Transcranial Alternating Current Stimulation Reduces Network Hypersynchrony and Persistent Vertigo.

OBJECTIVES: Persistent oscillating vertigo that occurs after entrainment to periodic motion is known as Mal de Débarquement Syndrome (MdDS). Down-modulation of this oscillating vertigo is associated with reduction in long-range resting-state functional connectivity between fronto-parieto-occipital regions. In order to determine the association between this oscillating vertigo and hypersynchrony as measured by the auditory steady-state response (ASSR), we investigated the differences in ASSR between individuals with MdDS and healthy controls as well as the change in ASSR in individuals with MdDS before and after treatment with transcranial alternating current stimulation (tACS). MATERIALS AND METHODS: Individuals with treatment refractory MdDS lasting at least six months received single administrations of fronto-parieto-occipital tACS in an "n-of-1" double-blind randomized design: alpha-frequency in-phase, alpha-frequency antiphase, and gamma frequency antiphase control. The treatment protocol that led to the most acute reduction in symptoms and improved balance was administered for 10-12 sessions given over three days (each session 20-min at 2-4 mA). RESULTS: Twenty-four individuals with MdDS participated (mean age 53.0 ± 11.8 years [range: 22-66 years, median: 57.0 years]; mean duration of illness 38.6 ± 53.4 months [range: 6-240 months, median: 18.0 months]). Individuals with MdDS had elevated ASSR compared to healthy controls at baseline (t11 = 5.95, p < 0.001). There was a significant decrease in the 40 Hz-ASSR response between responders compared to nonresponders to tACS (t-test, t15 = -2.26, p = 0.04). Both in-phase and anti-phase alpha tACS lead to symptom improvement but only antiphase alpha-tACS led to a significant decrease of 40 Hz-ASSR (t-test, t12 = -9.6, p < 0.001). CONCLUSIONS: Our findings suggest that tACS has the potential to reduce network-level hypersynchrony and pathological susceptibility to entrainment by sensory input. To the best of our knowledge, this is the first successful demonstration of desynchronization by noninvasive brain stimulation leading to reduced vertigo. Other disease states associated with pathological functional coupling of neuronal networks may similarly benefit from this novel approach.

Transition Zone in Total Colonic Aganglionosis and Colorectal Hirschsprung's Disease Shows a Similar Trend of Mucosal Innervation: Image Processing and Analysis Study.

The aganglionic segment of bowel in Hirschsprung's disease (HD) varies in length. It is not clear whether total colonic aganglionosis (TCA) merely represents a long form of HD or a different phenotype of the disease. Animal model studies suggest that TCA may have a longer transition zone (TZ) than conventional colorectal HD. We compared mucosal innervation of TZ in 2 TCA cases and 10 conventional colorectal HD cases by quantifying calretinin-positive mucosal nerve fibers using image processing and analysis. One TCA was associated with esophageal atresia-tracheoesophageal fistula, the other with trisomy 21. The gradients of calretinin-stained pixel count increase per distance from the beginning of TZ (slope) for TCA were not significantly different from those for the conventional HD group. Given this observation, it is speculated that the length of TZ in TCA may fall within the range of and may not be much longer than conventional colorectal HD.

Exploring the relationship between geomagnetic activity and human heart rate variability.

PURPOSE: Both geomagnetic and solar activity fluctuate over time and have been proposed to affect human physiology. Heart rate variability (HRV) has substantial health implications regarding the ability to adapt to stressors and has been shown to be altered in many cardiovascular and neurological disorders. Intriguingly, previous work found significant, strong correlations between HRV and geomagnetic/solar activity. The purpose of this study to replicate these findings. We simultaneously measured HRV during a 30-day period. METHODS: We recruited 20 healthy participants and measured their HRV for a 30-day period. We also collected geomagnetic and solar activity during this period for investigating their relationship with the HRV data. RESULTS: In agreement with previous work, we found several significant correlations between short-term HRV and geophysical time-series. However, after correction for autocorrelation, which is inherent in time-series, the only significant results were an increase in very low frequency during higher local geomagnetic activity and a geomagnetic anticipatory decrease in heart rate a day before the higher global geomagnetic activity. Both correlations were very low. The loss of most significant effects after this correction suggests that previous findings may be a result of autocorrelation. A further note of caution is required since our and the previous studies in the field do not correct for multiple comparisons given the exploratory analysis strategy. CONCLUSION: We thus conclude that the effects of geomagnetic and solar activity are (if present) most likely of very small effect size and we question the validity of the previous studies given the methodological concerns we have uncovered with our work.

Targeting reduced neural oscillations in patients with schizophrenia by transcranial alternating current stimulation.

Transcranial alternating current stimulation (tACS) modulates endogenous neural oscillations in healthy human participants by the application of a low-amplitude electrical current with a periodic stimulation waveform. Yet, it is unclear if tACS can modulate and restore neural oscillations that are reduced in patients with psychiatric illnesses such as schizophrenia. Here, we asked if tACS modulates network oscillations in schizophrenia. We performed a randomized, double-blind, sham-controlled clinical trial to contrast tACS with transcranial direct current stimulation (tDCS) and sham stimulation in 22 schizophrenia patients with auditory hallucinations. We used high-density electroencephalography to investigate if a five-day, twice-daily 10Hz-tACS protocol enhances alpha oscillations and modulates network dynamics that are reduced in schizophrenia. We found that 10Hz-tACS enhanced alpha oscillations and modulated functional connectivity in the alpha frequency band. In addition, 10Hz-tACS enhanced the 40Hz auditory steady-state response (ASSR), which is reduced in patients with schizophrenia. Importantly, clinical improvement of auditory hallucinations correlated with enhancement of alpha oscillations and the 40Hz-ASSR. Together, our findings suggest that tACS has potential as a network-level approach to modulate reduced neural oscillations related to clinical symptoms in patients with schizophrenia.

Modulating neural oscillations by transcranial static magnetic field stimulation of the dorsolateral prefrontal cortex: A crossover, double-blind, sham-controlled pilot study.

Transcranial static magnetic field stimulation (tSMS) is a novel non-invasive brain stimulation technique that has been shown to locally increase alpha power in the parietal and occipital cortex. We investigated if tSMS locally increased alpha power in the left or right prefrontal cortex, as the balance of left/right prefrontal alpha power (frontal alpha asymmetry) has been linked to emotional processing and mood disorders. Therefore, altering frontal alpha asymmetry with tSMS may serve as a novel treatment to psychiatric diseases. We performed a crossover, double-blind, sham-controlled pilot study to assess the effects of prefrontal tSMS on neural oscillations. Twenty-four right-handed healthy participants were recruited and received left dorsolateral prefrontal cortex (DLPFC) tSMS, right DLPFC tSMS, and sham tSMS in a randomized order. Electroencephalography data were collected before (2 min eyes-closed, 2 min eyes-open), during (10 min eyes-open), and after (2 min eyes-open) stimulation. In contrast with our hypothesis, neither left nor right tSMS locally increased frontal alpha power. However, alpha power increased in occipital cortex during left DLPFC tSMS. Right DLPFC tSMS increased post-stimulation fronto-parietal theta power, indicating possible relevance to memory and cognition. Left and right DLPFC tSMS increased post-stimulation left hemisphere beta power, indicating possible changes to motor behavior. Left DLPFC tSMS also increased post-stimulation right frontal beta power, demonstrating complex network effects that may be relevant to aggressive behavior. We concluded that DLPFC tSMS modulated the network oscillations in regions distant from the location of stimulation and that tSMS has region specific effects on neural oscillations.

Interbrain phase synchronization during turn-taking verbal interaction-a hyperscanning study using simultaneous EEG/MEG.

Recently, neurophysiological findings about social interaction have been investigated widely, and hardware has been developed that can measure multiple subjects' brain activities simultaneously. These hyperscanning studies have enabled us to discover new and important evidences of interbrain interactions. Yet, very little is known about verbal interaction without any visual input. Therefore, we conducted a new hyperscanning study based on verbal, interbrain turn-taking interaction using simultaneous EEG/MEG, which measures rapidly changing brain activities. To establish turn-taking verbal interactions between a pair of subjects, we set up two EEG/MEG systems (19 and 146 channels of EEG and MEG, respectively) located ∼100 miles apart. Subjects engaged in verbal communication via condenser microphones and magnetic-compatible earphones, and a network time protocol synchronized the two systems. Ten subjects participated in this experiment and performed verbal interaction and noninteraction tasks separately. We found significant oscillations in EEG alpha and MEG alpha/gamma bands in several brain regions for all subjects. Furthermore, we estimated phase synchronization between two brains using the weighted phase lag index and found statistically significant synchronization in EEG and MEG data. Our novel paradigm and neurophysiological findings may foster a basic understanding of the functional mechanisms involved in human social interactions. Hum Brain Mapp 39:171-188, 2018. © 2017 Wiley Periodicals, Inc.

Zero TE-based pseudo-CT image conversion in the head and its application in PET/MR attenuation correction and MR-guided radiation therapy planning.

PURPOSE: To describe a method for converting Zero TE (ZTE) MR images into X-ray attenuation information in the form of pseudo-CT images and demonstrate its performance for (1) attenuation correction (AC) in PET/MR and (2) dose planning in MR-guided radiation therapy planning (RTP). METHODS: Proton density-weighted ZTE images were acquired as input for MR-based pseudo-CT conversion, providing (1) efficient capture of short-lived bone signals, (2) flat soft-tissue contrast, and (3) fast and robust 3D MR imaging. After bias correction and normalization, the images were segmented into bone, soft-tissue, and air by means of thresholding and morphological refinements. Fixed Hounsfield replacement values were assigned for air (-1000 HU) and soft-tissue (+42 HU), whereas continuous linear mapping was used for bone. RESULTS: The obtained ZTE-derived pseudo-CT images accurately resembled the true CT images (i.e., Dice coefficient for bone overlap of 0.73 ± 0.08 and mean absolute error of 123 ± 25 HU evaluated over the whole head, including errors from residual registration mismatches in the neck and mouth regions). The linear bone mapping accounted for bone density variations. Averaged across five patients, ZTE-based AC demonstrated a PET error of -0.04 ± 1.68% relative to CT-based AC. Similarly, for RTP assessed in eight patients, the absolute dose difference over the target volume was found to be 0.23 ± 0.42%. CONCLUSION: The described method enables MR to pseudo-CT image conversion for the head in an accurate, robust, and fast manner without relying on anatomical prior knowledge. Potential applications include PET/MR-AC, and MR-guided RTP.

Clinical evaluation of TOF versus non-TOF on PET artifacts in simultaneous PET/MR: a dual centre experience.

PURPOSE: Our objective was to determine clinically the value of time-of-flight (TOF) information in reducing PET artifacts and improving PET image quality and accuracy in simultaneous TOF PET/MR scanning. METHODS: A total 65 patients who underwent a comparative scan in a simultaneous TOF PET/MR scanner were included. TOF and non-TOF PET images were reconstructed, clinically examined, compared and scored. PET imaging artifacts were categorized as large or small implant-related artifacts, as dental implant-related artifacts, and as implant-unrelated artifacts. Differences in image quality, especially those related to (implant) artifacts, were assessed using a scale ranging from 0 (no artifact) to 4 (severe artifact). RESULTS: A total of 87 image artifacts were found and evaluated. Four patients had large and eight patients small implant-related artifacts, 27 patients had dental implants/fillings, and 48 patients had implant-unrelated artifacts. The average score was 1.14 ± 0.82 for non-TOF PET images and 0.53 ± 0.66 for TOF images (p < 0.01) indicating that artifacts were less noticeable when TOF information was included. CONCLUSION: Our study indicates that PET image artifacts are significantly mitigated with integration of TOF information in simultaneous PET/MR. The impact is predominantly seen in patients with significant artifacts due to metal implants.

Cognitive responses and cortical oscillatory processing at various stereoscopic depths - a simultaneous EEG/MEG study.

Due to the recent explosion in various forms of 3D content, the evaluation of such content from a neuroscience perspective is quite interesting. However, existing investigations of cortical oscillatory responses in stereoscopic depth perception are quite rare. Therefore, we investigated spatiotemporal and spatio-temporo-spectral features at four different stereoscopic depths within the comfort zone. We adopted a simultaneous EEG/MEG acquisition technique to collect the oscillatory responses of eight participants. We defined subject-specific retinal disparities and designed a single trial-based stereoscopic viewing experimental paradigm. In the group analysis, we observed that, as the depth increased from Level 1 to Level 3, there was a time-locked increase in the N200 component in MEG and the P300 component in EEG in the occipital and parietal areas, respectively. In addition, initial alpha and beta event-related desynchronizations (ERD) were observed at approximately 500 to 1000 msec, while theta, alpha, and beta event-related synchronizations (ERS) appeared at approximately 1000 to 2000 ms. Interestingly, there was a saturation point in the increase in cognitive responses, including N200, P300, and alpha ERD, even when the depth increased only within the comfort zone. Meanwhile, the magnitude of low beta ERD decreased in the dorsal pathway as depth increased. From these findings, we concluded that cognitive responses are likely to become saturated in the visual comfort zone, while perceptual load may increase with depth.

Zero TE MR bone imaging in the head.

PURPOSE: To investigate proton density (PD)-weighted zero TE (ZT) imaging for morphological depiction and segmentation of cranial bone structures. METHODS: A rotating ultra-fast imaging sequence (RUFIS) type ZT pulse sequence was developed and optimized for 1) efficient capture of short T2 bone signals and 2) flat PD response for soft-tissues. An inverse logarithmic image scaling (i.e., -log(image)) was used to highlight bone and differentiate it from surrounding soft-tissue and air. Furthermore, a histogram-based bias-correction method was developed for subsequent threshold-based air, soft-tissue, and bone segmentation. RESULTS: PD-weighted ZT imaging in combination with an inverse logarithmic scaling was found to provide excellent depiction of cranial bone structures. In combination with bias correction, also excellent segmentation results were achieved. A two-dimensional histogram analysis demonstrates a strong, approximately linear correlation between inverse log-scaled ZT and low-dose CT for Hounsfield units (HU) between -300 HU and 1,500 HU (corresponding to soft-tissue and bone). CONCLUSIONS: PD-weighted ZT imaging provides robust and efficient depiction of bone structures in the head, with an excellent contrast between air, soft-tissue, and bone. Besides structural bone imaging, the presented method is expected to be of relevance for attenuation correction in positron emission tomography (PET)/MR and MR-based radiation therapy planning.

Cortical Responses and Shape Complexity of Stereoscopic Image - A Simultaneous EEG/MEG Study.

BACKGROUND/AIMS: In exploring human factors, stereoscopic 3D images have been used to investigate the neural responses associated with excessive depth, texture complexity, and other factors. However, the cortical oscillation associated with the complexity of stereoscopic images has been studied rarely. Here, we demonstrated that the oscillatory responses to three differently shaped 3D images (circle, star, and bat) increase as the complexity of the image increases. METHODS: We recorded simultaneous EEG/MEG for three different stimuli. Spatio-temporal and spatio-spectro-temporal features were investigated by non-parametric permutation test. RESULTS: The results showed that N300 and alpha inhibition increased in the ventral area as the shape complexity of the stereoscopic image increased. CONCLUSION: It seems that the relative disparity in complex stereoscopic images may increase cognitive processing (N300) and cortical load (alpha inhibition) in the ventral area.

Feasibility of a deepithelialized superior gluteal artery perforator propeller flap for various lumbosacral defects.

Skin and soft tissue defects in the lumbosacral area are commonly encountered in the field of reconstructive surgery, and it is well documented that the superior gluteal artery perforator (SGAP) flap provides excellent coverage of these defects. In this article, we describe our experience using a modified version of the SGAP propeller flap, in which the distal redundant portion of an elevated SGAP flap is deepithelialized, thereby maximizing the effect of the soft tissue augmentation. Thirteen patients with lumbosacral soft tissue defects treated between May 2010 and June 2012 were included in this study. The wound causes were pressure ulcer (n = 9), pseudomeningocele (n = 2), and hardware exposure (n = 2). In all patients, an elevated SGAP flap was rotated 180 degrees over the defect area and the extra distal portion of the flap was deepithelialized and used as a soft tissue filler or tamponade. During the follow-up period (mean, 26 months), 12 of 13 flaps survived completely. One flap was totally necrosed due to progressive venous congestion and was reconstructed with local advancement flaps. No further complications were noted. Because of the redundancy and pliability of the tissue in the gluteal area, a flap relatively wider or longer than the defect can be elevated safely. Hence, the redundant tissue volume can be tucked inside to facilitate soft tissue augmentation of the area. We propose that the deepithelialized version of the SGAP propeller flap is an effective option for the reconstruction of various lumbosacral soft tissue defects because it offers thick and healthy soft tissue from a distant site to the defect areas.

The stem cell potential and multipotency of human adipose tissue-derived stem cells vary by cell donor and are different from those of other types of stem cells.

Human adipose tissue-derived mesenchymal stem cells (AT-MSCs) from various sites are applied in tissue engineering and cell therapy. The condition of AT-MSCs depends on the donor's age, body mass index (BMI), and gender. AT-MSCs from 66 human donors were analyzed, and the cells were sorted according to donor age (10-19 years: n = 1; 20-29 years: n = 5; 30-39 years: n = 12; 40-49 years: n = 22; 50-59 years: n = 12; 60-69 years: n = 9, and 70 years or older: n = 5), BMI (under 25, 25-30, and over 30), and gender (19 males and 48 females). Additionally, AT-MSCs were compared to bone marrow MSCs and chorionic tissue-derived MSCs. We measured the MSC yield, growth rate, colony-forming units, multipotency, and surface antigens. AT-MSC proliferation was greater in cells isolated from individuals aged less than 30 years compared to the proliferation of AT-MSCs from those over 50 years old. BMI was correlated with osteogenic differentiation potency; increased BMI enhanced osteogenesis. Adipogenic differentiation was more strongly induced in cells isolated from donors aged less than 30 years compared to those isolated from other age groups. Also, a BMI above 30 was associated with enhanced adipogenic differentiation compared to cells isolated from individuals with a BMI below 25. Bone marrow MSCs were strongly induced to differentiate along both osteogenic and adipogenic lineages, whereas AT-MSCs predominantly differentiated into the chondrogenic lineage. Therefore, the type of regeneration required and variations among potential donors must be carefully considered when selecting MSCs for use in applied tissue engineering or cell therapy.

TSANet: multibranch attention deep neural network for classifying tactile selective attention in brain-computer interfaces.

Brain-computer interfaces (BCIs) enable communication between the brain and a computer and electroencephalography (EEG) has been widely used to implement BCIs because of its high temporal resolution and noninvasiveness. Recently, a tactile-based EEG task was introduced to overcome the current limitations of visual-based tasks, such as visual fatigue from sustained attention. However, the classification performance of tactile-based BCIs as control signals is unsatisfactory. Therefore, a novel classification approach is required for this purpose. Here, we propose TSANet, a deep neural network, that uses multibranch convolutional neural networks and a feature-attention mechanism to classify tactile selective attention (TSA) in a tactile-based BCI system. We tested TSANet under three evaluation conditions, namely, within-subject, leave-one-out, and cross-subject. We found that TSANet achieved the highest classification performance compared with conventional deep neural network models under all evaluation conditions. Additionally, we show that TSANet extracts reasonable features for TSA by investigating the weights of spatial filters. Our results demonstrate that TSANet has the potential to be used as an efficient end-to-end learning approach in tactile-based BCIs. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00309-4.

A deep learning anthropomorphic model observer for a detection task in PET.

BACKGROUND: Lesion detection is one of the most important clinical tasks in positron emission tomography (PET) for oncology. An anthropomorphic model observer (MO) designed to replicate human observers (HOs) in a detection task is an important tool for assessing task-based image quality. The channelized Hotelling observer (CHO) has been the most popular anthropomorphic MO. Recently, deep learning MOs (DLMOs), mostly based on convolutional neural networks (CNNs), have been investigated for various imaging modalities. However, there have been few studies on DLMOs for PET. PURPOSE: The goal of the study is to investigate whether DLMOs can predict HOs better than conventional MOs such as CHO in a two-alternative forced-choice (2AFC) detection task using PET images with real anatomical variability. METHODS: Two types of DLMOs were implemented: (1) CNN DLMO, and (2) CNN-SwinT DLMO that combines CNN and Swin Transformer (SwinT) encoders. Lesion-absent PET images were reconstructed from clinical data, and lesion-present images were reconstructed with adding simulated lesion sinogram data. Lesion-present and lesion-absent PET image pairs were labeled by eight HOs consisting of four radiologists and four image scientists in a 2AFC detection task. In total, 2268 pairs of lesion-present and lesion-absent images were used for training, 324 pairs for validation, and 324 pairs for test. CNN DLMO, CNN-SwinT DLMO, CHO with internal noise, and non-prewhitening matched filter (NPWMF) were compared in the same train-test paradigm. For comparison, six quantitative metrics including prediction accuracy, mean squared errors (MSEs) and correlation coefficients, which measure how well a MO predicts HOs, were calculated in a 9-fold cross-validation experiment. RESULTS: In terms of the accuracy and MSE metrics, CNN DLMO and CNN-SwinT DLMO showed better performance than CHO and NPWMF, and CNN-SwinT DLMO showed the best performance among the MOs evaluated. CONCLUSIONS: DLMO can predict HOs more accurately than conventional MOs such as CHO in PET lesion detection. Combining SwinT and CNN encoders can improve the DLMO prediction performance compared to using CNN only.

A genome-wide map of human genetic interactions inferred from radiation hybrid genotypes.

Using radiation hybrid genotyping data, 99% of all possible gene pairs across the mammalian genome were tested for interactions based on co-retention frequencies higher (attraction) or lower (repulsion) than chance. Gene interaction networks constructed from six independent data sets overlapped strongly. Combining the data sets resulted in a network of more than seven million interactions, almost all attractive. This network overlapped with protein-protein interaction networks on multiple measures and also confirmed the relationship between essentiality and centrality. In contrast to other biological networks, the radiation hybrid network did not show a scale-free distribution of connectivity but was Gaussian-like, suggesting a closer approach to saturation. The radiation hybrid (RH) network constitutes a platform for understanding the systems biology of the mammalian cell.

An Investigation of Stochastic Variance Reduction Algorithms for Relative Difference Penalized 3D PET Image Reconstruction.

Penalised PET image reconstruction algorithms are often accelerated during early iterations with the use of subsets. However, these methods may exhibit limit cycle behaviour at later iterations due to variations between subsets. Desirable converged images can be achieved for a subclass of these algorithms via the implementation of a relaxed step size sequence, but the heuristic selection of parameters will impact the quality of the image sequence and algorithm convergence rates. In this work, we demonstrate the adaption and application of a class of stochastic variance reduction gradient algorithms for PET image reconstruction using the relative difference penalty and numerically compare convergence performance to BSREM. The two investigated algorithms are: SAGA and SVRG. These algorithms require the retention in memory of recently computed subset gradients, which are utilised in subsequent updates. We present several numerical studies based on Monte Carlo simulated data and a patient data set for fully 3D PET acquisitions. The impact of the number of subsets, different preconditioners and step size methods on the convergence of regions of interest values within the reconstructed images is explored. We observe that when using constant preconditioning, SAGA and SVRG demonstrate reduced variations in voxel values between subsequent updates and are less reliant on step size hyper-parameter selection than BSREM reconstructions. Furthermore, SAGA and SVRG can converge significantly faster to the penalised maximum likelihood solution than BSREM, particularly in low count data.

Reduction of zygomatic fracture segment with intermaxillary fixation screw.

OBJECTIVE: Generally, a wide exposure of the buttress and separation of the zygoma fracture segments from the adjacent soft tissue and muscle are recommended for zygomatic and infraorbital rim fractures. However, increased soft tissue complications, including cheek drooping, make the extent of the dissection smaller. We propose a useful technique for zygomatic and maxillary fracture reduction with minimal dissection and less soft tissue injury. METHODS: Between 2007 and 2008, a total of 41 patients with a diagnosis of zygomatic or isolated infraorbital rim fractures were reviewed retrospectively. One or 2 intermaxillary fixation screws and 24-gauge wires were applied to the exposed fracture segments without wide dissection. By pulling the wire with changing the vector to generate reduction force opposite direction to initially applied injury, we reduced the fracture fragment easily and successfully. RESULTS: No associated complication resulting from this method was observed. CONCLUSIONS: The advantages of our technique include easily controllable reduction vector, smaller dissection extent, and less injury to operation field compared with conventional methods.

Alpha transcranial alternating current stimulation reduces depressive symptoms in people with schizophrenia and auditory hallucinations: a double-blind, randomized pilot clinical trial.

People with schizophrenia exhibit reduced alpha oscillations and frontotemporal coordination of brain activity. Alpha oscillations are associated with top-down inhibition. Reduced alpha oscillations may fail to censor spurious endogenous activity, leading to auditory hallucinations. Transcranial alternating current stimulation (tACS) at the alpha frequency was shown to enhance alpha oscillations in people with schizophrenia and may thus be a network-based treatment for auditory hallucinations. We conducted a double-blind, randomized, placebo-controlled pilot clinical trial to examine the efficacy of 10-Hz tACS in treating auditory hallucinations in people with schizophrenia. 10-Hz tACS was administered in phase at the dorsolateral prefrontal cortex and the temporoparietal junction with a return current at Cz. Patients were randomized to receive tACS or sham for five consecutive days during the treatment week (40 min/day), followed by a maintenance period, during which participants received weekly tACS (40 min/visit) or sham. tACS treatment reduced general psychopathology (p < 0.05, Cohen's d = -0.690), especially depression (p < 0.005, Cohen's d = -0.806), but not auditory hallucinations. tACS treatment increased alpha power in the target region (p < 0.05), increased the frequency of peak global functional connectivity towards 10 Hz (p < 0.05), and reduced left-right frontal functional connectivity (p < 0.005). Importantly, changes in brain functional connectivity significantly correlated with symptom improvement (p < 0.05). Daily 10 Hz-tACS increased alpha power and altered alpha-band functional connectivity. Successful target engagement reduced depression and other general psychopathology symptoms, but not auditory hallucinations. Considering existing research of 10Hz tACS as a treatment for major depressive disorder, our study demonstrates its transdiagnostic potential for treating depression.

Increasing Trend of Calretinin-Positive Mucosal Innervation from Aganglionic Zone toward Transition Zone in Hirschsprung's Disease.

INTRODUCTION: Diagnosis of very short-segment Hirschsprung's disease (vsHD) by rectal suction biopsy is challenging as its aganglionic zone (AZ) overlaps with physiologic hypoganglionic zone and calretinin-positive mucosal nerves may extend from the transition zone (TZ) into AZ. We studied whether an increasing trend/gradient of calretinin-positive mucosal nerves along the distance from AZ toward TZ aids in diagnosis of HD. MATERIALS AND METHODS: In this study, 46 rectal suction biopsies from non-HD and HD, and 15 pull-through specimens from short-segment HD were evaluated by mucosal calretinin immunostain (CI) and image processing and analysis (IPA) to measure pixel count (PC, the percentage of calretinin stained pixels in the mucosa). Consecutive longitudinal sections of proximal AZ toward distal TZ in HD pull-through specimens were utilized as a vsHD surrogate model. First, we studied variability of mucosal CI in non-HD biopsies along the distance from dentate line. Second, we determined a cutoff point of mucosal CI by IPA that separated non-HD versus HD and applied this cutoff to longitudinal sections from proximal AZ to distal TZ segments in HD pull-through specimens. Third, we studied whether an increasing trend of mucosal CI was universally observed in HD pull-through. RESULTS: Our findings included a significant variability in PC along the biopsy distance in non-HD cases. Positive mucosal CI was found in proximal AZ in 6 (43%) of 14 HD pull-through, among which 1 case lacked submucosal nerve hypertrophy in the proximal AZ. All 14 HD pull-through cases showed an increasing trend/gradient of PC from AZ toward TZ. CONCLUSION: Based on our findings, the presence or absence of mucosal CI positivity and submucosal nerve hypertrophy may not reliably diagnose vsHD in rectal suction biopsy. While we acknowledge that the density of mucosal innervation in variable contexts and anatomical locations is unknown and yet to be explored, our study suggests that an increasing trend of positive mucosal CI from AZ toward TZ by IPA might prove to be a useful tool for the diagnosis of vsHD in the future.