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Results for “Dorsolateral Prefrontal Cortex”

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PubMed2006

Dorsolateral prefrontal cortex promotes long-term memory formation through its role in working memory organization.

Results from neuroimaging studies have shown that the dorsolateral prefrontal cortex (DLPFC) implements processes critical for organizing items in working memory (WM). Based on its role in WM, we hypothesized that the DLPFC should contribute to long-term memory (LTM) formation by strengthening associations among items that are organized in WM. We conducted an event-related functional magnetic resonance imaging (fMRI) study to test this hypothesis by investigating prefrontal activity during performance of two different WM tasks: on "rehearse" trials, participants actively maintained triplets of words during a brief delay, whereas on "reorder" trials, participants actively organized each triplet during the delay. After scanning, subjects performed an LTM test on words presented during both WM conditions. Behavioral results showed that WM processing in the reorder condition enhanced LTM by strengthening inter-item associations. fMRI results showed that DLPFC activity specifically during reorder trials was predictive of subsequent LTM. In contrast, activity in the posterior ventrolateral prefrontal cortex was predictive of LTM for words studied on both reorder and rehearse trials. These results support the view that the DLPFC contributes to LTM formation through its role in organization of information in WM.

Adult↗

PubMed2006

The influence of rTMS over the right dorsolateral prefrontal cortex on top-down attentional processes.

Repetitive Transcranial Magnetic Stimulation (rTMS) provides a unique opportunity to study causal relationships between activity in the dorsolateral prefrontal cortex (DLPFC) and executive functioning, by modulating brain activity in SHAM controlled designs. We devised a new Stroop task paradigm in which subjects must engage in both strategic and automatic attentional processes. In the current experiment, we manipulated subjects' expectancies for incongruent stimuli. Previous research demonstrated that when subjects have a high level of expectancy that a stimulus will be incongruent, they are able to strategically adjust the relative influence of word reading on color naming. The effect of high frequency (HF) rTMS on Stroop performance of 20 right-handed healthy female volunteers was tested using a double blind within subjects design by counterbalanced crossover sham (placebo) and active rTMS over the right DLPFC. Since mood remained unchanged after rTMS, the Stroop data could be evaluated independent of mood changes. Only in the high expectancy condition, we found a decreased response time to both congruent and incongruent trials on the Stroop task performance after HF rTMS. The SHAM placebo condition yielded no effects. We conclude that high frequency stimulation over the right DLPFC has an effect on top-down attentional processes by modulating the attentional set.

Adolescent↗

PubMed2006

The influence of rTMS over the right dorsolateral prefrontal cortex on intentional set switching.

High frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has an excitatory effect on neurons of a specific brain area. The dorsolateral prefrontal cortex (DLPFC) has been associated with executive functions, such as task set switching. One important experimental paradigm for investigating such higher order cognitive control is the task-switching (TS) paradigm. A TS paradigm requires switching between two conditional response tasks with mutually incompatible response-selection rules. In the present study, the influence of HF rTMS over the right DLPFC in healthy female volunteers on a modified TS paradigm was investigated. As expected, reaction time on cued switching trials decreased significant after rTMS, as compared to non-cued switch trials. No changes emerged after the placebo sham condition. Mood remained unchanged after rTMS. These findings demonstrate the role of the right DLPFC in cued intentional set switch initiation.

Adolescent↗

PubMed1983

Functional heterogeneity of single neuronal activity in the monkey dorsolateral prefrontal cortex.

Extracellular single unit recording during high fixed ratio bar press behavior, guided by multimodal cue stimuli for food intake, revealed functional heterogeneity in the monkey dorsolateral prefrontal cortex. Cells were found significantly more often in the ventral arcuate concavity, the dorsal arcuate concavity, the principal sulcal area and the inferior convexity which responded, respectively, to visual events, auditory events, visual plus auditory events and bar press.

Animals↗

PubMed2005

1H magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in bipolar disorder patients.

BACKGROUND: Magnetic resonance spectroscopy studies (MRS) reported abnormally low levels of N-acetylaspartate (NAA, a marker of neuronal integrity) in dorsolateral prefrontal cortex (DLPFC) of adult bipolar patients, suggesting possible neuronal dysfunction. Furthermore, recent MRS reports suggested possible lithium-induced increase in NAA levels in bipolar patients. We examined with in vivo (1)H MRS NAA levels in the DLPFC of adult bipolar patients. METHODS: Ten DSM-IV bipolar disorder patients (6 lithium-treated, 4 drug-free) and 32 healthy controls underwent a short echo-time 1H MRS session, which localized an 8 cm3 single-voxel in the left DLPFC using a STEAM sequence. RESULTS: No significant differences between the two groups were found for NAA, choline-containing molecules (GPC+PC), or phosphocreatine plus creatine (PCr+Cr) (Student t-test, p > 0.05). Nonetheless, NAA/PCr+Cr ratios were significantly increased in lithium-treated bipolar subjects compared to unmedicated patients and healthy controls (Mann-Whitney U-test, p < 0.05). LIMITATIONS: Relatively small sample size may have reduced the statistical power of our analyses and the utilization of a single-voxel approach did not allow for the examination of other cortical brain areas. CONCLUSIONS: This study did not find abnormally reduced levels of NAA in left DLPFC of adult bipolar patients, in a sample of patients who were mostly on medications. However, elevated NAA/PCr+Cr ratios were shown in lithium-treated bipolar patients. Longitudinal 1H MRS studies should further examine NAA levels in prefrontal cortex regions in untreated bipolar patients before and after mood stabilizing treatment.

Adult↗

PubMed1999

Ovarian hormones differentially influence immunoreactivity for dopamine beta- hydroxylase, choline acetyltransferase, and serotonin in the dorsolateral prefrontal cortex of adult rhesus monkeys.

Recent studies have shown that ovariectomy reduces, and subsequent hormone replacement restores the density of axons immunoreactive for tyrosine hydroxylase in the dorsolateral prefrontal cortex of adult female rhesus monkeys. The present study indicates that three additional extrathalamic frontal lobe afferents are also sensitive to changes in the ovarian hormone environment. Specifically, the combination of hormone manipulation with qualitative and quantitative analysis of immunocytochemistry for dopamine beta-hydroxylase, choline acetyltransferase, and serotonin in the primate prefrontal cortex revealed quantitative responses in both cholinergic and monoaminergic axons to changing ovarian hormone levels. However, whereas ovariectomy produced a modest net decrease in the density of fibers immunoreactive for choline acetyltransferase, this same treatment markedly increased the density of axons immunoreactive for dopamine beta-hydroxylase and for serotonin. Further, the effects of ovariectomy on these afferent systems were differentially attenuated by estrogen verses estrogen plus progesterone hormone replacement. Estrogen was as effective as estrogen plus progesterone in stimulating normal prefrontal immunoreactivity for choline acetyltransferase and dopamine beta-hydroxylase. The dual replacement of estrogen plus progesterone, however, was a much more potent influence than estrogen alone for serotonin immunoreactivity. Thus, ovarian hormones appear to provide stimulation that differentially affects each of four chemically identified extrathalamic prefrontal afferent systems examined to date, and may have roles in maintaining the normal balance and functional interactions between these neurotransmitter systems.

Acetylcholine↗

PubMed2004

The right dorsolateral prefrontal cortex is essential in time reproduction: an investigation with repetitive transcranial magnetic stimulation.

This study used repetitive transcranial magnetic stimulation (rTMS) to investigate the roles of the right dorsolateral prefrontal cortex (DLPFC) and supplementary motor area (SMA) in short (500 ms) and long (2 s) interval timing. The results were compared with rTMS over the leg area of motor cortex, an area not thought to be involved with time estimation. rTMS was delivered during one of two phases of a time reproduction task: at the onset of the Estimation Phase (presentation of the interval to be timed) and at the onset of the Reproduction Phase (subjects' reproduction of the timed interval). There was a significant main effect of Site (SMA vs. right DLPFC vs. leg motor area) due to the fact that rTMS over the right DLPFC caused subjects to underestimate time intervals compared with rTMS over the leg motor area. There was also a significant three-way interaction between Site, Duration and Phase (Estimation Phase vs. Reproduction Phase) that post hoc analyses showed was due to underestimation of long intervals when rTMS was given over the right DLPFC at the start of the Reproduction Phase. There was no effect of rTMS over the right DLPFC or SMA in the short interval task. This is consistent with previous studies showing that the right DLPFC is important in estimating time intervals in the seconds-range. In addition, we suggest that the selectivity of the rTMS effect for the Reproduction Phase indicates that the right DLPFC plays a particular role in memory processes.

Adult↗

PubMed2006

The influence of rTMS over the left dorsolateral prefrontal cortex on Stroop task performance.

Several studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) can improve cognitive processing. Neuroimaging studies have shown the engagement of the left dorsolateral prefrontal cortex (DLPFC) in executive functioning, and more specifically during selective attention. In the present study, the influence of high-frequency rTMS over the left DLPFC on Stroop task performance in healthy female volunteers was investigated. As expected, reaction time on both the incongruent and congruent trials decreased significantly after stimulation, and there was no difference with regard to the Stroop interference effect. Mood remained unchanged after rTMS. Such a pattern is consistent with the role of the left DLPFC in implementing top-down attentional control.

Adolescent↗

PubMed2005

Cluster analysis-based physiological classification and morphological properties of inhibitory neurons in layers 2-3 of monkey dorsolateral prefrontal cortex.

In primates, little is known about intrinsic electrophysiological properties of neocortical neurons and their morphological correlates. To classify inhibitory cells (interneurons) in layers 2-3 of monkey dorsolateral prefrontal cortex we used whole cell voltage recordings and intracellular labeling in slice preparation with subsequent morphological reconstructions. Regular spiking pyramidal cells have been also included in the sample. Neurons were successfully segregated into three physiological clusters: regular-, intermediate-, and fast-spiking cells using cluster analysis as a multivariate exploratory technique. When morphological types of neurons were mapped on the physiological clusters, the cluster of regular spiking cells contained all pyramidal cells, whereas the intermediate- and fast-spiking clusters consisted exclusively of interneurons. The cluster of fast-spiking cells contained all of the chandelier cells and the majority of local, medium, and wide arbor (basket) interneurons. The cluster of intermediate spiking cells predominantly consisted of cells with the morphology of neurogliaform or vertically oriented (double-bouquet) interneurons. Thus a quantitative approach enabled us to demonstrate that intrinsic electrophysiological properties of neurons in the monkey prefrontal cortex define distinct cell types, which also display distinct morphologies.

Action Potentials↗

PubMed1988

Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. IV. Further evidence for regional and behavioral specificity.

In previous studies we found that patients with chronic schizophrenia had lower regional cerebral blood flow (rCBF) in dorsolateral prefrontal cortex (DLPFC) than did normal subjects during performance of the Wisconsin Card Sort Test, an abstract reasoning task linked to DLPFC function. This was not the case during less complex tasks. To examine further whether this finding represented regionally circumscribed pathophysiology or a more general correlate of abstract cognition, 24 medication-free patients and 25 age- and sex-matched normal control subjects underwent rCBF measurements with the xenon 133 technique while they performed two tasks: Raven's Progressive Matrices (RPM) and an active baseline control task. While performing RPM, normal subjects activated posterior cortical areas over baseline, but did not activate DLPFC, as had been seen during the Wisconsin Card Sort Test. Like normal subjects, patients showed maximal rCBF elevations posteriorly and, moreover, they had no significant DLPFC or other cortical deficit while performing RPM. These results suggest that DLPFC dysfunction in schizophrenia is linked to pathophysiology of a regionally specific neural system rather than to global cortical dysfunction, and that this pathophysiology is most apparent under prefrontally specific cognitive demand.

Adult↗

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↗

PubMed1986

Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. II. Role of neuroleptic treatment, attention, and mental effort.

We conducted two xenon Xe 133 inhalation regional cerebral blood flow (rCBF) studies to clarify earlier findings of dorsolateral prefrontal cortex (DLPFC) dysfunction in medication-free patients with chronic schizophrenia. In the first study, 24 neuroleptic-treated patients and 25 normal controls underwent three rCBF procedures, first while at rest, then during the Wisconsin Card Sort (WCS), which tests DLPFC cognitive function, and during a number-matching task that controlled for aspects of the WCS-rCBF experience not specifically related to DLPFC. The results were qualitatively identical to those previously reported for medication-free patients. In the second study, rCBF was determined while 18 medication-free patients and 17 normal control subjects each performed two versions of a visual continuous performance task (CPT). No differences in DLPFC blood flow between the two groups were found during either CPT condition. These data suggest that DLPFC dysfunction in schizophrenia is independent of medication status and not determined simply by state factors such as attention, mental effort, or severity of psychotic symptoms. Dysfunction of DLPFC appears to be a cognitively linked physiologic deficit in this illness.

Adult↗

PubMed2001

Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder.

BACKGROUND: Bipolar disorder (BPD) is a mental illness in which depression and mania typically alternate, and both phases can present with psychotic features. The symptomatology of BPD, therefore, resembles major depressive disorder (MDD) and schizophrenia (SCHZ), posing diagnostic dilemmas. Distinct alterations in cellular architecture of the dorsolateral prefrontal cortex distinguish SCHZ and MDD, whereas the cellular neuropathology of BPD has not been studied. METHODS: Dorsolateral prefrontal area 9 was analyzed using a three-dimensional morphometric method in postmortem brains from 10 BPD patients and 11 matched nonpsychiatric control subjects. RESULTS: Area 9 in BPD was characterized by reduced neuronal density in layer III (16%-22%) and reduced pyramidal cell density in layers III and V (17%-30%). A 19% reduction in glial density was found in sublayer IIIc coupled with enlargement and changes in shape of glial nuclei spanning multiple layers. CONCLUSIONS: The morphologic signature of BPD, i.e., decreased neuronal and glial density in association with glial hypertrophy, is distinct from previously described elevations in neuronal density in SCHZ, instead resembling the reductions in cell density found in MDD. Thus, the neuropathologic distinctions between BPD and SCHZ are indicative of separate mental illnesses, each with a unique morphologic disturbance of specific neural circuits.

Adult↗

PubMed1988

Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. III. A new cohort and evidence for a monoaminergic mechanism.

We previously reported that compared with normals, patients with chronic schizophrenia have reduced regional cerebral blood flow (rCBF) in dorsolateral prefrontal cortex (DLPFC) during performance of the Wisconsin Card Sort Test (WCS), a DLPFC-related cognitive task, but not during nonprefrontal tasks, such as a simple number-matching (NM) test. We also found that unlike normals, patients failed to activate DLPFC during the WCS over their own baseline (NM) level. To explore the reproducibility of these findings, a new cohort of 16 medication-free patients underwent a series of xenon 133 inhalation rCBF studies under the following conditions: at rest, while performing the WCS, and while performing NM. The results confirmed our earlier findings. In addition, the concentrations in cerebrospinal fluid of homovanillic acid and 5-hydroxyindoleacetic acid correlated with prefrontal rCBF during the WCS but not during the NM test or at rest. The results show that behavior-specific hypofunction of DLPFC in schizophrenia is reproducible, and they implicate a monoaminergic mechanism.

Adult↗

PubMed2005

Emotion-modulated performance and activity in left dorsolateral prefrontal cortex.

Functional MRI (fMRI) was used to examine the relationship between processing of pleasant and unpleasant stimuli and activity in prefrontal cortex. Twenty volunteers identified the colors in which pleasant, neutral, and unpleasant words were printed. Pleasant words prompted more activity bilaterally in dorsolateral prefrontal cortex (DLPFC) than did unpleasant words. In addition, pleasant words prompted more activity in left than in right DLPFC. Response speed to pleasant words was correlated with DLPFC activity. These data directly link positive affect, enhanced performance, and prefrontal activity, providing some of the first fMRI evidence supporting models of emotional valence and frontal brain asymmetry based on electroencephalography (EEG).

Adult↗

PubMed2002

Layer-specific reductions in GFAP-reactive astroglia in the dorsolateral prefrontal cortex in schizophrenia.

Neuroimaging studies have implicated the prefronto-striatal loop as a substrate for the cognitive deficits in schizophrenia (SCHZ). Postmortem morphometric studies reveal that layers III and V of the dorsolateral prefrontal cortex (dlPFC), which gave rise to glutamatergic projections to neostriatum, demonstrate the most structural pathology in this region of the SCHZ. These neuronal alterations in SCHZ are not accompanied by marked glial changes as revealed by Nissl staining. We examined the glial-type specific pathology in SCHZ by analyzing the glial fibrillary acidic protein- (GFAP) immunoreactive astroglia in contrast to the Nissl-stained general pool of glial cells in dlPFC (area 9) from 9 subjects with SCHZ and 15 psychiatrically normal control subjects. In layer V of the dlPFC in SCHZ, there was a significant 32% reduction in the GFAP-area fraction, 81% increase in the density of the GFAP-positive cell bodies and a 14% decrease in the width of the cortical layer V, as compared to the control subjects. None of these parameters were affected in layers III and IV in the SCHZ. Therefore, only subtle, type- and layer-specific glial pathology is present in the dlPFC in SCHZ. Astroglial pathology in dlPFC may reflect disturbances of the neuron-glia interactions in layer V and may be related to the dysfunctional prefronto-striatal circuits, dopaminergic alterations and cognitive pathology in SCHZ.

Adult↗

PubMed2005

Dorsolateral prefrontal cortex prevents short-latency saccade and vergence: a TMS study.

This study explores whether vergence eye movements along the median plane can be triggered with short latencies, and the role of the dorsolateral prefrontal cortex (DLPFC) in controlling such movements. We used a gap paradigm and applied transcranial magnetic stimulation (TMS) in 10 humans making saccades or vergence. TMS over the motor cortex had no effect on any eye movement parameter. TMS over DLPFC influenced eye movement initiation but not their metrics. TMS over the right DLPFC accelerated the triggering of saccades bilaterally but did not influence divergence. TMS over the left DLPFC speeded up the triggering of ipsilateral saccades and exacerbated the anticipatory mode of triggering of divergence. For convergence, TMS effects were mild: rightward TMS increased the proportion of short latencies but failed to shorten the group mean latency; leftward TMS influenced triggering in some individuals only. For saccades and convergence under TMS, some subjects showed an emerging population of short latencies in their latency distribution. Horizontal saccadic intrusions (80% of trials) and vertical saccades (recorded in one subject) intruding on vergence were unlikely to assist vergence triggering. We conclude that the prefrontal mechanisms underlying voluntary eye movement control are similar for saccades and vergence although some specificities exist.

Adult↗

PubMed1997

31P magnetic resonance spectroscopy in the dorsolateral prefrontal cortex of schizophrenics with a volume selective technique--preliminary findings.

Pettegrew et al (Arch Gen Psychiatry 48:563-568, 1991) were the first to determine abnormalities concerning phospholipids and high energy metabolites in the dorsolateral prefrontal cortex of drug-naive schizophrenics with 31P magnetic resonance spectroscopy (MRS). Other investigations could not replicate these findings. We included in our study 13 schizophrenic inpatients and 14 age-matched controls. Whereas Pettegrew et al found increased levels of phosphodiesters and decreased levels of phosphomonoesters we measured decreased levels of phosphodiesters in the schizophrenics as compared to controls. One possible explanation for the contradictory findings of the both trials might be the different localization techniques used.

Adult↗