BACKGROUND/AIMS: Increasing evidence shows involvement of psychological disorders in functional dyspepsia (FD), but how psychological factors exert their influences upon FD remains largely unclear. The purpose of the present study was to explore the brain-based correlations of psychological factors and FD. METHODS: Based on Fluorine-18-deoxyglucose positron emission tomography-computed tomography, the altered cerebral glycometabolism was investigated in 40 FD patients compared with 20 healthy controls during resting state using statistical parametric mapping software. RESULTS: FD patients exhibited increased glucose metabolism in multiple regions relative to controls (P < 0.001, family-wise error corrected). After controlling for the dyspeptic symptoms, increased aberrations persisted within the insula, anterior cingulate cortex (ACC), middle cingulate cortex (MCC) and middle frontal cortex (midFC), which was related to anxiety and depression score. Interestingly, FD patients without anxiety/depression symptoms also showed increased glycometabolism within the insula, ACC, MCC and midFC. Moreover, FD patients with anxiety/depression symptoms exhibited more significant hypermetabolism within the above 4 sites compared with patients without anxiety/depression symptoms. CONCLUSIONS: Our results suggested that the altered cerebral glycometabolism may be in a vicious cycle of psychological vulnerabilities and increased gastrointestinal symptoms.
Anxiety ; Cerebral Cortex ; Depression ; Dyspepsia* ; Electrons ; Glucose ; Gyrus Cinguli ; Humans ; Metabolism ; Psychology*

PURPOSE: Population based structural and functional maps of the brain provide effective tools for the analysis and interpretation of complex and individually variable brain data. Brain MRI and PET standard templates and statistical probabilistic maps based on image data of Korean normal volunteers have been developed and probabilistic maps based on cytoarchitectonic data have been introduced. A quantification method using these data was developed for the objective assessment of regional intensity in the brain images. Materials and METHODS: Age, gender and ethnic specific anatomical and functional brain templates based on MR and PET images of Korean normal volunteers were developed. Korean structural probabilistic maps for 89 brain regions and cytoarchitectonic probabilistic maps for 13 Brodmann areas were transformed onto the standard templates. Brain FDG PET and SPGR MR images of normal volunteers were spatially normalized onto the template of each modality and gender. Regional uptake of radiotracers in PET and gray matter concentration in MR images were then quantified by averaging (or summing) regional intensities weighted using the probabilistic maps of brain regions. Regionally specific effects of aging on glucose metabolism in cingulate cortex were also examined. RESULTS: Quantification program could generate quantification results for single spatially normalized images per 20 seconds. Glucose metabolism change in cingulate gyrus was regionally specific: ratios of glucose metabolism in the rostral anterior cingulate vs. posterior cingulate and the caudal anterior cingulate vs. posterior cingulate were significantly decreased as the age increased. 'Rostral anterior'/ 'posterior' was decreased by 3.1% per decade of age (P< 10 (-11), r=0.81) and 'caudal anterior'/ 'posterior' was decreased by 1.7% (P< 10 (-8), r=0.72). CONCLUSION: Ethnic specific standard templates and probabilistic maps and quantification program developed in this study will be useful for the analysis of brain image of Korean people since the difference in shape of the hemispheres and the sulcal pattern of brain relative to age, gender, races, and diseases cannot be fully overcome by the nonlinear spatial normalization techniques.
Aging ; Brain* ; Continental Population Groups ; Glucose ; Gyrus Cinguli ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Metabolism ; Tomography, Emission-Computed, Single-Photon

PURPOSE: Gender differences in personality are considered to have biological bases. In an attempt to understand the gender differences of personality on neurobiological bases, we conducted correlation analyses between regional brain glucose metabolism and temperament factors of personality in males and females. MATERIALS AND METHODS: Thirty-six healthy right-handed volunteers (18 males, 33.8+/-17.6 y; 18 females, 36.2+/-20.4 y) underwent FDG PET at resting state. Three temperament factors of personality (novelty seeking (NS), harm avoidance (HA), reward dependence (RD)) were assessed using Cloninger's 240-item Temperament and Character Inventory (TCI) within 10 days of FDG PET scan. Correlation between regional glucose metabolism and each temperament factor was tested using SPM2. RESULTS: In males, a significant negative correlation between NS score and glucose metabolism was observed in the bilateral superior temporal gyri, the hippocampus and the insula, while it was found in the bilateral middle frontal gyri, the right superior temporal gyrus and the left cingulate cortex and the putamen in females. A positive HA correlation was found in the right midbrain and the left cingulate gyrus in males, but in the bilateral basal ganglia in females. A negative RD correlation was observed in the right middle frontal and the left middle temporal gyri in males, while the correlation was found in the bilateral middle frontal gyri and the right basal ganglia and the superior temporal gyrus in females. CONCLUSION: These data demonstrate different cortical and subcortical metabolic correlates of temperament factors of personality between males and females. These results may help understand biological substrate of gender differences in personality and susceptibility to neuropsychiatric illnesses.
Basal Ganglia ; Brain ; Female ; Glucose ; Gyrus Cinguli ; Hippocampus ; Humans ; Male ; Mesencephalon ; Metabolism ; Positron-Emission Tomography ; Putamen ; Reward ; Temperament* ; Volunteers

PURPOSE: Gender differences in personality are considered to have biological bases. In an attempt to understand the gender differences of personality on neurobiological bases, we conducted correlation analyses between regional brain glucose metabolism and temperament factors of personality in males and females. MATERIALS AND METHODS: Thirty-six healthy right-handed volunteers (18 males, 33.8+/-17.6 y; 18 females, 36.2+/-20.4 y) underwent FDG PET at resting state. Three temperament factors of personality (novelty seeking (NS), harm avoidance (HA), reward dependence (RD)) were assessed using Cloninger's 240-item Temperament and Character Inventory (TCI) within 10 days of FDG PET scan. Correlation between regional glucose metabolism and each temperament factor was tested using SPM2. RESULTS: In males, a significant negative correlation between NS score and glucose metabolism was observed in the bilateral superior temporal gyri, the hippocampus and the insula, while it was found in the bilateral middle frontal gyri, the right superior temporal gyrus and the left cingulate cortex and the putamen in females. A positive HA correlation was found in the right midbrain and the left cingulate gyrus in males, but in the bilateral basal ganglia in females. A negative RD correlation was observed in the right middle frontal and the left middle temporal gyri in males, while the correlation was found in the bilateral middle frontal gyri and the right basal ganglia and the superior temporal gyrus in females. CONCLUSION: These data demonstrate different cortical and subcortical metabolic correlates of temperament factors of personality between males and females. These results may help understand biological substrate of gender differences in personality and susceptibility to neuropsychiatric illnesses.
Basal Ganglia ; Brain ; Female ; Glucose ; Gyrus Cinguli ; Hippocampus ; Humans ; Male ; Mesencephalon ; Metabolism ; Positron-Emission Tomography ; Putamen ; Reward ; Temperament* ; Volunteers

Brain-derived neurotrophic factor (BDNF), a small dimeric secretory protein, plays a vital role in activity-dependent synaptic plasticity, learning and memory. It has been shown that BDNF in the hippocampus and amygdala participates in the formation of fear memory. However, little is known about the functional role of BDNF in the anterior cingulate cortex (ACC). To address this question, we examined the mRNA and protein levels of BDNF in the ACC of rats at various time points after fear conditioning, using quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). The results showed that BDNF exhibited a temporally specific increase in both mRNA and protein levels after CS (tone) and US (foot shock) was paired. Such increase did not occur after the animals were exposed to CS or US alone. When BDNF antibody was locally infused into the ACC prior to CS-US pairing, both contextual and auditory fear memories were severely impaired. Taken together, these results suggest that BDNF in the ACC is required for the formation of fear memory.
Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Fear ; Gyrus Cinguli ; metabolism ; Memory ; physiology ; RNA, Messenger ; metabolism ; Rats ; Real-Time Polymerase Chain Reaction

This study aimed to investigate the effect of treadmill exercise on neuropathic pain and to determine whether mitophagy of the anterior cingulate cortex (ACC) contributes to exercise-mediated amelioration of neuropathic pain. Chronic constriction injury of the sciatic nerve (CCI) was used to establish a neuropathic pain model in Sprague-Dawley (SD) rats. Von-Frey filaments were used to assess the mechanical paw withdrawal threshold (PWT), and a thermal radiation meter was used to assess the thermal paw withdrawal latency (PWL) in rats. qPCR was used to evaluate the mRNA levels of Pink1, Parkin, Fundc1, and Bnip3. Western blot was used to evaluate the protein levels of PINK1 and PARKIN. To determine the impact of the mitophagy inducer carbonyl cyanide m-chlorophenylhydrazone (CCCP) on pain behaviors in CCI rats, 24 SD rats were randomly divided into CCI drug control group (CCI+Veh group), CCI+CCCP low-dose group (CCI+CCCP0.25), CCI+CCCP medium-dose group (CCI+CCCP2.5), and CCI+CCCP high-dose group (CCI+CCCP5). Pain behaviors were assessed on 0, 1, 3, 5, and 7 days after modeling. To explore whether exercise regulates pain through mitophagy, 24 SD rats were divided into sham, CCI, and CCI+Exercise (CCI+Exe) groups. The rats in the CCI+Exe group underwent 4-week low-moderate treadmill training one week after modeling. The mechanical pain and thermal pain behaviors of the rats in each group were assessed on 0, 7, 14, 21, and 35 days after modeling. Western blot was used to detect the levels of the mitophagy-related proteins PINK1, PARKIN, LC3 II/LC3 I, and P62 in ACC tissues. Transmission electron microscopy was used to observe the ultrastructure of mitochondrial morphology in the ACC. The results showed that: (1) Compared with the sham group, the pain thresholds of the ipsilateral side of the CCI group decreased significantly (P < 0.001). Meanwhile, the mRNA and protein levels of Pink1 were significantly higher, and those of Parkin were lower in the CCI group (P < 0.05). (2) Compared with the CCI+Veh group, each CCCP-dose group showed higher mechanical and thermal pain thresholds, and the levels of PINK1 and LC3 II/LC3 I were elevated significantly (P < 0.05, P < 0.01). (3) The pain thresholds of the CCI+Exe group increased significantly compared with those of the CCI group after treadmill intervention (P < 0.001, P < 0.01). Compared with the CCI group, the protein levels of PINK1 and P62 were decreased (P < 0.001, P < 0.01), and the protein levels of PARKIN and LC3 II/LC3 I were increased in the CCI+Exe group (P < 0.01, P < 0.05). Rod-shaped mitochondria were observed in the ACC of CCI+Exe group, and there were little mitochondrial fragmentation, swelling, or vacuoles. The results suggest that the mitochondrial PINK1/PARKIN autophagy pathway is blocked in the ACC of neuropathic pain model rats. Treadmill exercise could restore mitochondrial homeostasis and relieve neuropathic pain via the PINK1/PARKIN pathway.
Rats ; Animals ; Mitophagy/physiology* ; Rats, Sprague-Dawley ; Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology* ; Gyrus Cinguli ; Neuralgia ; Ubiquitin-Protein Ligases/metabolism* ; Protein Kinases ; Membrane Proteins/metabolism* ; Mitochondrial Proteins/metabolism*

Novelty seeking (NS) and antisocial personality (ASP) are commonly exhibited by those who suffer from addictions, such as substance abuse. NS has been suggested to be a fundamental aspect of ASP. To investigate the neurobiological substrate of NS and ASP, we tested the relationship between regional cerebral glucose metabolism and the level of NS, determining the differences between individuals with and without ASP. Seventy-two healthy adults (43 males, mean age±SD=38.8±16.6 years, range=20~70 years; 29 females, 44.2±20.1 years, range=19~72 years) underwent resting-state brain positron emission tomography (PET) 40 minutes after 18F-fluorodeoxyglucose (FDG) injection. Within 10 days of the FDG PET study, participants completed Cloninger's 240-item Temperament and Character Inventory (TCI) to determine NS scores. Participants with and without ASP were grouped according to their TCI profiles. Statistical parametric mapping analysis was performed using the FDG PET and TCI profile data. NS scores positively correlated with metabolism in the left anterior cingulate gyrus and the insula on both sides of the brain and negatively correlated with metabolism in the right pallidum and putamen. Participants with ASP showed differences in cerebral glucose metabolism across various cortical and subcortical regions, mainly in the frontal and prefrontal areas. These data demonstrate altered regional cerebral glucose metabolism in individuals with NS and ASP and inform our understanding of the neurobiological substrates of problematic behaviors and personality disorders.
Adult ; Antisocial Personality Disorder* ; Brain ; Electrons* ; Female ; Globus Pallidus ; Glucose* ; Gyrus Cinguli ; Humans ; Male ; Metabolism* ; Personality Disorders ; Positron-Emission Tomography* ; Putamen ; Substance-Related Disorders ; Temperament ; Viperidae

PURPOSE: To investigate the effects of topiramate on cerebral glucose metabolism, we performed 18F-fluorodeoxy glucose positron emission tomography (FDG-PET) in patients with new-onset epilepsy. METHODS: Thirteen patients with new-onset epilepsy or without medication after epilepsy diagnosis were included. Pre- and post-drug FDG-PET were performed (before and after topiramate administration) in all subjects (M/F=9/4, 28.2+/-11.4 years). For SPM analysis, paired pre- and linearly transformed post-drug FDG-PETs were spatially normalized into a standard PET template, provided in SPM-99, using a 12-parameter affine and a non-linear transformation. Spatially normalized images were then smoothed by convolution using an isotopic Gaussian kernel with a 14 mm full width at half maximum. The paired t-test was used to compare pre- and post-drug PET images. RESULTS: Mean dose of topiramate at the time of post-drug FDG-PET scanning was 163+/-71 mg. Mean duration of topiramate administration was 169+/-54 days. Responses to topiramate medication were seizure free in 7, reduced seizures in 3, and no changes in 3 patients. Reported adverse events were headache in 2 patients. SPM analysis between post-drug and pre-drug FDG-PET images showed post-drug hypometabolism in the white matters of both parietal and right temporal lobes, and corpus callosum, both thalami, right cingulate gyrus, left midbrain, both superior frontal gyri, left middle frontal gyrus, right inferior- and left superior parietal lobules, and left inferior temporal gyrus (corrected p<0.05). No brain region showed post-drug hypermetabolism. CONCLUSION: Topiramate reduced glucose metabolism more in the corpus callosum, thalamus and white matters, and less in the cerebral cortex.
Brain ; Cerebral Cortex ; Corpus Callosum ; Diagnosis ; Epilepsy ; Glucose* ; Gyrus Cinguli ; Headache ; Humans ; Mesencephalon ; Metabolism* ; Positron-Emission Tomography ; Rabeprazole ; Seizures ; Temporal Lobe ; Thalamus

BACKGROUND: 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 post-operative 18F-fluorodeoxy glucose positron emission tomographic (FDG-PET) images. METHODS: We included 28 patients with MTLE who had under-gone 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 TLE patients were reversed to lateralize the epileptogenic zone to the left side in all patients. RESULTS: Application of the paired t-test in SPM to pre- and postoperative FDG-PETs showed that the postoperative glucose metabolism decreased in the caudate nucleus, pulvinar of thalamus, fusiform gyrus, lingual gyrus, and in 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 of 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. CONCLUSION: 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 while a postoperative decrease in glucose metabolism may be related to a permanent loss of afferents from resected anterior-mesial temporal structures.
Anterior Temporal Lobectomy ; Brain ; Caudate Nucleus ; Electrons ; Epilepsy, Temporal Lobe* ; Glucose ; Gyrus Cinguli ; Humans ; Magnetic Resonance Imaging ; Mesencephalon ; Metabolism ; Pathology ; Pulvinar ; Sclerosis ; Seizures ; Temporal Lobe* ; Thalamus

PURPOSE: This study aimed to identify the neural basis of executive function (EF) in amnestic mild cognitive impairment (aMCI) according to beta-amyloid (Aβ) positivity. Furthermore, we explored if the identified brain areas could serve as predictors for clinical progression. MATERIALS AND METHODS: We included individuals with aMCI using data from [¹⁸F]-florbetapir-positron emission tomography (PET), fluorodeoxyglucose-PET, and EF scores, as well as follow-up clinical severity scores at 1 and 5 years from baseline from the Alzheimer's Disease Neuroimaging Initiative database. The correlations between EF score and regional cerebral glucose metabolism (rCMglc) were analyzed separately for aMCI with low Aβ burden (aMCI Aβ−, n=230) and aMCI with high Aβ burden (aMCI Aβ+, n=268). Multiple linear regression analysis was conducted to investigate the associations between rCMglc and clinical progression. RESULTS: Longitudinal courses differed between aMCI Aβ− and aMCI Aβ+ groups. On average, aMCI Aβ− subjects maintained their level of clinical severity, whereas aMCI Aβ+ subjects showed progression. EF impairment in aMCI Aβ− was related to the anterior cingulate cortex (ACC), whereas that in aMCI Aβ+ was related to Alzheimer's Disease-vulnerable brain regions. ACC and the posterior cingulate cortex were associated with clinical progression in aMCI Aβ− and aMCI Aβ+, respectively. CONCLUSION: Our findings suggest that although MCI subjects showed similar behavioral phenotypes at the time of diagnosis, EF and further progression were associated with different brain regions according to Aβ burden. Clarification of the etiologies and nature of EF impairment in aMCI are critical for disease prognosis and management.
Alzheimer Disease ; Amyloid ; Brain ; Cognition ; Diagnosis ; Executive Function ; Follow-Up Studies ; Glucose ; Gyrus Cinguli ; Linear Models ; Metabolism ; Mild Cognitive Impairment ; Neuroimaging ; Phenotype ; Positron-Emission Tomography ; Prognosis