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Results for “Dorsolateral Prefrontal Cortex”

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PubMed2001

Wisconsin Card Sorting revisited: distinct neural circuits participating in different stages of the task identified by event-related functional magnetic resonance imaging.

The Wisconsin Card Sorting Task (WCST) has been used to assess dysfunction of the prefrontal cortex and basal ganglia. Previous brain imaging studies have focused on identifying activity related to the set-shifting requirement of the WCST. The present study used event-related functional magnetic resonance imaging (fMRI) to study the pattern of activation during four distinct stages in the performance of this task. Eleven subjects were scanned while performing the WCST and a control task involving matching two identical cards. The results demonstrated specific involvement of different prefrontal areas during different stages of task performance. The mid-dorsolateral prefrontal cortex (area 9/46) increased activity while subjects received either positive or negative feedback, that is at the point when the current information must be related to earlier events stored in working memory. This is consistent with the proposed role of the mid-dorsolateral prefrontal cortex in the monitoring of events in working memory. By contrast, a cortical basal ganglia loop involving the mid-ventrolateral prefrontal cortex (area 47/12), caudate nucleus, and mediodorsal thalamus increased activity specifically during the reception of negative feedback, which signals the need for a mental shift to a new response set. The posterior prefrontal cortex response was less specific; increases in activity occurred during both the reception of feedback and the response period, indicating a role in the association of specific actions to stimuli. The putamen exhibited increased activity while matching after negative feedback but not while matching after positive feedback, implying greater involvement during novel than routine actions.

Adolescent↗

PubMed1993

A test-retest study of cerebral blood flow during somatosensory stimulation in depressed patients with schizophrenia and major depression.

Six depressed patients with schizophrenia and 6 depressed patients with major depression were investigated before and during somatosensory stimulation (SS) with Tc-99m HMPAO SPECT. 8 controls were investigated only under resting conditions. The results can be summarized as follows: 1. Both psychiatric patient groups were hypofrontal (dorsolateral prefrontal cortex) compared to controls. 2. Hypofrontality was further enhanced by SS, significantly only in affective psychoses in the right inferior frontal lobe and in the right frontal hemisphere in total, in schizophrenia in the left dorsolateral prefrontal cortex. 3. Within the frontal lobes different regions were affected by SS in the two diagnostic groups. 4. In the right inferior parietal lobe SS response was significantly different in the two illnesses with schizophrenia showing a relative decrease, affective psychoses showing a relative increase of activity. 5. SS produced an increase of cerebral blood flow in subcortical regions (statistically significant contralateral to SS in thalamus and basal ganglia, ipsilateral to SS in cerebellum), a pattern which was common to all psychiatric patients. 6. Somatosensory cortex flow was not changed by SS. In conclusion, we could not fully confirm our hypotheses that similar blood flow abnormalities in different illnesses during SS are only caused by similarities in depressive psychopathology. Instead, depressed patients with schizophrenia were different from depressed patients with major depression in showing decreased activity in interrelating brain regions participating in an attentional network.

Adult↗

PubMed2002

Ischemic basis for deep white matter hyperintensities in major depression: a neuropathological study.

BACKGROUND: White matter hyperintensities on magnetic resonance imaging are increased in major depression in the deep white matter, especially in frontal areas. These lesions have been hypothesized to be ischemic in origin, but there have been no previous neuropathological studies in depression. We investigated the neuropathological basis of these lesions in depression, hypothesizing that they would be more frequently ischemic in origin in depressed subjects. METHODS: We carried out in vitro magnetic resonance imaging on 3 slices of brain tissue (2 frontal, 1 occipital) from 20 elderly subjects who had a history of major depression and 20 elderly controls. The films were blindly rated, and sections were prepared for neuropathological analysis from the same slices and stained conventionally and by means of immunohistochemistry for microglia, macrophages, and astroglia. Lesions on the films were identified in the tissue, blindly described neuropathologically, and subsequently divided into ischemic and nonischemic lesions. RESULTS: All the deep white matter hyperintensities in the depressed group were found to be ischemic, compared with less than a third of those in the control group, a highly significant difference (P<.001). This difference was due to smaller punctate lesions (<3 mm), which were predominantly ischemic in depressed subjects but not in control subjects. Larger lesions were usually ischemic in both groups. Compared with control subjects, ischemic lesions were significantly more likely to be in the dorsolateral prefrontal cortex compared with the anterior cingulate cortex (P =.003) and the occipital cortex (P =.01) in the depressed subjects. CONCLUSIONS: Deep white matter hyperintensities are more frequently due to cerebral ischemia, and such ischemic lesions are more frequently located at the level of dorsolateral prefrontal cortex in depressed subjects. Our findings strongly support the "vascular depression" hypothesis of late-life depression.

Age Factors↗

PubMed2004

Eye movement control by the cerebral cortex.

PURPOSE OF REVIEW: This review focuses on eye movement control by the cerebral cortex, mainly in humans. Data have emerged based on the important contribution of recent techniques such as transcranial magnetic stimulation and functional magnetic resonance imaging, which provide complementary results to those of the classical lesion and electrical stimulation studies. RECENT FINDINGS: The location of the human frontal eye field and its role in pursuit eye movement control were recently detailed. Cumulative evidence for the role of the dorsolateral prefrontal cortex in unwanted reflexive saccade inhibition, short-term spatial memory and prediction suggests that this area controls decisional processes governing ocular motor behaviour. The organization of spatial memory in the dorsolateral prefrontal cortex (short-term), the parahippocampal cortex (medium-term) and the hippocampal formation (long-term) is also reviewed with the results of recent transcranial magnetic stimulation studies. The relatively complicated anatomy of the posterior parietal cortex in humans is briefly described followed by some additional results concerning the location of the parietal eye field - within the posterior half of the intraparietal sulcus - and its role in visuo-spatial integration and attention. The other areas involved in spatial attention are also examined in the light of several recent contributing reports. Lastly, there are also new functional magnetic resonance imaging findings concerning the posterior cingulate cortex, which appears to be mainly involved in the control of externally guided eye movements and attentional mechanisms. SUMMARY: Many new findings on the organization of saccades and pursuit eye movements at the cortical level have recently been reported. Furthermore, eye movements are increasingly used as a tool to elucidate relatively complex neuropsychological processes such as attention, spatial memory, motivation and decisional processes, and a considerable number of reports dealing with these questions have been observed.

Animals↗

PubMed2005

The prefrontal substrate of reflexive saccade inhibition in humans.

BACKGROUND: Prefrontal dysfunction in neuropsychiatric disorders such as schizophrenia has been shown to impair inhibition of reflexive saccadic eye movements; however, it is unclear whether reflexive saccade inhibition can be attributed to a distinct subregion of the human prefrontal cortex. METHODS: We tested 15 patients with acute unilateral ischemic lesions of the prefrontal cortex and 20 control subjects with an antisaccade task. Lesions were reconstructed using Talairach coordinates, and possible candidate regions for reflexive saccade inhibition were identified. RESULTS: Significantly increased antisaccade error rates were observed in patients with lesions affecting a region in mid-dorsolateral prefrontal cortex or the white matter between this region and the anterior portions of the internal capsule. Antisaccade error rates of patients with lesions outside this region were normal. These findings were largely independent of lesion volume, postlesion delay, and subject age. CONCLUSIONS: Our findings suggest that inhibition of reflexive saccades depends on a circumscribed subregion of the human dorsolateral prefrontal cortex. This region closely corresponds to Brodmann area 46 as defined by recent cytoarchitectonic studies. Increased antisaccade error rates in patients with prefrontal pathology may be explained by dysfunction of this region.

Aging↗

PubMed2000

Cortical motor reorganization in akinetic patients with Parkinson's disease: a functional MRI study.

Using functional MRI (fMRI), we have studied the changes induced by the performance of a complex sequential motor task in the cortical areas of six akinetic patients with Parkinson's disease and six normal subjects. Compared with the normal subjects, the patients with Parkinson's disease exhibited a relatively decreased fMRI signal in the rostral part of the supplementary motor area (SMA) and in the right dorsolateral prefrontal cortex, as previously shown in PET studies. Concomitantly, the same patients exhibited a significant bilateral relative increase in fMRI signal in the primary sensorimotor cortex, lateral premotor cortex, inferior parietal cortex, caudal part of the SMA and anterior cingulate cortex. These fMRI data confirm that the frontal hypoactivation observed in patients with Parkinson's disease is restricted to the rostral part of the SMA and to the dorsolateral prefrontal cortex. These results also show that, apart from the lateral premotor and parietal cortices, increased fMRI signals can be found in other cortical motor areas of these patients, including the posterior SMA, the anterior cingulate cortex and the primary sensorimotor cortices, which are then likely to participate in the same putative attempt by the dopamine-denervated brain to recruit parallel motor circuits in order to overcome the functional deficit of the striatocortical motor loops.

Aged↗

PubMed2003

Altered cortical glutamate neurotransmission in schizophrenia: evidence from morphological studies of pyramidal neurons.

Multiple lines of evidence from pharmacological, neuroimaging, and postmortem studies implicate disturbances in cortical glutamate neurotransmission in the pathophysiology of schizophrenia. Given that pyramidal neurons are the principal source of cortical glutamate neurotransmission, as well as the targets of the majority of cortical glutamate-containing axon terminals, understanding the nature of altered glutamate neurotransmission in schizophrenia requires an appreciation of both the types of pyramidal cell abnormalities and the specific class(es) of pyramidal cells that are affected in the illness. In this chapter, we review evidence indicating that a subpopulation of pyramidal neurons in the dorsolateral prefrontal cortex exhibits reductions in dendritic spine density, a marker of the number of excitatory inputs, and in somal volume, a measure correlated with a neuron's dendritic and axonal architecture. Specifically, pyramidal neurons located in deep layer 3 of the dorsolateral prefrontal cortex and that lack immunoreactivity for nonphosphorylated neurofilament protein may be particularly involved in the pathophysiology of schizophrenia. The presence of similar changes in pyramidal neurons located in deep layer 3 of auditory association cortex suggests that a shared property, which remains to be determined, confers cell type-specific vulnerability to a subpopulation of cortical glutamatergic neurons in schizophrenia.

Glutamates↗

PubMed2004

When planning fails: individual differences and error-related brain activity in problem solving.

The neuronal processes underlying correct and erroneous problem solving were studied in strong and weak problem-solvers using functional magnetic resonance imaging (fMRI). During planning, the right dorsolateral prefrontal cortex was activated, and showed a linear relationship with the participants' performance level. A similar pattern emerged in right inferior parietal regions for all trials, and in anterior cingulate cortex for erroneously solved trials only. In the performance phase, when the pre-planned moves had to be executed by means of an fMRI-compatible computer mouse, the right dorsolateral prefrontal cortex was again activated jointly with right parahippocampal cortex, and displayed a similar positive relationship with the participants' performance level. Incorrectly solved problems elicited stronger bilateral prefrontal and left inferior parietal activations than correctly solved trials. For both individual ability and trial-specific performance, our results thus demonstrate the crucial involvement of right prefrontal cortex in efficient visuospatial planning.

Adult↗

PubMed2000

Functional brain imaging of tinnitus-like perception induced by aversive auditory stimuli.

Tinnitus is an aversive auditory percept of unknown origin. We tested the speculation that tinnitus may share neuronal processing mechanisms with aversive auditory percepts of known origin. This study revealed the functional neuroanatomy of the perception of aversive auditory stimuli. The stimuli were presented to 12 healthy volunteers so as to mimic the psychoacoustical features of tinnitus and its affective response in tinnitus sufferers. The regional cerebral blood flow distribution was measured by PET during four auditory processing conditions and one control condition. The aversive auditory stimuli activated primary and secondary auditory areas bilaterally, dorsolateral prefrontal attention areas, and structures in the limbic system which subserve emotional processing. Based on these results and findings from other functional neuroimages of tinnitus, we hypothesize that the perception of tinnitus may involve the functional linkage of these brain areas: secondary auditory cortex, dorsolateral prefrontal cortex, and limbic system.

Acoustic Stimulation↗

PubMed2002

Emotion and cognition: feeling and character identification in dreaming.

This study investigated the relationship between dream emotion and dream character identification. Thirty-five subjects provided 320 dream reports and answers to questions on characters that appeared in their dreams. We found that emotions are almost always evoked by our dream characters and that they are often used as a basis for identifying them. We found that affection and joy were commonly associated with known characters and were used to identify them even when these emotional attributes were inconsistent with those of the waking state. These findings are consistent with the finding that the dorsolateral prefrontal cortex, associated with short-term memory, is less active in the dreaming compared to the wake brain, while the paleocortical and subcortical limbic areas are more active. The findings are also consistent with the suggestion that these limbic areas have minimal input from the dorsolateral prefrontal cortex in the dreaming brain.

Adolescent↗

PubMed2004

Human dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain.

CONTEXT: The schizophrenia-susceptibility gene dysbindin (DTNBP1 on 6p22.3) encodes a neuronal protein that binds to beta-dystrobrevin and may be part of the dystrophin protein complex. Little is known about dysbindin expression in normal or schizophrenic brain. OBJECTIVES: To determine whether brain regions implicated in schizophrenia express dysbindin and whether abnormal levels of dysbindin messenger RNA (mRNA) may be found in this disorder and to test whether sequence variations in the dysbindin gene in the promoter region, 5' and 3' untranslated regions, or introns would affect dysbindin mRNA levels. METHODS: In patients with schizophrenia and controls, we compared dysbindin, synaptophysin, spinophilin, and cyclophilin mRNA levels in the dorsolateral prefrontal cortex and dysbindin mRNA levels in the midbrain by in situ hybridization. We genotyped brain DNA at 11 single nucleotide polymorphisms to determine whether genetic variation in the dysbindin gene affects cortical dysbindin mRNA levels. MAIN OUTCOME MEASURES: Quantitative assessment of dysbindin mRNA levels across various brain regions and comparative studies of dysbindin mRNA levels in brains of patients with schizophrenia compared with normal controls. RESULTS: Dysbindin mRNA was detected in the frontal cortex, temporal cortex, hippocampus, caudate, putamen, nucleus accumbens, amygdala, thalamus, and midbrain of the adult brain. Patients with schizophrenia had statistically significantly reduced dysbindin mRNA levels in multiple layers of the dorsolateral prefrontal cortex, whereas synaptophysin, spinophilin, and cyclophilin mRNA levels were unchanged. Dysbindin mRNA levels were quantitatively reduced in the midbrain of patients with schizophrenia, but not statistically significantly. Cortical dysbindin mRNA levels varied statistically significantly according to dysbindin genotype. CONCLUSIONS: Dysbindin mRNA is expressed widely in the brain, and its expression is reduced in schizophrenia. Variation in dysbindin mRNA levels may be determined in part by variation in the promoter and the 5' and 3' untranslated regions. These data add to the evidence that dysbindin is an etiologic factor in schizophrenia risk.

3' Untranslated Regions↗

PubMed2001

Lack of adverse cognitive effects of 1 Hz and 20 Hz repetitive transcranial magnetic stimulation at 100% of motor threshold over left prefrontal cortex in depression.

OBJECTIVE: The potential therapeutic effects of repetative transcranial magnetic stimulation (rTMS) are being examined in various neuropsychiatric illnesses. This study assesses the cognitive performance of depressed patients receiving high or low frequency rTMS for 10 days. METHODS: 18 depressed patients participated in a randomized double-blind cross-over study exploring the antidepressant effects of 2 weeks (10 daily) of sham, 1 Hz, or 20 Hz rTMS administered over the left dorsolateral prefrontal cortex at 100% of motor threshold (MT). A subgroup completed a battery of cognitive tests at baseline and following each 2-week phase of treatment, and differences in performance were assessed using paired t -tests and were correlated with the degree of clinical improvement using Hamilton Depression Rating Scale scores. RESULTS: There were no major changes in cognitive test scores as a result of 10 days of either 1 Hz or 20 Hz rTMS. Moreover, any minor attenuations in cognition were not related to the degree of clinical improvement. CONCLUSIONS: Cognitive functioning in many domains following 2 weeks of 1 Hz or 20 Hz rTMS at 100% MT over the left dorsolateral prefrontal cortex in depressed patients is not disrupted.

Adult↗

PubMed2006

Effects of a 14-day healthy longevity lifestyle program on cognition and brain function.

OBJECTIVE: The objective of this study was to determine the effects of a 14-day healthy longevity lifestyle program on cognition and cerebral metabolism in people with mild age-related memory complaints. METHODS: Seventeen nondemented subjects, aged 35-69 years (mean: 53 years, standard deviation: 10) with mild self-reported memory complaints but normal baseline memory performance scores were randomly assigned to 1) the intervention group (N = 8): a program combining a brain healthy diet plan, relaxation exercises, cardiovascular conditioning, and mental exercise (brain teasers and verbal memory training techniques); or 2) the control group (N = 9): usual lifestyle routine. Pre- and postintervention measures included self-assessments of memory ability, objective tests of cognitive performance, and determinations of regional cerebral metabolism during mental rest with [fluorine-18]fluorodeoxyglucose (FDG) positron emission tomography (PET). RESULTS: Subjects in the intervention group objectively demonstrated greater word fluency. Concomitantly, their FDG-PET scans identified a 5% decrease in activity in the left dorsolateral prefrontal cortex. The control group showed no significant change in any of the measures. CONCLUSIONS: A short-term healthy lifestyle program combining mental and physical exercise, stress reduction, and healthy diet was associated with significant effects on cognitive function and brain metabolism. Reduced resting activity in left dorsolateral prefrontal cortex may reflect greater cognitive efficiency of a brain region involved in working memory.

Adult↗

PubMed2000

Visualizing brain activation during planning: the tower of London test adapted for functional MR imaging.

BACKGROUND AND PURPOSE: Recent positron emission tomography and single-photon emission CT studies using the Tower of London test have shown that brain activation during planning activities primarily resides in the prefrontal cortex. In this study, we adapted the Tower of London test for functional MR imaging. METHODS: For use with functional MR imaging, a block design of the test was created, in which planning stages were contrasted with counting of colored balls. For nine healthy participants, multisection echo-planar functional MR imaging was performed to assess brain activation based on changes in blood oxygen level. Activation maps for individual participants and a group average map were created. RESULTS: In the group average map, activation in the dorsolateral prefrontal cortex, the anterior part of the cingulate cortex, the cuneus and precuneus, the supramarginal and angular gyrus in the parietal lobe, and the frontal opercular area of the insula was seen. These findings are in agreement with grouped data of previous positron emission tomography results. Functional MR imaging enabled us to investigate brain activation during planning activities with high spatial (and temporal) resolution in individual patients, showing that the dorsolateral prefrontal cortex was activated in all participants studied. CONCLUSION: Presented is a working functional MR imaging version of the planning task. The high sensitivity of functional MR imaging may allow the use of this test for patients with possible (pre)frontal disorders.

Adult↗

PubMed2004

Properties of delay-period neuronal activity in the primate prefrontal cortex during memory- and sensory-guided saccade tasks.

The dorsolateral prefrontal cortex (DLPFC) is involved in visuospatial short-term (or working) memory. Its cellular basis has been widely examined using the delayed-response paradigm in nonhuman primates. Sustained delay-period activity in DLPFC neurons with directional difference (i.e. directional delay-period activity) has been thought to represent visuospatial short-term (or working) memory. However, little is known about the activity of these neurons during a delay period when the sensory input remains. To address this issue, we examined neuronal activity in the DLPFC while macaque monkeys performed a memory-guided saccade (MGS) task and a delayed visually guided saccade (VGS) task. The MGS task required a memory-guided saccade for a remembered target location. The VGS task had the same temporal sequence as the MGS task, but the sensory stimulus remained during the delay period. We found that most of the DLPFC neurons with directional delay-period activity showed sustained activation during the 'delay' period in the VGS task only ('V-neurons', 49%), or in both tasks ('MV-neurons', 46%). Neurons showing directional delay-period activity in the MGS task only ('M-neurons') were only 5% of the DLPFC neurons with directional delay-period activity. These findings indicate that most DLPFC neurons that are active during the delay period are also active when the sensory stimulus remains, suggesting that DLPFC neurons driven by mnemonic information are also driven by sensory input. Such sustained representation of information should have potential utility in flexible cognitive controls of behaviour.

Action Potentials↗

PubMed1999

Mapping the network for planning: a correlational PET activation study with the Tower of London task.

We used the Tower of London task (TOL) and H(2)(15)O-PET to map the network of brain structures involved in planning. Six healthy right-handed subjects had 12 measurements of relative regional cerebral blood flow (rrCBF) during six conditions, each performed twice. There was one rest condition, and five sets of TOL problems at different complexity levels, performed on a touch-sensitive computer monitor with the right arm. Complexity was defined as the number of moves required to solve each problem. Activation was analysed in two ways: a category analysis comparing levels of rrCBF during rest and task was done to identify all structures involved in performance of the TOL; and a correlation analysis was carried out to delineate a subset of structures where the levels of rrCBF correlated with task complexity. Activated brain areas in which rrCBF increases did not correlate with complexity could be grouped into: (i) regions belonging to the dorsal stream of visual input processing, namely visual cortical areas 17, 18 and 19, and posterior parietal cortical areas 7 and 40; and (ii) regions involved in the execution and sequencing of arm movements (right cerebellum, left primary motor cortex and supplementary motor area). Brain regions where levels of rrCBF correlated with task complexity included lateral premotor cortex (area 6), rostral anterior cingulate cortex (areas 32 and 24), dorsolateral prefrontal cortex (areas 9 and 46) bilaterally, and right dorsal caudate nucleus. We propose that dorsolateral prefrontal, lateral premotor, anterior cingulate and caudate areas form a network for the planning of movement that interacts with brain areas primarily involved in visual processing and movement execution.

Aged↗

PubMed1996

Regionally specific pattern of neurochemical pathology in schizophrenia as assessed by multislice proton magnetic resonance spectroscopic imaging.

OBJECTIVE: Several single-voxel proton magnetic resonance spectroscopy (1H-MRS) studies of patients with schizophrenia have found evidence of reductions of N-acetyl-aspartate (NAA) concentrations in the temporal lobes. Multislice proton magnetic resonance spectroscopy imaging (1H-MRSI) permits simultaneous acquisition and mapping of NAA, choline-containing compounds (CHO), and creatine/phosphocreatine (CRE) signal intensities from multiple whole brain slices consisting of 1.4-ml single-volume elements. We have used 1H-MRSI to assess the regional specificity of previously reported changes of metabolite signal intensities in schizophrenia. Hippocampal volume was also measured to test the relationship between 1H-MRSI findings and tissue volume in this region. METHOD: Ratios of areas under the metabolite peaks of the proton spectra were determined (i.e., NAA/CRE, NAA/CHO, CHO/CRE) for multiple cortical and subcortical regions in 10 inpatients with schizophrenia. RESULTS: Patients showed significant reductions of NAA/CRE and NAA/CHO bilaterally in the hippocampal region and in the dorsolateral prefrontal cortex. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. No significant correlation was found between metabolite ratios in the hippocampal region and its volume. CONCLUSIONS: NAA-relative signal intensity reductions in schizophrenia appear to be remarkably localized, involving primarily the hippocampal region and the dorsolateral prefrontal cortex, two regions implicated prominently in the pathophysiology of this disorder.

Adult↗

PubMed1998

Clinicometabolic dissociation of cognitive functions and social behavior in frontal lobe lesions.

OBJECTIVE/BACKGROUND: Case studies suggest a dissociation between cognitive functions that have been impaired after damage to the dorsolateral prefrontal cortex and social skills disturbed when the ventromedial prefrontal areas are affected. Because this dissociation had not been confirmed in a clinical setting, clinicometabolic correlations were sought in 13 patients with various lesions of the prefrontal cortex. DESIGN/METHODS: The clinical assessment included extensive testing of executive functions and evaluation of behavioral abnormalities based on an informant questionnaire. Regional cerebral glucose metabolism (rCMRGlu) was measured with [l8F] fluorodeoxyglucose ([18F] FDG) and 31-slide high-resolution PET. RESULTS: Executive-function test performance was significantly correlated with rCMRGlu in the dorsolateral prefrontal cortex (Brodmann's areas 8, 9, 45, 46, and 47) and anterior cingulate cortex (Brodmann's areas 24 and 32). Behavioral scores were significantly correlated with rCMRGlu in the frontopolar (Brodmann's area 10) and orbitofrontal cortex (Brodmann's areas 11, 12, 13, and 14). CONCLUSION: These results show that impaired executive functions and serial skill deficits are associated with distinct metabolic patterns in patients with frontal lobe pathology. In agreement with activation studies in normal subjects, our data suggest the existence of a modular organization of the frontal cortex in humans, as previously reported in nonhuman primates.

Adult↗