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PubMed1990

Brain glucose utilization under high sensory activation: hypoactivation of prefrontal cortex.

Brain glucose metabolism was studied, using positron emission tomography and [F-18]-2-deoxy-2-fluoro-D-glucose, in 13 healthy young adult men, at rest and under conditions of high visual and auditory stimulation with minor motor involvement. Despite high individual variations, the mean cerebral metabolic rate for glucose was highly increased during stimulation. Furthermore, the regional pattern of cerebral glucose utilization showed consistent differences between resting and activated states. Several brain areas, including temporal, motor-premotor and parieto-occipital cortices, and striatum, thalamus, and cerebellum showed a level of activation statistically comparable to that of mean gray. Significant preferential activation was found only in the visual cortex. By contrast, prefrontal and mesial cortical areas were relatively hypoactivated by the task. Inasmuch as prefrontal cortex is known to receive visual associative afferents, these observations are tentatively interpreted in terms of the "parallel" mode of information processing, along specific routes according to the environmental state.

Adult↗
PubMed2004

Up-regulation of glutamate concentration in the putamen and in the prefrontal cortex of asymptomatic SIVmac251-infected macaques without major brain involvement.

We quantified putamen and prefrontal cortex metabolites in macaques with simian immunodeficiency virus infection and searched for virological and histological correlates. Fourteen asymptomatic macaques infected since 8-78 months (median: 38) were compared with eight uninfected ones. Absolute concentrations of acetate, alanine, aspartate, choline, creatine, GABA, glutamate, glutamine, lactate, myo-inositol, N-acetylaspartate, taurine and valine were determined by ex vivo proton magnetic resonance spectroscopy. Glutamate concentration in the CSF was determined by HPLC. Gliosis was assessed by glial fibrillary acidic protein and CD68 immunohistochemistry. Glutamate concentration was slightly increased in the prefrontal cortex (19%, p = 0.0152, t-test) and putamen (13%, p = 0.0354, t-test) of the infected macaques, and was unaffected in the CSF. Myo-inositol concentration was increased in the prefrontal cortex only (27%, p = 0.0136). The concentrations of glutamate and myo-inositol in the prefrontal cortex were higher in the animals with marked or intense microgliosis (p = 0.0114). The other studied metabolites, including N-acetylaspartate, were not altered. Glutamate concentration may thus increase in the cerebral parenchyma in asymptomatic animals, but is not accompanied by a detectable decrease in N-acetylaspartate concentration (neuronal dysfunction). Thus, there are probably compensatory mechanisms that may limit glutamate increase and/or counterbalance its effects.

Animals↗
PubMed1999

Alterations in synaptic proteins and their encoding mRNAs in prefrontal cortex in schizophrenia: a possible neurochemical basis for 'hypofrontality'.

An impairment of prefrontal cortical functioning in schizophrenia ('hypofrontality') has been suggested by clinical, neuroimaging, and postmortem brain tissue studies. We used Western immunoblot and Northern hybridization analyses of postmortem brain tissue obtained from 14 schizophrenic patients and 12 control patients of similar ages to measure tissue levels of synaptophysin (a structural synaptic vesicle protein) and of SNAP-25 (a 25-kDa presynaptic protein), and their encoding mRNAs, in Brodmann's area 10 of prefrontal cortex. There were significant decreases in tissue levels of both of these proteins in prefrontal cortex of schizophrenic patients relative to controls. In contrast, tissue levels for the mRNAs encoding these proteins were not decreased in schizophrenic patients. Subsequent labeling of the same Western immunoblots showed no difference in tissue levels of glial fibrillary acidic protein (GFAP) in schizophrenic and control patients. Similarly, subsequent hybridization of the same Northern hybridization membranes showed no difference in tissue levels of GFAP mRNA or of 28S rRNA in schizophrenic and control patients. These alterations in tissue levels of synaptophysin and SNAP-25 are consistent with the idea that the clinically observed 'hypofrontality' of schizophrenia arises from abnormalities of synaptic number or structural integrity in prefrontal cortex.

Adult↗
PubMed1989

Differential effect of cocaine on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens: comparison to amphetamine.

The technique of in vivo microdialysis was used to measure the extracellular levels of dopamine in the nucleus accumbens septi and medial prefrontal cortex of chloral-hydrate-anaesthetized rats following systemic administration of cocaine and amphetamine. Intravenous injection of cocaine increased the extracellular levels of dopamine in the medial prefrontal cortex and the nucleus accumbens septi in a dose-dependent manner. However, the magnitude of increase was significantly greater in nucleus accumbens than in medial prefrontal cortex. In comparison to cocaine, amphetamine increased the extracellular levels of dopamine in the nucleus accumbens and medial prefrontal cortex to the same degree. Based on the relatively small increase of extracellular dopamine levels in medial prefrontal cortex by cocaine, it is postulated that dopaminergic innervation of other structures besides medial prefrontal cortex may be involved in maintenance of cocaine self-administration.

Amphetamines↗
PubMed2005

Medial prefrontal cortex lesions abolish contextual control of competing responses.

There is much debate as to the extent and nature of functional specialization within the different subregions of the prefrontal cortex. The current study was undertaken to investigate the effect of damage to medial prefrontal cortex subregions in the rat. Rats were trained on two biconditional discrimination tasks, one auditory and one visual, in two different contexts. At test, they received presentations of audiovisual compounds of these training stimuli in extinction. These compounds had dictated either the same (congruent trials) or different (incongruent trials) responses during training. In sham-operated controls, contextual cues came to control responding to conflicting information provided by incongruent stimulus compounds. Experiment 1 demonstrated that this contextual control of responding was not evident in individual rats with large amounts of damage that included the prelimbic and cingulate subregions of the prefrontal cortex. Experiment 2 further dissociated the result of Experiment 1, demonstrating that lesions specific to the anterior cingulate cortex were sufficient to produce a deficit early on during presentation of an incongruent stimulus compound but that performance was unimpaired as presentation progressed. This early deficit suggests a role for the anterior cingulate cortex in the detection of response conflict, and for the medial prefrontal cortex in the contextual control of competing responses, providing evidence for functional specialization within the rat prefrontal cortex.

Animals↗
PubMed2004

Cooperation and biased competition model can explain attentional filtering in the prefrontal cortex.

Recent neurophysiological experimental results suggest that the prefrontal cortex plays an important role in filtering out unattended visual inputs. Here we propose a neurodynamical computational model of a part of the prefrontal cortex to account for the neural mechanisms defining this attentional filtering effect. Similar models have been employed to explain experimental results obtained during the performance of attention and working memory tasks. In this previous work the principle of biased competition was shown to successfully account for the experimental data. To model the attentional filtering effect, the biased competition model was extended to enable cooperation between stimulus selective neurons. We show that, in a biological relevant minimal model, competition and cooperation between the neurons are sufficient conditions for reproducing the attentional effect. Furthermore, a characterization of the parameter regime where the cooperation effect is observed is presented. Finally, we also reveal parameter regimes where the network has different modes of operation: selective working memory, attentional filtering, pure competition and noncompetitive amplification.

Animals↗
PubMed2003

Asymmetric activation in the prefrontal cortex by sound-induced affect.

This study is based on previous information regarding asymmetric activation in the prefrontal cortex by film-induced affects, as well as the inverse proportionality of prefrontal cortex activity to power in the alpha band of EEG. To search for a specific EEG band where the asymmetric activation in the prefrontal cortex by sound-induced affects is mainly reflected, we measured 32 college students' EEGs; 11 bands ranged from 6.5 to 35.0 Hz, at Fp1 and Fp2 sites. The power in the alpha band (8.0 to 13.0 Hz) at Fp2, especially in the alpha-2 band (9.0 to 11.0 Hz) increased while the students listened to music, during which participants reported positive affect. In contrast, the power at Fp1 increased while the students listened to noise, during which participants reported negative affect. These results imply that sound-induced positive affect increases relative left-sided activation in the prefrontal cortex, whereas induced negative affect elicits the opposite pattern of asymmetric activation.

Adult↗
PubMed1999

Right prefrontal cortex and episodic memory retrieval: a functional MRI test of the monitoring hypothesis.

Though the right prefrontal cortex is often activated in neuroimaging studies of episodic memory retrieval, the functional significance of this activation remains unresolved. In this functional MRI study of 12 healthy volunteers, we tested the hypothesis that one role of the right prefrontal cortex is to monitor the information retrieved from episodic memory in order to make an appropriate response. The critical comparison was between two word recognition tasks that differed only in whether correct responses did or did not require reference to the spatiotemporal context of words presented during a previous study episode. Activation in a dorsal midlateral region of the right prefrontal cortex was associated with increased contextual monitoring demands, whereas a more ventral region of the right prefrontal cortex showed retrieval-related activation that was independent of task instructions. This functional dissociation of dorsal and ventral right prefrontal regions is discussed in relation to a theoretical framework for the control of episodic memory retrieval.

Adult↗
PubMed1997

Dissociable forms of inhibitory control within prefrontal cortex with an analog of the Wisconsin Card Sort Test: restriction to novel situations and independence from "on-line" processing.

Attentional set-shifting and discrimination reversal are sensitive to prefrontal damage in the marmoset in a manner qualitatively similar to that seen in man and Old World monkeys, respectively (Dias et al., 1996b). Preliminary findings have demonstrated that although lateral but not orbital prefrontal cortex is the critical locus in shifting an attentional set between perceptual dimensions, orbital but not lateral prefrontal cortex is the critical locus in reversing a stimulus-reward association within a particular perceptual dimension (Dias et al., 1996a). The present study presents this analysis in full and extends the results in three main ways by demonstrating that (1) mechanisms of inhibitory control and "on-line" processing are independent within the prefrontal cortex, (2) impairments in inhibitory control induced by prefrontal damage are restricted to novel situations, and (3) those prefrontal areas involved in the suppression of previously established response sets are not involved in the acquisition of such response sets. These findings suggest that inhibitory control is a general process that operates across functionally distinct regions within the prefrontal cortex. Although damage to lateral prefrontal cortex causes a loss of inhibitory control in attentional selection, damage to orbitofrontal cortex causes a loss of inhibitory control in affective processing. These findings provide an explanation for the apparent discrepancy between human and nonhuman primate studies in which disinhibition as measured on the Wisconsin Card Sort Test is associated with dorsolateral prefrontal damage, whereas disinhibition as measured on discrimination reversal is associated with orbitofrontal damage.

Animals↗
PubMed2001

Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats.

This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age.

Animals↗
PubMed2004

Developmental changes in real life decision making: performance on a gambling task previously shown to depend on the ventromedial prefrontal cortex.

Patients with bilateral lesions of the ventromedial prefrontal cortex, when performing gambling tasks modeling real-life decision-making, opt for choices that yield high immediate gains in spite of higher future losses. Under the hypothesis that the prefrontal cortex is the last brain region to mature, it was examined whether young children would show a similar preference for immediate prospects. In Experiment 1, 4 age groups (6-9, 10-12, 13-15 and 18-25 years olds) performed 2 versions of a computerized variant of the original Iowa gambling task under 3 different feedback conditions (no feedback, global feedback, and option-specific feedback) and completed the Raven Standard Progressive Matrices as an index of inductive reasoning ability. In Experiment 2, 3 age groups (7-8, 11-12, and 15-16 year olds) performed both task versions in addition to a working memory task ("Digit Span Backwards"). Results showed a developmental increase in the sensitivity to future consequences, positive or negative, that could not be explained by developmental changes in working memory capacity or inductive reasoning. It was concluded that young children share with ventromedial prefrontal patients the failure to anticipate on future outcomes.

Adolescent↗
PubMed1997

Parcellation of the human prefrontal cortex using MRI.

A methodology was developed for dividing prefrontal cortical gray matter into insular, orbital, inferior, middle, superior, cingulate, and frontal pole regions using anatomical criteria. This methodology was developed as a follow-up to one that measured whole prefrontal gray and white matter volumes in schizophrenic and control subjects. This study showed no overall volume differences in prefrontal cortex between schizophrenic and control subjects. The parcellation of prefrontal cortex was done to increase the probability of detecting abnormalities that were circumscribed to a particular portion of the region. A 1.5 Tesla magnet was used to acquire contiguous 1.5-mm coronal slices of the entire brain. Volumes were then measured in a group of right-handed male (n = 15) subjects. Gray matter was parcellated using criteria that were mainly based on gross anatomy, as visualized in 3-dimensional renderings of the brain. Reliability of the parcellation scheme was very high (r(i) = 0.80 and above). This methodology should be useful in the study of cortical pathology in a number of neurological disorders, including schizophrenia.

Electronic Data Processing↗
PubMed2001

Transcranial magnetic stimulation of left prefrontal cortex impairs working memory.

OBJECTIVES: Several lines of evidence suggest that the prefrontal cortex is involved in working memory. Our goal was to determine whether transient functional disruption of the dorsolateral prefrontal cortex (DLPFC) would impair performance in a sequential-letter working memory task. METHODS: Subjects were shown sequences of letters and asked to state whether the letter just displayed was the same as the one presented 3-back. Single-pulse transcranial magnetic stimulation (TMS) was applied over the DLPFC between letter presentations. RESULTS: TMS applied over the left DLPFC resulted in increased errors relative to no TMS controls. TMS over the right DLPFC did not alter working memory performance. CONCLUSION: Our results indicate that the left prefrontal cortex has a crucial role in at least one type of working memory.

Adult↗
PubMed2003

Early social deprivation alters monoaminergic afferents in the orbital prefrontal cortex of Octodon degus.

The influence of early parental deprivation on the development of tyrosine hydroxylase- and 5-hydroxytryptamine-immunoreactive fiber innervation of subregions of the orbital prefrontal cortex (ventrolateral orbital, lateral orbital and agranular insular cortex) was quantitatively investigated in the precocious lagomorph Octodon degus. Forty-five-day-old degus from two groups were compared: 1) degus which were repeatedly separated from their parents during the first three postnatal weeks, and after weaning they were reared in social isolation; and 2) degus which were reared undisturbed in their families. Compared with the normal control animals the ventrolateral orbital prefrontal cortex and agranular insular cortex of the deprived animals displayed significantly increased density of tyrosine hydroxylase-immunoreactive fibers (up to 172% in the ventrolateral orbital prefrontal cortex and up to 143% in the agranular insular cortex). The lateral orbital prefrontal cortex showed increased 5-hydroxytryptamine-positive fiber densities (up to 118%). This altered balance between the serotonergic and dopaminergic cortical innervation in the orbital prefrontal cortex may reflect an anatomical and functional adaptation, which may be triggered by an altered activity of these transmitter systems during the phases of parental separation and social isolation.

Afferent Pathways↗
PubMed2006

Role of the prefrontal cortex in attentional control over bistable vision.

The primary source of top-down attentional control in object perception is the prefrontal cortex. This region is involved in the maintenance of goal-related information as well as in attentional selection and set shifting. Recent approaches have emphasized the role of top-down processes during elementary visual processes as exemplified in bistable vision where perception oscillates automatically between two mutually exclusive states. The prefrontal cortex might influence this process either by maintaining the dominant pattern while protecting it against the competing representation, or by facilitating perceptual switches between the two competing representations. To address this issue, we investigated reported perceptual reversals in patients with circumscribed lesions of the prefrontal cortex and healthy control participants in three experimental conditions: hold (maintaining the dominant view), speed (inducing as many perceptual switches as possible), and neutral (no intervention). Results indicated that although the patients showed normal switching rates in the neutral condition and were able to control perceptual switches in the hold condition as much as control subjects were, they were less able to facilitate reversals specifically in the speed condition. These results suggest that the prefrontal cortex is necessary to bias the selection of visual representations in accord with current goals, but is less essential for maintaining selected information active that is continuously available in the environment. As for attentional selection, the present results suggest that the prefrontal cortex initiates perceptual reversals by withdrawing top-down support from the dominant representation without (or prior to) boosting the suppressed view.

Attention↗
PubMed2001

Recent cytoarchitechtonic changes in the prefrontal cortex of schizophrenics.

A variety of lines of converging evidence implicate the prefrontal cortex (PFC) in schizophrenia. In the past studies have focused on the various neurotransmitter systems that appear to be involved in schizophrenia such as dopamine, glutamate and serotonin. Recently, the focus of research has shifted away from systems and towards cellular morphology due partly to studies suggesting an increase in neural density in various regions of the PFC (1,2). A plethora of research has come out suggesting possible cytoarchitectural changes in pyramidal cells in the prefrontal cortex as well as alterations of certain GABAergic cells. This review examines the recent data that shows cytoarchitechtonic changes in cells of the prefrontal cortex.

Humans↗
PubMed2006

The special involvement of the rostrolateral prefrontal cortex in planning abilities: an event-related fMRI study with the Tower of London paradigm.

Planning abilities are essential for the successful management of everyday life activities. Although several neuroimaging studies provide evidence that the prefrontal cortex is crucially involved in planning, the differential roles of its subregions are still a matter of debate. The aim of this study was to investigate the neural correlates of planning by focusing on the functional differentiation between the dorsolateral and rostrolateral prefrontal cortex using the Tower of London (ToL) task and a parametric event-related functional MRI design. In order to control for activations unspecific to planning, two control conditions were presented, which were matched for the length of single events in the ToL task. Seventeen right-handed healthy subjects participated in this study. All statistics were reported with corrections for multiple comparisons (p < 0.05). Compared to control conditions, activations in the ToL task were observed in the dorsolateral prefrontal cortex bilaterally, the right ventrolateral and left rostrolateral prefrontal cortex along with the thalamus, as well as in the parietal and premotor cortex bilaterally. Task complexity dependent analyses revealed that only the left rostrolateral prefrontal cortex showed a BOLD signal increase over the four planning levels, which could not be observed in the control conditions. Hence, current findings suggest that planning involves an extensive fronto-parieto-thalamic network. Within this network, the rostrolateral prefrontal cortex seems to be the only region that is exclusively reactive to planning specific processes, which we described in terms of simultaneous monitoring of internally generated and externally presented information.

Adult↗
PubMed1996

Enkephalin terminals form inhibitory-type synapses on neurons in the rat nucleus locus coeruleus that project to the medial prefrontal cortex.

Norepinephrine-containing fibres in the medial prefrontal cortex derive from the locus coeruleus, a brainstem nucleus which also receives a dense innervation of enkephalin-immunoreactive axon terminals. We combined immunogold-silver labelling of retrogradely transported FluoroGold from the medial prefrontal cortex with immunoperoxidase detection of leucine5-enkephalin in the same section of tissue through the locus coeruleus of adult rats. This dual-labelling experiment was conducted to determine whether axon terminals containing lecuine5-enkephalin target neurons in the locus coeruleus that project to the frontal cortex and, if so, what are their morphological characteristics. By light microscopy, enkephalin-labelled processes overlapped FluoroGold retrogradely labelled neurons in the locus coeruleus. By electron microscopy, retrogradely labelled perikarya and dendrites were commonly enveloped by astrocytic processes and received few afferents in the plane of section examined. However, at sites unoccupied by glial processes, abundant afferent input could be identified. In addition, some FluoroGold-labelled perikarya and dendrites lacked this glial ensheathment but were more frequently apposed by axon terminals. Of 163 FluoroGold-labelled perikarya and dendrites examined where enkephalin immunoreactivity was present in the neuropil, 42% were contacted by enkephalin-immunoreactive axon terminals. The peroxidase-labelled enkephalin terminals as well as the unlabelled terminals often contained both small, clear and large dense core vesicles. Both labelled and unlabelled terminals also formed primary symmetric synapses characteristic of inhibitory transmitters with retrogradely labelled perikarya and proximal dendrites. At times, more than one enkephalin-labelled terminal was found to converge on a common retrogradely labelled perikarya or dendrite. These results demonstrate cellular sites where enkephalin-containing afferents may directly modulate and most likely inhibit the activity of cortically projecting neurons in the locus coeruleus.

Animals↗