Operant conditioning of cortical visual evoked potentials in the curarized rat and control of simultaneous subcortical activity

Curarized rats were successfully trained to modify the amplitude of a certain portion of their cortical visual evoked potential. The positive results obtained enabled us to conclude that the influence of peripheral mediators on the generation of the conditioned response is highly improbable. Subcortical visual evoked potentials were simultaneously recorded in the lateral geniculate body, mesencephalic reticular formation, and superior colliculus. As the responses were almost identical throughout the entire experimental session, those structures cannot be held responsible for the conditioned modifications of the cortical evoked response. On the contrary, the nucleus posterior thalami responses paralleled the cortical modifications. But electrolytic lesions of this nucleus proved to have no effect on the evolution of the conditioning procedure. In the rat, the existence of a projection arising from the visual cortex to the nucleus posterior thalami is considered.     

Comparative electrophysiologic characteristics of afferent representation in the cortical and striatal portions of the turtle forebrain]

Visual and somatic representations are established in the subcortical striatal sections of the forebrain (pallial thickening, dorsal ventricular ridge and putamen) of immobilized weakly anaesthetized turtles. According to electrophysiological characteristics they are similar to the corresponding sensory representations in the general cortex. The absence of reliable discrepancy between the latencies of potentials in the cortex and striatum evoked by light flash or by the electric stimulation of the dorsal thalamus indicates that visual projectional fibres ascending from the lateral geniculate nucleus terminate both in cortical and striatal structures. Differences in the latency distribution of single unit responses in the cortex and striatum to visual and thalamic stimulations can be due to the existence, besides the geniculo-telencephalic pathway, of a rotundo-telencephalic visual channel having direct connections with the striatum and polysynaptic ones with the general cortex. Significant differences in latency between the evoked potentials and neuronal responses in cortical and subcortical structures to electric stimulation of the skin shows that somatic projectional fibres on their way to the cortex are relayed in the striatum, thus indicating a lower corticolization degree of the somatosensory system as compared with that of the visual one.     

Vestibular input to the caudate nucleus

Unilateral stimulation of peripheral vestibular nerve branches in encephale isolé cats evoked potentials of 3- to 7-msec latency in the banks of the contralateral anterior suprasylvian sulcus and 4- to 15-msec latency in the head of the caudate nucleus bilaterally. The responses were distributed in the dorsomedial region of the ipsilateral caudate and dorsolateral region of the contralateral caudate. Stimulation of peripheral cochlear nerve branches also evoked responses in areas of caudate partially overlapping those responsive to vestibular stimulation. Stimulation of the vestibular projection area of cortex evoked a response in caudate but did not alter the response to vestibular nerve stimulation. Ablation of the vestibular projection area of cortex did not alter the vestibular responses in caudate. However, caudate and cortical responses to vestibular nerve stimulation were severely decreased by lesions of the magnocellular portion of medial geniculate body. We conclude that there are vestibular projections to the caudate nuclei which require passage through the medial geniculate body and probably other thalamic nuclei, but not through the vestibular projection area of cortex.     

Changes in subcortical visual and auditory evoked potentials following amygdaloid kindling in cats

In this study we dealt with the changes in visual and auditory evoked potentials following kindling, to reveal the distant effects of epileptic activity. The experiments were performed using cats. Visual and auditory evoked potentials were obtained initially. Daily stimulation of 60 Hz (rectangular wave, 1 ms in duration, 500 microA in peak current, 2-s train) was given to the right amygdala, for kindling. After the completion of kindling, evoked responses were recorded again. In the auditory system the changes of responses in the cortex, medial geniculate nucleus, and cochlear nucleus were distinguished. The changes of potentials in the subcortex were larger than those at the cortical level. For visual evoked potentials there was a discrepancy between stimulation with light and electrical stimulation of the optic chiasm. There was no significant change in amplitude of visual evoked potentials by flash. In the case of optic chiasm stimulation, an enlargement of evoked responses was obtained. These results indicate modality-specific change of the auditory system and widespread subcortical change. These results might be caused by some vulnerability of the auditory system in the case of amygdaloid kindling, as a result of the epileptogenic process.     

Firing pattern of neurons in the rostral and ventral part of nucleus reticularis thalami during EEG spindles

The firing pattern of neurons in the rostral and ventral part of nucleus reticularis thalami during cortical EEG spindles was investigated in unanesthetized encéphale isolé cats. Spontaneous spindles as well as those induced by a single thalamic shock were accompanied by an increase in discharge frequency in 97% of the neurons in the rostral pole of the nucleus. In most cases the enhanced firing rate was tonically sustained throughout the duration of the spindles, although phasic bursts at EEG wave frequency were sometimes superimposed on the tonic cellular activation. Suppression of triggered spindles by conditioning fast-frequency stimulation in the mesencephalic reticular formation also abolished the rostral reticularis response. Intracellular recordings revealed a depolarizing shift of small amplitude which was sustained throughout the duration of triggered spindies. The majority of neurons in the ventral part of nucleus reticularis, in contrast, underwent a prolonged hyperpolarizing shift in membrane potential during cortical spindles, sustained for as long as 2 sec and interrupted by depolarizing waves. Both the prolonged membrane hyperpolarization and the depolarizing waves were reduced during the intracellular passage of polarizing currents, suggesting that the former was an inhibitory postsynaptic potential and the latter were disinhibitory potentials. Since neurons in dorsal thalamic nuclei, to which the reticularis axons project, are hyperpolarized concomitantly with cortical spindles, the results are viewed as being in agreement with the hypothesis that, during EEG spindles, neurons in the rostral pole but not in the ventral part of nucleus reticularis exert a tonic inhibitory influence on cells throughout the thalamus.     

Neuronal reactions of the reticular nucleus and adjacent thalamus structures in the cat to natural stimulation in a chronic experiment

Spike responses of 104 neurons of the nucleus reticularis thalami (R) and neighbouring thalamic nuclei to the acoustic stimuli, tactile and visual stimulation were studied in the chronic experiment. 29% of neurons responded to the acoustic stimulation and 11% of them were not specific to different acoustic stimuli. The minimal latency of the excitation to the acoustic stimulation was 12-37 ms and that of the inhibition--18-27 ms. The duration of the excitation in response to the acoustic stimulation was 50-250 ms and that of inhibition--27-190 ms. 16% of R neurons responded to the stimulation of different sensory systems. The majority of R neurons showed excitation in response to different stimuli and only 4-10% of neurons showed inhibition.     

Absence of spindle oscillations in the cat anterior thalamic nuclei

Intracellular recordings were performed in cat anterior thalamic nuclei (anterior ventral, medial and dorsal) which, according to a recent anatomical study, do not receive afferents from the reticularis thalami nucleus. Neurons of anterior nuclei did not display spontaneous membrane potential oscillations of the spindle type and such oscillations could neither be evoked in these cells by cortical stimulation. The absence of spontaneous and evoked spindling activity was observed despite that anterior thalamic cells displayed intrinsic membrane properties similar to those of thalamocortical cells in other nuclei. Electrographic recordings from cortical areas connected to anterior thalamic nuclei were also free of spindle activity. Taken together with the evidence that thalamic relay neurons deprived from their reticularis input by sections or kainic acid lesions lose their spindling activity, our results point to the essential role of the reticularis complex in the genesis of thalamic spindle waves.     

Thalamo-cortical processing of near-threshold somatosensory stimuli in humans

Somatosensory stimuli elicit complex cortical responses that are discernible as somatosensory evoked potentials (SEPs) in scalp electroencephalographic recordings. Whereas earlier SEP components, occurring up to 100 ms after stimulus delivery, have been labeled 'preconscious', later responses have been associated with stimulus awareness. To date, how far these processes are primarily cortical or comprise additional subcortical operations remains open. Therefore, we recorded thalamic and scalp SEPs evoked by perceived as well as unperceived median nerve stimulation in neurosurgical patients with electrodes implanted into the ventral intermediate nucleus of the thalamus for deep brain stimulation. At stimulation intensities below perceptual threshold, only thalamic SEP components appeared consistently during the first 75 ms after stimulus delivery. Stimulation that was perceived by the patients elicited cortical as well as thalamic SEPs that lasted longer than 75 ms. These results indicate that the thalamus remains active after the primary propagation of a sensory signal to the cortex, and suggest that the transition from elementary to higher-order somatosensory processing is based on thalamo-cortical interactions.     

Effect of septal and fimbrial stimulation on auditory and visual cortical evoked potentials in the cat

The effects of septal and fimbrial stimulation on auditory and visual cortical evoked potentials were determined. The cortical responses were recorded from the ectosylvian and marginal gyri respectively with both acutely and chronically implanted electrodes. After all recordings were completed, lesions were made in the septum in three of the cats and both auditory and visual cortical evoked potentials were again studied. Depending on the location within the septum, septal stimulation in acute preparations either attenuated or facilitated both auditory and visual cortical evoked potentials; stimulation of the fimbria had a facilitatory effect. With chronically implanted electrodes, septal stimulation led to decreases and fimbrial stimulation to increases in evoked response amplitudes. Certain of the previous effects were reversed after placement of the lesion in the septum. Auditory and visual cortical evoked potentials previously attenuated by septal stimulation were facilitated and fimbrial stimulation after the septal lesion resulted in the attenuation of previously facilitated cortical evoked potentials. These findings implicate the septum and fimbria in processing sensory information and give evidence that a uniprocess concept of septal functioning is no longer adequate.     

Reactions of lateral geniculate cells to chemical and electrical excitation of the visual cortex in rabbits

In anesthetized and paralyzed rabbits unitary discharges of lateral geniculate nucleus (LGN) were studied after cortical excitation by strychnine and following electrical stimulation of the visual cortex (VC). Results showed that local application of strychnine produced a general increase of the spontaneous and evoked activity of geniculate cells. By contrast, cortical depression with KCl led to a differential decrement of one of the evoked responses (on or off). Electrical cortical stimulation paired with on or off stimuli led to a differential increment of on or off responses. The results support the notion that, in rabbits, the corticogeniculate system is center-surround organized. A diagrammatic model is proposed to account for the relationship between the VC and the LGN in rabbits.     

Change in the evoked potentials in the visual centers of the rat brain following administration of tetanus toxin to the lateral geniculate body

Changes in visual evoked potentials were studied under conditions of tetanus-toxin injection into the lateral geniculate body in rats. The main abnormality of the evoked potentials in the geniculate body was the function of a new phase of the primary response. At the same time a strong increase in the amplitude of the first negative component of the evoked response in the ipsilateral cortical visual field was observed. The results show the formation of disturbances in the relay function of the lateral geniculate body during the formation of a generator of pathologically enhanced excitation in this nucleus.     

The role of 5-HT, GABA and opioid peptides in presynaptic inhibition of tooth pulp input from the medial brainstem

In decerebrate or chloralose-anaesthetized cats electrical stimulation in the spinal trigeminal nucleus evoked antidromic responses in the mandibular canine tooth pulp. Conditioning stimulation in nucleus raphe magnus (NRM) and in the adjacent contralateral medullary reticular formation, nucleus reticularis gigantocellularis (NRGC) and nucleus reticularis magnocellularis (NRMC), produced a decrease in the threshold for the antidromic responses in a proportion of the tooth pulp inputs. This was interpreted as being due to depolarization of the tooth pulp afferent terminals, reflecting presynaptic inhibition. The primary afferent depolarization (PAD) of tooth pulp afferent terminals by NRM stimulation could be selectively blocked by bicuculline applied intravenously or by iontophoresis in the terminal region. Intravenous naloxone, cinanserin and methysergide had no effect on the PAD evoked from NRM, NRGC or NRMC. Thus NRM appears to exert presynaptic inhibitory control of A delta tooth pulp input to the spinal trigeminal nucleus via GABA-containing neurones.     

Regulation of unit activity in nucleus reticularis thalami by the mesencephalic reticular formation and the frontal granular cortex.

Recruiting responses and related synchronous activities appear to be mediated by thalamic inhibition originating in nucleus reticularis thalami, a structure jointly regulated by an ascending projection from mesencephalic reticular formation and a descending influence from the frontal cortex. Extracellular unit activity was recorded in the anterior nucleus reticularis thalami (RVA) during recruiting responses, augmenting responses, stimulation of the mesencephalic reticular formation (MRF), and cryogenic blockade of the inferior thalamic peduncle (ITP). During recruiting responses, RVA units responded to medial thalamic (MT) stimulation with prolonged high frequency bursts. Analysis of the post-stimulus time histograms of these responses showed tham to have the same latency, duration, incrementing character, and envelope shape as the phasic thalamic inhibitory postsynaptic potentials (IPSPs) which appear to mediate recruiting responses. Brief stimulation of the MRF, which abolishes recruiting responses and thalamic IPSPs, prevented the response of RVA units to MT stimuli, and inhibited the spontaneous discharge of these units for 20 sec or more. We propose that the desynchronizing effect of MRF activation results from the abolition of thalamic inhibition originating in RVA. Cryogenic blockade of the ITP, which abolishes recruiting responses in the thalamus and cortex, also prevented R units from responding to MT stimuli. This result suggests that the MT activates R units via a thalamo-frontocortico-R pathway and explains the long latency of R bursts and thalamic IPSPs following MT stimulation. R cells that fired prolonged bursts during recruiting responses did not respond during augmenting responses. This result suggests that separate thalamic inhibitory mechanisms are involved in these two types of synchronization.     

Responses of globus pallidus neurons to cortical stimulation: intracellular study in the rat.

The responses of globus pallidus (GP) neurons to stimulation of the sensorimotor cortex, the neostriatum, and the subthalamic nucleus were intracellularly recorded in anesthetized rats. Stimulation of the cortex evoked a sequence of postsynaptic responses including an initial short EPSP, a short IPSP, and a late EPSP with multiple spikes in most of the repetitively firing GP neurons. The response pattern was very similar to those evoked by striatal stimulation, except that the latencies were longer. An acute knife cut placed immediately caudal to the substantia nigra caused no significant change in the responses to cortical and striatal stimulation. Stimulation of the subthalamic nucleus evoked a short latency EPSP overlapped with an IPSP. The polarity of all the IPSPs was reversed by a Cl- injection. A systemic injection of picrotoxin abolished all the IPSPs and unmasked large depolarizations with multiple spikes. An ibotenic acid lesion of the subthalamic nucleus eliminated both the initial short latency and late EPSPs to cortical and striatal stimulation and disclosed a prominent IPSP. Stimulation of the lesioned subthalamic nucleus also evoked large, short latency IPSPs without noticeable EPSPs. These results indicate that (i) the IPSPs evoked by cortical, striatal, and subthalamic stimulation were mediated by a GABAA receptor, (ii) both the initial and late EPSPs to cortical and striatal stimulation involved activation of the subthalamic nucleus but not brainstem nuclei, and (iii) cortically derived signals mediated through the neostriatum (i.e. long latency IPSPs) and the subthalamic nucleus (i.e. short latency EPSPs) converged on most GP neurons.     

Flash evoked cortical and subcortical potentials in neuro-ophthalmology

Visual evoked cortical and sub-cortical potentials are complementary to the electroretinogram in neuro-ophthalmology. By combining monocular stimulation with recordings from over the visual cortex of each cerebral hemisphere it is possible to accurately locate lesions which are both pre and post chiasmal. Chiasmal lesions can also be correctly identified using these techniques. The visual evoked sub-cortical potential, probably arising from a lateral geniculate or tectal site allows further post chiasmal variation. Flash and pattern reversal stimulation provide different information about the functioning of the visual system including the primary visual cortex and the association areas.     

Inhibition of hand muscle motoneurones by peripheral nerve stimulation in the relaxed human subject. Antidromic versus orthodromic input

In active muscle, a supramaximal conditioning stimulus to peripheral nerve produces a classic silent period in the EMG. The present experiments examined the effect of this type of conditioning stimulus on motoneurone excitability in relaxed muscle.EMG responses evoked by transcranial magnetic stimulation of the brain were recorded from the first dorsal interosseus muscle (FDI) in 10 healthy subjects and 5 patients with sensory neuropathy. These responses (motor evoked potentials) were conditioned by supramaximal peripheral nerve stimuli given 0–150 msec beforehand. In the normal subjects, the classic silent period in the FDI lasted about 100 msec. The same conditioning stimulus only abolished motor evoked potentials when the conditioning-test interval was so short that the antidromic peripheral nerve volley collided with the orthodromic volley set up by magnetic brain stimulation. At longer conditioning-test intervals, although remarkably inhibited (65% mean suppression between 10 and 40 msec), the test motor potential was never completely abolished and gradually recovered by 100 msec.Inhibition of cortically evoked motor potentials did not depend upon activity set up by the conditioning stimulus in peripheral nerve sensory fibres. The patients with complete peripheral sensory neuropathy had the same extent and time-course of inhibition as the normal subjects. We conclude that in relaxed subjects the inhibitory effect of peripheral conditioning results almost exclusively from the motoneuronal inhibitory mechanisms consequent to antidromic invasion.     

Effects of Caudate Stimulation on Unitary and Mass Responses of the Visual Cortex to Light

Effects of caudate stimulation on unitary and mass responses of the visual cortex to flash were studied in light barbiturate anesthetized, or immobilized cats. A conditioning shock to the caudate nucleus produced an increase in amplitude of the primary components of the photically evoked potential in the lateral gyrus. The increase in amplitude of the potential was caused by bilateral caudate stimulation. Marked effects of caudate stimulation were observed at several conditioning-test intervals. Unitary responses of the visual cortical neurons to light were enhanced or inhibited by the conditioning shock to the caudate nucleus. Enhancement of firing in response to light was more commonly seen in units which fired primarily after flash, but inhibition in those showing a primary neuronal silence and in those with irregular reaction and with no reaction. It is concluded that the caudate nucleus has an intimate functional interrelation with other structures in the brain stem.     

Hemianopia, hemianesthesia, and spatial neglect: a study with evoked potentials.

We recorded somatosensory or visual evoked potentials (SEPs, VEPs) to stimuli contralateral and ipsilateral to the lesion in three right-brain-damaged patients with left spatial hemineglect and in three left-brain-damaged patients without evidence of neglect, as assessed by visual exploratory tasks. All patients had contralateral homonymous hemianopia or hemianesthesia. The three neglect patients showed normal SEPs or VEPs to stimuli delivered to the left half-field or to the left hand, without conscious perception and verbal report of the stimulation. By contrast, the three left-brain-damaged patients without neglect showed no recognizable cortical evoked response to contralateral visual or somatosensory stimuli. In all patients, the cortical evoked responses to ipsilateral stimulation were normal. In patients with spatial hemineglect, hemianopia and hemianesthesia may be manifestations of the neglect syndrome (visual and somatosensory hemi-inattention), rather than representing primary sensory deficit. Visual and somatosensory hemi-inattention may be due to defective access to the neural processes subserving conscious perception by information that has undergone early sensory processing.     

Physiology of perception: cortical stimulation and recording in humans

OBJECTIVES: 1) To determine the effect of stimulus train duration (TD) on sensory perception using direct stimulation of somatosensory and visual cortices. 2) To investigate the occurrence of evoked potentials in response to stimulation that is subthreshold for perception. BACKGROUND: Studies of the mechanisms of conscious perception using direct cortical stimulation and recording techniques are rare. The clinical necessity to implant subdural electrode grids in epilepsy patients undergoing evaluation for surgery offers an opportunity to examine the role of stimulus parameters and evoked potentials in conscious perception. METHODS: Subjects included epilepsy patients with grids over somatosensory or occipital cortex. Single pulses (100 microseconds) and stimulus trains were applied to electrodes, and thresholds for perception were found. Evoked potentials were recorded in response to peripheral stimulation at intensities at, above, and below sensory threshold. RESULTS: During cortical stimulation, sensory threshold changed little for stimulus trains of 250 milliseconds and longer, but increased sharply as TD decreased below this level. Primary evoked activity was recorded in response to peripheral stimulations that were subthreshold for conscious perception. CONCLUSIONS: The results confirm a previous report of the effects of stimulus TD on sensory threshold. However, no motor responses occurred following somatosensory stimulation with short trains, as previously reported. The TD threshold pattern was similar in visual cortex. In agreement with the previous report, early components of the primary evoked response were not correlated with conscious sensory awareness.     

Lack of visual suppression in the rabbit lateral geniculate nucleus during blink reflex

Stimulation of the supraorbital branch of the trigeminal nerve (SO) elicited eye blinks in the rabbit, but did not decrease the amplitude of visual cortical evoked potential from stimulation of the optic chiasm (OX). In addition, the SO stimulation neither induced an inhibitory postsynaptic potential (IPSP) in LGN cells, nor activated inhibitory interneurons in the thalamic reticular nucleus (TRN), which proved to mediate both recurrent inhibition and saccadic suppression in the dorsal lateral geniculate nucleus (LGN). All these indicate that there is no visual suppression in the rabbit LGN during blink reflex.