SEARCH · PubMed Health

Results for “Prefrontal Cortex”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources

PubMed1999

Gonadectomy in adult life increases tyrosine hydroxylase immunoreactivity in the prefrontal cortex and decreases open field activity in male rats.

The prefrontal cortices in rats participate in a range of cognitive, emotional, and locomotor functions that are dependent on its rich catecholamine innervation. Sex differences identified in many of these functions suggest that the prefrontal cortex is also influenced by gonadal hormones. Previous studies have shown that prefrontal catecholamines can be modified by changes in the hormone environment in developing animals. The present analyses, carried out in male rats gonadectomized as adults, with and without supplementation with testosterone proprionate, and examined at intervals from two days to 10 weeks after surgery, revealed that both the anatomical organization of prefrontal catecholamine afferents, and a behavioral measure sensitive to their selective lesioning remain highly responsive to changes in testicular hormones in adulthood. Thus, gonadectomy in adult male rats rapidly led to a large but transient decrease in the density of tyrosine hydroxylase immunoreactivity in all layers of the dorsal anterior cingulate cortex. This was followed by a sustained period in which immunoreactivity in the supragranular layers returned to levels that were just below normal (between 72 and 79% of normal), and labeling in deep laminae stabilized at considerably elevated innervation densities (approximately 150% of normal). Neither the acute decrease nor the chronic over-innervation characteristic of gonadectomized animals was observed in rats that were gonadectomized and supplemented with testosterone proprionate. Open field activity assessed along a corresponding 10 week timeline showed that gonadectomized animals were significantly less active than hormonally intact controls, a behavioral pattern opposite to the hyperactivity which persists following prefrontal dopamine lesions. Gonadectomized animals supplemented with testosterone proprionate, on the other hand, had open field scores that were not significantly different from controls. Taken together, these findings indicate that the adult hormone environment provides a significant, and seemingly functionally significant influence over the catecholamine innervation of the rat prefrontal cortex. Such lifelong responsiveness of the prefrontal cortical catecholamines to circulating hormones suggests that gonadal steroids are an active component of the biology of normal adult cognition, and may also have relevance for cortical dysfunction in disorders such as schizophrenia which are not only strongly tied to the catecholamines, but exhibit considerable biases among men and women as well.

Age Factors↗

PubMed1996

Effect of a pharmacological stressor on glutamate efflux in the prefrontal cortex.

The anxiogenic beta-carboline, FG 7142 (20 mg/kg) significantly increased glutamate efflux in the prefrontal cortex of conscious rats as assessed by microdialysis. Pretreatment with the benzodiazepine receptor agonist, diazepam (5 mg/kg), abolished this effect. These findings indicate that anxiogenic compounds produce an effect similar to physical stressors on the outflow of glutamate, and implicate the GABA/benzodiazepine receptor complex in the stress-induced activation of glutamate systems in the prefrontal cortex.

Animals↗

PubMed2003

Distribution of mGluR1alpha and mGluR5 immunolabeling in primate prefrontal cortex.

Metabotropic glutamate receptors (mGluRs) mediate important modulatory glutamatergic influences throughout the brain. However, the specific localization and functions of group I mGluR subtypes (mGluR1alpha and mGluR5) in cortical neurotransmission are not well known, particularly in primates. To address this issue, we used immunoelectron microscopy to compare the subcellular localizations of mGluR1alpha and mGluR5 in the prefrontal cortex of macaque monkeys. Both receptor subtypes were found in a variety of subcellular compartments, including spines, dendrites, preterminal axons, axon terminals, and glia; however, quantitative differences were found in the relative abundance of labeled elements for each receptor. The mGluR1alpha-immunoreactive (-IR) elements were overwhelmingly the spines and dendrites, with labeled terminals, axons, and glia seen more rarely. The mGluR5-IR elements were also mostly spines and dendrites, but the proportion of labeled unmyelinated axons, terminals, and glia was higher than for mGluR1alpha-IR elements. Double labeling with SMI-32 and parvalbumin confirmed that both receptors were found in pyramidal cell and interneuron dendrites. The localization of mGluR1alpha to pyramidal cells in primate cortex contrasts with reports that mGluR1alpha is found almost exclusively in interneurons in rodent cortex. By using double labeling, we found no evidence for mGluR1alpha or mGluR5 in dopaminergic afferents to prefrontal cortex. The data presented here provide an anatomical substrate for a differential role of mGluR1alpha and mGluR5 in post-and presynaptic actions of glutamate in primate prefrontal cortex. They further suggest differences in the cortical distribution of group I mGluRs between primates and rodents.

Animals↗

PubMed1994

6-Hydroxydopamine lesions of the prefrontal cortex in monkeys enhance performance on an analog of the Wisconsin Card Sort Test: possible interactions with subcortical dopamine.

The effects of 6-hydroxydopamine lesions of the prefrontal cortex in monkeys were investigated on two cognitive tests of prefrontal function, spatial delayed response, and attentional set shifting. The latter test provided a componential analysis of the Wisconsin Card Sort Test, a commonly used clinical test of frontal lobe function in man. Acquisition of a visual compound discrimination requiring a shift of attention from one dimension to another (extradimensional shift), for example, shapes to lines, was significantly improved. This enhancement was behaviorally specific in that there were no effects on acquisition of a discrimination that required the continued maintenance of an attentional set toward one particular dimension (intradimensional shift), nor any effects on a series of visual or spatial discrimination reversals that involved the repeated shifting of responding between two exemplars from the same dimension. In contrast, spatial delayed response performance was impaired, in agreement with previous results. Neurochemical measures showed a marked depletion of dopamine limited to the prefrontal cortex and a smaller loss of prefrontal noradrenaline. This was accompanied by a long-term adaptive change in the striatum such that extracellular dopamine in the caudate nucleus, as measured by in vivo microdialysis, was elevated in response to potassium stimulation as long as 18 months postsurgery. It is proposed that attentional set shifting is mediated by a balanced interaction between prefrontal and striatal dopamine, and that elevated dopamine contributes to the improvement in attentional set-shifting ability. This interpretation is consistent with the impairment in attentional set-shifting ability observed in patients with Parkinson's disease or with damage to the frontal lobes using the same test as used here for infrahuman primates.

Animals↗

PubMed2003

Persistent activity in the prefrontal cortex during working memory.

The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in working memory. Notably, persistent activity in the DLPFC is often observed during the retention interval of delayed response tasks. The code carried by the persistent activity remains unclear, however. We critically evaluate how well recent findings from functional magnetic resonance imaging studies are compatible with current models of the role of the DLFPC in working memory. These new findings suggest that the DLPFC aids in the maintenance of information by directing attention to internal representations of sensory stimuli and motor plans that are stored in more posterior regions.

Journal Article↗

PubMed2004

The role of the medial prefrontal cortex in human religious activity.

Although religious practices are ubiquitous and universal throughout human history, their biological basis is little understood, particularly at the neural level. In this paper, I will first review the current understanding of the neural basis of human religious activity, and then present a hypothesis that the medial prefrontal cortex plays a vital role in the integrity of religious activity. In this hypothesis, optimal functions of the medial prefrontal cortex, such as error detection, compliance to social norms, self-reflection, and theory of mind, are a key prerequisite to the maintenance of integrated religious activity. Hyperreligiosity may result from the hyperfunction of the medial prefrontal cortex, including rigid legalism (excessive error detection), excessive concern over one's existence (excessive self-reflection), and delusional interpretation of God's mind (excess of theory of mind). Future research based on this hypothesis is proposed, and the potential implication of this hypothesis on our society is also discussed.

Forecasting↗

PubMed2007

TIMP-1 abolishes MMP-9-dependent long-lasting long-term potentiation in the prefrontal cortex.

BACKGROUND: Understanding of the molecular mechanisms of prefrontal cortex (PFC) plasticity is important for developing new treatment strategies for mental disorders such as depression and schizophrenia. Long-term potentiation (LTP) is a valid model for synaptic plasticity. The extracellular proteolytic system composed of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) has recently been shown to play major role in the hippocampal plasticity. METHODS: We tested whether induction of hippocampal-prefrontal LTP results in accumulation of tissue inhibitor of MMP-1, TIMP-1 mRNA, in the PFC of rats and whether adenovirally driven overexpression of TIMP-1 affects LTP. Additional study of slices was done with a specific MMP-9 inhibitor. RESULTS: The TIMP-1 is induced in the rat medial PFC by stimuli evoking late LTP; its overexpression blocks the gelatinolytic activity of the MMP family; its overexpression before tetanization blocks late LTP in vivo; and MMP-9 inhibitor prevents late LTP in vitro. CONCLUSIONS: We suggest a novel extracellular mechanism of late LTP in the PFC, engaging TIMP-1-controlled proteolysis as an element of information integration. Our results may also be meaningful to an understanding of mental diseases and development of new treatment strategies that are based on extracellular mechanisms of synaptic plasticity.

Animals↗

PubMedDate not supplied

Failure to respond autonomically to anticipated future outcomes following damage to prefrontal cortex.

Following damage to specific sectors of the prefrontal cortex, humans develop a defect in real-life decision making, in spite of otherwise normal intellectual performance. The patients so affected may even realize the consequences of their actions but fail to act accordingly, thus appearing oblivious to the future. The neural basis of this defect has resisted explanation. Here we identify a physiological correlate for the defect and discuss its possible significance. We measured the skin conductance responses (SCRs) of 7 patients with prefrontal damage, and 12 normal controls, during the performance of a novel task, a card game that simulates real-life decision making in the way it factors uncertainty, rewards, and penalties. Both patients and controls generated SCRs after selecting cards that were followed by penalties or by reward. However, after a number of trials, controls also began to generate SCRs prior to their selection of a card, while they pondered from which deck to choose, but no patients showed such anticipatory SCRs. The absence of anticipatory SCRs in patients with prefrontal damage is a correlate of their insensitivity to future outcomes. It is compatible with the idea that these patients fail to activate biasing signals that would serve as value markers in the distinction between choices with good or bad future outcomes; that these signals also participate in the enhancement of attention and working memory relative to representations pertinent to the decision process; and that the signals hail from the bioregulatory machinery that sustains somatic homeostasis and can be expressed in emotion and feeling.

Adult↗

PubMed1998

The role of prefrontal cortex in working memory: examining the contents of consciousness.

Working memory enables us to hold in our 'mind's eye' the contents of our conscious awareness, even in the absence of sensory input, by maintaining an active representation of information for a brief period of time. In this review we consider the functional organization of the prefrontal cortex and its role in this cognitive process. First, we present evidence from brain-imaging studies that prefrontal cortex shows sustained activity during the delay period of visual working memory tasks, indicating that this cortex maintains on-line representations of stimuli after they are removed from view. We then present evidence for domain specificity within frontal cortex based on the type of information, with object working memory mediated by more ventral frontal regions and spatial working memory mediated by more dorsal frontal regions. We also propose that a second dimension for domain specificity within prefrontal cortex might exist for object working memory on the basis of the type of representation, with analytic representations maintained preferentially in the left hemisphere and image-based representations maintained preferentially in the right hemisphere. Furthermore, we discuss the possibility that there are prefrontal areas brought into play during the monitoring and manipulation of information in working memory in addition to those engaged during the maintenance of this information. Finally, we consider the relationship of prefrontal areas important for working memory, both to posterior visual processing areas and to prefrontal areas associated with long-term memory.

Animals↗

PubMed2002

Contributions of the prefrontal cortex to the neural basis of human decision making.

The neural basis of decision making has been an elusive concept largely due to the many subprocesses associated with it. Recent efforts involving neuroimaging, neuropsychological studies, and animal work indicate that the prefrontal cortex plays a central role in several of these subprocesses. The frontal lobes are involved in tasks ranging from making binary choices to making multi-attribute decisions that require explicit deliberation and integration of diverse sources of information. In categorizing different aspects of decision making, a division of the prefrontal cortex into three primary regions is proposed. (1) The orbitofrontal and ventromedial areas are most relevant to deciding based on reward values and contribute affective information regarding decision attributes and options. (2) Dorsolateral prefrontal cortex is critical in making decisions that call for the consideration of multiple sources of information, and may recruit separable areas when making well defined versus poorly defined decisions. (3) The anterior and ventral cingulate cortex appear especially relevant in sorting among conflicting options, as well as signaling outcome-relevant information. This topic is broadly relevant to cognitive neuroscience as a discipline, as it generally comprises several aspects of cognition and may involve numerous brain regions depending on the situation. The review concludes with a summary of how these regions may interact in deciding and possible future research directions for the field.

Adaptation, Psychological↗

PubMed1998

Local activation of metabotropic glutamate receptors inhibits the handling-induced increased release of dopamine in the nucleus accumbens but not that of dopamine or noradrenaline in the prefrontal cortex: comparison with inhibition of ionotropic receptors.

On-line in vivo microdialysis was used to determine the effects of a 16-min handling period on release of dopamine (DA) in the nucleus accumbens and of DA and noradrenaline (NA) in the medial prefrontal cortex of awake, freely moving rats. DA and NA were determined in one HPLC run. Handling resulted in an immediate and strong increase of both catecholamines in the prefrontal cortex. Maximal values for DA were 295%, and for NA 225%, of controls. DA in the nucleus accumbens was also increased (to 135% of controls) but only after a short delay. Local inhibition of ionotropic glutamate receptors by continuous reversed dialysis of the drugs 6-cyano-7-nitroquinoxaline, D-2-amino-5-phosphonopentanoic acid, or dizocilpine did not significantly affect handling-induced increases in cortical DA and NA release. Neither did the agonist of metabotropic glutamate receptors, trans-(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), or the GABA-B agonist baclofen. Reversed dialysis of dizocilpine in the nucleus accumbens was equally ineffective, but ACPD inhibited the increase in DA release in this area. Stimulation of metabotropic glutamate receptors in the nucleus accumbens was previously reported to inhibit activation of DA release in that area after stimulation of glutamatergic or dopaminergic afferents. It is concluded that metabotropic receptors in the nucleus accumbens are important for the control of activation of DA release in the accumbens by physiological stimuli but that a similar mechanism is lacking in the prefrontal cortex.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2006

Perinatal allopregnanolone influences prefrontal cortex structure, connectivity and behavior in adult rats.

Cortical neurosteroid levels vary dramatically across development; during the second week of life elevated levels of allopregnanolone are associated with decreased GABA(A) receptor function. Since GABA(A) receptor modulation plays a role in proliferative regulation in developing neocortex, it is possible that endogenous neurosteroids such as allopregnanolone, acting through GABA(A) receptors, modulate cortical development. We augmented normally low levels with exogenous administration of allopregnanolone (10 mg/kg) during the first week of rodent life. The localization of parvalbumin-labeled cells was markedly altered; the ratio of cell number in the deep (layers V-VI) vs. superficial (layers I-III) layers of adult prefrontal cortex increased two-fold in rats administered allopregnanolone on postnatal day 1 or 5. The mechanism underlying these anatomical changes likely involves GABA(A) receptors because similar changes in interneuron placement were observed after neonatal benzodiazepine administration. Measures of mature cortical function were also altered after neonatal neurosteroid administration, including [(3)H]MK-801 binding, prepulse inhibition and amphetamine-induced locomotor activity. Moreover, neonatal allopregnanolone administration increases the number of parvalbumin-expressing neurons in medial dorsal nucleus of the thalamus while the total neuron number is decreased. These findings suggest that connectivity between the medial dorsal nucleus of the thalamus and prefrontal cortex is likely altered by neonatal neurosteroid administration and may result in a disinhibited frontal cortex. Disinhibition in the prefrontal cortex is associated with behavioral changes relevant to human psychosis and developmental disorders. If neurosteroids play a role in normal development of prefrontal/medial dorsal patency as suggested by these studies, then alterations in neurosteroid levels may contribute to abnormal neurodevelopment.

Animals↗

PubMed1999

Impairment of social and moral behavior related to early damage in human prefrontal cortex.

The long-term consequences of early prefrontal cortex lesions occurring before 16 months were investigated in two adults. As is the case when such damage occurs in adulthood, the two early-onset patients had severely impaired social behavior despite normal basic cognitive abilities, and showed insensitivity to future consequences of decisions, defective autonomic responses to punishment contingencies and failure to respond to behavioral interventions. Unlike adult-onset patients, however, the two patients had defective social and moral reasoning, suggesting that the acquisition of complex social conventions and moral rules had been impaired. Thus early-onset prefrontal damage resulted in a syndrome resembling psychopathy.

Adult↗

PubMed1994

Increase of extracellular dopamine in the prefrontal cortex: a trait of drugs with antidepressant potential?

Drugs differing in their primary mechanism of action but having in common the ability to act as antidepressants such as fluoxetine (10 mg/kg SC), clomipramine (10 mg/kg IP), imipramine (10 mg/kg IP), desipramine (10 mg/kg IP) and (+/-) 8-OHDPAT (0.03 mg/kg SC) increase extracellular concentrations of dopamine in the rat prefrontal cortex but not in the medial nucleus accumbens. Buspirone (1 mg/kg SC) increased dopamine both in the prefrontal cortex and in the nucleus accumbens. Extracellular 5HT was increased by fluoxetine, clomipramine and imipramine but not by desipramine while 8-OHDPAT and buspirone decreased it. These results raise the possibility that the property of stimulating dopamine transmission in the prefrontal cortex has a role in the antidepressant properties of these drugs.

Animals↗

PubMed1998

Antipsychotic drugs induce similar effects on the release of dopamine and noradrenaline in the medial prefrontal cortex of the rat brain.

In the present study we have compared the effects of the classical antipsychotic drug haloperidol and four different atypical antipsychotics (clozapine, risperidone, olanzapine, ziprasidone) on extracellular levels of dopamine and noradrenaline in the medial prefrontal cortex (MPFC) of conscious rats. Haloperidol (10, 100 and 800 nmol/kg), clozapine (0.3, 1, 10 and 30 micromol/kg), risperidone (100, 500 and 5000 nmol/kg), olanzapine (10, 100 and 500 nmol/kg) and ziprasidone (10, 100 and 1000 nmol/kg) were administered subcutaneously to rats. All compounds induced increases in dialysate levels of dopamine and noradrenaline in the medial prefrontal cortex. The increases induced by the four antipsychotic agents in extracellular levels of dopamine and noradrenaline displayed a striking co-variation both in dose and time. A similar co-variation was seen in the decrease of dopamine and noradrenaline, after administration of a low dose (30 nmol/kg, s.c.) of the dopamine D2/3 receptor agonist (+)-7-hydroxy-2-(N,N-di-n-propylamino) tetralin ((+)-7-OH-DPAT). It is concluded that there is a close coupling between the release of dopamine and noradrenaline in the medial prefrontal cortex. The mechanism of action of this interaction, that might be of importance for a better understanding of the mechanism of action of antipsychotic drugs, is discussed.

Animals↗

PubMed1994

Coactivation of prefrontal cortex and inferior parietal cortex in working memory tasks revealed by 2DG functional mapping in the rhesus monkey.

Functional studies of the dorsolateral prefrontal cortex and the inferior parietal lobe of the rhesus monkey have implicated the former in spatial mnemonic function and the latter in visuospatial processing. We used the 14C-2-deoxyglucose (2DG) method to assess the contribution of these cortical regions to the cognitive performance of monkeys on working memory tasks. In these experiments, one group of monkeys (WORK) was trained to perform tasks (delayed spatial alternation, spatial delayed response, or delayed object alternation) that specifically engaged working memory processing. Local cerebral glucose utilization (LCGU) rates in the WORK group was compared with LCGU rates for a second group of monkeys (CONT) tested on one of two tasks (visual pattern discrimination or sensory-motor) that relied upon associative memory. The results showed that in comparison to the CONT group, working memory performance significantly enhanced LCGU by 19% in the principal sulcus region of prefrontal cortex and by 11-20% in regions of the inferior parietal cortex corresponding to areas 7A, 7B, 7IP, and 7M. By contrast, LCGU in the auditory cortex was similar for both groups. In all areas examined, metabolic activation peaked in lower layer III where the majority of associational and callosal neurons lie. Correlation analyses of LCGU and behavioral task parameters indicated that LCGU in the parietal subdivisions was significantly related either to the accuracy of performance or to the number of trials completed on the 2DG test. In contrast, LCGU in the principal sulcus was positively correlated with task difficulty. These findings suggest that the enhancement of LCGU in the principal sulcus was primarily influenced by the mnemonic components of the tasks whereas LCGU in the inferior parietal cortex was influenced by their sensory-motor demands. These are the first results showing concurrent metabolic activation of the prefrontal and parietal cortex in monkeys performing working memory tasks and they support the suggestion that these cortical regions represent two important nodes in a neural network mediating spatial working memory in the monkey (Goldman-Rakic, 1988). Further, the present report reinforces the power of the 2DG method for functional mapping as these areal and laminar results could not be readily appreciated at this resolution in any other methodological context.

Animals↗

PubMed2004

Altered neurotrophin receptor function in the developing prefrontal cortex leads to adult-onset dopaminergic hyperresponsivity and impaired prepulse inhibition of acoustic startle.

BACKGROUND: Survival and differentiation of neurons and the formation and maintenance of synapses in the cerebral cortex may be affected in schizophrenia. Since neurotrophins play an important role in these events, behavioral effects relevant to schizophrenia were investigated in rats that had compromised neurotrophin function during prefrontal cortical development. METHODS: Neonatal rat pups were injected into the developing prefrontal cortex with a depot preparation of p75 receptor antibody conjugated to saporin. Animals were tested for dopaminergic hyperresponsivity and prepulse inhibition of acoustic startle at 5 or 10 weeks. Neonatal and adult brain sections were examined for morphologic abnormality. RESULTS: Animals that received neonatal injections of p75 antibody conjugated to saporin showed significantly increased amphetamine-induced locomotion and rearing and impairment of prepulse inhibition of acoustic startle at 10 weeks of age but not at 5 weeks. Examination of adult brain sections revealed apparently normal structure, whereas neonatal brain sections showed apoptotic cells in the developing prefrontal cortex in pups that received p75 antibody conjugated to saporin. CONCLUSIONS: Compromised p75 neurotrophin receptor function in the developing prefrontal cortex may be associated with the manifestation of adult-onset dopaminergic hyperresponsivity and impaired prepulse inhibition and therefore may be involved in the pathogenesis of schizophrenia.

Acoustic Stimulation↗

PubMed1994

CRF receptor antagonist attenuates stress-induced noradrenaline release in the medial prefrontal cortex of rats.

Noradrenaline release in rat medial prefrontal cortex (PFC) was measured using a brain microdialysis technique. Immobilization stress increased noradrenaline release to a maximum level of 248.7 +/- 12.8% of the basal release, which was significantly attenuated by preinjection of alpha-helical CRF9-41 (50 micrograms/rat) into the lateral cerebroventricle. Intracerebroventricular injection of CRF also increased noradrenaline release in the medial PFC. These results suggest that immobilization-stress facilitates noradrenaline release in the medial PFC through activation of the CRF system in the brain.

Animals↗