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Results for “Dorsolateral Prefrontal Cortex”

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PubMed1998

Cognitive functioning and the inhibition of alcohol-induced aggression.

OBJECTIVE: A highly replicable research finding is that alcohol intoxication tends to induce aggressive responding. Recent research investigating the role of cognitive function in this relationship has shown that individuals who perform poorly on certain cognitive tasks have difficulty responding to contingencies to inhibit aggression, while high performers do not. High performers, however, do show increased aggression while intoxicated. This study investigated whether subjects with above average cognitive functioning would, when intoxicated, inhibit aggression in order to attain monetary reward. METHOD: Men (N = 43), aged 18-30, selected on the basis of high performance on a neuropsychological test putatively assessing function of dorsolateral prefrontal cortex, the spatial conditional associative learning task, participated in a modified version of the Taylor Aggression Task. Half the subjects were acutely alcohol intoxicated, the other half were sober. Furthermore, half the subjects in each of these groups received contingent monetary reward for choosing lower shocks. Aggression was defined as shock intensity delivered to a sham opponent. RESULTS: Contrary to the hypothesis, intoxicated subjects, even though significantly impaired cognitively relative to their nonintoxicated peers (F = 4.29, 1/41 df, p < .05), appeared to have no difficulty inhibiting their aggression in order to gain monetary reward. That is, there was no difference between intoxicated and nonintoxicated subjects on the dependent variable, shock intensity, when contingent money was available (F = .01, 1/20 df, p = .935). CONCLUSION: This finding provides further evidence that alcohol-induced aggression is not a uniform phenomenon, and it suggests a neuropsychological mechanism that may mediate the relationship. It may be that individuals with above average cognitive abilities retain sufficient residual functioning to inhibit aggressive responding, even when acutely alcohol intoxicated.

Adult↗

PubMed2006

A functional magnetic resonance imaging study of the long-term influences of early indomethacin exposure on language processing in the brains of prematurely born children.

BACKGROUND: Previous studies have demonstrated that indomethacin lowers the incidence and decreases the severity of intraventricular hemorrhage, as well as improves the cognitive outcome, in prematurely born male infants. OBJECTIVE: The purpose of this work was to use functional magnetic resonance imaging to test the hypothesis that neonatal indomethacin treatment would differentially affect brain activation across genders in school-aged, prematurely born children during performance of a language task. METHODS: Forty-seven prematurely born children (600-1250-g birth weight) and 24 matched term control subjects were evaluated using a functional magnetic resonance imaging passive language task and neurodevelopmental assessments that included the Wechsler Intelligence Scale for Children-III and the Peabody Picture Vocabulary Test-Revised. Neural activity was assessed during both phonologic and semantic processing in the functional magnetic resonance imaging protocol. RESULTS: Neurodevelopmental assessments demonstrated significant differences in full-scale, verbal, and performance intelligence quotient, as well as Peabody Picture Vocabulary Test scores, between the preterm and term control subjects. Rates of perinatal complications did not differ significantly across preterm treatment groups, but male preterm subjects randomly assigned to saline tended to have lower Peabody Picture Vocabulary Test-Revised scores than did all of the other preterm groups. During phonological processing, a significant treatment-by-gender effect was demonstrated in 3 brain regions: the left inferior parietal lobule, the left inferior frontal gyrus (Broca's area), and the right dorsolateral prefrontal cortex. CONCLUSIONS: These data demonstrate a differential effect of indomethacin administration early in postnatal life on the subsequent development of neural systems that subserve language functioning in these male and female preterm infants.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1975

Prefrontal unit activity during delayed-response and delayed-alternation performances.

In order to examine whether or not the single unit activity of the dorsolateral prefrontal cortex of the rhesus monkey activated during delayed-response task is involved in a delayed-alternation task, the same prefrontal single unit activities were recorded extracellularly using tungsten electrodes while the monkey was performing the two tasks alternatively. Visual signals were given to two different locations (left and right) as visual cues and response cues. A total of 95 units were recorded. Two-thirds of them were activated during visual and response cue phases and were regarded as the visuokinetic units as defined in a previous paper (KUBOTA et al., 1974). Visuokinetic units with no different discharge rate between left and right trials of delayed-response did not show a difference in delayed-alternation. Visuokinetic units with a differential rate in delayed-response trials did not necessarily show a difference in delayed-alternation. Visuokinetic units with no spontaneous activity in the intertrial interval time were considered as the E unit activity of delayed-alternation in a previous paper (KUBOTA and NIKI, 1971). Remaining one-third of units were activated or depressed during visual cues or during response cues and their activities were not different from each other between two tasks. No differential activity was found which could be correlated to the alternative choice of the reward in delayed-alternation. Discussions were made on possible mnemonic functions relevant to previous studies.

Animals↗

PubMed2000

Differential brain responses to satiation in obese and lean men.

Knowledge of how the brain contributes to the regulation of food intake in humans is limited. We used positron emission tomography and measures of regional cerebral blood flow (rCBF) (a marker of neuronal activity) to describe the functional anatomy of satiation (i.e., the response to a liquid meal) in the context of extreme hunger (36-h fast) in 11 obese (BMI > or =35 kg/m2, age 27+/-5 years, weight 115+/-11 kg, 38+/-7% body fat; mean +/- SD) and 11 lean (BMI < or =25 kg/m2, age 35+/-8 years, weight 73+/-9 kg, 19+/-6% body fat) men. As in lean men, satiation in obese men produced significant increases in rCBF in the vicinity of the ventromedial and dorsolateral prefrontal cortex and significant decreases in rCBF in the vicinity of the limbic/paralimbic areas (i.e., hippocampal formation, temporal pole), striatum (i.e., caudate, putamen), precuneus, and cerebellum. However, rCBF increases in the prefrontal cortex were significantly greater in obese men than in lean men (P < 0.005). rCBF decreases in limbic/paralimbic areas, temporal and occipital cortex, and cerebellum were also significantly greater in obese men than in lean men (P < 0.005), whereas rCBF decreases in the hypothalamus and thalamus were attenuated in obese men compared with lean men (P < 0.05). This study raises the possibility that the brain responses to a meal in the prefrontal areas (which may be involved in the inhibition of inappropriate response tendencies) and limbic/paralimbic areas (commonly associated with the regulation of emotion) may be different in obese and lean men. Additional studies are required to investigate how these differential responses are related to the pathophysiology of obesity.

Adult↗

PubMed2005

The influence of low-frequency left prefrontal repetitive transcranial magnetic stimulation on memory for words but not for faces.

Brain imaging studies suggest localization of verbal working memory in the left dorsolateral prefrontal cortex (DLPFC) while face processing and memory is localized in the inferior temporal cortex and other brain areas. The goal of this study was to assess the effect of left DLPFC low-frequency repetitive transcranial magnetic stimulation (rTMS) on verbal recall and face recognition. The study revealed a significant decrease of free recall in word encoding under rTMS (110% of motor threshold, 0.9 Hz) in comparison with sham stimulation (p=0.03), while no significant difference was found with facial memory tests. Our findings support the essential role of the left DLPFC in word but not facial memory and confirm the content specific arrangement of cortical areas involved in semantic memory. As a non-invasive tool, rTMS is useful for cognitive brain mapping and the functional localization of the category specific memory system.

Adult↗

PubMed2004

The neural bases of the effects of item-nonspecific proactive interference in working memory.

We reanalyzed the behavioral and fMRI data from seven previously published studies of working memory in order to assess the behavioral and neural effects of item-nonspecific proactive interference (PI; attributable to the accrual of antecedent information independent of the repetition of particular items). We hypothesized that item-nonspecific PI, implicated in age-related declines in working memory performance, is mediated by the same mechanism(s) that mediate item-specific PI (occurring when an invalid memory probe matches a memorandum from the previous trial). Reaction time increased across trials as a function of position within the block, a trend that reversed across the duration of each multiblock experiment. The fMRI analyses revealed sensitivity to item-nonspecific PI during the probe epoch in the left anterior inferior frontal gyrus and the left dorsolateral prefrontal cortex(PFC). They also revealed a negative trend, across trials, in the transient probe-evoked component of the global signal. A common PFC-based mechanism may mediate many forms of PI.

Adult↗

PubMed2003

High-frequency repetitive transcranial magnetic stimulation decreases cigarette smoking.

BACKGROUND: The mesolimbic dopaminergic reward system seems to play a crucial role in reinforcing effects of nicotine. Recently, acute high-frequency repetitive transcranial magnetic stimulation (rTMS) of frontal brain regions has been shown to efficiently modulate the mesostriatal and mesolimbic dopaminergic system in both animals and humans. For this reason, we investigated whether high-frequency rTMS would be able to influence nicotine-related behavior by studying rTMS effects on craving and cigarette smoking. METHOD: Fourteen treatment-seeking smokers were included in a double-blind crossover trial, conducted in 2002, comparing single days of active versus sham stimulation. Outcome measures were rTMS effects on number of cigarettes smoked during an ad libitum smoking period and effects on craving after a period of acute abstinence. RESULTS: High-frequency (20-Hz) rTMS of left dorsolateral prefrontal cortex reduced cigarette smoking significantly (p <.01) in an active stimulation compared with sham stimulation. Levels of craving did not change significantly. CONCLUSION: High-frequency rTMS may be useful for treatment in smoking cessation.

Adult↗

PubMed2004

No deterioration of cognitive performance in an aggressive unilateral and bilateral antidepressant rTMS add-on trial.

BACKGROUND: Cognitive functions were assessed before and following a course of repetitive transcranial magnetic stimulation (rTMS) in patients with depression participating in a sham-controlled, randomized trial of rTMS as adjunct to antidepressant treatment. METHOD: Forty-one medicated inpatients with a DSM-IV diagnosis of a depressive episode were consecutively randomly assigned to 1 of 3 groups comparing 2 active rTMS conditions with sham stimulation. The rTMS was applied either at high frequency over the left dorsolateral-prefrontal cortex (DLPFC) (10 sessions x 10 trains x 10 seconds 20 Hz at 100% motor threshold [MT], 90-second intertrain interval) or in a combined high- and low-frequency manner to the left and right DLPFC, respectively (10 sessions x 1 train x 10 minutes at 120% MT). Thirty-eight patients completed a neuropsychological test battery at baseline and following day 14. The cognitive assessment focused on motor skills, attention, executive functions, learning, and memory. Data were collected from November 1999 to August 2002. RESULTS: Active treatment groups did not differ with respect to assessed cognitive measures and thus were pooled. A comparison of short-term changes (baseline-day 14) in neuropsychological performance revealed a more favorable time course of the actively treated patients for encoding in the verbal memory test compared with the sham-stimulated patients. CONCLUSIONS: Unilateral rTMS as well as bilateral combined rTMS revealed no detrimental effects on cognition, as compared with the sham group. Moreover, neither the add-on design nor the used aggressive parameters had a negative impact on cognitive measures in comparison with sham. Repetitive transcranial magnetic stimulation might have mild beneficial cognitive effects partly independent of its antidepressant efficacy.

Adult↗

PubMed2004

A 3-month, follow-up, randomized, placebo-controlled study of repetitive transcranial magnetic stimulation in depression.

BACKGROUND/OBJECTIVE: There is evidence for an antidepressant effect of repetitive transcranial magnetic stimulation (rTMS), but little is known about posttreatment course. Therefore, we conducted a placebo-controlled, double-blind study in depressed patients in order to investigate the effect of rTMS on depression over 12 weeks after completion of the 2-week stimulation period. METHOD: 55 patients with a moderate or severe DSM-IV major depressive episode were randomly assigned to rTMS or sham treatment. rTMS was given daily for 10 days over the left dorsolateral prefrontal cortex with the following treatment parameters: 20 Hz, 20 trains of 2 seconds, 30 seconds between trains, and 80% motor threshold. The effect of rTMS on depression was rated repeatedly with the 17-item Hamilton Rating Scale for Depression (HAM-D) during the 2-week period of stimulation and the 12-week follow-up period conducted from 1997 to 2001. RESULTS: We found a modest, clinically nonrelevant decrease in HAM-D scores in both rTMS and sham patients over 2 weeks of treatment. However, over the subsequent 12-week follow-up, the rTMS group continued to improve significantly compared with the placebo group. CONCLUSION: Decrease of depressive symptoms may continue after the cessation of rTMS stimulation.

Comorbidity↗

PubMed2005

Add-on rTMS for medication-resistant depression: a randomized, double-blind, sham-controlled trial in Chinese patients.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been developed as a novel tool for improving depression by delivering magnetic stimulation to the brain. However, the apparent effects of rTMS on depression have been varied in different studies. The aims of this study were to determine whether left dorsolateral prefrontal cortex rTMS can alleviate medication-resistant depression in Chinese patients and to investigate what demographic variables or clinical features may predict better response. METHOD: We designed a 2-week randomized, double-blind, sham-controlled study of add-on rTMS. A total of 30 medication-resistant patients with DSM-IV major depressive disorder or bipolar disorder, depressed episode completed 10 sessions of active or sham rTMS-10 patients at each of 2 frequencies, faster (20 Hz) or slower (5 Hz) at 100% motor threshold, and 10 patients at sham stimulation. RESULTS: Patients at both stimulation frequencies demonstrated a superior reduction of depression severity compared to sham stimulation (active = 55.7% vs. sham = 16.3%). The response rate for active rTMS was 60%, in contrast to 10% for the sham treatment. No difference in clinical response was observed between 5 Hz and 20 Hz active rTMS. Clinical variables showed that younger age and less severe depression at entry may predict the clinical response to rTMS. Except for 1 patient in which rTMS appeared to induce mania, this procedure posed no safety problem. CONCLUSIONS: To our knowledge, this is the first study to demonstrate the clinical efficacy and safety of rTMS in Chinese patients. Since not all the rTMS trials in previous reports had positive results, further larger trials are still warranted.

Adult↗

PubMed2004

The neural correlates of cognitive time management: a review.

Cognitive time management is an important aspect of human behaviour and cognition that has so far been understudied. Functional imaging studies in recent years have tried to identify the neural correlates of several timing functions, ranging from simple motor tapping to higher cognitive time estimation functions. Several regions of the frontal lobes, in particular dorsolateral prefrontal cortex (DLPFC), inferior prefrontal cortex (IFC), anterior cingulate gyrus (ACG) and the supplementary motor area (SMA), alongside non-frontal brain regions such as the inferior parietal lobes, the cerebellum and the basal ganglia have been found to be involved in tasks of motor timing and time estimation. In this paper we review and discuss the involvement of these brain regions in different tasks of cognitive time management, illustrating it with own findings on motor timing and time perception tasks using functional magnetic resonance imaging (fMRI). The review shows that the same brain regions are involved in both motor timing and time estimation, suggesting that both functions are probably inseparable and mediated by common neural networks.

Basal Ganglia↗

PubMed2002

The physiological role of 5-HT2A receptors in working memory.

Dorsolateral prefrontal cortex has an essential role in the cognitive process of working memory, dysfunction of which is considered to be a core deficit in schizophrenia. Although this cortical region is densely innervated with 5-HT2A receptors to which atypical antipsychotic drugs bind with high affinity, little is known of the influence of this serotonin receptor subtype on prefrontal function. We addressed this issue by examining the effects of iontophoresis of selective receptor ligands on prefrontal neurons possessing spatially tuned delay activity, or "memory fields," in monkeys performing a delayed-response task. Memory fields of putative pyramidal cells were attenuated by iontophoresis of 5-HT2A antagonists, which primarily produced a reduction in delay activity for preferred target locations. Conversely, 5-HT2A stimulation by alpha-methyl-5-HT or 5-HT itself, accentuated the spatial tuning of these neurons by producing a modest increase in activity for preferred target locations and/or a reduction in activity for nonpreferred locations. The agonist effects could be reversed by the selective antagonist MDL100,907, and were dose-dependent, such that high levels attenuated spatial tuning by profoundly reducing delay activity. A role for feedforward inhibitory circuitry in these effects was supported by the finding that 5-HT2A blockade also attenuated the memory fields of putative interneurons. We conclude that prefrontal 5-HT2A receptors have a hitherto unrecognized role in the cognitive function of working memory, which involves actions at both excitatory and inhibitory elements within local circuitry.

Action Potentials↗

PubMed2002

Prefrontal dopamine D1 receptors and working memory in schizophrenia.

Studies in nonhuman primates documented that appropriate stimulation of dopamine (DA) D1 receptors in the dorsolateral prefrontal cortex (DLPFC) is critical for working memory processing. The defective ability of patients with schizophrenia at working memory tasks is a core feature of this illness. It has been postulated that this impairment relates to a deficiency in mesocortical DA function. In this study, D1 receptor availability was measured with positron emission tomography and the selective D1 receptor antagonist [11C]NNC 112 in 16 patients with schizophrenia (seven drug-naive and nine drug-free patients) and 16 matched healthy controls. [11C]NNC 112 binding potential (BP) was significantly elevated in the DLPFC of patients with schizophrenia (1.63 +/- 0.39 ml/gm) compared with control subjects (1.27 +/- 0.44 ml/gm; p = 0.02). In patients with schizophrenia, increased DLPFC [11C]NNC 112 BP was a strong predictor of poor performance at the n-back task, a test of working memory. These findings confirm that alteration of DLPFC D1 receptor transmission is involved in working memory deficits presented by patients with schizophrenia. Increased D1 receptor availability observed in patients with schizophrenia might represent a compensatory (but ineffective) upregulation secondary to sustained deficiency in mesocortical DA function.

Adult↗

PubMed1998

Traumatic Brain Injury and Psychosis: What Is the Connection?

Psychotic syndromes occur more frequently in individuals who have had a traumatic brain injury (TBI) than in the general population. Psychotic syndromes following a TBI can present in the period of post-traumatic anmesia, in association with post-traumatic epilepsy, in association with TBI-related mood disorders, and as a chronic, schizophrenia-like syndrome. Individuals with schizophrenia (a chronic psychotic disorder) have a higher frequency of prior TBI than individuals with other psychiatric disorders. These observations suggest an intriguing link between psychosis and TBI. The study of the neuroanatomical and neuropathological substrate of schizophrenia, and of the core symptoms of the disorder ("negative" symptoms, hallucinations, delusions), suggests that abnormalities in the structure and function of certain brain regions play a role in the genesis and maintenance of these core symptoms. The key brain regions include the dorsolateral prefrontal cortex, temporal lobe structures, basal ganglia, thalamus, and cingulate gyrus. These brain regions are commonly injured in many patients with TBI, suggesting a possible mechanism underlying the observed link between TBI and psychosis. This article reviews the literature on TBI and psychosis, and suggests an approach to the evaluation and treatment of individuals with TBI and psychosis.

Journal Article↗

PubMed1999

Impaired somatosensory discrimination of shape in Parkinson's disease: association with caudate nucleus dopaminergic function.

Tactile discrimination of macrogeometric objects in a two-alternative forced-choice procedure represents a demanding task involving somatosensory pathways and higher cognitive processing. The objects for somatosensory discrimination, i.e., rectangular parallelepipeds differing only in oblongness, were presented in sequential pairs to normal volunteers and 12 parkinsonian patients. The performance of patients was significantly impaired compared to normal volunteers. From a biochemical point of view, the patients were characterized by a severely reduced 6-[18F]-fluoro-L-dopa (FDOPA) tracer metabolism in the basal ganglia, as measured using positron emission tomography (PET). Furthermore, reduced specific FDOPA metabolism in the putamen was consistent with the impaired motor capacities of the patients. The reduced specific FDOPA-uptake within the caudate nucleus was associated with additionally diminished somatosensory discrimination. This association, of low perception during task performance and decreased FDOPA-uptake, provides direct evidence for the role of the caudate nucleus in the cognitive part of the task. We suggest that directed attention and working memory were critically involved as a result of disturbed interactions between the head of the caudate nucleus and the dorsolateral prefrontal cortex. Furthermore, there were indications of an additional involvement of the mesolimbic system, which might be of importance during challenging situations such as forced choice. We conclude that differential effects on parts of the basal ganglia, during evolution of the degenerative process characteristic of Parkinson's disease, have profound consequences on the performance of skills, as shown here for a somatosensory discrimination task.

Adult↗

PubMed2000

Destruction and creation of spatial tuning by disinhibition: GABA(A) blockade of prefrontal cortical neurons engaged by working memory.

Local circuit neurons in the dorsolateral prefrontal cortex (dPFC) of monkeys have been implicated in the cellular basis of working memory. To further elucidate the role of inhibition in spatial tuning, we iontophoresed bicuculline methiodide (BMI) onto functionally characterized neurons in the dPFC of monkeys performing an oculomotor delayed response task. This GABA(A) blockade revealed that both putative interneurons and pyramidal cells possess significant inhibitory tone in the awake, behaving monkey. In addition, BMI application primarily resulted in the loss of previously extant spatial tuning in both cell types through reduction of both isodirectional and cross-directional inhibition. This tuning loss occurred in both the sensorimotor and mnemonic phases of the task, although the delay activity of prefrontal neurons appeared to be particularly affected. Finally, application of BMI also created significant spatial tuning in a sizable minority of units that were untuned in the control condition. Visual field analysis of such tuning suggests that it is likely caused by the unmasking of normally suppressed spatially tuned excitatory input. These findings provide the first direct evidence of directional inhibitory modulation of pyramidal cell and interneuron firing in both the mnemonic and sensorimotor phases of the working memory process, and they implicate a further role for GABAergic interneurons in the construction of spatial tuning in prefrontal cortex.

Action Potentials↗

PubMed2000

Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain.

The indirect catecholamine agonist methylphenidate (Ritalin) is the drug treatment of choice in attention deficit/hyperactivity disorder (AD/HD), one of the most common behavioral disorders of childhood (DSM-IV), although symptoms may persist into adulthood. Methylphenidate can enhance cognitive performance in adults and children diagnosed with AD/HD (Kempton et al., 1999; Riordan et al., 1999) and also in normal human volunteers on tasks sensitive to frontal lobe damage, including aspects of spatial working memory (SWM) performance (Elliott et al., 1997). The present study investigated changes in regional cerebral blood flow (rCBF) induced by methylphenidate during performance of a self-ordered SWM task to define the neuroanatomical loci of the beneficial effect of the drug. The results show that the methylphenidate-induced improvements in working memory performance occur with task-related reductions in rCBF in the dorsolateral prefrontal cortex and posterior parietal cortex. The beneficial effects of methylphenidate on working memory were greatest in the subjects with lower baseline working memory capacity. This is to our knowledge the first demonstration of a localization of a drug-induced improvement in SWM performance in humans and has relevance for understanding the treatment of AD/HD.

Adrenergic Uptake Inhibitors↗

PubMed2000

Cognitive effects of 1- and 20-hertz repetitive transcranial magnetic stimulation in depression: preliminary report.

OBJECTIVE: To determine the cognitive effects of daily repetitive transcranial magnetic stimulation (rTMS) administered under the conditions of a treatment trial for major depression. BACKGROUND: Although daily left dorsal prefrontal rTMS has improved mood in some patients with treatment-refractory depression, potential cognitive side effects of extended daily treatment have not been systematically studied. METHOD: In a randomized double-blind treatment study, 10 subjects (mean age, 42 +/- 15 years) with an episode of major depression received either 2 weeks of low-frequency (1 Hz) or high-frequency (20 Hz) rTMS (800 pulses, 20 trains over 20 minutes, 80% of motor threshold, 5 days per week) to the left dorsolateral prefrontal cortex and then were crossed over to the other treatment condition. Patients received cognitive testing at baseline and after the first and second weeks of low- or high-frequency rTMS, which was examined by repeated-measures ANOVA. RESULTS: Of 16 cognitive measures tested after 1 or 2 weeks of rTMS compared with baseline status, none showed deterioration, and the only significant main treatment effect indicated improvement on a list-recall test from pre- to post-rTMS after 1 week (p <0.05). CONCLUSIONS: These preliminary data suggest no gross deleterious cognitive effects of 2 weeks of 1- or 20-Hz rTMS at 80% of motor threshold over the left prefrontal cortex. Further cognitive studies of the effects of rTMS at other parameters used in clinical trials for mood disorders remain to be undertaken.

Adult↗