Alertness Deficits Research Articles

General low alertness in people with obstructive sleep apnea.

In patients with obstructive sleep apnea (OSA), a previous study using a Go/No-Go task reported an average attention deficit. However, the temporal dynamics of such a deficit are unknown. Here, we investigated whether attention deficits in different subdomains increased as the test progressed. We also investigated the effect of target frequency and speed of stimulus presentation on performance. Twenty-seven untreated people with OSA and 27 age- and sex-matched controls underwent a 15-minute Go/No-Go task, divided into 6 blocks. Each block was subdivided into 3 different interstimulus intervals (1, 2, and 4 seconds). Three blocks had a low and three had a high target probability (20% and 80%, respectively). Reaction time (alertness), variability of reaction time (sustained attention), commission errors (response inhibition), and omission errors (focused attention) were measured. Alertness was lower in the group with OSA compared with controls, as evidenced by a significantly higher average reaction time. This effect was seen from the start of the task and continued until the end but did not increase in test progression. The temporal pattern of intrinsic alertness deficits in patients with OSA was found to be independent of target frequency or interstimulus interval. The primary attention problem in OSA is on the alertness subdomain irrespective of the number of required responses or speed of stimulus presentation. The present results support the notion that OSA is distinct from other neurological and psychiatric conditions, such as depression or chronic pain. The results also suggest significant concerns regarding daily life activities (eg, driving). de Souza Bezerra ML, van Duinkerken E, Simões E, Schmidt SL. General low alertness in people with obstructive sleep apnea. J Clin Sleep Med. 2024;20(5):689-698.

Use of the psychomotor vigilance test to aid in the selection of risk controls in an air medical transport operation.

This study evaluated the utility and ecological validity of the 3-minute psychomotor vigilance test (PVT) completed by safety-critical personnel in an air medical transport operation as part of a fatigue risk management program. Crewmembers in an air medical transport operation self-administered an alertness assessment incorporating a 3-minute PVT at different time points during their duty schedule. The prevalence of alertness deficits was evaluated based on a failure threshold of 12 errors considering both lapses and false starts. To evaluate the ecological validity of the PVT, the relative frequency of failed assessments was evaluated relative to crewmember position, timing of the assessment within the duty schedule, time of day, and sleep quantity in the last 24 h. 2.1% of assessments were associated with a failing PVT score. Crewmember position, timing of assessment within the duty shift, time of day, and sleep quantity in the last 24 h were found to affect the relative frequency of failed assessments. Obtaining less than 7-9 h of sleep was associated with systematic increases in the failure rate (F[1, 54 612] = 168.1, p < .001). Obtaining less than 4 h of sleep was associated with a frequency of a failed assessment 2.99 times higher than the frequency of a failed assessment when obtaining 7-9 h of sleep. Results provide evidence for the utility and ecological validity of the PVT as well as the suitability of the PVT failure threshold to support fatigue risk management in safety-critical operations.

Paradoxical effects from stimulus density manipulation provide new insight into the impact of sleep deprivation on PVT performance.

The psychomotor vigilance test (PVT), a 10-min one-choice reaction time task with random response-stimulus intervals (RSIs) between 2 and 10 s, is highly sensitive to behavioral alertness deficits due to sleep loss. To investigate what drives the performance deficits, we conducted an in-laboratory total sleep deprivation (TSD) study and compared performance on the PVT to performance on a 10-min high-density PVT (HD-PVT) with increased stimulus density and truncated RSI range between 2 and 5 s. We hypothesized that the HD-PVT would show greater impairments from TSD than the standard PVT. n = 86 healthy adults were randomized (2:1 ratio) to 38 h of TSD (n = 56) or corresponding well-rested control (n = 30). The HD-PVT was administered when subjects had been awake for 34 h (TSD group) or 10 h (control group). Performance on the HD-PVT was compared to performance on the standard PVTs administered 1 h earlier and 1 h later. The HD-PVT yielded approximately 60% more trials than the standard PVT. The HD-PVT had faster mean response times (RTs) and equivalent lapses (RTs > 500 ms) compared to the standard PVT, with no differences between the TSD effects on mean RT and lapses between tasks. Further, the HD-PVT had a dampened time-on-task effect in both the TSD and control conditions. Contrary to expectation, the HD-PVT did not show greater performance impairment during TSD, indicating that stimulus density and RSI range are not primary drivers of the PVT's responsiveness to sleep loss.

A study of brain functional network and alertness changes in temporal lobe epilepsy with and without focal to bilateral tonic\u2013clonic seizures

BackgroundTemporal lobe epilepsy (TLE) is commonly refractory. Epilepsy surgery is an effective treatment strategy for refractory epilepsy, but patients with a history of focal to bilateral tonic-clonic seizures (FBTCS) have poor outcomes. Previous network studies on epilepsy have found that TLE and idiopathic generalized epilepsy with generalized tonic-clonic seizures (IGE-GTCS) showed altered global and nodal topological properties. Alertness deficits also were found in TLE. However, FBTCS is a common type of seizure in TLE, and the implications for alertness as well as the topological rearrangements associated with this seizure type are not well understood.MethodsWe obtained rs-fMRI data and collected the neuropsychological assessment data from 21 TLE patients with FBTCS (TLE- FBTCS), 18 TLE patients without FBTCS (TLE-non- FBTCS) and 22 controls, and constructed their respective functional brain networks. The topological properties were analyzed using the graph theoretical approach and correlations between altered topological properties and alertness were analyzed.ResultsWe found that TLE-FBTCS patients showed more serious impairment in alertness effect, intrinsic alertness and phasic alertness than the patients with TLE-non-FBTCS. They also showed significantly higher small-worldness, normalized clustering coefficient (γ) and a trend of higher global network efficiency (gE) compared to TLE-non-FBTCS patients. The gE showed a significant negative correlation with intrinsic alertness for TLE-non-FBTCS patients.ConclusionOur findings show different impairments in brain network information integration, segregation and alertness between the patients with TLE-FBTCS and TLE-non-FBTCS, demonstrating that impairments of the brain network may underlie the disruptions in alertness functions.

126 Exposure to simulated military operational stress decreases alertness in the morning but not the evening

Abstract Introduction Alertness, essential for optimal performance, may be modulated by acute stressors including: sleep loss, caloric restriction, cognitive load, and physical exertion. Prior sleep may attenuate sleep loss-related alertness decrements, thereby influencing performance and safety. We examined the effects of prior sleep and changes in alertness throughout the day and across days during a simulated military operational stress (SMOS) protocol. Methods As part of a 5-day SMOS protocol, fifty-eight active-duty or recently-separated military personnel (45 men; 26±6 years) completed subjective (Profile of Mood States, Vigor subscale) and objective (3-minute Psychomotor Vigilance Task; PVT) alertness assessments each morning (~0900) and evening (~2200). PVT outcomes included median reaction time (RT) and lapses. Day 2 (D2) reflected baseline testing, in which participants received an 8-hour sleep opportunity (2300-0700) and 100% of their estimated caloric need. Day 4 (D4) reflected peak stress, after two nights of participants receiving two 2-hour sleep opportunities (0100-0300, 0500-0700) and 50% of their estimated caloric need. Mixed effects ANOVAs were used to assess the effects of day (D2, D4) and time (Morning, Evening) on alertness. D2 and D4 reflected alertness at baseline and peak stress, respectively. Separate ANOVAs were performed to assess the effects of prior sleep: the Pittsburgh Sleep Quality Index (PSQI) assessed at intake, baseline polysomnography-measured sleep efficiency (SE), and baseline frontal slow wave activity (SWA; 0.5-4Hz). All analyses controlled for age. Results No significant interaction or main effects of day and time were found for Vigor or PVT lapses. Participants with higher PSQI scores reported lower Vigor (p=.01, η_p^2=.11). A significant interaction was found for PVT RT (p=.04, η_p^2=.07); morning RT was slower on D4 than D2, while evening RT did not differ across days. SE and SWA did not significantly influence alertness. Conclusion SMOS led to objective alertness deficits in the morning but not evening. Subjective alertness did not change during SMOS but was influenced by prior sleep quality (PSQI). Thus, both circadian and prior sleep-related factors influence performance during operational stress. Fatigue mitigation strategies delivered before and during military operations may support performance and safety. Support (if any) Department of Defense Award #W81XWH-17-2-0070

Intrinsic Alertness Is Impaired in Patients with Nigrostriatal Degeneration: A Prospective Study with Reference to [123I]FP-CIT SPECT and [18F]FDG PET.

Variations in alertness and attention are common in Lewy body diseases (LBD) and among the core features of dementia with Lewy bodies (DLB). Dopamine transporter SPECT is an accurate biomarker of nigrostriatal degeneration (NSD) in LBD. The present study investigated performance on a computerized alertness test as a potential measure of attention in patients with NSD compared to patients without NSD. Thirty-six patients with cognitive impairment plus at least one core feature of DLB referred for [123I]FP-CIT SPECT imaging were prospectively recruited. Performance in a computerized test of intrinsic alertness was compared between patients with and those without NSD as assessed by [123I]FP-CIT SPECT. Reaction times to auditory stimuli (adjusted for age, sex, and education) were significantly longer in patients with NSD compared to those with a normal [123I]FP-CIT SPECT scan (p < 0.05). Statistical analyses revealed no significant differences comparing reaction times to visual stimuli or dispersion of reaction times between groups. Exploratory analysis in a subgroup of patients with available [18F]FDG PET revealed that longer reaction times were associated with decreased glucose metabolism in the prefrontal cortex (statistical parametric mapping, adjusted for age and sex; p < 0.005, cluster extent > 50 voxels). Computerized assessment of auditory reaction times is able to detect alertness deficits in patients with NSD and might help to measure alertness deficits in patients with LBD and NSD. Future studies in larger samples are needed to evaluate the diagnostic utility of computerized alertness assessment for the differential diagnosis of LBD.

The Cognitive Profile of Ethosuximide in Children.

Although ethosuximide is one of the oldest antiepileptic drugs (AEDs), little information is available about the cognitive side effects of ethosuximide. The aim of this study was to investigate the cognitive profile of ethosuximide. In this cross-sectional study, we used an extensive neuropsychological test battery in patients with epilepsy aged 6-16years who were treated with monotherapy ethosuximide. We evaluated the efficacy of the drug by seizure frequency (seizure free or not). We included 61 patients with a mean age of 9.4 years [standard deviation (SD) 2.7] who used on average 686 mg/day (SD 245) ESM as monotherapy. ESM was effective in the majority of the patients (70% were seizure free for at least 6 months at moment of inclusion). The total study population showed impairments of intelligence, visuomotor, and attentional function including activation/alertness. Comparisons between the well-controlled patients and patients who were not in remission showed significantly lower intelligence values and lower performance on the visual-perceptual and attentional tasks for the group with ongoing seizures. Our results suggested that the higher order cognitive dysfunctions (such as intelligence and visual-perceptual functions) may be regarded as seizure or aetiology effects and that the impaired fluid cognitive functions, such as activation/alertness, sustained auditory attention and attentional control or switching, were due to ESM. This study suggests the attentional dysfunction resulting in psychomotor slowing and alertness deficits may be regarded as effects of ethosuximide. Although no untreated baseline assessment was available, these effects are comparable to those of other AEDs, and ethosuximide may therefore be considered an AED with only mild effects on cognition. As ethosuximide is a first-line therapy for absence seizures in childhood, and drug-induced cognitive impairment may interfere with development, learning, and academic achievement, these findings are of interest to clinicians who prescribe this drug, especially when informing parents.

Inter-hemispheric activation asymmetry and trial-to-trial fluctuations in alertness: An electrophysiological and pupillometric investigation

Event Abstract Back to Event Inter-hemispheric activation asymmetry and trial-to-trial fluctuations in alertness: An electrophysiological and pupillometric investigation Daniel Newman1*, Gerard Loughnane2, Rafael Abe3, Marco Zoratti3, Simon Kelly4, Mark Bellgrove1 and Redmond O’Connell5 1 Monash University, School of Psychological Sciences, Australia 2 Trinity College Dublin, School of Engineering and Trinity centre for Bioengineering, Ireland 3 Federal University of Mato Grosso, Faculty of Medicine, Brazil 4 City College of the City University of New York, Department of Biomedical Engineering, United States 5 Trinity College Dublin, Trinity College Institute of Neuroscience and School of Psychology, Ireland Introduction: Corbetta and Shulman's model of networks for attention suggests that alertness is underpinned by a right-hemisphere-lateralized ventral network, which receives slightly asymmetric (right > left hemisphere) input from the brainstem locus coeruleus/norepinephrine (LC/NE) system. Supporting this, the well characterised increase in parieto-occipital alpha (8-14Hz) with decreased alertness occurs in concert with a rightward shift in the inter-hemispheric balance of alpha power (alpha asymmetry), such that alpha increases more over the right relative to the left hemisphere with time-on-task. Such time-on-task manipulations capture tonic decreases in alertness but fail to account for trial-to-trial fluctuations in alertness which are also influenced by LC/NE. Thus we sought to test the hypothesis that parieto-occipital alpha asymmetry is related to pre-target pupil diameter on a trial-by-trial level. Methods: Healthy participants (50) were exposed to a repetitive random dot motion task lasting ~40mins while pupillometry, EEG and behaviour were recorded. Participants were required to make a speeded button press if they detected coherent motion. Results: As expected the increase in alpha power with time-on-task occurred with a significant rightward shift in hemispheric alpha asymmetry and a significant decrease in behavioural accuracy. Further, reaction time was significantly slower on trials with more rightward alpha asymmetry and on trials with smaller pre-target pupil diameter. Crucially, participants displayed significantly smaller pre-target pupil diameter during trials with more rightward pre-target alpha asymmetry. Conclusion: We show that greater alpha activity over the right relative to the left hemisphere is linked with both decreased tonic alertness and trial-to-trial fluctuations in alertness. These results support Corbetta and Shulman's model which explains the common coupling of spatial and alertness deficits after right hemisphere damage. Keywords: spatial attention, alpha band, alertness, pupil diameter, hemispheric asymmetry Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Attention Citation: Newman D, Loughnane G, Abe R, Zoratti M, Kelly S, Bellgrove M and O’Connell R (2015). Inter-hemispheric activation asymmetry and trial-to-trial fluctuations in alertness: An electrophysiological and pupillometric investigation. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00297 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Mr. Daniel Newman, Monash University, School of Psychological Sciences, Melbourne, Australia, dan.newman86@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Daniel Newman Gerard Loughnane Rafael Abe Marco Zoratti Simon Kelly Mark Bellgrove Redmond O’Connell Google Daniel Newman Gerard Loughnane Rafael Abe Marco Zoratti Simon Kelly Mark Bellgrove Redmond O’Connell Google Scholar Daniel Newman Gerard Loughnane Rafael Abe Marco Zoratti Simon Kelly Mark Bellgrove Redmond O’Connell PubMed Daniel Newman Gerard Loughnane Rafael Abe Marco Zoratti Simon Kelly Mark Bellgrove Redmond O’Connell Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

How does phasic alerting improve performance in patients with unilateral neglect? A systematic analysis of attentional processing capacity and spatial weighting mechanisms

In visual hemi-neglect, non-spatial deficits such as reduced intrinsic alertness can significantly modulate the degree of left visual field inattention. However, to date, the precise mechanisms mediating this effect are hardly understood. In the present study, we assessed the influence of increased alertness on both general attentional capacity (perceptual processing speed) and spatial attentional selection processes (spatial distribution of attentional weighting). For this purpose, a whole-report paradigm based on Bundesen's ‘theory of visual attention’ (TVA) was combined with a non-spatial, visual alerting cue. Three different cue-target stimulus onset asynchronies (SOAs; of 80, 200, and 650ms), allowed us to observe the time course of the alerting-cue effects. A group of six patients with visual hemi-neglect was examined and their performance compared with six healthy control subjects matched for age, gender, and education.In neglect patients, the alerting cue evoked a phasic increase of perceptual processing speed. However, this effect was mainly found in the ipsilateral, i.e. in the “preserved” hemifield. Importantly, however, patients displayed a fast-evolving and short-lasting, phasic modulation of spatial attentional weighting, with a re-distribution of attentional weights from the pathological rightward bias to a normal, more balanced distribution of visual attention. In control participants, the cueing effects on perceptual processing speed and spatial weighting were generally less pronounced than in neglect patients. Replicating results of a prior study, cueing induced a stable, slightly leftward, distribution of attentional weights, whilst in the no-cue condition, a temporary rightward shift of attentional weights was found.This pattern of effects suggests a close interaction between alertness and spatial-attentional weighting in the syndrome of visual hemi-neglect. It supports the hypothesis that the manifestation of spatial neglect involves at least in part intrinsic alertness deficits. It also provides clues to a more detailed account of the mechanisms responsible for alleviating neglect in patients following manipulations of the alertness level, both in the short (cueing) and in the long term (alertness training).

Beta band oscillations as a correlate of alertness — Changes in aging

Older adults (>60years) show attentional deficits in comparison to younger people (18–30years). As beta-band EEG activity has been previously postulated to indicate attentional modulation in the visual system, we searched for possible deficits in beta power in elderly subjects performing an attentional task with spatial differentiation between visual stimuli. We found that in older adults a lower level of beta activity correlated with decreased behavioral performance. As compared to young subjects, older adults expressed decreased activation in beta band during an attentional task, which displayed two different dynamics during the anticipatory period. Those dynamics were accompanied by one of two different behavioral pattern deficits. We hypothesize that one group of elderly participants suffered from difficulty in the activation of attentional processes (alertness deficits), while the other — from difficulty in sustaining those processes (vigilance deficits).

Efficacy of alertness training in a case of brainstem encephalitis: Clinical and theoretical implications

Although attention functions are often impaired after stroke, traumatic brain injury or inflammatory diseases, little is known about the time course and the long-term efficacy of training-induced improvement. The present single case study evaluates the time course and longitudinal stability of attention improvement after alertness training by repeatedly testing the subject between individual training sessions as well as one and seven months after the end of the training. The outpatient (M.P.) trained developed severe alertness deficits following brainstem encephalitis in 2003 without signs of cortical damage, and since then had not achieved full recovery. In 2008, M.P. participated in 15 treatment sessions on 15 separate working days over a period of three weeks. In each session a 45-minute alertness training task was administered, using the CogniPlus ALERT computer training program. Attention performance was assessed by neuropsychological tests four years, one year, and immediately before the therapy after every third training session and three times after the termination of therapy. Furthermore, a self-report questionnaire measured subjective experience of attention in everyday life situations. In order to compare the performance between training sessions, a procedure specialised for psychometric single-case diagnosis was used to analyse the data. Surprisingly, even after three consecutive training sessions, M.P. showed immense improvement in alertness. Furthermore, after two weeks she felt more energetic and more able to concentrate. Six months after the end of the training the improvement remained stable. The unexpectedly fast time course of recovery induced by the training, as well as the stable long-term effects, probably depend on intact cortical structures. In M.P. it appeared that top-down control of the alertness network on impaired brainstem arousal structures had been re-activated by the training procedure and had remained stable across a long time period.

Tonic and phasic alertness training: a novel behavioral therapy to improve spatial and non-spatial attention in patients with hemispatial neglect

Hemispatial neglect is a debilitating disorder marked by a constellation of spatial and non-spatial attention deficits. Patients’ alertness deficits have shown to interact with lateralized attention processes and correspondingly, improving tonic/general alertness as well as phasic/moment-to-moment alertness has shown to ameliorate spatial bias. However, improvements are often short-lived and inconsistent across tasks and patients. In an attempt to more effectively activate alertness mechanisms by exercising both tonic and phasic alertness, we employed a novel version of a continuous performance task (tonic and phasic alertness training, TAPAT). Using a between-subjects longitudinal design and employing sensitive outcome measures of spatial and non-spatial attention, we compared the effects of 9 days of TAPAT (36 min/day) in a group of patients with chronic neglect (N = 12) with a control group of chronic neglect patients (N = 12) who simply waited during the same training period. Compared to the control group, the group trained on TAPAT significantly improved on both spatial and non-spatial measures of attention with many patients failing to exhibit a lateralized attention bias at the end of training. TAPAT was effective for patients with a range of behavioral profiles and lesions, suggesting that its effectiveness may rely on distributed or lower-level attention mechanisms that are largely intact in patients with neglect. In a follow-up experiment, to determine if TAPAT is more effective in improving spatial attention than an active treatment that directly trains spatial attention, we trained three chronic neglect patients on both TAPAT and search training. In all three patients, TAPAT training was more effective in improving spatial attention than search training suggesting that, in chronic neglect, training alertness is a more effective treatment approach than directly training spatial attention.

Alerting deficits in children with attention deficit/hyperactivity disorder: Event-related fMRI evidence

Attention deficit/hyperactivity disorder (ADHD) is one of the most common but poorly understood developmental disorders in childhood. Although neuropsychological studies demonstrate that children with ADHD have attentional alerting deficits, the neurobiological bases of such deficits have not been examined extensively. In this study, by using functional magnetic resonance imaging (fMRI), we explored the neural correlates of intrinsic alertness and phasic alertness deficits in ADHD by comparing twelve boys with ADHD (13.4 ± 1.7 years) with 13 age-matched normal controls (13.2 ± 1.2 years) in a cued target detection task. Behaviorally, compared with the controls, the ADHD group showed a higher overall error rate and a larger reaction time variability in performing the task. At the neural level, children with ADHD showed less activation than the controls in frontal (middle and superior frontal gyrus), parietal (inferior parietal lobe, precuneus) and putamen regions. These results demonstrate that children with ADHD have deficits in alerting functions and these deficits are related to the abnormal activities in frontal and parietal regions subserving top-down attention control processes.

Ampakine (CX717) Effects on Performance and Alertness During Simulated Night Shift Work

Round-the-clock operations in both military and civilian sectors have increased the need for alertness- and performance-maintaining strategies. The potential performance and objective alertness-enhancing effects of CX717 (a novel cognitive enhancer currently being tested in Phase II clinical trials) were evaluated using a simulated night shift work paradigm. In this randomized, double-blind, placebo-controlled, parallel groups design, 48 volunteers underwent 4 consecutive nights of simulated shift work. Each "shift" consisted of the following: at approximately 2145 (just prior to the start of each simulated night shift), volunteers ingested a single oral dose of CX717 200 mg, CX717 400 mg, CX717 1000 mg, or placebo (N = 12 per drug dosage). Performance, alertness, mood, and symptoms were then assessed from 2300 to 0700, followed by a polysomnographically monitored daytime sleep period from 0800 to 1200. Performance and alertness significantly degraded across the simulated night shifts (P < 0.05). None of the dosages of CX717 reversed these effects (P > 0.05). CX717 exerted some effects on daytime sleep, most notably reduction of slow-wave sleep time (P < 0.05). CX71 7 caused very few side effects and none of those were serious or unexpected. At the doses tested, CX717 was not effective for reversing performance and alertness deficits associated with night shift work. Further work evaluating higher doses of CX717 may be warranted, as are studies in which CX717 effects are explored under other conditions (e.g., Alzheimer's dementia, attention deficit disorder).

Functional reorganisation in patients with right hemisphere stroke after training of alertness: a longitudinal PET and fMRI study in eight cases

In patients with alertness deficits due to right hemispheric vascular brain damage, training induced changes in the individual functional networks involved in intrinsic alertness were assessed in a longitudinal positron emission tomography (PET)/fMRI activation study. Patients were trained by administering the alertness routine of the AIXTENT computerized attention training or, in the control condition, by using a computerized training of verbal and topological memory. Before and after the training, both a PET/fMRI and a neuropsychological assessment were carried out. In this paper, we are presenting four patients after alertness training: three, whose alertness performance improved significantly after training, and one, who did not improve. In the patients showing behavioural improvement, the PET/fMRI activation after training revealed partial restitution of the right hemisphere (RH) functional network known to subserve intrinsic alertness in normal subjects, especially in the right dorsolateral or medial frontal cortex. For the patient without behavioural improvement, the PET activation after training showed an increase of activation only in the left hemisphere. Out of the four patients in the memory training control group only one showed significant improvement of alertness. Another patient had an increase of right frontal activation after the training but this did not correspond to behavioural improvement. In a control group of six normal participants, repetition of the alertness activation paradigm in fMRI revealed a decrease of right frontal and parietal activation from the first to a second measurement after 3 weeks, in contrast to the observed training induced effects in the patients.

The process of awakening: a PET study of regional brain activity patterns mediating the re-establishment of alertness and consciousness.

Awakening from sleep entails rapid re-establishment of consciousness followed by the relatively slow (20-30 min later) re-establishment of alertness--a temporal dissociation that facilitates specification of the physiological underpinnings of each of these facets of the awakening process. H(2)(15)O PET was used to assess changes in regional cerebral blood flow (rCBF) upon awakening from stage 2 sleep. Cerebral blood flow (CBF) was most rapidly re-established in centrencephalic regions (e.g. brainstem and thalamus), suggesting that the reactivation of these regions underlies the re-establishment of conscious awareness. Across the ensuing 15 min of wakefulness, further increases in CBF were evident primarily in anterior cortical regions, suggesting that the dissipation of sleep inertia effects (post-awakening performance and alertness deficits) is effected by reactivation of these regions. Concomitant shifts in correlation patterns of regional brain activity across the post-awakening period [in particular, a waning negative correlation between prefrontal cortex and mesencephalic reticular formation (RF) activity, and a waxing positive correlation between prefrontal cortex and ventromedial caudate nucleus (CAUD) activity] suggest that the post-awakening reversal of sleep inertia effects may be mediated by more than mere reactivation--it may also involve the functional reorganization of brain activity. Conversely, stable post-awakening correlations--such as those found between the anterior cingulate cortex (ACC) and most other brain regions--may denote the pattern of functional connectivity that underlies consciousness itself.