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Abstract Quantitative susceptibility mapping is a magnetic resonance imaging technique that measures brain tissues’ magnetic susceptibility, including iron deposition and myelination. This study examines the relationship between subcortical volume and magnetic susceptibility and determines specific differences in these measures among patients with major depressive disorder (MDD), patients with schizophrenia, and healthy controls (HCs). This was a cross-sectional study. Sex- and age- matched patients with MDD (n = 49), patients with schizophrenia (n = 24), and HCs (n = 50) were included. Magnetic resonance imaging was conducted using quantitative susceptibility mapping and T1-weighted imaging to measure subcortical susceptibility and volume. The acquired brain measurements were compared among groups using analyses of variance and post hoc comparisons. Finally, a general linear model examined the susceptibility–volume relationship. Significant group-level differences were found in the magnetic susceptibility of the nucleus accumbens and amygdala (p = 0.045). Post-hoc analyses indicated that the magnetic susceptibility of the nucleus accumbens and amygdala for the MDD group was significantly higher than that for the HC group (p = 0.0054, p = 0.0065, respectively). However, no significant differences in subcortical volume were found between the groups. The general linear model indicated a significant interaction between group and volume for the nucleus accumbens in MDD group but not schizophrenia or HC groups. This study showed susceptibility alterations in the nucleus accumbens and amygdala in MDD patients. A significant relationship was observed between subcortical susceptibility and volume in the MDD group’s nucleus accumbens, which indicated abnormalities in myelination and the dopaminergic system related to iron deposition.

Abstract Although many studies have demonstrated structural brain abnormalities associated with auditory verbal hallucinations (AVH) in schizophrenia, the results remain inconsistent because of the small sample sizes and the reliability of clinical interviews. We compared brain morphometries in 204 participants, including 58 schizophrenia patients with a history of AVH (AVH + ), 29 without a history of AVH (AVH−), and 117 healthy controls (HCs) based on a detailed inspection of medical records. We further divided the AVH+ group into 37 patients with and 21 patients without hallucinations at the time of the MRI scans (AVH++ and AVH+−, respectively) via clinical interviews to explore the morphological differences according to the persistence of AVH. The AVH + group had a smaller surface area in the left caudal middle frontal gyrus (F = 7.28, FDR-corrected p = 0.0008) and precentral gyrus (F = 7.68, FDR-corrected p = 0.0006) compared to the AVH− group. The AVH+ patients had a smaller surface area in the left insula (F = 7.06, FDR-corrected p = 0.001) and a smaller subcortical volume in the bilateral hippocampus (right: F = 13.34, FDR-corrected p = 0.00003; left: F = 6.80, FDR-corrected p = 0.001) compared to the HC group. Of these significantly altered areas, the AVH++ group showed significantly smaller bilateral hippocampal volumes compared to the AVH+− group, and a smaller surface area in the left precentral gyrus and caudal middle frontal gyrus compared to the AVH- group. Our findings highlighted the distinct pattern of structural alteration between the history and presence of AVH in schizophrenia, and the importance of integrating multiple criteria to elucidate the neuroanatomical mechanisms.

Regional anatomical structures of the brain are intimately connected to functions corresponding to specific regions and the temporospatial pattern of genetic expression and their functions from the fetal period to old age. Therefore, quantitative brain morphometry has often been employed in neuroscience investigations, while controlling for the scanner effect of the scanner is a critical issue for ensuring accuracy in brain morphometric studies of rare orphan diseases due to the lack of normal reference values available for multicenter studies. This study aimed to provide across-site normal reference values of global and regional brain volumes for each sex and age group in children and adolescents. We collected magnetic resonance imaging (MRI) examinations of 846 neurotypical participants aged 6.0–17.9 years (339 male and 507 female participants) from 5 institutions comprising healthy volunteers or neurotypical patients without neurological disorders, neuropsychological disorders, or epilepsy. Regional-based analysis using the CIVET 2.1.0. pipeline provided regional brain volumes, and the measurements were across-site combined using ComBat-GAM harmonization. The normal reference values of global and regional brain volumes and lateral indices in our study could be helpful for evaluating the characteristics of the brain morphology of each individual in a clinical setting and investigating the brain morphology of ultra-rare diseases.

Abstract Although widespread cortical thinning centered on the fronto-temporal regions in schizophrenia has been reported, the findings in at-risk mental state (ARMS) patients have been inconsistent. In addition, it remains unclear whether abnormalities of cortical thickness (CT) in ARMS individuals, if present, are related to their functional decline irrespective of future psychosis onset. In this multicenter study in Japan, T1-weighted magnetic resonance imaging was performed at baseline in 107 individuals with ARMS, who were subdivided into resilient (77, good functional outcome) and non-resilient (13, poor functional outcome) groups based on the change in Global Assessment of Functioning scores during 1-year follow-up, and 104 age- and sex-matched healthy controls recruited at four scanning sites. We measured the CT of the entire cortex and performed group comparisons using FreeSurfer software. The relationship between the CT and cognitive functioning was examined in an ARMS subsample (n = 70). ARMS individuals as a whole relative to healthy controls exhibited a significantly reduced CT, predominantly in the fronto-temporal regions, which was partly associated with cognitive impairments, and an increased CT in the left parietal and right occipital regions. Compared with resilient ARMS individuals, non-resilient ARMS individuals exhibited a significantly reduced CT of the right paracentral lobule. These findings suggest that ARMS individuals partly share CT abnormalities with patients with overt schizophrenia, potentially representing general vulnerability to psychopathology, and also support the role of cortical thinning in the paracentral lobule as a predictive biomarker for short-term functional decline in the ARMS population.

Abstract Introduction Free‐water (FW) imaging, a new analysis method for diffusion magnetic resonance imaging (MRI), can indicate neuroinflammation and degeneration. We evaluated FW in Alzheimer's disease (AD) using tau/inflammatory and amyloid positron emission tomography (PET). Methods Seventy‐one participants underwent multi‐shell diffusion MRI, 18F‐THK5351 PET, 11C‐Pittsburgh compound B PET, and neuropsychological assessments. They were categorized into two groups: healthy controls (HCs) (n = 40) and AD‐spectrum group (AD‐S) (n = 31) using the Centiloid scale with amyloid PET and cognitive function. We analyzed group comparisons in FW and PET, correlations between FW and PET, and correlation analysis with neuropsychological scores. Results In AD‐S group, there was a significant positive correlation between FW and 18F‐THK5351 in the temporal lobes. In addition, there were negative correlations between FW and cognitive function in the temporal lobe and cingulate gyrus, and negative correlations between 18F‐THK5351 and cognitive function in the same regions. Discussion FW imaging could be a biomarker for tau in AD alongside clinical correlations.

Objective: The aim of this study was to evaluate tau-related structural network metrics derived from gray matter magnetic resonance imaging (MRI) scans in cognitively normal (CN) older adults. Methods: We recruited 47 amyloid-negative CN older adults (mean age ± standard deviation, 65.0 ± 7.9 years; 26 women). All participants underwent 3D T1-weighted MRI and 11C-Pittsburgh compound-B and 18F-THK5351 positron emission tomography scans. Four local network metrics (betweenness centrality, clustering coefficient, characteristic path length, and degree) were computed and rendered on individual brain images. We then evaluated the correlations between 18F-THK5351 positron emission tomography images and local network metric images at the voxel level. Results: Significant positive correlations of the four local network metrics with 18F-THK5351 were detected in the bilateral caudate. Conclusion: Our findings suggest that tau and neuroinflammation in CN older adults may influence the gray matter structural network in the caudate.

Abstract Backgrounds Although neurofibrillary tangles (NFTs) mainly accumulate in the medial temporal lobe with human aging, only a few imaging studies have investigated correlations between NFT accumulation and gray matter (GM) volume in cognitively normal older adults. Here, we investigated the correlations between 18F-THK5351 accumulation and GM volume at the voxel level. Material and methods We recruited 47 amyloid-negative, cognitively normal, older adults (65.0 ± 7.9 years, 26 women), who underwent structural magnetic resonance imaging, 11C-Pittsburgh compound-B and 18F-THK5351 PET scans, and neuropsychological assessment. The magnetic resonance and 18F-THK5351 PET images were spatially normalized using Statistical Parametric Mapping 12. Voxel-wise correlations between 18F-THK5351 accumulation and GM volume were evaluated using the Biological Parametric Mapping toolbox. Results A significant negative correlation (p

Objective: This study aimed to examine the alterations in gray matter networks related to tau retention in Alzheimer's disease (AD) patients and cognitively normal (CN) older individuals. Methods: Eighteen amyloid-positive AD patients and 30 age- and sex-matched amyloid-negative CN controls were enrolled. All underwent 3D T1-weighted MRI, amyloid positron-emission tomography imaging (PET) with 11C-Pittsburgh Compound B (PiB), and tau PET with 18F-THK5351. The structural networks extracted from the T1-weighted MRI data based on cortical similarities within single subjects were analyzed. Based on graph theoretical approach, global and local network properties across the whole brain were computed. Group comparisons of global and local network properties were evaluated between the groups. Then, we correlated the global and local network measures with total cerebral 18F-THK5351 retention. Results: AD patients moved toward more randomized global network compared to controls and regional differences were observed in the default mode network (DMN) area. No significant correlations existed between global network properties and tau retention. On a local level, AD and controls showed opposite relationships between network properties and tau retention mainly in the DMN areas; CN controls showed positive correlations, whereas AD showed negative correlations. Conclusion: We found opposite relationships between local network properties and tau retention between amyloid-positive AD patients and amyloid-negative controls. Our findings suggest that the presence of amyloid and induced exacerbated tau retention alter the relationship of local network properties and tau retention.

Psychiatric and neurological disorders are afflictions of the brain that can affect individuals throughout their lifespan. Many brain magnetic resonance imaging (MRI) studies have been conducted; however, imaging-based biomarkers are not yet well established for diagnostic and therapeutic use. This article describes an outline of the planned study, the Brain/MINDS Beyond human brain MRI project (BMB-HBM, FY2018 ~ FY2023), which aims to establish clinically-relevant imaging biomarkers with multi-site harmonization by collecting data from healthy traveling subjects (TS) at 13 research sites. Collection of data in psychiatric and neurological disorders across the lifespan is also scheduled at 13 sites, whereas designing measurement procedures, developing and analyzing neuroimaging protocols, and databasing are done at three research sites. A high-quality scanning protocol, Harmonization Protocol (HARP), was established for five high-quality 3 T scanners to obtain multimodal brain images including T1 and T2-weighted, resting-state and task functional and diffusion-weighted MRI. Data are preprocessed and analyzed using approaches developed by the Human Connectome Project. Preliminary results in 30 TS demonstrated cortical thickness, myelin, functional connectivity measures are comparable across 5 scanners, suggesting sensitivity to subject-specific connectome. A total of 75 TS and more than two thousand patients with various psychiatric and neurological disorders are scheduled to participate in the project, allowing a mixed model statistical harmonization. The HARP protocols are publicly available online, and all the imaging, demographic and clinical information, harmonizing database will also be made available by 2024. To the best of our knowledge, this is the first project to implement a prospective, multi-level harmonization protocol with multi-site TS data. It explores intractable brain disorders across the lifespan and may help to identify the disease-specific pathophysiology and imaging biomarkers for clinical practice.

Abstract Introduction We propose a method to evaluate quantitatively the longitudinal structural changes in brain atrophy to provide early detection of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods We used existence probabilities obtained by segmenting magnetic resonance (MR) images at two different time points into four regions: gray matter, white matter, cerebrospinal fluid, and background. This method was applied to T1‐weighted MR images of 110 participants with normal cognition (NL), 165 with MCI, and 82 with AD, obtained from the Japanese Alzheimer's Disease Neuroimaging Initiative database. Results We obtained the coefficients of probability change (CPC) for each dataset. We found high area under the receiver operating characteristic curve (ROC) values (up to 0.908 of the difference of ROCs) for some CPC regions that are considered indicators of atrophy. Additionally, we attempted to establish a machine‐learning algorithm to classify participants as NL or AD. The maximum accuracy was 92.1% for NL‐AD classification and 81.2% for NL‐MCI classification using CPC values between images acquired at first and sixth months, respectively. Conclusion These results showed that the proposed method is effective for the early detection of AD and MCI.

Objective: In this study, we investigated the ability of fluid-attenuated inversion recovery (FLAIR) data coupled with machine-leaning algorithms to differentiate normal and epileptic brains and identify the laterality of focus side in temporal lobe epilepsy (TLE) patients with visually negative MRI.Materials and Methods: The MRI data were acquired on a 3-T MR system (Philips Medical Systems). After pre-proceeding stage, the FLAIR signal intensities were extracted from specific regions of interest, such as the amygdala, cerebral white matter, inferior temporal gyrus, middle temporal gyrus, parahippocampal gyrus, superior temporal gyrus, and temporal pole, and fed into a classification framework followed by a support vector machine as classifier. The proposed lateralization framework was assessed in a group of MRI-negative unilateral TLE patients (N = 42; 23 left TLE and 19 right TLE) and 34 healthy controls (HCs) based on a leave-one-out cross-validation strategy.Results: Using the FLAIR data, we obtained a 75% accuracy for discriminating the three groups, as well as 87.71, 83.01, and 76.19% accuracies for HC/right TLE, HC/left TLE, and left TLE/right TLE tasks, respectively.Interpretation: The experimental results show that FLAIR data can potentially be considered an informative biomarker for improving the pre-surgical diagnostic confidence in patients with MRI-negative TLE.

Background: Despite the importance of psychosis as a comorbidity of temporal lobe epilepsy (TLE), the underlying neural mechanisms are still unclear. We aimed to investigate abnormalities specific to psychosis in TLE, using diffusion MRI parameters and graph-theoretical network analysis.Material and Methods: We recruited 49 patients with TLE (20 with and 29 without interictal schizophrenia-like psychosis) and 42 age-/gender-matched healthy controls. We performed 3-tesla MRI scans including 3D T1-weighted imaging and diffusion tensor imaging in all participants. Among the three groups, fractional anisotropy (FA), mean diffusivity (MD), and global network metrics were compared by analyses of covariance. Regional connectivity strength was compared by network-based statistics.Results: Compared to controls, TLE patients showed significant temporal and extra-temporal changes in FA, and MD, which were more severe and widespread in patients with than without psychosis. We observed distinct differences between TLE patients with and without psychosis in the anterior thalamic radiation (ATR), inferior fronto-occipital fasciculus (IFOF), and inferior longitudinal fasciculus (ILF). Similarly, for network metrics, global, and local efficiency and increased path length were significantly reduced in TLE patients compared to controls, but with more severe changes in TLE with psychosis than without psychosis. Network-based statistics detected significant differences between TLE with and without psychosis mainly involving the left limbic and prefrontal areas.Conclusion: TLE patients with interictal schizophrenia-like psychosis showed more widespread and severe white matter impairment, involving the ATR, IFOF and ILF, as well as disrupted network connectivity, particularly in the left limbic and prefrontal cortex, than patients without psychosis.

Abstract Introduction The molecular mechanism of neurodegeneration, including tau and neurite complexity, is an important topic in Alzheimer's disease (AD) research. Methods We recruited 27 amyloid‐positive individuals identified through 11C‐Pittsburgh compound B (PiB) positron emission tomography (PET) and 31 amyloid‐negative individuals with normal cognition. All participants underwent 11C‐PiB and 18F‐THK5351 PET and magnetic resonance imaging (MRI) with neurite orientation dispersion and density imaging (NODDI) protocol. The neurite density index (NDI), orientation dispersion index (ODI), and PET images were analyzed to calculate voxel‐wise correlations among the imaging modalities and correlations with cognitions. Results In the amyloid‐positive participants, there were significant negative correlations between 18F‐THK5351 and NDI and between 18F‐THK5351 and ODI. The bilateral mesial and lateral temporal lobes were mainly involved. Regarding cognition, 18F‐THK5351 showed more marked associations with all cognitive domains than the other modalities. Discussion Tau and neuroinflammation in AD may reduce the neurite density and orientation dispersion, particularly in the mesial and lateral temporal lobes.

Background: Despite recent advances in diffusion MRI (dMRI), there is still limited information on neurite orientation dispersion and density imaging (NODDI) in temporal lobe epilepsy (TLE). This study aimed to demonstrate neurite density and dispersion in TLE with and without hippocampal sclerosis (HS) using whole-brain voxel-wise analyses. Material and methods: We recruited 33 patients with unilateral TLE (16 left, 17 right), including 14 patients with HS (TLE-HS) and 19 MRI-negative 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)-positive patients (MRI-/PET+ TLE). The NODDI toolbox calculated the intracellular volume fraction (ICVF) and orientation dispersion index (ODI). Conventional dMRI metrics, that is, fractional anisotropy (FA) and mean diffusivity (MD), were also estimated. After spatial normalization, all dMRI parameters (ICVF, ODI, FA, and MD) of the patients were compared with those of age- and sex-matched healthy controls using Statistical Parametric Mapping 12 (SPM12). As a complementary analysis, we added an atlas-based region of interest (ROI) analysis of relevant white matter tracts using tract-based spatial statistics. Results: We found decreased neurite density mainly in the ipsilateral temporal areas of both right and left TLE, with the right TLE showing more severe and widespread abnormalities. In addition, etiology-specific analyses revealed a localized reduction in ICVF (i.e., neurite density) in the ipsilateral temporal pole in MRI-/PET+ TLE, whereas TLE-HS presented greater abnormalities, including FA and MD, in addition to a localized hippocampal reduction in ODI. The results of the atlas-based ROI analysis were consistent with the results of the SPM12 analysis. Conclusion: NODDI may provide clinically relevant information as well as novel insights into the field of TLE. Particularly, in MRI-/PET+ TLE, neurite density imaging may have higher sensitivity than other dMRI parameters. The results may also contribute to better understanding of the pathophysiology of TLE with HS. Keywords: Temporal lobe epilepsy, Neurite orientation dispersion and density imaging, Diffusion MRI, MRI-negative focal epilepsy, Hippocampal sclerosis

Background: White matter hyperintensities (WMH) in the cholinergic pathways are associated with cognitive performance in Alzheimer's disease. This study aimed to evaluate the relationship between the volume reduction of cholinergic pathways and cognitive function in patients with multiple sclerosis (MS). Methods: Thirty-two MS patients underwent a brain MRI and cognitive measurements including the Mini-Mental State Examination (MMSE) and the Japanese version of the Montreal Cognitive Assessment (MoCA-J). The extent of WMH within the cholinergic pathways was assessed using the Cholinergic Pathways Hyperintensities Scale (CHIPS). Computerized WMH volumes were also obtained. FreeSurfer was used to measure regional volumes including the cortical and subcortical volumes. The correlations among the CHIPS, the WMH volume, and the clinical data were assessed, in addition to the correlations between the cognitive scores and regional volumes measured by FreeSurfer. Results: The CHIPS score and the WMH volume were strongly positively correlated with each other (r=0.87, P

Cognitive assessments and neuroimaging are routinely combined in clinical practice to diagnose dementia represented by Alzheimer's disease (AD). The Montreal Cognitive Assessment (MoCA) is reported to be more suitable than the Mini-Mental State Examination (MMSE) for screening mild cognitive impairment (MCI) and mild AD. On the other hand, attention to the subfield volumes of the medial temporal lobe has recently been considered important for the differential diagnosis and early detection of AD. The aim of this study was to uncover which specific hippocampal subfields and adjacent extrahippocampal structures contribute to deficits in cognitive assessment scores in patients with MCI and AD. We recruited from our institute 31 Japanese patients—14 with amnestic MCI and 17 with probable AD, with a clinical dementia rating (CDR) of 0.5 and 1, respectively—and 50 healthy elderly individuals with a CDR of 0. All participants underwent magnetic resonance imaging and cognitive assessments with the MMSE, Wechsler Memory Scale-Revised Logical Memory I and II, and Japanese version of the MoCA (MoCA-J). With adjustment for age and sex, we performed partial correlation analysis of the cognitive assessment scores with the subfield volumes of the medial temporal lobe measured by software-mediated automatic segmentation of hippocampal subfields using high-resolution T1-and T2-weighted images. Compared with normal controls, patients with MCI and AD showed subfield volume reductions in cornu ammonis (CA) 1, CA2, Brodmann area (BA) 35, BA36, the dentate gyrus (DG), the subiculum, and the entorhinal cortex (ERC). All participants showed high correlation coefficients (above 0.6) between cognitive assessment scores and subfield volumes in CA1, the DG, the subiculum, the ERC, and BA36. In patients with MCI and AD, the MoCA-J showed higher correlations than the MMSE with subfield volumes in CA1, the DG, the subiculum, and the ERC. These results suggest that the combination of the in vivo analysis of subfield morphometry of the medial temporal lobe with the MoCA-J paradigm provides important insights into whether changes within specific subfields are related to the cognitive profile in MCI and AD.

Background: Despite the increasing use of arterial spin labeling (ASL) in patients with epilepsy, little is known about its brain regional distribution pattern, including diaschisis, and its correspondence with FDG-PET. Here, we investigated the regional match and mismatch between FDG-PET and ASL in temporal lobe epilepsy (TLE).Methods: We recruited 27 patients with unilateral TLE, who underwent inter-ictal ASL and FDG-PET scans. These images were spatially normalized using Statistical Parametric Mapping 12, and the regional values in both ASL and FDG-PET were calculated using PMOD software within 20 volumes of interest (VOIs), including the temporal lobe, adjacent cortices, subcortical structures, and cerebellum. ASL images of 37 healthy controls were also analyzed and compared.Results: Whereas, ASL showed significant side differences, mainly in the temporal and frontal lobes, the significant abnormalities in FDG-PET were more widespread and included the insula and supramarginal gyrus. Ipsilateral thalamic reduction was found in FDG-PET only. The detectability of the focus side compared with the contralateral side was generally higher in FDG-PET. The discriminative values in ASL compared with healthy controls were higher in temporal neocortex and amygdala VOIs.Conclusions: There are similar and differing regional distributions between FDG-PET and ASL in TLE, possibly reflecting regional match and mismatch of cerebral blood flow and metabolism. At this stage, it seems that ASL couldn't present comparable clinical usefulness with FDG-PET. These findings deepen our knowledge of ASL imaging and are potentially useful for its further application.

PurposeThe pathophysiology of idiopathic generalized epilepsy (IGE) is still unclear, but graph theory may help to understand it. Here, we examined the graph-theoretical findings of the gray matter network in IGE using anatomical covariance methods.Materials and methodsWe recruited 33 patients with IGE and 35 age- and sex-matched healthy controls. Gray matter images were obtained by 3.0-T 3D T1-weighted MRI and were normalized using the voxel-based morphometry tools of Statistical Parametric Mapping 12. The normalized images were subjected to graph-theoretical group comparison using the Graph Analysis Toolbox with two different parcellation schemes. Initially, we used the Automated Anatomical Labeling template, whereas the Hammers Adult atlas was used for the second analysis.ResultsThe resilience analyses revealed significantly reduced resilience of the IGE gray matter networks to both random failure and targeted attack. No significant between-group differences were found in global network measures, including the clustering coefficient and characteristic path length. The IGE group showed several changes in regional clustering, including an increase mainly in wide areas of the bilateral frontal lobes. The second analysis with another region of interest (ROI) parcellation generated the same results in resilience and global network measures, but the regional clustering results differed between the two parcellation schemes.ConclusionThese results may reflect the potentially weak network organization in IGE. Our findings contribute to the accumulation of knowledge on IGE.

Background and purpose: Automated subfield volumetry of hippocampus is desirable for use in temporal lobe epilepsy (TLE), but its utility has not been established. Automatic segmentation of hippocampal subfields (ASHS) and the new version of FreeSurfer software (ver.6.0) using high-resolution T2-weighted MR imaging are candidates for this volumetry. The aim of this study was to evaluate hippocampal subfields in TLE patients using ASHS as well as the old and new versions of FreeSurfer. Materials and methods: We recruited 50 consecutive unilateral TLE patients including 25 with hippocampal sclerosis (TLE-HS) and 25 without obvious etiology (TLE-nonHS). All patients and 45 healthy controls underwent high-resolution T2-weighted and 3D-volume T1-weighted MRI scanning. We analyzed all of their MR images by FreeSurfer ver.5.3, ver.6.0 and ASHS. For each subfield, normalized z-scores were calculated and compared among groups. Results: In TLE-HS groups, ASHS and FreeSurfer ver.6.0 revealed maximal z-scores in ipsilateral cornu ammonis (CA) 1, CA4 and dentate gyrus (DG), whereas in FreeSurfer ver.5.3 ipsilateral subiculum showed maximal z-scores. In TLE-nonHS group, there was no significant volume reduction by either ASHS or FreeSurfer. Conclusions: ASHS and the new version of FreeSurfer may have an advantage in compatibility with existing histopathological knowledge in TLE patients with HS compared to the old version of FreeSurfer (ver.5.3), although further investigations with pathological findings and/or surgical outcomes are desirable.

The recent advent of tau-specific positron emission tomography (PET) has enabled in vivo assessment of tau pathology in Alzheimer’s disease (AD). However, because PET scanners have limited spatial resolution, the measured signals of small brain structures or atrophied areas are underestimated by partial volume effects (PVEs). The aim of this study was to determine whether partial volume correction (PVC) improves the precision of measures of tau deposits in early AD. We investigated tau deposits in 18 patients with amyloid-positive early AD and in 36 amyloid-negative healthy controls using 18F-THK5351 PET. For PVC, we applied the SPM toolbox PETPVE12. The PET images were then spatially normalized and subjected to voxel-based group analysis using SPM12 for comparison between the early AD patients and healthy controls. We also compared these two groups in terms of brain atrophy using voxel-based morphometry of MRI. We found widespread neocortical tracer retention predominantly in the posterior cingulate and precuneus areas, but also in the inferior temporal lobes, inferior parietal lobes, frontal lobes, and occipital lobes in the AD patients compared with the controls. The pattern of tracer retention was similar between before and after PVC, suggesting that PVC had little effect on the precision of tau load measures. Gray matter atrophy was detected in the medial/lateral temporal lobes and basal frontal lobes in the AD patients. Interestingly, only a few associations were found between atrophy and tau deposits, even after PVC. In conclusion, PVC did not significantly affect 18F-THK5351 PET measures of tau deposits. This discrepancy between tau deposits and atrophy suggests that tau load precedes atrophy.

The presentation and distribution of gray matter (GM) and white matter (WM) abnormalities in temporal lobe epilepsy (TLE) have been widely studied. Here, we investigated the GM and WM abnormalities in TLE patients with and without hippocampal sclerosis (HS) in five groups of participants: healthy controls (HCs) (n = 28), right TLE patients with HS (n = 26), right TLE patients without HS (n = 30), left TLE patients with HS (n = 25), and left TLE patients without HS (n = 27). We performed a flexible factorial statistical test in a whole-brain voxel-based morphometry analysis to identify significant GM and WM abnormalities and analysis of variance of hippocampal and amygdala regions among the five groups using the FreeSurfer procedure. Furthermore, we conducted multiple regression analysis to assess regional GM and WM changes with disease duration. We observed significant ipsilateral mesiotemporal GM and WM volume reductions in TLE patients with HS compared with HCs. We also observed a slight GM amygdala swelling in right TLE patients without HS. The regression analysis revealed significant negative GM and WM changes with disease duration specifically in left TLE patients with HS. The observed GM and WM abnormalities may contribute to our understanding of the root of epilepsy mechanisms.

This study aimed to investigate abnormalities in structural covariance network constructed from gray matter volume in myotonic dystrophy type 1 (DM1) patients by using graph theoretical analysis for further clarification of the underlying mechanisms of central nervous system involvement. Twenty-eight DM1 patients (4 childhood onset, 10 juvenile onset, 14 adult onset), excluding three cases from 31 consecutive patients who underwent magnetic resonance imaging in a certain period, and 28 age- and sex- matched healthy control subjects were included in this study. The normalized gray matter images of both groups were subjected to voxel based morphometry (VBM) and Graph Analysis Toolbox for graph theoretical analysis. VBM revealed extensive gray matter atrophy in DM1 patients, including cortical and subcortical structures. On graph theoretical analysis, there were no significant differences between DM1 and control groups in terms of the global measures of connectivity. Betweenness centrality was increased in several regions including the left fusiform gyrus, whereas it was decreased in the right striatum. The absence of significant differences between the groups in global network measurements on graph theoretical analysis is consistent with the fact that the general cognitive function is preserved in DM1 patients. In DM1 patients, increased connectivity in the left fusiform gyrus and decreased connectivity in the right striatum might be associated with impairment in face perception and theory of mind, and schizotypal-paranoid personality traits, respectively.

Psychosis is one of the most important psychiatric comorbidities in temporal lobe epilepsy (TLE), and its pathophysiology still remains unsolved. We aimed to explore the connectivity differences of structural neuroimaging between TLE with and without psychosis using a graph theoretical analysis, which is an emerging mathematical method to investigate network connections in the brain as a small-world system.We recruited 11 TLE patients with unilateral hippocampal sclerosis (HS) presenting psychosis or having a history of psychosis (TLE-P group). As controls, 15 TLE patients with unilateral HS without any history of psychotic episodes were also recruited (TLE-N group). For graph theoretical analysis, the normalized gray matter images of both groups were subjected to Graph Analysis Toolbox (GAT). As secondary analyses, each group was compared to 14 age- and gender-matched healthy subjects.The hub node locations were found predominantly in the ipsilateral hemisphere in the TLE-N group, and mainly on the contralateral side in the TLE-P group. The TLE-P group showed significantly higher characteristic path length, transitivity, lower global efficiency, and resilience to random or targeted attack than those of the TLE-N group. The regional comparison in betweenness centrality revealed significantly decreased connectivity in the contralateral temporal lobe, ipsilateral middle frontal gyrus, and bilateral postcentral gyri in the TLE-P group. The healthy subjects showed well-balanced nodes/edges distributions, similar metrics to TLE-N group except for higher small-worldness/modularity/assortativity, and various differences of regional betweenness/clustering.In TLE with psychosis, graph theoretical analysis of structural imaging revealed disrupted connectivity in the contralateral hemisphere. The network metrics suggested that the existence of psychosis can bring vulnerability and decreased efficiency of the whole-brain network. The sharp differences in structural networks between morphologically homogeneous groups are remarkable and may contribute to a better understanding of psychosis in TLE.

Schizophrenia is a common severe psychiatric disorder that affects approximately 1% of general population through the life course. Historically, in Kraepelin's time, schizophrenia was a disease unit conceptualized as dementia praecox; however, since then, the disease concept has changed. Recent MRI studies had shown that the neuropathology of the brain in this disorder was characterized by mild progression before and after the onset of the disease, and that the brain alterations were relatively smaller than assumed. Although genetic factors contribute to the brain alterations in schizophrenia, which are thought to be trait differences, other changes include factors that are common in psychiatric diseases. Furthermore, it has been shown that the brain differences specific to schizophrenia were relatively small compared to other changes, such as those caused by brain development, aging, and gender. In addition, compared to the disease and participant factors, machine and imaging protocol differences could affect MRI signals, which should be addressed in multi-site studies. Recent advances in MRI modalities, such as multi-shell diffusion-weighted imaging, magnetic resonance spectroscopy, and multimodal brain imaging analysis, may be candidates to sharpen the characterization of schizophrenia-specific factors and provide new insights. The Brain/MINDS Beyond Human Brain MRI (BMB-HBM) project has been launched considering the differences and noises irrespective of the disease pathologies and includes the future perspectives of MRI studies for various psychiatric and neurological disorders. The sites use restricted MRI machines and harmonized multi-modal protocols, standardized image preprocessing, and traveling subject harmonization. Data sharing to the public will be planned in FY 2024. In the future, we believe that combining a high-quality human MRI dataset with genetic data, randomized controlled trials, and MRI for non-human primates and animal models will enable us to understand schizophrenia, elucidate its neural bases and therapeutic targets, and provide tools for clinical application at bedside. [ABSTRACT FROM AUTHOR]