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At least 613 records · Page 34Linked to original sources

PubMed2003

Phineas gauged: decision-making and the human prefrontal cortex.

Poor social judgment and decision-making abilities have often been attributed to people who have suffered injury to the ventromedial prefrontal cortex (VMPFC). However, few laboratory tests of decision-making have been conducted on these patients. The exception to this is the Iowa Gambling Task which has often, but not always, demonstrated differential performance between patients and controls. Results from patients with prefrontal cortex lesions on a novel test of decision-making are presented. Participants explored and chose from pairs of gambles that differed in their underlying distributions, primarily in the variance of their respective outcomes. In accordance with many findings from the behavioral decision-making literature, both young normal participants and older patient controls demonstrated a marked avoidance of risk and selected largely from secure, low variance gambles. In contrast, patients with ventromedial lesions were divided into two clear sub-groups. One group behaved similarly to normals, showing a risk-averse strategy. The other group displayed a distinctive risk-seeking behavior pattern, choosing predominantly from the high-variance, high-risk decks. This research demonstrates some of the advantages of using methods and theories from traditional decision-making research to study the behavior of patients, as well as the benefits of examining individual participants, and provides new insights into the nature of the decision-making deficit in patients with ventromedial prefrontal cortex lesions.

Adult↗

PubMed2003

Neuronal activity in primate dorsolateral and orbital prefrontal cortex during performance of a reward preference task.

An important function of the prefrontal cortex (PFC) is the control of goal-directed behaviour. This requires information as to whether actions were successful in obtaining desired outcomes such as rewards. While lesion studies implicate a particular PFC region, the orbitofrontal cortex (OFC), in reward processing, neurons encoding reward have been reported in both the OFC and the dorsolateral prefrontal cortex (DLPFC). To compare and contrast their roles, we recorded simultaneously from both areas while two rhesus monkeys (Macaca mulatta) performed a reward preference task. The monkeys had to choose between pictures associated with different amounts of a juice reward. Neuronal activity in both areas reflected the reward amount. However, neurons in the DLPFC encoded both the reward amount and the monkeys' forthcoming response, while neurons in the OFC more often encoded the reward amount alone. Further, reward selectivity arose more rapidly in the OFC than the DLPFC. These results are consistent with reward information entering the PFC via the OFC, where it is passed to the DLPFC and used to control behaviour.

Action Potentials↗

PubMed1993

Stress preferentially increases extraneuronal levels of excitatory amino acids in the prefrontal cortex: comparison to hippocampus and basal ganglia.

The technique of intracerebral microdialysis was used to assess the effect of stress on the extracellular concentrations of excitatory amino acids, glutamate and aspartate, in the rat medial prefrontal cortex, hippocampus, striatum, and nucleus accumbens. A 20-min restraint procedure led to an increase in extracellular glutamate in all regions tested. The increase in glutamate levels was significantly higher in the prefrontal cortex than that observed in other regions. With the exception of the striatum, extracellular levels of aspartate were increased in all regions. Furthermore, the increase in aspartate levels was significantly higher in prefrontal cortex compared to hippocampus and nucleus accumbens. Local perfusion of tetrodotoxin during the restraint procedure significantly decreased the stress-induced increase in extracellular excitatory amino acids. In order to ensure that the above results were not an artifact of restraint not associated with stress (e.g., decreased mobility), we also examined the effect of swimming stress on the extracellular levels of excitatory amino acids in selected regions, i.e., striatum and medial prefrontal cortex. Both regions displayed a significant increase in extracellular levels of aspartate and glutamate following 20 min of swimming in room temperature water. This study provides direct evidence that stress increases the neuronal release of excitatory amino acids in a regionally selective manner. The implications of the present findings for stress-induced catecholamine release and/or hippocampal degeneration are discussed.

Animals↗

PubMed2000

Comparative effects of neurotensin, neurotensin(8-13) and [D-Tyr(11)]neurotensin applied into the ventral tegmental area on extracellular dopamine in the rat prefrontal cortex and nucleus accumbens.

Ejections of 10(-5)-10(-3)M neurotensin into the ventral tegmental area increased dopamine efflux measured by electrochemical approaches in the prefrontal cortex of anaesthetized rats. In the same conditions, the effects evoked on dopamine efflux by 10(-5)M neurotensin(8-13) and [D-Tyr(11)]neurotensin were different from each other and depended on the explored area: the prefrontal cortex and the caudal and rostral nucleus accumbens. In the prefrontal cortex, neurotensin(8-13) was as potent as neurotensin, whereas [D-Tyr(11)]neurotensin was ineffective. In the caudal nucleus accumbens, when considering the initial intensity of the effect, neurotensin(8-13) and neurotensin appeared more potent than [D-Tyr(11)]neurotensin. In contrast, in the rostral nucleus accumbens, neurotensin(8-13) was less potent than [D-Tyr(11)]neurotensin and neurotensin. These results support the differential involvement of two pharmacologically distinct neurotensin receptor entities on ventral tegmental area neurons in the modulation of mesolimbic and mesocortical dopaminergic activity.

Animals↗

PubMed1994

Prepulse inhibition of the acoustic startle response of rats is reduced by 6-hydroxydopamine lesions of the medial prefrontal cortex.

Prepulse inhibition (PPI) of the acoustic startle response (ASR) is impaired by dopamine (DA) overactivity in the nucleus accumbens and anteromedial striatum. Since there is evidence that DA in the medial prefrontal cortex exerts an inhibitory control on striatal DA systems, it was investigated whether depletion of prefrontal DA reduces PPI. Rats were tested for PPI both before and after injections (2 x 1 microliter per side) of vehicle, a low (3.0 microgram/microliter) or a high (6.0 microgram/microliter) dose of 6-hydroxydopamine hydrobromide (6-OHDA) into the prefrontal cortex. Only the high dose of 6-OHDA, leading to an 87% depletion of prefrontal DA, impaired PPI. The ability of an acoustic prepulse (75 dB, 10 kHz) to reduce the response to a startle pulse (100 dB noise burst) was maintained in sham lesioned rats, but was significantly disturbed in rats lesioned with the high dose of 6-OHDA. The 6-OHDA treatment did not affect the ASR amplitude in the absence of a prepulse. The reduction of PPI in lesioned rats correlated with the extent of DA depletion. These results suggest that the DA innervation of the prefrontal cortex is involved in the modulation of the ASR and they provide further evidence for opposite actions of prefrontal and subcortical DA systems in the control of behaviour. The present findings are discussed with regard to the potential role of prefrontal DA in schizophrenia.

Acoustic Stimulation↗

PubMed1994

Characteristics of stimulation-induced feeding sites in the sulcal prefrontal cortex.

Double pulse tests were used to infer the refractory periods of the substrate underlying stimulation-induced feeding in the sulcal prefrontal cortex of the rat. Eleven sites were examined, of which five supported the behaviour at currents of 250 to 400 microA; pulse duration was 100 microseconds. The average profile indicates a recovery function that begins at 0.5 ms and ends at 3.0 ms, with no apparent contribution from local potential summations. The mean effectiveness value corresponding to the asymptotic portion of the curves was 91%. These results suggest that there is substantial overlap in the excitability of neurons underlying stimulation-induced feeding in the sulcal prefrontal cortex and that reported for the medial forebrain bundle, but unlike the latter structure, there is no evidence of self-stimulation from the same sulcal prefrontal cortex placements. Response rates were collected for a maximum of 21 days from each of the cortical sites at which feeding was recorded and at the same currents used to evaluate the refractory periods underlying stimulation-induced feeding. The rates averaged between 0 and 3 responses per minute whether the current was available or not. These data represent the first demonstration of a site that supports stimulation-induced feeding in the absence of brain stimulation reward, at least at these specific placements and stimulation parameters.

Animals↗

PubMed1998

Prefrontal cortex activity in people with schizophrenia and control subjects. Evidence from positron emission tomography for remission of 'hypofrontality' with recovery from acute schizophrenia.

BACKGROUND: Hypo-activation of the left dorsolateral prefrontal cortex is inconsistently found in neuroimaging studies of schizophrenia. As the left dorsolateral prefrontal cortex is involved in the generation of action, disordered function in this region may be implicated in schizophrenic symptomatology. METHOD: We used H2 15O positron emission tomography to study dorsolateral prefrontal cortical function in men with schizophrenia (n = 13) and male control subjects (n = 6) performing joystick movements on two occasions, 4-6 weeks apart. The patients were initially in relapse. To clarify dorsolateral prefrontal cortical function we also scanned another group of control subjects (n = 5) performing mouth movements. RESULTS: The control subjects performing hand or mouth movements activated the left dorsolateral prefrontal cortex to a maximum when the movements were self-selected. The men with relapsed schizophrenia exhibited left dorsolateral prefrontal cortical hypoactivation, which remitted with symptomatic improvement. CONCLUSIONS: Hypofrontality in these patients is a dynamic phenomenon across time, possibly related to current symptomatology. The most appropriate question about the presence of hypofrontality in schizophrenia may be when, rather than whether, it will occur.

Adult↗

PubMed2000

Organization of working memory within the human prefrontal cortex: a PET study of self-ordered object working memory.

The prefrontal cortex plays a critical role in working memory, the active maintenance of information for brief periods of time for guiding future motor and cognitive processes. Two competing models have emerged to account for the growing human and non-human primate literature examining the functional neuroanatomy of working memory. One theory holds that the lateral frontal cortex plays a domain-specific role in working memory with the dorsolateral and ventrolateral cortical regions supporting working memory for spatial and non-spatial material, respectively. Alternatively, the lateral frontal cortex may play a process-specific role with the more dorsal regions becoming recruited whenever active manipulation or monitoring of information in working memory becomes necessary. Many working memory tasks do not allow for direct tests of these competing models. The present study used a novel self-ordered working memory task and positron emission tomography to identify whether dorsal or ventral lateral cortical areas are recruited during a working memory task that required extensive monitoring of non-spatial information held within working memory. We observed increased blood flow in the right dorsolateral, but not ventrolateral, prefrontal cortex. Increases in blood flow in the dorsolateral region correlated strongly with task performance. Thus, the results support the process-specific hypothesis.

Adult↗

PubMed1999

An antisense oligonucleotide reverses the footshock-induced expression of fos in the rat medial prefrontal cortex and the subsequent expression of conditioned fear-induced immobility.

The immediate-early genes, including c-fos, have been proposed to be involved in learning and memory. In this report, we examine stress-induced Fos-like immunoreactivity (Fos-li) in subregions of the prefrontal cortex during a conditioned fear paradigm. During the acquisition phase, the rats were conditioned to fear a formerly neutral tone by pairing the tone with a mild footshock. The rats were then tested for fearful behavior by reexposure to the tone without additional footshock. During acquisition, Fos-li was increased in the medial prefrontal cortex (infralimbic and prelimbic) but not the anterior cingulate and M1 motor cortex. However, during the extinction phase, no significant increase in Fos-li was observed in any region. These findings indicate that acquisition, but not extinction, of conditioned fear is associated with an increase in Fos-li in subregions of the medial prefrontal cortex. In other animals, an antisense oligonucleotide directed against the c-fos mRNA was injected into the infralimbic/prelimbic cortex 12 or 72 hr before the acquisition session. Antisense treatment given 12, but not 72, hr earlier suppressed Fos production without altering behavior during the acquisition session. Three days after the acquisition session, rats were tested for fearful behavior as before. The antisense oligonucleotide blockade of Fos production during acquisition was associated with a significantly less fearful response during the extinction session. These results support a role for Fos in the medial prefrontal cortex during the acquisition of aversive learning.

Acoustic Stimulation↗

PubMed2005

Microstimulation of the dorsolateral prefrontal cortex biases saccade target selection.

A long-standing issue concerning the executive function of the primate dorsolateral prefrontal cortex is how the activity of prefrontal neurons is linked to behavioral response selection. To establish a functional relationship between prefrontal memory fields and saccade target selection, we trained three macaque monkeys to make saccades to the remembered location of a visual cue in a delayed spatial match-to-sample saccade task. We electrically stimulated sites in the prefrontal cortex with subthreshold currents during the delay epoch while monkeys performed this task. Our results show that the artificially injected signal interacts with the neural activity responsible for target selection, biasing saccade choices either towards the receptive/movement field (RF/MF) or away from the RF/MF, depending on the stimulation site. These findings might reflect a functional link between prefrontal signals responsible for the selection bias by modulating the balance between excitation and inhibition in the competitive interactions underlying behavioral selection.

Animals↗

PubMed2003

Prefrontal cortex contribution to associative recognition memory in humans: an event-related functional magnetic resonance imaging study.

The present event-related fMRI study examined in ten healthy participants neural correlates of recognition memory for intact, rearranged, and new pairs of visual stimuli. The correct categorization of both intact and rearranged pairs relative to pairs of new, never presented before stimuli relies on the retrieval of associative information whereas the discrimination of rearranged pairs from intact pairs additionally involves a recall-to-reject process by which subjects retrieve additional information to reach a recognition decision. Relative to new pairs, both intact and rearranged pairs yielded activation in inferior prefrontal cortex bilaterally and left dorsolateral prefrontal cortex. Relative to intact pairs, rearranged pairs were associated with increased activity in left dorsolateral prefrontal cortex. The latter could reflect the neural correlates of a recall-to-reject process, a pivotal process of associative recognition memory.

Adult↗

PubMed1985

An excitant amino acid projection from the medial prefrontal cortex to the anterior part of nucleus accumbens in the rat.

High-affinity uptake of neurotransmitter substrates in synaptosome-containing homogenates and tissue concentrations of amino acids were examined in subcortical areas 5-6 days after bilateral N-methyl-D-aspartate lesions confined to rat medial prefrontal cortex. D-[3H]Aspartate (32% of control) and [3H] gamma-aminobutyric acid ( [3H]GABA) (60% of control) uptakes were significantly reduced in medial prefrontal cortex, whereas [3H]choline (110% of control) uptake was unchanged, suggesting the production of axon-sparing lesions. The uptake of D-[3H]aspartate (76% of control), but not of [3H]GABA or [3H]choline, was significantly reduced in nucleus accumbens, with no concomitant reduction in amino acid concentrations. When examined in serial coronal sections, reduced D-[3H]aspartate uptake was confined to the most anterior 500 micron of nucleus accumbens (67% of contralateral sample). No significant reductions of uptake or amino acid concentrations were observed in caudate putamen or ventral tegmental area. These results suggest a role for glutamate or aspartate as neurotransmitters in projections from medial prefrontal cortex to anterior nucleus accumbens. Medial prefrontal cortex may represent the major excitatory cortical input to the nucleus accumbens.

Amino Acids↗

PubMed2003

Cellular pathology in the dorsolateral prefrontal cortex distinguishes schizophrenia from bipolar disorder.

The classification of schizophrenia and bipolar disorder as two separate disease entities has been hotly debated almost from the moment of its inception with Kraepelin's descriptions of "dementia praecox" and "manic-depressive insanity" in 1896. Kraepelin's nosologic distinction was based on clinical observation of symptomatology and outcome, and even today, despite major advances in science and technology, differential diagnosis of psychosis relies on the clinical course of illness. However, new evidence from diverse fields, e.g., genetics, neuropsychology, and brain imaging, have refueled the debate about whether or not schizophrenia and bipolar disorder represent distinct diseases, leading some to postulate that schizophrenia and bipolar disorder represent different manifestations of psychosis along a continuum with schizoaffective disorder representing an intermediate subtype. To this discourse, we add our own recent postmortem anatomic findings indicating that cellular pathology in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder differs not just in magnitude but also in direction, in laminar scope, and in relative involvement of neuronal and glial cell types. Thus, distinct morphometric alterations in the dorsolateral prefrontal cortex underlie what appear on neuroimaging analysis to be similar abnormalities in structural and metabolic function in the prefrontal cortex, and the diverse cellular pathology in the dorsolateral prefrontal cortex in these two disorders may account for the greater deficit in schizophrenia on cognitive tasks involving memory, problem solving and abstraction.

Bipolar Disorder↗

PubMed1997

Peripubertal refinement of the intrinsic and associational circuitry in monkey prefrontal cortex.

The peripubertal elimination of axospinous synapses and dendritic spines in monkey prefrontal cortex suggests that this region undergoes substantial reorganization during late postnatal development. Understanding the functional impact of these maturational refinements requires knowledge of the specific presynaptic elements involved in these changes. Two potential sources of these presynaptic terminals are the intrinsic axon collaterals furnished by pyramidal cells within a region and the associational axons that arise from pyramidal neurons in other cortical regions in the same hemisphere. In the adult, both of these types of axon terminals form synapses predominantly with dendritic spines on other pyramidal neurons, and thus they may be preferentially involved in the peripubertal pruning of axospinous synapses and dendritic spines. In order to test this hypothesis, iontophoretic injections of the anterograde tracer biotinylated dextran amine were made into the superficial layers of areas 9 or 46 of the prefrontal cortex of four prepubertal juvenile (14.9-21.5 months old) and three young adult macaque monkeys. Tangential reconstructions revealed a stripe-like pattern of labeled terminals for intrinsic and associational projections in both juvenile and adult animals. During puberty, the intrinsic circuitry underwent extensive topographic refinement, as demonstrated by a 42.7% decrease in stripe area and a 28.0% increase in gap distance between stripes. Furthermore, the mediolateral tangential spread of labeled stripes around the injection site decreased by 27.0%. In contrast, topographic refinement was not evident in the associational circuitry. In both layers 1 and 3, the densities of varicosities and branch points on labeled axons decreased by about 50% in intrinsic stripes during puberty, but only by approximately 30% in associational stripes. These findings suggest that the spatial form and magnitude of peripubertal refinements in prefrontal cortical connectivity may be specific for certain neural elements.

Aging↗

PubMed1999

Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI.

Inhibition of an ongoing reaction tendency for adaptation to changing environments is a major function of the human prefrontal cortex. This function has been investigated frequently using the go/no-go task and set-shifting tasks such as the Wisconsin Card Sorting Test (WCST). Studies in humans and monkeys suggest the involvement of the dorsolateral prefrontal cortex in the two task paradigms. However, it remains unknown where in the dorsolateral prefrontal cortex this function is localized, whether a common inhibitory mechanism is used in these task paradigms and how this inhibitory function acts on two different targets, i.e. the go response in the go/no-go task and the cognitive set in the WCST. In the go/no-go task of this study, subjects were instructed to either respond (go trial) or not respond (no-go trial), depending on the cue stimulus presented. The signals of functional MRI (fMRI) related to the inhibitory function should be transient by nature. Thus, we used the temporal resolution of fMRI (event-related fMRI) by which transient signals in go and no-go trials can be analysed separately and compared with each other. We found a focus that showed transient no-go dominant activity in the posterior part of the inferior frontal sulcus in the right hemisphere. This was true irrespective of whether the subjects used their right or left hands. These results suggest that the transient activation in the right inferior prefrontal area is related to the neural mechanism underlying the response inhibition function. Furthermore, this area was found to be overlapped spatially with the area that was activated transiently during cognitive set shifting in the WCST. The transient signals in the go/no-go task peaked 5 s after the transient expression of the inhibitory function, and the transient signals in the WCST peaked 7s after the transient expression, reflecting different durations of neuronal activity in the two inhibitory task paradigms. These results imply that the right inferior prefrontal area is commonly involved in the inhibition of different targets, i.e. the go response during performance of the go/no-go task and the cognitive set during performance of the WCST.

Adaptation, Physiological↗

PubMed2002

Perceiving patterns in random series: dynamic processing of sequence in prefrontal cortex.

We demonstrate that regions within human prefrontal cortex develop moment-to-moment models for patterns of events occurring in the sensory environment. Subjects viewed a random binary sequence of images, each presented singly and each requiring a different button press response. Patterns occurred by chance within the presented series of images. Using functional magnetic resonance imaging (fMRI), we identified activity evoked by viewing a stimulus that interrupted a pattern. Prefrontal activation was evoked by violations of both repeating and alternating patterns, and the amplitude of this activation increased with increasing pattern length. Violations of repeating patterns, but not of alternating patterns, activated the basal ganglia.

Adolescent↗

PubMed1984

Homovanillic acid in rat caudate and prefrontal cortex following phencyclidine and amphetamine.

Phencyclidine (PCP) and d-amphetamine (AMP) had different effects upon homovanillic acid (HVA) levels in rat prefrontal cortex as compared to caudate. Lower doses of PCP increased HVA in prefrontal cortex only while lower doses of AMP decreased HVA in caudate alone. Higher doses of both drugs produced a decreased HVA in caudate and an increase in prefrontal cortex. At some doses PCP may selectively activate mesocortical dopaminergic neurons.

Animals↗

PubMed2003

Independent modulation of basal and feeding-evoked dopamine efflux in the nucleus accumbens and medial prefrontal cortex by the central and basolateral amygdalar nuclei in the rat.

Interactions of the central and basolateral nuclei of the amygdala with the mesocorticolimbic dopamine system are implicated in the acquisition and performance of conditioned responses for food reward. This study investigated whether dopamine transmission in the nucleus accumbens and the medial prefrontal cortex of the rat is influenced by the amygdala and if so, to assess the significance of the interaction in free feeding of a palatable food. To this end, we examined the effects of reverse-dialysis of the sodium channel blocker lidocaine into either the central or basolateral on dopamine efflux in the nucleus accumbens and the medial prefrontal cortex as determined by microdialysis and high-pressure liquid chromatography with electrochemical detection. The present results revealed for the first time that inactivation of the central decreased basal levels of dopamine efflux in the nucleus accumbens, but not in the medial prefrontal cortex. Furthermore, administration of lidocaine into the central significantly attenuated feeding-evoked increases in dopamine efflux in both terminal regions. These neurochemical effects were accompanied by feeding-related behaviours akin to the Klüver-Bucy syndrome. In contrast, inactivation of the basolateral affected neither food intake nor dopamine efflux in the nucleus accumbens, but triggered dramatic long-lasting oscillations in dopamine efflux in the medial prefrontal cortex, irrespective of whether food was presented or not. Overall, these findings indicate that the central and basolateral independently modulate dopamine transmission in both terminal regions of the mesocorticolimbic dopamine system. The central, in particular, and its influence on the dopamine system, may be involved in the regulation of food intake.

Amygdala↗