Prophylactic effect of pilocarpine on acute sialadenitis following radioactive iodine therapy in thyroid cancer patients.

Purpose: Our aim was to evaluate the effect of prophylactic pilocarpine on acute salivary symptoms after radioactive iodine (RAI) therapy in patients with differentiated thyroid cancer. Methods: We enrolled 88 patients (76 women and 12 men; mean age: 47 years; range: 20-74 years) with differentiated thyroid cancer who received RAI. Patients were divided into pilocarpine (51 patients) and control (37 patients) groups. Pilocarpine was given orally, at a dose of 5 mg three times a day, from 2 days before and 12 days after RAI therapy. Symptoms and signs of acute sialadenitis within 3 months of RAI therapy were recorded. Results: During the 3 months after RAI therapy, 13 of the 88 patients (14.7%) developed acute symptomatic sialadenitis (swelling or pain of salivary glands). Acute salivary symptoms were reported by 4 (7.8%) and 9 (24.3%) patients in the pilocarpine and control groups, respectively. Acute salivary symptoms were less frequent in the pilocarpine than control group (p = 0.04), but did not differ by age, sex, or RAI dose (p = 0.3357, p = 0.428, and p = 0.2792). Conclusions: Pilocarpine reduced the likelihood of acute sialadenitis after RAI therapy in patients with differentiated thyroid cancer.

The two-back task leads to activity in the left dorsolateral prefrontal cortex in schizophrenia patients with predominant negative symptoms: a fNIRS study and its implication for tDCS.

Transcranial direct current stimulation (tDCS) over left dorsolateral prefrontal cortex (DLPFC) has shown some potential as an adjunctive intervention for ameliorating negative symptoms of schizophrenia, but its efficacy requires optimization. Recently, 'functional targeting' of stimulation holds promise for advancing tDCS efficacy by coupling tDCS with a cognitive task where the target brain regions are activated by that task and further specifically polarized by tDCS.The study used 48-channel functional near infra-red spectroscopy (fNIRS) aiming to determine a cognitive task that can effectively induce a cortical activation of the left DLPFC in schizophrenia patients with predominant negative symptoms before running a tDCS trial. Sixty schizophrenia patients with predominant negative symptoms completed measures of clinical and psychosocial functioning characteristics and assessments across cognitive domains. Hemodynamic changes during n-back working memory tasks with different cognitive loads (1-back and 2-back) and verbal fluency test (VFT) were measured using fNIRS. For n-back tasks, greater signal changes were found when the task required elevated cognitive load. One sample t-test revealed that only 2-back task elicited significant activation in left DLPFC (t = 4.23, FDR-corrected p = 0.0007). During VFT, patients failed to show significant task-related activity in left DLPFC (one sample t-test, t = -0.25, FDR-corrected p > 0.05). Our study implies that 2-back task can effectively activate left DLPFC in schizophrenia patients with predominant negative symptoms. This neurophysiologically-validated task is considered highly potential to be executed in conjunction with high-definition tDCS for "functional targeting" of the left DLPFC to treat negative symptoms in a double-blind randomized sham-control trial, registered on ClinicalTrials.gov Registry (ID: NCT05582980).

SPECT/CT Radiomics for Differentiating between Enchondroma and Grade I Chondrosarcoma.

This study was performed to assess the value of SPECT/CT radiomics parameters in differentiating enchondroma and atypical cartilaginous tumors (ACTs) located in the long bones. Quantitative HDP SPECT/CT data of 49 patients with enchondromas or ACTs in the long bones were retrospectively reviewed. Patients were randomly split into training (n = 32) and test (n = 17) data, and SPECT/CT radiomics parameters were extracted. In training data, LASSO was employed for feature reduction. Selected parameters were compared with classic quantitative parameters for the prediction of diagnosis. Significant parameters from training data were again tested in the test data. A total of 12 (37.5%) and 6 (35.2%) patients were diagnosed as ACTs in training and test data, respectively. LASSO regression selected two radiomics features, zone-length non-uniformity for zone (ZLNUGLZLM) and coarseness for neighborhood grey-level difference (CoarsenessNGLDM). Multivariate analysis revealed higher ZLNUGLZLM as the only significant independent factor for the prediction of ACTs, with sensitivity and specificity of 85.0% and 58.3%, respectively, with a cut-off value of 191.26. In test data, higher ZLNUGLZLM was again associated with the diagnosis of ACTs, with sensitivity and specificity of 83.3% and 90.9%, respectively. HDP SPECT/CT radiomics may provide added value for differentiating between enchondromas and ACTs.

Robotic transcranial magnetic stimulation in the treatment of depression: a pilot study.

There has been an increasing demand for robotic coil positioning during repetitive transcranial magnetic stimulation (rTMS) treatment. Accurate coil positioning is crucial because rTMS generally targets specific brain regions for both research and clinical application with other reasons such as safety, consistency and reliability and individual variablity. Some previous studies have employed industrial robots or co-robots and showed they can more precisely stimulate the target cortical regions than traditional manual methods. In this study, we not only developed a custom-TMS robot for better TMS coil placement but also analyzed the therapeutic effects on depression. Treatment effects were evaluated by measuring regional cerebral blood flow (rCBF) using single-photon emission computed tomography and depression severity before and after rTMS for the two positioning methods. The rTMS preparation time with our robotic coil placement was reduced by 53% compared with that of the manual method. The position and orientation errors were also significantly reduced from 11.17 mm and 4.06° to 0.94 mm and 0.11°, respectively, confirming the superiority of robotic positioning. The results from clinical and neuroimaging assessments indicated comparable improvements in depression severity and rCBF in the left dorsolateral prefrontal cortex between the robotic and manual rTMS groups. A questionnaire was used to determine the patients' feelings about the robotic system, including the safety and preparation time. A high safety score indicated good acceptability of robotic rTMS at the clinical site.

Changes of regional cerebral blood flow after repeated transcranial direct current stimulation in healthy participants: a pilot study.

BACKGROUND: Transcranial direct current stimulation (tDCS) can potentially enhance brain function and cognition in healthy individuals as well as in patients with cognitive impairment. However, neural correlates of repeated tDCS remain relatively unexplored in a healthy population. PURPOSE: To assess the effects of repeated tDCS on regional cerebral blood flow (rCBF) in healthy volunteers in a pilot investigation. MATERIAL AND METHODS: Five healthy adults received bifrontal tDCS to the dorsolateral prefrontal cortex (F3-F4 montage, 1 mA intensity, 30 minutes/session, five sessions/week) over four weeks. All participants underwent brain single-photon emission computed tomography (SPECT) scans at baseline and one week after the last tDCS session. Changes in rCBF were examined using Statistical Parametric Mapping. RESULTS: Resting rCBF was significantly improved in the right superior frontal gyrus at the follow-up (P < 0.001). Adverse events were not reported and the stimulation was well-tolerated. CONCLUSION: Repeated tDCS may be effective for enhancing brain function in healthy participants. Larger sham-controlled studies should be performed to confirm our preliminary findings.

Resting-State EEG Connectivity at High-Frequency Bands and Attentional Performance Dysfunction in Stabilized Schizophrenia Patients.

Background and Objectives: Attentional dysfunction has long been viewed as one of the fundamental underlying cognitive deficits in schizophrenia. There is an urgent need to understand its neural underpinning and develop effective treatments. In the process of attention, neural oscillation has a central role in filtering information and allocating resources to either stimulus-driven or goal-relevant objects. Here, we asked if resting-state EEG connectivity correlated with attentional performance in schizophrenia patients. Materials and Methods: Resting-state EEG recordings were obtained from 72 stabilized patients with schizophrenia. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity between 84 intra-cortical current sources determined by eLORETA (exact low-resolution brain electromagnetic tomography) for five frequencies. The Conners' Continuous Performance Test-II (CPT-II) was administered for evaluating attentional performance. Linear regression with a non-parametric permutation randomization procedure was used to examine the correlations between the whole-brain functional connectivity and the CPT-II measures. Results: Greater beta-band right hemispheric fusiform gyrus (FG)-lingual gyrus (LG) functional connectivity predicted higher CPT-II variability scores (r = 0.44, p < 0.05, corrected), accounting for 19.5% of variance in the CPT-II VAR score. Greater gamma-band right hemispheric functional connectivity between the cuneus (Cu) and transverse temporal gyrus (TTG) and between Cu and the superior temporal gyrus (STG) predicted higher CPT-II hit reaction time (HRT) scores (both r = 0.50, p < 0.05, corrected), accounting for 24.6% and 25.1% of variance in the CPT-II HRT score, respectively. Greater gamma-band right hemispheric Cu-TTG functional connectivity predicted higher CPT-II HRT standard error (HRTSE) scores (r = 0.54, p < 0.05, corrected), accounting for 28.7% of variance in the CPT-II HRTSE score. Conclusions: Our study indicated that increased right hemispheric resting-state EEG functional connectivity at high frequencies was correlated with poorer focused attention in schizophrenia patients. If replicated, novel approaches to modulate these networks may yield selective, potent interventions for improving attention deficits in schizophrenia.

Online Left-Hemispheric In-Phase Frontoparietal Theta tACS Modulates Theta-Band EEG Source-Based Large-Scale Functional Network Connectivity in Patients with Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Clinical Trial.

EEG studies indicated that schizophrenia patients had increased resting-state theta-band functional connectivity, which was associated with negative symptoms. We recently published the first study showing that theta (6 Hz) transcranial alternating current stimulation (tACS) over left prefrontal and parietal cortices during a working memory task for accentuating frontoparietal theta-band synchronization (in-phase theta-tACS) reduced negative symptoms in schizophrenia patients. Here, we hypothesized that in-phase theta-tACS can modulate theta-band large-scale networks connectivity in schizophrenia patients. In this randomized, double-blind, sham-controlled trial, patients received twice-daily, 2 mA, 20-min sessions of in-phase theta-tACS for 5 consecutive weekdays (n = 18) or a sham stimulation (n = 18). Resting-state electroencephalography data were collected at baseline, end of stimulation, and at one-week follow-up. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity across 84 cortical regions at theta frequency (5-7 Hz). EEG data from 35 patients were analyzed. We found that in-phase theta-tACS significantly reduced the LPS between the posterior cingulate (PC) and the parahippocampal gyrus (PHG) in the right hemisphere only at the end of stimulation relative to sham (p = 0.0009, corrected). The reduction in right hemispheric PC-PHG LPS was significantly correlated with negative symptom improvement at the end of the stimulation (r = 0.503, p = 0.039). Our findings suggest that in-phase theta-tACS can modulate theta-band large-scale functional connectivity pertaining to negative symptoms. Considering the failure of right hemispheric PC-PHG functional connectivity to predict improvement in negative symptoms at one-week follow-up, future studies should investigate whether it can serve as a surrogate of treatment response to theta-tACS.

Brown fat activation demonstrated on FDG PET/CT predicts survival outcome.

PURPOSE: The purpose of this study was to compare the survival of patients with and without BAT activity on FDG PET/CT. METHODS: PET/CT exams from 3937 breast cancer patients were retrospectively reviewed for bilateral symmetric elongated FDG activity in the neck and chest, typical of BAT activation. A control group of age-matched (± 1 year) breast cancer patients who underwent PET/CT the same week was also enrolled for comparison. Kaplan-Meier curves of progression-free survival (PFS) and overall survival (OS) for BAT positive patients and the control group were calculated. Further sub-analysis was performed to account for the hormonal changes associated with menopause. RESULTS: 2.0% (80/3937) of the breast cancer patients who underwent PET/CT demonstrated BAT activation, and 80 additional patients were analyzed for comparison as the group without BAT activity. Mean follow-up was 76 months (range 1-225 months). There were 4 recurrences in the BAT group, compared to 12 in the control. The mean PFS for the BAT group was 127 months, which was significantly lower than the mean PFS of 180 months in the control (p = 0.047). Sub-analysis of premenopausal women again showed longer PFS for the BAT group (129 vs. 196 months, p = 0.095) while no difference was found in postmenopausal women (mean 102 vs. 135 months, p = 0.360). Presence of BAT activity was also a significant predictor variable for PFS on Cox regression. CONCLUSION: Patients with BAT activity showed longer progression-free survival than those without, emphasizing the need for further evaluation of its role in metabolism, treatment response, tumor microenvironment and long-term prognosis.

High-Frequency Transcranial Random Noise Stimulation Modulates Gamma-Band EEG Source-Based Large-Scale Functional Network Connectivity in Patients with Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Clinical Trial.

Schizophrenia is associated with increased resting-state large-scale functional network connectivity in the gamma frequency. High-frequency transcranial random noise stimulation (hf-tRNS) modulates gamma-band endogenous neural oscillations in healthy individuals through the application of low-amplitude electrical noises. Yet, it is unclear if hf-tRNS can modulate gamma-band functional connectivity in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled clinical trial to contrast hf-tRNS (N = 17) and sham stimulation (N = 18) for treating negative symptoms in 35 schizophrenia patients. Short continuous currents without neuromodulatory effects were applied in the sham group to mimic real-stimulation sensations. We used electroencephalography to investigate if a five-day, twice-daily hf-tRNS protocol modulates gamma-band (33-45 Hz) functional network connectivity in schizophrenia. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity from regions within the default mode network (DMN) and fronto-parietal network (FPN), and functional connectivity was computed using lagged phase synchronization. We found that hf-tRNS reduced gamma-band within-DMN and within-FPN connectivity at the end of stimulation relative to sham stimulation. A trend was obtained between the change in within-FPN functional connectivity from baseline to the end of stimulation and the improvement of negative symptoms at the one-month follow-up (r = -0.49, p = 0.055). Together, our findings suggest that hf-tRNS has potential as a network-level approach to modulate large-scale functional network connectivity pertaining to negative symptoms of schizophrenia.

High-Frequency Transcranial Random Noise Stimulation over the Left Prefrontal Cortex Increases Resting-State EEG Frontal Alpha Asymmetry in Patients with Schizophrenia.

Reduced left-lateralized electroencephalographic (EEG) frontal alpha asymmetry (FAA), a biomarker for the imbalance of interhemispheric frontal activity and motivational disturbances, represents a neuropathological attribute of negative symptoms of schizophrenia. Unidirectional high-frequency transcranial random noise stimulation (hf-tRNS) can increase the excitability of the cortex beneath the stimulating electrode. Yet, it is unclear if hf-tRNS can modulate electroencephalographic FAA in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled clinical trial to contrast hf-tRNS and sham stimulation for treating negative symptoms in 35 schizophrenia patients. We used electroencephalography to investigate if 10 sessions of hf-tRNS delivered twice-a-day for five consecutive weekdays would modulate electroencephalographic FAA in schizophrenia. EEG data were collected and FAA was expressed as the differences between common-log-transformed absolute power values of frontal right and left hemisphere electrodes in the alpha frequency range (8-12.5 Hz). We found that hf-tRNS significantly increased FAA during the first session of stimulation (p = 0.009) and at the 1-week follow-up (p = 0.004) relative to sham stimulation. However, FAA failed to predict and surrogate the improvement in the severity of negative symptoms with hf-tRNS intervention. Together, our findings suggest that modulating electroencephalographic frontal alpha asymmetry by using unidirectional hf-tRNS may play a key role in reducing negative symptoms in patients with schizophrenia.

Application of subject-specific helmets for the study of human visuomotor behavior using transcranial focused ultrasound: a pilot study.

BACKGROUND AND OBJECTIVE: As a novel non-invasive human brain stimulation method, transcranial focused ultrasound (tFUS) is receiving growing attention due to its superior spatial specificity and depth penetrability. Since the focal point of tFUS needs to be fixated precisely to the target brain region during stimulation, a critical issue is to identify and maintain the accurate position and orientation of the tFUS transducer relative to the subject's head. This study aims to propose the entire framework of tFUS stimulation integrating the methods previously proposed by the authors for tFUS transducer configuration optimization and a subject-specific 3D-printed helmet, and to validate this complete setup in a human behavioral neuromodulation study. METHODS: To find the optimal configuration of the tFUS transducer, a numerical method based on subject-specific tFUS beamlines simulation was used. Then, the subject-specific 3D-printed helmet has been applied to effectively secure the transducer at the estimated optimal configuration. To validate this tFUS framework, a common behavioral neuromodulation paradigm was chosen; the effect of the dorsolateral prefrontal cortex (DLPFC) stimulation on anti-saccade (AS) behavior. While human participants (n=2) were performing AS tasks, tFUS stimulations were randomly applied to the left DLPFC right after the fixation target disappeared. RESULTS: The neuromodulation result strongly suggests that the cortical stimulation using the proposed tFUS setup is effective in significantly reducing the error rates of anti-saccades (about -10 %p for S1 and -16 %p for S2), whereas no significant effect was observed on their latencies. These observed behavioral effects are consistent with the previous results based on conventional brain stimulation or lesion studies. CONCLUSIONS: The proposed subject-specific tFUS framework has been effectively used in human neuromodulation study. The result suggests that the tFUS stimulation targeted to the DLPFC can generate a neuromodulatory effect on AS behavior.

Changes of regional cerebral blood flow after deep brain stimulation in cervical dystonia.

INTRODUCTION: Cervical dystonia is considered as a network disorder affecting various brain regions in recent days. Presumably, deep brain stimulation (DBS) of the internal segment of globus pallidus (GPi) may exert therapeutic effects for cervical dystonia through modulation of the aberrant brain networks. In the present study, we investigated postoperative regional cerebral blood flow (rCBF) changes after GPi DBS using single-photon emission computed tomography (SPECT) to identify significant activity changes in several relevant brain areas of cervical dystonia patients. METHODS: A total of 9 patients with idiopathic cervical dystonia were recruited, and SPECT scans were conducted at baseline and 3 months after the bilateral GPi DBS. Voxel-wise changes of rCBF were analyzed using Statistical Parametric Mapping. Symptom severity of dystonia was measured using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) at the baseline, and 1 week, and 3 months after GPi DBS. RESULTS: At the 3-month follow-up after DBS, rCBF was increased in the left pons and right postcentral gyrus and decreased in the left middle frontal gyrus, left cerebellum, right putamen and pallidum, and left thalamus (p < 0.001). Severity of cervical dystonia assessed by TWSTRS was significantly decreased at 1-week and 3-month follow-up (p = 0.004). CONCLUSIONS: Clinical improvement of cervical dystonia after GPi DBS may be accompanied by rCBF changes in several brain areas of the cortico-basal ganglia-cerebellar network which are important for sensorimotor integration.

A Randomized, Double-Blind, Sham-Controlled Trial of Transcranial Direct Current Stimulation for the Treatment of Persistent Postural-Perceptual Dizziness (PPPD).

Background: Persistent postural-perceptual dizziness (PPPD) is a functional vestibular disorder that causes chronic dizziness interfering with daily activities. Transcranial direct current stimulation (tDCS) has reportedly improved dizziness in patients with phobic postural vertigo in an open-label trial. However, no randomized, double-blind, sham-controlled study has been conducted on its therapeutic efficacy in PPPD. Objective: This study was conducted to investigate the efficacy and safety of tDCS as an add-on treatment to pharmacotherapy in patients with PPPD. In addition, functional neuroimaging was used to identify the neural mechanisms underlying the effects of tDCS. Materials and Methods: In a randomized, double-blind, sham-controlled trial, 24 patients diagnosed with PPPD were randomized to receive active (2 mA, 20 min) or sham tDCS to the left dorsolateral prefrontal cortex (DLPFC), administered in 15 sessions over 3 weeks. The clinical measures that assess the severity of dizziness, depression, and anxiety were collected at baseline, immediate follow-up, 1-month follow-up, and 3-month follow-up. Adverse events were also observed. The effect of tDCS on regional cerebral blood flow (rCBF) was evaluated with single photon emission tomography before and after tDCS sessions. Results: For the primary outcome measure of the Dizziness Handicap Inventory (DHI) score, a significant main effect of time was found, but neither the treatment-by-time interaction effect nor the main effect of treatment was significant. For the Hamilton Depression Rating Scale (HDRS) score, there was a statistical significance for the treatment-by-time interaction effect and the main effect of time, but not for the main effect of treatment. However, the treatment-by-time interaction effect and the main effect of time on HDRS score appear to be due to one data point, an increase in depressive symptoms reported by the sham group at the 3-month follow-up. For the Activities-specific Balance Confidence (ABC) Scale and the Hamilton Anxiety Rating Scale scores, there were no significant main effects of time, treatment, and treatment-by-time interaction. In a comparison with the changes in rCBF between the groups, a significant treatment-by-time interaction effect was found in the right superior temporal and left hippocampus, controlling for age and sex. Conclusion: Active tDCS was not found to be significantly more efficacious than sham tDCS on dizziness symptoms in patients with PPPD. It is conceivable that tDCS targeting the DLPFC may not be an optimal treatment option for reducing dizziness symptoms in PPPD. Our findings encourage further investigation on the effects of tDCS in PPPD, which considers different stimulation protocols in terms of stimulation site or the number of sessions. Clinical Trial Registration: cris.nih.go.kr, identifier: KCT0005068.

Regional Cerebral Blood Flow Correlates of Neuropsychiatric Symptom Domains in Early Alzheimer's Disease.

Although various neuropsychiatric symptoms are frequently accompanied with Alzheimer's disease (AD) and pose a substantial burden to both patients and caregivers, their neurobiological underpinnings remain unclear. This study investigated associations between regional cerebral blood flow (rCBF) and neuropsychiatric symptom domains in early AD. A total of 59 patients with early AD underwent brain technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) scans. Neuropsychiatric symptoms were assessed by the Neuropsychiatric Inventory and clustered into the affective, apathy, hyperactivity, and psychotic domains. A voxel-wise multiple regression analysis was performed with four domain scores as independent variables and age, sex, and Mini-Mental State Examination scores as covariates. The affective domain score was negatively correlated with rCBF in the prefrontal cortex, thalamus, and caudate. The apathy domain score showed inverse correlations with rCBF in the prefrontal and pre/postcentral gyri and midbrain. Patients with higher hyperactivity domain scores had increased rCBF in the prefrontal and temporal lobes. The psychotic symptom domain was positively correlated with rCBF in the cuneus and negatively associated with rCBF in the prefrontal, cingulate, and occipital regions and putamen. The score of each neuropsychiatric symptom domain showed the differential correlates of brain perfusion, while altered rCBF in the prefrontal cortex was found in all domains. Although preliminary, our results may suggest common and distinct patterns of rCBF underlying neuropsychiatric symptoms in early AD. Further studies with larger samples and control participants are warranted to confirm these findings.

Short-Term Efficacy of Transcranial Focused Ultrasound to the Hippocampus in Alzheimer's Disease: A Preliminary Study.

Preclinical studies have suggested that low-intensity transcranial focused ultrasound (tFUS) may have therapeutic potential for Alzheimer's disease (AD) by opening the blood-brain barrier (BBB), reducing amyloid pathology, and improving cognition. This study investigated the effects of tFUS on BBB opening, regional cerebral metabolic rate of glucose (rCMRglu), and cognitive function in AD patients. Eight patients with AD received image-guided tFUS to the right hippocampus immediately after intravenous injection of microbubble ultrasound contrast agents. Patients completed magnetic resonance imaging (MRI), 18F-fluoro-2-deoxyglucose positron emission tomography (PET), and cognitive assessments before and after the sonication. No evidence of transient BBB opening was found on T1 dynamic contrast-enhanced MRI. However, immediate recall (p = 0.03) and recognition memory (p = 0.02) were significantly improved on the verbal learning test. PET image analysis demonstrated increased rCMRglu in the right hippocampus (p = 0.001). In addition, increases of hippocampal rCMRglu were correlated with improvement in recognition memory (Spearman's ρ = 0.77, p = 0.02). No adverse event was observed. Our results suggest that tFUS to the hippocampus of AD patients may improve rCMRglu of the target area and memory in the short term, even without BBB opening. Further larger sham-controlled trials with loger follow-up are warranted to evaluate the efficacy and safety of tFUS in patients with AD.

Acoustic Simulation for Transcranial Focused Ultrasound Using GAN-Based Synthetic CT.

Transcranial focused ultrasound (tFUS) is a promising non-invasive technique for treating neurological and psychiatric disorders. One of the challenges for tFUS is the disruption of wave propagation through the skull. Consequently, despite the risks associated with exposure to ionizing radiation, computed tomography (CT) is required to estimate the acoustic transmission through the skull. This study aims to generate synthetic CT (sCT) from T1-weighted magnetic resonance imaging (MRI) and investigate its applicability to tFUS acoustic simulation. We trained a 3D conditional generative adversarial network (3D-cGAN) with 15 subjects. We then assessed image quality with 15 test subjects: mean absolute error (MAE) = 85.72±9.50 HU (head) and 280.25±24.02 HU (skull), dice coefficient similarity (DSC) = 0.88±0.02 (skull). In terms of skull density ratio (SDR) and skull thickness (ST), no significant difference was found between sCT and real CT (rCT). When the acoustic simulation results of rCT and sCT were compared, the intracranial peak acoustic pressure ratio was found to be less than 4%, and the distance between focal points less than 1 mm.

Regional Cerebral Blood Flow Abnormalities in Neurosyphilis: A Pilot SPECT Study.

Objective: Clinical and radiological findings on neurosyphilis are fairly non-specific and there is a paucity of functional neuroimaging studies on neurosyphilis other than case reports and case series. The purpose of this study was to investigate brain perfusion abnormalities in patients with neurosyphilis. Methods: Four HIV-negative neurosyphilis patients and 4 healthy controls underwent clinical evaluation, brain technetium-99m ethyl cysteinate dimer (99mTc-ECD) single-photon emission computed tomography (SPECT) imaging, and neuropsychological assessments which included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Clinical Dementia Rating-Sum of Boxes (CDR-SOB), and Global Deterioration Scale (GDS). Voxel-wise differences in regional cerebral blood flow were compared between the two groups. Results: Neuropsychological test results indicated cognitive impairment in all patients. SPECT analysis revealed multifocal hypoperfusion predominantly in the frontal, insular, and posterior cingulate regions in neurosyphilis patients compared with healthy controls (family-wise error corrected p < 0.05). Conclusions: Together with previous findings, our results suggest that the hypoperfusion in the frontal, insular, and posterior cingulate regions may reflect cognitive impairments observed in neurosyphilis patients. Further studies with larger samples are needed to confirm our findings.

Online Left-Hemispheric In-Phase Frontoparietal Theta tACS for the Treatment of Negative Symptoms of Schizophrenia.

Negative symptoms represent an unmet need for schizophrenia treatment. The effect of theta frequency transcranial alternating current stimulation (theta-tACS) applied during working memory (WM) tasks on negative symptoms has not been demonstrated as of yet. We conducted a randomized, double-blind, sham-controlled trial of 36 stabilized schizophrenia patients, randomized to receive either twice daily, 6 Hz 2 mA, 20 min sessions of in-phase frontoparietal tACS or sham for five consecutive weekdays. Participants were concurrently engaged in WM tasks during stimulation. The primary outcome measure was the change over time in the Positive and Negative Syndrome Scale (PANSS) negative subscale score measured from baseline through to the 1-month follow-up. Secondary outcome measures were other symptom clusters, neurocognitive performance, and relevant outcomes. The intention-to-treat analysis demonstrated greater reductions in PANSS negative subscale scores at the end of stimulation in the active (-13.84%) than the sham (-3.78%) condition, with a large effect size (Cohen's d = 0.96, p = 0.006). The positive effect endured for at least one month. Theta-tACS also showed efficacies for cognitive symptoms, WM capacity, and psychosocial functions. Online theta-tACS offers a novel approach to modulate frontoparietal networks to treat negative symptoms of schizophrenia. The promising results require large-scale replication studies in patients with predominantly negative symptoms.

Hippocampal subregional alterations and verbal fluency in the early stage of type 2 diabetes mellitus.

Growing evidence indicates that type 2 diabetes mellitus (T2DM)-related cognitive dysfunction may develop in the early stage of the disease and is often accompanied by hippocampal structural alterations. In the current study, we investigated volume and shape alterations of the hippocampus at a subregional level in patients with T2DM. With the use of high-resolution brain structural images that were obtained from 30 T2DM patients with less than 5 years of disease duration and 30 healthy individuals, volumetric and shape analyses were performed. We also assessed the relationship between T2DM-related hippocampal structural alterations and performance on verbal fluency. In volumetric analysis, total hippocampal volume was smaller in the T2DM group, relative to the control group. At a subregional level, T2DM patients showed significant inward deformation and volume reduction of the right dentate gyrus and cornu ammonis 2/3 subregions as compared with healthy individuals. In particular, T2DM patients with lower performance on verbal fluency had smaller right dentate gyrus volumes relative to those with higher performance. These findings suggest that the hippocampus may undergo atrophy at a subregional level even in the early stage of T2DM, and this subregion-specific atrophy may be associated with reduced performance on verbal fluency.

A Review of Neuroimaging Studies in Persistent Postural-Perceptual Dizziness (PPPD).

Persistent postural-perceptual dizziness (PPPD) is a functional vestibular disease characterized by persistent dizziness, unsteadiness, and/or non-spinning vertigo, and is the most common vestibular syndrome in young adults. A stiffened postural control strategy, shift to reliance on visual over vestibular information, and hypervigilance to the environment have been suggested as possible pathophysiological mechanisms of PPPD. However, the exact mechanisms remain unclear. Recently, neuroimaging studies using magnetic resonance imaging and single photon emission computed tomography have provided pivotal insights into the pathophysiology of PPPD. The aim of this review was to evaluate and summarize the existing data on neuroimaging studies in PPPD. In summary, these studies fairly consistently reported decreased brain structure, function, and connectivity among the areas involved in multisensory vestibular processing and spatial cognition, and increased function and connectivity in the visual processing areas in patients with PPPD. The detected brain changes might reflect maladaptive and compensatory mechanisms including dysfunctional integration of multisensory vestibular information and visual dependence. Notably, various factors including personality traits (i.e., neuroticism), psychiatric comorbidities (i.e., anxiety and depression), and triggering factors (i.e., peripheral vestibular lesions) seem to modulate brain functional activity and connectivity patterns, possibly accounting for some differences across the results. Future studies should carefully control for these confounding effects in order to draw firm conclusions.