Catecholamine regulation of the prefrontal cortex

In order to contribute to the understanding of the biological properties of nafazatrom, an antithrombotic agent (NAP), we studied its effects on peroxidation of low density lipoproteins (LDL), lipid liposomes, heart homopgenate, and its interaction with alpha-tocopherol radical. NAP decreased the FeSO4 and H202-induced peroxidation of phosphatidylcholine liposomes and heart homogenate, and it decreased peroxidation of LDL induced by CuSO4 or 2,2'-azobis(2-amidinopropane). The antioxidant effect of NAF was about 3 times less potent than that of alpha-tocopherol (alpha-TOC) in phosphatidylcholine liposomes, and NAF was about 2-4 times more efficient to decrease peroxidation of LDL than alpha-TOC. Possible interaction of NAF with alpha-tocopherol radical (alpha-TR) was studied by EPR spectroscopy. NAF decreased the concentration of alpha-TR, but it was about 100-times less efficient than vitamin C. This may indicate that NAF does not interfere with alpha-TR formation and/or reduction of alpha-TR in biological system. The obtained results may help the explanation of biological effects of NAF.     

The somatic marker hypothesis and the possible functions of the prefrontal cortex

In this article I discuss a hypothesis, known as the somatic marker hypothesis, which I believe is relevant to the understanding of processes of human reasoning and decision making. The ventromedial sector of the prefrontal cortices is critical to the operations postulated here, but the hypothesis does not necessarily apply to prefrontal cortex as a whole and should not be seen as an attempt to unify frontal lobe functions under a single mechanism. The key idea in the hypothesis is that 'marker' signals influence the processes of response to stimuli, at multiple levels of operation, some of which occur overtly (consciously, 'in mind') and some of which occur covertly (non-consciously, in a non-minded manner). The marker signals arise in bioregulatory processes, including those which express themselves in emotions and feelings, but are not necessarily confined to those alone. This is the reason why the markers are termed somatic: they relate to body-state structure and regulation even when they do not arise in the body proper but rather in the brain's representation of the body. Examples of the covert action of 'marker' signals are the undeliberated inhibition of a response learned previously; the introduction of a bias in the selection of an aversive or appetitive mode of behaviour, or in the otherwise deliberate evaluation of varied option-outcome scenarios. Examples of overt action include the conscious 'qualifying' of certain option-outcome scenarios as dangerous or advantageous. The hypothesis rejects attempts to limit human reasoning and decision making to mechanisms relying, in an exclusive and unrelated manner, on either conditioning alone or cognition alone.     

Parcellation of the human prefrontal cortex using MRI

NMR spectroscopy and NMR imaging with magnetic field gradients make strange bedfellows, the requirements for one seemingly ruling out the other for human applications. Nevertheless, their stories are intertwined; the advent of high field imaging systems arose because of the desire for human spectroscopy. Localized spectroscopy is possible because of NMR imaging. Both have links to physics at Nottingham, at least in the personalized account that follows. Today, virtually all NMR spectroscopy experiments can be conceived with a localized in vivo spectroscopy counterpart.     

The role of prefrontal cortex in predictive fear learning.

Pavlovian fear conditioning depends on prediction error, or the discrepancy between actual and expected outcomes. We used immunohistochemistry, neuronal tract tracing, and reversible inactivation to study the role of prefrontal cortex and thalamocortical pathways in predictive fear learning. Unexpected, but not expected, conditioned stimulus (CS)–unconditioned stimulus (US) presentations caused increased c-Fos expression in the prefrontal cortex (PFC), midline thalamus, lateral amygdala, as well as retrograde labeled midline thalamic afferents to PFC. Reversible inactivation of dorsomedial PFC, but not infralimbic PFC, prevented the associative blocking of fear learning. These results suggest a role for dorsomedial PFC (dmPFC), and a thalamic → dmPFC pathway, in signaling whether or not aversive events are expected or unexpected and so whether they are to be learned about. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of the medial prefrontal cortex in the play fighting of rats.

Although decorticated rats are able to engage in play, their play is abnormal in three ways. First, decorticates do not display the normal, age-related shifts in defensive strategies during development. Second, decorticates do not modify their defensive tactics in response to the social identity of their partners. Third, decorticates display a global shift in defensive tactics from more complex to less complex strategies. It has been shown that lesions of the motor cortex (MC) selectively produce the abnormal developmental effects on play, and that lesions of the orbitofrontal cortex (OFC) selectively produce the deficits in behavioral discrimination between social partners. In the current set of experiments, we demonstrate that lesions of the medial prefrontal cortex (mPFC) produce the shift from more complex to less complex defensive tactics, while leaving intact the age-related and partner-related modulation of defensive strategies. Thus, we have evidence for a triple dissociation of function between the MC, the OFC, and the mPFC with respect to social play behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of prefrontal cortex in working memory: examining the contents of consciousness

Working memory enables us to hold in our 'mind's eye' the contents of our conscious awareness, even in the absence of sensory input, by maintaining an active representation of information for a brief period of time. In this review we consider the functional organization of the prefrontal cortex and its role in this cognitive process. First, we present evidence from brain-imaging studies that prefrontal cortex shows sustained activity during the delay period of visual working memory tasks, indicating that this cortex maintains on-line representations of stimuli after they are removed from view. We then present evidence for domain specificity within frontal cortex based on the type of information, with object working memory mediated by more ventral frontal regions and spatial working memory mediated by more dorsal frontal regions. We also propose that a second dimension for domain specificity within prefrontal cortex might exist for object working memory on the basis of the type of representation, with analytic representations maintained preferentially in the left hemisphere and image-based representations maintained preferentially in the right hemisphere. Furthermore, we discuss the possibility that there are prefrontal areas brought into play during the monitoring and manipulation of information in working memory in addition to those engaged during the maintenance of this information. Finally, we consider the relationship of prefrontal areas important for working memory, both to posterior visual processing areas and to prefrontal areas associated with long-term memory.     

Integration of what and where in the primate prefrontal cortex

The visual system separates processing of an object's form and color ("what") from its spatial location ("where"). In order to direct action to objects, the identity and location of those objects must somehow be integrated. To examine whether this process occurs within the prefrontal (PF) cortex, the activity of 195 PF neurons was recorded during a task that engaged both what and where working memory. Some neurons showed either object-tuned (what) or location-tuned (where) delay activity. However, over half (52 percent, or 64/123) of the PF neurons with delay activity showed both what and where tuning. These neurons may contribute to the linking of object information with the spatial information needed to guide behavior.     

Glial reduction in the subgenual prefrontal cortex in mood disorders

Mood disorders are among the most common neuropsychiatric illnesses, yet little is known about their neurobiology. Recent neuroimaging studies have found that the volume of the subgenual part of Brodmann's area 24 (sg24) is reduced in familial forms of major depressive disorder (MDD) and bipolar disorder (BD). In this histological study, we used unbiased stereological techniques to examine the cellular composition of area sg24 in two different sets of brains. There was no change in the number or size of neurons in area sg24 in mood disorders. In contrast, the numbers of glia were reduced markedly in both MDD and BD. The reduction in glial number was most prominent in subgroups of subjects with familial MDD (24%, P = 0.01) or BD (41%, P = 0.01). The glial reduction in subjects without a clear family history was lower in magnitude and not statistically significant. Consistent with neuroimaging findings, cortical volume was reduced in area sg24 in subjects with familial mood disorders. Schizophrenic brains studied as psychiatric controls had normal neuronal and glial numbers and cortical volume. Glial and neuronal numbers also were counted in area 3b of the somatosensory cortex in the same group of brains and were normal in all psychiatric groups. Glia affect several processes, including regulation of extracellular potassium, glucose storage and metabolism, and glutamate uptake, all of which are crucial for normal neuronal activity. We thus have identified a biological marker associated with familial mood disorders that may provide important clues regarding the pathogenesis of these common psychiatric conditions.     

Neural activity in the primate prefrontal cortex during associative learning

The prefrontal (PF) cortex has been implicated in the remarkable ability of primates to form and rearrange arbitrary associations rapidly. This ability was studied in two monkeys, using a task that required them to learn to make specific saccades in response to particular cues and then repeatedly reverse these responses. We found that the activity of individual PF neurons represented both the cues and the associated responses, perhaps providing a neural substrate for their association. Furthermore, during learning, neural activity conveyed the direction of the animals' impending responses progressively earlier within each successive trial. The final level of activity just before the response, however, was unaffected by learning. These results suggest a role for the PF cortex in learning arbitrary cue-response associations, an ability critical for complex behavior.     

The specialty of neuropsychology.

[Correction Notice: An erratum for this article was reported in Vol 4(3) of Neuropsychology (see record 2010-01278-001). This article does not represent an attempt by the Division 40 Committee on Professional Affairs to define the specialty of clinical neuropsychology, and was not prepared at the request of the Division 40 Committee on Professional Affairs of the American Psychological Association. The publisher extends its apologies for any confusion this may have caused.] Presents an attempt by the Division 40 Committee on Professional Affairs of the American Psychological Association to define the specialty of clinical neuropsychology. The specialty should be defined for psychologists and consumers of psychological services (e.g., government agencies, insurance companies) so that all concerned can have a clearer sense of expectations of qualifications and standards of practice for this field. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The neuropsychology of post-polio fatigue

To test the hypothesis that post-polio fatigue and its concomitant cognitive deficits are associated with an impairment of attention and not of higher-level cognitive processes, six carefully screened polio survivors were administered a battery of neuropsychological tests. Only subjects reporting severe fatigue, and not those with mild fatigue, demonstrated clinically significant deficits on all tests of attention, concentration, and information processing speed while showing no impairments of cognitive ability or verbal memory. These findings suggest that an impaired ability to maintain attention and rapidly process complex information appears to be a characteristic in polio survivors reporting severe fatigue, because these deficits were documented even when their subjective rating of fatigue was low. This finding supports the hypothesis that a polio-related impairment of selective attention underlies polio survivors' subjective experience of fatigue and cognitive problems.     

Dissociable contributions of the prefrontal and neocerebellar cortex to time perception

We report a series a three psychophysical experiments designed to differentiate the contributions of the neocerebellar and prefrontal cortex to time perception. Comparison of patients with focal, unilateral neocerebellar or prefrontal lesions on temporal discrimination of 400-ms and 4-s intervals (Expt. 1) indicated that neocerebellar damage impaired timing in both millisecond and seconds ranges, whereas prefrontal damage resulted in deficits that were robust only at the longer duration. Patients with prefrontal lesions, however, also exhibited working memory deficits on a non-temporal task (Expt. 2), biases in point of subjective equality indicative of attentional deficits, and were disproportionately sensitive to strategic manipulations in a long-duration discrimination task (Expt. 3). In contrast, the pervasive timing deficits of cerebellar patients were relatively insensitive to strategic support and could not be readily explained by general deficits in working memory or attention. These findings support the hypothesis that neocerebellar regions subserve a central timing mechanism, whereas the prefrontal cortex subserves supportive functions associated with the acquisition, maintenance, monitoring and organization of temporal representations in working memory. Such functions serve to bridge the output of the central timing mechanism with behavior. Together, these regions appear to participate in a working memory system involved in discrimination of durations extending from a few milliseconds to many seconds.     

Neural correlates of directed forgetting in the avian prefrontal cortex.

The authors trained 2 homing pigeons (Columba livia) on a directed forgetting task with 3 cues: a remember cue that was followed by a memory test and the opportunity to obtain a reward, a forget cue that was not followed by a memory test or a reward, and a free-reward cue that was not followed by a memory test but was followed by a free reward. The authors examined the activity of single neurons in the avian nidopallium caudolaterale, an area equivalent to the primate prefrontal cortex. Following the remember cue there was sustained neural activity during the delay period, whereas following the forget cue the neural activity in the delay period was significantly reduced. The activity following the free-reward cue mirrored that following the remember cue. The authors discuss the extent to which the findings are in line with the view that the sustained activity reflects memory for the sample stimulus or memory for reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of the rat medial prefrontal cortex in novelty detection.

The prefrontal cortex in humans has been implicated in processes that underlie novelty detection and attention. This study examined the contribution of the rat medial prefrontal cortex to novelty detection using the targeting, or orienting, response (OR) as a behavioral index. Lesions to the medial prefrontal cortex (specifically the prelimbic and infralimbic cortices) influenced neither the OR to a novel visual stimulus from a localized light source (V1), nor the change in this OR over the course of a series of exposures to V1. However, after exposure to V1, the OR to a 2nd visual stimulus from the same source, V2, was more pronounced in control rats than in lesioned rats. These results suggest that the medial prefrontal cortex in the rat contributes to the process of novelty detection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The debt of neuropsychology to the epilepsies.

Both neuropsychology and psychology in general have been enhanced markedly by brain–behavior models derived from the study of the epilepsies. A significant body of neuropsychological concepts originated or were confirmed through epilepsy-based treatment and research. These concepts include the peri-Rolandic homunculus, the role of the hippocampal–temporal lobe complex in cognitive memory, hemisphere plasticity for speech in childhood, the intracarotid amytal procedure for determining hemisphere memory patency, and hemisphere-based models of cognition confirmed through human commissurotomy. Personality and social–emotional research in epilepsy are additional areas in which new conceptual models grounded in psychological science can both repay our debt to the epilepsies and provide much needed psychological research and treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Glutamatergic regulation of basal and stimulus-activated dopamine release in the prefrontal cortex

The present study was undertaken to determine whether basal and stimulus-activated dopamine release in the prefrontal cortex (PFC) is regulated by glutamatergic afferents to the PFC or the ventral tegmental area (VTA), the primary source of dopamine neurons that innervate the rodent PFC. In awake rats, blockade of NMDA or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors in the VTA, or blockade of AMPA receptors in the PFC, profoundly reduced dopamine release in the PFC, suggesting that the basal output of dopamine neurons projecting to the PFC is under a tonic excitatory control of NMDA and AMPA receptors in the VTA, and AMPA receptors in the PFC. Consistent with previous reports, blockade of cortical NMDA receptors increased dopamine release, suggesting that NMDA receptors in the PFC exert a tonic inhibitory control on dopamine release. Blockade of NMDA or AMPA receptors in the VTA as well as blockade of AMPA receptors in the PFC reduced the dopaminergic response to mild handling, suggesting that activation of glutamate neurotransmission also regulates stimulus-induced increase of dopamine release in the PFC. In the context of brain disorders that may involve cortical dopamine dysfunction, the present findings suggest that abnormal basal or stimulus-activated dopamine neurotransmission in the PFC may be secondary to glutamatergic dysregulation.     

Selective representation of relevant information by neurons in the primate prefrontal cortex

The severe limitation of the capacity of working memory, the ability to store temporarily and manipulate information, necessitates mechanisms that restrict access to it. Here we report tests to discover whether the activity of neurons in the prefrontal (PF) cortex, the putative neural correlate of working memory, might reflect these mechanisms and preferentially represent behaviourally relevant information. Monkeys performed a 'delayed-matching-to-sample' task with an array of three objects. Only one of the objects in the array was relevant for task performance and the monkeys needed to find that object (the target) and remember its location. For many PF neurons, activity to physically identical arrays varied with the target location; the location of the non-target objects had little or no influence on activity. Information about the target location was present in activity as early as 140ms after array onset. Also, information about which object was the target was reflected in the sustained activity of many PF neurons. These results suggest that the prefrontal cortex is involved in selecting and maintaining behaviourally relevant information.     

Peripubertal refinement of the intrinsic and associational circuitry in monkey prefrontal cortex

The peripubertal elimination of axospinous synapses and dendritic spines in monkey prefrontal cortex suggests that this region undergoes substantial reorganization during late postnatal development. Understanding the functional impact of these maturational refinements requires knowledge of the specific presynaptic elements involved in these changes. Two potential sources of these presynaptic terminals are the intrinsic axon collaterals furnished by pyramidal cells within a region and the associational axons that arise from pyramidal neurons in other cortical regions in the same hemisphere. In the adult, both of these types of axon terminals form synapses predominantly with dendritic spines on other pyramidal neurons, and thus they may be preferentially involved in the peripubertal pruning of axospinous synapses and dendritic spines. In order to test this hypothesis, iontophoretic injections of the anterograde tracer biotinylated dextran amine were made into the superficial layers of areas 9 or 46 of the prefrontal cortex of four prepubertal juvenile (14.9-21.5 months old) and three young adult macaque monkeys. Tangential reconstructions revealed a stripe-like pattern of labeled terminals for intrinsic and associational projections in both juvenile and adult animals. During puberty, the intrinsic circuitry underwent extensive topographic refinement, as demonstrated by a 42.7% decrease in stripe area and a 28.0% increase in gap distance between stripes. Furthermore, the mediolateral tangential spread of labeled stripes around the injection site decreased by 27.0%. In contrast, topographic refinement was not evident in the associational circuitry. In both layers 1 and 3, the densities of varicosities and branch points on labeled axons decreased by about 50% in intrinsic stripes during puberty, but only by approximately 30% in associational stripes. These findings suggest that the spatial form and magnitude of peripubertal refinements in prefrontal cortical connectivity may be specific for certain neural elements.