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PubMed2005

Executive system dysfunction occurs as early as middle-age in the rhesus monkey.

As our understanding of age-related cognitive decline advances, studies are now focusing on identification of those areas of cognitive function that undergo the first changes with age. In the present study, in order to determine whether executive function is sensitive to the aging process, we assessed the performance of 16 monkeys of middle-age (12-19 years of age) on the conceptual set-shifting task, an analogue of the Wisconsin Card Sorting Test (WCST). We compared their performance to that of seven young adult (5-9 years of age) and 18 aged monkeys (20-30). The findings showed that middle-aged monkeys, like those of advanced age, were significantly impaired on the conceptual set-shifting task (CSST). These findings parallel those of recent studies in humans demonstrating an increase in perseverative errors on the WCST by middle-aged as well as aged individuals and, in turn, support the notion that disruption of executive function is one of the earliest changes in cognition to occur in normal aging.

Age Factors↗
PubMed2001

Automatic and intentional activation of task sets.

Four experiments examined automatic and intentional activation of task sets in a switching paradigm. Experiment 1 demonstrated incidental task sequence learning that was not accompanied by verbalizable task sequence knowledge. This learning did not affect task shift cost and may be attributed to automatic task-set activation. In Experiment 2, both shift cost and learning effect increased when the response-cue interval was short, indicating the influence of residual, persisting activation of the preceding task set. In Experiment 3, learning disappeared with a long cue-stimulus interval (CSI), which resulted in a strong preparation effect. This preparation, however, reduced reaction time level but was not specific to task shifts. Finally, Experiment 4 showed that a within-subject C

Adult↗
PubMed2006

Involvement of hippocampal extracellular signal-regulated kinase 1/2 in spatial working memory in rats.

The role of the phosphorylation of hippocampal extracellular signal-regulated kinase 1/2 in spatial working memory in rats was assessed with a delayed spatial win-shift task in a radial arm maze. The task consisted of two phases, a training phase and a test phase, separated by a delay. Phosphorylated extracellular signal-regulated kinase 1/2 levels were significantly and transiently increased in the hippocampus by 60 min, and then returned to the control levels 120 min after the training phase. Bilateral microinjections of the PD98059, an inhibitor of the extracellular signal-regulated kinase 1/2 kinase MEK, into the hippocampus impaired performance in the test phase of the delayed spatial win-shift task at 5-min delay. These results suggest that extracellular signal-regulated kinase 1/2 activation in the hippocampus plays a crucial role in spatial working memory.

Animals↗
PubMed1999

Towards a cognitive phenotype for autism: increased prevalence of executive dysfunction and superior spatial span amongst siblings of children with autism.

Two studies were conducted to examine executive function skills in siblings of children with autism. In Study 1, four computerised tasks (three executive tasks: the ID/ED set-shifting task; a spatial working memory task; and the Tower of London planning task; and a control spatial span task) from the CANTAB battery were used to compare 31 siblings of children with autism with 32 siblings of children with developmental delay and 32 children from unaffected families. In Study 2, the two sibling groups were compared on two manually administered executive tasks (verbal fluency and list recall). As a group, autism siblings showed superior spatial and verbal span, but a greater than expected number performed poorly on the set-shifting, planning, and verbal fluency tasks. There were no group differences in working memory performance. The implications of these findings for the broader phenotype of autism is discussed.

Adolescent↗
PubMed2006

Effects of acute tryptophan depletion on cognition, memory and motor performance in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a neuropsychiatric disease, which is not only characterized by motor symptoms, but also by cognitive and psychiatric symptoms. It is hypothesized that some of the non-motor symptoms are related to the serotonergic deficiency that is present in PD. AIM: To study the influence of serotonin on cognition, memory and motor performance in PD. METHODS: In a double blind, randomized, placebo-controlled, cross-over design, the effect of acute tryptophan depletion (ATD) on the Visual Verbal Learning Task (VVLT), the Concept Shifting Task (CST), Simple Reaction Time Task (SRT), Finger Precuing Task (FPT) and the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS, Section 3) was investigated in 15 PD patients in early stages of their disease and 15 healthy volunteers, matched for age, sex and educational status. RESULTS: With the exception of the absence of a differential effect for PD patients with the long interval of the SRT, ATD produced similar effects in PD patients and control subjects on all tasks. These included impairment of delayed recall and delayed recognition on the VVLT, and improved SRT and FPT for 'short intervals'. The UPDRS in patients remained unaffected after ATD. CONCLUSION: Serotonin does not appear to play a disease-specific role in cognition and reaction time in early stage PD patients, nor does acute reduction of cerebral serotonin levels affect motor symptoms in a clinically relevant way.

Aged↗
PubMed1999

Human eye-head gaze shifts in a distractor task. I. Truncated gaze shifts.

This study examines two current ideas regarding the control of eye-head gaze shifts. The first idea stems from recent studies involving electrical stimulation in the primate superior colliculus that suggest that a residual feedback of gaze displacement persists for approximately 100 ms after completion of a gaze shift. In light of this hypothesis, we examined the accuracy of gaze shifts generated very soon after the end of a preceding gaze shift. Human subjects were presented with a visual or auditory target along with an accompanying stimulus of the other modality. The accompanying stimulus appeared either at the same place as the target or at the diametrically opposite position, in which case it was termed a distractor. Subjects often made an incorrect gaze shift (IGS) in the direction of the distractor, followed by a recorrect gaze shift (RGS) in the direction of the target. We found that RGSs were accurately driven to the target, even when they followed IGSs by <5 ms, regardless of the size of the IGS. The second idea is that a gaze shift cannot be cancelled in midflight. The end point of IGSs frequently fell short of the distractor. The dynamics of these movements, and of the head movement components during the IGSs in particular, suggests that these hypometric IGSs were planned for a much larger excursion but were truncated and superceded by the reversing RGSs. These results emphasize that the gaze shifting system can change the desired goal of a gaze shift in midflight and that the superceding movement is accurate regardless of the metrics or timing of the preceding movement.

Acoustic Stimulation↗
PubMed2006

Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania.

OBJECTIVE: Problems with inhibiting certain pathological behaviors are integral to obsessive-compulsive disorder (OCD), trichotillomania, and other putative obsessive-compulsive spectrum disorders. The authors assessed and compared motor inhibition and cognitive flexibility in OCD and trichotillomania for the first time, to their knowledge. METHOD: The Stop-Signal Task and the Intradimensiona/Extradimensional Shift Task were administered to 20 patients with OCD, 17 patients with trichotillomania, and 20 healthy comparison subjects. RESULTS: Both OCD and trichotillomania showed impaired inhibition of motor responses. For trichotillomania, the deficit was worse than for OCD, and the degree of the deficit correlated significantly with symptom severity. Only patients with OCD showed deficits in cognitive flexibility. CONCLUSIONS: Impaired inhibition of motor responses (impulsivity) was found in OCD and trichotillomania, whereas cognitive inflexibility (thought to contribute to compulsivity) was limited to OCD. This assessment will advance the characterization and classification of obsessive-compulsive spectrum disorders and aid the development of novel treatments.

Adult↗
PubMed1999

Seven steps to shift from tasks to outcomes.

Seven managerial strategies guide the evolution of nurses' abilities to plan patient outcomes rather than focus on tasks. The authors emphasize revitalizing report rituals to include discussion of patient-focused short- and long-term outcomes.

Humans↗
PubMed2003

Glutamate receptor binding in the frontal cortex and dorsal striatum of aged rats with impaired attentional set-shifting.

Aged Long-Evans rats exhibit deficits in attentional set shifting, an aspect of executive function, relative to adult rats. Impairments in set shifting and spatial learning are uncorrelated in aged rats, indicating a possible dissociation of the effects of ageing in prefrontal versus hippocampal systems. Ionotropic glutamate receptor binding was assessed using an in vitro autoradiography method in young and aged rats. The rats had been tested on a set-shifting task that measured attentional set shifts and reversal learning, as well as in a spatial learning task in the Morris water maze. [3H]Kainate, [3H]AMPA and NMDA-displaceable [3H]glutamate receptor binding were quantified in orbital cortex, cingulate cortex, medial frontal cortex, dorsolateral and dorsomedial striatum. Age-related decreases in [3H]kainate binding were apparent in all regions measured. Similarly, NMDA-displaceable [3H]glutamate binding was decreased in the aged rats in all the regions measured except for the medial frontal area where no age effects were observed. [3H]AMPA receptor binding was preserved with age in all the regions measured. Lower levels of [3H]kainate binding in the cingulate cortex were significantly correlated with poorer set-shifting performance, whereas higher levels of NMDA binding in the dorsomedial striatum were correlated with poorer set-shifting performance. There were no significant correlations between the levels of ionotropic glutamate receptors and performance in the reversal task or spatial learning in the Morris water maze. These results indicate that age-related behavioural deficits in attentional set shifting are selectively associated with neurobiological alterations in the cingulate cortex and dorsomedial striatum.

Aging↗
PubMed1988

Role of the posterior parietal association cortex in the processing of spatial event information.

Humans and monkeys with damage to the parietal association cortex (PC) exhibit deficits on visual-spatial tasks that are often dependent upon the attentional requirements of the task at hand. In order to test whether there is a correspondence between humans and rats in terms of the function of PC in the processing of spatial information, separate groups of rats were trained in two list-learning tasks, a win-stay task and a win-shift task, on an eight-arm radial maze. It is assumed that these two tasks vary in degree of required attention effort, because the win-shift rule is considerably easier for the rat to learn than the win-stay rule. One group of animals in each condition was given preoperative training before receiving bilateral aspiration lesions of PC. Another group in each condition received PC lesions prior to training. The results indicated that animals with PC lesions are unable to acquire either the win-stay or the win-shift rule. However, of the animals with preoperative training, only the win-stay trained animals were deleteriously affected by the brain lesion. The win-shift animals showed no postoperative decline in performance. Because rats with PC lesions are only impaired on the more demanding spatial task, these results are consistent with the human clinical observations.

Animals↗
PubMed2002

Relative contributions of balance and voluntary leg-coordination deficits to cerebellar gait ataxia.

Different cerebellar regions participate in balance control and voluntary limb coordination, both of which might be important for normal bipedal walking. We wanted to determine the relative contributions of balance versus leg-coordination deficits to cerebellar gait ataxia in humans. We studied 20 subjects with cerebellar damage and 20 control subjects performing three tasks: a lateral weight-shifting task to measure balance, a visually guided stepping task to measure leg- coordination, and walking. We recorded three-dimensional joint position data during all tasks and center of pressure coordinates during weight-shifting. Each cerebellar subject was categorized as having no detectable deficits, a balance deficit only, a leg-placement deficit only, or both deficits. We then determined the walking abnormalities associated with each of these categories. Five of 10 measures of gait ataxia were abnormal in cerebellar subjects with a balance deficit, but only 1 was abnormal in cerebellar subjects with a leg-placement deficit. Furthermore, subjects with a balance deficit performed worse than subjects with a leg-placement deficit on 9 of the 10 gait measures. Finally, performance on the balance task, but not the leg-placement task, explained a significant proportion of the variance in walking speed for the entire cerebellar group. We conclude that balance deficits are more closely related to cerebellar gait ataxia than leg-placement deficits. Our findings are consistent with animal literature, which has suggested that cerebellar control of balance and gait are interrelated, and dissociable from cerebellar control of voluntary, visually guided limb movements.

Adult↗
PubMed2006

Event-related potential correlates of extradimensional and intradimensional set-shifts in a modified Wisconsin Card Sorting Test.

Event-related potentials (ERPs) were recorded in healthy adult participants during the performance of a modified version of the Wisconsin Card Sorting Test that was designed to isolate the effects of extradimensional (ED) and intradimensional (ID) set-shifts. ERP averages were created for ED- and ID-Shift trials, as well as for the 5th trial in each block (Maintain-Rule). Differences in sensory and longer latency ERP components were found between the ED- and ID conditions, and between the two shift conditions and the Maintain-Rule trials. Consistent with the previous literature, these data indicated that ED- and ID-Shifts require different levels of neural resources. A secondary goal of this experiment was to use the excellent temporal resolution of ERPs to examine the neural correlates of various other aspects of the performance of a set-shift task, including differences between correct shifts and the commission of errors, and the differences between the reception of correct and error feedback. Comparisons were made between ERP averages to correct ED-Shift trials and ED-Error trials, and to feedback following a correct ED-Shift compared to feedback following an error. As expected, ERP differences were found between correct trials and error trials, and between the ERP correlates of receiving different types of feedback. Overall, these data further indicate the utility of using ERP methodology to study various aspects of complex neuropsychological paradigms.

Adolescent↗
PubMed1998

The functional emergence of prefrontally-guided working memory systems in four- to eight-year-old children.

The neural processes that underlie the functional emergence of human cognitive functions, particularly those associated with the prefrontal cortex (PFC), are of growing interest to developmental psychologists and neuroscientists. Specifically, working memory functions have been correlated with PFC activity in nonhuman primates and adult humans but have not been extensively studied in children. We examined the developmental emergence of functions involved in working memory through the use of the Cambridge Neuropsychological Test Automated Battery (CANTAB), a computerized battery of nonverbal visually-presented neuropsychological tests designed to dissociate frontal from temporal lobe behavioral functions. Participants were normal children, aged 4-8 (n = 181) and a small group of young adults (n = 24) who completed measures of Spatial Memory Span, Spatial Working Memory, the Tower of London planning task, Visual Pattern and Spatial Recognition tasks, and a Set-Shifting task. Findings indicate a general age-related progression in ability levels on frontal lobe tasks, with 4-year-olds performing worse than 5- to 7-year-olds on all measures. Eight-year-olds are superior to younger children in their ability to solve complex problems but have not yet reached adult levels of performance on the most difficult items of the Tower of London and Spatial Working Memory tasks. We conclude that the development of working memory functions proceeds dimensionally, starting with refinement of basic perceptual and sensorimotor functions and culminating with the physiological maturation of widespread neural networks that integrate complex processing demands inherent to working memory tasks.

Adolescent↗
PubMed2003

Cognitive functioning in young and middle-aged unmedicated out-patients with major depression: testing the effort and cognitive speed hypotheses.

BACKGROUND: Cognitive deficits are common in major depressive disorder, but their nature is unclear. The effort hypothesis states that performance on effortful tasks is disproportionately impaired compared with the performance on automatic tasks. The cognitive speed hypothesis states that depression is characterized by cognitive slowness, which is a source of cognitive dysfunctioning. The present study investigated both theories in unmedicated adult depressive patients. It was also investigated whether the cognitive deficits can be attributed to more general physical illness-related factors or specifically to depressive disorder. METHOD: Thirty non-psychotic depressive out-patients were compared with 38 healthy control subjects and 25 patients with severe allergic rhinitis. The effects of group on more automatic and more effortful aspects of cognitive tasks measuring cognitive speed (Concept Shifting Task, Stroop Colour Word Test, Memory Scanning Test) and memory retrieval (Visual Verbal Learning Task, Verbal Fluency Test) were evaluated by MANCOVA. Age, sex, education and pre-morbid intelligence were treated as covariates. RESULTS: The depressive group had cognitive deficits in the automatic processing subtask of the Stroop, memory scanning and memory span. Performance on more effortful tasks was not impaired. CONCLUSIONS: Our results are more consistent with the cognitive speed hypothesis. Cognitive functioning in depressive disorder seems to be characterized by a reduced speed of information processing in automatic subtasks.

Adult↗
PubMed2002

Preparatory processes in the task-switching paradigm: evidence from the use of probability cues.

The purpose of the investigations was to dissociate processes of task preparation from task execution in the task-switching paradigm. The basic assumption was that task repetitions have 2 advantages over task shifts: an activation advantage as a result of the execution of the same task type in the pretrial, and an expectation advantage, because participants, in general, implicitly expect a repetition. In Experiments 1-3, the authors explicitly manipulated expectancies by presenting cues that announced a shift and/or a repetition with probabilities of 1.00, .75, .50, or .25. Increasing latencies with decreasing probability for shifts and repetitions show that the expectation advantage can be equalized by preparation. However, the activation advantage represented by constant shift costs between tasks of the same probability is not penetrable by preparation. In Experiments 4 and 5, the authors found evidence that preparation involves activation of the expected task and inhibition of distracting tasks.

Adaptation, Psychological↗
PubMed1996

Specific cognitive deficits in tests sensitive to frontal lobe dysfunction in obsessive-compulsive disorder.

Forty patients with obsessive-compulsive disorder (OCD) were compared to matched healthy controls on neuropsychological tests which are sensitive to frontal lobe dysfunction. On a computerized version of the Tower of London test of planning, the patients were no different from healthy controls in the accuracy of their solutions. However, when they made a mistake, they spent more time than the controls in generating alternative solutions or checking that the next move would be correct. The results suggest that OCD patients have a selective deficit in generating alternative strategies when they make a mistake. In a separate attentional set-shifting task, OCD patients were impaired in a simple discrimination learning task and showed a continuous cumulative increase in the number who failed at each stage of the task, including the crucial extradimensional set shifting stage. This suggests that OCD patients show deficits in both acquiring and maintaining cognitive sets. The cognitive deficits in OCD may be summarized as: (i) being easily distracted by other competing stimuli; (ii) excessive monitoring and checking of the response to ensure a mistake does not occur; and (iii) when a mistake does occur, being more rigid at setting aside the main goal and planning the necessary subgoals. Both studies support the evidence of fronto-striatal dysfunction in OCD and the results are discussed in terms of an impaired Supervisory Attentional System.

Adolescent↗
PubMed2006

Altered attention and prefrontal cortex gene expression in rats after binge-like exposure to cocaine during adolescence.

Illicit use of drugs frequently begins and escalates during adolescence, with long-term adverse consequences. Because it is increasingly accepted that neural development continues through adolescence, addiction research has become more invested in understanding the behavioral and molecular consequences of early exposure to drugs of abuse. In a novel binge administration paradigm designed to model the pattern of human adolescent drug use, we administered ascending doses of cocaine or saline during a 12-d developmental period [postnatal day 35 (P35) to P46] corresponding to human adolescence. During adulthood (P70), rats treated with this regimen displayed increased responsiveness to the stimulant effects of cocaine. Adult rats also displayed abnormally rapid shifts in attention when performing an attentional set-shifting task, which measures the ability to shift attention between stimuli and whose performance requires an intact prefrontal cortex (PFC). Treatment with cocaine during adolescence also caused acute alterations in the expression of genes encoding cell adhesion molecules and transcription factors within the PFC. Furthermore, we observed decreases in histone methylation, which may indicate a role for chromatin remodeling in the observed changes in gene expression patterns. These findings suggest that exposure to cocaine during adolescence has far-reaching molecular and behavioral consequences in the rat PFC that develop over time and endure long after drug administration has ceased.

Age Factors↗