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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.

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.

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

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.

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.

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.

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).

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.

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.

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.

Several studies used automated segmentation of hippocampal subfield (ASHS) for detailed measurements of anatomic subregions of the hippocampus, especially in the field of neurodegenerative disorders. In this study, we investigated the hippocampal subfield volume of patients with early-stage nondementia PD compared with normal healthy subjects using the ASHS method. A total of 32 subjects were enrolled in this study (sixteen patients with drug naive nondementia PD and sixteen healthy controls). All subjects were scanned with a 1.5 tesla MRI. The volumes of the seven subfields were calculated separately, and then, the whole hippocampal volume was calculated by the summing of CA1, CA2-3, CA4-DG, subiculum, presubiculum, and fimbria, excluding the hippocampal fissure. There were significant diagnosis-by-hemisphere interactive effects on the total hippocampal volume (F = 5.197; p=0.031) and the subfield volume of CA2-3 (F = 7.586; p=0.010) and CA4-DG (F = 7.403; p=0.011). The volumes of CA2-3 (F = 19.911; p<0.001), CA4-DG (F = 20.273; p<0.001), and total hippocampus (F = 10.573; p=0.005) in the left hemisphere were reduced compared to the right hemisphere. We suggest that the hippocampal volume asymmetry, especially in CA4-DG and CA2-3, could be observed in drug-naïve PD patients even in the early stage of the disease.

Cerebellar mutism (CM) is a rare neurological condition characterized by lack of speech due to cerebellar lesions. CM is often reported in children. We describe a rare case of CM after spontaneous cerebellar hemorrhage. The patient showed mutism, irritability, decreased spontaneous movements and oropharyngeal apraxia. Diffusion tensor imaging revealed significant volume reduction of medial frontal projection fibers from the corpus callosum. In Tracts Constrained by UnderLying Anatomy (TRACULA) analysis, forceps major and minor and bilateral cingulum-angular bundles were not visualized. Cerebello-frontal pathway reconstructed from the FMRIB Software Library showed continuity of fibers, with decreased number of fibers on qualitative analysis. These results suggest that cerebello-frontal disconnection may be a neuroanatomical mechanism of CM. Damage of brain network between occipital lobe, cingulate and cerebellum caused by hemorrhage may also have role in the mechanism of CM in our case.

A single nucleotide polymorphism of rs1360780 in the FKBP5 gene is associated with a predisposition to developing major depressive disorder (MDD). We investigated the interactive effects of FKBP5 rs1360780 allelic variants, DNA methylation, and the diagnosis of MDD on structural changes of the entire brain. One hundred and fourteen patients with MDD and eighty-eight healthy controls underwent T1-weighted structural magnetic resonance imaging and FKBP5 rs1360780 genotyping, including DNA methylation of intron 7. We analyzed the volume of cortical and subcortical regions and cortical thickness using FreeSurfer. Significant genotype-by-diagnosis interactions were observed for volumes of the left pars triangularis, supramarginal gyrus, superior parietal lobule, right frontomarginal, and posterior midcingulate gyrus. The T allele was associated with significant volume reductions in these brain regions only in the MDD group except for the right posterior midcingulate gyrus. FKBP5 DNA methylation showed a positive correlation with the thickness of the right transverse frontopolar gyrus in the C allele homozygote group. Our findings suggest that the FKBP5 gene and its epigenetic changes could have influence on morphologic changes of several brain regions involved in emotion regulation, and that this process may be associated with the development of MDD.

Background and purpose Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that mainly affects the pyramidal motor system. However, recent studies have suggested that degeneration of the extramotor system plays a role in the disability experienced by patients with ALS. We investigated the local shape changes and mean volumes of the subcortical nuclei in sporadic ALS patients with preserved cognition. Methods The participants comprised 32 patients with ALS and 43 age- and sex-matched healthy controls. Three-dimensional T1-weighted structural images were acquired. Surface-based vertex analysis was performed with fully automated segmentation of both amygdalae, hippocampi, caudate nuclei, nuclei accumbens, putamina, pallida, and thalami, and the brainstem. The scalar distances from the mean surfaces of the individual subcortical nuclei were compared between groups, and correlations of the local shape distances with initial Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALS-FRS-R) scores and the delta FRS-R and with the disease duration were analyzed. Results ALS patients showed regional shape contractions on the lateral surfaces of both pallida, the lateroposterior surface of the right putamen, and the anterior basal surface of the right accumbens. Delta FRS-R scores were negatively correlated with local shape distances in the right hippocampus and the putamina. However, the initial ALS-FRS-R score and disease duration were not correlated with local shape distances. Conclusions Subcortical gray-matter structures are involved in the neurodegenerative process of ALS before cognitive impairment becomes evident.

Background The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). It is presumed to be involved in the pathophysiology of MDD through regulation of glutamate transmission in the brain. However, the involvement of this gene in microstructural changes in white matter (WM) tracts remains unclear. We aimed to investigate the influence of a polymorphism of this gene (rs1545853) on the structural integrity of WM tracts in the cortico-limbic network. Methods Eighty-six patients with MDD and 64 healthy controls underwent T1-weighted structural magnetic resonance imaging, including diffusion tensor imaging (DTI), and genotype analysis. We selected the genu of the corpus callosum, the uncinate fasciculus, cingulum, and fornix as regions of interest, and extracted fractional anisotropy (FA) values using the FMRIB Diffusion Toolbox software. Results FA values for the left parahippocampal cingulum (PHC) was significantly reduced in the patients with MDD compared to healthy control participants (p = 0.004). We also found that MDD patients with the A allele showed reduced FA values for the left PHC than did healthy controls with the A allele (p = 0.012). There was no significant difference in the FA value of left PHC for the comparison between the G homozygotes of MDD and healthy control group. Conclusions We observed an association between the risk allele of the SLC6A15 gene rs1545843 and the WM integrity of the PHC in MDD patients, which is known to play an important role in the neural circuit involved in emotion processing.

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 38:1299–1310, 2017. © 2016 Wiley Periodicals, Inc.

Recent studies have reported that methylation of the brain-derived neurotrophic factor (BDNF) gene promoter is associated with major depressive disorder (MDD). This study aimed to investigate the association between cortical thickness and methylation of BDNF promoters as well as serum BDNF levels in MDD. The participants consisted of 65 patients with recurrent MDD and 65 age- and gender-matched healthy controls. Methylation of BDNF promoters and cortical thickness were compared between the groups. The right medial orbitofrontal, right lingual, right lateral occipital, left lateral orbitofrontal, left pars triangularis, and left lingual cortices were thinner in patients with MDD than in healthy controls. Among the MDD group, right pericalcarine, right medical orbitofrontal, right rostral middle frontal, right postcentral, right inferior temporal, right cuneus, right precuneus, left frontal pole, left superior frontal, left superior temporal, left rostral middle frontal and left lingual cortices had inverse correlations with methylation of BDNF promoters. Higher levels of BDNF promoter methylation may be closely associated with the reduced cortical thickness among patients with MDD. Serum BDNF levels were significantly lower in MDD, and showed an inverse relationship with BDNF methylation only in healthy controls. Particularly the prefrontal and occipital cortices seem to indicate key regions in which BDNF methylation has a significant effect on structure.

BACKGROUND AND PURPOSE: The hippocampal atrophy of MDD has been known, but the region shape contractions of the hippocampus in MDD were inconsistent. Spheric harmonic shape analysis was applied to the hippocampus in female patients with unremitting MDD to evaluate morphometric changes of the hippocampus. MATERIALS AND METHODS: Shape analysis was performed by using T1-weighted MR imaging in 21 female patients with MDD and 21 age- and sex-matched healthy controls. Manually segmented hippocampi were parameterized, and the point-to-point–based group difference was compared by using the Hotelling T-squared test. The partial correlation analyses were tested between clinical variables and shape changes. RESULTS: Both hippocampal volumes were small in patients with MDD compared with healthy controls, and the right hippocampal volume was negatively correlated with the number of episodes at marginal significance. Regional shape contractions were found in the ambient gyrus, basal hippocampal head, posterior subiculum, and dorsal hippocampus of the left hemisphere. The right hippocampus showed a similar pattern but was less atrophic compared with the left hippocampus. A negative correlation was found between the HDRS and shape deformation in the CA3, ambient gyrus, posterior subiculum, and gyrus fasciolaris of the left hippocampus. CONCLUSIONS: We showed atrophy and regional shape contractions in the hippocampi of patients with MDD, which were more dominant on the left side. The causes of hippocampal damage could be the hypersecretion of glucocorticoids contributing to neuronal death or the failing of adult neurogenesis in the dentate gyrus.

Objective: To investigate gray matter concentration changes in the brains ofnarcoleptic patients. Materials and Methods: Twenty-nine narcoleptic patient with cataplexy and 29age and sex-matched normal subjects (mean age, 31 years old) underwent volu-metric MRIs. The MRIs were spatially normalized to a standard T1 template andsubdivided into gray matter, white matter, and cerebrospinal fluid (CSF). Thesesegmented images were then smoothed using a 12-mm full width at half maxi-mum (FWHM) isotropic Gaussian kernel. An optimized voxel-based morphome-try protocol was used to analyze brain tissue concentrations using SPM2 (statisti-cal parametric mapping). A one-way analysis of variance was applied to the con-centration analysis of gray matter images. Results: Narcoleptics with cataplexy showed reduced gray matter concentra-tion in bilateral thalami, left gyrus rectus, bilateral frontopolar gyri, bilateral shortinsular gyri, bilateral superior frontal gyri, and right superior temporal and left infe-rior temporal gyri compared to normal subjects (uncorrected p < 0.001).Furthermore, small volume correction revealed gray matter concentration reduc-tion in bilateral nuclei accumbens, hypothalami, and thalami (false discovery ratecorrected p < 0.05). Conclusion: Gray matter concentration reductions were observed in brainregions related to excessive daytime sleepiness, cognition, attention, and memo-ry in narcoleptics with cataplexy.arcolepsy is characterized by excessive daytime sleepiness (EDS), adisruption of sleep-wake behavior, cataplexy (a sudden loss of muscletone provoked by emotional stimuli), and other rapid eye movement(REM) sleep phenomena, such as, sleep paralysis and hypnagogic hallucinations (1).Numerous investigations, including neuroimaging studies, have been performed tocharacterize the pathophysiology of narcolepsy. An abnormality of the pontine reticu-lar formation, where REM sleep is generated, was reported in the brain MRIs of threeidiopathic narcoleptic patients (2), whereas another study found no evidence of apontine lesion (3).Several voxel-based morphometry (VBM) studies of brain MRIs in narcoleptics haveproduced controversial results. One distinct VBM study revealed reduced gray matter(GM) concentrations in the hypothalamus and nucleus accumbens (4). A subsequentstudy failed to find any changes of GM concentrations in the hypothalamus (5).Another study found reductions in bilateral inferior temporal and frontal regions (6).Recently, GM loss in the prefrontal and frontomesial cortices was found, but could notprovide functional significance with respect to the relevance to the pathophysiology ofEun Yeon Joo, MD

NARCOLEPSY IS CHARACTERIZED BY EXCESSIVE DAYTIME SLEEPINESS (EDS), A DISRUPTION OF SLEEP-WAKE BEHAVIOR, CATAPLEXY (SUDDEN LOSS of muscle tone provoked by emotional stimuli), and the other REM sleep phenomena, such as sleep paralysis and hypnagogic hallucination.1 Modafinil (a diphenylmethyl-sulfinyl-2-acetamide derivative) is a wake-promoting substance used for the treatment of hypersomnolence, particularly that associated with narcolepsy.2 Modafinil is an increasingly popular medication due to its safety profile. Most side effects that have been reported are headache (if the modafinil dose was high or increased too quickly) and insomnia or nervousness, which are usually transient and dose dependent.3 Modafinil has multiple modes of actions. It activates ɑ1- and β adrenergic receptors,4 promotes glutamate excitatory transmission in the thalamus, hippocampus, and cortex,5 reduces GABA outflow via a monoamine-mediated mechanism,6 and activates serotonergic receptors.7 Although numerous animal studies have been performed, the mechanism whereby modafinil promotes wakefulness is still under investigation. Modafinil was found to increase extracellular dopamine levels, as determined by microdialysis in the rat nucleus accumbens and prefrontal cortex, as well as in the caudate of narcoleptic dogs.8 It was revealed that administration of modafinil to rats produced wakefulness in association with activation of tuberomammillary nucleus and orexin neurons, two cell groups implicated in the control of normal wakefulness.9 Although the neurochemistry of this process remains obscure, it may involve histaminergic neurons in the tuberomammillary nucleus and hypocretin neurons in the perifornical area.5,9 Modafinil is effective in maintaining wakefulness in narcolepsy patients, who have a hypocretin neuron deficit. Other studies have suggested that the cerebral cortex,10 thalamus,5 hippocampus,5 and periaqueductal gray matter11 are also involved in the process of promoting wakefulness by modafinil. The aim of the present study was to investigate regional cerebral blood flow (rCBF) changes in human narcolepsy patients who experienced a marked EDS improvement after modafinil administration. To achieve this, we performed 99mTc-ethylcysteinate dimer single photon emission computed tomography (SPECT) before and after modafinil or placebo administration in drug-naiive narcoleptics with cataplexy.

To investigate abnormal cerebral perfusion in narcoleptics with cataplexy, 25 narcoleptics with cataplexy and 25 normal controls were enrolled in this study. Cerebral perfusion was measured by brain single photon emission computed tomography (SPECT) using 99mTc-ethylcysteinate dimer. Patients and normal controls had not received any medication prior to the SPECT scan. Differences in cerebral perfusion between narcoleptics and normal controls were subjected to statistical parametric mapping (SPM) analysis. Overnight polysomnography and multiple sleep latency test (MSLT) were performed in all patients. Brain SPECT was carried out on all patients and normal controls during the waking state. Clinical symptoms and MSLT results of all patients are in accord with the International Classification of Sleep Disorders criteria for narcolepsy. MSLT showed a short mean sleep latency (1.69 +/- 1.0 min) and 2-5 sleep onset REM periods in individual patient. SPM analysis of brain SPECT showed hypoperfusion of the bilateral anterior hypothalami, caudate nuclei, and pulvinar nuclei of thalami, parts of the dorsolateral/ventromedial prefrontal cortices, parahippocampal gyri, and cingulate gyri in narcoleptics [P0.05 by Student's t test with false discovery rate (FDR) correction]. Significant hypoperfusion in the white matter of frontal and parietal lobes was also noted in narcoleptics. This study shows reduced cerebral perfusion in subcortical structures and cortical areas in narcoleptics. The distribution of abnormal cerebral perfusion is concordant with the pathway of the cerebral hypocretin system and may explain the characteristic features of narcolepsy, i.e., cataplexy, emotional lability, and attention deficit.

To investigate postoperative changes in the cerebral glucose metabolism of patients with mesial temporal lobe epilepsy (MTLE), statistical parametric mapping (SPM) analysis was performed on pre- and postoperative (18)F-fluorodeoxyglucose PET (FDG-PET) images. We included 28 patients with MTLE who had undergone surgery and had been seizure-free postoperatively (16 had left MTLE and 12 right MTLE). All patients showed hippocampal sclerosis by pathology or brain MRI. FDG-PET images of the 12 right temporal lobe epilepsy patients were reversed to lateralize the epileptogenic zone to the left side in all patients. Application of the paired t-test in SPM to pre- and postoperative FDG-PETs showed that postoperative glucose metabolism decreased in the caudate nucleus, the pulvinar of the thalamus, fusiform gyrus, lingual gyrus and the posterior region of the insular cortex in the hemisphere ipsilateral to resection, whereas postoperative glucose metabolism increased in the anterior region of the insular cortex, temporal stem white matter, midbrain, inferior precentral gyrus, anterior cingulate gyrus and supramarginal gyrus in the hemisphere ipsilateral to resection. No significant postsurgical changes in cerebral glucose metabolism occurred in the contralateral hemisphere. Subtraction between pre- and postoperative FDG-PET images in individual patients produced similar findings to the SPM results, and additionally showed that postoperative glucose metabolism increased in the anterior thalamus in 12/28 patients (42.8%). SISCOM (subtraction ictal-interictal SPECT co-registered to MRI) performed in 17 patients showed ictal hyperperfusion in the ipsilateral temporal lobe, including the temporal stem white matter, midbrain, insular cortex and cingulate gyrus, bilateral basal ganglia and thalami, and multiple small regions in the frontoparietal lobes during seizures. This study suggests that brain regions showing a postoperative increase in glucose metabolism appear to represent the propagation pathways of ictal and interictal epileptic discharges in MTLE, whereas the postoperative decrease in glucose metabolism may be related to a permanent loss of afferents from resected anterior-mesial temporal structures.

Diffusion-tensor imaging (DTI) is a noninvasive medical imaging tool used to investigate the structure of white matter. The signal contrast in DTI is generated by differences in the Brownian motion of the water molecules in brain tissue. Postprocessed DTI scalars can be used to evaluate changes in the brain tissue caused by disease, disease progression, and treatment responses, which has led to an enormous amount of interest in DTI in clinical research. This review article provides insights into DTI scalars and the biological background of DTI as a relatively new neuroimaging modality. Further, it summarizes the clinical role of DTI in various disease processes such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's dementia, epilepsy, ischemic stroke, stroke with motor or language impairment, traumatic brain injury, spinal cord injury, and depression. Valuable DTI postprocessing tools for clinical research are also introduced.

A 22 year-old woman suffered from recurrent episodes of hypersomnia, apathy, and hyperphagia. The symptoms occurred 3 to 4 times per year, and each attack lasted 2 to 3 weeks. 99mTc-ethylcysteinate dimer brain single photon emission computed tomography (SPECT) was performed during symptomatic and asymptomatic periods. To localize brain regions with perfusion changes during symptomatic period, asymptomatic SPECT was subtracted from symptomatic SPECT. The subtracted SPECT showed significant hypoperfusion in the left hypothalamus, bilateral thalami, basal ganglia, bilateral medial and dorsolateral frontal regions, and left temporal lobe during the symptomatic period. These cerebral hypoperfusion areas support the diencephalic hypothesis and clinical symptoms of Kleine-Levin syndrome.

Background DNA methylation in the promoter region of the glucocorticoid receptor gene (NR3C1) is closely associated with childhood adversity and suicide. However, few studies have examined NR3C1 methylation in relation to major depressive disorder (MDD) and hippocampal subfield volumes. We investigated the possible association between NR3C1 methylation and structural brain alterations in MDD in comparison with healthy controls. Methods We compared the degree of NR3C1 promoter methylation in the peripheral blood of non-psychotic outpatients with MDD and that of healthy controls. Correlations among NR3C1 promoter methylation, structural abnormalities in hippocampal subfield volumes and whole-brain cortical thickness, and clinical variables were also analyzed. Results In total, 117 participants (45 with MDD and 72 healthy controls) were recruited. Patients with MDD had significantly lower methylation than healthy controls at 2 CpG sites. In MDD, methylations had positive correlations with the bilateral cornu ammonis (CA) 2–3 and CA4-dentate gyrus (DG) subfields. However, in healthy controls, methylations had positive correlation with the subiculum and presubiculum. There were no differences in total and subfield volumes of the hippocampus between patients with MDD and healthy controls. Compared with healthy controls, patients with MDD had a significantly thinner cortex in the left rostromiddle frontal, right lateral orbitofrontal, and right pars triangularis areas. Conclusions Lower methylation in the NR3C1 promoter, which might have compensatory effects relating to CA2-3 and CA4-DG, is a distinct epigenetic characteristic in non-psychotic outpatients with MDD. Future studies with a longitudinal design and a comprehensive neurobiological approach are warranted in order to elucidate the effects of NR3C1 methylation.

Purpose To investigate structural brain changes and their relationship with cognitive function by determining the alterations of white matter integrity and changes in hippocampal volume that occur during chronic obstructive pulmonary disease (COPD). Materials and Methods Diffusion tensor images and 3D-T1 MR images were acquired in 13 male nonhypoxemic COPD patients and 13 age- and gender-matched healthy controls. Global probabilistic tractography was used to assess a total of 18 major tracts. We examined the association between the hippocampal volume and diffusivity parameters of white matter tracts. Results A significant difference in diffusion parameters between groups was identified for 11 white matter bundles (p < 0.05). No association was demonstrated between the normalized hippocampus volume and diffusion parameters among the participants. Significant associations between Korean version of the Mini-Mental State Examination (K-MMSE) scores and diffusivities were found for six tracts (p < 0.05). Of note, the mean diffusivity (MD) and redial diffusivity (RD) of the left superior longitudinal fasciculus parietal segment showed a significant negative correlation with the K-MMSE score (MD: r = −0.623, p = 0.001; RD: r = −0.408, p = 0.048). Conclusion Altered white matter integrity was demonstrated across regional white matter bundles, including the superior longitudinal fasciculus, in COPD patients, and it was related to cognitive function. Changes in the volume of the hippocampus should be investigated in further studies.

BACKGROUND AND PURPOSE: Loss of dopaminergic neurons in the nigrostriatal pathway is well-documented in PD, whereas neuronal changes beyond the nigrostriatal pathway are uncertain. The purpose of our study was to estimate volume changes in the striatum and thalamus, which are areas of the basal ganglia, as well as in GM and WM located beyond the nigrostriatal pathway, in early-stage PD. MATERIALS AND METHODS: We enrolled 30 participants (15 healthy controls and 15 patients with PDND with H & Y stage I or II). Cognitive function was assessed by using the MMSE. ICV and the volumes of the caudate nucleus, putamen, thalamus, GM, and WM were calculated via 3D volume analysis by using MR imaging. RESULTS: A comparison of the PD group with the control group revealed an absence of significant differences between them regarding age and MMSE scores. Comparison of the volumes of regional brain structures of patients with PD with those of controls revealed the presence of significant differences in the caudate nucleus, thalamus, and WM (P < .05) between the groups. However, there were no significant differences in the volumes of the putamen and GM or in ICV between patients with PD and controls. The results of ANCOVA by using the covariates of age and ICV showed a significant difference in the caudate nucleus, thalamus, and WM between patients with PD and controls (P < .05). CONCLUSIONS: We suggest that loss of WM volume may occur in early disease stages and that variation of the volumes of the caudate nucleus and thalamus may be an early phenomenon of disease progression.

OBSTRUCTIVE SLEEP APNEA SYNDROME (OSA) IS A DISORDER CHARACTERIZED BY EXCESSIVE SNORING AND PERIODIC BREATHING WITH REPETITIVE apneas and arousals, which leads to fragmented sleep.1 OSA may cause daytime sleepiness, reduce work performance, increase the risk of a traffic accident, and diminish quality of life.2 Neurocognitive problems, such as deficits in memory, attention, and visuoconstructive abilities, frequently accompany OSA.3 The pathophysiology of these deficits remains controversial, although the main contributory factors are presumed to be sleep fragmentation and intermittent nocturnal hypoxemia during sleep apneas. Deterioration of cognitive performance has been significantly correlated with the degree of nocturnal hypoxemia4 and with the severity of nocturnal breathing irregularities.5 The structural changes seen on brain MRI imply a chronic state of disease rather than functional change of glucose metabolism or regional blood flow. Previous studies show that OSA patients have hippocampal atrophy,6 selective reduced gray matter volume in the hippocampus and parahippocampal gyrus,7,8 and frontoparietal cortices, temporal lobe, anterior cingulate, and cerebellum.9 This may suggest neuronal cell loss in untreated OSA brains and that significant morphologic changes in OSA brains may partly explain the incomplete modulation of upper airway motor function or cardiovascular and respiratory control during sleep,9 as well as cognitive decline during wakefulness.6 However, other investigators could not find any gray matter volume deficits or focal structural changes in patients with severe OSA compared to healthy volunteers.10 It has been presumed that inconsistent neuroimaging findings may reflect discrepancies in the procedure of data analysis or the characteristics of study subjects.11 Previous studies investigated gray matter volume (GMV) changes only.7,9,10 In this study, we tried to investigate not only GMV but also gray matter concentration (GMC) changes, using optimized VBM with modulated or unmodulated images. We hypothesized that severe patients with severe OSA, despite having visually normal brain MRIs, may show a decrease of GMV or GMC of brain compared to age-matched healthy volunteers.

BackgroundzzOne of the characteristics of hypoglycemic encephalopathy (HE) is selective vulnerability of different brain regions. Case ReportzzWe observed a patient with unilateral HE affecting the right internal capsule and the subcortical white matter. The patient had a preexisting stroke in the opposite hemisphere. The hemisphere that was affected by HE exhibited greater regional blood flow (single positron-emission tomography) and higher fractional anisotropy (diffusion-tensor imaging) than the unaffected hemisphere. ConclusionszzThis case suggests that the degree of metabolism required to maintain the function of brain structures and neuronal integrity is an important factor determining the selective vulnerability in HE. J Clin Neurol 2010;6:104-108

To investigate the effects of a wake-promoting drug, modafinil on regional cerebral blood flow (rCBF) in healthy volunteers, we performed (99m)Tc-ethylcysteinate dimer single photon emission computed tomography (SPECT) before and after modafinil or placebo administration. Twenty-one healthy subjects received single doses of 400 mg modafinil or placebo in a double blind randomized crossover study design. Administrations of modafinil or placebo in a subject were separated by a 2-week washout. Brain SPECT was performed twice before and 3 h after modafinil or placebo administration. For statistical parametric mapping analysis, all SPECT images were spatially normalized to the standard SPECT template and then smoothed using a 12-mm full width at half-maximum Gaussian kernel. The paired t-test was used to compare pre- versus post-modafinil and pre- versus post-placebo SPECT images. Differences in rCBF between post-modafinil and post-placebo conditions were also tested. Modafinil decreased Epworth and Stanford sleepiness scales whereas placebo did not. The post-modafinil condition was associated with increased rCBF in bilateral thalami and dorsal pons, whereas the post-placebo condition showed increased rCBF in a smaller area of the dorsal pons when compared with the drug naive baseline condition. Compared with the post-placebo condition, the post-modafinil condition showed higher rCBF in bilateral frontopolar, orbitofrontal, superior frontal, middle frontal gyri, short insular gyri, left cingulate gyrus, left middle/inferior temporal gyri, left parahippocampal gyrus, and left pons. In healthy volunteers, modafinil increased wakefulness and rCBF in the arousal-related systems and in brain areas related to emotion and executive function.