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PubMed2005

Influence of cocaine self-administration on learning related to prefrontal cortex or hippocampus functioning in rats.

RATIONALE: Individuals who abuse cocaine have cognitive deficits, particularly in functions associated with the orbitofrontal cortex. It is not clear to what extent the impact of cocaine on cognitive functioning is related to its role as a behavioral reinforcer. A preclinical means to investigate this issue is to use a yoked-triad procedure in which sets of three animals either contingently self-administer cocaine or receive passive administration of cocaine or saline in a noncontingent manner. OBJECTIVE: Using this procedure, we assessed cocaine's effect on learning that requires a functionally intact prefrontal cortex (prelimbic or insular/orbital subregions) or hippocampus. METHODS: Rats self-administering 1-mg/kg unit doses of cocaine responded under a fixed-ratio 5, time-out 20-s schedule of drug delivery. Testing took place in a radial-arm maze within the first 30 min after 2-hr drug sessions ended, beginning after 2.5 months of cocaine or saline exposure. RESULTS: Rats self-administering cocaine earned 14-18 infusions on average throughout different phases of the study. In groupwise comparisons, learning in the visually guided delayed win-shift (prelimbic prefrontal cortex-related) and win-shift (hippocampus-related) tasks was not influenced by contingent or noncontingent cocaine exposure. Session latency, though, was shorter in both cocaine-exposed groups during the win-shift task. During the odor-guided delayed win-shift task (insular/orbital prefrontal cortex-related), learning was disrupted in rats self-administering cocaine, with no influence of noncontingent cocaine exposure. CONCLUSIONS: Based on these and previous findings, learning related to functioning of the insular/orbital prefrontal cortex and amygdala is the most consistently disrupted in cocaine-intoxicated rats after long-term drug exposure.

Amygdala↗
PubMed1978

The effects of overtraining on mediational processes in elderly males.

To examine the effects of overtraining on mediational processes, 81 male residents (aged 55 or above) of a VA domicillary were tested using a two-choice discrimination task. Upon reaching criterion, the men were given, 0, 15, or 30 overtraining trials and then shifted to either a reversal, intradimensional, or extradimensional task. Analysis of the error scores resulted in a significant initial versus shift task main effect and type of shift by initial versus shift task interaction. Further analysis indicated no difference among the three shift groups for the initial task. However, in the shift task, the reversal group had significantly fewer errors than the other two groups who were not statistically different. Participants thus appeared to be mediationally sufficient when reversal and extradimensional tasks were compared, but mediationally deficient when intra- and extradimensional, and reversal and intradimensional tasks were contrasted. While overtraining had no significant effect, examination of the three way interaction suggested potentially facilitative effects of overtraining and a possible regression effect among participants not receiving overtraining.

Aged↗
PubMed1997

Neuropsychological function in young patients with unipolar major depression.

BACKGROUND: While neuropsychological studies have consistently reported impaired cognition in elderly patients with unipolar depression, studies of cognitive function in younger patients with depression have produced equivocal results. The aim of this study was to examine the presence and nature of cognitive deficits in young patients with depression. METHODS: Neuropsychological function was assessed in 20 young patients with unipolar depression, in comparison to 20 age-, education- and IQ- matched controls. Subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were employed, as this battery has proved sensitive to deficits in middle-aged and elderly patients with depression. RESULTS: The patients were not impaired for short-term memory capacity, spatial working memory, planning ability, cognitive speed, delayed matching to sample or recognition memory. Compared to controls, the patients showed impaired subsequent movement latencies on the Tower of London task, suggesting deficits in the ability to sustain motor responses in depression. The depression group were also impaired on the task of attentional set shifting, requiring more trials to criterion at the intradimensional stage of the task and being more likely to fail the task at the extradimensional shift stage than controls. Further analysis indicated that half of the depression group failed to complete all stages of the set shifting task. These patients were more likely to have required in-patient hospitalization at some time during their illness. CONCLUSIONS: These results indicate that there are specific cognitive deficits in young patients with depression and that their presence may be related to a history of hospitalization.

Adolescent↗
PubMed1984

Posterodorsal septal lesions impair performance on both shift and stay working memory tasks.

Two groups of rats were trained preoperatively on either a shift or a stay problem in a T-maze. Training trials consisted of two runs, an "information run" in which a subject was forced to go down one of the two arms of the T-maze, followed immediately by a "choice run" in which the subject could choose either arm. In the shift condition, rats were rewarded with wet mash only for choosing the arm opposite the one they entered on the information run. In the stay condition, rats were rewarded for entering the arm that was entered on the information run. In both conditions, rats ultimately learned to perform with median accuracy of 100%, but the shift group reached this level of performance after fewer trials than the stay group. In a subsequent phase, the delay between information runs and choice runs was increased from 0 to 30, 60, 90, 210 and then decreased back to 0 s. Choice accuracy in both groups declined as the delay increased and returned to 100% at the 0-s delay. Half of the subjects in each condition then received either lesions of the posterodorsal septum-aimed at disconnecting the septum and hippocampus-or control surgery. Postoperative retention deficits resulted from posterodorsal septal lesions in both shift and stay conditions. There was some recovery of performance but no indication of "savings" during postoperative training. These results indicate that deficits in maze performance by rats with septo-hippocampal damage are not restricted to tasks that require alternation of spatial locations. This finding falsifies the notion that maze deficits reflect a spontaneous alternation deficit or changed "spatial strategy," but it supports the hypothesis of a working memory deficit in these animals.

Animals↗
PubMed2002

Limitations in advance task preparation: switching the relevant stimulus dimension in speeded same-different comparisons.

When participants switch between relevant stimulus dimensions in speeded classification tasks, task-switching cost is reduced by advance preparation. Previous studies in which speeded classification tasks were used have suggested that this effect results from attending to the relevant stimulus dimension. Because selective attention to the relevant stimulus dimension in same-different judgments is relatively poor (e.g., Santee & Egeth, 1980), it was predicted that advance task preparation for a shift in the relevant stimulus dimension would be compromised. This prediction was borne out in two experiments comparing dimension shifts (shape vs.fill) with task rule shifts (same? vs. different? and shifts in the mapping of right-left keys to yes and no responses (yes-no vs. no-yes). The results indicate that advance attentional selection of the relevant dimension is an optional preparatory strategy in task switching, employed only in conditions enabling flexible refocusing of attention.

Attention↗
PubMed1981

Lateralized differences associated with semantically varied auditory material.

EEGs were recorded from 13 subjects while they listened to four tape-recorded passages differing in semantic content. The distribution of alpha band power over the two hemispheres, measured at T3/T4, was found to show significant task-dependent shifts. More reality-oriented passages tended to be processed with greater left-hemisphere involvement, while "pleasurable" material showed significant right-hemisphere involvement. Since the differences in laterality were not related to grammatical measures of linguistic complexity, the apparent shifts were attributed to semantic differences between the tasks. Explanation of the results is made in terms of a theory of the metacontrol of cerebral processing.

Dominance, Cerebral↗
PubMed2005

Subtle executive impairment in children with autism and children with ADHD.

BACKGROUND: The executive functions of inhibition, planning, flexible shifting of actions, and working memory are commonly reported to be impaired in neurodevelopmental disorders. METHOD: We compared these abilities in children (8-12 years) with high functioning autism (HFA, n = 17), attention deficit-hyperactivity disorder (ADHD, n = 21) and healthy controls (n = 32). Response inhibition was assessed using the Stroop Color and Word Test (Golden, 1978). Problem solving, set-shifting, and nonverbal memory were assessed using three tasks, respectively, from the CANTAB (Cambridge Cognition, 1996): the Stockings of Cambridge task; the Intra-Dimensional/Extra-Dimensional set-shifting task; and the Spatial Working Memory task (SWM) with tokens hidden behind 3, 4, 6, and 8 boxes. RESULTS: There were no group differences on the response inhibition, planning, or set-shifting tasks. On the SWM task, children with HFA made significantly more between-search errors compared with controls on both the most difficult problems (8-box) and on the mid-difficulty problems (6-box); however, children with ADHD made significantly more errors compared to controls on the most difficult (8-box) problems only. CONCLUSION: Our findings suggest that spatial working memory is impaired in both ADHD and HFA, and more severely in the latter. More detailed investigation is needed to examine the mechanisms that differentially impair spatial working memory, but on this set of tasks there appears to be sparing of other executive functions in these neuropsychiatric developmental disorders.

Attention Deficit Disorder with Hyperactivity↗
PubMed2006

Walking trajectory in neglect patients.

A lateral deviation of the walking trajectory is often observed in stroke patients with unilateral spatial neglect. However, existing research appears to be contradictory regarding the direction of this deviation. The aim of the present study was to gain more insight into the walking trajectory of neglect patients. Twelve right hemisphere stroke patients (six neglect, six no neglect), eight left hemisphere stroke patients (none neglect) and 10 healthy control subjects were instructed to walk towards a target while a two-dimensional ultrasonic positioning system recorded their walking trajectory. Patients' recovery of walking ability was assessed and they were tested for the presence of neglect. Neglect patients showed a larger lateral deviation in their walking trajectory compared to stroke patients without neglect or controls. Neglect patients with good walking ability showed a deviation to the contralesional side. Neglect patients with limited walking ability showed a deviation to the ipsilesional side. Within the neglect group we found no relation between the severity of neglect and lateral deviation. Differences in walking ability may account for the contradictory results between studies regarding the lateral deviation in neglect patients' walking trajectory. We suggest that when a neglect patient's walking ability is limited, walking towards a target becomes a dual task: heading control and walking. A limited walking ability will cause a higher task priority of walking compared to heading control. This shift in task priority may be causing the change in walking trajectory deviation.

Adult↗
PubMed2001

Time-related changes in task performance after lesions restricted to the frontal cortex.

Behavioural studies in patients and functional neuroimaging studies in normal subjects suggest that the right frontal cortex plays an important role in sustaining attention to a task. However, the contribution of different regions of the frontal lobe to performance changes has not been clearly established. First, the assessment of sustained attention has not been carried out in patients with lesions that are restricted to cortical regions of the frontal lobe. Second, although sustained attention is often measured by performance on a task requiring effortful attention, it may be more meaningful to measure changes in performance as a function of time-on-task. Two studies were carried out in five groups of subjects: patients with left or right frontal cortical resections, patients with left or right anterior temporal lobe resections, and normal controls. In the first experiment, a brief (4-min) selective attention task was performed. The right frontal group, unlike the other groups, did not show improved reaction times after the first minute on the task. The second experiment involved a long (30-min) shifting attention task. Both the left and right frontal groups were slower than control groups; however, reaction times in the right frontal group increased with time spent on the task. We conclude that the right frontal cortex plays an essential role in modulating arousal during performance of a task and may also underlie aspects of learning during the early stages of task performance.

Arousal↗
PubMed2004

Distance estimation in a dynamic simulated environment: a visual field dependence problem?

Egocentric distance estimation implies that the subject perceives his own location in the environment. In a simulated environment, subjects have to transpose perceptively their own observation point in order to assume their virtual body position. As only visual information specifies this position, their ability to perceive the camera viewpoint should be linked to the field dependence independence factor (FDI). Field-independent subjects underestimated the mid-distance between their own virtual body position and a far-located target; their bisection was located between the projective (2-D) and the simulated (3-D) mid-distance which indicates their difficulty in considering the in-depth simulated spatial references. High correlations between the vertical estimation in the rod-and-frame test and the egocentric-distance-estimation task (with shifted camera) suggest a similar perceptive process in both tasks. This result is confirmed by the better performances of the field-dependent subjects in this condition. In conclusion, we discuss the relationship between FDI and the sense of presence in virtual environments.

Adult↗
PubMed2001

Dissociation of grip/load-force coupling during a bimanual manipulative assignment.

The aim of the present study was to examine interlimb interactions of grasping forces during a bimanual manipulative assignment that required the execution of a drawer-opening task with the left hand and an object-holding task with the right hand. Compared with the unimanual performance, the grip/load-force ratio of the object-holding task was shifted towards that of the simultaneously executed drawer-opening task. This shows that force parameterization of the dynamic activity interacted with that of the static activity. That the increased force ratio only involved modification of grip force, while load force was held constant, indicates a disruption of the commonly observed co-variation of both forces during a manipulative action. These data are consistent with the notion that the coordinative constraint between grip and load force is a flexible parameter.

Adult↗
PubMed1997

Stimulus dimension shifts in patients with schizophrenia, with and without paranoid hallucinatory symptoms, or obsessive compulsive disorder: strategies, blocking and monoamine status.

Reversal, and intra-dimensional (ID) and extra-dimensional (ED) nonreversal discrimination shifts were studied to see if learned inattention to the irrelevant dimension differentially influenced the efficacy of learning and stimulus choice strategy. Performance was compared with conditioned blocking (CB) and monoamine metabolic status between healthy controls, patients with obsessive compulsive disorder (OCD) or schizophrenia with (PH) or without (NP) active paranoid hallucinatory symptoms. PH and NP patients improved learning with practice, but showed an impaired shift on each task. OCD patients were impaired only on the ED-shift. The NP patient's impairment was nonspecific and, unlike PH and controls, it related to reversal performance. All subjects acquired an attentional set for colour reflected in the length of stimulus-response sequences. Analysis of paired-stimulus choice-strategies showed that while all patients showed fewer correct win-stay choices, only PH patients perseverated with lose-stay choices. Learning about the added stimulus in the CB task related to ID-shift efficiency in NP patients. Increases of dopamine activity related to delayed learning but more switches of stimulus choice in the shift-tasks. Increases of serotonin activity correlated with faster learning in controls, OCD and PH patients. In NP patients the opposite held for dopamine and serotonin activity. Thus the two learned inattention tasks have different if related requirements and correlates: the data are consistent with the use of automatic exogenous attention strategies by NP patients, of inefficient controlled attention by PH patients and the automatization of endogenous processes in controls.

Adolescent↗
PubMed2001

Use of win-stay and win-shift strategies in place and cue tasks by medial caudate putamen (MCPu) lesioned rats.

This study investigated the behavioral function of the medial caudate putamen (MCPu) in the solving of maze tasks. MCPu lesioned rats (n = 35) and control rats (n = 35) were trained for the place or cue task (the four baited arms and four unbaited arms task) in an eight-arm radial maze, which requires the win-stay or the win-shift strategy. In Experiment 1, in which the place task was used, MCPu lesioned rats could learn the task in the win-shift condition, but not in the win-stay condition. MCPu lesioned rats made a lot of unbaited errors in the win-stay condition, as they persistently chose adjacent arms. Control rats could learn the tasks in both conditions. In Experiment 2, in which the cue task was used, MCPu lesioned rats and control rats could learn the tasks in both the win-stay and the win-shift conditions. If anything, the performance of MCPu rats was a little better than that of control rats in the win-stay condition. The results of these two experiments revealed that the MCPu was involved in solving the win-stay place task, but not the win-shift place, win-stay cue, and win-shift cue tasks. These findings suggest that the MCPu plays an important role in utilizing both spatial information and switching foraging strategies flexibly and efficiently, that is, processing complicated visuospatial cognition.

Animals↗
PubMed2002

Convergent and reciprocal modulation of a leak K+ current and I(h) by an inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones.

Neurotransmitters and volatile anaesthetics have opposing effects on motoneuronal excitability which appear to reflect contrasting modulation of two types of subthreshold currents. Neurotransmitters increase motoneuronal excitability by inhibiting TWIK-related acid-sensitive K+ channels (TASK) and shifting activation of a hyperpolarization-activated cationic current (I(h)) to more depolarized potentials; on the other hand, anaesthetics decrease excitability by activating a TASK-like current and inducing a hyperpolarizing shift in I(h) activation. Here, we used whole-cell recording from motoneurones in brainstem slices to test if neurotransmitters (serotonin (5-HT) and noradrenaline (NA)) and an anaesthetic (halothane) indeed compete for modulation of the same ion channels - and we determined which prevails. When applied together under current clamp conditions, 5-HT reversed anaesthetic-induced membrane hyperpolarization and increased motoneuronal excitability. Under voltage clamp conditions, 5-HT and NA overcame most, but not all, of the halothane-induced current. When I(h) was blocked with ZD 7288, the neurotransmitters completely inhibited the K+ current activated by halothane; the halothane-sensitive neurotransmitter current reversed at the equilibrium potential for potassium (E(K)) and displayed properties expected of acid-sensitive, open-rectifier TASK channels. To characterize modulation of I(h) in relative isolation, effects of 5-HT and halothane were examined in acidified bath solutions that blocked TASK channels. Under these conditions, 5-HT and halothane each caused their characteristic shift in voltage-dependent gating of I(h). When tested concurrently, however, halothane decreased the neurotransmitter-induced depolarizing shift in I(h) activation. Thus, halothane and neurotransmitters converge on TASK and I(h) channels with opposite effects; transmitter action prevailed over anaesthetic effects on TASK channels, but not over effects on I(h). These data suggest that anaesthetic actions resulting from effects on either TASK or hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in motoneurones, and perhaps at other CNS sites, can be modulated by prevailing neurotransmitter tone.

Anesthetics, Inhalation↗
PubMed2004

Interference with spatial working memory: an eye movement is more than a shift of attention.

In the present experiments, we examined whether shifts of attention selectively interfere with the maintenance of both verbal and spatial information in working memory and whether the interference produced by eye movements is due to the attention shifts that accompany them. In Experiment 1, subjects performed either a spatial or a verbal working memory task, along with a secondary task requiring fixation or a secondary task requiring shifts of attention. The results indicated that attention shifts interfered with spatial, but not with verbal, working memory, suggesting that the interference is specific to processes within the visuospatial sketchpad. In Experiment 2, subjects performed a primary spatial working memory task, along with a secondary task requiring fixation, an eye movement, or an attention shift executed in the absence of an eye movement. The results indicated that both eye movements and attention shifts interfered with spatial working memory. Eye movements interfered to a much greater extent than shifts of attention, however, suggesting that eye movements may contribute a unique source of interference, over and above the interference produced by the attention shifts that accompany them.

Attention↗
PubMedDate not supplied

Evidence of direction loss in elderly movement preparation is not due to spatial orienting effects.

Twenty elderly and young subjects performed matched movement plan restructuring and spatial orienting tasks. In the restructuring task, a precue stimulus was presented for 200 ms, followed by a preparation (PI; 250, 500, 1000, or 2000 ms), and the target stimulus. On 75% of the trials, the precue specified the aiming movement response enabling movement plan preparation concerning parameters of arm and direction. On 25% of the trials, the precue incorrectly specified the response requiring movement plan restructuring. The orienting task assessed shifts in perceptual localization of the precue and target stimuli for restructuring task conditions. At PIs of 1000 and 2000 ms, elderly, but not young, subjects restructured a movement plan for direction more quickly than for arm or both parameters. Spatial orienting shifts did not account for these effects.

Adolescent↗
PubMed1994

A behavioural analysis of rats with damage to the medial prefrontal cortex using the Morris water maze: evidence for behavioural flexibility, but not for impaired spatial navigation.

In this study, the functional properties of the medial prefrontal cortex (mPFC) of the rat were examined in a task for spatial navigation. The dorsomedial (dmPFC) and ventromedial (vmPFC) parts of the PFC differ in their connectivity with the hippocampus, vmPFC being the main recipient of hippocampal input. Therefore, it is hypothesized that in a spatial task known to be particularly sensitive to hippocampal, but also to prefrontal cortical damage, especially vmPFC is committed to proper spatial learning and memory. Using the Morris water maze task, with an invisible platform, male rats with either partial (dmPFC or vmPFC) or whole (mPFC) bilateral lesions were subjected to various procedures reflecting spatial learning and memory, including a spatial reversal. Animals with dmPFC, vmPFC and mPFC lesions learned and remembered the spatial task equally well as their controls, regardless of the size or site of the bilateral lesion. However, when presented with a spatial reversal, animals with whole mPFC lesions were initially slower in locating the invisible platform than controls and animals with partial mPFC damage, but this effect was only short-lasting. When subsequently presented with a visible platform, all animals with partial (dmPFC or vmPFC) or whole mPFC damage needed significantly more time to locate the platform than the controls. This effect was transient and lasted longer in the animals with whole mPFC damage than in animals with partial damage. On the basis of these findings we conclude that an intact mPFC is not necessary for proper spatial learning and memory. The impairments in the reversal task and especially in the visually-cued task can best be explained as a diminished behavioural flexibility when a shift in task demands occurs. Since the degree of this impairment was related to the size of these lesions, but not to their sites, these differences are ascribed to a 'mass action' of medial prefrontal cortex lesions.

Animals↗
PubMed2002

Components of switching intentional set.

Despite the intuition that we can shift cognitive set on instruction, some behavioral studies have suggested that set shifting might only be accomplished once we engage in performance of the new task. It is possible that set switching consists of more than one component cognitive process and that the component processes might segregated in time. We recorded event-related potentials (ERPs) during two set-switching tasks to test whether different component processes were responsible for (i) set initiation and reconfiguration when presented with the instruction to switch, and (ii) the implementation of the new set once subjects engaged in performing the new task. The response switching (RS) task required shifts of intentional set; subjects selected between responses according to one of two conflicting intentional sets. The results demonstrated the existence of more than one constituent process. Some of the processes were linked to the initiation and reconfiguration of the set prior to actual performance of the new task. Other processes were time locked to performance of new task items. Set initiation started with modulation of medial frontal ERPs and was followed by modulation over parietal electrodes. Implementation of intentional set was associated with modulation of response-related ERPs.

Adult↗