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Effects of d-amphetamine on the performance of rats in an animal analogue of the A-X continuous performance test.

Schizophrenia patients subjected to the A-X Continuous Performance Test (A-X CPT) show cognitive deficits that are thought to reflect impaired representation and maintenance of context information. An issue deserving attention is to what extent the acute amphetamine model of schizophrenia also models these cognitive deficits. The present experiment examined the effect of acute d-amphetamine (AMP) on the performance of rats in an animal analogue of the A-X CPT. Subjects first learned to solve an A --> X+, B --> X-, A --> Y- discrimination task, with A and B representing visual features; X and Y designating auditory target stimuli; --> signifying a serial presentation; and + and - referring to food reinforcement and non-reinforcement, respectively. Frequency of food-magazine visits was the dependent measure. After mastering the discrimination, rats received test trials under either saline or 0.5 mg/kg AMP (s.c.). At test, the interval between feature and target presentation was varied; reinforcement contingencies were maintained. AMP significantly impaired performance on the A --> X+/B --> X- discrimination by increasing the response level on B --> X- trials. AMP did not significantly affect performance on the A --> X+/A --> Y- discrimination. However, AMP also increased magazine responding in the absence of the presentation of features and targets. A parsimonious conclusion based on these preliminary results is that acute AMP does not affect processing of context information provided by the visual features in this procedure. It rather has a more non-specific response-enhancing effect, especially with respect to stimuli associated with the delivery of food.

Animals↗

Effect of valproate on cognitive functioning. Comparison with carbamazepine. The Department of Veterans Affairs Epilepsy Cooperative Study 264 Group.

OBJECTIVE: To assess the effects of carbamazepine vs valproate sodium on cognitive functioning in patients with epilepsy compared with normal control subjects. DESIGN: Patients with recently diagnosed, previously unmedicated seizures participated in a prospective randomized double-blind Department of Veterans Affairs multicenter study of the efficacy and toxicity of carbamazepine vs valproate. MAIN OUTCOME MEASURE: A behavioral toxicity battery was administered prior to treatment and again 6 and 12 months after the initiation of antiepileptic medication. RESULTS: There were no significant differences in the effect of carbamazepine vs valproate on motor speed and coordination, memory, or concentration and mental flexibility, and there was no significant decline in neuropsychological performance from pretreatment baseline levels for either drug. No significant differences in performance were found between patients with low (mean, 52.8 micrograms/mL) vs high (mean, 94.4 micrograms/mL) serum valproate levels within the therapeutic range. Patients treated with either carbamazepine or valproate did not show practice effects experienced by normal controls, a finding that may reflect a subtle compromise in cognitive functioning. CONCLUSION: The impact of carbamazepine and valproate monotherapy on cognitive functioning is similar: both drugs produce minimal negative effects compared with pretreatment baseline performance.

Adult↗

Human oscillatory brain activity near 40 Hz coexists with cognitive temporal binding.

Spontaneous oscillatory electrical activity at a frequency near 40 Hz in the human brain and its reset by sensory stimulation have been proposed to be related to cognitive processing and to the temporal binding of sensory stimuli. These experiments were designed to test this hypothesis and to determine specifically whether the minimal interval required to identify separate auditory stimuli correlates with the reset of the 40-Hz magnetic signal. Auditory clicks were presented at varying times, while magnetic activity was recorded from awake human subjects. Experimental and modeling results indicate a stimulus-interval-dependent response with a critical interval of 12-15 ms. At shorter intervals only one 40-Hz response, to the first stimulus, was observed. With longer intervals, a second 40-Hz wave abruptly appeared, which coincided with the subject's perception of a second distinct auditory stimulus. These results indicate that oscillatory activity near 40 Hz represents a neurophysiological correlate to the temporal processing of auditory stimuli. It also supports the view that 40-Hz activity not only relates to primary sensory processing, but also could reflect the temporal binding underlying cognition.

Adult↗

Emotion-induced changes in human medial prefrontal cortex: I. During cognitive task performance.

Regional cerebral blood flow (BF) was examined in regions of the medial prefrontal cortex (MPFC) with positron-emission tomography while subjects performed two cognitive tasks, reading nouns aloud and generating appropriate verbs for the same nouns. The control task was passive viewing of the same words. BF was reduced in regions of the MPFC during word reading and naive verb generation, relative to a control state in which the subjects passively viewed nouns. Practicing verb generation produced improved performance, as measured by response time, which was strongly correlated with further reductions in MPFC and hypothalamic BF. After practice, when verb generation was performed on a novel list of words, reaction times slowed and the pattern of MPFC BF reverted to that seen in the word reading and naive conditions. A separate behavioral study of the verb-generation task indicated that anxiety, high during naive use-generation as measured by heart rate and self-report, decreased with practice on the task but returned with the introduction of a novel list of words. Taken together, these results suggest that the MPFC is part of a network, including the hypothalamus and brainstem, whose activity reflects a dynamic interplay between cognitive task performance and emotion.

Adult↗

Is the strength of implicit alcohol associations correlated with alcohol-induced heart-rate acceleration?

BACKGROUND: Heart rate (HR) acceleration during the ascending limb of the blood alcohol curve has proven to be a reliable measure of the sensitivity to the activating effects of alcohol. In this study, we investigated the correlation between an ethanol-induced cardiac change and the strength of implicit alcohol-related arousal and approach associations and attentional bias for alcohol-related stimuli in heavy drinkers. These 3 types of implicit alcohol-related cognitions have been proposed to reflect the strength of incentive sensitization that is experienced after repeated alcohol use. METHODS: Forty-eight heavy drinking men performed a modified version of the Implicit Association Test (IAT) to measure their implicit alcohol arousal and approach-avoidance associations. A modified version of the emotional Stroop was used to measure attentional bias for alcohol-related stimuli (blocked and unblocked). Next, a high dose of alcohol (1.0 mL/kg body weight 95% USP alcohol) was administered in a short period of time. Resting baseline HR, blood alcohol concentrations, mood, and craving for alcohol were assessed before alcohol administration and for 2 hours post-alcohol consumption. RESULTS: Contrary to our hypothesis, a negative association was found between implicit arousal associations and alcohol-induced HR change. This indicates that strong arousal associations were correlated with a decrease in alcohol-induced HR. Approach associations and attentional bias were not correlated with alcohol-induced HR change, but both were correlated positively with each other. CONCLUSIONS: Alcohol-arousal associations and other implicit cognitions (attentional bias, approach associations) are not positively related to individual differences in the sensitivity to alcohol's activating effects, at least not in the present sample consisting primarily of family history-negative heavy drinkers.

Adolescent↗

[The effect of L-threo-DOPS on P-300 in parkinsonism].

The P-300 has been recently utilized as an objective electrophysiological index of cognitive function in some neurological disease. Hansch et al first described prolonged latency for the P-300 component in Parkinson disease patients and suggested these measures reflects a common, disrupted aspect of cognitive function in this disease. This cognitive disorder may be caused not only from the dysfunction of dopaminergic system but from non-dopaminergic lesions such as norepinephrine ones. On the other hand, L-threo-DOPS, a non-physiological precursor of norepinephrine, has been used for the treatment of some neurological illness such as the freezing phenomenon in Parkinsonism. In the present study we investigate the effect of L-threo-DOPS on cognitive function in Parkinsonism by measuring P-300 component succeedingly. Twenty-four patients, i.e. 19 cases of Parkinson disease (PD), 3 Juvenile Parkinsonism (JP) and 2 cerebrovascular Parkinsonism, are studied. The latencies of P-300 are significantly shortened after treatment of DOPS compared with those of the previous treatment and placebo administration respectively (p less than 0.05, p less than 0.01). The main factors which have influence upon these shortened latencies are analyzed multivariate analysis. The factor analysis and principal component analysis suggest three main factors such as DOPS, age (onset of age), and duration of illness. The patients' groups are divided into three by cluster analysis. The most effective group mainly consists of JP. The least effective one mainly consists of older, long-duration Parkinson disease patients. And there is another group which consists of younger, short-duration PD cases with moderate effect of DOPS. This tendency seems to suggest the different pathological findings between JP and PD. It is postulated that L-threo-DOPS would raise the level of attention and arousal mediated by norepinephrine neuronal system which may improve the cognitive disorder in Parkinsonism.

Aged↗

Effect of acute tryptophan depletion on pre-frontal engagement.

BACKGROUND: Serotonin is known to modulate cognitive functioning and has been implicated in the cognitive deficits associated with affective disorders. The present study examined regional brain activation during two tasks that are known to engage the pre-frontal cortex and are performed poorly by patients with depression and bipolar disorder. We tested the hypothesis that acute tryptophan depletion (ATD) would attenuate pre-frontal activation during both tasks. MATERIALS AND METHODS: Ten healthy right-handed volunteers were studied using functional MRI whilst performing a 2-back verbal working memory task and a phonological verbal fluency task. Subjects were studied in two separate sessions, after either a tryptophan-free or a balanced amino acid drink, in a double-blind design. Task performance and mood were measured online. RESULTS: Relative to sham depletion, ATD attenuated activation in the right superior frontal gyrus during the 2-back task and in the medial frontal gyrus and precuneus during the verbal fluency task. ATD lowered total plasma tryptophan by 79% but had no significant effect on either task performance or mood. CONCLUSIONS: The engagement of pre-frontal cortex during verbal working memory and verbal fluency tasks is significantly modulated by central serotonergic activity. The different location of these modulatory effects within the frontal cortex may reflect the engagement of distinct cognitive processes by the respective tasks.

Administration, Oral↗

Hemispheric asymmetry reduction in older adults: the HAROLD model.

A model of the effects of aging on brain activity during cognitive performance is introduced. The model is called HAROLD (hemispheric asymmetry reduction in older adults), and it states that, under similar circumstances, prefrontal activity during cognitive performances tends to be less lateralized in older adults than in younger adults. The model is supported by functional neuroimaging and other evidence in the domains of episodic memory, semantic memory, working memory, perception, and inhibitory control. Age-related hemispheric asymmetry reductions may have a compensatory function or they may reflect a dedifferentiation process. They may have a cognitive or neural origin, and they may reflect regional or network mechanisms. The HAROLD model is a cognitive neuroscience model that integrates ideas and findings from psychology and neuroscience of aging.

Aged↗

Overactive action monitoring in obsessive-compulsive disorder: evidence from functional magnetic resonance imaging.

The anterior cingulate cortex (ACC) in patients with obsessive-compulsive disorder (OCD) has been found to be hyperactive at rest, during symptom provocation, and after commission of errors in cognitive tasks. This hyperactivity might reflect an abnormality in conflict detection, a hypothesized basic mechanism for the action-monitoring function of the ACC. This hypothesis was tested using functional magnetic resonance imaging, by scanning 11 OCD patients and 13 matched control subjects while they performed a version of the continuous-performance task with four trial types that induced graded levels of response conflict. Although a behavioral index of conflict (i.e., accuracy) was similar for patients and control subjects, the ACC activation was increased in patients during high-conflict trials. The error-related activity in the same brain region was also higher in patients, consistent with previous electrophysiological findings. Both conflict- and error-related activity showed trends for positive correlations with severity of OCD symptoms, but not with anxiety. These findings suggest that as part of an overactive action-monitoring system, the ACC is more directly involved in the pathophysiology of OCD than previously thought.

Adult↗

Cognition after coronary artery surgery is not related to postoperative jugular bulb oxyhemoglobin desaturation.

During the early postoperative period after coronary artery bypass grafting (CABG) surgery, many patients experience jugular bulb oxyhemoglobin desaturation (SjO(2) < 50%). We sought to determine whether SjO(2) during cardiopulmonary bypass and the early postoperative period influenced long-term cognitive performance after CABG surgery. One hundred two patients completed a battery of cognitive tests the day before and 3 mo after CABG surgery. A General Cognitive Score was generated from these tests as an overall measure of cognitive function. Intraoperatively, SjO(2) was determined by intermittent blood sampling, and postoperatively, the area under the curve of SjO(2) < 50% and time was calculated from continuous reflectance oximetry. No significant correlations between cognitive performance and either intra- or postoperative SjO(2) were found. Preoperative cognitive performance was the main determinant of cognition at 3 mo (r(2) = 0.83, P<0.001), and palpable atheroma of the ascending aorta made a small, but significant, contribution to a decline in cognition (r(2) = 0.018, P = 0.001).

Aged↗

[Impulsiveness and impulse control. On the psychological and psychopathological conceptualization].

Impulsiveness and impaired impulse control are connected with an increasing number of psychic disorders. While impulsiveness presents an enduring, pervasive predisposition of personality, the DSM-IV category of "impulse control disorder not elsewhere classified" is operationalized by specific dysfunctional behaviors. So far, the construction of impulsiveness has really not been sufficiently clarified. What does it means and how can one describes it. Different means of conceptualization are presented from a psychological and psychopathological point of view. Their critical review leads to the hypothesis that impulsiveness subsumes a specific quality of drive, on the one hand, which is closely related to a person's temperament and control mechanisms on the other. Drive and impulse control represent enduring traits that act on all levels of personality function, including behavior, cognitive processing and affect regulation. Finally, a model of impulsiveness is suggested that reflects the close interactions among drive, affect and cognition in the regulation of behavior.

Disruptive, Impulse Control, and Conduct Disorders↗

Cognitive dysfunction in multiple sclerosis: a review of recent developments.

PURPOSE OF REVIEW: Nearly half of all patients diagnosed with multiple sclerosis will develop cognitive dysfunction, a symptom associated with significant decline in activities of daily living. The purpose of this review is to discuss recent literature investigating issues related to cognitive dysfunction in multiple sclerosis. RECENT FINDINGS: Recent studies, examined in this review, have provided increased understanding regarding specific cognitive processes affected in multiple sclerosis, as well as a characterization of its natural history. Studies have also continued to emphasize the extent to which cognitive deficits in the condition are associated with decline in daily living skills. Recent concerns regarding driving performance have been documented among cognitively impaired individuals. Studies have also examined correlates of cognitive dysfunction, with particular emphasis on neuroimaging techniques reflecting disease activity or lesion burden. With increased understanding of neurobiological correlates of cognitive deficits, investigators have begun to examine potential treatments for managing cognitive dysfunction. SUMMARY: This area of research has suggested that disease modifying medications can have an impact on magnetic resonance imaging disease activity by altering the cerebral demyelinating process resulting in a slower decline in cognitive functions over time and improved activities of daily living for patients with multiple sclerosis.

Activities of Daily Living↗

Executive functioning as a potential mediator of age-related cognitive decline in normal adults.

Critical requirements for the hypothesis that executive functioning is a potential mediator of age-related effects on cognitive functioning are that variables assumed to reflect executive functioning represent a distinct construct and that age-related effects on other types of cognitive functioning are reduced when measures of executive functioning are statistically controlled. These issues were investigated in a study involving 261 adults between 18 and 84 years of age. Although age-related effects on various cognitive abilities were substantially reduced after statistical control of the variance in measures hypothesized to represent executive functioning, there was only weak evidence for the existence of distinct constructs corresponding to executive functioning or to aspects of executive control concerned with inhibition, updating, or time sharing.

Adolescent↗

Neuroanatomical evidence for distinct cognitive and affective components of self.

This study examines whether the cognitive and affective components of self-reflection can be dissociated using functional magnetic resonance imaging. Using a simple paradigm in which subjects judged the personal relevance of personality characteristics that were either favorable (e.g., "honest") or unfavorable (e.g., "lazy", we found that distinct neural circuits in adjacent regions of the prefrontal cortex subserve cognitive and emotional aspects of self-reflection. The medial prefrontal cortex responded only to material that was self-descriptive, and this did not differ as a function of the valence of the trait. When material was judged to be self-relevant, the valence of the material was resolved in an adjacent region of ventral anterior cingulate. The nature of self is one of the most enduring questions in science, and researchers are now beginning to be able to decompose the neural operations that give rise to a unitary sense of self.

Adolescent↗

Compensatory recruitment of neural resources during overt rehearsal of word lists in Alzheimer's disease.

Functional neuroanatomical correlates subserving maintenance rehearsal relative to a reading control task were investigated with positron emission tomography imaging of cerebral blood flow in 6 healthy older participants and 6 patients with mild Alzheimer's disease (AD). Rehearsal and reading rates and number of unique words rehearsed did not differ significantly for the 2 groups. The right dorsolateral prefrontal cortex was activated in both groups during rehearsal, highlighting this region's role in short-term maintenance of verbal information. A shift in cortical processing resources to more anterior brain regions with increased rehearsal list length was seen, likely reflecting greater demands on frontal cortex as cognitive load grows. Whereas controls showed unilateral right frontal activation during rehearsal, AD patients demonstrated bilateral frontal activation, possibly reflecting compensatory recruitment of neural resources.

Adaptation, Physiological↗

Effects of white matter lesions and lacunes on cortical function.

BACKGROUND: Subcortical ischemic vascular dementia has been ascribed to prominent frontal lobe dysfunction secondary to ischemic lesions in frontothalamic circuits. Whether small-vessel disease in fact predominantly affects the frontal lobes is not well documented. OBJECTIVE: To investigate the effects of subcortical lesions (lacunes and white matter lesions [WML]) on cortical function, as reflected in glucose metabolism and cognitive function, in elderly individuals. DESIGN: Cross-sectional analyses of case series. SETTING: Multicenter, university-based study of subcortical vascular dementia. PATIENTS: Persons with normal cognition, mild cognitive impairment, or dementia and with and without lacunes on magnetic resonance images. MAIN OUTCOME MEASURES: Regional cerebral glucose metabolism, normalized regional metabolic activity, and neuropsychological test scores. Major hypotheses were that volume of lacunes and WML correlate selectively with hypometabolism of prefrontal cortex and failure of executive cognitive ability. RESULTS: Lacunes correlated with metabolic rates in dorsolateral frontal cortex (DLF); WML substantially reduced metabolic rates throughout cortex, most strongly so in DLF. When regional metabolic activity was normalized to whole brain activity, lacunes remained correlated with DLF activity, whereas the WML effect was no longer found, probably because of its general distribution. Regional cerebral glucose metabolism and normalized activity in DLF also correlated with cortical atrophy. Metabolic activity in DLF correlated with executive function, memory, and global cognitive function, while activity in middle temporal gyrus correlated with memory and global function but not executive function. CONCLUSIONS: The metabolic effects of lacunes and WML are most apparent in DLF, but the effects of WML are generalized and frontal hypometabolism correlates with memory and global impairment, cognitive as well as executive function. The effects of subcortical cerebrovascular disease appear to converge on the frontal lobes but are diffuse, complex, and of modest magnitude.

Aged↗

Should we continue teaching anatomy by dissection when ...?

The central role that human dissection has long held in clinical education is being reevaluated in many institutions. Despite the impression that many institutions are abandoning dissection, very few have and most of those have reinstated dissection within a few years. What are the inherent qualities that lead institutions back to dissection? In our efforts to redesign a shortened dissection course, our consultations with a broad range of clinicians lead us to understand how the rhythms of clinical practice are modeled and developed in the small-group setting of the dissection laboratory. Following further consultation with colleagues who have experimented with different models of anatomy instruction, we discuss three themes in support of dissection. First, problem-solving in the dissection laboratory develops the habits-of-mind of clinical practice. Second, relating dissection to imaging modalities develops the spatial reasoning skills needed to understand computer simulations, interpret imaging data, and interact with surgeons, radiologists, and patients. Third, the human face of dissection fosters self-reflection and integration of the cognitive and affective skills required for medical practice. Through group process, the collaborative effort of dissection teams develops essential of attributes of clinical professionalism.

Anatomy↗

Children's narratives following traumatic brain injury: linguistic structure, cohesion, and thematic recall.

Narrative discourse and intellectual functioning were examined 3 years following traumatic brain injury (TBI) in children 1 to 8 years of age at the time of injury. The language-impaired TBI group (n = 9) had language deficits during the subacute stage of recovery; their performance was contrasted with that of a TBI comparison group equated on neurologic and demographic variables that did not show subacute language impairment (n = 8) and a sibling comparison group (n = 9). The language-impaired TBI group had lower Verbal and Full-Scale IQ scores and produced fewer words and utterances than the sibling group on a story retelling task; their stories were characterized by fewer complete referential and lexical ties and more referential errors, indicating difficulty conjoining meaning across sentences. The language-impaired TBI group recalled approximately one-third of the propositions needed to maintain the story theme and made more errors sequencing the propositions than either the TBI or the sibling comparison groups. Group differences were not obtained on the Performance IQ scores or on measures of rate or fluency of speech production, mazes, use of conjunctives, or naming errors. The discourse deficiencies of children with TBI and acute language impairment were most pronounced at the level of cognitive organization of the text reflecting text macrostructure and were least apparent at the level of lexical and sentential organization reflecting text microstructure. Results are discussed in terms of the vulnerability of developing language abilities to disruption by brain injury.

Brain Injuries↗