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Purpose@#Increasing attention has been paid to low-intensity transcranial focused ultrasound (tFUS) for its potential therapeutic effects in Alzheimer's disease (AD). While preclinical studies have shown promising therapeutic effects of low-intensity tFUS in AD models, its efficacy and safety remain unclear in humans. In this pilot study, we investigated the effects of low-intensity tFUS on blood-brain barrier opening, the regional cerebral metabolic rate of glucose (rCMRglu), and cognition in patients with AD. @*Methods@#After receiving institutional review board approval, four patients with AD received tFUS to the hippocampus immediately after an intravenous injection of a microbubble ultrasound contrast agent. Sonication was delivered at low-intensity, at a pressure level below the threshold for blood-brain barrier opening. Patients underwent brain magnetic resonance imaging, 18F-fluoro-2-deoxyglucose positron emission tomography, and neuropsychological assessments before and after the tFUS procedure. A whole-brain voxel-wise paired t test was conducted to compare rCMRglu before and after tFUS. @*Results@#The sonication, as anticipated, did not show evidence of active blood-brain barrier opening on T1 dynamic contrast-enhanced magnetic resonance imaging. rCMRglu in the superior frontal gyrus (P<0.001), middle cingulate gyrus (P<0.001), and fusiform gyrus increased after tFUS (P=0.001). Patients demonstrated mild improvement in measures of memory, executive, and global cognitive function following tFUS. No adverse events were reported. @*Conclusion@#These results suggest that hippocampal sonication with low-intensity tFUS may have beneficial effects on cerebral glucose metabolism and cognitive function in patients with AD. Further larger studies are needed to confirm the therapeutic efficacy of tFUS in AD.
ABSTRACT
Ultrasound is an important theragnostic modality in modern medicine. Technical advancement of both acoustic focusing and transcranial delivery have enabled administration of ultrasound waves to localized brain areas with few millimeters of spatial specificity and penetration depth sufficient to reach the thalamus. Transcranial focused ultrasound (tFUS) given at a low acoustic intensity has been shown to increase or suppress the excitability of region-specific brain areas. The neuromodulatory effects can outlast the sonication, suggesting the possibility of inducing neural plasticity needed for neurorehabilitation.Increasing numbers of studies have shown the efficacy and excellent safety profile of the technique, yet comparisons among the safety-related parameters have not been compiled.This review aims to provide safety information and perspectives of tFUS brain stimulation.First, the acoustic parameters most relevant to thermal/mechanical tissue damage are discussed along with regulated parameters for existing ultrasound therapies/diagnostic imaging. Subsequently, the parameters used in studies of large animals, non-human primates, and humans are surveyed and summarized in terms of the acoustic intensity and the mechanical index. The pulse-mode operation and the use of low ultrasound frequency for tFUS-mediated brain stimulation warrant the establishment of new safety guidelines/ recommendations for the use of the technique among healthy volunteers, with additional cautionary requirements for its clinical translation.
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Objectives@#Despite growing attention to anxiety in bipolar disorder (BD), little research has assessed anxiety symptoms in the course of BD. The current prospective follow-up study examines the influence of subjectively and objectively measured anxiety symptoms on the course of BD. @*Methods@#A total of 49 patients with BD were followed-up prospectively for average of one year at an average of four months interval. The Korean version of the Beck Anxiety Inventory (K-BAI), the Hamilton Anxiety Rating Scale, heart rate variability (HRV) were used to measure anxiety subjectively, objectively and physiologically. Participants were divided into high and low anxiety groups based on their K-BAI scores. Kaplan-Meier survival analysis was performed to compare the recurrence of mood episode, suicide attempt, emergency room visit, and psychiatric hospitalization between two groups. Mediators were investigated with Cox proportional hazards models. @*Results@#Compared to the low anxiety group, the high anxiety group reported significantly higher impulsiveness (p = 0.016) and lower high frequency component on HRV (p = 0.007) after controlling for severity of BD. Regarding survival analysis, the high anxiety group showed hastened depressive episode recurrence (p = 0.048) and suicidal ideation was the mediator of the hazard ratio (HR) 1.089 (p = 0.029) in the Cox model. Moreover, the high anxiety group showed a tendency of accelerated suicide attempt (p = 0.12) and impulsivity was the risk factor of suicide attempt (HR = 1.089, p = 0.036). @*Conclusions@#This interim analysis of prospective study suggests that high anxiety level in BD may anticipate unfavorable course.Further studies are needed to understand the multifactorial mechanism of anxious bipolar patients.
ABSTRACT
Objectives@#Despite growing attention to anxiety in bipolar disorder (BD), little research has assessed anxiety symptoms in the course of BD. The current prospective follow-up study examines the influence of subjectively and objectively measured anxiety symptoms on the course of BD. @*Methods@#A total of 49 patients with BD were followed-up prospectively for average of one year at an average of four months interval. The Korean version of the Beck Anxiety Inventory (K-BAI), the Hamilton Anxiety Rating Scale, heart rate variability (HRV) were used to measure anxiety subjectively, objectively and physiologically. Participants were divided into high and low anxiety groups based on their K-BAI scores. Kaplan-Meier survival analysis was performed to compare the recurrence of mood episode, suicide attempt, emergency room visit, and psychiatric hospitalization between two groups. Mediators were investigated with Cox proportional hazards models. @*Results@#Compared to the low anxiety group, the high anxiety group reported significantly higher impulsiveness (p = 0.016) and lower high frequency component on HRV (p = 0.007) after controlling for severity of BD. Regarding survival analysis, the high anxiety group showed hastened depressive episode recurrence (p = 0.048) and suicidal ideation was the mediator of the hazard ratio (HR) 1.089 (p = 0.029) in the Cox model. Moreover, the high anxiety group showed a tendency of accelerated suicide attempt (p = 0.12) and impulsivity was the risk factor of suicide attempt (HR = 1.089, p = 0.036). @*Conclusions@#This interim analysis of prospective study suggests that high anxiety level in BD may anticipate unfavorable course.Further studies are needed to understand the multifactorial mechanism of anxious bipolar patients.
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Objectives@#To identify the clinical utility of the Korean version of the Barkley Deficits in Executive Functioning Scale (K-BDEFS) assessing executive functioning. @*Methods@#The patient group included 144 adult attention-deficit/hyperactivity disorder (ADHD) patients visiting the Adult ADHD Outpatient Clinic of the National Center for Mental Health. Adult ADHD Self-Report Scale version 1.1, Mini International Neuropsychiatric Interview, and K-BDEFS were used. The control subjects were 144 age, sex, and education-matched general adults who participated in the study of the validity of the K-BDEFS in Samsung Medical Center. @*Results@#An analysis of the mean total K-BDEFS score, executive functioning symptom count, and ADHD-executive function (EF) index score revealed a significant difference between the adult ADHD and control group (p<0.05). Five subscales of the K-BDEFS, which assess the specific domains of the executive function, revealed a significant difference between the ADHD group and control group (p<0.05). The area under curve (AUC) of the K-BDEFS total score, the EF symptom count, and the ADHD-EF index were 0.943, 0.949, and 0.908, respectively, in the analysis using the receiver operating characteristic curve. All AUC values were over 0.90. Therefore, KBDEFS is a reliable and valid screening instrument for diagnosing adult ADHD. In an assessment of the sensitivity and specificity of the cutoff scores, a cutoff of 183.5 points for the K-BDEFS total score, 26.5 points for the EF symptom count, and 23.5 points for the ADHD-EF index showed a reliable sensitivity and specificity above 80%. @*Conclusion@#To the best of the authors’ knowledge, this is the first study to examine the predictive validity and clinical utility of K-BDEFS in adult ADHD. The results suggest that the K-BDEFS could be used as a valid and reliable tool for the diagnosis and clinical intervention of adult ADHD.
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Objective@#More recently, attention has turned to the linkage between childhood trauma and emotional dysregulation, but the evidence in bipolar disorder (BD) is limited. To determine neurobiological relationships between childhood trauma, current anxiety, and impulsivity, we investigated cortical volumetric correlates of these clinical factors in BD. @*Methods@#We studied 36 patients with DSM-5 BD and 29 healthy controls. Childhood trauma, coexisting anxiety, and impulsivity were evaluated with the Korean version-Childhood Trauma Questionnaire (CTQ), the Korean version-Beck Anxiety Inventory (BAI), and the Korean version-Barratt Impulsiveness Scale (BIS). Voxel-based morphometry (VBM) was used to assess gray matter volume (GMV) alterations on the brain magnetic resonance imaging (MRI). Partial correlation analyses were conducted to examine associations between the GMV and each scale in the BD group. @*Results@#Childhood trauma, anxiety, and impulsivity were interrelated in BD. BD patients revealed significant inverse correlations between the GMV in the right precentral gyrus and CTQ scores (r=-0.609, p<0.0003); between the GMV in the left middle frontal gyrus and BAI scores (r=-0.363, p=0.044). Moreover, patients showed similar tendency of negative correlations between the GMV in the right precentral gyrus and BIS scores; between the GMV in the left middle frontal gyrus and CTQ scores. @*Conclusion@#The present study provides evidence for a neural basis between childhood trauma and affect regulations in BD. The GMV alterations in multiple frontal lobe areas may represent neurobiological markers for anticipating the course of BD.
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We present BioSubroutine, an open depository server that automatically categorizes various subroutines frequently used in bioinformatics research. We processed a large bioinformatics subroutine library called Bio.pl that was the first Bioperl subroutine library built in 1995. Over 1000 subroutines were processed automatically and an HTML interface has been created. BioSubroutine can accept new subroutines and algorithms from any such subroutine library, as well as provide interactive user forms. The subroutines are stored in an SQL database for quick searching and accessing. BioSubroutine is an open access project under the BioLicense license scheme.