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At least 397 records · Page 22Linked to original sources

PubMed2006

Differential involvement of regions of rostral prefrontal cortex (Brodmann area 10) in time- and event-based prospective memory.

Rostral prefrontal cortex (approximating Brodmann area 10) has been shown repeatedly to have a role in the maintenance and realization of delayed intentions that are triggered by event cues (i.e., event-based prospective memory). The cerebral organization of the processes associated with the use of time cues (time-based prospective memory) has however received less attention. In two positron emission tomography (PET) studies we therefore examined brain activity associated with time- and event-based prospective memory tasks. In the time-based condition of the first study, young healthy volunteers were asked to make a prospective response based on their self-estimation of the passage of time while engaged in an attention-demanding ongoing activity. In the time-based condition of the second study, participants had a clock available in the ongoing task display and did not need to estimate the time for the prospective response. In the event-based condition of both studies, participants were asked to make a prospective response when prospective cues were presented in ongoing trials. Both studies showed activation differences in rostral prefrontal cortex according to whether the task was time- or event-based. In study one, an area of left superior frontal gyrus was more active in the time-based condition. In study two, three rostral prefrontal regions were more active in the time-based condition: right superior frontal gyrus, anterior medial frontal lobe and anterior cingulate gyrus. A region in left superior frontal gyrus, different from the area found in the first study, was more active in the event-based condition. These results indicate involvement of multiple brain regions of rostral prefrontal cortex in time- and event-based prospective memory. The results are interpreted as reflecting the differing processing demands made by event- or time-based prospective memory tasks, and the differing demands of time-based tasks according to whether a clock is present as an aid.

Adult↗

PubMed2002

Delta(9)-tetrahydrocannabinol decreases extracellular GABA and increases extracellular glutamate and dopamine levels in the rat prefrontal cortex: an in vivo microdialysis study.

Cannabinoid modulation of prefrontal cortex and hippocampus neuronal functioning has been correlated to the disruptive action of marijuana on memory tasks. This study investigates the effects of delta(9)-tetrahydrocannabinol (delta(9)-THC) on dopamine, glutamate and GABA levels in vivo by brain microdialysis in the prefrontal cortex. Delta(9)-THC (1 mg/kg, i.v.) significantly increased extracellular dopamine and glutamate levels and decreased GABA levels. These effects were prevented by the cannabinoid antagonist SR141716A (1 mg/kg, i.v.), which per se was ineffective. These results suggest that delta(9)-THC disrupt the normal interplay between neurotransmitters in this area and may bear relevance in understanding neuronal mechanisms underlying cannabinoid-induced cognitive deficits.

Animals↗

PubMed1986

Role of dopaminergic and serotonergic neuronal systems in the prefrontal cortex of rats in phencyclidine-induced behaviors.

This study was designed to determine the action sites of phencyclidine (PCP) involved in the development of behaviors such as head-weaving, immobility, turning and backpedalling in relation to dopaminergic and serotonergic neuronal functions. Injection of PCP into the caudate nucleus or prefrontal cortex dose-dependently produced head-weaving, although the injection of PCP into the nucleus accumbens failed to produce head-weaving. The intensity of head-weaving induced by injection of PCP into the prefrontal cortex was relatively high when compared to that induced by injection of PCP into the caudate nucleus or lateral ventricle. Pretreatment with p-chlorophenylalanine (300 mg/kg), a serotonin (5-HT) synthesis inhibitor, attenuated head-weaving induced by injection of PCP into the prefrontal cortex. Injection of PCP (50-100 micrograms) into the prefrontal cortex also produced immobility for 5 min post-injection. Rats pretreated with pimozide (1 mg/kg), a dopamine (DA) antagonist, also produced immobility after the injection of PCP into the prefrontal cortex and this effect was attenuated by pretreatment with ritanserin, a 5-HT2 receptor antagonist. On the other hand, pretreatment with methamphetamine attenuated PCP (5 and 7.5 mg/kg)-induced turning and backpedalling but not head-weaving. Pretreatment with large doses of apomorphine, a DA agonist, also greatly attenuated PCP (7.5 mg/kg)-induced behaviors, i.e. head-weaving, turning and backpedalling. These effects of DA agonists were prevented by haloperidol (0.25 mg/kg), a DA antagonist. These results suggest that PCP-induced turning and backpedalling may be mediated by reducing dopaminergic transmission, although PCP-induced head-weaving and immobility may be produced by increasing serotonergic transmission in the prefrontal cortex.

Animals↗

PubMed2000

Dissociation of physical abstinence signs from changes in extracellular dopamine in the nucleus accumbens and in the prefrontal cortex of nicotine dependent rats.

The aim of the present study was to investigate the relationship between physical abstinence and changes in dopamine release in the nucleus accumbens and in the medial prefrontal cortex induced by mecamylamine and naloxone in rats chronically exposed to nicotine. The rats were implanted with osmotic minipumps (Alzet) delivering nicotine tartrate at a rate of 9 mg/kg/day (3.16 mg of free base) and 8 days later with a dialysis probe in the nucleus accumbens or in the medial prefrontal cortex. Steady-state dopamine output from the nucleus accumbens of the rats implanted with nicotine minipumps was higher than that of sham implanted rats; no differences were observed in the prefrontal cortex. In nicotine but not in sham implanted rats mecamylamine (1 mg/kg s.c.) precipitated a physical abstinence syndrome and brought dopamine output back to control values in the nucleus accumbens. In contrast mecamylamine (1 mg/kg s.c.) increased dopamine output in the medial prefrontal cortex of nicotine but not sham-implanted rats. Naloxone (2 mg/kg) precipitated a physical abstinence syndrome qualitatively similar to that produced by mecamylamine but failed to modify extracellular dopamine in the nucleus accumbens or in the prefrontal cortex of nicotine-implanted and sham-implanted rats. The results indicate that the mesolimbic and mesocortical dopamine system undergo opposite changes during mecamylamine-precipitated abstinence in rats chronically exposed to nicotine and that physical abstinence signs can be dissociated from changes in dopamine transmission.

Analysis of Variance↗

PubMedDate not supplied

Peptides and self-stimulation of the medial prefrontal cortex in the rat: effects of intracerebral microinjections of substance P and cholecystokinin.

The effects of intracerebral microinjections of substance P and cholecystokinin on self-stimulation of the medial prefrontal cortex of the rat were studied. Intracerebroventricular administration of substance P at doses of 2.5, 5, 10 and 20 micrograms produced a dose-related decrease in self-stimulation of the medial prefrontal cortex; spontaneous motor activity, measured as a control, was not affected. Unilateral microinjections into the medial prefrontal cortex of substance P at doses of 10 and 20 micrograms produced a decrease of self-stimulation of the ipsilateral side, but self-stimulation of the contralateral cortex, used as a control, was not affected. On the contrary, cholecystokinin in both intracerebroventricular administration at doses of 100, 200 and 400 ng, or intracortical microinjections into the medial prefrontal cortex at doses of 200, 400 and 800 ng, had no effect on self-stimulation of this cortical area. These results suggest that substance P, but not cholecystokinin, could be part of the neurochemical substrate underlying self-stimulation of the medial prefrontal cortex in the rat.

Animals↗

PubMed1987

Crossed corticothalamic and thalamocortical connections of macaque prefrontal cortex.

We have conducted a systematic comparison of the ipsilateral (uncrossed) and contralateral (crossed) thalamic connections of prefrontal cortex in macaque monkeys, using cortical implants of horseradish peroxidase pellets and tetramethyl benzidine histochemistry to demonstrate anterograde and retrograde thalamic labeling. Contrary to the prevailing belief that thalamocortical projections are entirely uncrossed, our findings indicate that a modest crossed projection to prefrontal cortex arises from the mesial thalamus, principally the anteromedial and midline nuclei. Also, while confirming that corticothalamic projections are bilateral, we found that the pattern of crossed projections differs from that of uncrossed projections. Projections to mesial thalamic nuclei, specifically to the anteromedial nucleus, the midline nuclei, and the magnocellular part of the mediodorsal nucleus are bilateral, the contralateral projection being nearly as dense as the ipsilateral projection. Projections to the parvicellular part of the mediodorsal and ventral anterior nuclei are also bilateral, but the contralateral projection is much weaker than the ipsilateral projection. Prefrontal projections to the reticular nucleus, medial pulvinar, suprageniculate nucleus, and limitans nucleus appear to be exclusively ipsilateral. These results indicate that prefrontal cortex has prominent bilateral and reciprocal connections with the nuclei of the mesial thalamic region. As this region of the diencephalon has been implicated by anatomical and behavioral studies in memory functions, our findings suggest that prefrontal cortex, through its connections with this region, may be involved in the bilateral integration of mnemonic systems.

Animals↗

PubMed1997

Effects of 5,7-dihydroxytryptamine lesions of the prefrontal cortex on consumption of sucrose-ethanol solutions: relationship to prefrontal monoamines.

Thirty adult male Wistar rats received 8 micrograms bilaterally of 5,7-dihydroxytryptamine into the medial prefrontal cortex (mPFC). Rats were then trained, via a sucrose, fading paradigm, to consume increasing concentrations of alcohol. After death, dopamine (DA), norepinephrine (NE), serotonin (5-HT), and their metabolites were measured in the mPFC, nucleus accumbens (NA), and raphe nucleus. The lesioned group demonstrated a reduction in 5-hydroxyindoleacetic acid (5-HIAA), DA, and NE in the mPFC (p < 0.05), and a trend toward reduction of 5-HT in the NA. In comparison with controls, lesioned animals consumed less of all solutions containing sucrose and alcohol. On regression analyses, monoamines in the mPFC (i.e., 5-HIAA, dihydrophenylacetic acid and NE) predicted consumption of the 5% ethanol solution (p = 0.009), 10% ethanol solution (p = 0.0006), and the 5% sucrose solutions (p = 0.0006), but not the 20% sucrose solutions. In each case, monoamine levels were positively correlated with consumption. No relationships were seen between monoamine levels in the NA and raphe, and in consummatory behavior.

5,7-Dihydroxytryptamine↗

PubMedDate not supplied

Control of the serotonergic system by the medial prefrontal cortex: potential role in the etiology of PTSD and depressive disorders.

The prefrontal cortex is involved in an array of higher brain functions that are altered in psychiatric disorders. Serotonergic neurons of the midbrain rapbe nuclei innervate the prefrontal cortex and are the cellular target for drugs used to treat mood disorders such as the selective serotonin (5-HT) reuptake inhibitors. Anatomical evidence supports the existence of projections from the medial prefrontal cortex (mPFC) to the dorsal raphe nucleus (DR). We report on a functional control of the activity of DR 5-HT neurons by projection neurons in the mPFC. The stimulation of the mPFC elicits two types of responses in DR 5-HT neurons, orthodromic excitations and inhibitions. Excitations are mediated by AMPA/KA and NMDA receptors whereas inhibitions are mediated by GABA(A) and 5-HT(1A) receptors. The activation of a subgroup of 5-HT neurons increases 5-HT release which subsequently activates 5-HT(1A) autoreceptors on other 5-HT neurons. GABA(A)-mediated inhibitions involve GABAergic elements in the DR or adjacent areas. Pyramidal neurons of the mPFC co-express postsynaptic 5-HT(1A) (inhibitory) and 5-HT(2A) (excitatory) receptors. Consistent with the above observations, the selective activation of both receptors in mPFC reduced and increased, respectively, the firing activity of DR 5-HT neurons and the 5-HT release in mPFC. Overall, these data indicate that the activity of the 5-HT system is strongly controlled by the mPFC. Thus, the abnormal prefrontal function in post-traumatic stress disorder and depressive patients may induce a disregulation of 5-HT neurons projecting to other brain areas that can underlie the existing symptomatology in these psychiatric disorders.

Journal Article↗

PubMed1995

Time-dependent changes in dopamine agonist-induced striatal Fos immunoreactivity are related to sensory neglect and its recovery after unilateral prefrontal cortex injury.

This study examined interactions between the corticostriatal glutamatergic system and the nigrostriatal dopaminergic system via immunocytochemical examination of dopamine (DA) agonist induction of the striatal immediate early gene product Fos following cortical injury. After unilateral aspiration of the medial agranular cortex (AGm) region of prefrontal cortex, rats were tested for orientation to visual, tactile, and auditory stimuli. Fos immunoreactivity induced by d-amphetamine (5 mg/kg) or apomorphine (5 mg/kg) was quantified in dorsolateral and ventrolateral regions of caudate-putamen (CPu) in rats still demonstrating sensory neglect (5 days postsurgery) and in rats recovered from sensory neglect produced by AGm ablation (29+ days postsurgery). The pattern of immunoreactivity of rats still demonstrating neglect differed from that of unlesioned rats or recovered AGm-ablated rats. In rats demonstrating sensory neglect, d-amphetamine or apomorphine induction of Fos in the ipsilateral CPu was reduced by about 40% compared to the contralateral CPu or to comparable readings in unlesioned controls. These asymmetries were restricted to dorsolateral CPu, the region receiving the densest input from AGm. In contrast, recovered AGm-ablated rats had DA agonist-induced striatal Fos immunoreactivity that was symmetrical between the two hemispheres and comparable to control values. These findings indicate that adaptations involving the striatal medium spiny neuron, a site of convergence of cortical glutamatergic and nigral dopaminergic afferents, may contribute to recovery from behavioral deficits resulting from neocortical injury.

Animals↗

PubMed2006

Learning hierarchically structured action sequences is unaffected by prefrontal-cortex lesion.

This study tested the impact of prefrontal-cortex lesion on learning hierarchically structured action sequences. Using a visual-manual serial reaction time task, we had subjects first perform five blocks of trials with a hierarchically structured 14-element action sequence and then tested for sequence-specific learning by introducing a pseudo-random transfer sequence. Relative to control subjects (N = 39), we found that both lateral frontal (N = 16) and medial frontal (N = 18) patients showed reduced overall performance benefits across the training phase. In contrast, the negative transfer test showed significantly increased reaction times in all patient groups, indicating robust sequence-specific learning. This learning was not significantly different from that of the control group. Taken together, the data suggest that learning hierarchically structured action sequences is unimpaired in patients with prefrontal-cortex lesion.

Adult↗

PubMed2002

Synchronized activity in prefrontal cortex during anticipation of visuomotor processing.

It is commonly presumed, though not well established, that the prefrontal cortex exerts top-down control of sensory processing. One aspect of this control is thought to be a facilitation of sensory pathways in anticipation of such processing. To investigate the possible involvement of prefrontal cortex in anticipatory top-down control, we studied the statistical relations between prefrontal activity, recorded while a macaque monkey waited for presentation of a visual stimulus, and subsequent sensory and motor events. Local field potentials were simultaneously recorded from prefrontal, motor, occipital and temporal cortical sites in the left cerebral hemisphere. Spectral power and coherence analysis revealed that during stimulus anticipation three of five prefrontal sites participated in a coherent oscillatory network synchronized in the beta-frequency range. Pre-stimulus network power and coherence were highly correlated with the amplitude and latency of early visual evoked potential components in visual cortical areas, and with response time. The results suggest that synchronized oscillatory networks in prefrontal cortex are involved in top-down anticipatory mechanisms that facilitate subsequent sensory processing in visual cortex. They further imply that stronger top-down control leads to larger and faster sensory responses, and a subsequently faster motor response.

Animals↗

PubMed2003

Prefrontal cortex lesions modify the spatial properties of hippocampal place cells.

It has previously been proposed that the prefrontal cortex has a role in 'executive processes' and memory function. These activities presumably require modulation of activity in posterior cortex. On the basis of this hypothesis, it was proposed that prefrontal cortex lesions might alter neural activity in the hippocampus, a region implicated in memory processing. A major feature of hippocampal activity is place-related firing. Single unit recordings of CA1 complex spike cells ('place cells'; n = 64) were made as rats with prefrontal lesions (n = 6) or sham surgeries (n = 7) foraged freely. The spatial information content provided by spikes in cells of lesion animals was significantly greater than in sham-group animals, although the size of their place fields was not affected. The location of the firing fields of lesion-group rats were less stable across time when either 5 h or 3 min intervals were inserted between successive recordings of the same cell. It was hypothesized that animals with prefrontal lesions may be overly influenced by local, less stable environmental cues than sham rats. This may explain both the spatial information content and stability findings. These findings indicate that prefrontal cortex normally modulates spatial responses in the hippocampus.

Action Potentials↗

PubMed1995

Increased sensitivity to the sensorimotor gating-disruptive effects of apomorphine after lesions of medial prefrontal cortex or ventral hippocampus in adult rats.

Sensorimotor gating of the startle reflex is impaired in humans with schizophrenia and in rats after mesolimbic D2 dopamine receptor activation. The loss of startle gating after D2 activation in rats has been used as an animal model of impaired sensorimotor gating in schizophrenia, because the ability of antipsychotics to restore startle gating in D2-activated rats correlates significantly with antipsychotic clinical potency. Substantial evidence indicates that the pathophysiology of schizophrenia includes structural and functional deficits in prefrontal and temporal regions, particularly the dorsolateral prefrontal cortex and the hippocampus and parahippocampal gyrus. The present study assessed startle gating in adult rats after ibotenic acid lesions of the medial prefrontal cortex or ventral hippocampus. Medial prefrontal cortex lesioned rats exhibited normal startle amplitude and normal sensorimotor gating, as reflected by prepulse inhibition (PPI) of the startle reflex. Hippocampus lesioned rats exhibited elevated startle amplitude, and similar to rats with medial prefrontal cortex lesions, did not show significant changes in basal PPI. Low doses of the mixed dopamine agonist apomorphine did not significantly reduce PPI in sham lesioned rats, but significantly disrupted PPI in both medial prefrontal cortex- and ventral hippo-campus lesioned rats. These data are consistent with the hypothesis that cell damage in frontal and temporal cortex increases the sensitivity to the sensorimotor gating-disruptive effects of dopamine receptor activation.

Animals↗

PubMed1999

Effects of endogenous glutamate on extracellular concentrations of GABA, dopamine, and dopamine metabolites in the prefrontal cortex of the freely moving rat: involvement of NMDA and AMPA/KA receptors.

Using microdialysis, interactions between endogenous glutamate, dopamine, and GABA were investigated in the medial prefrontal cortex of the freely moving rat. Interactions between glutamate and other neurotransmitters in the prefrontal cortex had already been studied using pharmacological agonists or antagonists of glutamate receptors. This research investigated whether glutamate itself, through the increase of its endogenous extracellular concentration, is able to modulate the extracellular concentrations of GABA and dopamine in the prefrontal cortex. Intracortical infusions of the selective glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) were used to increase the endogenous extracellular glutamate. PDC (0.5, 2, 8, 16 and 32 mM) produced a dose-related increase in dialysate glutamate in a range of 1-36 microM. At the dose of 16 mM, PDC increased dialysate glutamate from 1.25 to 28 microM. PDC also increased extracellular GABA and taurine, but not dopamine; and decreased extracellular concentrations of the dopamine metabolites DOPAC and HVA. NMDA and AMPA/KA receptor antagonists were used to investigate whether the increases of extracellular glutamate were responsible for the changes in the release of GABA, and dopamine metabolites. The NMDA antagonist had no effect on the increase of extracellular GABA, but blocked the decreases of extracellular DOPAC and HVA, produced by PDC. In contrast, the AMPA/KA antagonist blocked the increases of extracellular GABA without affecting the decreases of extracellular DOPAC and HVA produced by PDC. These results suggest that endogenous glutamate acts preferentially through NMDA receptors to decrease dopamine metabolism, and through AMPA/KA receptors to increase GABAergic activity in the medial prefrontal cortex of the awake rat.

Animals↗

PubMed2005

Early social environment interferes with the development of NADPH-diaphorase-reactive neurons in the rodent orbital prefrontal cortex.

The influence of early parental deprivation on the development of NADPH-diaphorase-(NO-synthase) reactive neuron numbers in subregions of the orbital prefrontal cortex (ventrolateral orbital, lateral orbital, and agranular insular cortex) was quantitatively investigated in the precocious lagomorph Octodon degus. Forty-five-day-old degus from three groups were compared: (1) repeated parental separation: degus that were repeatedly separated from their parents during the first three postnatal weeks and thereafter raised in undisturbed social conditions; (2) chronic isolation: degus that were raised under undisturbed social conditions until postnatal day 21, and then were reared in chronic social isolation; and (3) control: degus that were reared undisturbed in their families. Compared to the control animals the ventrolateral orbital prefrontal cortex and agranular insular cortex of the two deprived groups displayed significantly decreased density of NADPH-diaphorase-reactive neurons (down to 62% in the ventrolateral orbital prefrontal cortex of males, 70% in the agranular insular cortex, and in the lateral orbital prefrontal cortex 80% in both genders). These results confirm that early changes of social environment interferes with the development of limbic circuits, which might determine normal or pathological behaviors in later life.

Animals↗

PubMed2006

Prefrontal cortex lesions disrupt the contextual control of response conflict.

The prefrontal cortex has been implicated in multiple forms of goal-directed behavior. Rats with pretraining lesions to the prefrontal cortex (PFC) or specific lesions to the anterior cingulate cortex (ACC) were trained and tested on a novel behavioral procedure measuring aspects of cue and response competition typical of tests of prefrontal function in humans. Rats were trained on two biconditional discrimination tasks, one auditory and one visual, in two discriminably different contexts. At test, they received presentations of audiovisual compounds of these training stimuli in both contexts, in extinction. These compounds were formed in such way that the individual elements had dictated either the same (congruent trials) or different (incongruent trials) responses during training. Sham-operated rats used the contextual cues to disambiguate the conflicting response information provided by incongruent stimulus compounds. ACC lesions impaired the contextual control of instrumental responding during incongruent cues during only the initial period of cue presentation, whereas larger PFC lesions abolished incongruent cue performance completely. Neither biconditional discrimination acquisition, nor test performance during congruent stimulus compounds, were affected by the lesions. These findings are consistent with human and nonhuman primate studies, indicating a role for the PFC in the processes by which cues come to control behavior in the face of conflicting information and the ACC specifically in processes such as detection of response conflict. This procedure provides a good foundation for an improved understanding of the disruption to goal-directed behavior seen with frontal dysfunction in a number of neuropsychological disorders including schizophrenia.

Acoustic Stimulation↗

PubMed2002

Somatosensory processing in the human inferior prefrontal cortex.

Three inferior prefrontal regions in the monkey receive afferents from somatosensory cortices: the orbitofrontal cortex (OFC), the ventral area of the principal sulcus, and the anterior frontal operculum. To determine whether these areas show responses to tactile stimuli in humans, we examined data from an ongoing series of PET studies of somatosensory processing. Unlike previous work showing ventral frontal activity to hedonic (pleasant/unpleasant) sensory stimulation, the tactile stimuli used in these studies had a neutral hedonic valence. Our data provide evidence for at least two discrete ventral frontal brain regions responsive to somatosensory stimulation: 1) the posterior inferior frontal gyrus (IFG) and adjacent anterior frontal operculum, and 2) the OFC. The former region (posterior IFG/anterior frontal operculum) may have a more specific role in attending to tactile stimuli.

Adult↗

PubMed2006

Ethanol consumption and reward depend on norepinephrine in the prefrontal cortex.

We studied the involvement of norepinephrine in the medial prefrontal cortex in the rewarding/reinforcing effects of ethanol. We evaluated the effects of norepinephrine selective depletion in the medial prefrontal cortex of C57/BL6J inbred mice that are commonly used in molecular studies and are highly susceptible to the behavioral effects of ethanol. In mice with prefrontal norepinephrine depletion, ethanol did not induce conditioned place preference, and a clear-cut reduction of ethanol consumption and preference was evident. These results indicate that prefrontal norepinephrine transmission is a critical factor in the rewarding/reinforcing effects of ethanol.

Adrenergic Agents↗