Enhancing deep learning classification performance of tongue lesions in imbalanced data: mosaic-based soft labeling with curriculum learning.

BACKGROUND: Oral potentially malignant disorders (OPMDs) are associated with an increased risk of cancer of the oral cavity including the tongue. The early detection of oral cavity cancers and OPMDs is critical for reducing cancer-specific morbidity and mortality. Recently, there have been studies to apply the rapidly advancing technology of deep learning for diagnosing oral cavity cancer and OPMDs. However, several challenging issues such as class imbalance must be resolved to effectively train a deep learning model for medical imaging classification tasks. The aim of this study is to evaluate a new technique of artificial intelligence to improve the classification performance in an imbalanced tongue lesion dataset. METHODS: A total of 1,810 tongue images were used for the classification. The class-imbalanced dataset consisted of 372 instances of cancer, 141 instances of OPMDs, and 1,297 instances of noncancerous lesions. The EfficientNet model was used as the feature extraction model for classification. Mosaic data augmentation, soft labeling, and curriculum learning (CL) were employed to improve the classification performance of the convolutional neural network. RESULTS: Utilizing a mosaic-augmented dataset in conjunction with CL, the final model achieved an accuracy rate of 0.9444, surpassing conventional oversampling and weight balancing methods. The relative precision improvement rate for the minority class OPMD was 21.2%, while the relative [Formula: see text] score improvement rate of OPMD was 4.9%. CONCLUSIONS: The present study demonstrates that the integration of mosaic-based soft labeling and curriculum learning improves the classification performance of tongue lesions compared to previous methods, establishing a foundation for future research on effectively learning from imbalanced data.

In Vivo Serotonin 5-HT2A Receptor Availability and Its Relationship with Aggression Traits in Healthy Individuals: A Positron Emission Tomography Study with C-11 MDL100907.

Serotonergic neurotransmission has been associated with aggression in several psychiatric disorders. Human aggression is a continuum of traits, ranging from normal to pathological phenomena. However, the individual differences in serotonergic neurotransmission and their relationships with aggression traits in healthy individuals remain unclear. In this study, we explored the relationship between 5-HT2A receptor availability in vivo and aggression traits in healthy participants. Thirty-three healthy participants underwent 3-Tesla magnetic resonance imaging and positron emission tomography (PET) with [11C]MDL100907, a selective radioligand for 5-HT2A receptors. To quantify 5-HT2A receptor availability, the binding potential (BPND) was derived using the basis function implementation of the simplified reference tissue model, with the cerebellum as the reference region. The participants' aggression levels were assessed using the Buss-Perry Aggression Questionnaire. The voxel-based correlation analysis with age and sex as covariates revealed that the total aggression score was significantly positively correlated with [11C]MDL100907 BPND in the right middle temporal gyrus (MTG) pole, left fusiform gyrus (FUSI), right parahippocampal gyrus, and right hippocampus. The physical aggression subscale score had significant positive correlations with [11C]MDL100907 BPND in the left olfactory cortex, left orbital superior frontal gyrus (SFG), right anterior cingulate and paracingulate gyri, left orbitomedial SFG, left gyrus rectus, left MTG, left inferior temporal gyrus, and left angular gyrus. The verbal aggression subscale score showed significant positive correlations with [11C]MDL100907 BPND in the bilateral SFG, right medial SFG, left FUSI, and right MTG pole. Overall, our findings suggest the possibility of positive correlations between aggression traits and in vivo 5-HT2A receptor availability in healthy individuals. Future research should incorporate multimodal neuroimaging to investigate the downstream effects of 5-HT2A receptor-mediated signaling and integrate molecular and systems-level information in relation to aggression traits.

Alexithymia and frontal-amygdala functional connectivity in North Korean refugees.

BACKGROUND: Refugees commonly experience difficulties with emotional processing, such as alexithymia, due to stressful or traumatic experiences. However, the functional connectivity of the amygdala, which is central to emotional processing, has yet to be assessed in refugees. Thus, the present study investigated the resting-state functional connectivity of the amygdala and its association with emotional processing in North Korean (NK) refugees. METHODS: This study included 45 NK refugees and 40 native South Koreans (SK). All participants were administered the Toronto Alexithymia Scale (TAS), Beck Depression Inventory (BDI), and Clinician-administered PTSD Scale (CAPS), and differences between NK refugees and native SK in terms of resting-state functional connectivity of the amygdala were assessed. Additionally, the association between the strength of amygdala connectivity and the TAS score was examined. RESULTS: Resting-state connectivity values from the left amygdala to the bilateral dorsolateral prefrontal cortex (dlPFC) and dorsal anterior cingulate cortex (dACC) were higher in NK refugees than in native SK. Additionally, the strength of connectivity between the left amygdala and right dlPFC was positively associated with TAS score after controlling for the number of traumatic experiences and BDI and CAPS scores. CONCLUSIONS: The present study found that NK refugees exhibited heightened frontal-amygdala connectivity, and that this connectivity was correlated with alexithymia. The present results suggest that increased frontal-amygdala connectivity in refugees may represent frontal down-regulation of the amygdala, which in turn may produce alexithymia.

EEG signals during mouth breathing in a working memory task.

Background: Continuous mouth breathing results not only morphological deformations but also poor learning outcomes. However, there were few studies that observed correlations between mouth breathing and cognition. This study aimed at investigating the changes in brain activity during mouth breathing while the participant simultaneously performed a cognitive task using electroencephalography (EEG).Methods: Twenty subjects participated in this study, and EEG electrodes (32 channels, 250-Hz sampling rate) were placed on their scalp. Brain waves during a resting state and n-back tasks (0-back and 2-back) and physiological parameters such as SpO2, ETCO2, and the airway respiratory rate were measured. The pre-processed EEG signals were analyzed based on their frequencies as delta waves (0.5 ∼ 4 Hz), theta waves (4 ∼ 8 Hz), alpha waves (8 ∼ 13 Hz), beta waves (13 ∼ 30 Hz) and gamma waves (30 ∼ 50 Hz) using fast Fourier transform (FFT).Results: When compared with nose breathing, theta and alpha powers were lower during mouth breathing at rest and alpha wave presented low power at 0-back and 2-back tasks. Furthermore, beta and gamma waves exhibited low powers at 2-back task. However, the behavioral results (accuracy and response time) have no significant difference between two breathing methods (mouth and nose). Mouth breathing showed different brain activity patterns, compared to nose breathing, and these changes are related to cognitive regions.Conclusion: The reason for this change seems to relate to the decreased oxygen saturation during mouth breathing, suggesting that when cognitive abilities are required, mouth breathing can act as one of the variables that cause different outcomes in brain activities.

Relationship of self-transcendence traits with in vivo dopamine D2/3 receptor availability and functional connectivity: An [18 F]fallypride PET and fMRI study.

Genetic research has implicated dopamine neurotransmission in the expression of the self-transcendence trait in humans. However, molecular imaging of dopaminergic markers is undocumented in relation to this personality trait. In this multimodal imaging study, we first investigated the relationship between the self-transcendence trait and in vivo dopamine D2/3 receptor availability using [18 F]fallypride positron emission tomography (PET). We next conducted seed-based functional connectivity analyses using resting-state functional magnetic resonance imaging (rs-fMRI) data with regions derived from the PET analysis as seeds to explore the functional significance of D2/3 receptor availability foci associated with the self-transcendence trait. Twenty-one healthy subjects underwent high-resolution PET with [18 F]fallypride and a subset of 18 subjects also completed 3-Tesla rs-fMRI. The Temperament and Character Inventory was used to measure the self-transcendence trait. A voxel-based whole brain analysis revealed that the [18 F]fallypride binding potential (BPND ) within the cluster of the left insula was significantly positively correlated with self-transcendence trait scores. A region-of-interest analysis also showed a significant positive correlation between self-transcendence and [18 F]fallypride BPND in the left insula. The exploratory [18 F]fallypride BPND seed-based rs-fMRI analysis showed that the functional connectivity from the left insula seed to the prefrontal cortices (including the inferior frontal region) was negatively associated with self-transcendence trait scores. The results of the present study suggest that D2/3 receptor-mediated neurotransmission in the left insula may constitute a significant neurobiological factor in the self-transcendence trait. The negative associations between BPND seed-based functional connectivity and self-transcendence trait scores may suggest reduced prefrontal control in this personality trait.

Decreased regional brain activity in response to sleep-related sounds after cognitive behavioral therapy for psychophysiological insomnia.

AIM: Patients with psychophysiological insomnia (PI) experience hyperarousal, especially as a reaction to sound stimuli. In the current study, we explored brain activity changes in response to sleep-related sounds (SS) in patients with insomnia after cognitive behavioral therapy for insomnia (CBT-I). METHODS: In 14 drug-free PI patients, regional brain activity in response to SS, and to white noise sound (NS) as neutral stimuli, was investigated before and after individual CBT-I using functional magnetic resonance imaging. Blood oxygen level-dependent (BOLD) signals to SS and NS were compared before and after CBT-I. In addition, the association between clinical improvement after CBT-I and changes in brain activity in response to SS and NS was analyzed. RESULTS: Compared with baseline, regional brain activity in response to SS after CBT-I decreased in the left middle temporal and left middle occipital gyrus. In regression analysis, a reduction in the Dysfunctional Beliefs and Attitudes about Sleep (DBAS) Scale score after CBT-I was associated with decrease in brain activity in response to SS in both thalami. However, brain activity in response to NS showed no BOLD signal changes and no association with DBAS change. CONCLUSION: Cortical hyperactivity, which may cause hyperarousal in PI, was found to decrease after CBT-I. CBT-I targeting changes in beliefs and attitudes about sleep may induce its therapeutic effects by reducing thalamic brain activity in response to sleep-related stimuli.

Altered connectivity between striatal and extrastriatal regions in patients with schizophrenia on maintenance antipsychotics: an [18 F]fallypride PET and functional MRI study.

In addition to probing regional differences in receptor availability, molecular positron emission tomography (PET) is proving useful for investigating perturbations in neurotransmitter networks using interregional correlation analyses. In a multi-modal imaging study, we examined interregional correlations of dopamine D2/3 receptor availability between striatal and extrastriatal regions using [18 F]fallypride high-resolution PET in 11 patients with schizophrenia receiving low-dose maintenance atypical antipsychotics and 14 healthy control subjects, and investigated resting-state functional connectivity in the same subjects using seed-based functional magnetic resonance imaging (fMRI) analysis. In the healthy control group, there were no significant correlations of [18 F]fallypride binding potential (BPND ) between striatal regions and any cortical areas, whereas the patient group showed significant and widespread inter-correlations. Correlations between BPND in striatum, amygdala and insula with cortex were significantly higher in patients than in controls. In seed-based resting-state fMRI analysis, the healthy controls revealed positive and negative functional connectivity patterns, while patients exhibited a pattern of exclusively positive connectivity. Functional connectivity was significantly higher between striatal regions and extrastriatal areas including cortical regions in patients compared to controls. In this first such report, molecular and functional connectivity between striatal and extrastriatal regions was primarily characterized by increased interregional relationships in treated patients with schizophrenia. The results suggest that the spatial organization of D2/3 receptor availability and related functional connectivity are significantly perturbed in stable outpatients on maintenance antipsychotics. Future studies should include antipsychotic-naïve patients to determine if these relationships are illness-related characteristics, or arising due to chronic antipsychotic treatment.

The relationship between excitement symptom severity and extrastriatal dopamine D2/3 receptor availability in patients with schizophrenia: a high-resolution PET study with [18F]fallypride.

The purpose of this study was to investigate the relationship between specific symptom severity and D2/3 receptor availability in extrastriatal regions in outpatients with schizophrenia to shed light on the role of extrastriatal dopaminergic neurotransmission in the pathophysiology of symptoms of schizophrenia. Sixteen schizophrenia patients receiving relatively low-dose maintenance atypical antipsychotics and seventeen healthy controls underwent 3-Tesla magnetic resonance imaging and high-resolution positron emission tomography with [18F]fallypride. For D2/3 receptor availability, the binding potential with respect to non-displaceable compartment (BPND) was derived using the simplified reference tissue model. The BPND values were lower in patients on antipsychotic treatment than in controls across all regions with large effect sizes (1.03-1.42). The regions with the largest effect size were the substantia nigra, amygdala, and insula. Symptoms of schizophrenia were assessed using a five-factor model of the Positive and Negative Syndrome Scale (PANSS). The region of interest-based analysis showed that PANSS excitement factor score had a significant positive correlation with the [18F]fallypride BPND in the insula. The equivalent dose of antipsychotics was not significantly correlated with PANSS factor scores or regional BPND values. The voxel-based analysis also revealed a significant positive association between the PANSS excitement factor and the [18F]fallypride BPND in the insula. The present study revealed a significant association between excitement symptom severity and D2/3 receptor availability in the insula in schizophrenia, suggesting a possible important role of D2/3 receptor-mediated neurotransmission in the insula and related limbic system in the pathophysiology of this specific symptom cluster.

Individually differentiated serotonergic raphe nuclei measured with brain PET/MR imaging.

PURPOSE: To measure the activity of individual raphe nuclei with fluorine 18 fluorodeoxyglucose (FDG) and carbon 11 ((11)C) 3-amino-4-(2-dimethylaminomethylphenylthio) benzonitrile (DASB) imaging using a brain positron emission tomography(PET)/magnetic resonance (MR) imaging fusion system. MATERIALS AND METHODS: The study was approved by the Institutional Review Board of Gil Medical Center, and all volunteers provided written informed consent. FDG PET, (11)C-DASB PET, and T2*-weighted MR images from seven healthy volunteers were acquired by using a PET/MR imaging fusion system. The standard uptake value ratio (SUVR) of FDG (FDG-SUVR) and nondisplaceable binding potential (BPnd) of (11)C-DASB (DASB-BPnd) were determined for each raphe nucleus. A Pearson correlation analysis was performed to show the correlation between FDG-SUVR and DASB-BPnd for the raphe nuclei. RESULTS: Each raphe nucleus could be distinguished in both FDG (identifiability ratio, 0.86; κ = 0.77) and (11)C-DASB (identifiability ratio, 0.89; κ = 0.72) images. The mean values of DASB-BPnd for each raphe nucleus from dorsal to caudal direction were 6.08 (raphe nucleus 1), 5.93 (raphe nucleus 2), 3.86 (raphe nucleus 3), 3.18 (raphe nucleus 4), and 2.74 (raphe nucleus 5); the mean FDG-SUVR values were 1.00 (raphe nucleus 1), 1.00 (raphe nucleus 2), 0.87 (raphe nucleus 3), 0.94 (raphe nucleus 4), and 0.90 (raphe nucleus 5). FDG-SUVR and DASB-BPnd for the raphe nuclei were significantly correlated (r = 0.506, P = .002). CONCLUSION: Serotonergic activity, both glucose metabolism and transporter binding potential of raphe nuclei, were measured with a brain-dedicated PET/MR imaging system and showed a significant correlation.

Dopamine D(2/3) receptor availability and human cognitive impulsivity: a high-resolution positron emission tomography imaging study with [¹¹C]raclopride.

OBJECTIVE: Human impulsivity is a complex multidimensional construct encompassing cognitive, emotional, and behavioural aspects. Previous animal studies have suggested that striatal dopamine receptors play a critical role in impulsivity. In this study, we investigated the relationship between self-reported impulsiveness and dopamine D(2/3) receptor availability in striatal subdivisions in healthy subjects using high-resolution positron emission tomography (PET) with [11C]raclopride. METHODS: Twenty-one participants completed 3-T magnetic resonance imaging and high-resolution PET scans with [11C]raclopride. The trait of impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11). Partial correlation analysis was performed between BIS-11 scores and D(2/3) receptor availability in striatal subregions, controlling for the confounding effects of temperament characteristics that are conceptually or empirically related to dopamine, which were measured by the Temperament and Character Inventory. RESULTS: The analysis revealed that the non-planning (p = 0.004) and attentional (p = 0.007) impulsiveness subscale scores on the BIS-11 had significant positive correlations with D(2/3) receptor availability in the pre-commissural dorsal caudate. There was a tendency towards positive correlation between non-planning impulsiveness score and D(2/3) receptor availability in the post-commissural caudate. CONCLUSION: These results suggest that cognitive subtrait of impulsivity is associated with D(2/3) receptor availability in the associative striatum that plays a critical role in cognitive processes involving attention to detail, judgement of alternative outcomes, and inhibitory control.

In-vivo human brain molecular imaging with a brain-dedicated PET/MRI system.

Advances in the new-generation of ultra-high-resolution, brain-dedicated positron emission tomography-magnetic resonance imaging (PET/MRI) systems have begun to provide many interesting insights into the molecular dynamics of the brain. First, the finely delineated structural information from ultra-high-field MRI can help us to identify accurate landmark structures, thereby making it easier to locate PET activation sites that are anatomically well-correlated with metabolic or ligand-specific organs in the neural structures in the brain. This synergistic potential of PET/MRI imaging is discussed in terms of neuroscience and neurological research from both translational and basic research perspectives. Experimental results from the hippocampus, thalamus, and brainstem obtained with (18)F-fluorodeoxyglucose and (11)C-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile are used to demonstrate the potential of this new brain PET/MRI system.

Target registration errors in navigation-assisted mandibular surgery according to the tracking methods and the type of markers: experiments using human dry mandibular bone.

OBJECTIVES: This study was conducted to evaluate the accuracy of navigation process according to the type of tracking methods and registration markers. The target registration errors (TREs) were measured at seven anatomical landmarks of the mandible. METHODS: Four different experiments were performed to obtain the TREs using two tracking methods, the optical tracker (Polaris) and the electromagnetic (EM) tracker (Aurora), and two types of registration markers, invasive and noninvasive markers. All comparisons of TREs were statistically analyzed using SPSS and Python-based statistical package. RESULTS: The average TRE values obtained from the four experiments were as follows: (1) 0.85 mm (± 0.07) using invasive marker and Aurora, (2) 1.06 mm (± 0.12) using invasive marker and Polaris, (3) 1.43 mm (± 0.15) using noninvasive marker and Aurora, and (4) 1.57 mm (± 0.23) using noninvasive marker and Polaris. Comparisons between all the experimental results revealed statistically significant differences except for the type of tracking system. Although the comparison between the modality of the tracking system showed no significant differences, the EM-based approach consistently demonstrated better performances than the optical type in all comparisons. CONCLUSIONS: This study demonstrates that irrespective of the tracking modality, using invasive marker is a better choice in terms of accuracy. When using noninvasive marker, it is important to consider the increased TREs. In this study, the noninvasive marker caused a maximum increment of TREs of 0.81 mm compared with the invasive marker. Furthermore, using an EM-based tracker with invasive marker may result in the best accuracy for navigation.

The Relationship between Character Traits and In Vivo Cerebral Serotonin Transporter Availability in Healthy Subjects: A High-Resolution PET Study with C-11 DASB.

To elucidate the potential roles of serotonergic activity in human character traits (i.e., self-directedness, cooperativeness, and self-transcendence), we investigated the relationship between these character traits and serotonin transporter (5-HTT) in healthy subjects. Twenty-four participants underwent High-Resolution Research Tomograph-positron emission tomography scans with [11C]DASB. To quantify 5-HTT availability, binding potential (BPND) of [11C]DASB was obtained using the simplified reference tissue model. The Temperament and Character Inventory was used to assess subjects' levels of three character traits. There were no significant correlations between the three character traits. Self-directedness was significantly positively correlated with [11C]DASB BPND in the left hippocampus, left middle occipital gyrus, bilateral superior parietal gyrus, left inferior parietal gyrus, left middle temporal gyrus (MTG), and left inferior temporal gyrus (ITG). Cooperativeness was significantly negatively correlated with [11C]DASB BPND in the median raphe nucleus. Self-transcendence was significantly negatively correlated with [11C]DASB BPND in the right MTG and right ITG. Our results show significant correlations between the three character traits and 5-HTT availability in specific brain regions. In particular, self-directedness was significantly positively correlated with 5-HTT availability, suggesting that a goal-oriented, self-confident, and resourceful character may be related to higher serotonergic neurotransmission.

Glucose metabolism of the midline nuclei raphe in the brainstem observed by PET-MRI fusion imaging.

UNLABELLED: The brainstem contains various important monoaminergic neuronal centers, including the raphe nuclei which contain serotonergic neurons. The raphe nuclei, however, are not easily identifiable and located by conventional neuroimaging. METHODS: Fluorodeoxyglucose positron emission tomography (PET) and magnetic resonance imaging (MRI) were performed in seven healthy subjects using a new PET-MRI, which consists of a high-resolution research tomograph (HRRT) PET and 7.0 T-MRI. Glucose metabolism of raphe nuclei was semiquantitatively measured and identified along the midline brainstem region in vivo. RESULTS: Midline nuclei clustered in four groups appeared to be the raphe nuclei and could be clearly visualized; specifically, we identified the groups as the dorsal raphe, raphe reticularis centralis superior, raphe pontis, and raphe magnus group. CONCLUSION: FDG imaging of the midline raphe nuclei in vivo could potentially be an important tool for investigating brain diseases as well as conducting functional brain studies in the context of sleep disorders, depression, and neurodegenerative disease.

Differences in mGluR5 Availability Depending on the Level of Social Avoidance in Drug-Naïve Young Patients with Major Depressive Disorder.

Background: Previous research has shown that metabotropic glutamate receptor-5 (mGluR5) signaling is significantly involved in social avoidance. We investigated the relationship between levels of social avoidance and mGluR5 availability in drug-naïve young patients with major depressive disorder (MDD). Methods: Twenty non-smoking patients and eighteen matched non-smoking healthy controls underwent [11C]ABP688 positron emission tomography (PET) and magnetic resonance imaging scans. The binding potential (BPND) of [11C]ABP688 was obtained using the simplified reference tissue model. Patients' level of social avoidance was assessed using the Social Avoidance and Distress Scale (SADS). For [11C]ABP688 BPND, the region-of-interest (ROI)-based between-group comparisons and correlations with SADS scores were investigated. The frontal cortices were chosen as a priori ROIs based on previous PET investigations in MDD, and on literature underscoring the importance of the frontal cortex in social avoidance. Results: Independent samples t-tests revealed no significant differences in [11C]ABP688 BPND in the frontal cortices between the MDD patient group as a whole and healthy controls. One-way analysis of variance with post-hoc tests revealed significantly lower BPND in the bilateral superior frontal cortex (SFC) and left middle frontal cortex (MFC) in MDD patients with low levels of social avoidance (L-SADS) than in healthy controls. The L-SADS patients also had significantly lower BPND in the medial part of the right SFC than both MDD patients with high levels of social avoidance (H-SADS) and healthy controls. The L-SADS patients also showed significantly lower BPND in the orbital parts of the SFC, MFC, and inferior frontal cortex than H-SADS patients. No significant group differences were found between H-SADS patients and healthy controls. The ROI-based correlation analysis revealed significant positive correlations between social avoidance levels and frontal [11C]ABP688 BPND in the entire patients. Conclusion: Our exploratory study shows significant differences in frontal mGluR5 availability depending on the level of social avoidance in drug-naïve non-smoking MDD patients, suggesting that social avoidance should be considered as one of the clinical factors involved in mGluR5 signaling changes in depression.

Antipsychotic-associated mental side effects and their relationship to dopamine D2 receptor occupancy in striatal subdivisions: a high-resolution PET study with [11C]raclopride.

We examined the relationship between antipsychotic-associated mental side effects and dopamine D2 receptor occupancy in striatal subdivisions using high-resolution positron emission tomography with [11C]raclopride to better characterize the neurochemical mechanism underlying these adverse effects. Twenty-one patients with schizophrenia receiving stable doses of antipsychotics and 24 age- and sex-matched healthy controls completed 3-Tesla magnetic resonance imaging and high-resolution positron emission tomography scans with [11C]raclopride to measure D2 receptor binding potential (BP ND) in the striatum. The D2 receptor BP ND was obtained using a Logan plot, and receptor occupancy was calculated as the percentage reduction of receptor BP ND with drug treatment relative to baseline. The data obtained from age- and sex-matched healthy controls were used as an estimate of the patients' baseline, as previously proposed. Antipsychotic-associated mental side effects were measured with the Liverpool University Neuroleptic Side Effect Rating Scale. The whole striatal D2 receptor occupancy ranged from 54% to 95%. The analysis revealed that the Liverpool University Neuroleptic Side Effect Rating Scale score had significant positive associations with D2 occupancy in the precommissural dorsal caudate, postcommissural caudate, and ventral striatum. The results suggest that mental side effects of antipsychotics are associated with D2 receptor blockade in the associative and limbic subdivisions of the striatum, which are considered to play a crucial role in cognition and reward motivation.

Association Between Lack of Insight and Prefrontal Serotonin Transporter Availability in Antipsychotic-Free Patients with Schizophrenia: A High-Resolution PET Study with [11C]DASB.

BACKGROUND: Previous studies suggested a link between serotonergic neurotransmission and impaired insight in schizophrenia. In this study, we examined the relationship between serotonin transporter (SERT) availability in regions of the prefrontal cortex (dorsolateral, ventrolateral, ventromedial, and orbitofrontal cortices) and insight deficits in antipsychotic-free patients with schizophrenia using high-resolution positron emission tomography (PET) with [11C]DASB. METHODS: Nineteen patients underwent [11C]DASB PET and 7-Tesla magnetic resonance imaging scans. To assess SERT availability, the binding potential with respect to non-displaceable compartment (BPND) was derived using the simplified reference tissue model. Patients' level of insight was assessed using the Insight and Treatment Attitude Questionnaire (ITAQ). The relationship between ITAQ scores and [11C]DASB BPND values was examined using the region-of-interest (ROI)- and voxel-based analyses with relevant variables as covariates. The prefrontal cortex and its four subregions were selected as a priori ROIs since the prefrontal cortex has been implicated as the critical neuroanatomical substrate of impaired insight in schizophrenia. RESULTS: The ROI-based analysis revealed that the ITAQ illness insight dimension had significant negative correlations with the [11C]DASB BPND in the left dorsolateral, left orbitofrontal, and bilateral ventrolateral prefrontal cortices. The ITAQ treatment insight dimension had significant negative correlations with the [11C]DASB BPND in the bilateral dorsolateral, left orbitofrontal, and bilateral ventrolateral prefrontal cortices. The ITAQ total score showed significant negative correlations with the [11C]DASB BPND in the bilateral prefrontal cortex and three subregions (dorsolateral, ventrolateral, and orbitofrontal cortices). A supplementary voxel-based analysis corroborated a significant negative association between the ITAQ score and the [11C]DASB BPND in the prefrontal cortices. CONCLUSION: Our study provides in vivo evidence of significant negative correlations between insight deficits and prefrontal SERT availability in patients with schizophrenia, suggesting significant involvement of prefrontal serotonergic signaling in impaired insight, one of the core symptoms of schizophrenia.

Identification of Breathing Patterns through EEG Signal Analysis Using Machine Learning.

This study was to investigate the changes in brain function due to lack of oxygen (O2) caused by mouth breathing, and to suggest a method to alleviate the side effects of mouth breathing on brain function through an additional O2 supply. For this purpose, we classified the breathing patterns according to EEG signals using a machine learning technique and proposed a method to reduce the side effects of mouth breathing on brain function. Twenty subjects participated in this study, and each subject performed three different breathings: nose and mouth breathing and mouth breathing with O2 supply during a working memory task. The results showed that nose breathing guarantees normal O2 supply to the brain, but mouth breathing interrupts the O2 supply to the brain. Therefore, this comparative study of EEG signals using machine learning showed that one of the most important elements distinguishing the effects of mouth and nose breathing on brain function was the difference in O2 supply. These findings have important implications for the workplace environment, suggesting that special care is required for employees who work long hours in confined spaces such as public transport, and that a sufficient O2 supply is needed in the workplace for working efficiency.

Functional Analysis of Brain Imaging Suggests Changes in the Availability of mGluR5 and Altered Connectivity in the Cerebral Cortex of Long-Term Abstaining Males with Alcohol Dependence: A Preliminary Study.

Direct in vivo evidence of altered metabotropic glutamate receptor-5 (mGluR5) availability in alcohol-related disorders is lacking. We performed [11C]ABP688 positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI) in prolonged abstinent subjects with alcohol dependence to examine alterations of mGluR5 availability, and to investigate their functional significance relating to neural systems-level changes. Twelve prolonged abstinent male subjects with alcohol dependence (median abstinence duration: six months) and ten healthy male controls underwent [11C]ABP688 PET imaging and 3-Tesla MRI. For mGluR5 availability, binding potential (BPND) was calculated using the simplified reference tissue model with cerebellar gray matter as the reference region. The initial region-of-interest (ROI)-based analysis yielded no significant group differences in mGluR5 availability. The voxel-based analysis revealed significantly lower [11C]ABP688 BPND in the middle temporal and inferior parietal cortices, and higher BPND in the superior temporal cortex in the alcohol dependence group compared with controls. Functional connectivity analysis of the rs-fMRI data employed seed regions identified from the quantitative [11C]ABP688 PET analysis, which revealed significantly altered functional connectivity from the inferior parietal cortex seed to the occipital pole and dorsal visual cortex in the alcohol dependence group compared with the control group. To our knowledge, this is the first report on the combined analysis of mGluR5 PET imaging and rs-fMRI in subjects with alcohol dependence. These preliminary results suggest the possibility of region-specific alterations of mGluR5 availability in vivo and related functional connectivity perturbations in prolonged abstinent subjects.

In Vivo Cerebral Translocator Protein (TSPO) Binding and Its Relationship with Blood Adiponectin Levels in Treatment-Naïve Young Adults with Major Depression: A [11C]PK11195 PET Study.

Adiponectin is an adipokine that mediates cellular cholesterol efflux and plays important roles in neuroinflammatory processes. In this study, we undertook positron emission tomography (PET) with the translocator protein (TSPO) ligand [11C]PK11195 and measured serum adiponectin levels in groups of treatment-naïve young adult patients with major depressive disorder (MDD) and matched healthy controls. Thirty treatment-naïve MDD patients (median age: 24 years) and twenty-three healthy controls underwent [11C]PK11195 PET. We quantified TSPO availability in brain as the [11C]PK11195 binding potential (BPND) using a reference tissue model in conjunction with the supervised cluster analysis (SVCA4) algorithm. Age, sex distribution, body mass index, and serum adiponectin levels did not differ between the groups. Between-group analysis using a region-of-interest approach showed significantly higher [11C]PK11195 BPND in the left anterior and right posterior cingulate cortices in MDD patients than in controls. Serum adiponectin levels had significant negative correlations with [11C]PK11195 BPND in the bilateral hippocampus in MDD patients, but significant positive correlations in the bilateral hippocampus in the control group. Our results indicate significantly higher TSPO binding in the anterior and posterior cingulate cortices in treatment-naïve young MDD patients, suggesting microglial activation in these limbic regions, which are involved in cognitive and emotional processing. The opposite correlations between [11C]PK11195 BPND in the hippocampus with serum adiponectin levels in MDD and control groups suggest that microglial activation in the hippocampus may respond differentially to adiponectin signaling in MDD and healthy subjects, possibly with respect to microglial phenotype.