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Results for “Prefrontal Cortex”

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PubMed1998

D1 receptor in interneurons of macaque prefrontal cortex: distribution and subcellular localization.

Working memory performance is influenced by dopamine activation of D1 family dopamine receptors in the prefrontal cortex; working memory performance is maximal at moderate stimulation of D1 family receptors and is reduced by either higher or lower levels of D1 stimulation. The neuronal mechanisms that underlie this complex relationship are not yet understood. Previous work from this laboratory has demonstrated that the D1 family receptors, D1 and D5, are located in different compartments of pyramidal cells. Here we use an antibody specific to the D1 receptor and double-label immunohistochemistry at the light and electron microscopic level to demonstrate that D1-like immunoreactivity (D1-LIR) is also present in interneurons. D1 receptor is prevalent in parvalbumin-containing interneurons and is less common in calretinin-containing interneurons. At the ultrastructural level, D1-LIR is found associated with the Golgi apparatus and endoplasmic reticulum in the soma, with the membranes of vesicles in proximal dendrites, and with the plasma membrane on distal dendrites, where it is often located near asymmetric synapses. In addition, D1-LIR is also seen in presynaptic axon terminals, which give rise to symmetric synapses onto dendritic shafts and soma. These results raise the possibility that the circuit basis of working memory in the prefrontal cortex involves a D1-mediated inhibitory component.

Animals↗

PubMed1997

In vivo characterization of extracellular GABA release in the caudate nucleus and prefrontal cortex of the rhesus monkey.

Extracellular gamma amino butyric acid (GABA) levels were measured in the caudate nucleus and the prefrontal cortex of the rhesus monkey brain using in vivo microdialysis under isofluorane gas anesthesia. Evoked GABA release was investigated for voltage sensitivity and calcium (Ca2+) dependency. There was a multifold increase in extracellular GABA levels following local perfusion with: (1) high potassium (50 mM, KCI), (2) veratridine (10 microM), and (3) the GABA releasing agent and uptake blocker, (-) nipecotic acid (1 mM). Release of GABA was significantly reduced when veratridine or (-) nipecotic acid were coinfused in Ca(2+)-free cerebrospinal fluid (CSF). Coinfusion of nipecotic acid with TTX (10 microM) also resulted in attenuation of evoked GABA release. These results suggest that GABA levels recovered using in vivo microdialysis, from the caudate nucleus and the prefrontal cortex in the rhesus monkey, derive in significant part from vesicular pools and the exocytotic process is both Ca(2+)-dependent and voltage-sensitive.

Animals↗

PubMed2004

Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium.

Our previous electron microscopic study of the prefrontal cortex (PFC) demonstrated ultrastructural signs of apoptosis and necrosis of oligodendroglial cells in schizophrenia (SCH) and bipolar disorder (BPD). Using optical dissector methodology, we have now conducted a morphometric study of numerical density (Nv) of oligodendroglial cells in layer VI and in adjacent white matter of Brodmann area 9 (BA 9) of the Stanley Foundation Neuropathology Consortium (SFNC). The SFNC consists of 15 cases in each of four groups: schizophrenia, bipolar disorder, major depression (MDD) and unaffected controls. A significant reduction in Nv of oligodendroglial cells was found in layer VI of subjects with schizophrenia (-25%), bipolar disorder (-29%) and major depression (-19%) as compared to controls. In adjacent white matter, there were no significant differences between groups. The data suggest that lowered density of oligodendroglial cells that occurs in schizophrenia and mood disorders could contribute to the atrophy of neurones that has been described in the prefrontal cortex of subjects with severe mental illness.

Adult↗

PubMed2000

Proton magnetic resonance spectroscopy of the medial prefrontal cortex in patients with deficit schizophrenia: preliminary report.

OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) was used to study medial prefrontal metabolic impairments in schizophrenic patients with the deficit syndrome. METHOD: The subjects were 22 schizophrenic patients categorized as deficit (N=5) or nondeficit (N=17) and 21 healthy subjects. (1)H-MRS was performed for the right and the left medial prefrontal cortex. RESULTS: The patients with the deficit syndrome had significantly lower ratios of N-acetylaspartate to creatine plus phosphocreatine than did the healthy subjects or nondeficit patients. CONCLUSIONS: As N-acetylaspartate levels could reflect neuronal density and/or viability, this finding suggests a neuronal loss in the medial prefrontal cortex of deficit patients.

Aspartic Acid↗

PubMed2004

Dopaminergic modulation of visual attention and working memory in the rodent prefrontal cortex.

Converging evidence suggests that dopaminergic projections to the prefrontal cortex (PFC) modulate both attention and working memory processes that may be related to either insufficient or excessive dopamine activity specific to a D1 receptor mechanism. We examined the effects of bilateral intraprefrontal cortical infusions of the D1 agonist (SKF 81297) on a novel task specifically designed to assess the animals' ability to attend to a visual target (0.7 or 0.5 s) and then remember the location of that target over a variable delay (0-16 s) within the same test session. Bilateral prefrontal infusions of the low dose of SKF 81297 (0.01 microg) had no effect on visual attention or memory throughout the entire testing schedule. The medium (0.06 microg) dose preferentially increased attention to the stimulus target but only improved memory for that stimulus at a duration of 0.7 s, although in a delay-independent manner. The high dose (0.3 microg) of the D1 agonist also increased attentional accuracy. However, it was only under the more attention challenging condition (0.5 s) that this high dose also produced a baseline delay-dependent modulation of memory for the stimulus target. Specifically, good memory at the short delay was impaired and poor memory at the long delay was improved. These data provide the first demonstration that dopamine D1 receptor stimulation sufficient to improve attentional accuracy, can also disrupt, and facilitate short-term working memory performance in a delay-dependent manner.

Animals↗

PubMed1980

Subcortical connections of the prefrontal cortex in dogs: afferents to the orbital gyrus.

Afferent subcortical connections to the lateral prefrontal cortex (orbital gyrus) in the dog brain were investigated using the horseradish peroxidase retrograde transport method. It was shown that: (i) the main projection to this area derives from the ventral and intermediate regions of the mediodorsal nucleus of the thalamus, (ii) fairly rich projection arises from the midline, intralaminar as well as from ventromedial and lateroposterior thalamic nuclei, (iii) scanty extrathalamic projection to the lateral prefrontal area originates from several other structures like claustrum, hypothalamus, amygdala, ventral tegmental area, raphe nuclei and locus coeruleus. Distribution of labeled cells after particular injections showed that in the orbital gyrus two subdivisions may be distinguished: dorsal and ventral. It is suggested that the dorsal orbital subdivision in dog corresponds to the lateral prefrontal cortex in monkey.

Animals↗

PubMed2006

Functional specialization within rostral prefrontal cortex (area 10): a meta-analysis.

One of the least well understood regions of the human brain is rostral prefrontal cortex, approximating Brodmann's area 10. Here, we investigate the possibility that there are functional subdivisions within this region by conducting a meta-analysis of 104 functional neuroimaging studies (using positron emission tomography/functional magnetic resonance imaging). Studies involving working memory and episodic memory retrieval were disproportionately associated with lateral activations, whereas studies involving mentalizing (i.e., attending to one's own emotions and mental states or those of other agents) were disproportionately associated with medial activations. Functional variation was also observed along a rostral-caudal axis, with studies involving mentalizing yielding relatively caudal activations and studies involving multiple-task coordination yielding relatively rostral activations. A classification algorithm was trained to predict the task, given the coordinates of each activation peak. Performance was well above chance levels (74% for the three most common tasks; 45% across all eight tasks investigated) and generalized to data not included in the training set. These results point to considerable functional segregation within rostral prefrontal cortex.

Algorithms↗

PubMed2002

Dopaminergic modulation of high-level cognition in Parkinson's disease: the role of the prefrontal cortex revealed by PET.

This study examined the effects of L-dopa medication in patients with Parkinson's disease on cortical and subcortical blood flow changes during two tasks known to involve frontostriatal circuitry. Eleven patients with Parkinson's disease were scanned on two occasions, one ON L-dopa medication and one OFF L-dopa medication, during performance of the Tower of London planning task and a related test that emphasized aspects of spatial working memory. L-dopa-induced decreases were observed in the right dorsolateral prefrontal cortex during performance of both the planning and the spatial working memory tasks compared with the visuomotor control task. Conversely, L-dopa-induced blood flow increases were observed in the right occipital lobe during the memory task relative to the control task. Data from age-matched healthy volunteers demonstrated that L-dopa effectively normalized blood flow in these regions in the patient group. Moreover, a significant correlation was found between L-dopa-induced, planning related blood flow decreases in the right dorsolateral prefrontal cortex and L-dopa-induced changes in performance on the planning task. These data suggest that L-dopa ameliorates high-level cognitive deficits in Parkinson's disease by inducing relative blood flow changes in the right dorsolateral prefrontal cortex.

Brain↗

PubMed2002

Withdrawal duration differentially affects c-fos expression in the medial prefrontal cortex and discrete subregions of the nucleus accumbens in cocaine-sensitized rats.

Intermittent administration of cocaine can result in behavioral sensitization, which is indicated by an augmented behavioral response to a subsequent administration of cocaine. This increase in behavior can be seen after various periods of abstinence from the drug, and is believed to model the cravings of drug users and the onset of drug addiction. It is believed that behavioral sensitization is mediated by activity of the mesocorticolimbic dopamine system. In particular, the nucleus accumbens and prefrontal cortex have been shown to play integral roles in this phenomenon. Recently, it has been demonstrated that the shell portion of the nucleus accumbens can no longer be considered a homogeneous structure, and can be subdivided into five separate regions. The present study was designed to assess the activation of key neuronal populations in subdivisions of the accumbens and subdivisions of the medial prefrontal cortex in cocaine-sensitized rats, using the expression of the immediate early gene, c-fos, as a marker of neuronal activation. Repeated cocaine administration resulted in robust sensitization that correlated with a significant decrease in the density of c-fos nuclei in all three subdivisions of the medial prefrontal cortex, and two subdivisions of the nucleus accumbens only in animals challenged after a 2-day withdrawal period. After a 2-week withdrawal period, sensitized animals no longer showed any differences in the density of c-fos nuclei in any of the areas examined, with the exception of a significant increase in the intermediate zone of the shell. The results indicate that distinct adaptations in neural activation take place in cocaine-sensitized rats that have been drug-free for various lengths of time. Furthermore, while specific subregions of brain areas known to play a role in drug abuse can be uniquely involved in the manifestations of cocaine sensitization, the functional roles of these subregions may differ depending on the time at which the behavior is assessed.

Animals↗

PubMed1996

Activation of the prefrontal cortex during judgments of recency: a functional MRI study.

Animal and human lesion studies have consistently shown that damage to the prefrontal lobe disrupts performance on tasks requiring memory for temporal context. In this study, functional magnetic resonance imaging (fMRI) was used to explore the brain regions associated with judgements of relative recency in healthy humans. Bilateral dorsolateral prefrontal cortex (Brodmann's area [BA] 9) was more active during a verbal recency judgment task than during a non-mnemonic control task. Activation related to temporal context recognition was also observed in midline supplementary motor area (BA 6) and left precuneus (BA 7). This study provides further evidence that memory for temporal context requires the prefrontal cortex and is the first to demonstrate this association in healthy humans. The current findings also suggest the possibility that recognition of context and recognition of episodic content may involve similar brain systems.

Adult↗

PubMed1991

The novel 5-HT2 receptor antagonist, RP 62203, selectively blocks serotoninergic but not dopaminergic-induced inhibition in the rat prefrontal cortex.

The influence of the novel 5-hydroxytryptamine2 (5-HT2) receptor antagonist, RP 62203, on serotoninergic neurotransmission was investigated using an in vivo electrophysiological technique. For this purpose, the ability of RP 62203 (1-3 mg/kg i.p.) to block the inhibitory responses of prefrontal cortical neurons induced by electrical stimulation of the median raphe nucleus was examined in anesthetized rats. In addition, the effects of RP 62203 on the dopaminergic inhibitory responses induced in the prefrontal cortex by stimulation of the ventral tegmental area and on the enhancement of these responses by lysergic acid diethylamide (LSD, a 5-HT2 receptor agonist, 30 or 60 micrograms/kg i.p.), were analyzed. RP 62203 blocked the inhibition induced by median raphe nucleus stimulation in a dose-dependent and reversible fashion. In contrast, RP 62203 failed to affect the inhibitory responses induced in prefrontal cortical cells by stimulation of the ventral tegmental area. However, the enhancement by LSD of the inhibition induced by stimulation of the ventral tegmental area in the prefrontal cortex was blocked by RP 62203. These results demonstrate that RP 62203 selectively blocks serotoninergic, but not dopaminergic, neurotransmission in the prefrontal cortex.

Animals↗

PubMed1994

Architectonic subdivision of the orbital and medial prefrontal cortex in the macaque monkey.

The orbital and medial prefrontal cortex (OMPFC) of macaque monkeys is a large but little understood region of the cerebral cortex. In this study the architectonic structure of the OMPFC was analyzed with nine histochemical and immunohistochemical stains in 32 individuals of three macaque species. The stains included Nissl, myelin, acetylcholinesterase, Timm, and selenide stains and immunohistochemical stains for parvalbumin, calbindin, a nonphosphorylated neurofilament epitope (with the SMI-32 antibody), and a membrane-bound glycoprotein (with the 8b3 antibody). In addition to patterns of cell bodies and myelinated fibers, these techniques allow the visualization of markers related to metabolism, synapses, and neurotransmitters. A cortical area was defined as distinct if it was differentiated in at least three different stains and, as described in later papers, possessed a distinct set of connections. Twenty-two areas were recognized in the OMPFC. Walker's areas 10, 11, 12, 13, and 14 [J. Comp. Neurol. (1940) 73:59-86] have been subdivided into areas 10m, 10o, 11m, 11l, 12r, 12l, 12m, 12o, 13m, 13l, 13a, 13b, 14r, and 14c. On the medial wall, areas 32, 25, and 24a,b,c have been delineated, in addition to area 10m. The agranular insula also has been recognized to extend onto the posterior orbital surface and has been subdivided into medial, intermediate, lateral, posteromedial, and posterolateral agranular insula areas. The OMPFC, therefore, resembles other areas of primate cortex, such as the posterior parietal and temporal cortices, where a large number of relatively small, structurally and connectionally distinct areas have been recognized. Just as the area-specific neurophysiological properties of these parietotemporal areas underlie broader regional functions such as visuospatial analysis, it is likely that the many small areas of the OMPFC also make differential contributions to the general mnemonic, sensory, and affective functions of this region.

Acetylcholinesterase↗

PubMed1994

The relationship between learning performance and dopamine in the prefrontal cortex of the rat.

To clarify the relationship between dopamine (DA) release in the prefrontal cortex and learning performance, extracellular DA was measured by an in vivo microdialysis method during a discrimination learning task. Rats were trained to discriminate between lamp-on and -off states under an operant-type learning procedure. After stable discriminative behavior was established, a microdialysis experiment was conducted. Inverse relationships were seen between the relative ratio of DA after the beginning of a learning session to the basal level and the responses (total, correct and error responses) during a session. The results indicate that the degree of DA release in the prefrontal cortex is involve in the inhibitory mechanism of the response during discrimination learning performance.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1998

Memory for duration: role of hippocampus and medial prefrontal cortex.

In this task rats had to learn that a three-dimensional object stimulus (a rectangle) that was visible for 2 s would result in a positive (go) reinforcement for one object (a ball) and no reinforcement (no go) for a different object (a bottle). However, if the rectangle stimulus was visible for 8 s then there would be no reinforcement for the ball (no go), but a reinforcement for the bottle (go). After rats learned this conditional discrimination by responding differentially in terms of latency to approach the object, they received large (dorsal and ventral) lesions of the hippocampus, lesions of the medial prefrontal cortex (anterior cingulate and precentral cortex), lesions of the cortex dorsal to the dorsal hippocampus, or served as sham-operated controls. Following recovery from surgery they were retested. The results indicate that there were major impairments following hippocampal lesions, in contrast to cortical control and medial prefrontal cortex lesions, as indicated by smaller latency differences between positive and negative trials on postsurgery tests. In order to ensure that the deficits observed with hippocampal lesions were not due to a discrimination problem, new rats were trained in an object (gray cylinder) duration discrimination task. In this go/no go procedure, the rats were reinforced for a 2-s exposure (duration) of the gray cylinder, but not a 10-s duration, or vice versa. The results indicate that after hippocampal lesions, there was an initial deficit followed by complete recovery. There were no significant changes for the medial prefrontal, cortical control, or sham-operated animals. It appears that the hippocampus, but not the medial prefrontal cortex, is actively involved in representing in short-term memory temporal attribute information based on the use of markers for the beginning and end of the presence (duration) of a stimulus (object).

Animals↗

PubMed2003

Effects of TMS over the right prefrontal cortex on latency of saccades and convergence.

PURPOSE: The prefrontal cortex (PFC) is known to inhibit unwanted saccades through its connections to the superior colliculus (SC). Indeed, transcranial magnetic stimulation (TMS) of the PFC decreases saccade latency by increasing the rate of express saccades. This study examined whether a similar phenomenon exists for vergence. METHODS: In a gap paradigm, six healthy subjects were asked to look at LEDs placed in a horizontal plane and to make lateral saccades, pure convergence along the median plane, and combined eye movements. Eye movements were recorded binocularly. TMS was applied over the right (r)PFC synchronously with the onset of the target. In a control condition, TMS was applied over the motor cortex (MC). RESULTS: TMS over the MC had no effect on the latency of any type of eye movements. In contrast, TMS over the rPFC (1) decreased significantly (P = 0.00367) the latency of contralateral pure saccades, (2) had no effect on the latency of pure convergence, (3) and caused a mild decrease in the latency of both the saccadic and the convergence components of combined eye movements, and the effect was bilateral. Decreased latencies were mainly due to an increase of the rate of express movements. CONCLUSIONS: The inhibition exerted by PFC over SC and preventing express movements from occurring is presumably a saccade-specific mechanism. When the saccade is combined with convergence, the express triggering can be transferred to a certain extent to the convergence.

Adult↗

PubMed1992

Changes in the turnover of monoamines in prefrontal cortex of rats fed on vitamin E-deficient diet.

Turnover of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites has been measured after a 15-day vitamin E-deficient diet in adult rat prefrontal cortex. Turnover rates of 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxy-3-indoleacetic acid have been assayed from the disappearance rates after blocking by pargyline inhibition of monoamine oxidase. NA, DA, and 5-HT turnover rates have been measured as accumulation rates of NA, DA, and 5-HT after pargyline inhibition of monoamine oxidase. No change was found in the turnover rate of NA between control and experimental animals. In contrast, turnover rates of DA and homovanillic acid significantly increased in the animals fed on a low-vitamin E diet. However, the most striking results were found on the serotoninergic system. Levels of 5-HT and its main metabolite, 5-hydroxy-3-indoleacetic acid, and their respective turnover rates were lower in the vitamin E-deficient diet. These results could indicate that vitamin E is necessary for the normal functioning of the serotoninergic neurons in the rat prefrontal cortex. The involvement of vitamin E in preventing the formation of free radicals is well known. Therefore, this lack of protective effect after a 15-day vitamin E-deficient diet could be responsible for the neuronal damage to the serotoninergic system. The opposing results found in DA (increase) and 5-HT (decrease) turnover could provide further evidence for an inhibitory control of the serotoninergic ascending pathways to the dopaminergic system in the prefrontal cortex.

Animals↗

PubMed2001

Single-neuron responses to emotional visual stimuli recorded in human ventral prefrontal cortex.

Both lesion and functional imaging studies in humans, as well as neurophysiological studies in nonhuman primates, demonstrate the importance of the prefrontal cortex in representing the emotional value of sensory stimuli. Here we investigated single-neuron responses to emotional stimuli in an awake person with normal intellect. Recording from neurons within healthy tissue in ventral sites of the right prefrontal cortex, we found short-latency (120-160 ms) responses selective for aversive visual stimuli.

Adult↗

PubMed1999

Increase of extracellular dopamine in prefrontal cortex of gerbils during acquisition of the avoidance strategy in the shuttle-box.

We examined whether extracellular dopamine (DA) increase in medial prefrontal cortex is correlated with the establishment or with the retrieval of an auditory avoidance strategy in a shuttle-box. Using microdialysis from right medial prefrontal cortex (mPFC) in combination with behavioral measures, gerbils were trained on a tone-footshock combination in two sessions on two successive days. Sessions in each animal involving avoidance strategy formation and avoidance strategy retrieval were differentiated post hoc by using the percentage of conditioned responses (CR) and other behavioral measures of training sessions. It was found that exclusively strategy formation correlated with high DA levels in mPFC.

Acoustic Stimulation↗