EEG slowing during REM sleep in older adults with subjective cognitive impairment and mild cognitive impairment.

STUDY OBJECTIVES: In older adults with Alzheimer's disease, slowing of electroencephalographic (EEG) activity during REM sleep has been observed. Few studies have examined EEG slowing during REM in those with mild cognitive impairment (MCI) and none have examined its relationship with cognition in this at-risk population. METHODS: 210 older adults (mean age = 67.0, sd = 8.2 years) underwent comprehensive neuropsychological, medical, and psychiatric assessment and overnight polysomnography. Participants were classified as subjective cognitive impairment (SCI; n=75), non-amnestic MCI (naMCI, n=85), and amnestic MCI (aMCI, n=50). REM EEG slowing was defined as (delta + theta) / (alpha + sigma + beta) power and calculated for frontal, central, parietal, and occipital regions. Analysis of variance compared REM EEG slowing between groups. Correlations between REM EEG slowing and cognition, including learning and memory, visuospatial and executive functions, were examined within each subgroup. RESULTS: The aMCI group had significantly greater REM EEG slowing in the parietal and occipital regions compared to the naMCI and SCI groups (partial η2 = 0.06, p<0.05 and 0.06, p<0.05, respectively), and greater EEG slowing in the central region compared to SCI group (partial η2 = 0.03, p<0.05). Greater REM EEG slowing in parietal (r = -0.49) and occipital regions (r = -0.38 (O1/M2) and -0.33 (O2/M1) were associated with poorer visuospatial performance in naMCI. CONCLUSION: REM EEG slowing may differentiate older adults with memory impairment from those without. Longitudinal studies are now warranted to examine the prognostic utility of REM EEG slowing for cognitive and dementia trajectories.

Region-specific changes in brain activity and memory after continuous positive airway pressure therapy in obstructive sleep apnea: a pilot high-density electroencephalography study.

STUDY OBJECTIVES: Limited channel electroencephalography (EEG) investigations in obstructive sleep apnea (OSA) have revealed deficits in slow wave activity (SWA) and spindles during sleep and increased EEG slowing during resting wakefulness. High-density EEG (Hd-EEG) has also detected local parietal deficits in SWA (delta power) during NREM. It is unclear whether effective continuous positive airway pressure (CPAP) treatment reverses regional SWA deficits, and other regional sleep and wake EEG abnormalities, and whether any recovery relates to improved overnight memory consolidation. METHODS: A clinical sample of men with moderate-severe OSA underwent sleep and resting wake recordings with 256-channel Hd-EEG before and after 3 months of CPAP. Declarative and procedural memory tasks were administered pre- and post-sleep. Topographical spectral power maps and differences between baseline and treatment were compared using t-tests and statistical nonparametric mapping (SnPM). RESULTS: In 11 compliant CPAP users (5.2 ±â€…1.1 hours/night), total sleep time did not differ after CPAP but N1 and N2 sleep were lower and N3 was higher. Centro-parietal gamma power during N3 increased and fronto-central slow spindle activity during N2 decreased (SnPM < 0.05). No other significant differences in EEG power were observed. When averaged specifically within the parietal region, N3 delta power increased after CPAP (p = 0.0029) and was correlated with the change in overnight procedural memory consolidation (rho = 0.79, p = 0.03). During resting wakefulness, there were trends for reduced delta and theta power. CONCLUSIONS: Effective CPAP treatment of OSA may correct regional EEG abnormalities, and regional recovery of SWA may relate to procedural memory improvements in the short term.

Evaluation of children's cognitive load in processing and storage of their spatial working memory.

Working memory performance affects children's learning. This study examined objective (task performance), subjective (self-report), and physiological (pupil dilation) cognitive load (CL) while children completed a spatial working memory complex span task. Frist, 80 Taiwanese 11-year-olds (40 boys) who participated in Experiment 1 confirmed the suitability of the materials. Then, 72 Taiwanese 11-year-olds (35 boys) were assigned to high and low complexity groups to participate in Experiment 2 to test the study hypothesis. Children had to recall at the end of a dual-task list and answer two questions regarding the difficulty and mental effort involved in processing and storage. Their pupil diameters were recorded using an eye-tracker. Two-way mixed ANOVA found that the processing requirements and memory load reduced storage and aggravated the subjective CL of storage; the subjective CL of processing was higher under highly complex conditions. Stepwise regression analysis indicated that subjective CL of processing predicted memory performance in low CL conditions, and physiological CL of processing predicted it in high CL conditions.

Improvements in cognitive function and quantitative sleep electroencephalogram in obstructive sleep apnea after six months of continuous positive airway pressure treatment.

STUDY OBJECTIVES: Untreated obstructive sleep apnea (OSA) is associated with cognitive deficits and altered brain electrophysiology. We evaluated the effect of continuous positive airway pressure (CPAP) treatment on quantitative sleep electroencephalogram (EEG) measures and cognitive function. METHODS: We studied 167 patients with OSA (age 50 ±â€…13, AHI 35.0 ±â€…26.8) before and after 6 months of CPAP. Cognitive tests assessed working memory, sustained attention, visuospatial scanning, and executive function. All participants underwent overnight polysomnography at baseline and after CPAP. Power spectral analysis was performed on EEG data (C3-M2) in a sub-set of 90 participants. Relative delta EEG power and sigma power in NREM and EEG slowing in REM were calculated. Spindle densities (events/min) in N2 were also derived using automated spindle event detection. All outcomes were analysed as change from baseline. RESULTS: Cognitive function across all cognitive domains improved after six months of CPAP. In our sub-set, increased relative delta power (p < .0001) and reduced sigma power (p = .001) during NREM were observed after the 6-month treatment period. Overall, fast and slow sleep spindle densities during N2 were increased after treatment. CONCLUSIONS: Cognitive performance was improved and sleep EEG features were enhanced when assessing the effects of CPAP. These findings suggest the reversibility of cognitive deficits and altered brain electrophysiology observed in untreated OSA following six months of treatment.

Insomnia subtypes characterised by objective sleep duration and NREM spectral power and the effect of acute sleep restriction: an exploratory analysis.

Insomnia disorder (ID) is a heterogeneous disorder with proposed subtypes based on objective sleep duration. We speculated that insomnia subtyping with additional power spectral analysis and measurement of response to acute sleep restriction may be informative in overall assessment of ID. To explore alternative classifications of ID subtypes, insomnia patients (n = 99) underwent two consecutive overnight sleep studies: (i) habitual sleep opportunity (polysomnography, PSG) and, (ii) two hours less sleep opportunity (electroencephalography, EEG), with the first night compared to healthy controls (n = 25). ID subtypes were derived from data-driven classification of PSG, EEG spectral power and interhemispheric EEG asymmetry index. Three insomnia subtypes with different sleep duration and NREM spectral power were identified. One subtype (n = 26) had shorter sleep duration and lower NREM delta power than healthy controls (short-sleep delta-deficient; SSDD), the second subtype (n = 51) had normal sleep duration but lower NREM delta power than healthy controls (normal-sleep delta-deficient; NSDD) and a third subtype showed (n = 22) no difference in sleep duration or delta power from healthy controls (normal neurophysiological sleep; NNS). Acute sleep restriction improved multiple objective sleep measures across all insomnia subtypes including increased delta power in SSDD and NSDD, and improvements in subjective sleep quality for SSDD (p = 0.03), with a trend observed for NSDD (p = 0.057). These exploratory results suggest evidence of novel neurophysiological insomnia subtypes that may inform sleep state misperception in ID and with further research, may provide pathways for personalised care.

Single-channel EEG based insomnia detection with domain adaptation.

Insomnia is one of the most common sleep disorders which can dramatically impair life quality and negatively affect an individual's physical and mental health. Recently, various deep learning based methods have been proposed for automatic and objective insomnia detection, owing to the great success of deep learning techniques. However, due to the scarcity of public insomnia data, a deep learning model trained on a dataset with a small number of insomnia subjects may compromise the generalization capacity of the model and eventually limit the performance of insomnia detection. Meanwhile, there have been a number of public EEG datasets collected from a large number of healthy subjects for various sleep research tasks such as sleep staging. Therefore, to utilize such abundant EEG datasets for addressing the data scarcity issue in insomnia detection, in this paper we propose a domain adaptation based model to better extract insomnia related features of the target domain by leveraging stage annotations from the source domain. For each domain, two pairs of common encoder and private encoder are firstly trained to extract sleep related features and sleep irrelevant features, respectively. In order to further discriminate source domain and target domain, a domain classifier is introduced. Then, the common encoder of the target domain will be used together with the Long Short Term Memory (LSTM) network for insomnia detection. To the best of our knowledge, this is the first deep learning based domain adaptation model using single channel raw EEG signals to detect insomnia at subject level. We use the Montreal Archive of Sleep Studies (MASS) dataset which contains only healthy subjects as source domain and two datasets which contain both healthy and insomnia subjects as target domain to validate our model's generalizability. Experimental results on the two target domain datasets (a public one and an in-house one) demonstrate that our model generalizes well on two target domain datasets with different sampling rates. In particular, our proposed method is able to improve insomnia detection performance from 50.0% to 90.9% and 66.7%-79.2% in terms of accuracy on the two target domain datasets, respectively.

Spatial configuration processing in visual word form perception and reading abilities in Chinese.

The analysis of spatial relations among components of a character is important in identifying visual word forms. We investigated such spatial configuration processing for Chinese characters in dyslexic children (aged 9-12 years) and two groups of typically developing children, matched according to chronological age or reading level. In this study, we used real characters and noncharacters to manipulate the spatial configuration between character components while preserving their local features. Both characters were displayed either in an upright or inverted position. Participants were asked to quickly determine whether the two presented stimuli were identical. A significant interaction between character type and character orientation showed children's matching performance was better in upright real characters than in the inverted version, but such effect was absent in noncharacters. This indicated that regardless of reading skills, children developed the ability to use local configuration information to visually identify words. Dyslexic children performed poorly in both real-character and noncharacter conditions. Furthermore, compared with control groups, dyslexic children performed worse in real-character conditions, which were close to the noncharacter performance of other groups. This reflected an impairment of global visual word-form processing (i.e., spatial configuration between components) in dyslexia.

How different is the care of terminal pancreatic cancer patients in inpatient palliative care units and acute hospital wards? A nationwide population-based study.

BACKGROUND: Inpatient palliative care is important for patients with terminal pancreatic cancer. However, the differences between inpatient palliative care and acute hospital care for inpatients with pancreatic cancer have not been explored in a population-based study. METHODS: This population-based nationwide study was conducted using data from the Taiwan National Health Insurance database to analyze the differences between inpatient palliative care and acute hospital care for inpatients with pancreatic cancer. We identified 854 patients with terminal pancreatic cancer, who had received in-hospital end-of-life care between January 2003 and December 2006. These patients were then sub-divided and matched 1:1 (using propensity score matching) according to whether they received inpatient palliative care (n = 276) or acute hospital care (n = 276). These groups were subsequently compared to evaluate any differences in the use of aggressive procedures, prescribed medications, and medical costs. RESULTS: Inpatient palliative care was typically provided by family physicians (39%) and oncologists (25%), while acute hospital care was typically provided by oncologists (29%) and gastroenterologists (24%). The inpatient palliative care group used natural opium alkaloids significantly more frequently than the acute hospital care group (84.4% vs. 56.5%, respectively; P < 0.001). The inpatient palliative care group also had shorter hospital stays (10.6 ± 11.1 days vs. 20.6 ± 16.3 days, respectively; P < 0.001), fewer aggressive procedures, and lower medical costs (both, P < 0.005). CONCLUSIONS: Compared to patients in acute hospital wards, patients with pancreatic cancer in inpatient palliative care units received more frequent pain control treatments, underwent fewer aggressive procedures, and incurred lower medical costs. Therefore, inpatient palliative care should be considered a viable option for patients with terminal pancreatic cancer.

Cytokines are associated with postembolization fever and survival in hepatocellular carcinoma patients receiving transcatheter arterial chemoembolization.

OBJECTIVE: Cytokines play important roles in angiogenesis, inflammation, and cell growth. The present study aimed to investigate the correlation between cytokine changes and clinical characteristics in hepatocellular carcinoma (HCC) patients receiving transcatheter arterial chemoembolization (TACE). METHODS: Forty-one TACE-näive HCC patients receiving 73 sessions of TACE and 30 healthy controls were studied. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin, epidermal growth factor (EGF), epidermal growth factor receptor, and transforming growth factor ß1 (TGF-ß1) before and at 1, 3, 5, 7, and 14 days after TACE as well as clinical parameters were analyzed. RESULTS: Baseline serum levels of VEGF, bFGF, IL-6, IL-8, and TNF-α in HCC patients were significantly elevated, whereas EGF and TGF-ß1 levels were lower compared to those in healthy controls (p < 0.05 for all). Serum IL-6 increased rapidly and peaked on day 1 after TACE administration, whereas VEGF increased more slowly and peaked on day 14 after TACE administration. Patients with post-TACE fever had higher serum IL-6 levels on days 1, 3, and 5 (p < 0.005 for all). Patients with pre-TACE serum VEGF < 200 pg/ml had a longer survival than those with pre-TACE serum VEGF levels ≥ 200 pg/ml (22.2 months vs. 11.6 months, p = 0.014). Cox multivariate analysis showed that baseline serum VEGF significantly predicted survival for HCC patients receiving TACE. CONCLUSIONS: TACE is associated with the modulation of serum angiogenic, inflammatory, and cell growth cytokines in HCC patients. Serum IL-6 correlates with post-TACE fever, and baseline serum VEGF independently predicts patient survival.

Seeing visual word forms: spatial summation, eccentricity and spatial configuration.

We investigated observers' performance in detecting and discriminating visual word forms as a function of target size and retinal eccentricity. The contrast threshold of visual words was measured with a spatial two-alternative forced-choice paradigm and a PSI adaptive method. The observers were to indicate which of two sides contained a stimulus in the detection task, and which contained a real character (as opposed to a pseudo- or non-character) in the discrimination task. When the target size was sufficiently small, the detection threshold of a character decreased as its size increased, with a slope of -1/2 on log-log coordinates, up to a critical size at all eccentricities and for all stimulus types. The discrimination threshold decreased with target size with a slope of -1 up to a critical size that was dependent on stimulus type and eccentricity. Beyond that size, the threshold decreased with a slope of -1/2 on log-log coordinates before leveling out. The data was well fit by a spatial summation model that contains local receptive fields (RFs) and a summation across these filters within an attention window. Our result implies that detection is mediated by local RFs smaller than any tested stimuli and thus detection performance is dominated by summation across receptive fields. On the other hand, discrimination is dominated by a summation within a local RF in the fovea but a cross RF summation in the periphery.

Concurrence of UGT1A polymorphism and end-stage renal disease leads to severe toxicities of irinotecan in a patient with metastatic colon cancer.

AIMS AND BACKGROUND: Colorectal cancer is one of the most common malignancies in the world, and irinotecan (CPT-11) is useful in its treatment. However, the safety and pharmacokinetics of irinotecan in dialysis patients with metastatic colorectal cancer are unclear. CASE REPORT: We report the case of a 74-year-old man receiving chronic hemodialysis who had metastatic colorectal cancer. Palliative chemotherapy with irinotecan (80 mg/m2 weekly) was administered after hemodialysis. Blood samples were collected before and 1.5, 3, 6, 9, and 15 hours after administration of irinotecan. The peak serum concentrations (Cmax) of irinotecan and SN-38 in this patient were 1,480 and 17.8 ng/mL, respectively, which were similar to the reported values in patients with normal renal function after a similar dose of irinotecan (75 mg/m2). The area under the serum concentration-time curve (AUC0-∞) was 8,240 ng×h/mL for irinotecan and 619 ng×h/mL for SN-38. The AUC0-∞ for SN-38 was markedly higher than that for patients with normal renal function. Sequencing analysis of the UGT1A genes found that the patient had variant alleles of UGT1A1*28, UGT1A1*60 and UGT1A9*22, which may lead to decreased glucuronidation and excretion of SN-38, and may account for increased irinotecan-related toxicity. The patient developed febrile grade 4 neutropenia on day 7 after chemotherapy and died of septic shock on day 14. CONCLUSIONS: UGT1A polymorphisms and renal failure may lead to accumulation of SN-38, which may have played a role in the death of this patient. Irinotecan should be used cautiously in dialysis patients with metastatic colorectal cancer and screening for UGT1A polymorphisms may help in identifying patients with lower SN-38 glucuronidation rates and greater susceptibility to irinotecan-induced toxicity.

The inversion effect in visual word form processing.

Reading is one of the best well-practiced visual tasks for modern people. We investigated how the visual cortex analyzes spatial configuration in written words by studying the inversion effect in Chinese character processing. We measured the psychometric functions and brain activations for upright real-characters and non-characters and their inverted (upside down) versions. In the psychophysical experiment, the real-characters showed an inversion effect at both 1 degrees and 4 degrees eccentricities, while the non-characters showed no inversion effect for all eccentricities tested. In the functional magnetic resonance image (fMRI) experiment, the left fusiform gyrus and a small area in the bilateral lateral occipital regions showed a significant differential activation between upright and inverted real-characters. The bilateral fusiform gyri also show differential activation between upright real- and non-characters. The dorsal lateral occipital regions showed character-selective activation when compared with scrambled lines. The result suggested that the occipitoparietal regions may analyze the local features of an object regardless of its familiarity. Therefore, the lateral occipital regions may play an intermediate role in integrating the local information in an object. Finally, the fusiform gyrus plays a critical role in analyzing global configurations of a visual word form. This is consistent with the notion that the human visual cortex analyzes an object in a hierarchical way.