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Results for “Dorsolateral Prefrontal Cortex”

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PubMed2006

Influence of the stress hormone cortisol on fear conditioning in humans: evidence for sex differences in the response of the prefrontal cortex.

The stress hormone cortisol is known to influence declarative memory and associative learning. In animals, stress has often been reported to have opposing effects on memory and learning in males and females. In humans, the effects of cortisol have mainly been studied at the behavioral level. The aim of the present experiment was to characterize the effects of a single cortisol dose (30 mg) on the hemodynamic correlates of fear conditioning. In a double-blind group comparison study subjects (17 females and 17 males) received 30 mg cortisol or placebo orally before participating in a discriminative fear conditioning paradigm. Results revealed that cortisol impaired electrodermal signs of learning (the first interval response) in males, while no conditioned SCRs emerged for the females independent of treatment. fMRI results showed that cortisol reduced activity for the CS+ > CS- comparison in the anterior cingulate, the lateral orbitofrontal cortex and the medial prefrontal cortex in males. Opposite findings (increase in these regions under cortisol) were detected in females. In addition, cortisol reduced the habituation in the CS+ > CS- contrast in the dorsolateral prefrontal cortex independent of sex. Finally, cortisol also modified the response to the electric shock (the UCS) by enhancing the activity of the anterior as well as the posterior cingulate. In sum, these findings demonstrate that in humans cortisol mostly influences prefrontal brain activation during fear conditioning and that these effects appear to be modulated by sex.

Adult↗

PubMed2006

Correlates of movement initiation and velocity in Parkinson's disease: A longitudinal PET study.

Limited data exist concerning the mechanisms that underlie the different motor features of Parkinson's disease (PD) and their course over time. Our aims were (1) to identify longitudinal changes in PD patients and (2) to determine the neural correlates of the changes in movement initiation and velocity that occur in the course the disease. Thirteen early stage PD patients were scanned twice off antiparkinsonian medication with H(2)15O PET. Imaging was performed at baseline and again after 2 years while the subjects performed a motor task that was kinematically controlled across time. Paced reaching movements were made towards targets that were presented in a predictable order. Measures of movement onset time (OT) and mean velocity (MV) were recorded during PET. OT and MV decreased significantly from baseline to follow-up. With advancing disease, increasing subcortical activation was detected in the pallidum bilaterally and in the left putamen. In the cortex, motor-related activation increased in the right pre-SMA, anterior cingulate cortex and the left postcentral gyrus. Progressive delays in movement initiation (OT) correlated with increases in the right dorsal premotor cortex (dPMC). Slowing of movement (MV) was associated with declining activation in the left dorsolateral prefrontal cortex and dPMC. Our data suggest that with advancing PD, motor performance is associated with the recruitment of brain regions normally involved in the execution of more complex tasks.

Adult↗

PubMed1996

Changes in cortical activity during mental rotation. A mapping study using functional MRI.

Mental imagery is an important cognitive method for problem solving, and the mental rotation of complex objects, as originally described by Shepard and Metzler (1971), is among the best studied mental imagery tasks. Functional MRI was used to observe focal changes in blood flow in the brains of 10 healthy volunteers performing a mental rotation task. On each trial, subjects viewed a pair of perspective drawings of three-dimensional shapes, mentally rotated one into congruence with the other, and then determined whether the two forms were identical or mirror-images. The control task, which we have called the 'comparison' condition, was identical except that both members of each pair appeared at the same orientation, and hence the same encoding, comparison and decision processes were used but mental rotation was not required. These tasks were interleaved with a baseline 'fixation' condition, in which the subjects viewed a crosshair. Technically adequate studies were obtained in eight of the 10 subjects. Areas of increased signal were identified according to sulcal landmarks and are described in terms of the Brodmann's area (BA) definitions that correspond according to the atlas of Talaraich and Tournoux. When the rotation task was contrasted with the comparison condition, all subjects showed consistent foci of activation in BAs 7a and 7b (sometimes spreading to BA 40): 88% had increased signal in middle frontal gyrus (BA 8) and 75% showed extrastriate activation, including particularly BAs 39 and 19, in a position consistent with area V5/human MT as localized by functional and histological assays. In more than half of the subjects, hand somatosensory cortex (3-1-2) was engaged, and in 50% of subjects there was elevated signal in BA 18. In frontal cortex, activation was above threshold in half the subjects in BAs 9 and/or 46 (dorsolateral prefrontal cortex). Some (four out of eight) subjects also showed signal increases in BAs 44 and/or 46. Premotor cortex (BA 6) was active in half of the subjects during the rotation task. There was little evidence for lateralization of the cortical activity or of engagement of motor cortex. These data are consistent with the hypothesis that mental rotation engages cortical areas involved in tracking moving objects and encoding spatial relations, as well as the more general understanding that mental imagery engages the same, or similar, neural imagery as direct perception.

Adult↗

PubMed2004

Cortical mechanisms of smooth pursuit eye movements with target blanking. An fMRI study.

Smooth pursuit eye movements are evoked by retinal image motion of visible moving objects and can also be driven by the internal representation of a target due to extraretinal mechanisms (e.g. efference copy). To delineate the corresponding neuronal correlates, functional magnetic resonance imaging at 1.5 T was applied during smooth pursuit at 10 degrees /s with continuous target presentation and target blanking for 1 s to 16 right-handed healthy males. Eye movements were assessed during scanning sessions by infra-red reflection oculography. Smooth pursuit performance was optimal when the target was visible but decreased to a residual velocity of about 30% of the velocity observed during continuous target presentation. Random effects analysis of the imaging data yielded an activation pattern for smooth pursuit in the absence of a visual target (in contrast to continuous target presentation) which included a number of cortical areas in which extraretinal information is available such as the frontal eye field, the superior parietal lobe, the anterior and the posterior intraparietal sulcus and the premotor cortex, and also the supplementary and the presupplementary eye field, the supramarginal gyrus, the dorsolateral prefrontal cortex, cerebellar areas and the basal ganglia. We suggest that cortical mechanisms such as prediction, visuo-spatial attention and transformation, multimodal visuomotor control and working memory are of special importance for maintaining smooth pursuit eye movements in the absence of a visible target.

Adult↗

PubMed1997

Enduring cognitive deficits and cortical dopamine dysfunction in monkeys after long-term administration of phencyclidine.

The effects of the psychotomimetic drug phencyclidine on the neurochemistry and function of the prefrontal cortex in vervet monkeys were investigated. Monkeys treated with phencyclidine twice a day for 14 days displayed performance deficits on a task that was sensitive to prefrontal cortex function; the deficits were ameliorated by the atypical antipsychotic drug clozapine. Repeated exposure to phencyclidine caused a reduction in both basal and evoked dopamine utilization in the dorsolateral prefrontal cortex, a brain region that has long been associated with cognitive function. Behavioral deficits and decreased dopamine utilization remained after phencyclidine treatment was stopped, an indication that these effects were not simply due to direct drug effects. The data suggest that repeated administration of phencyclidine in monkeys may be useful for studying psychiatric disorders associated with cognitive dysfunction and dopamine hypofunction in the prefrontal cortex, particularly schizophrenia.

Animals↗

PubMed2006

Integration of target and effector information in the human brain during reach planning.

To plan a reaching movement, the brain must integrate information about the location of the target with information about the limb selected for the reach. Here, we applied rapid event-related 3-T fMRI to investigate this process in human subjects (n = 16) preparing a reach following two successive visual instruction cues. One cue instructed which arm to use; the other cue instructed the location of the reach target. We hypothesized that regions involved in the integration of target and effector information should not only respond to each of the two instruction cues, but should respond more strongly to the second cue due to the added integrative processing to establish the reach plan. We found bilateral regions in the posterior parietal cortex, the premotor cortex, the medial frontal cortex, and the insular cortex to be involved in target-arm integration, as well as the left dorsolateral prefrontal cortex and an area in the right lateral occipital sulcus to respond in this manner. We further determined the functional properties of these regions in terms of spatial and effector specificity. This showed that the posterior parietal cortex and the dorsal premotor cortex specify both the spatial location of a target and the effector selected for the response. We therefore conclude that these regions are selectively engaged in the neural computations for reach planning, consistent with the results from physiological studies in nonhuman primates.

Adult↗

PubMed2004

Genetic and neurochemical modulation of prefrontal cognitive functions in children.

OBJECTIVE: The catechol O-methyltransferase (COMT) gene affects how long dopamine acts in the prefrontal cortex. The Methionine polymorphism, which results in a slower breakdown of prefrontal dopamine, is associated with better adult prefrontal cortex function. The authors investigated the relation between the COMT gene polymorphism and cognitive performance in children. METHOD: Children were tested on cognitive tasks that depend on the dorsolateral prefrontal cortex and seem to be sensitive to the level of dopamine there (dots-mixed task), depend on that neural region but appear insensitive to its dopamine content (self-ordered pointing), and depend on other neural systems (recall memory and mental rotation). After data collection, cheek swabs were obtained from all children. DNA was extracted and genotyped for the COMT gene with polymerase chain reaction. RESULTS: Children who were homozygous for the Methionine polymorphism performed significantly better on the dots-mixed task but not on others. CONCLUSIONS: The findings provide an existence proof that genotypic differences can relate to differences in cognitive performance in typically developing children. The authors achieved a level of specificity never previously attempted; the COMT polymorphism was found to be differentially related to performance on tasks linked to the same prefrontal region by whether cognitive requirements of the tasks were sensitive to the level of dopamine found. These results challenge accepted notions that since dopamine is important for some cognitive functions dependent on the prefrontal cortex, it is important for all. The differential sensitivity of distinct cognitive abilities to specific neurotransmitters may make possible targeted pharmacological interventions.

Adolescent↗

PubMed2000

Activity in human frontal cortex associated with spatial working memory and saccadic behavior.

We examined, with event-related fMRI, two hypotheses about the organization of human working memory function in frontal cortex: (1) that a region immediately anterior to the frontal eye fields (FEF) (superior frontal cortex, SFC) is specialized for spatial working memory (Courtney, et al., 1998); and (2) that dorsolateral prefrontal cortex (PFC) plays a privileged role in the manipulation of spatial stimuli held in working memory (Owen, et al., 1996; Petrides 1994). Our delayed-response task featured 2-D arrays of irregularly arranged squares that were highlighted serially in a random sequence. The Forward Memory condition required maintenance of the spatio-temporal sequence, the Manipulate Memory condition required reordering this sequence into a new spatially defined order, the Guided Saccade condition required saccades to highlighted squares in the array, but no memory, and the Free Saccade condition required self-paced, horizontal saccades. The comparison of fMRI signal intensity associated with 2-D saccade generation (Guided Saccades) versus fMRI signal intensity associated with the delay period of the working memorials condition revealed no evidence for greater working memory-related activity than saccade-related activity in SFC in any individual subject, nor at the level of the group, and greater 2-D saccade than delay-period activity in three of five subjects. These results fail to support the hypothesis that spatial working memory-related activity is represented preferentially in a region of SFC anterior to the FEF (Courtney, et al., 1998). The comparison of maintenance versus manipulation of spatio-temporal information in working memory revealed significantly greater activity associated with the latter in dorsolateral PFC, but not in ventrolateral PFC or in SFC. These results suggest that the delay-related function of SFC is limited to the maintenance of spatial information, and that this region does not support the nonmnemonic executive control functions supported by dorsolateral PFC. These results also indicate that the preferential recruitment of dorsolateral PFC for the manipulation of information held in working memory applies to tasks employing spatial stimuli, as well as to tasks employing verbal stimuli (D'Esposito, et al., 1999); Petrides et al., 1993; Postle et al., 1999).

Acoustic Stimulation↗

PubMed2007

fMRI study of effort and information processing in a working memory task.

It is unclear how effort translates into brain function. In this study we endeavored to identify the activity in a working memory task that is related to the allocation of mental resources. Such activity, if present, would be a likely candidate to explain how effort works in terms of brain function. Eleven healthy participants performed a Sternberg task with a memory-set of one, three, or five consonants in an fMRI study. Probe stimuli were either one consonant or one digit. We expected digits to be processed automatically and consonants to require working memory. Because the probe type was unpredictable and subjects had to respond as fast as possible, we expected subjects to allocate mental resources on the basis of the memory-set size, not the probe type. Accordingly, we anticipated that activity in regions involved in effort would be a function of the size of the memory-set, but independent of the type of probe. We found that the reaction-time for digits increased in line with our expectation of automatic processing and the reaction time for letters increased in line with our expectation of controlled processing. fMRI revealed that activity in the right ventral-prefrontal cortex changed as a function of effort. The ventral anterior cingulate cortex and hypothalamus showed reduced activity as a function of effort. Activity in regions regarded as pivotal for working memory (among others, the left dorsolateral prefrontal cortex, anterior cingulate cortex) appeared to be predominantly related to information processing and not involved in effort.

Adult↗

PubMed2001

Error-related brain activation during a Go/NoGo response inhibition task.

Inhibitory control and performance monitoring are critical executive functions of the human brain. Lesion and imaging studies have shown that the inferior frontal cortex plays an important role in inhibition of inappropriate response. In contrast, specific brain areas involved in error processing and their relation to those implicated in inhibitory control processes are unknown. In this study, we used a random effects model to investigate error-related brain activity associated with failure to inhibit response during a Go/NoGo task. Error-related brain activation was observed in the rostral aspect of the right anterior cingulate (BA 24/32) and adjoining medial prefrontal cortex, the left and right insular cortex and adjoining frontal operculum (BA 47) and left precuneus/posterior cingulate (BA 7/31/29). Brain activation related to response inhibition and competition was observed bilaterally in the dorsolateral prefrontal cortex (BA 9/46), pars triangularis region of the inferior frontal cortex (BA 45/47), premotor cortex (BA 6), inferior parietal lobule (BA 39), lingual gyrus and the caudate, as well as in the right dorsal anterior cingulate cortex (BA 24). These findings provide evidence for a distributed error processing system in the human brain that overlaps partially, but not completely, with brain regions involved in response inhibition and competition. In particular, the rostal anterior cingulate and posterior cingulate/precuneus as well as the left and right anterior insular cortex were activated only during error processing, but not during response competition, inhibition, selection, or execution. Our results also suggest that the brain regions involved in the error processing system overlap with brain areas implicated in the formulation and execution of articulatory plans.

Adolescent↗

PubMed1976

Single unit analysis of auditory processing in squirrel monkey frontal cortex.

Clicks, tone bursts and species-specific vocalizations were used to test 315 units isolated in the dorsolateral prefrontal cortex. Acoustic responses were detected in about 20% of the units. Responsive units were scattered throughout the explored area, although more units responsive to vocalizations were found in the vicinity of sulcus principalis. Vocalizations were effective stimuli, driving 68% of the acoustic units. However, only 19% responded exclusively to vocalizations. Clicks were effective for 65% of the acoustic units, 27% of which responded only to clicks. Tones activated 39% of the acoustic units. Units generally responded to tones over a wide frequency range. Responses to tones, clicks and vocalization were similar, both within the same unit and between units. The biggest difference related to the background activity of the unit: Low rate cells produced a small number of relatively well-timed discharges per stimulus; high rate cells produced a longer, more poorly-timed response. Vocalizations differed in their effectiveness according to their physical structure. Noisy calls elicited 69% of all responses, although they accounted for only one-third of the test vocalizations. We conclude that frontal acoustic units are involved with at least two functional mechanisms, one related to attending to a large class of sounds, the other related to the detection of sounds with high motivational significance.

Acoustic Stimulation↗

PubMed2005

Deficits in social knowledge following damage to ventromedial prefrontal cortex.

Patients with damage to the frontal lobes frequently exhibit impaired social behavior, but it is not clear which specific processes are disrupted. The authors investigated the ability to interpret nonverbal emotional expression in patients with lesions involving ventromedial (N=20) or dorsolateral prefrontal cortex (N=9) and in healthy volunteers (N=23). As hypothesized, only patients with ventromedial prefrontal lesions showed impaired task performance relative to normal comparison subjects. These results suggest that deficits in social knowledge, namely difficulty interpreting nonverbal emotional expression, contribute to the aberrant social behavior observed following ventromedial prefrontal cortex lesions.

Adult↗

PubMedDate not supplied

Brain region and sex differences in age association with brain volume: a quantitative MRI study of healthy young adults.

There is evidence that some brain regions show age-associated volume decline and that men undergo more accelerated cerebral aging than women. However, limited information is available on age-associated changes during young adulthood. The authors performed quantitative magnetic resonance imaging in 116 healthy young adults (57 men, 59 women; age range: 18-49 years) to evaluate the relationship of age and sex with volumes of frontal and temporal regions, including selected limbic structures and the basal ganglia. Regardless of sex, increasing age was moderately associated with decrease in total gray matter (GM) and mildly with increase in sulcal cerebrospinal fluid (CSF). Associations of age with reduced GM volume were observed in all frontal and temporal cortical regions and some basal ganglia structures, but were generally less prominent in subcortical regions. The associations were stronger for men than women in the dorsolateral prefrontal cortex. Thus, in young, healthy adults, age-associated changes are selective as well as sex-specific, with men experiencing greater volume decrement across age-groups than women, particularly in the dorsolateral prefrontal regions. Reduced GM and increased CSF in this age range suggests that the aging process is a continuum, with changes evident before senescence. Thus, the biological changes commonly attributed to "aging" do, in fact, begin much earlier in the life-cycle.

Adult↗

PubMed2006

The impact of processing load on emotion.

This event-related fMRI study examined the impact of processing load on the BOLD response to emotional expressions. Participants were presented with composite stimuli consisting of neutral and fearful faces upon which semi-transparent words were superimposed. This manipulation held stimulus-driven features constant across multiple levels of processing load. Participants made either (1) gender discriminations based on the face; (2) case judgments based on the words; or (3) syllable number judgments based on the words. A significant main effect for processing load was revealed in prefrontal cortex, parietal cortex, visual processing areas, and amygdala. Critically, enhanced activity in the amygdala and medial prefrontal cortex seen during gender discriminations was significantly reduced during the linguistic task conditions. A connectivity analysis conducted to investigate theories of cognitive modulation of emotion showed that activity in dorsolateral prefrontal cortex was inversely related to activity in the ventromedial prefrontal cortex. Together, the data suggest that the processing of task-irrelevant emotional information, like neutral information, is subject to the effects of processing load and is under top-down control.

Adult↗

PubMed1984

Selective prefrontal cortical projections to the region of the locus coeruleus and raphe nuclei in the rhesus monkey.

Descending cortical projections to the region of the noradrenergic locus coeruleus (LC) and the serotonergic dorsal and central superior raphe nuclei were analyzed in the rhesus monkey using anterograde labeling techniques. HRP pellets or tritiated leucine were injected into one of 7 cortical areas: the dorsolateral prefrontal cortex, the dorsomedial prefrontal cortex, the orbital prefrontal cortex, the parietal association cortex, somatosensory cortex, the anterior portion of the inferior temporal gyrus, and the posterior portion of the inferior temporal gyrus. Anterogradely labeled fibers were found in and adjacent to the LC and raphe nuclei only following the dorsolateral and dorsomedial prefrontal cortical injections. Terminal labeling was densest at rostral levels of the LC, particularly in the area directly medial to the nucleus. Labeled fibers could not be followed beyond caudal levels of the LC. The projections to the contralateral LC and raphe nuclei were similar to, but less dense than that to the ipsilateral region. Injections into cortical areas other than the dorsal prefrontal cortex resulted in anterograde labeling of the pontine nuclei or pyramids, but not the LC/raphe region. These data, in conjunction with studies in the rat, suggest that the dorsal prefrontal cortex may be the only cortical area to have direct influence on the LC and raphe nuclei and secondary influence on the monoaminergic innervation of large areas of cerebral cortex.

Animals↗

PubMed1998

Cortical control of saccades.

Saccadic eye movements are controlled by a cortical network composed of several oculomotor areas that are now accurately localized. Clinical and experimental studies have enabled us to understand their specific roles better. These areas are: (1) the parietal eye field (PEF) located in the intraparietal sulcus involved in visuospatial integration and in reflexive saccade triggering; (2) the frontal eye field (FEF), located in the precentral gyrus, involved in the preparation and the triggering of purposive saccades; and (3) the supplementary eye field (SEF) on the medial wall of the frontal lobe, probably involved in the temporal control of sequences of visually guided saccades and in eye-hand coordination. A putative cingulate eye field (CEF), located in the anterior cingulate cortex, would be involved in motivational modulation of voluntary saccades. Besides these motor areas, the dorsolateral prefrontal cortex (dlPFC) in the midfrontal gyrus is involved in reflexive saccade inhibition and visual short-term memory.

Cerebral Cortex↗

PubMed2004

Increased MEG activation in OCD reflects a compensatory mechanism specific to the phase of a visual working memory task.

We examined spatio-temporal patterns of evoked magnetoencephalographic signals (MEG) in patients with obsessive-compulsive disorder (OCD) during the Encoding, Retention, and Retrieval phases of a Delayed Matching-to-Sample working memory task (DMST). The question was whether the mechanisms of abnormally increased cortical excitability, frequently reported in OCD, relate to a global cortical disinhibition and unselective over-processing of stimuli or, alternatively, to a compensatory mechanism of effortful enhanced inhibitory control. The DMST-related network of activation in OCD was found similar to that of Controls, and to that reported in other neuroimaging studies. The pattern of increased MEG activation in OCD patients was phase specific. During the Encoding phase, the activation was enhanced in the region of anterior insula and reduced in the posterior-inferior parietal cortex. During Retention, the activation was reduced in the occipital, parietal, superior temporal sulcus, and dorsolateral prefrontal cortex (BA 6/8/9). During Retrieval, a significant increase of activation was found in the right anterior insula extending towards the orbital region and right superior temporal sulcus, along with reduced activation in the left parietal cortex. The performance accuracy was high in OCD and comparable to Controls, although the RTs were prolonged. The results are discussed as being consistent with the hypothesis of a compensatory mechanism of effortful inhibitory control. This mechanism may be a major contributor to the increased cortical activation during Encoding and, in particular, Retrieval of the DMST task in patients suffering OCD. The findings do not support the concept of a faulty working memory mechanism per se in OCD.

Adult↗

PubMed2005

CASL fMRI of subcortico-cortical perfusion changes during memory-guided finger sequences.

Arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) is an attractive alternative to BOLD fMRI. Nevertheless, current ASL fMRI techniques are limited by several factors that hamper more routine applications in humans. One of these factors is restricted brain coverage so that whole-brain ASL fMRI studies have never been reported. The present study tested the ability of a multislice continuous ASL (CASL) fMRI approach using a small surface coil placed on the subject's neck to map changes in regional cerebral blood flow (rCBF) throughout the brain while healthy individuals (N = 15) performed memory-guided sequential finger movements at a mean rate of approximately 0.5 Hz. As predicted by results from a large number of studies, reliable task-related increases in flow were detected across subjects not only in primary and associative cortical areas but also in subcortical brain regions. When normalized to baseline, rCBF increased 31% in the hand representation area (HRA) of left primary motor cortex (M1), 13% in the left supplementary motor area proper (SMA), 10% in the left dorsolateral prefrontal cortex (DLPFC), 10-18% in the bilateral intraparietal sulci, 6% in the HRA of left putamen, 10% in the left thalamus, and 17% in the right anterior cerebellum. In addition to these increases, 6% and 4% decreases in rCBF were detected in the HRA of the right M1 and the bilateral posterior cingulate sulci, respectively. These results demonstrate that perfusion-based fMRI using CASL with a separate labeling coil can now be used to characterize task-related flow changes in most of the brain volume with adequate accuracy and sensitivity.

Adult↗