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Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Frailty increases the risk of poor health outcomes, disability, hospitalization, and death in older adults and affects 7%–12% of the aging population. Secondary impacts of frailty on psychological health and socialization are significant negative contributors to poor outcomes for frail older adults.

Videogame play (VGP) has been associated with numerous preferred and non-preferred effects. However, the effects of VGP on the development of microstructural properties in children, particularly those associated with negative psychological consequences of VGP, have not been identified to date. The purpose of this study was to investigate this issue through cross-sectional and longitudinal prospective analyses. In the present study of humans, we used the diffusion tensor imaging mean diffusivity (MD) measurement to measure microstructural properties and examined cross-sectional correlations with the amount of VGP in 114 boys and 126 girls. We also assessed correlations between the amount of VGP and longitudinal changes in MD that developed after 3.0±0.3 (s.d.) years in 95 boys and 94 girls. After correcting for confounding factors, we found that the amount of VGP was associated with increased MD in the left middle, inferior and orbital frontal cortex; left pallidum; left putamen; left hippocampus; left caudate; right putamen; right insula; and thalamus in both cross-sectional and longitudinal analyses. Regardless of intelligence quotient type, higher MD in the areas of the left thalamus, left hippocampus, left putamen, left insula and left Heschl gyrus was associated with lower intelligence. We also confirmed an association between the amount of VGP and decreased verbal intelligence in both cross-sectional and longitudinal analyses. In conclusion, increased VGP is directly or indirectly associated with delayed development of the microstructure in extensive brain regions and verbal intelligence.

The quantification of spontaneous calcium (Ca2+) oscillations (SCOs) in astrocytes presents a challenge because of the large irregularities in the amplitudes, durations, and initiation times of the underlying events. In this article, we use a stochastic context to account for such SCO variability, which is based on previous models for cellular Ca2+signaling. First, we found that passive Ca2+influx from the extracellular space determine the basal concentration of this ion in the cytosol. Second, we demonstrated the feasibility of estimating both the inositol 1,4,5-trisphosphate (IP3) production levels and the average number of IP3receptor channels in the somatic clusters from epifluorescent Ca2+imaging through the combination of a filtering strategy and a maximum-likelihood criterion. We estimated these two biophysical parameters using data from wild-type adult mice and age-matched transgenic mice overexpressing the 695-amino-acid isoform of human Alzheimer β-amyloid precursor protein. We found that, together with an increase in the passive Ca2+influx, a significant reduction in the sensitivity of G protein-coupled receptors might lie beneath the abnormalities in the astrocytic Ca2+signaling, as was observed in rodent models of Alzheimer's disease. This study provides new, to our knowledge, indices for a quantitative analysis of SCOs in normal and pathological astrocytes.

The elucidation of the complex machinery used by the human brain to segregate and integrate information while performing high cognitive functions is a subject of imminent future consequences. The most significant contributions to date in this field, known as cognitive neuroscience, have been achieved by using innovative neuroimaging techniques, such as electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI), which measure variations in both the time and the space of some interpretable physical magnitudes. Extraordinary maps of cerebral activation involving function-restricted brain areas, as well as graphs of the functional connectivity between them, have been obtained from EEG and fMRI data by solving some spatio-temporal inverse problems, which constitutes a top-down approach. However, in many cases, a natural bridge between these maps/graphs and the causal physiological processes is lacking, leading to some misunderstandings in their interpretation. Recent advances in the comprehension of the underlying physiological mechanisms associated with different cerebral scales have provided researchers with an excellent scenario to develop sophisticated biophysical models that permit an integration of these neuroimage modalities, which must share a common aetiology. This paper proposes a bottom-up approach, involving physiological parameters in a specific mesoscopic dynamic equations system. Further observation equations encapsulating the relationship between the mesostates and the EEG/fMRI data are obtained on the basis of the physical foundations of these techniques. A methodology for the estimation of parameters from fused EEG/fMRI data is also presented. In this context, the concepts of activation and effective connectivity are carefully revised. This new approach permits us to examine and discuss some future prospects for the integration of multimodal neuroimages.

Background & Aims: Activins belong to the transforming growth factor-@b superfamily. Recent studies have shown that activin and its natural antagonist, follistatin, are involved in tissue repair and inflammatory processes. The aim of this study was to determine whether neutralization of activins with follistatin would have an in vivo anti-inflammatory effect in several murine models of colitis. Methods: We assessed activin levels in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS). We subsequently tested the effects of an intraperitoneal injection of follistatin before or after induction of TNBS colitis. We also examined the established colitis induced by oral dextran sulfate sodium (DSS) as well as the spontaneous colitis that develops in interleukin (IL)-10 gene-deficient (IL-10^-^/^-) mice. Results: Levels of activin transcripts in the colon during the acute phase of TNBS colitis were up-regulated. Epithelial cells, infiltrating macrophages (M@f), and endothelial cells produced excess activin @bA. Pretreatment with follistatin increased the survival rate of mice with TNBS colitis from 33% to 82% and decreased the plasma levels of IL-6 and amyloid A. Administration of follistatin also reduced the histologic score and tissue myeloperoxidase activity in established TNBS and DSS colitis and reduced the severity of the colitis in IL-10^-^/^- mice. Based on results obtained from 3 mouse models and from in vitro experiments, follistatin promoted the proliferation of colonic epithelial cells. Conclusions: Neutralization of activins by follistatin promoted epithelial cell division and tissue repair, clearly suggesting a treatment modality for intestinal inflammation.

To investigate the damage mediated by anti-cancer drugs in normal cells, we examined the effect of such drugs on apoptosis of normal cells of the small intestinal epithelium and the bone marrow by in situDNA end-labelling and transmission electron microscopy. Mice received a single dose of 5-fluorouracil (5-FU) or cisplatin, or repeated daily doses of 5-FU for 7 days. In mice treated with a single dose of 5-FU 50 mg/kg or cisplatin 5 mg/kg, the number of apoptotic cells appearing in the small intestine 12 h after injection was relatively small, but increased steadily reaching a peak after 36 h and then decreasing to close to that in the control group by 48 h. In bone marrow cells, results were similar in mice treated with single doses of 5-FU 50 mg/kg but apoptosis increased much less in those treated with cisplatin 5 mg/kg. The proportion of apoptotic cells reached peak values earlier at higher concentrations of 5-FU or cisplatin both in small intestine and in bone marrow. In the mice treated repeatedly with 5-FU 50 mg/kg, the proportion of apoptotic small intestinal epithelial cells reached a succession of peaks at 48-h intervals. Mice treated repeatedly with 5-FU 50 mg/kg also showed a rapid increase in diarrhoea symptoms and a steady decrease in the height of villi. Our results suggest it may be possible to prevent the side-effects of anti-cancer drugs by inhibiting apoptosis in the gastrointestinal tract.

Repeated recognition of the face of a familiar individual is known to show semantic repetition priming effect. In this study, normal subjects were repeatedly presented faces of their colleagues, and the effect of repetition on the regional cerebral blood flow change was measured using positron emission tomography. They repeated a set of three tasks: the familiar-face detection (F) task, the facial direction discrimination (D) task, and the perceptual control (C) task. During five repetitions of the F task, familiar faces were presented six times from different views in a pseudorandom order. Activation reduction through the repetition of the F tasks was observed in the bilateral anterior (anterolateral to the polar region) temporal cortices which are suggested to be involved in the access to the long-term memory concerning people. The bilateral amygdala, the hypothalamus, and the medial frontal cortices, were constantly activated during the F tasks, and considered to be associated with the behavioral significance of the presented familiar faces. Constant activation was also observed in the bilateral occipitotemporal regions and fusiform gyri and the right medial temporal regions during perception of the faces, and in the left medial temporal regions during the facial familiarity detection task, which are consistent with the results of previous functional brain imaging studies. The results have provided further information about the functional segregation of the anterior temporal regions in face recognition and long-term memory.

By measuring regional cerebral blood flow using PET, we delineated the roles of the occipito-temporal regions activated by faces and scenes. We asked right-handed normal subjects to perform three tasks using facial images as visual stimuli: in the face familiar/unfamiliar discrimination (FF) task, they discriminated the faces of their friends and associates from unfamiliar ones; in the face direction discrimination (FD) task, they discriminated the direction of each unfamiliar face; in the dot location discrimination (DL) task, they discriminated the location of a red dot on a scrambled face. The activity in each task was compared with that in the control fixation (CF) task, in which they fixated on the centre of a display without visual stimuli. The DL task activated the occipital cortices and posterior fusiform gyri bilaterally. During the FD task, the activation extended anteriorly in the right fusiform gyrus and laterally to the right inferior temporal cortex. The FF task further activated the right temporal pole. To examine whether the activation due to faces was face-specific, we used a scene familiar/unfamiliar discrimination (SF) task, in which the subjects discriminated familiar scenes from unfamiliar ones. Our results suggest that (i) the occipital cortices and posterior fusiform gyri non-selectively respond to faces, scrambled faces and scenes, and are involved mainly in the extraction of physical features of complex visual images; (ii) the right inferior temporal/fusiform gyrus responds selectively to faces but not to non-face stimuli and is involved in the visual processing related to face perception, whereas the bilateral parahippocampal gyri and parieto-occipital junctions respond selectively to scenes and are involved in processing related to scene perception; and (iii) the right temporal pole is activated during the discrimination of familiar faces and scenes from unfamiliar ones, and is probably involved in the recognition of familiar objects.

Human cortical areas activated in relation to vergence eye movements were determined using positron emission tomography. Binocular disparity-driven visual stimuli were presented using a head-mounted display. Eye movements were monitored continuously by an infrared limbus tracker. A combination of a bar and a cross was used as the target. In the vergence task, subjects were instructed to follow an approaching bar, while ignoring a stationary cross. Activation in relation to vergence eye movement was discriminated from activation in relation to motion vision by using the ignore-bar task as the control. In the ignore-bar task, subjects were instructed to fixate on a stationary cross, while ignoring an approaching bar. The fixation task was used as the basic control for both the vergence and the ignore-bar tasks. Areas of activation in relation to vergence eye movements were found in the bilateral temporooccipital junction, the left inferior parietal lobule, and the right fusiform gyrus by comparing regional cerebral flow between the vergence and ignore-bar tasks and by the conjunctive analyses of vergence-vs-ignore comparison with vergence-vs-fixation comparison.

Social contact often initially depends on ascertaining the direction of the other person's gaze. We determined the brain areas involved in gaze monitoring by a functional neuroimaging study. Discrimination between the direction of gaze significantly activated a region in the left amygdala during eye-contact and no eye-contact tasks to the same extent. However, a region in the right amygdala was specifically activated only during the eye-contact task. Results confirm that the left amygdala plays a general role in the interpretation of eye gaze direction, and that the activity of the right amygdala of the subject increases when another individual's gaze is directed towards him. This suggests that the human amygdala plays a role in reading social signals from the face.Keywords: PET; regional cerebral blood flow; amygdala; gaze direction discrimination; social contact

The aims of this study were to develop an objective method for assessing rCBF deficits using a statistical image analysis protocol and to validate its effective use in clinical practice. 99Tcm-HMPAO brain SPET images were acquired for 40 normal subjects, 10 patients with Alzheimer's disease and 10 patients with depression. Automated image registration was used to standardize the size and shape of the brain structures for all subjects. The images of the first 30 normal subjects were used to construct a normal database. The CBF images of the other 10 normal subjects and the 20 patients were compared voxel by voxel with the normal database to map CBF abnormalities by statistical evaluation. The results were compared with the clinical reports of CBF images. The expert system detected all rCBF deficits reported by the nuclear physicians. Some additional areas with special information, like atrophy and bilateral asymmetry, were also identified by the expert system. We conclude that this expert system can delineate CBF deficits with sufficiently high accuracy, differentiating normal from abnormal CBF images using voxel-based comparisons. The use of an expert system improves rCBF SPET image evaluation.

WE examined the role of the parahippocampal regions in humans during two types of verbal recognition process, i.e. delayed matching and non-matching, by measuring regional cerebral blood flow (rCBF) using PET. The results showed differential activation of each parahippocampal region during verbal memory tasks in which the side activated shifted depending on the nature of the task employed; an increase in rCBF in the left parahippocampal gyrus was associated with retrieval strategy of non-matching, and an increase in rCBF in the right parahippocampal gyrus was associated with retrieval strategy of matching. We conclude that lateralized parahippocampal activation may depend on the type of response required.

Digesta samples were collected from rumen, omasum, abomasum, upper small intestine, middle small intestine, lower small intestine, cecum and colon to study the effects of dietary calcium levels on the concentration and solubility of minerals in the digestive tract of sheep.Calcium concentrations in digesta and supernatant increased and calcium solubilities tended to become lower with the elevation of dietary calcium level. In comparison with the concentrations of calcium, magnesium and potassium, the concentrations of phosphorus and sodium in digesta and supernatant were higher in the rumen and the omasum.A net absorption of calcium appeared to occur in the upper small intestine and that of phosphorus in the middle and the lower small intestine. Similar to calcium, a decrease in phosphorus solubility was found in the lower small intestine when high calcium rations were given. Supernatant concentrations of magnesium, sodium and potassium increased in the upper small intestine and decreased in the middle and lower small intestine. Although calcium, phosphorus and magnesium concentrations in digesta and supernatant did not decrease in the cecum and the colon, sodium and potassium lowered in these sites.

The ac conductivity of two samples of ytterbium nitrate crystal in the temperature range from −75 to 50°C and in the frequency range from 20 to 106Hz has been measured in several runs. We have observed metastable behavior of the conductivity in the region above −70°C, and stable behavior below this temperature. The conductivity shows different frequency dependence in the metastable and the stable states.

The spectra of ac conductivity in the frequency range from 50 Hz to 100 kHz at temperature in the range from 30°C to - 65°C have been measured in a terbium nitrate crystal. The experimental results indicate a metastable property in the crystal. Copyright 1993, 1999 Academic Press

Cerebral blood flow (CBF) during silent verb generation was measured at four Japanese PET centers. To minimize the variance of the measurement, speakers of a single language (Japanese) served as subjects and experimental conditions at the four PET centers were controlled as much as possible. Two types of activation patterns were observed: activations in the left dorsolateral prefrontal cortices and the medial frontal cortex (at the two centers with a 2D PET scanner) and additional activation in the left posterior temporal cortex (at the two centers with a 3D scanner). This suggests either a difference in the sensitivity of the two types of PET scanners (viz., a 3D scanner is generally more sensitive than a 2D scanner) and/or subject bias due to the small number of subjects at the individual centers. The pooled activation pattern was fundamentally similar to activation patterns obtained in the previous studies for verb generation in English and other European languages, suggesting that regions for verb generation are independent of particular languages. Regions relevant to verb generation are discussed.

Three thyroidectomized sheep were infused intravenously with porcine calcitonin at a rate of 30 mi.u./h per kg and three sham-operated sheep were infused with vehicle for 5 h. Saliva was collected from the left parotid duct by cannulation for 10 min in every hour. Salivary secretion rates were not changed in either thyroidectomized or sham-operated sheep throughout the experiment. Before the infusion, salivary phosphorus excretion was less in thyroidectomized sheep than in sham-operated animals. Calcitonin infusion increased salivary phosphorus excretion and decreased serum phosphorus concentrations in thyroidectomized sheep. Vehicle infusion did not affect salivary phosphorus excretion in sham-operated sheep. Serum concentrations and salivary excretion of calcium were decreased by calcitonin infusion into thyroidectomized sheep but were not changed in sham-operated sheep infused with vehicle. Calcitonin infusion increased serum parathyroid hormone concentrations in thyroidectomized sheep after the decrease of serum calcium concentrations. However, vehicle infusion did not affect serum parathyroid hormone concentrations in sham-operated sheep. There was little change of cyclic AMP excretion during the experiment in either thyroidectomized or sham-operated sheep. It is concluded that calcitonin increases salivary phosphorus excretion in sheep.J. Endocr.(1984) 102, 365–368

It is a familiar experience that we tend to close our eyes or divert our gaze when concentrating attention on cognitively demanding tasks. We report on the brain activity correlates of directing attention away from potentially competing visual processing and toward processing in another sensory modality. Results are reported from a series of positron-emission tomography studies of the human brain engaged in somatosensory tasks, in both "eyes open" and "eyes closed" conditions. During these tasks, there was a significant decrease in the regional cerebral blood flow in the visual cortex, which occurred irrespective of whether subjects had to close their eyes or were instructed to keep their eyes open. These task-related deactivations of the association areas belonging to the nonrelevant sensory modality were interpreted as being due to decreased metabolic activity. Previous research has clearly demonstrated selective activation of cortical regions involved in attention-demanding modality-specific tasks; however, the other side of this story appears to be one of selective deactivation of unattended areas.

Abstract The purpose of this study was to evaluate the effects of various covariants on the distribution pattern of Tc-99m HMPAO in patients with Alzheimer's disease by correlation analysis. Twenty patients with Alzheimer's disease and 15 age matched normal subjects participated. Tc-99m HMPAO brain SPECT and x ray computed tomography (CT) were acquired for each subject. SPECT images were transformed to a standard size and shape by automated image registration (AIR) and were used for group comparison by means of SPM96. Voxel based covariance analysis was performed on standardised images taking the age of patients, severity of disease (clinical dementia rating scale, mini mental state examination, physical self maintenance scale), and atrophy indices as variables. There was significantly decreased regional cerebral blood flow (rCBF) in the frontal, parietal, and temporal regions in the patient group (p<0.001), more marked in those patients having severe dementia. Covariance analysis disclosed that aging and severity of disease have a pronounced effect on rCBF, especially that of the left parietal region.

Abstract: The purpose of this study was to identify the brain regions activated in relation to oculomotor sequence learning. Nine healthy subjects participated in the study, which consisted of three positron emission tomography scans. In the initial learning task, subjects were instructed to track a sequence of seven successive positions of visual targets and to memorize the order of the targets as well as their spatial locations. In the saccade task, subjects were instructed to track visual targets presented at random locations. In the control task, subjects were instructed to gaze at a fixation point. Fields showing significant regional cerebral blood flow change were determined from task-minus-control subtraction images. We determined that fields in the pre-supplementary motor area (pre-SMA), the intraparietal cortex, and the prefrontal cortex were activated not only in the learning-minus-control images but also in the learning-minus-saccade images. Although prefrontal and parietal activations were bilateral, pre-SMA activation was confined to the left hemisphere. The results indicate that these fields function as a part of the neural network involved in the learning of sequential saccadic eye movements.

The a.c. conductivities along the c axis of caesium nitrate have been measured in the frequency range from 3 Hz to 100 kHz at temperatures between room temperature and 274·3°C. The a.c. conductivities show a different frequency dependence in the phases II and I. The temperature dependence of the conductivities shows a discontinuous jump, on increasing the temperature, at the structural phase transition point.

Three feeding trials were conducted with beef cattle in which a combination of supplemental vitamin E and K to a no-hay finishing ration resulted in superior performance. The vitamin supplemented cattle averaged 9% faster liveweight gains and improved feed conversion. A fourth cattle feeding trial was conducted in which supplemental selenium was added to a similar finishing cattle ration. The liveweight gain response from selenium was fully as high or higher than the responses obtained with supplemental vitamins. Also, supplemental selenium, as well as supplemental vitamin A, exerted a sparing action upon liver vitamin E. The possible importance of these results and some of the limitations in interpreting them in feeding practice were discussed.