B Libet

Publications of B Libet

• Time factors in conscious processes: reply to Gilberto Gomes.

  Authors: B Libet

  Consciousness and cognition. 04/2000; 9(1):1-12.

  The critical reinterpretations of Libet's research by G. Gomes make speculative, unwarranted, and untested assumptions. These assumptions and arguments are analyzed and their status relative toThe critical reinterpretations of Libet's research by G. Gomes make speculative, unwarranted, and untested assumptions. These assumptions and arguments are analyzed and their status relative to Libet's findings is criticized.

• Do the models offer testable proposals of brain functions for conscious experience?

  Authors: B Libet

  Advances in neurology. 02/1998; 77:213-7.

• The human locus coeruleus and anxiogenesis.

  Authors: B Libet, C A Gleason

  Brain research. 02/1994; 634(1):178-80.

  Electrical stimulation of locus coeruleus (LC), via permanently implanted electrodes with confirmed localization and effectiveness, did not elicit any subjective or behavioral manifestations ofElectrical stimulation of locus coeruleus (LC), via permanently implanted electrodes with confirmed localization and effectiveness, did not elicit any subjective or behavioral manifestations of anxiety. This is evidence against the hypothesis that LC is a mediator of anxiogenesis in man.

• Brain metabolism, "ferrin," and non-carbohydrate oxidation.

  Authors: B Libet

  The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 05/1993; 7(6):601-2.

• The neural time factor in conscious and unconscious events.

  Authors: B Libet

  Ciba Foundation symposium. 02/1993; 174:123-37; discussion 137-46.

  Our earlier evidence had indicated that a substantial duration of appropriate cerebral activity (up to about 0.5 s) is required for the production of a conscious sensory experience; this means theOur earlier evidence had indicated that a substantial duration of appropriate cerebral activity (up to about 0.5 s) is required for the production of a conscious sensory experience; this means the sensory world is experienced delayed with respect to real time. Subjective timing of the experience can be retroactively referred to the time of the earliest signal arriving at the cortex. Our 'time-on' theory states that the transition from an unconscious to a conscious mental function is determined, at least in part, by an increase in the duration of appropriate neural activities. Our experimental finding that conscious intention to act appears only after a delay of about 350 ms from the onset of specific cerebral activity that precedes a voluntary act provided indirect evidence for the theory. In a direct experimental test a signal (stimulus to somatosensory thalamus) was correctly detected in a forced-choice test even when the stimulus duration was too short to produce any awareness of the signal; to go from correct detection with no awareness to detection with awareness required an additional 400 ms of the repetitive identical neural volleys ascending to sensory cortex. 'Time-on' theory has important implications for a variety of unconscious-conscious interactions.

• Introduction to slow synaptic potentials and their neuromodulation by dopamine.

  Authors: B Libet

  Canadian journal of physiology and pharmacology. 02/1992; 70 Suppl:S3-11.

  The existence of two muscarinically mediated slow postsynaptic potentials (PSPs) and a noncholinergic (peptidergic) late-slow PSP was established in the 1960s. These have synaptic delays and PSPThe existence of two muscarinically mediated slow postsynaptic potentials (PSPs) and a noncholinergic (peptidergic) late-slow PSP was established in the 1960s. These have synaptic delays and PSP durations 100-10,000 times those for the nicotinic (fast) excitatory post-synaptic potential (EPSP). Evidence is reviewed for an against the proposal that, in rabbit superior cervical ganglia, the slow (s-) inhibitory postsynaptic potential requires a second transmitter, dopamine, released by muscarinic action on interneurones (the small, intensely fluorescent cells). The s-EPSP in frog ganglia appears only in already depolarized cells by a muscarinic closure of the M (voltage-sensitive K+) channels. But the large s-EPSP in mammalian neurones, not depolarized, is generated largely via other mechanisms, especially one involving cyclic GMP. Dopamine also produces a long-term enhancement (LTE) of the muscarinic slow PSPs in rabbit superior cervical ganglia, whether dopamine is applied exogenously or released intraganglionically by preganglionic nerve impulses at 10 s-1. LTE is producible heterosynaptically, and it persists well over 3 h; a noncholinergic (peptide?) transmitter may contribute to the initial 30 min of LTE. LTE is mediated by a D1 receptor coupled to cyclic AMP; it is blocked by cyclic GMP or low Ca2+ or calmidazolium (a calmodulin inhibitor). The modulatory process of LTE has certain similarities to, but also fundamental differences from, the long-term potentiation known in the hippocampus.

• Control of the transition from sensory detection to sensory awareness in man by the duration of a thalamic stimulus. The cerebral 'time-on' factor.

  Authors: B Libet, D K Pearl, D E Morledge, C A Gleason, Y Hosobuchi, N M Barbaro

  Brain : a journal of neurology. 09/1991; 114 ( Pt 4):1731-57.

  A 'time-on' theory to explain the cerebral distinction between conscious and unconscious mental functions proposes that a substantial minimum duration ('time-on') of appropriate neuronal activationsA 'time-on' theory to explain the cerebral distinction between conscious and unconscious mental functions proposes that a substantial minimum duration ('time-on') of appropriate neuronal activations up to about 0.5 s is required to elicit conscious sensory experience, but that durations distinctly below that minimum can mediate sensory detection without awareness. A direct experimental test of this proposal is reported here. Stimuli (72 pulses/s) above and below such minimum train durations (0-750 ms) were delivered to the ventrobasal thalamus via electrodes chronically implanted for the therapeutic control of intractable pain. Detection was measured by the subject's forced choice as to stimulus delivery in one of two intervals, regardless of any presence or absence of sensory awareness. Subjects also indicated their awareness level of any stimulus-induced sensation in each and every trial. The results show (1) that detection (correct greater than 50%) occurred even with stimulus durations too brief to elicit awareness, and (2) that to move from mere detection to even an uncertain and often questionable sensory awareness required a significantly larger additional duration of pulses. Thus simply increasing duration ('time-on') of the same repetitive inputs to cerebral cortex can convert an unconscious cognitive mental function (detection without awareness) to a conscious one (detection with awareness).

• Postsynaptic long-term enhancement (LTE) by dopamine may be mediated by Ca2+ and calmodulin.

  Authors: S Mochida, B Libet

  Brain research. 05/1990; 513(1):144-8.

  Long-term enhancement (LTE), of postsynaptic slow depolarizing responses to a muscarinic agonist (MCh), follows a brief exposure of the rabbit superior cervical ganglion to another transmitter,Long-term enhancement (LTE), of postsynaptic slow depolarizing responses to a muscarinic agonist (MCh), follows a brief exposure of the rabbit superior cervical ganglion to another transmitter, dopamine (DA). Either reduction of external Ca2+ (to 1.0 mM or 0.2 mM) or presence of a specific calmodulin antagonist (calmidazolium at 5 microM) blocked DA induction of this LTE. However, unlike LTP in hippocampus, induction of LTE is not mediated by depolarization-dependent influx of Ca2+.

• Stimulation of locus coeruleus in man. Preliminary trials for spasticity and epilepsy.

  Authors: B Feinstein, C A Gleason, B Libet

  Stereotactic and functional neurosurgery. 02/1989; 52(1):26-41.

  Stimulating electrodes were chronically implanted unilaterally (in 1975-1977) in the vicinity of the locus coeruleus (LC) in three patients, one with cerebral palsy-spastic quadriplegia, two withStimulating electrodes were chronically implanted unilaterally (in 1975-1977) in the vicinity of the locus coeruleus (LC) in three patients, one with cerebral palsy-spastic quadriplegia, two with epilepsy (one grand mal, one psychomotor). Effective excitation of efferent LC axons was indicated by measuring rises in 3-methoxy-4-hydroxyphenylethyleneglycol in the jugular and systemic venous blood following a 6-min stimulus with discontinuous bursts of pulses. There was a substantial reduction of spasticity during and after stimulation. Improvement was verified by double-blind failures of the stimulator, and the stimulus therapy is still in use after 9 years. There appeared to be a reduction in incidence and severity of both types of epileptic seizures, although this was not rigorously established. The patient with psychomotor epilepsy reported a considerable lengthening of preseizure auras (to 15-30 min), an unusual number of which terminated without a seizure.

• Long-term enhancement (LTE) of postsynaptic potentials following neural conditioning, in mammalian sympathetic ganglia.

  Authors: B Libet, S Mochida

  Brain research. 12/1988; 473(2):271-82.

  Orthodromic, preganglionic conditioning stimulation can consistently induce long-term enhancement (LTE) (greater than 3 h) of the muscarinically mediated slow excitatory postsynaptic potential andOrthodromic, preganglionic conditioning stimulation can consistently induce long-term enhancement (LTE) (greater than 3 h) of the muscarinically mediated slow excitatory postsynaptic potential and the slow inhibitory postsynaptic potential. This was shown for superior cervical ganglia of rabbit and rat. Effective conditioning stimuli are in a physiologically observed range (3/s for 7 min, 5/s for 4 min, 10/s for 2 min, 20/s for 1 min). LTE was producible both homosynaptically and heterosynaptically. LTE can thus be associative, with conditioning synaptic input in one line inducing long-term changes in postsynaptic responses to another (heterosynaptic) input. The dopamine antagonist butaclamol depressed LTE, particularly that following the initial postconditioning period of 30 min. Adrenergic antagonists had no effect. This pharmacological evidence, coupled with the heterosynaptic induction of LTE, supports the view that neurally induced LTE may be at least partly mediated by endogenous dopamine. Another non-cholinergic but non-adrenergic transmitter (possibly a peptide) might contribute to the LTE seen in the initial 30 min postconditioning. The present, orthodromically induced LTE is clearly different from the long-term potentiation widely studied in hippocampus, etc., in the modes of induction and synaptic mediation.

• Secondary late components of the muscarinic postsynaptic potentials, in rabbit superior cervical ganglion.

  Authors: S Mochida, B Libet

  Journal of the autonomic nervous system. 10/1988; 24(1-2):41-9.

  The well known muscarinic slow excitatory polysynaptic potential (s-EPSP) of rabbit superior cervical ganglion (SCG) peaking at about 1-2 s and lasting 5-10 s, is immediately followed by an abruptThe well known muscarinic slow excitatory polysynaptic potential (s-EPSP) of rabbit superior cervical ganglion (SCG) peaking at about 1-2 s and lasting 5-10 s, is immediately followed by an abrupt change in slope to a longer, lower depolarizing phase. A brief dip in the level of depolarization (DP) often separates the two depolarizing phases. The secondary phase of s-EPSP rises to its own peak at about 25 s; total duration 60-120 s. With repetition of orthodromic volleys secondary s-EPSP builds up more gradually than initial s-EPSP, but more rapidly than slow-slow (ss-) EPSP. The later 'secondary' depolarizing phase along with the antecedent 'dip in DP' are, like the 'initial' s-EPSP, eliminated by a muscarinic antagonist, quinuclinidyl benzilate hydrochloride (QNB). This distinguishes secondary s-EPSP from the even slower rising non-cholinergic ss-EPSP. The ss-EPSP, although relatively small in the responses to the usual 3-pulse test stimuli, rises to an extraordinary amplitude (equal to the compound action potential) during a 10 s-120 s train of pulses. Gallamine blocked most of the slow IPSP component in test responses but not initial or secondary s-EPSP. A preganglionic conditioning train (10/s for 2 min) induced a long-term-enhancement (LTE) of secondary s-EPSP lasting greater than 3 h, with maximum postconditioning percentage increases greater than for initial s-EPSP. Also enhanced was the dip in DP, now forming a deeper notch between initial and secondary s-EPSPs; this attains a maximum at about 30 min postconditioning but thereafter progressively loses the enhancement by about 90 min.(ABSTRACT TRUNCATED AT 250 WORDS)

• Stimulation of adenylate cyclase in relation to dopamine-induced long-term enhancement (LTE) of muscarinic depolarization in the rabbit superior cervical ganglion.

  Authors: S Mochida, H Kobayashi, B Libet

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 03/1987; 7(2):311-8.

  Dopamine (DA) induction of the long-term enhancement (LTE) of the slow muscarinic depolarizing response to methacholine (MCh), equivalent to the slow EPSP (S-EPSP), was previously found to beDopamine (DA) induction of the long-term enhancement (LTE) of the slow muscarinic depolarizing response to methacholine (MCh), equivalent to the slow EPSP (S-EPSP), was previously found to be mimicked by exogenous cyclic AMP (cAMP) in the rabbit superior cervical ganglion (SCG). DA-induced LTE of the S-EPSP was shown to be depressed by some DA antagonists. We now show that DA (15 microM), its analog, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN), and a D2 receptor antagonist, metoclopramide, each can induce both LTE of MCh depolarization and an increase in ganglionic cAMP. Conversely, antagonists of DA-induced LTE also depress DA-induced rises in cAMP; these antagonists include haloperidol (1 microM), both (+) and (-) enantiomers of butaclamol (0.7-7 microM), flupenthixol (1 microM), and (+)-R-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-o l (SCH-23390) (7 microM). The selective D2 antagonists sulpiride (10 microM) and domperidone (10 microM) affect neither DA action. Alpha-2 adrenergic agonists (alpha-methyl-norepinephrine and clonidine) produce no LTE; alpha-antagonist dihydroergotamine (35 microM) does not affect either DA action, although it can completely block the hyperpolarizing response to DA or other catecholamines. Beta-antagonist propranolol (5 microM) partially depresses DA-induced rises in cAMP but has no effect on the DA-induced LTE. (Butaclamol and propranolol in combination can completely block the cAMP rise induced by DA.) Beta-agonist isoproterenol can induce appreciable LTE of MCh depolarization, but this LTE is not depressed by propranolol (10 microM). Isoproterenol can elicit a substantial rise in cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

• Synaptic long-term enhancement (LTE) induced by a heterosynaptic neural input.

  Authors: S Mochida, B Libet

  Brain research. 04/1985; 329(1-2):360-3.

  The slow excitatory postsynaptic potential (s-EPSP) response of cat stellate ganglion can be enhanced for hours (long term enhancement, LTE) following a conditioning preganglionic train of lowThe slow excitatory postsynaptic potential (s-EPSP) response of cat stellate ganglion can be enhanced for hours (long term enhancement, LTE) following a conditioning preganglionic train of low frequency pulses, even when test s-EPSPs are elicited by an unconditioned input line. This provides another model for associational alterations of synaptic efficacy.

• Preparation- or intention-to-act, in relation to pre-event potentials recorded at the vertex.

  Authors: B Libet, E W Wright, C A Gleason

  Electroencephalography and clinical neurophysiology. 11/1983; 56(4):367-72.

  Pre-event potentials were compared in the same subject, for 3 types of forewarned events, in which the foreperiod for orienting or attention began several seconds before the event. All of thesePre-event potentials were compared in the same subject, for 3 types of forewarned events, in which the foreperiod for orienting or attention began several seconds before the event. All of these trials involved similar non-motor components (expectancy, attentiveness, general orienting to a salient stimulus) but differed in whether motor or non-motor responses were required. A prominent and consistent slow negative shift preceded the pre-set time for a motor response, even when the subject 'vetoed' his intention to act shortly before the pre-set time. Pre-event potentials were absent, or small and brief, when the event was a task-related skin stimulus not involving preparation to move. The findings selectively support the view that mental preparation/intention to act is a necessary and perhaps dominant process associated with the vertex-recorded pre-event, slow negative potential. They also show that such a pre-event potential can appear even when the subject knows he is going to veto his developing intention to act and does not actually move.

• Time of conscious intention to act in relation to onset of cerebral activity (readiness-potential). The unconscious initiation of a freely voluntary act.

  Authors: B Libet, C A Gleason, E W Wright, D K Pearl

  Brain : a journal of neurology. 10/1983; 106 (Pt 3):623-42.

  The recordable cerebral activity (readiness-potential, RP) that precedes a freely voluntary, fully endogenous motor act was directly compared with the reportable time (W) for appearance of theThe recordable cerebral activity (readiness-potential, RP) that precedes a freely voluntary, fully endogenous motor act was directly compared with the reportable time (W) for appearance of the subjective experience of 'wanting' or intending to act. The onset of cerebral activity clearly preceded by at least several hundred milliseconds the reported time of conscious intention to act. This relationship held even for those series (with 'type II' RPs) in which subjects reported that all of the 40 self-initiated movements in the series appeared 'spontaneously' and capriciously. Data were obtained in at least 6 different experimental sessions with each of 5 subjects. In series with type II RPs, onset of the main negative shift in each RP preceded the corresponding mean W value by an average of about 350 ms, and by a minimum of about 150 ms. In series with type I RPs, in which an experience of preplanning occurred in some of the 40 self-initiated acts, onset of RP preceded W by an average of about 800 ms (or by 500 ms, taking onset of RP at 90 per cent of its area). Reports of W time depended upon the subject's recall of the spatial 'clock-position' of a revolving spot at the time of his initial awareness of wanting or intending to move. Two different modes of recall produced similar values. Subjects distinguished awareness of wanting to move (W) from awareness of actually moving (M). W times were consistently and substantially negative to, in advance of, mean times reported for M and also those for S, the sensation elicited by a task-related skin stimulus delivered at irregular times that were unknown to the subject. It is concluded that cerebral initiation of a spontaneous, freely voluntary act can begin unconsciously, that is, before there is any (at least recallable) subjective awareness that a 'decision' to act has already been initiated cerebrally. This introduces certain constraints on the potentiality for conscious initiation and control of voluntary acts.

• Readiness-potentials preceding unrestricted 'spontaneous' vs. pre-planned voluntary acts.

  Authors: B Libet, E W Wright, C A Gleason

  Electroencephalography and clinical neurophysiology. 10/1982; 54(3):322-35.

  The nature of readiness-potentials (RPs) that may be associated with fully endogenous, 'freely' voluntary acts was investigated. Restriction on when to act were eliminated and instructions fosteredThe nature of readiness-potentials (RPs) that may be associated with fully endogenous, 'freely' voluntary acts was investigated. Restriction on when to act were eliminated and instructions fostered 'spontaneity.' The 'self-initiated' RPs exhibited in these conditions were categorizable into two (possibly three) types, all of which could be exhibited by the same subject. Type I had an early onset at about -1050 +/- 175 msec and a long ramp-like form, resembling self-paced RPs. In type II the main negative shift began at about -575 +/- 150 msec, and at about -240 +/- 50 msec in type III. Type II partially resembled the similarly timed NS' component in self-paced RPs. For acts produced at known, preset times, in which freedom of choice was eliminated but planning to act was required, RPs resembled self-initiated type I RPs and self-paced RPs. All RPs were maximal at the vertex, especially type II even though it was also bilaterally asymmetrical. These distributions suggest that cortical areas other than area 4 and 6 contribute importantly, especially to type II. All RPs, whether in self-initiated or pre-planned acts, appear related specifically to preparation for a motor action. When task-related skin stimuli replaced self-initiated movements, under similar conditions of attentiveness (and expectancy), there were either no or relatively small event-preceding-slow potential shifts. All post-stimulus P300 waves were very large. Two volitional processes are postulated: process I is associated with development of pre-planning or preparation to act in the near future (seconds), whether voluntary choice is present (type I RPs) or absent (pre-set RPs); process II, with an onset at roughly 0.5 sec before the act, is associated more uniquely with voluntary choice and with the more specific as well as endogenous urge or intention to act; it can be present in the comparative absence of or in sequence and overlapping with process I.

• Subjective referral of the timing for a conscious sensory experience: a functional role for the somatosensory specific projection system in man.

  Authors: B Libet, E W Wright, B Feinstein, D K Pearl

  Brain : a journal of neurology. 04/1979; 102(1):193-224.

  Subjective experience of a peripherally-induced sensation is found to appear without the substantial delay found for the experience of a cortically-induced sensation. To explain this finding, inSubjective experience of a peripherally-induced sensation is found to appear without the substantial delay found for the experience of a cortically-induced sensation. To explain this finding, in relation to the putative delay of up to about 500 ms for achieving the "neuronal adequacy" required to elicit the peripherally-induced experience, a modified hypothesis is proposed: for a peripheral sensory input, (a) the primary evoked response of sensory cortex to the specific projection (lemniscal) input is associated with a process that can serve as a 'time-marker'; and (b), after delayed neuronal adequacy is achieved, there is a subjective referral of the sensory experience backwards in time so as to coincide with this initial 'time-marker'. A crucial prediction of the hypothesis was experimentally tested in human subjects using suitably implanted electrodes, and the results provide specific support for the proposal. In this, the test stimuli to medial lemniscus (LM) and to surface of somatosensory cortex (C) were arranged so that a minimum train duration of 200 ms or more was required to produce any conscious sensory experience in each case. Each such cerebral stimulus could be temporally coupled with a peripheral one (usually skin, S) that required relatively negligible stimulus duration to produce a sensation. The sensory experiences induced by LM stimuli were found to be subjectively timed as if there were no delay relative to those for S, that is, as if the subjective experience for LM was referred to the onset rather than to the end of the required stimulus duration of 200 ms or more. On the other hand, sensory experiences induced by the C stimuli, which did not excite specific projection afferents, appeared to be subjectively timed with a substantial delay relative to those for S, that is, as if the time of the subjective experience coincided roughly with the end of the minimum duration required by the C stimuli. The newly proposed functional role for the specific projection system in temporal referral would be additional to its known role in spatial referral and discrimination. A temporal discrepancy between corresponding mental and physical events, i.e., between the timing of a subjective sensory experience and the time at which the state of 'neuronal adequacy' for giving rise to this experience is achieved, would introduce a novel experimentally-based feature into the concept of psychophysiological parallelism in the mind-brain relationship.

• Suppression of an eplieptiform type of electrocortical activity in the rat by stimulation in the vicinity of locus coeruleus.

  Authors: B Libet, C A Gleason, E W Wright, B Feinstein

  Epilepsia. 01/1978; 18(4):451-62.

  Stimulation of the locus coeruleus, or in the vicinity of this nucleus or of its ascending tracts, could markedly suppress the appearance of epileptiform-like ECoG bursts. The latter were induced inStimulation of the locus coeruleus, or in the vicinity of this nucleus or of its ascending tracts, could markedly suppress the appearance of epileptiform-like ECoG bursts. The latter were induced in rats by a subconvulsive dose of pentylenetetrazol. Electrode sites were identified histologically. A unilateral stimulus suppressed bursts bilaterally. An individual burst already in progress could be aborted, stopping within less than 0.5-1 sec after onset of a stimulus train. The antiepileptiform actions occurred with no evidence of any desynchronizing effect of the stimulus on the resting ECoG; they appear to be different in sites of origin and nature from those reported for stimulation of the reticular activating system. It is proposed that stimulation of the ascending noradrenergic system in the brain stem may limit the development and spread of hyperexcitatory, epileptiform states.

• Responses of human somatosensory cortex to stimuli below threshold for conscious sensation.

  Authors: B Libet, W W Alberts, E W Wright, B Feinstein

  Science (New York, N.Y.). 01/1968; 158(808):1597-600.

  Averaged evoked responses of somatosensory cortex, recorded subdurally, appeared with stimuli (skin, ventral posterolateral nucleus, cortex) which were subthreshold for sensation. Such responses wereAveraged evoked responses of somatosensory cortex, recorded subdurally, appeared with stimuli (skin, ventral posterolateral nucleus, cortex) which were subthreshold for sensation. Such responses were deficient in late components. Subthreshold stimuli could elicit sensation with suitable repetition. The primary evoked response was not sufficient for sensation. These facts bear on the problems of neurophysiological correlates of conscious and unconscious experience, and of "subliminal perception."

• Physiological mechanisms of tremor and rigidity in parkinsonism.

  Authors: W W Alberts, B Libet, E W Wright, B Feinstein

  Confinia neurologica. 02/1965; 26(3):318-27.