Non-specific Thalamo-cortical System Research Articles

Differential Effects of Deep Sedation with Propofol on the Specific and Nonspecific Thalamocortical Systems

The current state of knowledge suggests that disruption of neuronal information integration may be a common mechanism of anesthetic-induced unconsciousness. A neural system critical for information integration is the thalamocortical system whose specific and nonspecific divisions may play the roles for representing and integrating information, respectively. How anesthetics affect the function of these systems individually is not completely understood. The authors studied the effect of propofol on thalamocortical functional connectivity in the specific and nonspecific systems, using functional magnetic resonance imaging. Eight healthy volunteers were instructed to listen to and encode 40 English words during wakeful baseline, light sedation, deep sedation, and recovery in the scanner. Functional connectivity was determined as the temporal correlation of blood oxygen level-dependent signals with seed regions defined within the specific and nonspecific thalamic nuclei. Thalamocortical connectivity at baseline was dominantly medial and bilateral frontal and temporal for the specific system, and medial frontal and medial parietal for the nonspecific system. During deep sedation, propofol reduced functional connectivity by 43% (specific) and 79% (nonspecific), a significantly greater reduction in the nonspecific than in the specific system and in the left hemisphere than in the right. Upon regaining consciousness, functional connectivity increased by 58% (specific) and 123% (nonspecific) during recovery, exceeding their values at baseline. Propofol conferred differential changes in functional connectivity of the specific and nonspecific thalamocortical systems, particularly in left hemisphere, consistent with the verbal nature of stimuli and task. The changes in nonspecific thalamocortical connectivity may correlate with the loss and return of consciousness.

On the all-or-none rule of conscious perception

On the all-or-none rule of conscious perception

Is the basalo-cortical system simply an extra-thalamic relay of the ascending reticular activating system? A discourse with Mircea Steriade

As established in early studies, the basalo-cortical system serves as an extra-thalamic relay from the brainstem reticular activating system to the cerebral cortex. As Mircea Steriade documented, activating impulses are transmitted through either the nonspecific thalamo-cortical projection system or the basalo-cortical projection system to stimulate widespread, fast, cortical activity that is characteristic of the activation that occurs naturally during waking (W) and paradoxical sleep (PS) states. However, basal forebrain (BF) neurons are different from thalamic neurons in several ways. First, many cortically projecting BF neurons utilize acetylcholine (ACh), which has a crucial role in stimulating fast cortical activity. Second, ACh-releasing neurons discharge selectively during W and PS and cease firing during slow-wave sleep (SWS). Third, ACh-releasing neurons discharge rhythmically in bursts during cortical activation and can, thus, modulate the cortex in a slow rhythmic manner to facilitate coherent activity across broad cortical networks. Fourth, the rhythmic discharge by BF neurons that release ACh, GABA or glutamate and project to the cortex occurs at respiratory or theta frequencies of the olfactory and limbic cortices, which reveals the particular importance of these inputs as well as outputs within basalo-cortico-basalo circuits. Fifth, other noncholinergic BF neurons, including GABA-releasing neurons, are active selectively during sleep: some of these potentially promote slow-wave activity during SWS through cortical projections; and others might promote behavioral quiescence during SWS and PS through descending projections. Finally, BF neurons also project to the thalamus and might, thus, either recruit or join thalamic neurons in modulating cortical activity across the sleep–waking cycle.

Arousal systems.

The brain contains autochthonous neural systems that evoke waking from sleep in response to sensory stimuli, prolong or enhance arousal in response to special stimuli, and also generate and maintain wakefulness regardless of sensory stimuli during the active part of the day. Through ascending projections to the cortex, these arousal systems stimulate cortical activation, characterized by high frequency gamma and low frequency rhythmic theta activity, and through descending projections to the spinal cord, they stimulate muscle tonus along with sensory-motor responsiveness and activity. They are comprised of neuronal aggregates within the brainstem reticular formation, thalamus, posterior hypothalamus and basal forebrain, and they utilize multiple different neurotransmitters. Within the brainstem, neurons of the reticular formation, which predominantly utilize glutamate as a neurotransmitter, stimulate cortical activation by exciting the widespread projecting neurons of the nonspecific thalamo-cortical projection system, which similarly utilize glutamate, and neurons of the ventral extra-thalamic relay systems located in the posterior hypothalamus and basal forebrain, many of which also utilize glutamate. In addition, these systems have descending projections by which they can enhance or modulate muscle tonus and activity. Articulating with these are cholinergic neurons of the ponto-mesencephalic tegmentum and basal forebrain that promote cortical activation during waking and also during rapid eye movement sleep (REMS), in association therein with muscle atonia. Dopaminergic ventral mesencephalic neurons stimulate a highly motivated and positively rewarding state during waking and may also do so during REMS. In contrast, noradrenergic locus coeruleus neurons promote an aroused waking state and prevent REMS as well as slow wave sleep (SWS). Serotonergic raphe neurons promote a seemingly quiet or satiated waking state, which though exclusive of REMS, can actually be conducive to SWS. Histaminergic neurons of the posterior hypothalamus act like noradrenergic neurons in enforcing waking and are joined by neurons in the region that contain orexin, a neuropeptide recently shown to maintain waking and in absentia to be responsible for narcolepsy, or the inability to maintain wakefulness. These multiple arousal systems are grossly redundant, since no one system is absolutely necessary for the occurrence of waking; yet they are differentiated, since each plays a special role in waking and sleep. During SWS, they are submitted to an inhibitory influence arising in part at least from particular GABAergic neurons co-distributed with many neurons of the arousal systems and also concentrated within the basal forebrain and adjacent preoptic region.

Selective Action of Orexin (Hypocretin) on Nonspecific Thalamocortical Projection Neurons

As is evident from the pathological consequences of its absence in narcolepsy, orexin (hypocretin) appears to be critical for the maintenance of wakefulness. Via diffuse projections through the brain, orexin-containing neurons in the hypothalamus may act on a number of wake-promoting systems. Among these are the intralaminar and midline thalamic nuclei, which project in turn in a widespread manner to the cerebral cortex within the nonspecific thalamocortical projection system. Testing the effect of orexin in rat brain slices, in two nuclei of this system, centromedial (CM) nuclei and rhomboid nuclei, we found that it depolarized and excited all neurons tested through a direct postsynaptic action. An additional analysis of this effect in CM neurons indicates that it results from the decrease of a potassium conductance. By a detailed comparison of the effects of orexin A and B, we established that orexin B was more potent than orexin A, indicating the probable mediation by orexin type 2 receptors. In contrast to its effect on the nonspecific thalamocortical projection neurons, orexin had no effect on the specific sensory relay neurons of the somatic, ventral posterolateral, and visual dorsal lateral geniculate nuclei. Orexin differs in this regard from norepinephrine and acetylcholine, to which neurons in the specific and nonspecific systems are sensitive. Orexin may thus act in the thalamus to promote wakefulness by exciting neurons of the nonspecific thalamocortical projection system, which, through widespread projections to the cerebral cortex, stimulate and maintain cortical activation.

Participation of the thalamic CM-Pf complex in attentional orienting.

The centre médian-parafascicular (CM-Pf) complex is located at the posterior intralaminar nuclei of the thalamus and forms part of the nonspecific thalamocortical projection system and the internal circuit of the basal ganglia. However, the functional roles of this complex remain to be fully elucidated. Here we have examined whether the CM-Pf complex is involved in the process of covert attention. We trained two macaque monkeys to perform a task in which a visual target stimulus for button release appeared at either the same location as the preceding visual instruction cue (a "validly cued target") or a location on the opposite side (an "invalidly cued target"). Reaction times (RTs) to a validly cued target were significantly shorter than those to an invalidly cued target, leading to a "validity effect" of about 20 ms. We recorded the activity of 97 neurons in the CM-Pf while the monkeys performed the attention task with the hand that was contralateral to the neuronal recording. Seventy CM-Pf neurons showed task-related activity after the appearance of either the instruction cue or the target stimulus: 33 neurons responded with a prominent short-latency facilitation (SLF), whereas 37 responded with a short-latency suppression followed by a long-latency facilitation (LLF). Most of the SLF neurons responded preferentially to a cue appearing on the contralateral side (76%) and to an invalidly cued target appearing on the contralateral side (61%). In contrast, LLF neurons showed a short-latency suppression after the cue stimulus, regardless of whether the cue appeared on the contra- or ipsilateral side (84%). Inactivating the CM-Pf complex by local injection (1 microl) of the GABA(A) receptor agonist muscimol (1-5 microg/microl) resulted in a significant increase in the RT to a validly cued target presented on the contra- but not the ipsilateral side. In contrast, inactivating the CM-Pf complex did not affect RTs to invalidly cued targets on either the contra- or the ipsilateral side. Thus the validity effect was abolished only on the contralateral side. We conclude that the CM-Pf complex plays a specific and essential role in the process of attentional orienting to external events occurring on the contralateral side, probably through the projection of primary outputs to the striatum, which is involved in the action-selection mechanisms of the basal ganglia.

A Janusian perspective on the nature, development and structure of schizophrenia and schizotypy

A personal review is presented of the functional basis of activation, withdrawal and unreality, individual differences in schizophrenia that Venables et al. pioneered. Activated and withdrawn syndromes were delineated from the totality of symptoms by classifying unmedicated patients on the basis of lateral asymmetries in electrodermal responses. A neuropsychological syndrome translation led to a syndrome hemispheric imbalance model supported by a literature review disclosing widespread cortical and infracortical involvement extending to motoneurone excitability, with validation from tests of learning, memory and evoked responses including the P300. It is contended that the centrality of arousal, the extensive substrate and the evidence of asymmetry modification with recovery and treatment all implicate specific and nonspecific thalamo-cortical systems whose uncoupling may lead to dysfunction of input, cognition and to unreality symptoms (found inconsistently related to asymmetry). The three syndromes have developmental associations including immune competence, ventricular changes and lateral asymmetry, putative regressive neuronal changes in connectivity and electrocortical measures of connectivity, as well as sensory gating and anomalies of P50 suppression and habituation. Replication of the syndromal structure in psychometric schizotypy indicates that syndrome expression is based on the premorbid personality, compatible with evidence of early determinants of the approach/withdrawal balance in social encounters. Functional considerations for the nature of schizophrenia support neurophysiological approaches to treatment such as neurofeedback.

Calbindin-containing non-specific thalamocortical projecting neurons in the rat

Immunoreactivity for calcium binding proteins was used to demonstrate the neurochemical profiles of non-specific thalamocortical neurons located in the ventromedial nucleus, the centrolateral nucleus, and the nucleus reuniens that project to the somatosensory cortex in the adult rat. Cortical injections of fluorescent tracers combined with immunohistochemistry for calcium binding proteins revealed that retrogradely labeled neurons in these three thalamic nuclei are immunoreactive for calbindin. The present results suggest the presence of a chemically distinct non-specific thalamocortical system which terminates in the neocortex.

Chapter 5: The organization of central cholinergic systems and their functional importance in sleep-waking states

Since the demonstration some 50 years ago of the presence and synthesis of acetylcholine (ACh) in specific neuronal systems within the brain, a wealth of information concerning the organization and functional importance of central cholinergic neurons has emerged through immunohistochemical, neuroanatomical, pharmacological, biochemical and neurophysiological studies. Many of the original theses have proven valid concerning the key structural and functional position of cholinergic neurons within the central reticular core of the brain, where the basic sleep-waking cycle is determined. The two major cholinergic cell groups of this core, one within the pontomesencephalic tegmentum that projects rostrally into the non-specific thalamo-cortical relay system and the other within the basal forebrain that receives input from the brainstem reticular formation and projects in turn as the ventral, extrathalamic relay upon the cerebral cortex, are critically involved in processes of cerebral activation that accompany the states of wakefulness and paradoxical sleep. By interaction with other cell groups, including monoaminergic and GABAergic neurons, and by differential modes of firing, the cholinergic neurons may furthermore shape the responsiveness and activity of the reticular core and thalamo-cortical systems across the sleep-waking cycle.

Neurotoxic lesions of the dorsolateral pontomesencephalic tegmentum-cholinergic cell area in the cat. I. Effects upon the cholinergic innervation of the brain

Kainic acid was injected bilaterally (4.8 μg in 1.2 μl each side) into the dorsolateral pontomesencephalic tegmentum of cats in order to destroy cholinergic cells which are located within the pedunculopontine tegmental (PPT), laterodorsal tegmental (LDT), parabrachial (PB), and locus ceruleus (LC) nuclei in this species. The neurotoxic lesions resulted in the destruction of the majority (≅60%) of choline acetyltransferase (ChAT)-immunoreactive neurons and a minority (≅35%) of tyrosine hydroxylase (TH)-immunoreactive neurons, as well as in the destruction of other chemically unidentified neurons, in the region. The effects of these lesions upon the cholinergic innervation of the brain were investigated by comparison of brains with and without lesions which were processed for acetylcholinesterase (AChE) silver, copper thiocholine histochemistry and ChAT radio-immunohistochemistry. In the forebrain, a major and significant decrease in AChE staining, measured by microdensitometry, and associated with a decrease in ChAT immunoreactivity was found in certain thalamic nuclei, including the dorsal lateral geniculate, lateral posterior, pulvinar, intralaminar, mediodorsal and reticular nuclei. All of these nuclei receive a rich cholinergic innervation evident in both AChE histochemistry and ChAT immunohistochemistry. No significant difference in AChE staining or ChAT immunoreactivity was detected in other thalamic nuclei or in the subthalamus, hypothalamus or basal forebrain. In the brainstem, a significant decrease of AChE staining and ChAT immunoreactivity was found in the superior colliculus and the medullary reticular formation,where ChAT-immunoreactive fibers were moderately dense in the normal animal. These results indicate that the pontomesencephalic cholinergic neurons may influence the forebrain by major projections to the thalamus, involving both relay and non-specific thalamocortical projection systems, and thus act as an integral component of the ascending reticular system. They may influence the brainstem by projections onto deep tectal neurons and other reticular neurons, notably those in the medullary reticular formation, and thus also affect bulbar and bulbospinal systems.

The functional projections of the anterior ventralis nucleus, as revealed by autoradiography

The effect of stimulation of ventral anterior nuclei of the thalamus (VA) was studied in different areas of cat cortex (sensory, motor and association) with [ 3H]glycine autoradiography. One-hour VA stimulation resulted in the most intensive [ 3H]glycine incorporation in the second, third and fifth layers of the anterior suprasylvian gyrus and of the motor cortex. The labelling was less intensive in the sensory (auditory) and association (posterior middle suprasylvian association area) cortices, but the effect of VA stimulation reached these regions as well. The VA stimulation resulted in evoked potentials over the whole area examined, with highest amplitude and shortest latency in the anterior suprasylvian gyrus. It is suggested that the [ 3H]glycine autoradiography is suitable to study the functional projection of non-specific thalamocortical systems.

Neurophysiological aspects of distractability in schizophrenics. A theoretical analysis.

The aim of the present study was to discuss distractability in schizophrenics in neurophysiological terms. A review of the literature strongly suggested that schizophrenics may be abnormally distractible; that is, show an increased tendency to react to irrelevant stimuli. The neuroanatomical structures most clearly implicated in signs of distractability by neurophysiological and behavioural evidence are the prefrontal (orbital) cortex, the nonspecific thalamo-cortical projection system, and inhibitory regions of the reticular formation. The disturbed functioning of these structures, it is suggested, could come about as a result of a lowered task-related activation, primarily of the prefrontal cortices. Apparently, dopaminergic activity could influence the regions involved, suggesting a dopaminergic component in distractability in schizophrenics. The regions in question may also be influenced by other biochemical systems, such as the serotonergic and noradrenergic systems.

Striatal control of locomotion, intentional actions and of integrating and perceptive activity

The three parts of the striatum — putamen, caudate nucleus and fundus striati — control intentional actions and not simple movements without conscious representation. According to its integrative function the striatum consists of at least four distinct types of nerve cells, the bulk of which (more than 90%) is formed by the small “spiny” neurons with intrinsic axons. In each part of the striatum nine discrete types of synapses are distinguished: one axo-spinous and one axo-dendritic (or axo-somatic) from the substantia nigra (type I and II); from the cortical fields (type III and VII); from the center median-parafascicular complex of the thalamus (type IV and VII) and type V as axon-collateral of the large efferent neurons; type VI with flattened vesicles of so far unknown origin; type VIII as dendritic terminal of Golgi type II cells; and type IX as intrinsic contacts between the small intrinsic and the large efferent neurons. The transmitter of the nigral afferents is dopamine (DA), that of the cortical afferents glutamic acid, that of the intrinsic synapses acetylcholine (ACh) and that of center median-parafascicular afferents also perhaps ACh. The results of the integrating activities of this synaptic organization are conducted by GABA-ergic, mostly inhibitory, fibers to the substantia nigra and to both segments of the pallidum. The strio-pallidal neuronal chain forms a part of the nonspecific thalamo-cortical activating system, which we prefer to call trunco-thalamic system to avoid the equivocal term, nonspecific, and because it is anatomically more correct. The nonspecific input of the different sensory systems to the cortical sensory regions runs through the neuronal chains of the reticular formation to the trunco-thalamic nuclei which do not project directly to the cortical fields as the intralaminar nuclei and mainly the center median and parafascicular nuclei. These trunco-thalamic nuclei project to the three parts of the striatum or to the outer segment of the pallidum. All these impulses meet, finally, in the outer and inner segments of the pallidum. From there at least two, but probably more, pathways go to thalamic nuclei, such as V.o.a. (the anterior basal part of VL) and VA which project directly to cortical fields specifically or diffusely to the rostral part of the hemisphere and to the parietal lobe. This nonspecific action of the basal ganglia loop on the majority of cortical areas is also demonstrated by eliciting recruiting potentials in gross recording and field potential recordings. Each part of the striatum belongs to the trunco-thalamic activity-regulating system of the cerebral cortex. The direct functional role of the putamen is best revealed by the Hess method of near threshold stimulation in the unanesthetized, unrestrained cat: low frequency stimulation (1–9 Hz) produces a delayed inhibition or motor ritardando of any form of spontaneous or stimulus induced movement and a closing of the eyes with miosis, and intermediate frequency stimulation (15–50 Hz) produces an immediate arrest of all activities and opening of the eyes with mydriasis. A locomotor activity, turning to the side of stimulated putamen, is elicited at the same time and a spontaneous turning to this side is accelerated and a spontaneous turning to the nonstimulated side suppressed. In contrast, low and middle frequency pallidal stimulation elicits only excitatory effects with turning to the contralateral side and pupil dilatation; this is true for animal experiments and during stereotaxic operations in the human. From these data it is concluded that the function of the putamen is at the same time to focus the attention, the emotional participation and the excitability on one single event by simultaneously suppressing and fading out all other happenings and motivational objects, including those coming from the contralateral side. The pallidal function is horizontal locomotion to the contralateral side, the enhancing of the muscle tone of the contralateral side and directing of attention to the contralateral side; without this no conscious mental processes can go on.

Generalized paroxysmal discharges induced by visual stimuli and eye movements.

The generalized paroxysmal discharges (GPDs) induced by the visuo-sensory and oculomotor activations in a total of 30 patients were investigated. The patients consisted of 27 epileptics and 3 with sequelae of head trauma; all of them showed photoconvulsive response. The visuo-sensory activation with red-flicker of 15 cycles/sec or with visual stimuli containing patterns, "pattern," was carried out under the constant condition of 20 cd/m-2. In 22 cases (73%), G-type (simultaneous occurrence of GPD over all the areas) was induced by red-flicker, while in 28 cases (93%) P-type (GPD was preceded by posterior spikes) was induced by "pattern." With the oculomotor activation, paroxysmal discharges were induced in 11 cases of photogenic epilepsy; 10 cases (91%) were of A-type (GPD was preceded by anterior spikes), and one case (9%) showed focal spikes over the right frontal area. In 21 cases (70%), the type of GPD changed from G-type to P-type as the red-flicker activation was replaced by the "pattern" activation. Further, in seven (33%) out of the 21 cases it changed from P-type to A-type as the activation with "pattern" was replaced by the oculomotor activation. It was suggested that the non-specific thalamo-cortical system, the visual cortex, and the frontal eye field are chiefly concerned with the occurrences of G-type, P-type, and A-type, respectively, when such stimuli as described above are given independently.

Occipital spikes and their relation to visual evoked responses in epilepsy, with particular reference to photosensitive epilepsy

The responses to intermittent photic stimulation (IPS) at rates of 1–10 fl/sec were studied in seventy-two subjects, eighteen being normal controls, thirty-eight having photosensitive epilepsy and sixteen having epilepsy which was not clinically photosensitive. All patients showed abnormal responses to IPS. In most of the patients photic stimulation evoked negative occipital spikes with or without photoconvulsive responses. Comparison was made between the occipital spikes and the VERs in the same patient. This showed that there was no simple time relation between occipital spikes and components of the VERs. The VERs of the normal subjects showed no component with a latency corresponding to that of the negative occipital spikes seen in the patients. It is suggested that the non-specific thalamo-cortical system may be responsible for the genesis of the “epileptogenic” occipital spikes and that increased sensitivity of the occipital cortex is present in most photosensitive patients.

Abolition of a conditioned, surface-negative, cortical potential during cryogenic blockade of the non-specific thalamo-cortical system

Cryoprobes were implanted bilaterally in the region of the inferior thalamic peduncle (ITP) of three chronic cat preparations in order to block the non-specific thalamo-cortical system. Three other chronic animal preparations had cryoprobes placed more laterally in this forebrain region in the medial part of the anterior limb of the internal capsule. All six animals had stimulating electrodes placed in nucleus ventralis lateralis (VL) to produce augmenting responses and in nucleus centralis medialis (NCM) to produce recruiting responses. Transcortical recording electrodes were implanted ipsilaterally in the anterior sigmoid, coronal, anterior lateral and anterior suprasylvian cortices. 1. 1. Stimulation of NCM produced either no sustained steady-potential shift or a small positive one, whereas repetitive stimulation of VL produced a train of augmenting responses superimposed upon a large, negative, steady-potential shift which was followed after the cessation of stimulation by a post-stimulus wave of 300–400 msec duration. 2. 2. Reversible cryogenic blockade in the region of the ITP sufficient to abolish recruiting responses abolished or markedly reduced the VL-elicited steady potential and post-stimulus wave recorded in the anterior sigmoid and coronal cortices but did not affect the simultaneously recorded positive-negative augmenting-response components. Cryogenic blockade in the medial part of the anterior limb of the internal capsule did not affect the VL-elicited steady potential or post-stimulus wave, although it did reduced the amplitude of the augmenting response in the anterior sigmoid cortex. 3. 3. The three animals with cryoprobes in the ITP were exposed to a sensory-sensory conditioning paradigm in which a tone was reinforced with a mild electric shock to the skin of the neck. During early conditioning, surface-negative steady-potentials were recorded in the anterior sigmoid, coronal, and anterior lateral, i.e., marginal, cortices. After 500 additional trials, the surface-negative response had a longer latency of onset, occurring just before the start of the shock, and after overtraining, the conditioned negative response was recorded only in the frontal cortical region (anterior sigmoid). 4. 4. Cryogenic blockade in the region of the ITP abolished or markedly reduced the amplitude of the conditioned negative response recorded in the frontal cortical area during both early conditioning and overtraining. 5. 5. During ITP blockade, the simultaneous effect on the steady-potential shift, post-stimulus wave, and conditioned cortical response suggests a common underlying mechanism. 6. 6. It was shown that the VL-elicited steady-potential shift and post-stimulus wave recorded in the frontal and sensory-motor cortex, as well as the conditioned negative response recorded in the frontal cortical region, are affected by the non-specific thalamo-cortical system, a system that from previous studies has been shown to mediate recruiting responses, regulate specific sensory evoked potentials and underlie the performance of certain complex behavioral tasks. The previous work as well as the present is suggestive of a neural mechanism related to the focusing of attention, expectancy and selective perception.

Abolition of several forms of cortical synchronization during blockade in the inferior thalamic peduncle

Six chronic cat preparations were each implanted as follows: (1) A stimulating electrode was implanted in nucleus centralis medialis thalamicus for eliciting recruiting responses. (2) A stimulating electrode was implanted in nucleus ventralis lateralis thalamicus for producing augmenting responses. (3) A stimulating electrode was implanted in the head of the caudate nucleus for creating caudate spindles. (4) Transcortical recording electrodes were implanted in several frontal regions (anterior sigmoid, coronal and anterior lateral gyri) and in various posterior sites (anterior suprasylvian and posterior lateral gyri), and an indifferent electrode was implanted in the frontal sinus bone. (5) Bipolar cryoprobes were implanted in the region of the inferior thalamic peduncle (ITP) medial to the internal capsule and rostral to the thalamus. The model experimental preparation was one in which recruiting responses were abolished or markedly reduced by cryogenic blockade in the ITP, but augmenting responses were unaffected. Three control animals had identical stimulating and recording electrodes but had cryoprobes placed which were either lateral, dorsal or anterior to the critical region of the ITP. Several different forms of cortical synchronization were produced as follows: (1) barbiturate spindles by intravenous injections of sodium pentobarbital (35 mg/kg body weight); (2) atropine spindles by intravenous injection of atropine sulfate (1 mg/kg body weight); (3) THC spindles by intraperitoneal injection of marijuana extract (17% delta-1-tetrahydrocannabinol; 16 mg/kg body weight); (4) sleep spindles by sleep deprivation; (5) caudate spindles by single shock stimulation of the head of the caudate nucleus. Cryogenic blockade or permanent lesion in the region of the ITP sufficient to abolish recruiting responses but not to affect augmenting responses had the following effects on these various forms of cortical synchronization: (1) A 12 c/sec component of barbiturate spindles was abolished. (2) A 12 c/sec component of atropine spindles was abolished. (3) The sustained 12 c/sec synchronization of THC spindles was abolished. (4) A 12 c/sec component of sleep spindles was abolished. (5) Caudate spindles were abolished, and the short-latency, surface-positive response to the single shock was enhanced. None of the control animals showed any of these effects. All of the abolished components had fairly smooth wave forms, and the components remaining during blockade had complex wave forms with inflections in them. It was interpreted that the abolished components were the type II spindles of Spencer and Brookhart (1961b), since they had relatively smooth wave forms and spindle shapes and were abolished together with recruiting responses. The role of this form of cortical synchronization in higher nervous activities is not known, but blockade in the non-specific thalamo-cortical system sufficient to abolish the synchronization also renders an animal unable to perform certain learned tasks associated with selective perception, expectancy and attention.

Enhancement of visual and auditory evoked potentials during blockade of the non-specific thalamo-cortical system

Reversible cryogenic blockade of the non-specific thalamo-cortical system in the region of the inferior thalamic peduncle produces in chronic cat preparations: 1. 1. An enhancement of short-latency, visual evoked responses in widespread cortical regions (posterior sigmoid, anterior suprasylvian, primary visual and primary auditory cortices). 2. 2. An enhancement of both visual and auditory evoked responses. 3. 3. An enhancement of the first positive peak of the optic tract-elicited cortical response and the third and fourth peaks of the optic radiation-elicited potential, implying both a greater transmission through the lateral geniculate body and a greater cortical response to a constant afferent input. These electrophysiological results are correlated with behavioral deficits in response inhibition and directed attention.

Effects of diphenylhydantoin on spontaneous and evoked activity in the cat under chloralose anesthesia

1. 1. The effects of Dilantin in single acute doses of 10–85 mg/kg on spontaneous and evoked activity were investigated in eighteen cats anesthetized with α-chloralose. 2. 2. Spontaneous chloralose spikes were markedly depressed for periods of 30 min to 3 h by Dilantin in doses of 35–50 mg/kg. The non-specific thalamo-cortical projection system was similarly affected, as revealed by equally long lasting depression of cortical responses to single or repetitive stimulation of n.centrum medianum of the thalamus. 3. 3. Dilantin (40 mg/kg) abolished responses to click throughout the central auditory pathway without blocking responsiveness of the ascending pathway to electrical stimulation of the cochlear nucleus. Auditory nerve response to click was not similarly blocked. 4. 4. Responses evoked in both primary and polysensory cortical areas by photic and somesthetic stimuli were minimally or not at all depressed by Dilantin. 5. 5. The pharmacologic separation of chloralose spikes from enhancement of polysensory responses is interpreted as evidence that the two phenomena are relatively independent.

Electrophysiological and behavioral effects of blockade of the nonspecific thalamo-cortical system

A thalamo-cortical system with origins in the midline nonspecific thalamic nuclei and projections to the orbitofrontal granular cortex has been identified with an electrocortical synchronizing function related to internal inhibition. 30 acute and 14 chronic cat preparations have been utilized in the study of the nonspecific thalamo-cortical system, including its origins, pathways and cortical projections. Its functional role has been assessed in terms of its effect upon spindle bursts, recruiting and augmenting responses, sensory evoked potentials and the performance of certain learned behavioral tasks. Interruption of this nonspecific thalamo-cortical system has been produced by lesions or reversible cryogenic blockade, and by cortical ablations at 3 principal sites: n. ventralis anterior, the inferior thalamic peduncle (ITP), and the orbitofrontal cortex. Blockade of this thalamo-cortical synchronizing mechanism has resulted in 3 effects: (1) Reduction or abolition of recruiting responses elicited by stimulation of the midline thalamic nuclei, and reduction or abolition of spontaneous spindle bursts produced by lesion of the mesencephalic reticular formation. These effects involving the nonspecific thalamo-cortical system are contrasted with the specific sensory and motor systems whose augmenting responses are not affected by blockade of the thalamo-cortical system. (2) Enhancement of visual cortical responses elicited by photic or optic tract stimulation. This effect upon specific sensory responses contrasts with the reduction or abolition of spindle bursts and recruiting responses mediated by a nonspecific system. (3) Deficits in performance of learned behavioral tasks involving bar-pressing and single alternation. Complete cryogenic blockade in ITP interrupted bar-pressing whereas partial blockade only slowed bar-pressing rate but interfered with single alternation performance due to perseveration. The nonspecific thalamo-cortical system has been discussed in terms of its synchronizing and regulating influences upon electrocortical activity, its inhibitory role, and as a possible mechanism mediating attention and inattention.