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 1,279 records · Page 71Linked to original sources

PubMed1997

Motivation-dependent activity in the dorsolateral part of the prefrontal cortex in the monkey.

Field potentials were recorded on self-paced hand and mouth movements with implanted electrodes on the surface and at 2.0-3.0 mm depth in respective cortical areas in seven monkeys. Surface-negative (s-N), depth-positive (d-P) premovement slow potentials were recorded in the prefrontal cortex only when the movements were performed with an intense motivation for a reward. Such a motivation-dependent activity was mainly obtained in the rostral bank of the arcuate sulcus on both sides (except for the inferior limb of the arcuate sulcus in the left hemisphere). Three of the seven monkeys were also tasked with visuo-initiated hand movements. As motivation for reward decreased, s-N, d-P potentials at a latency of about 80 ms after stimulus onset became gradually smaller in the rostral bank of the arcuate sulcus in the right hemisphere. These facts suggest that motivation-dependent activity is represented in the dorsolateral part of the prefrontal cortex in monkeys, and that the cortical part is involved in motivational functions as well as in cognitive functions.

Animals↗

PubMed2003

Dementia rating and nicotinic receptor expression in the prefrontal cortex in schizophrenia.

BACKGROUND: The etiology of dementia that occurs in patients with schizophrenia is not well understood. Nicotinic acetylcholine receptors have been implicated in cognitive function, and deficits in these receptors have been reported in schizophrenia. METHODS: The present study investigates possible associations of nicotinic receptor subunit expression in the dorsal lateral prefrontal cortex, an area known to be affected in schizophrenia, and dementia rating. RESULTS: alpha7 immunoreactivity was reduced by 20% to 28% and [(3)H]epibatidine binding was increased twofold in groups of patients with schizophrenia compared to normal control subjects matched for age, postmortem delay, and low levels of brain nicotine and cotinine. In contrast, no significant differences in alpha4, alpha3, or beta2 immunoreactivity or alpha7 messenger RNA expression were observed in schizophrenia patients compared with control subject values. Clinical dementia ratings in patients with schizophrenia were correlated with neither [(3)H]epibatidine binding nor nicotinic receptor subunit expression. CONCLUSIONS: These data indicate no relationship between the trend for reduced neocortical alpha7 subunit protein expression in schizophrenia and dementia. Further investigations are required to establish whether the reduction in alpha7 protein in the dorsal lateral prefrontal cortex is associated with clinical features other than dementia in schizophrenia.

Aged↗

PubMed1997

Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers.

OBJECTIVE: Agents that antagonize the N-methyl-D-aspartic acid (NMDA) receptor, such as phencyclidine and ketamine, produce an acute psychotic state in normal individuals that resembles some symptoms of schizophrenia. The aim of this study was to determine which brain regions are involved in NMDA receptor-mediated psychosis. METHOD: Positron emission tomography with [18F]fluorodeoxyglucose was used to determine cerebral metabolic activity in 17 healthy volunteers while an acute psychotic state was induced simultaneously by the administration of subanesthetic doses of ketamine. RESULTS: Ketamine produced focal increases in metabolic activity in the prefrontal cortex and an acute psychotic state. A change in one psychotic symptom, conceptual disorganization, was significantly related to prefrontal activation. CONCLUSIONS: These data suggest that the prefrontal cortex may be involved in mediating NMDA receptor-induced psychosis.

Adult↗

PubMed2001

Variations in extracellular monoamines in the prefrontal cortex and medial hypothalamus after modafinil administration: a microdialysis study in rats.

The role of brain amines in mediating the effects of the wake-promoting agent modafinil, used in the treatment of sleepiness associated with narcolepsy is still uncertain. Therefore we studied the effects of modafinil on extracellular serotonin (5-HT), dopamine (DA) and noradrenaline (NA), in rat prefrontal cortex and in the medial hypothalamus area. Modafinil (128 mg/kg i.p.) significantly increased waking in the first 4 h of EEG sleep recording. This cortical and behavioral activation was associated with an initial increase in extracellular 5-HT, DA and NA during the first 60 min following modafinil administration. In the prefrontal cortex, 5-HT release remained high for 3 h after modafinil administration. In contrast, in the hypothalamus, only NA release was enhanced while DA and 5-HT levels remained low. In a first step, modafinil may generate waking partly via cortical monoamine release, particularly DA and 5-HT, and also hypothalamic NA. In a second step, maintenance of waking might depend on hypothalamic NA.

Animals↗

PubMed2003

Coordination of actions and habits in the medial prefrontal cortex of rats.

As animals learn novel behavioural responses, performance is maintained by two dissociable influences. Initial responding is goal-directed and under voluntary control, but overtraining of the same response routine leads to behavioural autonomy and the development of habits that are no longer voluntary or goal-directed. Rats normally show goal-directed performance after limited training, indexed by sensitivity to changes in the value of reward, but this sensitivity to goal value is lost with extended training. Rats with selective lesions of the prelimbic medial prefrontal cortex showed no sensitivity to goal value after either limited or extended training, whereas rats with lesions of the infralimbic region of the medial prefrontal cortex showed the opposite pattern of deficit, a marked sensitivity to goal value after both limited and extended training. This double-dissociation suggests that the prelimbic region is responsible for voluntary response performance and the infralimbic cortex mediates the incremental ability of extended training to override this goal-directed behaviour.

Animals↗

PubMed1995

Ultrastructural associations between dopamine terminals and local circuit neurons in the monkey prefrontal cortex: a study of calretinin-immunoreactive cells.

Dopamine terminals in the monkey prefrontal cortex (PFC) synaptically target the distal dendrites of both pyramidal cells and GABA interneurons. We sought to determine whether the latter input includes the innervation of interneurons that utilize calretinin (CalR) as a calcium-binding protein. Sections through prefrontal area 9 of cynomolgus monkeys were processed by immunoperoxidase for tyrosine hydroxylase (TH) to label dopamine varicosities and by pre-embedding immunogold for CalR. Electron microscopic examination of layers 1-3 revealed numerous TH-immunoreactive (TH-ir) terminals, but few were located in the vicinity of CalR-ir dendrites. Although close appositions were sometimes detected between these labeled processes, no synaptic inputs from TH-ir terminals to CalR-ir dendrites were observed. However, in adjacent sections from the same animals, TH-ir terminals were observed to synapse on GABA-ir dendrites. These findings suggest that dopamine afferents to the monkey PFC target the subclasses of GABA interneurons that do not contain CalR.

Animals↗

PubMed1999

Clozapine preferentially increases dopamine release in the rhesus monkey prefrontal cortex compared with the caudate nucleus.

Despite substantial differences between species in the organization and elaboration of the cortical dopamine innervation, little is known about the pharmacological response of cortical or striatal sites to antipsychotic medications in nonhuman primates. To examine this issue, rhesus monkeys were chronically implanted with guide cannulae directed at the principal sulcus, medial prefrontal cortex, premotor cortex, and caudate nucleus. Alterations in dopamine release in these discrete brain regions were measured in response to administration of clozapine or haloperidol. Clozapine produced significant and long-lasting increases in dopamine release in the principal sulcus, and to a lesser extent, in the caudate nucleus. Haloperidol did not produce a consistent effect on dopamine release in the principal sulcus, although it increased dopamine release in the caudate. Clozapine's preferential augmentation of dopamine release in the dorsolateral prefrontal cortex supports the idea that clozapine exerts its therapeutic effects in part by increasing cortical dopamine neurotransmission.

Animals↗

PubMed2001

Effect of noradrenergic denervation of medial prefrontal cortex and dentate gyrus on recovery after sleep deprivation in the rat.

The noradrenergic-locus coeruleus (LC) system has a regulatory influence on forebrain neuronal networks. We have previously shown that the amygdala is strongly implicated in the mechanism of rebound seen after a 10 h sleep deprivation (SD). In the present study, our objective was to determine whether the medial prefrontal cortex and dentate gyrus (DG) which receive an important innervation from the LC, play a role in the rebound mechanisms. We found that microinjection of the specific noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, into these regions had no effect on the increase in paradoxical sleep duration seen after SD, suggesting that noradrenergic (NA) innervation of the prefrontal cortex and DG are not involved in sleep rebound regulation.

Adrenergic Agents↗

PubMed2004

High-level expression of Dok-1 in neurons of the primate prefrontal cortex and hippocampus.

The docking protein p62Dok-1 (Dok-1) has a central role in cell signaling mediated by a wide range of protein tyrosine kinases, including intrinsic membrane kinases, such as the insulin-like growth factor-1 (IGF-1) receptor. To elucidate potential IGF signaling mechanisms, we used DNA array technology to investigate novel kinase targets expressed in the primate dorsolateral prefrontal cortex (DLPFC). Dok-1 transcripts were among the most abundant found in this structure. Because Dok-1 expression has not been characterized in brain, we evaluated its expression pattern using immunoblotting, in situ hybridization, and immunohistochemistry in the rhesus monkey prefrontal cortex and hippocampal formation. Dok-1 antibodies identified a 62-kDa band in lysates from the DLPFC, consistent with the known size for Dok-1. In situ hybridization showed that Dok-1 mRNA was expressed in all layers of the DLPFC and in all neuronal subregions of the hippocampal formation. Immunohistochemical analysis showed Dok-1 immunoreactivity concentrated in pyramidal neurons of cortical layers IV-V and throughout Ammon's horn and in granule neurons of the dentate gyrus. Dok-1 expression was also identified in endothelial cells of cerebral blood vessels. These expression patterns are very similar to those of the IGF-1 receptor and suggest that Dok-1 could be among the downstream targets of IGF signaling in areas of the primate brain involved in learning and memory.

Animals↗

PubMed2000

Group II metabotropic glutamate receptors are a common target of N-anisoyl-GABA and 1S,3R-ACPD in enhancing ACh release in the prefrontal cortex of freely moving SHRSP.

Aniracetam is a therapeutically useful cognition enhancer for treating various neuropsychiatric symptoms occurring after cerebral infarction. We recently reported that local perfusion of its major metabolites N-anisoyl-GABA and p-anisic acid, but not aniracetam itself, enhanced acetylcholine (ACh) release with a delayed onset in cerebral regions of stroke-prone spontaneously hypertensive rats (SHRSP). In this study, we examined the possible involvement of metabotropic and ionotropic glutamate (mGlu and AMPA) receptors in the N-anisoyl-GABA-induced ACh release using brain in vivo microdialysis. Basal ACh release in SHRSP was commonly lower in the nucleus reticularis thalami, dorsal hippocampus and prefrontal cortex than that in age-matched Wistar Kyoto rats. The delayed ACh release in the prefrontal cortex of SHRSP was completely blocked by MCPG, a group I and II mGlu receptor antagonist, and MCCG, a group II-selective mGlu receptor antagonist. In contrast, it was largely unaffected by AIDA, a group I-selective mGlu receptor antagonist, or by YM90K, an AMPA receptor antagonist. 1S,3R-ACPD, a preferential group II mGlu receptor agonist, enhanced ACh release with a similar latency and the effect was antagonized by MCCG, whereas AMPA induced a prompt ACh release. These results indicate that N-anisoyl-GABA and 1S,3R-ACPD share a common mechanism mediated by group II mGlu receptors in enhancing ACh release. The findings suggest a possible mechanism for aniracetam's clinical efficacy in stroke patients with cholinergic deficits.

Acetylcholine↗

PubMed2006

Functional modularity of the medial prefrontal cortex: involvement in human empathy.

To investigate medial frontal lobe mediation of human empathy, the authors analyzed the activation areas in statistical parametric maps of 80 studies reporting neural correlates of empathic processing. The meta-analysis revealed 6 spatially distinct activation clusters in the medial part of the frontal lobe dorsal to the intercommissural plane. The most dorsal cluster coincided with the left supplementary motor area (SMA). Rostrally adjacent was a cluster that overlapped with the right pre-SMA. In addition, there were 3 left-hemispheric and 1 right-hemispheric clusters located at the border between the superior frontal and anterior cingulate gyrus. A broad spectrum of cognitive functions were associated with these clusters, including attention to one's own action, which was related to activations in the SMA, and valuation of other people's behavior and ethical categories, which was related to activations in the most rostroventral cluster. These data complement the consistent observation that lesions of the medial prefrontal cortex interfere with a patient's perception of own bodily state, emotional judgments, and spontaneous behavior. The results of the current meta-analysis suggest the medial prefrontal cortex mediates human empathy by virtue of a number of distinctive processing nodes. In this way, the authors' findings suggest differentiated aspects of self-control of behavior.

Brain Injuries↗

PubMed2002

SKF 83959 is an antagonist of dopamine D1-like receptors in the prefrontal cortex and nucleus accumbens: a key to its antiparkinsonian effect in animals?

SKF 83959 that has a unique antiparkinson profile in animal models of Parkinson's disease is an in vitro dopamine D1 antagonist of receptors coupled to adenylyl cyclase. We hypothesized that SKF 83959, among others, interacts with dopamine D1 receptors coupled to adenylyl cyclase in the nucleus accumbens and the prefrontal cortex. Effects of intra-accumbal injections of SKF 83959 on locomotor activity were compared to effects of the dopamine D1 agonist SKF 81297 and the dopamine D1 antagonist SCH 39166. Similarly to SCH 39166, SKF 83959 did not affect locomotor activity, but counteracted SKF 81297-induced locomotor activity. Effects of unilateral intra-prefrontal injections of SKF 83959 on rotational behaviour were compared to the effects of the dopamine D1 agonist SKF 81297 and the dopamine D1 antagonists SCH 23390 and SCH 39166 in rats selected on basis of their high locomotor response to novelty and pretreated with a subcutaneous injection of 0.75 mg/kg dexamphetamine. Like SCH 39166 and SCH 23390, SKF 83959 induced a bias for contralateral rotating and blocked the SKF 81297-induced bias for ipsilateral rotating. In conclusion, SKF 83959 is an in vivo antagonist of dopamine D1 receptors that are coupled to adenylyl cyclase in the nucleus accumbens and the prefrontal cortex. The role of these receptors in the antiparkinson profile of SKF 83959 is discussed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1988

Dopamine enhances the neuronal activity of spatial short-term memory task in the primate prefrontal cortex.

The influence of dopamine and its antagonists on neuronal activity related to the delay period of a delayed response task was examined in the monkey prefrontal cortex. Iontophoretically applied dopamine enhanced the delay-related neuronal activity, while fluphenazine and haloperidol attenuated the activity. Sulpiride had no effect on the activity. The results suggest that dopamine promotes processing of spatial short-term memory by increasing memory-related activity in the primate prefrontal cortex, probably via D1-type dopamine receptor.

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↗

PubMed1997

Delay-period activity in the primate prefrontal cortex encoding multiple spatial positions and their order of presentation.

To investigate whether prefrontal neurons temporarily retain information regarding multiple spatial positions, single-neuron activity was recorded while monkeys performed a delayed sequential reaching task, in which they needed to remember two cue positions out of three and their temporal order of presentation. Most neurons were also tested on a conventional delayed reaching task, in which they needed to remember one cue position during the delay. Among 72 neurons that exhibited significant delay-period activity, one group of neurons (n = 19) exhibited delay-period activity only when a visual cue was presented at one of the three positions (position-dependent). Of these, 6 neurons exhibited this activity when a cue was presented at that position independent of the temporal order, whereas 13 neurons exhibited this activity only when a cue was presented at that position in a particular temporal order (e.g., as the first cue or the second cue). Another group of neurons (n = 39) exhibited delay-period activity only when visual cues were presented at two positions out of three (pair-dependent). Of these, 7 neurons exhibited pair-dependent activity independent of the temporal order of cue presentation. However, 32 neurons exhibited this activity only when two cues were presented in a particular temporal order. The remaining 11 neurons exhibited non-differential activity during the delay period and 3 neurons exhibited miscellaneous activity. These results show that a single prefrontal neuron can retain information regarding two spatial positions, and that, to retain two spatial positions and the temporal order of cue presentation, new types of delay-period activity emerged; i.e., pair-dependent activity and temporal order-dependent activity. Both types of activity could be a mechanism for simultaneously retaining two items of spatial information and for effectively combining multiple spatial information by a single neuron. In addition, the presence of delay-period activity with position-dependency, pair-dependency and temporal order-dependency suggests that the dorsolateral prefrontal cortex plays an important role in planning sequential behaviors.

Animals↗

PubMed1986

Dopamine autoreceptors modulate dopamine release from the prefrontal cortex.

Electrical stimulation (at 0.3, 1, or 10 Hz, 120 pulses each) produced a calcium-dependent overflow of radioactivity from slices of the rabbit prefrontal cortex preloaded with [3H]3,4-dihydroxyphenylethylamine ([3H]DA, [3H]dopamine) in the presence of desipramine. Flat frequency-release curves were observed. Apomorphine and LY-171555 inhibited in a concentration-dependent fashion the evoked overflow of DA, an effect antagonized by haloperidol. Stimulation frequencies comparable to normal firing rates of mesocortical neurons (10 Hz) drastically reduced apomorphine-induced inhibition of DA overflow. Haloperidol produced greater facilitation of DA overflow at 10 than at 1 Hz. Nomifensine, a neuronal uptake inhibitor, enhanced DA overflow. These results indicate that mesocortical DA neurons projecting to the prefrontal cortex have release modulatory autoreceptors of the D2 subtype.

Animals↗

PubMed2003

Characterization of empathy deficits following prefrontal brain damage: the role of the right ventromedial prefrontal cortex.

Impaired empathic response has been described in patients following brain injury, suggesting that empathy may be a fundamental aspect of the social behavior disturbed by brain damage. However, the neuroanatomical basis of impaired empathy has not been studied in detail. The empathic response of patients with localized lesions in the prefrontal cortex (n = 25) was compared to responses of patients with posterior (n = 17) and healthy control subjects (n = 19). To examine the cognitive processes that underlie the empathic ability, the relationships between empathy scores and the performance on tasks that assess processes of cognitive flexibility, affect recognition, and theory of mind (TOM) were also examined. Patients with prefrontal lesions, particularly when their damage included the ventromedial prefrontal cortex, were significantly impaired in empathy as compared to patients with posterior lesions and healthy controls. However, among patients with posterior lesions, those with damage to the right hemisphere were impaired, whereas those with left posterior lesions displayed empathy levels similar to healthy controls. Seven of nine patients with the most profound empathy deficit had a right ventromedial lesion. A differential pattern regarding the relationships between empathy and cognitive performance was also found: Whereas among patients with dorsolateral prefrontal damage empathy was related to cognitive flexibility but not to TOM and affect recognition, empathy scores in patients with ventromedial lesions were related to TOM but not to cognitive flexibility. Our findings suggest that prefrontal structures play an important part in a network mediating the empathic response and specifically that the right ventromedial cortex has a unique role in integrating cognition and affect to produce the empathic response.

Adult↗

PubMed2006

[Blocks of neuron correlates of behaviour in the monkey brain prefrontal cortex and striatum].

The dynamics of tonic neuron activity of the putamen and prefrontal cortex of monkey's brain is researched by studying sequential stages of executive behavior program. It is determined that tonic responses in both structures are classified in separate blocks. The blocks are timed to key moments of behavior connected with intermediate goals framed by a common task. As to the structures of the aforesaid blocks of tonic activity in cortex and striatum, they are different in instructive part of the program and similar in executive one. More differential attitude of cortex is revealed to the sequence of executive behavior activity.

Animals↗