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Results for “Prefrontal Cortex”

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PubMed1999

Contributions of prefrontal cortex to recognition memory: electrophysiological and behavioral evidence.

To clarify the involvement of prefrontal cortex in episodic memory, behavioral and event-related potential (ERP) measures of recognition were examined in patients with dorsolateral prefrontal lesions. In controls, recognition accuracy and the ERP old-new effect declined with increasing retention intervals. Although frontal patients showed a higher false-alarm rate to new words, their hit rate to old words and ERP old-new effect were intact, suggesting that recognition processes were not fundamentally altered by prefrontal damage. The opposite behavioral pattern was observed in patients with hippocampal lesions: a normal false-alarm rate and a precipitous decline in hit rate at long lags. The intact ERP effect and the change in response bias during recognition suggest that frontal patients exhibited a deficit in strategic processing or postretrieval monitoring, in contrast to the more purely mnemonic deficit shown by hippocampal patients.

Adult↗

PubMed2004

Expression of serotonin1A and serotonin2A receptors in pyramidal and GABAergic neurons of the rat prefrontal cortex.

Serotonergic 5-HT1A and 5-HT2A receptors are abundantly expressed in prefrontal cortex (PFC) and are targets of atypical antipsychotic drugs. They mediate, respectively, inhibitory and excitatory actions of 5-HT. The transcripts for both receptors are largely (approximately 80%) colocalized in rat and mouse PFC, yet their quantitative distribution in pyramidal and GABAergic interneurons is unknown. We used double in situ hybridization histochemistry to estimate the proportion of pyramidal and GABAergic neurons expressing these receptor transcripts in rat PFC. The number of GABAergic interneurons (expressing GAD mRNA) was a 22% of glutamatergic neurons (expressing vGluT1 mRNA, considered as putative pyramidal neurons). 5-HT2A receptor mRNA was present in a large percentage of pyramidal neurons (from 55% in prelimbic cortex to 88% in tenia tecta), except in layer VI, where it was localized only in 30% of those neurons. 5-HT2A receptor mRNA was present in approximately 25% of GAD-containing cells except in layer VI (10%). Likewise, approximately 60% of glutamatergic cells contained the 5-HT1A receptor transcript. We also found that approximately 25% of GAD-expressing cells contained the 5-HT1A receptor mRNA. These data help to clarify the role of 5-HT in prefrontal circuits and shed new light to the cellular elements involved in the action of atypical antipsychotics.

Animals↗

PubMed2004

The role of prefrontal cortex D1-like and D2-like receptors in cocaine-seeking behavior in rats.

RATIONALE: Evidence from preclinical and clinical studies indicates an important role for the mesocorticolimbic dopamine system in cocaine craving and relapse. OBJECTIVES: To investigate the relative involvement of prefrontal cortex D1-like and D2-like dopamine receptors in cocaine-primed, drug-seeking behavior. METHODS: Rats were trained to press a lever to self-administer cocaine (i.v., 0.25 mg per infusion) in daily 2-h sessions. Responding was reinforced, contingent on a modified fixed-ratio 5 schedule. Reinstatement tests began after lever-pressing behavior was extinguished in the absence of cocaine and conditioned cues (light and tone). Before each reinstatement test, rats received bilateral microinfusions of different doses of selective D1-like and D2-like antagonists, SCH 23390, and eticlopride, respectively, followed by intraperitoneal administration of 10 mg/kg cocaine; 3 min later the session started. Responding in the reinstatement test was reinforced only by the conditioned cues contingent on a fixed-ratio 5 schedule. RESULTS: Both drugs dose dependently decreased cocaine-primed reinstatement without affecting operant behavior maintained by food. Eticlopride, but not SCH 23390, increased cocaine self-administration and decreased food-primed reinstatement at the dose found to decrease cocaine-primed reinstatement. CONCLUSIONS: These data suggest that, although both D1-like and D2-like receptors in the prefrontal cortex are involved in cocaine-primed drug-seeking behavior, they may modulate different aspects of this process.

Animals↗

PubMed1995

Functional role of the prefrontal cortex in retrieval of memories: a PET study.

Retrieval of information from episodic memory involves the processes invoked by the attempt to remember (retrieval attempt) as well as processes associated with the successful retrieval of stored information (ecphory). Previous PET studies of memory have shown an activation of the prefrontal cortex in memory retrieval tasks, and we hypothesised that this activation represents retrieval attempt, not ecphory. This hypothesis was directly directed using [15O]H2 PET imaging in 19 healthy subjects who performed three matched tasks which involved different levels of retrieval attempt and ecphory. The results showed that retrieval attempt was associated with activation of the prefrontal cortex, right greater than left, while ecphory involved the posterior cortical regions. These findings illuminate the functional role of the different neuroanatomical regions involved in episodic remembering.

Adult↗

PubMed2004

Reduced GSK-3beta mRNA levels in postmortem dorsolateral prefrontal cortex of schizophrenic patients.

Glycogen Synthase Kinase (GSK)-3 is a ubiquitous serine/threonine protein kinase highly abundant in brain which plays a key role in neural development and neuron survival. We have previously reported that GSK-3beta protein levels and GSK-3 activity are reduced by over 40% in postmortem prefrontal cortex of schizophrenic patients compared to patients with bipolar illness, unipolar depression and to normal controls, and Emamian et al. have recently presented convergent evidence for impaired AKT1-GSK-3beta signaling in schizophrenia. Using specimens of dorsolateral prefrontal cortex tissue obtained from The Stanley Medical Research Institute's Brain Collection, from the same subjects used previously, we now show that GSK-3beta, but not GSK-3alpha, mRNA levels are 36% lower in the patients with schizophrenia compared to all other comparison groups. The present study lends further support to the finding of low GSK-3beta levels in schizophrenia and extends this observation by suggesting that the decrease in GSK-3beta may be due to reduced protein synthesis possibly due to altered transcriptional drive of the GSK-3beta gene.

Adult↗

PubMed2006

The role of prefrontal cortex in visuo-spatial planning: A repetitive TMS study.

The visuo-spatial planning process is based on an "opportunistic" combination of heuristics and strategies, carried out in small units during the execution of plans. In order to investigate the functional role of the prefrontal cortex in heuristic switching, 42 healthy controls performed a labyrinth crossing task (the Maps Test). During this computerized version of the Travelling Salesperson Problem, subjects had to decide which order of locations optimizes total travel time and distance. This task was performed with and without 1 Hz repetitive transcranial magnetic stimulation (rTMS), which exerts an inhibitory action on the targeted area, applied during the task over bilateral frontal sites (active stimulation) and parieto-occipital site (sham stimulation). Only repetitive bilateral rTMS over F3 and F4 significantly decreased the number of strategies with changes of heuristics, and increased the number of movements required to solve the task. This behaviour contrasts with the performance of healthy subjects in the planning task, but is consistent with the performance of frontal traumatic brain injury patients. The results indicate that, in a visuo-spatial problem-solving task, the prefrontal cortex is involved in the switching between heuristics during the execution of a plan.

Adult↗

PubMed1995

Cholinergic synaptic circuitry in the macaque prefrontal cortex.

Surprisingly little is known about the synaptic architecture of the cholinergic innervation in the primate cerebral cortex in spite of its acknowledged relevance to cognitive processing and Alzheimer's disease. To address this knowledge gap, we examined serially sectioned cholinergic axons in supra- and infragranular layers of the macaque prefrontal cortex by using an antibody against the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT). The tissue bound antibody was visualized with both immunoperoxidase and silver-enhanced diaminobenzidine sulfide (SEDS) techniques. Both methods revealed that cholinergic axons make synapses in all cortical layers and that these synapses are exclusively symmetric. Cholinergic axons formed synapses primarily on dendritic shafts (70.5%), dendritic spines (25%), and, to a lesser extent, cell bodies (4.5%). Both pyramidal neurons and cells exhibiting the morphological features of GABAergic cells were targets of the cholinergic innervation. Some spiny dendritic shafts received multiple, closely spaced synapses, suggesting that a subset of pyramidal neurons may be subject to a particularly strong cholinergic influence. Analysis of synaptic incidence of cholinergic profiles in the supragranular layers of the prefrontal cortex by the SEDS technique revealed that definitive synaptic junctions were formed by 44% of the cholinergic boutons. An unexpected finding was that cholinergic boutons were frequently apposed to spines and small dendrites without making any visible synaptic specializations. These same spines and dendrites often received asymmetric synapses, presumably of thalamocortical or corticocortical origin. Present ultrastructural findings suggest that acetylcholine may have a dual modulatory effect in the neocortex: one through classical synaptic junctions on dendritic shafts and spines, and the other through nonsynaptic appositions in close vicinity to asymmetric synapses. Further physiological studies are necessary to test the hypothesis of the nonsynaptic release of acetylcholine in the cortex.

Animals↗

PubMed2001

Unmasking of silent "task-related" neuronal activity in the monkey prefrontal cortex by a GABA(A) antagonist.

To examine the role of GABA on prefrontal neuronal activity in the control of behavior, a GABA(A) receptor antagonist, bicuculline methiodite (BMI), was iontophoretically applied to prefrontal neurons while monkeys performed a visual reaction time task. Iontophoretic application of BMI uncovered "task-related" activity of silent neurons (n=40), which did not show any activity during performance of the task. The distribution, by type, of these silent "task-related" neurons differed from that of standard (i.e. active) task-related neurons (N=95), and a particular type of silent "task-related" neuron was found most frequently. These findings suggest that GABA continuously and preferentially suppresses neuronal activity via GABA(A) receptors to limit the population of prefrontal neurons related to behavior, thereby organizing neuronal activities for behavior mediated by the prefrontal cortex.

Animals↗

PubMed2006

Context-dependent prefrontal cortex regulation of cocaine self-administration and reinstatement behaviors in rats.

Evidence of stimulus attribute-specificity within the prefrontal cortex (PFC) suggests that different prefrontal subregions may contribute to cocaine addiction in functionally distinct ways. Thus, the present study examined the effects of lidocaine-induced inactivation of two distinct PFC subregions, the prelimbic (PL) or dorsal agranular insular (AId) cortices, on drug-seeking and drug-taking behaviors under cocaine maintenance and reinstatement testing conditions in rats trained to self-administer 1 mg/kg cocaine under a second-order schedule of drug delivery. Throughout maintenance and reinstatement phases, rats were exposed to conditioned light cues and contextual odor or sound cues. Results showed that PL inactivation during maintenance test sessions significantly reduced drug-seeking and drug-taking behaviors, and disrupted patterns of responding in rats exposed to light-sound, but not light-odor, cues. Moreover, lidocaine-induced inactivation of the PL significantly attenuated drug-seeking behavior during cue-induced and cocaine prime-induced reinstatement in rats exposed to light-sound cues only. In contrast, AId inactivation significantly attenuated cue-induced reinstatement of drug-seeking behavior in rats exposed to light-odor cues only. Drug-seeking and drug-taking behaviors in these rats were not disrupted during maintenance and cocaine prime-induced reinstatement testing regardless of the type of contextual cues used. Together, these data suggest that PL and AId subregions play separate yet overlapping roles in regulating cocaine addiction in rats in ways that are dependent on the presence or absence of cocaine and on the types of contextual cues present in the cocaine self-administration environment.

Acoustic Stimulation↗

PubMed2006

Memory reactivation, dissociated from behavioural expression, decreases ERK phosphorylation in the rat prefrontal cortex and amygdala.

The involvement of MAPK pathways in retrieval was investigated in a situation where reactivation of memory was dissociated from its behavioural expression. In rats trained in a brightness avoidance discrimination task, exposure to the discriminative stimulus had behavioural and molecular consequences: a facilitation of the retention performance and a decrease in ERK phosphorylation in the prefrontal cortex and amygdala, but not in the hippocampus. These results indicate that reactivation processes engage a down-regulation of ERK, possibly related to increases in glucocorticoids, in the amygdala and prefrontal cortex already known to be involved in emotional retrieval.

Amygdala↗

PubMed1998

Saccadic eye movement and working memory deficits following damage to human prefrontal cortex.

A patient with a lesion confined largely to the right inferior frontal gyrus was found to be impaired on tests of spatial working memory and executive functioning. By contrast, his pattern recognition was good. The patient's selective impairments are consistent with the view that prefrontal cortex contributes to processes involved in spatial working memory. The patient was also tested on a range of oculomotor paradigms, some of which required the temporary suppression of a saccadic response. He was unable to suppress making contra- or ipsilesional reflexive glances to peripheral stimuli on the "anti-saccade" paradigm, but his performance improved on delayed saccade, memory-guided saccade and fixation tasks. Although reflexive glances were observed under these conditions they occurred more frequently in response to contralesional stimuli than ipsilesional ones. Furthermore, the patient had no difficulty in performing anti-point movements with his ipsilesional hand. Thus, his inability to suppress reflexive glances on the anti-saccade task is not due to a generalised problem of "distractibility". The patient's deficits are discussed in terms of models of anti-saccade generation and are related to recent findings regarding the role of prefrontal cortex in working memory and visual attention.

Attention↗

PubMed1999

Errors of memory-guided saccades in humans with lesions of the frontal eye field and the dorsolateral prefrontal cortex.

Behavioral studies in monkeys and humans suggest that systematic and variable errors of memory-guided saccades reflect distinct neuronal computations in primate spatial memory. We recorded memory-guided saccades with a 2-s delay in three patients with unilateral ischemic lesions of the frontal eye field and in three patients with unilateral ischemic lesions of the frontal eye field and the dorsolateral prefrontal cortex. Results suggest that systematic errors of memory-guided saccades originate in the frontal eye field and variable errors in the dorsolateral prefrontal cortex. These data are the first human lesion data to support the hypothesis that these regions provide functionally distinct contributions to spatial short-term memory.

Adult↗

PubMed2004

What does the prefrontal cortex "do" in affect: perspectives on frontal EEG asymmetry research.

This commentary provides reflections on the current state of affairs in research on EEG frontal asymmetries associated with affect. Although considerable progress has occurred since the first report on this topic 25 years ago, research on frontal EEG asymmetries associated with affect has largely evolved in the absence of any serious connection with neuroscience research on the structure and function of the primate prefrontal cortex (PFC). Such integration is important as this work progresses since the neuroscience literature can help to understand what the prefrontal cortex is "doing" in affective processing. Data from the neuroscience literature on the heterogeneity of different sectors of the PFC are introduced and more specific hypotheses are offered about what different sectors of the PFC might be doing in affect. A number of methodological issues associated with EEG measures of functional prefrontal asymmetries are also considered.

Affect↗

PubMed2002

An RT-PCR study of 5-HT(6) and 5-HT(7) receptor mRNAs in the hippocampal formation and prefrontal cortex in schizophrenia.

5-Hydroxytryptamine (5-HT; serotonin) 5-HT(6) receptors (5-HT(6)R) and 5-HT(7) receptors (5-HT(7)R) have been implicated in schizophrenia and as targets of atypical antipsychotic drugs. We have studied the expression of these receptors in the hippocampal formation and dorsolateral prefrontal cortex (DLPFC) of 17 subjects with schizophrenia and 17 controls using reverse transcription-polymerase chain reaction (RT-PCR) with cyclophilin co-amplification. In schizophrenia, 5-HT(6)R mRNA was decreased in the hippocampal formation, and 5-HT(7)R mRNA was decreased in the dorsolateral prefrontal cortex. The mRNAs were unchanged in rats treated for 2 weeks with haloperidol, chlorpromazine, risperidone, olanzapine or clozapine. Regional decreases in 5-HT(6)R and 5-HT(7)R expression in schizophrenia may contribute to the overall serotonergic alterations which occur in the disorder, in part through their interactions with other neurotransmitter systems including glutamate and acetylcholine.

Animals↗

PubMed1985

Functional interactions between inferotemporal and prefrontal cortex in a cognitive task.

Monkeys were trained to perform a visual short-term memory task (delayed matching to sample). In some of the animals, cooling probes were implanted over dorsolateral prefrontal cortex, covering sulcus principalis and adjacent areas; microelectrode pedestals were implanted over inferotemporal cortex. Other animals were fitted with converse implants: cooling probes over a portion of the inferotemporal cortical convexity and microelectrode pedestals over prefrontal cortex. In the awake and behaving monkeys, bilateral cooling of either the prefrontal or the inferotemporal region (to 20 degrees C) induced, in the other region, reversible changes of spontaneous and task-related cell discharge. In the two cortices remote cooling induced augmentations and diminutions of cell reaction to the color samples which the animal had to retain for correct performance of the task. The same was true for cell discharge during the delay, the retention period which followed each sample. However, a net effect of remote cooling was, in both cortices, a diminution of color-dependent differences in the reactions and delay-discharge of some cells. Concomitantly, errors of task-performance increased. Cells that as a result of remote cortical cooling showed changes of reaction to the color samples were found more commonly in supragranular than infragranular layers. The results are interpreted as evidence of mutual influences between inferotemporal and prefrontal areas, probably mediated by corticocortical connections. The single-cell data, together with the behavioral data, suggest that those influences are functionally important for visual discrimination and short-term memory.

Action Potentials↗

PubMed1990

Long-term potentiation in the prefrontal cortex following stimulation of the hippocampal CA1/subicular region.

We have examined single cell activity and field potentials in the prelimbic area of the prefrontal cortex of the rat to electrical stimulation of the CA1/subicular region of the temporal hippocampus. Excitatory unit responses were found in 50 out of 120 neurons recorded in the prelimbic area. Paired-pulse facilitation was found for both single cell responses and field potentials. High-frequency, tetanic stimulation of the temporal hippocampus produced a significant and persistent potentiation of prelimbic field potentials. The evidence suggests that the direct pathway from the temporal hippocampus to the prelimbic area of the prefrontal cortex in the rat is excitatory and can undergo long-term potentiation (LTP).

Animals↗

PubMed1994

Memantine-induced dopamine release in the prefrontal cortex and striatum of the rat--a pharmacokinetic microdialysis study.

Memantine (1-amino-3,5-dimethyl-adamantane) has therapeutic potential in Parkinson's disease and dementia. However, its effect on dopaminergic activity in the central nervous system is still unclear. Therefore, we studied the effect of memantine on dopamine release in prefrontal cortex and striatum, using in vivo microdialysis. Memantine (5, 10 and 20 mg/kg i.p.) caused a dose-dependent increase in dopamine release up to nearly 50% over basal levels. The output of the metabolites was of later onset and longer duration in prefrontal cortex and in striatum. After administration of 10 and 20 mg/kg, in both brain areas memantine levels could be detected over the investigated period of 160 min. The maximal concentrations (Cmax) differed dose dependently, whereas the time to reach this maximum (tmax) was almost identical (68.5 +/- 3.4 min). From the flat elimination profile a half-life of 2.8 +/- 0.5 h (range 2-3.4 h) was calculated. These data demonstrate enhanced dopamine release and metabolism after memantine treatment and support the assumption of an interaction between noncompetitive NMDA-receptor antagonists and dopaminergic systems.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2002

Recruitment of anterior dorsolateral prefrontal cortex in human reasoning: a parametric study of relational complexity.

Reasoning and problem solving depend on the ability to represent and integrate complex relationships among stimuli. For example, deciding whether an animal is dangerous requires integrating information about the type of animal, its size, its distance from oneself, and one's proximity to shelter. Relational complexity increases with the number of such interdependent elements that must be simultaneously considered to solve a problem. We used functional magnetic resonance imaging to identify brain regions that respond selectively in processing high levels of relational complexity. Performance on nonverbal reasoning problems in which relational complexity was varied parametrically was compared with performance on control problems in which relational complexity was held constant while difficulty was manipulated by adding distractor forms to the problems. Increasing complexity and adding distractors both led to increased activation in parietal and in dorsolateral prefrontal cortex, with high levels of relational complexity selectively activating anterior left prefrontal cortex. Our data provide evidence that brain regions specific to integrating complex relations among stimuli are distinct from those involved in coping with general task difficulty and with working-memory demands.

Adult↗