10x Your Memory Power

Memory Professor System

Memory Professor system is a program that uses natural techniques which have gone through a trial, testing and proven to work efficiently and help you gain a strong memory power of about 500% within 30 days only. The program is also offering a guarantee of full money refund within 60-days of purchase which means that this program is secure and has zero risks associated with it hence making it an excellent investment to try. Kit Stevenson is offering a discount to the first 100 people who will purchase this product, and on top of that, he is offering six special bonuses to all the members who buy the memory professor program. There are many benefits associated with this program some of them being, gaining self-esteem, enhancing getting better grades, improving business and personal relationships, enhancing your brain power and finally helping you be in a position to make sound and beneficial business deals. With all these benefits, I highly recommend memory professor system program to everyone who has not yet tried because it is a risk-free method. Hurry up and grab your space while the discounts last. More here...

Memory Professor System Summary

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Contents: Ebook
Author: Kit Stevenson
Official Website: memoryprofessor.com
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My Memory Professor System Review

Highly Recommended

I started using this ebook straight away after buying it. This is a guide like no other; it is friendly, direct and full of proven practical tips to develop your skills.

As a whole, this manual contains everything you need to know about this subject. I would recommend it as a guide for beginners as well as experts and everyone in between.

Preface How To Read This Book

I have tried to keep the book to a size that can be read in a couple of weeks (one or two chapters per day) and to write in a style that is not so dry as to make reading a trial in endurance. Hopefully, you will not find it too journalistic. Ideally, you would read the volume from start to finish. If you do so, you will notice that many important facts and ideas appear in several places, often described from different angles. This redundancy is intended to help memorize important issues and link facts and concepts to each other. If you find essential points missing, please follow my request in the last paragraph of this preface.

Lesion Induced Models

Amygdala, and the prefrontal cortex (PFC) might underlie social deficits in autism. On that basis several models of autism have been proposed (Tordjman et al. 2007). For example, neonatal ibotenic acid lesion of the amygdala on PND 7 in rat produces a spectrum of behavioral abnormalities resembling those described in autism decreased social interaction, increased stereotypic-like activity and decreased exploratory behavior. Similarly, neonatal ventral hippocampus lesion in rats leads to impaired social behaviors, motor hyperresponsiveness to stress, enhanced stereotypies, deficits in pre-pulse and latent inhibitions, and working memory problems. Rats with neonatal PFC lesions display reduced social play and non-play behavior in early adolescence, and reduced amount of self-grooming in adulthood. However, as these injuries destroy entire brain regions they have little relationship to the mild neu-roanatomical pathologies observed in autism. Furthermore, abilities to investigate genetic...

HT2CRMediated Contributions to Cognitive Behaviors

Behaviors traditionally associated with cognitive function, including different aspects of long and short-term memory, behavioral planning, and behavioral inhibition are organized across a broad extent of the neuraxis and encompass regions of the cortex, basal ganglia, hippocampus, amygdala, and extended amygdala. 5-HT2CR expression has been demonstrated in all of these regions (Eberle-Wang et al. 1997 Filip and Cunningham 2002 Huang et al. 2004 Krishnakumar et al. 2009 Pompeiano et al. 1994 Serrats et al. 2005). Thus, 5-HT2CRs may potentially regulate a large number of cognitive behaviors.

Overview and Pathogenesis of Alzheimers Disease

Synthesized in the cholinergic axon terminal from acetyl coenzyme A and choline by the enzyme choline acetyltransferase 4 . Once made, acetylcholine is packaged into storage vesicles for release when triggered by an action potential. There are two cholinesterase enzymes capable of metabolizing acetylcholine once it is released into the synaptic cleft. They are called acetylcholinesterase and butyrylcholinesterase, formerly known as pseudo-cholinesterase. When acetylcholine is metabolized in the synaptic cleft, it is broken down into choline. The resulting choline is taken back up into the presynaptic neuron and is recycled to make new acetylcholine molecules. There is some evidence that as Alzheimer's disease progresses, the level of acetylcholinesterase decreases and butylcholinesterase increases 5 . Researchers have shown that a deficiency in cholinergic functioning is related to impairment in memory, in particular short-term memory. Acetylcholine may also be involved in mood and...

Of D1nmda Occurs Receptor Interactions

DA concentration and the mode of release are also important. Phasic release may produce different effects from tonic release. MSSNs are constantly bombarded by cortical and thalamic inputs and tonic release of DA filters a sizable percentage of these glutamatergic inputs through D2 receptors located on presynaptic terminals.60 Higher local concentrations of DA occurring when it is phasically released are likely to activate D1 receptors and enhance selected corticostriatal synapses. For synaptic responses, studies in cortical pyramidal neurons revealed that the enhancement of NMDAR-mediated responses by DA follows an inverted U-shaped dose-response curve30 in agreement with the idea that optimal levels of D1 receptor activation are required for efficient working memory formation.61 Too much DA and hence too much activation of D1 receptors, as during stress, may be deleterious for cortical function.

Functional Relevance Of Danmda Receptor Interactions

The function of DA-NMDAR interactions may vary according to the area in which they occur. In the dorsal striatum, these interactions are important in motor control. In the ventral striatum, they provide mechanisms that may underlie addiction. In the frontal cortex, these interactions are implicated in working memory and cognition. In other areas such as the amygdala, their role is less clear. Overall, the D1-NMDAR interaction, when mediated by second messenger cascades, appears synergistic. The membrane-delimited physical interactions appear antagonistic and have more relevance to neuroprotection, with the caveat that DA agonists and antagonists can also directly modulate the NMDAR channel pore. In the cerebral cortex, D1 receptors and D1-NMDAR interactions play a very important role in working memory and cognitive function. In particular, accumulating evidence indicates that induction and maintenance of persistent activity in prefrontal cortex and related networks is dependent on...

Delayed Non MatchtoSample Task Definition

Derived from delayed-response principles, the delayed (non)match to sample task is a widely used test of working memory in animals. Typically, the animal is presented with a sample stimulus. After a short delay, the sample stimulus is shown again along with a novel alternative. In the nonmatching paradigm, the animal is rewarded for selecting the novel stimulus. In the matching paradigm, the animal is rewarded for selecting the sample stimulus thereby avoiding the novel stimulus. If different stimuli are used for every trial (trial unique''), then the test specifically measures visual recognition memory. If the same stimuli are used on every trial (trial nonunique''), then the test effectively measures the animal's ability to remember the most recent item. Delayed (non)matching tasks are considered tests of working memory because (a) the information to be remembered on each trial is independent from the next and (b) the response is contingent upon the information that was presented at...

An Hypothesis For Atypical Antipsychotic Drug Action

Clozapine and other atypical antipsychotic drugs have low or negligible affinity for dopamine D1 receptors at therapeutic doses.5-7 Thus, after clozapine administration, synaptic dopamine levels are high with very little occupancy of the dopamine D1 receptor by clozapine, resulting in an indirect activation of this particular dopamine receptor (Figure 3). In contrast, clozapine has moderate to high occupancy of dopamine D2 and D4 receptors.5-7 Moreover, haloperidol only weakly stimulates cortical dopamine efflux (see earlier), and it only does so at doses of the drug that likely occupy both cortical dopamine D1-like and D2-like receptors. As dopamine D1 receptors appear to be particularly important for working memory function,67 it may be that indirect activation of this receptor by clozapine-induced increases in cortical dopamine release is related to its cognitive effects. Our hypothesis suggests that direct dopamine D1 receptor agonists may be particularly effective in modulating...

Of translational substrates

NMDARs are involved in coordinated signaling immediately downstream of synap-tic activity during neuronal development, synaptic plasticity, and long-term memory. Based on the broad requirement for protein synthesis in these processes, it is not surprising to find evidence that NMDARs are intimately involved in many facets of translational control in neurons.

Imprinting And Xinactivation

Most genes in humans are expressed equally strong from both alleles. About 50 genes, however, are genomically imprinted. They often occur in clusters, i.e. several imprinted genes are located within one chromosomal region (see Figure 11.5 for an example). The expression of imprinted genes differs between the alleles inherited from the mother ('maternal') and father ('paternal'). Depending on the gene, expression differences between the maternal and paternal alleles may be found in every or in selected tissue, and they may be qualitative or quantitative. The most pronounced differences are found in fetal tissues and in the placenta. This observation underlies the 'battle of the sexes' hypothesis. According to this interpretation, genes preferentially expressed from the paternal allele promote growth of the fetus and the placenta, thereby straining the mother's ressources. In contrast, genes expressed from the maternal allele tend to limit growth. This interpretation fits amazingly well...

Dopaminemediated Learning Aging and pd

Sequential learning, involved with the processing of a variety of cognitive functions, such as linguistic expression, semantic sequencing, working memory, and procedural memory, is an important aspect of cognitive processing 88 . Sequential learning is impaired in PD patients, suggesting that altered dopamine neurotransmission may be responsible for serial reaction time learning deficits associated with this disease 89-90 . In animal studies, following neurotoxin, (MPTP)-mediated unilateral lesions in the striatum to deplete dopamine unilaterally in the striatum, show loss in learning sequential tasks 91-92 . Recent study using molecular imaging supports the notion that striatal dopamine is critical for motor sequential learning 88 . In aging, the deficiency of dopamine in the prefrontal cortex results in the deficit in working memory, whereas, in acute stress, excessive dopamine neurotransmission leads to impairment in working memory. These impairments can be attenuated by D1...

Avoidance Conditioning Paradigms Selected Studies I Selected Studies

The authors concluded that a-MSH inhibits extinction (preserves retention) only during the course of treatment (when the peptide is present in the body), whereas the effect observed for pitressin persisted beyond the duration of its presence in the body. It was concluded that one or more of the peptides contained in the pitressin solution was instrumental in preserving the conditioned response, that is, in forming a long-term memory of the experience. (5) the authors suggested that the failure of LVP to accelerate extinction in subjects given the response prevention trials might indicate that the peptide has no important role in facilitating the short-term memory processing involved in the new learning occurring during this interpolated experience. Whatever the basis for this effect, a subsequent replication study, with the exception that LVP was given after rather than before the interpolated experience, obtained the same results (Hagan, 1982 discussed in Chapter 9).

Acute Nicotinic Agonist Effects

Shown to reverse delay match to sample (DMTS) performance caused by aging, and facilitates performance in aged rats exhibiting deficits in spatial working memory1649 or poor passive avoidance performance due to a choline-deficient diet.58 In a series of studies it has been found that the radial-arm maze is a sensitive and reliable way to assess nicotinic effects on memory function in rats. The radial-arm maze test is a standard and sensitive measure of working memory performance. Traditionally, it consists of a central arena with eight arms extending outward. Additional arms can be added to provide a more challenging task and more response locations to assess working and reference memory separately. In the most common radial-arm maze procedure, the subjects are reinforced for one entry per arm. For optimal performance, animals must adopt a win-shift strategy once rewarded, responses must be switched and not repeated to receive additional reinforcement. Errors in this task are repeated...

Nicotinic Antagonists

Nicotine-induced memory improvements can be blocked by the nicotinic antagonist mecamylamine.435 43 Interestingly, the muscarinic antagonist scopolamine also can reverse memory enhancement induced by nicotine in rats.43 The effects of mecamy-lamine also appear to be related to task difficulty and dose, since some studies have not found mecamylamine-induced deficits,14 and have even found paradoxical improvements in performance.35 3654 As discussed later, these effects may be due to the degree of proactive interference involved in the task.

Behavioral Specification

Working memory is defined as memory with changing contents, as opposed to reference memory, which is defined as memory with fixed contents. Working memory can be differentiated from reference memory in the radial-arm maze by always baiting the same arms and not the others at the beginning of each session. Entries into baited arms are considered working memory and entries into unbaited arms are considered reference memory. Usually a 16-arm radial maze is used for assessing working and reference memory. This technique has been used to show the relative specificity of nicotine-induced improvement in working but not reference memory.29 Baiting 12 of the 16 arms presents a difficult working memory task, while still leaving 4 arms never baited allows for the assessment of reference memory. This technique has been used to show the relative specificity of nicotine-induced improvement in working but not reference memory.29 30 The specificity of the cognitive effects of nicotinic treatments can...

Nicotinic Receptor Subtype Involvement In Memory Function

In the central nervous system, although other prominent subunit combinations including the a402, a304, and a7 exist as well. The functional roles played by these subtypes are being discovered. Hippocampal a402, a304, and a7 receptors appear to be important for working memory functions. Studies have shown that most hippocampal neurons have nicotinic receptors that respond to nicotine with a Type IA nicotinic current characterized by rapid desensitization and blockade by MLA,2,13 a selective a7 nicotinic receptor antagonist.59 Fewer neurons have receptors that respond with Type II currents and are blocked by DH0E and Type III currents, which are blocked by mecamylamine and are more slowly desensitized.2 Some neurons show a mixed response termed Type IB which is partially blocked by either MLA or DH0E, but completely blocked by both antagonists.2 The pharmacological and kinetic properties of these currents support their correspondence to a7 (Type 1A), a402 (Type II), and a304 (Type III)...

Introductory Comments Retrograde Amnesia and Memory Retrieval

Generally speaking, retrograde amnesia (RA) refers to the inability to remember experiences that occurred just before a temporary but severe disturbance of the normal physiological activity of the brain. In the animal laboratory, RA can be produced by postlearning or preretention application of any of a variety of treatments that disrupt neural activity (e.g., carbon dioxide, electroconvulsive shock, or pentylenetetrazole) or inhibit protein synthesis (e.g., puromycin). Traditionally, the amnesia produced by immediate postlearning application of one of these amnesic agents has been attributed to a disruption of memory consolidation, the process by which fragile, temporary short-term memory is changed into resistant, permanent long-term memory.

Cognitive Deficit and D1 Receptors

Negative symptoms and cognitive dysfunctions in schizophrenia may be associated with hypofunc-tion of the prefrontal cortex. Hypometabolism and anatomical abnormalities have been demonstrated in the prefrontal cortex.4 The D1 dopamine receptors in the cortex, particularly the dorsolateral region, play an important role in working memory which is defective in schizophrenia. The receptors modulate the cortical output activities to subcortical regions such as nucleus accumbens and striatum.18 Depletion of dopamine in the prefrontal cortex of monkeys induced deficits in a delayed alteration spatial memory task.19 Local cerebral injection of selective D1 antagonists, but not of selective D2 antagonists, into the dorsolateral prefrontal cortex induced impairment in an oculomotor delayed-response task.20,21 On the other hand, low levels of D1 antagonists enhanced the task,22 and increased dopamine turnover in the cortex induced by anxiogenic drugs hindered spatial working memory performance...

CrosstaLk Between GCs and COX2 in the Control of Synaptic Plasticity and Learning Processes

Resulted in cognitive deficits that are associated with a parallel age-dependent increase in neuronal apoptosis (Andreasson et al., 2001). Nevertheless, the relevance of COX2 in cognitive processes is not limited to pathological deficits involving neuronal death. For instance, COX2-selec-tive inhibitors impair hippocampal-dependent, but not dorsal striate-dependent, memory consolidation (Rall et al., 2003 Teather et al., 2002). This effect was only observed when COX blockers were injected immediately after task training but not when they were administered 2 h later (Teather et al., 2002), suggesting a role of COX in the retention of short-term memory for subsequent consolidation. Other studies showed that the retention of hippocampus-dependent spatial learning was impaired by a COX2-selective inhibitor, but not by a COX1-selective inhibitor, suggesting the involvement of endocannabinoids. A physiological function for COX2 in the learning processes is further supported by the...

Question And Answer Session

WEINBERGER Well, again I think that is a whole other symposium, and there have been many. But our application of blood flow measurements was as another physiological assay of neuronal function. So the blood flow measurements I showed you were acquired during the specific cognitive processing of a working memory task and a sensory motor control task.

Nicotine As A Cognitive Enhancing Agent In Monkeys

The first study with nicotine also provided additional aspects of the drug's pharmacology not previously known. For example, the doses of nicotine used to enhance memory in our subjects were very low, ranging from 1 to 20 g kg, i.m. This range appeared to be much lower than those used in rodent studies for memory enhancement. Although plasma levels of nicotine were not measured, it is unlikely that they would have exceeded 100 nM. However, this concentration represents the threshold range used to achieve significant neurotransmitter release (e.g., Wilkie et al. and Reuben and Clarke56). This apparent discrepancy in the potency of nicotine for the two processes does not necessarily rule out a role for evoked transmitter release in nicotine's positive mnemonic actions. For example, it is possible that small, but important levels of transmitter release might occur below the sensitivity of most biochemical measures. In support of this possibility, Wesnes and colleagues78 reported that the...

On the Learning Phase of Memory Processing

Numerous studies by De Wied and colleagues led them to conclude that VP and OT exert a major influence on the consolidation of long-term memory and on its subsequent retrieval, but not on the learning phase of memory processing. However, the generalization that these neurohypophy-seal peptides do not influence learning needs some qualification because under certain conditions they have been observed to do so. Thus, VP may influence the rate of acquiring an active avoidance response when learning is slow or impaired as in completely hypophysectomized rats (Bohus et al., 1973 Lande et al., 1971) or at dose levels that are especially aversive (Gaffori and De Wied, 1985 see Chapter 3) or through its ability to interact with the subject's arousal level (Skopkova et al., 1991 see Chapter 3). OT has been observed to attenuate acquisition of active avoidance behavior in intact rats after intracerebroventricular administration (Bohus et al., 1978b).

Theoretical Propositions of the VPOT Central Memory Theory and Relevant Evidence

What is herein referred to as the VP OT Central Memory Theory'' comprises an evolving viewpoint as to how these neurohypophysial peptides operate to influence learning and memory. Underpinning this viewpoint is acceptance of the memory consolidation theory, which suggests that long-term memory is formed by consolidation, a time-dependent process that alters the memory trace from a temporary, fragile form to one that is durable and resistant to disruption by agents influencing neural activity and metabolism (e.g., electroshock, deep anesthesia, and protein synthesis inhibition). De Wied and colleagues also appear to accept the view that the short-term memory trace systems operating during learning are independent of those representing long-term memory, insofar as a given treatment can affect one without influencing the other. (see McGaugh, 1966, 2000, for further discussion of memory consolidation as a time-dependent process and the question of whether or not short-term and long-term...

Performance Deficits By Nicotinic Drugs

Abnormalities that occur in aged humans and AD patients. This assertion is based on observations that they begin to encounter learning and memory deficits during the second decade of life, with more substantial deficits apparent by the mid- to late 20s. With age, nonhuman primates have been shown to develop abnormal neurites, amyloid deposition, altered levels of neurotransmitters, and reductions in synaptic densities and pyramidal neurons with age. They also express the apoenzyme E isoform that is analogous to the human apoE4 isoform implicated as a risk factor in AD.59 60 Furthermore, improvements in DMTS performance by nicotine may be especially relevant since this working memory task engages many of the same neuronal substrates in monkeys as in humans (e.g., prefrontal cortex, hippocampus, etc.). A modified version of the DMTS paradigm has been used to study cognitive ability and impairment in AD patients, and delay dependent deficits in DMTS performance have been documented in...

Proposition 1 VP Facilitates Memory Consolidation and Retrieval

Initial evidence relevant to proposition 1 was obtained from experiments with rats, which found that surgical removal of the intermediate posterior lobes of the pituitary gland led to abnormally rapid rates of extinction of a learned shuttlebox shock avoidance response (De Wied, 1965). The facilitated extinction could not be adequately accounted for by the associated disturbance in water metabolism, and it was corrected by replacement therapy with pitressin as well as purified LVP. Moreover, the normalization of extinction induced by posterior pituitary hormone replacement therapy was not mediated by a VP-induced release of ACTH (De Wied, 1965). An investigation of the effects of ACTH-like peptides and VP on intact rats showed that both delayed extinction on active avoidance tasks, but unlike ACTH, which needed to be present in the body for full effectiveness, VP prolonged extinction for weeks after termination of treatment (De Wied, 1971 De Wied and Bohus, 1966). Clearly, the...

Tests for Memory Function

It is thus surprising that the cognitive deficit induced by antiepileptic drugs is only rarely studied in detail. Such laboratory tests like the one-trial passive avoidance procedures and maze tests (as exemplified by a Y-maze test) have shown that doses of anticonvulsant drugs that produce effects and or plasma concentrations comparable with those seen in clinical conditions in patients may produce impairments of short-term and long-term memory in rodents.24-27 For this reason, simple tests that are able to detect adverse cognitive effects of antiepileptic drugs need to be included in the battery of routinely performed preclinical tests in rodents. The passive avoidance task is believed to offer information pertaining to long-term memory28 and spontaneous alternation in the Y-shaped maze can be regarded as a measure involving spatial working memory.29

Basal Ganglia Contain 5HT Fibers and 5HT2C Receptors

The basal ganglia are subcortical structures involved in the control of motor and cognitive functions, including sensorimotor integration, procedural memory, formation of habits, and behavioral automatisms (Graybiel 2005 Mink 1996). Based on their functional connections, modern definitions of the basal ganglia include the dorsal striatum (caudate nucleus and putamen), internal and external segments of the globus pallidus (GPi-entopeduncular nucleus, EPN, in rodents and GPe,

Common Action of D2 Receptor Antagonism on Cortical D1 Receptors

The observation that the therapeutic potency of antipsychotic drugs directly correlates with their affinity for dopamine D2 receptors is a keystone of the dopamine hypothesis of schizophrenia.1 However, it still remains unclear where the D2 receptors are located to modulate most critically the symptoms of schizophrenia. It has recently been demonstrated that upregulation of the cortical D2 receptors after chronic treatment with antipsychotic drugs is accompanied by downregulation of the cortical D1 receptors in nonhuman primates.78,79 It appears that an appropriate interaction and balance between D1 and D2 activity is associated with clinical effects of antipsychotic drugs. Considering the finding that the activation of prefrontal D1 receptors in a narrow range of occupancy optimizes physiological signaling in prefrontal neurones engaged by working memory in nonhuman primates,22 it was suggested that the adjustment of cortical D1 receptor levels in combination with D2 receptor...

Concluding Comments

The dopamine hypothesis for schizophrenia has been supported mainly by the antipsychotic effect of D2 dopamine receptor antagonists.1 However, recent PET studies81-84 cast doubt on a variant of the dopamine hypothesis that schizophrenia is related to increased striatal D2 densities. The dopamine D1 receptor, which is highly expressed in the prefrontal cortex,15 has been implicated in the control of working memory,20-22 and working memory dysfunction is a prominent feature of schizophrenia.4,5 Although several postmortem studies have failed to produce a consistent finding of abnormal D1 receptor density, two recent PET studies have found decreased D1 receptors in schizophrenia.6,67 This inconsistency between in vitro postmortem studies and in vivo PET studies has been observed in the studies of D2 and 5-HT2 receptors in schizophrenia. In spite of postmortem studies reporting increased striatal D2 receptor density or decreased cortical 5-HT2 receptor density, PET studies of...

Receptor Properties

In both sexes (Klein et al., 2003 Mendizabal et al., 2003 Pagotto et al., 2006 Sanger, 2007 Wang et al., 2006). At central level, eCBs and congeners, via CBs, control pain, wake sleep cycles, thermogenesis, food intake, induce psychomotor disorders, tremor and spasticity, catalepsy, impair working memory, and memory consolidation, inhibits long-term potentiation and glutamatergic transmission (Elphick and Egertova, 2001 Fride, 2002 Pagotto et al., 2006 Wang et al., 2006). In CNS, often CBs are localized in same brain structures with possible differences in the distribution amid neuronal elements where they are localized, as it happens in the cerebellum, where CB1 has been localized in molecular and granular layers while CB2 has been found in Purkinje cells (Gong et al., 2006). At central level, AEA is suggested to act as a retrograde messenger to inhibit neurotransmitter release (Elphick and Egertova, 2001) it is released by postsynaptic neurons and binds CB1 located at presynaptic...

Vasculitis and sarcoidosis

Granulomatous vasculitis may complicate the course of chronic sarcoidosis and can be responsible for diffuse encephalopathy with psychiatric presentation and short-term memory deficit. Necrotizing vasculitis occurs in this context and induces ischemic lesions. This angiitic pattern of neurosarcoidosis has been demonstrated histologically in patients with neuro-ophthalmologic manifestations75 and in patients with sarcoid neuropathy (Said et al, unpublished). These cases pose the problem of their border with Wegener's granulomatosis, with which they share many features, but sarcoidosis, even in the cases with granulomatous angiitis, has a more benign course than Wegener's granulomatosis.76,77

Inconsistencies in the Research Literature Regarding the Putative Brattleboro Diabetes Insipidus Retention Deficit

(1983) observed no impairment in working memory in HODI relative to LENO rats in a T-maze alternation task tested with a short (8 s) delay between the forced-choice (information) and the free-choice run. Moreover, Brito and colleagues (Brito et al., 1981, 1982) observed that HODI rats retained a punishment-induced inhibition of a food-approach response longer than did LENO rats.

Vitamins and Memory Function New Results from the Basel Longitudinal Project IDA

Therefore, we have to classify different cognitive performance tasks based on actual knowledge about structures and functions of memory. We were interested in the unique predictive power of plasma antioxidant levels (ascorbic acid, p-carotene and a-tocopherol) collected in 1971 (Stahelin et al., 1991) and 1993 on different memory performances (priming, working-memory, free recall, recognition and vocabulary) measured in 1993. In multivariate regression analyses we corrected for potentially confounding factors such as systolic blood pressure, serum cholesterol and ferritin as well as age, gender and level of education. Different memory parameters (priming, working memory, free recall and recognition) were assessed for this study. The WAIS-R Vocabulary Test was administered in this standardized subtest of the Wechsler Adult Intelligence Scale, subjects have to give definitions of words, assessing aspects of semantic long-term memory. explicit memory (free recall, recognition), implicit...

Colony Specific Heritable Traits and Inconsistent Findings Concerning a Retention Deficit in the Brattleboro DI

The results were interpreted as indicating that the VP deficiency accounted for the fearfulness observed in the open field emergence test, but that colony-specific genetic and or early experiential factors, rather than a VP deficiency per se, contributed to the differences observed in long-term memory in the approach avoidance task (i.e., rate of recovery from the mouthshock experience) and in dispositional and representational memory in the DNMS task.

Cellular and Molecular Pathophysiology of Alzheimers Disease

Alzheimer's disease (AD) is the most prevalent form of dementia in the world today, afflicting approximately 4 million people, or 60-80 percent of the cases of dementia in the United States.2-4 The disease has both familial and sporadic forms, both of which cause dysfunction in behavioral regulation, higher cognitive function and, most strikingly, short-term memory. AD presents unique challenges from a social and medical view. Because it is insidious and progressive, society's costs, both direct and indirect, are high. Additionally, AD presents a problem in that most patients do not come to medical care until significant impairment has occurred. Thus, patients do not always benefit from early diagnosis and treatment. Finally, at this point, AD cannot be definitively diagnosed until autopsy. As clinicians expand the therapeutic arsenal for AD, a definite pathway for diagnosis pre-autopsy is of the utmost importance.

Caffeine and cognition

Effects on memory A major focus of cognitive psychology, memory has been studied intensively, and a number of investigations have addressed the effects of caffeine. Unfortunately, results in this important area of mental performance are quite mixed. First, a number of studies have found that caffeine enhances memory performance in several paradigms. It has been shown to improve delayed recall,120 recognition memory,138 semantic memory,89 and verbal memory in general.139 Other studies have shown significant increases in memory performance on both easy140 and difficult110 memory tasks. Females (but not males) in one study showed positive effects of caffeine on word list retention, though only when the words were presented at a slow rate.141 One study demonstrated that caffeine has cholinergic properties that can enhance cognitive functioning. In this investigation, the result was improved performance on short- and long-term memory retrieval, reading speed, and Complicating matters...

Phencyclidine PCP or Angel Dust

Discovered in 1926, phencyclidine is a hallucinogen that remained without significant utility until 30 years later when its potential to reduce or even eliminate pain was demonstrated in animal models. Briefly used as an analgesic-amnesic anesthetic, it was later abandoned due to high incidence of bizarre psychiatric effects such as delirium, agitation, disorientation, and hallucination (Abraham et al. 1996). Ketamine, a PCP derivative, is a well-known sedative, anesthetic, amnesic, and analgesic. PCP and similar compounds produce a dissociative phenomenon, in which the subject has an out of body experience. When taken orally, the effects develop in 1-2 h and last for about 10 h. Their mechanism of action is complex and includes agonist, partial agonist, and antagonist effects at various adrenergic, dopaminergic, and serotonin receptors (Abraham et al. 1996). Sympathetic activation, hallucination, delirium, amnesia, depression and, long-term memory and cognitive dysfunction are some...

Principles and Role in Psychopharmacology

Cognition is currently a much-employed term in psycho-pharmacology, referring to a collection of higher-order processes that intervene between sensory processing and motor output to produce behavior. Cognition is thus not a unitary construct and has to be carefully decomposed into its constituents, which can be modeled in terms of well-designed procedures that provide objective measures with good test-retest reliability. These constituents are derived from theories that provide operational definitions of constructs such as perception, attention, working memory, associative learning, and executive control. Further requirements are for tests that are validated in terms of their presumed psychological processes, neural basis, and sensitivity to drug effects. The ultimate requirement is to find procedures that can predict cognitive enhancing effects in humans with neurological or neuropsychiatric disorders. A secondary consideration is for the procedures to be sensitive to detrimental...

Modulation of Seizure Activity With Noradrenergic Receptor Agonists Antagonists

A2-AR agonist would be to stimulate just the postsynaptic a2A-AR. Guanfacine is the closest a2-AR agonist to meet this standard. Guanfacine has been shown to be more selective for the a2A-AR, with little affinity for serotonin and imidazole receptors. At high doses guanfacine has been shown to stimulate the postsynaptic a2A-AR and to enhance spatial working memory, an effect not observed with clonidine (80,81). Recent work with guanfacine in our laboratory has shown an anticonvulsant effect against flurothyl-induced seizures, whereas clonidine produced a proconvulsant effect. Further work needs to be performed to determine whether guanfacine possess an anticonvulsant effect against a variety of different convulsant agents, and its possible future as an anti-convulsant agent. The coadministration of AR agonists with antiepileptics such as val-proate has been shown to potentiate the anticonvulsant effect of these antiepileptic therapies (82,83).

Impact of Psychoactive Drugs

Evidence indicates that the major ascending neuromodula-tors, in particular dopamine, but also noradrenaline, ace-tylcholine and serotonin can influence working memory performance in humans. However, the effects of drugs that affect these neuromodulators depend on (1) the particular task demands under study, i.e., the stage (encoding, delay, probe) and type (e.g., spatial vs. non-spatial) of working memory, (2) the neural region that is targeted by the drug (e.g., the striatum or the prefrontal cortex), (3) the baseline neurochemical state of the system and (4) the receptor-specificity of the drug. Accordingly, drugs that A variety of paradigms are used to study working memory in humans. Examples of tasks in behavioral psycho-pharmacological studies include the self-ordered spatial working memory task from the Cambridge neuropsycho-logical test automated battery ( CANTAB), which requires self-ordered searching through a set of boxes to locate hidden tokens, tests of digit span and the...

Spatial Memory in Humans

Spatial memory describes information storage and retrieval required for identification and navigation of proximal or distal space. This is distinct from spatial working memory which refers to active representations stored and manipulated over seconds. Two main frames of reference have been described egocentric, which is related directly to the observer, and allocentric, which is dependent on the relational position of objects in space. Routes depend more on egocentric frames of reference, whereas maps are more flexible to landmark changes and thus depend more on allocentric frames of reference. Although often discussed separately, an emerging view is that both egocentric and allocentric spatial memories are coded but these may interact and depend on interacting brain regions. Spatial memories can be representations of salient cues for navigation or be more detailed representations, including topography, allowing reexperiencing of the environment (Moscovitch et al. 2005). A useful...

Introductory Comments

In one experimental strategy, De Wied and colleagues use metabolic derivatives that are virtually devoid of the antidiuretic, pressor, and cortico-trophic effects of the parent peptide but nevertheless produce the behavioral effect of the parent peptide. These AVP derivatives include desglycinamide vasopressin (DG-AVP and DG-LVP) and a number of C-terminal metabolic fragments such as pGlu4,Cys6 AVP(4-8), Cyt6 AVP(5-8), and Cyt6 AVP(5-9). The second strategy has been to show that on those occasions when a vasopressin analog does increase behavioral arousal, this arousal effect may influence the short-term memory processes involved in learning but is not essential for the effect of the peptide on long-term memory storage. a. Selected Study Skopkova et al. (1991) Skopkova et al. (1991) investigated whether the long-term behavioral effects of DG-AVP are the result of an initial increase in behavioral arousal during the learning phase. The subjects, male Wistar rats of a genetically...

Hippocampal Dependent Learning

The hippocampus has been widely related to spatial processing, as well as to long-term memory establishment, among other cognitive processes. It has been proposed that the hippocampus is part of a memory system involved in the processing of relationships between configurations of stimuli such as those required in the integration of spatial maps (cognitive mapping) (Jarrard 1993 O'Keefe and Nadel 1978 Poucet 1993). Based on this assumption, the hippocampus has been considered crucial in those learning tasks that involve spatial information such as spatial reference memory and spatial working memory, acting in concert with the prefrontal cortex (Jones and Wilson 2005 Puryear et al. 2006 van Asselen et al. 2006 Wang and Cai 2006).

Wisconsin Card Sorting Test

In this test, subjects are presented with a series of multidimensional stimuli, which they have to sort into piles, based on one of the stimulus dimensions, for example, color, number, and shape. After subjects have learned to sort according to one of the dimensions, the rule is changed, so that now subjects have to shift their attention and start sorting according to a different stimulus dimension. Adequate performance depends on accurate working memory representations of the currently relevant dimension as well as recently chosen stimuli.

Choline Enriched Diets

Cognitive Function Previous studies have shown that supplementation with choline during both pre- and postnatal development in rats can result in improved cognitive function when animals are tested as adults. Choline supplementation has produced long-term facilitation of memory function in a variety of tasks including the radial arm maze, water maze, and passive avoidance test (4-7). This increase in memory capacity might constitute a cognitive reserve to make prenatally choline-supple-mented animals resistant to memory impairment.

The Mnemonic Effects Of Mecamylamine In Monkeys

Recently we tested the hypothesis that low (i.e., g kg) doses could improve memory in aged rhesus monkeys.26 As indicated in Figure 8.1, some doses of mecamylamine appear to have the potential to improve working memory both at 10 min and 24 h after parenteral administration thus appearing to mimic certain memory-enhancing effects produced by nicotinic receptor agonists. The mechanism for this effect is not clear from this initial investigation. One might speculate that mecamylamine is in some manner acting as a partial agonist, or producing a low-level nicotinic antagonism (at these low doses), which produces a cellular response that may be analogous to nicotine-induced receptor desensitization. Several previous observations may have relevance to the memory enhancement induced by mecamy-lamine and they may relate to the excitatory electrophysiological effects of nicotine and (paradoxically) some nicotinic antagonists. For example, Freund and coworkers45 reported that two nicotinic...

The relationship between neurochemical and behavioral effects of caffeine

One approach to understanding the mechanisms underlying the behavioral effects of caffeine is to correlate changes in behavior with changes in neurochemical pathways and levels of specific neurotransmitters. Since caffeine is associated with enhanced cognition, and some aspects of cognition, such as memory, are closely linked to the specific neurotransmitter acetyl-choline (ACh), a series of investigations were undertaken to assess alterations in brain ACh induced by caffeine, individually and in combination with other drugs, and to correlate these changes with changes in short-term memory function.

The Dicarboxylate Amino Acid Cation Na or H Symporter Family Glutamate Transporters

The excitatory amino acid transporter-3 (EAAT-3) is a major neuronal transporter for glutamate in the brain. An EAAT-3 inhibitor may have therapeutic applications in schizophrenia, cognitive impairment (such as that associated with Alzheimer's disease) and other nervous system diseases where glutamate neurotransmission is deficient (http www.neurocrine.com html res_eaats.htm). Increasing the amount of glutamate released from certain nerve cells could improve learning, memory skills and overall cognitive function. A possible limitation to this approach is that glutamate can cause glutamate-induced retinal toxicity, and that long-term inhibition of glutamate transporter activity may cause neuronal damage. Increased knowledge of the structure and function of glutamate transporters is therefore of pivotal importance. So far, the only X-ray crystal structure with similarities in function and sequence with the glutamate transporters is that of the glutamate transporter homologue from...

O Antipsychotic Drugs

The DA hypothesis of schizophrenia (DHS) has been the principal neurochemical theory of schizophrenia for more than 30 years. The basis of the DHS lies in the capacity of antipsychotic drugs to block DA receptors (D2 receptor subtype) positively correlated to their clinical potency in alleviating the symptoms of schizophrenia.60,63 Nevertheless, the observed inactivity of D2-antagonists in some individuals with schizophrenia and the pharmacological independence of positive and negative symptoms indicate further level of complexity. Other variants of the DHS suggest an imbalance between dopamingeric pathways, which may be phasic in nature.64,65 With regard to symptomology, it is thought that a dysregula-tion in the mesocortical DA pathway contributes to negative symptoms.66,67 Positron emission tomography (PET) studies suggest that individuals with schizophrenia may have decreased densities of Di receptors in the prefrontal cortex.68 Presynaptic D1 receptors within the prefrontal...

Traumatic Brain Injury

Canavan Disease

Our recent studies with children have utilized Spectroscopic Imaging (SI), rather than the single voxel methodology described above 25 . A spectroscopic imaging slice was selected above the lateral ventricles to extend from the frontal lobe to the occipital and parietal lobes sampling both white and gray matter. Water suppressed PRESS localization with outer voxel suppression bands was used to excite parenchyma and avoid lipid artifact from the skull. See Figure 2 (panel A) for an example MRI image with superimposed SI grid. Patient recruitment and data analyses are ongoing. Here we report on NAA Cre ratios averaged across many voxels (predominantly white matter), with separate estimates for anterior and posterior halves of the data matrix. A large battery of cognitive tests was administered individual scores were standardized and averaged into these composites overall cognitive (as above), motor, language, visuo-motor, and working memory. The TBI children (N 28, mean age 13.6, SD...

Direct Downstream Effectors Of The G Protein Pathway

AC has also been shown to be important in numerous processes, such as long-term potentiation (LTP) and long-term memory, cell differentiation, development, and drug dependence (76,79). In some of these processes, the AC isoform involved is either activated or inhibited by calcium. For example, AC1 activity is stimulated by Ca2+ camodulin, and this AC isoform is important in LTP and long-term memory (76). In relation to GPCRs and Gas activation, AC in which Gas is coupled to P1-ARs functions in increasing cardiac rate and force of contraction Gas coupled to P2-ARs functions in smooth muscle relaxation Gas that is coupled to P3-ARs functions in lipolysis of white adipose tissue (80).

Modulation of Neurotransmission

Endocannabinoids not only mediate retrograde signaling, but also modulate synaptic transmission in various regions of the brain. Depolarization-mediated elevation of intracellular Ca2+ concentration causes endocannabinoid-mediated suppression of excitatory inhibitory synaptic transmission. Activation of G(q 11)-coupled receptors including group I metabotropic glutamate receptors (mGluRs) also produces endocannabinoid-mediated suppression of synaptic transmission 70 . In the hippocampus, CBi receptors are expressed on axon terminals of GABAergic inhibitory interneurons 71 . A well-known effect of cannabinoids is the impairment of cognitive processes, including short-term memory formation, by altering hippocampal and neocortical functions reflected in network activity. Acting on presynaptically located G protein-coupled receptors in the hippocampus, cannabinoids modulate the release of neurotransmitter molecules. Activation of CB1 receptors reduces GABA release from presynaptic...

Physiology and disease relevance

Dopamine was considered for a long time to be a precursor ofnoradrenaline, but eventually it was recognized as a neurotransmitter in its own right, fulfilling specific physiological roles including the control of different aspects of voluntary and involuntary motor movements and execution of learned motor programs. The central dopaminergic system also regulates the secretion of prolactin and corticotrophin, and is involved in the mediation of reward, control of mood, and working memory as well as goal-oriented behaviour. It is believed that several physiological effects of dopamine are linked to specific brain regions. Thus, the striatum which possesses the highest density of dopaminergic terminals is thought to control motor programs essential for the execution of complex motor acts. This concept is being continually redefined since current evidence suggests that it is the dorsolateral part of the

Physiological implications of modulation of nmda receptor function by ethanol

This LTP was inhibited by intraperitoneal injection of nonintoxicating doses of etha-nol (0.5 or 1.0 g kg) given prior to the LTP induction.100 Ethanol inhibition of LTP was observed not only in the hippocampus but also in other brain regions. NMDAR-dependent LTP in the dorsomedial striatum101 was recently reported to be abolished by ethanol at concentrations as low as 10 mM.20 LTP in the dorsolateral bed nucleus was also shown to be inhibited by ethanol.102 LTP is a cellular model of learning and memory4103, and in humans, ethanol disrupts performance on a variety of short-term memory tasks104-106 and ethanol inhibition of LTP may be associated with drinking-induced blackouts.107 Finally, ethanol inhibition of LTP in the hippocampus may underlie episodes of amnesia after alcohol binge drinking.108

Effects Of Heavy Drinking

NAA in frontal white matter was 6 lower in HD than LD. NAA loss was greater in female than male heavy drinkers despite similar drinking severity and greater in FH-negative HD than FH-positive HD. FH-negative compared to FH-positive HD also had higher ml in the brainstem and tended to have lower NAA and higher ml in frontal GM. In addition, greater frontal NAA loss in HD was found as a function of age. Lower frontal white matter NAA in HD correlated with lower executive and working memory functions and with greater P3 latency.

Abstract

In this tutorial chapter, the author reviews basics aboutfrequent pattern mining algorithms, including itemset mining, association rule mining, and graph mining. These algorithms can find frequently appearing substructures in discrete data. They can discover structural motifs, for example, from mutation data, protein structures, and chemical compounds. As they have been primarily used for business data, biological applications are not so common yet, but their potential impact would be large. Recent advances in computers including multicore machines and ever increasing memory capacity support the application of such methods to larger datasets. The author explains technical aspects of the algorithms, but do not go into details. Current biological applications are summarized and possible future directions are given.

Genetic Studies

Although LTP is absent in the adult GluR1 knockout, there is no deficiency in spatial learning (267). Because this form of synaptic plasticity is widely believed to be the synaptic basis of spatial learning, this was unexpected. Subsequent studies, however, found that although spatial reference memory is unaffected by GluR1 knockout, spatial working memory is profoundly deficient (269-271). It is noteworthy that spatial working memory is also preferentially affected by bilateral hippocampal lesion (271), and both spatial working memory (272) and hippocampal LTP (273) can be rescued by transgenic expression of GluR1.

Nonlinear Methods

Apart from the linear analysis tools mentioned above, there is an increasing interest in the use of methods that are intrinsically nonlinear. Nonlinear mapping (NLM) is a method that attempts to preserve the original Euclidean distance matrix when high-dimensional data are projected to lower (typically two) dimensions. However, NLM does not provide a quantitative relationship between activity and structural descriptors. At the present time, artificial neural networks (NNs) are probably the most commonly used nonlinear method in chemometric applications. NNs are computer-based simulations which contain some elements that appear to exist in living nervous systems. What makes these networks powerful is their potential for performance improvement over time as they acquire knowledge about a problem, and their ability to handle fuzzy real-world data. Fig. 2 shows a schematic representation of a neural network. During the training phase, a network is taught data patterns through iterative...

Meal Frequency

Timing of meal can influence the effects of meals on cognitive behavior. Early studies indicate that stunted and previously malnourished 9- and 10-year-old Jamaicans performed less well on tests of short-term memory and problem-solving ability when they had not eaten breakfast than when they had eaten a morning meal 189 . Undernourished children's performance on a test of verbal fluency was significantly better when they had consumed a school breakfast than when they had not 190 . Experimental evidence suggests that omitting breakfast negatively affects cognitive functioning 191 .

Introduction

Schultz et al. (1974) were the first investigators to suggest that OT may attenuate long-term memory in aversive learning situations. They compared the effects of daily pretesting injections of physiological doses of VP and OT on retention (rate of extinction) or a learned AA and PA response. Neither peptide influenced the rate of learning of the AA response in a platform-jump shock avoidance task, but in contrast to AVP, OT impaired retention (significantly accelerated response extinction) relative to its placebo control group. However, chronic treatment with the same dose concentrations did not produce the expected effects of these peptides on the PA task. In this task, the dependent variable was the amount of time in a 3-min session that the rat remained in the lighted compartment over successive test days after administration of a severe footshock on entry through a small hole into the adjacent dark compartment. With this measure of PA behavior, VP accelerated the rate of...

Prevention

The idea of a preemptive analgesic effect in postamputation pain was prompted by observations that the phantom pain in some cases seemed to be similar to pain experienced before the amputation, and that the presence of severe pain before the amputation was associated with a higher risk of postamputation phantom pain. These observations led to the theory that pre-amputation pain created an imprint in memorizing structures of the central nervous system, and that such an imprint could be responsible for persistent pain after amputation.

Behavioral Evidence

To determine whether Tat-3L4F interfering peptide is able to suppress the capacity of rats to learn and memorize, we recently examined the effects of this interfering peptide on the requisition and retrieval of spatial memory. A standard Morris water maze was conducted as previously described (Ferrarl et al. 1999 Hannesson and Corcoran 2000 Remondes and Schuman 2004). Briefly, the water maze was a circular plastic pool (200 cm diameter) filled with 22 1 C water made opaque so that rats could locate only a submerged platform for escape with the help of distinctive distal visual cues surrounding the pool. The escape latency and distance, i.e., the time and distance each rat required to locate the hidden platform, were used as an index of hippocampal-dependent spatial memory. Two experiments were conducted. Experiment 1 was designed to examine the effects of Tat-3L4F on spatial learning and memory with injection of the potent cannabinoid HU210 as positive control (Ferrarl et al. 1999...

Passive Avoidance

During the acquisition trial an animal is placed into the white, illuminated box facing the wall opposite to the door and then, after a certain time interval (e.g., 10 s) the door is opened. Once the animal enters the dark compartment with all four paws, the door is closed and a footshock is delivered. Usually animals enter the dark compartment within 10 to 30 s. Animals that enter the dark box with a considerably longer latency should be excluded from further testing. Because a footshock is used as a reinforcer for this task, the shock parameters are critical. The footshock duration is usually 1 to 5 s and the current intensities vary between 0.1 and 0.8 mA for mice and 0.4 and 1.0 mA for rats. The stimulus duration is relatively easy to determine, while the current intensity is not. The footshock strength depends on the sex and strain of the animals, as well as on the cleanliness of the grid floor (feces block and urine facilitates current passage). Therefore, several preliminary...

Chapter Overview

The research presented in Chapter 2 led De Wied and colleagues to conclude that vasopressin (VP) and oxytocin (OT) have important roles in modulating the formation of long-term memory, but are not importantly involved in the early learning phase of memory processing. Tested in both aversive and appetitive paradigms, peripherally administered VP consistently facilitated memory consolidation. The influence of OT was examined only in aversive paradigms in which, in general, it produced an amnestic effect. However, dose level and route of administration (central versus peripheral) were important parameters determining the specific type of memory modulation produced by this peptide. Although this early phase of their research launched the view herein referred to as the VP OT Central Memory Theory,'' the heavy reliance on the peripheral route of administration opened the door for a number of alternative explanations of the means by

Alzheimer Disease

Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that gradually destroys a person's memory and ability to learn, make judgments, communicate with the social environment and carry out daily activities. In the course of the disease, short-term memory is affected first, caused by neuronal dysfunction and cell death in the hippocampus and amygdala. As the disease progresses further, neurons also die in other cortical regions of the brain. At that stage, sufferers often experience dramatic changes in personality and behaviour, such as anxiety, suspiciousness or agitation, as well as delusions or hallucinations.

Cognitive Functions

The most frequently impaired cognitive function in patients with MS is memory. Patients with MS often show problems in tasks of working memory, but short-term memory assessed by memory span tasks often remains unimpaired. In long-term memory a relatively unlimited and permanent memory store impairment is commonly observed if spontaneous and free recall is required. Recognition memory is normal or less impaired than free recall. This special pattern in memory deficits in MS patients is put forward by some authors as evidence that in MS patients the encoding of information is unimpaired but they have problems in retrieving the stored information.5 Beatty et al,12 however, showed that only 53 of the MS patients examined exhibited a pattern of memory impairment in which the most marked feature was their inconsistent retrieval. Thornton and Raz13 found in their quantitative review that MS patients show impairments across all memory domains and that long-term memory dysfunctions are not...

Interventions

The pain experienced before the amputation, and that the presence of severe pain before the amputation was associated with a higher risk of postamputation phantom pain. These observations led to the theory that preamputation pain created an imprint in memorizing structures of the central nervous system, and that such an imprint could be responsible for persistent pain after amputation.

Reversal Learning

The serotonergic system regulates the main functions of the prefrontal cortex including emotional control, cognitive behaviors, and working memory (Buhot 1997 Williams et al. 2002). As a result, abnormalities in the serotonergic system have been implicated in the pathogenesis of mental disorders associated with prefrontal cortex dysfunction, such as depression, anxiety, obsessive-compulsive disorder (OCD), and schizophrenia (Doris et al. 1999 Gross et al. 2002 Lemonde et al. 2003). A common characteristic associated with these disorders is cognitive inflexibility, that is, an inability to spontaneously withhold, modify, or sustain adaptive behavior in response to changing situational demands. Thus, in order to study the role of the prefrontal cortex in sustaining behavioral flexibility, reversal learning tasks have been designed for humans (Fellows and Farah 2003 Murphy 2002 Rogers et al. 2000 Rolls et al. 1994), nonhuman primates (Butter et al. 1969 Clarke et al. 2004, 2005, 2007...

Place Learning

In a spatial working memory test with delay (delayed nonmatching to position task DNMTP ), cerebral serotonin depletion induced by the administration of 5,7-DHT in rats had no effects. After the authors applied DOI (100 and 300 mg kg IP), no effects on choice accuracy were observed (Ruotsalainen et al. 1998). Thus, evidence on 5-HT2C receptor directly affecting hippocampal-dependent test was not obtained. Although tests of working memory are prefrontally driven, the spatial component of this function implies hippocampal-prefrontal interactive relationships, and no effects after serotonin manipulation were observed.

Conclusion

Effect that appears to develop relatively little tolerance over time, but just as clearly this is not the only reason for its popularity. Caffeine also serves to improve performance on a variety of tasks (particularly those involving logical reasoning, semantic memory,89 and sustained attention21) elevates mood states,91 may partially offset the effects of alcohol,146 and increases the individual's sense of well-being,87 at least in habitual users. A more subtle but perhaps equally important effect is that on habituation. A major, centrally mediated process, habituation in the face of repetitive stimulation reduces arousal to what is likely to be an uncomfortably low level,76 subjectively described as boredom. Moreover, habituation is often very choppy, and caffeine smooths the habituation function, making the decremental process more even and perhaps more comfortable for the individual.21 Thus, in both slowing and smoothing habituation, caffeine may make a potentially aver-sive...

Measures

Measures of learning and memory have generally been focused on variants of serial learning such as words, numbers, etc. Rusted and colleagues have suggested that learning and memory tasks that involve effortful processing (as opposed to automatic processing) are more likely to demonstrate nicotinic effects or improvements. This may be due to the ability of nicotinic stimulation to enhance cognitive resources overall.72 In addition, attentional improvement during encoding may also be responsible for an improvement in the amount of information placed in working memory. There is also evidence for nicotinic effects on memory consolidation as well.52 72 73 An example of a useful measure in studies of learning with nicotinic stimulation with a significant effortful component is the selective reminding task (SRT). This measure involves serial list learning of unrelated words with the caveat that, from trial to trial, the only words repeated are words not recalled from the previous trial. In...

Schizophrenia

It has been shown by Bita Moghaddam (Moghaddam and Adams 1998, Cartmell et al., 1999, 2000) that stimulation of group II metabotropic glutamate receptors (using mGluR2 3 agonist, LY354740) attenuated the disruptive effects of phencyclidine (PCP) on working memory, stereotypy, locomotion and cortical glutamate release in rats. Phencyclidine (blocker of NMDA receptor) elicits positive and negative schizophrenia-like symptoms in animals (Zukin and Javitt 1989).

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