Biomedical subjects

Earl K Miller

Publications and source records attributed to Earl K Miller.

18 recordsLinked to original sources

PubMed2006

Microstimulation of frontal cortex can reorder a remembered spatial sequence.

Complex goal-directed behaviors extend over time and thus depend on the ability to serially order memories and assemble compound, temporally coordinated movements. Theories of sequential processing range from simple associative chaining to hierarchical models in which order is encoded explicitly and separately from sequence components. To examine how short-term memory and planning for sequences might be coded, we used microstimulation to perturb neural activity in the supplementary eye field (SEF) while animals held a sequence of two cued locations in memory over a short delay. We found that stimulation affected the order in which animals saccaded to the locations, but not the memory for which locations were cued. These results imply that memory for sequential order can be dissociated from that of its components. Furthermore, stimulation of the SEF appeared to bias sequence endpoints to converge toward a location in contralateral space, suggesting that this area encodes sequences in terms of their endpoints rather than their individual components.

Animals↗

PubMed2006

A comparison of abstract rules in the prefrontal cortex, premotor cortex, inferior temporal cortex, and striatum.

The ability to use abstract rules or principles allows behavior to generalize from specific circumstances. We have previously shown that such rules are encoded in the lateral prefrontal cortex (PFC) and premotor cortex (PMC). Here, we extend these investigations to two other areas directly connected with the PFC and the PMC, the inferior temporal cortex (ITC) and the dorsal striatum (STR). Monkeys were trained to use two abstract rules: "same" or "different". They had to either hold or release a lever, depending on whether two successively presented pictures were the same or different, and depending on which rule was in effect. The rules and the behavioral responses were reflected most strongly and, on average, tended to be earlier in the PMC followed by the PFC and then the STR; few neurons in the ITC reflected the rules or the actions. By contrast, perceptual information (the identity of the pictures used as sample and test stimuli) was encoded more strongly and earlier in the ITC, followed by the PFC; they had weak, if any, effects on neural activity in the PMC and STR. These findings are discussed in the context of the anatomy and posited functions of these areas.

Action Potentials↗

PubMed2005

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.

Algorithms↗

PubMed2005

Different time courses of learning-related activity in the prefrontal cortex and striatum.

To navigate our complex world, our brains have evolved a sophisticated ability to quickly learn arbitrary rules such as 'stop at red'. Studies in monkeys using a laboratory test of this capacity--conditional association learning--have revealed that frontal lobe structures (including the prefrontal cortex) as well as subcortical nuclei of the basal ganglia are involved in such learning. Neural correlates of associative learning have been observed in both brain regions, but whether or not these regions have unique functions is unclear, as they have typically been studied separately using different tasks. Here we show that during associative learning in monkeys, neural activity in these areas changes at different rates: the striatum (an input structure of the basal ganglia) showed rapid, almost bistable, changes compared with a slower trend in the prefrontal cortex that was more in accordance with slow improvements in behavioural performance. Also, pre-saccadic activity began progressively earlier in the striatum but not in the prefrontal cortex as learning took place. These results support the hypothesis that rewarded associations are first identified by the basal ganglia, the output of which 'trains' slower learning mechanisms in the frontal cortex.

Animals↗

PubMed2004

A parieto-frontal network for visual numerical information in the monkey.

Recent electrophysiological studies in monkeys have implicated the prefrontal cortex (PFC) and posterior parietal cortex (PPC) in numerical judgments. The functional organization and respective contributions of these (and other) cortical areas, however, are unknown; their neural activity during numerical judgments has not been directly compared. We surveyed activity in the PPC and the anterior inferior temporal cortex while monkeys performed a visual numerosity judgment task and compared it with a population of PFC neurons. In the PPC, the proportion of numerosity-selective neurons was highest in the fundus of the intraparietal sulcus; only few numerosity-selective neurons were found in other PPC areas or the anterior inferior temporal cortex. Further, neurons in the fundus of the intraparietal sulcus responded and conveyed numerosity earlier than PFC neurons, suggesting that numerosity information flows from the PPC to the lateral PFC. This finding suggests a parieto-frontal network for numerosity in monkeys and establishes homologies between the monkey and human brain.

Animals↗

PubMed2004

Analog numerical representations in rhesus monkeys: evidence for parallel processing.

Monkeys have been introduced as model organisms to study neural correlates of numerical competence, but many of the behavioral characteristics of numerical judgments remain speculative. Thus, we analyzed the behavioral performance of two rhesus monkeys judging the numerosities 1 to 7 during a delayed match-to-sample task. The monkeys showed similar discrimination performance irrespective of the exact physical appearance of the stimuli, confirming that performance was based on numerical information. Performance declined smoothly with larger numerosities, and reached discrimination threshold at numerosity "4." The nonverbal numerical representations in monkeys were based on analog magnitudes, object tracking process ("subitizing") could not account for the findings because the continuum of small and large numbers shows a clear Weber fraction signature. The lack of additional scanning eye movements with increasing set sizes, together with indistinguishable neuronal response latencies for neurons with different preferred numerosities, argues for parallel encoding of numerical information. The slight but significant increase in reaction time with increasing numerosities can be explained by task difficulty and consequently time-consuming decision processes. The behavioral results are compared to single-cell recordings from the prefrontal cortex in the same subjects. Models for numerosity discrimination that may account for these results are discussed.

Animals↗

PubMed2003

Neural circuits subserving the retrieval and maintenance of abstract rules.

Behavior is often governed by abstract rules or instructions for behavior that can be abstracted from one context and applied to another. Prefrontal cortex (PFC) is thought to be important for representing rules, although the contributions of ventrolateral (VLPFC) and dorsolateral (DLPFC) regions remain under-specified. In the present study, event-related fMRI was used to examine abstract rule representation in humans. Prior to scanning, subjects learned to associate unfamiliar shapes and nonwords with particular rules. During each fMRI trial, presentation of one of these cues was followed by a delay and then by sample and probe stimuli. Match and non-match rules required subjects to indicate whether or not the sample and probe matched; go rules required subjects to make a response that was not contingent on the sample/probe relation. Left VLPFC, parietal cortex, and pre-SMA exhibited sensitivity to rule type during the cue and delay periods. Delay-period activation in these regions, but not DLPFC, was greater when subjects had to maintain response contingencies (match, non-match) relative to when the cue signaled a specific response (go). In contrast, left middle temporal cortex exhibited rule sensitivity during the cue but not delay period. These results support the hypothesis that VLPFC interacts with temporal cortex to retrieve semantic information associated with a cue and with parietal cortex to retrieve and maintain relevant response contingencies across delays. Future investigations of cross-regional interactions will enable full assessment of this account. Collectively, these results demonstrate that multiple, neurally separable processes are recruited during abstract rule representation.

Acoustic Stimulation↗

PubMed2003

A comparison of primate prefrontal and inferior temporal cortices during visual categorization.

Previous studies have suggested that both the prefrontal cortex (PFC) and inferior temporal cortex (ITC) are involved in high-level visual processing and categorization, but their respective roles are not known. To address this, we trained monkeys to categorize a continuous set of visual stimuli into two categories, "cats" and "dogs." The stimuli were parametrically generated using a computer graphics morphing system (Sheltonelton, 2000) that allowed precise control over stimulus shape. After training, we recorded neural activity from the PFC and the ITC of monkeys while they performed a category-matching task. We found that the PFC and the ITC play distinct roles in category-based behaviors: the ITC seems more involved in the analysis of currently viewed shapes, whereas the PFC showed stronger category signals, memory effects, and a greater tendency to encode information in terms of its behavioral meaning.

Analysis of Variance↗

PubMed2003

V1 neurons signal acquisition of an internal representation of stimulus location.

A fundamental aspect of visuomotor behavior is deciding where to look or move next. Under certain conditions, the brain constructs an internal representation of stimulus location on the basis of previous knowledge and uses it to move the eyes or to make other movements. Neuronal responses in primary visual cortex were modulated when such an internal representation was acquired: Responses to a stimulus were affected progressively by sequential presentation of the stimulus at one location but not when the location was varied randomly. Responses of individual neurons were spatially tuned for gaze direction and tracked the Bayesian probability of stimulus appearance. We propose that the representation arises in a distributed cortical network and is associated with systematic changes in response selectivity and dynamics at the earliest stages of cortical visual processing.

Analysis of Variance↗

PubMed2003

From rule to response: neuronal processes in the premotor and prefrontal cortex.

The ability to use abstract rules or principles allows behavior to generalize from specific circumstances (e.g., rules learned in a specific restaurant can subsequently be applied to any dining experience). Neurons in the prefrontal cortex (PFC) encode such rules. However, to guide behavior, rules must be linked to motor responses. We investigated the neuronal mechanisms underlying this process by recording from the PFC and the premotor cortex (PMC) of monkeys trained to use two abstract rules: "same" or "different." The monkeys had to either hold or release a lever, depending on whether two successively presented pictures were the same or different, and depending on which rule was in effect. The abstract rules were represented in both regions, although they were more prevalent and were encoded earlier and more strongly in the PMC. There was a perceptual bias in the PFC, relative to the PMC, with more PFC neurons encoding the presented pictures. In contrast, neurons encoding the behavioral response were more prevalent in the PMC, and the selectivity was stronger and appeared earlier in the PMC than in the PFC.

Animals↗

PubMed2003

Coding of cognitive magnitude: compressed scaling of numerical information in the primate prefrontal cortex.

Whether cognitive representations are better conceived as language-based, symbolic representations or perceptually related, analog representations is a subject of debate. If cognitive processes parallel perceptual processes, then fundamental psychophysical laws should hold for each. To test this, we analyzed both behavioral and neuronal representations of numerosity in the prefrontal cortex of rhesus monkeys. The data were best described by a nonlinearly compressed scaling of numerical information, as postulated by the Weber-Fechner law or Stevens' law for psychophysical/sensory magnitudes. This nonlinear compression was observed on the neural level during the acquisition phase of the task and maintained through the memory phase with no further compression. These results suggest that certain cognitive and perceptual/sensory representations share the same fundamental mechanisms and neural coding schemes.

Action Potentials↗

PubMed2003

Neural correlates of categories and concepts.

The ability to readily adapt to novel situations requires something beyond storing specific stimulus-response associations. Instead, many animals can detect basic characteristics of events and store them as generalized classes. Because these representations are abstracted beyond specific details of sensory inputs and motor outputs, they can be easily generalized and adapted to new circumstances. Explorations of neural mechanisms of sensory processing and motor output have progressed to the point where studies can begin to address the neural basis of abstract, categorical representations. Recent studies have revealed their neural correlates in various cortical areas of the non-human primate brain.

Animals↗

PubMed2003

Neuronal activity in primate dorsolateral and orbital prefrontal cortex during performance of a reward preference task.

An important function of the prefrontal cortex (PFC) is the control of goal-directed behaviour. This requires information as to whether actions were successful in obtaining desired outcomes such as rewards. While lesion studies implicate a particular PFC region, the orbitofrontal cortex (OFC), in reward processing, neurons encoding reward have been reported in both the OFC and the dorsolateral prefrontal cortex (DLPFC). To compare and contrast their roles, we recorded simultaneously from both areas while two rhesus monkeys (Macaca mulatta) performed a reward preference task. The monkeys had to choose between pictures associated with different amounts of a juice reward. Neuronal activity in both areas reflected the reward amount. However, neurons in the DLPFC encoded both the reward amount and the monkeys' forthcoming response, while neurons in the OFC more often encoded the reward amount alone. Further, reward selectivity arose more rapidly in the OFC than the DLPFC. These results are consistent with reward information entering the PFC via the OFC, where it is passed to the DLPFC and used to control behaviour.

Action Potentials↗

PubMed2002

Representation of the quantity of visual items in the primate prefrontal cortex.

Deriving the quantity of items is an abstract form of categorization. To explore it, monkeys were trained to judge whether successive visual displays contained the same quantity of items. Many neurons in the lateral prefrontal cortex were tuned for quantity irrespective of the exact physical appearance of the displays. Their tuning curves formed overlapping filters, which may explain why behavioral discrimination improves with increasing numerical distance and why discrimination of two quantities with equal numerical distance worsens as their numerical size increases. A mechanism that extracts the quantity of visual field items could contribute to general numerical ability.

Animals↗

PubMed2002

The prefrontal cortex: categories, concepts and cognition.

The ability to generalize behaviour-guiding principles and concepts from experience is key to intelligent, goal-directed behaviour. It allows us to deal efficiently with a complex world and to adapt readily to novel situations. We review evidence that the prefrontal cortex-the cortical area that reaches its greatest elaboration in primates-plays a central part in acquiring and representing this information. The prefrontal cortex receives highly processed information from all major forebrain systems, and neurophysiological studies suggest that it synthesizes this into representations of learned task contingencies, concepts and task rules. In short, the prefrontal cortex seems to underlie our internal representations of the 'rules of the game'. This may provide the necessary foundation for the complex behaviour of primates, in whom this structure is most elaborate.

Animals↗

PubMed2002

Dynamics of neuronal sensitivity in visual cortex and local feature discrimination.

A striking aspect of natural scenes is that image features such as line orientation are strongly correlated at neighboring spatial locations but not at distant locations. Thus, during the viewing of a scene, eye movements are often accompanied by a change in the orientation structure of the image. How does this behavior influence the discrimination of local features and their encoding by visual cortical neurons? Here we examined the perceived changes in orientation induced by brief exposure to oriented image patterns in monkeys and humans, and then used reverse correlation to investigate dynamic changes in neuronal sensitivity in the primary visual cortex (V1) of behaving monkeys. Whereas brief adaptation to an oriented grating impaired identification of nearby orientations by broadening orientation selectivity and changing the preferred orientation of individual V1 neurons, it actually enhanced the identification of orthogonal orientations by sharpening neuronal selectivity. Hence, successive exposure to image patches of dissimilar spatial structure enhances both the ability to discriminate local features and the encoding of these features by V1 neurons.

Action Potentials↗

PubMed2002

Timecourse of object-related neural activity in the primate prefrontal cortex during a short-term memory task.

We studied the timecourse of neural activity in the primate (Macacca mulatta) prefrontal (PF) cortex during an object delayed-matching-to-sample (DMS) task. To assess the effects of experience on this timecourse, we conducted the task using both novel and highly familiar objects. In addition, noise patterns containing no task-relevant information were used as samples on some trials. Comparison of average PF ensemble activity relative to baseline activity generated by objects and noise patterns revealed three distinct activity periods. (i) Sample onset elicited a transient sensory visual response. In this sensory period, novel objects elicited stronger average ensemble activity than both familiar objects and noise patterns. (ii) An intermediate period of elevated activity followed, which began before sample offset, and continued well into the delay period. In the intermediate period, activity was elevated for noise patterns and novel objects, but near baseline for familiar objects. (iii) Finally, after average ensemble activity reached baseline activity at the end of the intermediate period, a reactivation period occurred late in the delay. Experience had little effect during reactivation, where activity was elevated for both novel and familiar objects compared to noise patterns. We show that the ensemble average resembles the activity timecourse of many single prefrontal neurons. These results suggest that PF delay activity does not merely maintain recent sensory input, but is subject to more complex experience-dependent dynamics. This has implications for how delay activity is generated and maintained.

Acoustic Stimulation↗

PubMed2002

Visual categorization and the primate prefrontal cortex: neurophysiology and behavior.

The ability to group stimuli into meaningful categories is a fundamental cognitive process. To explore its neuronal basis, we trained monkeys to categorize computer-generated stimuli as "cats" and "dogs." A morphing system was used to systematically vary stimulus shape and precisely define a category boundary. Psychophysical testing and analysis of eye movements suggest that the monkeys categorized the stimuli by attending to multiple stimulus features. Neuronal activity in the lateral prefrontal cortex reflected the category of visual stimuli and changed with learning when a monkey was retrained with the same stimuli assigned to new categories. Further, many neurons showed activity that appeared to reflect the monkey's decision about whether two stimuli were from the same category or not. These results suggest that the lateral prefrontal cortex is an important part of the neuronal circuitry underlying category learning and category-based behaviors.

Action Potentials↗