Normal Cognitive Processes Research Articles

ON REACTION DYNAMICS AT DOPAMINE SYNAPSES

Dopamine neurons play a key role in normal and pathological cognitive processes as well as in the effects of certain drugs of addiction. Models of the synapses of such neurons include transporter mechanisms and reaction dynamics. This article focuses attention on the fundamental reaction that converts tyrosine to DOPA, which involves a cofactor. The Michaelis-Menten formula for the rate of an enzymatic reaction is modified by the presence of cofactors, which may be either essential or nonessential. In the essential case, the reaction rate is found to depend on the relative magnitudes of the concentrations of the primary enzyme and the cofactor. The case of a nonessential cofactor is more complex and it is shown for the first time how this leads to reaction rate formulas that depend explicitly on the concentrations of the enzyme and cofactor. The extended Michaelis-Menten formulas are applied to the aforementioned reaction with tyrosine hydroxylase as enzyme and biopterin as cofactor. The results are useful in constructing accurate models of dopamine synapses.

Neuropsychological assessment and quality of life in patients with refractory temporal lobe epilepsy related to hippocampal sclerosis

INTRODUCTION: Epilepsy is a disorder that results in abnormal activity in a group of neurons that may have significant impact on the normal cognitive processes and behavior. Temporal lobe epilepsy (TLE) is the most frequent form of partial epilepsy in adults, and hippocampal sclerosis (HS) the most common neuropathologic finding in patients with medically refractory TLE. Patients with TLE often present cognitive difficulties that may be determined by the effects of epileptic discharges and side of the lesion. And its consequence is that patients have poor effects on quality of life (QOL). PURPOSE: We report the relationship between neuropsychological assessment and QOL under the hypotheses that patients with worst results in neuropsychological assessment have poorer QOL assessed by the QOLIE-31. RESULTS: Regarding seizure frequency, 23 (46%) had had 1-5, 20 (40%) 6-10 and 7 (14%) more than 10 seizures/month. In relation to seizure types, 5 (10%) had had auras, 37 (74%) complex partial seizures and 8 (16%) partial evolving to generalized tonic-clonic seizures (GTCS). Neuropsychological evaluation had a positive correlation with QOLIE-31 domains. QOL evaluations had the worst scores in QOLIE-31 were in Cognitive Function (45.0) and Social Function (46.0). The best was Overall QOL (62.0). CONCLUSION: People with epilepsy have great impact on their QOL not only because of daily seizures but because of the impact seizures cause in their cognitive functions. TLE is an example of how refractory epilepsy can exterminate any possibilities of work, study and live in a society that discriminates someone with epilepsy who also presents cognitive decline.

Knockdown of Nurr1 in the rat hippocampus: implications to spatial discrimination learning and memory.

Nurr1 expression is up-regulated in the brain following associative learning experiences, but its relevance to cognitive processes remains unclear. In these studies, rats initially received bilateral hippocampal infusions of control or antisense oligodeoxynucleotides (ODNs) 1 h prior to training in a holeboard spatial discrimination task. Such pre-training infusions of nurr1 antisense ODNs caused a moderate effect in learning the task and also impaired LTM tested 7 d later. In a second experiment, ODN infusions were given immediately after the animals had received two sessions of training, during which all animals showed normal learning. Although antisense treated rats were significantly impaired during the post-infusion stages of acquisition of the task, no group differences were observed during the LTM test given 7 d later. These animals were subjected 3 d later to reversal training in the same maze in the absence of any additional treatments. Remarkably, rats previously treated with antisense ODNs displayed perseveration: The animals were fixated with the previously learned pattern of baited holes, causing them to be significantly impaired in the extinction of acquired spatial preferences and future learning. We postulate that Nurr1 function in the hippocampus is important for normal cognitive processes.

Alpha-2 Adrenoceptor Activation Inhibits Phencyclidine-Induced Deficits of Spatial Working Memory in Rats

N-methyl-D-aspartate (NMDA)/glutamate receptor antagonists, such as phencyclidine (PCP), induce behavioral abnormalities (locomotor hyperactivity, sensorimotor gating deficits, impairments of cognition) in animals that are thought to model aspects of schizophrenia. The administration of PCP increases noradrenaline transmission in the rat prefrontal cortex, a brain structure required for normal cognitive processes. Noradrenaline, in turn, works through a set of receptors that have themselves been implicated directly in NMDA antagonist-induced deficits; we recently reported that the alpha-2 agonist, clonidine, is effective at preventing PCP-induced deficits of working memory and visual attention in rats. Here, we further investigated the role for alpha-2 adrenoreceptors in the effects of PCP on spatial working memory performance. The alpha-2 agonist clonidine (0.001-0.01 mg/kg, subcutaneously (s.c.)) produced a significant amelioration of PCP-induced working memory deficits; the effects of PCP (1.0 mg/kg, s.c.), but not clonidine, were reduced in noradrenaline-depleted rats. In addition, the alpha-2A-preferring agonist guanfacine (0.05-1.0 mg/kg, s.c.) dose-dependently prevented the deficits of spatial working memory performance produced by PCP. Although the highly selective alpha-2 receptor antagonist, atipamezole (ATI), failed to affect spatial working memory on its own, at the doses studied (0.1-0.5 mg/kg, s.c.), it dramatically enhanced the working memory deficit produced by PCP. These data indicate that alpha-2 adrenoreceptors tonically inhibit PCP-induced deficits of spatial working memory, suggesting an important role for these receptors in cognitive deficits associated with NMDA receptor hypofunction.

Chronic lithium decreases Nurr1 expression in the rat brain and impairs spatial discrimination

Lithium (Li +) is a drug used for the treatment of neuropsychiatric disorders, whereas Nuclear receptor-related factor 1 (Nurr1) has been implicated in normal and aberrant cognitive processes. Li +'s effects on cognition and Nurr1 expression were examined. Rats were exposed to Li + in their diet for 4 weeks and only those reaching Li + blood concentrations within the established clinically therapeutic range were used. Li + decreased rearing activity in rats, but did not affect horizontal locomotion nor object recognition memory. In contrast, Li + treated animals were significantly impaired in the initial, but not late, stages of acquisition of a hippocampal-dependent spatial discrimination task. In agreement with the behavioral results, chronic Li + caused a significant downregulation of basal Nurr1 expression in several brain regions. In particular, a significant negative correlation between Li + blood levels and Nurr1 expression was identified in the CA1 hippocampal subregion, but not in CA3, perirhinal cortex or the dorsal endopiriform nucleus. Upregulation of hippocampal Nurr1 levels to those of controls were observed in Li + treated rats following training in the spatial task. Overall, the results suggest that the effects of Li + on the brain may be particularly relevant to hippocampal-dependent cognitive processes involving Nurr1 expression.

Pharmacological Modulation of Cognitive Functions: Studies with fMRI

There is ample evidence that normal cognitive and emotional information processing is functionally dependent on the concerted activity of different interacting neurotransmitter systems. In a series of studies, we employed acute pharmacological challenge paradigms and subchronic pharmacological interventions in order to elucidate GABAergic and dopaminergic effects on functional brain imaging patterns subserving short-term working memory, learning processes and prediction uncertainty. An acute lorazepam challenge was associated with decreased cortical and subcortical activity during a 2-back working memory task. For alcohol-dependent patients, a blunted dopaminergic cerebellar response could be observed suggesting altered cerebellar GABAergic setpoints. On the other hand, fMRI activation during a prediction uncertainty task was found to be pronounced in the DLPFC after a dopaminergic methylphenidate challenge. Additionally, atypical antipsychotic drugs with a potential to enhance dopaminergic functions were associated with altered information processing not only in the PFC but also in an entire cortical-subcortical cerebellar circuitry in schizophrenic patients. Taken together, these findings indicate the regulatory capacity of both GABAergic and dopaminergic mechanisms and the existence of propagated effects involving changes in effective connectivity between segregated brain areas. Functional MRI appears to be a suitable tool to monitor the restoration of normal activation patterns during psychopharmacological interventions.

Event-related potential correlates selectively reflect cognitive dysfunction in schizophrenics

Schizophrenics show event-related potential (ERP) and particularly P3 abnormalities. To study the more detailed relationships between these ERP alterations and cognitive dysfunction we recorded and analyzed ERPs using a particular experimental approach. In 34 schizophrenics and 25 controls ERPs were obtained by a visual Go/Nogo task requiring response inhibition and were decomposed into temporally independent topographical components using Independent Component Analysis (ICA). ICA disentangled different subcomponents of P3. Subcomponent P3b with a parietal maximum amplitude was significantly reduced in the schizophrenics, probably reflecting their attentional deficits. Subcomponent P3ng with a frontal maximum amplitude and enhanced during Nogo condition appeared as an electrophysiological index of response inhibition. A significantly reduced P3ng enhancement, found in schizophrenics, probably reflects their impaired response control. ICA can successfully identify ERP subcomponents with distinct scalp topographies representing significant differential indices of normal and abnormal cognitive processing. Involvement of frontal brain areas in disturbed executive control in schizophrenics is supported by our ICA findings.

Independencia funcional del conocimiento numérico léxico y la representación de la magnitud: evidencia de un caso

The ultimate purpose of cognitive neuropsychology is to find out how normal cognitive processes work. To this end, it studies subjects who have suffered brain damage but who, until their accident, were competent in the skills that are later to become the object of study. It is therefore necessary to study patients who have difficulty in processing numbers and in calculating in order to further our knowledge of these processes in the normal population.Our aim was to analyse the relationships between the different cognitive processes involved in numeric knowledge.We studied the case of a female patient who suffered an ischemic infarct in the perisylvian region, on both a superficial and deep level. She presented predominantly expressive mixed aphasia and predominantly brachial hemiparesis. Numeric processing and calculation were evaluated. The patient still had her lexical numeric knowledge but her quantitative numeric knowledge was impaired. These alterations in the quantitative numeric knowledge are evidenced by the difficulties the patient had in numeric comprehension tasks, as well as the severe impairments displayed in calculation.These findings allow us to conclude that quantitative numeric knowledge is functionally independent of lexical or non-quantitative numeric knowledge. From this functional autonomy, a possible structural independence can be inferred.

The role of dopamine in cognition: evidence from functional imaging studies.

Functional imaging provides a sensitive means of studying the dopaminergic system in the brain. Both pre-synaptic and post-synaptic aspects of this system can be explored, and recent technical advances even allow the estimation of the synaptic level of dopamine in the striatum. However, only a few studies have used functional imaging to identify the role of dopamine in cognition. This paper reviews recent evidence provided by studies in healthy individuals and patients with Parkinson's disease or schizophrenia supporting the role of dopamine in normal and pathological cognitive processes.

Procesamiento numérico y cálculo: evidencia de un caso desde la neuropsicología cognitiva

This paper, which deals with cognitive Neuropsychology, attempts to contribute to the understanding of normal cognitive processing by examining and analysing the deficits acquired by individuals who have suffered brain damage.Our aim was to analyse the different cognitive processes involved in numerical processing (NP) and in calculation, together with the relations between them.A quadriplegic patient with sequelae that include motor aphasia and deep dysgraphia as the residual pathologies of a traumatic brain injury, with a history of over four years; language comprehension is preserved (both oral and written) and there is no verbal expression whatsoever. Expression is achieved functionally by means of a specially adapted laser pointer. Assessment of NP and calculation was performed.Alterations were observed in the calculation system, one in the recognition of arithmetical signs and the other in the execution of arithmetical operations.1. Calculation skills are independent of those required to perform numerical recoding and of lexical or encyclopaedic numerical knowledge. 2. Recognition of arithmetical signs is independent of, and therefore dissociated from, data retrieval and the execution of calculation procedures. 3. Data retrieval processes and those required for the execution of calculations are independent. Therefore, the calculation system consists of different elements that are independent from one another.

The neurobehavioural effects of kava.

This review considers the context in which kava is used, together with its underlying psychopharmacological mechanisms, to investigate the neurobehavioural effects associated with kava use. We conducted a systematic search using the computerized databases MEDLINE, OVID and PsychLIT for all articles containing any of the following words: kava, kavain, kawa and Piper methysticum. In the opinion of the authors, all articles from this collection containing data that could inform the neurological and cognitive sequelae of kava use were included for the purpose of this review. The use of kava occurs among indigenous populations in the South Pacific and in northern Australia, while also being used throughout the western world as a herbal medicine. Animal studies show that kava lactones alter neuronal excitation through direct interactions with voltage-dependent ion channels, giving rise to kava's muscle relaxant, anaesthetic, anxiolytic and anticonvulsive properties. Several isolated cases of psychotic and severe dystonic reactions following kava use suggest that kava also has psychoactive properties, yet there is no conclusive evidence that kava interferes with normal cognitive processes. Kava is effective in the treatment of tension and anxiety. There may be risk-factors for severe motor and psychiatric responses to kava use, although these are not well-understood. Given the increasingly widespread use of kava, further investigation is necessary to gain an understanding of its immediate neuropsychiatric effects and long-term cognitive effects.

Attentional phenotypes for the analysis of higher mental function.

We outline a strategy to relate normal cognitive processes to candidate genes. First, brain imaging is used to specify a cognitive process “attention” in terms of the neural networks involved. Next, evidence is presented showing that the operation of each network involves a dominant neuromodulator. Then we discuss development of a task designed to measure the efficiency of each network in normal individuals and consider evidence on the independence, reliability, and heritability of the networks. DNA from cheek swabs of subjects who performed the task are then used to examine candidate polymorphisms in genes related to the transmitters. We then examine the ability of these candidate alleles to predict the efficiency of relevant networks. This process has demonstrated that candidate genes are related to specific networks of attention to a greater degree than to overall performance as measured by reaction time and accuracy. These findings require replication and possible extension to other cognitive processes.

The expression of ccn3 (nov)* RNA and protein in the rat central nervous system is developmentally regulated

Aims—To establish the expression pattern of ccn3 (nov) in the central nervous system (CNS) of adult rats and to determine whether spatiotemporal variations in the expression of ccn3 (nov) are...

Interpreting PET and fMRI measures of functional neural activity: the effects of synaptic inhibition on cortical activation in human imaging studies

Human brain imaging methods such as postiron emission tomography and functional magnetic resonance imaging have recently achieved widespread use in the study of both normal cognitive processes and neurological disorders. While many of these studies have begun to yield important insights into human brain function, the relationship between these measurements and the underlying neuronal activity is still not well understood. One open question is how neuronal inhibition is reflected in these imaging results. In this paper, we describe how large-scale modeling can be used to address this question. Specifically, we identify three factors that may play a role in how inhibition affects imaging results: (1) local connectivity; (2) context; and (3) type of inhibitory connection. Simulation results are presented that show how the interaction among these three factors can explain seemingly contradictory experimental results. The modeling suggests that neuronal inhibition can raise brain imaging measures if there is either low local excitatory recurrence or if the region is not otherwise being driven by excitation. Conversely, with high recurrence or actively driven excitation, inhibition can lower observed values.

Classification criteria for mild cognitive impairment: a population-based validation study.

To evaluate the predictive validity and temporal stability of diagnostic criteria for mild cognitive impairment (MCI). MCI has been proposed as a nosologic entity referring to elderly persons with subclinical cognitive deficits due to incipient dementia. Classification criteria, which have been derived from small, selected clinical groups, are currently disputed, and have not yet been assessed within the general population. Subjects meeting current criteria for MCI and also age-associated cognitive decline (AACD-a similar concept that is assumed to be related to normal cognitive aging processes rather than incipient dementia) were identified within each of three waves of a longitudinal population study, which included a standardized neurologic examination. In the general population, the prevalence of MCI was estimated to be 3.2% and AACD 19.3%. MCI was a poor predictor of dementia within a 3-year period, with an 11.1% conversion rate. Subjects with MCI also constituted an unstable group, with almost all subjects changing category each year. Discriminant function analysis failed to isolate a homogeneous clinical group. Subjects classified as AACD, contrary to the theoretical assumptions underlying the disorder, represented a more stable group, with a 28.6% conversion rate to dementia over 3 years (relative risk = 21.2). MCI criteria perform poorly when applied to a representative population sample. The authors propose modifications to current diagnostic criteria to increase their capacity to detect incipient dementia.

The Neuropsychology of Frontal Variant Frontotemporal Dementia and Semantic Dementia. Introduction to the Special Topic Papers: Part II

The second part of this review, which accompanies 10 special topic articles dedicated to frontotemporal dementia (FTD), describes some of the advances in understanding frontal variant FTD (fvFTD) and semantic dementia, and the theoretical insights gained into normal cognitive processes from the study of these syndromes. Recent work has clarified the neuropsychiatric features that distinguish fvFTD from Alzheimer’s and has begun to spread light on the underlying deficits in social judgement, theory of mind, processing of emotional stimuli and decision making. With regard to central aspects of cognitive processing, such as memory, patients with fvFTD may have a distinctive profile of performance on tests of explicit and implicit memory, and contrary to current views some patients may even have a severe amnesic syndrome. There is also growing evidence that despite relatively well preserved general language skills, patients with fvFTD have particular problems with verb processing. Although there is agreement regarding the key features of semantic dementia, much controversy has surrounded the issue of whether the cognitive findings favour an explanation in terms of progressive breakdown of a central amodal semantic store or differential involvement of verbal and non-verbal systems. Other topics discussed include the impact of semantic breakdown on phonological processes and episodic memory. We also review recent structural and functional neuroimaging findings in semantic dementia.

ADVANCES IN NEUROLOGY VOLUME 81. PLASTICITY IN EPILEPSY: DYNAMIC ASPECTS OF BRAIN FUNCTION.: By Hermann Stefan, Frederick Andermann, Patrick Chauvel and Simon D. Shorvon. 1999. Philadelphia: Lippincott Williams & Wilkins. Price $149. Pp. 396. ISBN 0-7817-1446-X.

The development and long-term course of epilepsies are subserved by, and subject to dynamic changes of brain function, which in turn interfere with normal development and cognitive processes. Central nervous system plasticity, mediated by molecular mechanisms and gene expression, accounts for most of these changes, and permits pathological reorganization of the brain that may have important therapeutic consequences. In this respect, an overview of the current state of research on plasticity in epilepsy was mandatory, and this has been done, thanks to the publication of this issue of Advances in Neurology , developed from a symposium held in Germany at the end of the 1990s. Some readers will be somewhat disconcerted by the difficulty in finding links between the different chapters, the arrangement of which is not successful. In addition, several articles, although interesting, are not really relevant to the problem. Some figures would have benefited from colour printing, and figure captions are sometimes insufficient. Over 42 chapters, this book provides an expert coverage of most of the dynamic aspects of brain function as related to maturation, cerebral lesions, epileptic activity, antiepileptic drugs and epilepsy surgery. These different aspects are summarized in the following paragraphs, indicating the chapters in which they have been developed. In normal as well as in pathological conditions, cerebral representations are not static, but can be modified by normal learning and by compensation for impairments caused by brain lesions. In normal children under 10 years old, cerebral metabolism and blood flow measurements show that a transient hyperfunctionality may occur in all regions of the cortex, but the timing of its appearance is different, according to the ages at which cognitive functions sustained by the given regions develop (Chapter 11). This period, which could correspond to the period known in animals to be of maximal plasticity, may …

Emotion regulation in acceptance and commitment therapy.

Acceptance and Commitment Therapy (ACT) offers an alternative to traditional psychotherapies designed to regulate affect. ACT is based on the premise that normal cognitive processes distort and enhance the experience of unpleasant emotion, leading clients to engage in problematic behaviors designed to avoid or attenuate those unpleasant emotions. Such avoidant behavior patterns can hinder and prevent client movement toward valued goals and place the client in harmful situations. Rather than working to change cognitions or decrease levels of emotion, the ACT approach involves the client directly experiencing problematic emotions in a context in which the literal functions of language enhancing the negative implications of those emotions are stripped away. The focus throughout the treatment is facilitating the client's movement toward a more valued and personally fulfilling life, in a context in which previously obstructive unpleasant emotions no longer serve as obstructions. A case study is provided to illustrate some of ACT's core techniques.

The Relevance of the Dopamine-D1 Receptor in the Cognitive Symptoms of Schizophrenia

An understanding of the role of the prefrontal cortex in normal cognitive processes has advanced our comprehension of the pathophysiology underlying the cognitive deficits in schizophrenia. Studies of single-neuron activity in monkeys during performance of delayed-response tasks have confirmed the involvement of the prefrontal cortex in working memory. The “memory fields” of prefrontal neurons are analogous to the receptive fields of visual neurons and the cellular expression of a working memory process that allows mnemonic information to guide behavior. D1-dopamine antagonists produce a dose-dependent effect (U-shaped) on the firing rate of cells with memory fields during delayed-response tasks. Disordered cognitive processes in schizophrenia can be attributed to impairment of function in the prefrontal cortex, as evidenced by hypometabolic activity in the prefrontal cortex and selective impairment in working memory tasks. Advances in our understanding of the role of D1 receptors in the cognitive deficits observed in schizophrenia should provide us with a rational basis for developing alternative antipsychotic treatments and may provide insight into the cellular basis of the disorder.

Motivated Self-Deception in Child Molesters

ABSTRACT It is widely accepted that child molesters suffer from cognitive distortions in their thinking. In this article, the concept of motivated self-deception is introduced to explain how these distortions are likely to develop from normal cognitive processes. These processes include cognitive heuristics and optimistic biases that are magnified and embellished because of deviant motivations. Several different everyday heuristics and patterns of self-deception are described, with examples of how the resulting biased information is activated and progressively organized by molesters throughout the abuse chain to accomplish specific goals. A framework is provided that distinguishes between two major groups of self-deception based on the set of functions intrinsic to each. This is followed by a discussion of how it is possible for molesters to truly deceive themselves. Finally, several treatment suggestions are provided, with an emphasis on the implications for managing resistance and denial as well as fostering a sense of responsibility within molesters.