Age-Related Changes in Regional Brain Activation During Phonological Decoding and Printed Word Recognition

Using magnetic source imaging, age-related changes in spatiotemporal brain activation profiles associated with printed word recognition and phonological decoding (pseudoword reading) were examined in 27 adults and 22 children without reading problems. Adults showed a distinct spatiotemporal profile during reading of both types of print consisting of bilateral activation of occipital cortices, followed by strongly left-predominant activation of basal temporal regions, and, finally, left hemisphere temporoparietal (including the angular gyrus) and inferior frontal activation. Children lacked the clear temporal distinction in the engagement of basal and temporoparietal areas and displayed significantly weaker activation of the left inferior frontal gyrus. In addition, the consistent hemispheric asymmetries in the degree of activation of basal temporal regions that were present in the adult readers were not apparent in the children. In contrast, the strong left hemisphere preponderance in the degree of activation of temporoparietal areas was present in children as well as adults, regardless of the type of print they were asked to read. The data suggest that the degree of specialization of cortical regions for reading, as well as the pattern of regional interactions that supports this specialization, may change with age.     

Age-Related Changes in Proteoglycan Composition in Rat Brain

Brain proteoglycans play an important role in learning and memory processes and in the pathogenesis of neurodegenerative disease. Brain proteoglycans in Wistar rats and early aging OXYS rats at the age of 1, 2, and 14 months were compared. Proteoglycan content in OXYS rats aged 1 and 2 months is 2-fold lower than in Wistar. The content of proteoglycans 7-fold decreases in Wistar and OXYS rats with age at the expense of heparan sulfates and chondroitin sulfates and by the age of 14 months, the difference between the strains is leveled. These results indicate that cognitive and emotional disorders observed in OXYS rats by the age of 3 months develop against the background of significant changes in the content and composition of proteoglycans. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 12, pp. 691–693, December, 2008     

Optical Mapping of Brain Activation and Connectivity in Occipitotemporal Cortex During Chinese Character Recognition

In this study, functional near-infrared spectroscopy (fNIRS) was used to examine the brain activation and connectivity in occipitotemporal cortex during Chinese character recognition (CCR). Eighteen healthy participants were recruited to perform a well-designed task with three categories of stimuli (real characters, pseudo characters, and checkerboards). By inspecting the brain activation difference and its relationship with behavioral data, the left laterality during CCR was clearly identified in the Brodmann area (BA) 18 and 19. In addition, our novel findings also demonstrated that the bilateral superior temporal gyrus (STG), bilateral BA 19, and left fusiform gyrus were also involved in high-level lexical information processing such as semantic and phonological ones. Meanwhile, by examining functional brain networks, we discovered that the right BA 19 exhibited enhanced brain connectivity. In particular, the connectivity in the right fusiform gyrus, right BA 19, and left STG showed significant correlation with the performance of CCR. Consequently, the combination of fNIRS technique with functional network analysis paves a new avenue for improved understanding of the cognitive mechanism underlying CCR.     

How Does Arabic Orthographic Connectivity Modulate Brain Activity During Visual Word Recognition: An ERP Study

One of the unique features of the Arabic orthography that differentiates it from many other alphabetical ones is the fact that most letters connect obligatorily to each other. Hence, these letters change their forms according to the location in the word (i.e. beginning, middle, or end), leading to the suggestion that connectivity adds a visual load which negatively impacts reading in Arabic. In this study, we investigated the effects of the orthographic connectivity on the time course of early brain electric responses during the visual word recognition. For this purpose, we collected event-related potentials (ERPs) from adult skilled readers while performing a lexical decision task using fully connected (Cw), partially connected and non-connected words (NCw). Reaction times variance was higher and accuracy was lower in NCw compared to Cw words. ERPs analysis revealed significant amplitude and latency differences between Cw and NCw at posterior electrodes during the N170 component which implied the temporo-occipital areas. Our findings show that instead of slowing down reading, orthographic connectivity in Arabic skilled readers seems to impact positively the reading process already during the early stages of word recognition. These results are discussed in relation to previous observations in the literature.     

Phonological Activation in Pure Alexia

Pure alexia is a reading impairment in which patients appear to read letter-by-letter. This disorder is typically accounted for in terms of a peripheral deficit that occurs early on in the reading system, prior to the activation of orthographic word representations. The peripheral interpretation of pure alexia has recently been challenged by the phonological deficit hypothesis, which claims that a postlexical disconnection between orthographic and phonological information contributes to or is responsible for the disorder. Because this hypothesis was mainly supported by data from a single patient (IH), who also has surface dyslexia, the present study re-examined this hypothesis with another pure alexic patient (EL). In contrast to patient IH, EL did not show any evidence of a phonological deficit. Her pattern of performance in naming was not qualitatively different from that of normal readers; she appeared to be reading via a mode of processing resulting in strong serial and lexical effects, a pattern often observed in normal individuals reading unfamiliar stimuli. The present results do not obviously support the phonological hypothesis and are more consistent with peripheral interpretations of pure alexia. The peripheral and the phonological accounts of pure alexia are discussed in light of two current models of visual word recognition.     

Brain Activation Changes Before and After PAP Treatment in Obstructive Sleep Apnea

Study Objectives:

Obstructive sleep apnea syndrome (OSAS) is associated with cognitive and functional deficits, most of which are corrected after positive airway pressure (PAP) treatment. Previous studies investigating the neural underpinnings of OSAS failed to provide consistent results both on the cerebral substrates underlying cognitive deficits and on the effect of treatment on these anomalies. The aims of the study were a) to investigate whether never-treated OSA patients demonstrated differences in brain activation compared to healthy controls during a cognitive task; and b) to investigate whether any improvements in cognitive functioning found in OSA patients after treatment reflected a change in the underlying cerebral activity.

Design:

OSA patients and healthy controls underwent functional magnetic resonance imaging (fMRI) scanning. They were compared on performance and brain activation during a 2-back working-memory task. Patients were also re-evaluated after 3 months treatment with PAP. Cognitive functions were evaluated using neurocognitive tests. Sleepiness (ESS), mood (Beck Depression Inventory) and, quality-of-life (SF-36) were also assessed.

Setting:

The Sleep Disorders Center and CERMAC at the Vita-Salute San Raffaele University.

Patients or Participants:

17 OSA patients and 15 age- and education-matched healthy controls.

Interventions:

PAP treatment for 3 months.

Measurements and Results:

Compared to controls, never-treated OSA patients showed increased activations in the left frontal cortex, medial precuneus, and hippocampus, and decreased activations in the caudal pons. OSA patients showed decreases in activation with treatment in the left inferior frontal gyrus and anterior cingulate cortex, and bilaterally in the hippocampus. Most neurocognitive domains, impaired at baseline, showed significant improvement after treatment.

Conclusions:

OSA patients showed an overrecruitment of brain regions compared to controls, in the presence of the same level of performance on a working-memory task. Decreases of activation in prefrontal and hippocampal structures were observed after treatment in comparison to baseline. These findings may reflect a neural compensation mechanism in never-treated patients, which is reduced by effective treatment.

Citation:

Castronovo V; Canessa N; Ferini Strambi L; Aloia MS; Consonni M; Marelli S; Iadanza A; BruschiA; Falini A; Cappa SF. Brain activation changes before and after PAP treatment in obstructive sleep apnea. SLEEP 2009;32(9):1161-1172.     

Dynamic Brain Activation Patterns for Face Recognition: A Magnetoencephalography Study

Summary: The present study used magnetoencephalography (MEG) to investigate the spatiotemporal profile of neurophysiological activity associated with recognition of recently encountered human faces in seventeen healthy right-handed adults. Activity sources modeled as instantaneous equivalent current dipoles were found in ventral occipito-temporal regions during the early stages of stimulus processing and in lateral temporal cortices during later stages. Hemispheric asymmetries in regional activity were restricted to ventral occipitotemporal areas. The magnitude of magnetic flux originating in these regions was greater in the right hemisphere during the first 350 ms post-stimulus onset. In addition, the duration of neurophysiological activity was greater in the right hemisphere after 600 ms post-stimulus onset. The results indicate right hemisphere predominance in the degree of engagement of neurophysiological processes involved in both the pre- and post-recognition phases of face processing. This research was supported in part by a grant from Epilepsy Foundation of America to D. Lee.     

Comparative Analysis of Age-Related Changes in Activities of Monoamine Oxidase-B and Antioxidant Defense Enzymes in Various Structures of Human Brain

Activities of monoamine oxidase B, Cu-Zn-dependent superoxide dismutase (SOD), and catalase, and concentration of enzyme-active ceruloplasmin were measured in brain preparations from 43 humans died at the age of 21-92 years. Activity of monoamine oxidase B in the neocortex, cerebellum, basal ganglia, and stem structures increased with age, while SOD activity decreased and catalase and ceruloplasmin concentrations slightly increased. A contribution of age-related increase of cerebral monoamine oxidase activity into ontogenetic impairment of the antioxidant defense in human brain is discussed.     

Relationship Between Obstructive Sleep Apnea Severity and Brain Activation During a Sustained Attention Task

Study Objectives:

The objectives of this study were to (1) characterize cognitive and cerebral correlates of attention and response speed in patients with obstructive sleep apnea (OSA) and (2) assess the association of performance and brain activation with measures of OSA severity.

Design:

Patients with OSA and controls were compared on performance and brain activation during a sustained attention task. The association of reaction time and brain activation with apnea-hypopnea index, nocturnal hypoxia, and arousals was assessed.

Setting:

Functional magnetic resonance imaging was conducted while participants performed a Go–No-Go task. The ‘Go’ trials of the Go–No-Go task were used to index attention processing.

Participants:

Fourteen patients with OSA and 14 normal control subjects with equivalent age, body mass index, blood pressure, and education.

Interventions:

N/A.

Measurements and Results:

Patients with OSA showed decreased brain activation in cingulate, frontal, and parietal regions typically involved in attention tasks, compared with control subjects. Within the patients with OSA, increasing arousal index, but not desaturation index, was associated with slower mean reaction time and with decreased brain activation in areas involved in arousal and attention, response selection, motor response, and decision making. The apnea-hypopnea index, by itself, was not associated with changes in cerebral response.

Conclusions:

Patients with OSA showed decreased brain activation compared with control subjects during an attention task. The association of arousal index (but not hypoxia) with slow reaction times and brain activation suggests that alertness and reaction times show greater correlations with measures of sleep disruption than with measures of hypoxia.

Citation:

Ayalon L; Ancoli-Israel S; Aka AA; McKenna BS; Drummond SPA. Relationship between obstructive sleep apnea severity and brain activation during a sustained attention task. SLEEP 2009;32(3):373–381.     

Investigation of Age-Related Changes in Physiological Kinetic Tremor

Tremor is the most common movement disorder characterized by repetitive and stereotyped movements. Most investigations on tremor attempt to understand its relation to neuromuscular dysfunctions. Therefore, there is a lack of studies that aim to investigate the complex relation between the physiological tremor and aging, especially in kinetic conditions. In this context, the main motivation of this research was to quantify age-related changes in the kinetic tremor of clinically healthy individuals. For this, a number of features extracted from tremor activity, obtained from digitized drawings of Archimedes’ spirals, were analyzed. In total, 59 subjects participated in the experiments. These individuals were divided into seven groups according to their ages and two types of analysis were carried out. First, the tremor activity of young and elderly adults was investigated by means of traditional features commonly used in tremor analysis, and secondly, linear discriminant analysis (LDA) was employed for the study of the correlation between age and tremor. The results showed significant statistical differences between the kinetic tremor activity of the young and elderly groups. Furthermore, it was found that LDA allowed for the estimate of a unique feature, so-called LDA-value, which showed to be linearly correlated with age.     

Identification of Brain Regions Activated by Sevoflurane and Propofol and Regional Changes in Gene Expression

General anesthetics have different efficacies and side effect incidences based on their mechanism of action. However, detailed comparative studies of anesthetics are incomplete. In this study, target brain regions and gene expression changes in these brain regions were determined for sevoflurane and propofol to understand the mechanisms that cause differences among anesthetics. Rats were anesthetized with sevoflurane or propofol for 1 hr, and brain regions with anesthesia-induced changes in neuronal activity were examined by immunohistochemistry and in situ hybridization for c-Fos. Among the identified target brain regions, gene expression analysis was performed in the habenula, the solitary nucleus and the medial vestibular nucleus from laser microdissected samples. Genes altered by sevoflurane and propofol were different and included genes involved in the incidence of postoperative nausea and vomiting and emergence agitation, such as Egr1 and Gad2. GO enrichment analysis showed that the altered genes tended to be evenly distributed in all functional category. The detailed profiles of target brain regions and induced gene expression changes of sevoflurane and propofol in this study will provide a basis for analyzing the effects of each anesthetic agent and the risk of adverse events.     

阅读障碍儿童汉字字形、字音和字义启动效应

目的：探讨汉语阅读障碍儿童与正常者汉字字形、字音和字义启动效应的差异。方法：选取阅读障碍儿童（25人）及与之年龄和阅读水平相配比的两组对照儿童（各25人）。应用启动范式让被试进行真假字判断。真字启动条件分别设为形近、音同、义近和无关4类,无关字对作为基线,假字字对作为干扰刺激。考察被试在各启动条件下的反应时、启动量及应答错误率的差异。结果：阅读障碍组儿童汉字形、音、义校正启动量（-0.010、-0.010、0.001）明显低于对照组儿童（年龄对照组分别为0.026、0.026、0.022;阅读水平对照组分别为0.062、0.058、0.031）（F=17.91,P〈0.001）。正常儿童汉字启动效应可能的大小排序为：字形〉字音〉字义。阅读能力和启动效应间交互作用不显著。结论：阅读障碍儿童存在着一种普遍的字形和读音加工缺陷,支持联结模型关于阅读障碍的假设。     

Age-Related Changes of Noncalcified Collagen in Human Cortical Bone

It is well known that osteoid, which contains a noncalcified collagenous matrix, is formed during the initial stage of bone formation during the bone remodeling process. Thus, synthesis of defective collagen molecules in osteoid may cause abnormal bone formation, thereby leading to changes in bone quality. The objective of this study was to investigate age-related changes in noncalcified collagen molecules in osteoid and its likely effects on the mechanical integrity of human cortical bone. Thirty human cadaveric femurs were divided into three age groups: young adults, middle age, and the elderly, respectively. A novel high performance liquid chromatography approach was employed to quantify the denaturation of noncalcified collagenous matrix in addition to mechanical tests of bone. Bulk concentrations of both enzymatic and nonenzymatic collagen cross links in bone also were measured. Moreover, the number of newly formed osteons per unit area and the bony area fraction of these osteons were estimated. The results of this study indicate that denaturation of the noncalcified collagenous matrix in bone increases with increasing age. In addition, such collagen denaturation in osteoid exhibited a correlation with nonenzymatic collagen cross links as well as the strength and toughness of bone. These results suggest that age-related changes in the noncalcified collagenous matrix induced by bone remodeling may have likely effects on bone quality. © 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8718La, 8280Bg     

Age-Related Changes in Primary and Secondary Immune Organs of the Mouse

The present work describes the murine immune tissue evolution with age with special emphasis on the bone marrow. To that effect we monitored the weights of the thymus, spleen and axillary lymph nodes over the first year of life in C57BL/6 male and female mice. In addition, we monitored the relative proportions of erythroid, lymphoid and myeloid cells in the bone marrow, and performed in vitro migration assays of bone marrow cells to thymic supernatants, with the aim of determining whether the migration of such cells or the thymic attractive capacity are affected by age. Before puberty, a remarkable decline in the relative weight of the thymus, spleen and lymph nodes was observed; after that stage, however, only the thymus showed an involution. The proportion of myeloid cells in the bone marrow showed an increase with age. Furthermore, the migration of myeloid cells to thymic supernatants increased with age and paralleled the time-course of the myeloid cell increase found in the bone marrow. More interestingly, the proportion of lymphoid cells to total bone marrow cells showed a clear decline with age. The time-course of this decline closely paralleled that of thymus weight, suggesting that the involution of the thymus may be related to changes in the cell composition of the bone marrow.     

脑缺血再灌流过程中沙土鼠脑组织和血浆SOD、MDA含量的变

复制沙土鼠实验性脑缺血再灌流模型,测定了在缺血及再灌流不同阶段血清及脑组织中超氧化物歧化酶（ＳＯＤ）的活性和脂质过氧化反应最终产物（ＭＤＡ）的含量变化,结果发现单纯缺血组与再灌流各组脑组织ＭＤＡ的含量均高于正常对照组,且再灌流１ｈ、６ｈ组的ＭＤＡ含量明显高于单纯缺血组（Ｐ＜０．０５）,并有随再灌时间延长不断升高的趋势,但三个再灌流组之间比较无明显差异。单纯缺血组与再灌流各组比较脑组织ＳＯＤ的活性均较正常对照组降低,以再灌１ｈ、６ｈ最为明显,与单纯缺血组比较Ｐ＜０．０５。实验各组与正常对照组比较血浆ＳＯＤ的活性无显著差异。表明单纯缺血和再灌流后均发生了脂质过氧化反应,并认为自由基引起的损伤,在缺血后再灌流中比单纯缺血更为严重。     

Age-Related Changes in the Thickness of Cortical Zones in Humans

Structural neuroimaging studies have demonstrated that all regions of the cortex are not affected equally by aging, with frontal regions appearing especially susceptible to atrophy. The "last in, first out" hypothesis posits that aging is, in a sense, the inverse of development: late-maturing regions of the brain are preferentially vulnerable to age-related loss of structural integrity. We tested this hypothesis by analyzing age-related changes in regional cortical thickness via three methods: (1) an exploratory linear regression of cortical thickness and age across the entire cortical mantle (2) an analysis of age-related differences in the thickness of zones of cortex defined by functional/cytoarchitectural affiliation (including primary sensory/motor, unimodal association, heteromodal association, and paralimbic zones), and (3) an analysis of age-related differences in the thickness of regions of cortex defined by surface area expansion in the period between birth and early adulthood. Subjects were grouped as young (aged 18-29, n?=?138), middle-aged (aged 30-59, n?=?80), young-old (aged 60-79, n?=?60), and old-old (aged 80+, n?=?38). Thinning of the cortex between young and middle-aged adults was greatest in heteromodal association cortex and regions of high postnatal surface area expansion. In contrast, thinning in old-old age was greatest in primary sensory/motor cortices and regions of low postnatal surface area expansion. In sum, these results lead us to propose a sequential "developmental-sensory" model of aging, in which developmental factors influence cortical vulnerability relatively early in the aging process, whereas later-in more advanced stages of aging-factors specific to primary sensory and motor cortices confer vulnerability. This model offers explicitly testable hypotheses and suggests the possibility that normal aging may potentially allow for multiple opportunities for intervention to promote the structural integrity of the cerebral cortex.     

Age-Related Changes in the Composition of Proteoglycans in Sheep Cartilage

Age-related changes in the proteoglycans of costal, tracheal, nasal and xiphoid cartilages of sheep, starting at 100 days in utero to 1 year postnatally and in scapular cartilages up to 13 years of age, have been assessed. The amino acid compositions of the core proteins in the proteoglycans from one-year-old cartilages are indistinguishable on the basis of kind of cartilage or of earlier stages of development. At 13 years of age, the core protein in the proteoglycans of scapular cartilages contains less glutamic acid/glutamine and glycine and more lysine, histidine, arginine, and threonine than at one year of age.

Relative to the protein, the amount of chondroitin sulfates decreases with age but the amount of keratan sulfate increases. In part, this is a reflection of a decrease in the size of the chondroitin sulfate chains and an increase in the size of the keratan sulfate chains. Up to one year of age, the ratio of chondroitin-4-sulfate to chondroitin-6-sulfate increases in the scapular cartilages. From two to nine years of age, this ratio remains relatively constant at 1.7. At 100 days in utero, about 12% of the disaccharide repeats in the chondroitin sulfate are notsulfated, and this fraction progressively decreases to about 1% by two years postnatally.

After one year of age, the size of the proteoglycan monomers decreases. As indicated by sedimentation velocity analysis, the proportion of monomers in aggregate form increases up to 1–2 years of age and then decreases. At 100 days of age the “immature” core protein does not react in vitro with hyaluronan and link proteins to form aggregates discernable in the ultracentrifuge.     

Age-Related Changes in Primary and Secondary Immune Organs of the Mouse

The present work describes the murine immune tissue evolution with age with special emphasis on the bone marrow. To that effect we monitored the weights of the thymus, spleen and axillary lymph nodes over the first year of life in C57BL/6 male and female mice. In addition, we monitored the relative proportions of erythroid, lymphoid and myeloid cells in the bone marrow, and performed in vitro migration assays of bone marrow cells to thymic supernatants, with the aim of determining whether the migration of such cells or the thymic attractive capacity are affected by age. Before puberty, a remarkable decline in the relative weight of the thymus, spleen and lymph nodes was observed; after that stage, however, only the thymus showed an involution. The proportion of myeloid cells in the bone marrow showed an increase with age. Furthermore, the migration of myeloid cells to thymic supernatants increased with age and paralleled the time-course of the myeloid cell increase found in the bone marrow. More interestingly, the proportion of lymphoid cells to total bone marrow cells showed a clear decline with age. The time-course of this decline closely paralleled that of thymus weight, suggesting that the involution of the thymus may be related to changes in the cell composition of the bone marrow.