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Structural brain variation, age, and response time.

Response time (RT) generally slows with aging, but the contribution of structural brain changes to this slowing is unknown. We used voxel-based morphometry (VBM) to determine gray matter (GM) and white matter (WM) brain volumes in 9 middle-aged adults (38-58 years old) and 9 seniors (66-82 years old). We correlated brain volumes with RT assessed in both a simple visual stimulus-response task and a visual continuous recognition memory task. No GM correlations with simple RT were significant; there was one WM correlation in the right fusiform gyrus. In the memory task, faster RT was correlated (p < .05, corrected) with less GM in the globus pallidus, the parahippocampus, and the thalamus for both groups. Several Brodmann areas (BA) differed between the groups such that in each area, less GM was correlated with slower RTs in the middle-aged group but with faster RTs in the senior group (BAs 19, 37, 46, 9, 8, 6, 13, 10, 41, and 7). The results suggest that individual differences in specific brain structure volumes should be considered as potential moderating factors in cognitive brain imaging studies.

Adult↗

Brain structures and life-span in primate species.

In haplorhine primates, when the effect of body weight is removed, brain weight is correlated with maximum recorded life-span. In this paper we have analyzed the relationships between volumes of specific brain structures and life-span. When the effect of body weight is removed, the volumes of many brain structures are significantly, positively correlated with maximum recorded life-span. However, the volumes of the medulla and most first-order sensory structures do not correlate with life-span. The cerebellum is the brain structure that best correlates with life-span. Parts of the cerebellum are particularly vulnerable to age-related loss of mass in humans. For another measure of the life cycle, female reproductive age, a similar set of brain structures is significantly, positively correlated (again with the exceptions of the medulla and most first-order sensory structures). There are some differences between the structures correlated for life-span and female reproductive age. For example, the hippocampus and lateral geniculate nucleus correlate with female reproductive age but do not correlate with life-span. In strepsirhine primates, when the effect of body weight is removed, total brain weight does not significantly correlate with either life-span or female reproductive age. However, the volumes of some brain structures in strepsirhines do correlate with these life-cycle parameters. The centromedial complex of the amygdala is the only structure to correlate with life-span in both strepsirhine and haplorhine primates. This structure participates in the regulation of blood pressure and in the stress response, which may be key factors governing life-span.

Animals↗

Intracentral connections of the brain structures participating in the regulation of blood flow.

In this study, we conducted an investigation into the characteristics of hemodynamic reactions during electrical stimulation of the structures of the hypothalamus and during simultaneous stimulation of the sinus nerve and the hypothalamus in anesthetized cats. We also investigated the monosynaptic connections of the hypothalamus with the structures of the brain stem and spinal cord. The possible influence of the hypothalamus, following the activation of various descending pathways (both through the bulbar level of regulation and by-passing it), upon the efferent component of the regulation of blood circulation is discussed; a scheme of intracentral connections of the brain structures participating in the regulation of blood circulation is presented.

Animals↗

Structural modeling of dynamic changes in memory and brain structure using longitudinal data from the normative aging study.

This is an application of new longitudinal structural equation modeling techniques to time-dependent associations of memory and brain structure measurements. There were 225 participants aged 30-80 years at baseline who were measured again after a 7-year interval on both the lateral ventricular size and Wechsler memory score. Multiple regression analyses show nonlinear associations with age but no relationships among longitudinal changes. Mixed-effects latent growth curve analyses and analyses based on latent difference scores indicate that longitudinal changes in both variables are reasonably well described by an exponential or dual change model. Bivariate dynamic structural equation modeling analyses indicate age-lagged changes operate in a coupled-over-time fashion, with the brain measure (lateral ventricular size) as a leading indicator in time of memory (Wechsler memory score) declines.

Adult↗

[Correlation of changes in the electrical activity and indices of tissue respiration of brain structures in rabbits exposed systematically to vibration].

The electrical activity and tissue respiration of the cortex and subcortex (posterior hypothalamic nucleus, Deiters' vestibular nucleus) have been studied in the rabbits during 3-month exposure to vibration (60H2, for 3h daily). On days 15-30 of exposure to vibration the electrocorticogram demonstrated the prevalence of alfa-waves whereas in the subcortex the teta-waves were dominated. On long-term vibration exposure (2-3 months), the synchronized slow waves were recorded on the EEG. Comparison of a changed electrical activity of the various structures of the brain with the level of oxidizing metabolism enabled us to reveal their definite interrelationship. In the early stage of vibration exposure there has been observed an increased absorption of oxygen by the brain structures and the elevated activity of succinate dehydrogenase. The prolonged vibration resulted in a decreased level of tissue respiration and activity of respiratory enzyme. Under vibration exposure there has been revealed a statistically significant direct relationship between the content of absorbed oxygen, activity of succinate dehydrogenase and the shifts in the electrical activity of cerebral structures.

Animals↗

Down syndrome: MR quantification of brain structures and comparison with normal control subjects.

For quantification of brain structures from MR scans, a novel, powerful stereologic tool known as Cavalieri's principle was applied. This tool enables an objective estimation of volume. The method was applied to detect differences in various brain structures between persons with Down syndrome and control subjects. On the basis of absolute values, smaller volumes for the whole brain, cerebral cortex, white matter, and cerebellum were seen in persons with Down syndrome. Similar results were observed when a normalization procedure, based on the volume of cranial cavity, was used. Stereologic determinations of the volumes of brain structures from MR images can reliably identify volume differences between persons with Down syndrome and control subjects.

Adult↗

Brain structure and function and the outcomes of treatment for depression.

BACKGROUND: Depressed patients have a variety of brain structural alterations, the most common being atrophy and deep white-matter lesions. Alterations in brain function also are common, particularly regional decreases in cerebral metabolism and perfusion. METHOD: We review here the evidence that alterations in brain structure and function may explain some of the heterogeneity in outcomes of depression. We also report initial results suggesting that measurement of brain structure and function may help to predict outcomes of treatment for depression. Brain structure was examined using three-dimensional reconstruction and volumetric analysis of magnetic resonance imaging (MRI) scans. Brain function was examined using quantitative electroencephalography (QEEG), performed at baseline and serially during the course of treatment. QEEG measures included coherence (a measure of synchronized activity between brain regions) and cordance (a measure strongly associated with regional cerebral perfusion). RESULTS: Depressed patients have been reported to have larger volumes of white-matter lesions than controls. We have found that some types of white-matter lesions are associated with lower coherence and that subjects with low coherence had significantly poorer outcomes of treatment for depression at 2-year follow-up. Depressed subjects had low cordance at baseline, which decreased further during the course of effective treatment. Subjects who did not improve had little or no change in cordance. Changes in cordance were detected prior to the onset of clinical response, with decreases seen as early as 48 hours after the initiation of treatment in subjects who showed eventual response. CONCLUSION: These preliminary results suggest that functional imaging using QEEG may be useful for assessing, and possibly predicting, outcomes of treatment for depression.

Antidepressive Agents↗

Starving the brain: structural abnormalities and cognitive impairment in adolescents with anorexia nervosa.

Anorexia nervosa (AN) is one of the most common chronic illnesses afflicting adolescent girls and is associated severe medical complications. The structural abnormalities found in the brain of adolescents with AN are among the earliest and most striking physical consequences. In the past, it had been assumed that the brain abnormalities found in patients with AN reverse with weight-recovery. Recent evidence has shown that not all of these changes are completely reversible with weight recovery. To date, very little is known about the functional significance of these brain abnormalities. Several studies have shown that cognitive dysfunction is also a common feature of AN. Although current evidence suggests that there may be some degree of improvement in cognition with weight-recovery, it is unclear whether cognition recovers fully or equally across all neuropsychological domains. Furthermore, it remains unknown whether the reported functional consequences are associated with these structural brain changes. This article will review the current literature on structural brain abnormalities and cognitive dysfunction in adolescents with AN.

Anorexia Nervosa↗

Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes.

CONTEXT: For more than a century, it has been uncertain whether or not the major diagnostic categories of psychosis--schizophrenia and bipolar disorder--are distinct disease entities with specific genetic causes and neuroanatomical substrates. OBJECTIVE: To investigate the relationship between genetic risk and structural variation throughout the entire brain in patients and their unaffected relatives sampled from multiply affected families with schizophrenia or bipolar disorder. DESIGN: Analysis of the association between genetic risk and variation in tissue volume on magnetic resonance images. SETTING: Psychiatric research center. PARTICIPANTS: Subjects comprised 25 patients with schizophrenia, 36 of their unaffected first-degree relatives, 37 patients with bipolar 1 disorder who experienced psychotic symptoms during illness exacerbation, and 50 of their unaffected first-degree relatives. MAIN OUTCOME MEASURES: We used computational morphometric techniques to map significant associations between a continuous measure of genetic liability for each subject and variation in gray or white matter volume. RESULTS: Genetic risk for schizophrenia was specifically associated with distributed gray matter volume deficits in the bilateral fronto-striato-thalamic and left lateral temporal regions, whereas genetic risk for bipolar disorder was specifically associated with gray matter deficits only in the right anterior cingulate gyrus and ventral striatum. A generic association between genetic risk for both disorders and white matter volume reduction in the left frontal and temporoparietal regions was consistent with left frontotemporal disconnectivity as a genetically controlled brain structural abnormality common to both psychotic disorders. CONCLUSIONS: Genetic risks for schizophrenia and bipolar disorder are associated with specific gray matter but generic white matter endophenotypes. Thus, Emil Kraepelin's pivotal distinction was neither wholly right nor wholly wrong: the 2 major psychoses show both distinctive and similar patterns of brain structural abnormality related to variable genetic risk.

Adolescent↗

Structural brain abnormalities in schizophrenia: a family study.

Structural brain abnormalities such as ventricular enlargement are robust correlates of schizophrenia, but the degree of difference compared with unrelated normal controls is only moderate (< 1 standard deviation), and only 40% of patients have values on these measures that fall outside of the normal distribution. Family studies can help to clarify the meaning of this overlap by controlling for some of the non-schizophrenia-related genetic variation in neuroanatomical traits. Computerized tomographic scans of the brain were used to measure ventricular and sulcal cerebrospinal fluid (CSF) to brain ratios (VBR and SBR) for each hemisphere in 16 pairs of discordant siblings from the Copenhagen Schizophrenia High-Risk Project. Schizophrenics' values for VBR and SBR exceeded those of their nonschizophrenic siblings in 75% of the pairs; on average, patients' values on these measures were 1 and 5 standard deviations larger, respectively, than those of their nonschizophrenic siblings. Sulcal and left hemisphere effects were significantly more pronounced than ventricular and right hemisphere effects. After controlling for between-family variation, structural brain abnormalities appear to be more prevalent and more pronounced in schizophrenia than has previously been assumed, with relatively greater deviation observed for cortical and left hemisphere measures of CSF space enlargement.

Adult↗

An examination of cetacean brain structure with a novel hypothesis correlating thermogenesis to the evolution of a big brain.

This review examines aspects of cetacean brain structure related to behaviour and evolution. Major considerations include cetacean brain-body allometry, structure of the cerebral cortex, the hippocampal formation, specialisations of the cetacean brain related to vocalisations and sleep phenomenology, paleoneurology, and brain-body allometry during cetacean evolution. These data are assimilated to demonstrate that there is no neural basis for the often-asserted high intellectual abilities of cetaceans. Despite this, the cetaceans do have volumetrically large brains. A novel hypothesis regarding the evolution of large brain size in cetaceans is put forward. It is shown that a combination of an unusually high number of glial cells and unihemispheric sleep phenomenology make the cetacean brain an efficient thermogenetic organ, which is needed to counteract heat loss to the water. It is demonstrated that water temperature is the major selection pressure driving an altered scaling of brain and body size and an increased actual brain size in cetaceans. A point in the evolutionary history of cetaceans is identified as the moment in which water temperature became a significant selection pressure in cetacean brain evolution. This occurred at the Archaeoceti - modern cetacean faunal transition. The size, structure and scaling of the cetacean brain continues to be shaped by water temperature in extant cetaceans. The alterations in cetacean brain structure, function and scaling, combined with the imperative of producing offspring that can withstand the rate of heat loss experienced in water, within the genetic confines of eutherian mammal reproductive constraints, provides an explanation for the evolution of the large size of the cetacean brain. These observations provide an alternative to the widely held belief of a correlation between brain size and intelligence in cetaceans.

Animals↗

Structural brain abnormalities among relatives of patients with schizophrenia: implications for linkage studies.

Several studies suggest that the nonschizophrenic relatives of schizophrenic patients exhibit structural brain abnormalities that may be manifestations of genes that predispose to schizophrenia. In this work, we examine the utility of such measures for linkage analyses. Subjects were 45 nonpsychotic first-degree adult relatives of schizophrenic patients and 48 normal controls. Sixty contiguous 3-mm coronal, T1-weighted 3D magnetic resonance images of the entire brain were acquired on a 1.5-T magnet. We used factor analysis to derive MRI-based phenotypes for analysis. The factor analyses produced three factors that significantly discriminated relatives from controls. We used a linear combination of the three factor scores to derive an MRI phenotype. A receiver operating characteristic (ROC) analysis of this phenotype estimated an area under the curve (AUC) statistic of 0.85. The phenotype also discriminated nonpsychotic relatives having two schizophrenic relatives from those having only one. The nonpsychotic relatives of schizophrenic patients show deviant values on MRI measures of brain structure and the distribution of these deviations among relatives and controls suggests that if these results can be replicated, an MRI-derived phenotype could be useful for genetic linkage and association analyses.

Adult↗

[Relationship between structural brain abnormalities and psychopathologic profile in patients with schizophrenia].

Aim of this study was to determine the presence of structural brain abnormalities, dynamics of psychopathology three and seven years after the first hospitalisation and correlation between them. We examined 59 first admitted schizophrenic patients. We used computed tomography to examine structural brain abnormalities and BPRS-LA to measure the psychopathology level. CT and BPRS measures were both completed 3 years after the first admission. 7 years after the first admission the psychopathology level was measured with BPRS. We observed spaces in the brain and cortical sulci widened in 55 subjects (93%). The most commonly met structural brain pathology was a widening of the IIIrd ventricle and frontal cortex pathology. Assessment of the dynamics of psychopathology shows stability of the negative syndrome and increase of the positive syndrome and general psychopathology between the third and the seventh year of the illness. Three years after first admission, structural brain pathology in the left temporal cortex and frontal cortex correlate with the overall level of psychopathology measured with BPRS-LA, but this correlation vanishes in seventh-year catch-up. Seven years after first admission subcortical cerebral pathology, especially in the subcortical frontal area correlate significantly (p < 0.01) with a lower level of positive symptoms.

Adult↗

[Use of focused ultrasound for local destruction of different brain structures].

It was demonstrated that destruction of the brain can be accomplished by different combinations of ultrasound intensity and duration of irradiation. By experimental means cavitational thresholds of brain tissues were determined and a calculation was made of increased temperature in the zone of focus in each separate regime of irradiation. The authors describe the foci of lesions where the main mechanism of destruction was only warmth, either only cavitation, either warmth and cavitation together. Irradiation of deep brain structures was not accompanied by changes of the cortical and subcortical structures, located above the focus of necrosis along the path of the ultrasound ray (light microscopy). The probability of a target hit into the given brain structure corresponded to the preciseness allowed in a stereotaxic operation.

Animals↗

Managing and analysing data from a large-scale study on Framingham Offspring relating brain structure to cognitive function.

At the Framingham Heart Study under separate research grant funding from the National Institute of Aging, NIH, we are gathering brain structure and cognitive information on the Framingham Offspring, creating one of the largest known data sets to assess changes in brain structure associated with normative ageing and cognitive decline. Subject recruitment, data collection, data management and statistical analysis require a collaborative integrated effort on the part of the Framingham project team. Here we describe this effort, as well as the various brain structure and cognitive function parameters we are now collecting. We are currently performing analyses of data collected through 2002, and we discuss the statistical issues arising relating brain structure parameters to cognitive function.

Aged↗

Interactive effects of age and hypertension on volumes of brain structures.

BACKGROUND AND PURPOSE: Advanced age and hypertension have each been associated with changes in brain morphology and cognitive function. To investigate the interaction of age and hypertension with structural brain changes and neuropsychological performance in otherwise healthy patients with essential hypertension, we compared young-old (ages 56 to 69 years) and old-old (ages 70 to 84 years) hypertensive patients (n = 27) with 20 age-matched normotensive healthy control subjects, using quantitative volumetric MRI and a battery of neuropsychological tests. METHODS: Quantitative regions of interest and segmentation analyses were applied to MRI scans of brain to measure volumes of different brain structures and of cerebrospinal fluid (CSF). Severity of white matter hyperintensities (WMHs) was qualitatively rated in the MRI scans. A battery of neuropsychological tests was administered to each subject. RESULTS: The combined hypertensive group (young-old and old-old) had smaller volumes of thalamic nuclei and larger volumes of CSF in the cerebellum and temporal lobes and showed poorer performance in memory and language tests than did the control subjects. Main effects for age were significant in multiple brain regions of interest. The old-old hypertensive patients and age-matched control subjects demonstrated volume reductions in brain structures and increases in ventricular and peripheral CSF volumes compared with the younger subjects. There was a significant group x age-group interaction in temporal and occipital CSF, not related to WMH, with the old-old hypertensive patients having significantly larger CSF volumes in these regions than the young-old hypertensives and both healthy control groups. CONCLUSIONS: Hypertension exacerbates the morphological changes accompanying advanced age. Temporal and occipital regions appear most vulnerable to brain atrophy due to the interactive effects of age and hypertension.

Aged↗

Perinatal risk factors altering regional brain structure in the preterm infant.

Neuroanatomical structure appears to be altered in preterm infants, but there has been little insight into the major perinatal risk factors associated with regional cerebral structural alterations. MR images were taken to quantitatively compare regional brain tissue volumes between term and preterm infants and to investigate associations between perinatal risk factors and regional neuroanatomical alterations in a large cohort of preterm infants. In a large prospective longitudinal cohort study of 202 preterm and 36 term infants, MR scans at term equivalent were undertaken for volumetric estimates of cortical and deep nuclear grey matter, unmyelinated and myelinated white matter (WM) and CSF within 8 parcellated regions for each hemisphere of the brain. Perinatal correlates analysed in relation to regional brain structure included gender, gestational age, intrauterine growth restriction, bronchopulmonary dysplasia, white matter injury (WMI) and intraventricular haemorrhage. Results revealed region-specific reductions in brain volumes in preterm infants compared with term controls in the parieto-occipital (preterm mean difference: -8.1%; 95% CI = -13.8--2.3%), sensorimotor (-11.6%; -18.2--5.0%), orbitofrontal (-30.6%; -49.8--11.3%) and premotor (-7.6%; -14.2--0.9%) regions. Within the sensorimotor and orbitofrontal regions cortical grey matter and unmyelinated WM were most clearly reduced in preterm infants, whereas deep nuclear grey matter was reduced mainly within the parieto-occipital and subgenual regions. CSF (ventricular and extracerebral) was doubled in volume within the superior regions in preterm infants compared with term controls. Cerebral WMI and intrauterine growth restriction were both associated with a more posterior reduction in brain volumes, whereas bronchopulmonary dysplasia was associated with a more global reduction across all regions. In contrast degree of immaturity was not related to regional brain structure among preterm infants. In summary, preterm birth is associated with regional cerebral tissue reductions, with the adverse pattern varying between risk factors. These findings add to our understanding of the potential pathways leading to altered brain structure and outcome in the preterm infant.

Brain↗

Estrogen replacement therapy is associated with less progression of subclinical structural brain disease in normal elderly women: a pilot study.

BACKGROUND: Cortical atrophy, central atrophy, deep white-matter hyperintensities, and periventricular hyperintensities are reported in normal aging. OBJECTIVES: We examined the effects of estrogen replacement therapy (ERT) on these forms of 'subclinical structural brain disease' (SSBD) in normal, postmenopausal women in a pilot, naturalistic, longitudinal study of 15 subjects. METHODS: Two assessments were performed at least two years apart, with volumetric magnetic resonance imaging (MRI) and neuropsychological testing. RESULTS: Women receiving open-label ERT showed significantly less progression of SSBD than those who did not. CONCLUSIONS: The association between reduced SSBD progression and ERT suggests this intervention could help preserve normal brain structure in healthy elderly women.

Aged↗