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Results for “Dorsolateral Prefrontal Cortex”

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PubMed2001

The context of uncertainty modulates the subcortical response to predictability.

Implicit motor learning tasks typically involve comparisons of subject responses during a sequence versus a random condition. In neuroimaging, brain regions that are correlated with a sequence are described, but the temporal relationship of sequence versus nonsequence conditions is often not explored. We present a functional magnetic resonance imaging (fMRI) study describing activation related to sequential predictability in an implicit sensorimotor learning task and the history (context) dependence of these effects. Participants regarded four squares displayed horizontally across a screen and pressed a button when any one of the four targets was illuminated in a particular color. A repeating spatial sequence with varying levels of predictability was embedded within a random color presentation. Both the right dorsolateral prefrontal cortex (R DLPFC) and right caudate displayed a positive correlation to increasing predictability, whereas the left posterior parietal cortex (L PPC) displayed a negative correlation. However, the activation changes within the caudate were significant when transitioning from high predictability to low predictability but not for the reverse case, suggesting a sensitivity not only to predictability but to order effects as well. These results support the hypothesized relationship between basal ganglia and visuomotor sequential learning, but demonstrate the importance of context upon sequence learning.

Adult↗

PubMed2005

Neural correlates of memory for items and for associations: an event-related functional magnetic resonance imaging study.

Although results from cognitive psychology, neuropsychology, and behavioral neuroscience clearly suggest that item and associative information in memory rely on partly different brain regions, little is known concerning the differences and similarities that exist between these two types of information as a function of memory stage (i.e., encoding and retrieval). We used event-related functional magnetic resonance imaging to assess neural correlates of item and associative encoding and retrieval of simple images in 18 healthy subjects. During encoding, subjects memorized items and pairs. During retrieval, subjects made item recognition judgments (old vs. new) and associative recognition judgments (intact vs. rearranged). Relative to baseline, item and associative trials activated bilateral medial temporal and prefrontal regions during both encoding and retrieval. Direct contrasts were then performed between item and associative trials for each memory stage. During en- coding, greater prefrontal, hippocampal, and parietal activation was observed for associations, but no significant activation was observed for items at the selected threshold. During recognition, greater activation was observed for associative trials in the left dorsolateral prefrontal cortex and superior parietal lobules bilaterally, whereas item recognition trials showed greater activation of bilateral frontal regions, bilateral anterior medial temporal areas, and the right temporo-parietal junction. Post hoc analyses suggested that the anterior medial temporal activation observed during item recognition was driven mainly by new items, confirming a role for this structure in novelty detection. These results suggest that although some structures such as the medial temporal and prefrontal cortex play a general role in memory, the pattern of activation in these regions can be modulated by the type of information (items or associations) interacting with memory stages.

Adult↗

PubMed2005

Where memory meets attention: neural substrates of negative priming.

The negative priming (NP) effect refers to the observed increase in identification time for a current target stimulus or stimulus feature (the "probe") that has been employed as a distractor stimulus or stimulus feature on the previous trial (the "prime"), representing strong evidence that ignored information is actively processed to a high level by selective attention systems. However, theoretical accounts of NP differ in whether they attribute the effect to processes of selective inhibition or episodic memory retrieval. Here we derived neurophysiological predictions from the rival "selective inhibition" and "episodic retrieval" models of NP, and employed event-related fMRI in a color-naming Stroop task to assess neural responses to probe trials that were subject to either no priming or negative priming. Compared to no-priming probe trials, NP resulted in increased activation of the right dorsolateral prefrontal cortex, in a region which has been closely linked with episodic memory retrieval functions. NP was also accompanied by activation of the right thalamus, particularly the mediodorsal nucleus, which has been implicated in the pathophysiology of schizophrenia, a condition associated with diminished NP effects. Our results support the proposal that ignored stimulus information is fully encoded in memory, and that episodic retrieval, not selective inhibition, of such information affects selective attention performance on subsequent trials.

Adolescent↗

PubMed2006

Reward-period activity in primate dorsolateral prefrontal and orbitofrontal neurons is affected by reward schedules.

Reward-period activity observed in the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC) is thought to represent the detection of reward delivery. To investigate whether this activity plays the same role in these areas, we examined this activity under different reward schedules and whether the reward schedule has similar effects on this activity in each of these areas. A monkey performed an oculomotor delayed-response (ODR) task under two reward schedules. In the ODR-1 schedule, the monkey received a large amount of reward only after four successful trials, whereas in the ODR-2 schedule, it received a small amount of reward after every successful trial. Although reward-period activity was observed in both areas, more neurons exhibited this activity in the OFC. Reward-period activity was modulated by the proximity to reward delivery in both areas and this feature was observed more frequently in the OFC. The onset time of this activity also gradually advanced depending on the proximity to reward delivery. Moreover, many OFC neurons with this activity responded to free reward delivery. These results indicate that reward-period activity in the OFC represents the detection of reward delivery and that the gradual change in the magnitude and the onset time of this activity represents the expectation of reward delivery. Similar features of reward-period activity were observed in DLPFC neurons, although a significant number of DLPFC neurons did not respond to free reward delivery and no advance was observed in the onset time of this activity. These results suggest that reward-period activity in the DLPFC participates in whether or not correct performance was achieved. Thus, although similar reward-period activity was observed in both areas, the activity in the OFC represents the detection of reward delivery and is affected by the monkey's motivational state, whereas that in the DLPFC seems to participate in monitoring whether or not the necessary performance is achieved.

Action Potentials↗

PubMed2006

Age-related changes in brain activity across the adult lifespan.

A number of theories have emerged to explain the well-studied changes in memory that occur with age. Many of these theories invoke mechanisms that have the potential to affect multiple cognitive domains, in addition to memory. Such mechanisms include alterations in attentional or inhibitory function, or dysfunction of specific brain areas, such as the frontal lobes. To gain insight into these mechanisms, we used functional magnetic resonance imaging to examine brain activity during encoding and recognition tasks in young, middle-aged, and older adults to identify correlations between age and brain activity across the various tasks. The goal was to see whether these correlations were task-specific or common across tasks, and to determine whether age differences emerged in a linear fashion over the adult years. Across all memory tasks, at both encoding and recognition, linear increases of activity with age were found in areas normally decreased during task performance (e.g., medial frontal and parietal regions), whereas activity in regions with task-related activation (e.g., dorsolateral prefrontal cortex) decreased with age. These results suggest that there is a gradual, age-related reduction in the ability to suspend non-task-related or "default-mode" activity and engage areas for carrying out memory tasks. Such an alteration in the balance between default-mode and task-related activity could account for increased vulnerability to distraction from irrelevant information, and thereby affect multiple cognitive domains.

Adult↗

PubMed1999

Neural basis of endogenous and exogenous spatial orienting. A functional MRI study.

Whole-brain functional magnetic resonance imaging (MRI) was used to examine the neural substrates of internally (endogenous) and externally (exogenous) induced covert shifts of attention. Thirteen normal subjects performed three orienting conditions: endogenous (location of peripheral target predicted by a central arrow 80% of the time), exogenous (peripheral target preceded by noninformative central cue). Behavioral results indicated faster reaction times (RTs) for valid than for invalid trials for the endogenous condition but slower RTs for valid than for invalid trials for the exogenous condition (inhibition of return). The spatial extent and intensity of activation was greatest for the endogenous condition, consistent with the hypothesis that endogenous orienting is more effortful (less automatic) than exogenous orienting. Overall, we did not observe distinctly separable neural systems associated with the endogenous and exogenous orienting conditions. Both exogenous and endogenous orienting, but not the control condition, activated bilateral parietal and dorsal premotor regions, including the frontal eye fields. These results suggest a specific role for these regions in preparatory responding to peripheral stimuli. The right dorsolateral prefrontal cortex (BA 46) was activated selectively by the endogenous condition. This finding suggests that voluntary, but not reflexive, shifts of attention engage working memory systems.

Adult↗

PubMed2006

Consequences, action, and intention as factors in moral judgments: an FMRI investigation.

The traditional philosophical doctrines of Consequentialism, Doing and Allowing, and Double Effect prescribe that moral judgments and decisions should be based on consequences, action (as opposed to inaction), and intention. This study uses functional magnetic resonance imaging to investigate how these three factors affect brain processes associated with moral judgments. We find the following: (1) Moral scenarios involving only a choice between consequences with different amounts of harm elicit activity in similar areas of the brain as analogous non-moral scenarios; (2) Compared to analogous non-moral scenarios, moral scenarios in which action and inaction result in the same amount of harm elicit more activity in areas associated with cognition (such as the dorsolateral prefrontal cortex) and less activity in areas associated with emotion (such as the orbitofrontal cortex and temporal pole); (3) Compared to analogous non-moral scenarios, conflicts between goals of minimizing harm and of refraining from harmful action elicit more activity in areas associated with emotion (orbitofrontal cortex and temporal pole) and less activity in areas associated with cognition (including the angular gyrus and superior frontal gyrus); (4) Compared to moral scenarios involving only unintentional harm, moral scenarios involving intentional harm elicit more activity in areas associated with emotion (orbitofrontal cortex and temporal pole) and less activity in areas associated with cognition (including the angular gyrus and superior frontal gyrus). These findings suggest that different kinds of moral judgment are preferentially supported by distinguishable brain systems.

Adolescent↗

PubMed2006

Automaticity and reestablishment of executive control-an fMRI study.

The ability to exert control over automatic behavior is of particular importance as it allows us to interrupt our behavior when the automatic response is no longer adequate or even dangerous. However, despite the literature that exists on the effects of practice on brain activation, little is known about the neuroanatomy involved in reestablishing executive control over previously automatized behavior. We present a visual search task that enabled participants to automatize according to defined criteria within about 3 hr of practice and then required them to reassert control without changing the stimulus set. We found widespread cortical activation early in practice. Activation in all frontal areas and in the inferior parietal lobule decreased significantly with practice. Only selected prefrontal (Brodmann's areas [BAs] 9/46/8) and parietal areas (BAs 39/40) were specifically reactivated when executive control was required, underlining the crucial role of the dorsolateral prefrontal cortex in executive control to guide our behavior.

Adolescent↗

PubMed1990

Remediation of cognitive deficits in schizophrenia.

Studies have suggested that schizophrenia is characterized by an impairment in the dorsolateral prefrontal cortex that prevents learning of some elementary information processing tasks. To test this hypothesis, the authors administered the Wisconsin Card Sorting Test to 16 schizophrenic inpatients with standard instructions and either contingent or noncontingent reinforcement. Performance was markedly impaired under each condition. A second cohort (N = 12) was tested after receiving instructions plus rehearsal and feedback. These subjects' performance was comparable to nonpatient norms and was maintained on a subsequent day. The results indicate that deficits in performance on the Wisconsin Card Sorting Test are remediable, whether or not they are due to neurological impairment.

Adult↗

PubMed1992

Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins.

OBJECTIVE: The authors previously reported that in monozygotic twins discordant for schizophrenia the affected twin almost invariably had a smaller anterior pes hippocampus, measured with magnetic resonance imaging (MRI), and invariably had less regional cerebral blood flow (rCBF) in the dorsolateral prefrontal cortex during performance of the Wisconsin Card Sorting Test. The present study was an investigation of the relationship between hippocampal pathology and prefrontal hypofunction in the same twin pairs. METHOD: Nine pairs of monozygotic twins discordant for schizophrenia underwent MRI scanning for determination of anterior hippocampal volume and xenon-inhalation rCBF testing for determination of prefrontal physiological activation associated with the Wisconsin Card Sorting Test. RESULTS: The differences within twin pairs on the MRI and rCBF measures were strongly and selectively correlated. Specifically, the more an affected twin differed from the unaffected twin in left hippocampal volume, the more they differed in prefrontal physiological activation during the Wisconsin Card Sorting Test. In the affected twins as a group, prefrontal activation was strongly related to both left and right hippocampal volume. These relationships were not found in the group of unaffected twins. CONCLUSIONS: This finding is consistent with the notion that schizophrenia involves pathology of and dysfunction within a widely distributed neocortical-limbic neural network that has been implicated in, among other activities, the performance of cognitive tasks requiring working memory.

Adult↗

PubMed1998

Functional magnetic resonance imaging of human brain activation during cue-induced cocaine craving.

OBJECTIVE: Functional magnetic resonance imaging (MRI) was used to test whether brain activation was detectable in regions previously associated with cocaine cue-induced craving. METHOD: Blood oxygenation level dependent (BOLD) functional activation was measured during presentation of audiovisual stimuli containing alternating intervals of drug-related and neutral scenes to six male subjects with a history of crack cocaine use and six male comparison subjects. RESULTS: Significant activation was detected in the anterior cingulate and left dorsolateral prefrontal cortex in the cocaine-using group. In addition, a correlation between self-reported levels of craving and activation in these regions was found. CONCLUSIONS: These results suggest that functional MRI may be a useful tool to study the neurobiological basis of cue-induced craving.

Adult↗

PubMed1999

Limbic activation during cue-induced cocaine craving.

OBJECTIVE: Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during cue-induced craving in humans. METHOD: Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug-related and cocaine-related videos and during resting baseline conditions. RESULTS: During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the non-drug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex). CONCLUSIONS: These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards.

Adult↗

PubMed1999

Recalling word lists reveals "cognitive dysmetria" in schizophrenia: a positron emission tomography study.

OBJECTIVE: This study explored the neural circuitry used during recall of unstructured verbal material in schizophrenic patients and healthy volunteer subjects. METHOD: The subjects were 13 healthy volunteers and 14 schizophrenic patients. All patients were free of medication, and all subjects were right-handed. Two experimental cognitive conditions were used: recall of novel and practiced word lists (two 15-item lists from the Rey Auditory Verbal Learning Test). Both active recall tasks were compared with an eyes-closed resting baseline condition. A nonparametric randomization test was used to determine within- and between-group differences in regional cerebral blood flow. RESULTS: Performance on both the practiced and novel memory tasks was nonsignificantly different in the patients and control subjects. During the novel memory task, the patients showed decreased flow in the right anterior cingulate, right thalamus, and bilateral cerebellum (left greater than right) relative to the control subjects. When recalling the practiced word lists, the patients showed decreased flow in the left dorsolateral prefrontal cortex, bilateral medial frontal cortex, left supplementary motor area, left thalamus, left cerebellar regions, anterior vermis, and right cuneus. CONCLUSIONS: Patients with schizophrenia fail to activate cortical-cerebellar-thalamic-cortical circuitry during recall of both well-learned and novel word lists.

Adult↗

PubMed2006

Neuroimaging of inhibitory control areas in children with attention deficit hyperactivity disorder who were treatment naive or in long-term treatment.

OBJECTIVE: Difficulty with response inhibition is a cardinal symptom of attention deficit hyperactivity disorder (ADHD), combined type. Prefrontal and cingulate brain regions are known to be involved in inhibitory control. Event-related functional magnetic resonance imaging (fMRI) might establish if these regions differ in their activity in ADHD children relative to healthy comparison subjects. METHOD: Fifteen healthy comparison subjects and 17 children with ADHD, combined type, completed fMRI studies while performing the Stop Signal Task. Eight ADHD subjects were treatment naive; the remainder had a history of long-term treatment with stimulants, but they were medication free at the time of the fMRI. No subject had a learning disorder or a comorbid psychiatric condition (other than oppositional defiant disorder in the ADHD subjects). RESULTS: Both the ADHD and comparison subjects activated the right dorsolateral prefrontal cortex on "stop" trials relative to "go" trials; this increase was greater in ADHD subjects. When inhibition was unsuccessful (relative to successful inhibition), healthy comparison subjects strongly activated the anterior cingulate cortex and the left ventrolateral prefrontal cortex. In contrast, the ADHD subjects did not show these differences. Activations in treatment-naive and ADHD subjects treated in the long term did not differ significantly in any brain regions. CONCLUSIONS: In relation to comparison subjects, ADHD subjects failed to activate the anterior cingulate cortex and the left ventrolateral prefrontal cortex after unsuccessful inhibition. These findings appear in treatment-naive ADHD individuals and are unlikely to be an artifact of long-term treatment with stimulants or of abrupt termination of stimulants before imaging.

Adolescent↗

PubMed2006

Increased brain activation during working memory in cognitively intact adults with the APOE epsilon4 allele.

OBJECTIVE: Altered patterns of brain activity during cognitive tasks have been demonstrated using functional magnetic resonance imaging (fMRI) in mild cognitive impairment and Alzheimer's disease. However, there have been few studies of adults at genetic risk for Alzheimer's disease prior to the onset of symptoms. The purpose of this study was to determine whether brain activation patterns associated with working memory differ as a function of apolipoprotein E (APOE) genotype in cognitively intact adults. METHOD: Participants were cognitively intact, healthy adults who completed genotyping, comprehensive neuropsychological testing, and structural and functional neuroimaging. Twenty-two participants had the APOE epsilon3/epsilon3 genotype, and 13 participants had the APOE epsilon3/epsilon4 genotype. The study employed an auditory verbal N-back task to probe working memory-related brain activity. RESULTS: The epsilon3/epsilon3 and epsilon3/epsilon4 groups did not differ in demographic characteristics, cognitive ability, mood, or in-scanner task performance. The epsilon3/epsilon4 group showed greater activity during working memory in the medial frontal and parietal regions bilaterally and in the right dorsolateral prefrontal cortex. There were no regions in which the epsilon3/epsilon3 group showed greater activation than the epsilon3/epsilon4 group. CONCLUSIONS: These results indicate that differences in brain activity are evident in cognitively intact individuals who are at risk for late-onset Alzheimer's disease by virtue of their APOE allele status. As neuroprotective interventions become available, early detection will increase in importance. The combination of genetic and functional neuroimaging strategies may prove useful for monitoring individuals at risk for Alzheimer's disease before the onset of cognitive symptoms.

Adult↗

PubMed2007

A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has been reported to be as effective as electroconvulsive therapy (ECT) for major depression. The authors conducted a multicenter randomized, controlled trial to test the equivalence of rTMS with ECT. METHOD: Forty-six patients with major depression referred for ECT were randomly assigned to either a 15-day course of rTMS of the left dorsolateral prefrontal cortex (N=24) or a standard course of ECT (N=22). The primary outcome measures were the score on the 17-item Hamilton Depression Rating Scale (HAM-D) and the proportion of patients with remissions (Hamilton score, <or=8) at the end of treatment. Secondary outcomes included mood self-ratings on the Beck Depression Inventory-II and visual analogue mood scales, Brief Psychiatric Rating Scale (BPRS) score, and both self-reported and observer-rated cognitive changes. The patients were followed up after 6 months. RESULTS: HAM-D scores at the end of treatment were significantly lower for ECT, with 13 patients (59.1%) achieving remission in the ECT group and four (16.7%) in the rTMS group. However, at 6 months the HAM-D scores did not differ between groups. Beck scale, visual analogue mood scale, and BPRS scores were lower for ECT at the end of treatment and remained lower after 6 months. Self- and observer-rated cognitive measures were similar in the two groups. CONCLUSIONS: rTMS was not as effective as ECT, and ECT was substantially more effective for the short-term treatment of depression.

Aged↗

PubMed2001

Spatial working memory deficits in schizophrenia: relationship with tardive dyskinesia and negative symptoms.

OBJECTIVE: This study examined the interrelationship between negative symptoms, orofacial tardive dyskinesia, and specific neurocognitive processes, particularly those involved in memory and executive function, in patients with schizophrenia. METHOD: A set of computerized neurocognitive tasks, the Cambridge Neuropsychological Test Automated Battery, was used to assess executive and memory function in 54 hospitalized patients with chronic schizophrenia. Analysis of covariance was used to examine differences between groups with or without the topographical syndromes of orofacial tardive dyskinesia and between groups with high or low negative symptom scores. Principal-components and path analyses were used to examine further the influence of negative symptoms and orofacial tardive dyskinesia on performance on tests of memory and executive function. RESULTS: Both orofacial tardive dyskinesia and negative symptoms were significantly and independently associated with deficits on measures of spatial working memory span derived from principal-components analysis, but only orofacial tardive dyskinesia was associated with deficits on measures of spatial working memory strategy. Both were also associated with impairment on the delayed-matching-to-sample task, a test of memory. These associations were not explained by deficits in global intellectual function. Path analysis suggested that the relationships between the clinical symptoms and performance on the delayed-matching-to-sample task were mediated entirely through their relationship with the spatial working memory measures. CONCLUSIONS: In schizophrenia, orofacial tardive dyskinesia and evident negative symptoms are relatively independent markers of compromise of the cerebral systems that mediate spatial working memory. Candidate neural circuits include the frontal-striatal-thalamic systems, particularly those involving the dorsolateral prefrontal cortex.

Adult↗

PubMed2001

Inverse relationship between serotonin 5-HT(1A) receptor binding and anxiety: a [(11)C]WAY-100635 PET investigation in healthy volunteers.

OBJECTIVE: The authors investigated the relationship between anxiety--a facet of the Revised NEO Personality Inventory dimension of neuroticism--and serotonin 5-HT(1A) receptor binding potential. METHOD: Positron emission tomography with [(11)C]WAY-100635 was used to estimate regional 5-HT(1A) binding potential in 19 healthy volunteers who completed the Revised NEO Personality Inventory. Correlation coefficients were calculated to determine the degree of association between 5-HT(1A) binding potential and personality inventory measures. RESULTS: There was a significant negative correlation between 5-HT(1A) binding potential and anxiety in four regions: the dorsolateral prefrontal cortex, anterior cingulate cortex, parietal cortex, and occipital cortex. CONCLUSIONS: The inverse relationship between 5-HT(1A) receptor binding potential and anxiety is consistent with 1) animal models that have shown higher anxiety in mice lacking 5-HT(1A) receptors and 2) clinical trial data that have demonstrated antianxiety properties of partial 5-HT(1A) agonists.

Adult↗