Lesions of the perirhinal cortex but not of the frontal, medial prefrontal, visual, or insular cortex block fear-potentiated startle using a visual conditioned stimulus.

The present study is part of an ongoing series of experiments aimed at delineation of the neural pathways that mediate fear-potentiated startle, a model of conditioned fear in which the acoustic startle reflex is enhanced when elicited in the presence of a light previously paired with shock. A number of cortical areas that might be involved in relaying information about the visual conditioned stimulus (the light) in fear-potentiated startle were investigated. One hundred thirty-five rats were given 10 light-shock pairings on each of 2 consecutive days, and 1-2 d later electrolytic or aspiration lesions in various cortical areas were performed. One week later, the magnitude of fear-potentiated startle was measured. Complete removal of the visual cortex, medial prefrontal cortex, insular cortex, or posterior perirhinal cortex had no significant effect on the magnitude of fear-potentiated startle. Lesions of the frontal cortex attenuated fear-potentiated startle by approximately 50%. However, lesions of the anterior perirhinal cortex completely eliminated fear-potentiated startle. The effective lesions included parts of the cortex both dorsal and ventral to the rhinal sulcus and extended from approximately 1.8 to 3.8 mm posterior to bregma. Lesions slightly more posterior (2.3-4.8 mm posterior to bregma) or lesions that included only the perirhinal cortex dorsal to the rhinal sulcus had no effect. The region of the perirhinal cortex in which lesions blocked fear-potentiated startle projects to the amygdala, and thus may be part of the pathway that relays the visual conditioned stimulus information to the amygdala, a structure that is also critical for fear-potentiated startle. In addition, the present findings are in agreement with numerous studies in primates suggesting that the perirhinal cortex may play a more general role in memory.     

Auditory cortex lesions prevent the extinction of Pavlovian differential heart rate conditioning to tonal stimuli in rabbits

The present study examined the role of the auditory cortex in the extinction of differentially conditioned heart rate (HR) responses in rabbits. Lesions were placed bilaterally in wither the auditory cortex or the visual cortex. Three days after recovery from surgery, the auditory cortex lesion group and the visual cortex lesion control group were habituated to the tonal conditioned stimuli (CSs), and then given 2 days of Pavlovian differential conditioning (60 trials per day) in which one tone (CS+) was always paired with the unconditioned stimulus and another tone (CS−) was never paired with the uncondition stimulus. Animals that had demonstrated reliable differential conditioning (CS+ response at least 5 beats greater than the CS− response) were placed on an extinction schedule for 7 days. The extinction schedule was identical to the differential conditioning schedule with the exception that shock never followed the CS+. The results of the study indicate that auditory cortex lesions prevent the extinction of differential bradycardia conditioned responses (CRs) to tonal CSs. Whereas the bradycardia responses to the CS+ quickly extinguished in the group that had control lesions in the visual cortex, the auditory cortex lesion group continued to exhibit significantly larger bradycardiac HR CRs to the CS+ relative to the CS− during all 7 days of extinction. These results suggest that the animals in the auditory cortex lesioned group did not inhibit responses to a previously reinforced stimulus (i.e. CS+) as well as animals with control lesions in the visual cortex.     

Autonomic responses and efferent pathways from the insular cortex in the rat

The anatomical distribution of autonomic, particularly cardiovascular, responses originating in the insular cortex was examined by using systematic electrical microstimulation. The localization of these responses to cell bodies in the insular cortex was demonstrated by using microinjection of the excitatory amino acid, D,L-homocysteic acid. The efferents from the cardiovascular responsive sites were traced by iontophoretic injection of the anterograde axonal tracer Phaseoleus vulgaris leucoagglutinin (PHA-L). Two distinct patterns of cardiovascular response were elicited from the insular cortex: an increase in arterial pressure accompanied by tachycardia or a decrease in arterial pressure with bradycardia. The pressor responses were obtained by stimulation of the rostral half of the posterior insular cortex while depressor sites were located in the caudal part of the posterior insular area. Both types of site were primarily located in the dysgranular and agranular insular cortex. Gastric motility changes originated from a separate but adjacent region immediately rostral to the cardiovascular responsive sites in the anterior insular cortex. Tracing of efferents with PHA-L indicated a number of differences in connectivity between the pressor and depressor sites. Pressor sites had substantially more intense connections with other limbic regions including the infralimbic cortex, the amygdala, the bed nucleus of the stria terminalis and the medial dorsal and intralaminar nuclei of the thalamus. Alternatively, the depressor region of the insular cortex more heavily innervated sensory areas of the brain including layer I of the primary somatosensory cortex, a peripheral region of the sensory relay nuclei of the thalamus and the caudal spinal trigeminal nucleus. In addition, there were topographical differences in the projection to the lateral hypothalamic area, the primary site of autonomic outflow for these responses from the insular cortex. These differences in connectivity may provide the anatomic substrate for the specific cardiovascular responses and behaviors integrated in the insular cortex.     

Kindling of claustrum and insular cortex: comparison to perirhinal cortex in the rat

The perirhinal cortex has recently been implicated in the kindling of limbic generalized seizures. The following experiments in rats tested the selectivity of the perirhinal cortex's epileptogenic properties by comparing its kindling profile with those of the adjacent insular cortex, posterior (dorsolateral) claustrum and amygdala. The first experiment examined the kindling and EEG profiles, and found that both the claustrum and insular cortex demonstrated rapid epileptogenic properties similar to the perirhinal cortex, including very rapid kindling rates and short latencies to convulsion. Furthermore, electrical stimulation of all three structures led to a two-phase progression through stage-5 seizures which had characteristics of both neocortical and amygdaloid kindling. In a second experiment rats were suspended in a harness to allow for more detailed documentation of both forelimb and hindlimb convulsions. With this procedure we were able to detect subtle yet unique differences in convulsion characteristics from each of the kindled sites and stage-5 seizure phases. Some of these convulsive parameters were correlated with changes in FosB/DeltaFosB protein and BDNF mRNA expression measured two hours after the last convulsion. Overall, it appears that the perirhinal cortex is not unique in its property of rapid epileptogenesis. Moreover, the posterior claustrum exhibited the fastest kindling and most vigorous patterns of clonus, suggesting that it may be even more intimately associated with the motor substrates responsible for limbic seizure generalization than is the perirhinal cortex.     

How the insula speaks to the heart: Cardiac responses to insular stimulation in humans

Despite numerous studies suggesting the role of insular cortex in the control of autonomic activity, the exact location of cardiac motor regions remains controversial. We provide here a functional mapping of autonomic cardiac responses to intracortical stimulations of the human insula. The cardiac effects of 100 insular electrical stimulations into 47 epileptic patients were divided into tachycardia, bradycardia, and no cardiac response according to the magnitude of RR interval (RRI) reactivity. Sympathetic (low frequency , LF, and low to high frequency powers ratio, LF/HF ratio) and parasympathetic (high frequency power, HF) reactivity were studied using RRI analysis. Bradycardia was induced by 26 stimulations (26%) and tachycardia by 21 stimulations (21%). Right and left insular stimulations induced as often a bradycardia as a tachycardia. Tachycardia was accompanied by an increase in LF/HF ratio, suggesting an increase in sympathetic tone; while bradycardia seemed accompanied by an increase of parasympathetic tone reflected by an increase in HF. There was some left/right asymmetry in insular subregions where increased or decreased heart rates were produced after stimulation. However, spatial distribution of tachycardia responses predominated in the posterior insula, whereas bradycardia sites were more anterior in the median part of the insula. These findings seemed to indicate a posterior predominance of sympathetic control in the insula, whichever the side; whereas the parasympathetic control seemed more anterior. Dysfunction of these regions should be considered when modifications of cardiac activity occur during epileptic seizures and in cardiovascular diseases.     

Cortical and thalamic afferent connections of the insular and adjacent cortex of the rat

Thalamic and cortical afferents to the insular and perirhinal cortex of the rat were investigated. Unilateral injections of horseradish peroxidase (HRP) were made iontophoretically along the rhinal sulcus. HRP injections covered or invaded areas along the rhinal fissure from about the level of the middle cerebral artery to the posterior end of the fissure. The most anterior injection labeled a few cells in the mediodorsal nucleus. More posterior injections labeled neurons in the basal portion of the nucleus ventralis medialis, thus suggesting that this cortical region constitutes the rat's gustatory (insular) cortex. We consider the cortex situated posterior to the gustatory cortex in and above the rhinal sulcus as the core region of the rat's (associative) insular cortex, as this cortex receives afferents from the regions of and between the nuclei suprageniculatus and geniculatus medialis, pars magnocellularis. It includes parts of the cortex termed perirhinal in other studies. The cortex dorsal and posterior to the insular cortex we consider auditory cortex, as it receives afferents from the principal part of the medial geniculate nucleus, and the cortex ventral to the insular cortex (below the fundus of the rhinal sulcus) we consider to constitute the prepiriform cortex, which is athalamic. The posterior part of the perirhinal cortex (area 35) receives afferents from nonspecific thalamic nuclei (midline nuclei). Cortical afferents to the injection loci arise from a number of regions, above all from regions of the medial and sulcal prefrontal cortex. Those injections confined to the projection cortex of the suprageniculate-magnocellular medial geniculate nuclear complex also led to labeling in contralateral prefrontal regions, particularly in area 25 (infralimbic region). A comparison of our results with those on the insular cortex of cats and monkeys suggests that on the basis of thalamocortical connections, topographical relations, and involvements of neurons in information processing and overt behavior, the insular cortex has to be regarded as a heterogeneous region which may be separated into prefrontal insular, gustatory (somatosensory) insular, and associative insular portions.     

Plasma and organ catecholamine levels following stimulation of the rat insular cortex.

The posterior insular cortex of the rat contains an area of cardiac chronotropic representation within which tachycardia sites occur rostrally to those producing bradycardia. In the current study using ketamine-anesthetized rats, the insular cortex was stimulated for 1 h using a phasic technique synchronized with the cardiac cycle. Tachycardia was associated with an increase in plasma norepinephrine concentration; epinephrine remained unchanged. This indicates a neural origin of the norepinephrine increment. The tachycardia response was completely blocked by atenolol. Plasma catecholamine levels remained unchanged during stimulation of insular bradycardia sites. Atenolol was without effect during stimulation-induced bradycardia which was completely blocked by atropine. Total cardiac norepinephrine concentration inversely correlated with change in heart rate during stimulation of tachycardia sites. No correlation between intracardiac catecholamines and heart rate variables was found for the bradycardia or control sites. These results indicate that in the ketamine-anesthetized rat, whereas insular stimulation-induced tachycardia is dependent on the sympathetic nervous system, bradycardia elicited by insular cortex stimulation is mediated by parasympathetic mechanisms. No correlation was identified between renal or skeletal muscle norepinephrine levels and any heart rate parameter. This implies that the sympathetic effects of phasic insular microstimulation may be exerted mainly on cardiac nerves, and less so in other visceral beds.     

Brain activity associated with fear renewal

This is the first mapping study of the brain activity associated with the renewal of an extinguished conditioned response. Rats were given radiolabeled fluorodeoxyglucose, a glucose analog, to map brain effects of an extinguished tone during context-dependent renewal of conditioned fear. A tone conditioned stimulus was paired with a footshock unconditioned stimulus in a first context, followed by conditioned response extinction in a second context and conditioned response renewal in a third context. Control rats were treated identically, except that tone and shock were presented pseudorandomly. Compared with control subjects, rats with conditioned response renewal had increased tone-evoked fluorodeoxyglucose uptake in the auditory system (auditory cortex, medial geniculate, inferior colliculus and lateral lemniscal nuclei), as well as somatic and visceral sensory nuclei (external cuneate, spinal trigeminal, solitary tract and vestibular nuclei). In addition, perirhinal cortex, anterior lateral hypothalamus and ventrolateral periaqueductal gray showed conditioned response renewal effects. Brain-behavior correlations indicated that the activity of the external cuneate nucleus strongly predicted the conditioned response in the renewal group. It is suggested that context-dependent fear renewal is associated with (1) tone-evoked activation of the excitatory conditioned stimulus representation in the auditory system, (2) associative activation of the unconditioned stimulus representation in somatic and visceral sensory nuclei in the absence of the unconditioned stimulus, and (3) neural activation of the perirhinal cortex, hypothalamus and periaqueductal gray. These findings support Pavlov's stimulus-substitution theory as a neural mechanism contributing to the renewal effect.     

Ibotenic acid lesions in the amygdaloid central nucleus but not in the lateral subthalamic area prevent the acquisition of differential Pavlovian conditioning of bradycardia in rabbits

The present study examined the effect of ibotenic acid lesions in the amygdaloid central nucleus (ACe) or in the lateral zona incerta of the subthalamus (LZI) on the acquisition of differential Pavlovian conditioning of bradycardia in rabbits. Previous work has shown that bilateral electrolytic lesions in either ACe or LZI abolished the retention of conditioned heart rate (HR) responses. In order to determine whether these findings were due to destruction of cells intrinsic to ACe or LZI, ibotenic acid lesions were placed bilaterally in either structure or in control sites. Following recovery, animals were subjected to differential Pavlovian conditioning in which one tone (CS+) was paired with periorbital shock and a second tone (CS−) was presented alone. It was found that destruction of cell bodies in ACe, but not LZI, prevented the acquisition of the differential bradycardiac conditioned response. In addition, ACe lesions did not interfere with baseline HR, the HR orienting response, the HR unconditioned response to shock, or the concomitantly conditioned corneoretinal potential. The results of this study suggest that destruction of cells intrinsic to ACe selectively prevents the acquisition of differentially conditioned HR, and perhaps other conditioned responses related to conditioned arousal, but does not affect unlearned HR responses or specific somatomotor conditioned responses.     

The Effect of Kainic Acid Lesions of the Cerebellar Cortex on the Conditioned Nictitating Membrane Response in the Rabbit

In previous studies we have shown that aspiration lesions centred on lobule HVI in the cerebellar cortex of rabbits produce a profound loss of conditioned nictitating membrane (NM) responses. Because aspiration lesions of the cerebellar cortex cause retrograde degeneration in precerebellar nuclei we tested in rabbits whether excitotoxic lesions of the cerebellar cortex that spare these precerebellar nuclei also cause a loss of conditioned NM responses. Following discrete injections of kainic acid into HVI and rostral regions of the adjacent folia of crus I and crus II, we observed an immediate loss of conditioned NM responses. Following extensive retraining several subjects showed a gradual recovery of conditioned responses. But subjects with the most complete lesions never recovered more than a few conditioned responses. Kainic acid lesions did not change ipsilateral unconditioned reflex responses to a range of stimulus intensities. The kainic acid injections caused obvious degeneration of Purkinje and granule cells but not of the precerebellar nuclei. We conclude that HVI and parts of crus I and crus II are essential for normal retention of conditioned NM responses.     

Effects of insular cortex lesions on conditioned taste aversion and latent inhibition in the rat

The present study tested the hypothesis that lesions of the insular cortex of the rat retard the acquisition of conditioned taste aversions (CTAs) because of an impairment in the detection of the novelty of taste stimuli. Demonstrating the expected latent inhibition effect, nonlesioned control subjects acquired CTAs more rapidly when the conditioned stimulus (0.15% sodium saccharin) was novel rather than familiar (achieved by pre-exposure to the to-be-conditioned taste cue). However, rats with insular cortex lesions acquired taste aversions at the same slow rate regardless of whether the saccharin was novel or familiar. The pattern of behavioural deficits obtained cannot be interpreted as disruptions of taste detection or stimulus intensity, but is consistent with the view that insular cortex lesions disrupt taste neophobia, a dysfunction that consequently retards CTA acquisition because of a latent inhibition-like effect.     

Conditioned enhancement of antibody production is disrupted by insular cortex and amygdala but not hippocampal lesions.

Pavlovian conditioning procedures can be used to activate the immune system. A reliable conditioned increase of antibody production can be obtained in rats that have previously received a gustative or odor stimulus as the conditioned stimulus paired with an antigen, by exposing the animals to the conditioned stimulus alone. We showed evidence that an excitotoxic lesion bilaterally applied into the insular cortex or the amygdala, but not into the dorsal hippocampus, impaired the acquisition of both odor and gustatory conditioned immune enhancement. We found no effects of lesions on normal antibody production. These results suggest that the amygdala and the insular cortex are involved in the neural-immune interactions that mediate conditioned immunity.     

Functional mapping of the insular cortex: clinical implication in temporal lobe epilepsy

PURPOSE: We report the results of 75 intracortical electrical stimulations of the insular cortex performed in 14 patients during stereo-electroencephalography (SEEG) investigation of drug-resistant partial epilepsy. The insular cortex was investigated on electroclinical arguments suggesting the possibility of a perisylvian spread or a rapid multilobar diffusion of the discharges during video EEG. METHODS: In these 14 patients, 27 stereotactically implanted transopercular electrodes reached the insular cortex (11 the right insula, 16 the left insula). Square pulses of current were applied between the two deepest adjacent contacts of each transopercular electrode using low (1 Hz) or high-frequency (50 Hz) stimulation. Only symptoms evoked in the absence of afterdischarges were analyzed. RESULTS: Clinical responses were evoked in 10 of the 14 patients (in 20 of the 27 insular sites) and showed a clear topographic specificity inside the insular cortex. Viscerosensitive and visceromotor responses, similar to those evoked by temporomesial stimulation, were evoked by anterior insular stimulation and somesthetic sensation, similar to those evoked by opercular cortex stimulation, by posterior insular stimulation. CONCLUSIONS: The topographic organization of the induced responses within the insular cortex suggest that two different cortical networks, a visceral network extending to the temporomesial structures and a somesthetic network reaching the opercular cortex, are disturbed with stimulation of the anterior or the posterior insula, respectively. Thus ictal symptoms associated with the spread of the epileptic discharges to the insular cortex might be difficult to distinguish from those usually reported during temporomesial or opercular discharges.     

Lesions of the perirhinal cortex impair sensory preconditioning in rats

The effects of lesions of the perirhinal cortex on the development of associations between two conditioned stimuli (CSs) were examined with a sensory preconditioning procedure. Rats were given either bilateral electrolytic lesions of the perirhinal cortex or control surgery. They were then given either paired or unpaired presentations of a light CS and a tone CS. All of the rats were then given eyeblink conditioning procedures that involved paired presentations of either the light or tone and a periorbital shock unconditioned stimulus (US). The rats were finally given a test session that consisted of unpaired presentations of the tone and light CSs. Sensory preconditioning was established in the control group, but not in the lesion group. The findings are consistent with the view that the perirhinal cortex is involved in forming associations between neutral stimuli (even in the absence of reinforcement).     

Cortical,thalamic, and amygdaloid connections of the anterior and posterior insular cortices

Cortical, thalamic, and amygdaloid projections of the rat anterior and posterior insular cortices were examined using the anterograde transport of biocytin. Granular and dysgranular posterior insular areas between bregma and 2 mm anterior to bregma projected to the gustatory thalamic nucleus. Granular cortex projected to the subjacent dysgranular cortex which in turn projected to the agranular (all layers) and granular cortices (layers I and VI). Both granular and dysgranular posterior areas projected heavily to the dysgranular anterior insular cortex. Agranular posterior insular cortex projected to medial mediodorsal nucleus, agranular anterior insular and infralimbic cortices as well as granular and dysgranular posterior insula. No projections to the amygdala were observed from posterior granular cortex, although dysgranular cortex projected to the lateral central nucleus, dorsolateral lateral nucleus, and posterior basolateral nucleus. Agranular projections were similar, although they included medial and lateral central nucleus and the ventral lateral nucleus. Dysgranular anterior insular cortex projected to lateral agranular frontal cortex and granular and dysgranular posterior insular regions. Agranular anterior insular cortex projected to the dysgranular anterior and prelimbic cortices. Anterior insuloamygdaloid projections targeted the rostral lateral and anterior basolateral nuclei with sparse projections to the rostral central nucleus. The data suggest that the anterior insula is an interface between the posterior insular cortex and motor cortex and is connected with motor-related amygdala regions. Amygdaloid projections from the posterior insular cortex appear to be organized in a feedforward parallel fashion targeting all levels of the intraamygdaloid connections linking the lateral, basolateral, and central nuclei . J. Comp. Neurol. 399:440–468, 1998. © 1998 Wiley-Liss, Inc.     

Fear conditioned changes of heart rate in patients with medial cerebellar lesions

Fear conditioned changes of heart rate and skin conductance responses were investigated in patients with medial cerebellar lesions. A classical conditioning paradigm with a tone as the conditioned stimulus (CS) and an electrical shock as the unconditioned stimulus (US) was tested on five patients with medial cerebellar lesions due to surgery for astrocytoma and five controls. The CS preceded the US by 5900 ms and coterminated with the US. Changes in heart rate and skin conductance responses were obtained as measures for autonomic fear responses. Effects of conditioning were quantified by comparison of the habituation and extinction phases. Controls, but not cerebellar patients, showed a significant decrease of heart rate during fear conditioning. However, there were no significant fear conditioned changes in electrodermal responses in either group. In summary, the medial cerebellum seems to be involved in fear-conditioned bradycardia in humans.     

Efferent projections of the anterior perirhinal cortex in the rat

Because convulsive seizures develop very rapidly from kindling sites in the anterior perirhinal cortex, we studied perirhinal efferents by using the anterograde tracer Phaseolus vulgaris leucoagglutinin (PhAL). PhAL injections into the anterior perirhinal cortex labelled a prominent network of fibers within the frontal cortex that was most dense within layers I and II and layer VI. As individual PhAL injection sites within the perirhinal cortex were restricted to one or two adjacent laminae, we were able to determine that layer V was the main source of the perirhinofrontal projection. This was confirmed by frontal cortex injections of the retrograde tracer Fluorogold (FG). Other cortical areas with densely labelled fibers following perirhinal PhAL injections included the agranular insular, infralimbic, orbital, parietal, and entorhinal cortices. Moderate to mild fiber labelling was also noted in the posterior piriform, temporal and occipital cortices, and the claustrum. Subcortical labelling was seen in the nucleus accumbens; fundus striati; basal and lateral amygdala nuclei; thalamic nuclei, including the reuniens, posterior and ventral posteromedial nuclei; the “acoustic thalamus”; and the central grey. Several of these cortical and subcortical projections were bilateral. The different laminar origin of these perirhinal efferents is discussed. These results confirmed our prediction of extensive direct projections from the anterior perirhinal cortex to the frontal cortex in the rat. The significance of this projection is discussed with special reference to the anatomical basis of convulsive limbic seizures. © 1996 Wiley-Liss, Inc.     

Rabbit classically conditioned eyelid responses do not reappear after interpositus nucleus lesion and extensive post-lesion training.

The left eyelid responses of four rabbits were classical conditioned by pairing a tone conditioned stimulus and air puff unconditioned stimulus. After conditioned responses were well-established, the left interpositus nucleus was lesioned and 150-200 post-lesion training sessions, distributed over 10 months, were given. In three of the rabbits, no anticipatory conditioned responses were observed on paired trials and responses were at or below spontaneous blinking rates on 2,500 ms CS-alone trials that were also presented. Post-lesion conditioned responses were present when the right side was trained. The fourth rabbit showed few post-lesion conditioned responses on paired trials but eventually showed 80% conditioned responses on tone-alone trials. Histological analysis of the lesion extents indicate that a portion of the anterior interpositus nucleus was spared in this rabbit. These results argue that unlike other cerebellar lesion effects reported in the literature, where some recovery of function is normally noted, the effects of interpositus nucleus lesions are somewhat unique in that conditioned response abolition is seen as long as 10 months after the lesion.     

Cardiac chronotropic organization of the rat insular cortex

Clinical evidence implicates the cerebral cortex in the genesis of ECG changes and cardiac arrhythmias. Such findings are not infrequent following acute cortical stroke and during partial seizures. Electrical stimulation of the cerebral cortex, however, only rarely and inconsistently results in cardiac changes. When encountered, attendant alterations in blood pressure and respiration occur; consequently, it is unclear whether the cardiac effects are primary or secondary to these. Phasic insular cortex microstimulation linked to the ECG cycle, a new technique, elicits only heart rate effects, eliminating confounding variables. The insular cortex was chosen for study because of its profuse autonomic and limbic connectivity. Cardiac chronotropic sites were demonstrated in 37 chloralose-anesthetized rats, with tachycardia represented in the rostral posterior insula, and bradycardia in the caudal posterior insula. Both effects were abolished by atenolol but not by atropine, implying their mediation by respective increases or decreases in sympathetic activity. This is the first report of the demonstration of a cortical region wherein stimulation affects heart rate and no other parameter.     

Efferent projections of the insular and temporal neocortex of the cat

Anterograde degeneration resulting from small lesions placed in either the insular or temporal cortex were traced with the Fink-Heiner reduced silver procedure. In neocortical regions ipsilateral to the lesion axonal degeneration was present in auditory subdivisions AI, AII, Ep, I, T, in the second somatosensory are(SII), in the anterior and middle suprasylvian gyrus, in the posteromedial suprasylvian and posterior lateral gyri, in the posterior splenial gyrus, in the anterior two-thirds of the cingulate gyrus and in the orbitofrontal regions. With respect interhemispheric connections, evidence was obtained for a dual pattern of projection. In addition to significant amounts of axonal and terminal degeneration in the corresponding insular or temporal fields, axonal degeneration was also present in posterior AII.In the thalamus degeneration was found in the medial dorsal, suprageniculate, and lateral posterior-pulvinar nuclei. In the posterior nuclear group (Po) and the principal division of the medial geniculate (GMp) evidence was obtained for a topographic pattern of projection; significantly more degeneration occurred in caudal Po following insular lesions whereas with temporal lesions more degeneration occurred in caudal GMp. Degeneration was also found in the dorsal cortex of the ipsilateral inferior colliculus, bilaterally in the deep layers of the superior colliculus and the periventricular central gray region, ipsilaterally in the ventromedial aspects of the head and body of the caudate nucleus, and in the lateral and central nuclei of the amygdala. These findings are discussed in terms of their significance for a possible role for the insular and temporal neocortex (I-T) in both multimodal sensory discrimination and sensory-visceral integrative functions.