Midbrain-hypothalamic interrelationships in the control of aggressive behavior

Previous studies have suggested an involvement of the midbrain ventral tegmental area in the biting attack upon a rat elicited by electrical stimulation of the lateral hypothalamus in cats. In order assess further the relationship between these two regions, 12 cats were implanted with attack-eliciting electrodes in both the lateral hypothalamus and the midbrain ventral tegmental area. Following a lesion of the midbrain attack site, attack previously elicited from hypothalamic electrodes ipsilateral to the lesion was eliminated or significantly reduced in frequency. The attack elicited from electrodes in the hypothalamus contralateral to the lesion was unaffected. Midbrain lesions made at sites from which attack was never elicited had no effect on hypothalamically elicited attack. The midbrain lesion in some cases eliminated only certain components of the total attack pattern; for example, the approach of a cat to the rat frequently remained present while the bite was absent. Additionally, it was found that the attack elicited from rostral hypothalamic electrodes was disrupted to a greater degree by a single midbrain lesion than the attack elicited from more caudal hypothalamic electrodes. These finding are discussed in terms of the neural system mediating this form of aggressive behavior in cats.     

The neural pathways mediating quiet-biting attack behavior from the hypothalamus in the cat: A functional autoradiographic study

Electrical stimulation of the region of the lateral hypothalamus produced a consistent form of quiet-biting attack behavior in cats. In one series of experiments, cats, implanted with electrodes from which attack had been elicited, were anesthetized and then were injected with a bolus of ¹⁴C-2-deoxyglucose at the same time as electrical stimulation was delivered through the attack electrodes. Brains prepared for X-ray autoradiography revealed that lateral hypothalamic stimulation activated the classical medial forebrain bundle pathway supplying the septal region, diagonal band, lateral preoptic area, and ventral tegmental region. Stimulation of quiet-attack sites in perifornical hypothalamus resulted in the activation of a much more extensive projection system which included the central and lateral tegmental fields of the midbrain and pons, and central gray region, as well as the structures described above. In a second series of experiments, ³H-leucine was placed into the region of the electrode tip from which attack was elicited in order to identify more precisely the pathways arising from that site. In general, tritiated amino acid radioautography replicated the ¹⁴C-2-deoxyglucose findings. In addition, the amino acid radioautographic data revealed the presence of extensive projections from perifornical hypothalamus to such pontine structures as the nucleus locus coeruleus, motor nucleus of NV , and the lateral pontine tegmental field. The functional connections between the lateral hypothalamic “attack region” and lateral preoptic zone were also confirmed by electrophysiological methods.     

Visual aspects of centrally elicited attack behavior in the cat: “Patterned reflexes” associated with selection of and approach to a rat

It has been previously suggested that the electrical brain stimulation which elicits quiet-biting attack in the cat actively affects the way the central nervous system processes visual and tactile information concerned with the reflexes involved in the terminal aspects of attack. In order to examine the effects of brain stimulation on a nonterminal aspect of attack – the stimulated cat's selection of and approach to a rat – cats were implanted with attack-eliciting electrodes in both the lateral hypothalamus and the midbrain ventral tegmental area. These cats were then tested in an 8-ft-long cage, one end of which was divided into three, 2-ft-long parallel compartments, whose openings faced the end of the cage from which the cat commenced its approach. An anesthetized rat was placed at the back of one compartment, a bowl of food at the back of another compartment, and the third compartment contained no object. It was found in the first experiment that the attack elicited by nearly all electrodes was selectively directed at the rat. However, the success of the cat in finding the compartment containing the rat varied dramatically for different electrodes in the same cat. Further, these differences were stable and did not change as the cat gained experience with the task. The results suggested that the stimulation of different brain sites in the same cat differentially affected the visual neural mechanisms involved in guiding a cat to a rat. Previous studies have also suggested that the effects of brain stimulation which elicits quiet-biting attack are largely lateralized to the side of the brain stimulated. In order to determine if the effects of stimulation on the neural mechanisms mediating the visually guided approach of a cat to a rat were also lateralized, attempts were made in a second experiment to disrupt the visual input to one side of the brain by unilaterally transecting the optic tract. It was found that this manipulation interfered with the visually guided selective approach to a rat, if the cat was stimulated through hypothalamic or mid-brain electrodes ipsilateral to the optic tract transection, but not if the hypothalamic or midbrain stimulation was on the contralateral (visually intact) side of the brain. However, any final interpretation of the results was confounded by the finding in all of these cats of a complex syndrome of neglect of all contralateral sensory information.     

Aggressive behavior induced by electrical stimulation in the midbrain central gray of male rats

Electrical stimulation via electrodes implanted in the lateral hypothalamus may induce intraspecific aggressive behavior. Small electrolytic lesions placed via these electrodes resulted in a five– to tenfold increase in the current threshold for aggression. Degenerating fibers were stained by means of the Fink-Heimer method and could be followed caudally to the dorsal midbrain central gray and to the mammillary bodies. A few axons could be traced rostrally to the medial septum. Aggression could be induced from 10 of 112 electrodes implanted in the central gray; the other electrodes elicited either locomotion, vocalization, jump, or “alarm-like reactions.” The morphology of the induced aggression was similar to the morphology of the hypothalamically induced aggression, though it was often accompanied with motor disturbances and was less intense. Hypothalamic stimulation was combined with simultaneous central gray stimulation in rats with electrodes both in the hypothalamus and in the central gray. Hypothalamic thresholds for aggression could be lowered by this stimulation of the central gray, even when no aggressive responses were observed during central gray stimulation alone. This suggests that, although aggression is not manifest, electrical stimulation may activate neural tissue involved in aggressive behavior. It is concluded that in rats central gray and hypothalamus are part of the same neural network mediating intraspecific aggression.     

Attack, eating, drinking, and gnawing elicited by electrical stimulation of rat mesencephalon and pons.

Eating, drinking, and gnawing were electrically elicited from the rat mesencephalon in the vicinity of the lateral branch of the descending medial forebrain bundle, but attack was evoked from the dorsomedial tegmentum adjacent to the central gray. The effective zones continued further caudally to the dorsal posterior pons. Unlike hypothalamically elicited behavior, eating, drinking, and gnawing often persisted 5-40 sec after termination of stimulation. Vocalization and escape activity were obtained principally from the vicinity of central pain pathways originating from the anterolateral cord. Other electrodes produced eating, drinking, gnawing, and grooming, which began only after termination of stimulation.     

Mother-infant responsiveness: timing, mutual regulation, and interactional context

Mutual regulation during the naturalistic interaction of 150 mothers and their 4-month-old infants was investigated from a dynamic systems perspective. Microanalyses of a wide range of behaviors and analysis of contingencies indicated that a 3-s time period best captured contingencies. Both mothers and infants communicated primarily through vocal signals and responses, although maternal touches and infant looks also elicited responses. Although more expressive mothers did not have infants who behaved similarly, levels of contingent responsiveness between partners were significantly associated and occurred within distinct behavioral channels, suggesting coregulated interactional processes in which contingently responsive mothers shape their infants' communications toward mutual similarity. Mothers were more influential than infants over object play, whereas infants were more influential than mothers over expressive behavior. Interactional context consistently influenced contingent responsiveness; there was less mutual responsiveness when the infant was exploring, being held, or looking.     

Walking or talking? Behavioral and neurophysiological correlates of action verb processing

Brain activity elicited by visually presented words was investigated using behavioral measures and current source densities calculated from high-resolution EEG recordings. Verbs referring to actions usually performed with different body parts were compared. Behavioral data indicated faster processing of verbs referring to actions performed with the face muscles and articulators (face-related words) compared to verbs referring to movements involving the lower half of the body (leg-related words). Significant topographical differences in brain activity elicited by verb types were found starting approximately 250 ms after word onset. Differences were seen at recording sites located over the motor strip and adjacent frontal cortex. At the vertex, close to the cortical representation of the leg, leg-related verbs (for example, to walk) produced strongest in-going currents, whereas for face-related verbs (for example, to talk) the most in-going activity was seen at more lateral electrodes placed over the left Sylvian fissure, close to the representation of the articulators. Thus, action words caused differential activation along the motor strip, with strongest in-going activity occurring close to the cortical representation of the body parts primarily used for carrying out the actions the verbs refer to. Topographically specific physiological signs of word processing started earlier for face-related words and lasted longer for verbs referring to leg movements. We conclude that verb types can differ in their processing speed and can elicit neurophysiological activity with different cortical topographies. These behavioral and physiological differences can be related to cognitive processes, in particular to lexical semantic access. Our results are consistent with associative theories postulating that words are organized in the brain as distributed cell assemblies whose cortical distributions reflect the words' meanings.     

Phenylpropanolamine inhibits feeding, but not drinking, induced by hypothalamic stimulation.

In rats bearing lateral hypothalamic electrodes that elicited both feeding and drinking, intraperitoneal injection of the appetite suppressant drug phenylpropanolamine (Propadrine) inhibited only feeding. This occurred whether feeding and drinking were tested simultaneously or separately. Selective inhibition of lateral hypothalamic feeding also followed injection of this drug through lateral, but not medial, hypothalamic electrode cannulas. We conclude that hypothalamically induced feeding is under some of the same pharmacological controls as spontaneous feeding, that this control may be exerted, in part, in or near the lateral hypothalamus, and that the neural systems which induce feeding and drinking during hypothalamic stimulation can be pharmacologically separated.     

Event-related potentials and the interaction between orthographic and phonological information in a rhyme-judgment task

Event-related potentials (ERPs) were recorded from one midline and three pairs of lateral electrodes in three experiments involving a rhyme-judgment task. Experiment 1 employed sequentially presented word pairs consisting of orthographically similar and dissimilar rhyming and nonrhyming items (RUNG-SUNG, MAKE-ACHE, BEAD-DEAD, GIFT-ROAD). Comparison of the ERPs elicited by the dissimilar pairs revealed a rhyme/nonrhyme difference in the form of an increase in the amplitude of a late negative component (N450) for nonrhyming pairs; this effect was confined almost entirely to right-hemisphere electrodes. By contrast, rhyme/nonrhyme differences in the ERPs to orthographically similar word pairs were smaller in magnitude, later in onset, and bilaterally distributed. Experiment 2 showed that this pattern of ERP effects with orthographically similar items depended upon orthographic and not visual similarity. Experiment 3 tested the hypothesis that the lack of a right-hemisphere based N450 effect with orthographically similar items resulted from the operation of an orthographic priming mechanism. ERPs to nonrhyming pairs containing a word with an inconsistent segment (COAST-FROST) were compared with visually matched controls (SPARSE-CREASE). The rhyme/nonrhyme differences in the N450 components from these two conditions were indistinguishable, although subjects found it as difficult to make nonrhyme responses to "COAST-FROST" pairs as to the orthographically similar nonrhyming items in Experiment 1. It was concluded that while "orthographic priming" accounted for the behavioral data from these experiments, it could not explain the interaction between phonology and orthography observed in the concurrently recorded ERP data.     

Projection of the Magnocellular Red Nucleus to the Region of the Accessory Abducens Nucleus in the Rabbit

The projection of the magnocellular red nucleus (RNm) to the region of the accessory abducens nucleus (AABD) was traced in rabbit using the bidirectional tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP). In one set of animals, recordings of antidromic responses from RNm neurons elicited by electrical stimulation of the rubrospinal tract were used to localize injections of WGA-HRP for orthograde labeling of RNm terminals. In a different set of animals, horseradish peroxidase was injected into the retractor bulbi muscle to retrogradely label motoneurons of the AABD. The positions of RNm fibers and terminals were examined and compared to the locations and distribution of AABD cell bodies and labeled dendrites. Analyses revealed that along the entire rostrocaudal extent of the AABD, RNm efferents terminate primarily lateral to, or in the lateral aspects of, labeled motoneurons. For the rostral AABD, RNm efferents terminate only lateral to the nucleus. Although the terminals are not positioned to contact cell bodies of the AABD, they could overlap with dendrites that extend in the lateral direction. RNm efferents terminate more extensively within the posterior AABD, overlapping within both dendritic and cell body regions of the nucleus. Even in this posterior region, however, RNm efferents were distributed primarily over the lateral half of the nucleus. These data show that RNm can monosynaptically influence the AABD, through primarily its lateral and posterior aspects. Our findings also show that a major target of RNm efferents is the reticular cell population located lateral to the AABD, suggesting that the RNm also may affect AABD motoneuronal output indirectly through its projection to reticular cells.     

Value-based modulation of memory encoding involves strategic engagement of fronto-temporal semantic processing regions

A number of prior fMRI studies have focused on the ways in which the midbrain dopaminergic reward system coactivates with hippocampus to potentiate memory for valuable items. However, another means by which people could selectively remember more valuable to-be-remembered items is to be selective in their use of effective but effortful encoding strategies. To broadly examine the neural mechanisms of value on subsequent memory, we used fMRI to assess how differences in brain activity at encoding as a function of value relate to subsequent free recall for words. Each word was preceded by an arbitrarily assigned point value, and participants went through multiple study–test cycles with feedback on their point total at the end of each list, allowing for sculpting of cognitive strategies. We examined the correlation between value-related modulation of brain activity and participants’ selectivity index, which measures how close participants were to their optimal point total, given the number of items recalled. Greater selectivity scores were associated with greater differences in the activation of semantic processing regions, including left inferior frontal gyrus and left posterior lateral temporal cortex, during the encoding of high-value words relative to low-value words. Although we also observed value-related modulation within midbrain and ventral striatal reward regions, our fronto-temporal findings suggest that strategic engagement of deep semantic processing may be an important mechanism for selectively encoding valuable items.     

Emotional experience and expression in schizophrenia and depression.

The emotional responses of schizophrenic, depressed, and normal subjects and whether differences in the emotional responding of these groups depended on how emotional responses were elicited or measured were examined. Twenty-three blunted and 20 nonblunted schizophrenics, 17 unipolar depressed subjects, and 20 normal subjects were exposed to a series of affect-eliciting stimuli. The stimuli varied in valence (positive vs. negative) and in level of cognitive demand. Subjects reported their subjective experiences, and their facial expressions were videotaped. Blunted schizophrenics were the least facially expressive, although their reported subjective experiences did not differ from those of the other groups. The nonblunted schizophrenics were more responsive than the depressed subjects to the positive stimuli, although the two groups did not differ in their clinical ratings of affective flatness.     

Identification of a cortical site for stress-induced cardiovascular dysfunction

The evidence indicating that the insular cortex is a likely candidate to mediate stress-induced cardiovascular responses is reviewed. Both neuroanatomical and electrophysiological investigations demonstrate that the insular cortex receives an organized representation of visceral information. In addition, the insular cortex also receives highly processed association cortex information. The insular cortex is also highly interconnected with many subcortical limbic and autonomic regions. This combination of sensory input and limbic/autonomic connectivity would be necessary to permit the insular cortex to be a critical site for the integration of emotional and autonomic responses. Stimulation of the insular cortex elicits specific cardiovascular and autonomic responses from discrete sites. Phasic stimulation entrained to the cardiac cycle is even capable of causing severe arrhythmias. The efferent pathways and some of the neurotransmitter mechanisms have determined. It appears that the lateral hypothalamic area is the primary site of synapse for autonomic responses originating in the insular cortex and this information is relayed by NMDA glutamatergic receptors and modulated by neuropeptides including neuropeptide Y, neurotensin, leu-enkephalin and dynorphin. Finally, a rat stroke model, which includes the insular cortex in the infarct region indicates that disruption of the insula can produce substantial cardiac and autonomic abnormalities, which might be similar to those produced by stress. Some of the chronic neurochemical changes, including increases in opioids, neuropeptide Y and neurotensin in the central nucleus of the amygdala, which might be mediating these cardiovascular disturbances, have been determined.     

Attention, intention and domain-specific processing

Many researchers use subliminal priming to investigate domain-specific processing mechanisms, which have classically been defined in terms of their autonomy from other cognitive systems. Surprisingly, recent research has demonstrated that nonconsciously elicited cognitive processes are not independent of attention. By extension, these findings have been used to call into question the autonomy of domain-specific processing mechanisms. By contrast, we argue that the demonstrated modulation of nonconscious cognitive processes by attention occurs at a predomain-specific stage of processing. Thus, although we agree that attention might be a prerequisite of nonconscious processes, we suggest that there is no reason to think that higher-level cognitive systems directly modulate domain-specific processes.     

Comparison of taste qualities elicited by tactile,electrical, and chemical stimulation of single human taste papillae

Taste quality responses elicited by chemical, electrical, and tactile stimulation of 40 single fungiform papillae in four subjects were examined. A comparison of responses revealed differences in taste quality mediation for the three different classes of stimuli. Chemical stimulation elicited multiple taste qualities from a greater proportion of papillae than did either electrical or tactile stimulation. In addition, the chemical data revealed the presence of consistent bitter-sour and sour-salty confusions. Both tactile and electrical stimulation elicited relatively few bitter and sweet responses, as compared with either sour or salty responses. However, correct quality identification in these papillae for bitter and sweet compounds was no different from that for sour or salty compounds. In addition, electrical stimulation elicited a greater proportion of salty responses than did tactile stimulation. Comparison of the taste quality elicited by either tactile or electrical stimulation of a papilla with the taste quality exhibiting the greatest relative chemical sensitivity in the papilla also revealed independence of responding, and it was observed that both electrical and tactile stimulation elicited consistent taste quality responses from papillae in which these taste qualities could not be elicited by any concentration of any chemical test compound. The observed differences in quality judgments are discussed as possibly being the result of cross-modal gustatory associations resulting from nongustatory components of inadequate stimulation.     

Affective responses to body stimuli: comparing male and female bodies with cropped heads and masked faces

Three studies were conducted to determine whether headless bodies evoke affective responses that might confound neuroimaging and electrophysiological findings. In Experiment 1, 224 participants rated pictures, including bodies with cropped heads and masked faces, for disgust, fear, naturalness, valence and arousal. In Experiment 2, 38 participants viewed the same images during a free word association task, whilst in Experiment 3 galvanic skin responses were measured as 57 participants completed a similar rating task to that in Experiment 1. No differences were found between responses elicited by bodies without heads versus bodies with masked faces, although female bodies were thought of more positively than male bodies. This suggests that headless bodies are not abhorrent and are appropriate stimuli for investigating body-selective perceptual processes as they do not evoke face-processing mechanisms. Our findings also suggest that differences between male and female body viewing should be considered when investigating visual body perception.     

Sculptors,Architects, and Painters Conceive of Depicted Spaces Differently

Sculptors, architects, and painters are three professional groups that require a comprehensive understanding of how to manipulate spatial structures. While it has been speculated that they may differ in the way they conceive of space due to the different professional demands, this has not been empirically tested. To achieve this, we asked architects, painters, sculptors, and a control group questions about spatially complex pictures. Verbalizations elicited were examined using cognitive discourse analysis. We found significant differences between each group. Only painters shifted consistently between 2D and 3D concepts, architects were concerned with paths and spatial physical boundedness, and sculptors produced responses that fell between architects and painters. All three differed from controls, whose verbalizations were generally less elaborate and detailed. Thus, for the case of sculptors, architects, and painters, profession appears to relate to a different spatial conceptualization manifested through a systematically contrasting way of talking about space.     

Mesencephalic participation in the control of sexual behavior in the female rat

Electric stimuli applied to both pudendal nerves evoked field potentials, unit responses, and multiunit responses in the ventrolateral midbrain, in and around the peripeduncular nucleus. Bilateral lesions placed in this region suppressed sexual behavioral responses (lordosis and courting behavior) of ovariectomized rats primed with 5, 10, 100, and 1,000 microgram of estradiol benzoate and 2 mg of progesterone per kilogram of body weight. It is proposed that the region in question represents a relay station for the integration of sensory and endocrine information concerned in the control of receptive sexual behavior in the female rat.     

Neuroimmune stress responses: reciprocal connections between the hypothalamus and the brainstem

Hypothalamic nuclei, particularly the paraventricular nuclei (PVN), are important brain sites responsible for eliciting stress responses following a systemic immune challenge. The activation of PVN cells by a systemic immune challenge is critically dependent on the integrity of inputs from brainstem cells situated in the nucleus tractus solitarius (NTS) and ventrolateral medulla (VLM). Interestingly, a descending pathway from the PVN to the brainstem, recruited by systemic immune challenge, might also exist. It is well documented that PVN neurons innervate the NTS and VLM and recent evidence from our laboratory shows that lesions of the PVN reduce brainstem cell responses elicited by a systemic bolus of the proinflammatory cytokine interleukin-1beta (IL-1beta). Although a number of different PVN divisions are candidates for the source of inputs to the brainstem, we have demonstrated that the majority of descending PVN projections recruited by systemic IL-1beta arise from cell bodies localized in the medial and lateral parvocellular PVN. These findings suggest that central nervous system responses to an immune challenge are likely to involve complex reciprocal connections between the PVN and the brainstem, whereby brainstem cell populations could essentially act as integratory sites for descending and ascending immune signals. For instance, these brainstem pathways may have significant implications not only for the regulation of central hypothalamic and extra-hypothalamic targets but also the autonomic nervous system.     

Categorical perception for voicing contrasts in normal and lead-treated rhesus monkeys: electrophysiological indices

Categorical perception of voicing contrasts was evaluated in rhesus monkeys. The monkeys had been chronically exposed to subclinical levels of lead either from conception to birth, or for approximately 6 months postnatally beginning at birth, or were never exposed to lead. Auditory evoked responses were recorded at 1 year of age from scalp electrodes placed over the left and right hemispheres during stimulus presentation. A late component of the brain responses recorded from the right temporal region of all monkeys discriminated between stimuli in a categorical manner. This pattern of responses was noted to be similar to that previously reported for humans. Categorical discriminations were also noted earlier in the waveforms for control monkeys and for monkeys exposed to lead prenatally, although this discrimination pattern shifted to the left hemisphere of the latter group. No such effects were noted for monkeys exposed to lead postnatally. These results suggest that the neurocortical mechanisms associated with categorical perception for voicing information may be similar across human and nonhuman primates. However, early exposure to lead appears to alter these processes.