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At least 721 records · Page 40Linked to original sources

PubMed2005

Voxel-based morphometry and stereology provide convergent evidence of the importance of medial prefrontal cortex for fluid intelligence in healthy adults.

We investigated whether a relationship exists between frontal lobe volume and fluid intelligence as measured by both Cattell's Culture Fair test and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Performance scale, but not with crystallized intelligence as measured by the WAIS-R Verbal scale, in healthy adults, using two well-established image analysis techniques applied to high-resolution MR brain images. Firstly, using voxel-based morphometry (VBM), we investigated whether a significant relationship exists between gray matter concentration and fluid intelligence on a voxel-by-voxel basis. Secondly, we applied the Cavalieri method of modern design stereology in combination with point counting to investigate possible relationships between macroscopic volumes of relevant brain regions defined as dorsolateral, dorsomedial, orbitolateral, and orbitomedial prefrontal cortex on the basis of neuroanatomical landmarks, and fluid intelligence. We also examined the effect on these relationships of normalizing regional brain volumes to intracranial volume. VBM analysis revealed a positive correlation between gray matter concentration in the medial region of prefrontal cortex and Culture Fair scores (corrected for multiple comparisons), and also WAIS-R Performance Intelligence sum of scaled scores (SSS) (uncorrected for multiple comparisons before controlling for age, and this converges with the stereological finding of the positive correlation between volume of dorsomedial prefrontal cortex normalized to intracranial volume and Culture Fair scores after controlling for age. WAIS-R Verbal Intelligence SSS showed no correlations. We interpret our findings, from independent analyses of both VBM and stereology, as evidence of the importance of medial prefrontal cortex in supporting fluid intelligence.

Adult↗

PubMed1992

Effects of acute and chronic clozapine on dopaminergic function in medial prefrontal cortex of awake, freely moving rats.

We previously showed that chronic administration of the clinically atypical and clinically superior antipsychotic drug clozapine selectively reduces dopamine (DA) release in the nucleus accumbens but not neostriatum, and that this effect appears mediated by anatomically selective mesolimbic DA depolarization blockade. The present study extends that research to another mesocorticolimbic DA locus, the medial prefrontal cortex. Acute clozapine challenge (5-40 mg/kg i.p.) produced dose-dependent increased extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the medial prefrontal cortex of awake, free-moving rats as measured by in vivo brain microdialysis. Chronic clozapine treatment (20 mg/kg/day for 21 days) did not significantly change basal extracellular levels of DA, DOPAC or HVA. Acute clozapine challenge on day 22 in the chronic clozapine-treated animals produced no significant differences in medial prefrontal cortex DA, DOPAC or HVA as compared to chronic vehicle-treated animals, indicating that tolerance to clozapine does not develop in the mesocortical DA system, in contrast to the mesolimbic system. The DA agonist apomorphine (100 micrograms/kg) produced decreased basal extracellular levels of DA, DOPAC and HVA in medial prefrontal cortex of both chronic clozapine-treated and chronic vehicle-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

Cerebellar projections to the prefrontal cortex of the primate.

The cerebellum is known to project via the thalamus to multiple motor areas of the cerebral cortex. In this study, we examined the extent and anatomical organization of cerebellar input to multiple regions of prefrontal cortex. We first used conventional retrograde tracers to map the origin of thalamic projections to five prefrontal regions: medial area 9 (9m), lateral area 9 (9l), dorsal area 46 (46d), ventral area 46, and lateral area 12. Only areas 46d, 9m, and 9l received substantial input from thalamic regions included within the zone of termination of cerebellar efferents. This suggested that these cortical areas were the target of cerebellar output. We tested this possibility using retrograde transneuronal transport of the McIntyre-B strain of herpes simplex virus type 1 from areas of prefrontal cortex. Neurons labeled by retrograde transneuronal transport of virus were found in the dentate nucleus only after injections into areas 46d, 9m, and 9l. The precise location of labeled neurons in the dentate varied with the prefrontal area injected. In addition, the dentate neurons labeled after virus injections into prefrontal areas were located in regions spatially separate from those labeled after virus injections into motor areas of the cerebral cortex. Our observations indicate that the cerebellum influences several areas of prefrontal cortex via the thalamus. Furthermore, separate output channels exist in the dentate to influence motor and cognitive operations. These results provide an anatomical substrate for the cerebellum to be involved in cognitive functions such as planning, working memory, and rule-based learning.

Animals↗

PubMed2005

Effects of response conflict on pain-evoked medial prefrontal cortex activity.

Experimental studies of pain may introduce a response conflict, where the subject must inhibit an escape response and make a pain-rating response. Several lines of evidence have shown that the medial prefrontal cortex is activated by painful stimuli and by response conflict. It is not clear, however, to what extent pain-evoked medial prefrontal cortex activation reflects response conflict. We examined this question using the Simon task. The participants identified pain threshold and moderately painful target stimuli presented to the left or right sural nerves using their left or right hands. Response conflict occurred when the response was made with the hand contralateral to the target stimulus. The results suggest that pain-evoked medial prefrontal cortex activity occurring 70 to 190 ms poststimulus, as estimated from the sural nerve somatosensory evoked potential, is not involved in response conflict.

Adolescent↗

PubMed2002

Analysis of projections from the medial prefrontal cortex to the thalamus in the rat, with emphasis on nucleus reuniens.

The medial prefrontal cortex (mPFC) is involved in high-order cognitive processes, including, but not limited to, decision making, goal directed behavior, and working memory. Although previous reports have included descriptions of mPFC projections to the thalamus in overall examinations of mPFC projections throughout the brain, no previous study has comprehensively examined mPFC projections to the thalamus. The present report compares and contrasts projections from the four divisions of the mPFC, i.e., the infralimbic, prelimbic, anterior cingulate and medial agranular cortices, to the thalamus in the rat by using the anterograde anatomic tracer Phaseolus vulgaris-leucoagglutinin. We showed that (1) the infralimbic, prelimbic, anterior cingulate cortices distribute heavily and selectively to midline/medial structures of the thalamus, including the paratenial, paraventricular, interanteromedial, anteromedial, intermediodorsal, mediodorsal, reuniens, and the central medial nuclei; (2) the medial agranular cortex distributes strongly to the rostral intralaminar nuclei (central lateral, paracentral, central medial nuclei) as well as to the ventromedial and ventrolateral nuclei of thalamus; and (3) all four divisions of the mPFC project densely to the nucleus reuniens (RE) of the thalamus. The nucleus reuniens is the major source of thalamic afferents to the hippocampal formation. There are essentially no direct projections from the mPFC to the hippocampus. The present demonstration of pronounced mPFC projections to RE suggests that the nucleus reuniens is a critical relay in the transfer of information from the medial prefrontal cortex to the hippocampus. Our further demonstration of strong mPFC projections to several additional thalamic nuclei, particularly to the mediodorsal nucleus, suggests that these thalamic nuclei, like RE, represent important output stations (or gateways) for the actions of mPFC on diverse subcortical and cortical structures of the brain.

Animals↗

PubMedDate not supplied

Muscimol injected into the medial prefrontal cortex of the rat alters ethanol self-administration.

The role of the rodent prefrontal cortex in the regulation of ethanol self-administration has not been widely explored. Understanding the role of GABAergic transmission in this area in relation to ethanol self-administration is important, as the GABA system may be one of several targets for alcohol's actions in the brain. Rats were initiated to drink 10% ethanol from a dipper using a sucrose-substitution procedure. When baseline behavior was stable, bilateral microinjections of muscimol (a GABA(A) agonist) into the prefrontal cortex were tested at doses of 17.5, 30, 100 and 300 ng/microl. Ethanol self-administration was decreased by approximately 40% at the 30-ng dose and 30% at the 100-ng dose. No effects were observed at either the 17.5- or 300-ng dose. The effect on the pattern of self-administration was to shorten the size of the first run of drinking without affecting the rate of drinking. The hypothesis is put forward that the injections increased glutamatergic output to the nucleus accumbens (nAcc) that in turn increased accumbens output. This increased output is proposed as similar to the effects of dopaminergic (DA) manipulations within this system.

Alcohol Drinking↗

PubMed2006

Acute stress and nicotine cues interact to unveil locomotor arousal and activity-dependent gene expression in the prefrontal cortex.

BACKGROUND: This study examines the interactive effects of acute stress and nicotine-associated contextual cues on locomotor activity and activity-dependent gene expression in subregions of the prefrontal cortex. METHODS: Locomotor activity of rats was measured in a context associated with either low-dose nicotine or saline administration with or without 5 minutes of pre-exposure to ferrets, a nonphysical stressor. After 45 minutes in the test environment, plasma corticosterone levels and mRNA levels of the immediate-early genes Arc, NGFI-B, and c-Fos in prefrontal and primary motor cortical subregions were measured. RESULTS: Stress alone increased plasma corticosterone and prefrontal cortex gene expression. Low-dose nicotine cues had no effect on corticosterone levels nor did they elicit conditioned motor activation, and they caused minor elevations in gene expression. Stress and low-dose nicotine cues, however, interacted to elicit conditioned motor activation and further increases in early response gene expression in prefrontal but not in the primary motor cortical subregions. CONCLUSIONS: Stress interacts with nicotine-associated cues to uncover locomotor arousal, a state associated with prefrontal neuronal activation and immediate early gene expression. Thus, in nicotine-experienced individuals, stress may be an important determinant of subjective reactivity and prefrontal cortex activation that occurs in response to nicotine-associated cues.

AIDS-Related Complex↗

PubMed2000

Gene expression of PSD95 in prefrontal cortex and hippocampus in schizophrenia.

A number of studies have suggested that disturbance in glutamatergic transmission in the cerebral cortex may underlie, or contribute to the pathophysiology of schizophrenia. In this study we examined expression of the postsynaptic density protein 95 (PSD95) mRNA in the prefrontal cortex and hippocampus in postmortem material from neuroleptic-treated schizophrenics and normal controls. PSD95 is known to bind to NMDA receptor subunits and is known to be involved in synaptic plasticity. In situ hybridization analysis showed that the expression of PSD95 was significantly decreased in Brodmann area 9 of the prefrontal cortex but not in the hippocampus. These results further implicate the prefrontal cortex in the pathophysiology of schizophrenia and suggest dysfunction of NMDA receptors in the schizophrenic cortex.

Aged↗

PubMed1995

Age-related changes in [3H]GBR 12935 binding site density in the prefrontal cortex of controls and schizophrenics.

We investigated dopamine transporter receptor ligand binding in the prefrontal cortex as a function of age in schizophrenic and control postmortem brains. [3H]GBR 12935 binding constants were calculated by Scatchard analysis from the autopsied brains from 29 individuals with schizophrenia, and 28 control subjects. There were wide interindividual variations in Bmax and KD that were not related to gender, age, or postmortem interval (PMI) in controls. While there were no significant associations between gender, PMI, and Bmax, or KD in individuals with schizophrenia, there was a significant negative correlation between age and Bmax (r = -.44, p = .02). The slope of the regression lines between age and Bmax for the two groups was significantly different. The results suggest a differential effect of age, or something associated with age, on [3H]GBR 12935 binding sites in the prefrontal cortex of controls and individuals with schizophrenia.

Adult↗

PubMed2006

Preliminary evidence of differential relations between prefrontal cortex metabolism and sustained attention in depressed adults with bipolar disorder and healthy controls.

OBJECTIVES: To assess the relations between sustained attention as assessed by the Continuous Performance Test (CPT) and subgenual and dorsolateral prefrontal cortex metabolism in depressed patients with bipolar disorders and healthy controls. DESIGN: Cross-sectional case-control design. METHODS: Cerebral metabolic rates were assessed with 18F-fluoro-deoxyglucose and positron emission tomography (PET) in the regions of interest defined on co-registered structural magnetic resonance images in eight medication-free, depressed bipolar disorder patients and 27 healthy control participants. PET scans were obtained in a resting state and the CPT was administered within 1 week of the PET scan. RESULTS: Although there were no statistically significant differences in performance on the CPT or in cerebral metabolism between the two groups, our analyses revealed differential relations between the CPT and metabolism across the groups. Decreased subgenual prefrontal metabolism was associated with slower hit rate reaction time and more omission errors in the bipolar group, but not the control group. Decreased dorsolateral prefrontal metabolism in the bipolar group, but not the control group, was associated with more commission errors. CONCLUSIONS: This study extends previous neuroimaging findings of structural and functional relevance of the prefrontal region with attention to include depressed states in bipolar disorder. The results are consistent with interpretations that decreased prefrontal activity may represent failure to activate some areas of inhibitory control. Decreasing subgenual prefrontal cortex metabolism appears to relate to decreased attention whereas the decreased dorsolateral prefrontal cortex metabolism relates more to decreased inhibitory control.

Adult↗

PubMedDate not supplied

Adrenergic receptors in aging and Alzheimer's disease: decreased alpha 2-receptors demonstrated by [3H]p-aminoclonidine binding in prefrontal cortex.

Biochemical and pathological studies have described abnormalities in the brainstem locus coeruleus noradrenergic neurones in Alzheimer's disease (AD) and in aging. Loss of cortical noradrenergic fibers originating from the locus coeruleus may cause a decrease in presynaptic receptors or induce an increase in postsynaptic receptors, similar to "denervation supersensitivity" in animal models. Thus far it is unclear whether alpha 2-adrenergic receptors are affected in AD. In this study, we assessed the specific binding of [3H]p-aminoclonidine, an agonist at alpha 2-receptors and at imidazoline-preferring binding sites, to prefrontal cortex and other regions including hippocampus, temporal cortex, putamen and cerebellum from subjects with AD and aging controls. We particularly focused on the prefrontal cortex because of its relatively rich monoaminergic innervation and recent evidence suggesting involvement of noradrenergic mechanisms in cognition in aging nonhuman primates. The other regions, which are also innervated by noradrenergic fibers, were examined for comparison. Ligand binding to prefrontal cortex decreased with age of controls and was also significantly reduced by approximately 50% in AD subjects compared to age-matched controls. This change in AD was related to the maximum binding capacity (Bmax) rather than to an altered affinity of the ligand for the receptor. There were no significant changes in any of the other regions studied. Binding did not change with postmortem delay or with duration of tissue storage. We suggest that presynaptic alpha 2-receptors presumably labeled by [3H]p-aminoclonidine on noradrenergic synapses are those that are selectively decreased in the prefrontal cortex in AD and in aging.

Adult↗

PubMed2005

Differential prefrontal cortex activation during inhibitory control in adolescents with and without childhood attention-deficit/hyperactivity disorder.

The authors examined inhibitory control processes in 8 adolescents diagnosed with attention-deficit/ hyperactivity disorder (ADHD) during childhood and in 8 adolescent control participants using functional MRI with the Stimulus and Response Conflict Tasks (K. W. Nassauer & J. M. Halperin, 2003). No group differences in performance were evident on measures of interference control and/or response competition created by location and direction stimuli. However, the ADHD group demonstrated significantly greater activation of the left ventrolateral prefrontal cortex during interference control as well as greater activation of the left anterior cingulate cortex, right ventrolateral prefrontal cortex, and left basal ganglia during the dual task of interference control and response competition. The magnitude of the prefrontal and basal ganglia activation was positively correlated with severity of ADHD. Response competition alone did not yield group differences in activation.

Adolescent↗

PubMed2003

The role of prefrontal cortex in verbal episodic memory: rTMS evidence.

Long-term, episodic memory processing is supposed to involve the prefrontal cortex asymmetrically. Here we investigate the role of the dorsolateral prefrontal cortex (DLPFC) in encoding and retrieval of semantically related or unrelated word pairs. Subjects were required to perform a task consisting of two parts: a study phase (encoding), in which word pairs were presented, and a test phase (retrieval), during which stimuli previously presented had to be recognized among other stimuli. Consistently with our previous findings using pictures, repetitive transcranial magnetic stimulation (rTMS) had a significant impact on episodic memory. The performance was significantly disrupted when rTMS was applied to the left or right DLPFC during encoding, and to the right DLPFC in retrieval, but only for unrelated word pairs. These results indicate that the nature of the material to be remembered interacts with the encoding-retrieval DLPFC asymmetry; moreover, the crucial role of DLPFC is evident only for novel stimuli.

Adult↗

PubMed2003

Distinct prefrontal cortex activity associated with item memory and source memory for visual shapes.

In contrast to item memory, which refers to recognition or recall of previously presented information, source memory refers to memory for the context of previously presented information. The relatively few functional MRI (fMRI) source memory studies conducted to date have provided evidence that item memory and source memory are associated with differential activity in right and left prefrontal cortex, respectively. To both confirm this distinction in prefrontal cortex and to determine whether other differences in the neural substrates associated with these cognitive functions exist, an event-related fMRI study was conducted. In this study, item memory and source memory encoding phases were identical; participants viewed a series of abstract visual shapes presented on the left or right side of the screen and were instructed to remember each shape and its spatial location. During the item memory retrieval phase, shapes from the encoding phase were intermixed with new shapes and participants made an old-new judgment. During the source memory retrieval phase, all shapes were from the encoding phase and participants made a left-right judgment. An event-related analysis of item memory and source memory revealed a right and left prefrontal cortex distinction. Moreover, only item memory was associated with activity in the medial temporal lobes. These results confirm and extend previous findings that item memory and source memory are associated with distinct neural substrates.

Adult↗

PubMed2002

Cell adhesion molecule expression in the dorsolateral prefrontal cortex and anterior cingulate cortex in major depression in the elderly.

BACKGROUND: Neuroimaging studies have demonstrated changes in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in major depression. AIMS: We investigated the expression of cell adhesion molecules (CAMs) in the prefrontal cortex in depression. METHOD: Immunohistochemistry to localise CAMs in post-mortem tissue from 20 subjects with major depression and 20 controls, and image analysis to quantify their expression. RESULTS: We found significant increases in CAMs in the grey matter of the DLPFC in the depression group but no comparable differences in the ACC or occipital cortex. In the white matter there was a non-significant increase in intercellular adhesion molecule-I in the DLPFC in the depression group but no increase in the other areas or for vascular cell adhesion molecule-I in any area. Paired tests showed specificity for the DLPFC in the depression group only. CONCLUSIONS: The increase in CAM expression in the DLPFC suggests an inflammatory reaction and is consistent with ischaemia.

Aged↗

PubMed2003

Neurotransmission of cognition, part 3. Mechanism of action of selective NRIs: both dopamine and norepinephrine increase in prefrontal cortex.

ISSUE: Selective norepinephrine reuptake inhibitors exploit the fact that dopamine transporters are absent in prefrontal cortex, so dopamine has to hitchhike a ride on the norepinephrine transporter in order to be inactivated. Thus, blocking norepinephrine transporters leads to an increase in both dopamine and norepinephrine levels in prefrontal cortex as well as improvement in cognition in attention-deficit/hyperactivity disorder.

Adrenergic Uptake Inhibitors↗

PubMed1998

Ovarian hormones influence the morphology, distribution, and density of tyrosine hydroxylase immunoreactive axons in the dorsolateral prefrontal cortex of adult rhesus monkeys.

The maturation, adult functioning and dysfunction of the prefrontal cortex in disorders such as schizophrenia show gender biases in human and non-human primates. Although the basis for the hormone influence suggested in these observations is unknown, one possibility is that circulating hormones stimulate catecholamine innervation in the frontal lobe. This innervation is essential for prefrontal cortical function, and gonadal, especially ovarian hormones, profoundly influence catecholamine function and physiology in subcortical structures. This study was undertaken to determine whether influence is also exerted upon the catecholamine innervation of the association cortex by combining ovarian hormone manipulation with immunocytochemistry for tyrosine hydroxylase in the dorsolateral prefrontal cortex of adult female macaque monkeys. Qualitative and quantitative analyses of immunoreactive fibers were carried out and compared in cortices of ovariectomized animals, ovariectomized animals treated with estrogen, ovariectomized animals treated with estrogen followed by progesterone, and in intact, age- and sex-matched controls. These analyses revealed striking, layer-specific anomalies in fiber morphology and profound reductions in fiber density in ovariectomized animals. While hormone replacement with estrogen alone had limited influence, estrogen followed by progesterone was particularly effective in restoring tyrosine hydroxylase innervation in ovariectomized animals. Thus, ovarian hormones appear to be potent regulators of the catecholamine innervation of the primate prefrontal cortex. Such regulation is anticipated in the gender differences observed in prefrontal cortical development and function, and may also be relevant for the prefrontal dysfunction in disorders such as schizophrenia.

Analysis of Variance↗

PubMed2001

Dopamine release during stress in the prefrontal cortex of the rat decreases with age.

The effects of aging on the stress-induced increases of dopamine and the dopamine metabolites 3,4-dihydroxyphenylaectic acid (DOPAC) and homovalinic acid (HVA) in the medial prefrontal cortex of the awake rat were investigated using microdialysis. In young rats (2-3 months) handling stress produced an increase of dopamine by 205% and of the dopamine metabolites DOPAC by 120% and HVA by 155% of baseline as maximal increases. In middle-aged rats (14 months) the increase of dopamine was significantly lower than in young rats (155% of baseline), while in aged rats (30 months) stress produced no significant increases of dopamine in the prefrontal cortex. These results indicate that the effects of stress on dopamine release in the medial prefrontal cortex of the rat diminishes during the normal process of aging.

Aging↗