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Background Early neurodevelopmental deviations, such as abnormal cortical folding patterns, are candidate biomarkers of major depressive disorder (MDD). We aimed to investigate the association of MDD with the local gyrification index (LGI) in each cortical region at the whole-brain level, and the association of the LGI with clinical characteristics of MDD. Methods We obtained T1-weighted images from 234 patients with MDD and 215 healthy controls (HCs). The LGI values from 66 cortical regions in the bilateral hemispheres were automatically calculated according to the Desikan–Killiany atlas. We compared the LGI values between the MDD and HC groups using analysis of covariance, including age, sex, and years of education as covariates. The association between the clinical characteristics and LGI values was investigated in the MDD group. Results Compared with HCs, patients with MDD showed significantly decreased LGI values in the cortical regions, including the bilateral ventrolateral and dorsolateral prefrontal cortices, medial and lateral orbitofrontal cortices, insula, right rostral anterior cingulate cortex, and several temporal and parietal regions, with the largest effect size in the left pars triangularis (Cohen's f2 = 0.361; p = 1.78 × 10−13). Regarding the association of clinical characteristics with LGIs within the MDD group, recurrence and longer illness duration were associated with increased gyrification in several occipital and temporal regions, which showed no significant difference in LGIs between the MDD and HC groups. Conclusions These findings suggest that the LGI may be a relatively stable neuroimaging marker associated with MDD predisposition.

Objective A growing body of evidence reports on the effect of different types of childhood abuse on the structural and functional architecture of the brain. In the present study, we aimed to investigate the differences in cortical thickness according to specific types of childhood abuse between patients with major depressive disorder (MDD) and healthy controls (HCs).Methods A total of 61 patients with MDD and 98 HCs were included in this study. All participants underwent T1-weighted magnetic resonance imaging, and the occurrence of childhood abuse was assessed using the Childhood Trauma Questionnaire. We investigated the association between whole-brain cortical thickness and exposure to any type of childhood abuse and specific type of childhood abuse in the total sample using the FreeSurfer software.Results No significant difference was reported in the cortical thickness between the MDD and HC groups nor between the “any abuse” and “no abuse” groups. Compared to no exposure to childhood sexual abuse (CSA), exposure to CSA was significantly associated with cortical thinning in the left rostral middle frontal gyrus (p=0.00020), left (p=0.00240), right fusiform gyri (p=0.00599), and right supramarginal gyrus (p=0.00679).Conclusion Exposure to CSA may lead to cortical thinning of the dorsolateral prefrontal cortex, which is deeply involved in emotion regulation, to a greater extent than other types of childhood abuse.

Major depressive disorder (MDD) is one of the most common psychiatric disorders, and present various symptoms such as the dysregulation of mood, cognition, and behavior. The purpose of the present study was to investigate the morphometric change in MDD patients by voxel-based morphometry (VBM) and sulcal depth analyses. Forty-six MDD patients (mean age, SD; 36.07±14.34), and 23 age- and sex-matched normal controls (NML) (mean age, SD; 36.78±14.42) were included. Coronal 3D T1 magnetic resonance imaging (MRI) was obtained with the resolution of isotropic 1.0 mm. To check morphological changes of brain, T1 MRIs were objectively processed by VBM and sulcal depth methods. In sulcal depth analysis, depressed patients showed reduced sulcal depth in the areas of left posterior ramus of the lateral sulcus, superior frontal sulcus, supramarginal gyrus, central sulcus (Rolando's fissure), and Heschl's gyrus. And right posterior ramus of the lateral sulcus, temporal plane of the superior temporal gyrus, anterior transverse collateral sulcus, and central sulcus (Rolando's fissure) were also reduced compared to NML. But, VBM analyses did not showed significant finding. Reduced sulcal depth in the motor and emotion related areas were found in patients with MDD. Especially reduced sulcal depth in bilateral central sulci which are connecting between primary motor cortex and primary sensory cortex seems to be related with social and physical anhedonia in MDD.

Objective Considerable evidence suggests that neuroinflammation plays an important role in the pathophysiology of major depressive disorder (MDD). However, the relationship between serum C4 binding protein (C4BP) and white matter (WM) tract integrity in MDD has not been investigated.Methods We obtained diffusion tensor images of 44 patients with MDD and 44 healthy controls and performed TRActs Constrained by UnderLying Anatomy (TRACULA) analysis to assess WM tract integrity. Serum C4-binding protein alpha chain (C4BPA) and C4- binding protein beta chain (C4BPB) levels were measured and in-between group comparisons were obtained. The correlation between serum C4BP levels and WM tract integrity was examined.Results In comparison to healthy controls, both serum C4BPA and C4BPB were higher in MDD. Also, fractional anisotropy (FA) was increased in the left cingulum-angular bundle (CAB) in MDD, but not healthy controls (HCs). A significant correlation was found between serum C4BP and FA levels in the right cingulum-cingulate gyrus bundle (CCG) in MDD.Conclusion This study is the first to investigate the correlation between serum C4BP levels and WM tract integrity in MDD. We identified an increase in WM integrity in the left CAB region in MDD. Furthermore, serum C4BP levels were higher in MDD, and this finding correlated with increased WM integrity in the right CCG region.

Objective Advances in surface-based morphometric methods have allowed researchers to separate cortical volume into cortical thickness (CTh) and surface area (SA). Although CTh alterations in major depressive disorder (MDD) have been observed in numerous studies, few studies have described significant SA alterations. Our study aimed to measure patients’ SAs and to compare it with their CTh to examine whether SA exhibits alteration patterns that differ from those of CTh in drug-naïve patients with MDD.Methods A total of 71 drug-naïve MDD patients and 111 healthy controls underwent structural magnetic resonance imaging, and SA and CTh were analyzed between the groups.Results We found a smaller SA in the left superior occipital gyrus (L-SOG) in drug-naïve patients with MDD. In the CTh analysis, the bilateral fusiform gyrus, left middle occipital gyrus, left temporal superior gyrus, and right posterior cingulate showed thinner cortices in patients with MDD, while the CTh of the bilateral SOG, right straight gyrus, right posterior cingulate, and left lingual gyrus were increased.Conclusion Compared with the bilateral occipito-temporal changes in CTh, SA alterations in patients with MDD were confined to the L-SOG. These findings may improve our understanding of the neurobiological mechanisms of SA alteration in relation to MDD.

Objective Although bipolar II disorder (BD II) is not simply a mitigated form of bipolar I disorder (BD I), their neurobiological differences have not been elucidated. The present study aimed to explore cortical thickness (CT) and surface area (SA) in patients with BD I and BD II and healthy controls (HCs) to investigate the shared and unique neurobiological mechanisms of BD subtypes.Methods We enrolled 30 and 44 patients with BD I and BD II, respectively, and 100 HCs. We evaluated CT and SA using FreeSurfer and estimated differences in CT and SA among the three groups (BD I vs. BD II vs. HC). We adjusted for age, sex, educational level, and intracranial volume as confounding factors.Results We found widespread cortical thinning in the bilateral frontal, temporal, and occipital regions; cingulate gyrus; and insula in patients with BD. Alterations in SA, including increased SA of the pars triangularis and decreased SA of the insula, were noted in patients with BD. Overall, we found BD II patients demonstrated decreased SA in the right long insula compared to BD I patients.Conclusion Our results suggest that decreased SA in the right long insula is crucial for differentiating BD subtypes.

Background Temporal changes in the structural connectivity of major language tracts after stroke and their contribution to aphasia recovery are unclear. Objective To investigate longitudinal arcuate fasciculus (AF) integrity changes and their relationship with post-stroke aphasia recovery using diffusion tensor imaging (DTI). Methods Thirty-five patients with aphasia due to first-ever left hemispheric stroke underwent the Korean version of the Western Aphasia Battery and DTI at 1- and 6-month post stroke onset. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) of both AF tracts were analyzed to evaluate the temporal changes in tract integrity and determine the correlation between changes (Δ; follow-up − initial) in DTI parameters and language scores. Results At 6 months post-stroke, the mean FA decreased, and mean MD and RD increased in both hemispheres; however, compared with mean AD observed after 1 month, the mean observed at 6 months increased only in the left hemisphere ( P Conclusions: During the subacute stage, the integrity of AF decreased in both hemispheres in patients with aphasia, and the change in structural connectivity of the left AF was associated with language improvement.

Despite the growing number of refugees and their mental health issues, neurobiological mechanisms to explain clinical symptoms resulting from traumatic events, such as post-traumatic stress disorder (PTSD) or major depressive disorder (MDD), have not been extensively investigated. Research on the mental health of North Korean refugees (NKRs) who defected to South Korea for resettlement is still at an early stage but commonly reports structural and functional abnormalities in brain regions related to reward and motivational processing. The nucleus accumbens (NAc) and ventral pallidum (VP) are the major sites in subcortical structures that play key roles in reward and motivation.The present study examined subcortical structural abnormalities of 28 NKRs and age-, sex- matched South Korean Controls (SKCs) using shape analysis at the vertex level.Among the 28 NKRs, 18 had psychiatric disorders, including PTSD and MDD. The NKRs showed significantly reduced volumes in the right NAc and bilateral VP compared to the SKRs. The volume of the right VP showed a significant negative correlation with current PTSD severity in the NKR group.Our findings demonstrated that structural alterations of the NAc and VP may explain PTSD and MDD observed in the refugees and further suggest that the aftereffect of trauma, manifested as anhedonia and anxiety, may show chronically.

The Nod-like receptor pyrin containing 3 (NLRP3) inflammasome has been reported to be a convergent point linking the peripheral immune response induced by psychological stress and neuroinflammatory processes in the brain. We aimed to identify differences in the methylation profiles of the NLRP3 gene between major depressive disorder (MDD) patients and healthy controls (HCs). We also investigated the correlation of the methylation score of loci in NLRP3 with cortical thickness in the MDD group using magnetic resonance imaging (MRI) data. A total of 220 patients with MDD and 82 HCs were included in the study, and genome-wide DNA methylation profiling of the NLRP3 gene was performed. Among the total sample, 88 patients with MDD and 74 HCs underwent T1-weighted structural MRI and were included in the neuroimaging–methylation analysis. We identified five significant differentially methylated positions (DMPs) in NLRP3. In the MDD group, the methylation scores of cg18793688 and cg09418290 showed significant positive or negative correlations with cortical thickness in the occipital, parietal, temporal, and frontal regions, which showed significant differences in cortical thickness between the MDD and HC groups. Our findings suggest that NLRP3 DNA methylation may predispose to depression-related brain structural changes by increasing NLRP3 inflammasome-related neuroinflammatory processes in MDD.

Objective This study aimed to investigate the morphometric differences in the corpus callosum between patients with major depressive disorder (MDD) and healthy controls and analyze their relationship to gray matter changes.Methods Twenty female MDD patients and 21 healthy controls (HCs) were included in the study. To identify the difference in the regional gray matter concentration (GMC), VBM was performed with T1 magnetic resonance imaging. The shape analysis of the corpus callosum was processed. Diffusion tensor imaging (DTI) fiber-tracking was performed to identify the regional tract pathways in the damaged corpus callosal areas.Results In the shape analysis, regional shape contractions in the rostrum and splenium were found in the MDD patients. VBM analysis showed a significantly lower white matter concentration in the genu and splenium, and a significantly lower GMC in the frontal, limbic, insular, and temporal regions of the MDD patients compared to the HCs. In DTI fiber-tracking, the fibers crossing the damaged areas of the genu, rostrum, and splenium were anatomically connected to the areas of lower GMC in MDD patients.Conclusion These findings support that major depressive disorder may be due to disturbances in multiple neuronal circuits, especially those associated with the corpus callosum.

Background Numerous studies have suggested that structural changes in the cerebellum are implicated in the pathophysiology of bipolar disorder (BD). We aimed to investigate differences in the volume and cortical thickness of the cerebellar subregions between patients with BD and healthy controls (HCs). Methods Ninety patients with BD and one hundred sixty-six HCs participated in this study and underwent T1-weighted structural magnetic resonance imaging. We analyzed the volume and cortical thickness of each cerebellar hemisphere divided into 12 subregions using T1-weighted images of participants. One-way analysis of covariance was used to evaluate differences between the groups, with age, sex, medication, and total intracranial cavity volume used as covariates. Results The BD group had significantly increased cortical thickness of the cerebellum in all cerebellar subregions compared to the HC group. The cortical thicknesses of the whole cerebellum and each hemisphere were also significantly thicker in the BD group than in the HC group. The volume of the left lobule IX was significantly lower in patients with BD than in HCs, whereas no significant differences in the volumes were observed in the other subregions. Limitations Our cross-sectional design cannot provide a causal relationship between the increased cortical thickness of the cerebellum and the risk of BD. Conclusions We observed widespread and significant cortical thickening in all the cerebellar subregions. Our results provide evidence for the involvement of the cerebellum in BD. Further studies are required to integrate neurobiological evidence and structural brain imaging to elucidate the pathophysiology of BD.

Objective Although neuroimaging studies have shown volumetric reductions, such as the anterior cingulate, prefrontal cortices, and hippocampus in patients with major depressive disorder (MDD), few studies have investigated the volume of or shape alterations in the subcortical regions and the brainstem. We hypothesized that medication-naïve female adult patients with MDD might present with shape and volume alterations in the subcortical regions, including the brainstem, compared to healthy controls (HCs).Methods A total of 20 medication-naïve female patients with MDD and 21 age-matched female HCs, underwent 3D T1-weighted structural magnetic resonance scanning. We analyzed the volumes of each subcortical region and each brainstem region, including the midbrain, pons, and medulla oblongata. We also performed surface-based vertex analyses on the subcortical areas and brainstem.Results Female patients with MDD showed non-significant volumetric differences in the subcortical regions, whole brainstem, and each brainstem region compared to the HCs. However, in the surface-based vertex analyses, significant shape contractions were observed in both cerebellar peduncles located on the lateral wall of the posterior brainstem [threshold-free cluster enhancement, corrected for family-wise error (FWE) at p

Although structural alterations have been reported in patients with major depressive disorder (MDD), very few studies have compared the shape alterations of the subcortical regions between drug-naïve MDD patients and healthy controls (HCs). Therefore, we investigated and compared the subcortical shape alterations and volumetric changes between drug-naïve MDD patients and HCs in this study.This study included 45 drug-naïve MDD patients and 83 HCs, who underwent three-dimensional (3-D) T1-weighted structural magnetic resonance imaging. Surface-based vertex analysis (SVA) was performed with automated segmentation of the bilateral caudate nuclei, putamina, nuclei accumbens, thalami, pallidum, hippocampi, amygdalae, and brainstem. SVA revealed regional contractions of the thalamus (bilateral medial and lateral nuclei) and right caudate nucleus (medial wall and anterosuperior areas) in the drug-naïve MDD patients when compared to HCs RESULTS: In volume analysis, the drug-naïve MDD patients showed a significant decrease in the volume of bilateral thalami compared with HCs (after Bonferroni correction p 0.003). We identified morphometric contractions in bilateral thalami and right caudate nucleus in the drug-naïve MDD patients (p 0.05).The present study implied that with cortical shape changes, the subcortical brain alterations could contribute to emotional dysregulation in the drug-naïve MDD patients.

Plastic changes to brain structure and function have been reported in elite athletes of various sports. Interestingly, different regions of the brain were engaged according to the type of sports analyzed. Our laboratory reported no difference in total cerebellar volume of basketball players compared to that in the control group using the manual segmentation method. Further detailed analyses showed that elite basketball players had increased volume of the striatum and vermian lobules VI-VII of the cerebellum. We analyzed the brain magnetic resonance imaging (MRI) of basketball players to understand their cerebral cortical plasticity through automatic analysis tools for MRI.Brain MRI data were collected from 19 male university basketball players and 20 age-, sex-, and height-matched control groups. In order to understand the changes in the cerebral cortices of basketball players, we employed automated MRI brain analysis techniques, including voxel-based morphometry (VBM) and surface-based morphometry (SBM).VBM showed increased gray and white matter volume in both precentral gyri, paracentral lobules and increased gray matter volume in the right anterior superior temporal gyrus. SBM revealed a left dominant increase in both pericentral gyri. Fractal dimensional analysis showed an increase in the area of both precentral gyri, the left subcallosal gyrus, and the right posterior cingulate gyrus. These results suggest a significant role not only for the primary motor cortex, but also for the cingulate gyrus during basketball.Plastic changes of both precentral gyri, the pericentral area, paracentral lobules, and the right superior temporal gyrus were observed in elite basketball players. There was a strong increase of fractal complexity in both precentral gyri and a weak increase in the right posterior cingulate gyrus and left collateral gyrus. In this study, plastic regions linked to functional neuroanatomy were related to the competence required to play basketball.

Childhood abuse is associated with brain structural alterations; however, few studies have investigated the association between specific types of childhood abuse and cortical volume in patients with major depressive disorder (MDD). We aimed to investigate the association between specific types of childhood abuse and gray matter volumes in patients with MDD. Seventy-five participants with MDD and 97 healthy controls (HCs) aged 19-64 years were included. Cortical gray matter volumes were compared between MDD and HC groups, and also compared according to exposure to each type of specific childhood abuse. Emotional, sexual, and physical childhood abuse were assessed using the 28-item Childhood Trauma Questionnaire. Patients with MDD showed a significantly decreased gray matter volume in the right anterior cingulate gyrus (ACG). Childhood sexual abuse (CSA) was associated with significantly decreased gray matter volume in the right middle occipital gyrus (MOG). In the post-hoc comparison of volumes of the right ACG and MOG, MDD patients with CSA had significantly smaller volumes in the right MOG than did MDD patients without CSA or HCs. The right MOG volume decrease could be a neuroimaging marker associated with CSA and morphological changes in the brain may be involved in the pathophysiology of MDD.

s Background Bipolar disorder (BD) is one of the most heritable psychiatric disorders. A growing number of whole-exome sequencing (WES) studies for BD has been performed, however, no research has examined the association between single nucleotide variants (SNVs) from WES and structural magnetic resonance imaging (MRI) data. Methods We sequenced whole-exomes in 53 patients with BD and 82 healthy control participants at an initial discovery stage and investigated the impacts of SNVs in risk genes from WES analysis on the cortical gray-matter thickness and integrity of white matter tracts and in the following stage. Cortical thickness and white matter integrity were investigated using the FreeSurfer and TRACULA (Tracts Constrained by UnderLying Anatomy). Results We identified 122 BD-related genes including KMT2C, AHNAK, CDH23, DCHS1, FRAS1, MACF1 and RYR3 and observed 27 recurrent copy number alteration regions including gain on 8p23.1 and loss on 15q11.1 - q11.2. Among them, single nucleotide polymorphism (SNP) rs4639425 in KMT2C gene, which regulates histone H3 lysine 4 (H3K4) methylation involved in chromatin remodeling, was associated with widespread alterations of white matter integrity including the cingulum, uncinate fasciculus, cortico-spinal tract, and superior longitudinal fasciculus. Limitation The small sample size of patients with BD in the genome data may cause our study to be underpowered when searching for putative rare mutations. Conclusion This study first combined a WES approach and neuroimaging findings in psychiatric disorders. We postulate the rs4639425 may be associated with BD-related microstructural changes of white matter tracts.

Background:The hippocampus is not a uniform structure, but rather consists of multiple, functionally specialized subfields. Few studies have explored hippocampal subfield volume difference in the same sample of major depressive disorder (MDD) and bipolar disorder (BD) cases. We aimed to investigate the difference of hippocampal subfield volume between patents with MDD and BD and healthy controls (HCs).Methods:A total of 102 MDD and 55 BD patients and 135 HCs were recruited and underwent T1-weighted image. Hippocampal subfield volume was calculated by automated segmentation and volumetric procedures developed by Iglesias et al. and implemented in FreeSurfer. Volume differences between the groups were analyzed using the analysis of covariance and controlling for age, sex, and total intracranial cavity volume.Results:Patients with MDD had significantly reduced volumes in the bilateral cornu ammonis 1 (CA1), CA4, the granule cell layer (GCL), molecular layer (ML), whole hippocampus, the left CA2/3, and right presubiclum and subiculum. Patients with BD had significantly reduced volumes in the right CA1, GCL, and the whole hippocampus as compared to HCs. No significant volume differences were observed between the MDD and BD groups. Illness duration was negatively correlated with volumes of the left CA1, CA4, ML, presubiculum, subiculum, and the whole hippocampus in patients with BD.Conclusion:We observed hippocampal subfield volume reductions in both MDD and BD, a finding which more prominent in MDD. The inverse correlation between BD illness duration and hippocampal subfield volume may evidence the neuroprogressive nature of BD.

Background Although major depressive disorder (MDD) has been associated with volumetric abnormalities in the amygdala, studies investigating the association between structural alterations of the amygdala and depression have yielded varying results. Since the amygdala comprises several subregions, it is difficult to detect subtle regional changes by measuring the total amygdala volume. This study aimed to examine the volume in each amygdala subregion in adults with and without a diagnosis of MDD. Methods A total of 147 participants with a current history of major depression and 144 healthy participants ranging in age from 19 to 64 years underwent 3T magnetic resonance imaging scanning. Automatic segmentation of the nine nuclei of the amygdala was performed using FreeSurfer. One-way analysis of covariance, with individual volumes as dependent variables, and age, sex, and total intracranial volume as covariates, was performed to analyze volume differences. Results Patients with MDD had significantly lower volumes of the entire amygdala and subregions, including the lateral nucleus and anterior amygdaloid area, than healthy volunteers (HCs). There were no significant associations between subregion volumes and antidepressant use, illness duration, or depression severity. Limitations Our cross-sectional design cannot provide a causal relationship between the volume change in the amygdala subregion and the risk of MDD. Conclusion Our findings suggest that specific amygdala subregions are more susceptible to volumetric alterations in patients with MDD than in HCs. These findings may advance our understanding of the neuroanatomic basis on MDD.

Complex regional pain syndrome (CRPS) is a common poststroke complication. However, the neural substrates associated with CRPS remain unclear. We investigated the neural correlates associated with poststroke CRPS using voxel-based lesion‒symptom mapping (VLSM) analysis. Among 145 patients with ischemic stroke, 35 were diagnosed with CRPS and categorized into the poststroke CRPS group, and the remaining 110 into the control group. We compared the clinical characteristics between the groups. VLSM analysis was performed to identify the brain region associated with the development of poststroke CRPS. The clinical findings suggested that the poststroke CRPS group had lower muscle strength; lower scores on Fugl‒Meyer assessment, Manual Function Test, Mini-Mental Status Examination; and higher incidence of absent somatosensory evoked potentials in the median nerve than the control group. The head of the caudate nucleus, putamen, and white matter complexes in the corona radiata were significantly associated with poststroke CRPS development in ischemic stroke patients. These results facilitate an understanding of poststroke CRPS pathophysiology. Monitoring patients with lesions in these structures may aid the prevention and early treatment of poststroke CRPS.

Complex regional pain syndrome (CRPS) is a common poststroke complication. However, the neural substrates associated with CRPS remain unclear. We investigated the neural correlates associated with poststroke CRPS using voxel-based lesion‒symptom mapping (VLSM) analysis. Among 145 patients with ischemic stroke, 35 were diagnosed with CRPS and categorized into the poststroke CRPS group, and the remaining 110 into the control group. We compared the clinical characteristics between the groups. VLSM analysis was performed to identify the brain region associated with the development of poststroke CRPS. It suggested that damage to the caudate nucleus head, putamen, and white matter complexes in the corona radiata were significantly associated with poststroke CRPS development. The clinical findings suggested that the poststroke CRPS group had lower muscle strength; lower scores on Fugl‒Meyer assessment, Manual Function Test, Mini-Mental Status Examination; and higher incidence of absent somatosensory evoked potentials in the median nerve than the control group. The head of the caudate nucleus, putamen, and white matter complexes in the corona radiata were associated with poststroke CRPS development in ischemic stroke patients. These results facilitate an understanding of poststroke CRPS pathophysiology. Monitoring patients with lesions in these structures may aid the prevention and early treatment of poststroke CRPS.

Swallowing disorders occur more frequently in older adults. However, the effects of the aging process on neural activation when swallowing are unclear. We aimed to identify neural regions activated during swallowing and evaluate changes in neural activation and neural networks with aging. Using a general linear model (GLM) and independent component (IC) analyses, blood oxygen level-dependent (BOLD) signals were observed in the lateral precentral gyrus, postcentral gyrus, anterior insular cortices, supramarginal gyri, and medial frontal gyrus during swallowing. The right thalamus and anterior cingulate gyri were found to be active areas by GLM and IC analyses, respectively. In the correlational analyses, age was negatively correlated with BOLD signals of the lateral precentral gyri, postcentral gyri, and insular cortices in swallowing tasks. Additionally, correlation analyses between ICs of all participants and age revealed negative correlations in the right supramarginal gyrus, both anterior cingulate cortices, putamen, and cerebellum. In the network analysis, the BOLD signal positively correlated with age in the default mode network (DMN), and was negatively correlated in the lateral precentral gyri, postcentral gyri, and insular cortices. The amplitude of low-frequency fluctuations was significantly decreased in the DMN and increased in swallowing-related areas during swallowing tasks. These results suggest that aging has negative effects on the activation of swallowing-related regions and task-induced deactivation of the DMN. These changes may be used to detect early functional decline during swallowing.

BackgroundAn aberrant neural connectivity has been known to be associated with bipolar disorder (BD). Local gyrification may reflect the early neural development of cortical connectivity and has been studied as a possible endophenotype of psychiatric disorders. This study aimed to investigate differences in the local gyrification index (LGI) in each cortical region between patients with BD and healthy controls (HCs).MethodsLGI values, as measured using FreeSurfer software, were compared between 61 patients with BD and 183 HCs. The values were also compared between patients with BD type I and type II as a sub-group analysis. Furthermore, we evaluated whether there was a correlation between LGI values and illness duration or depressive symptom severity in patients with BD.ResultsPatients with BD showed significant hypogyria in various cortical regions, including the left inferior frontal gyrus (pars opercularis), precentral gyrus, postcentral gyrus, superior temporal cortex, insula, right entorhinal cortex, and both transverse temporal cortices, compared to HCs after the Bonferroni correction (p < 0.05/66, 0.000758). LGI was not associated with clinical factors such as illness duration, depressive symptom severity, and lithium treatment. No significant differences in cortical gyrification according to the BD subtype were found.ConclusionsBD appears to be characterized by a significant regionally localized hypogyria, in various cortical areas. This abnormality may be a structural and developmental endophenotype marking the risk for BD, and it might help to clarify the etiology of BD.

This study investigated factors associated with aphasia severity at both 2 weeks and 3 months after stroke using demographic and clinical variables, brain diffusion tensor imaging (DTI) parameters, and lesion volume measurements. Patients with left hemisphere stroke were assessed at 2 weeks (n = 68) and at 3 months (n = 20) after stroke. Demographic, clinical, and neuroimaging data were collected; language functions were assessed using the Western Aphasia Battery. For neuroimaging, DTI parameters, including the laterality index (LI) of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity, mean diffusivity and fibre density (FD) of the arcuate fasciculus (AF), and lesion volume, were measured. Lesion volume, cortical involvement, and the National Institutes of Health Stroke Scale score significantly predicted aphasia severity at 2 weeks after stroke, whereas the aphasia quotient and presence of depression during the early subacute stage were significant predictors at 3 months after stroke. According to Pearson correlation, LI-AD and LI-FD were significantly correlated with the aphasia quotient 2 weeks after ischaemic stroke, and the LI-FA was significantly correlated with the aphasia quotient 2 weeks after haemorrhagic stroke, suggesting that the extent and mechanism of AF injuries differ between ischaemic and haemorrhagic strokes. These differences may contribute to aphasia severity.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. However, no reliable biomarkers have been identified to represent the clinical status. This study aimed to investigate whether diffusion tensor imaging (DTI) findings are useful imaging biomarkers to indicate the clinical status of ALS patients. Ninety-six probable or definite ALS cases and 47 age- and sex-matched, normal controls were enrolled. Demographic and clinical data were collected at the time of DTI. DTI data were acquired using a 3-Tesla magnetic resonance imaging scanner and analysed by voxel-wise statistical analyses for fractional anisotropy, axial diffusivity, radial diffusivity, mean diffusivity, and mode of anisotropy. Compared with the healthy control group, the ALS group had significant differences in DTI scalars in the diffuse tracts of the brain, which was predominant in the corticospinal tract at the brainstem and cerebellar peduncle area. Furthermore, the DTI values correlated with the ALS functional rating scale-revised (ALSFRS-R) scores and the delta ALSFRS-R score representing the rate of disease progression. The subgroup analysis revealed a more severe and widespread brain degeneration was observed in rapidly progressive ALS. Therefore, our results suggest that DTI findings are useful as imaging biomarkers for evaluating the clinical severity and rate of disease progression in ALS.

Objectives: We evaluated the changes of arcuate fasciculus (AF), an important connecting pathway for language function, using DTI at 1-month and 6-month after stroke and investigated the relationship between structural changes of AF and improvement of post-stroke aphasia. Methods: We collected data from the STroke Outcome Prediction (STOP) database that is prospective data collecting system for functional recovery prediction after stroke based on neuroimaging study. Twenty-six patients with aphasia (PWA) who had first-ever stroke, presence of aphasia evaluated by Western Aphasia Battery (WAB) and no previous neurological or psychiatric diagnosis. The WAB and DTI data within 1 month (initial) and 6 months after (follow-up) stroke onset were used for analysis. And fractional anisotropy (FA), mean diffusivity (MD), fiber number (FN) and differences (Δ) at two time points of these parameters were obtained in bilateral AF in diffusion tensor tractography (DTT). Three types (I: not reconstructed, II: disrupted, discontinued or shallow, III: preserved) of classification according to integrity of AF was also included. Results: DTT parameters of bilateral AF showed statistically significant decrease in FA and increase in MD. Types of AF were changed in 6 patients (23%): 3 patients from type III to type II, 2 patients from type II to type I, and 1 patient from type II to type III. In Pearson’s correlation analysis, significant correlation was observed between 6-mon aphasia quotient (AQ) and parameters of left AF; positive correlation with FA (r=0.707, p Conclusions: The AF changes over time not only in dominant but also in nondominant hemispheres in patients with aphasia after stroke. But amount of changes (Δ) in AF parameters were not associated with language recovery. Acknowledgement: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (No. 2019R1A2C2003020).

Objective: Corticospinal tract (CST) changes with time after stroke. However, few studies have investigated longitudinal change of CST and its relationship with motor outcomes. Primary goal of this study is to investigate the changes of CST after stroke using diffusion tensor image (DTI) and the relationship between CST changes and functional motor outcome in upper and lower extremities at 6 months after onset of stroke. Methods: We collected data from STroke Outcome Prediction (STOP) database that is prospective data collecting system for functional recovery prediction after stroke based on neuroimaging study. Fifty-five patients with first-ever stroke who performed functional assessment and underwent DTI at 30 days and 6 months poststroke were included. Clinical evaluation included Fugl-Meyer Assessment (FMA), Manual Function Test (MFT), Berg Balance Scale (BBS), and Functional Ambulation Category (FAC). DTI parameters were fiber number (FN), average fiber length (AL), fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), radial diffusivity (RD), laterality index (LI) and delta (Δ) changes of these values. Also type of CST by diffusion tensor tractography was included for analysis. Results: FA decreased and diffusivity indices (AD, MD, RD) increased in ipsilesional hemisphere; Decrease of FA and increase of RD were also noted in contralesional side. Type of CST were changed in 19 patients (34.6%). Spearman correlation analysis showed strong correlations between DTI values (FN, AL, FA, RD) and motor outcomes (FMA, MFT, BBS, FAC) at 30 days and 6 months. However, ΔFA or ΔRD did not show significant correlation with Δ changes of motor outcomes. In the CART analysis, overall prediction accuracy of DTI parameters for 6-month motor outcome ranged from 81.8 to 90.9 %. Conclusion: The integrity of CST changed not only on the lesion side but also on contralesional side. Integrity of CST using DTI at early phase of rehabilitation is useful to predict 6-month motor outcome after stroke. Acknowledgement: No potential conflict of interests relevant to this article were reported. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1A2C2003020).

Tinnitus, the perception of sound without an external source, is a prevalent disease, but its underlying mechanism has not been fully elucidated. Recent studies have suggested the involvement of subcortical nuclei in tinnitus generation. We investigated changes in the local shape and volume of subcortical nuclei in relation to tinnitus. The participants included 53 patients with tinnitus and 52 age- and gender-matched normal controls. Individual 3D T1-weighted structural images were obtained using 3-T magnetic resonance imaging. Surface-based vertex analysis (SVA) was performed with automated segmentation of the bilateral caudate nuclei, putamina, nucleus accumbens, thalami, pallidum, hippocampi, amygdalae, and brainstem. The scalar distances from the mean surface and volumes of 15 nuclei were compared between the tinnitus and control groups and correlated with tinnitus handicap score (THI) and tinnitus duration. SVA revealed regional contractions in the accessory basal and lateral nuclei of the right amygdala and expansions in the left medial and right ventral posterior nuclei and lateral dorsal nucleus of both thalami. The surface distances of the right nucleus accumbens were positively correlated with tinnitus duration, while those of the left nucleus accumbens and left hippocampus were negatively correlated with THI. Regional atrophy of the amygdala may indicate self-modulation of emotional response regulation to diminish tinnitus-related emotional distress. Thalamic regional expansion may signify dysfunctional auditory gating in the thalamus, where inhibition of the tinnitus signal at the thalamus level is disrupted due to abnormal changes in the limbic system, ultimately leading to the tinnitus percept.

The serotonin-transporter-linked polymorphic region (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) Val66Met polymorphism have been implicated in the pathophysiology of major depressive disorder (MDD). We aimed to investigate the effects of genetic variants of the 5-HTTLPR and BDNF Val66Met polymorphisms and their interactions with MDD on cortical volume and white matter integrity. Ninety-five patients with MDD and 65 healthy participants aged 20-65 years were recruited. The subjects were genotyped for the 5-HTTLPR and BDNF Val66Met polymorphisms and scanned with T1-weighted and diffusion tensor imaging. The gray matter volumes of 24 gyri in the prefrontal and anterior cingulate cortices and the fractional anisotropy values of nine white matter tracts in both hemispheres were determined. In the pooled sample of subjects from both groups, 5-HTTLPR L-allele carriers had significantly decreased cortical volume in the right anterior midcingulate gyrus compared to S-allele homozygotes. A significant effect of the interaction of the BDNF Val66Met polymorphism and MDD on the fractional anisotropy values of the right uncinate fasciculus was observed. Our results suggested that these genetic polymorphisms play important roles in the neurostructural changes of emotion-processing regions in subjects with MDD.

Bipolar I disorder (BD-I) is often misdiagnosed, leading to inadequate treatment and significant disability along with reduced quality of life. Recent neural models suggest that the reward circuitry is affected in bipolar disorder. The purpose of the present study was to identify structural abnormalities in the brain reward-processing neural circuitry among patients with BD-I. 21 patients with BD-I and 21 healthy controls (HC) participated in this study. Structural magnetic resonance imaging was performed. Region-of-interest (ROI) voxel-based morphometry analysis was applied to assess the presence of structural changes between the BD-I patient group and the control group. The results of the reward circuitry ROI analysis revealed lower gray matter volumes in the left ventromedial prefrontal cortex (VMPFC), left dorsomedial prefrontal cortex (DMPFC), and left ventrolateral prefrontal cortex (VLPFC) in patients with BD-I compared to HC. Our results suggest that abnormalities in the brain reward-processing neural circuitry, especially those in the left VMPFC, left DMPFC, and left VLPFC, may play an important role in the pathophysiology of BD-I.

Two recent genome-wide association studies have suggested that rs7294919 is associated with changes in hippocampal volume. rs7294919 regulates the transcriptional products of the TESC gene, which is involved in neuronal proliferation and differentiation. We investigated the interactive effect of rs7294919 and major depressive disorder (MDD) on the volume of the hippocampal subfields and the integrity of the parahippocampal cingulum (PHC). We also investigated the correlation of these structural changes with the DNA methylation status of rs7294919. A total of 105 patients with MDD and 85 healthy control subjects underwent T1-weighted structural magnetic resonance imaging and diffusion tensor imaging. The rs7294919 was genotyped and its DNA methylation status was assessed in all the participants. We analyzed the hippocampal subfield volumes and PHC integrity using FreeSurfer and the Tracts Constrained by Underlying Anatomy (TRACULA) respectively. Significant interactive effects of rs7294919 and MDD were observed in the volumes of the dentate gyrus and CA4. The patients with MDD had increased methylation in two of the three CpG loci of rs7294919, and the methylation of CpG3 was significantly correlated with right PHC integrity in the MDD group. Our results provide neurobiological evidence for the association of rs7294919 with brain structural changes in MDD.

Substance P (SP) has been implicated in major depressive disorder (MDD), with SP antagonists being studied as potential antidepressants. Although impaired neural plasticity is considered a key mechanism in MDD pathophysiology, the association between SP and brain structural changes in depression has not been investigated. We investigated the correlations between SP levels and white matter (WM) integrity in 42 medication-naive patients with MDD and 57 healthy controls (HCs). Plasma levels of SP were determined, and diffusion tensor imaging (DTI) was performed to investigate microstructural changes in WM tracts. In patients, negative correlations between SP levels and fractional anisotropy (FA) values of the forceps minor of the corpus callosum, and positive correlations between SP levels and radial diffusivity (RD) and mean diffusivity (MD) values of the right corticospinal tract (CST) were observed, with no significant correlations in HCs. Linear regression analyses showed SP levels to significantly predict FA values of the forceps minor, and RD and MD values of the right CST in patients, but not in HCs. We consider our findings to contribute to the neurobiological evidence on the association between SP and brain structural changes in depression, which may be related with the pathophysiology and treatment of MDD.

The genetic variant of the vesicular monoamine transporter 1 gene (VMAT1) has been suggested to be associated with monoaminergic signaling and neural circuit activity related to emotion processing. We aimed to investigate microstructural changes in white matter tracts of patients with major depressive disorder (MDD), and examined the interaction effect between VMAT1 Thr136Ile (rs1390938) polymorphism and MDD on white matter integrity. Diffusion tensor imaging (DTI) and VMAT1 Thr136Ile (rs1390938) genotyping were performed on 103 patients diagnosed with MDD and 83 healthy control participants. DTI was used to investigate microstructural changes in white matter tracts in patients compared to healthy controls. The possible interaction effect between rs1390938 and MDD on white matter integrity was also assessed. Patients with MDD exhibited lower fractional anisotropy (FA) values of the forceps major (p

Chronic low-grade inflammation contributes to the pathophysiology of major depressive disorder (MDD). This study aimed to examine the association between serum levels of FAM19A5, a novel chemokine-like peptide that reflects reactive astrogliosis and inflammatory activation in the brain, and the neurodegenerative changes of MDD by investigating the correlation between serum FAM19A5 levels and cortical thickness changes in patients with MDD. We included 52 drug-naive patients with MDD and 60 healthy controls (HCs). Serum FAM19A5 levels were determined in peripheral venous blood samples using a sandwich enzyme-linked immunosorbent assay. All participants underwent T1-weighted structural magnetic resonance imaging. Serum FAM19A5 levels were greater in patients with MDD than in HCs. In the MDD group, there were significant inverse correlations between serum FAM19A5 levels and cortical thickness in the prefrontal regions (i.e., the left inferior and right medial superior frontal gyri), left posterior cingulate gyrus, right cuneus, and both precunei, which showed significantly reduced thickness in patients with MDD compared to HCs. However, no correlation between serum FAM19A5 level and cortical thickness was observed in the HC group. The results of our study indicate that serum FAM19A5 levels may reflect reactive astrogliosis and related neuroinflammation in MDD. Our findings also suggest that serum FAM19A5 may be a potential biomarker for the neurodegenerative changes of MDD.

Suicide is among the most important global health concerns; accordingly, an increasing number of studies have shown the risks for suicide attempt(s) in terms of brain morphometric features and their clinical correlates. However, brain studies addressing suicidal vulnerability have been more focused on demonstrating impairments in cortical structures than in the subcortical structures. Using local shape volumes (LSV) analysis, we investigated subcortical structures with their clinical correlates in depressed patients who attempted suicide. Then we compared them with depressed patients without a suicidal history and age‐ and sex‐matched healthy controls (HCs; i.e., 47 suicide attempters with depression, 47 non‐suicide attempters with depression, and 109 HCs). Significant volumetric differences were found between suicidal and nonsuicidal depressed patients in several vertices: 16 in the left amygdala; 201 in the left hippocampus; 1,057 in the left putamen; and 140 in the left pallidum; 1 in the right pallidum; and 6 in the bilateral thalamus. These findings indicated subcortical alterations in LSV in components of the limbic–cortical–striatal–pallidal–thalamic circuits. Moreover, our results demonstrated that the basal ganglia was correlated with perceived stress levels, and the thalamus was correlated with suicidal ideation. We suggest that suicidality in major depressive disorder may involve subcortical volume alterations., Using local shape volumes (LSV) analysis, significant volumetric differences were found between suicidal and nonsuicidal depressed patients in the left amygdala, left hippocampus, left putamen, bilateral pallidum, and thalamus. These findings propose that suicidality in major depressive disorder may involve subcortical volumetric alterations.

Background Genetic variations associated with major depressive disorder (MDD) may affect the structural aspects of neural networks mediated by the molecular pathways involved in neuronal survival and synaptic plasticity. However, few studies have applied a novel approach such as whole-exome sequencing (WES) analysis to investigate the genetic contribution to the neurostructural changes in MDD. Methods In the first part of the study, we investigated rare variants of selected genes from previous WES studies using a WES analysis in 184 patients with MDD and 82 healthy controls. In the second part of the study, we explored the association between the common genetic variants from the WES analysis and cortical thickness in 91 patients with MDD and 75 healthy controls. The gray-matter thickness of each cortical region was measured using FreeSurfer. Results We identified recurrent non-silent variants in 24 MDD-related genes including FASN, MYH13, UNC13D, LILRA1, CACNA1B, TRIO, HOMER3, and BCAR3, and observed eleven recurrently altered copy number alternations where a gain on 15q11.2 and losses on 7q34 and 15q11.1-q11.2 in MDD genomes. We also found that rs11592462 in CDH23, a calcium-dependent cell-adhesion molecule encoding gene, was significantly associated with thinning in the right anterior cingulate cortex. Limitation The small sample size may lead our findings to be underpowered regarding rare variants. Conclusion : The present study identified that non-synonymous rare variants were significantly associated with risk of MDD and found that genetic contributions to the development of MDD may be mediated by alterations in cortical thickness of emotion-processing neural circuits.

Subcortical aphasia results from damage to subcortical regions, but the exact underlying mechanism is unclear. We investigated the influence of arcuate fasciculus (AF) damage on the severity of subcortical aphasia after stroke using brain diffusion tensor imaging (DTI). We enrolled subjects from the “Stroke Outcome Prediction (STOP)” database: 41 patients with first-ever, left hemispheric subcortical stroke (33 with hemorrhagic, eight with ischemic stroke) who underwent the Western Aphasia Battery (WAB) evaluation and DTI. We performed a correlation analysis between lesion volume (LV) and the DTI parameters of the AF, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), and AF type, and the WAB scores, and a classification and regression tree (CART) analysis to identify significant neuroimaging predictors for subcortical aphasia. FA significantly correlated with the aphasia quotient (AQ) and the naming score, and LV with the AQ and several WAB subtests (fluency, repetition, naming). At the subgroup level, FA and AF type showed significant correlations with the AQ, comprehension, and naming in the ischemic stroke group, while LV was associated with naming in the hemorrhagic stroke group. LV and FA were significant predictors of the AQ in all subjects, while FA was the only predictor of the language score in the hemorrhagic stroke group. Damage to the AF may be an important underlying mechanism of subcortical aphasia, and the FA value representing the integrity of the AF is an important predictor of the severity of subcortical aphasia.

Background Morphologic changes of the brainstem in major depressive disorder (MDD) have rarely been reported in neuroimaging studies, even though, monoaminergic neurotransmitters are synthesized in several brainstem regions. We aimed to investigate volume changes in each region of the brainstem and their association with antidepressant use or the remission status of MDD. Methods A total of 126 patients with MDD and 101 healthy controls underwent T1-weighted structural magnetic resonance imaging. We analyzed volumes of each brainstem region, including the medulla oblongata, pons, midbrain, and superior cerebellar peduncle, and the volume of the whole brainstem using the FreeSurfer. Results The patients with MDD had significantly greater midbrain volumes (P=0.013) compared to healthy controls. In particular, drug-naive patients with MDD had significantly greater brainstem volumes compared to healthy controls (P=0.007), while no significant findings were observed between the antidepressant treatment group and healthy controls. The remitted patient group had reduced pons (P=0.002) and midbrain (P=0.005) volumes compared to healthy controls, while the non-remitted MDD patient group had significantly greater midbrain volumes compared to the healthy controls (P=0.017). Limitations We could not distinguish gray versus white matter volumes changes in our analysis. Conclusions We observed that the midbrain is enlarged in patients with a current depressive episode, who are not undergoing antidepressant treatment. This volume then returns to normal after antidepressant treatment, and is even reduced, when the patient is in remission. Further studies are needed to confirm our observations.

The tryptophan hydroxylase-2 (TPH2) gene is considered a promising genetic candidate regarding its association with a predisposition to major depressive disorder (MDD). Local gyrification reflects the early neural development of cortical connectivity, and is regarded as a potential neural endophenotype in psychiatric disorders. They aimed to investigate the alterations in the cortical gyrification of the prefrontal cortex and anterior cingulate cortex and their association with the TPH2 rs4570625 polymorphism in patients with MDD. One hundred and thirteen patients with MDD and eighty-six healthy controls underwent T1-weighted structural magnetic resonance imaging and genotyping for TPH2 rs4570625. The local gyrification index of 22 cortical regions in the prefrontal cortex and anterior cingulate cortex was analyzed using the FreeSurfer. The patients with MDD showed significant hypergyria in the right rostral anterior cingulate cortex (P = 0.001), medial orbitofrontal cortex (P = 0.003), and frontal pole (P = 0.001). There was a significant genotype-by-diagnosis interaction for the local gyrification index in the right rostral anterior cingulate cortex (P = 0.003). Their study revealed significant hypergyria of the anterior cingulate cortex and prefrontal cortex and an interactive effect between the diagnosis of MDD and the genotype in the anterior cingulate cortex. This might be associated with the dysfunction of neural circuits mediating emotion processing, which could contribute to pathophysiology of MDD. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.