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Late cortical-evoked responses in clinical use.

Direct-current (dc) deflections in the EEG in response to sensory stimuli were first described by Köhler who, however, employed relatively high intensities. Gumnit, as well as Caspers, working with physiological stimulus intensities in animals, and recording from the primary projection areas of the different sensory modalities then showed that the evoked dc potentials during stimulation were restricted to a relatively small area of the animal's cortex which conformed well to the locus of the chosen modality. In our laboratory, using a fully computerized dc recording averaging system with Beckman electrodes, placed normally on the vertex, we have developed a routine technique adapted for clinical use. By this means, all types of electric responses obtainable from the intact human skull so auditory, gustatory and olfactory stimuli can be plotted simultaneously including the dc shift duirng a relatively long-lasting train of clicks (perstimulatory dc shift). This technique has been applied both in normal and in pathological subjects in various hospitals (ENT and children's clinics, in our country. The results obtained using this technique are described in our contribution.

Adult↗

Unit activity changes elicited in amygdala and neocortex of anaesthetized rats by intraperitoneal injection of lithium chloride.

Intraperitoneal injection of 0.15 M LiCl (2% body weight) to anaesthetized rats elicited, after a 6 min latency, discharge of about 50% units i basolateral amygdala (n = 27). The activation lasted for 15 min on the average. Cortical neurones were not affected by the LiCl injection. It is suggested that the amygdalar reaction to LiCl administration may account for the association of the gustatory trace with the visceral signals of poisoning which mediates acquisition of conditioned taste aversion under anaesthesia.

Amygdala↗

Taste perception in patients with insular cortex lesions.

Research on nonhuman primates suggests that the primary taste cortex in humans is located in the rostrodorsal insula. Qualitative and quantitative assessment of taste perception was performed on 6 patients with unilateral damage to the insula, 3 patients with brain damage outside the insula, and 11 age-matched, normal subjects. Each subject identified the quality and intensity of the gustatory stimuli applied separately to the left and right sides of the anterior tongue. Damage to the right insula produced ipsilateral taste recognition and intensity deficits. Damage to the left insula caused an ipsilateral deficit in taste intensity but a bilateral deficit in taste recognition. The unexpected deficit in the left-hemispheric stroke patients for taste recognition on the right side of the tongue suggests that taste information from both sides of the tongue passes through the left insula.

Adult↗

Localization of binding sites for calcitonin gene-related peptide in rat brain by in vitro autoradiography.

The distribution of binding sites for calcitonin gene-related peptide (CGRP) in rat brain were studied using in vitro autoradiography. In a radioreceptor assay using [125I]human calcitonin gene-related peptide as the radioligand, with cerebellar cortical membranes, rat calcitonin gene-related peptide had a binding affinity constant of 1.16 +/- 0.23 X 10(10) M-1 and a site concentration of 43.4 +/- 3.4 fmol/mg protein. In this system, human calcitonin gene-related peptide had a binding affinity constant of 3.9 +/- 0.7 X 10(9) M-1 whereas salmon calcitonin was very weak with a binding affinity constant of only 6.8 +/- 4.0 X 10(5) M-1. CGRP binding localized by in vitro autoradiography, using [125I]rat calcitonin gene-related peptide, had a characteristic distinct distribution in the rat brain. There were high concentrations of binding found over the accumbens nucleus, the organum vasculosum of the lamina terminalis, ventral caudate putamen, median eminence, the arcuate nucleus, lateral amygdaloid nucleus and lateral mammillary nucleus, the superior and inferior colliculi, pontine nuclei, molecular and Purkinje cell layers of the cerebellar cortex, the nucleus of the solitary tract, the inferior olivary nuclei, hypoglossal complex and the vestibular and cochlear nuclei. The distribution of these binding sites suggests multiple roles for CGRP in the central nervous system including auditory, visual, gustatory and somatosensory processing, and in neuroendocrine control.

Animals↗

Developmental and adult expression of rat calcium-sensing receptor transcripts in neurons and oligodendrocytes.

The calcium-sensing receptor (CaSR) is a member of a growing family of heptahelical receptors with an unusually large extracellular domain. To further delineate its functions in neurons and glia, we have investigated the expression pattern of CaSR transcripts in the postnatal and adult rat brain, spinal cord and dorsal root ganglia by in situ hybridization. CaSR-expressing cells were spatially and temporally regulated in myelinated structures with a caudo-rostral pattern that paralleled that of myelin basic protein, a marker of myelination, with a downregulation observed in the adult. Double-labelling studies demonstrated that CaSR mRNA colocalizes with myelin basic protein-expressing cells within fibre tracts, suggesting that CaSR is expressed by mature oligodendrocytes. In cultured rat oligodendrocytes, Ca2+ induced stimulation of phosphatidylinositol hydrolysis with an EC50 of 1.4 mM and increased intracellular calcium. NPS R-568 (1 microM), a calcimimetic, significantly stimulates the inositol phosphate response, whereas a less potent stereoisomer, NPS S-568 (1 microM), was without effect. These data suggest that a functional CaSR is expressed in mature oligodendrocytes with a potential role in myelination. CaSR expression was also developmentally regulated in neurons of the orbital cortex and in the CA2 region of the hippocampus, and present in olfactory nuclei, hypothalamic areas and in the area postrema through postnatal days to adulthood. This expression is consistent with a role of CaSR in olfactory or gustatory signal integration, and with the regulation of fluid and mineral homeostasis. CaSR expression in a subpopulation of small cells in dorsal root ganglia suggests additional roles for extracellular Ca2+ in sensory nerves.

Animals↗

Taste responses of cortical neurons.

Branches of the facial, glossopharyngeal and vagus nerves which synapse with the receptor cells in the taste buds convey taste messages to the rostral part of the nucleus of the solitary tract. The second relay nucleus for ascending taste input is the parabrachial nucleus of the pons. The third relay nucleus is the medial parvocellular component of the ventrobasal complex of the thalamus. This thalamic nucleus projects to the cortical taste area. Another ascending projection site of the parabrachial nucleus is to the lateral hypothalamus, amygdala and bed nucleus of the stria terminalis. In monkeys, neurons from the gustatory area of the solitary nucleus directly reach the thalamic taste area, bypassing the parabrachial nucleus. Taste-elicited reflex activities are based on a hedonic (acceptable or rejective) aspect of taste, and are basically determined in the brain stem without activation of cortical neurons. The cerebral cortical taste area is located dorsal to the rhinal sulcus in or near the insular cortex in different species of animals. Besides this taste area, taste inputs also project to the tongue tactile area of the SI in monkeys, cats and rats. Taste-responsive neurons in SI area are also responsive to light tactile stimulation of the tongue. Human clinical case reports suggest that discrimination or recognition of taste quality are processed in the cortical taste area. In animal experiments, it is difficult to determine the functional significance of this area. However, recent behavioral studies using the conditioned taste aversion technique in rats suggest that the cortical taste area plays an important role in cognitive (learning, memorial, associative and discriminative) processes of taste sensation. Summated cortical evoked potentials have been recorded in human and rats to electrical and taste stimulations applied to the tongue surface. Recording of gustatory primary evoked potentials is unsuccessful in human subjects. The responses to taste stimulation are composed of an early component, which is induced by mechanical stimulation of a test solution poured on the tongue surface and a slow component, which is assumed to be the gustatory response. Essentially similar results are obtained for cortical summated responses to taste stimuli in rats. Besides these averaged evoked potentials, arousal changes of EEG occur in response to taste stimulation. There is a possibility that the arousal response can be used an objective indicator for intensity and hedonics of perceived taste sensation.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Caudate unit activity during operant feeding behavior in monkeys and modulation by cooling prefrontal cortex.

Activity was recorded from 351 neurons in the head of the caudate nucleus (CD) of monkeys during an operant feeding task consisting of: (1) food or non-food presentation (P); (2) bar pressing (B); and (3) food acquisition and ingestion (I). Of 45 neurons which responded in the P phase and were tested systematically, 27 responded to visual presentation of both food and non-food (non-specific response), and 18 responded to food presentation only (food specific response). The magnitude of food specific responses depended on the nature of the food and was inversely related to the latency of the onset of bar pressing. Thirty-five neurons responded in the B phase: 28 changed firing rate continuously with no correlation to individual bar presses, while the activity of the other 7 was related to each bar press. In the I phase, 62 neurons responded to separate events: the activity of more than half (39 neurons) was often related to chewing movement or gustatory stimuli, and that of one third (23 neurons) changed during individual arm movements. The neurons which responded in the P phase were found to be distributed widely in the head of the CD except for its central zone, while the neurons which responded in the I phase were in the medial part. Cooling of the dorsolateral prefrontal cortex abolished the continuous responses seen in the B phase, but did not abolish the feeding behavior. The data suggest that in the head of the CD there are several groups of neurons that have different functions and different distributions: food specific, sensory integration responses, non-motor responses driven by the frontal cortex, motor responses coupled to various movements, and sensory responses which apparently originate in the intra-oral cavity. These functions may arise sequentially, or in correspondence with integration of the sensory and motor systems to produce coordinated behavior.

Animals↗

Functional relations between the cortical gustatory area and the amygdala: electrophysiological and behavioral studies in rats.

The functional interconnections between the cortical gustatory area (CGA) and the amygdala were examined by electrophysiological and behavioral experiments in rats. The cortical neurons responsive to taste stimuli applied to the anterior part of the tongue were located in the Vth layer of the agranular insular cortex. Of a total of 27 cortical neurons recorded, 10 showed facilitatory and/or inhibitory responses with the mean onset latency of about 20 msec to electrical stimulation of the ipsilateral amygdala. On the other hand, of 18 amygdaloid neurons responsive to taste stimuli, 13 showed facilitatory and/or inhibitory responses to electrical shocks to the ipsilateral CGA, with a mean latency of about 16 ms. No cortical and amygdaloid neurons sampled responded antidromically to the electrical stimulation. These results suggest the existence of mutual polysynaptic fiber connections between the CGA and the amygdala. The behavioral experiment was performed by means of a conditioned taste aversion (CTA) technique. After acquisition of CTA to sucrose solution by pairing it with an i.p. injection of LiCl which produces sickness, bilateral small knife cuts between the CGA and the amygdala in the perirhinal region disrupted retention of CTA. Thus, these interconnections may play some role in association of taste-related cognitive processes with feeding behavior.

Amygdala↗

Involvement of the anterior insular gustatory neocortex in taste-potentiated odor aversion learning.

When an odor conditioned stimulus (CS) precedes illness (unconditioned stimulus; UCS), rats acquire relatively weak odor aversions. Conversely, when a compound odor-taste (flavor) CS precedes illness, rats acquire robust aversions both to the odor and to the taste components of a compound flavor CS. Thus, tastes potentiate odor-illness aversions during toxiphobic conditioning. Such conditioning effects have been referred to as taste-potentiated odor aversion learning (POA). Previous neurobehavioral experiments have shown that the anterior insular gustatory neocortex contributes to conditioned taste aversion (CTA) learning. The present experiment examined the involvement of the anterior insular gustatory neocortex in CTA learning and POA learning. To that end, four distinct groups of rats received bilateral electrolytic lesion placements in the orbitofrontal neocortex, the "somatic" gustatory neocortex, the anterior insular gustatory neocortex or the posterior insular neocortex. Control animals received anesthesia only. Subgroups of animals thereafter received aversion conditioning using either an odor (almond) CS or a compound odor-taste (almond-saccharin) CS. Aversions to the almond odorant and/or saccharin tastant were evaluated during extinction. Results indicated that animals lacking orbitofrontal neocortex or posterior insular neocortex acquired normal CTAs and POAs. Animals lacking somatic gustatory neocortex exhibited impaired CTA learning, yet those animals showed normal POA learning. Lesions centered in the anterior insular neocortex impaired both CTA learning and POA learning. These results demonstrate that the insular gustatory neocortex is uniquely involved in the higher-order integration of odors, tastes and illness.

Animals↗

Neural correlates of tasting concentrated quinine and sugar solutions.

Behavioral, ethological, and electrophysiological evidence suggests that the highly unpleasant, bitter taste of a concentrated quinine hydrochloride (QHCL) should activate the human amygdala. In the present study, healthy subjects tasted 0.02 M QHCL or water while regional cerebral blood flow (rCBF) was assayed with H(2)(15)O PET. Subjects were also studied while tasting a pleasant sucrose solution and resting with eyes closed (ECR). Tasting QHCL significantly increased rCBF within the left amygdala relative to control conditions of tasting water and ECR. Sucrose and water caused small to moderate rCBF increases in the amygdala relative to ECR, but sucrose did not significantly increase activity within either amygdalae relative to water. In the frontal lobe, QHCL and sucrose both activated the right posterior orbitofrontal cortex (OFC) relative to water, but portions of the anterior OFC and inferior frontal pole showed valence specific responses to QHCL. These data indicate that the left amygdala responds robustly to QHCL and more moderately to nonaversive sapid stimuli, both pleasant and unpleasant gustatory stimuli activate the right posterior OFC, and the left inferior frontal pole/anterior OFC demonstrates valence-specific responses to aversive gustatory stimuli.

Adolescent↗

Direct connectivity between pontine taste areas and gustatory neocortex in rat.

Horseradish peroxidase histochemistry was used to determine the course and extent of neuronal projections from the pontine taste area (PTA) to the gustatory neocortex (GN) in rat. Two distinct findings were encountered: (1) thalamocortical projections from posterior ventromedial thalamus to GN were confirmed, and (2) direct projections from cells located in the PTA to the GN were described. This novel anatomical finding supports previous suggestions that some gustatory information may be relayed to forebrain areas without making synaptic connection in the diencephalon.

Animals↗

Thalamocortical relations in taste aversion learning: I. Involvement of gustatory thalamocortical projections in taste aversion learning.

The anterior insular gustatory neocortex (AIGN) has been implicated as a functional substrate of conditioned taste aversion (CTA) learning. Results of previous neuroanatomical and neurobehavioral experiments indicate that projections from gustatory-responsive neurons in the posterior ventromedial thalamic nuclei (parvicellular division; VPMpc) may provide relevant input to the AIGN during CTA learning. In rat, gustatory thalamocortical projections from VPMpc thalamus traverse the ventrolateral neostriatum (VLS) enroute to the AIGN. In these experiments, various neuroanatomical and neurobehavioral manipulations in the VLS were used to examine the contribution of presumed gustatory thalamocortical projections to CTA learning. These experiments demonstrate that projections from VPMpc thalamus to the AIGN are essential for normal CTA learning. Because both VPMpc thalamus and the AIGN each have been implicated as functional substrates of CTA learning, the present results suggest that the gustatory thalamocortical relay per se is necessary for normal taste-illness learning.

Afferent Pathways↗

Afferent connections of the amygdalopiriform transition area in the rat.

The amygdalopiriform transition area (APir) is often considered part of the lateral entorhinal cortex (Entl). However, in contrast to Entl, APir densely innervates the central extended amygdala (EAc) and does not project to the dentate gyrus. In order to gain a more comprehensive understanding of these territories, the afferent connections of APir were examined in the rat with retrograde (cholera toxin B subunit or FluoroGold) and anterograde tracers (Phaseolus vulgaris leucoagglutinin) and compared to those of the neighboring Entl. The results suggest that APir and Entl are interconnected and receive topographically organized hippocampal projections. Both are targeted by the olfactory bulb, the piriform, posterior agranular insular and perirhinal cortices, the ventral tegmental area, dorsal raphe nucleus, and locus coeruleus. Most importantly, the data reveal that APir and Entl also have specific inputs and should be viewed as separate anatomical entities. The APir receives robust projections from structures affiliated with the EAc, including the anterior basomedial and posterior basolateral amygdaloid nuclei, the gustatory thalamic region, parasubthalamic nucleus, and parabrachial area. The Entl is a major recipient for amygdaloid projections from the medial part of the lateral nucleus and the caudomedial part of the basolateral nucleus. Moreover, the medial septum, subicular complex, nucleus reuniens, supramammillary region, and nucleus incertus, which are associated with the hippocampal system, preferentially innervate the Entl. These data underscore that APir processes olfactory and gustatory information and is tightly linked to EAc operations, suggesting that it may play a role in reward mechanisms, particularly in hedonic aspects of feeding.

Afferent Pathways↗

Electrical activation of visual pathways substitutes for tonic light input in triggering EEG correlates of food reward during conditioned behavior in cats.

Cats trained to press a lever for 1 cc of milk reward normally show during the consummatory response high voltage 6--8 c/sec EEG synchronization associated with epicortical positive steady potential shift over the primary and secondary visual projections. The emergence of this postreinforcement synchronization (PRS) and Reward Contingent Positive Variation (RCPV) is known to depend upon appropriate gustatory input and presence of ambient light, although visual perception of reward and/or environment is not essential as shown in cats wearing translucent "milky" contact lenses. Training the animals in a paradigm in which a "light-off" cue signaled the availability of reward, and thus assigned positively reinforcing quality to the dark condition, also failed to restore the PRS-RCPV phenomenon in the absence of light. However, brief electrical stimuli applied to either the optic tract or the lateral geniculate nucleus substituted for unpatterned light input and fully restored the PRS-RCPV in the dark. The suprathreshold stimuli were effective only during the consummatory response. Maximum effect could be produced during a brief time period between 0.8 and 1.5 sec after the onset of consummatory response as judged by lapping activity, thus showing the specificity of the effect of visual input. Even during a relaxed wakefulness after satiation or during slow wave sleep or REM sleep the same electric stimuli were ineffective although they produced well-developed evoked potentials with all characteristic wave components. The results indicate that brain pathways utilize unpatterned i.e. noisy visual input in complex integrative processes involving gustatory input.

Animals↗

Learned alcohol aversions in rats: gustatory and olfactory components.

The gustatory and olfactory basis of learned alcohol aversions was examined by testing rats with either gustatory neocortex ablations, olfactory bulb ablations, or a combination of both ablations. In the first experiment operated rats were compared with control rats in the acquisition of a learned alcohol aversion. In the second experiment, the effect of ablations on preoperatively-learned alcohol aversions was examined. Rats lacking gustatory neocortex learned and retained alcohol aversions normally although these rats extinguished the aversions faster than normal rats. Olfactory bulb ablation alone failed to disrupt normal aversion learning but completely eliminated retention of a previously acquired aversion. Combination ablations produced severe deficits both in acquisition and retention of learned alcohol aversions. The results indicate that, besides having gustatory qualities, the odor quality of alcohol is important in determining the associative and memorial characteristics of alcohol.

Animals↗

Partial recovery of gustatory function after neural tissue transplantation to the lesioned gustatory neocortex.

The ability of homotypic cortical tissue grafts to induce recovery of function after a gustatory neocortex (GN) lesion was studied using the conditioned taste aversion (CTA) paradigm. On acquisition day, 26 GN-lesioned and 8 sham-lesioned rats were presented with a saccharin solution, followed by an injection of the illness-inducing agent lithium chloride (LiCl). On the test day, 2 days later, saccharin was presented again. The GN-lesioned rats showed significantly less aversion to saccharin on the test day, indicating that the lesion impaired their ability to form taste-illness association. Nine of the lesioned rats were then bilaterally transplanted with fetal GN tissue. Nine weeks after the transplantation, the rats were presented with a LiCl solution, which served as both a tastant and an illness-inducing agent. An NaCl solution, which tasted very similar to the LiCl solution, was used to test the CTA to salt 3 days later. The nontransplanted rats consumed significantly more LiCl than the transplanted and sham-operated rats on the acquisition day, but both transplanted and nontransplanted rats consumed more NaCl than sham-operated rats on the test day. Nissl and Golgi stainings showed numerous somata and extensive arborization of neurons within the grafts. The results indicate that fetal GN grafts can restore the ability to integrate gustatory and visceral inputs but not to form long-lasting taste-illness associations.

Animals↗

Corticofugal effects on the activity of thalamic taste cells.

To examine corticofugal influences on afferent thalamic cell responses in the gustatory system, effects of cortical conditioning stimuli on the responses of thalamic taste cells to peripheral stimulation were examined in the rat. Two types of excitability change of thalamic cells were observed; one is inhibitory (for about 60 msec) (20%) and the other is inhibitory (for about 10 msec)--facilitatory (for about 60 msec) (40%) to conditioning stimulus applied to the ventral gustatory area, and half of the cells belonging to the latter type also showed a similar pattern with more marked and prolonged excitability changes to conditioning stimulus applied to the dorsal gustatory area. It was suggested that some of the response characteristics of thalamic and cortical taste cells were attributed to the corticofugal feedback loop.

Afferent Pathways↗

Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study.

Behavioural, electroencephalographic and neuropathological responses to increasing doses of pilocarpine (100-400 mg/kg) administered intraperitoneally to rats were studied. At the dose of 400 mg/kg pilocarpine produced a sequence of behavioural alterations including staring spells, olfactory and gustatory automatisms and motor limbic seizures that developed over 1-2 h and built up progressively into limbic status epilepticus. Smaller doses showed different threshold for these behavioural phenomena but a similar time course of development. The earliest electrographic alterations occurred in the hippocampus and then epileptiform activity propagated to amygdala and cortex. Subsequently electrographic seizures appeared in both limbic and cortical leads. The ictal periods recurred each 5-15 min and were followed by variable periods of depression of the electrographic activity. The sequence of electrographic changes correlated well with the development of behavioural phenomena. Histological examination of frontal forebrain sections revealed disseminated, apparently seizure-mediated pattern of brain damage. Neuropathological alterations were observed in the olfactory cortex, amygdaloid complex, thalamus, neocortex, hippocampal formation and substantia nigra. Pretreatment of animals with scopolamine (20 mg/kg) and diazepam (10 mg/kg) prevented the development of convulsive activity and brain damage. These results show that systemic pilocarpine in rats selectively elaborates epileptiform activity in the limbic structures accompanied by motor limbic seizures, limbic status epilepticus and widespread brain damage. It is suggested that a causative relationship between excessive stimulation of cholinergic receptors in the brain and epileptic brain damage may exist.

Animals↗