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We investigated associations of glycemic measures, and insulin resistance and secretion measures with hippocampal and subfield volumes. In this cross-sectional study, 7400 community-dwelling participants underwent brain MRI and health checkups between 2016 and 2018. Hemoglobin A 1c (HbA 1c ), glycated albumin (GA), homeostasis model assessment for insulin resistance (HOMA-IR), and HOMA of percent β-cell function (HOMA-β) were evaluated. The associations of each measure with a smaller volume of the hippocampus and twelve hippocampal subfields were investigated. As a result, higher HbA 1c or GA and lower HOMA-β levels were significantly associated with smaller volumes in multiple hippocampal subfields. Furthermore, even when we analyzed non-diabetic individuals, substantial associations remained between higher GA or lower HOMA-β levels and smaller volumes of the whole hippocampus or the fimbria. Our findings indicate that postprandial glucose fluctuations, postprandial hyperglycemia, and low insulin secretion have a specific effect on the development of smaller hippocampal volume, suggesting that primary prevention of diabetes and/or sufficient glucose control are important for the prevention of dementia., (© 2024. The Author(s).)

Background: Enlarged perivascular spaces (EPVS) of the brain may be involved in dementia, such as Alzheimer's disease and cerebral small vessel disease (CSVD). Hypertension has been reported to be a risk factor for dementia and CSVD, but the association between blood pressure (BP) and perivascular spaces is still unclear. The aim of this study was to determine the association between BP and EPVS volumes and to examine the interactions of relevant factors., Methods: A total of 9296 community-dwelling subjects aged ≥65 years participated in a brain magnetic resonance imaging and health status screening examination. Perivascular volume was measured using a software package based on deep learning that was developed in-house. The associations between BP and EPVS volumes were examined by analysis of covariance and multiple regression analysis., Results: Mean EPVS volumes increased significantly with rising systolic and diastolic BP levels ( P for trend = .003, P for trend<.001, respectively). In addition, mean EPVS volumes increased significantly for every 1-mmHg-increment in systolic and diastolic BPs (both P values <.001). These significant associations were still observed in the sensitivity analysis after excluding subjects with dementia., Conclusions: The present data suggest that higher systolic and diastolic BP levels are associated with greater EPVS volumes in cognitively normal older people., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Toshiharu Ninomiya received funds from the Japan Agency for Medical Research and Development and Suntory Holdings Limited (Osaka, Japan). The other authors assert that they have no competing interests.

Background: Not only gray matter lesions (GMLs) but also white matter lesions (WMLs) can play important roles in the pathology of Alzheimer's disease (AD). The progression of cognitive impairment (CI) and behavioral and psychological symptoms of dementia (BPSD) might be caused by a concerted effect of both GML and WML., Objective: This study aimed to investigate the association between GML and WML and how they are involved in the symptoms of CI and BPSD in dementia patients by means of imaging technology., Methods: Patients in our memory clinic, who were diagnosed with AD-type dementia or amnestic mild cognitive impairment (aMCI) and had undergone both single-photon emission computed tomography (SPECT) and brain MRI, were consecutively enrolled ( n = 156; 61 males and 95 females; 79.8 ± 7.4 years old). Symptoms of CI and BPSD were obtained from patients' medical records. For the analysis of GMLs and WMLs, SPECT data and MRI T1-weighted images were used, respectively. This study followed the Declaration of Helsinki, and all procedures were approved by the institutional ethics committee., Results: According to a multivariate analysis, disorientation and disturbed attention demonstrated a relationship between the precuneus and WMLs in both hemispheres. Hyperactivity in BPSD showed multiple correlations between GMLs on both sides of the frontal cortex and WMLs. Patients with aMCI presented more multiple correlations between GMLs and WMLs compared with those with AD-type dementia regarding dementia symptoms including BPSD., Conclusion: The interaction between GMLs and WMLs may vary depending on the symptoms of CI and BPSD. Hyperactivity in BPSD may be affected by the functional relationship between GMLs and WMLs in the left and right hemispheres. The correlation between GMLs and WMLs may be changing in AD-type dementia and aMCI.

Introduction: Present study was to investigate hs-CRP concentration, brain structural alterations, and cognitive function in the context of AD [Subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD]., Methods: We retrospectively included 313 patients (Mean age = 76.40 years, 59 SCD, 101 MCI, 153 AD) in a cross-sectional analysis and 91 patients (Mean age = 75.83 years, 12 SCD, 43 MCI, 36 AD) in a longitudinal analysis. Multivariable linear regression was conducted to investigate the relationship between hs-CRP concentration and brain structural alterations, and cognitive function, respectively., Results: Hs-CRP was positively associated with gray matter volume in the left fusiform (β = 0.16, p FDR = 0.023) and the left parahippocampal gyrus (β = 0.16, p FDR = 0.029). Post hoc analysis revealed that these associations were mainly driven by patients with MCI and AD. The interaction of diagnosis and CRP was significantly associated with annual cognitive changes (β = 0.43, p = 0.008). Among these patients with AD, lower baseline CRP was correlated with greater future cognitive decline ( r = -0.41, p = 0.013)., Conclusion: Our study suggests that increased hs-CRP level may exert protective effect on brain structure alterations and future cognitive changes among patients already with cognitive impairment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Tatewaki, Nakase, Liu, Tomita, Thyreau, Zheng, Muranaka, Takano, Nagasaka and Taki.)

The Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study (TMM Brain MRI Study) was established to collect multimodal information through neuroimaging and neuropsychological assessments to evaluate the cognitive function and mental health of residents who experienced the Great East Japan Earthquake (GEJE) and associated tsunami. The study also aimed to promote advances in personalized healthcare and medicine related to mental health and cognitive function among the general population. We recruited participants for the first (baseline) survey starting in July 2014, enrolling individuals who were participating in either the TMM Community-Based Cohort Study (TMM CommCohort Study) or the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). We collected multiple magnetic resonance imaging (MRI) sequences, including 3D T1-weighted sequences, magnetic resonance angiography (MRA), diffusion tensor imaging (DTI), pseudo-continuous arterial spin labeling (pCASL), and three-dimensional fluid-attenuated inversion recovery (FLAIR) sequences. To assess neuropsychological status, we used both questionnaire- and interview-based rating scales. The former assessments included the Tri-axial Coping Scale, Impact of Event Scale in Japanese, Profile of Mood States, and 15-item Depression, Anxiety, and Stress Scale, whereas the latter assessments included the Mini-Mental State Examination, Japanese version. A total of 12,164 individuals were recruited for the first (baseline) survey, including those unable to complete all assessments. In parallel, we returned the MRI results to the participants and subsequently shared the MRI data through the TMM Biobank. At present, the second (first follow-up) survey of the study started in October 2019 is underway. In this study, we established a large and comprehensive database that included robust neuroimaging data as well as psychological and cognitive assessment data. In combination with genomic and omics data already contained in the TMM Biobank database, these data could provide new insights into the relationships of pathological processes with neuropsychological disorders, including age-related cognitive impairment., Competing Interests: None, (Copyright © Japan Medical Association.)

Background: Atrial fibrillation (AF) is a strong risk factor for Alzheimer's disease (AD) independent of ischemic stroke. However, the clinicopathological impact of AF on the severity of AD has not been well elucidated. We aimed to investigate the clinical differences between dementia patients with AF and those without AF by means of imaging data., Methods: Following approval from the institutional ethics committee, patients with newly diagnosed AD or amnestic mild cognitive impairment (aMCI) were retrospectively screened (n = 170, 79.5 ± 7.4 years old). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Based on the MRI data, the cerebral volume, cerebral microbleeds (CMBs), periventricular white matter lesions (WMLs), and deep WMLs were evaluated. The regional cerebral blood flow (rCBF) was measured using 123 I-IMP SPECT., Results: Of the patients, 14 (8.2%) and 156 (91.8%) had AF (AF group) and sinus rhythm (SR group), respectively. The AF group had significantly lower MMSE scores than the SR group (average [standard deviation (SD)]: 19.4 [4.4] and 22.0 [4.4], respectively; p = 0.0347). Cerebral volume and CMBs did not differ between the two groups. The periventricular WMLs, but not the deep WMLs, were significantly larger in the AF group than in the SR group (mean [SD] mL: 6.85 [3.78] and 4.37 [3.21], respectively; p = 0.0070). However, there was no significant difference in rCBF in the areas related to AD pathology between the two groups., Conclusion: AD and aMCI patients with AF showed worse cognitive decline along with larger periventricular WMLs compared to those with SR, although the reduction of rCBF was not different between patients with AF and SR. The white matter lesions may be a more important pathology than the impairment of cerebral blood flow in dementia patients with AF. A larger study is needed to confirm our findings in the future., (© 2023. The Author(s).)

Background and Purpose: In terms of the gut-brain axis, constipation has been considered to be an important factor of neurodegenerative diseases, although the exact mechanism is still controversial. Herein, we aimed to investigate the contribution of constipation to the progression of dementia in a retrospective study., Methods: Patients of Alzheimer's disease(AD) and amnestic mild cognitive impairment were consecutively screened between January 2015 and December 2020, and those of whom brain MRI and neuropsychological tests were performed twice were enrolled in this study. Participants were classified into with constipation (Cons[+], n = 20) and without constipation (Cons[-], n = 64) groups. Laboratory data at the first visit were used. Regression analysis was performed in MMSE, ADAS-Cog, and the volumes of hippocampus on MRI-MPRAGE images and deep white matter lesions (DWMLs) on MRI-FLAIR images obtained at two different time points., Results: The main finding was that the Cons[+] group showed 2.7 times faster decline in cognitive impairment compared with the Cons[-] group, that is, the liner coefficients of ADAS-Cog were 2.3544 points/year in the Cons[+] and 0.8592 points/year in the Cons[-] groups. Ancillary, changes of DWMLs showed significant correlation with the time span (p < 0.01), and the liner coefficients of DWMLs were 24.48 ml/year in the Cons[+] and 14.83 ml/year in the Cons[-] group, although annual rate of hippocampal atrophy was not different between the two groups. Moreover, serum homocysteine level at baseline was significantly higher in the Cons[+] group than Cons[-] group (14.6 ± 6.4 and 11.5 ± 4.2 nmol/ml, respectively: p = 0.03)., Conclusion: There is a significant correlation between constipation and faster progression of AD symptoms along with expansion of DWMLs., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

White matter lesions (WML) commonly occur in older brains and are quantifiable on MRI, often used as a biomarker in Aging research. Although algorithms are regularly proposed that identify these lesions from T2-fluid-attenuated inversion recovery (FLAIR) sequences, none so far can estimate lesions directly from T1-weighted images with acceptable accuracy. Since 3D T1 is a polyvalent and higher-resolution sequence, it could be beneficial to obtain the distribution of WML directly from it. However a serious difficulty, both for algorithms and human, can be found in the ambiguities of brain signal intensity in T1 images. This manuscript shows that a cross-domain ConvNet (Convolutional Neural Network) approach can help solve this problem. Still, this is non-trivial, as it would appear to require a large and varied dataset (for robustness) labelled at the same high resolution (for spatial accuracy). Instead, our model was taught from two-dimensional FLAIR images with a loss function designed to handle the super-resolution need. And crucially, we leveraged a very large training set for this task, the recently assembled, multi-sites Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) cohort. We describe the two-step procedure that we followed to handle such a large number of imperfectly labeled samples. A large-scale accuracy evaluation conducted against FreeSurfer 7, and a further visual expert rating revealed that WML segmentation from our ConvNet was consistently better. Finally, we made a directly usable software program based on that trained ConvNet model, available at https://github.com/bthyreau/deep-T1-WMH., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Altruistic social activity, such as giving support to others, has shown protective benefits on dementia risk and cognitive decline. However, the pathological mechanism is unclear. In the present study, we investigated the association between altruistic social activity and brain regional gray matter. Furthermore, to explore the psychological interplay in altruistic social activity, we tested mediating effect of depressive symptoms on brain regional gray matter. We performed a cross-sectional voxel-based morphology (VBM) analysis including 8 695 old adults (72.9 ± 6.1 years) from Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) Cohort. We measured altruistic social activities by self-report questionnaires, depressive symptoms by Geriatric Depression Scale (GDS)-short version. We employed the whole-brain VBM method to detect relevant structural properties related to altruistic social activity. We then performed multiple regression models to detect the mediating effect of depressive symptoms on particular brain regional gray matter volume while adjusting possible physical and social lifestyle covariables. We found that altruistic social activity is associated with larger gray matter volume in posterior insula, middle cingulate gyrus, hippocampus, thalamus, superior temporal gyrus, anterior orbital gyrus, and middle occipital gyrus. Depressive symptoms mediated over 10% on altruistic social activity and hippocampus volume, over 20% on altruistic social activity and cingulate gyrus volume. Our results indicated that altruistic social activity might preserve brain regional gray matter which are sensitive to aging and cognitive decline. Meanwhile, this association may be explained by indirect effect on depressive symptoms, suggesting that altruistic social activity may mitigate the neuropathology of dementia., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Physical frailty has been associated with adverse outcomes such as dementia. However, the underlying structural brain abnormalities of physical frailty are unclear. We investigated the relationship between physical frailty and structural brain abnormalities in 670 cognitively unimpaired individuals (mean age 70.1 years). Total brain volume (TBV), hippocampal volume (HV), total white matter hypointensities volume (WMHV), and estimated total intracranial volume (eTIV) on the 3D T1-weighted images were automatically computed using FreeSurfer software. Participants were divided into two states of physical frailty (robust vs. prefrail) based on the revised Japanese version of the Cardiovascular Health Study criteria. The multivariable-adjusted mean values of the TBV-to-eTIV ratio was significantly decreased, whereas that of the WMHV-to-eTIV ratio was significantly increased in the prefrail group compared with the robust group. Slowness, one of the components of physical frailty, was significantly associated with reduced TBV-to-eTIV and HV-to-eTIV ratios, and slowness and weakness were significantly associated with an increased WMHV-to-eTIV ratio. Our results suggest that the prefrail state is significantly associated with global brain atrophy and white matter hypointensities. Furthermore, slowness was significantly associated with hippocampal atrophy., (© 2022. The Author(s).)

Atrial fibrillation (AF) predisposes patients to develop cognitive decline and dementia. Clinical and epidemiological data propose that catheter ablation may provide further benefit to improve neurocognitive function in patients with AF, but the underlying mechanism is poorly available. Here, we conducted a pilot prospective study to investigate whether AF ablation can alter regional cerebral blood flow (rCBF) and brain microstructures, using multimodal magnetic resonance imaging (MRI) technique. Eight patients (63 ± 7 years) with persistent AF underwent arterial-spin labeling (ASL) perfusion, 3D T1-structural images and cognitive test batteries before and 6 months after intervention. ASL and structural MR images were spatially normalized, and the rCBF and cortical thickness of different brain areas were compared between pre- and 6-month post-treatment. Cognitive-psychological function was improved, and rCBF was significantly increased in the left posterior cingulate cortex (PCC) ( p = 0.013), whereas decreased cortical thickness was found in the left posterior insular cortex ( p = 0.023). Given that the PCC is a strategic site in the limbic system, while the insular cortex is known to play an important part in the central autonomic nervous system, our findings extend the hypothesis that autonomic system alterations are an important mechanism explaining the positive effect of AF ablation on cognitive function.

Nutritional supplementation with medium-chain triglycerides (MCTs) has the potential to increase memory function in elderly patients with frailty and dementia. Our aim was to investigate the effects of MCT on cognitive and gait functions and their relationships with focal brain metabolism and functional connectivity even in healthy older adults. Participants were blindly randomized and allocated to two groups: 18 g/day of MCT oil and matching placebo formula (control) administered as a jelly stick (6 g/pack, ingested three times a day). Gait analysis during the 6-m walk test, cognition, brain focal glucose metabolism quantified by 18 F-fluorodeocyglucose positron emission tomography, and magnetic resonance imaging-based functional connectivity were assessed before and after a 3-month intervention. Sixty-three healthy, normal adults (females and males) were included. Compared with the control group, the MCT group showed better balance ability, as represented by the lower Lissajous index (23.1 ± 14.4 vs. 31.3 ± 18.9; P < 0.01), although no time × group interaction was observed in cognitive and other gait parameters. Moreover, MCT led to suppressed glucose metabolism in the right sensorimotor cortex compared with the control (P < 0.001), which was related to improved balance (r = 0.37; P = 0.04) along with increased functional connectivity from the ipsilateral cerebellar hemisphere. In conclusion, a 3-month MCT supplementation improves walking balance by suppressing glucose metabolism, which suggests the involvement of the cerebro-cerebellar network. This may reflect, at least in part, the inverse reaction of the ketogenic switch as a beneficial effect of long-term MCT dietary treatment., (© 2022. The Author(s), under exclusive licence to American Aging Association.)

Background : Decreased bone mineral density (BMD) was associated with poorer cognitive function and increased risk of Alzheimer's disease (AD). However, objective evidence for the relationship between osteoporosis and AD in humans has not been extensively described. Objectives : We aimed to evaluate the relationships between BMD and the cortical volumes of brain regions vulnerable to AD; hippocampus, parahippocampal gyrus, precuneus, posterior cingulate, and angular gyrus, using voxel-based morphometry (VBM), to investigate the association between bone loss and AD. Methods : A cohort of 149 consecutive elderly participants who complained of memory disturbance underwent high-resolution structural brain magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA). We used SPM12 software to conduct a voxel-based multiple regression analysis to examine the association between femoral neck BMD values and regional gray matter volume (rGMV) on structural T1-weighted MRI. Results : After adjusting for subject age, gender, total brain volume (TBV), and mini-mental state examination (MMSE) scores, the multiple regression analysis showed significant correlations between BMD loss and rGMV decline in the left precuneus, which is an important neural network hub vulnerable to AD. Conclusion : These data suggest that the bone and brain communicate with each other, as in "bone-brain crosstalk," and that control of BMD factors could contribute to cognitive function and help prevent AD., (Copyright © 2020 Takano, Tatewaki, Mutoh, Morota, Matsudaira, Thyreau, Nagasaka, Odagiri, Yamamoto, Arai and Taki.)

The parcellation of the human cortex into meaningful anatomical units is a common step of various neuroimaging studies. There have been multiple successful efforts to process magnetic resonance (MR) brain images automatically and identify specific anatomical regions, following atlases defined from cortical landmarks. Those definitions usually rely first on a high-quality brain surface reconstruction. On the other hand, when high accuracy is not a requirement, simpler methods based on warping a probabilistic atlas have been widely adopted. Here, we develop a cortical parcellation method for MR brain images based on Convolutional Neural Networks (ConvNets), a machine-learning method, with the goal of automatically transferring the knowledge obtained from surface analyses onto something directly applicable on simpler volume data. We train a ConvNet on a large (thousand) set of cortical ribbons of multiple MRI cohorts, to reproduce parcellations obtained from a surface method, in this case FreeSurfer. Further, to make the model applicable in a broader context, we force the model to generalize to unseen segmentations. The model is evaluated on unseen data of unseen cohorts. We characterize the behavior of the model during learning, and quantify its reliance on the dataset itself, which tends to give support for the necessity of large training sets, augmentation, and multiple contrasts. Overall, ConvNets can provide an efficient way to parcel MRI images, following the guidance established within more complex methods, quickly and accurately. The trained model is embedded within a open-source parcellation tool available at https://github.com/bthyreau/parcelcortex., Competing Interests: Declaration of Competing Interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript, (Copyright © 2020. Published by Elsevier B.V.)

Elongated axial length of the eye increases the morbidity of glaucoma. Myopia also associates with elongated axial length, and such ellipsoid shape of the eyeball strongly contributes its pathogenesis. Morphological features of the eyeballs, which could be important factors for developing glaucoma, have not been well described. The aim of this study was to investigate the three-dimensional (3D) topographic features of glaucomatous eyeballs with/without myopia to evaluate the potential of those features for predicting glaucoma. Using a 3.0-tesla MRI, volume-isotropic turbo-spin-echo acquisition T2-weighted images were obtained from 55 patients with glaucoma and 22 controls to delineate the eyeballs. Eyeball volumes, axial lengths and transverse lengths were semi-automatically calculated and compared between four groups: normal, myopia, glaucoma, and glaucoma with myopia. Both glaucoma and myopia increased the eyeball volume compared to the normal eyes. An increased anisotropy ratio (axial/transversus length) was observed in myopic eyes compared to normal, whereas in the glaucomatous eyes, with or without myopia, no increase in anisotropy ratio was observed. Increasing volume of eyes can be caused by myopia and glaucoma. Myopic eyes were ellipsoid in shape, but there was less anisotropy and a near-spherical shape in glaucomatous eyes, even in glaucomatous myopic eyes.

The human cerebellum plays an essential role in motor control, is involved in cognitive function (i.e., attention, working memory, and language), and helps to regulate emotional responses. Quantitative in-vivo assessment of the cerebellum is important in the study of several neurological diseases including cerebellar ataxia, autism, and schizophrenia. Different structural subdivisions of the cerebellum have been shown to correlate with differing pathologies. To further understand these pathologies, it is helpful to automatically parcellate the cerebellum at the highest fidelity possible. In this paper, we coordinated with colleagues around the world to evaluate automated cerebellum parcellation algorithms on two clinical cohorts showing that the cerebellum can be parcellated to a high accuracy by newer methods. We characterize these various methods at four hierarchical levels: coarse (i.e., whole cerebellum and gross structures), lobe, subdivisions of the vermis, and the lobules. Due to the number of labels, the hierarchy of labels, the number of algorithms, and the two cohorts, we have restricted our analyses to the Dice measure of overlap. Under these conditions, machine learning based methods provide a collection of strategies that are efficient and deliver parcellations of a high standard across both cohorts, surpassing previous work in the area. In conjunction with the rank-sum computation, we identified an overall winning method., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The hippocampus is a particularly interesting target for neuroscience research studies due to its essential role within the human brain. In large human cohort studies, bilateral hippocampal structures are frequently identified and measured to gain insight into human behaviour or genomic variability in neuropsychiatric disorders of interest. Automatic segmentation is performed using various algorithms, with FreeSurfer being a popular option. In this manuscript, we present a method to segment the bilateral hippocampus using a deep-learned appearance model. Deep convolutional neural networks (ConvNets) have shown great success in recent years, due to their ability to learn meaningful features from a mass of training data. Our method relies on the following key novelties: (i) we use a wide and variable training set coming from multiple cohorts (ii) our training labels come in part from the output of the FreeSurfer algorithm, and (iii) we include synthetic data and use a powerful data augmentation scheme. Our method proves to be robust, and it has fast inference (<30s total per subject), with trained model available online (https://github.com/bthyreau/hippodeep). We depict illustrative results and show extensive qualitative and quantitative cohort-wide comparisons with FreeSurfer. Our work demonstrates that deep neural-network methods can easily encode, and even improve, existing anatomical knowledge, even when this knowledge exists in algorithmic form., (Copyright © 2017 Elsevier B.V. All rights reserved.)

BACKGROUND The optic radiation (OR) is a white-matter bundle connecting the lateral geniculate body and the visual cortex. Phase difference-enhanced imaging (PADRE) is a new MRI technique that is able to achieve precise delineation of the OR. The aim of this study was to investigate the effect of age on the volume and signal intensity of the OR using PADRE, and to establish a volumetric reference of the OR from a healthy population, compared with diffusion tensor imaging (DTI). MATERIAL AND METHODS Thirty-nine healthy volunteers underwent MR imaging with PADRE and DTI sequences on a 3.0-T scanner. For the volumetric analysis with PADRE, the OR corresponding to the external sagittal stratum was manually traced, while an automated thresholding method was used for the DTI-based volumetric analysis of the OR. RESULTS The mean right and left OR volumes measured from the PADRE images were 1469.0±242.4 mm³ and 1372.6±310.2 mm³, respectively. Although OR volume showed no significant correlation with age, the normalized OR signal intensity showed a linear correlation with increasing age (r²=0.50-0.53; P<0.01). The OR signal intensity on PADRE and DTI-related quantitative parameters for the OR showed significant correlations (r²=0.46-0.49; P<0.01). CONCLUSIONS The PADRE technique revealed exceptional preservation of OR volume, even in later life. Moreover, PADRE was able to detect age-related changes in signal intensity of the OR and may contribute to future analyses of pathological neurodegeneration in patients with glaucoma and multiple sclerosis.

Spontaneous imitation is assumed to underlie the acquisition of important skills by infants, including language and social interaction. In this study, functional magnetic resonance imaging (fMRI) was used to examine the neural basis of 'spontaneously' driven imitation, which has not yet been fully investigated. Healthy participants were presented with movie clips of meaningless bimanual actions and instructed to observe and imitate them during an fMRI scan. The participants were subsequently shown the movie clips again and asked to evaluate the strength of their 'urge to imitate' (Urge) for each action. We searched for cortical areas where the degree of activation positively correlated with Urge scores; significant positive correlations were observed in the right supplementary motor area (SMA) and bilateral midcingulate cortex (MCC) under the imitation condition. These areas were not explained by explicit reasons for imitation or the kinematic characteristics of the actions. Previous studies performed in monkeys and humans have implicated the SMA and MCC/caudal cingulate zone in voluntary actions. This study also confirmed the functional connectivity between Urge and imitation performance using a psychophysiological interaction analysis. Thus, our findings reveal the critical neural components that underlie spontaneous imitation and provide possible reasons why infants imitate spontaneously., (© The Author (2015). Published by Oxford University Press.)

Background and Purpose: Quantitative signal targeting with alternating radiofrequency labeling of arterial regions (QUASAR) is a recent spin labeling technique that could improve the reliability of brain perfusion measurements. Although it is considered reliable for measuring gray matter as a whole, it has never been evaluated regionally. Here we assessed this regional reliability., Methods: Using a 3-Tesla Philips Achieva whole-body system, we scanned four times 10 healthy volunteers, in two sessions 2 weeks apart, to obtain QUASAR images. We computed perfusion images and ran a voxel-based analysis within all brain structures. We also calculated mean regional cerebral blood flow (rCBF) within regions of interest configured for each arterial territory distribution., Results: The mean CBF over whole gray matter was 37.74 with intraclass correlation coefficient (ICC) of .70. In white matter, it was 13.94 with an ICC of .30. Voxel-wise ICC and coefficient-of-variation maps showed relatively lower reliability in watershed areas and white matter especially in deeper white matter. The absolute mean rCBF values were consistent with the ones reported from PET, as was the relatively low variability in different feeding arteries., Conclusions: Thus, QUASAR reliability for regional perfusion is high within gray matter, but uncertain within white matter., (© 2014 The Authors. Journal of Neuroimaging published by the American Society of Neuroimaging.)

Background: Common variants in the oxytocin receptor gene (OXTR) have been shown to influence social and affective behavior and to moderate the effect of adverse experiences on risk for social-affective problems. However, the intermediate neurobiological mechanisms are not fully understood. Although human functional neuroimaging studies have reported that oxytocin effects on social behavior and emotional states are mediated by amygdala function, animal models indicate that oxytocin receptors in the ventral striatum (VS) modulate sensitivity to social reinforcers. This study aimed to comprehensively investigate OXTR-dependent brain mechanisms associated with social-affective problems., Methods: In a sample of 1445 adolescents we tested the effect of 23-tagging single nucleotide polymorphisms across the OXTR region and stressful life events (SLEs) on functional magnetic resonance imaging blood oxygen level-dependent activity in the VS and amygdala to animated angry faces. Single nucleotide polymorphisms for which gene-wide significant effects on brain function were found were then carried forward to examine associations with social-affective problems., Results: A gene-wide significant effect of rs237915 showed that adolescents with minor CC-genotype had significantly lower VS activity than CT/TT-carriers. Significant or nominally significant gene × environment effects on emotional problems (in girls) and peer problems (in boys) revealed a strong increase in clinical symptoms as a function of SLEs in CT/TT-carriers but not CC-homozygotes. However, in low-SLE environments, CC-homozygotes had more emotional problems (girls) and peer problems (boys). Moreover, among CC-homozygotes, reduced VS activity was related to more peer problems., Conclusions: These findings suggest that a common OXTR-variant affects brain responsiveness to negative social cues and that in "risk-carriers" reduced sensitivity is simultaneously associated with more social-affective problems in "favorable environments" and greater resilience against stressful experiences., (© 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.)

Humans perceive textual and nontextual information in visual perception, and both depend on language. In childhood education, students exhibit diverse perceptual abilities, such that some students process textual information better and some process nontextual information better. These predispositions involve many factors, including cognitive ability and learning preference. However, the relationship between verbal and nonverbal cognitive abilities and brain activation during visual perception has not yet been examined in children. We used functional magnetic resonance imaging to examine the relationship between nonverbal and verbal cognitive abilities and brain activation during nontextual visual perception in large numbers of children. A significant positive correlation was found between nonverbal cognitive abilities and brain activation in the right temporoparietal junction, which is thought to be related to attention reorienting. This significant positive correlation existed only in boys. These findings suggested that male brain activation differed from female brain activation, and that this depended on individual cognitive processes, even if there was no gender difference in behavioral performance., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Older children are more successful at producing unfamiliar, non-native speech sounds than younger children during the initial stages of learning. To reveal the neuronal underpinning of the age-related increase in the accuracy of non-native speech production, we examined the developmental changes in activation involved in the production of novel speech sounds using functional magnetic resonance imaging. Healthy right-handed children (aged 6-18 years) were scanned while performing an overt repetition task and a perceptual task involving aurally presented non-native and native syllables. Productions of non-native speech sounds were recorded and evaluated by native speakers. The mouth regions in the bilateral primary sensorimotor areas were activated more significantly during the repetition task relative to the perceptual task. The hemodynamic response in the left inferior frontal gyrus pars opercularis (IFG pOp) specific to non-native speech sound production (defined by prior hypothesis) increased with age. Additionally, the accuracy of non-native speech sound production increased with age. These results provide the first evidence of developmental changes in the neural processes underlying the production of novel speech sounds. Our data further suggest that the recruitment of the left IFG pOp during the production of novel speech sounds was possibly enhanced due to the maturation of the neuronal circuits needed for speech motor planning. This, in turn, would lead to improvement in the ability to immediately imitate non-native speech., (Copyright © 2014 Wiley Periodicals, Inc.)

Many disciplines/traditions that promote interoceptive (inner sensation of body parts) attention/awareness (IAA) train practitioners to both attend to and be aware of interoceptive sensory experiences in body parts. The effect of such practices has been investigated in previous imaging studies but limited to cerebral neural activity. Here, for the first time, we studied the impact of these practices on the spinal neural activity of experts and novices. We also attempted to clarify the effect of constant and deep breathing, a paradigm utilized in concentration practices to avoid mind wandering, on IAA-related spinal neural activity. Subjects performed IAA tasks with and without a deep and constant breathing pattern in two sessions. Results showed that neural activity in the spinal segment innervating the attended-to body area increased in experts (P = 0.04) when they performed IAA and that this increase was significantly larger for experts versus novices in each of the sessions (P = 0.024). The significant effects of IAA and expertise on spinal neural activity are consistent with and elaborate on previous reports showing similar effects on cerebral neural activity. As the spinal cord directly innervates body parts, the results might indicate that IAA has an instantaneous (possibly beneficial) effect on the physical body after extended training.

Introduction: Like sleeping and eating habits, the study habits adopted by children when they are at home are important contributors to lifestyle and they affect cognitive ability. It has recently been reported that sleeping and eating habits change the brain structure of children. However, no research on the effect of study habits at home on the brain structure of children has been conducted thus far. We investigated the effects of study habits at home on the brain structures of healthy children by examining correlations between study time at home and changes in brain structure over the course of 3 years., Methods: We used the brain magnetic resonance images of 229 healthy children aged 5.6-18.4 years and computed the changes (time 2-time 1) in regional gray matter and white matter volume (rWMV) using voxel-based morphometry. Whole-brain multiple regression analysis revealed a significant positive correlation between study time at home and changes in rWMV in the right superior frontal gyrus (SFG). Behaviorally, we found a significant positive correlation between study time at home and change in the verbal comprehension index (VCI), one of the subscales of the Wechsler Intelligence Scale for Children-third edition (WISC-III)., Results and Conclusions: Given that the SFG is involved in memory control and that the VCI measures abilities related to vocabulary, our results indicate that greater SFG involvement in the memorization component of longer study times may result in greater increases in the number of axons and more axon branching and myelination, causing plastic changes in the neural network involved in memory processes.

To investigate whether personality traits affect the rate of decline of gray matter volume, we analyzed the relationships between personality traits and the annual rate of changes of gray matter volume in 274 healthy community dwelling subjects with a large age range by applying a longitudinal design over 6 years, using brain magnetic resonance images (MRI) and the Revised NEO Personality Inventory (NEO-PI-R) at baseline. Brain MRI data were processed using voxel-based morphometry with a custom template by applying the DARTEL diffeomorphic registration tool. For each subject, we used NEO-PI-R to evaluate the five major personality traits, including neuroticism, extraversion, openness, agreeableness, and conscientiousness. The results show that the annual rate of change in regional gray matter volume in the right inferior parietal lobule was correlated significantly and negatively with a personality of openness, which is known to be related to intellect, intellectual curiosity, and creativity adjusting for age, gender, and intracranial volume. This result indicates that subjects with a personality trait of less openness have an accelerated loss of gray matter volume in the right inferior parietal lobule, compared with subjects with a personality trait of more openness. Because the right inferior parietal lobule is involved in higher cognitive function such as working memory and creativity, a personality trait of openness is thought to be important for preserving gray matter volume and cognitive function of the right inferior parietal lobule in healthy adults., (Copyright © 2012 Wiley Periodicals, Inc.)

Although elevated serum high-sensitivity C-reactive protein (hsCRP) is related to atherosclerosis, brain infarction, and cognitive decline, it has not been clarified whether increased hsCRP is associated with the decline in brain gray matter volume. Therefore, the purpose of this study was to determine the relationship between hsCRP levels and brain regional gray matter volume using brain magnetic resonance imaging (MRI) data from 109 community-dwelling healthy elderly subjects. Brain MRIs were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra (DARTEL) procedure. We found a significant negative correlation between regional gray matter volume of the posterior and lateral aspects of the left temporal cortex and hsCRP level after adjusting for age, gender, and intracranial volume. Our results suggest that subjects who have mild inflammation related to arteriosclerosis have decreased regional gray matter volume in the posterior and lateral aspects of the left temporal cortex. Thus, preventing the progression of arteriosclerosis may be important for preventing a decrease in gray matter volume in healthy elderly subjects., (Copyright © 2012 Wiley Periodicals, Inc.)

The aim of this study was to analyze correlations among the annual rate of gray matter volume change, age, gender, and cerebrovascular risk factors in 381 healthy community-dwelling subjects with a large age range by applying a longitudinal design over 6 years using brain magnetic resonance images (MRIs). Brain MRI data were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure. The annual rate of regional gray matter volume change showed significant positive correlations with age in several regions, including the bilateral temporal pole, caudate nucleus, ventral and dorsolateral prefrontal cortices, insula, hippocampus, and temporoparietal cortex, whereas significant negative correlations with age were observed in several regions including the bilateral cingulate gyri and anterior lobe of the cerebellum. Additionally, a significant age-by-gender interaction was found for the annual rate of regional gray matter volume change in the bilateral hippocampus. No significant correlations were observed between the annual rate of regional gray matter volume change and body mass index or systolic blood pressure. A significant positive correlation between the annual rate of gray matter volume change and age indicates that the region shows not linear but accelerated gray matter loss with age. Therefore, evaluating the annual rate of the gray matter volume change with age in healthy subjects is important in understanding how gray matter volume changes with aging in each brain region and in anticipating what cognitive functions are likely to show accelerated decline with aging., (Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.)

Empathizing is defined as the drive to identify the mental states of others in order to predict their behavior and respond with an appropriate emotion. Systemizing is defined as the drive to analyze a system in terms of the rules that govern it to predict its behavior. We undertook voxel-by-voxel investigations of regional white matter volume (rWMV) and fractional anisotropy (FA) of diffusion tensor imaging to discover the WM structural correlates of empathizing, systemizing, and their difference (D score: systemizing-empathizing). Whole brain analyses of covariance revealed that across both sexes, the D score was negatively correlated with rWMV in the WM area in the bilateral temporal lobe, near the right inferior frontal gyrus, near the ventral medial prefrontal cortex, and near the posterior cingulate cortex and positively correlated with FA in an area involving the superior longitudinal fasciculus. Post-hoc analyses revealed that these associations were generally formed by both the correlation between WM structures and empathizing as well as the opposite correlation between WM structures and systemizing. A significant effect of interaction between sex and the D score on rWMV, which was mainly observed because of a positive correlation between rWMV and empathizing in females and a negative correlation between rWMV and systemizing in females, was found in an area close to the right inferior parietal lobule and temporoparietal junction. Our results suggest that WM structures involving the default mode network and the mirror neuron system support empathizing, and that a WM structure relating to the external attention system supports systemizing. Further, our results revealed an overlap between positive/negative WM structural correlates of empathizing and negative/positive WM structural correlates of systemizing despite little correlation between empathizing and systemizing, which supports the previously held idea that there is a trade-off between empathizing and systemizing in the brain., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We examined linear and curvilinear correlations of gray matter volume and density in cortical and subcortical gray matter with age using magnetic resonance images (MRI) in a large number of healthy children. We applied voxel-based morphometry (VBM) and region-of-interest (ROI) analyses with the Akaike information criterion (AIC), which was used to determine the best-fit model by selecting which predictor terms should be included. We collected data on brain structural MRI in 291 healthy children aged 5-18 years. Structural MRI data were segmented and normalized using a custom template by applying the diffeomorphic anatomical registration using exponentiated lie algebra (DARTEL) procedure. Next, we analyzed the correlations of gray matter volume and density with age in VBM with AIC by estimating linear, quadratic, and cubic polynomial functions. Several regions such as the prefrontal cortex, the precentral gyrus, and cerebellum showed significant linear or curvilinear correlations between gray matter volume and age on an increasing trajectory, and between gray matter density and age on a decreasing trajectory in VBM and ROI analyses with AIC. Because the trajectory of gray matter volume and density with age suggests the progress of brain maturation, our results may contribute to clarifying brain maturation in healthy children from the viewpoint of brain structure., (Copyright © 2012 Wiley Periodicals, Inc.)

In this study, we examined linear and curvilinear correlations of fractional anisotropy (FA), mean diffusivity (MD), and white matter volume with age by using brain structural and diffusion-tensor magnetic resonance imaging (MRI) in a large number of healthy children and voxel-based morphometry (VBM) and region-of-interest (ROI) analyses. We collected data by brain structural MRI in 246 healthy children, aged 5-18 years. FA and MD images were normalized using the normalization parameter of the corresponding structural MRI. Next, we analyzed the correlations between FA and age and between MD and age by estimating linear and logarithmic functions. We also analyzed the correlation between white matter volume and age by linear, quadratic, and cubic functions. Correlations between FA and age and between MD and age showed exponential trajectories in most ROIs in boys and girls, except for several fibers, such as the corpus callosum connecting the bilateral rectal gyri in boys. The correlation between white matter volume and age showed significant positive linear trajectories in most ROIs in boys and girls, except for a few fibers, such as the bilateral uncinate fasciculus. Additionally, maturational rates differed among major fibers, and in girls, the left superior longitudinal fasciculus, which connects the frontal and temporal lobes, showed a slower rate of maturation than other fibers. Our results may help to clarify the mechanisms of normal brain maturation from the viewpoint of brain white matter., (Copyright © 2012 Wiley Periodicals, Inc.)

Introduction: Cigarette smoking decreases brain regional gray matter volume and is related to chronic obstructive lung disease (COPD). COPD leads to decreased pulmonary function, which is represented by forced expiratory volume in one second percentage (FEV1.0 %); however, it is unclear if decreased pulmonary function is directly related to brain gray matter volume decline. Because there is a link between COPD and cognitive decline, revealing a direct relationship between pulmonary function and brain structure is important to better understand how pulmonary function affects brain structure and cognitive function. Therefore, the purpose of this study was to analyze whether there were significant correlations between FEV1.0 % and brain regional gray and white matter volumes using brain magnetic resonance (MR) image data from 109 community-dwelling healthy elderly individuals., Methods: Brain MR images were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure., Results: We found a significant positive correlation between the regional white matter volume of the cerebellum and FEV1.0 % after adjusting for age, sex, and intracranial volume., Conclusion: Our results suggest that elderly individuals who have a lower FEV1.0 % have decreased regional white matter volume in the cerebellum. Therefore, preventing decreased pulmonary function is important for cerebellar white matter volume in the healthy elderly population.

Deception is related to the ability to inhibit prepotent responses and to engage in mental tasks such as anticipating responses and inferring what another person knows, especially in social contexts. However, the neural correlates of deception processing, which requires mentalizing, remain unclear. Using functional magnetic resonance imaging (fMRI), we examined the neural correlates of deception, including mentalization, in social contexts in normally developing children. Healthy right-handed children (aged 8-9 years) were scanned while performing interactive games involving deception. The games varied along two dimensions: the type of reply (deception and truth) and the type of context (social and less social). Participants were instructed to deceive a witch and to tell the truth to a girl. Under the social-context conditions, participants were asked to consider what they inferred about protagonists' preferences from their facial expressions when responding to questions. Under the less-social-context conditions, participants did not need to consider others' preferences. We found a significantly greater response in the right precuneus under the social-context than under less-social-context conditions. Additionally, we found marginally greater activation in the right inferior parietal lobule (IPL) under the deception than under the truth condition. These results suggest that deception in a social context requires not only inhibition of prepotent responses but also engagement in mentalizing processes. This study provides the first evidence of the neural correlates of the mentalizing processes involved in deception in normally developing children.

Recent studies have demonstrated developmental changes of functional brain networks derived from functional connectivity using graph theoretical analysis, which has been rapidly translated to studies of brain network organization. However, little is known about sex- and IQ-related differences in the topological organization of functional brain networks during development. In this study, resting-state fMRI (rs-fMRI) was used to map the functional brain networks in 51 healthy children. We then investigated the effects of age, sex, and IQ on economic small-world properties and regional nodal properties of the functional brain networks. At a global level of whole networks, we found significant age-related increases in the small-worldness and local efficiency, significant higher values of the global efficiency in boys compared with girls, and no significant IQ-related difference. Age-related increases in the regional nodal properties were found predominately in the frontal brain regions, whereas the parietal, temporal, and occipital brain regions showed age-related decreases. Significant sex-related differences in the regional nodal properties were found in various brain regions, primarily related to the default mode, language, and vision systems. Positive correlations between IQ and the regional nodal properties were found in several brain regions related to the attention system, whereas negative correlations were found in various brain regions primarily involved in the default mode, emotion, and language systems. Together, our findings of the network topology of the functional brain networks in healthy children and its relationship with age, sex, and IQ bring new insights into the understanding of brain maturation and cognitive development during childhood and adolescence.

Schizophrenia is a psychiatric disorder that has eluded characterization in terms of local abnormalities of brain activity, and is hypothesized to affect the collective, "emergent" working of the brain. Indeed, several recent publications have demonstrated that functional networks in the schizophrenic brain display disrupted topological properties. However, is it possible to explain such abnormalities just by alteration of local activation patterns? This work suggests a negative answer to this question, demonstrating that significant disruption of the topological and spatial structure of functional MRI networks in schizophrenia (a) cannot be explained by a disruption to area-based task-dependent responses, i.e. indeed relates to the emergent properties, (b) is global in nature, affecting most dramatically long-distance correlations, and (c) can be leveraged to achieve high classification accuracy (93%) when discriminating between schizophrenic vs control subjects based just on a single fMRI experiment using a simple auditory task. While the prior work on schizophrenia networks has been primarily focused on discovering statistically significant differences in network properties, this work extends the prior art by exploring the generalization (prediction) ability of network models for schizophrenia, which is not necessarily captured by such significance tests.

Medical imaging datasets often contain deviant observations, the so-called outliers, due to acquisition or preprocessing artifacts or resulting from large intrinsic inter-subject variability. These can undermine the statistical procedures used in group studies as the latter assume that the cohorts are composed of homogeneous samples with anatomical or functional features clustered around a central mode. The effects of outlying subjects can be mitigated by detecting and removing them with explicit statistical control. With the emergence of large medical imaging databases, exhaustive data screening is no longer possible, and automated outlier detection methods are currently gaining interest. The datasets used in medical imaging are often high-dimensional and strongly correlated. The outlier detection procedure should therefore rely on high-dimensional statistical multivariate models. However, state-of-the-art procedures, based on the Minimum Covariance Determinant (MCD) estimator, are not well-suited for such high-dimensional settings. In this work, we introduce regularization in the MCD framework and investigate different regularization schemes. We carry out extensive simulations to provide backing for practical choices in absence of ground truth knowledge. We demonstrate on functional neuroimaging datasets that outlier detection can be performed with small sample sizes and improves group studies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The impulsive behavior that is often characteristic of adolescence may reflect underlying neurodevelopmental processes. Moreover, impulsivity is a multi-dimensional construct, and it is plausible that distinct brain networks contribute to its different cognitive, clinical and behavioral aspects. As these networks have not yet been described, we identified distinct cortical and subcortical networks underlying successful inhibitions and inhibition failures in a large sample (n = 1,896) of 14-year-old adolescents. Different networks were associated with drug use (n = 1,593) and attention-deficit hyperactivity disorder symptoms (n = 342). Hypofunctioning of a specific orbitofrontal cortical network was associated with likelihood of initiating drug use in early adolescence. Right inferior frontal activity was related to the speed of the inhibition process (n = 826) and use of illegal substances and associated with genetic variation in a norepinephrine transporter gene (n = 819). Our results indicate that both neural endophenotypes and genetic variation give rise to the various manifestations of impulsive behavior.

As neuroimaging databases grow in size and complexity, the time researchers spend investigating and managing the data increases to the expense of data analysis. As a result, investigators rely more and more heavily on scripting using high-level languages to automate data management and processing tasks. For this, a structured and programmatic access to the data store is necessary. Web services are a first step toward this goal. They however lack in functionality and ease of use because they provide only low-level interfaces to databases. We introduce here PyXNAT, a Python module that interacts with The Extensible Neuroimaging Archive Toolkit (XNAT) through native Python calls across multiple operating systems. The choice of Python enables PyXNAT to expose the XNAT Web Services and unify their features with a higher level and more expressive language. PyXNAT provides XNAT users direct access to all the scientific packages in Python. Finally PyXNAT aims to be efficient and easy to use, both as a back-end library to build XNAT clients and as an alternative front-end from the command line.

In this paper we investigate the use of classical fMRI Random Effect (RFX) group statistics when analyzing a very large cohort and the possible improvement brought from anatomical information. Using 1326 subjects from the IMAGEN study, we first give a global picture of the evolution of the group effect t-value from a simple face-watching contrast with increasing cohort size. We obtain a wide activated pattern, far from being limited to the reasonably expected brain areas, illustrating the difference between statistical significance and practical significance. This motivates us to inject tissue-probability information into the group estimation, we model the BOLD contrast using a matter-weighted mixture of Gaussians and compare it to the common, single-Gaussian model. In both cases, the model parameters are estimated per-voxel for one subgroup, and the likelihood of both models is computed on a second, separate subgroup to reflect model generalization capacity. Various group sizes are tested, and significance is asserted using a 10-fold cross-validation scheme. We conclude that adding matter information consistently improves the quantitative analysis of BOLD responses in some areas of the brain, particularly those where accurate inter-subject registration remains challenging., (Copyright © 2012 Elsevier Inc. All rights reserved.)