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Results for “Prefrontal Cortex”

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At least 1,621 records · Page 90Linked to original sources

PubMed1997

Clozapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation.

Clozapine (1-10 mg/kg s.c.) produces a selective increase in dopamine release in rat prefrontal cortex which is, in large part (approximately 50%), mediated via activation of 5-HT1A receptors. Clozapine is a moderately potent, partial 5-HT1A receptor agonist and activation of 5-HT1A receptors may contribute to its efficacy against negative symptoms and reduced extrapyramidal side effect liability. Agonist affinity for 5-HT1A receptors could thus be a desirable feature in the design of new antipsychotics.

Animals↗

PubMed2003

From rule to response: neuronal processes in the premotor and prefrontal cortex.

The ability to use abstract rules or principles allows behavior to generalize from specific circumstances (e.g., rules learned in a specific restaurant can subsequently be applied to any dining experience). Neurons in the prefrontal cortex (PFC) encode such rules. However, to guide behavior, rules must be linked to motor responses. We investigated the neuronal mechanisms underlying this process by recording from the PFC and the premotor cortex (PMC) of monkeys trained to use two abstract rules: "same" or "different." The monkeys had to either hold or release a lever, depending on whether two successively presented pictures were the same or different, and depending on which rule was in effect. The abstract rules were represented in both regions, although they were more prevalent and were encoded earlier and more strongly in the PMC. There was a perceptual bias in the PFC, relative to the PMC, with more PFC neurons encoding the presented pictures. In contrast, neurons encoding the behavioral response were more prevalent in the PMC, and the selectivity was stronger and appeared earlier in the PMC than in the PFC.

Animals↗

PubMed1991

Dopaminergic activity is reduced in the prefrontal cortex and increased in the nucleus accumbens of rats predisposed to develop amphetamine self-administration.

Individual vulnerability to the reinforcing effects of drugs appear to be a crucial factor in the development of addiction in humans. In the rat, individuals at risk for psychostimulant self-administration (SA) may be identified from their locomotor reactivity to a stress situation such as exposure to a novel environment. Animals with higher locomotor responses to novelty (High Responders, HR) tend to acquire amphetamine SA, while animals with the lower responses (Low Responders, LR) do not. In this study, we examined whether activity of dopaminergic (DA) and serotoninergic (5-HT) systems differed between HR and LR animals. These transmitter systems are thought to be involved in the reinforcing effects of psychostimulants. Animals from both groups were sacrificed under basal conditions and after exposure for 30 or 120 min to a novel environment, and the DA, 3,4-dihydroxyphenylacetic acid (DOPAC), 5-HT, and 5-hydroxyindolacetic acid (5-HIAA) contents were determined in the prefrontal cortex, nucleus accumbens and striatum. The HR rats displayed a specific neurochemical pattern: a higher DOPAC/DA ratio in the nucleus accumbens and striatum and a lower one in the prefrontal cortex. Furthermore, HR animals had lower overall 5-HT and 5-HIAA levels, corresponding to the mean of these compounds for the three structures studied over the three environmental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed2005

Comparison of the effects of bilateral orbital prefrontal cortex lesions and amygdala lesions on emotional responses in rhesus monkeys.

The present study examines the effects of bilateral orbital prefrontal cortex (PFo) lesions on monkeys' emotional responses in two different contexts: in the presence of a rubber snake and in the presence of a human intruder. For comparison, we also assessed the responses of rhesus monkeys with selective amygdala lesions on these same tasks. Monkeys with PFo lesions, like those with amygdala lesions, displayed blunted emotional responses to the fake snake. Unlike monkeys with amygdala lesions, however, monkeys with PFo lesions displayed more mild aggression than controls in the presence of a human intruder. The findings support the idea that the PFo helps integrate sensory signals in the service of choosing among competing responses. In addition, they point to a divergence of the roles of the PFo and amygdala in responding to a social stimulus, the human intruder.

Amygdala↗

PubMed2002

Anxiety and affective style: role of prefrontal cortex and amygdala.

This article reviews the modern literature on two key aspects of the central circuitry of emotion: the prefrontal cortex (PFC) and the amygdala. There are several different functional divisions of the PFC, including the dorsolateral, ventromedial, and orbital sectors. Each of these regions plays some role in affective processing that shares the feature of representing affect in the absence of immediate rewards and punishments as well as in different aspects of emotional regulation. The amygdala appears to be crucial for the learning of new stimulus-threat contingencies and also appears to be important in the expression of cue-specific fear. Individual differences in both tonic activation and phasic reactivity in this circuit play an important role in governing different aspects of anxiety. Emphasis is placed on affective chronometry, or the time course of emotional responding, as a key attribute of individual differences in propensity for anxiety that is regulated by this circuitry.

Amygdala↗

PubMed1978

Dorsolateral prefrontal cortex lesions and discrimination of movement-produced cues by rhesus monkeys.

Rhesus monkeys were trained on a conditional discrimination in which sequences of either 32 or 64 lever presses served as discriminative stimuli. For half the subjects, reinforcement was contingent upon choice of a red response key following a sequence of 32 presses (FR 32), and a white key after FR 64, with the position of the two key colors randomized across trials. The remaining subjects were reinforced for left key presses after FR 64, and right key presses after FR 32, with key color again randomized across trials. Ablation of dorsolateral prefrontal cortex resulted in postoperative deficits in all subjects, although 6 of 8 eventually remastered the task. This recovery was investigated in a second experiment, in which psychophysical functions were generated by varying the length of the shorter FR. Although dorsolateral lesions again produced a severe disruption in performance, the post-operative functions eventually obtained were identical to the preoperative functions. This pattern of marked impairment in retention of fixed ratio discriminations, but no change in asymptotic capacity, suggests participation of dorsolateral prefrontal cortex in processing kinesthetic information, possibly analogous to the role of inferior temporal cortex in processing visual information.

Animals↗

PubMed2003

Functional specialization within the anterior medial prefrontal cortex: a functional magnetic resonance imaging study with human subjects.

This study investigated the functional neuroanatomy of the anterior medial prefrontal cortex (aMPFC). Previous studies have shown that the aMPFC is involved in evaluative judgment and self-referential processes. Specifically, different sections of the aMPFC are differentially influenced by attention demanding processes. Whereas the dorsal section is supposed to be involved in self-referential processes, the ventral section is assumed to be attenuated during attention demanding processes. The present study investigates the involvement of the dorsal and ventral aMPFC in evaluative judgment by using functional magnetic resonance imaging with spin-echo echo-planar-imaging. Processes involved in evaluative judgment are attention-demanding, self-referential and activate regions in the dorsal and ventral section of the aMPFC. Attention demanding tasks do not necessarily lead to an attenuation of the ventral section of the aMPFC, a region mainly involved in emotional and affective processing.

Adult↗

PubMed2004

Area-selective neuronal activity in the dorsolateral prefrontal cortex for information retrieval and action planning.

We compared how neurons in the dorsal and ventral regions of the dorsolateral prefrontal cortex (dl-PFC) participate in processing 2 sets of sensory signals, given at intervals, to generate plans for future actions. For the first set of visual signals, neurons in the ventral region of dl-PFC responded preferentially to the visuospatial properties of the signal, whereas neurons in the dorsal region of dl-PFC were involved primarily in retrieving information from the signal, such as the location of the target or which arm to use. For the second set of visual signals, most ventral dl-PFC neurons reflected either the sensory properties of the signals or the information retrieved from each signal. By contrast, dorsal neurons were involved more in integrating information about the target location and which arm to use to reach the target, thereby generating information that could be used to plan future actions. Thus sensorimotor transformations in the dorsolateral PFC appear to be time-variant and region-selective.

Animals↗

PubMed1998

Prefrontal cortex and caudate nucleus in conditional associative learning: dissociated effects of selective brain lesions in rats.

Rats with lesions to prefrontal cortex (PFC) or caudate nucleus (CN) were compared on tests of conditional associative learning (CAL) that placed varying demands on conditional rule learning and working-with-memory operations that are essential for response selection. Damage to either structure impaired performance, but the respective deficits resulted from disruption of different processes. CN lesions produced a consistent learning deficit that was thought to reflect a basic impairment in forming stimulus-response (S-R) associations. The behavior of PFC rats was more variable and depended on task requirements. When S-R learning or response selection was relatively easy, the PFC was not critical. However, when either component was made more difficult, thus requiring the contribution of strategic processes, PFC damage produced profound impairments. In addition to clarifying the roles of the PFC and CN in CAL, the results provide further evidence that multiple brain regions participate in relatively simple behavioral tasks and that their respective contributions can be dissociated.

Animals↗

PubMed2006

Rhesus monkeys with orbital prefrontal cortex lesions can learn to inhibit prepotent responses in the reversed reward contingency task.

Monkeys with lesions of the orbital prefrontal cortex (PFo) are impaired on behavioral tasks that require the ability to respond flexibly to changes in reward contingency (e.g., object reversal learning and extinction). These and related findings in rodents and humans have led to the suggestion that PFo is critical for the inhibitory control needed to overcome prepotent responses. To test this idea, we trained rhesus monkeys with PFo lesions and unoperated controls on acquisition of the reversed reward contingency task. In this task, selecting the smaller of 2 food quantities (1 half peanut [1P]) leads to receipt of the larger quantity (4 half peanuts [4P]) and vice versa. Choice of a larger quantity of food is a reliable prepotent response, and, accordingly, all monkeys initially selected 4P rather than one. With experience, however, all monkeys learned to select 1P in order to receive 4. Surprisingly, monkeys with PFo lesions learned as quickly as unoperated controls. Thus, PFo lesions do not yield a deficit in all tests that require the inhibition of a prepotent response.

Animals↗

PubMed1993

Extraneuronal noradrenaline in the prefrontal cortex of morphine-dependent rats: tolerance and withdrawal mechanisms.

The changes in extracellular concentrations of noradrenaline (NA) in the prefrontal cortex of morphine-dependent rats were studied by microdialysis following an acute morphine challenge and during naloxone-precipitated withdrawal. Animals were implanted with morphine- or placebo-containing pellets for 5 days. In control rats a challenge dose of morphine (5 mg/kg s.c.) induced a maximum decrease in NA output of about 45% of pre-drug levels. In contrast, morphine challenge had no effect on extraneuronal NA concentrations in morphine-implanted animals. In control animals, naloxone (2 mg/kg i.p.) produced no behavioral effect nor changed NA levels. However, in morphine-dependent animals naloxone suddenly increased extraneuronal NA by 175% of baseline dialysate levels in the first sample after the injection and precipitated a morphine-withdrawal symptomatology that paralleled the changes in NA output. Thus, chronic morphine treatment in rats results in the development of tolerance to the acute inhibitory effect of morphine on extraneuronal NA and is associated with a stimulation of prefrontocortical NA output during naloxone-precipitated withdrawal.

Animals↗

PubMed2006

Event frequency modulates the processing of daily life activities in human medial prefrontal cortex.

Event sequence knowledge is necessary to learn, plan, and perform activities of daily life. Clinical observations suggest that the prefrontal cortex (PFC) is crucial for goal-directed behavior such as carrying out plans, controlling a course of actions, or organizing everyday life routines. Functional neuroimaging studies provide further evidence that the PFC is involved in processing event sequence knowledge, with the medial PFC (Brodmann area 10) primarily engaged in mediating predictable event sequences. However, the exact role of the medial PFC in processing event sequence knowledge depending on the frequency of corresponding daily life activities remains obscure. We used event-related functional magnetic resonance imaging while healthy volunteers judged whether event sequences from high- (HF), moderate- (MF), and low-frequency (LF) daily life activities were correctly ordered. The results demonstrated that different medial PFC subregions were activated depending on frequency. The anterior medial Area 10 was differentially activated for LF and the posterior medial Area 10 for HF activities. We conclude that subregions of the medial PFC are differentially engaged in processing event sequence knowledge depending on how often the activity was reportedly performed in daily life.

Activities of Daily Living↗

PubMed2004

Neuronal representation of response-outcome in the primate prefrontal cortex.

For flexible control of behaviour, it is important to associate preceding behavioural response with its outcome. Since the dorsolateral prefrontal cortex (dlPFC) plays a major role in such control, it is likely that this area has a neuronal mechanism of coding response-outcome, such as reward/non-reward, based on the nature of the behavioural response made immediately before. To test this hypothesis, we examined neuronal activity in the dlPFC while monkeys performed a variant of the oculomotor delayed-response (ODR) task that had two reward conditions. In this task, the correct response was rewarded in half of the trials only and the subject could not expect the outcome (reward/non-reward). The response was followed by a fixation of 2 s (F2-period). We also employed a fixation (FIX) task that required monkeys to fixate on the peripheral target only, with two reward conditions that were similar to those in the ODR task. Post-response activity of a subset of dlPFC neurons was modulated by both the direction of the preceding response and its outcome. None of these neurons showed directional F2-period activity in the FIX task. These results suggest that a subset of dlPFC neurons represent response-outcome (i.e. reward/non-reward associated with directional saccade made immediately before).

Algorithms↗

PubMed2005

Injections of baclofen into the ventral medial prefrontal cortex block the initiation, but not the expression, of cocaine sensitization in rats.

RATIONALE: Increased excitatory output from the medial prefrontal cortex (mPFC) is thought to play a key role in the development of sensitization to cocaine. Gamma-aminobutyric acid (GABA) inhibits this excitatory output. OBJECTIVES: The present studies were designed to determine the effects of intra-mPFC injections of the GABA(B) agonist baclofen on cocaine-induced motor activity and on the development of sensitization to cocaine. METHODS: Rats received bilateral cannula implants above the ventral mPFC. Initial studies examined the dose-response effects of injection of baclofen (0.05-0.5 nmol/side) into the mPFC on the acute motor-stimulant response to cocaine (15 mg/kg, i.p.). Additional studies determined whether coadministration of intra-mPFC baclofen (0.5 nmol/side) and systemic cocaine (15 mg/kg, i.p.) could alter the initiation and/or expression of cocaine-induced behavioral sensitization. RESULTS: Intra-mPFC baclofen dose-dependently blocked cocaine-induced motor activity. In sensitization studies, intra-mPFC baclofen was able to prevent the initiation, but not the expression of cocaine-induced sensitization. CONCLUSIONS: The data suggest that the ability of GABA to modulate excitatory output from the mPFC may be attenuated in animals sensitized to cocaine.

Animals↗

PubMedDate not supplied

Extracellular dopamine in the rat prefrontal cortex during reward-, punishment- and novelty-associated behaviour. Effects of diazepam.

Variations of extracellular dopamine (DA(ext)) levels in prefrontal cortex were assessed by in vivo microdialysis. In rats trained in an operant fixed interval (FI(30s)) schedule of food delivery, acute exposure to contingent foot shocks resulted in a suppression of responding that was reversed by diazepam (4 mg/kg, ip). No changes in cortical DA(ext) levels occurred during this period in both control and treated rats. By contrast, in control rats, cortical DA(ext) levels increased (+25-40%) during the nonpunished component of the operant session, and during noncontingent food delivery (+25%). Control rats placed into an unfamiliar brightly lit openfield exhibited a marked increase in cortical DA(ext) levels (+100%). This effect occurred neither in rats given diazepam at a dose (2 mg/kg) which stimulated motor activity, nor during a second exposure to the openfield. In conclusion, a benzodiazepine-sensitive activation of mesoprefrontal DA neurones is induced by exposure to novel stressful surroundings and by food availability and consumption. The fact that cortical DA(ext) levels remained unchanged in rats that exerted complete control upon negative stimuli indicates that an activation of the mesoprefrontal DA system is not required for punishment-induced behavioural blockade.

Animals↗

PubMed2001

Rostrolateral prefrontal cortex involvement in relational integration during reasoning.

Patient and neuroimaging studies indicate that complex reasoning tasks are associated with the prefrontal cortex (PFC). In this study, we tested the hypothesis that the process of relational integration, or considering multiple relations simultaneously, is a component process of complex reasoning that selectively recruits PFC. We used fMRI to examine brain activation during 0-relational, 1-relational, and 2-relational problems adapted from the Raven's Progressive Matrices and hypothesized that PFC would be preferentially recruited by the 2-relational problem type. Event-related responses were modeled by convolving a canonical hemodynamic response function with the response time (RT) associated with each trial. The results across different analyses revealed the same pattern: PFC activation was specific to the comparison between 2- and 1-relational problems and was not observed in the comparison between 1- and 0-relational problems. Furthermore, the process of relational integration was specifically associated with bilateral rostrolateral PFC (RLPFC; lateral area 10) and right dorsolateral PFC (areas 9 and 46). Left RLPFC showed the greatest specificity by remaining preferentially recruited during 2-relational problems even after comparisons were restricted to trials matched for RT and accuracy. The link between RLPFC and the process of relational integration may be due to the associated process of manipulating self-generated information, a process that may characterize RLPFC function.

Adolescent↗

PubMed2000

Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance.

BACKGROUND: Working memory (WM) deficits in schizophrenia have been associated with dorsolateral prefrontal cortex (DLPFC) dysfunction in neuroimaging studies. We previously found increased DLPFC activation in schizophrenic versus normal subjects during WM performance (Manoach et al 1999b). We now have investigated whether schizophrenic subjects recruit different brain regions, particularly the basal ganglia and thalamus, components of frontostriatal circuitry thought to mediate WM. METHODS: We examined regional brain activation in nine normal and nine schizophrenic subjects during WM performance using functional magnetic resonance imaging. Subjects performed a modified version of the Sternberg Item Recognition Paradigm that included a monetary reward for correct responses. We compared high and low WM load conditions to each other and to a non-WM baseline condition. We examined activation in both individual subjects and averaged group data. RESULTS: Relative to normal subjects, schizophrenic subjects exhibited deficient WM performance, at least an equal magnitude of right DLPFC activation, significantly greater left DLPFC activation, and increased spatial heterogeneity of DLPFC activation. Furthermore, only the schizophrenic group activated the basal ganglia and thalamus, even when matched for task performance with the normal group. CONCLUSIONS: Aberrant WM performance and brain activation in schizophrenia may reflect dysfunction of frontostriatal circuitry that subserves WM. Future studies will elucidate the contribution of the anatomical components of this circuitry to WM deficits.

Adult↗

PubMed2002

Models of functional organization of the lateral prefrontal cortex in verbal working memory: evidence in favor of the process model.

Research on the functional organization of the lateral prefrontal cortex (PFC) in working memory continues to be fairly equivocal between two major frameworks: organization-by-process or organization-by-material. Although there is fairly strong evidence for organization-by-process models from event-related fMRI studies, some investigators argue that the nature of the stimulus material better defines the functional organization of the lateral PFC, particularly in more ventral regions (BA 47/45/44). Specifically, the anterior region of the ventrolateral PFC (BA 47/45) is hypothesized to subserve semantic processing while the posterior region (BA 44) may subserve phonological processing. In the current event-related fMRI study, we directly compared process-related versus material-related organizational principles in a verbal working memory task. Subjects performed a modified delayed response task in which they (1) retained a list of five words or five nonwords during the delay period ("maintenance"), or (2) performed a semantic (size reordering) or phonological (alphabetical reordering) task on the word or nonword lists, respectively ("manipulation"). We did not find evidence during the delay period of our task to support claims of anterior-posterior specializations in the ventrolateral PFC for semantic versus phonological processing. Subjects did, however, display greater neuronal activity during the delay period of manipulation trials than maintenance trials in both the dorsolateral PFC and posterior ventrolateral regions. These data are more consistent with the process model of the organization of lateral PFC in verbal working memory.

Adolescent↗