The prefrontal cortex: no simple matter.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
E K Miller
Publications and source records attributed to E K Miller.
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↗
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↗
Neurobiology. Straight from the top.
Explore the source record for details and available documents.
Animals↗
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↗
The prefrontal cortex: complex neural properties for complex behavior.
Explore the source record for details and available documents.
Animals↗
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↗
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↗
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↗
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↗
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↗
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↗
Neural mechanisms of visual working memory in prefrontal cortex of the macaque.
Prefrontal (PF) cells were studied in monkeys performing a delayed matching to sample task, which requires working memory. The stimuli were complex visual patterns and to solve the task, the monkeys had to discriminate among the stimuli, maintain a memory of the sample stimulus during the delay periods, and evaluate whether a test stimulus matched the sample presented earlier in the trial. PF cells have properties consistent with a role in all three of these operations. Approximately 25% of the cells responded selectively to different visual stimuli. Half of the cells showed heightened activity during the delay after the sample and, for many of these cells, the magnitude of delay activity was selective for different samples. Finally, more than half of the cells responded differently to the test stimuli depending on whether they matched the sample. Because inferior temporal (IT) cortex also is important for working memory, we compared PF cells with IT cells studied in the same task. Compared with IT cortex, PF responses were less often stimulus-selective but conveyed more information about whether a given test stimulus was a match to the sample. Furthermore, sample-selective delay activity in PF cortex was maintained throughout the trial even when other test stimuli intervened during the delay, whereas delay activity in IT cortex was disrupted by intervening stimuli. The results suggest that PF cortex plays a primary role in working memory tasks and may be a source of feedback inputs to IT cortex, biasing activity in favor of behaviorally relevant stimuli.
Animals↗
The lack of predictive value of prostate specific antigen density in the detection of prostate cancer in patients with normal rectal examinations and intermediate prostate specific antigen levels.
PURPOSE: The management of patients with a normal digital rectal examination and a prostate specific antigen (PSA) level of 4.0 to 10.0 ng./ml. remains controversial. To improve the specificity of cancer detection in this group, PSA density has been recommended with biopsies based on a PSA density of 0.15 or more. To evaluate PSA density as a discriminator of prostate cancer we enrolled patients in a prospective study. MATERIALS AND METHODS: A prospective evaluation was done of 44 consecutive patients with a palpably normal digital rectal examination and a serum PSA level of 4.0 to 10.0 ng./ml. enrolled during a 13-month period. All patients underwent transrectal ultrasound with sextant biopsies regardless of calculated PSA density. RESULTS: Overall, 8 of 44 men (18%) had prostate cancer. There was no significant difference in the mean PSA density between the patients with positive and negative biopsies (mean 0.12 and 0.15, respectively, p = 0.258). Also, there was no significant association between PSA or PSA density and a positive biopsy in multivariate analysis (p = 0.863). Receiver operating characteristic curves for PSA and PSA density failed to demonstrate any superior benefit for PSA density in this patient population. A PSA density of 0.15 was an unreliable indicator of cancer (sensitivity 12.5%, specificity 61.1% and positive predictive value 6.7%). CONCLUSIONS: In our study, PSA density did not discriminate between patients with positive and negative biopsies, and in fact most cancers would not have been detected if a PSA density of 0.15 or more had been used as the sole indication for biopsy. Therefore, we recommend systematic biopsies in these patients independent of calculated PSA density.
Aged↗
Liver biopsy findings in patients with alcoholic liver disease complicated by chronic hepatitis C virus infection.
OBJECTIVE: To identify the features of concurrent hepatitis C virus (HCV) infection in liver biopsies from patients thought to have alcoholic liver disease. PATIENTS: Fifty-five patients with a history of excess alcohol consumption were studied. METHODS: All patients underwent liver biopsy. RESULTS: Eight of the 55 patients studied were found to be HCV-positive. CONCLUSION: The histological features found to be most useful for identifying concurrent HCV infection were the presence of lymphoid aggregates in portal tracts (predictive value 100%), the presence of lymphocytes in the lobules (predictive value 83%), and the pattern of fibrosis, particularly periportal spurring rather than perivenular fibrosis (predictive value 75%).
Adult↗
Parallel neuronal mechanisms for short-term memory.
Although objects that have just been seen may persist in memory automatically for a time and interact passively with incoming stimulation, some tasks require that the memory be actively maintained and used. To test for the existence of separate automatic and volitional mechanisms of short-term memory, recordings were made from neurons in the inferior temporal cortex of monkeys while the monkeys held a sample picture "in mind" and signaled when it was repeated in a sequence of pictures, ignoring other stimulus repetitions. Some neurons were suppressed by any picture repetition, regardless of relevance, whereas others were enhanced, but only when a picture matched the sample. Short-term memory appears to reflect the parallel operation of these two mechanisms--one being automatic and the other active.
Analysis of Variance↗
Synthesis of platelet-derived growth factor by cells of splenic red pulp in normal rats.
A population of cells in the spleens of normal rats was found to contain platelet-derived growth factor (PDGF) B chain mRNA. These cells were found predominantly in the red pulp and nuclear morphology of some was consistent with that of macrophages. Similar cells were also shown by immunocytochemical staining to contain PDGF-AB/BB. These PDGF-positive cells were also found almost exclusively in the red pulp. It has been suggested by others that PDGF plays an important role in the function of the lymphohemopoietic microenvironment.
Animals↗
Cell size and the heat-shock response in rat brain.
The expression of mRNAs encoding two members of the heat-shock protein 70 family, the constitutively-expressed heat-shock cognate (hsc70) mRNA and the strictly heat-inducible (hsp70) mRNA, was quantitated in cerebellar and hippocampal cells of rats 3 h after amphetamine-induced or heat-induced hyperthermia. Intracellular heat-shock mRNA levels in specific cell types were compared with those of total polyadenylic acid [poly(A)] mRNA or 18S rRNA in the same cell type. Levels of poly(A) mRNAs, 18S rRNAs, and hsc70 mRNAs were highest in large neurons and lowest in glia. hsp70 mRNAs were also present at highest levels in large neurons, suggesting that hsp70 mRNAs accumulated as rapidly in these cell types as they did in small neurons and glia. However, compared with levels of intracellular poly(A) mRNAs or levels of rRNAs, large neurons contained two- to 12-fold lower levels of hsp70 mRNAs than neurons of intermediate size and five- to 30-fold lower levels than glia. These results suggest that hsp70 mRNAs accumulated as rapidly in large neurons as in small neurons and glia, but that the large size of these neurons precluded intracellular hsp70 mRNA concentrations increasing as quickly. The susceptibility of large neurons to stress-induced cell death could be due, in part, to their inability to synthesize rapidly hsp70 in sufficient amounts to protect these cells from the initial molecular consequences of stress.
Amphetamine↗