Conscious intention and human action: Review of the rise and fall of the readiness potential and Libet's clock.

Is consciousness-the subjective awareness of the sensations, perceptions, beliefs, desires, and intentions of mental life-a genuine cause of human action or a mere impotent epiphenomenon accompanying the brain's physical activity but utterly incapable of making anything actually happen? This article will review the history and current status of experiments and commentary related to Libet's influential paper (Brain 106:623-664, 1983) whose conclusion "that cerebral initiation even of a spontaneous voluntary act …can and usually does begin unconsciously" has had a huge effect on debate about the efficacy of conscious intentions. Early (up to 2008) and more recent (2008 on) experiments replicating and criticizing Libet's conclusions and especially his methods will be discussed, focusing especially on recent observations that the readiness potential (RP) may only be an "artifact of averaging" and that, when intention is measured using "tone probes," the onset of intention is found much earlier and often before the onset of the RP. Based on these findings, Libet's methodology was flawed and his results are no longer valid reasons for rejecting Fodor's "good old commonsense belief/desire psychology" that "my wanting is causally responsible for my reaching.

PARP inhibition in vivo blocks alcohol-induced brain neurodegeneration and neuroinflammatory cytosolic phospholipase A2 elevations.

Chronic alcoholism promotes brain damage that impairs memory and cognition. High binge alcohol levels in adult rats also cause substantial neurodamage to memory-linked regions, notably, the hippocampus (HC) and entorhinal cortex (ECX). Concurrent with neurodegeneration, alcohol elevates poly (ADP-ribose) polymerase-1 (PARP-1) and cytosolic phospholipase A2 (cPLA2) levels.

Combinatorial Preconditioning of Rat Brain Cultures with Subprotective Ethanol and Resveratrol Concentrations Promotes Synergistic Neuroprotection.

Preconditioning brain cultures with moderate concentrations of ethanol (EtOH) or trans-resveratrol (RES), key red wine constituents, can prevent amyloid-β (Aβ) neurotoxicity. Past studies have indicated that moderate EtOH activates synaptic N-methyl-D-aspartate receptors (NMDAR) that, in part, signal via protein kinase C (PKC) to increase protective antioxidant proteins such as peroxiredoxin-2 (Prx2). RES preconditioning also is reported to involve NMDAR and PKC.

Ethanol preconditioning of rat cerebellar cultures targets NMDA receptors to the synapse and enhances peroxiredoxin 2 expression.

Epidemiological studies indicate that light-moderate alcohol (ethanol) consumers tend to have reduced risks of cognitive impairment and progression to dementia during aging. Exploring possible mechanisms, we previously found that moderate ethanol preconditioning (MEP, 20-30mM) of rat brain cultures for several days instigated neuroprotection against β-amyloid peptides. Our biochemical evidence implicated the NMDA receptor (NMDAR) as a potential neuroprotective "sensor", specifically via synaptic NMDAR signaling.