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Results for “Prefrontal Cortex”

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PubMed2004

Selective reduction of chromogranin A-like immunoreactivities in the prefrontal cortex of schizophrenic subjects: a postmortem study.

It is suggested that secretogranins/chromogranins play a role in regulating secretion of various proteins and amines, including neurotransmitters from secretory granules. Several studies have implicated the importance of altered synaptic connectivity in schizophrenia. We employed immunohistochemical techniques to determine if the level of chromogranin A (CgA)-immunoreactivity (IR) was altered in the subjects with schizophrenia. Nine subjects with schizophrenia and nine age- and sex-matched control subjects were selected for this study. Immunohistochemistry using specific antibody against CgA was performed on sections of prefrontal cortex and hippocampus. Images of CgA-IR were analyzed by computer-based image analyzing software. CgA-IR was significantly decreased in layers III-V of the prefrontal cortex in schizophrenic subjects compared with control subjects. In the hippocampus, no significant difference was observed between two groups. The results indicate that there may be a decrease in the number of CgA positive large dense-core vesicles per terminal, and/or in the number of CgA positive terminals, suggesting possible functional impairment of prefrontal synaptic contact in schizophrenia.

Adolescent↗

PubMed1995

Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys.

Previous studies have shown that the orbital and medial prefrontal cortex (OMPFC) is extensively connected with medial temporal and cingulate limbic structures. In this study, the organization of these projections was defined in relation to architectonic areas within the OMPFC. All of the limbic structures were substantially connected with the following posterior and medial orbital areas: the posteromedial, medial, intermediate, and lateral agranular insular areas (Iapm, Iam, Iai, and Ial, respectively) and areas 11m, 13a, 13b, 14c and 14r. In contrast, lateral orbital areas 12o, 12m, and 12l and medial wall areas 24a,b and 32 were primarily connected with the amygdala, the temporal pole, and the cingulate cortex. Data were not obtained on the posteroventral medial wall. Three distinct projections were recognized from the basal amygdaloid nucleus: 1) The dorsal part projected to area 12l; 2) the ventromedial part projected to most areas in the posterior and medial orbital cortex except for area Iai, 12o, 13a, and 14c; and 3) the ventrolateral part projected to orbital areas 12o, Iai, 13a, 14c, and to the medial wall areas. The accessory basal and lateral amygdaloid nuclei projected most strongly to areas in the posterior and medial orbital cortex. The medial, anterior cortical, and central amygdaloid nuclei and the periamygdaloid cortex were connected with the posterior orbital areas. The projection from the hippocampus originated from the rostral subiculum and terminated in the medial orbital areas. The same region was reciprocally connected with the anteromedial nucleus of the thalamus, which received input from the rostral subiculum. The parahippocampal cortical areas (including the temporal polar, entorhinal, perirhinal, and posterior parahippocampal cortices) were primarily connected with posterior and medial orbital areas, with some projections to the dorsal part of the medial wall. The rostral cingulate cortex sent fibers to the medial wall, to the medial orbital areas, and to lateral areas 12o, 12r, and Iai. The posterior cingulate gyrus, including the caudomedial lobule, was especially strongly connected with area 11m.

Amygdala↗

PubMed2006

Disruption of right prefrontal cortex by low-frequency repetitive transcranial magnetic stimulation induces risk-taking behavior.

Decisions require careful weighing of the risks and benefits associated with a choice. Some people need to be offered large rewards to balance even minimal risks, whereas others take great risks in the hope for an only minimal benefit. We show here that risk-taking is a modifiable behavior that depends on right hemisphere prefrontal activity. We used low-frequency, repetitive transcranial magnetic stimulation to transiently disrupt left or right dorsolateral prefrontal cortex (DLPFC) function before applying a well known gambling paradigm that provides a measure of decision-making under risk. Individuals displayed significantly riskier decision-making after disruption of the right, but not the left, DLPFC. Our findings suggest that the right DLPFC plays a crucial role in the suppression of superficially seductive options. This confirms the asymmetric role of the prefrontal cortex in decision-making and reveals that this fundamental human capacity can be manipulated in normal subjects through cortical stimulation. The ability to modify risk-taking behavior may be translated into therapeutic interventions for disorders such as drug abuse or pathological gambling.

Adult↗

PubMed1994

Postnatal development of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) positive neurons in rat prefrontal cortex.

First nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d)-positive perikarya in rat prefrontal cortex (PFC) are present at birth. On postnatal day (P) 1, there is an increase of NADPH-d-positive neurons in all developing layers of PFC. From P1 to P7, a further increase in the overall number of positive neurons is observed. First laminar and area shifts are noted on P21, while morphological maturation of NADPH-d-positive neurons is finished around P30. In conclusion, the postnatal development of NADPH-d neurons in PFC is in concordance with other developmental events in rat cerebral cortex.

Aging↗

PubMed2003

Sleep spindles in human prefrontal cortex: an electrocorticographic study.

To investigate the sleep spindle activity of the human prefrontal cortex (PFC), we simultaneously recorded whole nights of polysomnographic and electrocorticographic (ECoG) activities during the natural sleep of epileptic patients. Subjects were nine patients with intractable epilepsy who had subdural electrodes surgically attached to the orbital (seven cases), medial (three cases), or dorsolateral (two cases) PFC, and in one case to the frontal pole. To examine spindle frequencies, fast Fourier transformation (FFT) and auto-correlation analyses were performed on the PFC ECoG and Cz EEG data, primarily on epochs of stage 2 sleep. Lower sigma band ECoG oscillations of about 12 Hz were widely distributed across all prefrontal cortical areas including the frontal limbic regions, but none of the PFC sigma frequency peaks coincided with the faster (about 14 Hz) Cz EEG sleep spindles. Combining our results with anatomical and electrophysiological facts, it is suggested that the thalamofrontal circuit involving the rostral reticular and the mediodorsal nucleus of the thalamus is responsible for the generation of 12 Hz frontal spindles in humans.

Adult↗

PubMed2003

When the same response has different meanings: recoding the response meaning in the lateral prefrontal cortex.

The ability to adapt our behavioral repertoire to different situations and tasks is crucial for our behavioral control. Since the same motor behavior can have different meanings in different task situations, we often have to change the meaning of our responses when we get into a different task context. In a functional MRI experiment we manipulated this response recoding process. Subjects were required to execute two simple spatial tasks in a task switching paradigm. In one condition both tasks required the same set of responses, hence each response had two different meanings depending on the relevant task (bivalent condition). In the other condition subjects used a separate set of responses for each task (univalent condition). While subjects were required to recode the meaning when switching from one task to the next in the bivalent condition, response recoding was not required in the univalent condition. We demonstrate that the lateral prefrontal cortex is involved in recoding of response meaning. These results extend previous assumptions on the role of the prefrontal cortex in behavioral control.

Adult↗

PubMed1997

Dissociating working memory from task difficulty in human prefrontal cortex.

A functional magnetic resonance imaging (fMRI) study was conducted to determine whether prefrontal cortex (PFC) increases activity in working memory (WM) tasks as a specific result of the demands placed on WM, or to other processes affected by the greater difficulty of such tasks. Increased activity in dorsolateral PFC (DLPFC) was observed during task conditions that placed demands on active maintenance (long retention interval) relative to control conditions matched for difficulty. Furthermore, the activity was sustained over the entire retention interval and did not increase when task difficulty was manipulated independently of WM requirements. This contrasted with the transient increases in activity observed in the anterior cingulate, and other regions of frontal cortex, in response to increased task difficulty but not WM demands. Thus, this study established a double-dissociation between regions responsive to WM versus task difficulty, indicating a specific involvement of DLPFC and related structures in WM function.

Adult↗

PubMed2002

Visual categorization and the primate prefrontal cortex: neurophysiology and behavior.

The ability to group stimuli into meaningful categories is a fundamental cognitive process. To explore its neuronal basis, we trained monkeys to categorize computer-generated stimuli as "cats" and "dogs." A morphing system was used to systematically vary stimulus shape and precisely define a category boundary. Psychophysical testing and analysis of eye movements suggest that the monkeys categorized the stimuli by attending to multiple stimulus features. Neuronal activity in the lateral prefrontal cortex reflected the category of visual stimuli and changed with learning when a monkey was retrained with the same stimuli assigned to new categories. Further, many neurons showed activity that appeared to reflect the monkey's decision about whether two stimuli were from the same category or not. These results suggest that the lateral prefrontal cortex is an important part of the neuronal circuitry underlying category learning and category-based behaviors.

Action Potentials↗

PubMed1985

The thalamic relations of the caudal inferior parietal lobule and the lateral prefrontal cortex in monkeys: divergent cortical projections from cell clusters in the medial pulvinar nucleus.

The thalamic relations of the caudal inferior parietal lobule and the dorsolateral prefrontal cortex in monkeys have been investigated with both anterograde and retrograde neuroanatomical tracing techniques. The results of these experiments indicate that the medial pulvinar nucleus (Pul.m.) is the principal thalamic relay to the gyral surface of the caudal inferior parietal lobule (area 7a). Within the Pul.m. there are two or three disklike aggregates of neurons which project to area 7a; these disklike neuronal aggregates are oriented from dorsomedial to ventrolateral and extend over most of the rostrocaudal extent of the nucleus. Within these disks there are rodlike clusters of neurons which are elongated in the rostrocaudal dimension of the thalamus, and which project in a topographically ordered manner to area 7a. Thus, the more rostrally located neurons within the Pul.m. disks project to more rostral parts of area 7a and, conversely, the more caudally located neurons project to the caudal part of this cortical field. Similarly, the medial part of each disk projects to the lateral part of area 7a while the laterally placed neurons project to the medial part of the cortical field. In addition to its input from the Pul.m., area 7a is also reciprocally connected with the magnocellular division of the nucleus ventralis anterior, with the nuclei which abut upon the medullary capsule of the laterodorsal nucleus, and with the suprageniculate nucleus and the nucleus limitans. The cortex on the lateral bank of the intraparietal sulcus (the so-called lateral intraparietal area, LIP) projects principally to the lateral pulvinar nucleus (Pul.l) of the thalamus rather than to Pul.m. Area LIP has been found to project to the pregeniculate nucleus, the zona incerta, the anterior pretectal nucleus, and the superior colliculus. Area 7a projects to none of these structures, but it does project to the posterior pretectal nucleus. The thalamic relations of the neighboring cortical regions, such as the prelunate gyrus and area 7b, are also distinct from those of area 7a. It thus seems that the prelunate gyrus is primarily interconnected with the Pul.l., and area 7b with the oral pulvinar nucleus. Taken together these different subcortical relationships provide further evidence for the view that the caudal inferior parietal lobule is not a homogeneous cortical area, but is composed of a number of subsidiary fields. The projection from the Pul.m. to the lateral prefrontal cortex arises from disklike aggregates of neurons, similar in their orientation to the neuronal disks that project to area 7a.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2006

Stimulation of group I mGlu receptors in the ventrotegmental area enhances extracellular dopamine in the rat medial prefrontal cortex.

Group I mGlu receptors have been implicated in the control of brain dopamine release. However, the receptor subtype involved and the precise site of action have not been determined. In this study we show that (R,S)3,5-dihydroxyphenylglycine (DHPG; 6 and 60 nmol ICV), a selective group I mGlu receptor agonist, raised extracellular dopamine respectively by 176% and 243% of basal values in the medial prefrontal cortex as assessed by in vivo microdialysis in conscious rats. (R,S)2-chloro-5-hydroxyphenylglycine (60 nmol ICV), a selective mGlu5 receptor agonist, raised extracellular dopamine by 396% of basal values. Intra-VTA DHPG (0.6-6 nmol) mimicked ICV injection whereas intracortical infusion (1-1000 micromol/L) had no effect. DHPG-induced rise of extracellular dopamine was reversed by tetrodotoxin and by the selective mGlu1 and mGlu5 receptor antagonists 7(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate (CPCCOEt) and 2-methyl-6-(phenylethynyl)pyridine (MPEP) either ICV or into the ventrotegmental area (VTA), suggesting that neuronal release and both mGlu1 and mGlu5 receptors were involved. These results support the existence of functional mGlu1 and mGlu5 receptors in the VTA regulating the release of dopamine in the medial prefrontal cortex.

Animals↗

PubMed1996

The role of the prefrontal cortex in higher cognitive functions.

The higher cognitive functions, working memory, mental imagery and willed action, are all intimately associated with consciousness. The common process underlying all these functions is that information is "held in mind" for a period of time. This information, which may be about stimuli or responses, can be derived from the past or generated for the future. Brain imaging studies show that "holding something in mind" is associated with activity in an extended system which involves both prefrontal cortex and more posterior areas whose location is determined by the nature of the information being held in mind. Automatic actions and perceptions which do not involve consciousness are associated with activity in the relevant posterior areas, but not in the prefrontal cortex. These studies demonstrate that activity occurs in the same posterior area whether the associated information comes from the outside world or is internally generated. This raises the problem of how we know whether our experience derives from mental imagery or from something happening in the outside world. There is evidence that patients with schizophrenia have precisely this problem since they perceive their own thoughts and even sub-vocal speech as coming from outside (hallucinations). Recent brain imaging studies suggest that there is a disconnection between prefrontal and posterior areas in these patients which could explain their characteristic misperceptions.

Choice Behavior↗

PubMed2005

Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers.

This paper describes the quantitative areal and laminar distribution of identified neuron populations projecting from areas of prefrontal cortex (PFC) to subcortical autonomic, motor, and limbic sites in the rat. Injections of the retrograde pathway tracer wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) were made into dorsal/ventral striatum (DS/VS), basolateral amygdala (BLA), mediodorsal thalamus (MD), lateral hypothalamus (LH), mediolateral septum, dorsolateral periaqueductal gray, dorsal raphe, ventral tegmental area, parabrachial nucleus, nucleus tractus solitarius, rostral/caudal ventrolateral medulla, or thoracic spinal cord (SC). High-resolution flat-map density distributions of retrogradely labelled neurons indicated that specific PFC regions were differentially involved in the projections studied, with medial (m)PFC divided into dorsal and ventral sectors. The percentages that WGA-HRP retrogradely labelled neurons composed of the projection neurons in individual layers of infralimbic (IL; area 25) prelimbic (PL; area 32), and dorsal anterior cingulate (ACd; area 24b) cortices were calculated. Among layer 5 pyramidal cells, approximately 27.4% in IL/PL/ACd cortices projected to LH, 22.9% in IL/ventral PL to VS, 18.3% in ACd/dorsal PL to DS, and 8.1% in areas IL/PL to BLA; and 37% of layer 6 pyramidal cells in IL/PL/ACd projected to MD. Data for other projection pathways are given. Multiple dual retrograde fluorescent tracing studies indicated that moderate populations (<9%) of layer 5 mPFC neurons projected to LH/VS, LH/SC, or VS/BLA. The data provide new quantitative information concerning the density and distribution of neurons involved in identified projection pathways from defined areas of the rat PFC to specific subcortical targets involved in dynamic goal-directed behavior.

Animals↗

PubMed2001

Increased extracellular glutamate in rat prefrontal cortex: movement artifact contribution.

Extracellular glutamate levels were measured by microdialysis in the prefrontal cortex (PFC) of anaesthetised rats in response to a short, experimenter-provoked mechanical movement of the animal head. Movement caused significant, nerve impulse-independent elevations of glutamate levels (maximum increase, 300+/-30% of baseline). This study reveals a possible artifact in the measurement of extracellular glutamate concentrations by microdialysis and suggests that, in awake animals, treatments associated with stimulation of motor activity can cause non-specific efflux of glutamate in the PFC.

Anesthesia↗

PubMed2005

Increased capacity and density of choline transporters situated in synaptic membranes of the right medial prefrontal cortex of attentional task-performing rats.

Cholinergic neurons innervating the cortex have been conceptualized as a major component of the attention system of the brain. Because of recent evidence indicating plastic mechanisms regulating choline transporter (CHT)-mediated high-affinity choline uptake, which is the rate-limiting step of acetylcholine synthesis, the present experiment determined the capacity of cholinergic terminals to transport choline, and the proportion of choline transporters localized in the membrane of synaptic terminals, in several brain regions of rats performing a cognitive vigilance task (CVT) and a simple reaction time task (SRTT) and nonperforming (NP) rats. Compared with evidence from NP rats, increased choline transporter capacity [as indicated by maximum transporter velocity (Vmax)] and an increased density of CHTs situated in synaptic plasma membrane, relative to intracellular locations, were observed in the medial prefrontal cortex of the right but not left hemisphere of CVT-performing animals. Furthermore, right medial prefrontal Vmax values of CVT-performing rats correlated positively and left medial Vmax values correlated negatively with the animals' performance in signal trials. Measures of CHT function in the brains of SRTT-performing animals did not differ significantly from those in NP rats. The present data support the hypothesis that an increased capacity of choline transporters in the right medial prefrontal cortex, primarily attributable to increased trafficking of transporters from intracellular compartments to the terminal membrane, represents a cellular mechanism contributing to the mediation of attentional performance.

Analysis of Variance↗

PubMed1991

Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drug-naive schizophrenics. A pilot study of the dorsal prefrontal cortex by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy.

In this pilot study, membrane phospholipid and high-energy phosphate metabolism were studied in the dorsal prefrontal cortex of 11 drug-naive, first-episode schizophrenic patients and compared with those of 10 healthy control volunteers comparable in age, education, and parental education. The schizophrenic patients had significantly reduced levels of phosphomonoesters and inorganic orthophosphate and significantly increased levels of phosphodiesters and adenosine triphosphate compared with the controls. The levels of phosphocreatine and adenosine diphosphate did not differ in the two subject groups. The adenosine triphosphate and inorganic orthophosphate findings suggest functional hypoactivity of the dorsal prefrontal cortex. The phosphomonoester and phosphodiester findings are compatible with either premature aging or an exaggeration of normal programmed regressive events occurring in the neural systems sampled.

Adult↗

PubMed2006

Dopamine and noradrenaline efflux in the medial prefrontal cortex during serial reversals and extinction of instrumental goal-directed behavior.

The prefrontal cortex (PFC) of the rat supports cognitive flexibility, the ability to spontaneously adapt goal-directed behavior in response to radically changing situational demands. We have shown previously that transient inactivation of the rat medial PFC (mPFC) impairs initial reversal learning in a spatial 2-lever discrimination task. Given the importance of dopamine (DA) for PFC function, we studied DA (and noradrenaline [NA]) efflux in the mPFC during reversal learning. We observed a higher and more extended increase in DA efflux in rats performing the first reversal compared with controls performing the previously acquired discrimination. The results of an additional experiment suggest that such a difference between the reversal- and control-induced DA increases was absent during a third reversal. During the extinction session, DA efflux did not increase from basal levels. Increases in NA efflux were less than in DA and did not differ between control and any condition. We conclude that prefrontal DA activity is increased during execution of instrumental discrimination tasks and that this increase is amplified during the acquisition of a first, but not of later reversals. These data corroborate our previous findings and indicate that DA is critically involved in this form of cognitive flexibility.

Animals↗

PubMed1986

An immunohistochemical characterization of somatostatin-28 and somatostatin-281-12 in monkey prefrontal cortex.

The distribution of the prosomatostatin-derived peptides (PSDP) somatostatin-28 (SS-28) and somatostatin-281-12 (SS-281-12) was characterized immunohistochemically in the prefrontal cortical regions of both Old World cynomolgus monkeys (Macaca fascicularis) and New World squirrel monkeys (Saimiri sciureus). Comparison of staining with antisera specific for each peptide revealed that these antigens were segregated within immunoreactive neurons such that SS-28 was largely confined to the perinuclear region of the cell body whereas SS-281-12 was primarily found in axons and dendrites. The laminar pattern of immunoreactive fibers was similar in all areas of the prefrontal cortex. The most dense terminal arborization was in layers I, II, and superficial III. Deep III and IV were traversed by radial fibers that had little arborization. Layers V and VI contained both radial fibers and a moderately dense terminal plexus. Labeled fibers were less numerous in the white matter. There were marked regional differences in fiber density. Areas 12 and 24 had the greatest density of immunoreactive fibers, areas 9, 11, and 25 were of intermediate density, and areas 10 and 46 were the least dense. Most of the immunoreactive cells appeared to be multipolar or bitufted. They were found throughout all cortical layers and the white matter. The largest number were located in layers II, superficial III, and deep V and VI. There were also marked regional differences in cell body density, which paralleled the regional differences in fiber density. Area 24 (anterior cingulate) had the greatest density of immunoreactive cell bodies (148 +/- 14/mm2), area 9 was of intermediate density (109 +/- 13/mm2), and area 46 was the least dense (83 +/- 12/mm2). Our findings indicate that PSDP compose a complex and extensive cortical system that is largely or totally intrinsic. The substantial regional heterogeneity in density exhibited by PSDP-containing neurons has not previously been reported for an intrinsic cortical system. The laminar and regional innervation patterns of these fibers and cell bodies suggest that the PSDP cortical system may play an important role in the polymodal information processing that occurs in association regions of prefrontal cortex.

Animals↗

PubMed2000

Differential vulnerability of hippocampus, basal ganglia, and prefrontal cortex to long-term NMDA excitotoxicity.

In human brain, nonartherosclerotic calcification is associated with normal aging and several pathological conditions without any clear significance. In all situations, calcification appears predominantly in the basal ganglia, but is also frequent in the hippocampus and cerebral cortex. alpha-Amino-(3-hydroxi-5-methyl-4-isoxazol-4-il)-propionic acid-induced lesion of the globus pallidus is associated in rats with the formation of calcium deposits similar to those observed in the human brain. To determine whether direct neuronal activation may induce calcification, N-methyl-d-aspartate (NMDA) was microinjected in rat hippocampus, globus pallidus, and lateral prefrontal cortex. Two months later, neuronal death was associated with calcium deposits that were characterized in terms of distribution and size. A unique population of deposits was present in the hippocampus and prefrontal cortex, whereas in the globus pallidus two main groups could be differentiated. Calcification was always associated with a significant microglial reaction as shown by the peripheral benzodiazepine receptor autoradiography. Monoamine oxidase B autoradiography, reflecting the astroglial reaction, was also significantly increased. Our results provide evidence that acute NMDA neuronal activation leads with time to calcification associated with a glial reaction and indicate that nonartherosclerotic calcification in the human brain may develop from an acute NMDA receptor activation. A key role of the metabotropic mGluR1 receptor is also suggested.

Animals↗