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Biomedical subjects

E K Miller

Publications and source records attributed to E K Miller.

At least 19 recordsLinked to original sources
PubMed2001

Single neurons in prefrontal cortex encode abstract rules.

The ability to abstract principles or rules from direct experience allows behaviour to extend beyond specific circumstances to general situations. For example, we learn the 'rules' for restaurant dining from specific experiences and can then apply them in new restaurants. The use of such rules is thought to depend on the prefrontal cortex (PFC) because its damage often results in difficulty in following rules. Here we explore its neural basis by recording from single neurons in the PFC of monkeys trained to use two abstract rules. They were required to indicate whether two successively presented pictures were the same or different depending on which rule was currently in effect. The monkeys performed this task with new pictures, thus showing that they had learned two general principles that could be applied to stimuli that they had not yet experienced. The most prevalent neuronal activity observed in the PFC reflected the coding of these abstract rules.

Animals↗
PubMed2001

Categorical representation of visual stimuli in the primate prefrontal cortex.

The ability to group stimuli into meaningful categories is a fundamental cognitive process. To explore its neural 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 the category boundary. Neural activity in the lateral prefrontal cortex reflected the category of visual stimuli, even when a monkey was retrained with the stimuli assigned to new categories.

Animals↗
PubMed2001

Responses of neurons in macaque area V4 during memory-guided visual search.

In a typical scene with many different objects, attentional mechanisms are needed to select relevant objects for visual processing and control over behavior. To test the role of area V4 in the selection of objects based on non-spatial features, we recorded from V4 neurons in the monkey, using a visual search paradigm. A cue stimulus was presented at the center of gaze, followed by a blank delay period. After the delay, a two-stimulus array was presented extrafoveally, and the monkey was rewarded for detecting the target stimulus matching the cue. The array was composed of one 'good' stimulus (effective in driving the cell when presented alone) and one 'poor' stimulus (ineffective in driving the cell when presented alone). When the choice array was presented in the receptive field (RF) of the neuron, many cells showed suppressive interactions between the stimuli as well as strong attention effects. Within 150--200 ms of array onset, responses to the array were determined by the target stimulus. If the target was the good stimulus, the response to the array became equal to the response to the good stimulus presented alone. If the target was the poor stimulus, the response approached the response to that stimulus presented alone. Thus the influence of the nontarget stimulus was filtered out. These effects were reduced or eliminated when the poor stimulus was located outside the RF and, therefore, no longer competing for the cell's response. Overall, the results support a 'biased competition' model of attention, according to which objects in the visual field compete for representation in the cortex, and this competition is biased in favor of the behaviorally relevant object.

Animals↗
PubMed2001

An integrative theory of prefrontal cortex function.

The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed

Animals↗
PubMed2000

Effects of visual experience on the representation of objects in the prefrontal cortex.

The perception and recognition of objects are improved by experience. Here, we show that monkeys' ability to recognize degraded objects was improved by several days of practice with these objects. This improvement was reflected in the activity of neurons in the prefrontal (PF) cortex, a brain region critical for a wide range of visual behaviors. Familiar objects activated fewer neurons than did novel objects, but these neurons were more narrowly tuned, and the object representation was more resistant to the effects of degradation, after experience. These results demonstrate a neural correlate of visual learning in the PF cortex of adult monkeys.

Animals↗
PubMed2000

The prefrontal cortex and cognitive control.

One of the enduring mysteries of brain function concerns the process of cognitive control. How does complex and seemingly willful behaviour emerge from interactions between millions of neurons? This has long been suspected to depend on the prefrontal cortex--the neocortex at the anterior end of the brain--but now we are beginning to uncover its neural basis. Nearly all intended behaviour is learned and so depends on a cognitive system that can acquire and implement the 'rules of the game' needed to achieve a given goal in a given situation. Studies indicate that the prefrontal cortex is central in this process. It provides an infrastructure for synthesizing a diverse range of information that lays the foundation for the complex forms of behaviour observed in primates.

Animals↗
PubMed2000

Task-specific neural activity in the primate prefrontal cortex.

Real-world behavior is typically more complicated than a one-to-one mapping between a stimulus and response; the same stimulus can lead to different behaviors depending on the situation, or the same behavior may be cued by different stimuli. In such cases, knowledge of the formal demands of the task at hand is required. We found that in monkeys trained to alternate between three tasks, the activity of many neurons in the prefrontal cortex was task dependent. This included changes in overall firing rate, in firing-rate profiles (shape of responses over time), and in stimulus and response selectivity. These findings support the hypothesis that a major prefrontal function is the acquisition and implementation of task context and the "rules" used to guide behavior.

Animals↗
PubMed1999

Prospective coding for objects in primate prefrontal cortex.

We examined neural activity in prefrontal (PF) cortex of monkeys performing a delayed paired associate task. Monkeys were cued with a sample object. Then, after a delay, a test object was presented. If the test object was the object associated with the sample during training (i.e., its target), they had to release a lever. Monkeys could bridge the delay by remembering the sample (a sensory-related code) and/or thinking ahead to the expected target (a prospective code). Examination of the monkeys' behavior suggested that they were relying on a prospective code. During and shortly after sample presentation, neural activity in the lateral PF cortex primarily reflected the sample. Toward the end of the delay, however, PF activity began to reflect the anticipated target, which indicated a prospective code. These results provide further confirmation that PF cortex does not simply buffer incoming visual inputs, but instead selectively processes information relevant to current behavioral demands, even when this information must be recalled from long-term memory.

Action Potentials↗
PubMed1998

Memory fields of neurons in the primate prefrontal cortex.

Many prefrontal (PF) neurons convey information about both an object's identity (what) and its location (where). To explore how they represent conjunctions of what and where, we explored the receptive fields of their mnemonic activity (i.e., their "memory fields") by requiring monkeys to remember both an object and its location at many positions throughout a wide portion of central vision. Many PF neurons conveyed object information and had highly localized memory fields that emphasized the contralateral, but not necessarily foveal, visual field. These results indicate that PF neurons can simultaneously convey precise location and object information and thus may play a role in constructing a unified representation of a visual scene.

Animals↗
PubMed1998

Selective representation of relevant information by neurons in the primate prefrontal cortex.

The severe limitation of the capacity of working memory, the ability to store temporarily and manipulate information, necessitates mechanisms that restrict access to it. Here we report tests to discover whether the activity of neurons in the prefrontal (PF) cortex, the putative neural correlate of working memory, might reflect these mechanisms and preferentially represent behaviourally relevant information. Monkeys performed a 'delayed-matching-to-sample' task with an array of three objects. Only one of the objects in the array was relevant for task performance and the monkeys needed to find that object (the target) and remember its location. For many PF neurons, activity to physically identical arrays varied with the target location; the location of the non-target objects had little or no influence on activity. Information about the target location was present in activity as early as 140ms after array onset. Also, information about which object was the target was reflected in the sustained activity of many PF neurons. These results suggest that the prefrontal cortex is involved in selecting and maintaining behaviourally relevant information.

Animals↗
PubMed1998

Neural activity in the primate prefrontal cortex during associative learning.

The prefrontal (PF) cortex has been implicated in the remarkable ability of primates to form and rearrange arbitrary associations rapidly. This ability was studied in two monkeys, using a task that required them to learn to make specific saccades in response to particular cues and then repeatedly reverse these responses. We found that the activity of individual PF neurons represented both the cues and the associated responses, perhaps providing a neural substrate for their association. Furthermore, during learning, neural activity conveyed the direction of the animals' impending responses progressively earlier within each successive trial. The final level of activity just before the response, however, was unaffected by learning. These results suggest a role for the PF cortex in learning arbitrary cue-response associations, an ability critical for complex behavior.

Animals↗
PubMed1998

Responses of neurons in inferior temporal cortex during memory-guided visual search.

Responses of neurons in inferior temporal cortex during memory-guided visual search. J. Neurophysiol. 80: 2918-2940, 1998. A typical scene will contain many different objects, few of which are relevant to behavior at any given moment. Thus attentional mechanisms are needed to select relevant objects for visual processing and control over behavior. We examined this role of attention in the inferior temporal cortex of macaque monkeys, using a visual search paradigm. While the monkey maintained fixation, a cue stimulus was presented at the center of gaze, followed by a blank delay period. After the delay, an array of two to five choice stimuli was presented extrafoveally, and the monkey was rewarded for detecting a target stimulus matching the cue. The behavioral response was a saccadic eye movement to the target in one version of the task and a lever release in another. The array was composed of one "good" stimulus (effective in driving the cell when presented alone) and one or more "poor" stimuli (ineffective in driving the cell when presented alone). Most cells showed higher delay activity after a good stimulus used as the cue than after a poor stimulus. The baseline activity of cells was also higher preceding a good cue, if the animal expected it to occur. This activity may depend on a top-down bias in favor of cells coding the relevant stimulus. When the choice array was presented, most cells showed suppressive interactions between the stimuli as well as strong attention effects. When the choice array was presented in the contralateral visual field, most cells initially responded the same, regardless of which stimulus was the target. However, within 150-200 ms of array onset, responses were determined by the target stimulus. If the target was the good stimulus, the response to the array became equal to the response to the good stimulus presented alone. If the target was a poor stimulus, the response approached the response to that stimulus presented alone. Thus the influence of the nontarget stimulus was eliminated. These effects occurred well in advance of the behavioral response. When the array was positioned with stimuli on opposite sides of the vertical meridian, the contralateral stimulus appeared to dominate the response, and this dominant effect could not be overcome by attention. Overall, the results support a "biased competition" model of attention, according to which 1) objects in the visual field compete for representation in the cortex, and 2) this competition is biased in favor of the behaviorally relevant object by virtue of "top-down" feedback from structures involved in working memory.

Animals↗
PubMed1997

Integration of what and where in the primate prefrontal cortex.

The visual system separates processing of an object's form and color ("what") from its spatial location ("where"). In order to direct action to objects, the identity and location of those objects must somehow be integrated. To examine whether this process occurs within the prefrontal (PF) cortex, the activity of 195 PF neurons was recorded during a task that engaged both what and where working memory. Some neurons showed either object-tuned (what) or location-tuned (where) delay activity. However, over half (52 percent, or 64/123) of the PF neurons with delay activity showed both what and where tuning. These neurons may contribute to the linking of object information with the spatial information needed to guide behavior.

Animals↗
PubMed1997

Object and place memory in the macaque entorhinal cortex.

Lesions of the entorhinal cortex in humans, monkeys, and rats impair memory for a variety of kinds of information, including memory for objects and places. To begin to understand the contribution of entorhinal cells to different forms of memory, responses of entorhinal cells were recorded as monkeys performed either an object or place memory task. The object memory task was a variation of delayed matching to sample. A sample picture was presented at the start of the trial, followed by a variable sequence of zero to four test pictures, ending with a repetition of the sample (i.e., a match). The place memory task was a variation of delayed matching to place. In this task, a cue stimulus was presented at a variable sequence of one to four "places" on a computer screen, ending with a repetition of one of the previously shown places (i.e., a match). For both tasks, the animals were rewarded for releasing a bar to the match. To solve these tasks, the monkey must 1) discriminate the stimuli, 2) maintain a memory of the appropriate stimuli during the course of the trial, and 3) evaluate whether a test stimulus matches previously presented stimuli. The responses of entorhinal cortex neurons were consistent with a role in all three of these processes in both tasks. We found that 47% and 55% of the visually responsive entorhinal cells responded selectively to the different objects or places presented during the object or place task, respectively. Similar to previous findings in prefrontal but not perirhinal cortex on the object task, some entorhinal cells had sample-specific delay activity that was maintained throughout all of the delay intervals in the sequence. For the place task, some cells had location-specific maintained activity in the delay immediately following a specific cue location. In addition, 59% and 22% of the visually responsive cells recorded during the object and place task, respectively, responded differently to the test stimuli according to whether they were matching or non-matching to the stimuli held in memory. Responses of some cells were enhanced to matching stimuli, whereas others were suppressed. This suppression or enhancement typically occurred well before the animals' behavioral response, suggesting that this information could be used to perform the task. These results indicate that entorhinal cells receive sensory information about both objects and spatial locations and that their activity carries information about objects and locations held in short-term memory.

Analysis of Variance↗