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Understanding the neurobiology and properties of these networks is indispensable to bipolar depression 6 months order amitriptyline 50 mg fast delivery reaching understanding of the functions of the prefrontal cortex depression test beck discount amitriptyline 25mg on-line. This chapter deals with the anatomical and physiological nature of cognitive networks depression symptoms sigecaps generic 10mg amitriptyline mastercard, not only in the prefrontal cortex but also in the neocortex at large. This comprehensive treatment of cortical cognition is essential because all cognitive functions of the prefrontal cortex are dependent on its close interactions with other cortices, as well as several subcortical structures. This interdependence is a direct consequence of the widely distributed and interactive character of cortical cognitive networks. Thus, the first objective of this chapter is to describe those networks in terms of their neurobiology, their distribution, their hierarchical organization, and the associative character of the memory they contain, represent, and enact. From the empirical evidence gathered in this volume, the following executive functions emerge as being cardinal. The first is executive attention, which adopts three complementary forms: preparatory set, working memory, and control of interference. The second function is planning, which is a combination of set and prospective memory for the longer term. As we have seen in previous chapters, none can be safely localized in any particular area of prefrontal cortex, though there are certain areas of dominance for each. That dominance depends not so much on the function itself as on the particular cognitive content (the cognit or cognits) with which it operates at any given time. After successively discussing the major executive functions of the prefrontal cortex, we will discuss its role in emotional behavior, which primarily involves its orbitomedial areas. In general, it is the generic, action-related character of both executive and emotional prefrontal functions that, despite the obstacles to localize them, allows us to draw inferences about them that appear to be valid for several animal species. Indeed, although the discussion in this chapter is centered on the prefrontal cortex of primates, it stands to reason that the basic functional principles enunciated below apply to other kinds of mammals as well. Nevertheless, there are valid reasons to conclude that the various frontal functions described here are not equally shared by different species, as the anatomy differs, homologies remain uncertain, and behaviors are to a large degree species-specific. That specificity is most evident in two forms of activity that are characteristic of the human and in which the prefrontal cortex is profoundly involved: language and creative intelligence. After discussing them in separate sections, the chapter closes with a few neurophilosophical reflections on two other subjects that are key to the human "agenda" and thus germane to prefrontal physiology: consciousness and free will. This dichotomy prevails at all levels, beginning at the lowest, in the spinal cord. This applies to cognitive functions as well, for the cortex of the occipital, parietal, and temporal lobes largely supports perception and perceptual memory, while the cortex of the frontal lobe supports action and executive or motor memory. Indeed, the frontal cortex is "motor cortex" in the broadest sense of the expression. Perceptual Networks in Posterior Cortex Most of our behavior is anchored in experience. Much of it consists of learned habits, sequences of more or less automatic responses to internal and external stimuli. Some of it, most characteristically in our species, depends not only on habit but also on educated choice, and leads to the purposeful creation of new changes in the environment and new relationships between us and the environment. This form or part of behavior can appropriately be termed deliberate, for it is guided by the cognitive deliberation of alternatives, expected risk and value, and deliberate purpose. In humans and other primates, the postcentral (post-Rolandic) cortical areas are largely devoted to perceptual memory and processing and to the representation of images and constructs of the external world. There is now substantial evidence that the memory storage and processing of perceptions are functions of large networks of interconnected neurons of posterior cortex. These perceptual networks or cognits transcend anatomical areas and modules by any structural definition.
Whether that system is first or primarily affected at subcortical level depression definition emedicine buy cheap amitriptyline 75mg line, the cortex of dementia patients has consistently been found to mood disorder va disability rating discount amitriptyline line be deficient in muscarinic receptors (Rinne et al depression nutrition purchase amitriptyline 10 mg mastercard. However, inasmuch as many of the cognitive impairments characteristic of dementia. Therein lies the rationale for using cholinergic substances, especially acelylcholinesterase inhibitors, to treat dementia (Iversen, 1998). Prominent among such substances is physostigmine, which in the monkey reverses the scopolamineinduced deficit in delayed-response behavior (Rupniak et al. These substances and their synaptic receptors are already present in the prefrontal cortex at birth. Thereafter, they generally develop in synchrony to reach the highest levels in young adulthood. It serves not only the local prefrontal circuitry but also the excitatory connectivity of the prefrontal cortex with striatal, thalamic, and limbic structures. It serves all the inhibitory interneurons, which are found practically everywhere in the nervous system. They are part of the mesocorticolimbic system, which is heavily involved in motivation and the experience of reward. Serotonin, like the other two monoamines, interacts with other transmitters in the prefrontal cortex and in other structures with which it is connected. In addition to the monoamines, the prefrontal cortex, like the rest of the neocortex, receives profuse afferents from the subcortical components of the cholinergic system. These include the mesencephalic reticular formation and the nucleus basalis of Meynert. The prefrontal cortex is the recipient of substantial and widespread cholinergic influences that modulate its neuronal circuits in cognitive functions. A number of pathological conditions of more or less definite genetic etiology have been attributed to disorders in neurotransmitter systems. In most, if not all, of those conditions, more than one neurotransmitter is implicated. Drugs of abuse induce neurochemical alterations in numerous limbic and paralimbic structures, notably the nucleus accumbens in the ventral striatum, the amygdala, and the orbitomedial prefrontal cortex. Endogenous depression, as it occurs in bipolar illness, is a hereditable disorder that is generally accompanied, if not caused, by deficits in one or more monoamine systems, notably serotonergic. The major neurodegenerative diseases affecting the prefrontal cortex have some degree of hereditability. Modulation by central and basolateral amygdalar nuclei of dopaminergic correlates of feeding to satiety in the rat nucleus accumbens and medial prefrontal cortex. Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex. Distribution of cholinergic neurons in rat brain: demonstrated by the immunocytochemical localization of choline acetyltransferase. Catecholamine and second messenger influences on prefrontal cortical networks of "representational knowledge": a rational bridge between genetics and the symptoms of mental illness. Methylphenidate improves prefrontal cortical cognitive function through alpha2 adrenoceptor and dopamine D1 receptor actions: relevance to therapeutic effects in Attention Deficit Hyperactivity Disorder. Noise stress impairs prefrontal cortical cognitive function in monkeys: evidence for a hyperdopaminergic mechanism. The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes. Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys. Relationship of prefrontal connections to inhibitory systems in superior temporal areas in the rhesus monkey. Decision making, impulse control and loss of willpower to resist drugs: a neurocognitive perspective. Convergent thalamic and mesencephalic projections to the anterior medial cortex in the rat.
This substance is secreted by hypothalamic cells and neurally transported to depression test cmha buy amitriptyline in united states online other subcortical and cortical structures depression definition causes proven 25mg amitriptyline. Apparently by interacting with ascending and descending reticular systems of the brainstem the great depression definition wikipedia generic amitriptyline 25 mg without a prescription, orexin plays important roles in sleep, arousal, attention, and autonomic functions. It is presumably through those interactions that orexin exerts significant roles in arousal and attention. Nitric oxide, another non-conventional "neurotransmitter" (Dawson and Snyder, 1994), may play an important role in prefrontal physiology. The reverse relationship (hippocampus to prefrontal) may occur by intervention of those transmitters, glutamate and nitric oxide, in the formation of the associative executive memory of the prefrontal cortex. Arguably, this is the clearest example of failure of a given neurotransmitter in a given part of the brain leading to a clear-cut disease syndrome. In terms of neurotransmitter pathology, however, that type of relation is the exception, not the rule. Below, we review the role of the various neurotransmitters in some of the major neuropsychiatric syndromes. In no case can we unequivocally attribute a disease entity to deficit or malfunction of one specific transmitter, though in each syndrome some disordered neurotransmitters play more of a role than others. The reasons for that lack of pathogenetic neurotransmitter specificity are to be found in the fact that these chemicals work in complex systems, as do the neurons they serve. The idea that a cell uses only one transmitter is false, as now we know that neurons can contain more than one transmitter. Then, a transmitter does different things in different brain structures, since what it does is defined by the structure and the connectivity that it serves within it. Such is the case in the prefrontal cortex, with its many transmitters and myriad connections. Nevertheless, despite our ignorance regarding the nature of many electrochemical transactions in this part of the brain, there is an emerging body of knowledge about the malfunction of neurotransmission in some major disease categories that affect the frontal lobe, as well as a solidifying rationale about how to treat them by chemical means. Much of that knowledge is empirical, derived from experiment and clinical experience; some of it is inferential. Attention Disorders Attention is a complex cognitive function biologically based on the limitations of the nervous system to process an excessive amount of relevant or adaptive information at a given time. The prefrontal cortex, as we shall see, has much to do with selective and adaptive processing. The narrow phenomenological definition of attention coincides with that of the so-called focus of attention, which refers to the selective informational content that is in the field or "stream" of consciousness at any given time. The ability willfully and persistently to maintain that selective content in consciousness is what we understand as the capacity to concentrate attention. It is argued that this concept of attention, based on focused and maintained content, includes working memory (Fuster, 2003), which after all is attention focused on an internal representation. That narrow definition of attention, however, which may be called "inclusionary" (for what the focus of attention includes), is incomplete because it does not account for the exclusionary (inhibitory) aspect of attention. James (1890) was the most prominent proponent of the first aspect of attention, Broadbent (1958) of the second. In the primate, we know that all three major prefrontal regions play major roles in attention. The medial prefrontal cortex, which includes anterior cingulate, paralimbic, and medial premotor areas, is the prime recipient of inputs from the limbic, mesencephalic, and diencephalic structures (Chapter 2) involved in arousal, drive, and motivation. Oversimplifying somewhat for the sake of clarity, we could conclude that the medial areas contribute to attention the elementary neural "energy" it needs. Thus, to sum up, it seems appropriate to attribute to the medial, lateral, and orbital prefrontal cortices the major roles in the intensive, inclusionary, and exclusionary aspects of attention, respectively. It should be kept in mind, however, that the three "functions" work intimately together, and that none of the three regions has the exclusive control of any function. As we saw earlier in this chapter, there are certain differences in the regional distribution of neurotransmitters in the prefrontal cortex. In any region it seems to be the rule that any pyramidal neuron co-localizes more than one transmitter, each transmitter possibly serving a different cognitive function depending on the connectivity of the neuron. It is not surprising, therefore, that several transmitters are implicated in practically any of the attentive functions of the prefrontal cortex.
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