RESUMEN
Coordination of strategies for transitioning psychoactive pharmacological compounds from basic laboratory research to the field environment has been an ongoing effort among military laboratories. Several workshops have been held specifically to address the operationally relevant issues and other military and scientific challenges as they relate to the enhancement and sustainability of cognitive performance. In this preface, we tie together recommendations of the Pharmacological Strategies Focus Team for one such Workshop, review current literature, and discuss findings reported at recent professional meetings. The papers presented within this pharmacology section are discussed. These section papers are organized into three areas of operational relevance--the first assesses the effectiveness of a treatment given for migraines, a condition with known detrimental effects on productivity and readiness; the second discusses ethical considerations surrounding the use of pharmaceutical countermeasures for fatigue in the operational environment; and the third discusses a case report highlighting the aeromedical considerations regarding selective serotonin reuptake inhibitors (SSRIs) and aviator flight performance, particularly as assessed with neuropsychological testing. The papers and commentaries in this section encourage us to consider the complex variables effecting the decisions to administer pharmacological agents, as the impact of their use is weighed against the cognitive performance effects they may have in the operational environment.
Asunto(s)
Cognición/efectos de los fármacos , Medicina Militar , Personal Militar/psicología , Psicotrópicos , Análisis y Desempeño de Tareas , Congresos como Asunto , Fatiga/prevención & control , Humanos , Investigación OperativaRESUMEN
Changes in maximal saccadic velocity (SV), initial pupil diameter (IPD), constriction latency (CL) and constriction amplitude (CA) determined by the pupillary light reflex have been found to be sensitive indicators of impairment as a result of drugs, sleepiness, and/or fatigue. Ambient illuminance and time of day are controlled when these indices are applied as repeated measures in fitness-for-duty determinations. The application of oculometrics in unrestricted operational environments, where ambient illuminance and time-of-day testing are not constant, requires understanding of, and potential compensation for, the effects of, and interactions among, these multiple uncontrolled variables. SV, IPD, CL, and CA were evaluated in the morning and evening on two consecutive days following adequate nightly sleep under one baseline ambient illuminance and seven test ambient illuminances. Sixteen healthy volunteers (21-38 years, eight females/eight males) participated. Within and across days, SV was unaffected by decreasing ambient light or time-of-day effects. With the increase of ambient light from 670 to 3300 lx, CL decreased by 1%, while IPD and CA decreased by 17% and 20%, respectively. IPD increased with time of day by 1-10% (IPD was smaller in the morning). The results show that SV and CL are essentially resistant to changes in ambient light and time-of-day effects, simplifying their application in uncontrolled operational environments.
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Iluminación , Reflejo Pupilar , Movimientos Sacádicos , Adulto , Femenino , Humanos , Masculino , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
Sleep loss temporarily impairs vigilance and sustained attention. Because these cognitive abilities are believed to be mediated predominantly by the right cerebral hemisphere, this article hypothesized that continuous sleep deprivation results in a greater frequency of inattention errors within the left versus right visual fields. Twenty-one participants were assessed several times each day during a 40-h period of sustained wakefulness and following a night of recovery sleep. At each assessment, participants engaged in a continuous serial addition task while simultaneously monitoring a 150 degrees visual field for brief intermittent flashes of light. Overall, omission errors were most common in the leftmost peripheral field for all sessions, and did not show any evidence of a shift in laterality as a function of sleep deprivation. Relative to rested baseline and postrecovery conditions, sleep deprivation resulted in a global increase in omission errors across all visual locations and a general decline in serial addition performance. These findings argue against the hypothesis that sleep deprivation produces lateralized deficits in attention and suggest instead that deficits in visual attention produced by sleep deprivation are global and bilateral in nature.
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Atención/fisiología , Lateralidad Funcional/fisiología , Privación de Sueño/fisiopatología , Campos Visuales/fisiología , Adulto , Femenino , Humanos , Masculino , Estimulación Luminosa/métodos , Desempeño Psicomotor/fisiología , Tiempo de Reacción/fisiología , Factores de TiempoRESUMEN
BACKGROUND: High-frequency EEG (HFE) as a potential predictor of alertness/drowsiness was first proposed by Kaplan and Loparo. Sampling EEG at 950 Hz, they established an HFE bandwidth of interest ranging from 100-475 Hz. We extend their work by applying discrete Fourier transform (DFT) of HFE signals sampled at 1000 Hz and partitioned into spectral bands along specific frequency ranges for the assessment of sleep-wake state transition, sleep, and active cognitive engagement. METHODS: There were 13 volunteers (6 men, 7 women, 30 +/- 3 yr) who participated in a 40-h sleep-deprivation study, during which time they performed multiple cognitive tasks. EEG, in synchrony with other physiological signals, was collected at a sampling rate of 1000 Hz. EEG and task performance results from two volunteers are discussed in this preliminary analysis of the C3-C4 region data. Spectral components obtained from DFT are delineated into five main frequency bands: low, (LFB, 1-15 Hz); intermediate (IFB, 16-50 Hz); and 3 high frequency bands: HFB1 (51-100 Hz); HFB2 (101-200 Hz); and HFB3 (201-500 Hz) for analysis purposes. RESULTS: LFB in the 1-15 Hz range at 0.40 spectrum proportion indicated declining alertness; LFB above 0.50 signals transition to sleep; and LFB at 0.70 indicates Stage 2/3 sleep. HFB3 in the 201-500 Hz range at 0.25 and above was a marker of cognitive function and/or capacity. CONCLUSIONS: HFE may provide a quantitative measure of cognitive function capacity. LFB may provide a measure for awake, asleep, or awake-sleep transition, and HFB3 an estimate of cognitive task engagement. HFE may be applied for electroencephalographic monitoring of cognitive performance.
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Cognición/fisiología , Electroencefalografía , Adulto , Nivel de Alerta/fisiología , Atención/fisiología , Femenino , Análisis de Fourier , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Sueño/fisiología , Privación de Sueño/fisiopatología , Análisis y Desempeño de Tareas , Percepción Visual/fisiologíaRESUMEN
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.
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Antioxidantes/farmacología , Ritmo Circadiano , Hipnóticos y Sedantes/farmacología , Melatonina/farmacología , Desempeño Psicomotor/efectos de los fármacos , Piridinas/farmacología , Sueño/efectos de los fármacos , Adolescente , Adulto , Antioxidantes/administración & dosificación , Antioxidantes/análisis , Cognición/efectos de los fármacos , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Masculino , Melatonina/administración & dosificación , Melatonina/análisis , Recuerdo Mental/efectos de los fármacos , Piridinas/administración & dosificación , Saliva/química , Vigilia/efectos de los fármacos , ZolpidemRESUMEN
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.
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Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/uso terapéutico , Cafeína/farmacología , Cafeína/uso terapéutico , Estimulantes del Sistema Nervioso Central/farmacología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Fatiga/tratamiento farmacológico , Desempeño Psicomotor/efectos de los fármacos , Privación de Sueño , Adolescente , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , ModafiniloRESUMEN
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.