Localised grey matter atrophy in multiple sclerosis is network-based: a coordinate-based meta-analysis.

AIM: To test the network degeneration hypothesis in multiple sclerosis (MS) with a two-stage coordinate-based meta-analysis by: (1) characterising regional selectivity of grey matter (GM) atrophy and (2) testing for functional connectivity involving these regions. MATERIALS AND METHODS: Meta-analytic sources included 33 journal articles (1,666 MS patients and 1,269 healthy controls) with coordinate-based results from voxel-based morphometry analysis demonstrating GM atrophy. Mass univariate and multivariate coordinate-based meta-analyses were performed to identify a convergent pattern of GM atrophy and determine inter-regional co-activation (as a surrogate of functional connectivity), with anatomical likelihood estimation and functional meta-analytic connectivity modelling, respectively. RESULTS: Localised GM atrophy was demonstrated in the thalamus, putamen, caudate, sensorimotor cortex, insula, superior temporal gyrus, and cingulate gyrus. This convergent pattern of atrophy displayed significant inter-regional functional co-activations. CONCLUSION: In MS, GM atrophy was regionally selective, and these regions were functionally connected. The meta-analytic model-based results of this study are intended to guide future development of quantitative neuroimaging markers for diagnosis, evaluating disease progression, and monitoring treatment response.

White Matter Tract Pathology in Pediatric Anoxic Brain Injury from Drowning.

BACKGROUND AND PURPOSE: Although drowning is a leading cause of mortality and morbidity in young children, the neuropathologic consequences have not been fully determined. The purpose of this article was to quantitatively characterize white matter microstructural abnormalities in pediatric anoxic brain injury from nonfatal drowning and investigate the correlation with motor function. MATERIALS AND METHODS: Whole-brain T1-weighted and diffusion-weighted MR imaging datasets were acquired in 11 children with chronic anoxic brain injury and 11 age- and sex-matched neurotypical controls (4-12 years of age). A systematic evaluation form and scoring system were created to assess motor function. Tract-Based Spatial Statistics was used to quantify between-group alterations in the diffusion tensor imaging indices of fractional anisotropy and mean diffusivity and to correlate with per-subject functional motor scores. RESULTS: Group-wise Tract-Based Spatial Statistics analyses demonstrated reduced fractional anisotropy in the bilateral posterior limbs of the internal capsule and the splenium of the corpus callosum (P < .001). Mean diffusivity was more diffusely increased, affecting the bilateral superior corona radiata, anterior and posterior limbs of the internal capsule, and external capsules (P < .001). Individual-subject fractional anisotropy and mean diffusivity values derived from the ROIs of the bilateral posterior limbs of the internal capsule strongly correlated with motor scores and demonstrated more potent between-group effects than with ROIs of the entire corticospinal tract. CONCLUSIONS: These data particularly implicate the deep white matter, predominantly the posterior limbs of the internal capsule, as targets of damage in pediatric anoxic brain injury with drowning. The substantial involvement of motor-system tracts with relative sparing elsewhere is notable. These results localize white matter pathology and inform future diagnostic and prognostic markers.

Genome-wide significant loci for addiction and anxiety.

BACKGROUND: Psychiatric comorbidity is common among individuals with addictive disorders, with patients frequently suffering from anxiety disorders. While the genetic architecture of comorbid addictive and anxiety disorders remains unclear, elucidating the genes involved could provide important insights into the underlying etiology. METHODS: Here we examine a sample of 1284 Mexican-Americans from randomly selected extended pedigrees. Variance decomposition methods were used to examine the role of genetics in addiction phenotypes (lifetime history of alcohol dependence, drug dependence or chronic smoking) and various forms of clinically relevant anxiety. Genome-wide univariate and bivariate linkage scans were conducted to localize the chromosomal regions influencing these traits. RESULTS: Addiction phenotypes and anxiety were shown to be heritable and univariate genome-wide linkage scans revealed significant quantitative trait loci for drug dependence (14q13.2-q21.2, LOD=3.322) and a broad anxiety phenotype (12q24.32-q24.33, LOD=2.918). Significant positive genetic correlations were observed between anxiety and each of the addiction subtypes (ρg=0.550-0.655) and further investigation with bivariate linkage analyses identified significant pleiotropic signals for alcohol dependence-anxiety (9q33.1-q33.2, LOD=3.054) and drug dependence-anxiety (18p11.23-p11.22, LOD=3.425). CONCLUSIONS: This study confirms the shared genetic underpinnings of addiction and anxiety and identifies genomic loci involved in the etiology of these comorbid disorders. The linkage signal for anxiety on 12q24 spans the location of TMEM132D, an emerging gene of interest from previous GWAS of anxiety traits, whilst the bivariate linkage signal identified for anxiety-alcohol on 9q33 peak coincides with a region where rare CNVs have been associated with psychiatric disorders. Other signals identified implicate novel regions of the genome in addiction genetics.

Meta-connectomics: human brain network and connectivity meta-analyses.

Abnormal brain connectivity or network dysfunction has been suggested as a paradigm to understand several psychiatric disorders. We here review the use of novel meta-analytic approaches in neuroscience that go beyond a summary description of existing results by applying network analysis methods to previously published studies and/or publicly accessible databases. We define this strategy of combining connectivity with other brain characteristics as 'meta-connectomics'. For example, we show how network analysis of task-based neuroimaging studies has been used to infer functional co-activation from primary data on regional activations. This approach has been able to relate cognition to functional network topology, demonstrating that the brain is composed of cognitively specialized functional subnetworks or modules, linked by a rich club of cognitively generalized regions that mediate many inter-modular connections. Another major application of meta-connectomics has been efforts to link meta-analytic maps of disorder-related abnormalities or MRI 'lesions' to the complex topology of the normative connectome. This work has highlighted the general importance of network hubs as hotspots for concentration of cortical grey-matter deficits in schizophrenia, Alzheimer's disease and other disorders. Finally, we show how by incorporating cellular and transcriptional data on individual nodes with network models of the connectome, studies have begun to elucidate the microscopic mechanisms underpinning the macroscopic organization of whole-brain networks. We argue that meta-connectomics is an exciting field, providing robust and integrative insights into brain organization that will likely play an important future role in consolidating network models of psychiatric disorders.

Co-activation based parcellation of the human frontal pole.

Historically, the human frontal pole (FP) has been considered as a single architectonic area. Brodmann's area 10 is located in the frontal lobe with known contributions in the execution of various higher order cognitive processes. However, recent cytoarchitectural studies of the FP in humans have shown that this portion of cortex contains two distinct cytoarchitectonic regions. Since architectonic differences are accompanied by differential connectivity and functions, the frontal pole qualifies as a candidate region for exploratory parcellation into functionally discrete sub-regions. We investigated whether this functional heterogeneity is reflected in distinct segregations within cytoarchitectonically defined FP-areas using meta-analytic co-activation based parcellation (CBP). The CBP method examined the co-activation patterns of all voxels within the FP as reported in functional neuroimaging studies archived in the BrainMap database. Voxels within the FP were subsequently clustered into sub-regions based on the similarity of their respective meta-analytically derived co-activation maps. Performing this CBP analysis on the FP via k-means clustering produced a distinct 3-cluster parcellation for each hemisphere corresponding to previously identified cytoarchitectural differences. Post-hoc functional characterization of clusters via BrainMap metadata revealed that lateral regions of the FP mapped to memory and emotion domains, while the dorso- and ventromedial clusters were associated broadly with emotion and social cognition processes. Furthermore, the dorsomedial regions contain an emphasis on theory of mind and affective related paradigms whereas ventromedial regions couple with reward tasks. Results from this study support previous segregations of the FP and provide meta-analytic contributions to the ongoing discussion of elucidating functional architecture within human FP.

The role of the right temporoparietal junction in attention and social interaction as revealed by ALE meta-analysis.

The right temporoparietal junction (rTPJ) is frequently associated with different capacities that to shift attention to unexpected stimuli (reorienting of attention) and to understand others' (false) mental state [theory of mind (ToM), typically represented by false belief tasks]. Competing hypotheses either suggest the rTPJ representing a unitary region involved in separate cognitive functions or consisting of subregions subserving distinct processes. We conducted activation likelihood estimation (ALE) meta-analyses to test these hypotheses. A conjunction analysis across ALE meta-analyses delineating regions consistently recruited by reorienting of attention and false belief studies revealed the anterior rTPJ, suggesting an overarching role of this specific region. Moreover, the anatomical difference analysis unravelled the posterior rTPJ as higher converging in false belief compared with reorienting of attention tasks. This supports the concept of an exclusive role of the posterior rTPJ in the social domain. These results were complemented by meta-analytic connectivity mapping (MACM) and resting-state functional connectivity (RSFC) analysis to investigate whole-brain connectivity patterns in task-constrained and task-free brain states. This allowed for detailing the functional separation of the anterior and posterior rTPJ. The combination of MACM and RSFC mapping showed that the posterior rTPJ has connectivity patterns with typical ToM regions, whereas the anterior part of rTPJ co-activates with the attentional network. Taken together, our data suggest that rTPJ contains two functionally fractionated subregions: while posterior rTPJ seems exclusively involved in the social domain, anterior rTPJ is involved in both, attention and ToM, conceivably indicating an attentional shifting role of this region.

Cytoarchitecture, probability maps and functions of the human frontal pole.

The frontal pole has more expanded than any other part in the human brain as compared to our ancestors. It plays an important role for specifically human behavior and cognitive abilities, e.g. action selection (Kovach et al., 2012). Evidence about divergent functions of its medial and lateral part has been provided, both in the healthy brain and in psychiatric disorders. The anatomical correlates of such functional segregation, however, are still unknown due to a lack of stereotaxic, microstructural maps obtained in a representative sample of brains. Here we show that the human frontopolar cortex consists of two cytoarchitectonically and functionally distinct areas: lateral frontopolar area 1 (Fp1) and medial frontopolar area 2 (Fp2). Based on observer-independent mapping in serial, cell-body stained sections of 10 brains, three-dimensional, probabilistic maps of areas Fp1 and Fp2 were created. They show, for each position of the reference space, the probability with which each area was found in a particular voxel. Applying these maps as seed regions for a meta-analysis revealed that Fp1 and Fp2 differentially contribute to functional networks: Fp1 was involved in cognition, working memory and perception, whereas Fp2 was part of brain networks underlying affective processing and social cognition. The present study thus disclosed cortical correlates of a functional segregation of the human frontopolar cortex. The probabilistic maps provide a sound anatomical basis for interpreting neuroimaging data in the living human brain, and open new perspectives for analyzing structure-function relationships in the prefrontal cortex. The new data will also serve as a starting point for further comparative studies between human and non-human primate brains. This allows finding similarities and differences in the organizational principles of the frontal lobe during evolution as neurobiological basis for our behavior and cognitive abilities.

Neural network of cognitive emotion regulation--an ALE meta-analysis and MACM analysis.

Cognitive regulation of emotions is a fundamental prerequisite for intact social functioning which impacts on both well being and psychopathology. The neural underpinnings of this process have been studied intensively in recent years, without, however, a general consensus. We here quantitatively summarize the published literature on cognitive emotion regulation using activation likelihood estimation in fMRI and PET (23 studies/479 subjects). In addition, we assessed the particular functional contribution of identified regions and their interactions using quantitative functional inference and meta-analytic connectivity modeling, respectively. In doing so, we developed a model for the core brain network involved in emotion regulation of emotional reactivity. According to this, the superior temporal gyrus, angular gyrus and (pre) supplementary motor area should be involved in execution of regulation initiated by frontal areas. The dorsolateral prefrontal cortex may be related to regulation of cognitive processes such as attention, while the ventrolateral prefrontal cortex may not necessarily reflect the regulatory process per se, but signals salience and therefore the need to regulate. We also identified a cluster in the anterior middle cingulate cortex as a region, which is anatomically and functionally in an ideal position to influence behavior and subcortical structures related to affect generation. Hence this area may play a central, integrative role in emotion regulation. By focusing on regions commonly active across multiple studies, this proposed model should provide important a priori information for the assessment of dysregulated emotion regulation in psychiatric disorders.

Relationship between fractional anisotropy of cerebral white matter and metabolite concentrations measured using (1)H magnetic resonance spectroscopy in healthy adults.

Fractional anisotropy (FA) of water diffusion in cerebral white matter (WM), derived from diffusion tensor imaging (DTI), is a sensitive index of microscopic WM integrity. Physiological and metabolic factors that explain intersubject variability in FA values were evaluated in two cohorts of healthy adults of different age spans (N=65, range: 28-50years; and N=25, age=66.6±6.2, range: 57-80years). Single voxel magnetic resonance spectroscopy (MRS) was used to measure N-acetylaspartate (NAA), total choline-containing compounds, and total creatine, bilaterally in an associative WM tract: anterior corona radiata (ACR). FA values were calculated for the underlying, proximal and two distal WM regions. Two-stage regression analysis was used to calculate the proportion of variability in FA values explained by spectroscopy measurements, at the first stage, and subject's age, at the second stage. WM NAA concentration explained 23% and 66% of intersubject variability (p<0.001) in the FA of the underlying WM in the younger and older cohorts, respectively. WM NAA concentration also explained a significant proportion of variability in FA of the genu of corpus callosum (CC), a proximal WM tract where some of the fibers contained within the spectroscopic voxel decussate. NAA concentrations also explained a significant proportion of variability in the FA values in the splenium of CC, a distal WM tract that also carries associative fibers, in both cohorts. These results suggest that MRS measurements explained a significant proportion of variability in FA values in both proximal and distal WM tracts that carry similar fiber-types.

Differentiated parietal connectivity of frontal regions for "what" and "where" memory.

In a previous meta-analysis across almost 200 neuroimaging experiments, working memory for object location showed significantly stronger convergence on the posterior superior frontal gyrus, whereas working memory for identity showed stronger convergence on the posterior inferior frontal gyrus (dorsal to, but overlapping with Brodmann's area BA 44). As similar locations have been discussed as part of a dorsal frontal-superior parietal reach system and an inferior frontal grasp system, the aim of the present study was to test whether the regions of working-memory related "what" and "where" processing show a similar distinction in parietal connectivity. The regions that were found in the previous meta-analysis were used as seeds for functional connectivity analyses using task-based meta-analytic connectivity modelling and task-independent resting state correlations. While the ventral seed showed significantly stronger connectivity with the bilateral intraparietal sulcus (IPS), the dorsal seed showed stronger connectivity with the bilateral posterior inferior parietal and the medial superior parietal lobule. The observed connections of regions involved in memory for object location and identity thus clearly demonstrate a distinction into separate pathways that resemble the parietal connectivity patterns of the dorsal and ventral premotor cortex in non-human primates and humans. It may hence be speculated that memory for a particular location and reaching towards it as well as object memory and finger positioning for manipulation may rely on shared neural systems. Moreover, the ensuing regions, in turn, featured differential connectivity with the bilateral ventral and dorsal extrastriate cortex, suggesting largely segregated bilateral connectivity pathways from the dorsal visual cortex via the superior and inferior parietal lobules to the dorsal posterior frontal cortex and from the ventral visual cortex via the IPS to the ventral posterior frontal cortex that may underlie action and cognition.

Modelling neural correlates of working memory: a coordinate-based meta-analysis.

Working memory subsumes the capability to memorize, retrieve and utilize information for a limited period of time which is essential to many human behaviours. Moreover, impairments of working memory functions may be found in nearly all neurological and psychiatric diseases. To examine what brain regions are commonly and differently active during various working memory tasks, we performed a coordinate-based meta-analysis over 189 fMRI experiments on healthy subjects. The main effect yielded a widespread bilateral fronto-parietal network. Further meta-analyses revealed that several regions were sensitive to specific task components, e.g. Broca's region was selectively active during verbal tasks or ventral and dorsal premotor cortex were preferentially involved in memory for object identity and location, respectively. Moreover, the lateral prefrontal cortex showed a division in a rostral and a caudal part based on differential involvement in task set and load effects. Nevertheless, a consistent but more restricted "core" network emerged from conjunctions across analyses of specific task designs and contrasts. This "core" network appears to comprise the quintessence of regions, which are necessary during working memory tasks. It may be argued that the core regions form a distributed executive network with potentially generalized functions for focussing on competing representations in the brain. The present study demonstrates that meta-analyses are a powerful tool to integrate the data of functional imaging studies on a (broader) psychological construct, probing the consistency across various paradigms as well as the differential effects of different experimental implementations.

Cortical sulcal areas in baboons (Papio hamadryas spp.) with generalized interictal epileptic discharges on scalp EEG.

Brain MRI studies in people with idiopathic generalized epilepsies demonstrate regional morphometric differences, though variable in magnitude and location. As the baboon provides an excellent electroclinical and neuroimaging model for photosensitive generalized epilepsy in humans, this study evaluated MRI volumetric and morphometric differences between baboons with interictal epileptic discharges (IEDs) on scalp EEG and baboons with normal EEG studies. Seventy-seven baboons underwent high-resolution brain MRI and scalp EEG studies. The scans were acquired using an 8-channel primate head coil (Siemens TRIO 3T scanner, Erlangen, Germany). After spatial normalization, sulcal measurements were obtained by object-based-morphology methods. One-hour scalp EEG studies were performed in animals sedated with ketamine. Thirty-eight (22F/16M) baboons had normal EEGs (IED-), while 39 (22F/17M) had generalized IEDs (IED+). The two groups were compared for age, total brain volume, and sulcal areas (Hotelling's Trace) as well as between-subjects comparison of 11 individual sulcal areas (averaged between left and right hemispheres). There were no differences between IED- and IED+ groups with respect to age or total brain (gray or white matter) volume, and multivariate tests demonstrated a marginally significant decrease of sulcal areas in IED+ baboons (p=0.075). Tests of between-subjects effects showed statistically significant decreases in the intraparietal (p=0.002), central (p=0.03) and cingulate sulci (p=0.02), and marginal decreases involving the lunate (p=0.07) and superior temporal sulci (p=0.08). Differences in sulcal areas in IED+ baboons may reflect global developmental abnormalities, while decreases of areas of specific sulci reflect anatomical markers for potential generators or cortical nodes of the networks underlying spontaneous seizures and photosensitivity in the baboon.

A study of the reproducibility and etiology of diffusion anisotropy differences in developmental stuttering: a potential role for impaired myelination.

Several diffusion tensor imaging (DTI) studies have reported fractional anisotropy (FA) reductions within the left perisylvian white matter (WM) of persistent developmental stutterers (PSs). However, these studies have not reached the same conclusions in regard to the presence, spatial distribution (focal/diffuse), and directionality (elevated/reduced) of FA differences outside of the left perisylvian region. In addition, supplemental DTI measures (axial and radial diffusivities, diffusion trace) have yet to be utilized to examine the potential etiology of these FA reductions. Therefore, the present study sought to reexamine earlier findings through a sex- and age-controlled replication analysis and then to extend these findings with the aforementioned non-FA measures. The replication analysis showed that robust FA reductions in PSs were largely focal, left hemispheric, and within late-myelinating associative and commissural fibers (division III of the left superior longitudinal fasciculus, callosal body, forceps minor of the corpus callosum). Additional DTI measures revealed that these FA reductions were attributable to an increase in diffusion perpendicular to the affected fiber tracts (elevated radial diffusivity). These findings suggest a hypothesis that will be testable in future studies: that myelogenesis may be abnormal in PSs within left-hemispheric fiber tracts that begin a prolonged course of myelination in the first postnatal year.

Genetics of microstructure of cerebral white matter using diffusion tensor imaging.

We analyzed the degree of genetic control over intersubject variability in the microstructure of cerebral white matter (WM) using diffusion tensor imaging (DTI). We performed heritability, genetic correlation and quantitative trait loci (QTL) analyses for the whole-brain and 10 major cerebral WM tracts. Average measurements for fractional anisotropy (FA), radial (L( perpendicular)) and axial (L( vertical line)) diffusivities served as quantitative traits. These analyses were done in 467 healthy individuals (182 males/285 females; average age 47.9+/-13.5 years; age range: 19-85 years), recruited from randomly-ascertained pedigrees of extended families. Significant heritability was observed for FA (h(2)=0.52+/-0.11; p=10(-7)) and L( perpendicular) (h(2)=0.37+/-0.14; p=0.001), while L( vertical line) measurements were not significantly heritable (h(2)=0.09+/-0.12; p=0.20). Genetic correlation analysis indicated that the FA and L( perpendicular) shared 46% of the genetic variance. Tract-wise analysis revealed a regionally diverse pattern of genetic control, which was unrelated to ontogenic factors, such as tract-wise age-of-peak FA values and rates of age-related change in FA. QTL analysis indicated linkages for whole-brain average FA (LOD=2.36) at the marker D15S816 on chromosome 15q25, and for L( perpendicular) (LOD=2.24) near the marker D3S1754 on the chromosome 3q27. These sites have been reported to have significant co-inheritance with two psychiatric disorders (major depression and obsessive-compulsive disorder) in which patients show characteristic alterations in cerebral WM. Our findings suggest that the microstructure of cerebral white matter is under a strong genetic control and further studies in healthy as well as patients with brain-related illnesses are imperative to identify the genes that may influence cerebral white matter.

Genetic control over the resting brain.

The default-mode network, a coherent resting-state brain network, is thought to characterize basal neural activity. Aberrant default-mode connectivity has been reported in a host of neurological and psychiatric illnesses and in persons at genetic risk for such illnesses. Whereas the neurophysiologic mechanisms that regulate default-mode connectivity are unclear, there is growing evidence that genetic factors play a role. In this report, we estimate the importance of genetic effects on the default-mode network by examining covariation patterns in functional connectivity among 333 individuals from 29 randomly selected extended pedigrees. Heritability for default-mode functional connectivity was 0.424 +/- 0.17 (P = 0.0046). Although neuroanatomic variation in this network was also heritable, the genetic factors that influence default-mode functional connectivity and gray-matter density seem to be distinct, suggesting that unique genes influence the structure and function of the network. In contrast, significant genetic correlations between regions within the network provide evidence that the same genetic factors contribute to variation in functional connectivity throughout the default mode. Specifically, the left parahippocampal region was genetically correlated with all other network regions. In addition, the posterior cingulate/precuneus region, medial prefrontal cortex, and right cerebellum seem to form a subnetwork. Default-mode functional connectivity is influenced by genetic factors that cannot be attributed to anatomic variation or a single region within the network. By establishing the heritability of default-mode functional connectivity, this experiment provides the obligatory evidence required before these measures can be considered as endophenotypes for psychiatric or neurological illnesses or to identify genes influencing intrinsic brain function.

Processing speed is correlated with cerebral health markers in the frontal lobes as quantified by neuroimaging.

We explored relationships between decline in cognitive processing speed (CPS) and change in frontal lobe MRI/MRS-based indices of cerebral integrity in 38 healthy adults (age 57-90 years). CPS was assessed using a battery of four timed neuropsychological tests: Grooved Pegboard, Coding, Symbol Digit Modalities Test and Category Fluency (Fruits and Furniture). The neuropsychological tests were factor analyzed to extract two components of CPS: psychomotor (PM) and psychophysical (PP). MRI-based indices of cerebral integrity included three cortical measurements per hemisphere (GM thickness, intergyral and sulcal spans) and two subcortical indices (fractional anisotropy (FA), measured using track-based spatial statistics (TBSS), and the volume of hyperintense WM (HWM)). MRS indices included levels of choline-containing compounds (GPC+PC), phosphocreatine plus creatine (PCr+Cr), and N-acetylaspartate (NAA), measured bilaterally in the frontal WM bundles. A substantial fraction of the variance in the PM-CPS (58%) was attributed to atrophic changes in frontal WM, observed as increases in sulcal span, declines in FA values and reductions in concentrations of NAA and choline-containing compounds. A smaller proportion (20%) of variance in the PP-CPS could be explained by bilateral increases in frontal sulcal span and increases in HWM volumes.

Genetics of primary cerebral gyrification: Heritability of length, depth and area of primary sulci in an extended pedigree of Papio baboons.

Genetic control over morphological variability of primary sulci and gyri is of great interest in the evolutionary, developmental and clinical neurosciences. Primary structures emerge early in development and their morphology is thought to be related to neuronal differentiation, development of functional connections and cortical lateralization. We measured the proportional contributions of genetics and environment to regional variability, testing two theories regarding regional modulation of genetic influences by ontogenic and phenotypic factors. Our measures were surface area, and average length and depth of eleven primary cortical sulci from high-resolution MR images in 180 pedigreed baboons. Average heritability values for sulcal area, depth and length (h(2)(Area)=.38+/-.22; h(2)(Depth)=.42+/-.23; h(2)(Length)=.34+/-.22) indicated that regional cortical anatomy is under genetic control. The regional pattern of genetic contributions was complex and, contrary to previously proposed theories, did not depend upon sulcal depth, or upon the sequence in which structures appear during development. Our results imply that heritability of sulcal phenotypes may be regionally modulated by arcuate U-fiber systems. However, further research is necessary to unravel the complexity of genetic contributions to cortical morphology.

3D modeling of the total electric field induced by transcranial magnetic stimulation using the boundary element method.

Transcranial magnetic stimulation (TMS) delivers highly localized brain stimulations via non-invasive externally applied magnetic fields. This non-invasive, painless technique provides researchers and clinicians with a unique tool capable of stimulating both the central and peripheral nervous systems. However, a complete analysis of the macroscopic electric fields produced by TMS has not yet been performed. In this paper, we addressed the importance of the secondary E-field created by surface charge accumulation during TMS using the boundary element method (BEM). 3D models were developed using simple head geometries in order to test the model and compare it with measured values. The effects of tissue geometry, size and conductivity were also investigated. Finally, a realistically shaped head model was used to assess the effect of multiple surfaces on the total E-field. Secondary E-fields have the greatest impact at areas in close proximity to each tissue layer. Throughout the head, the secondary E-field magnitudes typically range from 20% to 35% of the primary E-field's magnitude. The direction of the secondary E-field was generally in opposition to the primary E-field; however, for some locations, this was not the case (i.e. going from high to low conductivity tissues). These findings show that realistically shaped head geometries are important for accurate modeling of the total E-field.

Effect of aging on regional cerebral blood flow responses associated with osmotic thirst and its satiation by water drinking: a PET study.

Levels of thirst and ad libitum drinking decrease with advancing age, making older people vulnerable to dehydration. This study investigated age-related changes in brain responses to thirst and drinking in healthy men. Thirst was induced with hypertonic infusions (3.1 ml/kg 0.51M NaCl) in young (Y) and older (O) subjects. Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET). Thirst activations were identified by correlating rCBF with thirst ratings. Average rCBF was measured from regions of interest (ROI) corresponding to activation clusters in each group. The effects of drinking were examined by correlating volume of water drunk with changes in ROI rCBF from maximum thirst to postdrinking. There were increases in blood osmolality (Y, 2.8 +/- 1.8%; O, 2.2 +/- 1.4%) and thirst ratings (Y, 3.1 +/- 2.1; O, 3.7 +/- 2.8) from baseline to the end of the hypertonic infusion. Older subjects drank less water (1.9 +/- 1.6 ml/kg) than younger subjects (3.9 +/- 1.9 ml/kg). Thirst-related activation was evident in S1/M1, prefrontal cortex, anterior midcingulate cortex (aMCC), premotor cortex, and superior temporal gyrus in both groups. Postdrinking changes of rCBF in the aMCC correlated with drinking volumes in both groups. There was a greater reduction in aMCC rCBF relative to water drunk in the older group. Aging is associated with changes in satiation that militate against adequate hydration in response to hyperosmolarity, although it is unclear whether these alterations are due to changes in primary afferent inflow or higher cortical functioning.

High prevalence of pineal cysts in healthy adults demonstrated by high-resolution, noncontrast brain MR imaging.

BACKGROUND AND PURPOSE: Although the prevalence of pineal cysts in autopsy series has been reported as being between 25% and 40%, MR studies have documented their frequency to range between 1.5% and 10.8%. The purpose of this high-resolution brain MR imaging study at 1.9T was to determine the prevalence of pineal cysts in healthy adults. MATERIALS AND METHODS: Brain MR images of 100 healthy young volunteers were randomly selected from our International Consortium for Brain Mapping project data base. Cysts were detected as circular areas of isointensity relative to CSF on both 3D gradient-echo T1-weighted and 2D fast spin-echo T2-weighted images. The inner diameters of all visualized pineal cysts were measured, and a criterion of 2.0 mm of the largest inner cross-sectional diameter was used to categorize cysts as being either small cystic changes (<2.0-mm diameter) or pineal cysts (>2.0-mm diameter). RESULTS: Twenty-three percent (23/100) of the volunteers had pineal cysts with a mean largest inner cross-sectional diameter of 4.3 mm (range, 2-14 mm); 13% (13/100) demonstrated cystic changes involving the pineal gland with the largest inner cross-sectional diameter of less than 2.0 mm. There was a slight female predominance. Two subjects with long-term follow-up scans showed no symptoms or changes in the size of their pineal cysts. CONCLUSION: On high-resolution MR imaging, the prevalence of pineal cysts was 23% in our healthy group of adults, which is consistent with previous autopsy studies. Long-term follow-up studies of 2 cases demonstrated the stability of the cysts.