Substituted judgment by surrogates is not more accurate than random chance. Discussion between patient and surrogate about life support correlated with more accurate substituted judgment.

Patients with nonthyroid illness (NTI) often have reduced serum T3, free T3, T4, and free T4 concentrations. Paradoxically, serum TSH is usually in the normal range. The data suggest a diagnosis of hypothalamic hypothyroidism, in which TSH may have reduced biological activity because TRH, which is necessary for key steps in the glycosylation of TSH, is deficient. To study the glycosylation of TSH in patients with NTI, we measured the serum TSH concentration in 36 such patients hospitalized on our intensive care units and compared the results with those from a group of 18 normal subjects. Serum TSH was measured in 2 assays: 1) a sensitive TSH RIA of unextracted serum (TSH-RIA) and 2) a RIA of serum TSH after its extraction with Concanavalin-A (Con-A), a lectin which binds glycoproteins containing mannose residues in their oligosaccharide side-chains (TSH-Con-A). The ratio of TSH-Con-A to TSH-RIA was significantly reduced in the NTI patients [0.61 +/- 0.03 (+/- SE) vs. 0.89 +/- 0.05 in the normal subjects] due to reduced binding of the TSH to the Con-A. This change was not dependent on the extent of the abnormalities of thyroid hormone levels. The data suggest that the TSH secreted in NTI has altered glycosylation which is associated with reduced biological activity. This finding may explain in part the low serum T4 level in NTI patients in the face of an apparently normal immunoreactive TSH level.

Substituted judgment by surrogates is not more accurate than random chance. Discussion between patient and surrogate about life support correlated with more accurate substituted judgment.

Growing evidence supports the idea that the ultimate biofeedback is to reward sensory pleasure (e.g., enhanced visual clarity) in real-time to neural circuits that are associated with a desired performance, such as excellent memory retrieval. Neurofeedback is biofeedback that uses real-time sensory reward to brain activity associated with a certain performance (e.g., accurate and fast recall). Working memory is a key component of human intelligence. The challenges are in our current limited understanding of neurocognitive dysfunctions as well as in technical difficulties for closed-loop feedback in true real-time. Here we review recent advancements of real time neurofeedback to improve memory training in healthy young and older adults. With new advancements in neuromarkers of specific neurophysiological functions, neurofeedback training should be better targeted beyond a single frequency approach to include frequency interactions and event-related potentials. Our review confirms the positive trend that neurofeedback training mostly works to improve memory and cognition to some extent in most studies. Yet, the training typically takes multiple weeks with 2–3 sessions per week. We review various neurofeedback reward strategies and outcome measures. A well-known issue in such training is that some people simply do not respond to neurofeedback. Thus, we also review the literature of individual differences in psychological factors e.g., placebo effects and so-called “BCI illiteracy” (Brain Computer Interface illiteracy). We recommend the use of Neural modulation sensitivity or BCI insensitivity in the neurofeedback literature. Future directions include much needed research in mild cognitive impairment, in non-Alzheimer’s dementia populations, and neurofeedback using EEG features during resting and sleep for memory enhancement and as sensitive outcome measures.

W HY DOES ONE SLEEP? Although this question has undoubtedly been pondered since the dawn of man, the answer is not much closer now than in 1605 when William Shakespeare wrote, in Macbeth, "Sleep, that knits up the raveled sleeve of care, the death of each day's life, sore labor's bath, balm of hurt minds, great nature's second course, chief nourisher in life's feast" (Act II, Scene 1). It is known that sleep occurs throughout the animal kingdom, suggesting it serves an important purpose. As we know from our own sleep indiscretions, sleep is necessary for normal neurologic and other physiologic functioning. This article will focus on relevant aspects of normal sleep and common sleep disorders and their management. NORMAL SLEEP Stages of SleepWith the advent of electroencephalography in the early 20th century, we have found that sleep in mammals and birds comprises 2 distinct entities: rapid eye movement (REM) sleep and non-REM sleep, which is itself divided into 4 stages: stage 1 is transition from wake, stage 2 is light sleep, and stages 3 and 4 are termed delta sleep, slow wave sleep, or deep sleep. REM sleep and deep sleep correlate with restful sleep, and the amount of REM and deep sleep generally are found to increase in recovery sleep after partial or total sleep deprivation. REM sleep is a very active state for the brain, during which dreaming occurs, typically representing about 20% to 25% of the sleep time. REM sleep is associated with an active inhibition of movement of all muscles except diaphragm and extraocular muscles. Deep sleep is characterized by slow, synchronous brain waves and low brain metabolism; it represents from 25% of sleep in young adults to little or none in healthy elderly people. There is a normal oscillation of about 90 minutes' duration, termed an ultradian rhythm, between deep and REM sleep; REM sleep episodes become longer and deep sleep episodes shorter as the sleep period progresses. Sleep PhysiologyThe sleep-wake switch. The sleep and awake states are promoted by competing neural pathways Sleep and wake states involve interaction among many brain centers via multiple neurotransmitters, including dopamine, norepinephrine, hypocretin, acetylcholine, histamine and serotonin (wake promoting), and γ amino butyric acid (GABA) and melatonin (sleep promoting). Most medications for insomnia or hypersomnia act on elements of these neural systems. Initial treatment of insomnia includes sleep hygiene measures. Cognitive-behavioral therapy for insomnia is useful. Medications approved by the Food and Drug Administration for insomnia act on GABA receptors or on melatonin receptors. A frequent cause of insomnia is restless legs syndrome, which is linked to reduced dopaminergic activity in brain structures; idiopathic restless legs syndrome is best treated with dopamine agonists such as ropinerole or pramipexole. Excessive daytime sleepiness is most often due to insufficient sleep hours or sleep apnea but is also caused by medications, illnesses, narcolepsy, or idiopathic hypersomnia. Stimulant...