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Biomedical subjects

Thomas J Balkin

Publications and source records attributed to Thomas J Balkin.

16 recordsLinked to original sources
PubMed2006

The effects of caffeine, dextroamphetamine, and modafinil on humor appreciation during sleep deprivation.

STUDY OBJECTIVES: Sleep loss consistently impairs performance on measures of alertness, vigilance, and response speed, but its effects on higher-order executive functions are not well delineated. Similarly, whereas deficits in arousal and vigilance can be temporarily countered by the use of several different stimulant medications, it is not clear how these compounds affect complex cognitive processes in sleep-deprived individuals. DESIGN: We evaluated the effects of double-blind administration of 3 stimulant medications or placebo on the ability to appreciate humor in visual (cartoons) or verbal (headlines) stimuli presented on a computer screen following 49.5 hours of sleep deprivation. SETTING: In-residence sleep-laboratory facility at the Walter Reed Army Institute of Research. PARTICIPANTS: Fifty-four healthy adults (29 men, 24 women), ranging in age from 18 to 36 years. INTERVENTIONS: Each participant was randomly assigned to 1 of 3 stimulant medication groups, including caffeine, 600 mg, n = 12; modafinil, 400 mg, n = 11; dextroamphetamine, 20 mg, n = 16; or placebo, n = 14. MEASUREMENTS AND RESULTS: Humor appreciation for cartoon stimuli was enhanced by modafinil relative to both placebo and caffeine, but there was no effect of any stimulant medication on the appreciation of verbal humor during sleep loss. In contrast, all 3 stimulants improved psychomotor response speed, whereas only caffeine and dextroamphetamine improved ratings of subjective sleepiness. CONCLUSIONS: Findings suggest that, despite similar alerting and vigilance-promoting effects, these 3 compounds have significantly different effects on those highly complex cognitive abilities mediated by the pre-frontal cortex.

Adolescent↗
PubMed2006

Impaired decision making following 49 h of sleep deprivation.

Sleep deprivation reduces regional cerebral metabolism within the prefrontal cortex, the brain region most responsible for higher-order cognitive processes, including judgment and decision making. Accordingly, we hypothesized that two nights of sleep loss would impair decision making quality and lead to increased risk-taking behavior on the Iowa Gambling Task (IGT), which mimics real-world decision making under conditions of uncertainty. Thirty-four healthy participants completed the IGT at rested baseline and again following 49.5 h of sleep deprivation. At baseline, volunteers performed in a manner similar to that seen in most samples of healthy normal individuals, rapidly learning to avoid high-risk decks and selecting more frequently from advantageous low-risk decks as the game progressed. After sleep loss, however, volunteers showed a strikingly different pattern of performance. Relative to rested baseline, sleep-deprived individuals tended to choose more frequently from risky decks as the game progressed, a pattern similar to, though less severe than, previously published reports of patients with lesions to the ventromedial prefrontal cortex. Although risky decision making was not related to participant age when tested at rested baseline, age was negatively correlated with advantageous decision making on the IGT, when tested following sleep deprivation (i.e. older subjects made more risky choices). These findings suggest that cognitive functions known to be mediated by the ventromedial prefrontal cortex, including decision making under conditions of uncertainty, may be particularly vulnerable to sleep loss and that this vulnerability may become more pronounced with increased age.

Adult↗
PubMed2006

Age and individual variability in performance during sleep restriction.

The effect of sleep loss on reaction time (RT) performance varies as a function of age, with RTs of older subjects typically showing less decrement (relative to rested baseline) than those of younger subjects. In the current paper, we examined the nature of this relationship in a 7-day sleep restriction study. The number of repeated measures made it possible to model both intra-individual trajectories over days and individual differences in these trajectories. Results revealed (a) consistent individual differences in RT patterns over time after controlling for experimental design effects; (b) less cumulative RT decline among older individuals regardless of the degree of sleep restriction; and (c) consistent individual variability in performance patterns even after accounting for the effects of age.

Adult↗
PubMed2005

Daytime sleep and performance following a zolpidem and melatonin cocktail.

STUDY OBJECTIVES: Pharmacologic enhancement of daytime sleep may help sustain optimal cognitive performance. At effective doses, zolpidem induces sleep but also impairs performance. Combining melatonin with low-dose zolpidem may promote daytime sleep without exacerbating performance impairments seen with high-dose zolpidem alone. DESIGN AND METHODS: Following an 8-hour undisturbed nighttime sleep period, 80 subjects (50 men, 30 women) were administered oral zolpidem 0, 5, 10, or 20 mg at 10:00 am (n = 20 per group) and then oral melatonin 0 or 5 mg at 10:30 am (thus, n = 10 per drug combination) in a double-blind randomized fashion. Subjects napped from 10:00 am to 11:30 am, at which time they were awakened and cognitive tests administered (Restricted Reminding, Paired-Associates, and Psychomotor Vigilance). A second nap ensued from 12:45 pm to 4:00 pm, followed immediately by further testing. RESULTS: Melatonin 5 mg plus zolpidem 0 mg enhanced daytime sleep (P < .05) with no memory or performance impairment (P > .05). Zolpidem 20 mg plus melatonin 0 mg also enhanced daytime sleep (albeit nonsignificantly), but memory and vigilance were impaired (P < .05). Melatonin's sleep-promoting effects were not evident until the second nap. CONCLUSIONS: No advantages to administering melatonin plus zolpidem "cocktails" were evident. Unlike zolpidem, melatonin 5 mg alone improved daytime sleep without impairing memory and vigilance. Functional coupling of sleep-inducing and memory-impairing effects may be specific to benzodiazepine-receptor agonists such as zolpidem, suggesting potential advantages to using melatonin in the operational environment. That melatonin's sleep-promoting effects were delayed for several hours presents a practical consideration that may limit melatonin's usefulness when daytime sleep periods cannot be reliably anticipated or planned in advance.

Adolescent↗
PubMed2005

Performance and alertness effects of caffeine, dextroamphetamine, and modafinil during sleep deprivation.

Stimulants may provide short-term performance and alertness enhancement during sleep loss. Caffeine 600 mg, d-amphetamine 20 mg, and modafinil 400 mg were compared during 85 h of total sleep deprivation to determine the extent to which the three agents restored performance on simple psychomotor tasks, objective alertness and tasks of executive functions. Forty-eight healthy young adults remained awake for 85 h. Performance and alertness tests were administered bi-hourly from 8:00 hours day 2 to 19:00 hours day 5. At 23:50 hours on day 4 (after 64 h awake), subjects ingested placebo, caffeine 600 mg, dextroamphetamine 20 mg, or modafinil 400 mg (n=12 per group). Performance and alertness testing continued, and probe tasks of executive function were administered intermittently until the recovery sleep period (20:00 hours day 5 to 8:00 hours day 5). Bi-hourly postrecovery sleep testing occurred from 10:00 hours to 16:00 hours day 6. All three agents improved psychomotor vigilance speed and objectively measured alertness relative to placebo. Drugs did not affect recovery sleep, and postrecovery sleep performance for all drug groups was at presleep deprivation levels. Effects on executive function tasks were mixed, with improvement on some tasks with caffeine and modafinil, and apparent decrements with dextroamphetamine on others. At the doses tested, caffeine, dextroamphetamine, and modafinil are equally effective for approximately 2-4 h in restoring simple psychomotor performance and objective alertness. The duration of these benefits vary in accordance with the different elimination rates of the drugs. Whether caffeine, dextroamphetamine, and modafinil differentially restore executive functions during sleep deprivation remains unclear.

Adult↗
PubMed2005

Caffeine effects on recovery sleep following 27 h total sleep deprivation.

INTRODUCTION: Caffeine is widely used to reverse alertness and performance decrements. However, caffeine's effects on subsequent recovery sleep and post-recovery performance are not well documented and, therefore, were evaluated. METHODS: Six habitually low (LC: < or = 100 mg x d(-1)) and three habitually high (HC: > or = 400 mg x d(-1)) caffeine users completed a randomized crossover design. After 20 h of wakefulness, repeated doses of caffeine gum [0 (placebo) mg, 100 (low dose) mg, or 300 (high dose) mg] were administered at 03:00, 05:00, and 07:00. At 10:00 (27 h sleep deprivation) subjects slept for 8 h, followed by Psychomotor Vigilance Task (PVT) administration at 33 and 65 min post-awakening. RESULTS: Low dose caffeine increased stage 1 minutes only. However, high dose caffeine impaired sleep maintenance (reduced total sleep time/increased wake) and reduced sleep depth (increased stage 1 minutes/percentage and slow-wave sleep (SWS) latency, and reduced SWS minutes during the first third of the sleep period). With high dose caffeine, LC users had less SWS percentage as compared with HC users. The HC users had reduced stage 2 percentage with high dose caffeine as compared with placebo and low dose caffeine. Caffeine dose and habitual caffeine use did not influence post-recovery sleep PVT performance. DISCUSSION: Caffeine exerts mild deleterious dose-response effects on recovery sleep following total sleep deprivation, primarily early in the sleep period, with potential recovery from these effects after sufficient sleep as suggested by lack of post-recovery sleep performance deficits. Habitual caffeine use appears to minimally reduce caffeine effects.

Adolescent↗
PubMed2004

Comparative utility of instruments for monitoring sleepiness-related performance decrements in the operational environment.

As both military and commercial operations increasingly become continuous, 24-h-per-day enterprises, the likelihood of operator errors or inefficiencies caused by sleep loss and/or circadian desynchrony also increases. Avoidance of such incidents requires the timely application of appropriate interventions--which, in turn, depend on the ability to measure and monitor the performance capacity of individuals in the operational environment. Several factors determine the potential suitability of candidate measures, including their relative sensitivity, reliability, content validity, intrusiveness and cumbersomeness/fieldability. In the present study, the relative sensitivity (defined as the ratio of effect size to 95% confidence interval) of several measures to the effects of sleep loss was compared in a sleep restriction experiment, in which groups were allowed 3, 5, 7, or 9 h time in bed (TIB) across seven consecutive nights. Of the measures compared, the Psychomotor Vigilance Test was among the most sensitive to sleep restriction, was among the most reliable with no evidence of learning over repeated administrations, and possesses characteristics that make it among the most practical for use in the operational environment.

Adult↗
PubMed2004

Fatigue models for applied research in warfighting.

The U.S. Department of Defense (DOD) has long pursued applied research concerning fatigue in sustained and continuous military operations. In 1996, Hursh developed a simple homeostatic fatigue model and programmed the model into an actigraph to give a continuous indication of performance. Based on this initial work, the Army conducted a study of 1 wk of restricted sleep in 66 subjects with multiple measures of performance, termed the Sleep Dose-Response Study (SDR). This study provided numerical estimation of parameters for the Walter Reed Army Institute of Research Sleep Performance Model (SPM) and elucidated the relationships among several sleep-related performance measures. Concurrently, Hursh extended the original actigraph modeling structure and software expressions for use in other practical applications. The model became known as the Sleep, Activity, Fatigue, and Task Effectiveness (SAFTE) Model, and Hursh has applied it in the construction of a Fatigue Avoidance Scheduling Tool. This software is designed to help optimize the operational management of aviation ground and flight crews, but is not limited to that application. This paper describes the working fatigue model as it is being developed by the DOD laboratories, using the conceptual framework, vernacular, and notation of the SAFTE Model. At specific points where the SPM may differ from SAFTE, this is discussed. Extensions of the SAFTE Model to incorporate dynamic phase adjustment for both transmeridian relocation and shift work are described. The unexpected persistence of performance effects following chronic sleep restriction found in the SDR study necessitated some revisions of the SAFTE Model that are also described. The paper concludes with a discussion of several important modeling issues that remain to be addressed.

Aviation↗
PubMed2004

Modulating the homeostatic process to predict performance during chronic sleep restriction.

BACKGROUND: In most current sleep/performance models, the homeostatic process is generally conceived as a simple reservoir in which performance capacity increases exponentially during sleep and decays either linearly or exponentially during wakefulness. Models that include this notional homeostatic process have been successful for describing sleep-performance data under conditions of irregular sleep schedules, jet lag, and short periods of total sleep loss. However, recently described data from sleep restriction studies indicate that recovery following chronically restricted sleep is considerably slower than would be predicted by these models. These findings suggest that chronic sleep restriction induces relatively long-term, slow-recovering changes in brain physiology that affect alertness and performance. METHODS: This paper describes, both conceptually and mathematically, a generic modification to sleep/performance models that facilitates the ability to predict the rate at which alertness and performance restoration occurs during recovery sleep following chronic sleep restriction. Weighted nonlinear least-squares methods were used to compare the proposed modulated homeostatic model with recent sleep/performance observations during chronic sleep restriction and recovery. RESULTS: When compared with the classical Walter Reed homeostatic model, this proposed model was found to provide a better description of sleep restriction and recovery observations. The proposed model was also found to be consistent with the data from a recent University of Pennsylvania study. CONCLUSIONS: These two models make significantly different predictions of performance during both the recovery phase and the chronic sleep restriction phase.

Data Interpretation, Statistical↗
PubMed2004

Modafinil vs. caffeine: effects on fatigue during sleep deprivation.

INTRODUCTION: The extent to which modafinil and caffeine reverse fatigue effects (defined as performance decrements with time on task) during total sleep deprivation was investigated. METHODS: There were 50 healthy young adults who remained awake for 54.5 h (06:30 day 1 to 13:00 day 3). A 10-min vigilance test was administered bi-hourly from 08:00 day 1 until 22:00 day 2. At 23:55 day 2 (after 41.5 h awake), double-blind administration of one of five drug doses (placebo; modafinil 100, 200, or 400 mg; or caffeine 600 mg; n = 10 per group) was followed by hourly testing from 00:00 through 12:00 day 3. Response speed (reciprocal of reaction time) across the 10-min task (by 1-min block) was analyzed prior to and after drug administration. RESULTS: A fatigue effect (response speed degradation across the 10-min task) was exacerbated by sleep deprivation and circadian rhythmicity. Prior to the drug, this effect was maximal between 08:00 and 12:00 day 3 (24-28 h sleep deprivation). Modafinil 400 mg attenuated fatigue in a manner comparable to that seen with caffeine 600 mg; these effects were especially salient during the circadian nadir of performance (06:00 through 10:00); modafinil 200 mg also reversed fatigue, but for a shorter duration (3 min) than modafinil 400 mg (8 min) or caffeine 600 mg (6 min). DISCUSSION AND CONCLUSIONS: Time-on-task effects contributed to the performance degradation seen during sleep deprivation; effects which were reversed by caffeine and, at appropriate doses, by modafinil. Because the duration of efficacy for reversing time-on-task effects was shorter at lower drug dosages, the latter must be considered when determining the appropriate dose to use during sustained operations.

Adolescent↗
PubMed2003

Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study.

Daytime performance changes were examined during chronic sleep restriction or augmentation and following subsequent recovery sleep. Sixty-six normal volunteers spent either 3 (n = 18), 5 (n= 16), 7 (n = 16), or 9 h (n = 16) daily time in bed (TIB) for 7 days (restriction/augmentation) followed by 3 days with 8 h daily TIB (recovery). In the 3-h group, speed (mean and fastest 10% of responses) on the psychomotor vigilance task (PVT) declined, and PVT lapses (reaction times greater than 500 ms) increased steadily across the 7 days of sleep restriction. In the 7- and 5-h groups speed initially declined, then appeared to stabilize at a reduced level; lapses were increased only in the 5-h group. In the 9-h group, speed and lapses remained at baseline levels. During recovery, PVT speed in the 7- and 5-h groups (and lapses in the 5-h group) remained at the stable, but reduced levels seen during the last days of the experimental phase, with no evidence of recovery. Speed and lapses in the 3-h group recovered rapidly following the first night of recovery sleep; however, recovery was incomplete with speed and lapses stabilizing at a level comparable with the 7- and 5-h groups. Performance in the 9-h group remained at baseline levels during the recovery phase. These results suggest that the brain adapts to chronic sleep restriction. In mild to moderate sleep restriction this adaptation is sufficient to stabilize performance, although at a reduced level. These adaptive changes are hypothesized to restrict brain operational capacity and to persist for several days after normal sleep duration is restored, delaying recovery.

Adaptation, Psychological↗
PubMed2002

The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers.

OBJECTIVE: The purpose of this study was to evaluate the rate of absorption and relative bioavailability of caffeine from a Stay Alert chewing gum and capsule formulation. METHODS: This was a double blind, parallel, randomized, seven treatment study. The treatment groups were: 50, 100, and 200 mg gum, 50, 100, and 200 mg capsule, and a placebo. Subjects consisted of 84 (n=12 per group); healthy, non-smoking, males who had abstained from caffeine ingestion for at least 20 h prior to dosing and were randomly assigned to the treatment groups. Blood samples were collected pre-dose and at 5, 15, 25, 35, 45, 55, 65, 90 min and 2, 3, 4, 6, 8, 12, 16 and 29 h post administration. Plasma caffeine levels were analyzed by a validated UV-HPLC method. RESULTS: Mean Tmax for the gum groups ranged from 44.2 to 80.4 min as compared with 84.0-120.0 min for the capsule groups. The Tmax, for the pooled data was significantly lower (P<0.05) for the gum groups as compared with the capsule groups. Differences in Tmax were significant for the 200 mg capsule versus 200 mg gum (P<0.05). The mean ka values for the gum group ranged from 3.21 to 3.96 h-1 and for the capsule groups ranged from 1.29 to 2.36 h-1. Relative bioavailability of the gum formulation after the 50, 100 and 200 mg dose was 64, 74 and 77%, respectively. When normalized to the total drug released from the gum (85%), the relative bioavailability of the 50, 100 and 200 mg dose were 75, 87, and 90%, respectively. No statistical differences were found for Cmax and AUCinf for comparisons of the gum and capsule formulations at each dose. Within each dose level, there were no significant formulation related differences in Cmax. No significant differences were observed in the elimination of caffeine after the gum or capsule. CONCLUSIONS: The results suggest that the rate of drug absorption from the gum formulation was significantly faster and may indicate absorption via the buccal mucosa. In addition, for the 100 and 200 mg groups, the gum and capsule formulations provide near comparable amounts of caffeine to the systemic circulation. These findings suggest that there may be an earlier onset of pharmacological effects of caffeine delivered as the gum formulation, which is advantageous in situations where the rapid reversal of alertness and performance deficits resulting from sleep loss is desirable.

Adolescent↗
PubMed2002

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.

Adult↗
PubMed2001

Maintaining alertness and performance during sleep deprivation: modafinil versus caffeine.

RATIONALE: The performance and alertness effects of modafinil were evaluated to determine whether modafinil should replace caffeine for restoring performance and alertness during total sleep deprivation in otherwise healthy adults. OBJECTIVES: Study objectives were to determine (a) the relative efficacy of three doses of modafinil versus an active control dose of caffeine 600 mg; (b) whether modafinil effects are dose-dependent; and (c) the extent to which both agents maintain performance and alertness during the circadian trough. METHODS: Fifty healthy young adults remained awake for 54.5 h (from 6:30 a.m. day 1 to 1:00 p.m. on day 3) and performance and alertness tests were administered bi-hourly from 8:00 a.m. day 1 until 10:00 p.m. day 2. At 11:55 p.m. on day 2 (after 41.5 h awake), subjects received double blind administration of one of five drug doses: placebo; modafinil 100, 200, or 400 mg; or caffeine 600 mg ( n=10 per group), followed by hourly testing from midnight through 12:00 p.m. on day 3. RESULTS: Performance and alertness were significantly improved by modafinil 200 and 400 mg relative to placebo, and effects were comparable to those obtained with caffeine 600 mg. Although a trend toward better performance at higher modafinil doses suggested a dose-dependent effect, differences between modafinil doses were not significant. Performance enhancing effects were especially salient during the circadian nadir (6:00 a.m. through 10:00 a.m.). Few instances of adverse subjective side effects (nausea, heart pounding) were reported. CONCLUSIONS: Like caffeine, modafinil maintained performance and alertness during the early morning hours, when the combined effects of sleep loss and the circadian trough of performance and alertness trough were manifest. Thus, equivalent performance- and alertness-enhancing effects were obtained with drugs possessing different mechanisms of action. However, modafinil does not appear to offer advantages over caffeine (which is more readily available and less expensive) for improving performance and alertness during sleep loss in otherwise normal, healthy adults.

Administration, Oral↗