Richard Olmstead

Real-Time Analysis of EEG Indexes of Alertness, Cognition, and Memory Acquired With a Wireless EEG Headset

The integration of brain monitoring into the man-machine interface holds great promise for real-time assessment of operator status and intelligent allocation of tasks between machines and humans. This article presents an integrated hardware and software solution for acquisition and real-time analysis of the electroencephalogram (EEG) to monitor indexes of alertness, cognition, and memory. Three experimental paradigms were evaluated in a total of 45 participants to identify EEG indexes associated with changes in cognitive workload: the Warship Commander Task (WCT), a simulated navy command and control environment that allowed workload levels to be systematically manipulated; a cognitive task with three levels of difficulty and consistent sensory inputs and motor outputs; and a multisession image learning and recognition memory test. Across tasks and participants, specific changes in the EEG were identified that were reliably associated with levels of cognitive workload. The EEG indexes were also shown to change as a function of training on the WCT and the learning and memory task. Future applications of the system to augment cognition in military and industrial environments are discussed.

Sleep Loss Activates Cellular Inflammatory Signaling

BACKGROUND Accumulating evidence suggests that sleep disturbance is associated with inflammation and related disorders including cardiovascular disease, arthritis, and diabetes mellitus. This study was undertaken to test the effects of sleep loss on activation of nuclear factor (NF)-kappaB, a transcription factor that serves a critical role in the inflammatory signaling cascade. METHODS In 14 healthy adults (seven women; seven men), peripheral blood mononuclear cell NF-kappaB was repeatedly assessed, along with enumeration of lymphocyte subpopulations, in the morning after baseline sleep, partial sleep deprivation (awake from 11 pm to 3:00 am), and recovery sleep. RESULTS In the morning after a night of sleep loss, mononuclear cell NF-kappaB activation was significantly greater compared with morning levels following uninterrupted baseline or recovery sleep, in which the response was found in female but not in male subjects. CONCLUSIONS These results identify NF-kappaB activation as a molecular pathway by which sleep disturbance may influence leukocyte inflammatory gene expression and the risk of inflammation-related disease.

Neural Substrates of Resisting Craving during Cigarette Cue Exposure

BACKGROUND In cigarette smokers, the most commonly reported areas of brain activation during visual cigarette cue exposure are the prefrontal, anterior cingulate, and visual cortices. We sought to determine changes in brain activity in response to cigarette cues when smokers actively resist craving. METHODS Forty-two tobacco-dependent smokers underwent functional magnetic resonance imaging, during which they were presented with videotaped cues. Three cue presentation conditions were tested: cigarette cues with subjects allowing themselves to crave (cigarette cue crave), cigarette cues with the instruction to resist craving (cigarette cue resist), and matched neutral cues. RESULTS Activation was found in the cigarette cue resist (compared with the cigarette cue crave) condition in the left dorsal anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and precuneus. Lower magnetic resonance signal for the cigarette cue resist condition was found in the cuneus bilaterally, left lateral occipital gyrus, and right postcentral gyrus. These relative activations and deactivations were more robust when the cigarette cue resist condition was compared with the neutral cue condition. CONCLUSIONS Suppressing craving during cigarette cue exposure involves activation of limbic (and related) brain regions and deactivation of primary sensory and motor cortices.

Sleep Disturbance and Depression Recurrence in Community-Dwelling Older Adults: A Prospective Study

OBJECTIVE A prior depressive episode is thought to increase the risk of depression. However, among older adults with prior depression, it is unclear whether sleep disturbance predicts depression recurrence independent of other depressive symptoms. METHOD A 2-year prospective cohort study was conducted with 351 community-dwelling older adults ages 60 years and older: 145 persons with a history of major or nonmajor depression in full remission and 206 without a prior history of depression or any mental illness. The participants were assessed at baseline, 6 weeks, 1 year, and 2 years for depressive episodes, depressive symptoms, sleep quality, and chronic medical disease. RESULTS Twenty-three subjects (16.9%) with prior depression developed depressive episodes during follow-up, compared to only one person in the group without prior mental illness (0.5%). Within the group with prior depression, depression recurrence was predicted by sleep disturbance, and this association was independent of other depressive symptoms, chronic medical disease, and antidepressant medication use. CONCLUSIONS This study is the first to demonstrate that sleep disturbance acts as an independent risk factor for depression recurrence in community-dwelling older adults. To identify older adults at risk for depression, a two-step strategy can be employed, which involves assessment of the presence of a prior depressive episode along with sleep disturbance.

Yoga for persistent fatigue in breast cancer survivors: A randomized controlled trial

Cancer‐related fatigue afflicts up to 33% of breast cancer survivors, yet there are no empirically validated treatments for this symptom.

Clinical pharmacokinetics of nasal nicotine delivery : A review and comparison to other nicotine systems

SummaryRapid drug delivery (arterial ‘boli’) and high drug concentrations occur with nicotine inhaled in smoke. These are believed to be key elements in producing addiction to cigarettes. Preparations which reduce the rate of delivery and/or concentration of nicotine have been introduced as treatments for smoking cessation.These nicotine medications work by relieving withdrawal and preventing relapse associated with abrupt cessation of smoking. The pharmacokinetics of each system are expected to affect efficacy and treatment dependence. Nasal administration systems have been developed to more closely approximate cigarette delivery for improved efficacy in clinical application and for more control in systematic testing of nicotine. With laboratory tested nasal application systems (clinical drug and experimental devices), venous plasma concentrations after a single dose range between 5 and 12 µg/L.Higher steady-state blood nicotine concentrations (16 to 29µg/L) have been reported for ad libitum clinical self-administration with a nicotine nasal spray. Time to peak plasma concentration (tmax) with nasal administration is around 11 to 13 minutes for 1mg doses. This rise time is slower than for cigarette delivery but faster than the other nicotine treatments. Venous plasma concentrations are considerably lower than tobacco product concentrations and fall within the range of the lower dose nicotine treatments (e.g. 2mg gum vs 4mg gum).The profile of nasal nicotine administration was designed for certain subsets of smokers. Efficacy trials show consistent superiority of nasal administration over placebo although the comparative efficacy among nicotine treatments remains to be determined. The more rapid onset and user control of nasal nicotine may impose a higher risk for treatment dependence compared with a slower, passive system such as the patch. It may not produce more dependence than other faster-acting treatment systems (e.g. nicotine gum).

Sleep loss activates cellular markers of inflammation: sex differences.

Sleep disturbance is associated with inflammation and related disorders including cardiovascular disease, arthritis, and diabetes mellitus. Given sex differences in the prevalence of inflammatory disorders with stronger associations in females, this study was undertaken to test the effects of sleep loss on cellular mechanisms that contribute to proinflammatory cytokine activity. In 26 healthy adults (11 females; 15 males), monocyte intracellular proinflammatory cytokine production was repeatedly assessed at 08:00, 12:00, 16:00, 20:00, and 23:00h during a baseline period and after partial sleep deprivation (awake from 23:00 to 3.00h). In the morning after a night of sleep loss, monocyte production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) differentially changed between the two sexes. Whereas both females and males showed a marked increase in the lipopolysaccharide (LPS) - stimulated production of IL-6 and TNF-alpha in the morning immediately after PSD, production of these cytokines during the early- and late evening was increased in the females as compared to decreases in the males. Sleep loss induces a functional alteration of monocyte proinflammatory cytokine responses with females showing greater cellular immune activation as compared to changes in males. These results have implications for understanding the role of sleep disturbance in the differential risk profile for inflammatory disorders between the sexes.

Augmenting immune responses to varicella zoster virus in older adults: a randomized, controlled trial of Tai Chi.

OBJECTIVES: To evaluate the effects of a behavioral intervention, Tai Chi, on resting and vaccine‐stimulated levels of cell‐mediated immunity (CMI) to varicella zoster virus (VZV) and on health functioning in older adults.

Sleep loss exacerbates fatigue, depression, and pain in rheumatoid arthritis.

STUDY OBJECTIVES Disturbances of sleep are hypothesized to contribute to pain. However, experimental data are limited to healthy pain-free individuals. This study evaluated the effect of sleep loss during part of the night on daytime mood symptoms and pain perceptions in patients with rheumatoid arthritis in comparison with control subjects. DESIGN A between-groups laboratory study with assessment of mood symptoms and pain perception before and after partial night sleep deprivation (PSD; awake 23:00 hr to 03:00 hr). SETTING General clinical research center. PARTICIPANTS Patients with rheumatoid arthritis (n = 27) and volunteer comparison control subjects (n = 27). MEASUREMENTS Subjective reports of sleep, mood symptoms and pain, polysomnographic assessment of sleep continuity, and subjective and objective assessment of rheumatoid arthritis-specific joint pain. RESULTS PSD induced differential increases in self-reported fatigue (P < 0.09), depression (P < 0.04), anxiety (P < 0.04), and pain (P < 0.01) in patients with rheumatoid arthritis compared with responses in control subjects, in whom differential increases of self-reported pain were independent of changes in mood symptoms, subjective sleep quality, and objective measures of sleep fragmentation. In the patients with rheumatoid arthritis, PSD also induced increases in disease-specific activity as indexed by self-reported pain severity (P < 0.01) and number of painful joints (P < 0.02) as well as clinician-rated joint counts (P < 0.03). CONCLUSION This study provides the first evidence of an exaggerated increase in symptoms of mood and pain in patients with rheumatoid arthritis after sleep loss, along with an activation of rheumatoid arthritis-related joint pain. Given the reciprocal relationship between sleep disturbances and pain, clinical management of pain in patients with rheumatoid arthritis should include an increased focus on the prevention and treatment of sleep disturbance in this clinical population.

Ventral Striatal Dopamine Release in Response to Smoking a Regular vs a Denicotinized Cigarette

Prior studies have demonstrated that both nicotine administration and cigarette smoking lead to dopamine (DA) release in the ventral striatum/nucleus accumbens. In tobacco-dependent individuals, smoking denicotinized cigarettes leads to reduced craving, but less pleasure, than smoking regular cigarettes. Using denicotinized cigarettes and 11C-raclopride positron emission tomography (PET) scanning, we sought to determine if nicotine is necessary for smoking-induced DA release. Sixty-two tobacco-dependent smokers underwent 11C-raclopride PET scanning, during which they smoked either a regular or denicotinized cigarette (double-blind). Change in 11C-raclopride binding potential (BP) in the ventral striatum from before to after smoking was determined as an indirect measure of DA release. Cigarette craving, anxiety, and mood were monitored during scanning. Smoking a regular cigarette resulted in a significantly greater mean reduction in ventral striatal 11C-raclopride BP than smoking a denicotinized cigarette. Although both groups had reductions in craving and anxiety with smoking, the regular cigarette group had a greater improvement in mood. For the total group, change in BP correlated inversely with change in mood, indicating that greater smoking-induced DA release was associated with more smoking-related mood improvement. Thus, nicotine delivered through cigarette smoking appears to be important for ventral striatal DA release. Study findings also suggest that mood improvement from smoking is specifically related to ventral striatal DA release.