changes in frontal (but not non-frontal) white matter volume are associated with changes in rest of brain and basal ganglia, a group of subcortical nuclei functionally linked to ‘executive control’. Results suggest a central role for frontal white matter in explaining neocortex and frontal lobe hyperscaling, brain size variation and higher neural structural connectivity in anthropoids.     

Speeded Near Infrared Spectroscopy (NIRS) Response Detection

The hemodynamic response measured by Near Infrared Spectroscopy (NIRS) is temporally delayed from the onset of the underlying neural activity. As a consequence, NIRS based brain-computer-interfaces (BCIs) and neurofeedback learning systems, may have a latency of several seconds in responding to a change in participants'' behavioral or mental states, severely limiting the practical use of such systems. To explore the possibility of reducing this delay, we used a multivariate pattern classification technique (linear support vector machine, SVM) to decode the true behavioral state from the measured neural signal and systematically evaluated the performance of different feature spaces (signal history, history gradient, oxygenated or deoxygenated hemoglobin signal and spatial pattern). We found that the latency to decode a change in behavioral state can be reduced by 50% (from 4.8 s to 2.4 s), which will enhance the feasibility of NIRS for real-time applications.     

改良2, 4-二硝基苯肼法测定脑内源甲醛

内源甲醛代谢失衡所造成的脑慢性损伤被认为是衰老过程中记忆丢失的危险因素之一,因此,有必要准确测定脑内不同区域甲醛的含量为相关研究提供参考.作者通过2,4-二硝基苯肼(2,4-DNPH)偶联高效液相色谱(UV-HPLC),测定了家猪脑额叶、顶叶、颞叶、枕叶、海马、小脑、脑干内源甲醛含量(75.5～83.4μmol/kg).采用10%三氯乙酸处理脑组织匀浆(pH=1.0),不但可以避免蛋白质及其他分子的干扰,还可以省略现有方法中的萃取步骤,且提高了测试的灵敏度(P<0.05).该方法的回收率约95.96%～102.04%,相对标准偏差(n=5)小于10%.结果表明,改良2,4-DNPH法用于脑内源甲醛的测定,其操作简便、可信度高.     

急性高原低氧环境对不同情绪状态脑电功率的影响*

目的: 探讨急性高原低氧环境对不同情绪状态脑电功率的影响。方法:本研究为双因素多水平试验设计(氧气环境2个水平×情绪类型4个水平)。通过编写情绪图片诱导12名年龄在20～25岁之间的男性被试产生四类不同情绪:低效价低唤醒(LVLA)、高效价低唤醒(HVLA)、低效价高唤醒(LVHA)、高效价高唤醒(HVHA) ,分别近似于沮丧、轻松、恐惧、快乐四类情绪,并使用Brain Products 32导脑电采集设备采集不同情绪状态下的脑电信号;次日,采用常压低氧舱模拟4 300 m的高原低氧环境,同一批被试在低氧10 h 后使用相同试验范式采集脑电信号。对采集来的脑电信号进行功率谱分析(FFT),同时对额叶(F3\Fz\F4)脑电的五个频段(delta、theta、alpha、beta、gamma)进行两因素重复测量方差分析。结果:功率谱分析发现:急性低氧前后,四类情绪状态下alpha波的全脑分布差异主要集中在额叶、顶叶及部分颞叶;HVLA情绪状态下alpha波全脑分布差异最小。两因素重复测量方差分析结果发现:①delta、beta频段功率受氧气环境影响显著(P＜0.05),低氧环境下功率增强。②theta、alpha频段功率指标上,氧气环境和情绪类型交互作用显著(P＜0.05),低氧环境下除HVLA情绪状态外,theta、alpha频段功率皆出现了显著增强。③两因素对gamma频段影响都不显著(P＞0.05)。结论:在四类情绪状态下,氧气环境的变化对大脑活动的影响差异区域主要集中在额叶、顶叶及部分颞叶;低氧环境对沮丧、恐惧、快乐情绪状态有明显影响,低氧与情绪类型对于theta及alpha频段功率的改变具有协同作用。     

Prenatal testosterone improves the spatial learning and memory by protein synthesis in different lobes of the brain in the male and female rat

The high density of the steroid hormone receptors in the structures of temporal lobe involved in learning and memory, such as the hippocampus, perirhinal cortex, entorhinal cortex and amigdaloid complex, shows that there must be a direct relationship between gonadal hormones and organizational effects of steroid hormones in those structures during development of the nervous system. The present study was undertaken in order to investigate the effect of testosterone administration during the third week of gestation on the spatial memory formation of the offspring rats and the level of soluble proteins in the temporal lobe and frontal lobe of brain, as evidence of important organizational effects of androgens during prenatal development in brain sexual dimorphism. Animals have received testosterone undecanoate on days 14, 15, 16 and 19, 20, 21 of gestation. Learning and memory tests were started 100 days after the testosterone treatment. At the end of the experiments, the temporal and frontal lobes of brain were removed for assessing the level of soluble proteins. Testosterone treatment significantly improved spontaneous alternations percentage of male offspring in Y-maze task comparative with female offspring and reference memory in radial 8 arm-maze task (decreasing in number of reference memory errors in both male and female offspring groups), suggesting effects of both short and long-term memory. Also, testosterone significantly increased the brain soluble protein level of treated female rats in 14–16 prenatal days compared with the control group as well as the brain soluble protein level of treated male rats. These results suggest that steroid hormones play an important role in the spatial learning and memory formation by means of protein synthesis in different lobes of the brain.     

Down syndrome’s brain dynamics: analysis of fractality in resting state

To the best knowledge of the authors there is no study on nonlinear brain dynamics of down syndrome (DS) patients, whereas brain is a highly complex and nonlinear system. In this study, fractal dimension of EEG, as a key characteristic of brain dynamics, showing irregularity and complexity of brain dynamics, was used for evaluation of the dynamical changes in the DS brain. The results showed higher fractality of the DS brain in almost all regions compared to the normal brain, which indicates less centrality and higher irregular or random functioning of the DS brain regions. Also, laterality analysis of the frontal lobe showed that the normal brain had a right frontal laterality of complexity whereas the DS brain had an inverse pattern (left frontal laterality). Furthermore, the high accuracy of 95.8 % obtained by enhanced probabilistic neural network classifier showed the potential of nonlinear dynamic analysis of the brain for diagnosis of DS patients. Moreover, the results showed that the higher EEG fractality in DS is associated with the higher fractality in the low frequencies (delta and theta), in broad regions of the brain, and the high frequencies (beta and gamma), majorly in the frontal regions.     

Frontal Lobe Contusion in Mice Chronically Impairs Prefrontal-Dependent Behavior

Traumatic brain injury (TBI) is a major cause of chronic disability in the world. Moderate to severe TBI often results in damage to the frontal lobe region and leads to cognitive, emotional, and social behavioral sequelae that negatively affect quality of life. More specifically, TBI patients often develop persistent deficits in social behavior, anxiety, and executive functions such as attention, mental flexibility, and task switching. These deficits are intrinsically associated with prefrontal cortex (PFC) functionality. Currently, there is a lack of analogous, behaviorally characterized TBI models for investigating frontal lobe injuries despite the prevalence of focal contusions to the frontal lobe in TBI patients. We used the controlled cortical impact (CCI) model in mice to generate a frontal lobe contusion and studied behavioral changes associated with PFC function. We found that unilateral frontal lobe contusion in mice produced long-term impairments to social recognition and reversal learning while having only a minor effect on anxiety and completely sparing rule shifting and hippocampal-dependent behavior.     

Separation of fNIRS Signals into Functional and Systemic Components Based on Differences in Hemodynamic Modalities

In conventional functional near-infrared spectroscopy (fNIRS), systemic physiological fluctuations evoked by a body''s motion and psychophysiological changes often contaminate fNIRS signals. We propose a novel method for separating functional and systemic signals based on their hemodynamic differences. Considering their physiological origins, we assumed a negative and positive linear relationship between oxy- and deoxyhemoglobin changes of functional and systemic signals, respectively. Their coefficients are determined by an empirical procedure. The proposed method was compared to conventional and multi-distance NIRS. The results were as follows: (1) Nonfunctional tasks evoked substantial oxyhemoglobin changes, and comparatively smaller deoxyhemoglobin changes, in the same direction by conventional NIRS. The systemic components estimated by the proposed method were similar to the above finding. The estimated functional components were very small. (2) During finger-tapping tasks, laterality in the functional component was more distinctive using our proposed method than that by conventional fNIRS. The systemic component indicated task-evoked changes, regardless of the finger used to perform the task. (3) For all tasks, the functional components were highly coincident with signals estimated by multi-distance NIRS. These results strongly suggest that the functional component obtained by the proposed method originates in the cerebral cortical layer. We believe that the proposed method could improve the reliability of fNIRS measurements without any modification in commercially available instruments.     

Origins of spatial working memory deficits in schizophrenia: an event-related FMRI and near-infrared spectroscopy study

Abnormal prefrontal functioning plays a central role in the working memory (WM) deficits of schizophrenic patients, but the nature of the relationship between WM and prefrontal activation remains undetermined. Using two functional neuroimaging methods, we investigated the neural correlates of remembering and forgetting in schizophrenic and healthy participants. We focused on the brain activation during WM maintenance phase with event-related functional magnetic resonance imaging (fMRI). We also examined oxygenated hemoglobin changes in relation to memory performance with the near-infrared spectroscopy (NIRS) using the same spatial WM task. Distinct types of correct and error trials were segregated for analysis. fMRI data indicated that prefrontal activation was increased during WM maintenance on correct trials in both schizophrenic and healthy subjects. However, a significant difference was observed in the functional asymmetry of frontal activation pattern. Healthy subjects showed increased activation in the right frontal, temporal and cingulate regions. Schizophrenic patients showed greater activation compared with control subjects in left frontal, temporal and parietal regions as well as in right frontal regions. We also observed increased 'false memory' errors in schizophrenic patients, associated with increased prefrontal activation and resembling the activation pattern observed on the correct trials. NIRS data replicated the fMRI results. Thus, increased frontal activity was correlated with the accuracy of WM in both healthy control and schizophrenic participants. The major difference between the two groups concerned functional asymmetry; healthy subjects recruited right frontal regions during spatial WM maintenance whereas schizophrenic subjects recruited a wider network in both hemispheres to achieve the same level of memory performance. Increased "false memory" errors and accompanying bilateral prefrontal activation in schizophrenia suggest that the etiology of memory errors must be considered when comparing group performances. Finally, the concordance of fMRI and NIRS data supports NIRS as an alternative functional neuroimaging method for psychiatric research.     

颞叶癫痫脑“默认模式”的fMRI研究

功能磁共振成像(functional magnetic resonance imaging,fMRI)被用于检测静息时脑功能神经网络.作者运用静息fMRI检测海马硬化颞叶癫痫(temporal lobe epilepsy,TLE)脑"默认模式",采用感兴趣区域功能连接分析检测16例TLE患者和16名正常对照静息时脑的"默认模式",并进行组内和组间分析.研究发现,与正常对照相比,TLE静息时海马、颞极、额叶、颞叶、壳核及楔前叶等脑区与后扣带回的功能连接增强.研究结果表明TLE患者的固有脑功能组织模式有可能出现紊乱.这一研究将有助于从脑功能的角度了解癫痫患者某些临床症状的发病机理,为今后癫痫诊治的发展提供一定的帮助.     

Direct observation of two distinct affinity conformations in the T state human deoxyhemoglobin

The main features of cooperative oxygenation of human hemoglobin have been described by assuming the equilibrium between two affinity conformations of the entire molecule, T and R. However, the molecular basis for explaining the wide variation in the O(2) affinities of the deoxy T state has remained obscure. We address this long-standing issue by trapping the conformational states of deoxyhemoglobin molecules within wet porous transparent silicate sol-gels. The equilibrium O(2) binding measurements of the encapsulated deoxyhemoglobin samples showed that deoxyhemoglobin free of anions coexists in two conformations that differ in O(2) affinity by 40 times or more, and addition of inositol hexaphosphate to this anion-free deoxyhemoglobin brings about a very slow redistribution of these affinity conformations. These results are the first, direct demonstration of the existence of equilibrium between two (at least two) functionally distinguishable conformational states in the T state deoxyhemoglobin.     

Closed-loop Neuro-robotic Experiments to Test Computational Properties of Neuronal Networks

Information coding in the Central Nervous System (CNS) remains unexplored. There is mounting evidence that, even at a very low level, the representation of a given stimulus might be dependent on context and history. If this is actually the case, bi-directional interactions between the brain (or if need be a reduced model of it) and sensory-motor system can shed a light on how encoding and decoding of information is performed. Here an experimental system is introduced and described in which the activity of a neuronal element (i.e., a network of neurons extracted from embryonic mammalian hippocampi) is given context and used to control the movement of an artificial agent, while environmental information is fed back to the culture as a sequence of electrical stimuli. This architecture allows a quick selection of diverse encoding, decoding, and learning algorithms to test different hypotheses on the computational properties of neuronal networks.     

The brain and its main anatomical subdivisions in living hominoids using magnetic resonance imaging

Primary comparative data on the hominoid brain are scarce and major neuroanatomical differences between humans and apes have not yet been described satisfactorily, even at the gross level. Basic questions that involve the evolution of the human brain cannot be addressed adequately unless the brains of all extant hominoid species are analyzed. Contrary to the scarcity of original data, there is a rich literature on the topic of human brain evolution and several debates exist on the size of particular sectors of the brain, e.g., the frontal lobe.In this study we applied a non-invasive imaging technique (magnetic resonance) on living human, great ape and lesser ape subjects in order to investigate the overall size of the hominoid brain. The images were reconstructed in three dimensions and volumetric estimates were obtained for the brain and its main anatomical sectors, including the frontal and temporal lobes, the insula, the parieto-occipital sector and the cerebellum.A remarkable homogeneity is present in the relative size of many of the large sectors of the hominoid brain, but interspecific and intraspecific variation exists in certain parts of the brain. The human cerebellum is smaller than expected for an ape brain of human size. It is suggested that the cerebellum increased less than the cerebrum after the split of the human lineage from the African ancestral hominoid stock. In contrast, humans have a slightly larger temporal lobe and insula than expected, but differences are not statistically significant.Humans do not have a larger frontal lobe than expected for an ape brain of human size and gibbons have a relatively smaller frontal lobe than the rest of the hominoids. Given the fact that the frontal lobe in humans and great apes has similar relative size, it is parsimonious to suggest that the relative size of the whole of the frontal lobe has not changed significantly during hominid evolution in the Plio-Pleistocene.     

Creatine phosphokinase BB distribution in different structures of the human brain

Regional localization of creatine phosphokinase BB was studied in postmortem human brain and its stability was shown. The content of CPK BB in different brain structures was unequal: from 0.5 mcg/mg of protein in the occipital lobe and tuber cinereum to 4.5 mcg/mg in the frontal lobe. In the regional localization of CPK BB in the postmortem brain of schizophrenia patients, some changes in isoenzyme content were found as compared to the control group. The reduction of CPK BB concentration at schizophrenia was found in the frontal lobe (45%, P less than 0.001) and s. nigra (70%, P less than 0.001); the concentration was higher in the thalamus and occipital lobe (15%, P less than 0.001), as well as in the parietal lobe, cingulate gyrus, tuber cinereum, cerebellum cortex, inferior olive--50-80%, P less than 0.001.