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Biomedical subjects

B Libet

Publications and source records attributed to B Libet.

At least 37 records · Page 2Linked to original sources

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

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 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.

Adult

Pharmacological properties and monoaminergic mediation of the slow IPSP, in mammalian sympathetic ganglion.

Phenoxybenzamine can selectively eliminate the s-IPSP, in the presence of anti-cholinesterases that enhance s-IPSP and s-EPSP; and the alpha 2-antagonist, yohimbine, can partially but consistently depress s-IPSP selectively. The results provide positive pharmacological support for the monoaminergic nature of the transmitter for s-IPSP in mammalian sympathetic ganglia and argue against suggestions that the s-IPSP is a direct hyperpolarizing response to acetylcholine.

Animals

Two muscarinic depolarizing mechanisms in mammalian sympathetic neurons.

A voltage-sensitive outward membrane current ('M') and a consequent change in conductance (delta G) appear with a slow time-constant, in principal neurons of rabbit superior cervical ganglion (SCG), only when membrane potentials (Vm) are depolarized to less than -60 mV. Effects of muscarine on the voltage-current curves indicate that, in this depolarized range of less than -60 mV, suppression of M-current could contribute a muscarinic depolarization accompanied by a decrease in G; but that, at all Vms tested (about -90 to -40 mV), there is an additional larger muscarinic depolarization with no delta G. Thus, the muscarinic depolarizing response and the equivalent slow excitatory postsynaptic potential in the rabbit SCG may consist of two different components: one is due to the suppression of M-current and is substantial only in the depolarized range; the other is probably mediated via an intracellular increase in cyclic GMP and can account for most or all of the response at Vms more negative than -55 mV.

Action Potentials

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

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 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.

Brain

Metoclopramide mimics a D-1 type of dopamine action in rabbit superior cervical ganglion.

Metoclopramide (MCP) in a sufficiently high concentration (100 microM) induced a large and persisting potentiation of slow-excitatory postsynaptic potentials (s-epsp) and slow-inhibitory postsynaptic potentials (s-epsp) but depressed in fast epsp. This modulatory action of metoclopramide was markedly suppressed by (+)-butaclamol (7 microM) and, to a lesser extent, by spiroperidol (2.5-4 microM). Metoclopramide also possessed weak anti-acetylcholinesterase activity(I50% = 245 microM; measured by Dr N. Inestrosa), but this was shown not to account for the potentiating actions of metoclopramide. Thus, although metoclopramide is a D-2 antagonist, it appears to mimic the D-1 action of dopamine in modulating the slow psps.

Action Potentials

Brain stimulation in the study of neuronal functions for conscious sensory experiences.

Some features of cerebral neuronal functions that are uniquely related to generation of conscious sensory responses, have been discovered. Included are two temporal factors: (1) Substantial delays, of up to about 0.5 sec, before achieving cerebral "neuronal adequacy" appear to be required for eliciting a sensory experience. This includes the demonstration that a cortical stimulus (C) can retroactively modify a skin (S)-induced sensation even when C stimulus begins up to 500 msec after S stimulus. (2) However, there appears to be a subjective referral of the experience back to the time of the cortical primary evoked response to S; subjectively the skin sensation would thus appear to have no delay. Stimuli that are inadequate for eliciting conscious sensory experience can nevertheless evoke considerable neuronal activity, including that represented in direct cortical responses or in primary (early) components of evoked potentials. Virtually all the qualities of somatic sensation (except pain) can be elicited by stimuli at post-central gyrus, when intensities of suitable trains of pulses are kept down to liminal levels. Some additional implications, for the manner in which mental and neural events are related, are discussed.

Arousal

Modulation of slow postsynaptic potentials by dopamine, in rabbit sympathetic ganglion.

(1) Temporary exposure of rabbit's superior cervical ganglion (SCG) to dopamine (DA), in the presence of an inhibitor of catechol-o-methyltransferase (COMT) is consistently followed by a potentiation of the slow (s)-EPSP and s-IPSP, lasting for some hours. The fast (f)-EPSP is not significantly increased, but it is better maintained than in control ganglia. (2) Exposure to the COMT-inhibitor U-0521 alone induces less but substantial potentiations of both s-PSPs. This effect is explained as due to protection of DA released intraganglionically at rest. (3) This evidence suggests that COMT may significantly limit the access of catecholamines to postsynaptic receptors, for at least certain types of neuron-to-neuron synaptic actions. (4) The potentiation of both s-PSPs, whether induced by DA in the presence of U-0521 or by U-0521 alone, is depressed by DA-1 antagonists that have been found to depress DA-stimulation of adenyl cyclase in rabbit SCG; these are spiroperidol, butaclamol and, to a lesser extent, bromocriptine. The specific 'DA-2' antagonists metoclopramide and sulpiride, and the alpha-adrenergic antagonist dihydroergotamine, did not depress potentiation. (5) Potentiation of s-EPSP is viewed as identical in nature to the previously discovered DA-modulatory enhancement of direct muscarinic depolarizing actions (by acetylcholine or its agonists). Potentiation of s-IPSP may be due to a similar DA-modulation of other muscarinic response(s) involved in mediating the s-IPSP. The consistency and comparative ease with which these DA-modulatory effects can be induced, under presently described experimental conditions, should facilitate future study of this mode of synaptic action.

Animals

Orthodromic production of non-cholinergic slow depolarizing response in the superior cervical ganglion of the rabbit.

1. A late slow depolarization in the rabbit superior cervical ganglion, recorded extracellularly as ;late late negative' (l.l.n.) response, can be elicited by suitably repetitive stimulation of cervical sympathetic nerve. The l.l.n. response is not blocked by strong nicotinic, muscarinic or adrenergic antagonists; it appears with latencies in seconds, rise times in minutes, durations of up to 20 min or more, and extracellular amplitudes that can exceed 1 mV when recorded in an air-gap chamber.2. The l.l.n. component is a graded post-synaptic response that decreases with a length constant similar to those of the known p.s.p.s (fast e.p.s.p., slow i.p.s.p., and slow e.p.s.p.). This and its other characteristics indicate that the l.l.n. response is neuronally generated and represents a non-cholinergic late slow depolarization. The term ;slow slow e.p.s.p.' is suggested for this response, to replace both ;slow depolarization' and ;late slow e.p.s.p.'.3. The amplitudes, evaluated relative to the compound action potentials, and the durations of l.l.n. responses recorded from intact neurones of rabbit superior cervical ganglion were considerably greater and more consistently producible than the non-cholinergic slow depolarizations recorded by others from impaled neurones of guinea-pig inferior mesenteric ganglion.4. The l.l.n. response does not exhibit the special sensitivity to sodium azide previously found for the muscarinic ;late negative' or slow e.p.s.p. response.5. The total number of orthodromic volleys is the chief determinant of the amplitude and duration of the l.l.n. response. Increases in pulse frequency, with no change in pulse number, exert only a minor influence on amplitude and duration of the l.l.n. response but can markedly decrease latency and rise time.6. Even very low pulse frequencies (e.g. 1/sec) are almost as effective as higher frequencies if a sufficiently large number of stimulus pulses is applied.7. The features of orthodromic production of the l.l.n., slow slow e.p.s.p. response, as well as the amplitudes and durations of this depolarization, indicate that this non-cholinergic post-synaptic response could, like the muscarinic slow e.p.s.p., play a significant role in mediating physiological activities of sympathetic ganglia.

Animals

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

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, 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.

Brain Mapping

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

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 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.

Animals

Concomitant changes in formaldehyde-induced fluorescence of dopamine interneurones and in slow inhibitory post-synaptic potentials of the rabbit superior cervical ganglion, induced by stimulation of the preganglionic nerve or by a muscarinic agent.

1. Dopamine was identified by formaldehyde histochemistry and cytospectrofluorometry in the rabbit's superior cervical ganglion. Dopamine was localized to the intraganglionic ;small intensely fluorescent' cells, and also to the characteristically beaded fibres forming a network in close contact with virtually all ganglion cell bodies. The extensive beaded fibres are therefore presumed to be processes of the small intensely fluorescent cells.2. Changes in the dopamine content of these interneurones were studied by recording alterations in their relative fluorescence intensity in conjunction with changes in the slow inhibitory post-synaptic potential (s.-i.p.s.p.) response of the ganglion to orthodromic nerve input.3. Dopamine content was lower after several hours in vitro even without special stimulation; this was in accord with a regularly observed spontaneous reduction of the s.-i.p.s.p. response.4. After a period of conditioning stimulation of the preganglionic nerve, in the presence of an anticholinesterase agent (eserine) and an inhibitor of catecholamine synthesis (alpha-methyl-p-tyrosine), the s.-i.p.s.p. was selectively and markedly reduced. The dopamine fluorescence in the small intensely fluorescent cell interneurones was also significantly reduced, to a mean value of about 55 or 60% of the fluorescence in the dopamine interneurones of the paired but unstimulated control ganglion. A significant reduction in dopamine fluorescence was always accompanied by a marked loss of s.-i.p.s.p. response; the reverse was not always true.5. Treatment with the muscarinic agent bethanechol for 30 min, with no alpha-methyl-p-tyrosine or eserine present, similarly resulted in reductions in the s.-i.p.s.p. response of the ganglia and in the formaldehyde-induced fluorescence of the dopamine interneurones.6. A functional uptake of extrinsic dopamine by the dopamine interneurones was also demonstrated: temporary exposure to dopamine restored a large fraction of both the s.-i.p.s.p. response and the dopamine fluorescence of the small intensely fluorescent cells, in ganglia already subjected either to the conditioning stimulation of the preganglionic nerve or to the action of bethanechol.7. It is concluded that (a) preganglionic impulses, by a cholinergic muscarinic synaptic action, can induce a release of dopamine from dopamine interneurones (small intensely fluorescent cells) in the superior cervical ganglion, (b) the ability of the ganglion to respond with a s.-i.p.s.p. to orthodromic input may be viewed as being dependent on the supply of functionally releasable dopamine in these interneurones, (c) the functionally releasable transmitter in vitro appears to comprise roughly 50% of the total dopamine content of the interneurones, and (d) the results fulfil some of the requirements of the hypothesis that a dopamine interneurone is activated muscarinically by preganglionic nerve impulses and mediates the production of s.-i.p.s.p. in sympathetic ganglion cells.

Action Potentials