Showing papers in "Human Brain Mapping in 2010"

The role of puberty in the developing adolescent brain.

Abstract: Adolescence refers to the period of physical and psychological development between childhood and adulthood. The beginning of adolescence is loosely anchored to the onset of puberty, which brings dramatic alterations in hormone levels and a number of consequent physical changes. Puberty onset is also associated with profound changes in drives, motivations, psychology, and social life; these changes continue throughout adolescence. There is an increasing number of neuroimaging studies looking at the development of the brain, both structurally and functionally, during adolescence. Almost all of these studies have defined development by chronological age, which shows a strong-but not unitary-correlation with pubertal stage. Very few neuroimaging studies have associated brain development with pubertal stage, and yet there is tentative evidence to suggest that puberty might play an important role in some aspects of brain and cognitive development. In this paper we describe this research, and we suggest that, in the future, developmental neuroimaging studies of adolescence should consider the role of puberty.

Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder

Abstract: In recent years, a change in perspective in etiological models of attention deficit hyperactivity disorder (ADHD) has occurred in concordance with emerging concepts in other neuropsychiatric disorders such as schizophrenia and autism. These models shift the focus of the assumed pathology from regional brain abnormalities to dysfunction in distributed network organization. In the current contribution, we report findings from functional connectivity studies during resting and task states, as well as from studies on structural connectivity using diffusion tensor imaging, in subjects with ADHD. Although major methodological limitations in analyzing connectivity measures derived from noninvasive in vivo neuroimaging still exist, there is convergent evidence for white matter pathology and disrupted anatomical connectivity in ADHD. In addition, dysfunctional connectivity during rest and during cognitive tasks has been demonstrated. However, the causality between disturbed white matter architecture and cortical dysfunction remains to be evaluated. Both genetic and environmental factors might contribute to disruptions in interactions between different brain regions. Stimulant medication not only modulates regionally specific activation strength but also normalizes dysfunctional connectivity, pointing to a predominant network dysfunction in ADHD. By combining a longitudinal approach with a systems perspective in ADHD in the future, it might be possible to identify at which stage during development disruptions in neural networks emerge and to delineate possible new endophenotypes of ADHD.

Neural representation of abstract and concrete concepts: a meta-analysis of neuroimaging studies.

Abstract: A number of studies have investigated differences in neural correlates of abstract and concrete concepts with disagreement across results. A quantitative, coordinate-based meta-analysis combined data from 303 participants across 19 functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) studies to identify the differences in neural representation of abstract and concrete concepts. Studies that reported peak activations in standard space in contrast of abstract > concrete or concrete > abstract concepts at a whole brain level in healthy adults were included in this meta-analysis. Multilevel kernel density analysis (MKDA) was performed to identify the proportion of activated contrasts weighted by sample size and analysis type (fixed or random effects). Meta-analysis results indicated consistent and meaningful differences in neural representation for abstract and concrete concepts. Abstract concepts elicit greater activity in the inferior frontal gyrus and middle temporal gyrus compared to concrete concepts, while concrete concepts elicit greater activity in the posterior cingulate, precuneus, fusiform gyrus, and parahippocampal gyrus compared to abstract concepts. These results suggest greater engagement of the verbal system for processing of abstract concepts and greater engagement of the perceptual system for processing of concrete concepts, likely via mental imagery.

Hippocampal Atrophy Patterns in Mild Cognitive Impairment and Alzheimer’s Disease

Abstract: Background: Histopathological studies and animal models suggest that hippocampal subfields may be differently affected by aging, Alzheimer's disease (AD), and other diseases. High-resolution images at 4 Tesla depict details of the internal structure of the hippocampus allowing for in vivo volumetry of different subfields. The aims of this study were as follows: (1) to determine patterns of volume loss in hippocampal subfields in normal aging, AD, and amnestic mild cognitive impairment (MCI). (2) To determine if measurements of hippocampal subfields provide advantages over total hippocampal volume for differentiation between groups. Methods: Ninety-one subjects (53 controls (mean age: 69.3 ± 7.3), 20 MCI (mean age: 73.6 ± 7.1), and 18 AD (mean age: 69.1 ± 9.5) were studied with a high-resolution T2 weighted imaging sequence aimed at the hippocampus. Entorhinal cortex (ERC), subiculum, CA1, CA1-CA2 transition zone (CA1-2), CA3 & dentate gyrus (CA3&DG) were manually marked in the anterior third of the hippocampal body. Hippocampal volume was obtained from the Freesurfer and manually edited. Results: Compared to controls, AD had smaller volumes of ERC, subiculum, CA1, CA1-2, and total hippocampal volumes. MCI had smaller CA1-2 volumes. Discriminant analysis and power analysis showed that CA1-2 was superior to total hippocampal volume for distinction between controls and MCI. Conclusion: The patterns of subfield atrophy in AD and MCI were consistent with patterns of neuronal cell loss/reduced synaptic density described by histopathology. These preliminary findings suggest that hippocampal subfield volumetry might be a better measure for diagnosis of early AD and for detection of other disease effects than measurement of total hippocampus. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.

Noninvasive optical measures of CBV, StO2, CBF index, and rCMRO2 in human premature neonates' brains in the first six weeks of life

Abstract: The article to which this erratum refers was published in Hum Brain Mapp 2010 (Vol. 31), DOI: 10.1002/hbm.20868.

Scan-rescan reliability of subcortical brain volumes derived from automated segmentation.

Abstract: Large-scale longitudinal studies of regional brain volume require reliable quantification using automated segmentation and labeling. However, repeated MR scanning of the same subject, even if using the same scanner and acquisition parameters, does not result in identical images due to small changes in image orientation, changes in prescan parameters, and magnetic field instability. These differences may lead to appreciable changes in estimates of volume for different structures. This study examined scan-rescan reliability of automated segmentation algorithms for measuring several subcortical regions, using both within-day and across-day comparison sessions in a group of 23 normal participants. We found that the reliability of volume measures including percent volume difference, percent volume overlap (Dice's coefficient), and intraclass correlation coefficient (ICC), varied substantially across brain regions. Low reliability was observed in some structures such as the amygdala (ICC = 0.6), with higher reliability (ICC = 0.9) for other structures such as the thalamus and caudate. Patterns of reliability across regions were similar for automated segmentation with FSL/FIRST and FreeSurfer (longitudinal stream). Reliability was associated with the volume of the structure, the ratio of volume to surface area for the structure, the magnitude of the interscan interval, and the method of segmentation. Sample size estimates for detecting changes in brain volume for a range of likely effect sizes also differed by region. Thus, longitudinal research requires a careful analysis of sample size and choice of segmentation method combined with a consideration of the brain structure(s) of interest and the magnitude of the anticipated effects.

Event-related potential and functional MRI measures of face-selectivity are highly correlated: a simultaneous ERP-fMRI investigation.

Abstract: A face-selective neural signal is reliably found in humans with functional MRI and event-related potential (ERP) measures, which provide complementary information about the spatial and temporal properties of the neural response. However, because most neuroimaging studies so far have studied ERP and fMRI face-selective markers separately, the relationship between them is still unknown. Here we simultaneously recorded fMRI and ERP responses to faces and chairs to examine the correlations across subjects between the magnitudes of fMRI and ERP face-selectivity measures. Findings show that the face-selective responses in the temporal lobe (i.e., fusiform gyrus--FFA) and superior temporal sulcus (fSTS), but not the face-selective response in the occipital cortex (OFA), were highly correlated with the face-selective N170 component. In contrast, the OFA was correlated with earlier ERPs at about 110 ms after stimulus-onset. Importantly, these correlations reveal a temporal dissociation between the face-selective area in the occipital lobe and face-selective areas in the temporal lobe. Despite the very different time-scale of the fMRI and EEG signals, our data show that a correlation analysis across subjects may be informative with respect to the latency in which different brain regions process information.

Layer-specific BOLD activation in human V1.

Abstract: The neocortex is known to have a distinct laminar structure which has previously been probed in animals using high-resolution fMRI. Detection of layer-specific activation in humans has however to date proven elusive. In this study we demonstrate for the first time such layer-specific activation, specifically at a depth corresponding to layer IV of human primary visual cortex (V1). We used a gradient-echo (GE) sequence at 3T with an isotropic resolution of 0.75 mm, in which a stria at the depth of layer IV was visible in the averaged time series, and could be used as an anatomical landmark. Upon visual stimulation (7.5 Hz flickering checkerboard) the signal increase of 3% in layer IV was significantly higher than in the neighboring laminae. The width of this activation peak was 0.8-1 mm. Based on this result and known laminar organization of the intracortical vasculature we conclude that in the direction perpendicular to the cortical surface the intrinsic spatial resolution of the GE-BOLD fMRI signal is in the submillimetre range. Human laminar fMRI is a significant development which may improve our understanding of intracortical activation patterns and of the way in which different cortical regions interact.

Optimal transcranial magnetic stimulation coil placement for targeting the dorsolateral prefrontal cortex using novel magnetic resonance image-guided neuronavigation

Abstract: The dorsolateral prefrontal cortex (DLPFC) has been implicated in the pathophysiology of several psychiatric illnesses including major depressive disorder and schizophrenia. In this regard, the DLPFC has been targeted in repetitive transcranial magnetic stimulation (rTMS) studies as a form of treatment to those patients who are resistant to medications. The '5-cm method' and the '10-20 method' for positioning the transcranial magnetic stimulation (TMS) coil over DLPFC have been scrutinised due to poor targeting accuracies attributed to inter-subject variability. We evaluated the accuracy of such methods to localise the DLPFC on the scalp in 15 healthy subjects and compared them with our novel neuronavigational method, which first estimates the DLPFC position in the cortex based on a standard template and then determines the most appropriate position on the scalp in which to place the TMS coil. Our neuronavigational method yielded a scalp position for the left DLPFC between electrodes F3 and F5 in standard space and was closest to electrode F5 in individual space. Further, we found that there was significantly less inter-subject variability using our neuronavigational method for localising the DLPFC on the scalp compared with the '5-cm method' and the '10-20 method'. Our findings also suggest that the '10-20 method' is superior to the '5-cm method' in reducing inter-subject variability and that electrode F5 should be the stimulation location of choice when MRI co-registration is not available.

FMRI Study of Mesial Temporal Lobe Epilepsy Using Amplitude of Low-Frequency Fluctuation Analysis

Abstract: Various functional imaging tools have been used to detect epileptic activity in the neural network underlying mesial temporal lobe epilepsy (mTLE). In the present fMRI study, a data-driven approach was employed to map interictal epileptic activity in mTLE patients by measuring the amplitude of low-frequency fluctuation (ALFF) of the blood oxygen level-dependent (BOLD) signal. Twenty-four left mTLE patients and 26 right mTLE patients were investigated by comparing with 25 healthy subjects. In the patients, the regions showing increased ALFF were consistently distributed in the mesial temporal lobe, thalamus, and a few of other cortical and subcortical structures composing a mesial temporal epilepsy network proposed previously, while the regions showing decreased ALFF were mostly located in the areas of so-called default-mode network. Data of simultaneous EEG-fMRI from a portion of the patients suggested that the increases in ALFF might be associated with the interictal epileptic activity. Individual analyses based on statistic parametric mapping revealed a moderate sensitivity and a fairly high specificity for the lateralization of unilateral mTLE. We conclude that the ALFF analysis may provide a useful tool in fMRI study of epilepsy.

Childhood psychiatric disorders as anomalies in neurodevelopmental trajectories.

Abstract: Childhood psychiatric disorders are rarely static; rather they change over time and longitudinal studies are ideally suited to capture such dynamic processes. Using longitudinal data, insights can be gained into the nature of the perturbation away from the trajectory of typical development in childhood disorders. Thus, some disorders may reflect a delay in neurodevelopmental trajectories. Our studies in children with attention-deficit/hyperactivity disorder (ADHD) suggest that cortical development is delayed with a rightward shift along the age axis in cortical trajectories, most prominent in prefrontal cortical regions. Other disorders may be characterized by differences in the velocity of trajectories: the basic shape of neurodevelopmental curves remains intact, but with disrupted tempo. Thus, childhood onset schizophrenia is associated with a marked increase during adolescence in the velocity of loss of cerebral gray matter. By contrast, in childhood autism there is an early acceleration of brain growth, which overshoots typical dimensions leading to transient cerebral enlargement. Finally, there may be more profound deviations from typical neurodevelopment, with a complete "derailing" of brain growth and a loss of the features which characterize typical brain development. An example is the almost complete silencing of white matter growth during adolescence of patients with childhood onset schizophrenia. Adopting a longitudinal perspective also readily lends itself to the understanding of the neural bases of differential clinical outcomes. Again taking ADHD as an example, we found that remission is associated with convergence to the template of typical development, whereas persistence is accompanied by progressive divergence away from typical trajectories.

Emotional Imagery: Assessing Pleasure and Arousal in the Brain's Reward Circuitry

Abstract: Research on emotional perception and learning indicates appetitive cues engage nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), whereas amygdala activity is modulated by the emotional intensity of appetitive and aversive cues. This study sought to determine patterns of functional activation and connectivity among these regions during narrative emotional imagery. Using event-related fMRI, we investigate activation of these structures when participants vividly imagine pleasant, neutral, and unpleasant scenes. Results indicate that pleasant imagery selectively activates NAc and mPFC, whereas amygdala activation was enhanced during both pleasant and unpleasant imagery. NAc and mPFC activity were each correlated with the rated pleasure of the imagined scenes, while amygdala activity was correlated with rated emotional arousal. Functional connectivity of NAc and mPFC was evident throughout imagery, regardless of hedonic content, while correlated activation of the amygdala with NAc and mPFC was specific to imagining pleasant scenes. These findings provide strong evidence that pleasurable text-driven imagery engages a core appetitive circuit, including NAc, mPFC, and the amygdala.

Disorder‐specific inferior prefrontal hypofunction in boys with pure attention‐deficit/hyperactivity disorder compared to boys with pure conduct disorder during cognitive flexibility

Abstract: Background. Problems with cognitive flexibility have been observed in patients with attention deficit hyperactivity disorder (ADHD) and in patients with conduct disorder (CD), characterized by the violation of societal rules and the rights of others. Functional magnetic resonance imaging (fMRI) of cognitive switching, however, has only been investigated in patients with ADHD, including comorbidity with CD, finding frontostriatal and temporoparietal underactivation. This study investigates disorder-specific functional abnormalities during cognitive flexibility between medication-naive children and adolescents with noncomorbid CD and those with noncomorbid ADHD compared to healthy controls. Methods. Event-related fMRI was used to compare brain activation of 14 boys with noncomorbid, childhood-onset CD, 14 boys with noncomorbid ADHD, and 20 healthy comparison boys during a visual–spatial Switch task. Results. Behaviorally, children with ADHD compared to children with CD had significantly slower reaction times to switch compared to repeat trials. The fMRI comparison showed that the patients with ADHD compared to both controls and patients with CD showed underactivation in right and left inferior prefrontal cortex. No disorder-specific brain underactivation was observed in patients with CD. Only when compared with controls alone, the disruptive behavior group showed reduced activation in bilateral temporoparietal and occipital brain regions. Conclusions. The findings extend previous evidence for disorder-specific underactivation in patients with ADHD compared to patients with CD in inferior prefrontal cortex during tasks of inhibitory control to the domain of cognitive flexibility. Inferior prefrontal underactivation thus appears to be a disorder-specific neurofunctional biomarker for ADHD when compared with patients with CD. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.

Cognitive and default-mode resting state networks: Do male and female brains “rest” differently?

Abstract: Variability in human behavior related to sex is supported by neuroimaging studies showing differences in brain activation patterns during cognitive task performance. An emerging field is examining the human connectome, including networks of brain regions that are not only temporally-correlated during different task conditions, but also networks that show highly correlated spontaneous activity during a task-free state. Both task-related and task-free network activity has been associated with individual task performance and behavior under certain conditions. Therefore, our aim was to determine whether sex differences exist during a task-free resting state for two networks associated with cognitive task performance (executive control network (ECN), salience network (SN)) and the default mode network (DMN). Forty-nine healthy subjects (26 females, 23 males) underwent a 5-min task-free fMRI scan in a 3T MRI. An independent components analysis (ICA) was performed to identify the best-fit IC for each network based on specific spatial nodes defined in previous studies. To determine the consistency of these networks across subjects we performed self-organizing group-level ICA analyses. There were no significant differences between sexes in the functional connectivity of the brain areas within the ECN, SN, or the DMN. These important findings highlight the robustness of intrinsic connectivity of these resting state networks and their similarity between sexes. Furthermore, our findings suggest that resting state fMRI studies do not need to be controlled for sex.

Distortion correction for diffusion-weighted MRI tractography and fMRI in the temporal lobes.

Abstract: Single shot echo-planar imaging (EPI) sequences are currently the most commonly used sequences for diffusion-weighted imaging (DWI) and functional magnetic resonance imaging (fMRI) as they allow relatively high signal to noise with rapid acquisition time. A major drawback of EPI is the substantial geometric distortion and signal loss that can occur due to magnetic field inhomogeneities close to air-tissue boundaries. If DWI-based tractography and fMRI are to be applied to these regions, then the distortions must be accurately corrected to achieve meaningful results. We describe robust acquisition and processing methods for correcting such distortions in spin echo (SE) EPI using a variant of the reversed direction k space traversal method with a number of novel additions. We demonstrate that dual direction k space traversal with maintained diffusion-encoding gradient strength and direction results in correction of the great majority of eddy current-associated distortions in DWI, in addition to those created by variations in magnetic susceptibility. We also provide examples to demonstrate that the presence of severe distortions cannot be ignored if meaningful tractography results are desired. The distortion correction routine was applied to SE-EPI fMRI acquisitions and allowed detection of activation in the temporal lobe that had been previously found using PET but not conventional fMRI.

The neural control of bimanual movements in the elderly: Brain regions exhibiting age-related increases in activity, frequency-induced neural modulation, and task-specific compensatory recruitment.

Abstract: Coordinated hand use is an essential component of many activities of daily living. Although previous studies have demonstrated age-related behavioral deficits in bimanual tasks, studies that assessed the neural basis underlying such declines in function do not exist. In this fMRI study, 16 old and 16 young healthy adults performed bimanual movements varying in coordination complexity (i.e., in-phase, antiphase) and movement frequency (i.e., 45, 60, 75, 90% of critical antiphase speed) demands. Difficulty was normalized on an individual subject basis leading to group performances (measured by phase accuracy/stability) that were matched for young and old subjects. Despite lower overall movement frequency, the old group "overactivated" brain areas compared with the young adults. These regions included the supplementary motor area, higher order feedback processing areas, and regions typically ascribed to cognitive functions (e.g., inferior parietal cortex/dorsolateral prefrontal cortex). Further, age-related increases in activity in the supplementary motor area and left secondary somatosensory cortex showed positive correlations with coordinative ability in the more complex antiphase task, suggesting a compensation mechanism. Lastly, for both old and young subjects, similar modulation of neural activity was seen with increased movement frequency. Overall, these findings demonstrate for the first time that bimanual movements require greater neural resources for old adults in order to match the level of performance seen in younger subjects. Nevertheless, this increase in neural activity does not preclude frequency-induced neural modulations as a function of increased task demand in the elderly.

The “Task B problem” and other considerations in developmental functional neuroimaging

Abstract: Functional neuroimaging provides a remarkable tool to allow us to study cognition across the lifespan and in special populations in a safe way. However, experimenters face a number of methodological issues, and these issues are particularly pertinent when imaging children. This brief article discusses assessing task performance, strategies for dealing with group performance differences, controlling for movement, statistical power, proper atlas registration, and data analysis strategies. In addition, there will be discussion of two other topics that have important implications for interpreting fMRI data: the question of whether functional neuroanatomical differences between adults and children are the consequence of putative developmental neurovascular differences, and the issue of interpreting negative blood oxygenation-level dependent (BOLD) signal change.

Overall brain connectivity maps show cortico-subcortical abnormalities in schizophrenia

Abstract: Abnormal interactions between areas of the brain have been pointed as possible causes for schizophrenia. However, the nature of these disturbances and the anatomical location of the regions involved are still unclear. Here, we describe a method to estimate maps of net levels of connectivity in the resting brain, and we apply it to look for differential patterns of connectivity in schizophrenia. This method uses partial coherences as a basic measure of covariability, and it minimises the effect of major physiological noise. When overall (net) connectivity maps of a sample of 40 patients with schizophrenia were compared with the maps from a matched sample of 40 controls, a single area of abnormality was found. It is an area of patient hyper-connectivity and is located frontally, in medial and orbital structures, clearly overlapping the anterior node of the default mode network (DMN). When this area is used as a region of interest in a second-level analysis, it shows functional hyper-connections with several cortical and subcortical structures. Interestingly, the most significant abnormality is found with the caudate, which has a bilateral pattern of abnormality, pointing to a possible DMN-striatum deviant relation in schizophrenia. However, hyper-connectivity observed with other regions (right hippocampus and amygdala, and other cortical structures) suggests a more pervasive alteration of brain connectivity in this disease.

Assessment of white matter tract damage in mild cognitive impairment and Alzheimer's disease.

Abstract: Diffusion tensor MRI-based tractography was used to investigate white matter (WM) changes in the major limbic (i.e., fornix and cingulum) and cortico-cortical association pathways [i.e., the uncinate fasciculus, the inferior fronto-occipital fasciculus, the inferior longitudinal fasciculus (ILF), the superior longitudinal fasciculus, and the corpus callosum] in 25 Alzheimer's disease (AD) patients, 19 amnestic mild cognitive impairment (aMCI) patients, and 15 healthy controls (HC). Mean diffusivity (MD), fractional anisotropy (FA), as well as axial (DA) and radial (DR) diffusivities were measured for each tract, using an atlas-based tractography approach. The association of WM tract integrity with hippocampal volume was also assessed. MD values were significantly different among groups in all WM tracts (P values ranging from 0.002 to 0.03), except in the fornix (P = 0.06) and the inferior fronto-occipital fasciculus (P = 0.09). Conversely, FA was significantly different among groups in the fornix only (P = 0.02). DA values were significantly different among groups in all WM tracts (P values ranging from 0.001 to 0.01), except in the fornix (P = 0.13) and the cingulum (P = 0.29). Significantly different DR values among groups were found in the fornix (P = 0.02) and the ILF (P = 0.01). In the fornix and cingulum, DR was significantly more increased than DA in both patient groups compared to HC. No difference in DA versus DR was found in cortico-cortical WM tracts. DA values in the fornix were significantly correlated with the hippocampal volume. This study demonstrates a different pattern of WM involvement in the limbic and cortico-cortical association pathways in aMCI and AD patients.

Neural plasticity of development and learning.

Abstract: Development and learning are powerful agents of change across the lifespan that induce robust structural and functional plasticity in neural systems. An unresolved question in developmental cognitive neuroscience is whether development and learning share the same neural mechanisms associated with experience-related neural plasticity. In this article, I outline the conceptual and practical challenges of this question, review insights gleaned from adult studies, and describe recent strides toward examining this topic across development using neuroimaging methods. I suggest that development and learning are not two completely separate constructs and instead, that they exist on a continuum. While progressive and regressive changes are central to both, the behavioral consequences associated with these changes are closely tied to the existing neural architecture of maturity of the system. Eventually, a deeper, more mechanistic understanding of neural plasticity will shed light on behavioral changes across development and, more broadly, about the underlying neural basis of cognition.

Intellectual abilities and white matter microstructure in development: A diffusion tensor imaging study

Abstract: Higher-order cognitive functions are supported by distributed networks of multiple interconnected cortical and subcortical regions. Efficient cognitive processing depends on fast communication between these regions, so the integrity of the connections between them is of great importance. It is known that white matter (WM) development is a slow process, continuing into adulthood. While the significance of cortical maturation for intellectual development is described, less is known about the relationships between cognitive functions and maturation of WM connectivity. In this cross-sectional study, we investigated the associations between intellectual abilities and development of diffusion tensor imaging (DTI) derived measures of WM microstructure in 168 right-handed participants aged 8-30 years. Independently of age and sex, both verbal and performance abilities were positively related to fractional anisotropy (FA) and negatively related to mean diffusivity (MD) and radial diffusivity (RD), predominantly in the left hemisphere. Further, verbal, but not performance abilities, were associated with developmental differences in DTI indices in widespread regions in both hemispheres. Regional analyses showed relations with both FA and RD bilaterally in the anterior thalamic radiation and the cortico-spinal tract and in the right superior longitudinal fasciculus. In these regions, our results suggest that participants with high verbal abilities may show accelerated WM development in late childhood and a subsequent earlier developmental plateau, in contrast to a steadier and prolonged development in participants with average verbal abilities. Longitudinal data are needed to validate these interpretations. The results provide insight into the neurobiological underpinnings of intellectual development.

Genetic and environmental contributions to neonatal brain structure: A twin study

Abstract: Twin studies have found that global brain volumes, including total intracranial volume (ICV), total gray matter, and total white matter volumes are highly heritable in adults and older children. Very little is known about genetic and environmental contributions to brain structure in very young children and whether these contributions change over the course of development. We performed structural imaging on a 3T MR scanner of 217 neonatal twins, 41 same-sex monozygotic, 50 same-sex dizygotic pairs, and 35 "single" twins-neonates with brain scans unavailable for their co-twins. Tissue segmentation and parcellation was performed, and structural equation modeling was used to estimate additive genetic, common environmental, and unique environmental effects on brain structure. Heritability of ICV (0.73) and total white matter volume (0.85) was high and similar to that described in older children and adults; the heritability of total gray matter (0.56) was somewhat lower. Heritability of lateral ventricle volume was high (0.71), whereas the heritability of cerebellar volume was low (0.17). Comparison with previous twin studies in older children and adults reveal that three general patterns of how heritability can change during postnatal brain development: (1) for global white matter volumes, heritability is comparable to reported heritability in adults, (2) for global gray matter volume and cerebellar volume, heritability increases with age, and (3) for lateral ventricle volume, heritability decreases with age. More detailed studies of the changes in the relative genetic and environmental effects on brain structure throughout early childhood development are needed.

A Parametric Empirical Bayesian framework for fMRI-constrained MEG/EEG source reconstruction

Abstract: We describe an asymmetric approach to fMRI and MEG/EEG fusion in which fMRI data are treated as empirical priors on electromagnetic sources, such that their influence depends on the MEG/EEG data, by virtue of maximizing the model evidence. This is important if the causes of the MEG/EEG signals differ from those of the fMRI signal. Furthermore, each suprathreshold fMRI cluster is treated as a separate prior, which is important if fMRI data reflect neural activity arising at different times within the EEG/MEG data. We present methodological considerations when mapping from a 3D fMRI Statistical Parametric Map to a 2D cortical surface and thence to the covariance components used within our Parametric Empirical Bayesian framework. Our previous introduction of a canonical (inverse-normalized) cortical mesh also allows deployment of fMRI priors that live in a template space; for example, from a group analysis of different individuals. We evaluate the ensuing scheme with MEG and EEG data recorded simultaneously from 12 participants, using the same face-processing paradigm under which independent fMRI data were obtained. Because the fMRI priors become part of the generative model, we use the model evidence to compare (i) multiple versus single, (ii) valid versus invalid, (iii) binary versus continuous, and (iv) variance versus covariance fMRI priors. For these data, multiple, valid, binary, and variance fMRI priors proved best for a standard Minimum Norm inversion. Interestingly, however, inversion using Multiple Sparse Priors benefited little from additional fMRI priors, suggesting that they already provide a sufficiently flexible generative model. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.

Whole brain-based analysis of regional white matter tract alterations in rare motor neuron diseases by diffusion tensor imaging

Abstract: Different motor neuron disorders (MNDs) are mainly defined by the clinical presentation based on the predominance of upper or lower motor neuron impairment and the course of the disease. Magnetic resonance imaging (MRI) mostly serves as a tool to exclude other pathologies, but novel approaches such as diffusion tensor imaging (DTI) have begun to add information on the underlying pathophysiological processes of these disorders in vivo. The present study was designed to investigate three different rare MNDs, i.e., primary lateral sclerosis (PLS, N = 25), hereditary spastic paraparesis (HSP, N = 24), and X-linked spinobulbar muscular atrophy (X-SBMA, N = 20), by use of whole-brain-based DTI analysis in comparison with matched controls. This analysis of white matter (WM) impairment revealed widespread and characteristic patterns of alterations within the motor system with a predominant deterioration of the corticospinal tract (CST) in HSP and PLS patients according to the clinical presentation and also in patients with X-SBMA to a lesser degree, but also WM changes in projections to the limbic system and within distinct areas of the corpus callosum (CC), the latter both for HSP and PLS. In summary, DTI was able to define a characteristic WM pathoanatomy in motor and extra-motor brain areas, such as the CC and the limbic projectional system, for different MNDs via whole brain-based FA assessment and quantitative fiber tracking. Future advanced MRI-based investigations might help to provide a fingerprint-identification of MNDs.

Population neuroscience: Why and how

Abstract: Population neuroscience endeavours to identify environmental and genetic factors that shape the function and structure of the human brain; it uses tools and knowledge of genetics, epidemiology, and cognitive neuroscience. Here, I focus on the application of population neuroscience in studies of brain development. By describing in some detail four existing large-scale magnetic resonance (MR) imaging studies of typically developing children and adolescents, I provide an overview of their design, including population sampling and recruitment, assessments of environmental and genetic "exposures," and measurements of brain and behavior "outcomes." I then discuss challenges faced by investigators carrying out such MR-based studies, including quality assurance, quality control and intersite coordination, and provide a brief overview of the achievements made so far. I conclude by outlining future directions vis-a-vis population neuroscience, such as design strategies that can be used to evaluate the presence of absence of causality in associations discovered by observational studies.

The envious brain: the neural basis of social comparison.

Abstract: Humans have a drive to evaluate themselves by examining their abilities and outcomes in comparison to others. The present study examined the emotional and neural correlates of upward social comparison (comparison with those who have more) and downward social comparison (comparison with those who have less). Two experiments were conducted with volunteers in an interactive game of chance, in which a putative player won or lost more money than the participant. The results showed that even when participants lost money, they expressed joy and schadenfreude (gloating) if the other player had lost more money. On the other hand when they actually won money, but the other player had won more they expressed envy. This pattern was also demonstrated in a differential BOLD response in the ventral striatum. Comparing the activations between an actual gain and a relative gain indicated that even when a person loses money, merely adding information about another person's greater loss may increase ventral striatum activations to a point where these activations are similar to those of an actual gain. We suggest that the ventral striatum plays a role in mediating the emotional consequences of social comparison.

Anterior cingulate activity and the self in disorders of consciousness.

Abstract: Objectives: The aim of this study was to investigate the relationship between medial cortical activation and the presence of self and consciousness in healthy subjects and patients with vegetative state and minimally conscious state using functional magnetic resonance imaging (fMRI). Experiment design: We first conducted two fMRI experiments in healthy subjects to identify brain regions specifically associated with self-perception through the use of different auditory stimuli that had different grades of self-relatedness. We then applied these regions as functional localizers to examine the relationship between neural activity changes during self-relatedness and consciousness level in the patients with disorders of consciousness (DOC). Principal observations: We demonstrated recruitment of various anterior medial cortical regions including the anterior cingulate cortex (ACC) in healthy subjects during auditory perception of self-related stimuli. We further showed that patients with DOC showed signal changes in the ACC during auditory perception of self-related stimuli. Finally, it was shown that these signal changes correlate with the level of consciousness in the patients with DOC. Conclusion: The degree of consciousness in patients with DOC was correlated with neural activity in the ACC induced by self-related stimuli. Our results not only shed light on the pathophysiology of DOC, but may also suggest a useful neural, and thus diagnostic, marker of the dysfunction of consciousness in vegetative patients. Hum Brain Mapp 31:1993-2002, 2010. (C) 2010 Wiley-Liss, Inc.

Fronto-cingulate effective connectivity in obsessive compulsive disorder: a study with fMRI and dynamic causal modeling.

Abstract: Evidence suggests that obsessive compulsive disorder (OCD) is associated with an overactive error control system. A key role in error detection and control has been ascribed to the fronto-cingulate system. However, the exact functional interplay between the single components of this network in OCD is largely unknown. Therefore, the present study combined a univariate data analysis and effective connectivity analysis using dynamic causal modeling (DCM) to examine error control in 21 patients with OCD and 21 matched healthy controls. All subjects performed an adapted version of the Stroop color-word task while undergoing fMRI scans. Enhanced activation in the fronto-cingulate system could be detected in OCD patients during the incongruent task condition. Additionally, task-related modulation of effective connectivity from the dorsal ACC to left DLPFC was significantly stronger in OCD patients. These findings are consistent with an overactive error control system in OCD subserving suppression of prepotent responses during decision-making.

Effects of acute psychosocial stress on working memory related brain activity in men

Abstract: r Abstract: Acute psychosocial stress in humans triggers the release of glucocorticoids (GCs) and influ- ences performance in declarative and working memory (WM) tasks. These memory systems rely on the hippocampus and prefrontal cortex (PFC), where GC-binding receptors are present. Previous stud- ies revealed contradictory results regarding effects of acute stress on WM-related brain activity. We combined functional magnetic resonance imaging with a standardized psychosocial stress protocol to investigate the effects of acute mental stress on brain activity during encoding, maintenance, and re- trieval of WM. Participants (41 healthy young men) underwent either a stress or a control procedure before performing a WM task. Stress increased salivary cortisol levels and tended to increase WM ac- curacy. Neurally, stress-induced increases in cortical activity were evident in PFC and posterior parie- tal cortex (PPC) during WM maintenance. Furthermore, hippocampal activity was modulated by stress during encoding and retrieval with increases in the right anterior hippocampus during WM encoding and decreases in the left posterior hippocampus during retrieval. Our study demonstrates that stress increases activity in PFC and PPC specifically during maintenance of items in WM, whereas effects on hippocampal activity are restricted to encoding and retrieval. The finding that psychosocial stress can increase and decrease activity in two different hippocampal areas may be relevant for understanding the often-reported phase-dependent opposing behavioral effects of stress on long-term memory. Hum Brain Mapp 00:000-000, 2010. V C 2010 Wiley-Liss, Inc.

The role of the unaffected hemisphere in motor recovery after stroke

Abstract: The contribution of the ipsilateral (nonaffected) hemisphere to recovery of motor function after stroke is controversial. Under the assumption that functionally relevant areas within the ipsilateral motor system should be tightly coupled to the demand we used fMRI and acoustically paced movements of the right index finger at six different frequencies to define the role of these regions for recovery after stroke. Eight well-recovered patients with a chronic striatocapsular infarction of the left hemisphere were compared with eight age-matched participants. As expected the hemodynamic response increased linearly with the frequency of the finger movements at the level of the left supplementary motor cortex (SMA) and the left primary sensorimotor cortex (SMC) in both groups. In contrast, a linear increase of the hemodynamic response with higher tapping frequencies in the right premotor cortex (PMC) and the right SMC was only seen in the patient group. These results support the model of an enhanced bihemispheric recruitment of preexisting motor representations in patients after subcortical stroke. Since all patients had excellent motor recovery contralesional SMC activation appears to be efficient and resembles the widespread, bilateral activation observed in healthy participants performing complex movements, instead of reflecting maladaptive plasticity.