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Results for “Dorsolateral Prefrontal Cortex”

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PubMed1994

Decreased regional cortical gray matter volume in schizophrenia.

OBJECTIVE: The authors hypothesized that cortical gray matter volume reduction in schizophrenia is greatest in the heteromodal association cortex. This area comprises a highly integrated, reciprocally interconnected system that coordinates higher order cortical functions. METHOD: Total brain and regional gray matter volumes were calculated in 46 schizophrenic patients and 60 age and sex-matched comparison subjects by using magnetic resonance images. Disease specificity was examined by assessing 27 patients with bipolar disorder. Approximations to the dorsolateral prefrontal cortex, inferior parietal lobule, and superior temporal gyrus were selected as regions of interest for the heteromodal association cortex. Occipital and sensorimotor areas were used as comparison regions to test the hypothesis for regional specificity. RESULTS: Gray matter volume was reduced in schizophrenic patients in index regions even after covariance for overall brain volume, sex, and age. Bipolar disorder patients did not exhibit heteromodal gray matter reduction. Comparison regions did not differ among the three groups. Global gray matter volume was not different among groups after covariance for global brain volume. Comprehensive individual region post hoc analysis found no additional gray matter differences. CONCLUSIONS: These findings support the theory of disproportionate reduction of gray matter volume in the heteromodal association cortex specific to schizophrenia.

Adult↗

PubMed2004

Shared and distinct neurophysiological components of the digits forward and backward tasks as revealed by functional neuroimaging.

The digits forward (DF) and backward (DB) tasks are widely used neuropsychological measures believed to tap overlapping systems of phonological processing and working memory. Studies of focal brain lesions have partially elucidated the brain regions essential for these tasks; however relatively little information exists on the underlying functional neuroanatomy in the intact brain. We therefore examined the shared and separate neural systems of these tasks in two positron emission tomography (PET) experiments. In Experiment 1, eight healthy participants performed verbal DF, DB, and a sensorimotor control task during measurement of regional cerebral blood flow (rCBF). DF and DB each activated frontal, parietal, and cerebellar regions as well as prominently activating medial occipital cortex. To eliminate possible visuospatial confounds, Experiment 2 replicated the first experiment in six additional healthy participants who were blindfolded during the study. No differences in activation were found between the two experimental groups. Combined data from both experiments demonstrate that DF and DB rely upon a largely overlapping functional neural system associated with working memory, most notably right dorsolateral prefrontal cortex (DLPFC) and bilateral inferior parietal lobule (IPL) as well as the anterior cingulate, a region associated with attentional effort. The degree of activation increased linearly with increasing task difficulty in DF. DB additionally recruited bilateral DLPFC, left IPL, and Broca's area. Medial occipital cortex (including higher and lower visual processing areas) was robustly activated in both DF and DB and could not be attributed to visual processing per se, suggesting a possible visual imagery strategy for these aural-verbal tasks.

Adolescent↗

PubMedDate not supplied

Eye movement task related to frontal lobe functioning in children with attention deficit disorder.

OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) has been postulated to be related to dysfunction of the prefrontal cortex. In the oculomotor delayed response task, a subject is cued as to where he or she should look (shift visual gaze to) but must delay a short period and then shift gaze to the location where the cue previously existed but no longer exists (a memory-guided saccade). Dependent measures from this task provide information on three functions tentatively tied to prefrontal cortex functioning: the ability to inhibit response (during the delay period), preparation of motor response (inversely tied to the latency of shifting visual gaze), and accuracy of working visuospatial memory (accuracy of the memory-guided saccade). METHOD: Thirteen children with ADHD and 10 normal controls, aged 9 to 12 years, were tested using an 800-msec delay period. RESULTS: Children with ADHD showed, relative to normal controls, deficits on inhibiting response during the delay period but no differences in latency (preparation of motor response) or accuracy of visuospatial memory. CONCLUSIONS: These results support the hypothesis that the primary deficit in ADHD is difficulty in inhibition of response. This deficit may be associated with pathology located outside the dorsolateral prefrontal cortex.

Adolescent↗

PubMed1987

Implications of normal brain development for the pathogenesis of schizophrenia.

Recent research on schizophrenia has demonstrated that in this disorder the brain is not, strictly speaking, normal. The findings suggest that nonspecific histopathology exists in the limbic system, diencephalon, and prefrontal cortex, that the pathology occurs early in development, and that the causative process is inactive long before the diagnosis is made. If these findings are valid and not epiphenomena, then the pathogenesis of schizophrenia does not appear to fit either traditional metabolic, posttraumatic, or neurodegenerative models of adult mental illness. The data are more consistent with a neurodevelopmental model in which a fixed "lesion" from early in life interacts with normal brain maturational events that occur much later. Based on neuro-ontological principles and insights from animal research about normal brain development, it is proposed that the appearance of diagnostic symptoms is linked to the normal maturation of brain areas affected by the early developmental pathology, particularly the dorsolateral prefrontal cortex. The course of the illness and the importance of stress may be related to normal maturational aspects of dopaminergic neural systems, particularly those innervating prefrontal cortex. Some implications for future research and treatment are considered.

Adolescent↗

PubMed2004

Planning ability in Parkinson's disease is influenced by the COMT val158met polymorphism.

Parkinson's disease (PD) patients show a range of executive deficits involving dopaminergic transmission in the prefrontal cortex. In this study, we have investigated the impact of catechol-O-methyl-transferase (COMT) val(158)met polymorphisms on performance of the Tower of London (TOL) test of planning by PD patients. Motor and cognitive assessments were performed on 288 patients as part of a population-based study of PD. These patients were subsequently genotyped for the COMT val(158)met polymorphism. Patients with high activity COMT genotypes performed significantly better at the TOL task than those with low activity genotypes. Subgroup analyses suggest that this effect is greatest in patients exposed to dopaminergic agents. We hypothesise that the inferior performance in patients with the low activity COMT genotype is attributable to a state of relative hyperdopaminergic activity in the dorsolateral prefrontal cortex compared with that in the striatum. We suggest that polymorphisms of common genes, which regulate central nervous system dopaminergic transmission, can influence some of the phenotypic manifestations of PD.

Adult↗

PubMed2005

Decision-making and impulse control after frontal lobe injuries.

PURPOSE OF REVIEW: For a long time, the prefrontal cortex has been considered a 'nonfunctional' brain area, and understanding its function has lagged behind other areas. This is no longer true since appreciation of the vital role that this brain region plays in adaptive behaviors, and especially decision-making, is now evident more than ever. The present review highlights recent progress made in this area of research. RECENT FINDINGS: Decision-making is a term often referred to in the psychological literature as one of the 'executive functions' that play a role in managing (like an executive) other cognitive functions, such as memory, attention, and language. Considerable research efforts have been directed towards differentiating various processes of executive functions, but much of this effort in the past has focused on the dorsolateral prefrontal cortex sector. Here we will review findings that address decision-making and its link to the ventromedial prefrontal cortex. SUMMARY: Decision-making impairments as encountered in neurological and psychiatric patients are costly in terms of individual human suffering and in financial terms. In addition to its obvious value in advancing fundamental knowledge in neuroscience, understanding the neural mechanisms of decision-making is likely to have important practical consequences, including the understanding and management of neuropsychiatric disorders such as addiction, as well as the management of a considerable number of elderly people suffering from a decline in cognitive functions critical for decision-making, in spite of relatively intact memory and general intellect, which impact real-life matters that are important to themselves and their family.

Brain Injuries↗

PubMed2005

mRNA expression of AMPA receptors and AMPA receptor binding proteins in the cerebral cortex of elderly schizophrenics.

L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate the majority of the fast excitatory transmission in the CNS. To determine whether gene expression of AMPARs and/or AMPAR binding proteins, which control response/sensitivity of AMPAR-bearing neurons to glutamate, are altered in schizophrenia, mRNA expression and abundance of AMPAR subunits (GluR1-4) and several AMPAR binding proteins (SAP97, PICK1, GRIP, ABP) were measured in the dorsolateral prefrontal cortex (DLPFC) and the occipital cortex of elderly schizophrenia patients (n = 36) and matched normal controls (n = 26) by quantitative real-time PCR. The mRNA expression of GluR1, GluR4, and GRIP in the DLPFC and expression of the GluR4, GRIP, and ABP in the occipital cortex were significantly elevated in schizophrenics. GluR1 and ABP mRNA expression in the occipital cortex and GluR2, GluR3, SAP97, and PICK1 expression in either cortical area were not significantly altered. The data also demonstrated significant differences in the abundances of mRNAs encoding GluR1-4 subunits (GluR2 > GluR3 > GluR1 > GluR4) and of AMPAR binding proteins (SAP97 > PICK1 > GRIP > ABP) in both diagnostic groups. GluR2 (58-64%) and GluR3 (24-29%) were the major components of the AMPAR mRNA in both cortical areas, implying that the major AMPAR complexes in the human cortex are probably those containing GluR2 and GluR3 subunits. Small but significant differences in the amounts of GluR2, GluR3, and GRIP mRNAs were detected between the two cortical areas: more GluR3 and GRIP but less GluR2 were detected in the DLPFC than in the occipital cortex.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Functional magnetic resonance imaging of proactive interference during spoken cued recall.

Though lesions to frontal cortex can increase susceptibility to interference from previously established but irrelevant memories ("proactive interference"), the specific regions underlying this problem are difficult to determine because the lesions are typically large and heterogeneous. We used event-related functional magnetic resonance imaging to investigate proactive interference in healthy volunteers performing an "AB-AC" paired-associate cued-recall paradigm. At Study, participants intentionally encoded semantically related visual word pairs, which were changed three times (high interference), repeated three times (low interference), or presented only once. At Test, participants were presented with the first word of each pair and attempted to recall its most recent associate from the Study phase. To overcome the problem of image artifacts caused by speech-related head motion, we cued speech during a gap between image acquisitions. Regions in left inferior frontal cortex and bilateral frontopolar cortex showed interference effects during both Study and Test. The pattern of responses in these regions differed, however. Left inferior frontal regions showed mainly reduced responses associated with low interference, whereas frontopolar regions showed mainly increased responses associated with high interference. When incorrect as well as correct trials were analyzed at Test, additional activation associated with high interference was observed in right dorsolateral prefrontal cortex. These data suggest that distinct regions within prefrontal cortex subserve different functions in the presence of proactive interference during cued recall.

Artifacts↗

PubMed2004

Neuronal responses related to long-term recognition memory processes in prefrontal cortex.

Much evidence indicates that prefrontal cortex plays an important role in long-term recognition memory processes. Here, we report primate prefrontal neuronal responses carrying information necessary for long-term visual recognition memory. The responses of many neurons signaled stimulus familiarity even when the period over which stimuli had to be remembered extended to 24 hr. Such responses occurred frequently in ventromedial, orbitofrontal, and anterior cingulate but not dorsolateral prefrontal cortex. Prefrontal information processing, as indicated by the response latencies, started after that in inferior temporal cortex and might be related to retrieval processes, as responses were typically larger for familiar than for novel stimuli.

Action Potentials↗

PubMed1995

Functional neuroanatomy of antisaccade eye movements investigated with positron emission tomography.

Increasing interest in the role of the frontal lobe in relation to psychiatric and neurologic disorders has popularized tests of frontal function. One of these is the antisaccade task, in which both frontal lobe patients and schizophrenics are impaired despite normal performance on (pro)saccadic tasks. We used position emission tomography to examine the cerebral blood flow changes associated with the performance of antisaccades in normal individuals. We found that the areas of the brain that were more active during antisaccades than saccades were highly consistent with the oculomotor circuit, including frontal eye fields (FEFs), supplementary motor area, thalamus, and putamen. Superior parietal lobe and primary visual cortex were also significantly more active. In contrast, prefrontal areas 46 and 9 were not more active during antisaccades than during saccades. Performance of some frontal patients on the antisaccade task has been likened to a bradykinesia, or the inability to initiate a willed movement. It is the necessity to will the movement and inhibit competing responses that intuitively linked this task to the dorsolateral prefrontal cortex in frontal patients. Our data suggest that it is the FEFs in prefrontal cortex that differentiate between conditions in which the required oculomotor response changes while the stimulus remains the same, rather than areas 46 and 9, which, in human studies, have been linked to the performance of complex cognitive tasks. Such a conclusion is consistent with single-unit studies of nonhuman primates that have found that the FEFs, the executive portion of the oculomotor circuit, can trigger, inhibit, and set the target of saccades.

Adult↗

PubMed2004

Negative correlation between right prefrontal activity during response inhibition and impulsiveness: a fMRI study.

Behavioral disinhibition in Go/No-Go task is thought to be associated with impulsiveness in humans. Recent imaging studies showed that neural circuits involving diverse areas of the frontal cortex and other association cortex sites such as the parietal cortex are implicated in the inhibition of response during No-Go trials. The aim of the present study was to investigate the association between regional cerebral activation during No-Go trials and impulsiveness. Seventeen right-handed healthy volunteers participated in the study. We used functional magnetic resonance imaging to measure the brain activation during a Go/No-Go task. The Barratt Impulsiveness Scale, 11(th) version (BIS-11) was used to measure impulsiveness. Activated regions included the right middle frontal gyrus and the inferior parietal lobe, which is consistent with previous neuroimaging studies. A negative correlation was observed between the motor impulsiveness of BIS-11 and No-Go-related activation in the right dorsolateral prefrontal cortex (RDLPFC). Our results suggest that the RDLPFC is the area most sensitive to differences in individual motor impulsiveness and its activity may be an indicator of the individual capacity for response inhibition.

Adult↗

PubMed2005

New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical electrostimulations.

Despite a better understanding of the organization of the cortical network underlying the semantic system, very few data are currently available regarding its anatomo-functional connectivity. Here, we report on a series of 17 patients operated on under local anaesthesia for a cerebral low-grade glioma located within the dominant hemisphere. Prior to and during resection, intraoperative electrical stimulation was used to map sensorimotor and language structures so that permanent neurological deficits could be avoided. In a number of cases, cortical and subcortical stimulation caused semantic paraphasias. Using postoperative MRI, we correlated these functional findings with the anatomical locations of the sites where semantic errors were elicited by stimulation, especially at the subcortical level, with the aim of studying the connectivity underlying the semantic system. In temporal gliomas, cortical sites involved in semantic processing were found around the posterior part of the superior temporal sulcus, with subcortical pathways reproducibly located under the depth of this sulcus. In insular gliomas, although stimulation elicited no semantic disturbances at the cortical level, such semantic paraphasias were generated at the level of the anterior floor of the external capsule. In frontal tumours, cortical regions implicated in semantics were detected in the lateral orbitofrontal region and dorsolateral prefrontal cortex, with subcortical fibres located under the inferior frontal sulcus. All these eloquent structures were systematically preserved, thereby avoiding permanent postoperative deficits. Our results provide arguments in favour of the existence of a main ventral subcortical pathway underlying the semantic system, within the dominant hemisphere, joining the two essential cortical epicentres of this network: the posterior and superior temporal areas, and the orbitofrontal and dorsolateral prefontal regions. Such a ventral stream might anatomically partly correspond to the inferior fronto-occipital fasciculus.

Adolescent↗

PubMed2004

Targeting the dopamine D1 receptor in schizophrenia: insights for cognitive dysfunction.

BACKGROUND AND RATIONALE: Reinstatement of the function of working memory, the cardinal cognitive process essential for human reasoning and judgment, is potentially the most intractable problem for the treatment of schizophrenia. Since deficits in working memory are associated with dopamine dysregulation and altered D(1) receptor signaling within prefrontal cortex, we present the case for targeting novel drug therapies towards enhancing prefrontal D(1) stimulation for the amelioration of the debilitating cognitive deficits in schizophrenia. OBJECTIVES: This review examines the role of dopamine in regulating cellular and circuit function within prefrontal cortex in order to understand the significance of the dopamine dysregulation found in schizophrenia and related non-human primate models. By revealing the associations among prefrontal neuronal function, dopamine and D(1) signaling, and cognition, we seek to pinpoint the mechanisms by which dopamine modulates working memory processes and how these mechanisms may be exploited to improve cognitive function. RESULTS AND CONCLUSIONS: Dopamine deficiency within dorsolateral prefrontal cortex leads to abnormal recruitment of this region by cognitive tasks. Both preclinical and clinical studies have demonstrated a direct relationship between prefrontal dopamine function and the integrity of working memory, suggesting that insufficient D(1) receptor signaling in this region results in cognitive deficits. Moreover, working memory deficits can be ameliorated by treatments that augment D(1) receptor stimulation, indicating that this target presents a unique opportunity for the restoration of cognitive function in schizophrenia.

Animals↗

PubMed1997

Visuomotor transformations for reaching to memorized targets: a PET study.

Positron emission tomography (PET) was used to identify cortical and subcortical regions involved in the control of reaching to visual targets. Regional cerebral blood flow (rCBF) was measured in eight healthy subjects using H2(15)O PET during the performance of three different tasks. All tasks required central fixation while a 400-ms target was flashed every 5 s at a random location around a virtual circle centered on the fixation target. Additional instructions differed according to the task: (i) visual detection of the target without overt responses; (ii) immediate pointing to the most recent target in the sequence, and (iii) pointing to the previous target in the sequence. By design, the two motor tasks differed in the cognitive processing required. In each trial of immediate pointing, the spatial location of only the most recent target needed to be processed. In each trial of pointing to the previous, instead, while the most recent target was stored in memory for the movement of the next trial, the previous target had to be retrieved from memory to direct the current movement. Limb trajectories were comparable between the two motor tasks in terms of most spatiotemporal parameters examined. Significant rCBF increases were identified using analysis of covariance and t statistics. Compared with visual detection there was activation of primary sensorimotor cortex, ventrolateral precentral gyrus, inferior frontal gyrus in the opercular region, supramarginal gyrus, and middle occipital gyrus, all these sites in the hemisphere (left) contralateral to the moving limb, and cerebellar vermis, during both immediate pointing and pointing to the previous. During immediate pointing there was additional activation of left inferior parietal lobule close to the intraparietal sulcus, and when compared with pointing to the previous, dorsolateral prefrontal cortex bilaterally. During pointing to the previous, instead, there was additional activation of supplementary motor cortex, anterior and midcingulate, and inferior occipital gyrus in the left hemisphere; superior parietal lobule, supramarginal gyrus, and posterior hippocampus in the right hemisphere; lingual gyri and cerebellar hemispheres bilaterally; anterior thalamus; and pulvinar. The activation of two partially distinct cerebral networks in these two motor tasks reflects the different nature of signal processing involved. In particular, the specific activation of intraparietal sulcus and prefrontal cortex in immediate pointing appears characteristic of a network for visuospatial working memory. By contrast, the corticolimbic network engaged in pointing to the previous could mediate spatial attention and the sequence of encoding, recording, and decoding of spatial memories required by a dual task with two competing targets.

Adult↗

PubMed2005

When visual perception causes feeling: enhanced cross-modal processing in grapheme-color synesthesia.

In synesthesia, stimulation of one sensory modality (e.g., hearing) triggers a percept in another, non-stimulated sensory modality (e.g., vision). Likewise, perception of a form (e.g., a letter) may induce a color percept (i.e., grapheme-color synesthesia). To date, the neural mechanisms underlying synesthesia remain to be elucidated. We disclosed by fMRI, while controlling for surface color processing, enhanced activity in the left intraparietal cortex during the experience of grapheme-color synesthesia (n = 9). In contrast, the perception of surface color per se activated the color centers in the fusiform gyrus bilaterally. The data support theoretical accounts that grapheme-color synesthesia may originate from enhanced cross-modal binding of form and color. A mismatch of surface color and grapheme induced synesthetically felt color additionally activated the left dorsolateral prefrontal cortex (DLPFC). This suggests that cognitive control processes become active to resolve the perceptual conflict resulting from synesthesia.

Acoustic Stimulation↗

PubMed2002

Right prefrontal rTMS treatment for refractory auditory command hallucinations - a neuroSPECT assisted case study.

Auditory command hallucinations probably arise from the patient's failure to monitor his/her own 'inner speech', which is connected to activation of speech perception areas of the left cerebral cortex and to various degrees of dysfunction of cortical circuits involved in schizophrenia as supported by functional brain imaging. We hypothesized that rapid transcranial magnetic stimulation (rTMS), by increasing cortical activation of the right prefrontal brain region, would bring about a reduction of the hallucinations. We report our first schizophrenic patient affected with refractory command hallucinations treated with 10 Hz rTMS. Treatment was performed over the right dorsolateral prefrontal cortex, with 1200 magnetic stimulations administered daily for 20 days at 90% motor threshold. Regional cerebral blood flow changes were monitored with neuroSPECT. Clinical evaluation and scores on the Positive and Negative Symptoms Scale and the Brief Psychiatric Rating Scale demonstrated a global improvement in the patient's condition, with no change in the intensity and frequency of the hallucinations. NeuroSPECT performed at intervals during and after treatment indicated a general improvement in cerebral perfusion. We conclude that right prefrontal rTMS may induce a general clinical improvement of schizophrenic brain function, without directly influencing the mechanism involved in auditory command hallucinations.

Attention↗

PubMed1996

A positron emission tomography study of the short-term maintenance of verbal information.

Positron emission tomography (PET) was used to investigate the functional brain anatomy associated with the short-term maintenance of linguistic information. Subjects were asked to retain five related words, unrelated words, or pseudowords silently for the duration of a 40 sec PET scan. When brain activity during these short-term maintenance tasks was compared with a visual fixation control task, increases were found bilaterally in the dorsolateral prefrontal cortex and cerebellum, and medially in the supplementary motor area. Furthermore, effects of stimulus condition and recall performance were found in the left frontal operculum. To investigate the role of articulatory systems in the maintenance of verbal information, regional activation was compared across the maintenance tasks and a covert articulation task (silent counting). The cerebellum was active in both task conditions, whereas activation in prefrontal regions was specific to the maintenance condition. Conversely, greater activation was found in a left middle insular region in the silent counting than in the maintenance tasks. Based on converging results in this and previous studies, dorsolateral prefrontal cortical areas appear to contribute to the maintenance of both verbal and nonverbal information, whereas left frontal opercular regions appear to be involved specifically in the rehearsal of verbal material. Contrary to results found in other studies of working memory, activation was not found in the inferior parietal cortex, suggesting that this area is involved in aspects of stimulus encoding and retrieval, which were minimized in the present study.

Adult↗

PubMed2001

Attention versus intention in the primate premotor cortex.

One challenging issue in cognitive neuroscience has been to dissociate a variety of mental processes from one another in order to elucidate brain functions. Attention, in particular, has been a recurrent issue because of its strong links with perceptual, cognitive, and motor performances. This paper reviews data from neurophysiological experiments designed to dissociate neuronal activity related to visuo-spatial attention from preparatory activity in the monkey brain. Cell activity was recorded from the dorsal premotor area (PMd) and compared to the dorsolateral prefrontal cortex (DLPf), from which it receives inputs. PMd has been implicated in the planing and execution of voluntary movements (PMd), and the majority of its cells are active during tasks with instructed delay time. However, the activity of many PMd cells is not specifically correlated with movement preparation, as is observed when the animal is attending to a visual stimulus, although the proportion of attention-related cells is much lower than in the DLPf. The distribution of attention-related and intention-related neurons within PMd tends to vary along the rostrocaudal axis, with the former more frequent rostrally (PMdr) and the latter more predominant caudally (PMdc). In a functional magnetic resonance imaging (fMRI) study in humans, we compared the premotor activation in two tasks: a spatial attention/memory task and a motor preparation task. The results suggest a rostrocaudal specialization within PMd of the human brain, with attention-related activation rostrally and medially and intention-related activation caudally. These studies indicate strong similarities in the functional organization of dorsal premotor cortex of human and monkey.

Animals↗