Voxel Based Morphometry

The understanding of empathy from a neuroscientific perspective has recently developed quickly, with numerous functional MRI studies associating different brain regions with different components of empathy. A recent meta-analysis across 40 fMRI studies revealed  that affective empathy is most often associated with increased activity in the insula, whereas cognitive empathy is most often associated with activity in the midcingulate cortex and adjacent dorsomedial prefrontal cortex (MCC/dmPFC). To date, however, it remains unclear whether individual differences in brain morphometry in these regions underlie different dispositions in affective and cognitive empathy. In order to test this hypothesis, voxel-based morphometry (VBM) was used to examine the extent to which gray matter density predicts scores from an established empathy measure (Questionnaire of Cognitive and Affective Empathy; QCAE). One hundred and seventy-six participants completed the QCAE and underwent MRI in order to acquire a high-resolution, three-dimensional T1-weighted structural scans. A factor analysis of the questionnaire scores revealed two distinct factors of empathy, affective and cognitive, which confirmed the validity of the QCAE. VBM results revealed gray matter density differences associated with the distinct components of empathy.  Higher scores on affective empathy were associated with greater gray matter density in the insula cortex and higher scores of cognitive empathy were associated with greater gray matter density in the MCC/dmPFC. Taken together, these results provide validation for empathy being a multi-component construct, suggesting that affective and cognitive empathy are differentially represented in brain morphometry as well as providing convergent evidence for empathy being represented by different neural and structural correlates.

Personality dimensions such as novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (PER) are said to be heritable, stable across time and dependent on genetic and neurobiological factors. Recently a better understanding of the relationship between personality traits and brain structures/systems has become possible due to advances in neuroimaging techniques. This Magnetic Resonance Imaging (MRI) study investigated if individual differences in these personality traits reflected structural variance in specific brain regions. A large sample of eighty five young adult participants completed the Three-dimensional Personality Questionnaire (TPQ) and had their brain imaged with MRI. A voxel-based correlation analysis was carried out between individuals' personality trait scores and grey matter volume values extracted from 3D brain scans. NS correlated positively with grey matter volume in frontal and posterior cingulate regions. HA showed a negative correlation with grey matter volume in orbito-frontal, occipital and parietal structures. RD was negatively correlated with grey matter volume in the caudate nucleus and in the rectal frontal gyrus. PER showed a positive correlation with grey matter volume in the precuneus, paracentral lobule and parahippocampal gyrus. These results indicate that individual differences in the main personality dimensions of NS, HA, RD and PER, may reflect structural variance in specific brain areas.

This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results. Criteria for the 3 variants of PPA-nonfluent/agrammatic, semantic, and logopenic-were developed by an international group of PPA investigators who convened on 3 occasions to operationalize earlier published clinical descriptions for PPA subtypes. Patients are first diagnosed with PPA and are then divided into clinical variants based on specific speech and language features characteristic of each subtype. Classification can then be further specified as "imaging-supported" if the expected pattern of atrophy is found and "with definite pathology" if pathologic or genetic data are available. The working recommendations are presented in lists of features, and suggested assessment tasks are also provided. These recommendations have been widely agreed upon by a large group of experts and should be used to ensure consistency of PPA classification in future studies. Future collaborations will collect prospective data to identify relationships between each of these syndromes and specific biomarkers for a more detailed understanding of clinicopathologic correlations. Neurology ® 2011;76:1-1 GLOSSARY AD ϭ Alzheimer disease; FTLD ϭ frontotemporal lobar degeneration; PPA ϭ primary progressive aphasia.

Background: Recent genetic results have indicated that the two major, classically distinct forms of psychosisschizophrenia and bipolar disordermay share causative factors in common. However it is not clear to what extent they may also have similar profiles of brain abnormality. We used meta-analytic techniques to generate and compare maps of brain structural abnormality in the large samples of patients with both disorders that have been studied using magnetic resonance imaging. Method: A systematic search was conducted for voxel-based morphometry studies examining gray matter in patients with schizophrenia or bipolar disorder. The anatomical distribution of the co-ordinates of gray matter differences was meta-analysed using Anatomical Likelihood Estimation. Results: Forty-two schizophrenia studies including 2058 patients with schizophrenia and 2131 comparison subjects were compared with fourteen bipolar studies including 366 patients with bipolar disorder and 497 comparison subjects. In schizophrenia, there were extensive gray matter deficits in frontal, temporal, cingulate and insular cortex and thalamus, and increased gray matter in the basal ganglia. In bipolar disorder, gray matter reductions were present in the anterior cingulate and bilateral insula. These substantially overlapped with areas of gray matter reduction in schizophrenia, except for a region of anterior cingulate where gray matter reduction was specific to bipolar disorder. Implications: In bipolar disorder studies there were consistent regional gray matter reductions in paralimbic regions (anterior cingulate and insula) implicated in emotional processing. Gray matter reductions in schizophrenia studies were more extensive and involved limbic and neocortical structures as well as the paralimbic regions affected in bipolar disorder.

Background: This study aims to investigate brain gray matter density (GMD) changes in adolescents with Internet addiction (IA) using voxel-based morphometry (VBM) analysis on high-resolution T1-weighted structural magnetic resonance images. Methods: Eighteen IA adolescents and 15 age-and gender-matched healthy controls took part in this study. High-resolution T1-weighted magnetic resonance imaging scans were performed on the two groups. VBM analysis was used to compare the GMD between the two groups. Results: Compared with healthy controls, IA adolescents had lower GMD in the left anterior cingulate cortex, left posterior cingulate cortex, left insula, and left lingual gyrus. Conclusions: Our findings suggested that brain structural changes were present in IA adolescents, and this finding may provide a new insight into the pathogenesis of IA.

Image registration is an important enabling technology in medical image analysis. The current emphasis is on development and validation of application-specific non-rigid techniques, but there is already a plethora of techniques and terminology in use. In this paper we discuss the current state of the art of non-rigid registration to put on-going research in context and to highlight current and future clinical applications that might benefit from this technology. The philosophy and motivation underlying non-rigid registration is discussed and a guide to common terminology is presented. The core components of registration systems are described and outstanding issues of validity and validation are confronted.

Cannabis abuse is related to impairments in a broad range of cognitive functions. However, studies on cannabis abuse in relation to brain structure are sparse and results are inconsistent, probably due to differences in imaging methodology, severity of cannabis abuse, and use of other substances. The goal of the current MRI study was to investigate brain morphology related to current and lifetime severity of cannabis use and dependence in heavy cannabis users without intensive use of other illicit drugs. Voxel-based morphometry was used to assess differences in regional grey and white matter volume between 33 heavy cannabis users and 42 matched controls. Within heavy cannabis users, grey and white matter volume was correlated with measures of cannabis use and dependence. Analyses were focused a priori on the orbitofrontal cortex, anterior cingulate cortex, striatum, amygdala, hippocampus, and cerebellum, regions implicated in substance dependence and/or with high cannabinoid receptor-1 concentrations. Regional grey matter volume in the anterior cerebellum was larger in heavy cannabis users. Within the group of heavy cannabis users, grey matter volume in the amygdala and hippocampus correlated negatively with the amount of cannabis use or dependence. No associations were found between white matter volume and measures of cannabis use or dependence. These findings indicate that associations between heavy cannabis use and altered brain structure are complex. Differential patterns of structural changes for various cannabis use levels imply that alterations in brain structure are associated with specific characteristics of cannabis use and dependence.

Therapeutic interventions that incorporate training in mindfulness meditation have become increasingly popular, but to date little is known about neural mechanisms associated with these interventions. Mindfulness-Based Stress Reduction (MBSR), one of the most widely used mindfulness training programs, has been reported to produce positive effects on psychological well-being and to ameliorate symptoms of a number of disorders. Here, we report a controlled longitudinal study to investigate pre-post changes in brain gray matter concentration attributable to participation in an MBSR program. Anatomical magnetic resonance (MR) images from 16 healthy, meditation-naïve participants were obtained before and after they underwent the 8-week program. Changes in gray matter concentration were investigated using voxel-based morphometry, and compared with a waiting list control group of 17 individuals. Analyses in a priori regions of interest confirmed increases in gray matter concentration within the left hippocampus. Whole brain analyses identified increases in the posterior cingulate cortex, the temporo-parietal junction, and the cerebellum in the MBSR group compared with the controls. The results suggest that participation in MBSR is associated with changes in gray matter concentration in brain regions involved in learning and memory processes, emotion regulation, self-referential processing, and perspective taking.

Early emotional stress is associated with a life-long burden of risk for later depression and stressful life events contribute to the development of depressive episodes. In this study we investigated whether childhood stress is associated with structural brain alterations in patients with major depression (MD). Forty-three patients with MD and 44 age as well as gender matched healthy control subjects were investigated using high-resolution magnetic resonance imaging (MRI). Region of interest analysis of the hippocampus, whole brain voxel-based morphometry (VBM) and assessment of childhood stress was carried out. Significantly smaller hippocampal white matter and prefrontal gray matter volume was observed in patients with MD compared to healthy controls. In particular left hippocampal white matter was smaller in patients, who had emotional childhood neglect, compared to those without neglect. For male patients this effect was seen in the left and right hippocampus. Moreover, physical neglect during childhood affected prefrontal gray matter volume in healthy subjects. Both emotional neglect and brain structural abnormalities predicted cumulative illness duration and there was a significant interaction between emotional neglect and prefrontal volumes as well as hippocampal white matter on the illness course. Childhood neglect resulted in hippocampal white matter changes in patients with major depression, pronounced at the left side and in males. Most interestingly, childhood stress and brain structure volumes independently predicted cumulative illness course. Subjects with both, structural brain changes and childhood emotional neglect seem to be at a very high risk to develop a more severe illness course.

Total brain volume accounts for about 16% of the variance in general intelligence scores (IQ), but how volumes of specific regions-of-interest (ROIs) relate to IQ is not known. We used voxel-based morphometry (VBM) in two independent samples to identify substantial gray matter (GM) correlates of IQ. Based on statistical conjunction of both samples (N = 47; P < 0.05 corrected for multiple comparisons), more gray matter is associated with higher IQ in discrete Brodmann areas (BA) including frontal (BA 10, 46, 9), temporal (BA 21, 37, 22, 42), parietal (BA 43 and 3), and occipital (BA 19) lobes and near BA 39 for white matter (WM). These results underscore the distributed neural basis of intelligence and suggest a developmental course for volume -IQ relationships in adulthood. D

Neural regions modulating prepulse inhibition (PPI) of the startle response, an operational measure of sensorimotor gating, are well established from animal studies using surgical and pharmacological procedures. The limbic and cortico-pallido-striato-thalamic circuitry is thought to be responsible for modulation of PPI in the rat. The involvement of this circuitry in human PPI is suggested by observations of deficient PPI in a number of neuropsychiatric disorders characterized by abnormalities at some level in this circuitry and recent functional neuroimaging studies in humans. The current study sought to investigate structural neural correlates of PPI in a sample of twentyfour right-handed, healthy subjects (10 men, 14 women). Subjects underwent magnetic resonance imaging (MRI) at 1.5 T and were assessed (off-line) on acoustic PPI using electromyographic recordings of the orbicularis oculi muscle beneath the right eye. Optimized volumetric voxel-based morphometry (VBM) implemented in SPM99 was used to investigate the relationship of PPI (prepulse onset-to-pulse onset interval 120 ms) to regional grey matter volumes, covarying for sex. Significant positive correlations were obtained between PPI and grey matter volume in the hippocampus extending to parahippocampal gyrus, basal ganglia including parts of putamen, globus pallidus, and nucleus accumbens, superior temporal gyrus, thalamus, and inferior frontal gyrus. These findings identify the relationship between PPI and grey matter availability on a highly spatially localized scale in brain regions shown to be activated in recent functional neuroimaging studies in association with PPI in healthy humans and demonstrate the validity of structural neuroimaging methods in delineating the neural mechanisms underlying human PPI. D

Background: Voxel-based morphometry (VBM) has been widely used to quantify structural brain changes associated with Major Depressive Disorder (MDD). While some consistent findings have been reported, individual studies have also varied with respect to the key brain regions affected by the illness, and how these abnormalities are related to patients' clinical characteristics. Here, we aimed to identify those brain regions that most consistently showed gray matter anomalies in MDD, and their clinical correlates, using meta-analytic techniques. Methods: A systematic search of VBM studies was applied in MDD. Signed differential mapping, a new coordinate based neuroimaging meta-analysis technique, was applied to data collated from a total of 23 studies comparing regional gray matter volumes of 986 MDD patients and 937 healthy controls. Results: Gray matter was significantly reduced in a confined cluster located in the rostral anterior cingulate cortex (ACC). There were also gray matter reductions in dorsolateral and dorsomedial prefrontal cortex and decrease in the latter region was evident in patients with multiple-episodes. Amygdala and parahippocampal gray matter volumes were significantly reduced in studies including patients with comorbid anxiety disorders, as well as in firstepisode/drug free samples. Conclusions: Gray matter reduction in rostral ACC was the most consistent finding in VBM studies of MDD. The evidence for reductions in other regions within fronto-subcortical and limbic regions was less consistent. The associations between these gray matter anomalies and clinical characteristics, particularly measures relating to illness duration, suggest that chronic MDD has a robust and deleterious, albeit spatially focal, effect on brain structure.

Numerous studies have begun to address how the brain's gray and white matter may be shaped by meditation. This research is yet to be integrated, however, and two fundamental questions remain: Is meditation associated with altered brain structure? If so, what is the magnitude of these differences? To address these questions, we reviewed and meta-analyzed 123 brain morphology differences from 21 neuroimaging studies examining ∼300 meditation practitioners. Anatomical likelihood estimation (ALE) meta-analysis found eight brain regions consistently altered in meditators, including areas key to meta-awareness (frontopolar cortex/BA 10), exteroceptive and interoceptive body awareness (sensory cortices and insula), memory consolidation and reconsolidation (hippocampus), self and emotion regulation (anterior and mid cingulate; orbitofrontal cortex), and intra-and interhemispheric communication (superior longitudinal fasciculus; corpus callosum). Effect size meta-analysis (calculating 132 effect sizes from 16 studies) suggests a global 'medium' effect size (Cohen'sd = 0.46;r = .19). Publication bias and methodological limitations are strong concerns, however. Further research using rigorous methods is required to definitively link meditation practice to altered brain morphology.

Background: Patients affected by schizophrenia show deficits in social cognition, with abnormal performance on tasks targeting theory of mind (ToM) and empathy (Emp). Brain imaging studies suggested that ToM and Emp depend on the activation of brain networks mainly localized at the superior temporal lobe and temporo-parietal junction. Methods: Participants included 24 schizophrenia patients and 20 control subjects. We used brain blood oxygen level dependent fMRI to study the neural responses to tasks targeting ToM and Emp. We then studied voxel-based morphometry of grey matter in areas where diagnosis influenced functional activation to both tasks. Outcomes were analyzed in the context of the general linear model, with global grey matter volume as nuisance covariate for structural MRI. Results: Patients showed worse performance on both tasks. We found significant effects of diagnosis on neural responses to the tasks in a wide cluster in right posterior superior temporal lobe , in smaller clusters in left temporo-parietal junction and temporal pole (BA 38 and 39), and in a white matter region adjacent to medial prefrontal cortex (BA 10). A pattern of double dissociation of the effects of diagnosis and task on neural responses emerged. Among these areas, grey matter volume was found to be reduced in right superior temporal lobe regions of patients. Conclusions: Functional and structural abnormalities were observed in areas affected by the schizophrenic process early in the illness course, and known to be crucial for social cognition, suggesting a biological basis for social cognition deficits in schizophrenia.

Using high-resolution magnetic resonance imaging and voxel-based morphometry in 41 healthy individuals, this study evaluated the association between the personality traits of extraversion and neuroticism, on the one hand, and individual di¡erences in localized brain volume and gray matter concentration, on the other, with a special focus on the amygdala. Extraversion was positively correlated with gray matter concentration in the left amygdala, whereas neuroticism was negatively correlated with gray matter concentration in the right amygdala. Given that neuroticism is a risk factor for depression, our ¢nding o¡ers one explanation as to why prior structural imaging studies of depressed patients (which did not control for personality) produced con£icting ¢ndings. Furthermore, our data are consistent with the view that amygdala reduction seen in depressed patients precedes the onset of the disease, rather than being a consequence of the illness. NeuroReport 16:1905^1908

Sex differences in human brain structure have repeatedly been described, but results are inconsistent. However, these studies hardly controlled for cycle phase of women or the use of hormonal contraceptives. Our study shows that these factors are not negligible, but have a considerable influence on human brain structure. We acquired high-resolution structural images from the brains of 14 men, 14 women, who did not use, and 14 women, who did use hormonal contraceptives. Women, who did not use hormonal contraceptives, were scanned twice, once during their early follicular and once during their mid-luteal cycle-phase.

Machiavellianism is a personality style marked by the use of such tactics as deception and manipulation so as to perform well and achieve power, status, or material wealth. Based on the assumption that Machiavellians are very sensitive to status seeking in social contexts, which leads over time to changes in neuroplasticity, we hypothesize and find that salespeople who score high versus low on the Mach IV Machiavellianism scale exhibit changes in gray matter volume in the following brain regions: basal ganglia, prefrontal cortex, insula, and hippocampus. A Voxel-Based Morphometry (VBM) advanced MRI technique is used to test the hypothesis on a sample of 43 healthy salespeople. Conjectures are made on the linkage between social psychological research on Machiavellianism and neuroscience research on the brain regions in question as they relate to social behavior.

Background: Childhood maltreatment represents a strong risk factor for the development of depression and posttraumatic stress disorder (PTSD) in later life. In the present study, we investigated the neurobiological underpinnings of this association. Since both depression and PTSD have been associated with increased amygdala responsiveness to negative stimuli as well as reduced hippocampal gray matter volume, we speculated that childhood maltreatment results in similar functional and structural alterations in previously maltreated but healthy adults.

Like language, music engagement is universal, complex and present early in life. However, $4% of the general population experiences a lifelong deficit in music perception that cannot be explained by hearing loss, brain damage, intellectual deficiencies or lack of exposure. This musical disorder, commonly known as tone-deafness and now termed congenital amusia, affects mostly the melodic pitch dimension. Congenital amusia is hereditary and is associated with abnormal grey and white matter in the auditory cortex and the inferior frontal cortex. In order to relate these anatomical anomalies to the behavioural expression of the disorder, we measured the electrical brain activity of amusic subjects and matched controls while they monitored melodies for the presence of pitch anomalies. Contrary to current reports, we show that the amusic brain can track quarter-tone pitch differences, exhibiting an early right-lateralized negative brain response. This suggests near-normal neural processing of musical pitch incongruities in congenital amusia. It is important because it reveals that the amusic brain is equipped with the essential neural circuitry to perceive fine-grained pitch differences. What distinguishes the amusic from the normal brain is the limited awareness of this ability and the lack of responsiveness to the semitone changes that violate musical keys. These findings suggest that, in the amusic brain, the neural pitch representation cannot make contact with musical pitch knowledge along the auditory-frontal neural pathway. Abbreviations: ERAN = early right anterior negativity; ERPs = event-related potentials; IFG = inferior frontal gyrus; MBEA = Montreal battery of evaluation of amusia; MRI = magnetic resonance imaging; VBM = voxel-based morphometry calculia, dysphasia and dyslexia, and is thought to result from a musical pitch disorder. In many laboratories, including our own, the test that is most diagnostic of amusia requires participants to detect out-of-key notes in conventional but unfamiliar melodies. A behavioural failure on this test is diagnostic because there is

Archaeological recording of structures and excavations in high mountain areas is greatly hindered by the scarce availability of both space, to transport material, and time. The Madriu-Perafita-Claror, InterAmbAr and PCR Mont Lozère high mountain projects have documented hundreds of archaeological structures and carried out many archaeological excavations. These projects required the development of a technique which could record both structures and the process of an archaeological excavation in a fast and reliable manner.

The combination of DGPS, close-range terrestrial stereophotogrammetry and voxel based GIS modelling offered a perfect solution since it helped in developing a strategy which would obtain all the required data on-site fast and with a high degree of precision. These data are treated off-site to obtain georeferenced orthoimages covering both the structures and the excavation process from which site and excavation plans can be created. The proposed workflow outputs also include digital surface models and volumetric models of the excavated areas from which topography and archaeological profiles were obtained by voxel-based GIS procedures. In this way, all the graphic recording required by standard archaeological practices was met.

Voxel-based-morphometry (VBM) is a whole-brain, unbiased technique for characterizing regional cerebral volume and tissue concentration differences in structural magnetic resonance images. We describe an optimized method of VBM to examine the effects of age on grey and white matter and CSF in 465 normal adults. Global grey matter volume decreased linearly with age, with a significantly steeper decline in males. Local areas of accelerated loss were observed bilaterally in the insula, superior parietal gyri, central sulci, and cingulate sulci. Areas exhibiting little or no age effect (relative preservation) were noted in the amygdala, hippocampi, and entorhinal cortex. Global white matter did not decline with age, but local areas of relative accelerated loss and preservation were seen. There was no interaction of age with sex for regionally specific effects. These results corroborate previous reports and indicate that VBM is a useful technique for studying structural brain correlates of ageing through life in humans.

The parieto-frontal integration theory (P-FIT) nominates several areas distributed throughout the brain as relevant for intelligence. This theory was derived from previously published studies using a variety of both imaging methods and tests of cognitive ability. Here we test this theory in a new sample of young healthy adults (N = 100) using a psychometric battery tapping fluid, crystallized, and spatial intelligence factors. High resolution structural MRI scans (3T) were obtained and analyzed with Voxel-based Morphometry (VBM). The main findings are consistent with the P-FIT, supporting the view that general intelligence (g) involves multiple cortical areas throughout the brain. Key regions include the dorsolateral prefrontal cortex, Broca's and Wernicke's areas, the somato-sensory association cortex, and the visual association cortex. Further, estimates of crystallized and spatial intelligence with g statistically removed, still share several brain areas with general intelligence, but also show some degree of uniqueness.

Recent research has examined anxiety and hyperactivity in the amygdala and the anterior hippocampus while processing aversive stimuli. In order to determine whether these functional differences have a structural basis, optimized voxel-based morphometry was used to study the relationship between gray matter concentration in the brain and scores on a Behavioral Inhibition System measure (the Sensitivity to Punishment scale) in a sample of 63 male undergraduates. Results showed a positive correlation between Sensitivity to Punishment scores and gray matter volume in the amygdala and the hippocampal formation, that is, in areas that . The neuropsychology of anxiety. Oxford: Oxford Medical Publications. associated with the Behavioral Inhibition System.

Learning is based on neuroplasticity, i.e. on the capability of the brain to adapt to new experiences. Different mechanisms of neuroplasticity have been described, ranging from synaptic remodeling to changes in complex neural circuitry. To further study the relationship between changes in neural activity and changes in gray matter density associated with learning, we performed a combined longitudinal functional and morphometric magnetic resonance imaging (MRI) study on healthy volunteers who learned to decipher Morse code. We investigated 16 healthy subjects using functional MR imaging (fMRI) and voxel-based morphometry (VBM) before and after they had learned to decipher Morse code. The same set of Morse-code signals was presented to participants pre-and post-training. We found an increase in task-specific neural activity in brain regions known to be critically involved in language perception and memory, such as the inferior parietal cortex bilaterally and the medial parietal cortex during Morse code deciphering. Furthermore we found an increase in gray matter density in the left occipitotemporal region, extending into the fusiform gyrus. Anatomically neighboring sites of functional and structural neuroplasticity were revealed in the left occipitotemporal/inferior temporal cortex, but these regions only marginally overlapped. Implications of this morpho-functional dissociation for learning concepts are discussed.

Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to healthy older subjects; (ii) investigate the association between naming and semantic knowledge in aMCI and AD; (iii) examine if the semantic impairment was present in different modalities; and (iv) study the relationship between semantic performance and grey matter volume using voxel-based morphometry. Results indicate that both naming and semantic knowledge of objects and famous people were impaired in aMCI and early AD groups, when compared to healthy age-and education-matched controls. Item-by-item analyses showed that anomia in aMCI and early AD was significantly associated with underlying semantic knowledge of famous people but not with semantic knowledge of objects. Moreover, semantic knowledge of the same concepts was impaired in both the visual and the verbal modalities. Finally, voxel-based morphometry analyses revealed that semantic impairment in aMCI and AD was associated with cortical atrophy in the anterior temporal lobe (ATL) region as well as in the inferior prefrontal cortex (IPC), some of the key regions of the semantic cognition network. These findings suggest that the semantic impairment in aMCI may result from a breakdown of semantic knowledge of famous people and objects, combined with difficulties in the selection, manipulation and retrieval of this knowledge.

Structural brain changes have been described in both mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, less is known about whether structural changes are detectable earlier, in the asymptomatic phase. Using voxel-based morphometry (VBM) and shape analyses of magnetic resonance imaging (MRI) data, we investigated structural brain differences between groups of healthy subjects, stratified by subsequent diagnoses of MCI or AD during a 10-year follow-up. Images taken at baseline, at least 4 years before any cognitive symptoms, showed that subjects with future cognitive impairment (preclinical AD and MCI) had reduced brain volume in medial temporal lobes, posterior cingulate/precuneus, and orbitofrontal cortex, compared with matched subjects who remained cognitively healthy for 10 years (HC). For only those subjects later diagnosed as AD, significantly greater atrophy at baseline was detected in the right medial temporal lobe, which was also confirmed by shape analysis of the right hippocampus in these subjects. Our results demonstrate that structural brain changes occur years before clinical cognitive decline in AD and are localized to regions affected by AD neuropathology.

Schizophrenia affects approximately 1% of the population and is associated with reductions in brain volume, but when these are first evident is unknown. Magnetic resonance imaging (MRI) has demonstrated abnormalities of brain structure, particularly of the temporal lobes, in schizophrenia. A study of brain structure in individuals destined to develop schizophrenia, before they do so, is crucial to understanding the illness. We used Voxel Based Morphometry (VBM) to map changes in Grey Matter Density (GMD) in 65 young adults at high risk of schizophrenia, for familial reasons, and 19 healthy young adults, over a period of approximately 2 years. All subjects were antipsychotic naive at both scans. No increases in GMD were found in any of the groups. Within the high-risk group significant declines in GMD were found in the temporal lobes, the right frontal lobe and right parietal lobe. In the control group a decline was found in the right gyrus rectus. No significant differences over time were found between any of the groups. Those individuals at high risk who had transient or isolated psychotic symptoms showed a different spatial pattern of reductions in GMD than those who did not in within group comparisons. In addition, those individuals at high risk who later developed schizophrenia also showed a different spatial pattern of reductions in GMD in the left temporal lobe and right cerebellum, from 2 to 3 years before they were diagnosed. These particular reductions may therefore be able to predict the later onset of schizophrenia. D

Brain development continues actively during adolescence. Previous MRI studies have shown complex patterns of apparent loss of grey matter (GM) volume and increases in white matter (WM) volume and fractional anisotropy (FA), an index of WM microstructure. In this longitudinal study (mean follow-up = 2.5 ± 0.5 years) of 24 adolescents, we used a voxel-based morphometry (VBM)-style analysis with conventional T1-weighted images to test for age-related changes in GM and WM volumes. We also performed tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) data to test for age-related WM changes across the whole brain. Probabilistic tractography was used to carry out quantitative comparisons across subjects in measures of WM microstructure in two fiber tracts important for supporting speech and motor functions (arcuate fasciculus [AF] and corticospinal tract [CST]). The whole-brain analyses identified agerelated increases in WM volume and FA bilaterally in many fiber tracts, including AF and many parts of the CST. FA changes were mainly driven by increases in parallel diffusivity, probably reflecting increases in the diameter of the axons forming the fiber tracts. FA values of both left and right AF (but not of the CST) were significantly higher at the end of the follow-up than at baseline. Over the same period, widespread reductions in the cortical GM volume were found. These findings provide imaging-based anatomical data suggesting that brain maturation in adolescence is associated with structural changes enhancing longdistance connectivities in different WM tracts, specifically in the AF and CST, at the same time that cortical GM exhibits synaptic "pruning".

Extraverted individuals are sociable, behaviorally active, and happy. We report data from a voxel based morphometry study investigating, for the first time, if regional volume in gray and white matter brain regions is related to extraversion. For both gray and white matter, all correlations between extraversion and regional brain volume were negative, i.e. the regions were larger in introverts. Gray matter correlations were found in regions that included the right prefrontal cortex and the cortex around the right temporo-parietal junction -regions that are known to be involved in behavioral inhibition, introspection, and social-emotional processing, e.g. evaluation of social stimuli and reasoning about the mental states of others. White matter correlations extended from the brainstem to widespread cortical regions, and were largely due to global effects, i.e. a larger total white matter volume in introverts. We speculate that these white matter findings may reflect differences in ascending modulatory projections affecting cortical regions involved in behavioral regulation. (L.J. Forsman). closely related to the corresponding constructs in other personality models, including Cattell's 16 PF and a third influential model: Eysenck's three-factor PEN model . Indeed, traits identical to or closely related to extraversion are probably identified in almost all personality models (see , for a review). Eysenck's approach to personality was pioneering in that he integrated psychometrical, behavioral, and neurobiological perspectives in a search for the biological basis of the main dimensions of personality . A fourth important and likewise biologically rooted personality model has been developed by . Cloninger's model is based on genetic, neurobiological and psychometric considerations and currently includes four temperament traits (harm avoidance, novelty seeking, reward dependence, and persistence) and three character traits (self-directedness, cooperativeness, and self-transcendence). Each of these traits shows substantial correlations with several factors of the five-factor model and the PEN models .

We investigated the relationship between prefrontal cortex (PFC) and hippocampal volume and executive functioning in patients with temporal lobe epilepsy (TLE). Prefrontal volume and hippocampal volume were studied using stereology in conjunction with point counting and voxel-based morphometry on MR images. Executive functioning was assessed using tests routinely incorporated into presurgical neuropsychological evaluation. Relative to 30 healthy controls, 43 patients (26 left, 17 right) with TLE had volume atrophy of the ipsilateral hippocampus and bilateral dorsal PFC. Performance on the working memory index of the Wechsler Memory Scale was positively correlated with the volume of all prefrontal regions, and the Controlled Oral Word Association Test with the left dorsal PFC, whole left PFC, and left hippocampus. Stroop Color-Word Interference performance was not related to volume of dorsal PFC. The ''extratemporal neuropsychological profile" frequently observed in patients with TLE may be due to extended damage to brain regions remote from the epileptogenic focus. In particular, volume atrophy of the dorsal PFC may account for deficits in executive functioning.

■ Abstract Brain abnormalities of schizophrenia probably consist of deviation related to the vulnerability and pathological changes in association with overt psychosis. We conducted a cross-sectional comparison in brain morphology between patients with overt schizophrenia and schizotypal disorder, a schizophrenia-spectrum disorder without florid psychotic episode. Voxelbased morphometry was applied to assess gray matter volume in 25 patients with schizophrenia, 25 patients with schizotypal disorder, and 50 healthy control subjects. In comparison with controls, schizophrenia patients showed gray matter reductions in the bilateral medial frontal, inferior frontal, medial temporal, and septal regions, and the left middle frontal, orbitofrontal, insula, and superior temporal regions, and an increased gray matter in the left basal ganglia. Schizotypal disorder patients showed reductions in the left inferior frontal, insula, superior temporal, and medial temporal regions. There was a significant reduction in the left orbitofrontal region of schizophrenia compared with schizotypal disorder. Gray matter reductions that are common to both patient groups such as those in the left medial temporal and inferior frontal regions may represent vulnerability to schizophrenia, and additional involvement of several frontal regions may be crucial to florid psychosis.

The development of musical skills by musicians results in specific structural and functional modifications in the brain. Surprisingly, no functional magnetic resonance imaging (fMRI) study has investigated the impact of musical training on brain function during long-term memory retrieval, a faculty particularly important in music. Thus, using fMRI, we examined for the first time this process during a musical familiarity task (i.e., semantic memory for music). Musical expertise induced supplementary activations in the hippocampus, medial frontal gyrus, and superior temporal areas on both sides, suggesting a constant interaction between episodic and semantic memory during this task in musicians. In addition, a voxel-based morphometry (VBM) investigation was performed within these areas and revealed that gray matter density of the hippocampus was higher in musicians than in nonmusicians. Our data indicate that musical expertise critically modifies long-term memory processes and induces structural and functional plasticity in the hippocampus.

Abstract
Background: Studying the distribution of anatomical abnormalities over the entire cortical surface can help identify key neural circuits implicated in generating symptoms of neuropsychiatric disorders. There is a significant inconsistency among studies investigating the neuroanatomy of Obsessive Compulsive Disorder (OCD) due to the confounding influence of comorbid depression, medication use and the lack of unbiased estimation of whole brain morphometric changes. It is also unknown whether the distinct surface anatomical properties of thickness, surface area and gyrification, which collectively contribute to grey matter volume, are independently affected in OCD.
Methods: The cortical maps of thickness, gyrification and surface areal change were acquired from 23 unmedicated OCD patients and 20 healthy controls using an unbiased whole brain surface based morphometric (SBM) method to detect regional changes in OCD. Subcortical structures were not assessed in the present study.
Results:  Patients showed a significant increase in the right inferior parietal cortical thickness. Significant increases in gyrification was also noted in the left insula, left middle frontal and left lateral occipital region extending to the precuneus and right supramarginal gyrus in OCD. Areal contraction/expansion maps revealed no significant regional differences between the patients and the controls. In patients, gyrification of the insula significantly predicted the symptom severity measured using Yale-Brown Obsessive-Compulsive Scale (YBOCS).
Conclusions:  An alteration in the cortical surface anatomy is an important feature of OCD seen in unmedicated samples that relates to the severity of the illness. The results underscore the presence of a neurodevelopmental aberration underlying the pathophysiology of OCD.
Key words: Surface Based Morphometry, Cortical Thickness, Gyrification, Surface Area, Insula, Obsessive Compulsive Disorder.

Recent research has examined anxiety and hyperactivity in the amygdala and the anterior hippocampus while processing aversive stimuli. In order to determine whether these functional differences have a structural basis, optimized voxel-based morphometry was used to study the relationship between gray matter concentration in the brain and scores on a Behavioral Inhibition System measure (the Sensitivity to Punishment scale) in a sample of 63 male undergraduates. Results showed a positive correlation between Sensitivity to Punishment scores and gray matter volume in the amygdala and the hippocampal formation, that is, in areas that Gray, J.A., and McNaughton, N.J. (2000). The neuropsychology of anxiety. Oxford: Oxford Medical Publications. associated with the Behavioral Inhibition System.

Background: In animals, dendritic arborization and levels of brain derived neurotrophic factor are positively associated with intake of the omega-3 fatty acids. Here, we test whether omega-3 fatty acid intake in humans varies with individual differences in gray matter volume, an in vivo, systems-level index of neuronal integrity. Methods: Fifty-five healthy adults completed two 24 h dietary recall interviews. Intake of long-chain omega-3 fatty acids was categorized by tertiles. Regional gray matter volumes in a putative emotional brain circuitry comprised of the anterior cingulate cortex (ACC), amygdala and hippocampus were calculated using optimized voxel-based morphometry on high-resolution structural magnetic resonance images. Results: Region of interest analyses revealed positive associations between reported dietary omega-3 intake and gray matter volume in the subgenual ACC, the right hippocampus and the right amygdala, adjusted for total gray matter volume of brain. Unconstrained whole-brain analyses confirmed that higher intake of omega-3 fatty acids was selectively associated with increased greater gray matter volume in these and not other regions. Conclusions: Higher reported consumption of the long-chain omega-3 fatty acids is associated with greater gray matter volume in nodes of a corticolimbic circuitry supporting emotional arousal and regulation. Such associations may mediate previously observed effects of omega-3 fatty acids on memory, mood and affect regulation.

Music is a highly complex and versatile stimulus for the brain that engages many temporal, frontal, parietal, cerebellar, and subcortical areas involved in auditory, cognitive, emotional, and motor processing. Regular musical activities have been shown to effectively enhance the structure and function of many brain areas, making music a potential tool also in neurological rehabilitation. In our previous randomized controlled study, we found that listening to music on a daily basis can improve cognitive recovery and improve mood after an acute middle cerebral artery stroke. Extending this study, a voxel-based morphometry (VBM) analysis utilizing cost function masking was performed on the acute and 6-month post-stroke stage structural magnetic resonance imaging data of the patients (n = 49) who either listened to their favorite music [music group (MG), n = 16] or verbal material [audio book group (ABG), n = 18] or did not receive any listening material [control group (CG), n = 15] during the 6month recovery period. Although all groups showed significant gray matter volume (GMV) increases from the acute to the 6-month stage, there was a specific network of frontal areas [left and right superior frontal gyrus (SFG), right medial SFG] and limbic areas [left ventral/subgenual anterior cingulate cortex (SACC) and right ventral striatum (VS)] in patients with left hemisphere damage in which the GMV increases were larger in the MG than in the ABG and in the CG. Moreover, the GM reorganization in the frontal areas correlated with enhanced recovery of verbal memory, focused attention, and language skills, whereas the GM reorganization in the SACC correlated with reduced negative mood. This study adds on previous results, showing that music listening after stroke not only enhances behavioral recovery, but also induces fine-grained neuroanatomical changes in the recovering brain. Structural changes induced by daily music listening in the recovering brain after middle cerebral artery stroke: a voxel-based morphometry study. Front. Hum. Neurosci. 8:245.

Experimental animal studies have shown that physical exercise, associated with planning and execution of complex movements, are related to changes in brain structure. In humans, changes in cortical tissue density in relation to physical activity are yet to be fully determined and quantified. We investigated differences on gray matter volume in judo players by using voxel-based morphometry. Comparison between a group of eight internationally competitive judo players and a group of 18 healthy controls showed a significantly higher gray matter tissue density in brain areas of judo players. 11 12 13 14 15

The ability to decode letters into language sounds is essential for reading success, and accurate identification of children at high risk for decoding impairment is critical for reducing the frequency and severity of reading impairment. We examined the utility of behavioral (standardized tests), and functional and structural neuroimaging measures taken with children at the beginning of a school year for predicting their decoding ability at the end of that school year. Specific patterns of brain activation during phonological processing and morphology, as revealed by voxel-based morphometry (VBM) of gray and white matter densities, predicted later decoding ability. Further, a model combining behavioral and neuroimaging measures predicted decoding outcome significantly better than either behavioral or neuroimaging models alone. Results were validated using cross-validation methods. These findings suggest that neuroimaging methods may be useful in enhancing the early identification of children at risk for poor decoding and reading skills.

Previous studies suggest organizing effects of sex hormones on brain structure during early life and puberty, yet little is known about the adult period. The aim of the present study was to elucidate the role of 17βestradiol, progesterone, and testosterone on cortical sex differences in grey matter volume (GM) of the adult human brain. To assess sexual dimorphism, voxel-based morphometry (VBM) was applied on structural magnetic resonance images of 34 healthy, young adult humans (17 women, 17 men, 26.6 ± 5 years) using analyses of covariance. Subsequently, circulating levels of sex hormones were associated with regional GM using linear regression analyses. After adjustment for sex and total GM, significant associations of regional GM and 17β-estradiol were observed in the left inferior frontal gyrus (β = 0.39, p = 0.02). Regional GM was inversely associated with testosterone in the left inferior frontal gyrus (β = −0.16, p = 0.04), and with progesterone in the right temporal pole (β = −0.39, p = 0.008). Our findings indicate that even in young adulthood, sex hormones exert organizing effects on regional GM. This might help to shed further light on the underlying mechanisms of both functional diversities and congruence between female and male brains.

■ Cognitive control allows humans to overrule and inhibit habitual responses to optimize performance in challenging situations. Contradicting traditional views, recent studies suggest that cognitive control processes can be initiated unconsciously. To further capture the relation between consciousness and cognitive control, we studied the dynamics of inhibitory control processes when triggered consciously versus unconsciously in a modified version of the stop task. Attempts to inhibit an imminent response were often successful after unmasked (visible) stop signals. Masked (invisible) stop signals rarely succeeded in instigating overt inhibition but did trigger slowing down of response times. Masked stop signals elicited a sequence of dis-tinct ERP components that were also observed on unmasked stop signals. The N2 component correlated with the efficiency of inhibitory control when elicited by unmasked stop signals and with the magnitude of slowdown when elicited by masked stop signals. Thus, the N2 likely reflects the initiation of inhibitory control, irrespective of conscious awareness. The P3 component was much reduced in amplitude and duration on masked versus unmasked stop trials. These patterns of differences and similarities between conscious and unconscious cognitive control processes are discussed in a framework that differentiates between feedforward and feedback connections in yielding conscious experience.

Sex steroids exert important organizational effects on brain structure. Early in life, they are involved in brain sexual differentiation. During puberty, sex steroid levels increase considerably. However, to which extent sex steroid production is involved in structural brain development during human puberty remains unknown. The relationship between pubertal rises in testosterone and estradiol levels and brain structure was assessed in 37 boys and 41 girls (10-15 years). Global brain volumes were measured using volumetric-MRI. Regional gray and white matter were quantified with voxel-based morphometry (VBM), a technique which measures relative concentrations ('density') of gray and white matter after individual global differences in size and shape of brains have been removed.

Language Structural plasticity VBM a b s t r a c t While functional changes linked to second language learning have been subject to extensive investigation, the issue of learning-dependent structural plasticity in the fields of bilingualism and language comprehension has so far received less notice. In the present study we used voxel-based morphometry to monitor structural changes occurring within five months of second language learning. Native English-speaking exchange students learning German in Switzerland were examined once at the beginning of their stay and once about five months later, when their German language skills had significantly increased. We show that structural changes in the left inferior frontal gyrus are correlated with the increase in second language proficiency as measured by a paper-and-pencil language test. Contrary to the increase in proficiency and grey matter, the absolute values of grey matter density and second language proficiency did not correlate (neither on first nor on second measurement). This indicates that the individual amount of learning is reflected in brain structure changes, regardless of absolute proficiency. ª

Voxel-based morphometry (VBM) is a popular tool for mapping neuroanatomical changes in schizophrenia patients. Several recent meta-analyses have identified the brain regions in which patients most consistently show grey matter reductions, although they have not examined whether such changes reflect differences in grey matter concentration (GMC) or grey matter volume (GMV). These measures assess different aspects of grey matter integrity, and may therefore reflect different pathological processes. In this study, we used the Anatomical Likelihood Estimation procedure to analyse significant differences reported in 37 VBM studies of schizophrenia patients, incorporating data from 1646 patients and 1690 controls, and compared the findings of studies using either GMC or GMV to index grey matter differences. Analysis of all studies combined indicated that grey matter reductions in a network of frontal, temporal, thalamic and striatal regions are among the most frequently reported in literature. GMC reductions were generally larger and more consistent than GMV reductions, and were more frequent in the insula, medial prefrontal, medial temporal and striatal regions. GMV reductions were more frequent in dorso-medial frontal cortex, and lateral and orbital frontal areas. These findings support the primacy of frontal, limbic, and subcortical dysfunction in the pathophysiology of schizophrenia, and suggest that the grey matter changes observed with MRI may not necessarily result from a unitary pathological process.

In this work we present the results of computer-based techniques employed to obtain volumetric measures of the whole brain, lateral ventricle, and hippocampi. Research has shown that pathological changes in these three areas have strong correlations with Alzheimer’s disease. Our adopted methods seek to provide consistent measures of these pathologies by applying advanced image processing techniques to quantify volumetric changes of the aforemen-tioned structures from longitudinal brain MRIs. Our cohort provided by the MICCAI NIBAD 2012 workshop is a longitudinal data set made up of 69 sub-jects whose disease states and scan time points are blinded to the challenge par-ticipants. The results we obtained after employing state-of-the-art medical im-age processing algorithms are evaluated by investigating the volume change with respect to the baseline MRI scans. We report the largest volume change measured for the whole data set for the three regions (whole brain, lateral ven-tricle and hippocampus). While our whole brain atrophy and lateral ventricle enlargement results reach close agreement with those reported in the literature, the hippocampus atrophy measure presents uncertainties. Generally, our the re-ported results correlate with the fact that with time, there is loss in volume of the brain parenchyma, enlargement of the lateral ventricle and loss in volume of the hippocampus

Tinnitus, the phantom perception of sound, is a frequent disorder that causes significant morbidity. The pathophysiological mechanisms involved in tinnitus generation are still under exploration. Electrophysiological and functional neuroimaging studies give increasing evidence for abnormal functioning both within the central auditory system and in non-auditory brain areas. However, observed changes show great variability, hence lacking a conclusive picture. Recently, structural alterations in the central nervous system have been detected in tinnitus patients by voxel-based morphometry (VBM). Here we aimed to replicate these findings in an independent study sample. We performed structural MRI scans in 28 tinnitus patients with normal audiometry and used VBM to compare results with a control group, matched for age, sex and hearing status. As major results we found significant grey matter decreases in the tinnitus group in the right inferior colliculus and in the left hippocampus. However, neither changes in the subcallosal area nor in the thalamus as described recently have been observed. Our results underscore that (1.) VBM allows to detect structural alterations in tinnitus patients, which seem to be related to tinnitus pathophysiology. (2.) Both, areas in the auditory and the limbic system are involved giving further evidence for the important role of the limbic system in the pathophysiology of tinnitus. (3.) Even groups with similar clinical characteristics might differ in the underlying neurobiological changes.

Functional amnesia (FA) is characterized by an extensive retrograde memory loss in the absence of detectable structural brain damage. The two main hypotheses put forward to explain this disturbance involve a global retrieval deficit (affecting both pre-and post-onset memories) and a selective inability to explicitly retrieve pre-onset memories.

We used voxel-based morphometry (VBM), an automatic whole-brain MR image analysis technique, to investigate gray matter abnormalities in patients with temporal lobe epilepsy (TLE), in whom hippocampal atrophy (HA) was demonstrated by application of the Cavalieri method of modern design stereology. VBM results (P < 0.05, corrected) indicated preferential gray matter concentration (GMC) reduction in anterior hippocampus in patients with left HA and posterior hippocampus in patients with right HA. GMC reduction was also found in right dorsal prefrontal cortex in left and right HA patients. Prefrontal atrophy may be due to epileptiform excitotoxic discharges from the reciprocally connected pathological hippocampus, and may be the underlying biological cause for executive dysfunction in patients with TLE. GMC excess in ipsilateral parahippocampal, cerebellar, and pericallosal regions was common to both left and right HA groups relative to controls, and is hypothesized to reflect diminished gray-white matter demarcation, underlying white matter atrophy, or structural displacement due to cerebrospinal fluid expansion. However, bilateral temporal lobe GMC excess was observed in left HA patients, while ipsilateral temporal lobe GMC excess was observed in right HA patients. This work demonstrates methodological consistency between automated VBM and manual stereological analysis of the hippocampus in group comparisons, indicates widespread extrahippocampal gray matter abnormalities in unilateral HA, and suggests that there may be inherent differences in the effect of TLE on temporal lobe structures depending on the side of HA. © 2002 Elsevier Science (USA)