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Cognitive and Emotional Factors

Increasingly, it has been recognised that even each of these specific cognitive abilities itself comprises complex processes. 'Memory', for example, involves the acquisition, retention and retrieval of information (Loftus, 1979). Acquisition refers to a process involving (a) the perception of the material by a sensory register, where it is retained for a very brief period, before being transferred to (b) working memory (Baddeley, 1986). The material is stored for only as long as it receives attention in the form of rehearsal or other conscious routines. It is related to current knowledge of the world imported from long-term memory before passing to (c) long-term, more permanent, memory. Retention refers to the period of time between encoding and recollection, while retrieval involves the person bringing the information from short-term or long-term memory back into awareness. Memory problems may therefore reflect one or a number of difficulties at different stages for example,...

M1 Muscarinic Receptor Activation Protects From Ab Toxicity

In AD a degeneration of presynaptic cholinergic neurons that ascend from the basal forebrain to cortical and hippocampal areas has been observed 39,40 . The Mi muscarinic receptor is expressed in the cerebral cortex and hippocampus, and its major role is in cognitive processing including short-term memory 41,42 . In relation to AD, it is well known that M1 agonists increase the nonamyloidogenic processing of the amyloid precursor protein (APP), reducing Ap production 43-35 and also Tau phosphorylation 46,47 . Although the precise mechanism by which M1 muscarinic receptor activation may promote neuroprotection remain unclear a possibility is through inhibition of GSK-3p.

Models of Cognition and Specific Architectures

Man is describable as a dual processor, dual memory system with extensive input-output buffering within each system. The input-output system appears to have substantial peripheral computing power itself. But man is not modeled by a dual processor computer. The two processors of the brain are asymmetric. The semantic memory processor is a serial processor with a list structure memory. The image memory processor may very well be a sophisticated analog processor attached to an associative memory. When we propose models of cognition it would perhaps be advisable if we specified the relation of the model to this system architecture and its associated addressing system and data structure. (Hunt, 1973, pp. 370-371)

Accuracy of Recall and Summary Processes

We have suggested that conclusions about respondents' ability to accurately recall and summarize the past are vital to determining how one collects data. Key to appreciating the limits of autobiographical memory is understanding the process of recording, retrieval, and summary of information about past experience. How, then, do we generate recall of and summarize our past states Research indicates that the process of generating such memories is more accurately characterized as reconstruction (Menon Recall is also influenced by semantic memory, that is, generalized knowledge or belief (e.g., about myself, about work Robinson and Clore, 2002 Ross, 1989). This may be especially prevalent when memories of an event, which may or may not be accurate, do not spring into mind. Memories constructed in this way are often adjusted to make them conform to logical scripts about events based on broader beliefs about behavior (in general or one's own) - they represent what should have happened or...

Implications for Global Reports

Evaluating the impact of accuracy and summary processes on global reports is difficult because it is not clear exactly how global assessment should line up with actual experience. If one assumes that global questions are meant to or are interpreted as reflecting experience - perhaps not an unreasonable assumption in many cases -then all of the troublesome processes associated with recall reports are applicable. Furthermore, there is evidence that ambiguity about what information is sought by a question and or the inability to access that information from memory disposes respondents to answer on the basis of semantic memory (Robinson and Clore, 2002). Particularly when it is not clear what memories are relevant over what period, global questions will tend to pull for answers based on beliefs and attitudes. Although semantic memory has a connection to experience, that connection can be a loose one because other factors, such as beliefs, personality, and contextual cues. If it is actual...

Tolllike Receptor Impact on the Study of Innate Immunity

The biological defense mechanism of higher organisms, including humans, is generally divided into innate immunity and adaptive immunity (Dranoff, 2004). In the adaptive immune response, gene rearrangement by T cells and B cells enables the establishment of a defense mechanism of high specification against the molecular microstructure of a foreign substance, and this mechanism is immunologically memorized. However, as it takes a few days to induce adaptive immune responses, innate immunity works as an early defense mechanism. Innate immunity has existed as a biological defense mechanism from the earliest stages of evolution for example, insects have only innate immunity as a defense mechanism. Cells involved in innate immunity include macrophages, neutrophils, NK cells, NKT cells, and y T cells. Important humoral factors include complements, lectins, and interferons (IFNs) (Biron, 2001). Key notions in the paradigm of modern immunology are the presentation of the antigen by...

Attention and Concentration

Similar to perception, attentional processes are tapped by numerous neurocognitive tests, but select tests disproportionately target attention. Basic attention refers to the ability to focus on, or perceive, specific information. Complex attention (including working memory) tasks require the examinee to hold information in mind while manipulating it in some way. Concentration (or vigilance) refers to the ability to maintain basic or complex attention over a period of time. Attentional deficits may occur at one, some, or all of these levels, and neurocognitive testing helps to distinguish among these respective functions. For example, the Digits Forward portion of the Digit Span test of the Wechsler Adult Intelligence Scales (WAIS) assesses basic attention. Examinees are asked to immediately recall strings of digits spoken by the examiner at an approximate rate of one digit per second. The digit sequences increase in length until participants fail two trials of a particular length. In...

Prototypes Creating Representations of Illness and Targets for Management

The schemata and or prototypes in declarative and procedural memory that underlie representations and shape behavioral strategies and the prototype checks (PCs) that activate and connect schemata to ongoing experiences are likely more stable and therefore better targets for assessment. Numerous studies have assessed and demonstrated the importance of the check mechanisms in predicting care-seeking. However, the empirical literature for assessing prototypes is less robust and not well integrated with findings regarding representations and the check process.

Levodopa and Dopamine Agonists

That levodopa affects only certain components of cognitive functions is consistent with the findings of Fournet et al. (127), who reported poorer performance only on working memory tasks in patients with PD after withdrawal from levodopa, and of Lange et al. (128), who also found that levodopa withdrawal impacted performance on only a minority of executive function measures. Levodopa's rather selective effects on working memory and certain executive functions may be related to its mediation of dorsolateral frontal cortex blood flow in response to executive task activation (129).

Circadian Clocks and Event Timers Are Localized to Different Areas of the Nervous System

While there is no direct relationship between the SCN and event timers, event timing does have a direct relationship with the hippocampus. The hippocampus has played a starring role in mammalian learning and memory since the lesioning of the human subject H.M.'s medial temporal lobes in the 1950s. After the surgery, H.M. was completely unable to form new declarative memories (Churchland and Sejnowski, 1994). Declarative memories are akin to semantic memory in the sense that the memory is based on the learning of semantic statement. Procedural memory, for which H.M. showed only minor deficit, is based on a kind of implicit function learning. For example, H.M. was perfectly capable of learning a motor skill, but he would be unlikely to remember that he had learned it. The function of the hippocampus has also been established in the formation of episodic memory, but not necessarily in its retrieval (Fletcher et al., 1997). Episodic memory is typically associated with the ability to...

Segregation and Integration

Anatomical segregation entails that important correlates of specific functional brain states are found in localized changes of neuronal activity within specialized populations. However, segregated and specialized brain regions and neuronal populations must interact to generate functional dynamics. Coherent perceptual and cognitive states require the coordinated activation, i.e. the functional integration, of very large numbers of neurons within the distributed system of the cerebral cortex (Bressler, 1995 Friston, 2002). Electrophysio-logical studies have shown that perceptual or cognitive states are associated with specific and highly dynamic (short-lasting) patterns of temporal correlations (functional connectivity) between different regions of the thalamocortical system. Bressler has carried out numerous studies examining task-dependent large-scale networks of phase synchronization in primate and human cortex (Liang et al., 2000 Bressler and Kelso, 2001 Brovelli et al., 2004)....

Social And Procedural Context

A recent study in our laboratory illustrates this approach. We sought to discover whether different kinds of shifts of attention activate different brain areas. One kind of attention-shift is required when one must change which of several objects is currently relevant for behavior. For example, an airline pilot may be monitoring the cockpit windshield, and shift attention to the radar display to check for other nearby objects. Another type of attention-shift is between attributes of objects a pilot may switch attention from the location of objects on the radar to their apparent velocity. In addition to the object and attribute switching described above, the study also manipulated whether attention-switching was performed on items stored in working memory ( internal representations) or whether they were available on-screen ( external representations). Figure 2.10 shows results from different types of attention shift in a group of 38 participants.

Sexual incentive properties of odors

I mentioned in Chapter 3 that a biologically irrelevant novel odor stimulated sexual arousal and copulatory behaviors in male monkeys as much as vaginal secretions did. An entertaining experiment evaluated the possible effects of this kind of odor on the attractiveness of women. Male psychology undergraduates were told that they participated in a study of factors determining the 'first impression of others'. Each male was paired with a female confederate and subjected to an interview during which the subject was sitting side by side with the confederate. Completely non-controversial questions like, 'What are your favorite leisure time activities ' were asked and the confederate was instructed to give equally non-controversial answers according to a memorized script. After the interview, the subject (and the confederate) was asked to answer a questionnaire evaluating the attractiveness of the partner. Some confederates wore a perfume with the poetic name of Jungle Gardenia and others...

Inferential Context

Researchers have inferred that romantic love and retribution involve reward system activation because these conditions activate the caudate nucleus (Aron et al., 2005 de Quervain et al., 2004), that social rejection is like physical pain because it activates the anterior cingulate (Eisen-berger, Lieberman, & Williams, 2003), among countless similar conclusions. The trouble is that both these regions are involved in motor control and cognitive planning and flexibility in a wide range of tasks, including basic shifting of attention, working memory, and inhibition of simple motor responses (Bush, Luu, & Posner, 2000 Kastner & Ungerleider, 2000 Paus, 2001 Wager, Jonides, & Reading, 2004 Wager, Jonides, Smith, & Nichols, 2005). One meta-analytic review concluded that cingulate activity was related most reliably to task difficulty In a large range of tasks (Paus, Koski, Caramanos, & Westbury, 1998). Thus, the assumption that one can make reverse inferences in this case is seriously flawed.

Scalar Timing and Patch Departure The Marginal Value Theorem

The reference memory is defined as a probability density function with bins corresponding to travel times each assigned a probability, and the total area under the function always equal to 1. Following each travel, the reference memory is updated in two steps. First, a fraction (a) of the area under the probability function is subtracted by devaluing each bin in proportion to its probability value at the time, such that the sum of the devaluations equals a. Second, an area the size of a is added back to the probability in the bin corresponding to the current travel time in working memory. Thus, following updating, the total area under the probability density function remains at unity, but the shape of the distribution is shifted toward the most recently experienced travel time, with the size of this shift controlled by the value of the parameter a. Low values of a correspond to little weight being given to recent experience, as would be predicted in a stable environment, whereas high...

Inducible expression of the fragment of human DISC1

By regulating expression of DISC1-cc, the neurobehavioral effects of the dominant-negative DISC1-cc construct were compared between mice that expressed DISC1-cc at postnatal day 7 vs. adulthood. DISC1-cc mice were tested in a spatial working memory test the delayed non-matched to place (DNMTP) task . The adult DISC1-cc transgenic mice with induction at postnatal day 7 showed decreased percentage of correct DNMTP choices compared with adult WT mice treated with tamoxifen, adult DISC1-cc transgenic or adult WT mice treated with vehicle. Importantly, no differences between DISC1-cc and WT mice treated with tamoxifen were found when this compound was injected in adulthood. The results clearly showed that disruption of DISC1 function early in development but not adulthood was responsible for deficient spatial working memory. As Gasadult mice did not have any changes in spatial learning but were inferior in the impaired spatial memory phase of MWM, the authors hypothesized that adult...

The Relationship of Transformational Grammar to Semantics and to Human Performance

T he implications of assuming a semantic memory for what we might call generative psycholinguistics are that dichotomous judgments of semantic well-formedness versus anomaly are not essential or inherent to language performance that the transformational component of a grammar is the part most relevant to performance models that a generative grammar's role should be viewed as restricted to language production, whereas sentence understanding should be treated as a problem of extracting a cognitive representation of a text's message that until some theoretical notion of cognitive representation is incorporated into linguistic conceptions, they are unlikely to provide either powerful language-processing programs or psychologically relevant theories.

Brief Description Of Five Models Of Nonverbal Number Representation

The mode-control model was originally developed as an adaptation of the information-processing model of animal timing behavior by Gibbon and Church (1984). Like the pure timing model, the mode-control model is composed of a pacemaker, accumulator, working memory buffer, reference memory, and comparator (see Figure 6.11a). At the onset of a relevant stimulus, pulses are gated into an accumulator, which then integrates the number of pulses over time. The critical innovation for the mode-control model is the addition of a mode switch, which allows the system to work like a timer or a counter. Pulses are gated into the accumulator by one of three different modes, depending on the nature of the stimulus. These three modes provide the mechanism with the ability to act as both a counter and a timer. In the run mode, the initial stimulus starts an accumulation process that continues until the end of the signal or trial in the stop mode, the process occurs whenever the stimulus is physically...

Differentiating The Models

First, Meck and Church (1983) trained rats in the duration bisection procedure to make one response to a 2-sec two-cycle stimulus and another distinct response to an 8-sec eight-cycle stimulus. Rats were then tested with duration held constant at 4 sec and number varied, or number held constant at 4 and duration varied. In both cases, the rats' behavior was modulated by the stimulus dimension that varied, showing that the rats had encoded both number and time when the two were confounded. Second, when the probability of making a long or many response was plotted against stimulus duration or number, the point of subjective equality (PSE) was equivalent for time and number and the functions were virtually identical. The PSE is the value at which the animals were equally likely to categorize the stimulus as long or short, or many or few. Third, when the rats were administered methamphetamine, they showed the same leftward shift in the psychophysical curve that relates the probability of...

Basic processes learning and memory

Memory provides mental continuity across time by allowing information from one point in time to be used at a later point in time. That time span can be in seconds or minutes (short-term or working memory), hours, days, or longer (long-term or reference memory). It forms the basis for learning, since without memory the influence of past not yet been demonstrated. It is likely that animals have very long-duration memory capacity, especially for conceptual information. reference memory was discussed previously. Reference memory can also be divided into declarative (explicit, or conscious) and non-declarative (implicit, or unconscious) aspects. Declarative memory is further subdivided into episodic and semantic memory. Semantic memory refers to memory for information, in other words, generic knowledge. Episodic memory refers to memory for particular events or experiences and implies that the memory involves revisiting that event or experience. This aspect of episodic memory can be...

Agerelated Memory Impairments In The

Selective memory loss may signal a transition into dementia. For example, mild cognitive impairment (MCI) is characterized by a selective impairment in memory and is thought to represent early or prodromal Alzheimer's disease. In the dog, we have developed two protocols for assessing age-related changes in memory function. One involves measuring task performance as a function of increasing the amount of information to be used in working memory. The second involves increasing the amount of time that information must be held in working memory. Learning deficits can be dissociated from memory deficits in the dog, revealing that a dog may be learning impaired but its memory is excellent, or that a dog can learn quickly but have a poor memory. Spatial memory Aged humans and patients with neurodegenerative diseases are often impaired on tests of spatial memory (Freedman and Oscar-Berman, 1989). Old dogs that do not exhibit spatial learning deficits may exhibit impairments when the memory...

Executive Dysfunction In The Aging Canine

Working memory incorporates a system for temporary storage and a mechanism for on-line manipulation of stored information during a wide variety of cognitive activities (Baddeley, 2001). In this context, maintenance is defined as the transferring, maintaining, and matching of

Sources Of Developmental Changes In Interval Timing

7.5.1 Long-Term Memory Sources of Developmental Changes in Timing Our developmental models of interval timing suggest that the increase with age in the sensitivity to time in the temporal bisection and generalization tasks is due to a decrease in the variability of the long-term memory representations of the standard durations. In short, young children have a fuzzier memory of durations. The issue is Why do they have a fuzzier memory representation of time A first working hypothesis is to consider that the standard durations have been correctly encoded and stored in long-term memory, in the form of a distribution with means equal to the standard values and some given coefficient of variation. In this case, the higher variability of time representation in memory obtained from young children could be attributed to a greater degradation over time, in other words, to a larger degree of memory decay for durations. This decay would erase memory traces of the standard durations and would...


Finally, the chronic low dose model consists of intravenous injections of a low dose of MPTP administration over a 5- to 13-month period (77). This model is characterized by cognitive deficits consistent with frontal lobe dysfunction reminiscent of PD or normal-aged monkeys. These animals have impaired attention and short-term memory processes and perform poorly in tasks of delayed response or delayed alternation. Since gross parkinsonian motor symptoms are essentially absent at least in early stages, this model is well adapted for studying cognitive deficits analogous to those that accompany idiopathic PD.

Cortical dopaminergic hypofunction

Since depletion of dopamine in the prefrontal cortex impairs working memory in monkeys (Brozoski et al., 1979) and working memory deficits are central to schizophrenia, it has been thought that altered dopamine input to the prefrontal cortex could be involved in the cognitive deficits of schizophrenia. Rather than a hyperfunction of the prefrontal dopamine system, as measured in the striatum and postulated by the original hypothesis of schizophrenia, a hypofunc-tion of the prefrontal dopamine system was proposed (Davis et al., 1991 Weinberger, 1987). Direct evidence for a decrease in presynaptic dopamine synthesis was later provided by a postmortem study that showed a decrease in tyrosine hydroxylase immunoreactivity in the prefrontal cortex (Akil et al., 1999). If in schizophrenia the cortical dopaminergic projections are indeed hypoactive, D1 receptors may be upregu-lated in the cortex of patients, to compensate for decrease in dopamine release. Using 11C NNC as a D1-specific PET...

Typical Transcriptional Activator

In yeast, genes that are transcribed recently are also marked by a specific pattern of histone methylation (Hampsey and Reinberg, 2003). This is achieved by the recruitment of the HMT Setl to the genes by the elongating RNAP (Ng et al., 2003). Interestingly, the Setl-mediated histone methylation pattern persists for some time even after the genes are no longer transcribed. Unlike the long-term memory of active genes mediated by trxG proteins in Drosophila (which can last for several generations), Setl-mediated marking of recently active genes in yeast is only short term (up to several hours). In addition, while the consequence of the trxG-mediated marking is to maintain the genes on, the yeast Setl-mediated system only marks the recently transcribed genes without actually keeping them on. Interestingly, yeast Setl is also involved in the long-term memory of gene silencing (Bryk et al., 2002 Krogan et al., 2002). Another case of activator-induced memory is noteworthy in this context....

Tests of Cognitive Function and Brain Regions Important for Cognitive Function

2003) and involve deficits in the nigral-striatal pathways. The prefrontal cortex is involved with working memory executive function, whereas the temporal lobe-hippocampal region is involved in spatial memory (Bartus, 1978 Rapp, 1989). It is clear that consistent with a recent report (Lacreuse et al., 1995) female rhesus monkeys are faster in this task than males.

Diffusion Magnetic Resonance Imaging DTI

In addition to these viral load associations, several groups began assessing DTI measures with respect to cognitive variables. For instance, the Ragin et al. (82) study not only demonstrated that FA was reduced in the whole brain of HIV+ patients, but that it was also significantly associated with the degree of dementia of these patients (84). In 2005, Ragin et al. again showed that DTI metrics were significantly related with loss of function in specific cognitive domains (85). Significant relationships were identified between measures for putamen and verbal memory (75), visual memory (FA), working memory (FA), and overall cognitive impairment (75). The caudate only demonstrated a significant correlation between FA and visual memory, whereas metrics for the centrum semiovale showed significant correlation with visual memory deficits (75) and visuoconstruction (FA). In 2006, Wu et al. evaluated diffusion alterations in the CC and associations with cognitive performance and motor...

Functional Magnetic Resonance Imaging fMRI

Research using fMRI in HIV-infected patients is limited though there have been a few studies examining attention, working memory, and or motor function in HIV patients. The Chang et al. (90) study of 11 HIV-infected patients and 11 seronegative controls demonstrated an increase parietal activation for subjects participating in a simpler task of attention, a simple reaction time task (92). As the task demands were increased, additional activation of frontal lobes was required to accomplish the task with the HIV-infected patients exhibiting significantly more activation in these areas compared to controls. Ernst et al. (2002) demonstrated a similar finding among asymptomatic HIV-infected patients (93). These results extend the Chang et al (92) findings by demonstrating abnormal activation pattern earlier in the disease process (92). However, the additional activation differences were only noted in the lateral prefrontal cortex during the more complex attention task, while the simpler...

An ultrashort introduction to the principles of learning

The last form of learning I want to mention is the least understood. It is called social learning and is characterized by modifications of behavior as a result of social interactions, including observations of the behavior of other individuals, and in the absence of reinforcement. One form of social learning is called observational learning. It consists of observing someone and copying her behavior. A couple of conditions need to be satisfied if observational learning is to occur. These include the rather obvious necessity of paying attention to the person being observed and a detailed retention of the observed behavior in memory. The observer must also have the motor capacities for a replication of the behavior that was observed. This is not enough, though, for the socially learned behavior to manifest itself. Appropriate motivation is necessary and appropriate circumstances are required. A simplistic example may illustrate some of these principles. Imagine that we come to an airport...

Other mouse models showing changes in PDE activity

Mice with ENU-induced mutations in the schizophrenia candidate gene Disc1 also show PDE4 alterations (Clapcote et al., 2007). The Disc1 Q31L mutant exhibits depressive-related (forced swim test, tail suspension test, antidepressant responsivity) and schizophrenia-related pheno-types (sensorimotor gating deficit in PPI, working memory deficit, decreased sociality, decreased brain volume). The L100P mutant also shows schizophrenia-related phenotypes (hyperactivity, sensorimotor gating deficits in PPI, working memory deficits, antipsychotic responsivity, decreased brain volume Clapcote et al., 2007). The overlapping but separable nature of the behavioral phenotypes of these two mutants may be related to alterations in PDE4B. Both the Disc1 Q31L and L100P mutants show decreased binding to PDE4B, in vitro (Clapcote et al., 2007). In vivo, however, only the Q31L mutant exhibits reduced PDE4B activity. Consistent with this observation, the L100P but not the Q31L mice show behavioral rescue...

With Smoking Phenotypes in Neuroimaging Studies

DelC variant and COMT Val Val genotype) and increased endogenous opioid binding (OPRM1 AA genotype) had greater regional abstinence-induced rCBF increases that may increase risk for relapse (Wang et al, 2008b). Jacobsen and colleagues (2006) investigated the association between the DRD2 C957T polymorphism and brain activation during a working memory task called the N-back task following pretreatment with either nicotine or placebo patch. The N-back task requires responses based on certain rules if the current stimulus is identical to the stimuli that have appeared previously. For example in the 1-back condition the participant is required to respond if the stimulus on the screen is identical to the one that appeared right before the current one. The task is progressively more difficult as the participant has to keep in their working memory stimuli that have appeared 2 (2-back) or 3 (3-back) times before the current one, increasing their working memory load (Loughead et al, 2009)....

The Assessment of Cognitive Functions in the Haart Era The Typical Neuropsychological Assessment

By a formal neuropsychological examination. Global impairment is defined by a deficit of at least one standard deviation below the normative mean in a minimum of two cognitive domains. This cut-off is relatively strict and may be more relevant to the research context as there is a 15 false-positive classification rate for the ANI category. The assessment needs to be comprehensive enough to assess abilities of attention working memory, speed of information processing, learning, delayed recall, verbal functioning, abstraction problem solving and motor functions. While a step-down battery exists (7) as well as brief cognitive scales such as the HIVdementia scale (8, 9), it is recommended to use these instruments either as screening tools or as part of a more comprehensive assessment. It is also important to use demographically-corrected norms even for these screening tools (10). However, it should be said that these brief instruments may be of practical importance in limited-resource...

Dopamine And Attention Sharing

In rats, the peak time in gap trials was found to be delayed relative to PI trials for approximately the duration of the gap (Meck et al., 1984 Roberts, 1981 Roberts and Church, 1978). These data were taken to suggest that rats stop their timing process during the gap and resume it where they left off after the gap. To address these data, Gibbon et al. (1984) proposed an on-off switch mechanism controlled by the presence of the to-be-timed stimulus. In PI trials, the switch is closed, pulses from the pacemaker reach the accumulator, and the response rate reaches a peak near the time of reinforcement. During the gap, the switch is open, so that pulses from the pacemaker fail to reach the accumulator. The pulses accumulated during the pregap interval are not lost, however, due to their proposed maintenance in working memory. Therefore, in accord with experimental data in rats (Meck et al., 1984 Roberts, 1981 Roberts and Church, 1978), the peak time in gap trials is delayed by the...

Is the Pattern of HAND Changing with Aging

There have been several publications demonstrating an increase in cognitive impairment in older HIV-infected individuals compared to younger HIV-infected individuals (86-88). Interestingly, a relatively old publication by Hinkin et al. (89) demonstrated a similar level and pattern of deficit between young individuals with HAD and older healthy individuals as compared with healthy young individuals. This pattern was characterized by a predominance of psychomotor slowing, working memory, and complex attention deficits. The authors hypothesized that HAD was a form of premature aging and this hypothesis rebounded in the HAART era with the increasing aging of the HIV-infected individuals (90). Some authors have suggested that an additive or interactive effect of age on HIV may amplify some minor neu-rocognitive disturbances (91). However, the exact neuropsychological consequences remain to be thoroughly explored. Normal aging is mainly associated with decreased cognitive speed (92) and...

Behavioral analysis of DISC1 mouse models Table

Degrees of validity (Arguello and Gogos, 2006). Sensorimotor gating is a neurophysiological process that is essentially the same in rodents and humans, making it an excellent endophenotype (Swerdlow et al., 1999). It can be assessed by the prepulse inhibition (PPI) test. PPI deficit is detected in patients with a variety of neurological disorders, including SZ (Geyer, 2006). A similar deficit has been described in the Q31L and L100P mutants (Clapcote et al., 2007) and in the constitutive CaMK-AC Tg (although it is much milder in the latter) (Hikida et al., 2007). Another measure of attention is latent inhibition, which is also impaired in SZ and can be assessed in mouse models (Lubow, 2005). Q31L and L100P mutants (Clapcote et al., 2007) and BAC-AC Tg (Shen et al., 2008) were subjected to this test and all of them were impaired. Other cognitive tests are harder to correlate with human tests. The T maze (delayed non-match to place) test has detected abnormalities in the working memory...

Experiments to treat the behavioral abnormalities in DISC1 mouse models

Behaviorally, PPI deficits have been detected in NRG1 transmembrane domain KO (Stefansson et al., 2002) and type III KO mice (Chen et al., 2008), but not in EGF-like domain KO (Duffy et al., 2008) or Ig-like domain KO (Rimer et al., 2005). Impaired latent inhibition has been demonstrated in an NRG1 Ig-like domain KO (Rimer et al., 2005). The T maze paradigm detected working memory impairment in the NRG1-type III KO mice (Chen et al., 2008). The Morris water maze

Simulation studies comparing different distributed inverse solutions

Tion, N-back working memory task) may provide a better test of various source localization algorithms. Additionally, physiological validation through other neuroimaging techniques would provide converging evidence. As reviewed in Section 4.3.1., encouraging cross-modal validity has started to emerge for the LORETA algorithm, particularly in studies comparing LORETA with functional fMRI (Mulert et al., 2004 Vitacco et al., 2002), structural MRI (Worrell et al., 2000), PET (Pizzagalli et al., 2004), and intracranial recordings (Seeck et al., 1998). Similar cross-modal validity will be necessary for evaluating the localization accuracy of other distributed source localization techniques.

Hippocampal Th Eta Wave

It has been proposed that the hippocampus serves as a working memory buffer for many types of information, including temporal information (e.g., Meck et al., 1984). We recorded hippocampal theta in both the T-task and C-task. The rat had to evaluate the duration of auditory stimuli in the former task, either 2- or 8-sec durations, and choose to respond to one of the two levers. On the other hand, the rat does not need to attend to the duration of the stimulus in the latter task only a 2-sec tone is presented, and the rat is only required to respond on one lever. No significant differences were observed between reaction times in the T-task and the C-task (724 70 and 757 122 msec, respectively F(1, 8) 0.13, not significant (n.s.)). Those spectral distributions of hippocampal theta were calculated by fast Fourier transforms (FFT) to compare the involvement of working memory in both tasks. We removed the data for one animal because of contamination by artifacts. We also calculated...

Shortinterval Timing

An emerging distinction between models concerns the perception of durations shorter than a couple of seconds vs. the perception of durations longer than a couple of seconds. One proposal is that different systems are involved in timing events on these two scales (Ivry, 1996 Ivry and Hazeltine, 1995). For event durations shorter than a couple of seconds (e.g., the time intervals defined by successive beats in a musical performance), it has been suggested that temporal regularity plays more of a role in timing processes than explicit memory because patterns of event durations on this scale form directly perceivable rhythms (e.g., music and speech) hence, timing in this range is predictable by virtue of the exogenous timing cues provided by stimulus markers (Fraisse, 1963 Jones, 1976 Jones and Boltz, 1989 Port, 1995). This issue and related ones pertaining to effects of rhythmic context on time perception have recently generated interest from dynamical systems and information-processing...

Neurobehavioral Changes

Many of the age-related changes in cognitive capacity are also observed in diabetic subjects (Mooradian, 1988b, 1997a, 1997b). Clinical studies in subjects with type 2 diabetes have shown moderate cognitive impairment, particularly in tasks involving verbal memory and complex information processing, whereas basic attention process, motor reaction time, and short-term memory are relatively unaffected (Mooradian et al., 1988 Strachan et al., 1997).

Diffusion Imaging and Brain Connectivity Issues and Considerations

The large variability across subjects away from tract centers raises the possibility that when correlations of FA and some behavioural or functional measure are found at tissue interfaces, that they may arise simply from the increased variability in FA in these regions. Many published results of voxel-based assessment of group FA differences or FA correlations have identified significant effects in regions of more variable FA. These tend to be located at interfaces of white matter with gray matter or CSF (as seen on Ti-weighted images), or in regions of complex fibre architecture. An example of one such finding is shown in Fig. 14, where correlations of FA with performance on a working-memory task were strongest at tissue interfaces. Because of the error introduced by imperfect registration, residual noise from flow artifact and partial volume effects, as well as the application of smoothing filters (see below), most authors have interpreted such findings with caution. In fact,...

Cortico Striatallike Auditory Processing Module

Recall that the songbird learns its song by producing prototypes and using the auditory template to shape the primitive song into the final song (Tchernichovski et al., 2001) (see Section 16.2.1). The activity in HVC that occurs with the onset of song production can precede the song by up to 2 sec (McCasland, 1987). The premotor drive for each prototype comes to transmit two motor signals a primary signal toward RA via HVC RA and a secondary signal to Area X (see Figure 16.2). The secondary signal for each syllable prototype will activate a population of HVC X neurons. Keep in mind that with each vocalized syllable, there is ongoing real-time auditory feedback into the auditory processing module that contains a representation of the memorized tutor's song. The objective for the juvenile songbird is to modulate the prototype syllables so that vocal feedback engages these same PC ensembles that are tuned to the memorized song. In doing this continuously, a sequence of dopaminergic...

Neurogenetic Syndromes

In the field of neurogenetic conditions, fragile X syndrome (FXS) is somewhat unique in that the primary genetic cause of the disease has been traced to the inactivation of a single gene. Affecting approx 1 4000-6000 live births, FXS is the most common form of inherited mental retardation resulting from a known gene (40). The physical characteristics include macroorchidism, large ears, and a long face (41). A distinct neurobehavioral phenotype, which differs between males and females, is present. Males with FXS are typically quite affected, with mild to severe mental retardation and learning disability. Deficits are present in short-term memory speech and How these anatomic changes relate to the genetic, molecular, and behavioral characteristics of FXS is still unclear. Mostofsky et al. have found significant correlations between the size of the posterior vermis and verbal (Partial regression coefficient pr2 0.150 p 0.01) and performance (pr2 0.099 p 0.05) IQ in 37 females with FXS...

Does the sdy mouse model aspects of schizophrenia

While the Dtnbp1sdy mutation has not been found in schizophrenia cases, homozygous sdy mice share multiple biological, behavioral, and cognitive features of schizophrenia. Like homozygous sdy mice as described above, schizophrenia cases display reduced synaptic dysbindin-1 (Talbot et al., 2004, 2009 Tang et al., 2009), evidence of hyperactive mesolimbic dopamine pathways (Laruelle, 2003), and disrupted glutamatergic-GABAergic interactions in prefrontal cortex (Lewis and Moghaddam, 2006). Schizophrenia cases also display the reduced PPI, decreased social interactions, and multiple cognitive deficits of homozygous sdy mice described above that are shared with other proposed mouse models of schizophrenia (Powell and Miyakawa, 2006 Maz-zoncini et al., 2009). Indeed, the spatial memory deficits displayed by homozygous mice in the Morris water maze (Cox et al., 2009) and the T-maze (Takao et al., 2008) resemble those displayed by schizophrenia cases in a virtual Morris water maze task...

Relationship to Behavioural and Neural Functioning

Only a few studies have attempted to relate magnetization transfer measurements to measures reflecting brain function. A serial MTR study in the optic nerves of 29 patients with acute optic neuritis was performed with measurements of visual system functioning using visual evoked potentials (VEP) (Hickman et al. 2004). No significant differences in MTR were observed between patients and controls at the onset of optic neuritis, although the MTR did decrease in patients over a period of one year. There did not seem to be any direct relationship between MTR and VEP measurements. Another study of 18 patients with early-stage multiple sclerosis (Au Duong et al. 2005) demonstrated a correlation between functional connectivity between left Brodmann areas 45 46 and 24 using an fMRI working memory task, and the MTR of normal appearing white matter and also with brain T2 lesion load. Consequently, the functional connectivity relationship with MTR suggests that changes in the functional working...

Auditory Scene Analysis

Many of the grouping processes are considered automatic or primitive because they can occur irrespective of a listener's expectancy and attention. Therefore, an initial stage of auditory scene analysis following basic feature extraction involves low-level processes in which fine spectral and temporal analyses of the acoustic waveform are employed so that distinct perceptual objects can be formed. However, the perception of our auditory world is not always imposed upon us. Our knowledge from previous experiences with various listening situations can influence how we process and interpret complex auditory scenes. These higher-level schema-driven processes involve the selection and comparison between current auditory stimulation and prototypical representations of sounds held in long-term memory. It is thought that both primitive and schema-driven processes are important for the formation of auditory objects, and these two types of mechanisms might interact with each other to constrain...

Schema Driven and Attention Dependent Processes

Current models of auditory scene analysis postulate both low-level automatic processes and higher-level controlled or schema-based processes (Alain and Arnott, 2000 Bregman, 1990) in forming an accurate representation of the incoming acoustic wave. Whereas automatic processes use basic stimulus properties such as frequency, location, and time to segregate the incoming sounds, controlled processes use previously learned criteria to group the acoustic input into meaningful sources and hence require interaction with long-term memory. Therefore, in addition to bottom-up mechanisms, it is also important to assess how aging affects top-down mechanisms of auditory scene analysis. Musical processing provides another real-world example that invokes both working memory representations of current acoustic patterns and long-term memory representations of previous auditory structures. Evidence suggests that young and older adults perform equally well in processing melodic patterns that are...

Behavioral and Psychosocial Intervention

Similar research has examined the association of socioeconomic status (SES), parental social standing, and perceived life stress with brain circuitry supporting cognitive or mood disorders and vulnerabilities to physical illness (Gianaros et al, 2008b, 2009). Low SES increases risk for medical and psychiatric disorders and is also associated with deficits in working memory and cognitive control and language (see Fig. 51.4B). Further, language ability (i.e., phonological awareness) of low, but not high, SES children was observed by Noble and colleagues (2006) to correlate strongly with activity within the left fusiform cortex during a listening task (see Fig. 51.4c), suggesting poor language abilities within lower SES children was associated with a failure of neural activity underlying phonological processing. Similar results are reported by Raizada and colleagues (2008) who observed greater hemispheric specialization within Broca's area with higher SES. Interventions informed by this...

Normative Emotional States

The dorsolateral PFC is a neocortical structure involved in mediating working memory and setting goals for behavioral responses (Goldman-Rakic, 1996). It is densely connected to the motor cortex and the hippocampus and plays a key role in integrating behavior with existing circumstances in the external environment, including the regulation of emotional behavior. Imaging studies have shown that the dorsolateral PFC is activated during performance of reappraisal tasks that require regulation of emotion (Ochsner and Gross, 2005).

Functional Brain Changes in MDD

Research in healthy volunteers shows that distraction by negative pictures during performance of a working memory task is associated with increased activity in the inferior frontal gyrus (IFG), and that less IFG activity to emotional distracters is observed in subjects who rate emotional distracters as less distracting (Dolcos and McCarthy, 2006).

Other Large Scale Modeling Work

Deco et al. (2004) modeled the mechanisms that underlie working memory-related activity during the execution of delay tasks that have a what -then- where design (with both object and spatial delayed responses within the same trial). They were interested in examining two notions related to the topographical and functional organization of the PFC (1) organization-by-stimulus-domain, which proposes that dorsolateral PFC is involved with spatial processing and ventrolateral PFC is specialized for object processing (e.g., Wilson et al. 1993) (2) organization-by-process, which puts forward a hierarchical organization of the PFC, with non-memory related higher order functions (e.g., manipulation of items in memory) associated with dorsolat-eral PFC regions, and short-term memory maintenance functions ascribed to ventral PFC (e.g., Petrides 1994). Deco and colleagues utilized a network composed of integrate-and-fire neurons to model both single-neuron and fMRI

Pros and Cons of the Accumulator Model of PD Timing Effects

As discussed earlier, SET and related models impose timescale independence as a central feature of the stochastic modeling of timing. This scale independence limits SET's capacity to explain duration-dependent timing errors. This simple pacemaker-accumulator model sheds light on the specific problematic features of SET. SET assumes that memory function in the accumulator as well as in short-term memory is linear in the sense that the function relating objective and subjective time is a straight line with an intercept of zero (barring the effects of attention on the latency to start and stop timing). The current model instead produces a curvilinear relationship between subjective and objective time, controlled by two parameters. If both parameters are under experimental control, such curvilinear functions can give rise to migration or other duration-dependent phenomena. If we divorce this mathematical fact from the implementation at hand, then we can modify other aspects of the SET...

Specific language impairment SLI

Measures commonly used to assess language ability include the CELF-R, which consists of tests for expressive language and receptive syntactic-language abilities (the ordering of words in phrases and sentences). An additional test of non-word repetition, where subjects repeat nonsense words of increasing complexity such as ''contra-mptionist,'' has also been developed. This test is a good index of phonological short-term memory and thought to be a sensitive measure for language impairment (Bishop et al., 1999). The Test of Language Development (TLD), which assesses comprehension, expression, syntax, grammar and phonology, can also be used to measure language impairment. Alternatively, the Children's Communication checklist (CCC) allows parents and teachers to evaluate communication impairments and avoid lengthy clinical assessments of children.

Language Enables the Rehearsal of Thought and Thereby Commitment to Long Term Memory

E ven a human being today (hence, a fortiori, a remote ancestor of contemporary human beings) cannot easily or ordinarily maintain uninterrupted attention on a single problem for more than a few tens of seconds. Yet we work on problems that require vastly more time. The way we do that (as we can observe by watching ourselves) requires periods of mulling to be followed by periods of recapitulation, describing to ourselves what seems to have gone on during the mulling, leading to whatever intermediate results we have reached. This has an obvious function namely, by rehearsing these interim results we commit them to memory, for the immediate contents of the stream of consciousness are very quickly lost unless rehearsed Given language, we can describe to ourselves what seemed to occur during the mulling that led to a judgment, produce a rehearsable version of the reaching-a-judgment process, and commit that to long-term memory by in fact rehearsing it. (Margolis, 1987, p. 60)

The P300 and other late positivities

These observations led Donchin (1981 Donchin & Coles, 1988a,b) to propose that the P300 may be a manifestation of a process related to the updating of models of the environment or context in working memory. Such an updating will depend on the processing of the current event but will also have implications for the processing of and the response to future events (including the subsequent memory for the event itself). Other theories of hypothesized that individuals with low working memory capacity would need to process changes in a sequence of random but equiprobable stimuli more than high-working memory subjects (as indexed by a larger P300 to sequential changes). This prediction was confirmed (see also Brumback et al., in preparation), suggesting that memory templates of targets stimuli are interfered with by the presence of other stimuli in low-span subjects.

Attention and Duration

Works showing that active processing in working memory is only required during the timing of longer intervals (Fortin, this volume Fortin and Breton, 1995 Fortin et al., 1993 Rammsayer and Lima, 1991) temporal processing in the milliseconds range is unaffected by level of arousal (Rammsayer, 1989 Rammsayer and Vogel, 1992), but does depend on sensory processes (Rammsayer and Lima, 1991) and pharmacological agents, such as LSD and mescaline, know to interfere with cognitive processing, disrupting the timing of multiple seconds but not of milliseconds (Mitri-ani et al., 1977). On the basis of these findings, at least two authors (Mitriani et al., 1977 Rammsayer, 1999) have separately suggested that intervals in the milliseconds range are measured more or less automatically, while intervals in the multiseconds range require active processing under direct cognitive control.

ERP effects associated with subsequent memory

The relationship between P300 and memory has been tested in various paradigms. For example, Karis, Fabiani, and Donchin (1984) recorded ERPs to words presented in a series that contained a distinctive word (an isolate cf. von Restorff, 1933). The isolation was achieved by changing the size of the characters in which the word was displayed. As is well documented (von Restorff, 1933 Wallace, 1965), isolated items are better recalled than are comparable non-deviant items (the von Restorff effect). The isolated items, being rare and task-relevant, can be expected to produce large P300s. Thus, it was predicted that the recall variance would be related to the very factors that are known to elicit and control P300 amplitude. Karis et al. (1984) found that the magnitude of the von Restorff effect depends on the mnemonic strategy employed by the subjects. Rote memorizers (i.e., subjects who rehearse the words by repeating them over and over) showed a large von Restorff effect, and poor recall...

Feeding ecology and diet

The hiding of food for later consumption is a characteristic of corvids. It confers obvious benefits for species that have a sudden abundance of food and a need to eke out their supplies to cover leaner periods. Studies of spotted nutcrackers in Siberia show that these birds are completely dependent on cached pine seeds from the fall until May. Each individual hides about 100,000 seeds and needs to find about a quarter of these to survive. Research on Eurasian jays indicates that these birds memorize the position of trees and other landmark features, so that they are able to retrieve buried acorns successfully. Although gray jays of boreal forest are unable to find food buried on the forest floor during winter when the ground is covered in deep snow, they solve this problem by gluing insects and pieces of meat onto the bark of trees using their own saliva.

The Motor System and Duration

Analogous to the overlapping use of the motor system for motor control and timing, we imagine that the cognitively controlled system may use neural circuits that are typically invoked for other cognitive operations, but can be recruited, when appropriate, for storing and processing information for temporal processes. Hence, we envisage that the cognitively controlled timing system draws on flexible, multipurpose cognitive modules within the prefrontal and parietal cortex, and thus shows overlap in functional imaging experiments with many other cognitive tasks. Following from the conclusions of Rammsayer (1999) and Mitriani et al. (1977) that cognitively controlled timing draws on active working memory and attention, we might therefore predict the involvement of the premotor cortex (PMC) or dorsolateral prefrontal cortex (DLPFC), both of which are known for working memory processing (Petrides, 1994 Smith and Jonides, 1999), and of some portion of the attentional system, currently...

Bone marrow transplant

Protocol for allogeneic transplants is considerably more aggressive than autologous transplants, there is no apparent significant difference in the incidence of HHV-6 recurrence between these transplants nor sibling versus unrelated donor grafts in a pediatric population (Yoshikawa et al., 2002 Savolainen et al., 2005). HHV-6 reactivation is common in BMT transplant patients (Wang et al., 2002) and associated with skin rash and fever, the same symptoms often manifested at the time of primary infection in children. Idiotypic myelosuppression is characterized by delayed ne-utrophil and platelet engraftment and is highly associated with the reactivation of HHV-6 (Dobryski et al., 1993 Carrigan and Knox, 1994). Bethge et al. (1999) has reported two cases of BMT patients with HHV-6 PCR-positive spinal fluid who display neurological symptoms, including disorientation, sleepiness, and short-term memory loss and showed improvement following treatment with foscarnet. Appleton et al. (1995)...

Zebrafish as a model to study behavior

Schizophrenia is characterized by a multitude of positive and negative symptoms including hallucinations, delusions and social withdrawal as well as cognitive deficits (Lewis and Lieber-man, 2000 Harvey et al., 2002). In the field of schizophrenia research, the mouse is typically used as a model to study the behavioral abnormalities seen in schizophrenia including deficits in working memory, impaired sensory motor gating and increased activity hyperloco-motion (Lipska and Weinberger, 2000 Arguello and Gogos, 2006 Powell et al., 2009). It is difficult to generate an animal model that can recapitulate all of clinical symptoms of a complex behavioral disease like schizophrenia. However, zebrafish provide the unique opportunity to perform large forward genetic screens to identify new genes involved in a particular behavior in addition to studying behavior in a genetically characterized mutant line.

Age differences in memory processing speed and interval timing

Perbal et al. (2002) examined the relations between young and older adults' scores on neuropsychological tests and their performance on different interval timing tasks. The neuropsychological measures included were designed to differentially emphasize processing speed, passive short-term memory storage, working memory (online storage and processing), and long-term, delayed memory storage. The inter Standard age and divided attention effects were found on the timing tasks, with older adults overproducing and underreproducing the target intervals to a greater extent than did young adults. Performance on the neuropsychological measures of working memory and long-term memory was moderately correlated with accurate performance on the timing tasks, especially reproduction. There was some tendency for these correlations, especially for long-term memory, to be greater for longer (14 and 38 sec) than shorter (5 sec) intervals. Moreover, when age differences in working memory and long-term...

Pharmacological Toxicological Effects 51 Endocrine Effects

Commercially available P. ginseng products have been reported to have stimulant effects on the central nervous system (CNS) in humans (34) (see Section 5). In animal models, ginseng extracts have been shown to have CNS-stimulant effects (35). Ginsenoside Rg1 inhibits neuronal apoptosis in vitro (35), and ginsenoside Rb1 reverses short-term memory loss in rats (4).

Review Activities

The consolidation of short-term memory into long-term memory appears to be a function of function of the cerebral hemispheres. Propose some experiments that would reveal the lateralization of function in the two hemispheres. What evidence do we have that Wernicke's area may control Broca's area What evidence do we have that the angular gyrus has input to Wernicke's area State two reasons why researchers distinguish between short-term and long-term memory. Describe evidence showing that the hippocampus is involved in the consolidation of short-term memory. After long-term memory is established, why may there be no need for hippocampal involvement Can we be aware of a reflex action involving our skeletal muscles Is this awareness necessary for the response Explain, identifying the neural pathways involved in the reflex response and the conscious awareness of a stimulus.

ERPs and the locus of selective attention

Additional recent studies have also explored the effects of attention on these early visual and auditory components in people that are selected according to specific characteristics. For example, Brumback, Low, Gratton, & Fabiani (2004) reported that individuals selected for having either very high or very low loaded working memory span differ in the amplitude of their auditory N1s and visual P150s in response to stimuli in simple oddball tasks. Similarly, Parasuraman, Greenwood, and Sunderland (2002) have examined the effects of the ApoE-4 allele on attention and brain activity.

Michael Feuerstein

Clinically, it is critical that we understand and address the concerns of the individual survivor presenting in our offices with persistent pain, recurrent bouts of fatigue, working memory deficits, emerging health risks or illnesses other than those related to cancer, and recurrence of tumor or metastases (Part II). These challenges need to be dealt with using evidence-based and timely approaches at a cost that is in line with patient and societal expectations (Part III). As approaches for these problems become more widely used in daily practice, access also needs to be considered. It is not enough to have these approaches available they need to be available to all who need them. We also must adequately address psychosocial factors and biology from the perspective of diversity. Not because government tells us to or because there is funding for the topic, but because it is the right thing to do and it is logical if our goal is to help all.


The autobiographies of 49 eminent psychologists were content analyzed in terms of autobiographically consequential experiences (ACEs). Most memories for ACE were not single episodes. Episodic ACEs did, however, share many characteristics of flashbulb and vivid memories elicited in studies using more traditional experimental procedures. Memories were concentrated during the college and early adult years. Thus, as in other autobiographical memory studies that have used older Ss, there was a pronounced reminiscence effect. Results are considered in light of Erikson's theory (E. Erikson et al., 1986) of adult personality development. (Reprinted with permission of the American Psychological Association, publisher of Psychological Abstracts and the PsychLIT database. All rights reserved.)

BOLD physiology

Another important question is whether BOLD signal increases reflect neural excitation or inhibition. Some research supports the idea that much of the glucose and oxygen extraction from the blood is driven by glutamate metabolism, a major (usually) excitatory transmitter in the brain. Shulman and Rothman (Shulman & Rothman, 1998) suggest that increased glucose uptake is controlled by astrocytes, whose end-feet contact the endothelial cells lining the walls of blood vessels. Glutamate, the primary excitatory neurotransmitter in the brain, is released by some 60-90 of the brain's neurons. When glutamate is released into synapses, it is taken up by astrocytes and transformed into glutamine. When glutamate activates the uptake transporters in an astrocyte, it may signal the astro-cyte to increase glucose uptake from the blood vessels. Although it remains plausible that some metabolic (and BOLD) increases could be caused by increased inhibition of a region, in many tasks where both BOLD...

Retinoid X Receptors

Tion (Table 3.7).374,375 The RXR genes, like the RAR family, are expressed widely, in a partially overlapping but subtly distinct pattern in a number of tissues. Both RARa and RXRft are ubiquitously expressed, while RXRa and RXR 7 expression is restricted to distinct organ sys-tems.21,376 Also similar to RARs, RXR single knockout animals exhibit distinct phenotypes, demonstrating that the RXRs are not functionally redundant but have evolved sufficiently following gene duplication to perform distinct cellular functions. Examples of this specialization include roles for RXRft and -7 in long-term memory and spermatogenesis, respec-tively.377,378 Some of the phenotypes observed in RXR-deficient animals are linked to its involvement in RAR signaling and retinoid metabolism. Evaluation of knockout phenotypes, therefore, must consider potential inactivation of partner function through RXR loss of function. In fact, in at least one case (PPAR7), the RXRa phenotype has been nearly phenocopied...

Testing Adults

Because of a lack of time, perception of the test tasks as meaningless, fear of doing badly, or other factors, older adults are often more reluctant to be tested than other age groups. Laboratory-type tasks such as memorizing a set of numerical digits or nonsense syllables or solving math problems and puzzles may strike an older adult as silly and irrelevant to real life. In addition, older adults tend to be slower, more cautious, more distractible, and

Scalar Timing Theory

The current estimate of elapsed time, mt, can be transferred either to working memory for immediate use or to reference memory, where it can be stored for future reference. In a fixed-interval schedule the usual cue for transferring a value to reference memory is the delivery of food. When food is delivered (i.e., t FI, the value of the fixed interval), the scalar timing theory assumes that the value of mt, which we will now refer to as mFI, is transferred to reference memory as

Memory Storage

Table 4-1 is a glossary of memory terms. As indicated by the terms sensory memory or sensory register, the first stage of memory is a sensory impression of the material to be recalled. This stage lasts only a few seconds, until the impression is registered in short-term memory (STM or primary memory). A familiar example of primary memory, which lasts no longer than half a minute, is remembering a specific telephone number only until it has been dialed. To be remembered for a longer period of time, that is, to be Explicit memory Intentional, conscious memory. Implicit memory Memory occurring without conscious intention to remember. Long-term memory (LTM) Secondary or tertiary memory. Memory that lasts at least 10-20 minutes and involves more permanent storage in the brain. Procedural memory E. Tulving's term for stored knowledge of skilled, automatic actions or procedures. Secondary memory Fairly short-term memory having a capacity of more than 5 to 7 bits of information, based on...


People with amnesia have an impaired ability to remember facts and events, which some scientists have called declarative memory. This system of memory can be divided into two major categories short-term memory and long-term memory. People with head trauma, for example, and patients who undergo electroconvulsive shock (ECS) therapy may lose their memory of recent events but retain their older memories. Recent evidence suggests that the consolidation of long-term memory requires the activation of genes, leading to altered protein synthesis and synaptic connections. The consolidation of short-term memory into long-term memory is the function of the medial temporal lobe, an area that includes the hippocampus, amygdaloid nucleus, and adjacent areas of the cerebral cortex (fig. 8.14). Once the memory is put into long-term storage, however, it is independent of the medial temporal lobe. Surgical removal of the right and left medial temporal lobes was performed in one patient, designated...

Concluding remarks

All of the DISC1 mouse models display some kind of neuroanatomical or cytoarchitectural abnormalities relevant to SZ. The cytoarchitectural changes have been found mainly in the hippo-campal dentate gyrus. Two (CaMK-AC Tg, and BAC-AC Tg) out of the three models in which this feature was investigated showed reduced parval-bumin immunoreactivity. All of the DISC1 mouse models have behavioral abnormalities relevant to SZ. Most of the models have cognitive abnormalities when subjected to the relevant tests impaired attention as demonstrated by the PPI and latent inhibition tests and impaired working memory in the delayed non-match to place task. Most of the models have normal spatial learning and memory as judged by the Morris water maze test. Positive symptoms in the form of psychomo-tor agitation as modeled by hyperactivity during the first 30 min in a novel open field have been demonstrated only in one model (L100P mutant). In the domain of negative depression-like symptoms, the forced...


The P2 components in the hippocampus were prominent during the T-task, and the P2 latency was almost the same time for the hippocampus and the cerebellum. This result suggested that the information processing related to working memory might be carried out simultaneously in the course of the task and be observed concurrently with the activation of the clock mechanism. The idea here is that certain aspects of memory processing may be required for the initialization of working The hippocampal theta power increased more in the T-task than in the C-task at the onset of stimuli. The peak frequency shifted toward a higher range in the T-task than in the C-task, as shown in Figure 13.4. These results suggest that the hippocampus was initialized for temporal processing by the resetting of working memory at stimulus onset. According to the information-processing model outlined above, the pacemaker will generate pulses that go through a switch into an accumulator. On a new trial, the timing...

Cognitive Regulation

We have also recently reviewed our research on the relationship between HRV and cognitive regulation (Thayer et al, 2009). Attentional regulation and the ability to inhibit prepotent but inappropriate responses are important for health in a complex environment. Many tasks important for survival in today's world involve cognitive functions such as working memory, sustained attention, behavioral inhibition, and general mental flexibility. These tasks are all associated with prefrontal cortical activity (Arnsten and Goldman-Rakic, 1998). Deficits in these cognitive functions tend to accompany aging and are also present in negative affective states and dispositions such as depression and anxiety. Stress can also impair cognitive function and may contribute to the cognitive deficits observed in various mental disorders. It is also possible that autonomic dysregulation contributes to decline in attention and cognitive performance. Importantly, we have shown that HRV is related to these...

Learning and Memory

When learning and memory problems occur among patients with CMD, they tend to involve learning efficiency and retrieval, particularly on tasks requiring the processing of large quantities of new or complex information that is difficult to organize (e.g., California Verbal Learning Test, Complex Figure Test). However, other problems with specific processes associated with learning and memory have also been described. For example, working memory is often affected in patients with CMD (137, 157, 158). Difficulties with semantic processes and priming associated with learning and memory have also been described (159). Yet, problems with semantic memory are not always evident (137, 157, 160) and relate more to executive dysfunction than to memory encoding or storage per se when they occur (161). It should be noted however that there is recent evidence that in the current era of HAART, HIV may be causing greater hip-pocampal damage and hippocampal-associated memory impairments. Moore et al....

Proviral DNA

Against this backdrop, it is important that while incidence has declined, people continue to develop HIV-associated dementia despite HAART (241, 242). A significant relationship has been shown between levels of circulating provirus and HIV-associated dementia, not only in this country but in other parts of the world, where AIDS is less well-controlled (243). Recently, Shiramizu et al. demonstrated that circulating HIV proviral DNA is significantly associated with neurocognitive function as well (215). In fact, HIV-DNA levels correlated with performance across many different cognitive domains, including learning and memory, motor function, attention and working memory, executive functioning and language, independent of age, ethnicity, intellectual level, and plasma viral load. Yet, baseline HIV-DNA levels did not predict change in these cognitive functions over time. Therefore, it is likely that cognitive function varies in its relationship to changes in HIV proviral DNA over time.

V1v2 A1a2

Assemblies of basic units, each of which is an interacting excitatory-inhibitory leaky integrator neuronal pair that represents a simplified cortical column (Wilson & Cowan 1972). Although there are many attributes that can be used to characterize an object (e.g., shape, color, texture), we chose to focus on shape and assumed that the basic feature, based on the work of Hubel and Wiesel (Hubel & Wiesel 1977), is line orientation. So, the excitatory neurons in the V1 V2 module were constructed to respond in a retinotopically configured manner to lines oriented in particular directions (for computational simplicity, we use only horizontal and vertical lines). The V4 module is similar to the V1 V2 one in that it is retinotopically organized, and contains neurons with horizontal and vertical line orientation selectivity. It also contains neurons that respond to a combination of features (i.e., neurons that respond best to a change in line orientation, what can be called second-derivative...


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