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Results for “Dorsolateral Prefrontal Cortex”

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PubMed2000

Association analysis of GABAAbeta2 and gamma2 gene polymorphisms with event-related prefrontal activity in man.

Gamma-aminobutyric acid (GABA)A-receptors play a crucial role in the generation of electroencephalogram (EEG) oscillations and evoked potentials (ERPs). The present association study was designed to test whether EEG and ERPs are modulated by genetic variations of the human GABAA beta2 (GABRB2) and gamma2 (GABRG2) genes on chromosome 5q33. The genotypes of two nucleotide substitution polymorphisms of the GABRB2 and GABRG2 genes were assessed in 95 psychiatrically healthy subjects of German descent. Neurophysiological phenotyping was performed with four factorized EEG/ERP parameters: EEG activation, anterior and posterior EEG synchronization, and event-related activity (N100/ P200-complex). No genotypic association was found for the GABRB2 nucleotide exchange polymorphism with any electrophysiological parameter. A significant association was found between the genotype of the intronic GABRG2 G-->A nucleotide exchange and the event-related N100/P200 (ANOVA: F=3.81; df=2; P=0.026). A comparison of homozygous subjects carrying either the G/G or A/A genotype of the GABRG2 polymorphism consistently revealed an even stronger difference in the effect-size (ANOVA: F=11.13; df=1; P=0.002). Post hoc analysis of this association with current density analysis in three-dimensional neuroanatomic Talairach space-time showed a reduction in the event-related signal power after 120 ms in the right dorsolateral prefrontal cortex. Taking into account the risk of false-positive association findings attributable to multiple testing, our results encourage further replication studies to examine the phenotype-genotype relationship of GABRG2 gene variants and event-related prefrontal activity.

Adult↗

PubMed2002

Brain chemistry reflects dual states of pain and anxiety in chronic low back pain.

The neurobiology of the interaction between pain and anxiety is unknown. The present study examined interrelationships between: regional brain chemistry (as identified by in vivo proton magnetic resonance spectroscopy [(1)H-MRS] in dorsolateral prefrontal cortex [DLPFC], orbitofrontal cortex [OFC], cingulate and thalamus), pain (as measured by short form of the McGill Pain Questionnaire [SF-MPQ]), and anxiety (measured by the State-Trait Anxiety Inventory) in chronic low back pain (CLBP) patients, and contrasted to the relationship between brain chemistry and anxiety in sex and age-matched normal subjects. The results show that brain chemistry depends on a 3-way interaction of brain regions examined, subject groups (normal vs. CLBP), and anxiety levels (high vs. low). The concentration of N-Acetyl aspartate (the largest peak in (1)H-MRS) in OFC could distinguish between anxiety levels and between subject groups. Chemical-perceptual relationships were analyzed by calculating correlations between regional chemicals and perceptual measures of pain and anxiety. To isolate pain from anxiety, these maps were subdivided based on anxiety and, in the CLBP patients along anxiety-more-related vs. anxiety-less-related pain descriptors and along sensory vs. affective pain descriptors. There was a precise relationship between perception and brain chemistry. The chemical-perceptual network best related to pain in CLBP patients was comprised of the DLPFC and OFC; the chemical-anxiety network was best related to the OFC chemistry in normals and to all four regions studied in CLBP patients; and the cingulate was best related to the affective component of pain. We conclude that the chemical-perceptual mapping differentiates between closely related perceptual states of pain and anxiety in chronic pain and provides a brain regional-chemical-perceptual description of the long-term reorganization that occurs with chronic pain.

Adult↗

PubMed2003

Association between dorsolateral prefrontal N-acetyl aspartate and depression in chronic back pain: an in vivo proton magnetic resonance spectroscopy study.

Most studies of pain, including chronic pain, agree that depression and pain are interrelated, although the neurobiology of this relationship remains unknown. Neuroimaging studies suggest a specific role of the prefrontal brain regions in the mechanisms of mood disorders and chronic pain. The present study examines the interrelationships between regional brain N-Acetyl aspartate (NAA) levels (as identified by in vivo proton magnetic resonance spectroscopy in the right and left dorsolateral prefrontal cortex [DLPFC], orbitofrontal cortex, cingulate and thalamus), depression (as measured by the Beck Depression Inventory), and pain (as measured by short form of the McGill Pain Questionnaire) in 10 chronic back pain (CBP) patients with depression, and compared to the relationship between regional brain NAA levels and depression in 10 normal subjects (sex and age-matched). Reduction of NAA levels was demonstrated in the right DLPFC of CBP patients with depression, as compared to the normal controls (p < 0.02, two-tailed t-test). The depression levels in CBP patients were highly correlated with NAA levels in the right DLPFC (r = -0.99, p < 0.0001), and were unrelated to the other studied regional NAA in both groups, including the right DLPFC in normal subjects (p < 10(-6); comparing the difference between r values in the right DLPFC between the two groups). The pain levels in CBP patients were also associated with the right DLPFC (r = -0.62, p < 0.05), although these relationships were much weaker as compared to depression-NAA correlations (p < 0.0001; comparing the difference between r values). The interrelationships between NAA across brain regions were examined using correlation analysis, which detected different connectivity patterns between CBP patients with depression and normal subjects. These findings provide evidence for a stronger association of prefrontal NAA to depression than to pain in CBP, which may reflect the common neurobiological substrate underlying these conditions in CBP patients. Spectroscopic brain mapping of NAA, the marker of neuronal density and function, to the depression and pain measures might be used for segregation of their circuitries in the chronic pain brain.

Adult↗

PubMed2003

Extrastriatal dopamine D(2) receptors in Parkinson's disease: a longitudinal study.

Most antiparkinsonian drugs are known to act through central dopamine D(2) receptor agonism. A previous longitudinal positron emission tomography (PET) study has indicated that, in the striatum of Parkinson's disease (PD) patients, dopamine D(2) receptor binding declines at a relatively fast annual rate of 2-4% (compared to the rate of <1%/year in healthy individuals). In the present study, the examination of longitudinal changes in D(2) receptors was extended to extrastriatal brain regions in PD. Eight early PD patients were examined twice with PET, approximately 3 years apart, using a high-affinity extrastriatal D(2)/D(3) receptor tracer, [(11)C]FLB 457. Both the MRI-referenced region-of-interest method and the voxel-based statistical analysis method were used independently in the analysis. Regional D(2)-like availabilities (binding potentials) in the left dorsolateral prefrontal cortex, the left temporal cortex and the left and right medial thalami were significantly decreased at the second examination by 20-37% (corresponding to an annual decline of 6-11%). Thus, the annual loss of extrastriatal D(2) availability in PD is up to three times faster than the rate previously reported in the putamen. Our longitudinal study shows first evidence concerning cortical D(2) receptor loss in the progression of PD, although it is not possible to distinguish between the effects of the therapy and the disease.

Aged↗

PubMed2004

Changes in negative symptoms and EEG in schizophrenic patients after repetitive transcranial magnetic stimulation (rTMS): an open-label pilot study.

The effects of repetitive transcranial magnetic stimulation (rTMS) on schizophrenic negative symptoms (NS) and EEG topography were investigated in this pilot study. 10 patients with predominant NS were treated with 10 Hz rTMS over the left dorsolateral prefrontal cortex for 5 days. For NS ratings, the Scale for the Assessment of Negative Symptoms (SANS) was used. Both ratings and EEG recordings were obtained pre- and post-rTMS. Electrical activity changes were computed by Low Resolution Brain Electromagnetic Tomography. SANS showed an improvement after rTMS, from 49.0 (SD: 10.7) to 44.7 (SD: 11.8) (means). EEG frequency bands were changed fronto-temporally (right) and were mainly decreases in delta- and beta- and increases in alpha1-activity, as well as decreases in beta-activity in the temporal and parieto-occipital regions (left). Although we are aware of the limitations of this study, we assume a slight improvement in NS. The EEG findings refer to a possible neurophysiologic correlate of their improvement after rTMS.

Adult↗

PubMed2003

Executive dyscontrol in normal aging: normative data, factor structure, and clinical correlates.

Although there is ample evidence of frontal system dysfunction in old age, the clinical significance of these impairments has not been well studied. In this article, we examine the factor structure of putative executive measures in a sample of well elderly subjects. Three stable factors emerged, but only one was associated with measures of functional status. This factor was most strongly associated with relatively simple bedside executive measures that might prove useful in dementia screening. In contrast, a second factor, dominated by the Wisconsin Card Sorting Task, was weakly associated with disability. These data suggest that certain executive measures may be more relevant to functional outcomes, and hence dementia case finding, than others. Moreover, associations with functional status should not be casually extrapolated from regional frontal clinical correlations, particularly with the dorsolateral prefrontal cortex.

Aged↗

PubMed1994

Relationship of prefrontal and temporal lobe MRI measures to neuropsychological performance in chronic schizophrenia.

This preliminary study focused on the relationship between prefrontal and temporal lobe MRI measures and neuropsychological performance in chronic schizophrenia. Seventeen schizophrenic inpatients received an MRI and a neuropsychological test battery after clinical stabilization, on average 2 months after admission. The central finding was a significant inverse correlation between neurocognitive measures of prefrontal function and dorsolateral prefrontal cortex (DLPFC) area, strongest in the left hemisphere. Neurocognitive performance did not correlate significantly with orbital frontal area or total temporal lobe volume. The correlations of neuropsychological performance with total frontal volume and whole brain volume were generally not significant, although the pattern was similar to that associated with the DLPFC. Because a number of executive-attention and abstraction measures were significantly associated with the DLPFC, dysfunctions of this region may underlie a syndrome of cognitive dysfunctions. Long-term memory functions were also significantly correlated with the DLPFC, raising the possibility that recall memory defects in schizophrenia are, in part, associated with prefrontal contributions of attention, abstract reasoning, and executive function. This study needs replication with a larger sample of patients and more comprehensive volumetric morphometric analyses.

Adolescent↗

PubMed1976

Prefrontal unit activity and delayed response: relation to cue location versus direction of response.

Two monkeys were trained to perform 3 kinds of spatial tasks (right-left DR, up-down DR, and conditional position discrimination with delay). In the conditional position task, the animal was required to respond to the right (left) choice key when the cue had been presented on the upper (lower) position. Single unit activity was recorded from the principalis area of the dorsolateral prefrontal cortex while the animal was performing the tasks. Once a differential delay unit (i.e., unit showing specificity during the delay period for two kinds of trials) was found in right-left DR (or up-down DR), the same unit was tested in the other tasks. A total of 32 differential delay units were investigated sufficiently to allow comparison of all 3 conditions. The results indicate that there are two types of differential delay units. The first type showed a clear dependence on the cue location, while the second type was related to the direction of the impending response. Activity of the second type of differential delay unit during the delay period served to predict the occurrence of errors, whereas this relation between unit discharge and correct or incorrect responses was not seen for the first type of differential delay unit.

Animals↗

PubMed1979

Prefrontal and cingulate unit activity during timing behavior in the monkey.

Single unit activity was recorded from the dorsolateral prefrontal cortex and the anterior cingulate cortex while monkeys were performing a modified differential reinforcement of long latencies (DRLL) task. A total of 252 prefrontal units and 218 anterior cingulate units showed an obvious change in discharge rate (increase or decrease) in association with one or more of the events of a DRLL task. Related units were classified into 3 main groups: S--R event units, reward-error units, and timing units. S--R event units consisted of three subtypes: stimulus-related, response-related, and stimulus--response-related units. Reward-error units contained reward-related units and error-recognition units. Error-recognition units showed a vigorous increase in firing only after incorrect responses. These units were also responsive to omission of reinforcement on correct trials. Three types of timing units were distinguishable. The first one showed an anticipatory change prior to stimulus onset, and the second one exhibited a gradual anticipatory change preceding the time of responding. The third one manifested a sustained change during delay and an abrupt cessation of change in firing at the time of response initiation.

Animals↗

PubMed1996

Studies of working memory using 18FDG-positron emission tomography in normal controls and subjects with epilepsy.

We have studied three groups of subjects with a working memory paradigm, using 18FDG-PET. Controls show the greatest increase on uptake in dorsolateral prefrontal cortex, basal forebrain and angular gyrus. A group of subjects with focal frontal epilepsy did not show increases compared to a control task of attention. Primary generalized epilepsy subjects show the greatest changes in angular gyrus, dorsal temporal, medial frontal and parietal regions. Factor and regression analyses extend these observations and show reliance of both patient groups on the medial and inferior temporal lobe. We propose that the normal network of working memory is disrupted by these two forms of epilepsy and different networks are accessed. Declarative memory may be used as a compensatory system, which results in decreased performance.

Adult↗

PubMed1994

Impaired problem solving in Parkinson's disease: impact of a set-shifting deficit.

Parkinson's disease (PD) is associated with specific cognitive deficits in the absence of dementia, including the inability to suppress previously learned responses in a changed context. Our goal was to determine whether this set-shifting deficit is sufficient to account for impaired performance on a problem-solving task, or, instead, whether it is necessary to postulate deficits in one or more other cognitive capacities, such as logical deduction. Deductive reasoning and other conceptual abilities were assessed in 15 nondemented subjects with PD who had never been medicated, 15 nondemented subjects with PD who were currently receiving medication, and 15 healthy elderly control subjects. On a deductive reasoning task, Poisoned Food Problems, the PD groups made more errors than the control group. The PD groups' error pattern was characterized by intrusions of information from previous problems. By contrast, the PD groups made appropriate assessments of redundant and irrelevant information that appeared in these problems, and performed normally on other tests of concept formation and problem solving that did not require set shifting, indicating that the capacities for logical deduction and concept formation were intact. The set-shifting deficit, conceptualized as a difficulty in suppressing a prepotent response, appears to be a primary cognitive impairment in PD and presumably arises from dysfunction of the nigrostriatal-dorsolateral prefrontal cortex complex loop.

Aged↗

PubMed1978

Effects of d-amphetamine and prefrontal cortical cooling on delayed matching-to-sample behavior.

The interaction was examined between d-amphetamine (s-A) and dysfunction induced by localized cooling of the dorsolateral prefrontal cortex. Saline or d-A(0.1,0.2 or 0.4 mg/kg) was administered to monkeys in two conditions; normal cortical temperature (no cooling -NC) and frontal cooling (FC). Errors, reaction time (RT), eye movements, and motor activity were recorded during performance of a delayed matching-to-sample task with intratrial delays of 1-32 sec. Although d-A and FC had little effect on percentage of correct responses at the shortest delay, each of the two treatments significantly decreased correct responses, at longer delays; drug and FC combined produced a significantly greater decrease than either treatment alone. Motor activity and eye movements were increased by either d-A or FC; the two treatments combined had an even greater effect. In the NC condition, two-choice RT was decreased by the drug; it was increased by drug-FC combinations. These findings indicate that d-A and FC potentiate each other in their behavioral effects.

Animals↗

PubMed1982

Thalamic mediodorsal nucleus and memory: a critical evaluation of studies in animals and man.

Following a general description of the anatomical organization of the thalamic mediodorsal nucleus (MD) of animals and man, the involvement of this nucleus in the processing of memory related information has been evaluated by reviewing stimulation, electrophysiological, and lesion studies in animals, and by reviewing research on induced lesions, degenerative changes and vascular damage of MD in humans. Neither the results from animal experiments nor those from studies on humans provide clear-cut evidence for a specific, memory related role of MD. However, the findings here presented do support the theory that MD is one of several, possible memory related relay stations. While therapeutically induced and circumscribed lesions of MD rarely result in long-lasting memory deficits, pathological processes in MD are more likely to be followed by severe memory disturbances if one or more particular structures in addition to MD are included in the lesioned regions. Consequently, it is emphasized that only the disruption of more than one site along memory related pathways will result in severe and enduring memory deficits. To account for apparent inter-species differences in the involvement of MD in memory related processes, it has been argued that MD and its principal cortical target region might basically be involved in arousal and emotional processes, but that for primates and especially for man the phylogenetically young parvocellular sector of MD and its cortical projection region, the dorsolateral prefrontal cortex, are furthermore involved in memory functions, which are modulated by emotional factors via the rest of MD and the prefrontal cortex.

Afferent Pathways↗

PubMed1993

Factors of the Wisconsin Card Sorting Test as measures of frontal-lobe function in schizophrenia and in chronic alcoholism.

The purpose of this study was to examine the factor structure of the Wisconsin Card Sorting Test (WCST). The scores of 22 patients with schizophrenia, 20 patients with chronic alcoholism, and 16 normal control subjects were entered into a principal components analysis, which yielded three factors: Perseveration, Inefficient Sorting, and Nonperseverative Errors. WCST performance of seven patients with lesions invading the dorsolateral prefrontal cortex, available from another study, provided criterion validity for the Perseveration factor and, less strongly, for the Inefficient Sorting factor. Two patterns of performance characterized the three patient groups: the schizophrenic group and frontal lobe group had the highest Perseveration factor scores, whereas the alcoholic group had the highest Inefficient Sorting scores; the Nonperseverative Errors factor showed no significant group differences. Construct validity of these factors involved assessing, in all but the frontal group, the degree of overlap (convergent validity) and separation (discriminant validity) of each WCST factor with scores from tests of other cognitive functions. The convergent and discriminant validity of the Perseveration factor, but not the remaining two factors, received support only within the group of schizophrenic patients.

Adult↗

PubMed1994

Patterns of neuropsychological deficit in cases of schizophrenia spectrum disorder with and without a family history of psychosis.

This study was designed to identify the types of neuropsychological deficits that are unique to familial and nonfamilial forms of schizophrenia. Seventy-two patients who met Research Diagnostic Criteria for schizophrenia or schizoaffective disorder, mainly schizophrenic, were divided into two groups on the basis of the presence or absence of a family history of psychosis. The two groups were then compared for differences on six neuropsychological parameters as well as for differences in psychotic symptoms. Multivariate analyses indicated that schizophrenic patients with a family history of psychosis showed significantly higher levels of overall neuropsychological deficit and significantly greater deficits on tests of motor-control and abstraction and problem-solving. Factor analyses indicate that schizophrenic patients with a family history of psychosis show a pattern of specific neuropsychological deficits, while schizophrenic patients without a family history show a pattern of more consistent cognitive deficits. The results of this study indicate that recent-onset schizophrenic patients with and without a family history of psychosis show distinctly different patterns of neuropsychological dysfunction. These data suggest that abnormalities in the dorsolateral prefrontal cortex and nonprimary motor areas may be associated with an increased familial risk for psychotic disorder.

Adult↗

PubMed1995

Schizophrenic syndrome and Wisconsin Card Sorting Test dimensions.

A principal component analysis of Wisconsin Card Sorting Test (WCST) scores has recently shown three factors. Only the Perseveration factor may measure the activity of the dorsolateral prefrontal cortex in schizophrenic patients. Liddle has hypothesized that a dysfunction in this area is specifically related to the negative syndrome and not to other schizophrenic syndromes (positive and disorganization). The factor analysis of the WCST was replicated with similar results in 38 schizophrenic or schizoaffective patients. In the total group, the correlation between the negative syndrome and the Perseveration factor did not reach significant levels. In the patients with a DSM-III-R diagnosis of schizophrenia (n = 30), the correlations did reach significant levels.

Adult↗

PubMed1996

On the nature of Wisconsin Card Sorting Test performance in schizophrenia.

Performance on the Wisconsin Card Sorting Test (WCST) is widely reported to be impaired in patients with schizophrenia. It has been hypothesized that the performance deficit on the WCST in schizophrenia is related to a dysfunction of the frontal lobe, specifically the dorsolateral prefrontal cortex. This hypothesis was tested by comparing a group of patients with schizophrenia to patients with low grade right or left frontal lobe tumors and a group of patients with non-frontal high grade tumors. The results demonstrated a remarkable similarity in performance on the WCST between patients with schizophrenia and patients with right frontal lobe tumors. Patients with left frontal lobe tumors, non-frontal tumors, and normal control subjects did not show the same pattern of performance. This study provides support for frontal lobe dysfunction in the symptomatology of schizophrenia.

Adult↗

PubMed1991

Characterization of [125I]SCH 23982 binding in human brain: comparison with [3H]SCH 23390.

We studied binding of [125I]SCH 23982 in two regions of human brain, the caudate and the dorsolateral prefrontal cortex. Binding characteristics of [125I]SCH 23982 and of the non-iodinated tritiated analogue, [3H]SCH 23390, were compared. In caudate, binding of [125I]SCH 23982 was consistent with binding to D1 dopamine receptors while in frontal cortex, [125I]SCH 23982 bound mostly to serotonergic 5HT2 receptors. In contrast to [3H]SCH 23390, no evidence of binding of [125I]SCH 23982 to D1 receptors could be found in human frontal cortex. This indicates that iodination of SCH 23390 induces a decrease in its relative D1 versus 5HT2 selectivity that prohibits the use of [125I]SCH 23982 to label D1 receptors in human cortex.

Adult↗