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Results for “Dorsolateral Prefrontal Cortex”

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PubMed1999

Functional neuroanatomical double dissociation of mnemonic and executive control processes contributing to working memory performance.

We used event-related functional MRI to investigate the neural bases of two categories of mental processes believed to contribute to performance of an alphabetization working memory task: memory storage and memory manipulation. Our delayed-response tasks required memory for the identity and position-in-the-display of items in two- or five-letter memory sets (to identify load-sensitive regions) or memory for the identity and relative position-in-the-alphabet of items in five-letter memory sets (to identify manipulation-sensitive regions). Results revealed voxels in the left perisylvian cortex of five of five subjects showing load sensitivity (as contrasted with alphabetization-sensitive voxels in this region in only one subject) and voxels of dorsolateral prefrontal cortex in all subjects showing alphabetization sensitivity (as contrasted with load-sensitive voxels in this region in two subjects). This double dissociation was reliable at the group level. These data are consistent with the hypothesis that the nonmnemonic executive control processes that can contribute to working memory function are primarily prefrontal cortex-mediated whereas mnemonic processes necessary for working memory storage are primarily posteriorly mediated. More broadly, they support the view that working memory is a faculty that arises from the coordinated interaction of computationally and neuroanatomically dissociable processes.

Cerebral Cortex↗

PubMed1997

Human cortico-hippocampal activity related to auditory discrimination revealed by neuromagnetic field.

We carried out multi-dipole estimation and pursued spatio-temporal brain activity on a time scale of several milliseconds during an auditory discrimination task using a whole-cortex type SQUID system. Neuronal activities were estimated in the medial (hippocampus, parahippocampal gyrus, etc.) and lateral temporal cortices (superior and middle temporal gyri, etc.), the dorsolateral prefrontal cortex (middle and inferior frontal gyri, etc.) and the parietal cortex (supramarginal gyrus, etc.) in the 280-400 ms latency range. The activity in the posterior hippocampal region was the most prominent and long-lasting in parallel with the activities in the other regions. Therefore, the posterior hippocampal region is a central structure engaged in auditory discrimination. The whole-cortex neuromagnetic measurements provided the possibility of imaging the time-varying activities of the human cortico-hippocampal neural networks.

Adult↗

PubMed1972

The frontal lobe system: cortical-subcortical interrelationships.

The prefrontal cortex in the monkey is related structurally and functionally to several subcortical structures in such a way as to suggest that they constitute a neural system. Both anatomical and behavioral evidence justify implicating in such a system the prefrontal cortex itself, the head of the caudate nucleus, the globus pallidus, the substantia nigra, the subthalamic nucleus, the septal nuclei, the hippocampus, the centromedian nucleus, and the hypothalamus. There is, furthermore, an indication that this system is organized into at least two well-defined subsystems: a "dorsal" system originating in the dorsolateral prefrontal cortex involving the anterodorsal sector of the caudate, the lateral pallidum, the subthalamic nucleus, and the hippocampus; an "orbital" system originating in the orbital prefrontal cortex and involving the ventrolateral sector of the caudate nucleus, the medial pallidum, the centrornedian nucleus, the hypothalamus and the septal nuclei. While the anatomical and behavioral dissociation between these two systems is emphasized, attention is also drawn to the many possibilities for the two systems to converge upon one another.

Animals↗

PubMed2000

Left prefrontal activation predicts therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) in major depression.

There is evidence that repetitive transcranial magnetic stimulation (rTMS) applied to the prefrontal cortex has antidepressive properties. In the present study we evaluated the clinical status and the hemodynamic responses during mental work in the prefrontal cortex before therapeutic rTMS. Twelve patients diagnosed with major depression (DSM-IV) were randomized in a sham-controlled cross-over treatment protocol of 4 weeks' duration consisting of two periods of 5 days with rTMS separated by 9 days of no stimulation. rTMS (10 Hz) was applied to the left dorsolateral prefrontal cortex. Hemodynamic changes in the prefrontal cortex during mental work were evaluated by multi-site near-infrared spectroscopy (NIRS). Scores on the Hamilton Depression Rating Scale (HAMD) decreased significantly by -5.4 points after 5 days of active stimulation, whereas it did not change (+1.6 points) after sham stimulation. Absence of a task-related increase of total hemoglobin concentrations at the stimulation site (P<0.005), but not at other locations, before the first active rTMS significantly predicted the clinical response to active rTMS. Clinical benefits of rTMS are predicted by low local hemodynamic responses and support the idea of activation-dependent targeting of rTMS location.

Brain Mapping↗

PubMed2001

Neuroimaging studies of autobiographical event memory.

Commonalities and differences in findings across neuroimaging studies of autobiographical event memory are reviewed. In general terms, the overall pattern across studies is of medial and left-lateralized activations associated with retrieval of autobiographical event memories. It seems that the medial frontal cortex and left hippocampus in particular are responsive to such memories. However, there are also inconsistencies across studies, for example in the activation of the hippocampus and dorsolateral prefrontal cortex. It is likely that methodological differences between studies contribute to the disparate findings. Quantifying and assessing autobiographical event memories presents a challenge in many domains, including neuroimaging. Methodological factors that may be pertinent to the interpretation of the neuroimaging data and the design of future experiments are discussed. Consideration is also given to aspects of memory that functional neuroimaging might be uniquely disposed to examine. These include assessing the functionality of damaged tissue in patients and the estimation of inter-regional communication (effective connectivity) between relevant brain regions.

Autobiographies as Topic↗

PubMed2004

Upregulation of CB1 receptors and agonist-stimulated [35S]GTPgammaS binding in the prefrontal cortex of depressed suicide victims.

Endogenous and exogenous cannabinoids (CBs) acting through the CB(1) receptors have been implicated in the regulation of several behavioral and neuroendocrine functions. Modulation of endocannabinoidergic system by ethanol in mouse brain, and the association of suicide and mood disorders with alcoholism suggest possible involvement of the cannabinoidergic system in the pathophysiology of depression and suicide. Therefore, the present study was undertaken to examine the levels of CB(1) receptors and mediated signaling in the dorsolateral prefrontal cortex (DLPFC) of subjects with major depression who had died by suicides (depressed suicides, DS). [(3)H]CP-55,940 and CB(1) receptor-stimulated [(35)S]GTPgammaS binding sites were analyzed in membranes obtained from DLPFC of DS (10) and matched normal controls (10). Upregulation (24%, P<0.0001) of CB(1) receptor density (B(max)) was observed in DS (644.6+/-48.8 fmol/mg protein) compared with matched controls (493.3+/-52.7 fmol/mg protein). However, there was no significant alteration in the affinity of receptor (DS; 1.14+/-0.08 vs control; 1.12+/-0.10 nM). Higher density of CB(1) receptors in DS (38%, P<0.001) was also demonstrated by Western blot analysis. The CB(1) receptor-stimulated [(35)S]GTPgammaS binding was significantly greater (45%, P<0.001) in the DLPFC of DS compared with matched controls. The observed upregulation of CB(1) receptors with concomitant increase in the CB(1) receptor-mediated [(35)S]GTPgammaS binding suggests a role for enhanced cannabinoidergic signaling in the prefrontal cortex of DS. The cannabinoidergic system may be a novel therapeutic target in the treatment of depression and/or suicidal behavior.

Adolescent↗

PubMed2003

Dissociation of egocentric and allocentric spatial processing in prefrontal cortex.

Monkeys with lesions of areas 9 and 46 performed three variants of the spatial delayed response (SDR) task. There were no impairments in allocentric spatial memory in which geometrical relationships between environmental cues were used to identify spatial location; thus, memory of a 3D environmental map is intact. In contrast, there were severe impairments in egocentric spatial memory guided by visual or tactile cues that monkeys can relate to their viewing perspective during testing. These results strongly suggest that dorsolateral prefrontal cortex selectively mediates spatial memory tasks that are solved by referencing the location of targets to the body's orientation.

Animals↗

PubMed1991

The prefrontal cortex and its relation to behavior.

The prefrontal cortex is critical for temporal organization of behavior. It mediates cross-temporal sensory-motor contingencies, integrating motor action (including speech) with recent sensory information. It performs this role through cooperation of two cognitive functions represented in its dorsolateral areas: short-term memory (STM) and preparatory set. Supporting data have been obtained from monkeys performing delay tasks, which epitomize the principle of cross-temporal contingency. In a given trial, the animal performs an act contingent on a sensory cue given a few seconds or minutes earlier. During the delay between cue and response, cells in dorsolateral prefrontal cortex show sustained activation. Two cell categories can be identified in tasks in which cue and response are spatially separate. Cells of the first participate in STM: Their activation tends to diminish as the delay progresses; in some, the activation level depends on the particular cue received. Similar cells are found elsewhere in cortex. Cells of the second category seem to take part in preparation of motor response: Their activation tends to increase in anticipation of it and may be attuned to the particular movement the cue calls for. This cell type is rare outside of frontal cortex. The temporally integrative function of the prefrontal cortex is probably based on local interactions between "memory" and "motor-set" cells, as well as on neural associations between prefrontal cortex and posterior cortical areas.

Animals↗

PubMed2002

Maintenance and manipulation in spatial working memory: dissociations in the prefrontal cortex.

Two experiments were conducted to compare thec ries of the functional organization of spatial working memory within the human prefrontal cortex. In Experiment I, memory set size for locations was parametrically varied, allowing for the assessment of BOLD signal across maintenance requirements. In the sec ond experiment, manipulation of spatial information held in working memory was contrasted with simple maintenance of that information. Both experiment evoked significant activity in a distributed spatia working memory network. Although dorsolateral prefrontal activation increased monotonically with memory set size, this region was differentially engaged in task conditions involving explicit manipulation of in ternal representations. Activation in the superior frontal sulcal region was associated with maintenance of spatial information, increasing with memory se size. In contrast, ventrolateral prefrontal activation was present only at the highest memory set size, possibly due to the differential use of organizational strategies with more complex stimuli. These results sup port claims that the dorsolateral prefrontal cortex is involved in the manipulation of internal representa tions and that the superior frontal sulcal region is involved in the maintenance of spatial information but they suggest a complex role for the ventrolatera prefrontal region.

Algorithms↗

PubMed2004

The irrelevant speech effect and working memory load.

Irrelevant speech impairs the immediate serial recall of visually presented material. Previously, we have shown that the irrelevant speech effect (ISE) was associated with a relative decrease of regional blood flow in cortical regions subserving the verbal working memory, in particular the superior temporal cortex. In this extension of the previous study, the working memory load was increased and an increased activity as a response to irrelevant speech was noted in the dorsolateral prefrontal cortex. We suggest that the two studies together provide some basic insights as to the nature of the irrelevant speech effect. Firstly, no area in the brain can be ascribed as the single locus of the irrelevant speech effect. Instead, the functional neuroanatomical substrate to the effect can be characterized in terms of changes in networks of functionally interrelated areas. Secondly, the areas that are sensitive to the irrelevant speech effect are also generically activated by the verbal working memory task itself. Finally, the impact of irrelevant speech and related brain activity depends on working memory load as indicated by the differences between the present and the previous study. From a brain perspective, the irrelevant speech effect may represent a complex phenomenon that is a composite of several underlying mechanisms, which depending on the working memory load, include top-down inhibition as well as recruitment of compensatory support and control processes. We suggest that, in the low-load condition, a selection process by an inhibitory top-down modulation is sufficient, whereas in the high-load condition, at or above working memory span, auxiliary adaptive cognitive resources are recruited as compensation.

Adult↗

PubMed1997

Morphometric methods for studying the prefrontal cortex in suicide victims and psychiatric patients.

Neurochemical studies demonstrate altered numbers of monoaminergic receptors in the prefrontal cortex in suicide and depression victims, implicating dysfunction of the prefrontal cortex in the neuropathology of suicide and psychiatric disorders. Neuroimaging studies in vivo have revealed an altered pattern of cortical metabolism and reductions in frontal lobe volume in patients with schizophrenia (SCZ) or depression. However, the precise morphopathology underlying these abnormalities and their relevance to suicide are unknown. Our recent three-dimensional cell counting of dorsolateral prefrontal cortex from 16 postmortem SCZ brains (10 suicide completers) revealed cellular changes (increased neuronal density, and reduced laminar width and neuronal size) that may be associated with neuroimaging observations. Evaluation of the same morphometric parameters in the prefrontal cortex in seven bipolar brains (three committed suicide) revealed similarities (decreased cortical and laminar thickness) and differences (unchanged overall neuronal density and laminar densities) between morphopathology of SCZ and bipolar disorder. In another population of suicide victims with major depression (nonpsychotic), further morphopathological differences from SCZ and similarities to bipolar disorder were observed in the prefrontal cortex. From these data we can conclude that the morphopathology observed in brain tissue from suicide victims appears to vary based on psychiatric symptomatology. In order to confirm this hypothesis and to establish the specificity of morphometric findings in relation to psychiatric disorders and suicide, additional studies are warranted in nonsuicide subjects with SCZ, major depression, or bipolar disorder.

Humans↗

PubMed2005

Hypofrontality in men with first-episode psychosis.

BACKGROUND: Decreased metabolic activity in the prefrontal cortex during cognitive activation is a recurrent finding and a likely functional marker of schizophrenia. AIMS: To investigate the occurrence of hypofrontality in patients with first-episode psychosis, with or without evolution to schizophrenia. METHOD: We used fluorodeoxyglucose positron emission tomography during the performance of an attention task and magnetic resonance imaging to study the dorsolateral prefrontal region in 13 men with a first episode of psychosis. Data from patients who progressed to schizophrenia were compared with those of patients who did not meet criteria for this diagnosis after 2 years. RESULTS: Patients who developed schizophrenia demonstrated a significant hypofrontality in the dorsolateral prefrontal cortex in comparison with the non-schizophrenia and control groups. CONCLUSIONS: Our results suggest that hypofrontality could be a marker of schizophrenia at the time of the first psychotic episode, in agreement with neurodevelopmental theories of schizophrenia.

Adult↗

PubMed2001

Neural correlates of change detection and change blindness.

Functional magnetic resonance imaging (fMRI) of subjects attempting to detect a visual change occurring during a screen flicker was used to distinguish the neural correlates of change detection from those of change blindness. Change detection resulted in enhanced activity in the parietal and right dorsolateral prefrontal cortex as well as category-selective regions of the extrastriate visual cortex (for example, fusiform gyrus for changing faces). Although change blindness resulted in some extrastriate activity, the dorsal activations were clearly absent. These results demonstrate the importance of parietal and dorsolateral frontal activations for conscious detection of changes in properties coded in the ventral visual pathway, and thus suggest a key involvement of dorsal-ventral interactions in visual awareness.

Adult↗

PubMed2005

Neuroimaging of marijuana smokers during inhibitory processing: a pilot investigation.

Neuropsychological investigations of substance abusers have reported impairments on tasks mediated by the frontal executive system, including functions associated with behavioral inhibition and decision making. The higher order or executive components which are involved in decision making include selective attention and short term storage of information, inhibition of response to irrelevant information, initiation of response to relevant information, self-monitoring of performance, and changing internal and external contingencies in order to "stay the course" towards the ultimate goal. Given the hypothesized role of frontal systems in decision making and the previous evidence that executive dysfunctions and structural brain changes exist in subjects who use illicit drugs, we applied fMRI and diffusion tensor imaging (DTI) techniques in a pilot investigation of heavy cannabis smokers and matched control subjects while performing a modification of the classic Stroop task. Marijuana smokers demonstrated significantly lower anterior cingulate activity in focal areas of the anterior cingulate cortex and higher midcingulate activity relative to controls, although both groups were able to perform the task within normal limits. Normal controls also demonstrated increased activity within the right dorsolateral prefrontal cortex (DLPFC) during the interference condition, while marijuana smokers demonstrated a more diffuse, bilateral pattern of DLPFC activation. Similarly, although both groups performed the task well, marijuana smokers made more errors of commission than controls during the interference condition, which were associated with different brain regions than control subjects. These findings suggest that marijuana smokers exhibit different patterns of BOLD response and error response during the Stroop interference condition compared to normal controls despite similar task performance. Furthermore, DTI measures in frontal regions, which include the genu and splenium of the corpus callosum and bilateral anterior cingulate white matter regions, showed no between group differences in fractional anisotropy (FA), a measure of directional coherence within white matter fiber tracts, but a notable increase in trace, a measure of overall isotropic diffusivity in marijuana smokers compared to controls. Overall, results from the present study indicate significant differences in the magnitude and pattern of signal intensity change within the anterior cingulate and the DLPFC during the Stroop interference subtest in chronic marijuana smokers compared to normal controls. Furthermore, although chronic marijuana smokers were able to perform the task reasonably well, the functional activation findings suggest they utilize different cortical processes from the control subjects in order to do so. Findings from this study are consistent with the notion that substance abusers demonstrate evidence of altered frontal neural function during the performance of tasks that involve inhibition and performance monitoring, which may affect the ability to make decisions.

Adolescent↗

PubMed2004

Four types of novelty-familiarity responses in associative recognition memory of humans.

Animal studies show that, like inferior temporal neurons, dorsolateral prefrontal and parietal neurons often respond more strongly to individual novel than to individual familiar stimuli. It is currently unclear whether the novelty preference of prefrontal and parietal neurons extends to associative memory. We used electromagnetic recordings (MEG/EEG) and functional magnetic resonance imaging in two groups of healthy young adults to identify neural populations outside the inferior temporal cortex that exhibit associative novelty (stronger responses for new than for old configurations of two familiar items), and to distinguish them from associative familiarity (stronger responses for old than for new configurations of two familiar items). Subjects were required to learn and were later tested for associations based on the spatial configurations of two stimuli (a face and a tool). At test, learned (old) and rearranged (new) spatial stimulus configurations had to be discriminated. This recognition memory test could only be solved through the associative relationship between individual items because all component items of the stimulus configurations were equally familiar. In both imaging modalities, right dorsolateral prefrontal cortex and right parietal cortex showed an associative novelty response, whereas the right superior temporal cortex showed an associative familiarity response. With EEG/MEG only, the right extrastriate cortex showed an early associative familiarity and a late associative novelty response, whereas the opposite pattern emerged in bilateral frontopolar cortex. Thus, through a multimodal approach, it was possible to identify four types of associative novelty/familiarity responses outside the inferior temporal cortex.

Adult↗

PubMed2004

Age-associated changes of cerebral glucose metabolic activity in both male and female deaf children: parametric analysis using objective volume of interest and voxel-based mapping.

Quantitative analysis of brain activity in the brains of children requires the establishment of age-associated norms. We investigated regional differences in age-associated changes in fluorodeoxyglucose (FDG) uptake in the developmental brains. From 87 (44 male and 43 female) deaf children from the age of 1 to 15, brain FDG positron emission tomography (PET) images were examined after spatial normalization, smoothing, and global normalization to identify brain regions showing a correlation between FDG uptake and age. Using population-based probabilistic volume of interests (VOIs), an objective VOI analysis was performed where normalized relative FDG uptake was measured and their correlations with age were examined in both genders. For the voxel-based analyses, the correlations with age were examined in a general linear model using statistical parametric mapping (SPM99). Both methods revealed that FDG uptake linearly increases with age both in the bilateral inferior prefrontal/orbitofrontal gyri and the right dorsomedial frontal gyrus and decreases in the inferior temporal gyrus and internal capsule white matter. Male children showed age-associated increases of FDG uptake in the right dorsomedial frontal gyrus, and female children in the left dorsolateral prefrontal cortex and thalamus. These changes in FDG uptake in various brain regions may suggest changes in synaptic density or regional activity resulting from normal maturation or deaf-induced adaptation. Caution should be exercised in interpreting the differences in the brain of child patients when compared with adult control's or with a different gender. Further research will be needed to examine if gender difference is manifested in the development rate of behavioral/cognitive functions in association with the age-associated changes of the right medial frontal (male) or the left dorsolateral prefrontal cortices.

Adolescent↗

PubMed2001

Responses of human frontal cortex to surprising events are predicted by formal associative learning theory.

Learning depends on surprise and is not engendered by predictable occurrences. In this functional magnetic resonance imaging (fMRI) study of causal associative learning, we show that dorsolateral prefrontal cortex (DLPFC) is associated specifically with the adjustment of inferential learning on the basis of unpredictability. At the outset, when all associations were unpredictable, DLPFC activation was maximal. This response attenuated with learning but, subsequently, activation here was evoked by surprise violations of the learned association. Furthermore, the magnitude of DLPFC response to a surprise event was sensitive to the relationship that had been learned and was predictive of subsequent behavioral change. In short, the physiological response properties of right DLPFC satisfied specific predictions made by associative learning theory.

Adult↗

PubMed2026

Distinct cellular phenotypes of language and executive decline in amyotrophic lateral sclerosis.

Cognitive manifestations, including impairments in language and executive functions, are seen in amyotrophic lateral sclerosis (ALS), but the underlying mechanisms remain unclear. We mapped prefrontal cortex regions from ALS patients by integrating spatial and single-nucleus transcriptomics in a cognitively stratified patient cohort. We uncover that cognitive impairment in ALS is associated with distinct patterns of neuronal dysfunction and glial-vascular dysregulation that vary by region and cognitive subtype. Executive dysfunction is linked to reduced mitochondrial and synaptic activity in deep-layer dorsolateral prefrontal cortex neurons, whereas language-related deficits track with a diffuse pan-regional response involving glial and vascular abnormalities. Our analyses, validated by multiplexed imaging, further identify signatures in the prefrontal cortex that span both motor and cognitive phenotypes, including a multicellular gliosis response. The findings reveal that clinical heterogeneity in ALS is driven by phenotype-specific cellular interactions in motor and non-motor regions of the brain.

Amyotrophic Lateral Sclerosis↗