The architecture of cognitive control in the human prefrontal cortex

The prefrontal cortex (PFC) subserves cognitive control: the ability to coordinate thoughts or actions in relation with internal goals. Its functional architecture, however, remains poorly understood. Using brain imaging in humans, we showed that the lateral PFC is organized as a cascade of executive processes from premotor to anterior PFC regions that control behavior according to stimuli, the present perceptual context, and the temporal episode in which stimuli occur, respectively. The results support an unified modular model of cognitive control that describes the overall functional organization of the human lateral PFC and has basic methodological and theoretical implications.     

Nicotinic acetylcholine receptor β2 subunits in the medial prefrontal cortex control attention

More than one-third of all people are estimated to experience mild to severe cognitive impairment as they age. Acetylcholine (ACh) levels in the brain diminish with aging, and nicotinic ACh receptor (nAChR) stimulation is known to enhance cognitive performance. The prefrontal cortex (PFC) is involved in a range of cognitive functions and is thought to mediate attentional focus. We found that mice carrying nAChR β2-subunit deletions have impaired attention performance. Efficient lentiviral vector-mediated reexpression of functional β2-subunit-containing nAChRs in PFC neurons of the prelimbic area (PrL) completely restored the attentional deficit but did not affect impulsive and motivational behavior. Our findings show that β2-subunit expression in the PrL PFC is sufficient for endogenous nAChR-mediated cholinergic regulation of attentional performance.     

归纳推理的神经机制

当前对归纳推理神经机制的研究主要以对脑损伤病人的研究和神经成像学研究为主.归纳推理实质上是假设生成和选择的过程,其核心是相关信息的选择.通过对近几年的文献综述发现,归纳推理主要激活了左侧前额叶皮层,且归纳推理中所涉及的关系整合难度也会特别地激活双侧前额皮层嘴部和右前额皮层背侧.此外,事件相关电位技术(ERP)的研究表明,P300可能揭示了假设的生成.     

Brain lesions in birds: effects on discrimination acquisition and reversal

Bobwhite quail (Colinus virginianus) with lesions of the cortex and the dorsal portion of the hyperstriatum (or " wulst") showed a considerable deficit in ability to reverse a learned discrimination between horizontal and vertical stripes. Two birds that had been run on 25 such reversals before ablation showed the same result. Lesioned birds did not, however, differ from controls in the Original acquisition of the discrimination. Analysis of performance indicated that the reversal deficit was not due to difficulties in discrimination, interference with motor ability, or lack of motivation. The deficit appeared to be based on perseveration of response to the previous positive stimulus during reversal training.     

Neurochemical modulation of response inhibition and probabilistic learning in humans

Cognitive functions dependent on the prefrontal cortex, such as the ability to suppress behavior (response inhibition) and to learn from complex feedback (probabilistic learning), play critical roles in activities of daily life. To what extent do different neurochemical systems modulate these two cognitive functions? Here, using stop-signal and probabilistic learning tasks, we show a double dissociation for the involvement of noradrenaline and serotonin in human cognition. In healthy volunteers, inhibition of central noradrenaline reuptake improved response inhibition but had no effect on probabilistic learning, whereas inhibition of central serotonin reuptake impaired probabilistic learning with no effect on response inhibition.     

Representation of the quantity of visual items in the primate prefrontal cortex

Deriving the quantity of items is an abstract form of categorization. To explore it, monkeys were trained to judge whether successive visual displays contained the same quantity of items. Many neurons in the lateral prefrontal cortex were tuned for quantity irrespective of the exact physical appearance of the displays. Their tuning curves formed overlapping filters, which may explain why behavioral discrimination improves with increasing numerical distance and why discrimination of two quantities with equal numerical distance worsens as their numerical size increases. A mechanism that extracts the quantity of visual field items could contribute to general numerical ability.     

Learned behavior of Rhesus monkeys following neonatal bilateral prefrontal lobotomy

Bilateral ablation of dorsolateral frontal cortex in the newborn animal failed to produce the frontal lobe syndrome typical of the adolescent and adult stages. The crucial tests (delayed response, string tests, and discrimination learning) were performed 3 to 4 months postoperatively. At this time, no significant differences between normal animals and animals with prefrontal lesions were found.     

Reversal learning and forgetting in bird and fish

Pigeons and goldfish were trained in red-green discrimination in daily sessions, with the rewarded color changed every 2 days. Improvement in the performance of the pigeons could be traced to decrements in retention from each day to the next. The goldfish showed no improvement and no decrements in retention. The results suggest that progressive improvement in habit reversal is a product of proactive interference, and that the absence of improvement in the fish is due, not to the lack of some higher-order process which operates to produce improvement in higher vertebrates, but to a difference in learning-retention mechanisms.     

Memory in mice as affected by intracerebral puromycin

The antibiotic, puromycin, caused loss of memory of avoidance discrimination learning in mice when injected intracerebrally. Bilateral injections of puromycin involving the hippocampi and adjacent temporal cortices caused loss of short-term memory; consistent loss of longer-term memory required injections involving, in addition, most of the remaining cortices. Spread of the effective memory trace from the temporal-hippocampal areas to wide areas of the cortices appears to require 3 to 6 days, depending upon the individual animal. Recent reversal learning was lost while longer-term initial learning was retained after bilateral injections into the hippocampal-temporal areas.     

Behavioral response rates in pigeons: effect of alpha-methyl-m-tyrosine

An intramuscular injection of alpha-methyl-m-tyrosine ( 100 mg/ kg), which differentially depletes serotonin and norepinephrine in both brain and heart, was given to two groups of pigeons trained to peck at a key for food. The first group received an injection 12 hours before the daily session and showed no behavioral effect. Response rates of birds in the second group, which were injected 30 minutes after the start of the daily session, decreased and returned to normal within 9 hours after injection. Preliminary data on brain serotonin of pigeons indicate that the disruption of the behavior follows the same time course as the change in serotonin.     

Olfactory discrimination in the rabbit olfactory glomerulus

Slow potentials evoked by odor stimulation were recorded from individual glomeruli in the olfactory bulb. Systematic analysis of responses to nine different, arbitrarily selected stimuli strongly suggests a certain amount of discrimination. This fact seems to reflect in the first synapse of the olfactory tract the type of discrimination that was recently demonstrated within olfactory neuroepithelium.     

Protein kinase C overactivity impairs prefrontal cortical regulation of working memory

The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.     

Dissociation of impairment after lateral and medial prefrontal lesions in dogs

Dogs were trained before operation on a go, no-go test with symmetrical reinforcement. Lesions situated on the medial surface of the prefrontal cortex caused slight or no impairment in retention, whereas removal of the lateral prefrontal cortex induced severe and long-lasting impairment. The lateral prefrontal cortex is probably related to selection of the proper instrumental responses to corresponding stimuli.     

Sporadic autonomic dysregulation and death associated with excessive serotonin autoinhibition

Sudden infant death syndrome is the leading cause of death in the postneonatal period in developed countries. Postmortem studies show alterations in serotonin neurons in the brainstem of such infants. However, the mechanism by which altered serotonin homeostasis might cause sudden death is unknown. We investigated the consequences of altering the autoinhibitory capacity of serotonin neurons with the reversible overexpression of serotonin 1A autoreceptors in transgenic mice. Overexpressing mice exhibited sporadic bradycardia and hypothermia that occurred during a limited developmental period and frequently progressed to death. Moreover, overexpressing mice failed to activate autonomic target organs in response to environmental challenges. These findings show that excessive serotonin autoinhibition is a risk factor for catastrophic autonomic dysregulation and provide a mechanism for a role of altered serotonin homeostasis in sudden infant death syndrome.     

Brain serotonin concentration: elevation following intraperitoneal administration of melatonin

The intraperitoneal administration of melatonin to rats caused an increase in brain serotonin concentration, especially in the midbrain. This effect could be demonstrated within 20 minutes of melatonin administration and was not associated with changes in norepinephrine concentration.     

The prefrontal cortex: response selection or maintenance within working memory?

It is controversial whether the dorsolateral prefrontal cortex is involved in the maintenance of items in working memory or in the selection of responses. We used event-related functional magnetic resonance imaging to study the performance of a spatial working memory task by humans. We distinguished the maintenance of spatial items from the selection of an item from memory to guide a response. Selection, but not maintenance, was associated with activation of prefrontal area 46 of the dorsal lateral prefrontal cortex. In contrast, maintenance was associated with activation of prefrontal area 8 and the intraparietal cortex. The results support a role for the dorsal prefrontal cortex in the selection of representations. This accounts for the fact that this area is activated both when subjects select between items on working memory tasks and when they freely select between movements on tasks of willed action.     

Selective attention from voluntary control of neurons in prefrontal cortex

Animals can learn to voluntarily control neuronal activity within various brain areas through operant conditioning, but the relevance of that control to cognitive functions is unknown. We found that rhesus monkeys can control the activity of neurons within the frontal eye field (FEF), an oculomotor area of the prefrontal cortex. However, operantly driven FEF activity was primarily associated with selective visual attention, and not oculomotor preparation. Attentional effects were untrained and were observed both behaviorally and neurophysiologically. Furthermore, selective attention correlated with voluntary, but not spontaneous, fluctuations in FEF activity. Our results reveal a specific association of voluntarily driven neuronal activity with "top-down" attention and suggest a basis for the use of neurofeedback training to treat disorders of attention.     

Paleomagnetic Study of a Reversal of the Earth's Magnetic Field

A detailed record of a field reversal has been obtained from the natural remanent magnetization of the Tatoosh intrusion in Mount Rainier National Park, Washington. The reversal took place at 14.7 +/- 1 million years and is interpreted to be from reverse to normal. A decrease in the intensity of the field of about an order of magnitude occurs immediately before the reversal, while its orientation remains substantially unchanged. The onset of the reversal is marked by abrupt swinging of the virtual geomagnetic pole along an arc of a great circle. During the reversal the pole traces a path across the Pacific. In the last stage of the process recorded in the sections, the succession of virtual geomagnetic poles is very similar to those generated by secular variation in the recent past. Although the cooling rate of the intrusion is not sufficiently well known to permit a useful calculation of the duration of the reversal process, an estimate based on the length of the supposed secular variation cycles gives 1 to 4 x 103 years for the reversal of field direction and approximately 1 x 104 years for the time scale of the intensity changes.     

Platelet-derived serotonin mediates liver regeneration

The liver can regenerate its volume after major tissue loss. In a mouse model of liver regeneration, thrombocytopenia, or impaired platelet activity resulted in the failure to initiate cellular proliferation in the liver. Platelets are major carriers of serotonin in the blood. In thrombocytopenic mice, a serotonin agonist reconstituted liver proliferation. The expression of 5-HT2A and 2B subtype serotonin receptors in the liver increased after hepatectomy. Antagonists of 5-HT2A and 2B receptors inhibited liver regeneration. Liver regeneration was also blunted in mice lacking tryptophan hydroxylase 1, which is the rate-limiting enzyme for the synthesis of peripheral serotonin. This failure of regeneration was rescued by reloading serotonin-free platelets with a serotonin precursor molecule. These results suggest that platelet-derived serotonin is involved in the initiation of liver regeneration.