C-fos Expression During Vocal Mobbing in the New World Monkey Saguinus fuscicollis

In order to find brain areas involved in the vocal expression of emotion, we compared c-fos expression in three groups of saddle-back tamarins (Saguinus fuscicollis). One group, consisting of three animals, was made to utter more than 800 mobbing calls by electrical stimulation of the periaqueductal grey of the midbrain (PAG). A second group, consisting of two animals, was stimulated in the PAG with the same intensity and for the same duration as the first group but at sites that did not produce vocalization. These sites lay somewhat medial to the vocalization-eliciting sites. A third group, consisting of two animals, was stimulated at vocalization-eliciting sites in the PAG but with an intensity below vocalization threshold. Fos-like immunoreactivity that was found in the vocalizing but not in the non-vocalizing animals was located in the dorsomedial and ventrolateral prefrontal cortex, anterior cingulate cortex, ventrolateral premotor cortex, sensorimotor face cortex, insula, inferior parietal cortex, superior temporal cortex, claustrum, entorhinal and parahippocampal cortex, basal amygdaloid nucleus, anterior and dorsomedial hypothalamus, nucleus reuniens, lateral habenula, Edinger-Westphal nucleus, ventral and dorsolateral midbrain tegmentum, nucleus cuneiformis, sagulum, pedunculopontine and laterodorsal tegmental nuclei, ventral raphe, periambigual reticular formation and solitary tract nucleus. For some of these structures (e.g. anterior cingulate cortex and periambigual reticular formation), there is evidence also from electrical stimulation, lesioning and single-unit recording studies that they are involved in vocal control. For other structures (e.g. lateral habenula, Edinger-Westphal nucleus), the available evidence speaks against such a role. Fos activation in these cases is probably related to non-vocal reactions accompanying the electrically elicited vocalizations. A third group of structures consists of areas for which a role in vocal control cannot be excluded but for which the present study presents the first evidence for such a role (e.g. claustrum and sagulum). These structures deserve further studies using more specific methods.     

Afferents of vocalization-controlling periaqueductal regions in the squirrel monkey

In order to determine the input of vocalization-controlling regions of the midbrain periaqueductal gray (PAG), wheat germ agglutinin-horseradish peroxidase was injected in six squirrel monkeys (Saimiri sciureus) at PAG sites yielding vocalization when injected with the glutamate agonist homocysteic acid. Brains were scanned for retrogradely labeled areas common to all six animals. The results show that the vocalization-eliciting sites receive a widespread input, with the heaviest projections coming from the surrounding PAG, dorsomedial and ventromedial hypothalamus, medial preoptic region, substantia nigra pars diffusa, zona incerta and reticular formation of the mesencephalon, pons, and medulla. The heaviest cortical input reaches the PAG from the mediofrontal cortex. Moderate to weak projections come from the insula, lateral prefrontal, and premotor cortex as well as the superior and middle temporal cortex. Subcortical moderate to weak projections reach the PAG from the central and medial amygdala, nucleus of the stria terminalis, septum, nucleus accumbens, lateral preoptic region, lateral and posterior hypothalamus, globus pallidus, pretectal area, deep layers of the superior colliculus, the pericentral inferior colliculus, mesencephalic trigeminal nucleus, locus coeruleus, substantia nigra pars compacta, dorsal and ventral raphe, vestibular nuclei, spinal trigeminal nucleus, solitary tract nucleus, and nucleus gracilis. The input of the periaqueductal vocalization-eliciting regions thus is dominated by limbic, motivation-controlling afferents; input, however, also comes from sensory, motor, arousal-controlling, and cognitive brain areas.     

Cortical lesion effects and vocalization in the squirrel monkey

The effects of bilateral destruction of the cortical face area, anterior and posterior supplementary motor area and anterior cingular cortex on spontaneous vocalization were studied in 16 squirrel monkeys (Saimiri sciureus). Each type of lesion was made in two groups of two animals each. Both animals of a group received the same type of lesion at the same day. Each group was recorded for 10 sessions of one hour before operation and 10 sessions after operation. Pre- and post-operative vocalizations were compared in respect to total number and acoustic structure. It was found that none of the lesions affected acoustic structure as judged by a sonagraphic analysis. However, lesions in the anterior supplementary motor area (at the level of the callosal genu) reduced the total vocalization number significantly. This decrease was essentially due to a drastic reduction of the so-called isolation peep, a long-distance contact call. The results suggest: (i) that the cortical face area is only involved in the control of learnt vocal utterances (such as human speech and song) but not in the production of genetically preprogrammed utterances (such as monkey calls and human pain groans); (ii) that the anterior cingulate cortex is necessary for the volitional initiation of vocalization but not for the initiation of calls in an emotional situation; (iii) that the posterior supplementary motor area does not play any role in vocal behaviour of monkeys; and (iv) that the anterior supplementary motor area is involved in the production of vocalizations which are not triggered directly by external events.     

Glutamate-induced vocalization in the squirrel monkey

In the squirrel monkey, 164 brain sites yielding vocalization when electrically stimulated were tested for their capability to produce vocalization when injected with mono-sodium-L-glutamate. The sites were located in the anterior limbic cortex, n. accumbens, substantia innominata, amygdala, n. striae terminalis, hypothalamus, midline thalamus, field H of Forel, substantia nigra, periventricular and periaqueductal gray, inferior colliculus, reticular formation of midbrain, pons and medulla, inferior olive, lateral reticular nucleus and nucleus of solitary tract. Of the 164 sites tested, 31 were positive. These were located in the substantia innominata, caudal periventricular and periaqueductal gray, lateral pontine and medullary reticular formation. While all the calls obtained from the forebrain and midbrain had a normal acoustic structure, most pontine and all medullary vocalizations had an artificial character. It is concluded that: the substantia innominata, caudal periventricular and periaqueductal gray, lateral pontine and medullary reticular formation represent relay stations of vocalization-controlling pathways; the periaqueductal gray represents the lowest relay station above the level of motor coordination; neurons responsible for motor coordination of vocalization lie in the reticular formation around the caudal brachium conjunctivum, the superior olive, n. facialis, n. ambiguus and below the n. solitarius; not all areas from which vocalization can be obtained by electrical stimulation of nerve cell bodies, dendrites and nerve endings (in contrast to fibers en passage) also yield vocalization when stimulated with glutamate.     

2-Deoxyglucose uptake during vocalization in the squirrel monkey brain

In the squirrel monkey (Saimiri sciureus), the cerebral 2-deoxyglucose uptake was compared between animals made to vocalize by electrical stimulation of the periaqueductal grey and animals stimulated in the same structure, but sub-threshold for vocalization. A significantly higher 2-deoxyglucose uptake in the vocalizers than the non-vocalizers was found in the dorsolateral prefrontal cortex, supplementary and pre-supplementary motor area, anterior and posterior cingulate cortex, primary motor cortex, claustrum, centrum medianum, perifornical hypothalamus, periaqueductal grey, intercollicular region, dorsal mesencephalic reticular formation, peripeduncular nucleus, substantia nigra, nucl. ruber, paralemniscal area, trigeminal motor, principal and spinal nuclei, solitary tract nucleus, nucl. ambiguus, nucl. retroambiguus, nucl. hypoglossus, ventral raphe and large parts of the medullary reticular formation. The study makes clear that vocalization, even in the case of genetically pre-programmed patterns, depends upon an extensive network, beyond the well-known periaqueductal grey, nucl. retroambiguus and cranial motor nuclei pathway.     

The Effects of Periaqueductally Injected Transmitter Antagonists on Forebrain-elicited Vocalization in the Squirrel Monkey

In 15 squirrel monkeys, vocalization-eliciting electrodes were implanted into the following forebrain structures: anterior cingulate cortex, genu of the internal capsule, amygdala, bed nucleus of the stria terminalis, hypothalamus, midline thalamus, inferior thalamic peduncle and periventricular grey. Then, injections of 29 transmitter antagonists were made into the midbrain periaqueductal grey (PAG) and their effects tested on the elicitability of vocalization from the forebrain. Vocalization could be blocked completely with glutamate antagonists. NMDA receptor antagonists as well as kainate/quisqualate receptor antagonists were effective. Facilitatory effects, i.e. a decrease in threshold of forebrain-elicited vocalization, was obtained with GABA-A receptor, glycine and opioid antagonists. The facilitatory effect of the opioid antagonist naloxone was limited to vocalizations expressing aversive emotional states. GABA-A receptor antagonists not only facilitated forebrain-induced vocalization but also produced vocalization themselves, i.e. without concomitant forebrain stimulation. No effects were obtained with antagonists of muscarinic and nicotinic receptors, with the GABA-B receptor antagonist phaclofen and antagonists of the monoamines dopamine, noradrenaline, adrenaline, serotonin and histamine. It is concluded that the PAG represents a crucial relay station of the vocalization-controlling system. In this station, transmission of vocalization-relevant information depends upon the activation of glutamatergic synapses. Inhibitory control is exerted by GABA, glycine and endogenous opioids. Acetylcholine, dopamine, noradrenaline, adrenaline, serotonin and histamine may play a transient modulatory role; forebrain-induced vocalization, however, does not depend upon the cholinergic or monoaminergic activation of PAG neurons.     

Projections from the 'cingular' vocalization area in the squirrel monkey.

In 5 squirrel monkeys the anatomical projections from the 'cingular' vocalization area were studied by the autoradiographic tracing technique. The 'cingular' vocalization area lies around the sulcus cinguli at the level of the genu of the corpus callosum; its electrical stimulation yields purring and cackling calls. The following efferent connections were found: corticocortical fibers could be traced into the orbital cortex (areas 10 and 11), dorsomedial frontal cortex (areas 9, 8 and 6), limbic cortex (areas 25, 24 and 23), Broca's area (area 44), frontal operculum (area 50), insula (areas 13 and 14), and auditory association cortex (area 22). Subcortical terminal fields within the telencephalon were found in the nucleus caudatus, putamen, claustrum, globus pallidus, olfactory tubercle, preoptic region and nucleus centralis and basolateralis amygdalae. Fibers reached most of these structures along different trajectories. In the diencephalon terminal fields lay in the dorsal hypothalamus, the subthalamus, lateral habenular nucleus, and the following thalamic nuclei: nucleus reticularis, ventralis anterior, centralis medialis, centralis superior lateralis, centralis inferior, submedius, medialis dorsalis and centrum medianum. In the midbrain, the periaqueductal gray was the only projection area, extending into the parabrachial nuclei at the pontomesencephalic transition. The most caudal terminal field was found in the medial pontine gray. No terminals were detected in the nucleus ambiguus, nucleus n. hypoglossi or in any other cranial motor nucleus involved in phonation processes. A comparison of this projection system with the whole of structures producing vocalization when electrically stimulated yielded only partial overlap. Not all vocalization areas lie within the 'cingular' projection system, and inversely, not the whole projection system yielded vocalization. Overlap took place in the anterior limbic cortex, preoptic region, central amygdaloid nucleus, midline thalamus, dorsal hypothalamus, periaqueductal gray and parabrachial nuclei. These structures are considered to compose a functionally coherent vocalization system. The projections into Broca's area, nucleus ventralis anterior thalami, frontoopercular cortex within the lateral fissure, pontine nuclei and superior temporal gyrus are discussed in their possible relationship to vocalization processes.     

Call type-specific differences in vocalization-related afferents to the periaqueductal gray of squirrel monkeys (Saimiri sciureus)

In a recent retrograde tracing study in the squirrel monkey, we found that regions in the midbrain periaqueductal gray (PAG) producing different call types when pharmacologically stimulated, receive their input largely from the same structures. The aim of the present study was to find out, whether there are quantitative differences in this input. For this reason, we counted retrogradely labeled neurons in various brain regions after injections of wheatgerm agglutinin-conjugated horseradish peroxidase (WGA-HRP) into three different vocalization-eliciting PAG sites: one site producing non-aversive contact calls (clucking); a second site producing slightly aversive social mobbing calls (cackling); and a third site producing highly aversive defensive threat calls (shrieking). Cell counting was carried out by the help of the optical fractionator technique. Six squirrel monkeys were used, two for each call type. In some regions, marked differences in the number of retrogradely labeled cells between the three call type groups occured. Such regions are the nucl. accumbens, preoptic area, posterior hypothalamus, anterior cingulate cortex, subcallosal gyrus and the nucl. striae terminalis. In some of these regions, the number of retrogradely labeled cells correlated positively (posterior hypothalamus) or negatively (preoptic area, nucl. striae terminalis) with the "aversiveness" of the elicited call type. Other regions of interest, e.g., the dorsomedial prefrontal and precallosal cortex, amygdala and hypothalamic regions surrounding the fornix, revealed no clear differences in their afferent projections to the different vocalization-eliciting PAG sites. The results make clear that distinct vocalization-controlling regions in the PAG receive a qualitatively similar but quantitatively differentiated input.     

Common input of the cranial motor nuclei involved in phonation in squirrel monkey

Our aim was to locate brain regions projecting to all cranial motor nuclei involved in phonation simultaneously, that is, the ambiguus, trigeminal motor, facial, and hypoglossal nuclei. For this purpose, four squirrel monkeys (Saimiri sciureus) were injected with horseradish peroxidase, each of the four nuclei in a different animal. Those regions retrogradely labeled in all four cases then were injected in another 29 animals with [3H]leucine for anterograde tracing. We found that the only region connected directly with all phonatory motor nuclei is a restricted portion of the pontine and medullary reticular formation, including the nucl. subceruleus ventralis, nucl. parvocellularis and nucl. centralis myelencephali. It is assumed that these nuclei are involved in the integration of vocal fold adduction, articulation, and respiration during vocal utterances.     

Laryngeal afferent inputs during vocalization in the cat.

To reveal the kind of information about the larynx which is transmitted to the central nervous system during vocalization, we studied discharge patterns of single fibers of the laryngeal afferent nerve during electrically induced vocalization in ketamine-anesthetized cats. Recorded fibers were classified into four types based on their discharge patterns. Type A fibers responded to vocal fold vibration during vocalization. Type B fibers increased their activity during vocalization without synchronization with vocal fold vibration. Type C fibers decreased their activity during vocalization. Type D fibers discharged only at the onset of vocal fold adduction and abduction. We discuss the functional properties of these afferents and the possibility that these afferent inputs participate in the feedback control of vocalization.     

Intracranial stimulation study of lateralization of affect

As part of their evaluation for epilepsy surgery, 53 patients underwent stimulation of depth or subdural electrodes. Responses obtained from depth stimulation included motor responses at 34 sites, sensory responses at 114 sites, language alterations at 6 sites, and affective responses at 22 sites. Responses obtained from subdural stimulation included motor responses at 19 sites, sensory responses at 31 sites, speech alterations at 10 sites, and affective responses at 1 site. Of 23 affective responses, 21 were dysphoric responses of fear, a sense of dying, or unpleasantness with or without some type of experiential phenomenon. Dysphoric responses were statistically associated (P=0.01) with right-sided stimulation (N=18) as compared with left-sided stimulation (N=3) of mesial frontal, orbitofrontal, mesial temporal, and insular stimulation sites. Two euphoric responses occurred, one with left-sided and one with right-sided stimulation. No affective responses were obtained with convexity or neocortical stimulation.     

Frontal eye field as defined by intracortical microstimulation in squirrel monkeys, owl monkeys, and macaque monkeys. II. Cortical connections

Physiological (intracortical microstimulation) and anatomical (transport of horseradish peroxidase conjugated to wheat germ agglutinin as shown by tetramethyl benzidine) approaches were combined in the same animals to reveal the locations, extents, and cortical connections of the frontal eye fields (FEF) in squirrel, owl, and macaque monkeys. In some of the same owl and macaque monkeys, intracortical microstimulation was also used to evoke eye movements from dorsomedial frontal cortex (the supplementary motor area). In addition, in all of the owl and squirrel monkeys, intracortical microstimulation was also used to evoke body movements from the premotor and motor cortex situated between the central dimple and the FEF. These microstimulation data were directly compared to the distribution of anterogradely and retrogradely transported label resulting from injections of tracer into the FEF in each monkey. Since the injection sites were limited to the physiologically defined FEF, the demonstrated connections were solely those of the FEF. To aid in the interpretation of areal patterns of connections, the relatively smooth cortex of owl and squirrel monkeys was unfolded, flattened, and cut parallel to the flattened surface. Cortex of macaque monkeys, which has numerous deep sulci, was cut coronally. Reciprocal connections with the ipsilateral frontal lobe were similar in all three species: dorsomedial cortex (supplementary motor area), cortex just rostral (periprincipal prefrontal cortex) to the FEF, and cortex just caudal (premotor cortex) to the FEF. In squirrel and owl monkeys, extensive reciprocal connections were made with cortex throughout the caudal half of the lateral fissure and, to a much lesser extent, cortex around the superior temporal sulcus. In macaque monkeys, only sparse connections were present with cortex of the lateral fissure, but extensive and dense connections were made with cortex throughout the caudal one-third to one-half of the superior temporal sulcus. In addition, very dense reciprocal connections were made with the cortex of the lateral, or inferior, bank of the intraparietal sulcus. Contralateral reciprocal connections in all three species were virtually limited to regions that correspond in location to the FEF and the supplementary motor area. The results of this study reveal connections between the physiologically defined frontal eye field and cortical regions known to participate in higher order visual processing, short-term memory, multimodal, visuomotor, and skeletomotor functions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Anatomical and physiological evidence for a relationship between the ‘cingular’ vocalization area and the auditory cortex in the squirrel monkey

With the aid of the autoradiographic tracing technique the projections from cortical limbic vocalization areas to the auditory cortex in the superior temporal gyrus were studied in the squirrel monkey. The vocalization areas were identified by exploring the anterior limbic cortex with moving electrodes until a site was found where electrical stimulation yielded vocalization. Projections from the region around the cingulate sulcus and supracallosal anterior cingulate gyrus have their terminal fields in the lower part of the superior temporal gyrus (STG) and upper bank of the superior temporal sulcus. Injections just in front of the genu of the corpus callosum and in the subcallosal gyrus and gyrus rectus lead to terminal fields in the middle part of STG. No projections were found in the upper part of STG, i.e. the primary auditory cortex.To test the functional properties of this pathway, action potentials of single neurons in the auditory cortex were recorded during electrical stimulation of the cingular vocalization area. From a total of 135 STG neurons, an effect on spontaneous activity was seen in 27 cells. All except one of these neurons also reacted to acoustic stimuli. In most cases, stimulation of the cingular area caused a decrease in the discharge rate of the STG neurons. In 4 neurons, stimulation of the vocalization area had an influence on the acoustic reactivity of the STG neurons. The results provide evidence that during phonation the ‘cingular’ vocalization area exerts a predominantly inhibitory influence on auditory cortex neurons. This effect probably is mediated via the extreme capsule. Its possible function is discussed.     

Vocal‐motor and auditory connectivity of the midbrain periaqueductal gray in a teleost fish

The midbrain periaqueductal gray (PAG) plays a central role in the descending control of vocalization across vertebrates. The PAG has also been implicated in auditory‐vocal integration, although its precise role in such integration remains largely unexplored. Courtship and territorial interactions in plainfin midshipman fish depend on vocal communication, and the PAG is a central component of the midshipman vocal‐motor system. We made focal neurobiotin injections into the midshipman PAG to both map its auditory‐vocal circuitry and allow evolutionary comparisons with tetrapod vertebrates. These injections revealed an extensive bidirectional pattern of connectivity between the PAG and known sites in both the descending vocal‐motor and the ascending auditory systems, including portions of the telencephalon, dorsal thalamus, hypothalamus, posterior tuberculum, midbrain, and hindbrain. Injections in the medial PAG produced dense label within hindbrain auditory nuclei, whereas those confined to the lateral PAG preferentially labeled hypothalamic and midbrain auditory areas. Thus, the teleost PAG may have functional subdivisions playing different roles in vocal‐auditory integration. Together the results confirm several pathways previously identified by injections into known auditory or vocal areas and provide strong support for the hypothesis that the teleost PAG is centrally involved in auditory‐vocal integration. J. Comp. Neurol. 521:791–812, 2013. © 2012 Wiley Periodicals, Inc.     

A reinvestigation of the analgesic effects induced by stimulation of the periaqueductal gray matter in the rat. I. The production of behavioral side effects together with analgesia

It has been shown that stimulation-produced-analgesia (SPA) in the cat elicited from the periaqueductal gray matter (PAG) is obtained from sites located in the ventral part, particularly the dorsal raphé nucleus (DRN). These data contrast with the numerous studies performed in the rat in which efficient sites seem widely distributed throughout the PAG. These discrepancies led us to reinvestigate SPA from PAG and adjacent structures in the rat. Central stimulation was delivered through bipolar concentric electrodes (one for each animal). Analgesia was evaluated (before and during central stimulation) by measuring the modification in the vocalization threshold induced by electrical tail shocks or by considering the reaction of the animal to pinch. In contrast with the majority of previous studies, these experiments were performed on the totally freely-moving rat. The most striking result was that, in order to obtain analgesia from all regions of the PAG, it was necessary to apply intensities of central stimulation which also triggered other strong behavioral reactions. With intensities of PAG stimulation which did not induce such side effects, very few effective analgesic sites were found (21/129 sites of which 14/83 were strictly located in the PAG). However, it was possible to define two 'pure analgesic regions', both located in the ventral PAG: one centered on the dorsomedial part of the DRN and the other one situated in the ventrolateral PAG. No modification of nociceptive thresholds was observed when stimulating the dorsal and dorsolateral parts of the PAG as well as structures adjacent to these regions; in some rats, an increase in pain reactivity was even noted. When the intensity of central stimulation (applied to the various parts of the PAG) was increased, some stereotyped 'behavioral responses' occurred depending on the location of the stimulation site: motor effects (gnawing, rotation or tremor) in the ventral PAG and aversive effects (flight, jumping and on occasions, distress vocalizations) in the dorsal, dorsolateral PAG and in the ventral region just surrounding the cerebral aqueduct. Under these conditions, analgesia was obtained from practically the entire PAG, the vocalization threshold being increased dramatically on occasions. It must be emphasized that antinociceptive effects associated with other obvious behavioral manifestations (aversive ones) were also obtained from sites located outside the PAG (colliculi and tectum adjacent to the dorsal and dorsolateral PAG).(ABSTRACT TRUNCATED AT 400 WORDS)     

Systematic mapping of descending inhibitory control by the medulla of nociceptive spinal neurones in cats

Inhibition descending the spinal cord from the medullary brainstem was systematically mapped in two dimensions in anaesthetized cats. Fifty-four ipsi- and contralateral sites and 27 ipsilateral sites were electrically stimulated with concentric bipolar or with monopolar electrodes, respectively, whilsr extracellularly recording firing of dorsal horn neurones to noxious heat. Effective bipolar stimulation, but not monopolar stimulation caused gross lesions at the stimulated sites. There were 3 ipsilateral sites at which descending inhibition was evoked with the smallest stimuli. These areas corresponded to nucleus raphe magnus, nucleus reticularis magnocellularis and the lateral tegmental field. Contralateral stimulation was as effective or more effective than ipsilateral stimulation. The inhibition of dorsal horm neurones was not due to the cardiovascular changes which sometimes accompanied stimulation of the brainstem. The data are discussed in relation to the analgesia which results from stimulating these areas of the brainstem.     

Ipsilateral facial sensory and motor responses to basal fronto-temporal cortical stimulation: evidence suggesting direct activation of cranial nerves

To clarify the generator mechanism of sensory and motor facial responses ipsilateral to electrical stimulation of the inferior fronto-temporal cortex in epilepsy patients. Out of 30 patients who have been evaluated with chronically implanted subdural electrodes for medically intractable partial seizure or brain tumor involving the basal frontal or temporal cortex, 4 patients (age ranging 24-57 years) showed sensory and motor responses in the ipsilateral face to high frequency electrical cortical stimulation of the inferior fronto-temporal cortex. We investigated motor evoked potentials (MEPs) in the facial muscle by single pulse stimulation in 2 out of 4 patients. Three patients showed both sensory symptoms and muscle contraction in the ipsilateral lower face when the orbitofrontal or basal temporal cortex was stimulated with 50 Hz electric current. One patient had only sensory symptoms in the lower face when ipsilateral basal temporal area was stimulated. MEPs at the left orbicularis oris muscle were constantly elicited with the onset latency of 7 ms throughout the stimulus rate of 2-30 Hz in 1 patient out of 2 patients was tested. In another patient, MEP onset latency was 3.0 ms with 11 Hz stimulation. With electrical stimulation of the basal fronto-temporal cortex, the ipsilateral facial twitch might occur through either the direct activation of the facial nerve by the current spread in the middle cranial fossa or through the mechanism similar to blink reflex.     

The effectiveness of low-frequency stimulation for mapping cortical function

OBJECTIVE: To establish the efficacy and safety of low-frequency electrical stimulation for cortical brain mapping. METHODS: Cortical function was mapped using electrical stimulation in epilepsy patients with chronically implanted intracranial subdural electrodes. Contacts overlying motor, sensory, visual, and language cortex were stimulated at frequencies of 5, 10, and 50 Hz, using current levels ranging from 1 to 17.5 mA for 3-5 s. The current intensity and incidence at which functional alterations and afterdischarges (ADs) occurred were recorded. The modified McNemar test for nonindependent measures was used to analyze the data. RESULTS: 122 electrode contact pairs were electrically stimulated at least two different frequencies in 14 patients. Functional alterations were obtained at all stimulation frequencies (5, 10, and 50 Hz) at generally similar rates. The likelihood of producing an AD correlated with stimulation frequency, and lower-frequency stimulation was less likely to provoke an AD. Higher current intensity was required to induce both functional responses and ADs at low-frequency stimulation than high-frequency stimulation. While overall rates of producing functional changes were similar, differences in functional response with regard to frequency were noted at individual cortical sites. CONCLUSION: 5- and 10-Hz stimulation are as effective for mapping cortical function as 50-Hz stimulation and produce fewer ADs. We recommend that mapping of cortical function be started with 5-Hz-frequency stimulation. Higher frequencies should be used in suspect cortex if no symptoms or signs are produced with 5-Hz stimulation.     

A reinvestigation of the analgesic effects induced by stimulation of the periaqueductal gray matter in the rat. II. Differential characteristics of the analgesia induced by ventral and dorsal PAG stimulation

This study consists of a detailed analysis of the analgesic effects induced by stimulation of the various parts of the periaqueductal gray matter (PAG) in the freely moving rat. In order to characterize the analgesia, two criteria are considered: (1) the evaluation of the degree of analgesia and behavioral side effects evoked during central stimulation; and (2) the presence of post-effects. Central stimulation (50 Hz sine waves) was delivered via bipolar concentric electrodes and analgesia was quantified by the change in the vocalization threshold induced by electrical stimulation of the tail. Within the ventral PAG, the vocalization threshold increased gradually with the intensity of the central stimulation, the degree of analgesia generally being powerful. There was no relationship between the strength of the analgesic effects and the motor disturbances also produced by stimulation of this region. Antinociceptive effects generally disappeared when the stimulation ceased. Only when the intensity of the stimulation was strong enough to induce very powerful analgesic effects were post-stimulation analgesic effects noticed. Within the dorsal and dorsolateral PAG as well as in the ventral region just surrounding the aqueduct, analgesia appeared suddenly, was generally less pronounced and was always concomitant with strong aversive reactions. In contrast with the analgesia from the ventral PAG, marked post-effects were observed. These latter characteristics were also obtained from stimulation of regions located outside the PAG (colliculi, intercollicular commissure and tectum adjacent to the dorsolateral PAG) although these zones were not extensively studied. By consideration of various data in the literature, it is concluded from this study, which clearly distinguishes stimulation-produced-analgesia (SPA) from ventral PAG versus dorsal PAG, that analgesia induced from this midbrain area involves at least two different neuronal substrates. Whilst the ventral PAG seems to be more preferentially involved in pain modulation, the authenticity of 'analgesia' triggered by stimulation of aversive regions (which are widely spread over the PAG) is questioned and proposals to explain the simultaneous appearance of analgesic effects and aversion are considered.     

Representation of the face and intraoral structures in area 3b of the squirrel monkey (Saimiri sciureus) somatosensory cortex,with special reference to the ipsilateral representation

Studies of the representation of the trigeminal nerve in the thalamus and cerebral cortex of mammals have revealed representations of both contra- and ipsilateral intraoral structures. However, the relative extent of both representations is subject to considerable species variation. The present study employed microelectrode mapping and anatomical tracing to investigate the location and extent of the ipsilateral representation in area 3b of the somatosensory cortex of squirrel monkeys. A small region, approximately 2 mm², was found to be responsive to stimulation of ipsilateral intraoral structures. This region was located on the anteromedial border of area 3b, surrounded by the representation of the contralateral roof of the mouth. This region corresponded to areas of intense anterograde labeling following injections placed in the ventromedial portion of the ventral posterior medial nucleus of the thalamus at the only sites where neural responses could be elicited by stimulation of ipsilateral intraoral structures. The amount of thalamus and cortex given over to the ipsilateral representation in the squirrel monkey is small compared with that of the macaque monkey. This difference may be related to the lack of cheek pouches in the squirrel monkey, and therefore a different strategy for eating. The representation of the contralateral lower lip in area 3b was split by the representation of the contralateral upper lip. This split representation is in agreement with previous studies of the trigeminal representation in area 3b of the macaque monkey and may be a general feature of the representation of the trigeminal nerve in area 3b of primate cerebral cortex. © 1995 Wiley-Liss Inc.