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Results for “Prefrontal Cortex”

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At least 793 records · Page 44Linked to original sources

PubMed2005

Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex.

Catechol-O-methyltransferase (COMT) degrades the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. A functional polymorphism in the COMT gene (val158met) accounts for a fourfold variation in enzyme activity. The low-activity met158 allele has been associated with improved working memory but with higher risk for anxiety-related behaviors. Using functional magnetic resonance imaging, we assessed the effects of COMT genotype on brain activation by standardized affective visual stimuli (unpleasant, pleasant, and neutral) in 35 healthy subjects. The analysis of genotype effects was restricted to brain areas with robust activation by the task. To determine genedose effects, the number of met158 alleles (0, 1, or 2) was correlated with the blood oxygen level-dependent (BOLD) response elicited by pleasant or unpleasant stimuli compared with neutral stimuli. COMT genotype had no significant impact on brain activation by pleasant stimuli but was related to the neural response to unpleasant stimuli: reactivity to unpleasant stimuli was significantly positively correlated with the number of met158 alleles in the limbic system (left hippocampus, right amygdala, right thalamus), connected prefrontal areas (bilateral ventrolateral prefrontal cortex, right dorsolateral prefrontal cortex), and the visuospatial attention system (bilateral fusiform gyrus, left inferior parietal lobule). Genotype explained up to 38% of interindividual variance in BOLD response elicited by unpleasant stimuli. We conclude that (1) genetic variations can account for a substantial part of interindividual variance in task-related brain activation and that (2) increased limbic and prefrontal activation elicited by unpleasant stimuli in subjects with more met158 alleles might contribute to the observed lower emotional resilience against negative mood states.

Adult↗

PubMed2000

Abnormalities in the thalamus and prefrontal cortex during episodic object recognition in schizophrenia.

BACKGROUND: Many patients with schizophrenia demonstrate memory deficits. We studied patterns of brain activity during episodic recognition of new and previously seen three-dimensional objects. METHODS: We used (15)O positron emission tomography to study regional cerebral blood flow in eight normal subjects and nine patients with schizophrenia during a visual object recognition task. RESULTS: In comparison with control subjects, patients with schizophrenia showed less regional cerebral blood flow increases in the pulvinar region of the right thalamus and the right prefrontal cortex during the recognition of new objects and significantly greater left prefrontal cortex regional cerebral blood flow increases during the recognition of previously seen objects. Patients with schizophrenia exhibited alarm rates to new objects similar to those of control subjects, but significantly lower recognition rates for previously seen objects. CONCLUSIONS: Schizophrenia is associated with attenuated right thalamic and right prefrontal activation during the recognition of novel visual stimuli and with increased left prefrontal cortical activation during impaired episodic recognition of previously seen visual stimuli. This study provides further evidence for abnormal thalamic and prefrontal cortex function in schizophrenia.

Adult↗

PubMed1997

FMRI of the prefrontal cortex during overt verbal fluency.

Verbal fluency is known to be associated with activity in the left prefrontal cortex. Recent positron emission tomography (PET) results confirmed this finding. In the present study, high resolution functional magnetic resonance imaging (fMRI) was used to further localize activity in the prefrontal cortex related to verbal fluency. Activation was observed in three behavioral tasks: (1) Repeat-subjects repeated words, (2) Opposite-subjects produced the antonym of words, and (3) Generate-subjects generated words beginning with a given letter. When comparing Generate with both Repeat and Opposite, we observed small areas of activation in the left inferior frontal gyrus and anterior cingulate, similar to the centers of mass reported using PET. We also found additional activation around the superior frontal sulcus.

Adult↗

PubMed2000

Orbital and medial prefrontal cortex and psychostimulant abuse: studies in animal models.

One approach to pursuing questions about the neural substrates that support substance abuse-related behaviors involves the use of animal models. Carefully controlled animal experiments can be conducted without the confounds commonly found in studies of human addicts, such as polydrug abuse, variable drug history and premorbid psychiatric conditions. The present paper considers the orbitofrontal and related limbic prefrontal cortex in the context of such models of substance abuse. First, the importance of recognizing the heterogeneous structural and functional nature of orbitofrontal cortex in both rodents and primates is addressed, and the results of studies involving the prefrontal cortex in substance abuse-related behaviors are considered in light of this diversity. Second, data from metabolic mapping studies are described that indicate that the pattern of functional activity within medial and orbitofrontal cortex shifts as the duration of exposure to drugs such as cocaine is extended. These functional differences, in turn, may reflect progressive phases of the addictive process. In order to understand the neurobiological consequences of long-term drug use, it will be important to establish the differing roles played by distinct anatomical territories within orbital and medial prefrontal cortex during the course of chronic substance abuse.

Animals↗

PubMedDate not supplied

Extinction of conditioned taste aversion depends on functional protein synthesis but not on NMDA receptor activation in the ventromedial prefrontal cortex.

We investigated the role of the ventromedial prefrontal cortex (vmPFC) in extinction of conditioned taste aversion (CTA) by microinfusing a protein synthesis inhibitor or N-methyl-d-asparate (NMDA) receptors antagonist into the vmPFC immediately following a non-reinforced extinction session. We found that the protein synthesis blocker anisomycin, but not the NMDA receptors antagonist D,L-2-amino-5-phosphonovaleric acid, impaired CTA extinction in the vmPFC. Anisomycin microinfusion into vmPFC had no effect on CTA acquisition and by itself did not induce CTA. These findings show the necessary role functional protein synthesis is playing in the vmPFC during the learning of CTA extinction.

2-Amino-5-phosphonovalerate↗

PubMed1991

Contrasting effects of stress on medial and sulcal prefrontal cortex self-stimulation.

Male Wistar rats were subjected to either 25 controllable or uncontrollable footshocks and then tested for changes in fixed-interval 5-second (FI-5) self-stimulation of the medial prefrontal cortex (MPC), sulcal prefrontal cortex (SPC) or nucleus accumbens (NAS). Controllable footshock caused a moderate facilitation of MPC self-stimulation (30% above baseline rates) but inhibited SPC self-stimulation (32% below baseline rates). Uncontrollable footshock had no effect on MPC self-stimulation but inhibited SPC self-stimulation (52% below baseline rates). An inhibition of SPC self-stimulation was also evident 24 hours following controllable or uncontrollable footshock. NAS self-stimulation was unaffected by footshock. Changes in locomotor activity were not consistently related to changes in self-stimulation following footshock. These results are discussed in terms of the different effects of mild stress on the release of reward-relevant neurotransmitters in the MPC, SPC and NAS. The possible role of stress-induced hypoalgesia in determining the stress-induced facilitation of MPC self-stimulation is also discussed.

Animals↗

PubMed1996

Mediodorsal thalamic evoked responses in the rat prefrontal cortex: influence of the mesocortical DA system.

The prefrontal cortex (PFC) receives a dopaminergic (DA) innervation from the ventral tegmental area (VTA) and is reciprocally connected with the mediodorsal thalamic nucleus (MD). The present study was performed in anaesthetized rats to determine the influence of the mesocortical DA system on excitatory responses evoked in the PFC by stimulation of MD: (1) short latency (< 4 ms) responses resulting from activation of the MD-PFC pathway; (2) long latency responses (> 10 ms) resulting from activation of recurrent collaterals of PFC neurons projecting to MD. Local DA application and VTA stimulation did not affect short latency responses but blocked long latency responses. These results suggest that the mesocortical DA system inhibits excitations by recurrent collaterals of the PFC-MD neurones but not the excitatory MD inputs to the PFC.

Animals↗

PubMed2003

Inactivation of the infralimbic prefrontal cortex reinstates goal-directed responding in overtrained rats.

Over the course of extended training, instrumental responding in rats shows a transition from goal-dependent performance to goal-independent performance, as assessed by sensitivity to reward-devaluation induced by taste aversions or specific satiety. It has been suggested that this reflects the gradual dominance of reflexive, habit-based responding over voluntary, goal-directed actions. Previous research suggests that lesions of the medial prefrontal cortex disrupt this interaction between goal-directed and habitual responding. More specifically, whereas lesions of the prelimbic prefrontal cortex appear to disrupt normal goal-directed responding, lesions of the infralimbic prefrontal cortex cause animals to remain goal-directed even after substantial overtraining. The current experiment explored further the nature of this interaction between actions and habits. Rats were given extended training of an instrumental lever press response before bilateral intracerebral cannulae giving access to the infralimbic cortex were implanted. Following further reminder training all animals were given a test of goal sensitivity by specific-satiety devaluation of the instrumental outcome, or a matched reward, prior to extinction tests. Before these tests, half of the animals received bilateral infusions of muscimol into the infralimbic cortex, and the remainder, control vehicle infusions. As expected after extended instrumental training, control-infused animals showed habitual performance that was not selectively influenced by devaluation of the instrumental outcome. In contrast, animals receiving temporary inactivation of the infralimbic cortex by muscimol showed selective sensitivity to devaluation of the instrumental outcome, indicating a reinstatement of goal-directed responding in these animals. This suggests that the development of habitual responding reflects the active inhibition of goal-directed responses that are mediated by action-outcome associations.

Analysis of Variance↗

PubMed2004

Neural mechanisms of spatial working memory: contributions of the dorsolateral prefrontal cortex and the thalamic mediodorsal nucleus.

The dorsolateral prefrontal cortex (DLPFC) has been known to play an important role in working memory. Neurophysiological studies have revealed that delay period activity observed in the DLPFC is a neural correlate of the temporary storage mechanism for information and that this activity represents either retrospective or prospective information, although the majority represents retrospective information. However, the DLPFC is not the only brain area related to working memory. The analysis of neural activity in the thalamic mediodorsal (MD) nucleus reveals that the MD also participates in working memory. Although similar task-related activities were observed in the MD, the directional bias of these activities and the proportion of presaccadic activity are different between the MD and the DLPFC. These results indicate that, although the MD participates in working memory, the way it participates in this process is different between these two areas, in that the MD participates more in motor control aspects than the DLPFC does.

Animals↗

PubMed2005

Repetitive transcranial magnetic stimulation of dorsolateral prefrontal cortex increases tolerance to human experimental pain.

Dorsolateral prefrontal cortex (DLPFCx) has been implicated in pain perception and in a pain modulation pathway. However, the precise participation of this region is not completely understood. The aim of this study was to evaluate whether 1 Hz rTMS of DLPFCx modifies threshold and tolerance in experimental pain. The effect of 1 Hz rTMS during 15 min at 100% motor threshold was tested in one hundred and eighty right-handed healthy volunteers, using a parallel-group stimulation design. The stimulation sites were right or left DLPFCx, right or left motor cortex, vertex or sham. rTMS was applied in two experimental contexts: (1) To evaluate its transitory effect (interference or facilitation) during cold pressor threshold (CPTh) and tolerance (CPTt) and (2) to evaluate its long-term effect by stimulating before CPTh, CPTt, pain heat thermal threshold, pain pressure threshold and tolerance. During rTMS of right DLPFCx, an increase in left hand CPTt (mean +/- SD; 17.63 s +/- 5.58 to 30.94 s +/- 14.84, P < 0.001) and in right hand CPTt (18.65 s +/- 6.47 to 26.74 s +/- 11.85, P < 0.001) were shown. No other stimulation site modified any of the pain measures during or after rTMS. These results show that 1 Hz rTMS of right DLPFCx has a selective effect by increasing pain tolerance and also sustains a right hemisphere preference in pain processing.

Adolescent↗

PubMed2005

Metabotropic glutamate receptor protein expression in the prefrontal cortex and striatum in schizophrenia.

We investigated the expression of metabotropic glutamate receptors (mGluR) in the prefrontal cortex (PFC) and striatum in schizophrenia. mGluRs modulate the release and reuptake of synaptic glutamate and mediate some molecular correlates of neuroplasticity, including long-term potentiation. The mGluRs are expressed widely in the PFC and striatum, regions often implicated in the pathophysiology of schizophrenia. Thus, we hypothesized that abnormal expression of mGluRs might contribute to glutamatergic dysfunction observed in the PFC and striatum in schizophrenia. Accordingly, we measured the expression of metabotropic glutamate receptors (mGluRs) in Brodmann areas 9, 11, 32, and 46 in the prefrontal cortex (PFC) and the caudate, putamen, and nucleus accumbens in schizophrenia (16 cases, 9 controls) by Western blot analysis. We found an increase in the expression of mGluR1a and mGluR2/3 immunoreactivity in the PFC in schizophrenia, while no changes in the expression of mGluR4a or mGluR5 were detected in this region. In the striatum we found no changes in the expression of any of the mGluRs studied. These results suggest that alterations of mGluR1a and mGluR2/3 expression in the PFC may contribute to the pathophysiology of schizophrenia, and support targeting these receptors for the generation of novel treatment modalities for this disabling illness.

Aged↗

PubMed2003

Convergence and interaction of hippocampal and amygdalar projections within the prefrontal cortex in the rat.

The orbital and medial prefrontal cortex (OMPFC) receives inputs from the CA1/subicular (CA1/S) region of the ventral hippocampus and the basolateral nucleus of the amygdala (BLA). Despite many studies about these projections, little is known as to how CA1/S and BLA inputs converge and interact within the OMPFC. Extracellular recordings of single-unit activity in the OMPFC were performed in sodium pentobarbitone-anesthetized rats. OMPFC neurons driven by CA1/S or BLA stimulation were more frequently encountered in the ventral portion of the prelimbic (v-PrL) and infralimbic cortex (IL). OMPFC neurons showing excitatory convergence of both inputs from the CA1/S and BLA were also located predominantly in the v-PrL and IL. The excitatory latencies of these neurons from both the CA1/S and BLA revealed almost identical values. Excitatory responses of OMPFC neurons to CA1/S (or BLA) stimulation were markedly augmented by simultaneous BLA (or CA1/S) stimulation, whereas the inhibitory influence of the BLA (or CA1/S) on CA1/S-induced (or BLA-induced) excitation was apparent when BLA (or CA1/S) stimulation was given 20-40 msec before CA1/S (or BLA) stimulation. Similar results were also observed when reciprocal connections between the CA1/S and BLA were severed to exclude the influences of these connections on one another. From these studies, we concluded that excitatory and inhibitory inputs from the hippocampus and amygdala converge and interact in the v-PrL and IL. Furthermore, the results indicate that simultaneous activation of hippocampal and amygdalar neurons may be important for amplification of OMPFC neuronal activity.

Action Potentials↗

PubMed1996

A pharmacological analysis of the burst events induced in midbrain dopaminergic neurons by electrical stimulation of the prefrontal cortex in the rat.

Electrical stimulation of the prefrontal cortex produces an inhibition-excitation (IE) activity pattern in the majority of responsive midbrain dopaminergic neurons. The excitatory phase often contains events, time-locked to the stimulation, which resemble natural bursts. The present study investigated the relationship between the inhibition and time-locked bursts by reducing the impact of the inhibition through membrane hyperpolarisation with the dopamine agonist apomorphine (i.v.) or antagonism with the GABAA antagonist picrotoxin (i.v. and iontophoretic). Apomorphine abolished or reduced time-locked bursting in all IE cells. Picrotoxin reduced the initial inhibition in the majority of IE cells, and abolished or reduced time-locked bursting at the highest intravenous dose. However, reductions in the initial inhibition were not systematically related to reductions in time-locked bursting. Hence, the phenomena do not appear to be causally related. Instead, time-locked bursts appear to be based on a straightforward excitation, which makes them closely analogous to natural bursts.

Animals↗

PubMed2003

Different roles of group I and group II metabotropic glutamate receptors on phencyclidine-induced dopamine release in the rat prefrontal cortex.

The dopamine system in the limbic-prefrontal cortex has been assumed to play an important role in the cognitive dysfunction of schizophrenia and phencyclidine (PCP)-induced psychosis. In the present study, the role of metabotropic glutamate (mGlu) receptor subtypes on PCP-induced cortical dopamine release was investigated using the microdialysis technique. Infusion of 50 and 100 microM of non-selective mGlu receptor agonist trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid inhibited PCP-induced dopamine release, while the basal dopamine level was not significantly affected. A similar inhibition of PCP-induced dopamine release was observed with 100 and 500 microM of selective group I mGlu receptor agonist, (+)-3-hydroxy-phenylglycine. On the other hand, infusion of 10 microM of selective group II mGlu receptor agonist, 2-(2, 3-dicarboxycyclopropyl)-glycine, enhanced the PCP-induced dopamine increase. These results suggest that group I and II mGlu receptors exert opposite modulations on the PCP-induced dopamine release.

Animals↗

PubMed2004

Representation of attended versus remembered locations in prefrontal cortex.

A great deal of research on the prefrontal cortex (PF), especially in nonhuman primates, has focused on the theory that it functions predominantly in the maintenance of short-term memories, and neurophysiologists have often interpreted PF's delay-period activity in the context of this theory. Neuroimaging results, however, suggest that PF's function extends beyond the maintenance of memories to include aspects of attention, such as the monitoring and selection of information. To explore alternative interpretations of PF's delay-period activity, we investigated the discharge rates of single PF neurons as monkeys attended to a stimulus marking one location while remembering a different, unmarked location. Both locations served as potential targets of a saccadic eye movement. Although the task made intensive demands on short-term memory, the largest proportion of PF neurons represented attended locations, not remembered ones. The present findings show that short-term memory functions cannot account for all, or even most, delay-period activity in the part of PF explored. Instead, PF's delay-period activity probably contributes more to the process of attentional selection.

Action Potentials↗

PubMed2004

Normal aging results in decreased synaptic excitation and increased synaptic inhibition of layer 2/3 pyramidal cells in the monkey prefrontal cortex.

Executive system function, mediated largely by the prefrontal cortex (PFC), often declines significantly with normal aging in humans and non-human primates. The neural substrates of this decline are unknown, but age-related changes in the structural properties of PFC neurons could lead to altered synaptic signaling and ultimately to PFC dysfunction. The present study addressed this issue using whole-cell patch clamp assessment of excitatory and inhibitory postsynaptic currents (PSCs) in layer 2/3 pyramidal cells in in vitro slices of the PFC from behaviorally characterized young (< or =12 years old) and aged (> or =19 years old) rhesus monkeys. Behaviorally, aged monkeys were significantly impaired in performance on memory and executive system function tasks. Physiologically, the frequency of spontaneous glutamate receptor-mediated excitatory PSCs was significantly reduced in cells from aged monkeys, while the frequency of spontaneous GABAA receptor-mediated inhibitory PSCs was significantly increased. In contrast, there was no effect of age on the frequency, amplitude, rise time or decay time of action potential-independent miniature excitatory and inhibitory PSCs. The observed change in excitatory-inhibitory synaptic balance likely leads to significantly altered signaling properties of layer 2/3 pyramidal cells in the PFC with age.

Aging↗

PubMed2005

Noradrenaline and dopamine elevations in the rat prefrontal cortex in spatial working memory.

The role of prefrontal cortical dopamine (DA) in the modulation of working memory functions is well documented, but substantial evidence indicates that the locus ceruleus noradrenergic system also modulates working memory via actions within the prefrontal cortex (PFC). This study shows that PFC noradrenaline (NA) and DA dialysate levels phasically increase when rats perform correctly in a delayed alternation task in a T-maze, a test of spatial working memory. However, NA levels were markedly enhanced in animals trained to alternate compared with rats that acquired the spatial information about the location of food in the maze but were untrained to make a choice to obtain the reward. In contrast, PFC DA elevations occurred independently of whether the animal had acquired the trial-specific information for correct task execution. The contribution of anticipatory responses to catecholamine efflux was also evaluated by exposing rats to an environment signaling the presence of the reward in the successive alternation task. No conditioned NA efflux was observed in either group. In contrast, in both groups, DA efflux increased in the anticipatory phase of the test to the same levels of those reached during the task. These data provide the first direct evidence for a selective activation of PFC NA transmission during a spatial working memory task. We propose that, in the working memory task, DA is primarily associated with reward expectancy, whereas NA is involved in the active maintenance of the information about a goal and the rules to achieve it.

Analysis of Variance↗

PubMed2004

The neurotensin agonist PD149163 increases Fos expression in the prefrontal cortex of the rat.

Dopaminergic axons innervating the prefrontal cortex (PFC) target both pyramidal cells and GABAergic interneurons. Many of these dopamine (DA) axons in the rat coexpress the peptide neurotransmitter neurotensin. Previous electrophysiological data have suggested that neurotensin activates GABAergic interneurons in the PFC. Activation of D2-like DA receptors increases extracellular GABA levels in the PFC, as opposed to the striatum, where D2 receptor activation inhibits GABAergic neurons. Because activation of presynaptic D2 release-modulating autoreceptors in the PFC suppresses DA release but increases release of the cotransmitter neurotensin, D2 agonists may enhance the activity of GABAergic interneurons via release of neurotensin. In order to determine if neurotensin can activate GABAergic interneurons, we treated rats with the peptide neurotensin agonist, PD149163, and examined Fos expression in PFC neurons. Systemic administration of PD149163 increased overall Fos expression in the PFC, but not in the dorsal striatum. PD149163 induced Fos in PFC interneurons, as defined by the presence of calcium-binding proteins, and in pyramidal cells. Pretreatment with the high-affinity neurotensin antagonist, SR48692, blocked neurotensin agonist-induced Fos expression. These data suggest that neurotensin activates interneurons in the PFC of the rat.

Animals↗