Cerebral perfusion is not impaired in persons with moderate obstructive sleep apnoea when awake.

PURPOSE: It is well established that, together with a multitude of other adverse effects on health, severe obstructive sleep apnoea causes reduced cerebral perfusion and, in turn, reduced cerebral function. Less clear is the impact of moderate obstructive sleep apnoea (OSA). Our aim was to determine if cerebral blood flow is impaired in people diagnosed with moderate OSA. METHODS: Twenty-four patients diagnosed with moderate OSA (15 ≤ apnoea-hypopnea index (AHI) < 30) were recruited (aged 32-72, median 59 years, 10 female). Seven controls (aged 42-73 years, median 62 years, 4 female) with an AHI < 5 were also recruited. The OSA status of all participants was confirmed at baseline by unattended polysomnography and they had an MRI arterial-spin-labelling scan of cerebral perfusion. RESULTS: Neither global perfusion nor voxel-wise perfusion differed significantly between the moderate-OSA and control groups. We also compared the average perfusion across three regional clusters, which had been found in a previous study to have significant perfusion differences with moderate-severe OSA versus control, and found no significant difference in perfusion between the two groups. The perfusions were also very close, with means of 50.2 and 51.8 mL/100 g/min for the moderate-OSAs and controls, respectively, with a negligible effect size (Cohen's d = 0.10). CONCLUSION: We conclude that cerebral perfusion is not impaired in people with moderate OSA and that cerebral flow regulatory mechanisms can cope with the adverse effects which occur in moderate OSA. This is an important factor in clinical decisions for prescription of continuous positive airway pressure therapy (CPAP).

Predicting regression of cervical intraepithelial neoplasia grade 2 in women under 25 years.

BACKGROUND: A number of retrospective and prospective studies have documented substantial rates of regression in cervical intraepithelial neoplasia grade 2 lesions in young women. Initial observational management of cervical intraepithelial neoplasia grade 2 is increasingly accepted as appropriate for women under 25 years of age with screen-detected abnormalities and is included in a number of clinical guidelines. However, there has been a paucity of large prospective studies on observational management with strict inclusion criteria. A number of important questions remain, specifically regarding the clinical variables that are associated with the risk of progression or persistence of disease. To investigate these factors and to ensure that young women with cervical intraepithelial neoplasia grade 2 undergoing observational management were being managed in a well-monitored and an appropriately informed fashion, we conducted a large, multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 in women under 25 years. OBJECTIVE: This study aimed to determine the regression rates and clinical, cytologic, and pathologic predictors of regression of cervical intraepithelial neoplasia grade 2 in women under 25 years undergoing observational management over 24 months. STUDY DESIGN: This study was a multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 (ie, repeat colposcopy, cytology, and cervical biopsy every 6 months) for up to 24 months. A total of 615 consenting women under 25 years with newly-diagnosed, biopsy-proven cervical intraepithelial neoplasia grade 2 were recruited (from 2010 to 2016) through 16 hospital-based colposcopy units in New Zealand and Australia. RESULTS: At completion, 326 women had confirmed regression, 156 had persistent high-grade cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ, and 24 had unconfirmed regression (ie, first regression at the 24-month follow-up). A total of 109 women did not complete the protocol (41 because of delayed follow-up, 41 lost to follow-up, 22 elected treatment, 4 refused a biopsy, and 1 died of an unrelated cause). Confirmed regression was observed in 53% (326 of 615) of all women enrolled in the study and, when missing data were imputed, it was estimated that 64% of women (95% confidence interval, 60%-68%) would have experienced regression. Similarly, lesions regressed in 64% (326 of 506) of women who completed the observational protocol. Based on a multivariable analysis, detection of human papillomavirus 16 in a liquid-based cytology sample at the time of initial colposcopy decreased the chance of regression by 31% (risk ratio, 0.69; 95% confidence interval, 0.56-0.86; P<.001). In addition, at initial colposcopy, low-grade or normal colposcopic impression, later year of diagnosis, low-grade or normal cytology, and being a nonsmoker were all independently associated with an increased chance of regression. CONCLUSION: More than half of women under 25 years with cervical intraepithelial neoplasia grade 2 will regress to cervical intraepithelial neoplasia grade 1 or normal within 24 months without destructive treatment. The absence of human papillomavirus 16 is the most important predictor of regression.

Evaluation of guidelines for observational management of cervical intraepithelial neoplasia 2 in young women.

BACKGROUND: A high rate of regression in young women with cervical intraepithelial neoplasia grade 2 has been recorded. However, there are few prospective data by which to evaluate management guidelines. OBJECTIVE: This study evaluates the American Society for Colposcopy and Cervical Pathology recommendations for follow-up of young women with cervical intraepithelial neoplasia 2 using data created by a large prospective multicenter study of observational management. MATERIALS AND METHODS: Participants were 616 women under 25 years with biopsy-diagnosed cervical intraepithelial neoplasia 2 following a referral to colposcopy for an abnormal smear with no previous high-grade abnormality. The protocol included colposcopy, cytology, and colposcopically directed biopsy at the initial visit and at 6- and 12-month follow-ups visits, and these data were analyzed. Histology from the corresponding cervical biopsy was treated as the reference diagnostic test. For young women with cervical intraepithelial neoplasia 2, we aimed to determine the following: (1) the ability of colposcopy to identify women with cervical intraepithelial neoplasia 3 or worse at 6 months; and (2) the ability of colposcopy, cytology, and a combination of cytology and colposcopy to identify residual high-grade abnormalities at 12 months. In addition, although not specified in the guidelines, we investigated the ability of high-risk human papillomavirus positivity alone or with cytology as a co-test to identify residual high-grade abnormalities at 12 months. RESULTS: At 6 months, cervical intraepithelial neoplasia 3+ colposcopic appearance identified only 28% (95% confidence interval, 18-40%) of women diagnosed with cervical intraepithelial neoplasia 3. At 12 months, a high-grade colposcopic appearance identified only 58% (95% confidence interval, 48-68%) of women with residual histological cervical intraepithelial neoplasia 2 or 3. At 12 months, high-grade cytology identified only 58% (95% confidence interval, 48-68%) of women with cervical intraepithelial neoplasia 2 or 3. However, the combination of either high-grade cytology or colposcopic appearance proved substantially more sensitive (81%; 95% confidence interval, 72-88%). High-risk human papillomavirus positivity at 12 months was a sensitive (96%; 95% confidence interval, 89-99%) indicator of persisting high-grade histology. However, this sensitivity came at the expense of specificity (52%; 95% confidence interval, 45-58%). A co-test of high-risk human papillomavirus positivity or high-grade cytology at 12 months provided a high sensitivity (97%; 95% confidence interval, 90-99%) but low specificity (51%; 95% confidence interval, 45%-58%). CONCLUSION: Colposcopy and cytology are limited in their ability to exclude persistent high-grade abnormality for young women undergoing observational management for cervical intraepithelial neoplasia 2. We recommend biopsy for all women at 12 months. High-risk human papillomavirus positivity is a sensitive indicator of persistent abnormality and should be considered in those not having a biopsy.

Temporal evolution of neural activity and connectivity during microsleeps when rested and following sleep restriction.

Even when it is critical to stay awake, such as when driving, sleep deprivation weakens one's ability to do so by substantially increasing the propensity for microsleeps. Microsleeps are complete lapses of consciousness but, paradoxically, are associated with transient increases in cortical activity. But do microsleeps provide a benefit in terms of attenuating the need for sleep? And is the neural response to microsleeps altered by the degree of homeostatic drive to sleep? In this study, we continuously monitored eye-video, visuomotor responsiveness, and brain activity via fMRI in 20 healthy subjects during a 20-min visuomotor tracking task following a normally-rested night and a sleep-restricted (4-h) night. As expected, sleep restriction led to an increased number of microsleeps and an increased variability in tracking error. Microsleeps exhibited transient increases in regional activity in the fronto-parietal and parahippocampal area. Network analyses revealed divergent transient changes in the right fronto-parietal, dorsal-attention, default-mode, and thalamo-cortical functional networks. In all subjects, tracking error immediately following microsleeps was improved compared to before the microsleeps. Importantly, post-microsleep recovery in tracking response speed was associated with hyperactivation in the thalamo-cortical network. The temporal evolution of functional connectivity within the frontal and posterior nodes of the default-mode network and between the right fronto-parietal and default-mode networks was associated with temporal changes in visuomotor responsiveness. These findings demonstrate distinct brain-network-level changes in brain activity during microsleeps and suggest that neural activity in the thalamo-cortical network may facilitate the transient recovery from microsleeps. The temporal pattern of evolution in brain activity and performance is indicative of dynamic changes in vigilance during the struggle to stay awake following sleep loss.

Time-varying effective connectivity of the cortical neuroelectric activity associated with behavioural microsleeps.

An episode of complete failure to respond during an attentive task accompanied by behavioural signs of sleep is called a behavioural microsleep. We proposed a combination of high-resolution EEG and an advanced method for time-varying effective connectivity estimation for reconstructing the temporal evolution of the causal relations between cortical regions when microsleeps occur during a continuous visuomotor task. We found connectivity patterns involving left-right frontal, left-right parietal, and left-frontal/right-parietal connections commencing in the interval [-500; -250] ms prior to the onset of microsleeps and disappearing at the end of the microsleeps. Our results from global graph indices derived from effective connectivity analysis have revealed EEG-based biomarkers of all stages of microsleeps (preceding, onset, pre-recovery, recovery). In particular, this raises the possibility of being able to predict microsleeps in real-world tasks and initiate a 'wake-up' intervention to avert the microsleeps and, hence, prevent injurious and even multi-fatality accidents.

Attention lapses and behavioural microsleeps during tracking, psychomotor vigilance, and dual tasks.

This study examined the incidence of attention lapses and microsleeps under contrasting levels of task complexity during three tasks: PVT, 2-D tracking and a dual task combining the two. More attention lapses per participant (median 15vs. 3; range 1-74vs. 0-76, p=0.001), with the greatest increase with time spent-on-task (p=0.002), were evident on the more cognitively-demanding dual task than on the PVT. Conversely, fewer microsleeps (median 0vs. 0; range 0-1vs. 0-18, p=0.022) occurred during the more complex task compared to the tracking task. An increase in microsleep rate with time spent-on-task (p=0.035) was evident during the tracking task but not the dual task. These results indicate that the higher cognitive load, associated with an increase in task complexity, increased the likelihood of attention lapses, while a reduction in task complexity increased the likelihood of microsleeps.

Losing the struggle to stay awake: divergent thalamic and cortical activity during microsleeps.

Maintaining alertness is critical for safe and successful performance of most human activities. Consequently, microsleeps during continuous visuomotor tasks, such as driving, can be very serious, not only disrupting performance but sometimes leading to injury or death due to accidents. We have investigated the neural activity underlying behavioral microsleeps--brief (0.5-15 s) episodes of complete failure to respond accompanied by slow eye-closures--and EEG theta activity during drowsiness in a continuous task. Twenty healthy normally-rested participants performed a 50-min continuous tracking task while fMRI, EEG, eye-video, and responses were simultaneously recorded. Visual rating of performance and eye-video revealed that 70% of the participants had frequent microsleeps. fMRI analysis revealed a transient decrease in thalamic, posterior cingulate, and occipital cortex activity and an increase in frontal, posterior parietal, and parahippocampal activity during microsleeps. The transient activity was modulated by the duration of the microsleep. In subjects with frequent microsleeps, power in the post-central EEG theta was positively correlated with the BOLD signal in the thalamus, basal forebrain, and visual, posterior parietal, and prefrontal cortices. These results provide evidence for distinct neural changes associated with microsleeps and with EEG theta activity during drowsiness in a continuous task. They also suggest that the occurrence of microsleeps during an active task is not a global deactivation process but involves localized activation of fronto-parietal cortex, which, despite a transient loss of arousal, may constitute a mechanism by which these regions try to restore responsiveness.

Distinct neural correlates of time-on-task and transient errors during a visuomotor tracking task after sleep restriction.

Sleep loss leads to both time-on-task slowing of responsiveness and increased frequency of transient response errors. The consequences of such errors during real-world visuomotor tasks, such as driving, are serious and life threatening. To investigate the neuronal underpinning of time-on-task and transient errors during a visuomotor tracking task following sleep restriction, we performed fMRI on 20 healthy individuals when well-rested and when sleep-restricted while they performed a 2-D pursuit-tracking task. Sleep restriction to 4-h time-in-bed was associated with significant time-on-task decline in tracking performance and an increased number of transient tracking errors. Sleep restriction was associated with time-on-task decreases in BOLD activity in task-related areas, including the lateral occipital cortex, intraparietal cortex, and primary motor cortex. In contrast, thalamic, anterior cingulate, and medial frontal cortex areas showed overall increases irrespective of time-on-task after sleep-restriction. Furthermore, transient errors after sleep-restriction were associated with distinct transient BOLD activations in areas not involved in tracking task per se, in the right superior parietal cortex, bilateral temporal cortex, and thalamus. These results highlight the distinct cerebral underpinnings of sustained and transient modulations in alertness during increased homeostatic drive to sleep. Ability to detect neuronal changes associated with both sustained and transient changes in performance in a single task allowed us to disentangle neuronal mechanisms underlying two important aspects of sustained task performance following sleep loss.

Endometrial cancer diagnoses prompted by routine cervical cytology: a retrospective case study.

AIMS: Endometrial cancer is the commonest gynaecological cancer in New Zealand. Some women have their diagnosis of endometrial cancer prompted by an abnormal cervical cytology screening test. When high-risk human papillomavirus (hr-HPV) testing becomes the primary test for cervical screening, this avenue of incidental diagnosis will be reduced. Therefore, our aims were to estimate the proportion of women whose diagnosis of endometrial cancer follows incidental detection on routine cervical cytology, and to understand the clinicopathologic characteristics of these cases. METHODS: Retrospective analysis of patient medical records from women of cervical screening age diagnosed with endometrial cancer between 2015-2019 in the South Island of New Zealand. RESULTS: Of 334 women, 26 (7.8%) had endometrial cancer diagnosis prompted by abnormal cervical cytology. Most women had low-grade (17/26, 65.4%), low-stage (18/26, 69.2%) disease of endometrioid histologic subtype (21/26, 80.8%). The small cohort prevented significant correlations with clinicopathologic characteristics and outcomes. Overall, cervical cytology had low sensitivity (32.3%) for the detection of endometrial cancer in the 6 months before diagnosis. CONCLUSIONS: A small number of women currently have diagnoses of endometrial cancer prompted by routine cervical screening with cytology. However, the undefined clinical benefit from and poor sensitivity of cervical cytology for detecting endometrial cancer does not justify its use in screening, or opposition to hr-HPV cervical screening.

Increased cerebral activity during microsleeps reflects an unconscious drive to re-establish consciousness.

BACKGROUND: Microsleeps are brief instances of sleep, causing complete lapses in responsiveness and partial or total extended closure of both eyes. Microsleeps can have devastating consequences, particularly in the transportation sector. STUDY OBJECTIVES: Questions remain regarding the neural signature and underlying mechanisms of microsleeps. This study aimed to gain a better understanding of the physiological substrates of microsleeps, which might lead to a better understanding of the phenomenon. METHODS: Data from an earlier study, involving 20 healthy non-sleep-deprived subjects, were analysed. Each session lasted 50 min and required subjects to perform a 2-D continuous visuomotor tracking task. Simultaneous data collection included tracking performance, eye-video, EEG, and fMRI. A human expert visually inspected each participant's tracking performance and eye-video recordings to identify microsleeps. Our interest was in microsleeps of ≥4-s duration, leaving us with a total of 226 events from 10 subjects. The microsleep events were divided into four 2-s segments (pre, start, end, and post) (with a gap in the middle, between start and end segments, for microsleeps >4 s), then each segment was analysed relative to its prior segment by examining changes in source-reconstructed EEG power in the delta, theta, alpha, beta, and gamma bands. RESULTS: EEG power increased in the theta and alpha bands between the pre and start of microsleeps. There was also increased power in the delta, beta, and gamma bands between the start and end of microsleeps. Conversely, there was a reduction in power between the end and post of microsleeps in the delta and alpha bands. These findings support previous findings in the delta, theta, and alpha bands. However, increased power in the beta and gamma bands has not been previously reported. CONCLUSIONS: We contend that increased high-frequency activity during microsleeps reflects unconscious 'cognitive' activity aimed at re-establishing consciousness following falling asleep during an active task.

RoWDI: rolling window detection of sleep intrusions in the awake brain using fMRI.

Objective.Brief episodes of sleep can intrude into the awake human brain due to lack of sleep or fatigue-compromising the safety of critical daily tasks (i.e. driving). These intrusions can also introduce artefactual activity within functional magnetic resonance imaging (fMRI) experiments, prompting the need for an objective and effective method of removing them.Approach.We have developed a method to track sleep-like events in awake humans via rolling window detection of intrusions (RoWDI) of fMRI signal template. These events can then be used in voxel-wise event-related analysis of fMRI data. To test this approach, we generated a template of fMRI activity associated with transition to sleep via simultaneous fMRI and electroencephalogram (EEG) (N= 10). RoWDI was then used to identify sleep-like events in 20 individuals performing a cognitive task during fMRI after a night of partial sleep deprivation. This approach was further validated in an independent fMRI dataset (N= 56).Main results.Our method (RoWDI) was able to infer frequent sleep-like events during the cognitive task performed after sleep deprivation. The sleep-like events were associated with on average of 20% reduction in pupil size and prolonged response time. The blood-oxygen-level-dependent activity during the sleep-like events covered thalami-cortical regions, which although spatially distinct, co-existed with, task-related activity. These key findings were validated in the independent dataset.Significance.RoWDI can reliably detect spontaneous sleep-like events in the human brain. Thus, it may also be used as a tool to delineate and account for neural activity associated with wake-sleep transitions in both resting-state and task-related fMRI studies.

Trends in the diagnosis of high-grade cervical abnormalities in young women in the post-vaccination era.

BACKGROUND: Most cervical cancers are associated with human papillomavirus (HPV) types 16 and 18. In 2008, New Zealand commenced a quadrivalent HPV (virus-like particles of types 6, 11, 16 and 18) vaccination programme. AIM: Document trends in number of colposcopy referrals and number and grade of cervical abnormalities diagnosed in women (20-24 years) referred to three large colposcopy clinics over time. METHOD: Retrospective analysis of colposcopy clinic data. RESULTS: The dataset included 5,012 episodes from 4,682 women. In Auckland (2013-2017), there was a 38% decrease in colposcopy referrals and 55% decrease in cervical intraepithelial neoplasia grade 2 (CIN2) or worse diagnoses. In Waikato (2011-2017), there was an 8% decrease in referrals and 22% reduction in CIN2 or worse diagnoses. In Canterbury (2011-2017), there was a 24% decrease in referrals and 49% reduction in CIN2 or worse diagnoses. Across all centres, the decrease in cervical intraepithelial neoplasia grade 3 (CIN3) or worse diagnoses was marked and more consistent than in CIN2 diagnoses. However, while the proportion of biopsies reported as CIN3 or worse decreased in non-Maori (24% in 2013 vs 16% in 2017, nptrend z=-4.24, p>|z| <.001), there was no change in Maori women (31% in 2013 vs 29% in 2017, nptrend z=-0.12, p>|z| =.90). CONCLUSIONS: We observed a decreased number of CIN diagnoses in young women over time, with a particularly large drop in the number of CIN3/AIS/CGIN diagnoses. However, compared to non-Maori, Maori women having biopsies are more likely to have CIN3 or worse and there was a smaller reduction in the total number of Maori women diagnosed with CIN2 or worse.

Changes in human papillomavirus genotypes associated with cervical intraepithelial neoplasia grade 2 lesions in a cohort of young women (2013-2016).

In 2008, a quadrivalent human papillomavirus (HPV) vaccine (genotypes 6, 11, 16, 18) became available in New Zealand. This study investigated whether the proportion of cervical intraepithelial neoplasia grade 2 (CIN2) lesions associated with HPV genotypes 16 and 18 changed over time in young women recruited to a prospective CIN2 observational management trial (PRINCess) between 2013 and 2016. Partial HPV genotyping (16, 18, or other high risk HPV) was undertaken on n = 392 women under 25 years (mean age 21.8, range 17-24) with biopsy-diagnosed CIN2. High risk HPV genotypes were detected in 96% of women with CIN2 lesions. Between 2013 and 2016, the proportion of women whose liquid-based cytology samples were HPV 16 or 18 positive decreased from 43% to 13%. HPV vaccination status was known for 78% of women. Between 2013 and 2016, the proportion of HPV 16/18 positivity did not significantly change in HPV-vaccinated women, but decreased from 66% to 17% in unvaccinated women. The reducing proportion of HPV 16/18-related CIN2 in our cohort of young New Zealand women may be attributable to the introduction of a national HPV vaccination program. The substantial decrease in HPV 16/18 positivity observed in unvaccinated women is likely to be due to a herd effect.

Sensory-motor and cognitive tests predict driving ability of persons with brain disorders.

OBJECTIVE: Brain disorders can lead to a decreased ability to perform the physical and cognitive functions necessary for safe driving. This study aimed to determine how accurately a battery of computerized sensory-motor and cognitive tests (SMCTests) could predict driving abilities in persons with brain disorders. METHODS: SMCTests and an independent on-road driving assessment were applied to 50 experienced drivers with brain disorders referred to a hospital-based driving assessment service. The patients comprised 36 males and 14 females, a mean age of 71.3 years (range 43-85 years) and diagnoses of 35 stroke, 4 traumatic brain injury, 4 Alzheimer's disease, and 7 other. Binary logistic regression (BLR) and nonlinear causal resource analysis (NCRA) were used to build model equations for prediction of on-road driving ability based on SMCTests performance. RESULTS: BLR and NCRA correctly classified 94% and 90% of referrals respectively as on-road pass or fail. Leave-one-out cross-validation estimated that BLR and NCRA would correctly predict the classification of 86% and 76% respectively of an independent referral group as on-road pass or fail. CONCLUSIONS: Compared with other studies, SMCTests have shown the highest predictive accuracy against true on-road driving ability as estimated in an independent data set and in persons with brain disorders. SMCTests also have the advantage of being able to comprehensively and objectively assess both sensory-motor and higher cognitive functions related to driving.

Prediction of driving ability: Are we building valid models?

The prediction of on-road driving ability using off-road measures is a key aim in driving research. The primary goal in most classification models is to determine a small number of off-road variables that predict driving ability with high accuracy. Unfortunately, classification models are often over-fitted to the study sample, leading to inflation of predictive accuracy, poor generalization to the relevant population and, thus, poor validity. Many driving studies do not report sufficient details to determine the risk of model over-fitting and few report any validation technique, which is critical to test the generalizability of a model. After reviewing the literature, we generated a model using a moderately large sample size (n=279) employing best practice techniques in the context of regression modelling. By then randomly selecting progressively smaller sample sizes we show that a low ratio of participants to independent variables can result in over-fitted models and spurious conclusions regarding model accuracy. We conclude that more stable models can be constructed by following a few guidelines.

Decreased Regional Cerebral Perfusion in Moderate-Severe Obstructive Sleep Apnoea during Wakefulness.

STUDY OBJECTIVES: To investigate gray matter volume and concentration and cerebral perfusion in people with untreated obstructive sleep apnea (OSA) while awake. DESIGN: Voxel-based morphometry to quantify gray matter concentration and volume. Arterial spin labeling perfusion imaging to quantify cerebral perfusion. SETTING: Lying supine in a 3-T magnetic resonance imaging scanner in the early afternoon. PARTICIPANTS: 19 people with OSA (6 females, 13 males; mean age 56.7 y, range 41-70; mean AHI 18.5, range 5.2-52.8) and 19 controls (13 females, 6 males; mean age: 50.0 y, range 41-81). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: There were no differences in regional gray matter concentration or volume between participants with OSA and controls. Neither was there any difference in regional perfusion between controls and people with mild OSA (n = 11). However, compared to controls, participants with moderate-severe OSA (n = 8) had decreased perfusion (while awake) in three clusters. The largest cluster incorporated, bilaterally, the paracingulate gyrus, anterior cingulate gyrus, and subcallosal cortex, and the left putamen and left frontal orbital cortex. The second cluster was right-lateralized, incorporating the posterior temporal fusiform cortex, parahippocampal gyrus, and hippocampus. The third cluster was located in the right thalamus. CONCLUSIONS: There is decreased regional perfusion during wakefulness in participants with moderate-severe obstructive sleep apnea, and these are in brain regions which have shown decreased regional gray matter volume in previous studies in people with severe OSA. Thus, we hypothesize that cerebral perfusion changes are evident before (and possibly underlie) future structural changes.

Optimal EEG feature selection from average distance between events and non-events.

Biosignal classification systems often have to deal with extraneous features, highly imbalanced datasets, and a low SNR. A robust feature selection/reduction method is a crucial step in this process. Sets of artificial data were generated to test a prototype EEG-based microsleep detection system, consisting of a combination of EEG and 2-s bursts of 15-Hz sinusoids of varied signal-to-noise ratios (SNRs) ranging from 16 to 0.03. The balance between events and non-events was varied between evenly balanced and highly imbalanced (e.g., events occurring only 2% of the time). Features were spectral estimates of various EEG bands (e.g., alpha band power) or ratios between them. A total of 34 features for each of the 16 channels yielded a total of 544 features. Five minutes of EEG from a total of eight subjects were used in the generation of the artificial data. Several feature reduction and classifier structures were investigated. Taking only a single feature corresponding to the maximum of average distance between events and non-events (ADEN) on unbalanced data yielded a phi correlation of 0.94 on the mock data with an SNR of 0.3, compared with a phi coefficient of 0.00 for principal component analysis (PCA). ADEN consistently outperformed alternative system configurations, independent of the classifier utilized. While ADEN's high performance may be due to the nature of the artificial dataset, this simulation has demonstrated strong potential compared to other feature selection/reduction methods.

Efficient and regular patterns of nighttime sleep are related to increased vulnerability to microsleeps following a single night of sleep restriction.

Sleep-deprived people, or those performing extended monotonous tasks, can exhibit brief episodes in which they suspend performance and appear to fall asleep momentarily-behavioral microsleeps ("microsleeps"). In this study, microsleeps were identified using eye video and tracking response during a 20-min continuous tracking task undertaken by 16 healthy volunteers (mean age 24.9 yrs; 8 females, 8 males) in the early afternoon following a normally rested night and a night of restricted sleep (time-in-bed restricted to 4 h). Sessions were 1 wk apart and counterbalanced. Wrist actigraphy, self-reported sleepiness, and sleep quality were also recorded. We hypothesized that high microsleep rates when normally rested or after a night of sleep restriction would be related to poor sleep quality, sleep disturbance, circadian type, irregular sleep patterns, low daily sleep duration, or poor sleep efficiency. We also hypothesized that prior performance on a 10-min psychomotor vigilance task (PVT) (mean reaction time or number of PVT lapses) would be related to the number of microsleeps during the tracking task and that PVT performance could, therefore, be used as a fitness-for-duty indicator. The number of microsleeps during the tracking task increased following sleep restriction (mean 11.4 versus 27.9; p = 0.03). There were no correlations between the number of microsleeps in the normally rested session and any of the actigraphically measured or self-reported sleep measures. However, the number of microsleeps following sleep restriction was correlated with sleep efficiency (r = 0.73, p = 0.001), sleep onset latency (r = -0.57, p = 0.02), and sleep onset time-of-day standard deviation (r = -0.54, p = 0.03) over 11 normally rested nights. There was no correlation between PVT performance and the subsequent number of microsleeps during the tracking task in either session. Attributes usually associated with beneficial nighttime sleep patterns-going to sleep at a similar time each night, falling asleep quickly, and infrequent arousals-were related to greater vulnerability to microsleeps following sleep restriction. There were intercorrelations between all the sleep measures associated with microsleep rate following sleep restriction, indicating that the measures form a pattern of behaviors and are not independently related to microsleep rate. Perhaps some people maintain a regular sleep pattern because they experience sleepiness the following day when their pattern is disrupted. Conversely, people with more variation in their sleep pattern may do so because this does not substantially increase sleepiness the following day. We conclude that people with consistent sleep patterns and efficient sleep may be more prone to microsleeps than other people when their usual regular pattern is disrupted by sleep restriction.

Predicting on-road assessment pass and fail outcomes in older drivers with cognitive impairment using a battery of computerized sensory-motor and cognitive tests.

OBJECTIVES: To generate a robust model of computerized sensory-motor and cognitive test performance to predict on-road driving assessment outcomes in older persons with diagnosed or suspected cognitive impairment. DESIGN: A logistic regression model classified pass­fail outcomes of a blinded on-road driving assessment. Generalizability of the model was tested using leave-one-out cross-validation. SETTING: Three specialist clinics in New Zealand. PARTICIPANTS: Drivers (n=279; mean age 78.4, 65% male) with diagnosed or suspected dementia, mild cognitive impairment, unspecified cognitive impairment, or memory problems referred for a medical driving assessment. MEASUREMENTS: A computerized battery of sensory-motor and cognitive tests and an on-road medical driving assessment. RESULTS: One hundred fifty-five participants (55.5%) received an on-road fail score. Binary logistic regression correctly classified 75.6% of the sample into on-road pass and fail groups. The cross-validation indicated accuracy of the model of 72.0% with sensitivity for detecting on-road fails of 73.5%, specificity of 70.2%, positive predictive value of 75.5%, and negative predictive value of 68%. CONCLUSION: The off-road assessment prediction model resulted in a substantial number of people who were assessed as likely to fail despite passing an on-road assessment and vice versa. Thus, despite a large multicenter sample, the use of off-road tests previously found to be useful in other older populations, and a carefully constructed and tested prediction model, off-road measures have yet to be found that are sufficiently accurate to allow acceptable determination of on-road driving safety of cognitively impaired older drivers.

Cerebral perfusion differences between drowsy and nondrowsy individuals after acute sleep restriction.

OBJECTIVES: To investigate changes in resting cerebral blood flow (CBF) after acute sleep restriction. To investigate the extent to which changes in CBF after sleep restriction are related to drowsiness as manifested in eye-video. DESIGN: Participants were scanned for 5 min using arterial spin labeling (ASL) perfusion imaging after both sleep-restricted and rested nights. Participants were rated for visual signs of drowsiness in the eye-video recorded during the scan. SETTING: Lying supine in a 3-Tesla magnetic resonance imaging scanner. PARTICIPANTS: Twenty healthy adults (age 20-37 yr) with no history of neurologic, psychiatric, or sleep disorder, and with usual time in bed of 7.0-8.5 h. INTERVENTIONS: In the night before the sleep-restricted session, participants were restricted to 4 h time in bed. RESULTS: There was an overall reduction in CBF in the right-lateralized fronto-parietal attentional network after acute sleep restriction, although this was largely driven by participants who showed strong signs of drowsiness in the eye-video after sleep restriction. Change in CBF correlated with change in drowsiness in the basal forebrain-cingulate regions. In particular, there was a pronounced increase in CBF in the basal forebrain and anterior and posterior cingulate cortex of participants who remained alert after sleep restriction. CONCLUSIONS: The pattern of cerebral activity after acute sleep restriction is highly dependent on level of drowsiness. Nondrowsy individuals are able to increase activity in the arousal-promoting brain regions and maintain activity in attentional regions. In contrast, drowsy individuals are unable to maintain arousal and show decreased activity in both arousal-promoting and attentional regions.