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PubMed2005

Task sets under reconstruction: effects of partially incorrect precues.

To perform a task that differs from a previously performed one, it is necessary to prepare for the new task as well as to disable the task set of the preceding task. In a series of three experiments we examined whether preparation for a task shift implies a direct update of the task set that is carried over from the preceding trial. To this end, in Experiments 1 and 2 we factorially varied the relation of the task in trial n, first, to the task in trial n - 1 (intertask relation) and, second, to the task that was precued for trial n (precue-to-task relation). Invalid precues resulted in substantial costs, which increased with longer precueing intervals. However, this increasing effect of the precue-to-task relation was not accompanied by a decreasing effect of the intertask relation. Furthermore, both effects had different qualitative properties. These findings suggest that two tasks can be represented concurrently but on two different levels of representation. In Experiment 3 we observed that the persistence of the effect of the intertask relation depends on the possibility that task repetitions can occur in trials in which a task shift is precued. This suggests that the persistence of the effect of the intertask relation is controlled in a context-sensitive way.

Adolescent↗
PubMed2002

Relationship between attentional performance and corpus callosum morphometry in patients with Alzheimer's disease.

There has been considerable interest in cognitive deficits associated with Alzheimer's disease (AD) and relationships between these impairments and specific cortical atrophies. Two previous studies [Neuropsychologia 28 (1990) 1197; Dementia 3 (1992) 350] have found that AD patients exhibit significant impairments in the attentional ID/ED set-shifting tasks of the CANTAB battery which involved attentional shifting abilities. But, at present, no study has examined the neural bases of these abilities in AD patients. In the present study, the relationship between performances on this attentional test and morphometry of the anterior and posterior corpus callosum is examined in AD patients in the mild to moderate stages of the disease (n=30, mean age=74.1+/-4.9 years, mean MMSE score=23.9+/-2.6). A control group is constituted (n=20, mean age=73.15+/-5.5 years) for comparison of cerebral measurements. The stepwise multiple regression analysis indicates that the relative contribution for the total callosal and the anterior CC areas of the simple discrimination subtest is significantly positive whereas for the posterior callosal areas the relative contribution of the more complex subtest is significantly positive. AD patients from the subgroup "low", who failed to do the nine subtests of the attentional set-shifting tasks, exhibit smaller callosal areas than control subjects. There is no significant difference for all callosal measurements between AD patients from the subgroup "high", who completely succeeded the test, and control subjects. Our findings suggest that the anterior corpus callosum would be related to attentional shifting abilities in AD patients. Moreover, these patients with probable AD seem heterogeneous for performances in the attentional test of the CANTAB and for callosal atrophies.

Aged↗
PubMed2006

Gestational methylazoxymethanol acetate treatment impairs select cognitive functions: parallels to schizophrenia.

Gestational methylazoxymethanol acetate (MAM) exposure has been suggested to produce neural and behavioral abnormalities similar to those seen in schizophrenia. In order to assess MAM treatment as a model of schizophrenia, pregnant female rats were injected with MAM (22 mg/kg) on gestational day 17 and their offspring were assessed in adulthood on a series of cognitive tasks. The first experiment involved an attentional set-shifting task, a rodent analog of the Wisconsin card sort task. In experiment 2, animals were tested on the 5-choice serial reaction time task, a rodent analog of the continuous performance task. In the final experiment animals were assessed on a differential reinforcement of low rate of responding 20 s schedule of reinforcement (DRL-20), a task that is sensitive to changes in inhibitory control. In the first experiment, MAM-treated animals required a greater number of trials than controls to successfully learn an extradimensional shift on the set-shifting task, and had difficulties in learning to reverse a previously acquired discrimination. In contrast, MAM-treated animals showed little impairment on the 5-choice task, aside from a modest but consistent increase in premature responding. Finally, MAM exposed animals showed substantial impairments in DRL performance. Post-mortem analysis of brain tissue showed significant decreases in tissue weight in the hippocampus, parietal cortex, prefrontal cortex, and dorsal striatum of MAM-treated animals. These results support the notion that MAM treatment may simulate some aspects of schizophrenic cognition.

Animals↗
PubMed2001

High levels of estradiol disrupt conditioned place preference learning, stimulus response learning and reference memory but have limited effects on working memory.

The present study investigated the effects of high levels of estradiol in female rats on four different radial arm maze tasks: the hippocampus-dependent spatial working-reference memory task; the prefrontal cortex-hippocampus dependent delayed win-shift task; the striatum-dependent cued win-stay task; and the amygdala-dependent conditioned place preference task. Ovariectomized female rats were injected daily with either 10 microg of estradiol benzoate or sesame oil vehicle approximately 4 h prior to testing. In Experiment 1, treatment with estradiol disrupted learning on the spatial working-reference memory task by increasing the number of reference memory errors to reach criterion. In Experiment 2, treatment with estradiol had no significant effect on the delayed win-shift task. In Experiment 3, treatment with estradiol resulted in impaired performance on a striatum-dependent cued win-stay task. In Experiment 4, treatment with estradiol impaired the acquisition of a conditioned place-preference task. Taken together these findings suggest that high levels of estradiol inhibit reference memory, stimulus response learning, and amygdala-dependent appetitive conditioning while having little effect on working memory.

Amygdala↗
PubMed1994

Attention and control deficits following closed head injury.

This study was aimed at identifying the impaired attentional components in patients who had sustained a severe CHI several years before. A group of 14 CHI patients and a Control group (matched for age, sex and education) were tested. Experiment 1 used a dual-task paradigm (Umiltà et al., 1992). The double task-single task difference was greater for the CHI group, indicating a specific damage at a central executive stage where decision are made and responses are coordinated. Experiment 2 used a task-shifting paradigm (Morra and Roncato, 1986). The cost of shifting from one task to the other was greater for the CHI group, but only in the Short Series Condition where a new task-program could be pre-activated. Experiment 3 studied visual selective attention using Navon paradigm (1977); in this case, there was no difference between patients and controls.

Adult↗
PubMed2006

Impairment of executive functions in boys with attention deficit/hyperactivity disorder.

The main aim of the present study is to compare the efficiency of executive control processes in 24 boys with attention deficit/hyperactivity disorder (ADHD) and 58 normal controls of similar age (between 8 and 11 years). Three reaction time (RT) paradigms were utilized: a dual task that requires coordination of two tasks responses, a shift task that makes it necessary to disengage attention from one task and engage into another one, and a stimulus-response spatial compatibility task that requires participants to inhibit a prepotent response. Another purpose of the study is to examine whether Barkley's (1997) executive dysfunction or Sergeant et al.'s (1999) resource allocation/arousal model best account for the behavioral deficits associated with ADHD. Examination of raw RT data showed significantly poorer performance in ADHD children with respect to age-matched controls on both the higher-level cognitive functions of executive control and on lower-level abilities (e.g., speed of processing) of all tasks of this study. However, using proportional transformations of raw RT data, we could demonstrate that, in addition to differences in processing speed, also executive control processes were significantly impaired in children with ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

A dissociation in attentional control: evidence from methamphetamine dependence.

BACKGROUND: Selective attention comprises multiple, dissociable component processes, including task shifting and selective inhibition. The goal of this study was to test whether task-shifting, selective inhibition, or both processes were impaired in long-term but currently abstinent methamphetamine-dependent individuals. METHODS: Participants were 34 methamphetamine-dependent subjects and 20 nonsubstance abusing controls who were tested on an alternating-runs switch task with conflict sequences that required subjects to switch tasks on every second trial (AABBAABB). RESULTS: Methamphetamine-dependent individuals committed more errors on trials that required inhibition of distracting information compared with controls (methamphetamine = 17%; controls = 13%; p = .02). By contrast, error rates did not differ between the groups on switch trials (methamphetamine = 7%; controls = 6%; p = .68). CONCLUSIONS: These results indicate that selective inhibition, but not task switching, is selectively compromised by methamphetamine.

Adult↗
PubMed2005

Impairment in perceptual attentional set-shifting following PCP administration: a rodent model of set-shifting deficits in schizophrenia.

RATIONALE: Impaired ability to shift perceptual attentional set forms a core feature of schizophrenic illness and is associated with prefrontal cortical dysfunction. A pharmacological model producing equivalent deficits in rodents may enable the development of novel therapeutic strategies for effective treatment of cognitive impairments in schizophrenia. OBJECTIVE: This study was designed to investigate the effects of phencyclidine (PCP) administration on performance in a rodent attentional set-shifting task and the neural correlates of PCP-induced deficits in task performance. METHODS: Twenty-four hours following acute administration of 2.58 mg/kg PCP or vehicle, rats were tested on a perceptual attentional set shifting task (Birrell and Brown in J Neurosci 20:4320-4324, 2000). Following completion of the task, in situ hybridisation was employed to detect concurrent regional alterations in zif-268 and parvalbumin mRNA expression. RESULTS: PCP administration selectively decreased the ability of rats to shift attentional set between perceptual dimensions (extra-dimensional shift, EDS). This impairment was accompanied by, and correlated with, decreases in expression of zif-286 in the infralimbic cortex and of parvalbumin in the dorsal reticular nucleus of the thalamus. CONCLUSION: Acute administration of PCP produces deficits in perceptual set shifting comparable to an aspect of executive dysfunction in schizophrenia. Moreover, this impairment is associated with altered medial prefrontal cortical and reticular thalamic activity. Therefore, this rodent paradigm may model the set-shifting deficits that form a core feature of schizophrenic pathology.

Animals↗
PubMed1993

A triple dissociation of memory systems: hippocampus, amygdala, and dorsal striatum.

This study investigated the respective roles of the hippocampus, the amygdala, and the dorsal striatum in learning and memory. A standard set of experimental conditions for studying the effects of lesions to the three brain areas using an 8-arm radial maze was used: a win-shift version, a conditioned cue preference (CCP) version, and a win-stay version. Damage to the hippocampal system impaired acquisition of the win-shift task but not the CCP or win-stay tasks. Damage to the lateral amygdala impaired acquisition of the CCP task but not the win-shift or win-stay tasks. Damage to the dorsal striatum impaired acquisition of the win-stay task but not the win-shift or CCP tasks. These results are consistent with the hypothesis that the mammalian brain may be capable of acquiring different kinds of information with different, more-or-less independent neural systems. A neural system that includes the hippocampus may acquire information about the relationships among stimuli and events. A neural system that includes the amygdala may mediate the rapid acquisition of behaviors based on biologically significant events with affective properties. A neural system that includes the dorsal striatum may mediate the formation of reinforced stimulus-response associations.

Amygdala↗
PubMed2004

Performance on Cambridge Neuropsychological Test Automated Battery subtests sensitive to frontal lobe function in people with autistic disorder: evidence from the Collaborative Programs of Excellence in Autism network.

Recent structural and functional imaging work, as well as neuropathology and neuropsychology studies, provide strong empirical support for the involvement of frontal cortex in autism. The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a computer-administered set of neuropsychological tests developed to examine specific components of cognition. Previous studies document the role of frontal cortex in performance of two CANTAB subtests: the Stockings of Cambridge, a planning task, and the Intradimensional/Extradimensional Shift task, a measure of cognitive set shifting. To examine the integrity of frontal functions, these subtests were administered to 79 participants with autism and 70 typical controls recruited from seven universities who are part of the Collaborative Programs of Excellence in Autism network. The two groups were matched on age, sex, and full-scale IQ. Significant group differences were found in performance on both subtests, with the autism group showing deficits in planning efficiency and extradimensional shifting relative to controls. Deficits were found in both lower- and higher-IQ individuals with autism across the age range of 6 to 47 years. Impairment on the CANTAB executive function subtests did not predict autism severity or specific autism symptoms (as measured by the ADI-R and ADOS), but it was correlated with adaptive behavior. If these CANTAB subtests do indeed measure prefrontal function, as suggested by previous research with animals and lesion patients, this adds to the accumulating evidence of frontal involvement in autism and indicates that this brain region should remain an active area of investigation.

Adolescent↗
PubMed2005

Impairment of executive function but not memory in first-degree relatives of patients with bipolar I disorder and in euthymic patients with unipolar depression.

OBJECTIVE: The authors' goal was to characterize cognitive flexibility and verbal learning in relatives of patients with bipolar disorder and in euthymic patients with recurrent major depression. METHOD: The intradimensional/extradimensional shift task and California Verbal Learning Test were administered to 27 first-degree relatives of probands with bipolar I disorder, 15 euthymic outpatients with recurrent unipolar depression, and 47 healthy comparison subjects. RESULTS: The relatives of patients with bipolar I disorder and the euthymic patients with unipolar depression were more likely to fail the intradimensional/extradimensional shift task than the healthy comparison subjects. The impairments at the extradimensional shift stage were pronounced. Verbal learning, delayed recall, and recognition were unimpaired in all groups. CONCLUSIONS: Attentional set shifting may represent an endophenotype in mood disorder, related to underlying vulnerability rather than the actual disease phenotype.

Adolescent↗
PubMed2006

The role of the rat prelimbic/infralimbic cortex in working memory: not involved in the short-term maintenance but in monitoring and processing functions.

Contrary to human and primate, working memory in the rodent is usually considered as a simple short term memory buffer and mainly investigated using delayed response paradigms. The aim of the present study was to further investigate the role of the rat prelimbic/infralimbic cortex in different spatial delayed tasks in order to dissociate its involvement in temporary storage from other information processes, such as behavioral flexibility and attention. In experiment 1 rats were trained in a standard elimination win-shift task in a radial-arm maze after which a 1-min delay was inserted mid trial. Prelimbic/infralimbic lesions induced only a transient disruption of performance following introduction of the delay. In experiment 2, rats were trained directly in a win-shift task with a 5-min delay that was subsequently extended to 30 min. Prelimbic/infralimbic lesions did not significantly affect behavior. Nevertheless, transient disruptions of performance (correlated with lesion extent) were noted repeatedly in lesioned rats when sets of interfering events were presented. The present findings indicate that prelimbic/infralimbic cortex is not directly involved in the short term maintenance of specific information but is implicated when changes, such as sudden introduction of a delay or exposure to unexpected interfering events, alter the initial situation. It appears that working memory in rodents should be considered, as in humans and primates, to encompass both storage and monitoring functions. The present results along with previous ones strongly suggest that prelimbic/infralimbic cortex is not involved in the temporary on-line storage but rather in the control of information required to prospectively organize the ongoing action.

Animals↗
PubMed1999

Emotional bias and inhibitory control processes in mania and depression.

BACKGROUND: Despite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. The disinhibited behaviour characteristic of mania and evidence that subgenual prefrontal cortex is differentially activated in mania and depression both suggest that dissociable deficits will emerge on tasks that require inhibitory control and are subserved by ventromedial prefrontal cortex. METHODS: Manic patients and controls undertook computerized neuropsychological tests of memory and planning ability. In addition, manic and depressed patients were directly compared with controls on a novel affective shifting task that requires inhibitory control over different components of cognitive and emotional processing. RESULTS: Manic patients were impaired on tests of memory and planning. Importantly, affective shifting performance of manic patients differed from that of depressed patients. Manic patients were impaired in their ability to inhibit behavioural responses and focus attention, but depressed patients were impaired in their ability to shift the focus of attention. Depressed patients exhibited an affective bias for negative stimuli, and we believe this to be the first demonstration of an affective bias for positive stimuli in manic patients. CONCLUSIONS: Observed impairments on tests of memory and planning suggest a global pathology for mania consistent with previous profiles for this disorder and similar to established profiles for depression. The results on the affective shifting task demonstrate the presence of mood-congruent bias and dissociable components of inhibitory control in mania and depression. Against a background of memory and planning impairments in the two groups, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood-cognition relationships.

Adult↗
PubMed1999

Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI.

Inhibition of an ongoing reaction tendency for adaptation to changing environments is a major function of the human prefrontal cortex. This function has been investigated frequently using the go/no-go task and set-shifting tasks such as the Wisconsin Card Sorting Test (WCST). Studies in humans and monkeys suggest the involvement of the dorsolateral prefrontal cortex in the two task paradigms. However, it remains unknown where in the dorsolateral prefrontal cortex this function is localized, whether a common inhibitory mechanism is used in these task paradigms and how this inhibitory function acts on two different targets, i.e. the go response in the go/no-go task and the cognitive set in the WCST. In the go/no-go task of this study, subjects were instructed to either respond (go trial) or not respond (no-go trial), depending on the cue stimulus presented. The signals of functional MRI (fMRI) related to the inhibitory function should be transient by nature. Thus, we used the temporal resolution of fMRI (event-related fMRI) by which transient signals in go and no-go trials can be analysed separately and compared with each other. We found a focus that showed transient no-go dominant activity in the posterior part of the inferior frontal sulcus in the right hemisphere. This was true irrespective of whether the subjects used their right or left hands. These results suggest that the transient activation in the right inferior prefrontal area is related to the neural mechanism underlying the response inhibition function. Furthermore, this area was found to be overlapped spatially with the area that was activated transiently during cognitive set shifting in the WCST. The transient signals in the go/no-go task peaked 5 s after the transient expression of the inhibitory function, and the transient signals in the WCST peaked 7s after the transient expression, reflecting different durations of neuronal activity in the two inhibitory task paradigms. These results imply that the right inferior prefrontal area is commonly involved in the inhibition of different targets, i.e. the go response during performance of the go/no-go task and the cognitive set during performance of the WCST.

Adaptation, Physiological↗
PubMed2006

Diffusion tensor imaging of frontal white matter and executive functioning in cocaine-exposed children.

BACKGROUND: Although animal studies have demonstrated frontal white matter and behavioral changes resulting from prenatal cocaine exposure, no human studies have associated neuropsychological deficits in attention and inhibition with brain structure. We used diffusion tensor imaging to investigate frontal white matter integrity and executive functioning in cocaine-exposed children. METHODS: Six direction diffusion tensor images were acquired using a Siemens 3T scanner with a spin-echo echo-planar imaging pulse sequence on right-handed cocaine-exposed (n = 28) and sociodemographically similar non-exposed children (n = 25; mean age: 10.6 years) drawn from a prospective, longitudinal study. Average diffusion and fractional anisotropy were measured in the left and right frontal callosal and frontal projection fibers. Executive functioning was assessed using two well-validated neuropsychological tests (Stroop color-word test and Trail Making Test). RESULTS: Cocaine-exposed children showed significantly higher average diffusion in the left frontal callosal and right frontal projection fibers. Cocaine-exposed children were also significantly slower on a visual-motor set-shifting task with a trend toward lower scores on a verbal inhibition task. Controlling for gender and intelligence, average diffusion in the left frontal callosal fibers was related to prenatal exposure to alcohol and marijuana and an interaction between cocaine and marijuana exposure. Performance on the visual-motor set-shifting task was related to prenatal cocaine exposure and an interaction between cocaine and tobacco exposure. Significant correlations were found between test performance and fractional anisotropy in areas of the frontal white matter. CONCLUSIONS: Prenatal cocaine exposure, alone and in combination with exposure to other drugs, is associated with slightly poorer executive functioning and subtle microstructural changes suggesting less mature development of frontal white matter pathways. The relative contribution of postnatal environmental factors, including characteristics of the caregiving environment and stressors associated with poverty and out-of-home placement, on brain development and behavioral functioning in polydrug-exposed children awaits further research.

Child↗
PubMed1991

Amygdaloid lesions and stimulus-reward associations in the rat.

Rats with amygdaloid lesions were trained on learning set tasks designed to tax stimulus-reward associations. Lesions centred in the medial and ventral half of the amygdala had no effect on the acquisition of two object discriminations but did impair successive reversals of the second discrimination. The same lesions had no effect, however, on the acquisition of a spatial win-stay lose-shift task which taxed one-trial place-reward associations. In a second experiment it was found that lesions in the central and basolateral regions of the amygdala disrupted performance of the same spatial win-stay lose-shift task although, as before, acquisition was unaffected. Taken together these findings support a role for the amygdala in stimulus-reward associations and indicate that it may be particularly important when differing values of reward must be distinguished.

Amygdala↗
PubMed1995

Shifting behavior: an analysis of response patterns of Parkinson patients in discrimination learning.

Parkinson patients often show decreased performance on what is generally referred to as "shift tasks." This does not necessarily imply that Parkinson patients have problems with shifting, since task performance reflects not only shifting but also other factors. Using a discrimination learning task, we analyzed response patterns to determine the decision rules used. As well, we varied the manner of problem alternation (implicit versus explicit) and the type of problem alternation (extradimensional versus intradimensional shifts). In accordance with the literature, we found that Parkinson patients needed more trials to solve the problems. However, the response patterns of the Parkinson patients and controls were practically the same. An important finding was that Parkinson patients did not hold on longer to a rule, which was correct in a former problem, than controls did. Therefore, we concluded that Parkinson patients are able to shift from one decision rule to another.

Adult↗
PubMed2000

Switching attention--additional aspects for the analysis.

Problems related to attentional functions have often been reported within the neurotoxicology of long-term exposure to solvents, but knowledge about neuroanatomical sites involved in this degenerative process is still rare. However, some studies have emphasized the frontal cortex as a region of structural or functional changes in long-term exposed patients or accidental intoxications. Neurobehavioral tests using active switching tasks are widely used to detect frontal lobe dysfunction. Test batteries used in neurotoxicology provide such tasks but standard test interpretations often neglect these aspects. Rotogravure printing workers exclusively exposed to toluene were investigated in a longitudinal study with cross-sectional design. Data from two examination periods are presented. In the first sample 333 male workers were investigated. In the second examination period 278 workers could be retested. The workers differed with respect to level and duration of lifetime exposure to toluene. All subjects completed a neurobehavioral test battery including the task switching attention (EURONES). Different parameters were computed for consecutive trials with constant vs. shifted tasks and repetitions vs. changes of the response direction. In general the expected interaction between the two sequence factors could not be observed. In both examination periods the alternative strategy revealed no marked differences between task/response shifts. Considering the result of previous studies on task/response shifts, the results were highly unexpected. One explanation might be the strong deviations from equality for the relative frequencies of the four sequence conditions, resulting in biased expectancies. These may have superimposed on the basic effects of task shifts. However, in both examination periods weak effects of task shift could be revealed in the subgroup of the long-term exposed workers. In further studies it is necessary to balance conditions more carefully in order to exploit the sensitivity that the measurement of shift costs promises to provide. The exposure-related results of this study support this aspect.

Adult↗