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Control of complex conation and emotion in the neocortex by the limbic entorhinal, subicular, and cingulate cortices and the hypothalamus, mammillary body, and thalamus.

The neocortex appears to contain columnar neuron populations that function as unitary information structures. The interactions between these structures, and the sensorimotor relationships they process, are regulated by subcortical regions. The reticular formation, hypothalamus, thalamus and basal ganglia have been proposed as a hierarchical control system that regulates the processing carried out by hierarchies of the cortical information structures in basic behavioral states. The regulation is carried out by means of operations on conative information components that circulate through the subcortical-neocortical system. It is proposed that in complex behavioral states, composite modalities of conative information are formed. These are processed in a complex-state system that involves parts of the limbic lobe and related nuclei: the entorhinal cortex, subiculum, mammillary body, thalamus, and posterior and anterior cingulate cortices. This system can accommodate new modalities of conation, including those relating to social behavior. Genetic specification of engrams in the system provides for evolution of conative and emotional states, matching increases in sophistication of cognitive processing.

Animals↗

Corticosteroid actions from neuronal membrane to behavior: neurophysiological mechanisms underlying rapid behavioral effects of corticosterone.

Investigation of the rapid suppression of male courtship clasping behavior by corticosterone in roughskin newts (Taricha granulosa) has led to the identification of a specific neuronal membrane receptor for this stress steroid. This paper describes studies of the neurophysiological effects of the rapid, membrane receptor mediated action of corticosterone on neurons that are involved in the control of clasping. In freely behaving newts, medullary neurons, including reticulospinal neurons, process clasp-triggering sensory signals and participate in control of clasping movements. Corticosterone injection causes these brainstem neurons to show selective depression of clasping-related sensorimotor function. These corticosterone effects appear in 3-10 min and are closely associated with the simultaneous depression of clasping. In addition to these functionally specific effects, corticosterone simultaneously causes widespread, primarily depressive effects on neuronal activity and excitability in the medulla and elsewhere in the brain. Thus, the membrane actions of corticosterone lead to diverse neural effects, including changes in membrane excitability as well as specific, network-level actions that are apparent only during behavior. These rapid corticosterone effects strongly interact with actions of the neuropeptides vasotocin and corticotropin-releasing factor, such that the form and magnitude of the steroid's effects depend on the prevailing neuroendocrine state of the brain.

Adrenal Cortex Hormones↗

The reorganization of sensorimotor function in children after hemispherectomy. A functional MRI and somatosensory evoked potential study.

Children who have suffered extensive unilateral brain injury early in life may show a remarkable degree of residual sensorimotor function. It is generally believed that this reflects the high capacity of the immature brain for cerebral reorganization. In this study, we investigated 17 patients who had undergone hemispherectomy for relief from seizures; eight of the patients had congenital brain damage and nine had sustained their initial insult at the age of 1 year or older. Sensorimotor functions of the hand were investigated using functional MRI (fMRI) during a passive movement task, somatosensory evoked potentials (SEPs) arising from electrical and vibration stimulation, and behavioural tests including grip strength, double simultaneous stimulation and joint position sense. On fMRI, two of the eight patients studied with this technique (one with congenital damage and one with damage acquired at the age of 3 years) showed activation in the sensorimotor cortex of the remaining hemisphere with passive movement of the hemiplegic hand. The location of the ipsilateral brain activation was similar to that found on movement of the normal contralateral hand, although the latter was greater in spatial extent. In one of these patients, a greater role was demonstrated for the ipsilateral secondary sensorimotor area (compared with the ipsilateral primary sensorimotor area) for movement of the hemiplegic hand than for movement of the normal hand. Median nerve stimulation of the hemiplegic hand showed reproducible early-latency ipsilateral SEP components in the remaining sensorimotor cortex in 10 of the 17 patients (five with congenital and five with acquired disease). Five of the patients who demonstrated ipsilateral electrical SEPs also showed ipsilateral vibration SEPs (two with congenital and three with acquired disease). The behavioural tests revealed residual sensorimotor function in 14 of the patients; however, not all of the patients who exhibited ipsilateral SEP or fMRI responses had residual sensorimotor function in the hemiplegic hand. Ipsilateral sensorimotor responses were demonstrated both in patients with congenital disease and those with acquired disease, suggesting that factors additional to aetiology and age at injury may influence the degree of residual sensorimotor function and cerebral reorganization.

Adolescent↗

Sensorimotor slowing with ageing is mediated by a functional dysregulation of motor-generation processes: evidence from high-resolution event-related potentials.

The objective of the present study was to identify the origin(s) of ageing-related behavioural slowing in sensorimotor tasks. For this aim, event-related potentials (ERPs) were analysed at 64 electrodes to evaluate the strength and timing of different stages of information processing in the brain. Electrophysiological indices of stimulus processing, sensorimotor integration/response selection and motor-related processing were used to compare the processing speed of young (n = 13, mean age = 22.5 years) and older adults (n = 14, mean age = 58.3 years) in simple- and choice-reaction tasks presented in two modalities, auditory and visual. The behavioural results showed significant ageing-related slowing, but only in the choice-reaction task. The quantification of separate central processing stages, in combination with advanced ERP methodology, helped to reveal that this slowing did not originate from the early processes of stimulus processing and response selection. Instead, it was produced by slower activation patterns over the contralateral motor cortex underlying response generation. It is concluded that ageing is accompanied by a functional dysregulation of motor cortex excitability during sensorimotor processing, with this deficit becoming progressively evident with greater task complexity.

Acoustic Stimulation↗

Sound-localization performance in the cat: the effect of restraining the head.

In oculomotor research, there are two common methods by which the apparent location of visual and/or auditory targets are measured, saccadic eye movements with the head restrained and gaze shifts (combined saccades and head movements) with the head unrestrained. Because cats have a small oculomotor range (approximately +/-25 degrees), head movements are necessary when orienting to targets at the extremes of or outside this range. Here we tested the hypothesis that the accuracy of localizing auditory and visual targets using more ethologically natural head-unrestrained gaze shifts would be superior to head-restrained eye saccades. The effect of stimulus duration on localization accuracy was also investigated. Three cats were trained using operant conditioning with their heads initially restrained to indicate the location of auditory and visual targets via eye position. Long-duration visual targets were localized accurately with little error, but the locations of short-duration visual and both long- and short-duration auditory targets were markedly underestimated. With the head unrestrained, localization accuracy improved substantially for all stimuli and all durations. While the improvement for long-duration stimuli with the head unrestrained might be expected given that dynamic sensory cues were available during the gaze shifts and the lack of a memory component, surprisingly, the improvement was greatest for the auditory and visual stimuli with the shortest durations, where the stimuli were extinguished prior to the onset of the eye or head movement. The underestimation of auditory targets with the head restrained is explained in terms of the unnatural sensorimotor conditions that likely result during head restraint.

Acoustic Stimulation↗

[Effect of the enkephalin derivative DAGO on neuronal behavior and activity in the neocortex and hippocampus of rabbits during the acquisition of conditioned defense and inhibitory reflexes].

After subcutaneous injection of 25 mkg/kg morphine-like opiate--DAGO a decrease was observed of probabilities of rabbits movements at light flashes--defensive reflex signal. The level of the background neuronal impulse activity became gradually lower in the sensorimotor cortex and the hippocampus and did not change in the visual cortex. Decrease and restoration of responses to the reinforcing stimulus (electrocutaneous limb stimulation) in all studied cortical zones proceeded in one direction while there were significant differences in dynamics of responses to inhibitory and reinforced light flashes depending on the studied cortical zone and biological significance of the stimulus. Appearance is discussed of particular characteristics of neurones systemic organization during learning at change of reinforcement properties under the influence of the studied substance, as well as similarity of some features of mechanisms of internal inhibition elaboration in a defensive situation and of properties of positive reinforcement.

Animals↗

Antipsychotic potential of CCK-based treatments: an assessment using the prepulse inhibition model of psychosis.

Systemic injections of cholecystokinin (CCK), a "gut-brain" peptide, have been shown to modulate brain dopamine function and produce neuroleptic-like effects on such dopamine-regulated behaviors as locomotor activity. However, clinical trials of CCK agonists in schizophrenia patients showed mixed results. To re-examine the antipsychotic potential of CCK-based treatments, we examined systemic injections of CCK analogs in an animal model with strong face and construct validity for sensorimotor-gating deficits seen in schizophrenia patients and with strong predictive validity for antipsychotic drug activity. Prepulse inhibition (PPI) occurs when a weak acoustic lead stimulus ("prepulse") inhibits the startle response to a sudden loud sound ("pulse"). PPI is significantly reduced in schizophrenia patients and rats treated with dopamine agonists. Antipsychotics reverse decreased PPI in rats to a degree highly correlated with their clinical efficacy. Subcutaneous (s.c.) injections of caerulein (10 micrograms/kg) a mixed CCKA/B agonist, partially reversed amphetamine-induced reduction of PPI; whereas, s.c. haloperidol (0.5 mg/kg) totally reversed amphetamine-induced disruption of PPI. Caerulein's effect on PPI was blocked by pretreatment with a CCKA antagonist (devazepide) but not a CCKB antagonist (L-365,260). CCK-4, a preferential CCKB agonist, had no significant effect on PPI. These results suggest that caerulein produces a weak neuroleptic-like effect on PPI that is mediated by stimulation of CCKA receptors. Possible circuities in this effect are discussed. In a separate experiment, s.c. caerulein produced to a more potent neuroleptic-like profile on amphetamine-induced hyperlocomotion, suggesting that selection of preclinical paradigms may be important in evaluating the antipsychotic potential of CCK-based treatments.

Animals↗

Behavioral functions of nucleus accumbens dopamine: empirical and conceptual problems with the anhedonia hypothesis.

Nucleus accumbens (DA) has been implicated in a number of different behavioral functions, but most commonly it is said to be involved in "reward" or "reinforcement". In the present article, the putative reinforcement functions of accumbens DA are summarized in a manner described as the "General Anhedonia Model". According to this model, the DA innervation of the nucleus accumbens is conceived of as a crucial link in the "reward system", which evolved to mediate the reinforcing effects of natural stimuli such as food. The reward system is said to be activated by natural reinforcing stimuli, and this activation mediates the reinforcing effects of these natural stimuli. According to this view, other stimuli such as brain stimulation and drugs can activate this system, which leads to these stimuli being reinforcing as well. Interference with DA systems is said to blunt the reinforcing effects of these rewarding stimuli, leading to "extinction". This general model of the behavioral functions of accumbens DA is utilized widely as a theoretical framework for integrating research findings. Nevertheless, there are several difficulties with the General Anhedonia Model. Several studies have observed substantial differences between the effects of extinction and the effects of DA antagonism or accumbens DA depletions. Studies involving aversive conditions indicate that DA antagonists and accumbens DA depletions can interfere with avoidance behavior, and also have demonstrated that accumbens DA release is increased by stressful or aversive stimuli. Although accumbens DA is important for drug abuse phenomena, particularly stimulant self-administration, studies that involve other reinforcers are more problematic. A large body of evidence indicates that low doses of dopamine antagonists, or depletions of accumbens DA, do not impair fundamental aspects of food motivation such as chow consumption and simple instrumental responses for food. This is particularly important, in view of the fact that many behavioral researchers consider the regulation of food motivation to be a fundamental aspect of food reinforcement. Finally, studies employing cost/benefit analyses are reviewed, and in these studies considerable evidence indicates that accumbens DA is involved in the allocation of responses in relation to various reinforcers. Nucleus accumbens DA participates in the function of enabling organisms to overcome response costs, or obstacles, in order to obtain access to stimuli such as food. In summary, nucleus accumbens DA is not seen as directly mediating food reinforcement, but instead is seen as a higher order sensorimotor integrator that is involved in modulating response output in relation to motivational factors and response constraints. Interfering with accumbens DA appears to partially dissociate the process of primary reinforcement from processes regulating instrumental response initiation, maintenance and selection.

Animals↗

Cortical stimulation improves skilled forelimb use following a focal ischemic infarct in the rat.

Improving functional recovery following cerebral strokes in humans will likely involve augmenting brain plasticity. This study examined skilled forelimb behavior, neocortical evoked potentials, and movement thresholds to assess cortical electrical stimulation concurrent with rehabilitative forelimb usage following a focal ischemic insult. Adult rats were trained on a task that required skilled usage of both forelimbs. They then underwent an acute focal ischemic insult to the caudal forelimb area of sensorimotor cortex contralateral to their preferred forelimb. During the same procedure, they also received a stimulation electrode over the infarct area and two depth electrodes anterior to the lesion to record evoked potentials. One week following the surgery, rats received cortical stimulation during performance of the skilled task. Evoked potentials and movement thresholds were also determined. Functional assessment revealed that cortical stimulation resulted in superior performance compared to the no stimulation group, and this was initially due to a shift in forelimb preference. Cortical stimulation also resulted in enhanced evoked potentials and a reduction in the amount of current required to elicit a movement, in a stimulation frequency dependent manner. This study suggests that cortical stimulation, concurrent with rehabilitative training, results in better forelimb usage that may be due to augmented synaptic plasticity.

Analysis of Variance↗

Tolerance and sensitization to inhaled 1,1,1-trichloroethane in mice: results from open-field behavior and a functional observational battery.

RATIONALE: 1,1,1-Trichloroethane (TCE), a representative abused solvent, has well described acute behavioral effects in animals. Much less is known about repeated high-concentration exposures as would be encountered in inhalant abusers. Tolerance has been demonstrated in some, but not all, studies with TCE while sensitization has also been seen with other abused solvents. OBJECTIVE: The present study was designed to further characterize changes in the effects of repeated exposure to TCE on a variety of mouse behaviors. METHODS: Mice were tested using locomotor activity as well as a functional observational battery (FOB) both before and after a regimen of daily exposures to various concentrations of TCE. RESULTS: The initial locomotor effects of acute 30-min exposures to TCE were biphasic with concentration-dependent increases in activity at lower concentrations and decreases observed at higher concentrations. The profile of acute effects as measured by the FOB included changes in posture, decreased arousal, disturbances in gait, delayed righting reflexes, and decreased sensorimotor reactivity. Animals were then divided into five groups and exposed 30 min/day to either air or one of four concentrations of TCE (2,000, 6,000, 10,000, or 13,300 ppm) for 15 consecutive days. The TCE concentration used primarily affected the magnitude of change, not whether tolerance or sensitization occurred. Tolerance developed on the measures of forelimb grip strength, inverted screen, and number of rears. Conversely, sensitization developed to measures of locomotor activity. CONCLUSION: Depending on the behavioral measure, both tolerance and sensitization can occur in mice with repeated exposure to TCE. Both of these phenomena are characteristic of drugs of abuse.

Administration, Inhalation↗

Step cycle-related oscillatory properties of inferior olivary neurons recorded in ensembles.

This study was conducted to characterize patterns of discharge from the dorsal accessory olive during different behavioural states. To accomplish this goal, adult rats were chronically implanted with arrays of microwires (25-50 microns) to record from as many as 23 neurons from the dorsal accessory olive bilaterally during locomotor paradigms or at rest. Olivary neurons discharged sporadically at low firing frequencies (1-5 Hz) when the rat was at rest. However, during locomotor paradigms involving constant speed treadmill locomotion, olivary neurons discharged rhythmically at frequencies which closely matched step cycle frequencies. The rhythmic nature of olivary discharge was maintained even during brief periods of inconsistent gait. During treadmill locomotion utilizing variable acceleration/deceleration paradigms olivary neurons discharged at 3 Hz frequencies. Electrical stimulation of peripheral afferents resulted in rhythmic discharge of olivary neurons at frequencies harmonic with the rate of stimulation. These data suggest that oscillatory patterns of discharge exhibited by the inferior olivary nucleus are only seen during rhythmic behavioral tasks or stimulation paradigms. Further, the dissociation between the rhythmic nature of the task and the continued oscillation suggests that oscillatory activity of the inferior olive may be due both to an intrinsic rhythm as well as related to ongoing sensorimotor input.

Animals↗

Discovery of genes involved with learning and memory: an experimental synthesis of Hirschian and Benzerian perspectives.

The biological bases of learning and memory are being revealed today with a wide array of molecular approaches, most of which entail the analysis of dysfunction produced by gene disruptions. This perspective derives both from early "genetic dissections" of learning in mutant Drosophila by Seymour Benzer and colleagues and from earlier behavior-genetic analyses of learning and in Diptera by Jerry Hirsh and coworkers. Three quantitative-genetic insights derived from these latter studies serve as guiding principles for the former. First, interacting polygenes underlie complex traits. Consequently, learning/memory defects associated with single-gene mutants can be quantified accurately only in equilibrated, heterogeneous genetic backgrounds. Second, complex behavioral responses will be composed of genetically distinct functional components. Thus, genetic dissection of complex traits into specific biobehavioral properties is likely. Finally, disruptions of genes involved with learning/memory are likely to have pleiotropic effects. As a result, task-relevant sensorimotor responses required for normal learning must be assessed carefully to interpret performance in learning/memory experiments. In addition, more specific conclusions will be obtained from reverse-genetic experiments, in which gene disruptions are restricted in time and/or space.

Animals↗

A role for neural integrators in perceptual decision making.

Decisions based on uncertain information may benefit from an accumulation of information over time. We asked whether such an accumulation process may underlie decisions about the direction of motion in a random dot kinetogram. To address this question we developed a computational model of the decision process using ensembles of neurons whose spiking activity mimics neurons recorded in the extrastriate visual cortex (area MT or V5) and a sensorimotor association area of the parietal lobe (area LIP). The model instantiates the hypothesis that neurons in sensorimotor association areas compute the time integral of sensory signals from the visual cortex, construed as evidence for or against a proposition, and that the decision is made when the integrated evidence reaches a threshold. The model explains a variety of behavioral and physiological measurements obtained from monkeys.

Action Potentials↗

[Sensorimotor reactivity (acoustic startle response) in rats with experimental depressive syndrome].

Alterations of the sensorimotor responses in Wistar rats with experimental dopamine deficit-dependent depressive syndrome induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine were measured by acoustic startle. In rats with innate high level of anxiety the development of behavioral depression was accompanied by the decrease in startle amplitude. In rats with innate low level of anxiety the decrease in startle amplitude did not reach the statistical significance. Correlation between the anxiety-phobic level and the expression of behavioral depression was not revealed. Independently of the initial anxiety-phobic level, in rats with depressive syndrome at the stage of behavioral rehabilitation after the neurotoxin withdrawal the prepulse inhibition of the acoustic startle was decreased as compared to control animals. It is suggested that the decrease in startle amplitude and, to a greater extent, the decrease in prepulse inhibition may characterize the development of dopamine deficit-dependent states.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Somatosensory and motor disturbances in patients with parietal lobe lesions.

Lesion studies show that a wide range of integrative sensorimotor functions can be selectively disturbed in patients with parietal lobe damage. Lesions restricted to the somatosensory representations on the anterior parietal lobe produce somatosensory deficits that resemble deafferentated states, including the secondary effects on motor control. Slightly more posterior lesions often are associated with impairment of more complex synthetic somatosensory functions similar to those observed after dorsal column lesions. Damage of the posterior parietal lobe can selectively interfere with virtually every aspect of somatosensory function. These perceptive and cognitive disturbances may or may not be associated with complex motor disturbances of the apractic type. The frequent association of astereognosia and tactile apraxia illustrate the mutual interdependence of the sensorimotor processes involved in active touch and the proximity of the respective processing modules. Parietal lobe function is critical for the control of force and posture, and for the formation of the body image and its relation to external space (the guidance of movements, including the eyes, to external objects). Imaging studies underscore the prominent role of the parietal cortex as a sensorimotor interface and provide complementary information about the interrelationship between perception and action. Action observation activates premotor cortex, but parietal cortex is also recruited whenever an action involves objects, thus emphasizing the significance of parietal cortex for object-directed motor behavior. In contrast to the ventral-dorsal route processing dichotomy in the visual system, both the perceptual-cognitive and motor aspects of somatosensory processing are compromised after parietal damage, demonstrating a different functional architecture of the two sensory systems. The preservation of the comprehension of the meaning of gestures or of object use in patients with lesions restricted to the parietal lobe reveals that the semantic aspects of motor behavior are mediated in the temporal lobe.

Animals↗

Synaptic plasticity and learning: selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-D-aspartate receptor antagonist AP5.

This paper reports a series of 5 experiments concerned with a possible role for N-methyl-D-aspartate (NMDA) receptors in certain types of learning. The results show that chronic intraventricular infusion of the NMDA receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (D,L-AP5) caused an impairment of spatial but not of visual discrimination learning in rats. Such selectivity of the learning impairment occurred despite widespread distribution of the drug throughout the CNS. AP5 sometimes caused a disturbance of sensorimotor function during learning, but one experiment addressing whether this disturbance could be responsible for the spatial learning impairment established that it was statistically independent. Another experiment showed that AP5 did not affect the retention of previously acquired spatial information. These behavioral effects were all obtained with a concentration of AP5 that, in a final study, was found to be sufficient to block hippocampal long-term potentiation (LTP) in vivo without affecting normal synaptic transmission. Taken together, these observations (1) implicate NMDA receptors in certain types of learning, and (2) extend recent work showing that saturation of LTP causes an anterograde spatial amnesia (McNaughton et al., 1986). A preliminary report of parts of this work has been published (Morris et al., 1986a).

Animals↗

The lateral hypothalamic area revisited: ingestive behavior.

This article discusses the role of the lateral hypothalamic area (LHA) in feeding and drinking and draws on data obtained from lesion and stimulation studies and neurochemical and electrophysiological manipulations of the area. The LHA is involved in catecholaminergic and serotonergic feeding systems and plays a role in circadian feeding, sex differences in feeding and spontaneous activity. This article discusses the LHA regarding dietary self-selection, responses to high-protein diets, amino acid imbalances, liquid and cafeteria diets, placentophagia, "stress eating," finickiness, diet texture, consistency and taste, aversion learning, olfaction and the effects of post-operative period manipulations by hormonal and other means. Glucose-sensitive neurons have been identified in the LHA and their manipulation by insulin and 2-deoxy-D-glucose is discussed. The effects on feeding of numerous transmitters, hormones and appetite depressants are described, as is the role of the LHA in salivation, lacrimation, gastric motility and secretion, and sensorimotor deficits. The LHA is also illuminated as regards temperature and feeding, circumventricular organs and thirst and electrolyte dynamics. A discussion of its role in the ischymetric hypothesis as an integrative Gestalt concept concludes the review.

Animals↗