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The neural effect of stimulus-response modality compatibility on dual-task performance: an fMRI study.

Recent fMRI studies suggest that the inferior frontal sulcus (IFS) is involved in the coordination of interfering processes in dual-task situations. The present study aims to further specify this assumption by investigating whether the compatibility between stimulus and response modalities modulates dual-task-related activity along the IFS. It has been shown behaviorally that the degree of interference, as measured by dual-task costs, increases in modality-incompatible conditions (e.g. visual-vocal tasks combined with auditory-manual tasks) as compared to modality-compatible conditions (e.g. visual-manual tasks combined with auditory-vocal tasks). Using fMRI, we measured IFS activity when participants performed modality-compatible and modality-incompatible single and dual tasks. Behaviorally, we replicated the finding of higher dual-task costs for modality-incompatible tasks compared to modality-compatible tasks. The fMRI data revealed higher activity along the IFS in modality-incompatible dual tasks compared with modality-compatible dual tasks when inter-individual variability in functional brain organization is taken into account. We argue that in addition to temporal order coordination (Szameitat et al., 2002), the IFS is involved in the coordination of cognitive processes associated with the concurrent mapping of sensory information onto corresponding motor responses in dual-task situations.

Association Learning↗

Effects of an enkephalin analog on complex learning in the rhesus monkey.

Facilitation of the learning of a discrimination reversal task for a reward of food was found in rhesus monkeys after subcutaneous administration of a potent pentafluorinated enkephalin analog. (D-Ala2)-F5-Phe4-enkephalin-NH2. General activity, short-term memory, startle, and analgesia, however, were not significantly affected. In a within-subject design, each of 6 monkeys (3 males and 3 females) received each of 5 doses of the enkephalin analog (0.1, 1, 10, 100, and 1,000 microgram/kg). One daily injection was made for 7 consecutive days, including pre- and posttests on the first and last days with the diluent control. The enkephalin doses, with the exception of the 0.1 microgram/kg level, produced significantly faster learning than the diluent. Some sex differences were suggested by the data, but these effects are difficult to interpret. The results suggest that relatively small amounts of this analog given systematically can exert a reliable effect on a complex behavior such as reversal learning at doses devoid of opiate effects, due perhaps to enhanced cognitive flexibility rather than improvement in short-term memory or association formation.

Analgesia↗

Active reversal of motor memories reveals rules governing memory encoding.

Learning systems must be able to store memories reliably, yet be able to modify them when new learning is required. At the mechanistic level, new learning may either reverse the cellular events mediating the storage of old memories or mask the old memories with additional cellular changes that preserve the old cellular events in a latent form. Behavioral evidence about whether reversal or masking occurs in a particular circuit can constrain the cellular mechanisms used to store memories. Here we examine these constraints for a simple cerebellum-dependent learning task, motor learning in the vestibulo-ocular reflex (VOR). Learning can change the amplitude of the VOR in two opposite directions. Contrary to previous models about memory encoding by the cerebellum, our results indicate that these behavioral changes are implemented by different plasticity mechanisms, which reverse each other with unequal efficacy.

Animals↗

CA1-specific N-methyl-D-aspartate receptor knockout mice are deficient in solving a nonspatial transverse patterning task.

In both humans and animals, the hippocampus is critical to memory across modalities of information (e.g., spatial and nonspatial memory) and plays a critical role in the organization and flexible expression of memories. Recent studies have advanced our understanding of cellular basis of hippocampal function, showing that N-methyl-d-aspartate (NMDA) receptors in area CA1 are required in both the spatial and nonspatial domains of learning. Here we examined whether CA1 NMDA receptors are specifically required for the acquisition and flexible expression of nonspatial memory. Mice lacking CA1 NMDA receptors were impaired in solving a transverse patterning problem that required the simultaneous acquisition of three overlapping odor discriminations, and their impairment was related to an abnormal strategy by which they failed to adequately sample and compare the critical odor stimuli. By contrast, they performed normally, and used normal stimulus sampling strategies, in the concurrent learning of three nonoverlapping concurrent odor discriminations. These results suggest that CA1 NMDA receptors play a crucial role in the encoding and flexible expression of stimulus relations in nonspatial memory.

Animals↗

Convergence of sensory systems in the orbitofrontal cortex in primates and brain design for emotion.

In primates, stimuli to sensory systems influence motivational and emotional behavior via neural relays to the orbitofrontal cortex. This article reviews studies on the effects of stimuli from multiple sensory modalities on the brain of humans and some other higher primates. The primate orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odors is represented. A somatosensory input is revealed by neurons that respond to the viscosity of food in the mouth, to the texture (mouth feel) of fat in the mouth, and to the temperature of liquids placed into the mouth. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas. Information about each of these modalities is represented separately by different neurons, but in addition, other neurons show convergence between different types of sensory input. This convergence occurs by associative learning between the visual or olfactory input and the taste. In that emotions can be defined as states elicited by reinforcers, the neurons that respond to primary reinforcers (such as taste and touch), as well as learn associations to visual and olfactory stimuli that become secondary reinforcers, provide a basis for understanding the functions of the orbitofrontal cortex in emotion. In complementary neuroimaging studies in humans, it is being found that areas of the orbitofrontal cortex are activated by pleasant touch, by painful touch, by taste, by smell, and by more abstract reinforcers such as winning or losing money. Damage to the orbitofrontal cortex in humans can impair the learning and reversal of stimulus-reinforcement associations and thus the correction of behavioral responses when these are no longer appropriate because previous reinforcement contingencies change. It is striking that humans and other catarrhines, being visual specialists like other anthropoids, interface the visual system to other sensory systems (e.g., taste and smell) in the orbitofrontal cortex.

Afferent Pathways↗

Studies of marginal zinc deprivation in rhesus monkeys. VIII. Effects in early adolescence.

Arrested adolescent growth and sexual maturation are striking symptoms of severe dietary zinc deprivation. More general implications of mild or marginal Zn deficiency during adolescence are not known. Five marginally Zn-deprived (ZD) male monkeys (4 mg Zn/kg diet) were compared with five controls pair fed a diet containing 100 mg Zn/kg during early adolescence. Mean plasma Zn levels were 38% lower in ZD group than in controls when evaluations began. During rapid growth plasma Zn decreased in controls but not ZD animals. ZD animals had delayed onset of accelerated weight gain and linear growth; loss of subcutaneous fat typical of early adolescence did not occur. ZD monkeys required two to three times more trials for both learning and reversal a visual discrimination task. Immune function was depressed 20-30% as reflected in early reduced proliferative response of peripheral lymphocytes and later lower immunoglobulin levels. Marginal dietary Zn deprivation affects growth and function in adolescence without producing frank developmental retardation.

Aging↗

Multivariate analysis of putative measures of activity, exploration, emotionality, and spatial behavior in the hooded rat (Rattus norvegicus).

Hooded rats were tested in six situations representing the variables of activity, exploration, emotionality, and spatial preference, detection of change, and learning. The activity, exploration, and emotionality variables and spatial variables were analyzed in separate multivariate analyses, followed by an analysis of the entire set. The first of these resulted in four components: activity, exploration and emotionality, reactivity to handling, and autonomic reactivity (defecation). Four components, defined by the following variables, emerged from the spatial analysis: (a) the tendency to circle, circling direction, and spatial learning; (b) heading error in spatial learning and reversal and open-field directional preference; (c) spatial reversal and direction of turn to escape restraint; and (d) detection of change in spatial arrangement and directional preference in the detection task. The final analysis investigated relations between the activity, exploration, and emotionality variables and the spatial variables, finding only two. The clear dimensionality of these behavioral repertoires emphasizes how important it is to recognize the distinctions among them.

Animals↗

Visual discrimination learning in zebrafish (Danio rerio).

Three experiments demonstrated visual discrimination learning in zebrafish (Danio rerio). In each experiment, zebrafish were given a choice between two visually distinct arms of a T-maze. Choice of one stimulus was always followed by a food reward, but choice of the other stimulus was not rewarded. Different colored sleeves fitted around the arms of the T-maze were used in Experiments 1 (green and purple) and 2 (red and blue). The stimuli used in Experiment 3 were white sleeves lined with horizontal or vertical black stripes. In all three experiments, zebrafish acquired a significant preference for the stimulus that led to a food reward. Experiments 1 and 2 also showed that zebrafish could learn a reversal of the discrimination. Finally, the effect of discontinuing food rewards was examined after reversal training in Experiment 2 and after initial discrimination training in Experiments 1 and 3. Non-reinforcement led to a decrease in correct responding in Experiments 2 and 3 independent of stimulus identity, but to an asymmetrical pattern of responding in Experiment 1. The median latency to make a choice response decreased over the course of acquisition in all three experiments; during extinction, median response times did not change at all in Experiment 1 and increased only very slightly in Experiment 2, but showed a substantial increase in Experiment 3. The implications of these results for the zebrafish as a model system for genetic studies of learning and memory are discussed.

Animals↗

Differential effects of unilateral and bilateral caudate lesions on side preference and passive avoidance behavior in rats.

The effects of unilateral and bilateral caudate lesions on side preferences, passive avoidance learning and locomotor activity were determined in rats. Unilateral lesions ipsilateral to preoperative side preferences increased side preference and facilitated passive avoidance learning. Contralateral lesions reversed side preferences and impaired passive avoidance learning. Bilateral lesions increased side preference in some rats and decreased or reversed side preference in other rats; the increase or decrease in side preference was related to a lesser or greater impairment in learning, respectively. All caudate lesions increased locomotor activity. It is suggested that an intrinsic nigro-striatal asymmetry has a modulatory role in learning and that the effects of bilateral caudate lesions are, in part, attributable to very slight asymmetries in lesion locations. The effect of a unilateral caudate lesion will depend upon whether the lesion is placed in the more or less active striatum.

Animals↗

Characteristics of memory dysfunction in olfactory bulbectomized rats and the effects of cholinergic drugs.

The memory impairment of olfactory bulbs (OB)-lesioned rats was characterized using 4 different tasks of learning/memory, and the effects of certain cholinergic drugs on such memory impairment were examined. In reference memory and working memory tasks using a 3-panel runway apparatus, OB-lesioned rats showed a marked increase in errors. In the 3-lever operant task using delayed matching to a sample (DMTS) procedure, OB lesions significantly decreased the correct response in choice (test) trials without affecting the in sample (training) trials. An interesting finding is that impairment in the DMTS performance did not appear immediately after the OB lesion, but tended to appear after a delay. Based on this finding, it is unlikely that memory impairment in the OB-lesioned rats is due to the olfactory deficit itself. However, OB lesions significantly reduced the choice accuracy and delayed the choice reaction time during the 3-choice serial time task for assessing attentional function, using a 3-lever operant apparatus. These findings suggest that marked impairment of learning and memory in OB-lesioned rats may be caused by the attention deficit. Furthermore, the memory impairment in OB-lesioned rats was reduced by cholinesterase inhibitors, physostigmine and NIK-247. These finding suggest that dysfunction of the cholinergic system is involved, at least in part, in the memory impairment of OB-lesioned rats.

Animals↗

Beyond spatial memory: the anterior thalamus and memory for the temporal order of a sequence of odor cues.

Influential recent proposals state that the anterior thalamic (AT) nuclei constitute key components of an "extended hippocampal system." This idea is, however, based on lesion studies that used spatial memory tasks and there has been no evidence that AT lesions cause deficits in any hippocampal-dependent nonspatial tasks. The present study investigated the role of the AT nuclei in nonspatial memory for a sequence of events based on the temporal order of a list of odors, because this task has recently been shown to depend on the integrity of the hippocampal formation. After preoperative training, rats with excitotoxic lesions of the AT nuclei showed a severe and selective postoperative impairment when required to remember the order of pseudorandom sequences of six odors. The rats with AT lesions were able instead to learn two new tasks that required recognition memory and the identification of the prior occurrence of events independent of their order. These results strongly matched those described after hippocampal lesions and provide the first unequivocal evidence of a detrimental effect of an AT lesion on a nonspatial hippocampal-dependent memory task.

Animals↗

Stimulation of 5-HT1A receptors in the dorsal raphe reverses the impairment of spatial learning caused by intrahippocampal scopolamine in rats.

This study investigated the effect of stimulating 5-HT1A receptors in the dorsal raphe on the impairment of learning caused by 4 microg/microL scopolamine injected in the CA1 region of the dorsal hippocampus in rats performing a two-platform spatial discrimination task. At 1 (but not 0.2) microg/0.5 microL administered in the dorsal raphe on each acquisition training day 5 min before bilateral intrahippocampal injection of 4 microg/microL scopolamine, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, had no effect on choice accuracy and latency or errors of omission but completely antagonized the impairment of choice accuracy by intrahippocampal scopolamine. Administered into the dorsal raphe at 0.2 and 1 microg/0.5 microL, WAY 100635, a 5-HT1A receptor antagonist, had no effect on rats' performance or on the impairment caused by intrahippocampal scopolamine but dose-dependently antagonized the effect of 1 microg/0.5 microL 8-OH-DPAT on the scopolamine-induced deficit. The results show that stimulation of presynaptic 5-HT1A receptors in the dorsal raphe reverses the deficit caused by intrahippocampal scopolamine, probably by facilitating the transfer of facilitatory information from the entorhinal cortex to the hippocampus. Together with a previous study showing that blockade of postsynaptic hippocampal 5-HT1A receptors antagonized the effect of intrahippocampal scopolamine in the two-platform spatial discrimination task (Carli et al., 1995b), the results suggest that drugs with presynaptic stimulatory and postsynaptic blocking actions on 5-HT1A receptors, such as partial agonists at these receptors, may be useful in the symptomatic treatment of human memory disturbances associated with loss of cholinergic innervation to the hippocampus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Behavioral effects of 5-HT receptor ligands in the aversive brain stimulation, elevated plus-maze and learned helplessness tests.

In order to illustrate the use of animal models in the study of the anxiolytic and antidepressant properties of drugs acting on 5-HT receptors, a series of experiments is described. With electrical stimulation of the midbrain central gray (CG), an aversive area of the brain, the 5-HT-1 receptor antagonist propranolol raised the aversive threshold in a dose-dependent way, following its microinjection into the CG. This antiaversive effect of propranolol, which is similar to that of benzodiazepine anxiolytics, was prevented by microinjection into the same brain site of the 5-HT-2 receptor blocker ritanserin. Ritanserin itself and the 5-HT-1A receptor ligand ipsapirone caused either little or no effect. In another animal model of anxiety, the elevated plus-maze, intra-CG propranolol also caused an anxiolytic-like effect, antagonized by ritanserin, indicating a 5-HT mediation. However, systemically injected isamoltane, a congener of propranolol, was ineffective in the elevated plus-maze, whereas ipsapirone caused an anxiolytic effect. Ritanserin was again inactive. Finally, both ipsapirone as well as another 5-HT-1A receptor ligand BAY R 1531, given IP, reversed the learning deficit resulting from exposure to uncontrollable foot-shocks, an effect characteristic of antidepressant drugs.

Animals↗

Conditioned discrimination of airborne odorants by garter snakes (Thamnophis radix and T. sirtalis sirtalis).

For snakes, the nasal chemical senses are critical in intraspecific communication and prey recognition. Although it is known that garter snakes can respond differentially to airborne odorants, no previous study has demonstrated that snakes can learn a task with airborne odors as discriminative stimuli. In Experiment 1, 7 plains garter snakes (Thamnophis radix) were trained in a two-choice apparatus to move into a compartment containing lemon-scented chips for a food reward. All 7 snakes improved performance when the first 10 and last 10 trials of the 100 trials of conditioning were compared. Four of the snakes were subsequently trained to move away from the scented compartment into the unscented compartment. The 4 snakes rapidly learned this reversal. In Experiment 2, 7 common garter snakes (T. sirtalis sirtalis) were trained to traverse a two-choice maze with the presence or absence of amyl acetate odor as the conditioned stimulus. The snakes were pretested for odor versus nonodor preference and were trained to go to the initially nonpreferred stimulus. Of the 7 snakes, 5 achieved a predetermined criterion (two training sessions with cumulative correct responding above the .05 confidence level) within 85 trials.

Animals↗

Department of Psychology, State University of New York at Albany.

The effects of prenatal alcohol on learning and retention of passive avoidance and discriminated shock escape were examined in offspring of rats who consumed isocaloric liquid diets containing either 35, 17.5 or 0% ethanol derived calories (EDC) or lab chow during pregnancy. Alcohol exposed progeny required more trials to reach criterion during passive avoidance acquisition and had shorter second trail latencies into the shock compartment than did controls. Both these measures were found to be direct functions of prenatal alcohol exposure. No differences between groups were evident during retention testing (1, 3, or 7 days later). During the 25 trial acquisition phase of T-maze escape, alcohol exposed progeny made more errors despite equivalent group performance by the end of training. During retention testing 24 hours later, these offspring again evidenced more errors regardless of whether or not the original contingencies were reversed. Both learning and retention deficits in the T-maze were directly related to the percent EDC consumed by the mother during pregnancy.

Analysis of Variance↗

Enduring effects of early lead exposure: evidence for a specific deficit in associative ability.

Long-Evans dams were exposed to Pb acetate in the drinking water during both gestation and lactation, or lactation only. This report presents the results of an automated, olfactory, serial reversal task administered to the adult offspring. Although overall learning rate was not significantly affected by Pb exposure, analyses of specific phases of the learning process revealed that all three exposed groups required significantly more trials than controls to reach criterion from the point at which perseverative responding to the previously correct cue ended. These in-depth analyses revealed that the reversal learning impairment of the Pb-exposed animals was not due to a deficit in inhibiting responses to the previously correct cue, the mechanism commonly assumed to underlie impaired reversal learning. Instead, the analyses revealed that two other independent Pb effects were responsible for the prolonged postperseverative learning period: a response bias and an impaired ability to associate cues and/or actions with affective consequences. The contribution of these two factors varied as a function of the timing and intensity of the Pb exposure. It is hypothesized that the Pb-induced associative deficit may reflect lasting damage to the amygdala and/or nucleus accumbens, which comprise a system thought to modulate the process by which environmental cues acquire affective significance.

Animals↗

Studies of marginal zinc deprivation in rhesus monkeys: infant behavior.

Rhesus monkey infants were marginally deprived of zinc (4 ppm diet) from conception and were compared to controls (100 ppm diet) during the first year of life in development of reflexes and motor patterns, mother-infant interaction, delayed response performance, discrimination learning and reversal, and open field behavior. Deficits in amount and variety of behavior were recorded in deprived infants; spontaneous locomotor activity was 50% below control levels in males at 1 mo of age; spontaneous activity was 7-10% lower in both males and females at 3 mo of age; response latencies were 50% lower than controls at 7-9 mo; failure to reach discrimination reversal criterion was seen in 71% of deprived infants as compared to 10% of controls at 10 mo of age; and abnormally low levels of climbing and exploration were seen in two of six deprived infants at 12 mo of age. No abnormalities in the rate of behavioral development or in emotional adaptability were observed. These and other results suggest that syndromes of lethargy, apathy, and hypoactivity are characteristic of behavioral effects of marginal zinc deprivation in primates.

Animals↗