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Results for “Dorsolateral Prefrontal Cortex”

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PubMed2001

The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia.

BACKGROUND: The specific intracellular effects of antipsychotic drugs are largely unknown. Studies in animals have suggested that antipsychotics modify the expression of various intraneuronal proteins, but no analogous in vivo data in humans are available. The objective of the present study was to assess whether antipsychotics modify N-acetylaspartate (an intraneuronal marker of neuronal functional integrity) measures in brains of patients with schizophrenia. METHODS: We used proton magnetic resonance spectroscopic imaging to study 23 patients with schizophrenia (DSM-IV diagnosis) using a within-subject design. Patients were studied twice: once while on a stable regimen of antipsychotic drug treatment (for at least 4 weeks) and once while off medication for at least 2 weeks. Several cortical and subcortical regions were assessed, including the dorsolateral prefrontal cortex and the hippocampal area. RESULTS: Analysis of variance showed that, while on antipsychotics, patients had significantly higher N-acetylaspartate measures in the dorsolateral prefrontal cortex (p =.002). No other region showed any significant effect of treatment. CONCLUSIONS: These results indicate that antipsychotic drugs increase N-acetylaspartate measures selectively in the dorsolateral prefrontal cortices of patients with schizophrenia, suggesting that these drugs modify in a regionally specific manner the function of a population of cortical neurons. N-Acetylaspartate measures may provide a useful tool to further investigate the effects of antipsychotics at the intracellular level.

Adult↗

PubMed2001

Attention-deficit disorder in adults with or without hyperactivity: where is the difference? A study in humans using short echo (1)H-magnetic resonance spectroscopy.

The DSM-IV distinguishes three subtypes of attention deficit hyperactivity disorder: The predominantly inattentive subtype (ADD), the hyperactive-impulsive subtype (ADHD) and the combined subtype. We used short echo time (1)H-magnetic resonance spectroscopy (TE=30 ms, TR=3000 ms) for absolute quantification of neurometabolites using the LC model algorithm to investigate a possible metabolic neuropathology in adult patients with ADD and ADHD and compared their spectra with healthy controls (n=5 in each group). Spectra were acquired in the left dorsolateral prefrontal cortex and the left striatum. There was a significant group difference in N-acetylaspartate (NAA) concentration in the left dorsolateral prefrontal cortex distinguishing patients with the ADHD from patients with pure ADD and healthy controls. The absolute NAA concentration was significantly reduced only in the ADHD group. Since NAA-depletion reflects a state of neuronal dysfunction, this finding indicates evidence of subtle left prefrontal neuropathology in ADHD in adults.

Adult↗

PubMed2005

Cerebral atrophy and its relation to cognitive impairment in Parkinson disease.

OBJECTIVE: Voxel-based morphometry was used to compare the amounts of gray matter in the brains of patients with Parkinson disease (PD) and normal control subjects (NCs) and to identify the specific regions responsible for cognitive dysfunction in PD. METHODS: Patients were classified into nondemented (ND) and demented (D) groups according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.), and a group comparison was performed. In the ND patients, a correlation was also performed between local gray matter density and the score on Raven Colored Progressive Matrices (RCPM), a test of executive and visuospatial function. RESULTS: In patients with advanced ND-PD vs NCs, atrophic changes were observed in the limbic/paralimbic areas and the prefrontal cortex. In D vs ND patients, atrophic change was observed widely in the limbic/paralimbic system, including the anterior cingulate gyrus and hippocampus as well as the temporal lobe, dorsolateral prefrontal cortex, thalamus, and caudate nucleus. The RCPM score was positively correlated with the gray matter density in the dorsolateral prefrontal cortex and the parahippocampal gyrus. CONCLUSIONS: In patients with Parkinson disease (PD), atrophic changes occur mainly in the limbic/paralimbic and prefrontal areas. These atrophic changes may be related to the development of dementia in PD.

Aged↗

PubMed2001

Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus.

Dopamine is implicated in movement, learning, and motivation, and in illnesses such as Parkinson's disease, schizophrenia, and drug addiction. Little is known about the control of dopamine release in humans, but research in experimental animals suggests that the prefrontal cortex plays an important role in regulating the release of dopamine in subcortical structures. Here we used [(11)C]raclopride and positron emission tomography to measure changes in extracellular dopamine concentration in vivo after repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in healthy human subjects. Repetitive TMS of the left dorsolateral prefrontal cortex caused a reduction in [(11)C]raclopride binding in the left dorsal caudate nucleus compared with rTMS of the left occipital cortex. There were no changes in binding in the putamen, nucleus accumbens, or right caudate. This shows that rTMS of the prefrontal cortex induces the release of endogenous dopamine in the ipsilateral caudate nucleus. This finding has implications for the therapeutic and research use of rTMS in neurological and psychiatric disorders.

Adult↗

PubMed2005

Variations in differential gene expression patterns across multiple brain regions in schizophrenia.

Large-scale gene expression studies in schizophrenia (SZ) have generally focused on the dorsolateral prefrontal cortex. Despite a wealth of evidence implicating multiple other brain regions in the disease, studies of other brain regions have been less frequent and have rarely been performed in the same subjects. We analyzed postmortem gene expression in the frontal, cingulate, temporal, parietal and occipital cortices (Brodmann areas 8, 10, 44, 46, 23/31, 24/32, 20, 21, 22, 36/28, 7 and 17, respectively) as well as in the hippocampus, caudate nucleus and putamen of persons with schizophrenia and control subjects (N's = 13) using Affymetrix GeneChip microarrays. Under identical data filtering conditions, the superior temporal cortex (BA22) of schizophrenia subjects showed the maximal number of altered transcripts (approximately 1200) compared to controls. Anterior and posterior cingulate cortices (BA23/31, 24/32) and the hippocampus followed the superior temporal cortex with two-times lower numbers of altered transcripts. The dorsolateral prefrontal cortex (BA46), a frequent target of SZ-associated studies, showed substantially fewer altered transcripts (approximately 33). These regional differences in differentially expressed genes could not be accounted for by factors such as total numbers of genes expressed or the filtering conditions and criteria used for identification of differentially expressed genes. These findings suggest that the temporal and cingulate cortices and the hippocampal formation represent brain regions of particular abnormality in SZ and may be more susceptible to the disease process(es) than other regions thus far studied.

Aged↗

PubMed2000

Hypofrontality and negative symptoms in patients with dementia of Alzheimer type.

OBJECTIVE: The purpose of the current study was to examine the relation between regional cerebral blood flow (rCBF) and negative symptoms (NS) in patients with dementia of Alzheimer type (DAT). BACKGROUND: Negative symptoms in neuropsychiatric disorders were associated with altered rCBF in frontal cortex. METHODS: Twenty-five subjects with a diagnosis of DAT were administered the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptom Scale, the Hamilton Rating Scale for Depression, and the Mini-Mental State Examination. The subjects were divided into two groups by means of a median split with regard to NS severity (high NS group, N = 12; low NS group, N = 13). Each patient underwent a single photon emission tomography scan using 99mTc-HMPAO at rest. Cortical and subcortical regions of interest were symmetrically defined in each hemisphere. Cortical-to-cerebellar perfusion ratios were established quantitatively using ADAC software. RESULTS: High NS group subjects had a significantly lower rCBF than low NS group subjects in the frontal cortex and cingulate gyrus (MANOVA: p = 0.022) as a result of differences in the dorsolateral prefrontal cortex bilaterally (right: F = 12.12, p = 0.002; left: F = 6.55, p = 0.02) and in the frontal cortex, mainly in the right hemisphere (right: F = 6.33, p = 0.02; left: F = 3.26, p = 0.08). For all the subjects (N = 25), there were negative correlations between the SANS total score and rCBF, most prominently in the dorsolateral prefrontal cortex bilaterally (right: r = -0.48, p <0.01; left: r = -0.49, p = 0.01). No significant correlation was found between rCBF in any of the regions of interest and either the Mini-Mental State Examination or the Hamilton Rating Scale for Depression scores. CONCLUSIONS: This study indicates that decreased perfusion in the frontal cortex is associated with NS severity but not with measures of cognitive impairment or depressive symptoms in DAT patients. These results support the hypothesis that the frontal lobes may be involved in the cause of NS in DAT, and they underscore the importance of NS evaluation in neuroimaging studies.

Aged↗

PubMed1999

Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI.

Inhibition of an ongoing reaction tendency for adaptation to changing environments is a major function of the human prefrontal cortex. This function has been investigated frequently using the go/no-go task and set-shifting tasks such as the Wisconsin Card Sorting Test (WCST). Studies in humans and monkeys suggest the involvement of the dorsolateral prefrontal cortex in the two task paradigms. However, it remains unknown where in the dorsolateral prefrontal cortex this function is localized, whether a common inhibitory mechanism is used in these task paradigms and how this inhibitory function acts on two different targets, i.e. the go response in the go/no-go task and the cognitive set in the WCST. In the go/no-go task of this study, subjects were instructed to either respond (go trial) or not respond (no-go trial), depending on the cue stimulus presented. The signals of functional MRI (fMRI) related to the inhibitory function should be transient by nature. Thus, we used the temporal resolution of fMRI (event-related fMRI) by which transient signals in go and no-go trials can be analysed separately and compared with each other. We found a focus that showed transient no-go dominant activity in the posterior part of the inferior frontal sulcus in the right hemisphere. This was true irrespective of whether the subjects used their right or left hands. These results suggest that the transient activation in the right inferior prefrontal area is related to the neural mechanism underlying the response inhibition function. Furthermore, this area was found to be overlapped spatially with the area that was activated transiently during cognitive set shifting in the WCST. The transient signals in the go/no-go task peaked 5 s after the transient expression of the inhibitory function, and the transient signals in the WCST peaked 7s after the transient expression, reflecting different durations of neuronal activity in the two inhibitory task paradigms. These results imply that the right inferior prefrontal area is commonly involved in the inhibition of different targets, i.e. the go response during performance of the go/no-go task and the cognitive set during performance of the WCST.

Adaptation, Physiological↗

PubMed2006

The neural processing of moral sensitivity to issues of justice and care.

The empirical and theoretical consideration of ethical decision making has focused on the process of moral judgment; however, a precondition to judgment is moral sensitivity, the ability to detect and evaluate moral issues [Rest, J. R. (1984). The major components of morality. In W. Kurtines & J. Gewirtz (Eds.), Morality, moral behaviour, and moral development (pp. 24-38). New York, NY: Wiley]. Using functional magnetic resonance imaging (fMRI) and contextually standardized, real life moral issues, we demonstrate that sensitivity to moral issues is associated with activation of the polar medial prefrontal cortex, dorsal posterior cingulate cortex, and posterior superior temporal sulcus (STS). These activations suggest that moral sensitivity is related to access to knowledge unique to one's self, supported by autobiographical memory retrieval and social perspective taking. We also assessed whether sensitivity to rule-based or "justice" moral issues versus social situational or "care" moral issues is associated with dissociable neural processing events. Sensitivity to justice issues was associated with greater activation of the left intraparietal sulcus, whereas sensitivity to care issues was associated with greater activation of the ventral posterior cingulate cortex, ventromedial and dorsolateral prefrontal cortex, and thalamus. These results suggest a role for access to self histories and identities and social perspectives in sensitivity to moral issues, provide neural representations of the subcomponent process of moral sensitivity originally proposed by Rest, and support differing neural information processing for the interpretive recognition of justice and care moral issues.

Adult↗

PubMed1999

Some remarks on etiological aspects of early-onset schizophrenia.

Neurophysiological, neuropsychological, neuroanatomical, and neuroradiological findings in schizophrenic psychoses demonstrate that subcortical (e.g., mesolimbic and diencephalic regions) as well as neocortical structures (e.g., dorsolateral prefrontal cortex, superior temporal and inferior parietal cortices) are involved. Special significance is accorded to the neuroanatomical connection between limbic structures and the dorsolateral prefrontal cortex. Here myelinization begins relatively late in humans, during the second and third decade of life - a particularly vulnerable period for schizophrenic onset. The nature of prepsychotic behavioral abnormalities in patients with early-onset schizophrenia as well as the existence of typical cognitive dysfunctions preceding the manifestation of psychotic symptoms points to the importance of a dynamic imbalance of neocortical-subcortical interactions in the etiology of schizophrenia. Based on the crucial importance of the prefrontal-hippocampal circuitry a stimulus barrier model of schizophrenic psychoses is elaborated, which integrates recent neurobiological findings as well as results of research in modern developmental psychology. One of the implications of this model is the multidimensional treatment of schizophrenic patients.

Age Factors↗

PubMed2002

Putative tests of frontal lobe function: a PET-study of brain activation during Stroop's Test and verbal fluency.

Stroop's test and the Verbal Fluency test are commonly argued to be measures of the integrity of the prefrontal cortex. This assumption has only to some degree been confirmed by lesion studies. In the present study, Positron Emission Tomography (PET) with H(2)(15)O was used to further validate Stroop's test and the Verbal Fluency as measures of frontal lobe function; both tests were implemented as activation paradigms during scanning of normal middleaged individuals. Stroop interference was found to activate the left anterior cingulate cortex, the supplementary motor cortex, thalamus, and the cerebellum. Although the prominent anterior cingulate activation is in the frontal lobe, it is not prefrontal. Verbal Fluency activated the left inferior frontal cortex and the left dorsolateral prefrontal cortex, the supplementary motor cortex, the anterior cingulate cortex and the cerebellum. These results bring this latter test closer to being a specific test of prefrontal function.

Adult↗

PubMed2000

Chemical heterogeneity of the living human brain: a proton MR spectroscopy study on the effects of sex, age, and brain region.

Brain chemistry was compared between 19 male and female normal volunteers in the age group 19-31 years, across six brain regions and nine metabolites using in vivo proton magnetic resonance spectroscopy. The relative concentrations of N-acetyl aspartate, choline, glutamate, glutamine, GABA, inositol, glucose, and lactate were measured relative to creatine within 8-cm(3) brain voxels. These measurements were performed in six brain regions: thalamus and cingulate, insula, sensorimotor, dorsolateral prefrontal, and orbital frontal cortices in the left hemisphere. Total metabolite concentration was highest in prefrontal regions (28% higher in orbital frontal cortex and 18.7% higher in dorsolateral prefrontal cortex compared with insula and thalamus, P < 10(-7)). Subjects 25-31 years of age demonstrated a significant increase in total metabolite concentration in the orbital frontal cortex (35%, P < 10(-7)) and sensorimotor cortex (16.7%, P < 10(-5)) compared to those 19-20 years of age. These two brain regions also showed gender dependence, with women demonstrating increased metabolite concentrations compared to men (9% increase in sensorimotor cortex, P < 0.002, and 2.1% in orbital frontal cortex). Most other brain regions showed no gender- or age-dependent differences. The results indicate that the living human brain is chemically heterogeneous. The chemical heterogeneity is sex and age dependent and specific for brain region.

Adult↗

PubMed2004

Spatial and temporal dissociation in prefrontal cortex during action execution.

It is widely accepted that dorsolateral prefrontal cortex (DLPFC) is activated at the time of action generation in humans. However, the previous functional neuroimaging studies that have supported this hypothesis temporally integrated brain dynamics and therefore could not demonstrate when DLPFC underwent activation relative to the emergence of voluntary behavior. Data that are time-locked to the instant of voluntary action execution do not reveal DLPFC activation at that moment. Rather, activated foci are seen at the frontal poles. We investigated this apparent conundrum through three differentially constrained experiments, utilizing functional magnetic resonance imaging to identify those prefrontal areas exhibiting functional change at the moment of spontaneous action execution. We observed profound functional dissociation between anterior and dorsolateral regions, compatible with their involvement at different points during the temporal evolution of action: bilaterally the frontal poles activated at the moment of execution, while simultaneously (and relative to a prior activation state) left DLPFC 'deactivated.'

Adult↗

PubMed2003

Antidepressant efficacy of two different rTMS procedures. High frequency over left versus low frequency over right prefrontal cortex compared with sham stimulation.

BACKGROUND: This placebo-controlled study was designed to investigate the influence of two different stimulation procedures of repetitive transcranial magnetic stimulation (rTMS) on depressive symptoms in patients with depressive disorders. Furthermore, effects on cognitive functions and psychomotor functioning were tested. METHODS: Thirty patients with depression (22 females and 8 males; mean age of 56.4 years) were included. They were treated with a stable dosage of antidepressant medication. They received either high frequency rTMS (20 Hz) over the left dorsolateral prefrontal cortex (LDLPFC), low frequency rTMS (1 Hz) over the right dorsolateral prefrontal cortex (RDLPFC) or sham stimulations (10 patients in each group) as add on treatment at 10 days within 2 weeks. Depressive symptoms were registered by means of observer ratings (Hamilton Depression Rating Scale - HDRS) and self reports (Beck Depression Inventory - BDI). Psychomotor retardation was investigated by the Motor Agitation and Retardation Scale and cognitive function by d2 test. RESULTS AND CONCLUSIONS: Differences between the rTMS procedures regarding depressive symptoms could not be found. Motor abnormalities, however, significantly improved exclusively after real stimulation procedures. Patients with less severe deficits in psychomotor speed and concentration responded more intensively than patients with severe deficits.

Aged↗

PubMed1999

Evolution of functional reorganization in hemiplegic stroke: a serial positron emission tomographic activation study.

We used serial positron emission tomography (PET) to study the evolution of functional brain activity within 12 weeks after a first subcortical stroke. Six hemiplegic stroke patients and three normal subjects were scanned twice (PET 1 and PET 2) by using passive elbow movements as an activation paradigm. Increases of regional cerebral blood flow comparing passive movements and rest and differences of regional cerebral blood flow between PET 1 and PET 2 in patients and normal subjects were assessed by using statistical parametric mapping. In controls, activation was found in the contralateral sensorimotor cortex, supplementary motor area, and bilaterally in the inferior parietal cortex with no differences between PET 1 and PET 2. In stroke patients, at PET 1, activation was observed in the bilateral inferior parietal cortex, contralateral sensorimotor cortex, and ipsilateral dorsolateral prefrontal cortex, supplementary motor area, and cingulate cortex. At PET 2, significant increases of regional cerebral blood flow were found in the contralateral sensorimotor cortex and bilateral inferior parietal cortex. A region that was activated at PET 2 only was found in the ipsilateral premotor area. Recovery from hemiplegia is accompanied by changes of brain activation in sensory and motor systems. These alterations of cerebral activity may be critical for the restoration of motor function.

Aged↗

PubMed2001

Deriving numerosity and shape from identical visual displays.

We presented identical displays of three to five dots in a functional magnetic resonance imaging (fMRI) experiment with normal volunteers. Two distinct directed attention tasks were performed on these displays: In one condition, subjects assessed the numerosity of the display; in the other condition, they assessed the shape of the display. Decisions based on numerosity activated differentially striate and extrastriate visual processing areas as well as left inferior frontal cortex. Decisions based on shape derived from arrangement activated differentially temporoparietal cortex bilaterally, medial posterior cingulate cortex, and left dorsolateral prefrontal cortex. These divergent neural activations in response to identical stimuli suggest that attentional mechanisms are deployed in very different ways in rapid enumeration of visual objects and in linking spatially discrete elements to one form.

Adult↗

PubMed2002

The effects of tryptophan depletion on cognitive and affective processing in healthy volunteers.

RATIONALE: Cognitive impairment is a common feature of depressive illness. While accumulating evidence suggests that brain serotonin (5-HT) pathways play an important role in the neurobiology of depression, the extent to which altered 5-HT function is responsible for the associated changes in cognition and emotion remains unclear. OBJECTIVE: The present study examined the effects of acute dietary depletion of tryptophan (TRP) on cognitive and affective processing in healthy volunteers and explored the putative role of 5-HT in the neuropsychology of depression. METHODS: We administered computerised cognitive tests to healthy control participants following ingestion of TRP-free and nutritionally balanced amino acid drinks in a double-blind, placebo-controlled, crossover design. RESULTS: The TRP-free amino acid mixture significantly lowered plasma total and free TRP concentrations relative to baseline values and produced selective deficits similar to those observed previously in cases of clinical depression. In particular, TRP depletion increased response times for happy but not sad targets in an affective go/no-go task and slowed responding in a visual discrimination and reversal learning task. These deficits were not due to a global sedative effect, as planning ability was unimpaired. CONCLUSIONS: The present data indicate that serotonergic factors may be more involved in the disrupted inhibitory and emotional processing characteristic of depression than in other aspects of executive function, such as planning ability. These findings support the recent proposal that serotonergic manipulation may have greater effects on tasks mediated by frontal circuitry that includes the orbitofrontal cortex than by dorsolateral prefrontal cortex circuitry.

Adult↗

PubMed1994

Activation of specific cortical regions by apomorphine: an [15O]H2O PET study in humans.

The purpose of this study was to investigate the functional effects of apomorphine, a non-selective dopamine agonist, on regional neuronal activity using regional cerebral blood flow, measured using [15O]H2O and positron emission tomography (PET), as an index. Eight normal volunteers were scanned twice before and twice after receiving 10 micrograms/kg subcutaneous apomorphine. Apomorphine produced the expected side-effects and endocrine response. Analysis of the PET scans revealed that apomorphine increased regional cerebral blood flow (rCBF), presumably reflecting a change in neuronal activity, in the anterior cingulate, ventral motor cortex and the dorsolateral prefrontal cortex along with a decrease in rCBF in the retrosplenial cingulate region. These regions form a functional network of brain regions modulated by the dopaminergic system.

Adult↗

PubMed2006

Brain mechanisms of expectation associated with insula and amygdala response to aversive taste: implications for placebo.

The experience of aversion is shaped by multiple physiological and psychological factors including one's expectations. Recent work has shown that expectancy manipulation can alter perceptions of aversive events and concomitant brain activation. Accruing evidence indicates a primary role of altered expectancies in the placebo effect. Here, we probed the mechanism by which expectation attenuates sensory taste transmission by examining how brain areas activated by misleading information during an expectancy period modulate insula and amygdala activation to a highly aversive bitter taste. In a rapid event-related fMRI design, we showed that activations in the rostral anterior cingulate cortex (rACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex to a misleading cue that the taste would be mildly aversive predicted decreases in insula and amygdala activation to the highly aversive taste. OFC and rACC activation to the misleading cue were also associated with less aversive ratings of that taste. Additional analyses revealed consistent results demonstrating functional connectivity among the OFC, rACC, and insula. Altering expectancies of upcoming aversive events are shown here to depend on robust functional associations among brain regions implicated in prior work on the placebo effect.

Adolescent↗