Changes in prefrontal neuronal activity after learning to perform a spatial working memory task

The prefrontal cortex is considered essential for learning to perform cognitive tasks though little is known about how the representation of stimulus properties is altered by learning. To address this issue, we recorded neuronal activity in monkeys before and after training on a task that required visual working memory. After the subjects learned to perform the task, we observed activation of more prefrontal neurons and increased activity during working memory maintenance. The working memory-related increase in firing rate was due mostly to regular-spiking putative pyramidal neurons. Unexpectedly, the selectivity of neurons for stimulus properties and the ability of neurons to discriminate between stimuli decreased as the information about stimulus properties was apparently present in neural firing prior to training and neuronal selectivity degraded after training in the task. The effect was robust and could not be accounted for by differences in sampling sites, selection of neurons, level of performance, or merely the elapse of time. The results indicate that, in contrast to the effects of perceptual learning, mastery of a cognitive task degrades the apparent stimulus selectivity as neurons represent more abstract information related to the task. This effect is countered by the recruitment of more neurons after training.     

Experience-dependent sharpening of visual shape selectivity in inferior temporal cortex

Whereas much is known about the visual shape selectivity of neurons in the inferior temporal cortex (ITC), less is known about the role of visual learning in the development and refinement of ITC shape selectivity. To address this, we trained monkeys to perform a visual categorization task with a parametric set of highly familiar stimuli. During training, the stimuli were always presented at the same orientation. In this experiment, we recorded from ITC neurons while monkeys viewed the trained stimuli in addition to image-plane rotated versions of those stimuli. We found that, concomitant with the monkeys' behavioral performance, neuronal stimulus selectivity was stronger for stimuli presented at the trained orientation than for rotated versions of the same stimuli. We also recorded from ITC neurons while monkeys viewed sets of novel and familiar (but not explicitly trained) randomly chosen complex stimuli. We again found that ITC stimulus selectivity was sharper for familiar than novel stimuli, suggesting that enhanced shape tuning in ITC can arise for both passively experienced and explicitly trained stimuli.     

A stable topography of selectivity for unfamiliar shape classes in monkey inferior temporal cortex

The inferior temporal (IT) cortex in monkeys plays a central role in visual object recognition and learning. Previous studies have observed patches in IT cortex with strong selectivity for highly familiar object classes (e.g., faces), but the principles behind this functional organization are largely unknown due to the many properties that distinguish different object classes. To unconfound shape from meaning and memory, we scanned monkeys with functional magnetic resonance imaging while they viewed classes of initially novel objects. Our data revealed a topography of selectivity for these novel object classes across IT cortex. We found that this selectivity topography was highly reproducible and remarkably stable across a 3-month interval during which monkeys were extensively trained to discriminate among exemplars within one of the object classes. Furthermore, this selectivity topography was largely unaffected by changes in behavioral task and object retinal position, both of which preserve shape. In contrast, it was strongly influenced by changes in object shape. The topography was partially related to, but not explained by, the previously described pattern of face selectivity. Together, these results suggest that IT cortex contains a large-scale map of shape that is largely independent of meaning, familiarity, and behavioral task.     

Comparison of associative learning-related signals in the macaque perirhinal cortex and hippocampus

Strong evidence suggests that the macaque monkey perirhinal cortex is involved in both the initial formation as well as the long-term storage of associative memory. To examine the neurophysiological basis of associative memory formation in this area, we recorded neural activity in this region as monkeys learned new conditional-motor associations. We report that a population of perirhinal neurons signal newly learned associations by changing their firing rate correlated with the animal's behavioral learning curve. Individual perirhinal neurons signal learning of one or more associations concurrently and these neural changes could occur before, at the same time, or after behavioral learning was expressed. We also compared the associative learning signals in the perirhinal cortex to our previous findings in the hippocampus. We report global similarities in both the learning-related and task-related activity seen across these areas as well as clear differences in the within and across trial timing and relative proportion of different subtypes of learning-related signals. Taken together, these findings emphasize the important role of the perirhinal cortex in new associative learning and suggest that the perirhinal cortex together with the hippocampus contribute importantly to conditional-motor associative memory formation.     

Properties of Simulated Neurons from a Model of Primate Inferior Temporal Cortex

The physiological properties of neurons in inferior temporal(IT) cortex of the macaque monkey suggest that this corticalarea plays a major role in visual pattern recognition. Basedon the properties of IT, and one of its major sources of inputV4, a model is proposed that can account for some of the shaperecognition properties of IT neurons including selectivity forcomplex visual stimuli and tolerance to the size and locationof the stimuli. The model is composed of three components. Firststimulus location tolerance is modeled after the complex-cell-likeproperties observed in some V4 neurons. The second componentof the model is an attentionally controlled scaling mechanismthat facilitates size-invariant shape recognition. The transitionfrom edge orientation-selective neurons in V4 to neurons withmore complicated stimulus preference in IT is explained by thethird component of the model, a competitive learning mechanism.Single-unit analysis of receptive field properties, stimulusselectivity, and stimulus size and position tolerance was performedon "neurons" from the simulation. Comparison of results fromthe simulation and a study of actual IT neurons shows that theset of mechanisms incorporated into the simulation is sufficientto emulate the physiological data.     

How many maps are there in visual cortex?

In addition to a topographic map of the retina, mammalian visual cortex contains superimposed, orderly periodic maps of features such as orientation, eye dominance, direction of motion and spatial frequency. There is evidence that these maps are overlaid so as to ensure that all combinations of the different parameters are represented as uniformly as possible across visual space. However, it is unknown to what extent geometrical factors limit the number of periodic maps which might simultaneously be present, given this constraint. This paper attempts to investigate the question by using a dimension reduction model to generate maps of simple, many- dimensional feature spaces onto a model two-dimensional cortex. The feature space included a model retina, plus N binary variables, corresponding to parameters such as ocular dominance or spatial frequency. The results suggest that geometrical factors do not sharply limit the ability of the cortex to represent combinations of parameters in spatially superimposed maps of similar periodicity. Considerations of uniform coverage suggest an upper limit of six or seven maps. A higher limit, of about nine or ten, may be imposed by the numbers of neurons (or minicolumns) available to represent each of 2(N) features within a given small region of cortex.     

Interhemispheric differences in auditory processing revealed by fMRI in awake rhesus monkeys

Lesion studies in monkeys have suggested a modest left hemisphere dominance for processing species-specific vocalizations, the neural basis of which has thus far remained unclear. We used contrast agent-enhanced functional magnetic resonance imaging to map the regions of the rhesus monkey brain involved in processing conspecific vocalizations as well as human speech and emotional sounds. Control conditions included scrambled versions of all 3 stimuli and silence. Compared with silence, all stimuli activated widespread parts of the auditory cortex and subcortical auditory structures with a right hemispheric bias at the level of the auditory core. However, comparing intact with scrambled sounds revealed a leftward bias in the auditory belt and the parabelt. The left-sided dominance was stronger and more robust for human speech than for rhesus vocalizations and hence does not reflect conspecific call selectivity but rather the processing of complex spectrotemporal patterns, such as those present in human speech and in some of the rhesus monkey vocalizations. This was confirmed by regressing brain activity with a model-derived parameter indexing the prevalence of such patterns. Our results indicate that processing of vocal sounds in the lateral belt and parabelt is asymmetric in monkeys, as predicted from lesion studies.     

Determining a role for ventromedial prefrontal cortex in encoding action-based value signals during reward-related decision making

Considerable evidence has emerged to implicate ventromedial prefrontal cortex in encoding expectations of future reward during value-based decision making. However, the nature of the learned associations upon which such representations depend is much less clear. Here, we aimed to determine whether expected reward representations in this region could be driven by action-outcome associations, rather than being dependent on the associative value assigned to particular discriminative stimuli. Subjects were scanned with functional magnetic resonance imaging while performing 2 variants of a simple reward-related decision task. In one version, subjects made choices between 2 different physical motor responses in the absence of discriminative stimuli, whereas in the other version, subjects chose between 2 different stimuli that were randomly assigned to different responses on a trial-by-trial basis. Using an extension of a reinforcement learning algorithm, we found activity in ventromedial prefrontal cortex tracked expected future reward during the action-based task as well as during the stimulus-based task, indicating that value representations in this region can be driven by action-outcome associations. These findings suggest that ventromedial prefrontal cortex may play a role in encoding the value of chosen actions irrespective of whether those actions denote physical motor responses or more abstract decision options.     

Dissociable functions in the medial and lateral orbitofrontal cortex: evidence from human neuroimaging studies

Recent imaging studies show that the orbitofrontal cortex (OFC) is activated during a wide variety of paradigms, including guessing tasks, simple delayed matching tasks and sentence completion. We suggest that, as with other regions of the prefrontal cortex, activity in the OFC is most likely to be observed when there is insufficient information available to determine the appropriate course of action. In these circumstances the OFC, rather than other prefrontal regions, is more likely to be activated when the problem of what to do next is best solved by taking into account the likely reward value of stimuli and responses, rather than their identity or location. We suggest that selection of stimuli on the basis of their familiarity and responses on the basis of a feeling of 'rightness' are also examples of selection on the basis of reward value. Within the OFC, the lateral regions are more likely to be involved when the action selected requires the suppression of previously rewarded responses.     

The neural basis of visual skill learning: an fMRI study of mirror reading

The learning of perceptual skills is thought to rely upon multiple regions in the cerebral cortex, but imaging studies have not yet provided evidence about the changes in neural activity that accompany visual skill learning. Functional magnetic resonance imaging (fMRI) was used to examine changes in activation of posterior brain regions associated with the acquisition of mirror-reading skill for novel and practiced stimuli. Multiple regions in the occipital lobe, inferior temporal cortex, superior parietal cortex and cerebellum were involved in the reading of mirror-reversed compared to normally oriented text. For novel stimuli, skilled mirror-reading was associated with decreased activation in the right superior parietal cortex and posterior occipital regions and increased activation in the left inferior temporal lobe. These results suggest that learning to read mirror- reversed text involves a progression from visuospatial transformation to direct recognition of transformed letters. Reading practiced, relative to unpracticed, stimuli was associated with decreased activation in occipital visual cortices, inferior temporal cortex and superior parietal cortex and increased activation in occipito-parietal and lateral temporal regions. By examining skill learning and item- specific repetition priming in the same task, this study demonstrates that both of these forms of learning exhibit shifts in the set of neural structures that contribute to performance.      

Impairment and facilitation of transverse patterning after lesions of the perirhinal cortex and hippocampus, respectively

We have recently suggested that certain effects of perirhinal cortex removals in monkeys can be attributed to the lesion compromising complex configural representations of visual stimuli. On this view, monkeys with perirhinal cortex lesions will be impaired on acquisition of discrimination problems that possess high "feature ambiguity," that is, those in which many of the same features belong to both rewarded and unrewarded stimuli. A subclass of feature-ambiguous problems includes "configural" discrimination problems in which all features are ambiguous. In the present study, we tested control monkeys and monkeys with bilateral lesions of perirhinal cortex on a configural discrimination problem, the transverse-patterning task (i.e., A+ vs. B-, B+ vs. C-, C+ vs. A-), using complex 2-dimensional visual stimuli. In addition, we investigated the effects of lesions to another structure that has been implicated in configural learning, the hippocampus. Monkeys with perirhinal cortex lesions were impaired, whereas monkeys with selective hippocampal lesions were facilitated, on acquisition of the transverse-patterning task. These data do not provide support for mass action theories of medial temporal lobe function, which cannot account for the opposing effects of the 2 lesions. These results are, however, compatible with a view that perirhinal cortex, and not the hippocampus, contains complex configural representations of visual stimuli critical to the solution of the transverse-patterning task.     

Functional organization of color domains in V1 and V2 of macaque monkey revealed by optical imaging

Areas V1 and V2 of Macaque monkey visual cortex are characterized by unique cytochrome-oxidase (CO)-staining patterns. Initial electrophysiological studies associated CO blobs in V1 with processing of surface properties such as color and brightness and the interblobs with contour information processing. However, many subsequent studies showed controversial results, some supporting this proposal and others failing to find significant functional differences between blobs and interblobs. In this study, we have used optical imaging to map color-selective responses in V1 and V2. In V1, we find striking "blob-like" patterns of color response. Fine alignment of optical maps and CO-stained tissue revealed that color domains in V1 strongly associate with CO blobs. We also find color domains in V1 align along centers of ocular dominance columns. Furthermore, color blobs in V1 have low orientation selectivity and do not overlap with centers of orientation domains. In V2, color domains coincide with thin stripes; orientation-selective domains coincide with thick and pale stripes. We conclude that color and orientation-selective responses are preferentially located in distinct CO compartments in V1 and V2. We propose that the term "blob" encompasses both the concept of "CO blob" and "color domain" in V1.     

Mechanisms of Stereopsis in Monkey Visual Cortex

A substantial proportion of neurons in the striate and prestriatecortex of monkeys have stereoscopic properties; that is, theyrespond differentially to binocular stimuli that are known inhumans to provide cues for stereoscopic depth perception. Stereoscopicneurons, as these cells may be called, are selective for horizontalpositional disparity (i.e., display disparity selectivity) andfor the textural correlation between images over their receptivefields (i.e., they show correlation selectivity). Many neuronshave tuned disparity response profiles that collectively coverthe entire range of physiological disparities. Neurons withpeak responses at or about the zero disparity ("tuned zero neurons,"excitatory or inhibitory) have narrow and symmetrical profiles.Neurons that are tuned to larger disparities, either crossed("tuned near neurons") or uncrossed ("tuned far neurons"), havebroader excitatory profiles that are asymmetrically wider towardthe smaller disparities, and commonly include an inhibitorycomponent about the zero disparity. Other stereoscopic neuronshave reciprocal profiles ("near" or "far" neurons, respectively)in the sense that they respond with excitation to crossed oruncrossed disparities, and with suppression to disparities ofopposite sign. Stereoscopic neurons can also signal the texturalcorrelation between paired retinal images by giving differentresponses to random-dot patterns that have, and to those thatdo not have, the same dot distribution over the neuron's leftand right receptive fields. Tuned-zero excitatory neurons characteristicallyrespond to uncorrelation with suppression; tuned-zero inhibitoryneurons, with excitation; and both types give the opposite responsesto correlated stereopatterns. Neurons selective for nonzerodisparities, both tuned and reciprocal, also give excitatoryresponses to uncorrelated stimuli, but these responses are smallerand more variable than those evoked by correlated patterns atthe effective disparities. These findings suggest that stereoscopicneurons in the visual cortex of the macaque comprise three operationalsystems: (1) a zero-disparity system that is involved in finedepth discrimination with the obligatory singleness of vision,and the maintenance of vergence; and (2) a near-, and (3) afar-disparity system that together signal qualitative estimatesof depth with double vision, and vergence responses to largedisparities.     

Perceptual and Cognitive Visual Functions of Parietal and Temporal Cortices in the Cat

We used reversible cooling deactivation to compare the functionsof cortices lining the middle suprasylvian (MS) sulcus and formingthe ventral portion of the posterior suprasylvian (vPS) gyrus.A battery of attentional, motion and mnemonic processing taskswere used and performance was examined during deactivation ofeach region. The results show a clear dissociation of functions.Deactivation of MS cortex resulted in profound deficits on avisual orienting task and on the discrimination of directionof motion, whereas deactivation of vPS cortex severely impairedboth retention and learning of novel and overlearned objectdiscriminations. In addition, deactivation of either MS or vPScortex impaired discrimination of learned patterns when componentsof the patterns were in motion, whereas only deactivation ofvPS cortex impaired the discrimination when all components werestatic. Together, these results show that a region of parietalcortex contributes to the processing of visual motion and toattentional processes, whereas a region of temporal cortex contributesto the learning and recognition of three-dimensional objectsand two-dimensional patterns. This functional dissociation islinked to differences in underlying visual pathways, which havemany features in common with the parietal and temporal visualprocessing streams previously identified in monkeys and humans.Furthermore, the broad similarity in neural operations carriedout in parietal and temporal cortices of cats, monkeys and humanssuggests the existence of a common plan for cortical processingmachinery within mammals with well developed cerebral cortices.     

Regional brain activation during concurrent implicit and explicit sequence learning

We used event-related fMRI to identify the brain regions engaged during explicit and implicit sequence learning (ESL and ISL, respectively). Twenty-four subjects performed a concurrent ESL and ISL task. Behavior showed learning in both conditions. Prefrontal (PFC), striatal, anterior cingulate cortex (ACC) and visual regions (V1, V2 and V3) were engaged during both ESL and ISL. With ESL there was increased activity in the visual regions on the predictable (i.e. learned pattern) trials. With ISL, however, there was a relative decrease in activity in visual regions. The opposite patterns in the visual regions highlight the different effects of ESL and ISL. The learning process was distinguished from the result of learning, by fitting subjects' functional magnetic resonance imaging data to their learning curve. This analysis revealed more extensive PFC activity during ESL and caudal ACC activity specific for the result of learning analysis, when the expected response was violated. Our results suggest a relative dissociation of the brain regions engaged during ESL and ISL, whereby ESL and ISL can be viewed as partially distinct but overlapping parallel processes.     

Action observation and acquired motor skills: an FMRI study with expert dancers

When we observe someone performing an action, do our brains simulate making that action? Acquired motor skills offer a unique way to test this question, since people differ widely in the actions they have learned to perform. We used functional magnetic resonance imaging to study differences in brain activity between watching an action that one has learned to do and an action that one has not, in order to assess whether the brain processes of action observation are modulated by the expertise and motor repertoire of the observer. Experts in classical ballet, experts in capoeira and inexpert control subjects viewed videos of ballet or capoeira actions. Comparing the brain activity when dancers watched their own dance style versus the other style therefore reveals the influence of motor expertise on action observation. We found greater bilateral activations in premotor cortex and intraparietal sulcus, right superior parietal lobe and left posterior superior temporal sulcus when expert dancers viewed movements that they had been trained to perform compared to movements they had not. Our results show that this 'mirror system' integrates observed actions of others with an individual's personal motor repertoire, and suggest that the human brain understands actions by motor simulation.     

Dopaminergic modulation of auditory cortex-dependent memory consolidation through mTOR

Previous studies in the auditory cortex of Mongolian gerbils on discrimination learning of the direction of frequency-modulated tones (FMs) revealed that long-term memory formation involves activation of the dopaminergic system, activity of the protein kinase mammalian target of rapamycin (mTOR), and protein synthesis. This led to the hypothesis that the dopaminergic system might modulate memory formation via regulation of mTOR, which is implicated in translational control. Here, we report that the D1/D5 dopamine receptor agonist SKF-38393 substantially improved gerbils' FM discrimination learning when administered systemically or locally into the auditory cortex shortly before, shortly after, or 1 day before conditioning. Although acquisition performance during initial training was normal, the discrimination of FMs was enhanced during retraining performed hours or days after agonist injection compared with vehicle-injected controls. The D1/D5 receptor antagonist SCH-23390, the mTOR inhibitor rapamycin, and the protein synthesis blocker anisomycin suppressed this effect. By immunohistochemistry, D1 dopamine receptors were identified in the gerbil auditory cortex predominantly in the infragranular layers. Together, these findings suggest that in the gerbil auditory cortex dopaminergic inputs regulate mTOR-mediated, protein synthesis-dependent mechanisms, thus controlling for hours or days the consolidation of memory required for the discrimination of complex auditory stimuli.     

Frontal-temporal disconnection abolishes object discrimination learning set in macaque monkeys

Two previous studies have shown that frontal-temporal disconnection in monkeys, produced by unilateral ablation of frontal cortex in one hemisphere and of visual inferior temporal cortex in the opposite hemisphere is entirely without effect on visual object-reward association learning in concurrent discrimination tasks. This is a surprising finding in light of the severe impairments that follow frontal-temporal disconnection in many other tests of visual learning and memory, including delayed matching-to-sample and several conditional learning tasks. To explore the limits of this preserved object-reward association learning, we trained monkeys on visual object discrimination learning set (DLS) prior to frontal-temporal disconnection. As a result of training with single object-reward associations, the monkeys acquired a proficient learning set, evidenced by the rapid learning of new single object-reward association problems. This rapid learning was not affected by unilateral ablations of either inferior temporal cortex alone or frontal cortex alone but was severely impaired after final surgery to complete the disconnection. Moreover, each individual monkey now learned single object-reward association problems at the slow rate at which that individual had learned such problems before the formation of learning set. This result shows that frontal-temporal disconnection abolishes visual learning set.     

Volume of left Heschl's Gyrus and linguistic pitch learning

Research on the contributions of the human nervous system to language processing and learning has generally been focused on the association regions of the brain without considering the possible contribution of primary and adjacent sensory areas. We report a study examining the relationship between the anatomy of Heschl's Gyrus (HG), which includes predominately primary auditory areas and is often found to be associated with nonlinguistic pitch processing and language learning. Unlike English, most languages of the world use pitch patterns to signal word meaning. In the present study, native English-speaking adult subjects learned to incorporate foreign pitch patterns in word identification. Subjects who were less successful in learning showed a smaller HG volume on the left (especially gray matter volume), but not on the right, relative to learners who were successful. These results suggest that HG, typically shown to be associated with the processing of acoustic cues in nonspeech processing, is also involved in speech learning. These results also suggest that primary auditory regions may be important for encoding basic acoustic cues during the course of spoken language learning.     

Olfactory learning modifies predisposition for long-term potentiation and long-term depression induction in the rat piriform (olfactory) cortex

Learning-related modifications in predisposition for long-term potentiation (LTP) and long-term depression (LTD) were studied in brain slices of the rat piriform cortex following olfactory learning. Rats were trained to discriminate between pairs of odors until they demonstrated rule learning. We have previously shown that such training is accompanied by enhanced neuronal excitability and increased synaptic transmission in the intrinsic synaptic pathway. Here we show that the susceptibility for further enhancing synaptic connectivity by inducing LTP in slices from trained rats is markedly reduced after training, compared with slices from pseudo-trained and naive rats. Accordingly, while 900 stimuli at 1 Hz did not induce LTD in slices from control rats, it induced significant LTD in slices from trained rats. Post-tetanic potentiation (PTP) was also reduced after training, indicating that synaptic release is enhanced after odor learning, as previously suggested. We suggest that learning-related cellular modifications and activity-dependent synaptic plasticity share a common mechanism in the primary olfactory cortex. Our data also support the prediction generated according to the sliding modification threshold theory that learning should be accompanied by reduced capability of inducing LTP and increased susceptibility for LTD induction.