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Previous working memory (WM) research based on non-human primate electrophysiology and human EEG has shown that frontal brain regions maintain frequencies of flutter stimulation across different sensory modalities by means of a supramodal parametric WM code. These findings imply that frontal regions encode the memorized frequencies in a sensory-unspecific, quantitative format. Here, we explored which brain regions maintain information about frequencies provided by different sensory modalities at the level of activity pattern across fMRI voxel populations. Moreover, we sought evidence for a supramodal multivariate WM representation. Participants maintained the same set of frequencies of tactile vibration and visual flicker for a 6 s WM delay in a frequency discrimination task. A support vector regression model for multivariate pattern analysis was applied. We observed that sensory cortices were only selective for memoranda of their corresponding modalities, while frontoparietal regions exhibited distinguishable activity patterns to memorized frequencies regardless of sensory modality. A common multivariate code was not evident in our data. Collectively, we show that mnemonic representations for stimulus frequencies are maintained throughout the cortical hierarchy, in line with the suggested transformation of information across different representational formats. Although evidence for a supramodal multivariate code is absent, our findings underpin the generalized role of the frontoparietal cortex for maintaining quantitative information across sensory modalities.

The term neurosteroids applies to those steroids that are both synthesized in the nervous system, either de novo from cholesterol or from steroid hormone precursors, and that accumulate in the nervous system to levels that are at least in part independent of steroidogenic gland secretion rates. Neurosteroids consist of 17- or 20-oxosteroids and accumulate in brains as unconjugated form and their sulfates, fatty acid esters and sulfolipid conjugates.An assay method for pregnenolone and its 3-stearate in brains has been developed using liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) operating in the positive ion mode. The method was applied to the determination of these steroids in the gray matters and olfactory bulbs of rat brains. Although pregnenolone in both regions of the rat brains increased more than five times after acute stress, its 3-stearate decreased after the stress.The existence of classical and guaiacol estrogens in rat brains were also clarified using GC/MS^n. The usefulness of estrogen replacement therapy for dementia of the Alzheimer type and the existence of the estrogen receptor in brains have been reported, our data suggested that estrogen exists in brains as neurosteroids or neuroactive steroids. 高齢化社会を迎え,老人性痴呆は大きな社会的問題となっており,各種の抗痴呆薬の開発が進んでいる.しかし,認可が取り消されるそれが相次いでおり,開発の困難さを示唆している.ところで最近,ほ乳類の脳内に末梢血中の10倍以上ものステロイドホルモンが見出され多大の注目を集めている.これらはneurosteroidsあるいはneuroactive steroidsと呼ばれ,17-又は20-オキソステロイドの遊離型,各種抱合型(sulfate,fatty acid ester,sulpholipid抱合体など)より構成され脳内で生合成されることが知られている.このような折,pregnenoloneやestrogenの老人性痴呆薬としての有用性が示唆され,上記の知見との関連が注目されている.そこで,HPLC,LC/MSを駆使してラット脳を検索したところ,新たにpregnenolone,dehydroepiandrosteroneの3-stearate,-palmitate(計4種)を同定することに成功した.この際,各種oxime誘導体へ導くことが,分子量関連ピークの検出を容易とし,LC/MSでの同定上極めて有用なことも見出した.さらに,上記脂肪酸抱合体がストレスにより減弱し,逆に遊離型neurosteroidsが増加することを明らかとした.また,脳内におけるclassical estrogen及びguaiacol estrogenの存在をGC/MS/MSで初めて確認した.従来の研究では脳内におけるエストロゲンレセプターの存在は明らかとされているが,estrogenの脳内における存否については不確かであった.Estrogenの投与が老人性痴呆に有用であるとの疫学的知見も得られており,本研究は今後の抗痴呆薬の開発研究に一つの方向を示唆したものとして評価される. 出典：研究課題「老人性痴呆治療薬の開発を志向した脳内ステロイドホルモンの分析」課題番号09557188（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-09557188/095571881998kenkyu_seika_hokoku_gaiyo/）を加工して作成 研究課題/領域番号:09557188, 研究期間(年度):1997-1998 金沢大学自然科学研究科薬学系

The unthresholded statistical maps for baseline VBM PSP HC (gray and white matter), longitudinal VBM correlations (gray and white matter) with PSPRS, and the 27 rMT network ROIs

EEG signály u měřených subjektů obsahují různé vzory podle toho, co měřený subjekt vykonával. ERD/ERS jsou příklady právě takovýchto vzorů, které jsou svázány s pohybem ruky, prstu nebo nohy. Tato diplomová práce se zabývá detekováním pohybu v EEG signálu na základě vzorů ERD a ERS. Příznakové vektory jsou konstruovány buď pomocí všech hodnot z ERD/ERS nebo z hodnot, počítaných právě z těchto vzorů, jako například MAV nebo rozptyl. Tyto vektory jsou klasifikovány neuronovou sítí, která se stává z jedné vstupní vrstvy, třech skrytých vrstev a z jedné výstupní vrstvy, kde první skrytá vrstva obsahuje 400 neuronů, druhá 200 neuronů a třetí 100 neuronů. Pro natrénování této neuronové sítě je použita trénovací množina tvořená příznakovými vektory a pro následné přenastavování vah je použit algoritmus Backpropagation. Takto nastavená neuronová síť je schopna klasifikovat pohyb v EEG záznamech s průměrnou přesností 90,05%. Obhájeno The EEG signals of the measured subjects contain different patterns depending on what the measured subject was doing. ERD/ERS are examples of such patterns that are tied to hand, finger or foot movements. This paper deals with the detection of motion in EEG signal based on ERD and ERS patterns. Symptom vectors are constructed using either all the values from ERD/ERS or values computed from just these patterns, such as MAV or dispersion. These vectors are classified by a neural network that consists of an input layer, three hidden layers and one output layer, where the first hidden layer contains 400 neurons, the second 200 neurons and the third 100 neurons. A training set consisting of symptom vectors is used to train this neural network and Backpropagation algorithm is used for subsequent rebalancing. This tuned neural network is able to classify the motion in EEG recordings with an average accuracy of 90.05%.

OpenfMRI ds000107

Patients with Amyotrophic lateral sclerosis (ALS) often experience cognitive impairment that accompanies degeneration of the motor system. A valuable tool for assessing cognitive control over behaviour is the antisaccade task which requires: 1) inhibition of the automatic response to look towards an eccentric visual stimulus (prosaccade) to instead 2) redirect gaze in the opposite direction of the stimulus (antisaccade). Psychometric tests were used to quantify the degree of impairment, while eye tracking, functional magnetic resonance imaging (fMRI) and structural MRI were combined to identify the neural correlates of cognitive impairment in ALS. We predict ALS patients will have executive dysfunction and grey matter loss in executive and oculomotor control areas that will affect antisaccade performance and will alter the corresponding brain activation. ALS patients and age-matched controls participated in a rapid-event-related fMRI design with interleaved pro- and antisaccade trials. Catch trials (no stimulus presented after instructional cue to prepare pro- or antisaccade) allowed us to discern the preparatory period from the execution period. ALS patients were biased towards automatic saccade responses, and had greater difficulty with antisaccades relative to controls in terms of correct and timely responses. We found that worsened antisaccade performance in ALS correlated with the degree of cognitive impairment. Generally, we found trends of increased brain activation during the preparatory period of antisaccades in ALS patients compared to controls in most oculomotor areas; meanwhile few differences were seen during execution. Structural analyses revealed ALS patients had decreased grey matter thickness in frontotemporal and oculomotor regions such as the frontal and supplementary eye fields (FEF, SEF) and the dorsolateral prefrontal cortex (DLPFC). These findings suggest that loss of structural integrity and executive dysfunction may elicit compensation mechanisms to improve functional and behavioural performance. Despite this compensation, ALS patients still performed worse on antisaccades than controls. Further investigation to expand the current data set should improve our ability to assuredly identify the neural correlates of cognitive decline in ALS, and may provide a model system to use for critical evaluation of future therapies and interventions for ALS.

Background: Adequate and timely identification of depression is essential to improve patient care. A potential method to achieve this is by using neuroimaging. Many neuroimaging studies have revealed widespread abnormalities in brain structure and function in patients with depression, but in most studies only single neuroimaging modalities were used. Links between abnormalities in brain structure and function need to be therefore further explored in order to define diagnostic and therapeutic applications. Methods: A systematic literature review according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines was conducted. Results: Out of 2,516 articles, only 14 studies were eligible to be included. These studies combined structural and functional neuroimaging methods in depressed patients compared to controls. Four studies reported a negative relationship between brain structure and function within the default mode network: reduced gray or white matter integrity in depressed patients compared to healthy controls was associated with enhanced neural activity or connectivity. The other studies reported positive relationships (two studies), mixed relationships (two studies), or no link (six studies) between structural and functional brain abnormalities. Conclusion: This systematic literature review revealed no robust relationship between abnormalities in brain structure and function in patients with depression. Remarkably, only 14 studies could be included and four of these suggested enhanced default mode network connectivity associated with reduced structural brain integrity. In the ongoing development of the diagnostic and treatment applications of neuroimaging, large-scale studies that combine structural with functional neuroimaging are required to determine the relationship between structural and functional abnormalities in depression.

Data from the Brainomics project (localizer protocol, from Neurospin).

Background: Over the past decade, the functional importance of white matter pathways has been increasingly acknowledged in neurosurgical planning. A method to directly study anatomo-functional correlations is direct electrical stimulation (DES). DES has been widely accepted by neurosurgeons as a reliable tool to minimize the occurrence of permanent postoperative motor, vision and language deficits. In recent years, DES has also been used for stimulation mapping of other cognitive functions, such as executive functions and visuospatial awareness. Methods: The aim of this review is to summarize the evidence so far from DES studies on subcortical pathways that are involved in visuospatial awareness and in the following three executive functions: (1) inhibitory control, (2) working memory and (3) cognitive flexibility. Results: Eleven articles reported on intraoperative electrical stimulation of white matter pathways to map the cognitive functions and explicitly clarified which subcortical tract was stimulated. The results indicate that the right SLF-II is involved in visuospatial awareness, the left SLF-III and possibly the right SLF-I are involved in working memory and the cingulum is involved in cognitive flexibility. Conclusions: We were unable to draw any more specific conclusions, nor unequivocally establish the critical involvement of pathways in executive functions or visuospatial awareness due to the heterogeneity of the study types and methods, and the limited number of studies that assessed these relationships. Possible approaches for future research to obtain converging and more definite evidence for the involvement of pathways in specific cognitive functions are discussed.

Aging is an extremely complex, multifactorial process that is characterized by a gradual and continuous loss of physiological functions and responses, particularly marked in the brain. A common hallmark in aging and age-related diseases is an increase in oxidative stress and the failure of antioxidant defense systems. Current knowledge indicates that the level of glutathione progressively declines during aging. Because nerve cells are the longest-living cells that exhibit a high consumption rate of oxygen throughout an individual’s lifetime, the brain may be especially vulnerable to oxidative damage and this vulnerability increases during aging. In addition, the brain contains high concentrations of polyunsaturated fatty acids and transition metals and low antioxidative defense mechanisms. Although aging is an inevitable event, a growing volume of data confirms that antioxidant supplementation in combination with symptomatic drug treatments reduces oxidative stress and improves cognitive function in aging and age-related diseases. The present review discusses the neuroprotective effects of antioxidants in the aging brain.