14 research outputs found

    A Conserved Behavioral State Barrier Impedes Transitions between Anesthetic-Induced Unconsciousness and Wakefulness: Evidence for Neural Inertia

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    One major unanswered question in neuroscience is how the brain transitions between conscious and unconscious states. General anesthetics offer a controllable means to study these transitions. Induction of anesthesia is commonly attributed to drug-induced global modulation of neuronal function, while emergence from anesthesia has been thought to occur passively, paralleling elimination of the anesthetic from its sites in the central nervous system (CNS). If this were true, then CNS anesthetic concentrations on induction and emergence would be indistinguishable. By generating anesthetic dose-response data in both insects and mammals, we demonstrate that the forward and reverse paths through which anesthetic-induced unconsciousness arises and dissipates are not identical. Instead they exhibit hysteresis that is not fully explained by pharmacokinetics as previously thought. Single gene mutations that affect sleep-wake states are shown to collapse or widen anesthetic hysteresis without obvious confounding effects on volatile anesthetic uptake, distribution, or metabolism. We propose a fundamental and biologically conserved concept of neural inertia, a tendency of the CNS to resist behavioral state transitions between conscious and unconscious states. We demonstrate that such a barrier separates wakeful and anesthetized states for multiple anesthetics in both flies and mice, and argue that it contributes to the hysteresis observed when the brain transitions between conscious and unconscious states

    Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins.

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    A molecular test for Alzheimer's disease could lead to better treatment and therapies. We found 18 signaling proteins in blood plasma that can be used to classify blinded samples from Alzheimer's and control subjects with close to 90% accuracy and to identify patients who had mild cognitive impairment that progressed to Alzheimer's disease 2-6 years later. Biological analysis of the 18 proteins points to systemic dysregulation of hematopoiesis, immune responses, apoptosis and neuronal support in presymptomatic Alzheimer's disease

    Dissociations between motor timing, motor coordination, and time perception after the administration of alcohol or caffeine

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    RATIONALE: The impacts of psychoactive drugs on timing have usefully informed theories of timing and its substrates. OBJECTIVES: The objectives of the study are to test the effects of alcohol and caffeine on the explicit timing involved in tapping with the implicit timing observed in the coordinated picking up of an object, and with the temporal discrimination. MATERIALS AND METHODS: Participants in the "alcohol" experiment (N = 16) received placebo, "low" (0.12 g/kg or 0.14 g/kg for women/men, respectively) or "high" (0.37 g/kg or 0.42 g/kg, respectively) doses of alcohol, and those in the "caffeine" experiment (N = 16) received placebo, 200 or 400 mg caffeine. Time production variability was measured by repetitive tapping of specified intervals, and sources of variance attributable to central timer processes and peripheral motor implementation were dissociated. The explicit timing in tapping was compared with the implicit timing in the coordinated picking up of an object. Time perception was measured as discrimination thresholds for intervals of similar duration. Drug effects on reaction time were also measured. RESULTS: For tapping, alcohol significantly increased timer variability, but not motor variability; it did not affect coordination timing in the grip-lift task. Conversely, for time perception, the low dose of alcohol improved temporal discrimination. Caffeine produced no effects on any of the timing tasks, despite significantly reducing reaction times. CONCLUSIONS: The effects of alcohol argue against a common clock process underlying time interval perception and production in the range below 1 s. In contrast to reaction time measures, time perception and time production appear relatively insensitive to caffeine
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