Long-term effects of sequential cortical infarcts on scar size, brain volume and cognitive function

Focal ischemia induces long-term pathophysiological consequences in widespread brain areas. Here we analyzed long-term effects of sequential cortical lesions on brain volume and cognitive function. Rats received either single photothrombotic lesions in the forelimb sensorimotor cortex (SL) or two lesions in sequence either immediately (DL0), 2 days (DL2), 7 days (DL7), or 10 days (DL10) after the first surgery in the homotopic contralateral area. Infarct and global brain volume were measured 7 days (SL and DL2 groups) and one month (all groups) after the last period of ischemia. In the weeks following a stroke, the single lesion shrank considerably. This shrinkage was accentuated by a further lesion received either earlier or later. Thirty-one days after obtaining the second lesion, the lesion scars on both sides had a mean volume of 5.8 +/- 2.3 mm3 in DL2 as compared to 8.5 +/- 3.5 mm3 in SL-animals. In addition, there was a super-additive loss of residual brain volume by 2.2-8.0% in each hemisphere in animals with sequential lesions. In the watermaze, this loss of brain volume corresponded to a slight but significant impairment in performance. The present study revealed a complex interaction of lesions in animals with sequential strokes associated with global reduction of brain volume and cognitive impairment indicating degenerative processes beyond the lesions itself.     

Visual reaction time as a function of locus,area, and complexity of stimulus

Summary Reaction time (RT) of normal subjects to square-wave gratings of two different frequencies were related to locus of presentation, area, and stimulus complexity. Each frequency was presented to either side of the horizontal meridian (half size stimulus) or both sides simultaneously (full size stimulus). The two different frequencies were also flashed simultaneously to both hemifields (compound stimulus). Stimulus position affected RT with the 1 c/deg stimulus, RT being faster for the lower hemifield. With presentation on both sides of the horizontal meridian simultaneously or of the two spatial frequencies, the resulting RT was equal to that of the faster component. Implications of the results for the functional organization of the visual system are discussed.     

An evaluation of dipole reconstruction accuracy with spherical and realistic head models in MEG.

MEG forward problem has been solved for about 2000 dipoles placed on the brain surface using a very fine 3-layer realistic model of the head and the boundary element method (BEM). For each dipole, spherical models, one-layer realistic BEM models and coarser 3-layer realistic BEM models, were used to reconstruct the dipole. It was found that the localization bias induced by using a spherical model of the head increased from 2.5 mm in the upper part of the head to 12 mm in the lower part, on average. It was also found that, for the same computing time, a 3-layer model of the head gave on average 2 mm better localization errors than a one-layer model of the head. Orientation errors of less than 20 degrees could only be retrieved with a 3-layer realistic model. Localization and orientation errors highly depended on the dipole position in the brain.     

Variability of the paracingulate sulcus and morphometry of the medial frontal cortex: associations with cortical thickness, surface area, volume, and sulcal depth

The structural and functional consequences of interindividual variations in cortical morphology are poorly understood. In this study, we examined the relationship between one well-characterized variation of the medial frontal lobes, variability of the paracingulate sulcus (PCS), and grey matter volume, cortical thickness, surface area, and sulcal depth of the adjacent anterior cingulate cortex (ACC) and paracingulate cortex (PaC). Seventy-seven healthy individuals were assigned to one of four groups depending on PCS incidence in both hemispheres: left-present, right-absent; left-absent, right-present; both absent; or both present. Comparing these groups on each measure yielded four primary findings: (1) The presence of a PCS was associated with increased PaC and decreased ACC grey matter volume in the hemisphere in which it was apparent, with an almost identical pattern being observed for surface area; (2) there was a more complex relationship between PCS variability and regional thickness, such that a PCS in the left hemisphere was associated with increased left PaC and right ACC thickness, with no comparable effects being observed for the presence of a right PCS; (3) the depths of all major left hemisphere sulci in the region were strongly positively correlated, whereas no such associations were apparent in the right hemisphere; and (4) a leftward asymmetry in PaC thickness was specifically associated with better performance on a test of spatial working memory ability. These results provide evidence for a complex interhemispheric relationship between sulcal variability and cortical morphometry, and indicate that such relationships may be important for understanding individual differences in cognitive abilities.     

The effect of age,diagnosis, and their interaction on vertex-based measures of cortical thickness and surface area in autism spectrum disorder

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that is accompanied by an atypical development of brain maturation. So far, brain development has mainly been studied during early childhood in ASD, and using measures of total or lobular brain volume. However, cortical volumetric measures are a product of two distinct biological neuroanatomical features, cortical thickness, and surface area, which most likely also have different neurodevelopmental trajectories in ASD. Here, we therefore examined age-related differences in cortical thickness and surface area in a cross-sectional sample of 77 male individuals with ASD ranging from 7 to 25 years of age, and 77 male neurotypical controls matched for age and FSIQ. Surface-based measures were analyzed using a general linear model (GLM) including linear, quadratic, and cubic age terms, as well as their interactions with the main effect of group. When controlling for the effects of age, individuals with ASD had spatially distributed reductions in cortical thickness relative to controls, particularly in fronto-temporal regions, and also showed significantly reduced surface area in the prefrontal cortex and the anterior temporal lobe. We also observed significant group × age interactions for both measures. However, while cortical thickness was best predicted by a quadratic age term, the neurodevelopmental trajectory for measures of surface area was mostly linear. Our findings suggest that ASD is accompanied by age-related and region-specific reductions in cortical thickness and surface area during childhood and early adulthood. Thus, differences in the neurodevelopmental trajectory of maturation for both measures need to be taken into account when interpreting between-group differences overall.     

Effects of sex and age on regional prefrontal brain volume in two human cohorts

This study examined interactive effects of sex and age on prefrontal brain anatomy in humans. It specifically targeted ranges of the adult life span and regions of cortex that previously showed male-female differences. Participants were 68 healthy human males and females aged 20-72 years. Data collection and analysis were conducted in parallel across two cohorts (laboratories) to investigate reproducibility of effects in relation to sex and age. Volumes for four regional prefrontal subfields per hemisphere were obtained from high-resolution MRI. Regional sex by age interactions were replicated across cohorts. In men, age effects were greatest in medial prefrontal volume, with decreases in dorsal medial and orbital medial regions. In women, age-related changes in medial prefrontal regions were limited to the dorsal volume, with additional decreases observed in lateral subfields. Cohort and Cohort x Age effects in total brain and total prefrontal volume were linked to a combination of methodological and sampling-related factors. Findings indicated that neuroanatomical changes throughout adulthood unfold along different time scales in men and women. Results also showed that sex differences in ageing localized to medial prefrontal regions were particularly robust to variation across cohorts.     

Comparison of overall brain volume and midsagittal corpus callosum surface area as obtained from NMR scans and direct anatomical measures: a within-subject study on autopsy brains

Formalin fixed brains obtained from autopsy were studied by magnetic resonance imaging, using FLASH and MPR sequences. The overall volume and the midsagittal surface area of the corpus callosum (cc) of these brains were also directly measured by water displacement for overall volume determination and morphometry for cc surface area measures, allowing comparisons of these measures in a within-subject design. Thin NMR sections (1 mm thickness for FLASH and 1.25 mm for MPR) yielded overall brain volume estimates that did not differ significantly from direct volume estimations but thicker (5 mm) sections led to a significant overestimation of brain volume for NMR measures relative to direct displacement measures. There was no overall effect of type of NMR measure: FLASH and MPR scans did not yield significantly different values for overall brain volume or callosal surface area. Direct and NMR measures of the corpus callosum surface at midsagittal level did not yield significantly different estimates.     

Maths performance as a function of sex,laterality, and age of pubertal onset

Sex differences in math/spatial performance demand explanations. Within the biological view, the complexity and number of variables make the explanation difficult at best. Laterality and age of pubertal onset have been investigated prominently in this context but rarely considered as interactions in the same study. Some 468 college subjects with SAT MATH (SAT M) scores were divided into 12 groups defined by sex, laterality, and age (early, middle, and late) of pubertal onset. Significant main effects for sex and age of onset emerged, as did an interaction between lateral preference and pubertal onset. Generally males outperformed females. The combination of maleness, sinistrality, and early maturation was associated with high SAT M scores. Sinistrality and late maturation among females predicted very poor math performance.     

Maths performance as a function of sex, laterality, and age of pubertal onset

Sex differences in math/spatial performance demand explanations. Within the biological view, the complexity and number of variables make the explanation difficult at best. Laterality and age of pubertal onset have been investigated prominently in this context but rarely considered as interactions in the same study. Some 468 college subjects with SAT MATH (SAT M) scores were divided into 12 groups defined by sex, laterality, and age (early, middle, and late) of pubertal onset. Significant main effects for sex and age of onset emerged, as did an interaction between lateral preference and pubertal onset. Generally males outperformed females. The combination of maleness, sinistrality, and early maturation was associated with high SAT M scores. Sinistrality and late maturation among females predicted very poor math performance.     

Cognitive function, P3a/P3b brain potentials, and cortical thickness in aging

The purpose of the study was to assess the relationship between the P3a/P3b brain potentials, cortical thickness, and cognitive function in aging. Thirty-five younger and 37 older healthy participants completed a visual three-stimuli oddball ERP (event-related potential)-paradigm, a battery of neuropsychological tests, and MRI scans. Groups with short vs. long latency, and low vs. high amplitude, were compared on a point by point basis across the entire cortical mantle. In the young, thickness was only weakly related to P3. In the elderly, P3a amplitude effects were found in parietal areas, the temporoparietal junction, and parts of the posterior cingulate cortex. P3b latency was especially related to cortical thickness in large frontal regions. Path models with the whole sample pooled together were constructed, demonstrating that cortical thickness in the temporoparietal cortex predicted P3a amplitude, which in turn predicted executive function, and that thickness in orbitofrontal cortex predicted P3b latency, which in turn predicted fluid function. When age was included in the model, the relationship between P3 and cognitive function vanished, while the relationship between regional cortical thickness and P3 remained. It is concluded that thickness in specific cortical areas correlates with scalp recorded P3a/P3b in elderly, and that these relationships differentially mediate higher cognitive function.     

Seizure length in electroconvulsive therapy as a function of age, sex, and treatment number

Most electroconvulsive therapy (ECT) research indicates that seizure length does not correlate with clinical efficacy. However, it is common in practice for clinicians to undertake measures to prolong seizures if the duration seems to be too short, although there is no universally agreed upon minimum seizure duration for ECT. We felt it would be informative for the ECT field to report mean seizure durations over the course of treatments based on age and sex in a very large cohort to provide norms for reference. We studied 519 patients' courses of ECT and recorded treatment number, sex, and age along with motor and electroencephalogram seizure duration. We found that women have longer seizures, but only at the first treatment session. There is a strong inverse correlation between age and seizure length. The biggest drop in seizure duration along a course of treatments occurs between the first and second treatments; beyond that, seizure duration remains relatively constant.     

Visual reaction time as a function of locus, area, and complexity of stimulus.

Reaction time (RT) of normal subjects to square-wave gratings of two different frequencies were related to locus of presentation, area, and stimulus complexity. Each frequency was presented to either side of the horizontal meridian (half size stimulus) or both sides stimultaneously (full size stimulus). The two different frequencies were also flashed simultaneously to both hemifields (compound stimulus). Stimulus position affected RT with the 1 c/deg stimulus, RT being faster for the lower hemifield. With presentation on both sides of the horizontal median simultaneously or of the two spatial frequencies, the resulting RT was equal to that of the faster component. Implications of the results for the functional organization of the visual system are discussed.     

Regional protein levels of cytosolic phospholipase A2 and cyclooxygenase-2 in Rhesus monkey brain as a function of age

Limited evidence suggests that brain cytosolic phospholipase A(2) (cPLA(2)), which selectively releases arachidonic acid (AA) from membrane phospholipids, and cyclooxygenase-2 (COX-2), the rate-limiting enzyme for AA metabolism to prostanoids, change as a function of normal aging. In this study, we examined the protein levels of cPLA(2) and COX-2 enzymes in hippocampus, frontal pole and cerebellum from young (2-5 years old), middle-aged (8-11 years old) and old (23 years old) male and female Rhesus monkeys. In the cerebellum, cPLA(2) protein level was higher in the young brain as compared to levels seen at both middle-aged and old. Similarly, in the frontal pole, the young brain showed a higher level of COX-2 protein as compared to the levels seen at both older ages. For both, once an animal reached 8-11 years of age the levels appeared to remain relatively constant over the next decade. Immunohistochemistry of COX-2 protein within the brain demonstrated no significant change in the localization to neurons within the frontal pole. Qualitatively, a greater number of neurons were positively stained for COX-2 in the young brain than in the aged brain. Based on the previous reports of localization of cPLA(2) and COX-2 at post-synaptic sites in neurons results from the current study suggest that the elevated protein levels of the two enzymes seen in the younger brain is related to the greater potential for synaptic plasticity across multiple neurons as a function of age and that cPLA(2) and COX-2 may be considered as post-synaptic markers.     

Brain development during adolescence: A mixed‐longitudinal investigation of cortical thickness,surface area,and volume

What we know about cortical development during adolescence largely stems from analyses of cross‐sectional or cohort‐sequential samples, with few studies investigating brain development using a longitudinal design. Further, cortical volume is a product of two evolutionarily and genetically distinct features of the cortex ‐ thickness and surface area, and few studies have investigated development of these three characteristics within the same sample. The current study examined maturation of cortical thickness, surface area and volume during adolescence, as well as sex differences in development, using a mixed longitudinal design. 192 MRI scans were obtained from 90 healthy (i.e., free from lifetime psychopathology) adolescents (11‐20 years) at three time points (with different MRI scanners used at time 1 compared to 2 and 3). Developmental trajectories were estimated using linear mixed models. Non‐linear increases were present across most of the cortex for surface area. In comparison, thickness and volume were both characterised by a combination of non‐linear decreasing and increasing trajectories. While sex differences in volume and surface area were observed across time, no differences in thickness were identified. Furthermore, few regions exhibited sex differences in the cortical development. Our findings clearly illustrate that volume is a product of surface area and thickness, with each exhibiting differential patterns of development during adolescence, particularly in regions known to contribute to the development of social‐cognition and behavioral regulation. These findings suggest that thickness and surface area may be driven by different underlying mechanisms, with each measure potentially providing independent information about brain development. Hum Brain Mapp 37:2027–2038, 2016. © 2016 Wiley Periodicals, Inc.     

Amplified somatosensory and visual cortical projections to a core auditory area,the anterior auditory field,following early‐ and late‐onset deafness

Cross‐modal reorganization following the loss of input from a sensory modality can recruit sensory‐deprived cortical areas to process information from the remaining senses. Specifically, in early‐deaf cats, the anterior auditory field (AAF) is unresponsive to auditory stimuli but can be activated by somatosensory and visual stimuli. Similarly, AAF neurons respond to tactile input in adult‐deafened animals. To examine anatomical changes that may underlie this functional adaptation following early or late deafness, afferent projections to AAF were examined in hearing cats, and cats with early‐ or adult‐onset deafness. Unilateral deposits of biotinylated dextran amine were made in AAF to retrogradely label cortical and thalamic afferents to AAF. In early‐deaf cats, ipsilateral neuronal labeling in visual and somatosensory cortices increased by 329% and 101%, respectively. The largest increases arose from the anterior ectosylvian visual area and the anterolateral lateral suprasylvian visual area, as well as somatosensory areas S2 and S4. Consequently, labeling in auditory areas was reduced by 36%. The age of deafness onset appeared to influence afferent connectivity, with less marked differences observed in late‐deaf cats. Profound changes to visual and somatosensory afferent connectivity following deafness may reflect corticocortical rewiring affording acoustically deprived AAF with cross‐modal functionality. J. Comp. Neurol. 523:1925–1947, 2015 © 2015 Wiley Periodicals, Inc.     

The human brain in 1700 pieces: design and development of a three-dimensional, interactive and reference atlas

As the human brain is the most complex living organ, constructing its detailed model with exploration capabilities in a form of an atlas is a challenge. Our overall goal is to construct an advanced, detailed, parcellated, labeled, accurate, interactive, three-dimensional (3D), and scalable whole human brain atlas of structure, vasculature, tracts and systems. The objectives of this work are three-fold; to present: (1) method of atlas design and development including design principles, accuracy requirements, atlas content, architecture, functionality, user interface, and customized tools; (2) creation of an atlas of structure and systems including its modeling method and validation; and (3) integration of this atlas with the cerebrovasculature and tracts created earlier.The atlas is created from multiple in vivo 3/7 T scans. Its design based on “pyramidal principle” enables scalability while preserving design principles and exploits interaction paradigm “from blocks to brain”. The atlas contains (1) navigator with modules for system/object/object state management, interaction, user interfacing, and rendering; and (2) brain model with cerebrum, cerebellum, brainstem, spinal cord, white matter, deep structures, systems, ventricles, arteries, veins, sinuses, and tracts. The brain model is parcellated, labeled, consistent, realistic, of high resolution, polygonal/volumetric, dissectible, extendable, and deformable. It has over 1700 3D components. The atlas has sub-voxel accuracy of 0.1 mm and the smallest vessels of 80 μm. Brain exploration includes dynamic scene composition, manipulation-independent 3D labeling, interaction combined with animation, meta-labeling, and quantification.This atlas is useful in education, research, and clinical applications. It can potentially be foundation for a multi-level molecular-cellular-anatomical-physiological-behavioral platform.     

Stimulant-mediated c-fos induction in striatum as a function of age, sex, and prenatal cocaine exposure

Induction of the immediate-early gene c-fos by the stimulants cocaine and amphetamine (AMPH) was analyzed by Fos immunocytochemistry at different ages in the brains of prenatally cocaine-treated and control rats. Cocaine and AMPH induced c-fos in patches of striatal neurons during the first postnatal week, and thereafter produced a progressively more homogeneous pattern that was more dense medially. Quantification of Fos-immunoreactive cells in older rats revealed differences related to sex and prenatal cocaine treatment. Both cocaine and AMPH produced dose-dependent increases in the number of Fos-immunoreactive cells in striatum. Prenatal cocaine exposure resulted in increased Fos in males in response to AMPH (2 mg/kg) at P18 and cocaine (10 mg/kg) at 1–2 months. In females, prenatal cocaine treatment resulted in a reduced response to cocaine at 1–2 months. Increased c-fos induction was observed in control females compared to control males in response to low doses of stimulants; no such sex difference was observed in prenatally cocaine-treated rats. The dopamine D1 antagonist SCH23390 blocked cocaine-mediated c-fos induction in all groups. The NMDA antagonist MK-801 blocked cocaine-mediated c-fos induction in the medial striatum. In females only, MK-801 pretreatment resulted in a dramatic increase in the number of Fos-immunoreactive cells in lateral striatum. These findings indicate differences in the neural basis of c-fos induction in males and females, and changes in stimulant-mediated c-fos induction resulting from prenatal cocaine exposure.     

X-Linked adrenoleukodystrophy: overview and prognosis as a function of age and brain magnetic resonance imaging abnormality. A study involving 372 patients

The phenotypic expression of X-linked adrenoleukodystrophy (X-ALD) ranges from the rapidly progressive childhood cerebral form to the milder adrenomyeloneuropathy (AMN) in adults. It is not possible to predict phenotype by mutation analysis or biochemical assays. This study reports on 372 patients ranging in age from less than 3 years to adulthood, who have been followed at the Kennedy Krieger Institute. With the aim of determining whether a method could be developed to predict clinical course by analysis of data available at time of first contact, the patients were subdivided into 18 subgroups on the basis of age and the extent of brain magnetic resonance (MRI) abnormality utilizing the MRI scoring system devised by Loes et al. Scores to grade degree of neurologic and neuropsychologic impairment were also developed. There was strong correlation between MRI and the neurology and neuropsychology scores at baseline. Information based exclusively on age and MRI score at time of first contact was highly predictive of future clinical course and should aid the evaluation of the effects of bone marrow transplantation and the selection of patients for this procedure, as well as the evaluation of other therapies that may be developed in the future.     

Effects of culture,sex, and age on the distribution of handedness: An evaluation of the sensitivity of three measures of handedness

The present study examined the effects of culture, age, and sex on three measures of handedness: writing hand, Annett's primary handedness items, and a measure based on hand preference for 11 activities. Using data from a large international study, the relationship between the culture in which participants learned to write (as defined by Hofstede's cultural dimensions) and adult handedness was examined. Participants who learned to write in formal cultures were less likely to be classified as left‐handed than those who learned in less formal cultures. Older participants and those who learned to write in formal cultures were more likely to be classified as left‐handed by the Annett and 11 item measures than by the writing hand classification. Across measures females were less likely to be classified as left‐handed than males. Handedness for writing was found to be more sensitive to cultural influences than the other measures. These results suggest that some measures of handedness may be more sensitive to specific handedness aetiologies than others.