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Results for “Prefrontal Cortex”

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PubMed1991

Prefrontal cortex self-stimulation and energy balance.

The relation between sulcal prefrontal cortex (SPC) and medial prefrontal cortex (MPC) self-stimulation and energy balance was investigated in rats. SPC but not MPC self-stimulation induced feeding but not the gnawing of wooden blocks. SPC but not MPC self-stimulation enhanced weight gain over several weeks of exposure to stimulation. Food deprivation (48 hr but not 24 hr) increased SPC self-stimulation rates under a 5-s fixed-interval reinforcement schedule and decreased current thresholds for SPC self-stimulation. MPC self-stimulation was unaffected by food deprivation. Insulin (4 U/kg) and 2-deoxy-D-glucose (300 mg/kg) inhibited both SPC and MPC self-stimulation, probably through interfering with performance. Satiety induced by prolonged intake of a sweetened solution or deprivation-induced feeding moderately facilitated SPC self-stimulation. Overall, it appears that SPC but not MPC self-stimulation modulates, and is modulated by, energy balance.

Animals↗

PubMedDate not supplied

Reversible deficit in haptic delay tasks from cooling prefrontal cortex.

The main purpose of this study was to explore the role of dorsolateral prefrontal cortex in skilled and sequential haptic performance. Monkeys were trained to perform a delayed matching-to-sample task that required the memorization of three-dimensional objects perceived either by palpation (haptically) or by sight. At the start of a trial the animal was allowed to touch or view an object, the sample; after a period of delay, during which the object remained out of touch and out of sight, the animal was presented with two side-by-side objects--one of them the sample--for either tactile or visual recognition, and the choice of the sample (correct match) was rewarded. Three variants of the task were used: (1) visual sample, haptic match; (2) haptic sample, visual match; and (3) haptic sample, haptic match. The temporary bilateral cooling of dorsolateral prefrontal cortex to 15 degrees C induced a reversible deficit in performance of all three tasks. Cooling to the same degree a portion of posterior parietal cortex of equivalent size did not significantly alter either performance or reaction time. These findings indicate that the functional integrity of the dorsolateral prefrontal cortex is important for performance of sequential behavior dependent on haptic skill. Further, the results suggest that the role of this cortex in active memory, already well documented for spatially and nonspatially defined visual information, extends also to tactile information and associated motor acts.

Animals↗

PubMed1998

Layer-specific dendritic regression of pyramidal cells with ageing in the human prefrontal cortex.

The dendritic field of pyramidal neurons in cortical layers IIIc and V of the prefrontal cortex in ageing humans was studied. The three-dimensional branching pattern of the basilar dendrites of Golgi-Cox impregnated neurons was analysed in the middle frontal gyrus (areas 9 and 46) in eight subjects between the ages of 49 and 90 years, all without a neurological or psychiatric disorder. The results revealed a significant regression of the layer V dendritic pattern with increasing age, but the layer IIIc neurons did not show any age-related changes. Together with our earlier data on the postnatal development of the same cell types in the prefrontal cortex, we hypothesize that the layer V neurons in the prefrontal cortex start to regress from the fifth decade onwards, in contrast to the layer IIIc neurons which remain stable from puberty on. We conclude that pyramidal cells in layer IIIc and V in a similar cortical region undergo a differential ageing effect.

Aged↗

PubMed2001

Exposure of a 'witness rat' to one treated with beta-carboline FG 7142 does not increase dopamine turnover in the medial prefrontal cortex of the 'witness rat'.

A method for selectively activating the dopaminergic field of the prefrontal cortex would be highly useful for studies of mesocortical dopamine systems. When a rat ('witness' rat) is exposed to a rat that is undergoing footshock, prefrontocortical dopamine metabolism is selectively increased in the witness rat. Since the anxiogenic beta-carboline FG 7142 mimics many of the effects of footshock, we hypothesized that exposure of a witness-rat to a rat treated with FG 7142 would also increase dopamine metabolism in the prefrontal cortex. We found that while as expected, FG 7142 itself increased prefrontal cortex dopamine metabolism, there was no significant change in dopamine metabolism in the witness rat. Thus exposure to a rat treated with FG 7142 does not selectively activate the mesocortical dopamine system.

Animals↗

PubMed2001

Dissociable mechanisms of attentional control within the human prefrontal cortex.

Neuropsychological tests that require shifting an attentional set, such as the Wisconsin Card Sorting Test, are sensitive to frontal lobe damage. Although little information is available for humans, an animal experiment suggested that different regions of the prefrontal cortex may contribute to set shifting behavior at different levels of processing. Behavioral studies also suggest that set shifting trials are more time consuming than non-set shifting trials (i.e. switch cost) and that this may be underpinned by differences at the neural level. We determined whether there were differential neural responses associated with two different levels of shifting behavior, that of reversal of stimulus-response associations within a perceptual dimension or that of shifting an attentional set between different perceptual dimensions. Neural activity in the antero-dorsal prefrontal cortex increased only in attentional set shifting, in which switch costs were significant. Activity in the postero-ventral prefrontal cortex increased not only in set shifting but also in reversing stimulus-response associations, in which switch costs were absent. We conclude that these distinct regions in the human prefrontal cortex provide different levels of attention control in response selection. Thus, the antero-dorsal prefrontal cortex may be critical for higher order control of attention, i.e. attentional set shifting, whereas the postero-ventral area may be related to a lower level of shift, i.e. reorganizing stimulus-response associations.

Adult↗

PubMed1985

Effects of ketanserin on neuronal responses to serotonin in the prefrontal cortex, lateral geniculate and dorsal raphe nucleus.

The ability of the putative serotonin2 (5-HT2) antagonist ketanserin, to alter serotonin (5-HT)-induced responses in cell firing was examined in the prefrontal cortex, the lateral geniculate nucleus and the dorsal raphe nucleus of the rat by microiontophoretic extracellular single unit recording techniques. In the prefrontal cortex, ketanserin failed to antagonize the inhibitory effects of 5-HT recorded in cerveau isolé or preparations anesthetized with chloral hydrate (pure excitatory responses to 5-HT were not observed in either of these preparations). Paradoxically, the inhibitory response produced by 5-HT (but not gamma-aminobutyric acid, tryptamine or norepinephrine) was potentiated, even in cells where ketanserin alone did not alter spontaneous firing rates. The systemic administration of ketanserin (5 mg/kg, i.p.) had effects similar to those observed in the microiontophoretic experiments in the prefrontal cortex. In the dorsal raphe nucleus of animals anesthetized with chloral hydrate, ketanserin neither attenuated nor potentiated the inhibition of serotonergic neurons by 5-HT. In the lateral geniculate nucleus, as in the prefrontal cortex, ketanserin potentiated rather than attenuated, the inhibitory effect of 5-HT. Ketanserin was found to attenuate the excitatory responses produced by norepinephrine, an alpha 1-adrenoceptor-mediated response, in the lateral geniculate nucleus. The observed potentiation by ketanserin of inhibitory responses to 5-HT but not those of gamma-aminobutyric acid, tryptamine or norepinephrine, recorded in the prefrontal cortex, may be consistent with the proposed interaction between ketanserin and a specific 5-HT2 binding site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2001

Dissociable contributions of the orbitofrontal and lateral prefrontal cortex of the marmoset to performance on a detour reaching task.

To gain insight into the nature and neural specificity of the relationship between simple problem solving, inhibitory control and prefrontal cortex, comparison of the effects of excitotoxic lesions of the orbitofrontal and lateral prefrontal cortex were examined on the performance of common marmosets on a detour reaching task. Monkeys were required to inhibit reaching directly for food reward in a transparent box and instead make a detour reach around to the side of the box either having had (i) no prior experience on the task (experiment 1) or (ii) previous experience in reaching around the sides of an opaque box (experiment 2). Whilst monkeys with orbitofrontal lesions had difficulty in inhibiting direct reaches to visible food reward (experiment 1), they could resist this prepotent response tendency following extensive prior experience of detour reaching with an opaque box (experiment 2). In marked contrast, monkeys with lateral prefrontal lesions exhibited no difficulty in inhibiting reaching to visible food reward or acquiring detour reaching per se (experiment 1). However, having been given the opportunity to acquire an efficient detour reaching strategy to hidden food reward these lateral prefrontal lesioned monkeys were impaired at transferring this strategy to the new context in which the food reward was made visible (experiment 2). This double dissociation between the effects of orbitofrontal and lateral prefrontal lesions on detour reaching provides evidence for a clear distinction in the level of control over responding exerted by the orbitofrontal and lateral prefrontal cortex, consistent with hierarchical ordering of response control processes within prefrontal cortex.

Animals↗

PubMed2001

A neuropsychological investigation of prefrontal cortex involvement in acute mania.

OBJECTIVE: Mania has received little attention from a contemporary neuropsychological perspective despite its clear resemblance to the disinhibition syndrome sometimes seen after frontal brain injury, particularly injury to the inferior aspect of the prefrontal cortex. The purpose of this investigation was to describe the neuropsychological profile of severe acute mania by using a range of tasks selected primarily for the detection of localized neural disruption within the prefrontal cortex. METHOD: Fifteen acutely manic inpatients were compared with 30 nonpsychiatric subjects on tasks from the Cambridge Automated Neuropsychological Test Battery (Tower of London, spatial working memory, intradimensional-extradimensional attentional shift, and rapid visual information processing tasks) and on the Iowa Gambling Task, Stroop Color and Word Test, a verbal fluency task, and the California Verbal Learning Test. RESULTS: Discriminant function analysis identified deficits in sustained attention (on the rapid visual information processing task) and verbal learning (on the California Verbal Learning Test) as the best indicators of manic performance, rather than deficits on any of the tests of executive functioning. The model correctly classified 91% of subjects overall and 87% of manic subjects. Manic patients did not resemble patients with ventromedial prefrontal cortex damage in their performance on the Iowa Gambling Task. CONCLUSIONS: Acute mania is characterized by core deficits in verbal memory and sustained attention against a background of milder impairments in functions that are traditional measures of prefrontal cortex integrity (attentional set shifting, planning, working memory). The data do not implicate ventral prefrontal cortex disruption as a locus of pathology in acute mania. Verbal memory and sustained attention deficits may relate differentially to the state and trait characteristics of bipolar disorder.

Acute Disease↗

PubMed2005

Noradrenergic modulation of cognitive function in rat medial prefrontal cortex as measured by attentional set shifting capability.

The brain noradrenergic system is thought to facilitate neuronal processes that promote behavioral activation, alertness, and attention. One region in which norepinephrine may exert such effects is the medial prefrontal cortex, which has been implicated in many cognitive functions including arousal, attention, motivation, working memory, response inhibition, and behavioral flexibility. The present study addressed the modulatory influence of noradrenergic neurotransmission in medial prefrontal cortex on cognitive function in rats, as measured by performance in an attentional set shifting task. In experiment 1, we tested effects of increasing and decreasing brain noradrenergic neurotransmission by systemic administration of the alpha2-adrenergic autoreceptor antagonist and agonist drugs, atipamezole and clonidine, respectively. Atipamezole pretreatment significantly improved performance on the stages of the attentional task requiring an extradimensional shift in attention, and those involving stimulus reversals, whereas clonidine had no effect at any stage. In experiment 2, we then tested effects of microinjecting alpha1- or beta-adrenergic receptor antagonists into medial prefrontal cortex on the enhancement of performance on the extradimensional task produced by atipamezole. The atipamezole-induced enhancement of performance on the extradimensional set shifting task was blocked by alpha1-, but not beta-adrenergic receptor antagonists in medial prefrontal cortex. Neither antagonist alone had any effect on extradimensional set shift performance in the absence of atipamezole-induced enhancement. These results indicate that elevating noradrenergic activity at alpha1-receptors in medial prefrontal cortex facilitates cognitive performance of rats in an attentional set-shifting task, which may contribute to the role of norepinephrine in behavioral state changes such as arousal, or to the beneficial cognitive effects of psychotherapeutic drugs that target noradrenergic neurotransmission.

Adrenergic alpha-Agonists↗

PubMed1996

The effects of antipsychotic drugs on Fos protein expression in the prefrontal cortex: cellular localization and pharmacological characterization.

The assessment of immediate-early gene induction has proven to be a useful method for delineating the neural systems that subserve antipsychotic drug actions. In order to differentiate the sites and mechanisms of action of typical and atypical antipsychotic drugs, we examined the effects of antipsychotic drugs on Fos protein expression in the medial prefrontal cortex. The atypical antipsychotic drug clozapine selectively increased the number of neurons that expressed Fos-like immunoreactivity in the prefrontal cortex, targeting the deep layers of the infralimbic and prelimbic cortices. Pyramidal cells were the major cell type in which Fos was expressed. A small number of calbindin-like immunoreactive, but not parvalbumin- or reduced nicotinamide adenine dinucleotide phosphate diaphorase-containing, interneurons also expressed Fos after clozapine challenge. Immunoblot studies revealed that clozapine induced Fos protein in the infralimbic and prelimbic cortices. Other antipsychotic drugs that are D2 receptor antagonists, including haloperidol, raclopride, sulpiride, remoxipride and loxapine, did not alter Fos expression. The clozapine-induced increase in Fos expression was also not attributable to actions at the D1 dopamine receptor, nor to serotonin type 2a/2c receptor antagonism or combined serotonin type 2-D2 dopamine receptor antagonism. The ability of clozapine to block alpha 1-adrenergic or muscarinic cholinergic receptors did not contribute to the unique actions of clozapine. Despite the inability of dopamine receptor antagonists other than clozapine to elicit an increase in Fos expression, both the mixed D1-D2 dopamine agonist apomorphine and the D2-like agonist quinpirole increased Fos protein levels in the prefrontal cortex. However, neither pretreatment with sulpiride to block D2/3/4 dopamine receptors or SCH 23390 to block D1/5 dopamine receptors modified the Fos response to clozapine. Since dopamine receptor antagonist pretreatments did not attenuate the clozapine-elicited Fos expression, but D2 agonists increased cortical Fos expression, clozapine may act in the prefrontal cortex on an as yet undefined dopamine receptor. In contrast to the nucleus accumbens shell, where all antipsychotic drugs increase Fos expression, only clozapine induced Fos in the medial prefrontal cortex. These observations suggest that the ability of clozapine to treat schizophrenic patients who are resistant to the therapeutic benefits of conventional antipsychotic drugs may occur through actions in the prefrontal cortex.

Animals↗

PubMed1997

Dopamine, the prefrontal cortex and schizophrenia.

Dysfunction of the prefrontal cortex (PFC) in schizophrenia has been suspected based on observations from clinical, neuropsychological and neuroimaging studies. Since the PFC receives a dense dopaminergic innervation, abnormalities of the mesocortical dopamine system have been proposed to contribute to the pathophysiology of schizophrenia. In this review, aspects of the anatomy, physiology and pharmacology of the mesencephalic-frontal cortical dopamine system as they may relate to schizophrenia are described, and evidence for altered dopaminergic neurotransmission in the frontal cortex of schizophrenic patients is presented.

Antipsychotic Agents↗

PubMed2006

Acute changes in frontoparietal activity after repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex in a cued reaction time task.

Lesion and functional imaging studies in humans have suggested that the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and intraparietal sulcus (IPS) are involved in orienting attention. A functional magnetic resonance imaging study supplemented by a behavioral experiment examined the effects of 5 Hz repetitive transcranial magnetic stimulation (rTMS) conditioning to the right and left DLPFC on reaction times and synaptic activity as indexed by changes in the blood oxygenation level-dependent (BOLD) signal during a cued choice reaction time task. Orienting precues were either correct (valid) or incorrect (invalid) with respect to the subsequent move cue. The effects of real and sham rTMS were compared for each site of stimulation. Invalid trials showed a significant increase in response times and increases in the BOLD signal in right frontal and parietal regions when compared with valid trials. Conditioning left DLPFC with rTMS led to decreased BOLD signal during performance of this reorienting task in areas including left VLPFC and left IPS. Comparing invalid to valid trials after right DLPFC conditioning revealed decreased BOLD signal in right VLPFC. Data from the behavioral study showed that right DLPFC rTMS selectively increases response times in invalid trials. This effect was only present in the first 10 min after rTMS conditioning. No effect was found in either validly or invalidly cued trials with left DLPFC conditioning. These results suggest that 5 Hz rTMS over right DLPFC exerts remote effects on the activity of areas that functionally interact with the DLPFC during attentional processes, particularly when the reorienting of attention is more demanding as in invalid trials.

Adult↗

PubMed1987

Electrophysiological effects of phencyclidine in the medial prefrontal cortex of the rat.

The effects of local applications of phencyclidine (PCP) and dopamine (DA) on neurons of the medial prefrontal cortex were investigated using single unit recording techniques. The activity of the majority of cells in the deeper layers of the medial prefrontal cortex was depressed by both phencyclidine and DA, whereas increases, as well as decreases, in the firing rates were observed in cells located in the superficial cortical layers. The stereospecificity of the responses of deeper cells to phencyclidine was demonstrated using the enantiomers of 1-(-1-phenylcyclohexyl)-3-methylpiperidine (PCMP). Phencyclidine was found to be 1.5 times more potent than (+) PCMP and 3 times more potent than (-) PCMP. Finally, the DA receptor antagonist fluphenazine, blocked the phencyclidine-elicited depressions of unit activity in the deep prefrontal cortex. Taken together, the data indicate that the DA-like effects of phencyclidine on neurons of the medial prefrontal cortex are mediated by DA receptors and provide pharmacological support for the idea that psychomotor stimulant drugs have specific actions on targets of the ventral tegmental area (A10) dopamine system.

Animals↗

PubMed2006

Revisiting the role of the prefrontal cortex in the pathophysiology of attention-deficit/hyperactivity disorder.

Most neural models for the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) have centered on the prefrontal cortex and its interconnections with the striatum and other subcortical structures. However, research only partially supports these models, and they do not correspond with the development of the prefrontal cortex and its interrelated neurocircuitry. The neural and functional development of the prefrontal cortex more closely parallels recovery from ADHD as indicated by the developmental remission of symptomatology. The authors hypothesize that ADHD is due to noncortical dysfunction that manifests early in ontogeny, remains static throughout the lifetime, and is not associated with the remission of symptomatology. Data supporting this neurodevelopmental model of prefrontal cortex function in ADHD are reviewed. Research and treatment implications are discussed.

Attention Deficit Disorder with Hyperactivity↗

PubMed2000

The prefrontal cortex: response selection or maintenance within working memory?

It is controversial whether the dorsolateral prefrontal cortex is involved in the maintenance of items in working memory or in the selection of responses. We used event-related functional magnetic resonance imaging to study the performance of a spatial working memory task by humans. We distinguished the maintenance of spatial items from the selection of an item from memory to guide a response. Selection, but not maintenance, was associated with activation of prefrontal area 46 of the dorsal lateral prefrontal cortex. In contrast, maintenance was associated with activation of prefrontal area 8 and the intraparietal cortex. The results support a role for the dorsal prefrontal cortex in the selection of representations. This accounts for the fact that this area is activated both when subjects select between items on working memory tasks and when they freely select between movements on tasks of willed action.

Animals↗

PubMed1975

Effects of electrical stimulation of the lateral aspect of the prefrontal cortex upon attack behavior in cats.

An experiment was performed to determine the role of the lateral aspect of the prefrontal cortex upon quiet biting attack behavior elicited from the hypothalamus in the cat. The results of this experiment indicate that stimulation of 19 of 28 electrode sites sampled in the lateral prefrontal cortex produced a statistically significant inhibition of attack behavior elicited from the hypothalamus of the ipsilateral side. Stimulation of sites in the prefrontal cortex on the side contralateral to the hypothalamus from which attack was elicited had no effect upon this response. No systematic effect of prefrontal stimulation upon flight behavior was observed. Anatomical studies suggest that the lateral prefrontal cortex may inhibit attack behavior by modulating neurons in either the mediodorsal thalamic nucleus or ventral tegmental area.

Acoustic Stimulation↗

PubMed2004

Excitotoxic lesions of the prefrontal cortex attenuate the potentiation of amphetamine-induced locomotion by repeated neurotensin receptor activation.

This study was aimed at determining the role of prefrontal cortex neurons in the development of the potentiation of amphetamine-induced locomotor activity by repeated central injections of D-Tyr[11]neurotensin. Excitotoxic lesions of the prefrontal cortex were made by injecting bilaterally at three anterior-posterior placements 2 microg/microl of ibotenic acid. Ten days after surgery, locomotor responses to an intracerebroventricular injection of 0.18 or 18 nmol/10 microl of D-Tyr[11]neurotensin, or vehicle-saline, were measured in different groups of lesioned and sham rats. Ambulatory, non-ambulatory and vertical movements were measured for 2 h in activity cages starting immediately after the injection. This training phase was repeated on four occasions, every second day. One week after the last day of the training phase (day 14), locomotor responses to a single injection of amphetamine (0.75 mg/kg, IP) were measured in all rats. Results show that D-Tyr[11]neurotensin produced in sham animals a dose-dependent initial suppression of locomotor activity followed by an augmentation. The latter behavioral effect tended to be smaller in the lesioned rats, but not statistically different than in sham, suggesting that prefrontal cortex neurons do not play a major role in the stimulant effect of neurotensin on locomotor activity. However, sham rats pre-exposed to the high dose of D-Tyr[11]neurotensin showed stronger non-ambulatory and vertical movements than saline pre-exposed rats when tested with amphetamine; this sensitization effect was not observed in lesioned rats. The present results show that prefrontal cortex neurons are part of the neural circuitry involved in the development of amphetamine sensitization by repeated activation of central neurotensin receptors.

Amphetamine↗

PubMed2002

Decreased levels of N-acetylaspartate in dorsolateral prefrontal cortex in a case of intractable severe sympathetically mediated chronic pain (complex regional pain syndrome, type I).

In our previous in vivo proton magnetic resonance spectroscopy ((1)H MRS) study we found reduced levels of N-acetylaspartate in dorsolateral prefrontal cortex of chronic back pain patients. This study tests whether these chemical abnormalities can be detected in other pain states. Using (1)H MRS, we measured levels for N-acetylaspartate and other identifiable chemicals relative to creatine in four bilateral brain regions, including dorsolateral prefrontal cortex, orbitofrontal cortex, cingulate, and thalamus, in a case of intractable severe sympathetically mediated chronic pain [complex regional pain syndrome (CRPS) type I]. The subject's chemical variations in the brain were compared to the same regional chemicals in 10 normal subjects (age- and sex-matched). Univariate statistics showed reduced levels of N-acetylaspartate in bilateral dorsolateral prefrontal cortex and increased levels of myo-inositol in left orbitofrontal cortex of the patient with intractable severe CRPS type I. These data support our original hypothesis that depletion of N-acetylaspartate in dorsolateral prefrontal cortex is a chemical marker of chronic pain, indicating for neuronal degeneration. Unpredicted changes of orbitofrontal myo-inositol may be related to the specific mood/affective state in an extreme pain perception. This is the first report, which identifies chemical markers in the prefrontal cortex for objective measurement and monitoring of CRPS type I. This information might lead to valuable insights into diagnosis and future effective interventions of CRPS type I (e.g., prefrontal brain stimulation).

Adult↗