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Feed-forward associative learning for volitional movement control.

One of the most difficult problems in motor learning is determining the source of a learning signal, sometimes called an error signal. This problem is hidden in the adaptations of simple reflexive movements by attributing its source to sensory organs. The feed-forward associative motor learning theory proposed here attributes the source to the movement system itself. When a subject performs a corrective movement after his primary movement, the proposed neural learning device learns to associate the primary motor command with the corrective motor command by using a place-coding system. In the subsequent trials, the primary movement will involve a correction due to the participation of this mechanism, thus resulting in better performance. The theory assumes three conditions, namely, that a motor center and the learning device share the same place-encoded motor information; the motor center issues a command and a learning signal simultaneously from the same unit; and a learning signal issued with a corrective command has a heterosynaptic interaction with the previous primary command. The cerebellum is a reasonable candidate for the device satisfying these conditions. The reaction time of a corrective movement, usually 100-300 ms, almost satisfies the coincidence condition for long-term depression of the granule-to-Purkinje synapses. As an application, this theory is demonstrated to account for behavioral results regarding saccadic adaptation.

Association Learning↗

Associative learning shapes the neural code for stimulus magnitude in primary auditory cortex.

Since the dawn of experimental psychology, researchers have sought an understanding of the fundamental relationship between the amplitude of sensory stimuli and the magnitudes of their perceptual representations. Contemporary theories support the view that magnitude is encoded by a linear increase in firing rate established in the primary afferent pathways. In the present study, we have investigated sound intensity coding in the rat primary auditory cortex (AI) and describe its plasticity by following paired stimulus reinforcement and instrumental conditioning paradigms. In trained animals, population-response strengths in AI became more strongly nonlinear with increasing stimulus intensity. Individual AI responses became selective to more restricted ranges of sound intensities and, as a population, represented a broader range of preferred sound levels. These experiments demonstrate that the representation of stimulus magnitude can be powerfully reshaped by associative learning processes and suggest that the code for sound intensity within AI can be derived from intensity-tuned neurons that change, rather than simply increase, their firing rates in proportion to increases in sound intensity.

Acoustic Stimulation↗

MRI-assessed volume of cerebellum correlates with associative learning.

Richard F. Thompson's cerebellar model of classical eyeblink conditioning highlights Purkinje cells in cerebellar cortex and principal cells in the deep cerebellar nucleus as the integrating cells for acquisition of conditioned responses (CRs). CR acquisition is significantly slower in rabbits with lesions to cerebellar cortex and in Purkinje cell-deficient mice that lose all cerebellar cortical Purkinje cells. Purkinje cells are the largest neurons in the cerebellum and contribute significantly to cerebellar volume. Magnetic resonance imaging (MRI) was used to assess cerebellar volume in humans. Cerebellar volume was related to eyeblink conditioning (400-ms delay procedure) in 8 adults (21-35 years) and compared to 8 older adults (77-95 years) tested previously (Woodruff-Pak, Goldenberg, Downey-Lamb, Boyko, & Lemieux, 2000). In the young adult sample, there was a high correlation between percentage of CRs in a session and cerebellar volume (corrected for total intracranial volume [TIV], r =.58, p =.066). There were statistically significant age differences in cerebellar volume, t(14) = 8.96, p <.001, and percentage of CRs, t(14) = 3.85, p <.002, but no age difference in TIV. Combining the young and older adult sample, the correlation between percentage of CRs and cerebellar volume (corrected for TIV) was.832 (p <.001). Cerebellar volume showed age-related deficits likely due to Purkinje cell loss. Individual differences in classical eyeblink conditioning are associated with differences in cerebellar volume, supporting Thompson's model of a cerebellar cortical role in facilitating this form of associative learning.

Adult↗

Associative learning in degenerative neostriatal disorders: contrasts in explicit and implicit remembering between Parkinson's and Huntington's diseases.

The performances of 12 patients with Parkinson's disease (PD), 16 with Huntington's disease (HD), and young and old healthy controls were assessed on a number of tests of verbal and nonverbal declarative memory, on a test of nonmotor conditional associative learning (words and colors), and on a number of reaction time (RT) tasks. The RT tasks consisted of cued simple and choice reactions. The relationship between the precue and the imperative stimulus in the S1-S2 paradigm was nonarbitrary in the first series and arbitrary in the second series. The series with arbitrary S1-S2 associations was repeated across two successive blocks of trials. The rationale of the study was to investigate the function of the basal ganglia "complex loop," and it was postulated that HD patients would show greater deficits because of greater involvement of the caudate nucleus. The patients with HD had the slowest RTs. Across the two blocks with arbitrary S1-S2 associations, the patients with HD but not PD nevertheless showed evidence of learning in their precued RTs. In contrast, the patients with PD were better able to remember the associations in free recall than were the HD patients. It is concluded that patients with PD have relatively greater deficits in procedural learning, whereas those with HD have relatively more impairments in declarative memory, and the greater level of cognitive impairment in HD overall is interpreted as being due to more serious damage to the caudate loop.

Adult↗

Linear relation between the magnitude of long-term potentiation in the dentate gyrus and associative learning in the rat. A demonstration using commissural inhibition and local infusion of an N-methyl-D-aspartate receptor antagonist.

Field potentials were recorded in the dentate gyrus of freely-moving rats in a classical conditioning paradigm in which high-frequency stimulation of the perforant path served as a conditioned stimulus. Paired or unpaired perforant path stimulus-footshock presentations were given to animals engaged in a previously acquired food-motivated lever-pressing task. Conditioned suppression of lever-pressing was the behavioural measure of conditioning. Perforant path stimulus trains at an intensity above spike threshold induced long-term potentiation of synaptic transmission in the dentate gyrus. In this condition, animals learned the perforant path stimulus-shock association. Three strategies were employed to block the induction or reduce the magnitude of long-term potentiation induced by the conditioned stimulus: (1) reduction of the intensity of the stimulus below the spike threshold resulted in no long-term potentiation and a failure by the animals to learn the perforant path stimulus-shock association; (2) inhibitory modulation of long-term potentiation by high-frequency activation of commissural input to the dentate gyrus resulted in learning deficits; (3) chronic infusion of DL-2-amino-5-phosphonovalerate, a selective antagonist of the N-methyl-D-aspartate subtype of glutamate receptor, blocked the induction of long-term potentiation and prevented associative learning. A highly significant linear relation emerged from a correlational analysis between the magnitude of the change in synaptic efficacy at the activated synapses and the amount the animals learned about the perforant path stimulus-shock association. The results presented in this paper are consistent with the hypothesis that associative learning depends on the development of lasting changes in synaptic function. We propose that the activation of N-methyl-D-aspartate receptors in the dentate gyrus is involved in this process and that the more change in synaptic efficacy is produced in the activated network, the more the animals learn.

2-Amino-5-phosphonovalerate↗

Three Drosophila mutations that block associative learning also affect habituation and sensitization.

Drosophila melanogaster has been cultured with shock to avoid various odors. Mutants that failed to learn this task have been isolated. Here we report tests on these mutants for more elementary types of behavioral plasticity--habituation and sensitization of a reflex. Fruit flies have taste receptors on their feet. When a starved, water-satiated fly has sucrose applied to one foot, it usually responds by extending its proboscis. In normal flies this feeding reflex shows habituation: application of sugar to one foot depresses responsiveness through the contralateral leg for at least 10 min. The reflex also shows brief sensitization application of concentrated sucrose solution to the proboscis increases subsequent responsiveness to tarsal stimulation for 2-5 min. In three associative learning mutants , the proboscis-extension reflex is present with a normal threshold but behavioral modulation of the response is altered. The dunce, turnip, and rutabaga mutants all habituate less than normal flies. In addition, sensitization wanes unusually rapidly in dunce and rutabaga flies, lasting less than a minute in the case of dunce.

Animals↗

Corticotropin-releasing factor receptors couple to multiple G-proteins to activate diverse intracellular signaling pathways in mouse hippocampus: role in neuronal excitability and associative learning.

Corticotropin-releasing factor (CRF) exerts a key neuroregulatory control on stress responses in various regions of the mammalian brain, including the hippocampus. Using hippocampal slices, extracts, and whole animals, we investigated the effects of human/rat CRF (h/rCRF) on hippocampal neuronal excitability and hippocampus-dependent learning in two mouse inbred strains, BALB/c and C57BL/6N. Intracellular recordings from slices revealed that application of h/rCRF increased the neuronal activity in both mouse inbred strains. Inhibition of protein kinase C (PKC) by bisindolylmaleimide I (BIS-I) prevented the h/rCRF effect only in hippocampal slices from BALB/c mice but not in slices from C57BL/6N mice. Inhibition of cAMP-dependent protein kinase (PKA) by H-89 abolished the h/rCRF effect in slices from C57BL/6N mice, with no effect in slices from BALB/c mice. Accordingly, h/rCRF elevated PKA activity in hippocampal slices from C57BL/6N mice but increased only PKC activity in the hippocampus of BALB/c mice. These differences in h/rCRF signal transduction were also observed in hippocampal membrane suspensions from both mouse strains. In BALB/c mice, hippocampal CRF receptors coupled to G(q/11) during stimulation by h/rCRF, whereas they coupled to G(s), G(q/11), and G(i) in C57BL/6N mice. As expected on the basis of the slice experiments, h/rCRF improved context-dependent fear conditioning of BALB/c mice in behavioral experiments, and BIS-I prevented this effect. However, although h/rCRF increased neuronal spiking in slices from C57BL/6N mice, it did not enhance conditioned fear. These results indicate that the CRF system activates different intracellular signaling pathways in mouse hippocampus and may have distinct effects on associative learning depending on the mouse strain investigated.

Animals↗

Muscarinic cholinergic neuromodulation reduces proactive interference between stored odor memories during associative learning in rats.

Previous electrophysiological studies and computational modeling suggest the hypothesis that cholinergic neuromodulation may reduce olfactory associative interference during learning (M. E. Hasselmo, B. P. Anderson, & J. M. Bower, 1992; M. E. Hasselmo & J. M. Bower, 1993). These results provide behavioral evidence supporting this hypothesis. A simultaneous discrimination task required learning a baseline odor pair (A+B-) and then, under the influence of scopolamine, a novel odor pair (A-C+) with an overlapping component (A) versus a novel odor pair (D+E-) with no overlapping component. As predicted by the model, rats that received scopolamine (0.50 and 0.25 mg/kg) were more impaired at acquiring overlapping than nonoverlapping odor pairs relative to their performance under normal saline or methylscopolamine. These results support the prediction that the physiological effects of acetylcholine can reduce interference between stored odor memories during associative learning.

Animals↗

Effects of configuration on the paired-associate learning of blissymbols by preschool children with normal cognitive abilities.

Translucency appears to be a potent variable in the learning of Blissymbols by preschool children with normal cognitive abilities. Complexity does not appear to influence learning for these individuals when there is a concurrent condition of high translucency. However, a condition of high complexity seems to enhance the learnability of Blissmbols having low translucency. For the present experiment, an attempt was made to determine if symbol configuration affects the learning of highly complex Blissymbols that bear little relationship to their referents. A paired-associate learning paradigm was used to present 30 Blissymbols to 20 cognitively normal preschool children. These symbols were evenly divided into superimposed and nonsuperimposed groups. Results indicated that the children learned more superimposed symbols than their nonsuperimposed counterparts. The implications of this finding for the teaching of Blissymbols are discussed.

Child Language↗

Interaction of inferior temporal cortex with frontal cortex and basal forebrain: double dissociation in strategy implementation and associative learning.

Macaque monkeys learned a strategy task in which two groups of visual objects needed to be treated differently, one with persistent and one with sporadic object choices, to obtain food rewards. After preoperative training, they were divided into two surgical groups of three monkeys each. One group received crossed unilateral removals of frontal cortex and inferior temporal cortex (IT x FC) and were severely impaired in performing the strategy task. The other group received bilateral transection of anterior temporal stem, amygdala, and fornix (TS+AM+FX) and were unimpaired in performing the strategy task. Subsequently the same animals were tested in visual object-reward association learning. Here, confirming previous results, group IT x FC was unimpaired, whereas group TS+AM+FX was severely impaired. The results show that the amnesic effects of TS+AM+FX cannot be generally attributed to the partial temporal-frontal disconnection that this lesion creates, and therefore support the hypothesis that the amnesic effects of this lesion are caused primarily by the disconnection of temporal cortex from ascending inputs from the basal forebrain. The results also show that temporal-frontal interaction in strategy implementation does not require those routes of temporal-frontal interaction that are interrupted in TS+AM+FX, and therefore support the hypothesis that projections to other posterior cortical areas allow temporal and frontal cortex to interact with each other by multisynaptic corticocortical routes in strategy implementation.

Amygdala↗

Associative learning.

This chapter reviews evidence demonstrating the essential role of the cerebellum and its associated circuitry in the learning and memory of classical conditioning of discrete behavioral responses (e.g., eyeblink, limb flexion, head turn). It now seems conclusive that the memory traces for this basic category of associative learning are formed and stored in the cerebellum. Lesion, neuronal recording, electrical microstimulation, and anatomical procedures have been used to identify the essential conditioned stimulus (CS) circuit, including the pontine mossy fiber projections to the cerebellum; the essential unconditioned stimulus (US) reinforcing or teaching circuit, including neurons in the inferior olive (dorsal accessory olive) projecting to the cerebellum as climbing fibers; and the essential conditioned response (CR) circuit, including the interpositus nucleus, its projection via the superior cerebellar peduncle to the magnocellular red nucleus, and rubral projections to premotor and motor nuclei. Each major component of the eyeblink CR circuit was reversibly inactivated both in trained animals and over the course of training. In all cases in trained animals, inactivation abolished the CR (and the UR as well when motor nuclei were inactivated). When animals were trained during inactivation (and not exhibiting CRs) and then tested without inactivation, animals with inactivation of the motor nuclei, red nucleus, and superior peduncle had fully learned, whereas animals with inactivation of a very localized region of the cerebellum (anterior interpositus and overlying cortex) had not learned at all. Consequently, the memory traces are formed and stored in the cerebellum. Several alternative possibilities are considered and ruled out. Both the cerebellar cortex and the interpositus nucleus are involved in the memory storage process, suggesting that a phenomenon-like long-term depression (LTD) is involved in the cerebellar cortex and long-term potentiation (LTP) is involved in the interpositus. The experimental findings reviewed in this chapter provide perhaps the first conclusive evidence for the localization of a basic form of memory storage to a particular brain region, namely the cerebellum, and indicate that the cerebellum is indeed a cognitive machine.

Animals↗

Dissociation of recognition memory and associative learning by a restricted lesion of the chick forebrain.

Bilateral lesions of a restricted part of the chick forebrain (IMHV) have been shown to impair the acquisition and retention of imprinting preferences. The present study sought to determine the effects of such lesions on an operant conditioning task in which the reward was the presentation of one of two conspicuous objects, a stuffed jungle fowl or an illuminated red box. Twelve hours after hatching 28 domestic chicks received bilateral lesions of IMHV. Thirty-two chicks served as sham-operated controls. On the following day all birds underwent two sessions of operant training. After the second session the chicks were given a preference test. In this test the reinforcing object (box or fowl) and a novel object (fowl or box, whichever had not been seen before) were simultaneously presented. One test was given 2 hr and a second 24 hr after the termination of the operant task. The lesioned birds were not impaired on the operant task or on measures of general activity. In contrast, these birds failed to show a preference for the reinforcing object whereas the sham-operated controls strongly preferred this object. These results suggest that object recognition and associative learning can be dissociated in young chicks. This dissociation is reminiscent of certain human amnesias. The lesion did not impair an expected increase in preference for the stuffed fowl which developed in all birds between the 2-hr and 24-hr preference tests.

Animals↗

Visuo-motor conditional associative learning after frontal and temporal lesions in the human brain.

It has been shown that damage to the human lateral frontal cortex results in a severe impairment on conditional associative tasks requiring learning of arbitrary associations between a set of stimuli and a set of responses (Petrides, M., Neuropsychologia, 1985, 23, 601-614; 1990, 28, 137-149). In these studies, which first demonstrated the impairment after frontal lesions, training was by a trial-and-error procedure, during which the subject performed the various responses when a given stimulus was presented and the experimenter provided feedback until the correct response was performed. In the present experiment, patients with unilateral frontal- or temporal-lobe excisions were tested on a visuo-motor conditional associative task with a modified procedure. The subjects had to learn arbitrary associations between a set of coloured stimuli and a set of hand postures. Training in the present experiment consisted of a series of demonstration trials followed by test trials. In the demonstration trials, the experimenter showed the subject the associations between the stimuli and the responses and, in the test trials that followed, the subject was tested on these associations. If an error was made on the test trials, the correct response was demonstrated by the experimenter. Despite these changes in the training procedure, namely the demonstration of the stimulus-response associations and the provision of the correct response immediately following an error, patients with left or right frontal-lobe excisions were severely impaired in learning this task. These findings, together with those of the earlier studies (Petrides, M., Neuropsychologia, 1985, 23, 601-614; 1990, 28, 137-149), demonstrate that the impairment in conditional learning after frontal lesions is not dependent on the type of the training procedure and therefore that it reflects a specific impairment in learning.

Adolescent↗

Genetic control of development of the mushroom bodies, the associative learning centers in the Drosophila brain, by the eyeless, twin of eyeless, and Dachshund genes.

Mushroom bodies (MBs) are the centers for olfactory associative learning and elementary cognitive functions in the Drosophila brain. By high-resolution neuroanatomy, we show that eyeless (ey), twin of eyeless, and dachshund (dac), which are implicated in eye development, also are expressed in the developing MBs. Mutations of ey completely disrupted the MB neuropils, and a null mutation of dac resulted in marked disruption and aberrant axonal projections. Genetic analyses demonstrated that, whereas ey and dac synergistically control the structural development of the MBs, the two genes are regulated independently in the course of MB development. These data argue for a distinct combinatorial code of regulatory genes for MBs as compared with eye development and suggest conserved roles of Pax6 homologs in the genetic programs of the olfactory learning centers of complex brains.

Animals↗

Neuronal modifications during visuomotor association learning assessed by electric brain tomography.

In everyday life specific situations need specific reactions. Through repetitive practice, such stimulus-response associations can be learned and performed automatically. The aim of the present EEG study was the illustration of learning dependent modifications in neuronal pathways during short-term practice of visuomotor associations. Participants performed a visuomotor association task including four visual stimuli, which should be associated with four keys, learned by trial and error. We assumed that distinct cognitive processes might be dominant during early learning e.g., visual perception and decision making. Advanced learning, however, might be indicated by increased neuronal activation in integration- and memory-related regions. For assessment of learning progress, visual- and movement-related brain potentials were measured and compared between three learning stages (early, intermediate, and late). The results have revealed significant differences between the learning stages during distinct time intervals. Related to visual stimulus presentation, Low Resolution Electromagnetic Brain Tomography (LORETA) revealed strong neuronal activation in a parieto-prefrontal network in time intervals between 100-400 ms post event and during early learning. In relation to the motor response neuronal activation was significantly increased during intermediate compared to early learning. Prior to the motor response (120-360 ms pre event), neuronal activation was detected in the cingulate motor area and the right dorsal premotor cortex. Subsequent to the motor response (68-430 ms post event) there was an increase in neuronal activation in visuomotor- and memory-related areas including parietal cortex, SMA, premotor, dorsolateral prefrontal, and parahippocampal cortex. The present study has shown specific time elements of a visuomotor-memory-related network, which might support learning progress during visuomotor association learning.

Adult↗

Emotional and behavioral correlates of the anterior cingulate cortex during associative learning in rats.

Neuronal activity was recorded from the anterior cingulate cortex of behaving rats during discrimination and learning of conditioned stimuli associated with or without reinforcements. The rats were trained to lick a protruding spout just after a conditioned stimulus to obtain reward (intracranial self-stimulation or sucrose solution) or to avoid aversion. The conditioned stimuli included both elemental (auditory or visual stimuli) and configural (simultaneous presentation of auditory and visual stimuli predicting reward outcome opposite to that predicted by each stimulus presented alone) stimuli. Of the 62 anterior cingulate neurons responding during the task, 38 and four responded differentially and non-differentially to the conditioned stimuli (conditioned stimulus-related neurons), respectively. Of the 38 differential conditioned stimulus-related neurons, 33 displayed excitatory (n = 10) and inhibitory (n = 23) responses selectively to the conditioned stimuli predicting reward. These excitatory and inhibitory differential conditioned stimulus-related neurons were located mainly in the cingulate cortex areas 1 and 3 of the rostral and ventral parts of the anterior cingulate cortex, respectively. The remaining 20 neurons responded mainly during intracranial self-stimulation and/or ingestion of sucrose (ingestion/intracranial self-stimulation-related neurons). Increase in activity of the ingestion/intracranial self-stimulation-related neurons was correlated to the first lick to obtain rewards during the task, suggesting that the activity reflected some aspects of motor functions for learned instrumental behaviors. These ingestion/intracranial self-stimulation-related neurons were located sparsely in cingulate cortex area 1 of the rostral part of the anterior cingulate cortex and densely in frontal area 2 of the caudal and dorsal parts of the anterior cingulate cortex. Analysis by the multidimensional scaling of responses of 38 differential conditioned stimulus-related neurons indicated that the anterior cingulate cortex categorized the conditioned stimuli into three groups based on reward contingency, regardless of the physical characteristics of the stimuli, in a two-dimensional space; the three conditioned (two elemental and one configural) stimuli predicting sucrose solution, the three conditioned (two elemental and one configural) stimuli predicting no reward, and the lone conditioned stimulus predicting intracranial self-stimulation. The results suggest that the anterior cingulate cortex is organized topographically; stimulus attributes predicting reward or no reward are represented in the rostral and ventral parts of the anterior cingulate cortex, while the caudal and dorsal parts of the anterior cingulate cortex are related to execution of learned instrumental behaviors. These results are in line with recent neuropsychological studies suggesting that the rostral part of the anterior cingulate cortex plays a crucial role in socio-emotional behaviors by assigning a positive or negative value to future outcomes.

Acoustic Stimulation↗

Non-associative learning in the mouse. Effect of morphine and naloxone.

The study evaluates the effect of morphine and naloxone on the process of non-associative learning in the mouse. Exploratory behavior was measured in thirty-six male albino mice (Suisse) placed on a Boissier and Simon hole-board, the procedure being repeated 24 h later after administration of naloxone and/or morphine, or bidistilled water i.p. The results show that the inhibitory effect naloxone has on the recollection process of the mnemonic traces appears to be masked by morphine.

Animals↗