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Results for “Dorsolateral Prefrontal Cortex”

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PubMed1999

Neural correlates of a decision in the dorsolateral prefrontal cortex of the macaque.

To make a visual discrimination, the brain must extract relevant information from the retina, represent appropriate variables in the visual cortex and read out this representation to decide which of two or more alternatives is more likely. We recorded from neurons in the dorsolateral prefrontal cortex (areas 8 and 46) of the rhesus monkey while it performed a motion discrimination task. The monkey indicated its judgment of direction by making appropriate eye movements. As the monkey viewed the motion stimulus, the neural response predicted the monkey's subsequent gaze shift, hence its judgment of direction. The response comprised a mixture of high-level oculomotor signals and weaker visual sensory signals that reflected the strength and direction of motion. This combination of sensory integration and motor planning could reflect the conversion of visual motion information into a categorical decision about direction and thus give insight into the neural computations behind a simple cognitive act.

Animals↗

PubMed2003

Neuropathological evidence for ischemia in the white matter of the dorsolateral prefrontal cortex in late-life depression.

BACKGROUND: Signal hyperintensities on magnetic resonance imaging in late-life depression are associated with treatment resistance and poor outcome. These lesions are probably vascular in origin and proposed sites for vascular damage include the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). METHODS: We therefore examined white matter in these areas for microvascular disease and evidence of ischemia using intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). We obtained postmortem tissue from elderly depressed (n = 20) and control (n = 20) subjects and blindly rated microvascular disease and ICAM-1 and VCAM-1 amount using quantitative image analysis in sections of the DLPFC, ACC and occipital cortex (OC; control area). RESULTS: We found a significant increase in ICAM-1 in the deep white matter of the DLPFC in the depressed group (p = 0.01) and a trend towards an increase for VCAM-1 (p = 0.10). In the gyral white matter there was a trend towards significance for both molecules (p = 0.07 and 0.10). No differences were found in the ACC or OC or for microvascular disease in any area. CONCLUSIONS: These findings are consistent with white matter ischemia in the DLPFC and lend support to the 'vascular depression' hypothesis. They implicate the DLPFC as an important site in the pathogenesis of late-life depression and have major implications for the understanding and management of late-life depression and raise the possibility of novel treatments being introduced in the future.

Aged↗

PubMed2005

Genetic polymorphisms of the RGS4 and dorsolateral prefrontal cortex morphometry among first episode schizophrenia patients.

Polymorphisms of the gene encoding the regulator of G-protein signaling subtype 4 (RGS4) may confer risk for schizophrenia.(1) DNA microarray studies of postmortem brain samples have shown RGS4 underexpression in the dorsolateral prefrontal cortex (DLPFC, area 9), motor and visual cortices in schizophrenia patients relative to control subjects.(2) Underexpression of RGS4 in DLPFC is pathophysiologically significant because DLPFC pathology in schizophrenia has been supported by neurocognitive,(3,4) structural(5) and functional(6,7) imaging, postmortem,(8) cellular(9,10) and molecular(11) pathological studies. For these reasons, we examined the association of DLPFC gray matter volume with RGS4 polymorphisms in a series of antipsychotic-naive first-episode schizophrenia patients and control subjects. We hypothesized that volumetric alterations of the DLPFC would be associated with RGS4 polymorphisms and that these differences would be more pronounced in patients than in controls. We observed robust volumetric differences across the genotypes in the pooled sample of patients and control subjects; when separately analyzed, we observed differences within the patient group (n = 30) but not in control subject (n = 27) group. The findings suggest that RGS4 polymorphisms may contribute to structural alterations in the DLPFC.

Adult↗

PubMed2004

Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia.

Genetic linkage and association have implicated neuregulin-1 (NRG-1) as a schizophrenia susceptibility gene. We measured mRNA expression levels of the three major isoforms of NRG-1 (ie type I, type II, and type III) in the postmortem dorsolateral prefrontal cortex (DLPFC) from matched patients and controls using real-time quantitative RT-PCR. Expression levels of three internal controls-GAPDH, cyclophilin, and beta-actin-were unchanged in schizophrenia, and there were no changes in the absolute levels of the NRG-1 isoforms. However, type I expression normalized by GAPDH levels was significantly increased in schizophrenia DLPFC (by 23%) and positively correlated with antipsychotic medication dosage. Type II/type I and type II/type III ratios were significantly decreased (18 and 23% respectively). There was no effect on the NRG-1 mRNA levels of genotype at two SNPs previously associated with schizophrenia, suggesting that these alleles are not functionally responsible for abnormal NRG-1 expression patterns in patients. Subtle abnormalities in the expression patterns of NRG-1 mRNA isoforms in DLPFC may be associated with schizophrenia.

Autopsy↗

PubMed2002

The role of the dorsolateral prefrontal cortex: evidence from the effects of contextual constraint in a sentence completion task.

Although the prefrontal cortices, in particular the dorsolateral prefrontal cortex (DLPFC), have been examined in numerous imaging and neuropsychological studies, it has proved difficult to assign a specific function to this brain region. The aim of this study was therefore to delineate the function of the DLPFC first by using positron emission tomography with a word generation task and second by comparing these findings with a series of different circumstances in which the DLPFC is activated in association with response selection. Six healthy volunteers were presented with a sentence completion task based on the Hayling test. In each of two conditions, (A) response initiation and (B) response suppression, volunteers saw a sentence with the final word omitted. In condition A they had to provide a word that fitted at the end of the sentence and in condition B they had to provide a word that did not fit. The corpus of sentences used varied systematically in their level of contextual constraint, ranging from low to high. With all levels of constraint combined, significant greater activation was observed in the left DLPFC (BA46/9) under the suppression condition and in the medial orbitofrontal cortex (BA11) under the initiation condition. Under the high-constraint condition with both tasks combined, significant right middle temporal activity (BA21) was observed, whereas under low constraint, the left DLPFC was significantly activated. An interaction of task and constraint revealed that the left DLPFC was significantly more active in the suppression task at all levels of constraint, but only under the low-constraint conditions in the initiation task. The reaction time analyses mirrored the pattern of activity observed, with slower reaction times under conditions of suppression and under conditions of initiation with low constraint. By comparing these findings with other studies of response selection, we argue that the most likely single cognitive function of the DLPFC is to specify a set of responses suitable for a given task and to bias these for selection (sculpting the response space). This function resembles the biasing of competition between stimuli in the model of Desimone and Duncan and is analogous to the component of the Supervisory Attentional System that modulates the contention scheduling system.

Adult↗

PubMed2003

Event-related FMRI study of context processing in dorsolateral prefrontal cortex of patients with schizophrenia.

Context processing is conceptualized as an executive function involved in voluntary, complex actions such as overcoming automatic responses. The present study tested the hypothesis that context-processing deficits in patients with schizophrenia are associated with a dysfunction of left dorsolateral prefrontal cortex (DLPFC). Using event-related functional magnetic resonance imaging (fMRI), 17 controls and 17 medicated patients performed a version of the AX task in which a learned, automatic response had to be inhibited. In controls, left DLPFC activity increased when preparing to overcome an automatic response, whereas patients with schizophrenia showed no differential activation. In controls, context processing appeared to be associated with the differential representation of cues associated with the need to provide top-down support for overcoming automatic responses. This mechanism appeared to be impaired in patients with schizophrenia.

Adult↗

PubMed1983

Cholinergic role in monkey dorsolateral prefrontal cortex during bar-press feeding behavior.

Cholinergic involvement in the neuronal activity of the dorsolateral (DL) prefrontal cortex in the monkey was investigated during bar-press feeding behavior. Iontophoretic application of ACh increased the firing rate of more than half of the cells through muscarinic receptors. Activity of ACh-sensitive cells did not correlate with any particular event during the feeding task. Continuous application of ACh markedly enhanced increases in response to events during the feeding task, and application of an ACh antagonist diminished response levels. This indicates that ACh release may occur during the feeding task and affect cortical cells to improve the signal-to-noise ratio of the excitatory input. Decreased responses to events during the feeding task diminished during ACh application. Driven discharges in the cells were evoked by stimulation of the basal nucleus of Meynert (BNM) where ACh containing cells are localized. This response was specifically blocked by iontophoretic application of atropine. In conclusion, cholinergic inputs arising from the BNM are distributed profusely among the cortical cells and modulate their excitability during bar-press feeding behavior.

Acetylcholine↗

PubMed2005

Activation in dorsolateral prefrontal cortex in response to maternal criticism and praise in recovered depressed and healthy control participants.

BACKGROUND: High family levels of expressed emotion reliably predict relapse in patients with schizophrenia and mood disorders; however, the neural mechanisms linking expressed emotion and relapse are unexplored. Dysfunctional activity in the dorsolateral prefrontal cortex (DLPFC) has been implicated in the pathophysiology of depression. Functional magnetic resonance imaging (fMRI) was used to assess focal activation changes in DLPFC in response to a novel psychosocial challenge stimulus developed from the expressed emotion construct. METHODS: Healthy control subjects and fully remitted unipolar depressed participants completed blood oxygen level-dependent fMRI while they heard their own mothers making critical and praising comments about them. RESULTS: Relative to control subjects, participants with a history of depression failed to activate DLPFC when they heard critical remarks. There were no differences between the two groups in their DLPFC responses to maternal praise. CONCLUSIONS: Even if fully well at the time of testing, participants with a known vulnerability to depression respond differently to the psychosocial challenge of being criticized. These findings might have implications for our understanding of vulnerability to depression and to depressive relapse.

Acoustic Stimulation↗

PubMed2005

Dorsolateral prefrontal cortex morphology and short-term outcome in first-episode schizophrenia.

Several clinical predictors of outcome in schizophrenia have been described; however, very few studies have examined neurobiological factors that predict outcome. The objective of this study was to examine the value of the morphology of the dorsolateral prefrontal cortex (DLPFC) determined by magnetic resonance imaging (MRI) as a predictor of short-term functional outcome in antipsychotic-naive patients with first-episode schizophrenia or schizoaffective disorder. Twenty-seven consecutive patients with first-episode schizophrenia or schizoaffective disorder underwent structural MRI at baseline. Functional outcome - a composite measure of social and employment subscales of the Strauss-Carpenter Scale - was assessed at 1 and 2 years. Volume of the left DLPFC at baseline predicted functional outcome in schizophrenia at 1 but not at 2 years. Specific cognitive functions regulated by the left DLPFC may be critical for functional outcome.

Adult↗

PubMed2005

A proton magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in acute mania.

BACKGROUND: Several neurochemical abnormalities have been reported in bipolar disorder (BD), but the exact mechanisms that underlie its pathophysiology remain to be elucidated. Proton magnetic resonance spectroscopy (1HMRS) allows in vivo measurements of certain neurometabolites in the human brain. 1HMRS was used to investigate the dorsolateral prefrontal cortex (DLPFC) in bipolar subjects during a manic or mixed phase. N-acetyl-L-aspartate (NAA), choline-containing molecules (Cho), creatine plus phosphocreatine (Cr) and myoinositol (Ino) were measured. METHOD: Ten bipolar patients (nine manic, one mixed), diagnosed by a semi-structured clinical interview (SCID), and ten age- and gender-matched healthy volunteers were studied. Absolute neurometabolites levels were measured from two 8 cm3 voxels placed in left and right DLPFC using a short TE 1HMRS method at 1.5 T. T1- and T2-weighted anatomical magnetic resonance imaging was performed to exclude any neuroanatomical abnormality. RESULTS: No significant differences were found for NAA, Cho, Cr, Ino, NAA/Cr, Cho/Cr or Ino/Cr between patients and controls. Manic/mixed patients had significantly higher left-to-right myoinositol ratios in DLPFC (p = 0.044). CONCLUSIONS: Increased left-to-right myoinositol ratios in the DLPFC in bipolar patients during acute mania may represent a dysfunction in the phosphoinositide-signaling pathway. Longitudinal studies with larger samples of unmedicated patients assessing pre- and post-treatment times will be required for further clarification of the time course of these abnormalities and the relationship with treatment effects.

Acute Disease↗

PubMed1998

The effects of transcranial magnetic stimulation over the dorsolateral prefrontal cortex on suppression of habitual counting during random number generation.

Random number generation is an attention-demanding task that engages working memory and executive processes. Random number generation requires holding information 'on line', suppression of habitual counting, internally driven response generation and monitoring of responses. Evidence from PET studies suggests that the dorsolateral prefrontal cortex (DLPFC) is involved in the generation of random responses. We examined the effects of short trains of transcranial magnetic stimulation (TMS) over the left or right DLPFC or medial frontal cortex on random number generation in healthy normal participants. As in previous evidence, in control trials without stimulation participants performed poorly on the random number generation task, showing repetition avoidance and a tendency to count. Brief disruption of processing with TMS over the left DLPFC changed the balance of the individuals' counting bias, increasing the most habitual counting in ones and reducing the lower probability response of counting in twos. This differential effect of TMS over the left DLPFC on the balance of the subject's counting bias was not obtained with TMS over the right DLPFC or the medial frontal cortex. The results suggest that, with disruption of the left DLPFC with TMS, habitual counting in ones that has previously been suppressed is released from inhibition. From these findings a network modulation model of random number generation is proposed, whereby suppression of habitual responses is achieved through the modulatory influence of the left DLPFC over a number-associative network in the superior temporal cortex. To allow emergence of appropriate random responses, the left DLPFC inhibits the superior temporal cortex to prevent spreading activation and habitual counting in ones.

Adult↗

PubMed2004

Reduced GSK-3beta mRNA levels in postmortem dorsolateral prefrontal cortex of schizophrenic patients.

Glycogen Synthase Kinase (GSK)-3 is a ubiquitous serine/threonine protein kinase highly abundant in brain which plays a key role in neural development and neuron survival. We have previously reported that GSK-3beta protein levels and GSK-3 activity are reduced by over 40% in postmortem prefrontal cortex of schizophrenic patients compared to patients with bipolar illness, unipolar depression and to normal controls, and Emamian et al. have recently presented convergent evidence for impaired AKT1-GSK-3beta signaling in schizophrenia. Using specimens of dorsolateral prefrontal cortex tissue obtained from The Stanley Medical Research Institute's Brain Collection, from the same subjects used previously, we now show that GSK-3beta, but not GSK-3alpha, mRNA levels are 36% lower in the patients with schizophrenia compared to all other comparison groups. The present study lends further support to the finding of low GSK-3beta levels in schizophrenia and extends this observation by suggesting that the decrease in GSK-3beta may be due to reduced protein synthesis possibly due to altered transcriptional drive of the GSK-3beta gene.

Adult↗

PubMed2004

Taste-related activity in the human dorsolateral prefrontal cortex.

Taste remains one of the least-explored human senses. Cortical taste responses were investigated using neuroimaging in 40 subjects tasting a range of different taste stimuli compared to a neutral tasteless control. Activation was found in the anterior insula/frontal opercular taste cortex and caudal orbitofrontal cortex, both areas established as taste cortical areas by neuronal recordings in primates. A novel finding in this study was a highly significant response to taste in the dorsolateral prefrontal cortex. This may reflect an effect of taste on cognitive processing to help optimise or modify behavioural strategies involved in executive control; or it could reflect the engagement of this region in attentional processing by a taste input.

Adult↗

PubMed2004

Dorsolateral prefrontal cortex involvement in memory post-retrieval monitoring revealed in both item and associative recognition tests.

Post-retrieval monitoring is a process that contributes to episodic memory retrieval by allowing people to evaluate the relevance of retrieved information in relation to the task requirements. Previous studies have suggested that post-retrieval monitoring is supported by the dorsolateral prefrontal cortex (DLPFC). In this study, we used functional magnetic resonance imaging (fMRI) to evaluate involvement of the DLPFC in post-retrieval monitoring in two different recognition tests (item recognition and associative recognition). The item recognition memory test required subjects to make old/new judgments and the associative recognition memory test required them to make intact/rearranged judgments. Because the post-retrieval monitoring demand increases during old (hits) relative to new (correct rejections) item recognition trials, and also during rearranged (correct rejections) relative to intact (hits) associative recognition trials, we evaluated the brain activation associated with the interaction of Memory test (item versus associative) by Recognition trial (hit versus correct rejection). As expected, the DLPFC was activated in this interaction as well as for both old relative to new item recognition trials and rearranged relative to intact associative recognition trials. This study provides strong evidence that DLPFC activation supports post-retrieval monitoring across different types of recognition tasks.

Adult↗

PubMed2003

Localized functional neurochemical marker abnormalities in dorsolateral prefrontal cortex in pediatric obsessive-compulsive disorder.

BACKGROUND: Neurobiological abnormalities in the prefrontal cortex have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Although OCD commonly arises during childhood and adolescence, to our knowledge, no prior study has examined prefrontal cortex neurochemistry in pediatric patients with OCD. METHODS: A multislice spectroscopic imaging sequence with validated phantom replacement methodology was used to measure N-acetyl-aspartate (NAA), a putative neuronal marker; choline compounds (Cho); and creatine/phosphocreatine (Cr) in right and left dorsolateral prefrontal cortex (DLPFC) of 15 treatment-naïve OCD patients, 8-15 years of age, and 15 case-matched healthy comparison subjects. RESULTS: A significant increase (21% higher) in NAA was observed in left but not right DLPFC in OCD patients versus control subjects. No significant differences in Cho or Cr were observed between groups in left or right DLPFC. CONCLUSIONS: These results provide new evidence of localized functional neurochemical marker alterations in left DLPFC in pediatric OCD. Increased left DLPFC NAA may represent neuronal hypertrophy or hyperplasia, glial hypoplasia, and/or abnormal pruning of neural brain elements in DLPFC.

Adolescent↗

PubMed1994

Delayed-response deficit induced by local injection of the alpha 2-adrenergic antagonist yohimbine into the dorsolateral prefrontal cortex in young adult monkeys.

Two young adult monkeys (Macaca mullata) were trained to perform a delayed-response task that required the monkeys to remember a cued spatial position (left or right) over a delay interval and then to make a response to the cued position. Local injection of the alpha 2-adrenergic antagonist yohimbine (10 micrograms in 2 microliters saline) into the dorsolateral prefrontal cortex (Walker's area 46 and area 9) impaired the performance of the delayed-response task, and it was without effect on the performance of the task if there was no delay between the cue and choice signals. The main performing error after injection of yohimbine was that the monkeys responded to uncued position with higher rate. Local injection of the alpha 1-adrenergic antagonist prazosin (10 microgram in 2 microliters saline) or the beta-adrenergic antagonist propranolol (10 micrograms in 2 microliters saline) into the same cortical areas induced no significant effect on the performance of the task. The present study suggests that prefrontal alpha 2-adrenoceptors play an important role in the spatial working memory in young adult monkeys.

Animals↗

PubMed2000

The role of the dorsolateral prefrontal cortex in random number generation: a study with positron emission tomography.

Random number generation (RNG) engages a number of executive processes. We used positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in six volunteers who performed RNG and a control counting (COUNT) task at six rates paced by a tone. This provided a systematic variation of difficulty of RNG. Relative to COUNT, RNG was associated with significant activation of the left dorsolateral prefrontal cortex (DLPFC), the anterior cingulate, the superior parietal cortex bilaterally, the right inferior frontal cortex, and the left and right cerebellar hemispheres. Faster rates of RNG were associated with a significant decrease in regional cerebral blood flow (rCBF) in the left and right DLPFC and the right superior parietal cortex. rCBF in the left DLPFC was significantly and negatively associated with count score 1, a measure of habitual counting during RNG. These results are discussed in relation to the network modulation model of RNG developed on the basis of our previous studies using transcranial magnetic stimulation and dual task paradigms. This suggests that during RNG, suppression of habitual counting is achieved through the modulatory (inhibitory) influence of the left DLPFC over a number associative network distributed in the superior temporal cortex. At faster rates of RNG the synchronization demands of paced RNG result in the breakdown of this modulatory influence, which is evident from decreased rCBF in the left DLPFC and increased habitual counting at faster rates.

Adult↗

PubMed2003

Interstitial cells of the white matter in the dorsolateral prefrontal cortex in deficit and nondeficit schizophrenia.

An increased density of neurons in the white matter of the neocortex has been found in schizophrenia, and the original reports suggested this abnormality was restricted to a subgroup of patients. In a study of the inferior parietal cortex, we found that deficit schizophrenia subjects, but not nondeficit subjects, had an increased density of ICWMs. We extended that finding by comparing the density of microtubule-associated protein 2-immunoreactive ICWMs in deficit schizophrenia (N = 3), nondeficit schizophrenia (N = 4), and control (N = 5) subjects, using postmortem tissue from the dorsolateral prefrontal cortex (Brodmann area 46). The deficit group differed significantly from the other two groups; the respective mean (SD) density values for the deficit, nondeficit, and control groups were 1.27 (.10),.53 (.39), and.76 (.20) cells per 10-6 cubic microns. These group differences provide further evidence that deficit and nondeficit schizophrenia differ in their pathophysiology.

Adult↗