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Brain response to visceral aversive conditioning: a functional magnetic resonance imaging study.

BACKGROUND & AIMS: Brain-imaging studies to date have confounded visceral pain perception with anticipation. We used functional magnetic resonance imaging of the human brain to study the neuroanatomic network involved in aversive conditioning of visceral pain and, thus, anticipation. METHODS: Eight healthy volunteers (5 male) participated in the study. We used a classic conditioning paradigm in which 3 neutral stimuli (differently colored circles) that acted as conditioned stimuli were paired with painful esophageal distention, air puff to the wrist, or nothing, which acted as unconditioned stimuli. Neural activity was measured during learning, anticipation (pairing only 50% of conditioned stimuli with their unconditioned stimuli), and extinction (unpaired conditioned stimuli) phases. For magnetic resonance imaging, axial slices depicting blood oxygen level-dependent contrast were acquired with a 1.5-T system. RESULTS: Neural responses during the learning phase included areas commonly associated with visceral pain (anterior cingulate cortex, insula, and primary and secondary somatosensory cortices) and innocuous somatosensory perception (primary and secondary somatosensory cortices and insula). During the anticipation and extinction phases of aversive stimulation, brain activity resembled that seen during actual painful esophageal stimulation. In contrast, anticipation and extinction of the innocuous somatic stimulus failed to show that effect. CONCLUSIONS: We have shown that actual and anticipated visceral pain elicit similar cortical responses. These results have implications for the design and interpretation of brain-imaging studies of visceral pain. They not only contribute to our understanding of the processing of visceral pain, but also have clinical implications for the management of chronic pain states.

Adult↗

Learning letter identification in peripheral vision.

Performance for a variety of visual tasks improves with practice. The purpose of this study was to determine the nature of the processes underlying perceptual learning of identifying letters in peripheral vision. To do so, we tracked changes in contrast thresholds for identifying single letters presented at 10 degrees in the inferior visual field, over a period of six consecutive days. The letters (26 lowercase Times-Roman letters, subtending 1.7 degrees) were embedded within static two-dimensional Gaussian luminance noise, with rms contrast ranging from 0% (no noise) to 20%. We also measured the observers' response consistency using a double-pass method on days 1, 3 and 6, by testing two additional blocks on each of these days at luminance noise of 3% and 20%. These additional blocks were the exact replicates of the corresponding block at the same noise contrast that was tested on the same day. We analyzed our results using both the linear amplifier model (LAM) and the perceptual template model (PTM). Our results showed that following six days of training, the overall reduction (improvement across all noise levels) in contrast threshold for our seven observers averaged 21.6% (range: 17.2-31%). Despite fundamental differences between LAM and PTM, both models show that learning leads to an improvement of the perceptual template (filter) such that the template is more capable of extracting the crucial information from the signal. Results from both the PTM analysis and the double-pass experiment imply that the stimulus-dependent component of the internal noise does not change with learning.

Adult↗

Mood, memory, and social judgments in children.

The influence of positive and negative moods on children's recall and recognition memory and impression-formation judgments was investigated in a two-list experimental design. A total of 161 schoolchildren, 8 to 10 years old, were presented with audiovisual information containing positive and negative details about 2 target children. Each presentation was preceded by happy or sad mood manipulations. One day later, the children were again placed in a happy or sad mood, and their recall and recognition memory and impression-formation judgments were assessed. Results showed that memory was better when (a) the children felt happy during encoding, retrieval, or both; (b) the material was incongruent with learning mood; (c) the 2 target characters were encountered in contrasting rather than in matching mood states; and (d) recall mood matched encoding mood. A happy mood increased the extremity of both positive and negative impression-formation judgments. Results are contrasted with experimental data obtained with normal or depressed adults, and implications are considered for contemporary theories of mood effects on cognition and for social-developmental research.

Child↗

Hippocampal lesions facilitate instrumental learning with delayed reinforcement but induce impulsive choice in rats.

BACKGROUND: Animals must frequently act to influence the world even when the reinforcing outcomes of their actions are delayed. Learning with action-outcome delays is a complex problem, and little is known of the neural mechanisms that bridge such delays. When outcomes are delayed, they may be attributed to (or associated with) the action that caused them, or mistakenly attributed to other stimuli, such as the environmental context. Consequently, animals that are poor at forming context-outcome associations might learn action-outcome associations better with delayed reinforcement than normal animals. The hippocampus contributes to the representation of environmental context, being required for aspects of contextual conditioning. We therefore hypothesized that animals with hippocampal lesions would be better than normal animals at learning to act on the basis of delayed reinforcement. We tested the ability of hippocampal-lesioned rats to learn a free-operant instrumental response using delayed reinforcement, and what is potentially a related ability -- the ability to exhibit self-controlled choice, or to sacrifice an immediate, small reward in order to obtain a delayed but larger reward. RESULTS: Rats with sham or excitotoxic hippocampal lesions acquired an instrumental response with different delays (0, 10, or 20 s) between the response and reinforcer delivery. These delays retarded learning in normal rats. Hippocampal-lesioned rats responded slightly less than sham-operated controls in the absence of delays, but they became better at learning (relative to shams) as the delays increased; delays impaired learning less in hippocampal-lesioned rats than in shams. In contrast, lesioned rats exhibited impulsive choice, preferring an immediate, small reward to a delayed, larger reward, even though they preferred the large reward when it was not delayed. CONCLUSION: These results support the view that the hippocampus hinders action-outcome learning with delayed outcomes, perhaps because it promotes the formation of context-outcome associations instead. However, although lesioned rats were better at learning with delayed reinforcement, they were worse at choosing it, suggesting that self-controlled choice and learning with delayed reinforcement tax different psychological processes.

Animals↗

Stochastic correlative firing for figure-ground segregation.

Segregation of sensory inputs into separate objects is a central aspect of perception and arises in all sensory modalities. The figure-ground segregation problem requires identifying an object of interest in a complex scene, in many cases given binaural auditory or binocular visual observations. The computations required for visual and auditory figure-ground segregation share many common features and can be cast within a unified framework. Sensory perception can be viewed as a problem of optimizing information transmission. Here we suggest a stochastic correlative firing mechanism and an associative learning rule for figure-ground segregation in several classic sensory perception tasks, including the cocktail party problem in binaural hearing, binocular fusion of stereo images, and Gestalt grouping in motion perception.

Acoustic Stimulation↗

Rule-based learning impairment in rats with lesions to the dorsal striatum.

The present study examined the effects of lesions to the dorsal striatum (DS) in Sprague-Dawley rats, when tested on the acquisition and successive shifts in the position of a goal arm in an eight-arm radial maze. In the procedure we used, rats had to retrieve the location of one baited arm among the eight arms of the maze after it had just been presented as a sample during a forced trial. After attainment of a fixed learning criterion, rats were submitted to five successive shifts in the goal location. Results showed that DS rats were able to learn the position of the goal arm during the acquisition phase as efficiently as sham-operated rats. In contrast, when the position of the goal arm was shifted, although DS rats were able to learn its new position, they made significantly more errors and required more sessions to reach criterion than sham-operated rats. These results suggested that both groups did not solve the task using the same behavioral strategy. The analysis of responses made suggested that sham-operated rats solved the task using the pairing rule between the forced and the free run (matching-to-sample rule), while DS rats solved the task using only visuo-spatial processing. These data therefore suggest that the dorsal striatum plays an important role in rule-learning ability.

Animals↗

Metallothionein expression and neurocognitive function in mice.

Transition metals have been associated with impaired neurological development, and neurobehavioral activity. Metallothioneins are central components in the metabolism and detoxification of a variety of metals, however, little is known concerning their role in cognitive function. To determine the role of metallothionein in learning and memory, mice with deletions of two metallothionein genes (MT-1 and MT-2) were trained on a win-shift task in an 8-arm radial maze. The parental strain of mice learned the maze at a normal rate over an 18-session acquisition period. In contrast, the MT-1/MT-2-null mice, which had a similar choice accuracy level at the beginning of training, showed a poorer rate of learning during the training period. In addition, the MT-1/MT-2-null mice showed significantly less choice accuracy than the parental strain. The MT-1/MT-2-null mice also showed a significant hypoactivity during the early and middle parts of acquisition training, but they were not different from the wildtype controls during the final phase of training. Nicotine treatment, which can improve working memory, eliminated the impairment associated with the deletion of the MT-1 and MT-2 genes in a dose-related fashion after acquisition training in the aging adult mice. These results suggest that metallothioneins, through there roles in metal physiology or cellular protection, are involved in spatial learning and memory function.

Animals↗

Level and mechanisms of perceptual learning: learning first-order luminance and second-order texture objects.

Perceptual learning is an improvement in perceptual task performance reflecting plasticity in the perceptual system. Practice effects were studied in two object orientation tasks: a first order, luminance object task and a second-order, texture object task. Perceptual learning was small or absent in the first-order task, but consistently occurred for the second-order (texture) task, where it was limited to improvements in low external noise conditions, or stimulus enhancement [Dosher, B., & Lu, Z. -L. (1998). Perceptual learning reflects external noise filtering and internal noise reduction through channel reweighting. Proceedings of the National Academy of Sciences of the United States of America, 95 (23) 13988-13993; Dosher, B., & Lu, Z. -L. (1999). Mechanisms of perceptual learning. Vision Research, 39 (19) 3197-3221], analogous to attention effects in first- and second-order motion processing [Lu, Z. -L., Liu, C. Q., & Dosher, B. (2000). Attention mechanisms for multi-location first- and second-order motion perception. Vision Research, 40 (2) 173-186]. Perceptual learning affected the later, post-rectification, stages of perceptual analysis, possibly localized at V2 or above. It serves to amplify the stimulus relative to limiting internal noise for intrinsically noisy representations of second-order stimuli.

Attention↗

Group I metabotropic glutamate receptors interfere in different ways with pentylenetetrazole seizures, kindling, and kindling-related learning deficits.

LY 367385 (mGluR1) and MPEP (mGluR5), which are group I metabotropic glutamate receptor (mGluR) antagonists, were used to investigate their effects on pentylenetetrazole (PTZ) seizures, kindling, and kindling-related learning deficits. Both substances showed anticonvulsant efficacy against seizures induced by lower doses of PTZ (40 mg/kg), but they were ineffective in counteracting seizures evoked by higher PTZ doses. When these substances were given in the course of kindling induction, LY significantly depressed the progression of kindled seizure severity. In contrast, MPEP was ineffective in this experiment. Treatment with either LY or MPEP did not modify the reaction to challenge dose of PTZ. Kindling results in a worsening of shuttle-box learning. LY improved shuttle-box learning when administered in the course of kindling development or when given prior to the learning experiment. This suggests protective and restorative effectiveness. In contrast, MPEP was only effective on the learning performance of kindled rats when given prior to the shuttle-box experiment, which demonstrates restorative effectiveness. Kindling is associated with an increase in glutamate binding. LY counteracted this increase whereas MPEP was ineffective. It was concluded that mGluR1 and mGluR5 play a specific role in the convulsive component of kindling. The beneficial action of the antagonists on kindling-induced impairments in shuttle-box learning may be associated with their effect on glutamatergic synaptic activity.

Animals↗

Nimodipine on shuttle-box avoidance learning in mice: no impairment but slight improvement.

The dihydropyridine calcium channel antagonist nimodipine was tested in mice of CD-1, C57BL/6, and DBA/2 strains subjected to shuttle-box avoidance training. In contrast with some findings of other authors showing impairment of shuttle-box avoidance learning by low doses of the drug in rats, nimodipine given IP before each training session at doses of 0.25, 0.5, 1, 2.5, or 5 mg/kg never impaired avoidance acquisition in mice. On the contrary, one dose of nimodipine (1 mg/kg) significantly improved avoidance acquisition in mice of the DBA/2 strain. The drug failed to impair avoidance performance in DBA/2 mice even if given acutely in the middle (third session) or at the end (fifth session) of the training period. The results contradict studies showing cognitive impairment induced by calcium channel blockers, and may provide some limited evidence in support of improved cognitive function in normal animals, although this effect is much less evident than in aged or brain-damaged subjects.

Animals↗

Determining sociability, social space, and social presence in (a)synchronous collaborative groups.

The effectiveness of group learning in asynchronous distributed learning groups depends on the social interaction that takes place. This social interaction affects both cognitive and socioemotional processes that take place during learning, group forming, establishment of group structures, and group dynamics. Though now known to be important, this aspect is often ignored, denied or forgotten by educators and researchers who tend to concentrate on cognitive processes and on-task contexts. This "one-sided" educational focus largely determines the set of requirements in the design of computer-supported collaborative learning (CSCL) environments resulting in functional CSCL environments. In contrast, our research is aimed at the design and implementation of sociable CSCL environments which may increase the likelihood that a sound social space will emerge. We use a theoretical framework that is based upon an ecological approach to social interaction, centering on the concept of social affordances, the concept of the sociability of CSCL environments, and social presence theory. The hypothesis is that the higher the sociability, the more likely that social interaction will take place or will increase, and the more likely that this will result in an emerging sound social space. In the present research, the variables of interest are sociability, social space, and social presence. This study deals with the construction and validation of three instruments to determine sociability, social space, and social presence in (a)synchronous collaborating groups. The findings suggest that the instruments have potential to be useful as measures for the respective variables. However, it must be realized that these measures are "first steps."

Adult↗

Consistent contrast and correlation in free sorting.

Two experiments investigated free sorting, a type of unsupervised learning, with multiattribute drawings of alien animals. In previous research on concept formation, with simpler stimulus structure than ours, participants were insensitive to correlational structure in the stimuli, producing primarily "ID sorts," based on the values ofjust 1 dimension or attribute. Our experiments showed that participants used many strategies in categorizing but preferred to generate groupings that reflected the correlations in input when this did not violate consistent contrast. The second experiment used hierarchically structured stimuli to show that participants' sort strategies favor consistency within a set of contrasting categories, distinct from any preference for 1D sorting. Finally, both experiments show that correlational sorts are much more likely when the correlation-based sort contrasts consistently. Our data show complexity at work in free sort tasks: People are sensitive to multiple and sometimes conflicting biases for consistency and correlational structure in the category systems they create.

Humans↗

Attention to novel objects during verb learning.

Three experiments provided evidence that 3.5- to 4-year-old English-speaking children (N = 72) attend to the appearances of novel objects, not only when they hear a novel noun, but also when they hear a novel verb. Children learning nouns in the context of novel, moving objects attended exclusively to the appearances of objects, even though nouns were also related to the motions of those objects. Children learning verbs attended equally to the appearances of objects and their motions. The latter result contrasted with the results from adults (N = 20), who focused more strongly on motions than on the appearances of objects when learning verbs. When familiar objects were instead employed, child verb learners attended more to motions than to the appearances of objects. Children may attend to novel objects during verb learning because knowledge of an object may be prerequisite to understanding what a verb means in the context of that object.

Adult↗

Severe cognitive and motor coordination deficits in tenascin-R-deficient mice.

The extracellular matrix molecule tenascin-R (TN-R), predominantly expressed in the central nervous system, has been implied in a variety of functions, e.g. during myelination, cerebellar neurite fasciculation and hippocampal long-term potentiation. In this study, we investigated in detail the impact of TN-R deficiency on the living animal by analyzing the behavior of TN-R-deficient mice. The general state, gross sensory functions, reflexes and motoric capabilities appeared normal. In contrast, motor coordination on the rota-rod was compromised in these mice, indicating a deficit in cerebellar functions. In the open field and the hole board, the mutants interact differently with their environment, probably due to differences in their exploratory behavior. TN-R-deficient mice were able to learn a reference memory task in the Morris water maze. In contrast to wild-type mice, the mutants displayed an alternative strategy; swimming around the pool using a stereotypical circling pattern, crossing all possible platform positions after relocation of the escape platform (reversal). These results, confirmed by relocating the platform in the center of the pool, suggest that TN-R-deficient mice may be impaired in constructing a goal-independent representation of space. In addition, a two-way active avoidance test (shuttle box) revealed a severe deficit in associative learning in TN-R-deficient mice. Our results support important functions of TN-R in vivo in the central nervous system, in particular in the cerebellum and the hippocampus.

Animals↗

The treatment of anomia using errorless learning.

In the contemporary literature, errorless learning is thought to have benefits over more traditional trial-and-error methods. The most prominent investigations of errorless learning are those designed for rehabilitation of severe memory impairments, including numerous demonstrations of effective amelioration of word-finding difficulties (Baddeley & Wilson, 1994; Clare, Wilson, Breen, & Hodges, 1999; Clare et al., 2000; Evans et al., 2000). Despite this, there are very few reports on the application of purely errorless learning to people with aphasia (Fillingham, Hodgson, Sage, & Lambon Ralph, 2003). The aim of this study was to compare directly the efficacy of errorless and errorful learning in a case series of 11 aphasic people with pronounced word-finding difficulties. Previous studies of errorless learning and, more recently, studies of rehabilitation have suggested that cognition is an important factor for determining outcome (Helm-Estabrooks, 2002; Robertson & Murre, 1999). Therefore, a thorough language and neuropsychological assessment battery was completed with each participant. Naming therapy was carried out to contrast errorless and errorful therapy in a case series analysis. Errorless learning proved to be as effective as the more traditional, errorful approach in the majority of cases in terms of both immediate improvement and at follow up assessment. Without exception, the patients preferred the errorless learning therapy. Strikingly, it was found that language skill did not predict therapy outcome. Participants who responded better overall, had better recognition memory, executive/problem solving skills and monitoring ability. This replicates recent findings that frontal executive skills are crucial for rehabilitation (Robertson & Murre, 1999). Also, participants who did better at errorful treatment were those with the best working and recall memory, and attention. It is probable that these factors are essential cognitive components for providing effective monitoring and feedback systems to a more general learning mechanism.

Adult↗

Acquiring and adapting a novel audiomotor map in human grasping.

For sensorimotor transformations to be executed accurately, there must be mechanisms that can both establish and modify mappings between sensory and motor coordinates. Such mechanisms were investigated in normal subjects using a reach-to-grasp task. First, we replaced the normal input of visual information about object size with auditory information, i.e., we attempted to establish an 'audiomotor map'. The size of the object was log linearly related to the frequency of the sound, and we measured the maximum grip aperture (MGA) during the reaching phase to determine if the subjects had learned the relationship. Second, we changed the frequency-object size relationship to study adaptation in the newly acquired map. Our results demonstrate that learning of an audiomotor map consisted of three distinct phases: during the first stage (approximately 10-15 trials) subjects simply used MGAs large enough to grasp any reasonably sized object and there were no overt signs of learning. During the second stage, there was a period of fast learning where the slope of the relationship between MGA and object size became steeper until the third stage where the slope was constant. In contrast, when sensorimotor adaptation was studied in the established audiomotor map, there was rapid learning from the start of a size perturbation. We conclude that different learning strategies are employed when sensorimotor transformations are established compared to when existing transformations are modified.

Acoustic Stimulation↗

Intact implicit habit learning in Alzheimer's disease.

Habit learning refers to the incremental implicit learning of associations. Patients with Alzheimer's disease (AD) exhibit deficits in explicit memory and in conceptual implicit memory tasks that rely on the cortical areas damaged in AD. The authors tested patients with AD and controls on a probabilistic classification task in which participants implicitly acquire cue-outcome associations. Both groups showed evidence of learning across 50 trials, and performance did not differ significantly between the groups. In contrast, patients with AD exhibited a profound impairment in explicit memory for the testing episode. These results are consistent with the idea that habit learning relies on subcortical structures, including the basal ganglia, and is independent of the medial temporal and cortical areas damaged in AD.

Aged↗

Dissociating ventral and dorsal subicular dopamine D1 receptor involvement in instrumental learning, spontaneous motor behavior, and motivation.

A series of experiments investigating the role of dopamine D1 receptors in the ventral subiculum (vSUB) and dorsal subiculum (dSUB), 2 subregions of the hippocampal formation, found that D1 receptor antagonism (3.0 nmol/0.5 microl SCH-23390 bilaterally) in the vSUB impaired instrumental learning and performance, reduced break point in progressive ratio (PR) tests, and produced an intrasession decline in responding during test sessions, but had no effect on spontaneous motor or food-directed behavior. In contrast, D1 receptor blockade in the dSUB had no effect on instrumental learning, performance, PR break point, or food-directed behavior, but reduced spontaneous motor behavior. These results suggest a dissociation between the vSUB and dSUB with respect to the role of dopamine in various aspects of motivated and motor behavior. Further, D1 activation in the vSUB may be a critical component of motivational arousal associated with learned contextual cues.

Animals↗