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Results for “Dorsolateral Prefrontal Cortex”

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PubMed2003

Steady-state visual evoked potentials reveal frontally-mediated working memory activity in humans.

Steady-state visual evoked potentials (SSVEPs) reflect power changes at the stimulus driving frequency and have been used to assess brain activity reflecting cognitive processing. Only one study has demonstrated SSVEP modulation associated with working memory (WM), and none have compared the spatial localization of SSVEP modulations during WM performance with other brain imaging methods. Here we examined WM-related activity recorded with dense-array SSVEPs, analyzed using low resolution electromagnetic tomography, and compared the results to our previous findings using functional magnetic resonance imaging (fMRI). WM was associated with increased SSVEP activity over the right dorsolateral prefrontal cortex, paralleling our previous fMRI findings. Frontal WM-related SSVEP power correlated selectively with task performance. These results demonstrate the utility of SSVEPs for studying representational aspects of cognition.

Adolescent↗

PubMed2003

Rate dependency of the human cortical network subserving executive functions during generation of random number series--a functional magnetic resonance imaging study.

In a random number generation (RNG) task subjects are instructed to generate the numbers 1-10 in a random fashion. RNG performance is assumed to involve executive functions, as it requires controlled response generation and suppression of habitual responses. To investigate cerebral structures involved in RNG associated executive functions we investigated functional magnetic resonance imaging in eight healthy subjects while performing an RNG task at two different response rates (1 and 2 Hz). During the 1 Hz condition an activation was detected bilaterally in the dorsolateral prefrontal cortex (BA 9/46), the lateral premotor cortex (BA 6), the anterior cingulate (BA 32), the inferior and superior parietal cortex (BA 7/40) and the cerebellar hemispheres. In the 2 Hz condition behavioural data showed higher counting tendencies reflecting poorer executive control. In parallel, a homogenous diminution of the activity in the involved cortical areas was obtained. This finding would support the theory of a cortical network involved in executive functions consisting of distinct brain regions working together rather than a distinct fronto-cortical functional localisation.

Adult↗

PubMed1999

Do specific EEG frequencies indicate different processes during mental calculation?

EEG recordings during mental calculation and a control task (with presentation of stimuli with similar physical characteristics to the arithmetic symbols) were obtained in 10 subjects. Narrow band analyses of the EEG and distributed sources for each EEG frequency were calculated using variable resolution electromagnetic tomography. Significant differences between the sources for arithmetic and control tasks were observed at 3.9 Hz within Broca's and left parietotemporal cortices, suggesting that this frequency may be related with the production of internal speech, storage and rehearsal of verbal working memory. Differences at 5.46 Hz within the right dorsolateral prefrontal cortex were considered to be associated to sustained attention. The decrease at 12.46 Hz within the left parietal cortex was interpreted as a sign of retrieval of arithmetic facts from long term memory.

Adult↗

PubMed2000

Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study.

The neurobiology of chronic pain, including chronic back pain, is unknown. Structural imaging studies of the spine cannot explain all cases of chronic back pain. Functional brain imaging studies indicate that the brain activation patterns are different between chronic pain patients and normal subjects, and the thalamus, and prefrontal and cingulate cortices are involved in some types of chronic pain. Animal models of chronic pain suggest abnormal spinal cord chemistry. Does chronic pain cause brain chemistry changes? We examined brain chemistry changes in patients with chronic back pain using in vivo single- voxel proton magnetic resonance spectroscopy ((1)H-MRS). In vivo (1)H-MRS was used to measure relative concentrations of N-acetyl aspartate, creatine, choline, glutamate, glutamine, gamma-aminobutyric acid, inositol, glucose and lactate in relation to the concentration of creatine. These measurements were performed in six brain regions of nine chronic low back pain patients and 11 normal volunteers. All chronic back pain subjects underwent clinical evaluation and perceptual measures of pain and anxiety. We show that chronic back pain alters the human brain chemistry. Reductions of N-acetyl aspartate and glucose were demonstrated in the dorsolateral prefrontal cortex. Cingulate, sensorimotor, and other brain regions showed no chemical concentration differences. In chronic back pain, the interrelationship between chemicals within and across brain regions was abnormal, and there was a specific relationship between regional chemicals and perceptual measures of pain and anxiety. These findings provide direct evidence of abnormal brain chemistry in chronic back pain, which may be useful in diagnosis and future development of more effective pharmacological treatments.

Adult↗

PubMed2002

1H MRS brain measures and acute lorazepam administration in healthy human subjects.

The effects of acute lorazepam administration on 1H magnetic resonance spectroscopy (MRS) in vivo brain spectra were examined in the left dorsolateral prefrontal cortex (L-DLPFC) of healthy human subjects. We wanted to examine whether lorazepam administration would result in significant changes in the levels of 1H-MRS metabolites in this brain region. Ten healthy controls underwent a short echo-time 1H-MRS session immediately before, and a second one 1 h after lorazepam administration (2mg/orally). The measured 1H-metabolites included N-acetyl-aspartate, phosphocreatine+creatine, trimethylamines, myo-inositol, glutamate, and glutamine, which were expressed as absolute values and ratios. No significant differences were found after lorazepam administration for any of the measured metabolite levels or ratios (paired t-tests, p >.05). This study demonstrated that lorazepam can potentially be utilized to acutely sedate psychiatric subjects during in vivo 1H-MRS sessions, as it does not appear to produce significant changes in the 1H-MRS spectra in this specific brain region.

Adult↗

PubMed2002

Decision-making in a risk-taking task: a PET study.

As decision-making is central to motivated behavior, understanding its neural substrates can help elucidate the deficits that characterize various maladaptive behaviors. Twenty healthy adults performed a risk-taking task during positron emission tomography with (15)O-labeled water. The task, a computerized card game, tests the ability to weigh short-term rewards against long-term losses. A control task matched all components of the risk-taking task except for decision-making and the difference between responses to contingent and non-contingent reward and punishment. Decision-making (2 runs of the active task minus 2 runs of the control task) activated orbital and dorsolateral prefrontal cortex, anterior cingulate, insula, inferior parietal cortex and thalamus predominantly on the right side, and cerebellum predominantly on the left side. In an exploratory analysis, guessing (run 1 minus run 2 of the active task) accompanied activation of sensory-motor associative areas, and amygdala on the left side, whereas informed decision-making (run 2 minus run 1) activated areas that subserve memory (hippocampus, posterior cingulate) and motor control (striatum, cerebellum). The findings provide a framework for future investigations of decision-making in maladaptive behaviors.

Adult↗

PubMed2002

Repetitive transcranial magnetic stimulation (rTMS) in major depression: relation between efficacy and stimulation intensity.

Repetitive transcranial magnetic stimulation (rTMS) has been found to exert modest to substantial antidepressant effects in the majority of prior clinical studies. As effect sizes and stimulation conditions have varied greatly, controversy persists regarding effective stimulation parameters (e.g. intensity, frequency, localization). In the present controlled study, we investigated whether the antidepressant efficacy of rTMS may be related to the stimulation intensity applied. Thirty-one patients suffering from a pharmacotherapy-resistant major depressive episode were randomly assigned to three treatment groups receiving rTMS at different stimulation intensities: (1) intensity at the individual motor threshold (MT); (2) 90% subthreshold intensity; and (3) low intensity of standard sham rTMS. Each patient underwent 10 sessions of 10 Hz rTMS with 1500 stimuli/day over the left dorsolateral prefrontal cortex. Improvement of depressive symptoms after rTMS significantly increased with stimulation intensity across the three groups. A 30% to 33% reduction of baseline depression scores was observed after rTMS at MT intensity. Similarly, groups differed significantly regarding the clinical course after rTMS with the lowest number of antidepressant interventions and the shortest hospital stay in the MT intensity group. These findings support the hypothesis of a relationship between stimulation intensity of rTMS and its antidepressant efficacy.

Aged↗

PubMed1998

Reproducibility of proton magnetic resonance spectroscopic imaging in patients with schizophrenia.

Using proton magnetic resonance spectroscopic imaging (1H-MRSI) we found in a previous study a specific pattern of neuronal pathology in patients with schizophrenia as determined by relative loss of signal from N-acetyl-containing compounds (NAA). The purpose of the present study was to assess the reproducibility of the results of 1H-MRSI both in patients with schizophrenia and in normal controls. We studied twice 10 patients and 10 controls on 2 days separated by, on average, 3 months. Reproducibility was assessed with several statistical procedures including ANOVA, coefficients of variation (CVs) and intra-class correlation coefficients (ICC). Patients showed significant reductions of NAA/creatine-phosphocreatine (CRE) and NAA/choline-containing compounds (CHO) selectively in the hippocampal region (HIPPO) and in the dorsolateral prefrontal cortex (DLPFC) on both experimental days. A repeated measures ANOVA showed no effect of time on metabolite ratios in all subjects. CVs were fairly low (especially for NAA/CRE and CHO/CRE) and did not differ significantly between patients and controls. The ICCs of the ROIs reached statistical significance only in a few instances. The present multislice 1H-MRSI study shows that: (1) patients with schizophrenia, when compared as a group to normal controls, show a consistent 1H-MRSI pattern of group differences, i.e., bilateral reductions of NAA/CRE and NAA/CHO in HIPPO and DLPFC; (2)1H-MRSI data in both patients and controls do not show significant changes over this 90-day period; however, absolute metabolite ratios in individuals show low predictability over this time interval; (3) 1H-MRSI data show relatively low variability (as measured by the CVs) both in patients and normal controls, especially for NAA/CRE and CHO/CRE.

Acetylation↗

PubMed1998

Functional magnetic resonance imaging brain mapping in psychiatry: methodological issues illustrated in a study of working memory in schizophrenia.

Functional magnetic resonance imaging (fMRI) is a potential paradigm shift in psychiatric neuroimaging. The technique provides individual, rather than group-averaged, functional neuroimaging data, but subtle methodological confounds represent unique challenges for psychiatric research. As an exemplar of the unique potential and problems of fMRI, we present a study of 10 inpatients with schizophrenia and 10 controls performing a novel "n back" working memory (WM) task. We emphasize two key design steps: (1) the use of an internal activation standard (i.e., a physiological control region) to address activation validity, and (2) the assessment of signal stability to control for "activation" artifacts arising from unequal signal variance across groups. In the initial analysis, all but one of the patients failed to activate dorsolateral prefrontal cortex (DLPFC) during the working memory task. However, some patients (and one control) also tended to show sparse control region activation in spite of normal motor performance, a result that raises doubts about the validity of the initial analysis and concerns about unequal subject motion. Subjects were then matched for signal variance (voxel stability), producing a subset of six patients and six controls. In this comparison, the internal activation standard (i.e., motor activation) was similar in both groups, and five of six patients, including two whom were neuroleptic-naive, failed to activate DLPFC. In addition, a tendency for overactivation of parietal cortex was seen. These results illustrate some of the promise and pitfalls of fMRI. Although fMRI generates individual brain maps, a specialized survey of the data is necessary to avoid spurious or unreliable findings, related to artifacts such as motion, which are likely to be frequent in psychiatric patients.

Adult↗

PubMed2002

Decision making deficits in patients with first-episode and chronic schizophrenia.

A considerable body of evidence suggests that the dorsolateral prefrontal cortex is dysfunctional in schizophrenia. However, relatively few studies have explored the involvement of other areas of the frontal cortex. Research suggests that the orbitofrontal cortex (OFC) plays an important role in decision making processes. We assessed the decision making cognition of first-episode and chronic schizophrenic patients with a novel task sensitive to orbitofrontal dysfunction. Both first-episode and chronic patients with schizophrenia took longer than matched controls to make decisions, and both groups were also impaired on a measure of risk adjustment. The impairment in these measures was more severe in the chronic patients than in the first-episode patients, and only the chronic patients made significantly fewer optimal decisions than controls. These results contribute to increasing evidence of orbitofrontal dysfunction in schizophrenia, and suggest that disease progression or the effects of long term antipsychotic medication may influence performance on this task.

Analysis of Variance↗

PubMed2002

Longitudinal follow-up of neurochemical changes during the first year of antipsychotic treatment in schizophrenia patients with minimal previous medication exposure.

Reduced frontal N-acetylaspartate (NAA) has been repeatedly found in chronic schizophrenia and suggests neuronal loss or dysfunction. However, the potential confounding effect of antipsychotic drugs on NAA has not been resolved. The few studies of antipsychotic-nai;ve patients are inconclusive. A recent report suggests that antipsychotic drugs may increase NAA in the dorsolateral prefrontal cortex (DLPFC). We studied 10 minimally treated (less than 3 weeks lifetime exposure) schizophrenia patients and 10 normal controls with single-voxel proton magnetic resonance spectroscopy (1H-MRS) of the left frontal and occipital lobes. Concentrations of NAA, Cho, and Cre were determined and corrected for the proportion of cerebrospinal fluid (CSF) in the voxel. Patients were treated in a randomized-controlled double-blind design with either haloperidol or quetiapine. 1H-MRS was repeated within a year. There were no differences in frontal or occipital NAA between patients and controls at baseline. However, frontal NAA was reduced in the schizophrenia group within the first year of treatment. Patients had a clear clinical response to treatment but changes in frontal NAA were not correlated with symptom improvement. The well-described reduced frontal NAA in schizophrenia may not be a trait of the illness but may represent medication effect or progression of the disease.

Adult↗

PubMed2004

Working memory capacity in schizophrenia: a parametric fMRI study.

Impaired working memory (WM) function in schizophrenia has been associated with abnormal activation of the dorsolateral prefrontal cortex (DLPFC). It is, however, not clear whether abnormal activation is a sign of DLPFC pathology, or a correlate of poor performance. We address this question by examining activity in the WM brain system at different levels of task difficulty. A parametric fMRI paradigm is used to examine how the WM system responds to increasing load. A parametric fMRI design with four levels of a spatial N-back task was used to examine the relationships between working memory load, functional output (performance) and brain activity in 10 schizophrenic patients on atypical antipsychotic medication and to compare these to 10 healthy controls. In spite of increasingly poor performance in schizophrenic patients, activity increased normally in DLPFC and inferior parietal cortex bilaterally and in anterior cingulate, with increasing load. At 3-back, activity dropped in DLPFC in comparison with controls, but not in the other regions. The results indicate that peak activation of the WM-system is reached at a lower processing load in schizophrenic patients than in healthy controls. As a decline of DLPFC activity at high processing loads in itself is not abnormal, WM dysfunction in schizophrenia appears to be the result of an impaired functional output of the whole WM system, causing elevation of the effective burden imposed by WM tasks.

Adult↗

PubMed1998

Monetary reinforcement and Wisconsin Card Sorting performance in schizophrenia: why show me the money?

The Wisconsin Card Sorting Test (WCST) is a measure of concept formation and cognitive flexibility that has been associated with the integrity of the dorsolateral prefrontal cortex. Although patients show deficits on the WCST, training techniques that rely on enhanced instruction are often effective at improving performance, at least temporarily. The beneficial effects of monetary reinforcement alone, however, have not shown such clear-cut effects. Thirty-two schizophrenic inpatients were initially administered a computerized version of the WCST according to standard instructions and then assigned to one of four groups that differed by type of intervention. The level of reinforcement (high vs. low) and enhanced instruction (present vs. absent) were manipulated across the four groups. All patients received a repeat standard administration of the WCST at a 1-week follow-up. Although enhanced instruction showed an initial effect, performance gains fell off at the 1-week retest and approached baseline levels of performance. The level of reinforcement did not make a significant difference. The results indicate that the addition of enhanced verbal instruction yields a benefit, but that contingent monetary reinforcement does not. It appears that deficits on this test are not easily remediated by incentive manipulations.

Adult↗

PubMed1999

Mapping of grey matter changes in schizophrenia.

Studies of brain changes in schizophrenia have suggested that the disorder is associated with reductions in both global and regional grey matter. In this study, we used structural neuroimaging to differentiate between these two types of change and to examine regional grey matter throughout the whole brain. Grey matter from magnetic resonance images was segmented and transformed into stereotactic space, and patients with schizophrenia and controls were compared with respect to regional grey matter (after compensating for global grey matter differences). In two preliminary analyses to test our methodology, we demonstrated that: (1) in the transformed grey matter maps, voxel values at the location of the caudate nuclei were correlated with region-of-interest measurements of caudate area in native image space, and (2) the technique detected regional grey matter changes resulting from artificial lesions created in the native images. We then used a factorial design to examine data from two studies, comprising a total of 42 schizophrenics and 52 controls. Analysis of the main effect of schizophrenia on regional grey matter revealed significant reductions in (a) the right temporal pole, insula and amygdala, (b) the left temporal pole, insula and dorsolateral prefrontal cortex.

Adult↗

PubMed2000

Regional cerebral blood flow changes in drug-resistant depressed patients following treatment with transcranial magnetic stimulation: a statistical parametric mapping analysis.

Changes of regional cerebral blood flow (rCBF) in five drug-resistant depressed patients were examined by single photon emission computed tomography (SPECT) with 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) before and after treatment with transcranial magnetic stimulation (TMS). The SPECT images were analysed with the Statistical Parametric Mapping (SPM) package. TMS administered in the region of the left dorsolateral prefrontal cortex (DLPFC) of the depressed patients was associated with an increase of rCBF at a focal region some distance from the stimulation site. No change was observed at any other remote region.

Antidepressive Agents↗

PubMed2002

Correlation of cerebral blood flow and treatment effects of repetitive transcranial magnetic stimulation in depressed patients.

The aims of this study were to: (1) assess the effects of repetitive transcranial magnetic stimulation (rTMS) on brain activity in depressed patients as measured by single photon emission tomography (SPECT); (2) evaluate the predictive value of brain SPECT on the antidepressant efficacy of rTMS. Patients (n=17) received 1600 rTMS stimuli at a rate of 10 Hz, 5 days per week for 2 weeks to the left dorsolateral prefrontal cortex. Whole brain SPECT data were acquired using Tc99m-Bicisate. Regional cerebral blood flow (rCBF) was correlated with the % change in the 28-item Hamilton Depression Rating Scale Score (Delta-HDRS) and a semiquantitative region of interest (ROI) analysis was conducted. Prior to rTMS there was a significant left-right asymmetry favoring the right, whereas 2 weeks after the rTMS treatment this asymmetry was reversed. The rCBF in limbic structures was negatively correlated with the outcome and rCBF in several neocortical areas was positively correlated. Brain SPECT can provide information about mechanisms of action of rTMS and may have predictive value for the antidepressant efficacy of rTMS.

Adolescent↗

PubMed2003

The Danish PET/depression project: poor verbal fluency performance despite normal prefrontal activation in patients with major depression.

The verbal fluency (VF) test is associated with prefrontal and cingulate functioning. We used positron emission tomography (PET) to test the hypothesis that inactivity in these regions can explain why patients with depression often perform poorly on this test. Forty-one patients with major depression and 46 controls were scanned during rest and during activation with the VF test. The differences between the two conditions were mapped for each of the two groups, and between-group differences in the activation pattern were calculated on a voxel-by-voxel basis. As predicted, the patients performed significantly more poorly on the test. In both groups activations were seen in the left anterior cingulate region, the left dorsolateral prefrontal cortex, the left medial prefrontal cortex, and the right cerebellum. Performance was correlated to the cerebral perfusion in to the left occipitotemporal gyrus and the left cerebellum. However, no difference in activation between the two groups was significant. The present study had sufficient power to detect potential differences between the two groups, and the subtraction tasks were appropriate. Therefore, the result supports the notion that abnormalities in the prefrontal cortex in depression are qualitative in nature rather than quantitative; this suggests depression involves dys-coordination of neural activity in the frontal lobes rather than a simple reduction in activity.

Adult↗

PubMed2003

Anatomical and functional cerebral variables associated with basal symptoms but not risperidone response in minimally treated schizophrenia.

In schizophrenia, structural and functional cerebral variables show an unclear association with clinical features and their value as predictors of response to a typical antipsychotic agents has yet to be determined. The goal of this study was to investigate the relationships between clinical variables (baseline syndromes and response to risperidone) and anatomo-functional brain variables. We studied 19 minimally treated patients with schizophrenia of recent onset using magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) under resting conditions. The following brain variables were studied: volume of the cerebrospinal fluid (CSF) and gray matter (GM) of the dorsolateral prefrontal cortex (DLPFC) and temporal lobe; hippocampal metabolic activity and volume; and metabolic activity of the DLPFC, temporal lobe, putamen and caudate. Anatomical volume measurements were corrected for age and intracranial size using regression parameters determined from a matched sample of control subjects. Using stepwise multiple regression, we assessed the relation between these brain measures and basal scores of symptom dimensions (positive, disorganization, negative and total), as well as their change in response to risperidone. We found that positive and disorganization symptoms improved with risperidone treatment and that hippocampal metabolism, DLPFC CSF volume, and temporal CSF volume predicted baseline symptoms. However, none of the brain measures predicted response to treatment. We conclude that there is evidence of a significant association between basal symptoms and DLPFC atrophy and limbic hyperactivity at rest in recent-onset schizophrenic patients.

Adult↗