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PubMed2005

Age-dependent changes in distribution of P3a/P3b amplitude and thickness of the cerebral cortex.

With increasing age, the electrophysiological event-related potentials P3a/P3b tend to get a more frontal maximum. The cognitive significance of this so-called frontal shift is not known, but hypotheses have focused on changes in the integrity of the frontal lobes. The aim of the present study was to test how the thickness of the cerebral cortex is related to the frontal shift. Well screened elderly participants went through a visual three-stimuli oddball-task, a battery of neuropsychological tests and magnetic resonance imaging scans. It was found that participants with frontocentral maxima had a thicker cerebral cortex in distinct areas than participants with parietal maxima, both for P3a and for P3b, while the parietal P3b participants had a thicker cortex in the anterior cingulate. This is the first study to demonstrate that age-dependent changes in the scalp distribution of electrophysiological activity are related to differences in thickness of the cerebral cortex.

Aged↗

PubMed1994

Exposure to dust and rat urinary aeroallergens in research establishments.

As part of an epidemiological study rat urinary aeroallergen (RUA) and total dust concentrations were measured at three research establishments. Personal RUA measurements in nine exposure groups over a workshift showed highest exposure for animal technicians (geometric mean (GM) = 32.4 micrograms/m3) and lowest for workers in slide production and office (GM > or = 0.1 micrograms/m3). Except for slide production workers, contact with rats, their tissues, faeces, or urine comprised less than half the work shift. Exposure during contact with rats was considerably higher. Personal RUA measurements in nine task categories showed high RUA concentrations for handling rats (GM = 68.0 micrograms/m3) and cleaning out (GM = 53.6 micrograms/m3). Traces of RUA could still be measured in tearooms inside and near offices outside the animal houses. Total dust concentrations were low.

Allergens↗

PubMed2005

The plastic human brain cortex.

Plasticity is an intrinsic property of the human brain and represents evolution's invention to enable the nervous system to escape the restrictions of its own genome and thus adapt to environmental pressures, physiologic changes, and experiences. Dynamic shifts in the strength of preexisting connections across distributed neural networks, changes in task-related cortico-cortical and cortico-subcortical coherence and modifications of the mapping between behavior and neural activity take place in response to changes in afferent input or efferent demand. Such rapid, ongoing changes may be followed by the establishment of new connections through dendritic growth and arborization. However, they harbor the danger that the evolving pattern of neural activation may in itself lead to abnormal behavior. Plasticity is the mechanism for development and learning, as much as a cause of pathology. The challenge we face is to learn enough about the mechanisms of plasticity to modulate them to achieve the best behavioral outcome for a given subject.

Blindness↗

PubMed2002

Cerebellar damage impairs automaticity of a recently practiced movement.

It has been suggested that the cerebellum plays a critical role in learning to make movements more "automatic" (i.e., requiring less attention to the details of a movement). We hypothesized that cerebellar damage compromises learning of movement automaticity, resulting in increased attentional demands for movement control. The purpose of our study was to determine whether cerebellar damage disrupts the ability to make a practiced movement more automatic. We developed a dual task paradigm using two tasks that did not have overlapping sensory or motor requirements for execution. Our motor task required subjects to maintain an upright posture while performing a figure-8 movement using their arm. This motor task was chosen to simulate requirements of everyday movements (e.g., standing while reaching for objects), but it was novel enough to require practice for improvement. Our secondary task was an auditory vigilance task where subjects listened to letter sequences and were asked to identify the number of times a target letter was heard. We tested controls and people with cerebellar damage as they practiced the movement task alone and then performed it with the auditory task. We recorded 3D position data from the arm, trunk, and leg during the movement task. Errors were recorded for both the movement and the letter tasks. Our results show that cerebellar subjects can improve the movement to a very limited extent with practice. Unlike controls, the motor performance of cerebellar subjects deteriorates to prepractice levels when attention is focused away from the movement during dual task trials. Control subjects' insensitivity to dual task interference after practice was due to learned movement automaticity and was not a reflection of better dual task performance generally. Overall, our findings suggest that the cerebellum may be important for shifting movement performance from an attentionally demanding (unpracticed) state to a more automatic (practiced) state.

Adult↗

PubMed2000

Mechanism of protection against influenza A virus by DNA vaccine encoding the hemagglutinin gene.

Influenza A virus with its two major antigenic surface proteins hemagglutinin (HA) and neuraminidase (NA) is a widely used model to study DNA immunizations in mice and other animals. Natural protection against influenza A virus infection is mediated by antibodies, which mostly are not protective against antigenic shift or drift variants of the original virus. Therefore, it would be a major task to induce a protective cellular immune response to more conserved proteins or epitopes. Injection of plasmid encoding a viral antigen is known to induce cellular as well as humoral immunity. In this study we investigate the mechanism of protection after intramuscular vaccination of C57Bl/6 mice with a DNA vaccine encoding HA of influenza A/PR/8/34. After a single injection, only a small percentage of mice survive the lethal challenge with homologous virus. The amount of protection can be doubled by applying a booster injection. Furthermore, by coinjection of plasmids encoding cytokines GM-CSF and IL-12, respectively, nearly all of the mice are protected. Mice with specific defects in the cellular immune response [perforin knockout (P-/-) mice] and in the humoral immune response [IgD/IgM knockout (muMT) mice], respectively, have been immunized with HA DNA with or without cytokine DNA. Protection could only be induced in P-/- mice, whereas muMT mice succumbed to the infection. Moreover, when muMT mice were infected with only 0.75 x50% lethal dose they died all the same, whereby mice that had been depleted of CD8+ T cells before infection showed an even greater progression of illness. Altogether these results demonstrate that antibodies mediate protection after immunization with plasmid coding for HA of influenza A virus, and that booster immunizations and coinjection of plasmids encoding GM-CSF or IL-12 can improve this protection.

Animals↗

PubMed2004

Next steps for patient safety in Canadian healthcare.

Morgan outlines some important elements necessary for improving patient safety in Canadian healthcare. But these steps are likely to require considerable time and resources and may be difficult to implement. In the light of the evidence of adverse events in Canadian hospitals, all Canadian healthcare organizations need to begin to measure the numbers and types of adverse events experienced by their patients and clients. Staff need to learn new skills for investigating and improving care. A variety of tools and resources are available for these tasks. Leadership both in senior management and on the front lines must learn to shift the focus from blaming individuals to improving systems of care. Leaders must also acknowledge that most healthcare organizations have failed to gather the necessary information on adverse events, and they must invest in building knowledge and implementing practices that reduce the current levels of injury.

Adverse Drug Reaction Reporting Systems↗

PubMed2003

[From disease-oriented andrology to health-oriented andrology].

One of the main current trends of andrology is the paradigm shift from disease-oriented to health-oriented andrology. One of the major tasks we are faced with now is to establish an holistic concept of male reproductive health, then, starting from the needs and demands of male reproductive health, to identify the scope of andrology, as well as to develop a new research priorities and agenda. The progress and perspective of three main areas in the field of health-oriented andrology, namely, molecular andrology, andrology for aging and environment and male reproduction, were briefly reviewed and discussed.

Aging↗

PubMed2005

Cognitive and emotional processing at high altitude.

INTRODUCTION: Exposure to altitude reduces oxygen supply to the central nervous system and may cause a variety of neuropsychological impairments. We investigated the relationship between certain cognitive functions and cardiovascular and respiratory variables during acute hypobaric hypoxia. METHODS: There were three groups of seven men who were each exposed to a 2-h altitude profile (AP) involving 30 min at each of the following simulated altitudes (m): AP1, 450-1500-3000; AP2, 450-1500-4500; Control 450-650-650. The neuropsychological tests included word fluency and three word-association tasks tapping processes of cognitive flexibility and emotion regulation. A lateralized tachistoscopic lexical decision task with high and low emotional target words was also administered to assess possible shifts in hemispheric superiorities for positive and negative affect. RESULTS: No significant differences in word fluency, word association, or lateralized lexical decision performances were found, despite a significant oxygen desaturation and a drop in diastolic BP at 4500 m, indicating the beginning of central hypoxia in terms of a functional impairment of the vasomotor center. CONCLUSION: During acute exposure to hypobaric hypoxia, selected cognitive and affective functions mediated by the frontal lobe were preserved. Functional hemispheric asymmetries for emotional processes remained unchanged.

Acclimatization↗

PubMed2000

Task related changes in contingent negative variation (CNV) response of endogenous evoked potentials.

Contingent negative variation (CNV) is a slow negative cortical potential shift, which occurs during a warned foreperiod reaction time paradigm. Most studies of evoked potentials have concentrated on components occurring during the first 300 msec, although there are important and recordable aspects of signal processing occurring well beyond 300 msec e.g. late negative slow wave. CNV has proven sensitive to a number of psychological variables, none of which can yet be singled out as a definitive or exclusive correlate. Changes are expected if measured after a rigorous mental exercise. CNV was measured in 20 normal male subjects aged between 18 and 20 years. CNV was recorded twice in each subject before and after the administration of a mental task. The auditory mental task comprised repeating in reverse order string of random digits read out to the subject at a uniform speed of 1 per second. The visual mental task comprised reading laterally inverted type written text. Each subject had to undergo 2 sessions in separate sittings. The latency and amplitude of waves N1, P3, orientation (O), expectancy (E), CNV, reaction time (RT) were recorded. These values recorded before and after the task were compared statistically using student's unpaired t-test. The significant latencies recorded before and after the auditory task were, N1: 88.00 +/- 11.96 and 100.00 +/- 21.52 msec, P3: 289.00 +/- 54.85 and 299.00 +/- 52.91 msec, reaction time (RT): 102 +/- 17.05 msec and 123 +/- 17.5 msec, and in case of visual task, N1: 88 +/- 13.16 msec and 99.00 +/- 16.51 msec, reaction time (RT): 107 +/- 11.74 msec and 127 +/- 13.42 msec respectively. All other CNV wave latencies and amplitude changes were insignificant. Hence task effects sensory perception as reflected by increased latency of the long latency response N1 and the cortical integrative processes resulting in increased reaction time.

Adolescent↗

PubMed1994

Effect of practice on paw preference in a reaching task in cats.

Paw preference and performance were analyzed in twelve male adult cats during early and late practice of a complex visuo-motor reaching task towards a moving target. A strong bias towards left paw use was seen early in training: 80.7% of the trials being performed with the left paw, and left pawed cats (n = 11) significantly outnumbered right pawed cats (n = 1). After practice, a shift was observed towards right paw use, in that, overall, the proportion of trials executed using the left paw fell to 71.4%. Moreover two of the left pawed cats modified strongly their preference: one shifted to exclusive use of the right paw while the other one became ambidextrous. In non exclusive cats the comparison of visuo-motor scores for left and right paws during late practice showed that the usage of the paw which is both faster and more accurate had increased during training whether or not that paw was initially the preferred one. Furthermore, for cats where no systematic performance advantage was seen (i.e. one paw was faster, the other one more accurate) there was a shift towards ambidextry. As a conclusion, the results confirm a bias towards left paw use in cats performing a complex reaching task, and show that this bias is weakened by practice. The left hemisphere could take more importance when the new visuo-motor activity becomes progressively a well routinized one.

Animals↗

PubMed1990

Comparing the cerebral hemispheres on the speed of spatial shifts of visual attention: evidence from serial search.

We compared the speed at which visuo-spatial attention may be shifted from one stimulus to another as a function of the visual hemifield in which the items were displayed in a visual search task requiring serial processing. The increase in response time with the number of items displayed was similar for left- and right-hemifield presentations. This suggests that the rate at which visuo-spatial attention can be shifted from one stimulus to another during visual search does not differ between the cerebral hemispheres.

Adult↗

PubMed2005

Exploration of the neural substrates of executive functioning by functional neuroimaging.

This review presents neuroimaging studies that have explored the cerebral substrates of executive functioning. These studies have demonstrated that different executive functions not only recruit various frontal areas but also depend upon posterior (mainly parietal) regions. These results are in accordance with the hypothesis that executive functioning relies on a distributed cerebral network that is not restricted to anterior cerebral areas. However, there exists an important heterogeneity in the cerebral areas associated with these different processes, and also between different tasks assessing the same process. Since these discrepant results could be due to the paradigms used (subtraction designs), recent results obtained with conjunction and interaction analyses are presented, which confirm the role of parietal areas in executive functioning and also demonstrate the existence of some specificity in the neural substrates of the executive processes of updating, shifting and inhibition. Finally, functional magnetic resonance imaging studies show that the activity in cerebral areas involved in executive tasks can be transient or sustained. Consequently, to better characterize the functional role of areas associated with executive functioning, it is important to take into account not only the localization of cerebral activity but also the temporal pattern of this activity.

Cerebral Cortex↗

PubMed1986

A comparison of saccade evoked potentials recorded during reading and tracking tasks.

The influence of visual processing demands on saccade-triggered evoked potentials was investigated at P3, P4 and Oz recording sites during reading and tracking tasks. To maximize the physical similarities between tasks, subjects tracked a series of lights that flashed in a stereotypic reading pattern behind a page of text; eye movements recorded during reading initiated the light sequence. In the first experiment, a significant decrease observed in the latency of the major positive peak recorded from Oz during tracking was attributed to the smaller amplitude of tracking, relative to reading, saccades. To confirm this interpretation, the experiment was repeated with modification to the light display. As anticipated, equating saccade amplitudes across tasks eliminated waveform differences in the second experiment. Although peak latencies and amplitudes were not influenced reliably by visual processing demands, tracking potentials exhibited a negative DC shift relative to reading waveforms that was significant at 174 msec at the Oz site. These data suggest that the saccade-triggered evoked potential components generally are insensitive to task differences within the visual modality when visual configuration and eye movement parameters are controlled.

Adult↗

PubMed1998

Pointing errors reflect biases in the perception of the initial hand position.

By comparing the visuomotor performance of 10 adult, normal subjects in three tasks, we investigated whether errors in pointing movements reflect biased estimations of the hand starting position. In a manual pointing task with no visual feedback, subjects aimed at 48 targets spaced regularly around two starting positions. Nine subjects exhibited a similar pattern of systematic errors across targets, i.e., a parallel shift of the end points that accounted, on average, for 49% of the total variability. The direction of the shift depended on the starting location. Systematic errors decreased dramatically in the second condition where subjects were allowed to see their hand before movement onset. The third task was to use a joystick held by the left hand to estimate the location of their (unseen) right hand. The systematic perceptual errors in this condition were found to be highly correlated with the motor errors in the first condition. The results support the following conclusions. 1) Kinesthetic estimation of hand position may be consistently biased. Some of the mechanisms responsible for these biases are always active, irrespective of whether position is estimated overtly (e.g., with a matching paradigm), or covertly as part of the motor planning for aimed movements. 2) Pointing errors reflect to a significant extent the erroneous estimation of initial hand position. This suggests that aimed hand movements are planned vectorially, i.e., in terms of distance and direction, rather than in terms of absolute position in space.

Adult↗

PubMed2006

[Significance of the cognitive context in formation of unconscious visual sets].

The experimental evidence that the cognitive set shifting in healthy humans depends on the context of cognitive performance is discussed. Lability/rigidity of the experimentally formed unconscious visual set is largely determined by the type of additional task ("what?" or "where?", i. e., stimulus recognition or spatial localization, respectively) introduced into the context of the experiment. It is suggested that the acquired set more readily shifts to a new one more adequate to modified conditions in case of alternation of the ventral and dorsal visual pathways involved in the information processing in the context of cognitive performance.

Brain↗

PubMed2002

Cognitive enhancing effects of modafinil in healthy volunteers.

RATIONALE: Modafinil, a novel wake-promoting agent, has been shown to have a similar clinical profile to that of conventional stimulants such as methylphenidate. We were therefore interested in assessing whether modafinil, with its unique pharmacological mode of action, might offer similar potential as a cognitive enhancer, without the side effects commonly experienced with amphetamine-like drugs. OBJECTIVES: The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests. METHODS: Sixty healthy young adult male volunteers received either a single oral dose of placebo, or 100 mg or 200 mg modafinil prior to performing a variety of tasks designed to test memory and attention. A randomised double-blind, between-subjects design was used. RESULTS: Modafinil significantly enhanced performance on tests of digit span, visual pattern recognition memory, spatial planning and stop-signal reaction time. These performance improvements were complemented by a slowing in latency on three tests: delayed matching to sample, a decision-making task and the spatial planning task. Subjects reported feeling more alert, attentive and energetic on drug. The effects were not clearly dose dependent, except for those seen with the stop-signal paradigm. In contrast to previous findings with methylphenidate, there were no significant effects of drug on spatial memory span, spatial working memory, rapid visual information processing or attentional set-shifting. Additionally, no effects on paired associates learning were identified. CONCLUSIONS: These data indicate that modafinil selectively improves neuropsychological task performance. This improvement may be attributable to an enhanced ability to inhibit pre-potent responses. This effect appears to reduce impulsive responding, suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder.

Adult↗

PubMed2001

The emergence of coherence over the course of decision making.

Previous research has indicated that decision making is accompanied by an increase in the coherence of assessments of the factors related to the decision alternatives. In the present study, the authors investigated whether this coherence shift is obtained before people commit to a decision, and whether it is obtained in the course of a number of other processing tasks. College students were presented with a complex legal case involving multiple conflicting arguments. Participants rated agreement with the individual arguments in isolation before seeing the case and after processing it under various initial sets, including playing the role of a judge assigned to decide the case. Coherence shifts were observed when participants were instructed to delay making the decision (Experiment 1), to memorize the case (Experiment 2), and to comprehend the case (Experiment 3). The findings support the hypothesis that a coherence-generating mechanism operates in a variety of processing tasks, including decision making.

Adult↗

PubMed2006

Association between two distinct executive tasks in schizophrenia: a functional transcranial Doppler sonography study.

BACKGROUND: Schizophrenia is a severe mental disorder involving impairments in executive functioning, which are important cognitive processes that can be assessed by planning tasks such as the Stockings of Cambridge (SOC), and tasks of rule learning/abstraction such as the Wisconsin Card Sorting Test (WCST). We undertook this study to investigate the association between performance during separate phases of SOC and WCST, including mean cerebral blood flow velocity (MFV) measurements in chronic schizophrenia. METHODS: Functional transcranial Doppler sonography (fTCD) was used to assess bilateral MFV changes in the middle (MCA) and anterior (ACA) cerebral arteries. Twenty-two patients with chronic schizophrenia and 20 healthy subjects with similar sociodemographic characteristics performed SOC and WCST during fTCD measurements of the MCA and the ACA. The SOC was varied in terms of easy and difficult problems, and also in terms of separate phases, namely mental planning and movement execution. The WCST performance was assessed separately for maintaining set and set shifting. This allowed us to examine the impact of problem difficulty and the impact of separate phases of a planning task on distinct intervals of WCST. Simultaneous registration of MFV was carried out to investigate the linkage of brain perfusion during the tasks. RESULTS: In patients, slowing of movement execution during easy problems (SOC) was associated with slowing during maintaining set (WCST) (P < 0.01). In healthy subjects, faster planning and movement execution during predominantly difficult problems were associated with increased performance of WCST during set shifting (P < 0.01). In the MCA, patients showed a significant and positive correlation of MFV between movement execution and WCST (P < 0.01). CONCLUSION: The results of this study demonstrate performance and brain perfusion abnormalities in the association pattern of two different tasks of executive functioning in schizophrenia, and they support the notion that executive functions have a pathological functional correlate predominantly in the lateral hemispheres of the brain. This study also underpins the scientific potential of fTCD in assessing brain perfusion in patients with schizophrenia.

Adult↗