Predicting coma and other low responsive patients outcome using event-related brain potentials: a meta-analysis.

OBJECTIVE: A meta-analysis was performed to estimate the predictive power (odd ratio, OR) for awakening of auditory event-related potential (ERP) components in low responsive patients with stroke or hemorrhage, trauma, anoxic, post-operative, and metabolic encephalopathy etiologies. METHODS: We reviewed MEDLINE and analyzed citations for retrieved articles. Logistic regressions were applied on patient samples (Glasgow Coma Scale <12) across and for separate etiologies. RESULTS: For stroke and hemorrhage the ORs with 95% confidence intervals were: 2.05 [1.12-3.75] (N100), 4.47 [1.92-10.44] (MMN), 10.29 [2.00-52.79] (P300), for trauma: 1.63 [0.70-3.80] (N100), 4.72 [1.35-16.44] (MMN), 12.89 [4.82-34.43] (P300), anoxic: 8.03 [2.83-22.75] (N100), 15.50 [4.27-56.26] (MMN), 5.93 [2.38-14.77] (P300), post-operative: 10.66 [1.98-57.50] (N100), metabolic encephalopathy: 2.12 [0.34-13.13] (N100), 3.60 [0.28-46.36] (MMN), 7.71 [0.75-79.77] (P300), and all etiologies: 2.85 [1.91-4.27] (N100), 6.53 [3.55-12.01] (MMN), and 8.79 [4.88-15.83] (P300). Based on six N100 studies (N=548 patients), five MMN studies (N=470), and six P300 studies (N=313), the N100, MMN, or P300, when present, significantly predicted awakening, P300 and MMN being significantly better predictors than N100. CONCLUSIONS: The MMN and P300 appear to be reliable predictors of awakening. SIGNIFICANCE: The prognostic assessment of low responsive patients with auditory ERP should take into account both MMN and P300.

On cholinergic mechanisms in the optokinetic nystagmus of the frog: antagonistic effects of muscarinic and nicotinic systems.

In a monocular situation, an intravitreal injection of acetylcholine (ACh) agonists (especially muscarinic agonists like muscarine or oxotremorine) provoked both the suppression of the optokinetic nystagmus (OKN) related to the injected eye, and the appearance of a nasal-temporal (N-T) component in the OKN triggered by the contralateral non-injected eye. These two effects were added in a binocular condition. Similar results were obtained with ACh nicotinic antagonists (D-tubocurarine, alpha-bungarotoxin, hexamethonium and gallamine). ACh muscarinic antagonists (atropine, scopolamine) had only moderate effects and failed to provoke an N-T component in the contralateral OKN. These data show that ACh mechanisms are involved in the control of the frog OKN, especially in directional asymmetry, nicotinic and muscarinic systems acting in an antagonistic way.

Dopamine and melatonin interactions in the intact chicken eye. Electrooculographic and biochemical study.

Electrophysiological and biochemical techniques were used to investigate the interactions between dopamine (DA) and melatonin (MEL) in the intact chicken eye. Endogenous DA depletion induced by intraocular administration of alpha-methyl-para-tyrosine (alpha-MPT), a selective tyrosine hydroxylase inhibitor, decreases the transepithelial potential (TEP) of the retinal pigment epithelium and reduces the light peak (LP) recorded by an indirect electro-oculographic (EOG) method. An intraocular injection of MEL also reduces the TEP but does not reduce the LP. Retinal MEL is increased after endogenous DA depletion and a tight inverse correlation between DA and MEL contents was found. The present data, together with other findings support the hypothesis (1) that in the intact chicken eye, DA and MEL play respectively a role of light and dark signals on the TEP, and (2) that a balance between these two neurohormones may be responsible for the regulation of RPE events which are dependent on light-dark conditions.

Acute blockade of dopamine receptors with haloperidol: a retinal model to study impairments of dopaminergic transmission.

A pulse of dopamine produces a transient dose-correlated increase in the transepithelial potential (TEP) of the chicken eye, mimicking the light-induced response, the light peak (LP). Acute blockade of retinal dopaminergic transmission with haloperidol, a mixed antagonist, produced a dose-correlated TEP voltage decrease which was rapidly reversed by intravitreal injection of dopamine. The LP recorded thereafter was strongly reduced. These data confirm the hypothesis that dopamine released by light from amacrine cells triggers light-induced changes in the TEP of the intact chicken eye, and that these potentials could well provide an electrophysiological tool to evaluate retinal dopaminergic deficiency.

On GABAergic mechanisms in the optokinetic nystagmus of the frog: effects of bicuculline, allylglycine and SR 95103, a new GABA antagonist.

In a monocular situation, an intravitreal injection of the GABA antagonists, bicuculline or SR 95103 provoked both the suppression of the optokinetic nystagmus (OKN) related to the injected eye and the appearance of a Nasal-Temporal (N-T) component in the OKN triggered by the contralateral non-injected eye (this N-T component being absent in control OKN). These two effects were added in a binocular condition. Similar results were obtained with L-C allylglycine which reduces the endogenous GABA level, but these effects were delayed when compared to those of GABA antagonists. All these data are roughly analogous to those previously obtained with picrotoxin (a non-competitive GABA antagonist) and thus confirm that GABA mechanisms are involved in the control of the frog OKN. Furthermore, SR 95103 acted in this model as a potent selective GABA antagonist, as has been demonstrated in another system.

Anisotropic inhibition in the receptive field surround of the frog retinal ganglion cells, evidenced by bicuculline and SR 95103, a new GABA antagonist.

When GABA antagonists (picrotoxin, bicuculline methiodide and SR 95103) were intravitreally injected in the frog, they increased the number of spikes of transient retinal ganglion cells, as well as the duration of the response. Thus, the transient pattern of the response became more sustained. GABA antagonists also provoked a marked increase in the size of the receptive field, which might be due to the abolition of the inhibition exerted by the surround upon the centre of the field. In fact, a stimulus applied to the surround of the field simultaneously with one applied to the centre no longer provoked the reduction of the field area nor that of the number of spikes. These are effects which were always observed before drug injection. After picrotoxin injection, the enlarged field was concentric with the initial one, both angular diameters doubled, whereas after bicuculline or SR 95103, the enlarged field was not concentric with the initial one and only one diameter increased. Thus, GABA inhibition appears to be distributed according to an anisotropic spatial pattern. Whether this anisotropy might be an input for direction selectivity in the frog visual system is a topic of discussion. With respect to SR 95103, this compound proved to act like a selective GABA antagonist with long lasting effects.

Electrophysiological evidence of persisting unilateral auditory cortex dysfunction in the late outcome of Landau and Kleffner syndrome.

OBJECTIVES: In the late outcome of Landau and Kleffner syndrome (LKS), a childhood-acquired epileptic aphasia, most patients show after complete recovery of epilepsy a permanent one-ear extinction on dichotic listening tests contralateral to the temporal cortex previously affected by the epileptic focus. The pathophysiological significance of this dichotic extinction is not yet understood. It may be a consequence of a permanent dysfunction in the auditory system due to epileptic activity during the maturing period of the auditory system. Evoked potentials were used to check this hypothesis and to localize the level of the dysfunction along the auditory pathways. METHODS: Early, middle latency and late auditory evoked potentials were recorded in 5 right-handed children having recovered from LKS. They were compared with those of 5 control children paired for age and gender. RESULTS: In all 5 LKS patients, early and middle latency auditory evoked potentials were normal. But the amplitude of N1c (arising from associative auditory areas) was strongly reduced at temporal electrodes contralateral to the extinguished ear, whereas latency and amplitude of N1b (related to primary auditory areas) were in the normal range. CONCLUSIONS: Unilateral voltage reduction of late auditory evoked potentials over the temporal areas previously involved by epileptic discharges suggests a permanent dysfunction in the associative auditory cortex, the behavioral expression of which is the unilateral dichotic extinction.

Cerebral correlates of hemispheric lateralization during a pitch discrimination task: an ERP study in dichotic situation.

OBJECTIVE: Electrophysiological correlates of perceptual asymmetry for dichotic pitch discrimination were investigated in 12 right-handed volunteers, whose dichotic listening performances attested the classical 'right ear advantage' in a verbal discrimination task. METHODS: Event related potentials (ERPs), elicited by dichotic and binaural pairs of tones applied in a classical oddball paradigm including right ear targets, left ear targets and binaural targets (5% occurrence each) were recorded from medial and lateral scalp locations. Latencies and baseline to peak amplitudes were measured for P1, N1, P2, N2 and P3 components. RESULTS: ERPs recorded in response to dichotic (compared with binaural) target pairs, exhibited delayed latencies for N2 and P3, correlated with prolonged RTs, probably linked to greater difficulty in identification of the target. They also displayed enhanced N1 and P2 voltages, which may reflect the simultaneous activation of two different populations of neurons in the auditory cortical areas. We observed specific lateralization effects for pitch discrimination with a left ear advantage on latency of early components. CONCLUSIONS: Together with amplitude asymmetries in the N2 component, the findings bring strong electrophysiological support to Kimura's structural model for dichotic perceptions with a right hemisphere prevalence in a pitch discrimination task.

Effects of DL-alpha-amino adipic acid on Müller cells in frog and chicken retinae in vivo: relation to ERG b wave, ganglion cell discharge and tectal evoked potentials.

In both frog and chicken, an intravitreal injection of DL-alpha-amino-adipic acid, (DL-alpha aaa) provoked a progressive depression and eventually the disappearance of the ERG b wave that was concomitant with severe damage to the Müller cells without any apparent damage to retinal neurons. Ganglion cell discharges as well as tectal evoked potentials were still recorded, i.e. a visual message was still generated in the retina and transmitted to the optic tectum, when the Müller cells had been damaged to as to provoke an abolition of the ERG b-wave. The whole of the drug-induced effects proved to be reversible.

Evidence for both photopic and scotopic characteristics in the c-wave of chicken and frog ERG.

The electroretinographic c-wave was studied in two species with duplex retinas, the frog (rod-dominant) and the chicken (highly cone-dominant). In both species a cone driven c-wave was recorded in addition to the classical rod-driven c-wave. An attempt was made to specify the differential characteristics with respect to time-course, time integration, adaptational changes and spectral sensitivity of cone-driven vs rod-driven c-waves. These data confirm the generality of the c-wave generation by both rod and cone systems.

Light and dark induced variations of the c-wave voltage of the chicken eye after treatment with sodium aspartate.

Light and dark-induced variations of the ERG c-wave voltage were recorded in control chickens and after intravitreal injection of Na aspartate, a treatment whose main effect is to functionally disconnect the pigment epithelium-photoreceptor complex from second order neurons. After aspartate, the fast light rise which characterizes this preparation is no longer observed; it is substituted for by a potential variation of much slower time course and of lower magnitude. The data totally confirm previous findings obtained through an indirect EOG technique and suggest the participation of inner retinal layers in the generation of the light peak in the chicken eye.

Is dopamine involved in the generation of the light peak in the intact chicken eye?

The implication for dopamine (DA) in the modulation of the standing potential (SP) and the light peak (LP) was tested in intact chickens using an indirect EOG method. After an intravenous or intravitreal injection of DA, a transient, dose-dependent increase in the SP was observed. The LP, recorded after an intravenous injection, was preserved. But after an intravitreal injection, the LP was strongly reduced or even abolished depending on the dose of DA, whereas the photoreceptor response was unchanged. The data supports the hypothesis that the light peak, which is generated by a neural retina-pigment epithelium interaction, could be triggered by dopamine released at light onset from the inner retinal layers.

Physiological effects of muscarinic vs nicotinic ACh antagonists upon ganglion cell activity in the frog retina.

The intravitreal administration of ACh agonists (eserine, carbachol, oxotremorine) or that of ACh muscarinic antagonists (scopolamine, atropine) provoked a reduction of the On-Off ganglion cell discharges. The agonists depressed the Off discharges more than the On discharges, while the ACh muscarinic antagonists depressed the On- more than the Off discharges. These drugs did not modify the ganglion cell receptive field area; thus, the muscarinic cholinergic system seems not to be involved in the spatial organization of the On-Off ganglion cells, but rather seems to play an important part in the separation of On and Off information channels. ACh nicotinic antagonists [hexamethonium, D-tubocurarine (D-TC), alpha-bungarotoxin (alpha-BGTX)] provoked an increase of the receptive field area of On-Off ganglion cells, this enlargement being due to the suppression of the inhibition normally exerted by the surround upon the centre of the field. Moreover D-TC and alpha-BGTX, but but hexamethonium, increased the number of ganglion cell discharges. These data are analogous to those obtained after administration of GABA antagonists and show that through nicotinic receptors, ACh seems to be involved in the spatial organization of the On-Off ganglion cell.

[Auditory P300 in subjects in a post-anoxic coma. Preliminary data]. / Etude du P300 auditif chez des sujets en coma post-anoxique. Données préliminaires.

The first results concerning the role of event related potentials (P300) in assessing a prognosis in comatose patients reported in the literature have been encouraging. The cause of the coma is an important prognostic factor by itself, especially when traumatic and anoxic comas are compared, with a less favorable prognosis in anoxic coma. In our study, only anoxic patients have been investigated using somatosensory evoked potentials, brainstem auditory evoked potentials P300 auditory event-related potentials. Clinical evaluation was performed using Glasgow, Liege and Jouvet coma scales. In twenty patients studied, six had a positive P300 and three of them awake. Out of the 14 patients without a P300 only one awoke (5%), 12 patients died and one is in deep coma. Despite the small number of patients in this study, the first results confirm the interest of auditory P300, in addition to clinical evaluation and evoked potential testing.

[Event-related potentials and language processing]. / Potentiels cognitifs et traitement du langage.

The contribution of cognitive event-related potentials (ERPs) and particularly of the N400 component to the study of language processing is considered. After a general presentation of the various components of cognitive evoked potentials which are differentiated from early potentials (sensitive to perceptive parameters), the neurophysiological and psychological correlates of ERPs are discussed. Before the presentation of the main studies concerned with the correlation between specific late components and linguistic processes, it is proposed an introduction to some theoretical models of language processing which serve as conceptual framework supporting most of the experimental approaches in this field. The results of EPs studies devoted to functional asymetries in language processing are briefly mentioned. Then a number of studies are analysed, these demonstrate the sensitivity of event-related potential measures to linguistic manipulations. Finally, the studies concerned with the N400 are reviewed, this potential appears to be the more specifically language-related ERP component, even if its connection with specific linguistic processes or its differentiation from N200 are still under debate. Nevertheless language-related electrophysiological investigations may become in the near future a useful complementary approach to our understanding of language processing and language disorders.

Effects of intravitreal and intravenous administrations of dopamine on the standing potential and the light peak in the intact chicken eye.

We studied the modifications of the standing potential (SP) of the eye and of the light peak (LP) after exposure to dopamine, a neurotransmitter released at light by the inner retina and known to affect electrical properties of the retinal pigment epithelium. Intravenous or intravitreal injections of dopamine (DA) were performed on intact chickens. "Choroidal" application (through an intravenous injection) induced a transient increase of the SP and the LP was preserved. On the other hand, "apical" applications of DA (through an intraocular injection) also increased the SP but considerably depressed the LP. These results are in agreement with the hypothesis that the light-induced release of dopamine from the neuroretina may be responsible for the LP generation in the intact chicken eye.