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PubMed2005

Task switching and action sequencing.

We investigated if task switching affects late response processes that occur after the selection of a response. Subjects performed a sequence of two responses. The first and second response were selected, and then executed in close succession. The interresponse interval (IRI) was taken as a measure of late response processes. The two responses could either belong to different tasks (task-switch condition), or to the same task that was performed twice (task-repetition condition). In all three experiments, the IRI was found to be longer in the task-switch condition than in the task-repetition condition, consistent with the idea that task switching affected late response processes. However, the effects of the manipulation of the stimulus-onset asynchrony revealed that the tendency to perform the two responses as a sequence was reduced in the task-switch condition relative to the task-repetition condition. Thus, the data do not provide unequivocal evidence for task switching affecting late response processes. The data show, however, that task switching affected action sequencing. Two actions that do not belong to the same task context are less likely to be performed as an action sequence. We suggest that task switching interacts with higher-order control processes that cannot be studied within the traditional task-switching paradigm.

Adult↗
PubMed1990

Impaired verbal reasoning and constructional apraxia in subjects with right hemisphere damage.

In addition to causing visuospatial deficits, damage to the right cerebral hemisphere also impairs other cognitive abilities, including those requiring higher-order aspects of language. The present study used a standardized test battery to examine the relationship between visuospatial abilities and comprehension of narrative material in subjects having unilateral right hemisphere damage (RHD). In a series of 41 consecutively admitted RHD subjects, impairments in abstracting information from narrative passages were as prevalent and as severe in magnitude as constructional apraxia. Moreover, the extent of the visuospatial and linguistic impairments were highly correlated. Although age, educational levels, and degree of premorbid brain atrophy were all found to influence performance, analysis of a select subgroup of the population established that the covariation of visuospatial and verbal impairments is related to right hemisphere damage per se. Clinically, these findings may be of significance for understanding the pervasive cognitive impairments that are often evidenced by RHD patients.

Aged↗
PubMed1990

Visual impairments in macaques following inferior temporal lesions are exacerbated selectively by additional damage to superior temporal sulcus.

The present study examined the behavioural effects of removing the inferior temporal cortex (area TE) either on its own or in combination with the adjacent fundus and upper bank of the superior temporal sulcus (area STP). Comparisons with preoperative behaviour showed that the addition of superior temporal sulcal damage led to an increase in visual components of the Klüver-Bucy syndrome, i.e. an increased tendency to touch and examine objects coupled with a decrease in emotional reactivity, but no excessive orality, changes in food preference, or coprophagia. No group differences were found in the learning of 3 pattern discriminations, but the animals with additional superior temporal sulcal lesions were more impaired than the others on 3 colour discriminations, successive reversals of an object discrimination, and a learning-set task. These findings indicate that STP provides an important route, independent of the route via TE, by which visual information can reach limbic structures to evoke affective responses and contribute to visual learning.

Amygdala↗
PubMedDate not supplied

Long-term idebenone treatment of vascular and degenerative brain disorders of the elderly.

A multicentre study with an open experimental design was carried out on 118 patients suffering from mild to moderate cognitive decline due to cerebrovascular and degenerative disorders (chronic cerebrovascular disorders, CCVD; multi-infarct dementia, MID; aging brain, AB; dementia of Alzheimer's type, DAT). All patients, after a wash-out period of 3 weeks, were treated with idebenone (45 mg twice daily by oral route) for a period of 6 months. Behavioral and cognitive measures (Sandoz Clinical Assessment of Geriatrics, SCAG; Serial Learning Test) were applied to evaluate the long term therapeutical aspects. The results, analyzed by multivariate analysis of variance and chi2 test, showed a significant improvement of the cognitive profile in all patients, more evident in CCVD and AB groups. No remarkable side-effects were found in all groups of patients, thus confirming good tolerability of idebenone.

Journal Article↗
PubMed2006

fMRI investigation of cortical and subcortical networks in the learning of abstract and effector-specific representations of motor sequences.

A visuo-motor sequence can be learned as a series of visuo-spatial cues or as a sequence of effector movements. Earlier imaging studies have revealed that a network of brain areas is activated in the course of motor sequence learning. However, these studies do not address the question of the type of representation being established at various stages of visuo-motor sequence learning. In an earlier behavioral study, we demonstrated that acquisition of visuo-spatial sequence representation enables rapid learning in the early stage and progressive establishment of somato-motor representation helps speedier execution by the late stage. We conducted functional magnetic resonance imaging (fMRI) experiments wherein subjects learned and practiced the same sequence alternately in normal and rotated settings. In one rotated setting (visual), subjects learned a new motor sequence in response to an identical sequence of visual cues as in normal. In another rotated setting (motor), the display sequence was altered as compared to normal, but the same sequence of effector movements was used to perform the sequence. Comparison of different rotated settings revealed analogous transitions both in the cortical and subcortical sites during visuo-motor sequence learning-a transition of activity from parietal to parietal-premotor and then to premotor cortex and a concomitant shift was observed from anterior putamen to a combined activity in both anterior and posterior putamen and finally to posterior putamen. These results suggest a putative role for engagement of different cortical and subcortical networks at various stages of learning in supporting distinct sequence representations.

Adult↗
PubMed1999

Pharmacologic strategies for augmenting cognitive performance in schizophrenia.

There is recognition that the cognitive symptoms of schizophrenia have the most substantial impact on illness outcome. Domains of cognition reported to be significantly affected include serial learning, executive function, vigilance, and distractibility, to name a few. Dopamine activity at D1 receptors mediates many cognitive processes subserved by the prefrontal cortex (PFC), particularly working memory. The number of D1 receptors in the PFC is decreased in schizophrenics and is unaffected by chronic administration of typical neuroleptics. Therefore, medications that increase dopamine in the PFC, such as atypical neuroleptics, or that directly activate the D1 receptor may prove useful in the remediation of prefrontal-dependent cognitive deficits in schizophrenia. Decreased levels of cortical norepinephrine (NE) are associated with impaired learning and working memory in animal models, and can be reversed by drugs that restore NE activity. More specifically, alpha-2 adrenergic receptor agonists have been particularly effective in improving delayed response performance in young monkeys with localized 6-hydroxydopamine lesions in the PFC. Furthermore, human postmortem studies have demonstrated decreased NE in the frontal cortex of demented schizophrenic patients. Therefore, alpha-2 receptor agonists hold promise as drugs to improve cognitive performance on tasks dependent upon PFC function in schizophrenics. Finally, the finding that cortical choline acetyl transferase activity correlates with Clinical Dementia Rating scores in schizophrenic patients and that cholinomimetic drugs enhance cognition in healthy subjects suggests that cholinergic drugs may also treat cognitive symptoms in schizophrenia. Two potential types of cholinomimetics for use in schizophrenics are the acetylcholinesterase inhibitors and M1/M4 muscarinic agonists, both of which increase cortical cholinergic activity.

Acetylcholine↗
PubMed1979

Differential effects of age and cerebral atrophy upon span of immediate recall and paired-associate learning in older patients suspected of dementia.

Seventy-eight patients suspected of dementia, 50 years of age or older and without evidence of focal cerebral lesion or systemic illness, were administered the Digit-Span Forward and Paired-Associate Learning subtests of the Wechsler Memory Scale. Computerized axial tomography, allowing a visualization and measurement of the lateral ventricles and cortical sulci, was employed to measure cerebral atrophy. Four groups were defined as follows: (1) age 50-69, without atrophy (N = 27), (2) age 50-69, with atrophy (N = 17), (3) age 70-89, without atrophy (N = 18), (4) age 70-89, with atrophy (N = 16). Results of analyses of variance indicate that Digit-Span is affected by cerebral atrophy but not by age, while Paired-Associate Learning is affected by both age and cerebral atrophy. No interaction effect between age and cerebral atrophy was found for either task. These results are discussed within the context of previous research, and implications for both models of memory and theories of the effects of cerebral atrophy in different ag groups are suggested.

Age Factors↗
PubMed1991

The effects of excitotoxic lesions of the nucleus accumbens on a matching to position task.

The effects of bilateral ibotenic acid lesions of the nucleus accumbens in the rat were examined on a delayed matching to position task. The lesion induced a stable delay-dependent performance deficit suggestive of a short-term memory problem. Following analysis of the impaired performance on trials with long delays, using measures akin to signal detection indices, the deficit was interpreted as being largely due to the intrusion of a side-dependent response bias. Low-dose amphetamine (0.75 mg/kg) produced a similar disruption in the sham-operated rats, both in terms of accuracy impairment and degree of strategical bias. As well as mimicking the effects of low-dose amphetamine in sham-operated rats, the lesion also protected against the disruptive effects of the drug at low doses. Whilst exhibiting no performance deficit when the matching schedule lacked a delay component, the lesioned rats were very significantly impaired in switching their response strategies when exposed to a series of reversals. In addition, the lesioned rats were remarkably resistant to an extinction procedure. Both these findings indicate that the lesioned rats were unable to exhibit flexibility in their response patterns. These results, taken together with those of the delayed matching procedure, imply that one of the functions of the intact nucleus accumbens is to inhibit habitual responding under conditions of non-reward and low stimulus control, possibly via its connections to the dorsal striatal system.

Amphetamine↗