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.

Prefrontal White Matter Abnormalities Associated With Pain Catastrophizing in Patients With Complex Regional Pain Syndrome.

OBJECTIVE: To investigate altered prefrontal white matter integrity in complex regional pain syndrome (CRPS) and its relation with the degree of pain catastrophizing. DESIGN: Cross-sectional study. SETTING: University hospital. PARTICIPANTS: Twenty-one CRPS patients and 49 patients without CRPS (N=70). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The fractional anisotropy values within the prefrontal regions reflecting the structural integrity of white matter were measured in CRPS patients and patients without CRPS using diffusion tensor imaging. The degree of pain catastrophizing was also evaluated in CRPS patients. RESULTS: The structural integrity of the prefrontal white matter was lower in CRPS patients than in patients without CRPS (P=.03). In addition, lower structural integrity in the prefrontal cortex was correlated with a higher degree of pain catastrophizing among CRPS patients (r= -0.54, P=.01). CONCLUSIONS: Our findings suggest that pain catastrophizing, which is frequently reported in patients with CRPS, may be associated with the dysfunction of the prefrontal white matter.

Possible neuroprotective effects of rasagiline in Alzheimer's disease: a SPECT study.

BACKGROUND: The current lack of effective treatments for Alzheimer's disease (AD) and the rapidly increasing burden of the disease highlight the urgent need to find new treatments. Despite accumulating evidence of the beneficial effects of rasagiline in neurodegenerative diseases such as Parkinson's disease, the effects of rasagiline on the brains of patients with AD have not been elucidated. PURPOSE: To examine the effects of rasagiline on regional cerebral flow (rCBF) in patients with AD using single photon emission computed tomography (SPECT). MATERIAL AND METHODS: Among 22 patients with AD, 11 patients received adjunctive rasagiline at 1 mg/day in conjunction with acetylcholinesterase inhibitors (AChEI); 11 patients were only treated with AChEI for about 1.6 years. All patients underwent brain technetium-99m hexamethylpropylene amine oxime SPECT scans and clinical assessments at baseline and follow-up visits. Annual percent changes in rCBF were compared between the groups in a voxel-wise manner. RESULTS: SPECT analysis revealed that the rasagiline-treated group showed more increased rCBF in the cingulate gyrus, inferior frontal gyrus, putamen, and thalamus compared to the comparison group (P < 0.005). CONCLUSION: We demonstrated that adjunctive rasagiline treatment may have beneficial effects on brain perfusion in patients with AD, suggesting potential neuroprotective effects.

Alterations in structural rich-club connectivity of the precuneus are associated with depressive symptoms among individuals with subjective memory complaints.

The association between subjective memory complaints (SMCs) and depressive symptoms has been widely reported and both have been regarded as risk factors for dementia, such as Alzheimer's disease (AD). Although SMCs arise as early as in middle age, the exact neural correlates of comorbid depressive symptoms among individuals who are middle-aged and with SMCs have not yet been well investigated. Because rich-club organization of the brain plays a key role in the pathophysiology of various neuropsychiatric disorders, the investigation of rich club organization may provide insight regarding the neurobiological mechanisms of depressive symptoms in SMCs. In the current study, we compared the rich-club organization in the structural brain connectivity between individuals who have SMCs along with depressive symptoms (SMCD) and individuals with SMCs but without depressive symptoms (SMCO). A total of 53 individuals with SMCD and 91 individuals with SMCO participated in the study. For all participants, high-resolution, T1-weighted images and diffusion tensor images were obtained, and the network analysis was performed. Individuals with SMCD had lower connectivity strength between the precuneus and other rich-club nodes than those with SMCO, which was significant after adjusting for potential confounders. Our findings suggest that disruptions of rich-club connectivity strength of the precuenus are associated with depressive symptoms in middle-aged individuals with SMCs. Given that the precuneus is one of the commonly affected regions in the early stages of AD, our findings may imply that the concomitant depressive symptoms in middle-aged individuals with SMCs could reflect structural alterations related to AD.

Correction to: Cerebral perfusion abnormalities in patients with persistent postural-perceptual dizziness (PPPD): a SPECT study.

The authors inadvertently forgot to provide the following funding information in the original publication: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (2018R1A6A3A11041118).

Cerebral perfusion abnormalities in patients with persistent postural-perceptual dizziness (PPPD): a SPECT study.

Persistent postural-perceptual dizziness (PPPD) is a recently defined syndrome with chronic dizziness interrupting daily life. Although the high levels of anxiety and functional changes in postural control strategy and multi-sensory information processing and integration may be underlying the pathophysiology, its neural mechanisms are poorly understood. The aim of this study was to examine the regional cerebral blood flow (rCBF) in patients with PPPD using single photon emission computed tomography (SPECT). A total of 25 patients with PPPD and 25 healthy controls participated in the study. All participants underwent brain SPECT and the patients completed the Dizziness Handicap Inventory. SPECT images were compared between the groups, and the correlation of rCBF and disease severity/duration was assessed in patients. Compared with controls, PPPD patients showed a significantly decreased rCBF in the insula and frontal lobe, mainly in the left posterior insula, bilateral superior frontal gyrus, right inferior frontal gyrus, right precentral gyrus, and left medial orbital gyrus. Additionally, PPPD patients showed a significant rCBF increase in the bilateral cerebellum compared with controls. The results of our study suggest that the altered rCBF in the insular, frontal, and cerebellar cortices might be reflecting the process of maladaptation and the compensatory responses for the changes in PPPD.

Prediction of postoperative lung function in lung cancer patients using perfusion scintigraphy.

BACKGROUND: Predicting postoperative lung function is critical in lung cancer patients. Perfusion scintigraphy has been used to estimate postoperative function after lung resection. PURPOSE: To evaluate the usefulness of the posterior oblique method in relation to other conventional processing methods for predicting postoperative lung function using lung perfusion scintigraphy. MATERIAL AND METHODS: Fifty-five patients with non-small-cell lung cancer who underwent lobectomy were enrolled. Forced expiratory volume in 1 s (FEV1) values were obtained from preoperative and postoperative pulmonary function tests. After performing lung perfusion scintigraphy, predicted FEV1 values were calculated using the segment, conventional, posterior, and posterior oblique methods. Postoperative FEV1 values were compared with predicted FEV1 values. RESULTS: The mean value of the preoperative FEV1 was 2.29 L and that of the postoperative FEV1 was 1.89 L. The mean values of the predicted postoperative FEV1 values for the segment, conventional, posterior, and posterior oblique were 1.83 L, 1.94 L, 1.88 L, and 1.89 L, respectively. Between the observed and predicted FEV1 values, there was a strong correlation without significant difference except for conventional method. Bland-Altman analysis showed that segment and posterior methods underestimated the FEV1, whereas conventional and posterior oblique methods overestimated the FEV1. CONCLUSION: Predictions with each processing method of lung perfusion scintigraphy showed nearly similar results to the actual postoperative lung function. The posterior oblique method of lung perfusion scintigraphy showed a very small difference to such an extent as to be equal to the observed FEV1, implying that this method may be applied for predicting postoperative lung function in lung cancer patients.

Usefulness of feature analysis of breast-specific gamma imaging for predicting malignancy.

OBJECTIVES: The purpose of this study was to investigate which feature of the breast-specific gamma imaging (BSGI) uptake in women who were recently diagnosed with breast cancer was associated with malignancy. METHODS: Data on 231 newly diagnosed breast cancer patients who underwent preoperative BSGI were retrospectively reviewed. Feature analysis was done by classifying BSGI uptake into mass, non-mass, or focus/foci. Descriptors for mass, non-mass, or focus/foci were shape, distribution, number, and intensity. BSGI features of known malignancies and lesions that were additionally found by BSGI were correlated with mammographic breast density, histology, hormonal status, and clinical follow-up data obtained over at least 2 years. RESULTS: Among 372 breast lesions from 231 patients, 241 malignancies had been pathologically confirmed prior to BSGI and 131 additional lesions were found on BSGI. Irregular shape was more predictive of malignancy than oval shape (p=0.004) in mass uptake. Linear/ductal distribution was more predictive of malignancy than focal, regional, and segmental distribution (p<0.05) in non-mass uptake. Mammographic breast density was not associated with BSGI features. The lesion to normal ratio (LNR) was higher in the postmenopausal patients than that in the premenopausal patients (p=0.003). CONCLUSIONS: The feature analysis of radiotracer uptake in BSGI is useful in predicting whether breast lesions are malignant or benign. KEY POINTS: • The feature analysis of BSGI uptake is useful in predicting malignancy. • Irregular shape was predictive of malignancy in mass uptake. • Linear/ductal distribution was predictive of malignancy in non-mass uptake.

Validation of the Athens Insomnia Scale for screening insomnia in South Korean firefighters and rescue workers.

PURPOSE: Sleep problems are a major cause of occupational stress in firefighters and rescue workers. We evaluated the psychometric properties of the Athens Insomnia Scale (AIS) among South Korean firefighters and rescue workers. METHODS: Structured clinical interviews and self-report questionnaires were administered to 221 firefighters and rescue workers. The Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Short-Form 36-item Health Survey (SF36), and Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) were used to examine convergent and divergent validity. Test-retest reliability was calculated from a subsample (n = 24). Analysis of internal consistency, factor analysis, and receiver operator characteristic curve analysis were conducted. RESULTS: Cronbach's alpha was 0.88. The mean item-total correlation coefficient was 0.73. The test-retest reliability was excellent (ICC = 0.94). Significant correlations of the AIS with the PSQI, ISI, ESS, and SF36 confirmed convergent validity. Nonsignificant associations of the AIS with the AUDIT-C and socioeconomic status showed divergent validity. Factor analysis revealed a one-factor structure. For groups with different symptom severity, group-specific cutoff scores which may improve positive predictive values were suggested. CONCLUSIONS: The AIS may be a useful tool with good reliability and validity for screening insomnia symptoms in firefighters and rescue workers.

Validation of the Korean version of the Connor-Davidson Resilience Scale-2 in firefighters and rescue workers.

OBJECTIVE: Resilience has been considered as a protective factor against stress. Evaluating resilience in firefighters and rescue workers, who are frequently exposed to traumatic events, is important and relevant. This study examined the psychometric properties of the Korean version of the Connor-Davidson Resilience Scale-2 (CD-RISC2). METHODS: Two-hundred twenty-two current professional firefighters and rescue workers were assessed by standardized, semi-structured clinical interviews and self-report questionnaires. Internal consistency, correlation with the CD-RISC, convergent validity, divergent validity, and predictive validity of posttraumatic stress disorder (PTSD) symptom severity were analyzed. RESULTS: The CD-RISC2 demonstrated good internal consistency (α=0.75), item-total correlation (r=0.89-0.90), and convergent and divergent validity. The total score of the CD-RISC2 showed significant correlations with the subtotal of the remaining 23 CD-RISC items (r=0.77, p<0.001) and with the score of each CD-RISC item (r=0.15-0.66, all p<0.05). The magnitude of the relationship between the number of traumatic experiences and PTSD symptom severity was greater in the low resilience group than in the high resilience group (p for interaction=0.002). The likelihood-ratio test confirmed that the model predicting PTSD symptom severity based on the CD-RISC2 total score was not improved by the inclusion of subtotal scores of the remaining 23 CD-RISC items (χ(2)=0.31, p=0.58). CONCLUSIONS: These results suggest that the CD-RISC2 would be a valuable tool in evaluating resilience quickly and efficiently in firefighters and rescue workers.

Biopsychosocial factors of gaming disorder: a systematic review employing screening tools with well-defined psychometric properties.

Background and aims: Considering the growing number of gamers worldwide and increasing public concerns regarding the negative consequences of problematic gaming, the aim of the present systematic review was to provide a comprehensive overview of gaming disorder (GD) by identifying empirical studies that investigate biological, psychological, and social factors of GD using screening tools with well-defined psychometric properties. Materials and methods: A systematic literature search was conducted through PsycINFO, PubMed, RISS, and KISS, and papers published up to January 2022 were included. Studies were screened based on the GD diagnostic tool usage, and only five scales with well-established psychometric properties were included. A total of 93 studies were included in the synthesis, and the results were classified into three groups based on biological, psychological, and social factors. Results: Biological factors (n = 8) included reward, self-concept, brain structure, and functional connectivity. Psychological factors (n = 67) included psychiatric symptoms, psychological health, emotion regulation, personality traits, and other dimensions. Social factors (n = 29) included family, social interaction, culture, school, and social support. Discussion: When the excess amount of assessment tools with varying psychometric properties were controlled for, mixed results were observed with regards to impulsivity, social relations, and family-related factors, and some domains suffered from a lack of study results to confirm any relevant patterns. Conclusion: More longitudinal and neurobiological studies, consensus on a diagnostic tool with well-defined psychometric properties, and an in-depth understanding of gaming-related factors should be established to settle the debate regarding psychometric weaknesses of the current diagnostic system and for GD to gain greater legitimacy in the field of behavioral addiction.

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.

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.

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.

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.

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.

Prognostic value of pretreatment F-18 fluorodeoxyglucose PET/CT in colorectal cancer with unresectable metastasis.

PURPOSE: The aim of the study was to assess the prognostic value of pretreatment PET/computed tomography (CT) scans in colorectal cancer (CRC) patients with unresectable metastasis. MATERIALS AND METHODS: We retrospectively reviewed the pretreatment PET/CT images of 82 CRC patients with unresectable metastasis and their medical records. On PET/CT images, maximum standardized uptake value (SUVmax) of primary tumor, highest SUVmax of metastatic tumors and number of metastatic organs were identified. The patients were further divided into single and multiple organ metastases groups according to the extent of disease. Survival analysis was performed with the clinical variables and metabolic parameters from PET/CT. RESULTS: In a total of 82 patients, the age of patients, highest SUVmax of metastatic tumors and number of metastatic organs were independent prognostic factors for overall survival (OS) (all P < 0.05), whereas the SUVmax of primary tumor was not. On multivariate analysis, only the SUVmax of metastatic tumor was a significant prognostic factor in the single organ metastasis group (P = 0.047), whereas the age and highest SUVmax of metastatic tumors were independent prognostic factors in the multiple organ metastases group (all P < 0.05). CONCLUSION: The highest SUVmax of metastatic tumors was an independent prognostic factor for OS in CRC patients with unresectable metastasis.

A pilot clinical study of low-intensity transcranial focused ultrasound in Alzheimer's disease.

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.

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.