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Results for “Dorsolateral Prefrontal Cortex”

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PubMed2003

Functional neuroanatomical correlates of traumatic stress revisited 7 years later, this time with data.

Seven years ago we wrote a paper about the functional neuroanatomical correlates of the effects of stress on memory; however, at that time there were no data on the effects of stress on the brain in human subjects. Since that time an abundance of research has been carried out using neuroimaging to investigate the neuroanatomical correlates of the effects of stress on memory. These studies have corroborated our initial hypotheses that the functional neuroanatomy of stress involves a circuit of brain areas involved in both stress and memory function, including the hippocampus, amygdala, cingulate and medial prefrontal cortex, and dorsolateral prefrontal cortex. These studies have gone a long way toward advancing our understanding of the neuroanatomical correlates of traumatic stress. This understanding, in turn, will promote the development of future treatment advances for stress-related psychiatric disorders such as posttraumatic stress disorder.

Brain↗

PubMed2006

Computerized neuropsychological examination of impulsiveness: A selective review.

There is a rapidly accumulating body of knowledge related to the neurobiology of impulsiveness from multidisciplinary neuropsychological and neuroimaging studies. This paper reviews recent research on impulsiveness in the context of neuropsychological theory and research. It has been emphasized that the controversy regarding the results of neuropsychological studies is related to different aspects of impulsiveness. The term "impulsivity" is related to more than one anatomical network among several brain regions. Impaired inhibition control, which has cognitive and behavioral dimensions, has a heterogeneous nature. Analysis of performance suggests that impulsivity includes three cognitive mechanisms: "prepotent inhibition," "interruptive inhibition" and "interference control,' each having separate neurological bases. Based on neuropsychological data it has been stated that both the orbitofrontal cortex, dorsolateral prefrontal cortex and anterior cingulate cortex are functionally disturbed among impulsive individuals. Bringing together knowledge from clinical experience, neuroimaging examination and neuropsychological assessment will lead to better and wider understanding of behavioral symptoms in clinical psychiatric practice.

Anxiety Disorders↗

PubMed1998

Cortical control of human classical conditioning: autonomic and positron emission tomography data.

A recent positron emission tomography (PET) study on brain mechanisms in classical, or Pavlovian, conditioning is reviewed. The PET data were compared with skin conductance data recorded off-line. The participants were five men who participated in three different experimental phases. In the first (habituation) phase, a tone was repeated 24 times at random intervals. In the second (acquisition) phase, the tone was paired with a brief shock to the wrist. In the third (extinction) phase, the tone was presented alone again. Statistical parametric mapping analysis of the PET data showed significantly increased activation of the right hemisphere in the orbitofrontal cortex, dorsolateral prefrontal cortex, inferior and superior frontal cortices, and inferior and middle temporal cortices. In the left hemisphere, only Area 19 and the superior frontal cortex showed significant activation. The findings are discussed within a theoretical framework that argues for different brain mechanisms in acquisition and extinction in classical conditioning.

Adolescent↗

PubMed2002

The neural substrate of orientation short-term memory and resistance to distractor items.

We used Positron Emission Tomography to map the neural substrate of human short-term memory for orientation, defined as retaining a single orientation in memory over a long delay, by comparing a successive discrimination task with a 6-s delay to the same task with a brief 0.3 s delay and to an identification control task. Short-term memory engaged the superior parietal lobe bilaterally, the middle occipital gyrus bilaterally and the left dorsolateral prefrontal cortex. In addition, we studied the resistance to a distractor item by comparing the successive discrimination task with long delay, with and without an intervening distractor stimulus. This manipulative process engaged left ventral premotor cortex and left dorsolateral prefrontal cortex. The activation of left dorsolateral prefrontal cortex is interpreted as reflecting co-ordination between task components. These results, combined with those of two previous studies using an identical reduction strategy, underscore the functional heterogeneity in the prefrontal cortex during short-term and working memory.

Adolescent↗

PubMed2003

Basal-corticofrontal circuits in schizophrenia and obsessive-compulsive disorder: a controlled, double dissociation study.

BACKGROUND: Several lines of research suggest that prefrontal cortex dysfunctions observed in obsessive compulsive disorder (OCD) and schizophrenia (SKZ) are linked to two partially independent neuroanatomic systems: the ventromedial prefrontal cortex and the dorsolateral prefrontal cortex, with different neuroanatomic connections, including the striatum. The primary aim of this study was to test this hypothesis using a double dissociation study of neuropsychological tasks performance of the dorsolateral prefrontal cortex and ventromedial prefrontal cortex. METHODS: We administered the Wisconsin Card Sorting Test, the Gambling Task, and the four-disk version of the Tower of Hanoi to 110 SKZ and 67 OCD patients and 56 control subjects. RESULTS: A clear double dissociation of Wisconsin Card Sorting Test and Gambling Task performances was found, with SKZ patients performing the Wisconsin Card Sorting test significantly worse than OCD patients and control subjects and OCD patients performing the Gambling Task significantly worse than SKZ and control subjects. Both SKZ and OCD patients performed the Tower of Hanoi significantly worse than control subjects. CONCLUSIONS: Results from our double dissociation study confirm the hypothesis of involvement of different frontal lobe subsystems within basal-corticofrontal circuits function in SKZ and OCD.

Adult↗

PubMed2002

Memory trace in prefrontal cortex: theory for the cognitive switch.

The dorsolateral prefrontal cortex in human and non-human primates functions as the highest-order executor for the perception-action cycle. According to this view, when perceptual stimuli from the environment are novel or complex, the dorsolateral prefrontal cortex serves to set consciously a goal-directed scheme which broadly determines an action repertory to meet the particular demand from the environment. In this respect, the dorsolateral prefrontal cortex is a short-term activation device with the properties of a cognitive switch', because it couples a particular set of perceptual stimuli to a particular set of actions. Here, I suggest that, in order for the organism to react systematically to the environment, neural traces for the switch function must be stored in the brain. Thus, the highest-order, perception-action interface function of the dorsolateral prefrontal cortex per se depends on permanently stored neural traces in the dorsolateral prefrontal cortex and related structures. Such a memory system may be located functionally between two of the well-documented memory systems in the brain: the declarative memory system and the procedural memory system. Finally, based on available neurophysiological data, the possible mechanisms underlying the formation of cognitive switch traces are proposed.

Animals↗

PubMed2002

Cortical control of spatial memory in humans: the visuooculomotor model.

We review current knowledge of the cortical control of spatial memory, studied using visuooculomotor paradigms. Spatial memory is an essential cognitive process that can be involved in preparing motor responses. Our knowledge of spatial memory in humans recently has progressed thanks to the use of ocular saccades as a convenient model of motor behavior. Accuracy of memory-guided saccades, made to the remembered locations of visual targets, is a reflection of spatial memory. For the performance of memory-guided saccades with brief delays (up to 15-20 seconds), that is, involving short-term spatial memory, lesion studies have shown that the posterior parietal cortex, the dorsolateral prefrontal cortex, and the frontal eye field play significant roles. Studies of memory-guided saccades using transcranial magnetic stimulation have suggested that the right posterior parietal cortex is involved at the initial stage (<300 milliseconds) of visuospatial integration, whereas the dorsolateral prefrontal cortex in both hemispheres controls the following phase of short-term memorization, the frontal eye field mainly serving to trigger saccades. The new concept of a medium-term spatial memory has emerged from a behavioral study of memory-guided saccades in normal subjects, showing a paradoxical spontaneous improvement of spatial memory after delays of approximately 20 seconds. Lesion studies have shown that the parahippocampal cortex could specifically control this medium-term spatial memory. Last, different experimental and clinical arguments suggest that, after a few minutes, the hippocampal formation finally takes over the control of spatial memory for long-term spatial memorization. Therefore, spatial memory involved in the memorization of visual items could be successively controlled by the dorsolateral prefrontal cortex (short-term spatial memory), the parahippocampal cortex (medium-term spatial memory), and the hippocampal formation (long-term spatial memory), depending on specific periods of times. The applicability of this simple visuooculomotor model of spatial memory to other types of stimuli and general motoricity has yet to be confirmed.

Animals↗

PubMed2001

Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia.

OBJECTIVE: The dorsolateral prefrontal cortex has been implicated in both working memory and the pathophysiology of schizophrenia. A relationship among dorsolateral prefrontal cortex activity, working memory dysfunction, and symptoms in schizophrenia has not been firmly established, partly because of generalized cognitive impairments in patients and task complexity. Using tasks that parametrically manipulated working memory load, the authors tested three hypotheses: 1) patients with schizophrenia differ in prefrontal activity only when behavioral performance differentiates them from healthy comparison subjects, 2) dorsolateral prefrontal cortex dysfunction is associated with poorer task performance, and 3) dorsolateral prefrontal cortex dysfunction is associated with cognitive disorganization but not negative or positive symptoms. METHOD: Seventeen conventionally medicated patients with schizophrenia and 16 healthy comparison subjects underwent functional magnetic resonance imaging while performing multiple levels of the "n-back" sequential-letter working memory task. RESULTS: Patients with schizophrenia showed a deficit in physiological activation of the right dorsolateral prefrontal cortex (Brodmann's area 46/9) in the context of normal task-dependent activity in other regions, but only under the condition that distinguished them from comparison subjects on task performance. Patients with greater dorsolateral prefrontal cortex dysfunction performed more poorly. Dorsolateral prefrontal cortex dysfunction was selectively associated with disorganization symptoms. CONCLUSIONS: These results are consistent with the hypotheses that working memory dysfunction in patients with schizophrenia is caused by a disturbance of the dorsolateral prefrontal cortex and that this disturbance is selectively associated with cognitive disorganization. Further, the pattern of behavioral performance suggests that dorsolateral prefrontal cortex dysfunction does not reflect a deficit in the maintenance of stimulus representations per se but points to deficits in more associative components of working memory.

Adult↗

PubMed2003

Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms.

OBJECTIVE: The authors examined dopamine transporter density in the orbitofrontal cortex, dorsolateral prefrontal cortex, and amygdala in methamphetamine users and assessed the relationship of these measures to the subjects' clinical characteristics. METHOD: Positron emission tomography with [(11)C]WIN 35,428 was used to examine the regions of interest in 11 methamphetamine users and nine healthy comparison subjects. Psychiatric symptoms were evaluated with the Brief Psychiatric Rating Scale. RESULTS: Dopamine transporter density in the three regions studied was significantly lower in the methamphetamine users than in the comparison subjects. The lower dopamine transporter density in the orbitofrontal and dorsolateral prefrontal cortex was significantly correlated with the duration of methamphetamine use and the severity of psychiatric symptoms. CONCLUSIONS: Chronic methamphetamine use may cause dopamine transporter reduction in the orbitofrontal cortex, dorsolateral prefrontal cortex, and amygdala in the brain. Psychiatric symptoms in methamphetamine users may be attributable to the decrease in dopamine transporter density in the orbitofrontal cortex and the dorsolateral prefrontal cortex.

Adult↗

PubMed1996

Evidence for the importance of dopamine for prefrontal cortex functions early in life.

There is considerable evidence that dorsolateral prefrontal cortex subserves critical cognitive abilities even during early infancy and that improvement in these abilities is evident over roughly the next 10 years. We also know that (a) in adult monkeys these cognitive abilities depend critically on the dopaminergic projection to prefrontal cortex and (b) the distribution of dopamine axons within dorsolateral prefrontal cortex changes, and the level of dopamine increases, during the period that infant monkeys are improving on tasks that require the cognitive abilities dependent on prefrontal cortex. To begin to look at whether these cognitive abilities depend critically on the prefrontal dopamine projection in humans even during infancy and early childhood we have been studying children who we hypothesized might have a selective reduction in the dopaminergic innervation of prefrontal cortex and a selective impairment in the cognitive functions subserved by dorsolateral prefrontal cortex. These are children treated early and continuously for the genetic disorder, phenylketonuria (PKU). In PKU the ability to convert the amino acid, phenylalanine (Phe), into another amino acid, tyrosine (Tyr), is impaired. This causes Phe to accumulate in the bloodstream to dangerously high levels and the plasma level of Tyr to fall. Widespread brain damage and severe mental retardation result. When PKU is moderately well controlled by a diet low in Phe (thus keeping the imbalance between Phe and Tyr in plasma within moderate limits) severe mental retardation is averted, but deficits remain in higher cognitive functions. In a four-year longitudinal study we have found these deficits to be in the working memory and inhibitory control functions dependent upon dorsolateral prefrontal cortex in PKU children with plasma Phe levels 3-5 times normal. The fact that even infants showed these impairments suggests that dopaminergic innervation to prefrontal cortex is critical for the proper expression of these abilities even during the first year of life. To test the hypothesis about the underlying biological mechanism we have created the first animal model of early and continuously treated PKU. As predicted, the experimental animals had reduced levels of dopamine and the dopamine metabolite, homovanillic acid (HVA), in prefrontal cortex and showed impaired performance on delayed alternation, a task dependent on prefrontal cortex function. Noradrenaline levels were unaffected; however some reduction in serotonin levels and in dopamine levels outside the prefrontal cortex was found. If prefrontal cortex functions are vulnerable in children with a moderate plasma Phe:Tyr imbalance because of the special properties of the dopamine neurons that project to prefrontal cortex, then other dopamine neurons that share those same properties should also be vulnerable in these children. The dopamine neurons in the retina share these properties (i.e. unusually high firing and dopamine turnover rates), and we have found that PKU children with plasma Phe levels 3-5 times normal are impaired in their contrast sensitivity, a behavioural measure sensitive to retinal dopamine levels.

Animals↗

PubMed2000

Gender difference in premotor activity during active tactile discrimination.

To investigate possible gender differences in tactile discrimination tasks, we measured cerebral blood flow of seven men and seven women using positron emission tomography and (15)O water during tactile tasks performed with the right index finger. A nondiscrimination, somatosensory control task activated the left primary sensorimotor cortex and the left parietal operculum extending to the posterior insula without any gender difference. Compared with the control task, discrimination tasks activated the superior and inferior parietal lobules bilaterally, right dorsal premotor cortex, and dorsolateral prefrontal cortex in both genders, consistent with the notion of right hemisphere involvement during exploratory attentional movements. In both genders, symmetric activation of the superior and inferior parietal lobules and asymmetric activation of the right dorsolateral prefrontal cortex were confirmed. The former is consistent with the spatial representation of the tactile input and the latter with the spatial working memory. However, activation of the dorsal premotor cortex was asymmetric in men, whereas it was symmetric in women, the gender difference being statistically significant. This may suggest gender differences in motor programs for exploration in manipulospatial tasks such as tactile discrimination with active touch, possibly by greater interhemispheric interaction through the dorsal premotor cortices in women than in men.

Adult↗

PubMed2003

Prefrontal cortex contribution to associative recognition memory in humans: an event-related functional magnetic resonance imaging study.

The present event-related fMRI study examined in ten healthy participants neural correlates of recognition memory for intact, rearranged, and new pairs of visual stimuli. The correct categorization of both intact and rearranged pairs relative to pairs of new, never presented before stimuli relies on the retrieval of associative information whereas the discrimination of rearranged pairs from intact pairs additionally involves a recall-to-reject process by which subjects retrieve additional information to reach a recognition decision. Relative to new pairs, both intact and rearranged pairs yielded activation in inferior prefrontal cortex bilaterally and left dorsolateral prefrontal cortex. Relative to intact pairs, rearranged pairs were associated with increased activity in left dorsolateral prefrontal cortex. The latter could reflect the neural correlates of a recall-to-reject process, a pivotal process of associative recognition memory.

Adult↗

PubMed2005

Lateral and medial hypofrontality in first-episode schizophrenia: functional activity in a medication-naive state and effects of short-term atypical antipsychotic treatment.

OBJECTIVE: The dorsolateral prefrontal cortex and the anterior cingulate cortex are critical components of the brain circuitry underlying executive control. The objective of this study was to investigate control-related dorsolateral prefrontal cortex functioning and conflict-related anterior cingulate cortex functioning in a group of never medicated first-episode schizophrenia patients to determine whether both regions show dysfunction at illness onset. A second objective was to assess short-term effects of atypical antipsychotic medication on dorsolateral prefrontal cortex and anterior cingulate cortex functioning. METHOD: First-episode schizophrenia patients (N=23) and healthy comparison subjects (N=24) underwent event-related fMRI and performed a cognitive task designed to functionally dissociate the two regions. Four weeks after initiation of pharmacotherapy for patients, a subset of 11 patients and 16 comparison subjects underwent a repeat assessment. RESULTS: At baseline, patients exhibited hypoactivation in the dorsolateral prefrontal cortex and anterior cingulate cortex. After 4 weeks of antipsychotic treatment, the patients demonstrated improved functioning in the anterior cingulate cortex but not in the dorsolateral prefrontal cortex. CONCLUSIONS: These findings confirm the presence of dorsolateral prefrontal cortex dysfunction early in the course of schizophrenia and suggest that anterior cingulate cortex functioning may be altered at illness onset as well. Results also suggest that anterior cingulate cortex functioning may be especially sensitive to remedial antipsychotic treatment effects. These findings are consistent with an emerging literature documenting short-term benefits of atypical antipsychotic medication for the neural circuitry underlying cognitive deficits in schizophrenia.

Adult↗

PubMed2000

Extrastriatal dopamine D2 and D3 receptors in early and advanced Parkinson's disease.

OBJECTIVE: To investigate whether dopamine D2 and D3 receptor subtypes (D2/3Rs) outside the caudate-putamen are affected in PD. BACKGROUND: Alterations in striatal D2-like dopamine receptors in PD have been extensively demonstrated using PET, but there are no studies focusing on extrastriatal D2/3Rs. METHODS: Fourteen unmedicated patients with idiopathic early PD with predominantly left-sided symptoms, 14 levodopa-medicated patients with advanced PD, and 20 normal age-matched controls were examined using PET. PET scanning was performed with a novel high-affinity D2/3R radioligand ([11C]FLB 457) and a PET scanner in three-dimensional mode. RESULTS: In advanced PD, the binding potential of [11C]FLB 457 in the dorsolateral prefrontal cortex was decreased by 40% (p < 0.01), in the anterior cingulate cortex by 20% (p < 0.01), and in the medial thalamus by 17% (p < 0.05) compared with healthy controls. In early PD, the extrastriatal [11C]FLB 457 binding potentials were not significantly different compared with the control group. However, the binding potential in the anterior cingulate cortex (29%; p < 0. 05) was higher in early PD compared with advanced PD. CONCLUSIONS: These results imply that the D2/3 receptor subtypes outside the striatum are affected in advanced PD but not in the early stages of the disease, and that this receptor decline is present in the anterior cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus.

Brain↗

PubMed1995

Role of human prefrontal cortex in attention control.

Without a functioning dorsolateral prefrontal cortex, humans are stimulus bound and have little confidence in their ability to interact with the environment. Deficits in inhibitory control of external and internal processes coupled with impaired temporal coding of stimuli and detection capacity for novel events leave the patient functioning in a noisy internal environment without critical spatiotemporal cues. Some of these proposals are similar to those of Nauta (104). Based on connectivity of the prefrontal cortex, Nauta suggested that this region was ideally suited to generate and evaluate internal models of action. It is proposed that, in addition to this generation function, the prefrontal cortex is crucial for detecting changes in the external environment and for discriminating internally and externally derived models of the world. This chapter has described a cascade of deficits that result from damage to the dorsolateral prefrontal cortex. Awareness of the sensory world, and of the apparent stream of internal and external events, is impaired by deficits in novelty detection. Changes in the world, internal or external, may not be noticed in a noisy internal milieu. These deficits contribute to impaired reality monitoring and to a subsequent lack of confidence in behavior. An inability to bridge temporal gaps and temporally sequence internal events, together with deficits in inhibitory control systems, contribute to an impairment in the ability to generate coherent representations of alternate or counterfactual realities.

Animals↗

PubMed1999

The relationship between dorsolateral prefrontal N-acetylaspartate measures and striatal dopamine activity in schizophrenia.

BACKGROUND: Pathology of dorsolateral prefrontal cortex and dysregulation of dopaminergic neurons have been associated with the pathophysiology of schizophrenia, but how these phenomena relate to each other in patients has not been known. It has been hypothesized that prefrontal cortical pathology might induce both diminished steady-state and exaggerated responses of dopaminergic neurons to certain stimuli (e.g., stress). We examined the relationship between a measure of prefrontal neuronal pathology and striatal dopamine activity in patients with schizophrenia and in a nonhuman primate model of abnormal prefrontal cortical development. METHODS: In the patients, we studied in vivo markers of cortical neuronal pathology with NMR spectroscopic imaging and of steady-state striatal dopamine activity with radioreceptor imaging. In the monkeys, we used the same NMR technique and in vivo microdialysis. RESULTS: Measures of N-acetyl-aspartate concentrations (NAA) in dorsolateral prefrontal cortex strongly and selectively predicted D2 receptor availability in the striatum (n = 14, rho = -.64, p < .01), suggesting that the greater the apparent dorsolateral prefrontal cortex pathology, the less the steady-state dopamine activity in these patients. A similar relationship between NAA measures in dorsolateral prefrontal cortex and steady-state dopamine concentrations in the striatum was found in the monkeys (n = 5, rho = .70, p < .05). We then tested in the same monkeys the relationship of prefrontal NAA and striatal dopamine overflow following amphetamine infusion into dorsolateral prefrontal cortex. Under these conditions, the relationship was inverted, i.e., the greater the apparent dorsolateral prefrontal cortex pathology, the greater the dopamine release. CONCLUSIONS: These data demonstrate direct relationships between putative neuronal pathology in dorsolateral prefrontal cortex and striatal dopamine activity in human and nonhuman primates and implicate a mechanism for dopamine dysregulation in schizophrenia.

Adult↗

PubMed2005

Segregated neural representation of distinct emotion dimensions in the prefrontal cortex-an fMRI study.

Emotions are frequently characterized by distinct dimensions such as valence, intensity, and recognition. However, the exact neural representation of these dimensions in different prefrontal cortical regions remains unclear. One of the problems in revealing prefrontal cortical representation is that the very same regions are also involved in cognitive functions associated with emotion processing. We therefore conducted an fMRI study involving the viewing of emotional pictures (using the International Affective Picture System; IAPS) and controlled for associated cognitive processing like judgment and preceding attention. Functional activation was correlated with subjective post-scanning ratings of valence, intensity, and recognition. Valence significantly correlated with the functional response in ventromedial prefrontal cortex (VMPFC) and dorsolateral prefrontal cortex (DLPFC), intensity with activation in ventrolateral prefrontal cortex (VLPFC) and dorsomedial prefrontal cortex (DMPFC), and recognition with the functional response in perigenual anterior cingulate cortex (PACC). In conclusion, our results indicate segregated neural representation of the different emotion dimensions in different prefrontal cortical regions.

Adult↗

PubMed2001

Parsing cognition in schizophrenia using saccadic eye movements: a selective overview.

Eye movements provide a behavioural measure of sensorimotor processing and higher cognitive functions of the brain. With the development of novel paradigms that can be used for the study of various cognitive operations, saccadic eye movements in particular, have become increasingly popular. Patients with schizophrenia have neurocognitive impairments that can be readily investigated with these paradigms. From animal, human lesion and neuroimaging studies, the cerebral centres underlying saccadic eye movements have been identified. The areas of the prefrontal cortex include the dorsolateral prefrontal cortex, the frontal eye fields, the supplementary eye fields, and the anterior cingulate cortex. Pathology of saccadic eye movements, therefore, provides information on the functional status of the underlying neural circuitry in brain disorders such as schizophrenia. In this paper, we evaluate: (i) methodological considerations that are central to the design and application of saccadic paradigms; (ii) brain activation that is associated with saccadic paradigms; (iii) recent findings in healthy subjects and schizophrenic patients; (iv) saccadic abnormalities in other psychiatric and neurological disorders and in individuals at risk for developing schizophrenia.

Animals↗