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Results for “Prefrontal Cortex”

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PubMed2003

Early and persistent alterations in prefrontal cortex MAO A and B in Alzheimer's disease.

Both monoamine oxidase (MAO) A and MAO B in the brain have been implicated in the etiology of Alzheimer's disease. MAO B is elevated in plaque-associated glia in Alzheimer brain. Elevations in MAO A in Alzheimer neurons have been linked to increases in neurotoxic metabolites and neuron loss. We investigated the relationship between cognitive function in Alzheimer patients and post-mortem prefrontal cortex MAO A and B activities. Prefrontal cortex tissue from 92 Alzheimer patients and 74 neurologically normal subjects was obtained at autopsy and analyzed for activities of MAO A and B by radioenzymatic methods. Mini Mental Status Exam was performed on Alzheimer patients within 1 year of death. Alzheimer brains were analyzed for Braak stage, tangles, plaques and choline acetyltransferase activity. Prefrontal cortex MAO B activity was significantly increased by 16% in Alzheimer patients versus normals, whereas MAO A activity was significantly decreased by 17% in these same patients. Neither MAO A nor MAO B activities correlated with cognitive function (MMSE score), choline acetyltransferase activity, plaques, neurofibrillary tangles, Braak stage, or age of disease onset in the Alzheimer patients. With increasing Alzheimer duration or increasing Braak stage, MMSE scores and choline acetyltransferase activity declined, but levels of MAO A and B in prefrontal cortex were unchanged. Patients in the upper quintile for MAO A or B activity did not differ significantly from those in the lowest quintile with respect to MMSE scores or age of Alzheimer disease onset. We conclude that the changes in MAO A and B in the prefrontal cortex occur very early in Alzheimer's disease and remain relatively constant as the disease progresses.

Age of Onset↗

PubMed2000

Hemispheric activation of anterior and inferior prefrontal cortex during verbal encoding and recognition: a PET study of healthy volunteers.

Evidence of bilateral prefrontal activation during memory encoding and retrieval has increased attention given to anatomical subdivisions within the prefrontal cortex. The current study examined anterior and inferior aspects of the prefrontal cortex to determine their degree of functional and hemispheric overlap during encoding and recognition. Cerebral blood flow of 25 healthy volunteers was measured using PET (15)O-water methods during four conditions: resting baseline, sequential finger movement, word encoding, and word recognition. Resting and motor images were averaged to provide a single reference that was subtracted from encoding and recognition using statistical parametric mapping (SPM96). Memory conditions were also subtracted from each other to identify differences in regional activity. Subjects performed well (86% correct) and had a slightly conservative response bias. Baseline subtraction from encoding revealed focal activation of left inferior prefrontal cortex (area 45) without significant contralateral activation. Recognition minus baseline subtraction produced a focal right anterior prefrontal activation (areas 9 and 10) that was not present in the left hemisphere. Bilateral effects were seen in area 45 during recognition. Subtraction of memory tasks from each other did not reveal any areas of greater activity during encoding. However, the recognition task produced greater activation in right area 9 extending into the anterior cingulate. Greater activity during recognition was also observed in left insula and bilateral visual integration areas. These results are discussed in relation to the prevailing model of prefrontal hemispheric asymmetry during episodic memory.

Adult↗

PubMedDate not supplied

Close interrelation of motor development and cognitive development and of the cerebellum and prefrontal cortex.

Motor development and cognitive development may be fundamentally interrelated. Contrary to popular notions that motor development begins and ends early, whereas cognitive development begins and ends later, both motor and cognitive development display equally protracted developmental timetables. When cognitive development is perturbed, as in a neurodevelopmental disorder, motor development is often adversely affected. While it has long been known that the striatum functions as part of a circuit with dorsolateral prefrontal cortex, it is suggested here that the same is true for the cerebellum and that the cerebellum may be important for cognitive as well as motor functions. Like prefrontal cortex, the cerebellum reaches maturity late. Many cognitive tasks that require prefrontal cortex also require the cerebellum. To make these points, evidence is summarized of the close co-activation of the neocerebellum and dorsolateral prefrontal cortex in functional neuroimaging, of similarities in the cognitive sequelae of damage to dorsolateral prefrontal cortex and the neocerebellum, of motor deficits in "cognitive" developmental disorders, and of abnormalities in the cerebellum and in prefrontal cortex in the same developmental disorders.

Cerebellum↗

PubMed2004

Differential interactions of desipramine with amphetamine and methamphetamine: evidence that amphetamine releases dopamine from noradrenergic neurons in the medial prefrontal cortex.

Amphetamine is more effective than methamphetamine at raising dopamine levels in the prefrontal cortex. The current study tested the hypothesis that norepinephrine transporters are involved in this difference. Using microdialysis, dopamine, norepinephrine, and serotonin were measured in the rat prefrontal cortex after administration of methamphetamine or amphetamine, with and without perfusion of desipramine. Amphetamine raised norepinephrine levels more than methamphetamine did. Desipramine raised dopamine and serotonin levels but did not alter metabolite levels. Desipramine attenuated the increase in dopamine by amphetamine while increasing the dopamine released by methamphetamine. These data suggest that methamphetamine and amphetamine differ in altering prefrontal cortical dopamine levels and in interacting with norepinephrine transporters. It is proposed that amphetamine releases dopamine in the prefrontal cortex primarily through norepinephrine transporters, whereas methamphetamine interacts minimally with norepinephrine transporters.

Amphetamine↗

PubMed1993

The organization of projections from the mediodorsal nucleus of the thalamus to orbital and medial prefrontal cortex in macaque monkeys.

The organization of interconnections between the mediodorsal nucleus of the thalamus (MD) and the orbital and medial prefrontal cortex and the agranular insular cortex in the monkey was studied by retrograde and anterograde tracing techniques. In addition to the magnocellular and parvicellular divisions of MD, three other subdivisions can be recognized on the basis of myeloarchitecture, cytoarchitecture, and connections. The first two of these represent a parcellation of the magnocellular division into a lateral, fiber-rich MD pars fibrosa and a medial, poorly myelinated MD pars paramediana adjacent to the midline. The third is a small, poorly myelinated area located at the caudomedial and dorsal edges of MD; it is referred to as MD pars caudodorsalis. MD pars fibrosa is reciprocally interconnected primarily with areas 11, 12 and 13 in the central and lateral part of the orbital cortex. There is a general organization within this projection, with the rostrocaudal axis of the cortex represented from dorsal to ventral in the pars fibrosa, and the mediolateral cortical axis represented from medial to lateral. Cells that project to area 12 also extend laterally into the adjacent pars parvicellularis. MD pars paramediana is more heavily interconnected with the caudal and medial portions of the orbital region, particularly the agranular insular areas and the caudal parts of areas 13 and 14. Cells that project to two caudal areas, 13a and Iad, do not fit with the general organization, in that they are located in the dorsomedial parts of the pars fibrosa and pars paramediana, where they overlap with cells that project to area 14. The pars fibrosa and pars paramediana receive inputs from areas of the ventral forebrain such as the amygdala, piriform (olfactory) cortex, and entorhinal cortex, which project directly to the orbital and agranular insular cortex, as well as from the ventral pallidum. MD pars caudodorsalis is reciprocally interconnected with areas 14, 24, and 32 on the medial surface of the prefrontal cortex. In this part of the nucleus the dorsoventral axis of the medial prefrontal cortex is represented from caudal to rostral in the thalamus. The amygdala and other ventral forebrain structures do not send fibers into the pars caudodorsalis, even though some of these structures project directly to the medial prefrontal cortex. Ventral to MD, and separated from it by the internal medullary lamina, a small region was recognized that appears to be comparable to the anteroventral part of the submedial nucleus previously defined in the rat and cat.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1999

The role of the prefrontal cortex in recognition memory and memory for source: an fMRI study.

We employed fMRI to index neural activity in prefrontal cortex during tests of recognition and source memory. At study, subjects were presented with words displayed either to the left or right of fixation, and, depending on the side, performed one of two orienting tasks. The test phase consisted of a sequence of three 10-word blocks, displayed in central vision. For one block, subjects performed recognition judgements on a mixture of two old and eight new words (low density recognition). For another block, recognition judgements were performed on a mixture of eight old and two new words (high density recognition). In the remaining block, also consisting of eight old and two new items, the requirement was to judge whether each word had been presented at study on the left or the right. Relative to the low density condition, high density recognition was associated with increased activity in right and, to a lesser extent, left, anterior prefrontal cortex (BA 10), replicating the findings of two previous PET studies. Right anterior prefrontal activity did not show any further increase during the source task. Instead, greater activity was found, relative to high density recognition, in left BA 10, left inferior frontal gyrus (BA 45/47), and bilateral opercular cortices (BA 45/47). The findings are inconsistent with the proposal that activation of right anterior prefrontal cortex during memory retrieval reflects "postretrieval" processing demands, such demands being considerably greater for judgments of source than recognition. The findings provide further evidence that the left prefrontal cortex plays a role in episodic memory retrieval when the task explicitly requires recovery of contextual as well as item information.

Adult↗

PubMed2001

Material-specific lateralization in the medial temporal lobe and prefrontal cortex during memory encoding.

Numerous observations in patients with unilateral lesions of the medial temporal lobe (MTL) and the prefrontal cortex indicate that memory processes are lateralized according to content. Left-sided lesions interfere with verbal memory processes, whereas right-sided lesions interfere with visuospatial (non-verbal) memory processes. However, functional imaging studies have resulted in contradictory data, some studies showing lateralization in the prefrontal cortex determined by stage of processing (encoding versus retrieval) and others suggesting that lateralization is dependent on the type of material. Few studies have examined this issue in the MTL. In order to test the hypothesis that the lateralization of encoding processes in the MTL and frontal regions is dependent on the verbalizability of the material, we performed behavioural and functional imaging studies. We demonstrated differing verbalizabilities of three classes of non-verbal stimuli (scenes > faces > abstract patterns) using a dual-task verbal interference behavioural paradigm. A functional neuroimaging study of encoding was carried out using these three types of stimuli, plus words. During whole-brain functional MRI at 1.5 T, eight normal right-handed adults were presented with alternating blocks of novel and repeated stimuli under intentional memory encoding conditions. Verbal encoding resulted in left-lateralized activation of the inferior prefrontal cortex and the MTL. Pattern encoding activated the right inferior prefrontal cortex and the right MTL. Scenes and faces resulted in approximately symmetrical activation in both regions. The data indicate that the lateralization of encoding processes is determined by the verbalizability of stimuli.

Adolescent↗

PubMed1998

Human prefrontal cortex is not specific for working memory: a functional MRI study.

Lesion studies in monkeys have provided evidence that lateral prefrontal cortex is necessary for working memory, the cognitive processes involved in the temporary maintenance and manipulation of information. Monkey electrophysiological studies, however, have also observed prefrontal neuronal activity associated with cognitive processes that are nonmnemonic. We tested the hypothesis that the same regions of human prefrontal cortex that demonstrate activity during working memory tasks would also demonstrate activity during tasks without working memory demands. During echoplanar fMRI imaging, subjects performed a three-condition experiment (working memory task, nonworking memory task, rest). In the working memory task, subjects observed serially presented stimuli and determined if each stimulus was the same as that presented two stimuli back. The nonworking memory task in Experiment 1 required subjects to identify a single predetermined stimulus; in Experiment 2, subjects were required to make a button press to every stimulus. In all subjects in both experiments, the working memory task exhibited greater prefrontal cortical activity compared to either nonworking memory task. In these same prefrontal regions, greater activation was also observed during both nonworking memory tasks compared to rest. We conclude that human lateral prefrontal cortex supports processes in addition to working memory. Thus, reverse inference of the form "if prefrontal cortex is active, working memory is engaged" is not supported.

Adult↗

PubMed1996

Prefrontal cortex inputs of the nucleus accumbens-nigro-thalamic circuit.

The functional organization of the cortico-nucleus accumbens-substantia nigra pars reticulata circuit was investigated in the rat using combined anatomical and electrophysiological approaches. The nucleus accumbens neurons which project to the substantia nigra pars reticulata are located in a circumscribed region of the core immediately adjacent and extending dorsally to the anterior commissure. As shown by retrograde and anterograde transports of wheatgerm agglutinin conjugated to horseradish peroxidase, the region of the nucleus accumbens related to the substantia nigra was found to receive bilateral inputs from restricted areas of the medial and lateral prefrontal cortex, i.e., prelimbic/medial orbital and dorsal agranular insular areas. The electrical stimulation of these medial and lateral prefrontal cortical areas induced excitatory responses in nucleus accumbens neurons projecting to the dorsomedial substantia nigra pars reticulata. Interestingly, an important proportion (61%) of the nucleus accumbens-nigral cells responding to the stimulation of the lateral prefrontal cortex were also excited by the stimulation of the medial prefrontal cortex, demonstrating the existence of a convergent influence of these cortical areas on single nucleus accumbens cells. Furthermore, the present data also show that the stimulation of the medial prefrontal cortex results in a powerful inhibition of the tonic firing of the substantia nigra pars reticulata neurons. In conclusion, this study reveals the existence of a functional link between the prefrontal cortex (prelimbic/medial orbital and agranular insular areas) and the nucleus accumbens neurons which innervate the dorsomedial region of the substantia nigra pars reticulata. Since the dorsomedial region of substantia nigra pars reticulata is known to project to subfields of the mediodorsal and ventromedial thalamic nuclei related to the prefrontal cortex, the present data further demonstrate the existence of a prefrontal-nucleus accumbens-thalamo-cortical circuit involving the substantia nigra pars reticulata.

Animals↗

PubMed1983

Allocortical afferent connections of the prefrontal cortex in the cat.

Afferent connections of the prefrontal cortex of the cat arising in allocortical regions have been investigated using the horseradish peroxidase retrograde transport technique. Our results demonstrate the existence of projections from the olfactory peduncle, anterior and posterior prepiriform cortices, cortico-amygdaloid transition area, entorhinal cortex, ventral, caudal and dorsal subiculum and postsubiculum to the prefrontal cortex.

Afferent Pathways↗

PubMed2003

Neural correlates of retrieval processing in the prefrontal cortex during recognition and exclusion tasks.

Event-related fMRI was employed to contrast the neural activity elicited in prefrontal cortex during recognition memory and exclusion tests. The study phases preceding each memory test were identical, involving the presentation of study items (visually presented words) in one of two study contexts. For the recognition test subjects were required to respond positively to all old items regardless of study context, and to respond negatively to new items. For the exclusion task, positive responses were required to old items presented in one of the study contexts only; negative responses were required both to unstudied items and studied items from the alternative context (non-targets). No prefrontal region demonstrated greater activity for new items in the exclusion task. Thus, there was no evidence that retrieval cues were processed differently according to the specificity of the sought-for information. In several regions, most notably bilateral anterior prefrontal cortex, activity was greater for old than for new items regardless of task. Activity in right dorsolateral prefrontal cortex was also greater for old than for new items; these effects however were larger in the exclusion task. The findings are consistent with previous reports that activity in anterior prefrontal cortex elicited by recognition retrieval cues is sensitive to retrieval success, and extend these findings to the exclusion task. The findings for the right dorsolateral cortex add further weight to the proposal that this region supports post-retrieval monitoring of retrieved information.

Adult↗

PubMed2005

Repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex affects strategic decision-making.

Although decision-making is typically seen as a rational process, emotions play a role in tasks that include unfairness. Recently, activation in the right dorsolateral prefrontal cortex during offers experienced as unfair in the Ultimatum Game was suggested to subserve goal maintenance in this task. This is restricted to correlational evidence, however, and it remains unclear whether the dorsolateral prefrontal cortex is crucial for strategic decision-making. The present study used repetitive transcranial magnetic stimulation in order to investigate the causal role of the dorsolateral prefrontal cortex in strategic decision-making in the Ultimatum Game. The results showed that repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex resulted in an altered decision-making strategy compared with sham stimulation. We conclude that the dorsolateral prefrontal cortex is causally implicated in strategic decision-making in healthy human study participants.

Adult↗

PubMed2003

The mid-ventrolateral prefrontal cortex: insights into its role in memory retrieval.

Although it is widely known that the prefrontal cortex plays a role in memory, the specific contribution of particular prefrontal regions in mnemonic functions remains controversial. The present investigation examined whether the mid-ventrolateral prefrontal cortex is selectively involved in active memory retrieval in situations in which mnemonic traces are embedded in ambiguous relations and automatic recollection cannot lead to successful retrieval. Thirteen subjects participated in this event-related functional magnetic resonance imaging experiment. Throughout the scanning session, trials belonging to an experimental and a control condition were administered in a pseudorandom fashion. During the encoding phase of any particular trial, subjects were presented with a stimulus-complex that was a combination of a face and a spatial location on the screen. In the experimental active retrieval condition, a question cue following the encoding phase instructed the subjects to retrieve selectively one of the two aspects of the encoded stimulus-complex, i.e. the face or the location. In the control condition, the question cue that followed the encoding phase instructed the subjects simply to recall the initially presented stimulus-complex, so as to be able to make a decision during the test phase based on simple stimulus familiarity. The comparison of the signal obtained during the retrieval phase of these two conditions yielded an increase in activity selective to the right mid-ventrolateral prefrontal region. These results therefore establish a specific link between the mid-ventrolateral prefrontal cortex and active retrieval mechanisms.

Adult↗

PubMed2001

The muscarinic agonist xanomeline increases monoamine release and immediate early gene expression in the rat prefrontal cortex.

BACKGROUND: The muscarinic agonist xanomeline has been shown to reduce antipsychotic-like behaviors in patients with Alzheimer's disease. Because atypical antipsychotic agents increase dopamine release in prefrontal cortex and induce immediate early gene expression in prefrontal cortex and nucleus accumbens, the effect of xanomeline was determined on these indices. METHODS: The effect of xanomeline on extracellular levels of monoamines in brain regions was determined using a microdialysis technique, and changes in expression of the immediate early genes c-fos and zif/268 in brain regions were evaluated using in situ hybridization histochemistry. RESULTS: Xanomeline increased extracellular levels of dopamine in prefrontal cortex and nucleus accumbens but not in striatum. Xanomeline increased expression of c-fos and zif/268 in prefrontal cortex and nucleus accumbens. There was no change in immediate early gene expression in striatum. CONCLUSIONS: Xanomeline increased extracellular levels of dopamine, which is similar to the effects of the atypical antipsychotics clozapine and olanzapine. The regional pattern of immediate early gene expression induced by xanomeline resembled that of atypical antipsychotic agents. Based on the antipsychotic-like activity of xanomeline in Alzheimer's patients and the similarity to atypical antipsychotic agents, we suggest that xanomeline may be a novel antipsychotic agent.

Animals↗

PubMed2006

Effects of excitotoxic lesions of the medial prefrontal cortex on density of high affinity [125I-Tyr3]neurotensin binding sites within the ventral midbrain and striatum.

The present study was aimed at determining the extent to which excitotoxic lesions of the medial prefrontal cortex reduce neurotensin receptors within the striatum, the nucleus accumbens, the ventral tegmental area and the substantia nigra. The medial prefrontal cortex was unilaterally lesioned with ibotenic acid and 10 days later brain sections were processed for neurotensin receptor autoradiographic analysis using 0.1 nM [(125)I-Tyr3]neurotensin with, or without, levocabastine. Analysis revealed at least two sites, one levocabastine-insensitive neurotensin NT(1) and one levocabastine-sensitive neurotensin NT(2)-like. The proportion of the latter site was high within the caudal striatum, the nucleus accumbens and the medial prefrontal cortex. Lesions produced a 60% to 80% reduction in neurotensin NT(1) within the ipsilateral medial prefrontal cortex, but no change in the sub-cortical nuclei. An increase in neurotensin NT(2)-like receptors was found in ipsilateral dorso-caudal caudate. These results show that a significant amount of neurotensin NT(1) receptors are located on neurons within the medial prefrontal cortex but not on their efferent terminals.

Animals↗

PubMed1981

Delayed-alternation performance after selective lesions of the medial and sulcal prefrontal cortex of the guinea pig.

The sulcal or medial subdivision of the prefrontal cortex of the guinea pig was ablated after the animals had learned a spatial delayed-alternation task. Retention of this task was significantly impaired only after ablation of the medial prefrontal cortex. As the most critical cortical region for delayed-alternation performance in the rat is also situated in the medial prefrontal cortex, our findings suggest a close functional correspondence of the prefrontal cortices of these rodent species.

Afferent Pathways↗

PubMed2005

Increased expression of the astrocytic glutamate transporter GLT-1 in the prefrontal cortex of schizophrenics.

To verify whether altered glial glutamate uptake contributes to the reduced efficacy of glutamatergic transmission reported in the prefrontal cortex of schizophrenics, we studied the expression of GLT-1, the transporter responsible for most glutamate transport, in autoptic samples of prefrontal cortex using real time quantitative RT-PCR, immunocytochemistry, and functional assays. GLT-1 mRNA levels in medication-free patients were 2.5-fold higher than in controls, whereas they were normal or reduced in patients treated with antipsychotics. We also observed a 4-fold increase in L-[(3)H]-Glu uptake in Xenopus oocytes injected with mRNA from the prefrontal cortex of a medication-free schizophrenic and a 2-fold increase in GLT-1 protein in the same cortical area of another medication-free patient. Results suggest that GLT-1 mRNA, protein and function are increased in prefrontal cortex of schizophrenics.

Adult↗

PubMed1997

Dopamine-glutamate interactions in the prefrontal cortex of the conscious rat: studies on ageing.

The effects of apomorphine, a D1-D2 dopamine receptor agonist, on the extracellular concentration of glutamate were investigated in the medial prefrontal cortex of young, middle-aged and aged rats. In vivo intracerebral perfusions were undertaken in the conscious rat using a concentric push-pull cannula system. Glutamate concentration in the samples were determined by HPLC with fluorometric detection. Apomorphine produced an increase in extracellular concentration of glutamate in medial prefrontal cortex of young rats (178% of baseline) only at 10 microM, but not at 5 and 20 microM. This increase in glutamate concentration induced by apomorphine was significantly attenuated by blockade of D1-D2 dopamine receptors with haloperidol. Apomorphine, at 10 microM, failed to induce an increase in extracellular concentration of glutamate in the prefrontal cortex of middle-aged and aged rats. However, at 20 microM, apomorphine induced an increase in glutamate concentration in the prefrontal cortex of middle-aged rats, but not in aged rats. These data indicate that an interaction between dopamine and glutamate exists in the medial prefrontal cortex and that this interaction deteriorates with age.

Aging↗