Comparison of propofol-based sedation and midazolam sedation in pediatric bidirectional endoscopy conducted by pediatric gastroenterologists.

Objectives: The effectiveness and safety of propofol-based sedation and midazolam sedation in pediatric bidirectional endoscopy were compared. Methods: We retrospectively analyzed the cases of pediatric patients (≤15 years old) who had undergone bidirectional endoscopy, esophagogastroduodenoscopy, and colonoscopy by pediatric gastroenterologists. Demographic data, indications, sedatives/dosages, clinical outcomes, endoscopic findings, adverse events, and total patient time requirements (total time in which patients stay in our hospital) were compared in the two sedation groups. Results: Ninety-one children (51 boys, 40 girls, mean age 13 years, range 9-15) treated at our hospital were enrolled. Propofol alone or in combination with midazolam and/or pentazocine was administered to 51 patients (propofol-based sedation group). Midazolam alone or in combination with pentazocine was administered to the other 40 patients (midazolam sedation group). In the propofol group, the following mean doses were used: propofol, 96 mg (range 40-145 mg); midazolam, 4.9 mg (range 3-5 mg); and pentazocine, 7.5 mg. In the midazolam group, the mean doses of midazolam and pentazocine were 6.2 mg (range 4-10 mg) and 15 mg, respectively. All procedures were successfully completed by pediatric gastroenterologists. The total procedure times and endoscopic findings were similar in the two groups, but the median patient time requirement in the propofol group was significantly shorter versus the midazolam group (7.3 h vs. 8.4 h, p < 0.001). No adverse events occurred in either group. Conclusions: Propofol-based sedation in pediatric bidirectional endoscopy was safely and effectively performed by pediatric gastroenterologists, and its patient time requirement was shorter than that for midazolam sedation.

Cognitive functions relating to aberrant interactions between task-positive and task-negative networks: Resting fMRI study of patients with schizophrenia.

Brain functional connectivity in the resting-state represents intrinsic functional states and correlates with cognitive performance. In patients with schizophrenia, reports on the relationships between forms of functional disconnectivity in local areas and cognitive disability have used resting-state functional magnetic resonance imaging data. Meanwhile, cognitive deficits in relation to inter-network forms of functional connectivity on a large scale are not well understood. This study examines cognitive functions in relation to the number of resting-state inter-network forms of functional connectivity focusing on task-positive networks (fronto-parietal network [FPN] and cingulo-opercular network [CON]) and task-negative network (default mode network [DMN]). We compare patients with schizophrenia (SCH group) and healthy controls (HC group). We conducted a functional network analysis by applying graph theory and evaluated cognitive functions using the Brief Assessment of Cognition in Schizophrenia. The number of forms of functional connectivity between FPN and DMN and between CON and DMN were significantly higher in SCH group than in HC group, and those in SCH group were also weakly correlated with their attention scores. It is suggested that fewer than typical functional segregations between task-positive and task-negative networks in SCH group relate to inefficient distribution of cognitive resources and low attentional abilities.

Subjective Loudness Using External Noise Reflects the Loudness and Distress of Tinnitus: A Cross-Sectional Study.

OBJECTIVES: Subjective tinnitus loudness has been measured using loudness matches, which compare tinnitus loudness with pure tones from an audiometer. When patients compare the sound pressure of certain noises with the tinnitus loudness, however, there may be remarkable differences from the measurements according to loudness matches. Subjective loudness (SubL) is an estimation of the sound pressure of tinnitus loudness by comparison of noises considered to be most similar to tinnitus loudness of patient. We examine whether SubL is inferior to loudness matches in measurement of subjective tinnitus loudness. DESIGN: Single-group cross-sectional study. PATIENTS: Included in this study were a clinical group of 111 patients with the chief complaint of subjective tinnitus. Seven of the 111 patients were excluded due to missing audiometry or questionnaire data. METHODS: Patients assessed the tinnitus loudness and related distress using visual analogue scales (VAS-L and VAS-S) and answered the Tinnitus Handicap Inventory (THI). Hearing acuity, tinnitus pitch, and loudness were then measured using an audiometer. RESULTS: VAS-L, VAS-S, and THI scores significantly correlated with loudness match using Goodwin's method (SL2) and SubL. Subgroup analysis based on patient ages indicated that all correlations of SL2 with VAS-L, VAS-S, and THI scores were no longer seen in patients more than 60 years of age. Meanwhile, SubL correlated with VAS-L, VAS-S, and THI scores in all subgroups. CONCLUSIONS: SubL was a good reflection of self-reported loudness and distress of tinnitus. It may therefore be a simple and easy means of assessing tinnitus loudness and associated distress during pre-examination without an audiometer.

Microstructural abnormalities in callosal fibers and their relationship with cognitive function in schizophrenia: A tract-specific analysis study.

INTRODUCTION: The corpus callosum serves the essential role of relaying cognitive information between the homologous regions in the left and the right hemispheres of the brain. Cognitive impairment is a core dysfunction of schizophrenia, but much of its pathophysiology is unknown. The aim of this study was to elucidate the association between microstructural abnormalities of the corpus callosum and cognitive dysfunction in schizophrenia. METHODS: We examined stepwise multiple regression analysis to investigate the relationship of the fractional anisotropy (FA) of callosal fibers in each segment with z-scores of each brief assessment of cognition in schizophrenia subtest and cognitive composite score in all subjects (19 patients with schizophrenia [SZ group] and 19 healthy controls [HC group]). Callosal fibers were separated into seven segments based on their cortical projection using tract-specific analysis of diffusion tensor imaging. RESULTS: The FA of callosal fibers in the temporal segment was significantly associated with z-scores of token motor test, Tower of London test, and the composite score. In the SZ group, the FA of callosal fibers in the temporal segment was significantly associated with the z-score of the Tower of London test. In addition, the FA of callosal fibers in temporal segment showed significant negative association with the positive and negative syndrome scale negative score in the SZ group. Compared to the HC group, the FA in temporal segment was significantly decreased in the SZ group. CONCLUSION: Our results suggest that microstructural abnormalities in the callosal white matter fibers connecting bilateral temporal lobe cortices contribute to poor executive function and severe negative symptom in patients with schizophrenia.

Relationship between polyunsaturated fatty acid and eating disorders: Systematic review and meta-analysis.

OBJECTIVES: Eating disorders result in poor nutrition, poor physical conditions and even suicidality and mortality. Although polyunsaturated fatty acids (PUFAs) have attracted attention in the emerging field of nutritional psychiatry, their role in eating disorders remains unknown. This meta-analysis investigates the differences of PUFA levels between patients with eating disorders and healthy controls, and the potentially beneficial effects of PUFAs in such patients. METHODS: We conducted a systematic literature search and meta-analysis under the random effects model. RESULT: Eleven studies were included in the current meta-analysis. Compared with controls, 379 patients with eating disorders had significantly higher plasma levels of alpha-linolenic acid, eicosapentaenoic acid, stearidonic acid, osbond acid, palmitoleic acid, oleic acid, and total omega-3 fatty acids; and lower levels of total omega-6 fatty acids and omega-6/omega-3 ratio. Eating disorders were associated with significantly higher red blood cell membrane levels of palmitoleic acid and oleic acid and lower levels of adrenic acid, arachidonic acid, and total omega-6 fatty acids. In addition, PUFA supplements were associated with a benefit to body weight outcomes but not disease severity and mood symptoms in interventional trials. DISCUSSION: This meta-analysis indicates abnormal levels of PUFAs in peripheral blood tissues in patients with eating disorders. The relationship between PUFAs and eating disorders should be interpreted cautiously considering the specific lipid metabolism under starvation state. To investigate the role of PUFAs on psychopathological and therapeutic effects in eating disorders, further larger clinical studies are warranted.

A case of autoimmune autonomic ganglionopathy with prolonged delirium.

Autoimmune autonomic ganglionopathy (AAG) is a rare acquired immune-mediated disorder that leads to autonomic failure. It is sometimes complicated by mental and behavioral symptoms. We report a case of 72-year-old male with AAG who was admitted to the psychiatric department for prolonged severe delirium. Repeated loss of consciousness attributed to severe orthostatic hypotension disturbed recovery from delirium. In addition, intracerebral hemorrhage occurred during hospitalization, and this cerebrovascular event may have been substantially affected by unstable blood pressure due to AAG. This case suggests importance of differential diagnosis of AAG in patients with mental and behavioral symptoms accompanying severe autonomic failure.

A case report of the efficacy and usefulness of asenapine in the treatment of a cancer patient with delirium and aphagia.

OBJECTIVE: Controlling hyperactive and mixed delirium is extremely important for the continuation of cancer treatment in palliative care. In general, oral antipsychotics are the first-line drug therapy for delirium; however, oral administration is problematic in patients presenting dysphagia. In this case report, we describe an end-stage cancer patient with aphagia who developed delirium and responded to sublingual antipsychotic asenapine for treating delirium. We also discuss the effectiveness of asenapine in hyperactive delirium as well as its usefulness for treating delirium in palliative care. METHOD: A cancer patient with delirium was treated with several oral antipsychotics commonly used to treat delirium but did not respond to any of them. The patient subsequently developed aphagia with progression of the disease. Sublingual asenapine was therefore given to treat delirium. RESULT: Asenapine was effective in treating delirium without causing any obvious side effects. SIGNIFICANCE OF RESULTS: In the present case, asenapine was effective in treating hyperactive delirium that did not respond to commonly used antipsychotics. Because asenapine is a sublingual tablet, it can be used in patients with dysphagia and aphagia. In addition, this drug is anticipated to diminish the burden of end-stage patients from taking oral medications. Furthermore, its management is easier compared with injections, and can therefore also be easily used in homecare patients. Based on these perspectives, asenapine may become an important option for treating delirium in palliative care.

Widespread abnormalities in white matter integrity and their relationship with duration of illness in temporal lobe epilepsy.

OBJECTIVE: Elucidation of abnormal connections throughout the whole brain is necessary to understand temporal lobe epilepsy (TLE). We examined abnormalities in whole-brain white matter integrity and their relationship with duration of illness in patients with TLE. METHODS: The subjects were 15 patients with TLE and 17 healthy controls. Mean duration of illness in the TLE group was 21.6 years. Tract-based spatial statistics (TBSS) were used for diffusion tensor imaging (DTI) analysis. Four diffusion tensor metrics, that is, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated and then examined for differences between the TLE and healthy control groups. We also examined for correlations between DTI parameters and duration of illness in the TLE group. RESULTS: In the TLE group, compared with the healthy control group, FA was reduced, and MD and RD were increased, not only in the limbic and temporal lobe regions and their directly connecting regions in both hemispheres, but also in remote white matter regions. Duration of illness showed a significant negative correlation with mean whole-brain FA and a significant positive correlation with both mean whole-brain MD and RD. Brain regions showing correlation between disease duration and DTI metrics also extended to the limbic area and its connecting regions, and to remote white matter regions. SIGNIFICANCE: The results of this study suggest that widespread abnormalities in white matter integrity in patients with TLE are associated with long-term disease.

Omega-3 fatty acids related to cognitive impairment in patients with schizophrenia.

Cognitive impairment is strongly associated with functional outcome in patients with schizophrenia but its pathophysiology remains largely unclear. Involvement of omega-3 fatty acids in the cognitive function of healthy individuals and patients with neuropsychiatric disease has received increasing attention. The aim of this study was to examine the relationship between omega-3 fatty acids with cognitive function, social function, and psychiatric symptoms in patients with schizophrenia. The subjects included 30 patients with schizophrenia or schizoaffective disorder. Psychiatric symptoms, cognitive function, and social function were assessed using the Positive and Negative Syndrome Scale, the Brief Assessment of Cognition in Schizophrenia (BACS), and the Social Functioning Scale (SFS), respectively. Blood serum omega-3 fatty acids were assessed using gas chromatography. The BACS composite score was significantly correlated with blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. In addition, a daily dose of antipsychotic medication was negatively and significantly correlated with the blood DHA level and with the BACS composite score. Step-wise multiple regression analyses demonstrated that the SFS score was significantly associated with the BACS composite score. Our results indicate that reduced blood omega-3 fatty acids are associated with cognitive impairment, which then impacts social functioning outcomes in schizophrenia.

Interhemispheric disconnectivity in the sensorimotor network in bipolar disorder revealed by functional connectivity and diffusion tensor imaging analysis.

BACKGROUND: Little is known regarding interhemispheric functional connectivity (FC) abnormalities via the corpus callosum in subjects with bipolar disorder (BD), which might be a key pathophysiological basis of emotional processing alterations in BD. METHODS: We performed tract-based spatial statistics (TBSS) using diffusion tensor imaging (DTI) in 24 healthy control (HC) and 22 BD subjects. Next, we analyzed the neural networks with independent component analysis (ICA) in 32HC and 25 BD subjects using resting-state functional magnetic resonance imaging. RESULTS: In TBSS analysis, we found reduced fractional anisotropy (FA) in the corpus callosum of BD subjects. In ICA, functional within-connectivity was reduced in two clusters in the sensorimotor network (SMN) (right and left primary somatosensory areas) of BD subjects compared with HCs. FC between the two clusters and FA values in the corpus callosum of BD subjects was significantly correlated. Further, the functional within-connectivity was related to Young Mania Rating Scale (YMRS) total scores in the right premotor area in the SMN of BD subjects. LIMITATIONS: Almost all of our BD subjects were taking several medications which could be a confounding factor. CONCLUSIONS: Our findings suggest that interhemispheric FC dysfunction in the SMN is associated with the impaired nerve fibers in the corpus callosum, which could be one of pathophysiological bases of emotion processing dysregulation in BD patients.

Elucidating the aberrant brain regions in bipolar disorder using T1-weighted/T2-weighted magnetic resonance ratio images.

Although diffusion tensor imaging (DTI) have revealed brain abnormalities in bipolar disorder (BD) subjects, DTI methods might not detect disease-related abnormalities in the white matter (WM) where nerve fibers are crossing. We investigated BD myelin-related abnormal brain regions in both gray matter and WM for 29 BD and 33 healthy control (HC) participants using T1-weighted (T1w)/T2-weighted (T2w) ratio images that increase myelin-related contrast irrespective of nerve fiber orientation. To check effect of the brain volume, the results were compared with those of voxel-based morphometry (VBM). We found significantly lower T1w/T2w signal intensity in broad WM regions in BD subjects, including the corpus callosum, corona radiata, internal capsule, middle cerebellar peduncle and cerebellum. Regional volume reduction was found in the WM bilateral posterior thalami and retrolenticular part of the internal capsules of BD subjects. We also performed tract-based spatial statistics (TBSS) in 25 BD and 24 HC participants and compared those for the T1w/T2w ratio images. Both methods detected the BD corpus callosum abnormality. Further, the ratio images detected the corona radiata and the cerebellar abnormality in BD. These results suggest that T1w/T2w ratio image analysis could take a complementary role with the DTI method in elucidating myelin-related abnormalities in BD.

[rTMS (Repetitive Transcranial Magnetic Stimulation) for the Treatment of Depression].

The clinical introduction of rTMS for the treatment of depression is now progressing in Japan. On the basis of the successful results of a large-scale RCT, the US FDA approved an rTMS device in 2008, and four rTMS devices are now approved and used in several countries and the EC. The results of the meta-analysis of RCTs and the real-world naturalistic observa- tional studies show beneficial effects on treatment-resistant depression. The rTMS is generally well-tolerated and safe, but has a risk of seizure, with an estimated rate of approximately one in 1,000 patients. The rTMS is thought to be an effective treatment for those unable to benefit from initial antidepressant medication.

Use of T1-weighted/T2-weighted magnetic resonance ratio images to elucidate changes in the schizophrenic brain.

INTRODUCTION: One leading hypothesis suggests that schizophrenia (SZ) is a neurodevelopmental disorder caused by genetic defects in association with environmental risk factors that affect synapse and myelin formation. Recent magnetic resonance imaging (MRI) studies of SZ brain showed both gray matter (GM) reduction and white matter (WM) fractional anisotropy reduction. In this study, we used T1-weighted (T1w)/T2-weighted (T2w) MRI ratio images, which increase myelin-related signal contrast and reduce receiver-coil bias. METHODS: We measured T1w/T2w ratio image signal intensity in 29 patients with SZ and 33 healthy controls (HCs), and then compared them against bias-corrected T1w images. RESULTS: Mean T1w/T2w ratio signal intensity values across all SZ GM and WM voxels were significantly lower than those for the HC values (analysis of covariance with age, gender, handedness, and premorbid intelligence quotient as nuisance covariates). SZ mean WM T1w/T2w ratio values were related to Global Assessment of Functioning (GAF) scores and were inversely related to the positive psychotic symptoms of the Positive and Negative Syndrome Scale. Voxel-based analysis revealed significantly lower T1w/T2w ratio image signal intensity values in the right ventral putamen in SZ GM. T1w image intensities did not differ between the SZ and HC groups. CONCLUSIONS: T1-weighted/T2-weighted ratio imaging increased the detectability of SZ pathological changes. Reduced SZ brain signal intensity is likely due to diminished myelin content; therefore, mapping myelin-related SZ brain changes using T1w/T2w ratio images may be useful for studies of SZ brain abnormalities.

Alterations of Regional Cerebral Blood Flow in Tinnitus Patients as Assessed Using Single-Photon Emission Computed Tomography.

Tinnitus is the perception of phantom sound without an external auditory stimulus. Using neuroimaging techniques, such as positron emission tomography, electroencephalography, magnetoencephalography, and functional magnetic resonance imaging (fMRI), many studies have demonstrated that abnormal functions of the central nervous system are closely associated with tinnitus. In our previous research, we reported using resting-state fMRI that several brain regions, including the rectus gyrus, cingulate gyrus, thalamus, hippocampus, caudate, inferior temporal gyrus, cerebellar hemisphere, and medial superior frontal gyrus, were associated with tinnitus distress and loudness. To reconfirm these results and probe target regions for repetitive transcranial magnetic stimulation (rTMS), we investigated the regional cerebral blood flow (rCBF) between younger tinnitus patients (<60 years old) and the age-matched controls using single-photon emission computed tomography and easy Z-score imaging system. Compared with that of controls, the rCBF of tinnitus patients was significantly lower in the bilateral medial superior frontal gyri, left middle occipital gyrus and significantly higher in the bilateral cerebellar hemispheres and vermis, bilateral middle temporal gyri, right fusiform gyrus. No clear differences were observed between tinnitus patients with normal and impaired hearing. Regardless of the assessment modality, similar brain regions were identified as characteristic in tinnitus patients. These regions are potentially involved in the pathophysiology of chronic subjective tinnitus.

Evaluation of regional cerebral blood flow in patient with atypical senile dementia with asymmetrical calcification.

We report an 83-year-old woman with atypical senile dementia with Fahr-type calcification. Brain computed tomography demonstrated asymmetrical calcification predominant in the basal ganglia on the right side and pronounced diffuse cortical atrophy in the frontotemporal areas. The patient was clinically diagnosed with diffuse neurofibrillary tangles with calcification. Brain single photon emission computed tomography findings revealed that cerebral blood flow was reduced on the right side, as compared with the left side, in widespread areas. Hemispheric asymmetry in both calcification and cerebral blood flow suggests a relationship between calcification and vascular changes.

Microstructural abnormalities in anterior callosal fibers and their relationship with cognitive function in major depressive disorder and bipolar disorder: a tract-specific analysis study.

BACKGROUND: The corpus callosum modulates interhemispheric communication and cognitive processes. It has been suggested that white matter abnormalities in the corpus callosum are related to the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). The aim of this study was to examine microstructural abnormalities in callosal fibers separated by their connection to functional brain regions and determine the relationship of these abnormalities with cognitive function in MDD and BD. METHODS: The subjects were 18 patients with MDD, 20 patients with BD, and 21 healthy controls. The callosal fibers were divided into 6 segments based on their cortical projection using tract-specific analysis of diffusion tensor imaging. We examined differences in the fractional anisotropy (FA) of callosal fibers in six segments among the three subject groups and examined the correlation between the FA in each segment and cognitive performance in the 3 groups. RESULTS: The FA of anterior callosal fibers were reduced significantly in the MDD and BD groups compared to those in the HC group, and the FA of anterior callosal fibers correlated significantly with the raw scores of the digit sequencing task and symbol coding in the MDD group. LIMITATIONS: The patients were medicated at the time of scanning, and the MDD and BD groups were not matched for symptom severity. CONCLUSIONS: Our results suggest that MDD and BD have similar microstructural abnormalities in anterior callosal fibers connecting bilateral frontal cortices, and these abnormalities may be related to impairment of working memory and attention in MDD.

Reduction of cortical excitability and increase of thalamic activity in a low-frequency rTMS treatment for chronic tinnitus.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has received increasing attention for the treatment of tinnitus, but its therapeutic mechanisms are unclear. We performed low-frequency rTMS treatment for a patient with chronic tinnitus and examined changes of cortical excitability and cerebral blood flow using paired-pulse TMS and single-photon emission computed tomography. After the rTMS treatment, tinnitus loudness was decreased, cortical excitability was reduced, and blood flow in the thalamus was increased. Our results suggest that low-frequency rTMS treatment reduces tinnitus loudness by an inhibitory effect on the cortical excitability and a remote activation effect on the thalamus through the corticothalamic networks.

Brain regions responsible for tinnitus distress and loudness: a resting-state FMRI study.

Subjective tinnitus is characterized by the perception of phantom sound without an external auditory stimulus. We hypothesized that abnormal functionally connected regions in the central nervous system might underlie the pathophysiology of chronic subjective tinnitus. Statistical significance of functional connectivity (FC) strength is affected by the regional autocorrelation coefficient (AC). In this study, we used resting-state functional MRI (fMRI) and measured regional mean FC strength (mean cross-correlation coefficient between a region and all other regions without taking into account the effect of AC (rGC) and with taking into account the effect of AC (rGCa) to elucidate brain regions related to tinnitus symptoms such as distress, depression and loudness. Consistent with previous studies, tinnitus loudness was not related to tinnitus-related distress and depressive state. Although both rGC and rGCa revealed similar brain regions where the values showed a statistically significant relationship with tinnitus-related symptoms, the regions for rGCa were more localized and more clearly delineated the regions related specifically to each symptom. The rGCa values in the bilateral rectus gyri were positively correlated and those in the bilateral anterior and middle cingulate gyri were negatively correlated with distress and depressive state. The rGCa values in the bilateral thalamus, the bilateral hippocampus, and the left caudate were positively correlated and those in the left medial superior frontal gyrus and the left posterior cingulate gyrus were negatively correlated with tinnitus loudness. These results suggest that distinct brain regions are responsible for tinnitus symptoms. The regions for distress and depressive state are known to be related to depression, while the regions for tinnitus loudness are known to be related to the default mode network and integration of multi-sensory information.

Reduction of cortical GABAergic inhibition correlates with working memory impairment in recent onset schizophrenia.

BACKGROUND: Cognitive impairments are present during the early course of schizophrenia, and the contribution of GABAergic dysfunction to these cognitive impairments has received increasing attention. Cortical GABAergic inhibition can be assessed using short-interval intracortical inhibition (SICI) in a paired-pulse transcranial magnetic stimulation (ppTMS). The aim of this study was to examine the relationship between cortical GABAergic inhibition and cognitive function in recent onset schizophrenia patients using ppTMS and a neuropsychological battery. METHODS: The subjects were 20 healthy controls (HC group) and 20 patients with schizophrenia whose duration of illness was less than three years (SZ group). All subjects underwent ppTMS measurements of SICI and intracortical facilitation (ICF), and cognitive performance of the SZ group was assessed using the Brief Assessment of Cognition in Schizophrenia Japanese-language version. We examined group differences in ppTMS measurements (resting motor threshold, SICI, and ICF). In the SZ group, we assessed the relationship between SICI and cognitive performance, and the relationships between SICI and age, duration of illness, medications, and psychopathology. RESULTS: The SZ group showed a significant reduction of SICI compared to the HC group, and demonstrated a significant correlation between the reduction of SICI and impaired performance of a working memory task. The HC and the SZ groups did not differ significantly in resting motor threshold and ICF. The SZ group did not show any significant correlations between SICI and age, duration of illness, medications, or psychopathology. CONCLUSIONS: Our results suggest that the reduction of cortical GABAergic inhibition is related to impairment of working memory in patients with recent onset schizophrenia.