More attention must be paid: The neurobiology of attentional effort

Sarter, Martin; Gehring, William J.; Kozak, Rouba

doi:10.1016/j.brainresrev.2005.11.002

Cited by 476 publications

(491 citation statements)

References 174 publications

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“…Gold, 2004), as well as attention mechanisms that might be important for spatial working memory (cf. Sarter, Gehring and Kozak, 2006). The present findings suggest that there may be linkage between cholinergic functions and cognitive impairments in the Ts65Dn mice, particularly evident with the use of comparisons across ages.…”

Section: General Conclusionmentioning

confidence: 52%

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Chang

Gold

2008

Neurobiology of Learning and Memory

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Spatial working memory and the ability of a cholinesterase inhibitor to enhance memory were assessed at 4, 10, and 16 months of ages in control and Ts65Dn mice, a partial trisomy model of Down syndrome, with possibly significant relationships to Alzheimer's Disease as well. In addition, ACh release during memory testing was measured in samples collected from the hippocampus using in vivo microdialysis at 4, 10, and 22-25 months of age. When tested on a four-arm spontaneous alternation task, the Ts65Dn mice exhibited impaired memory scores at both 4 and 10 months. At 16 months, control performance had declined toward that of the Ts65Dn mice and the difference in scores across genotypes was not significant. Physostigmine (50 μg/kg) fully reversed memory deficits in the Ts65Dn mice in the 4-month-old group but not in older mice. Ts65Dn and control mice exhibited comparable baseline levels of ACh release at all ages tested; these levels did not decline significantly across age in either genotype. ACh release increased significantly during alternation testing only in the young Ts65Dn and control mice. However, the increase in ACh release during alternation testing was significantly greater in control than Ts65Dn mice at this age. The controls exhibited a significant age-related decline in the testing-related increase in ACh release. With only a small increase during testing in young Ts65Dn mice, the age-related decline in responsiveness of ACh release to testing was not significant in these mice. Overall, these results suggest that diminished responsiveness of ACh release in the hippocampus to behavioral testing may contribute memory impairments in Ts65Dn mice.

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Section: General Conclusionmentioning

confidence: 52%

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Chang

Gold

2008

Neurobiology of Learning and Memory

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“…The present study yielded a cueing Â cue validity Â drug interaction in the middle frontal gyrus within the right prefrontal cortex and within the left anterior cingulate cortex. It has been suggested that the anterior cingulate and prefrontal cortex are part of a system involved in effortful cognitive control, which is supposed to be mediated by cholinergic neurotransmission (Sarter et al, 2006). However, the question whether the anterior cingulate cortex is only involved in the detection of negative events (like, eg, errors) or rather represents an instance of control itself remains a matter of debate (Sarter et al, 2006).…”

Section: Neural Datamentioning

confidence: 99%

“…It has been suggested that the anterior cingulate and prefrontal cortex are part of a system involved in effortful cognitive control, which is supposed to be mediated by cholinergic neurotransmission (Sarter et al, 2006). However, the question whether the anterior cingulate cortex is only involved in the detection of negative events (like, eg, errors) or rather represents an instance of control itself remains a matter of debate (Sarter et al, 2006). Thus, the activation observed could, on the one hand, be linked to the processing of attentional effort related to reorienting attention in the two different cue validity conditions.…”

Section: Neural Datamentioning

confidence: 99%

Behavioral and Neural Effects of Nicotine on Visuospatial Attentional Reorienting in Non-Smoking Subjects

Vossel

Thiel

Fink

2007

Neuropsychopharmacol

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The cholinergic neurotransmitter system has been proposed to be involved in the processing of probabilistic top-down information provided by endogenous cues in location-cueing paradigms. It has been shown that the behavioral and neural effects of a nicotinic cholinergic stimulation resemble the effects obtained by manipulating the validity of the spatial cues: enhancing cortical nicotine levels and decreasing cue validity both reduce the reaction time difference between invalidly and validly cued targets (ie, the 'validity effect') as well as neural activity related to attentional reorienting in parietal brain regions. In the present study, we investigated whether the behavioral and neural effects of nicotine in location-cueing paradigms are dependent upon different a priori cue validities. Twenty-four subjects were investigated in a double-blind placebo-controlled between-subject design with functional magnetic resonance imaging. Nicotine was administered to non-smoking volunteers via polacrilex gums (Nicorette s , 2 mg) before performing a location-cueing paradigm with valid and invalid cues in the context of 90 and 60% cue validity in the MR scanner. Nicotine significantly reduced the validity effect in the 90% but not in the 60% cue validity condition. Fronto-parietal and cingulate regions showed stronger nicotinic reductions of reorientingrelated neural activity in the high than in the low cue validity condition. Our data reveal an interaction effect between the pharmacological and cognitive modulation of attentional reorienting, which is evident at both a behavioral as well as the neuronal level.

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“…Based on extensive evidence indicating the crucial role of the cortical cholinergic input system for attention Parikh et al, 2007;Sarter et al, 2006Sarter et al, , 2005a, the attentional symptoms of schizophrenia have been proposed to be mediated via abnormalities in the regulation and activity of this neuronal system Raedler et al, 2003Raedler et al, , 2007Sarter et al, 2005b). Recently, we demonstrated that in animals pretreated in accordance with an amphetamine (AMPH) regimen identical to the one used herein, the disruption of attentional performance triggered by AMPH challenges was a result, not just a correlate, of a prefrontal cholinergic input system that remained 'frozen' at baseline and failed to activate in response to the task onset .…”

Section: Introductionmentioning

confidence: 99%

Detection of the Moderately Beneficial Cognitive Effects of Low-Dose Treatment with Haloperidol or Clozapine in an Animal Model of the Attentional Impairments of Schizophrenia

Martı́nez

Sarter

2007

Neuropsychopharmacol

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The absence of effective cognition enhancers for the treatment of patients with schizophrenia limits the validation of animal models and behavioral tests used for drug finding and characterization. However, low doses of haloperidol and clozapine were documented to produce moderately beneficial effects in patients. Therefore, this experiment was designed to determine the attentional effects of such treatments in a repeated-amphetamine (AMPH) animal model. Animals were trained in an operant-sustained attention task and underwent a 40-day pretreatment period with saline or increasing doses (1-10 mg per kg) of AMPH. After regaining baseline performance following 10 days of saline treatment, animals were treated with haloperidol (0.025 mg per kg), clozapine (2.5 mg per kg), or vehicle for 10 days. Furthermore, the effects of AMPH challenges (1.0 mg per kg) were assessed. In AMPH-pretreated animals, the administration of AMPH challenges resulted in the disruption of attentional performance. Treatment with haloperidol and clozapine attenuated the detrimental performance effects of these challenges, with clozapine exhibiting more robust attenuation. Furthermore, clozapine, but not haloperidol, impaired the performance of control animals. In contrast, the performance of AMPH-pretreated animals remained unaffected by clozapine. As this animal model detects the moderately beneficial cognitive effects of haloperidol and clozapine, it may be useful for preclinical research designed to detect and characterize treatments for the cognitive symptoms of schizophrenia.

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More attention must be paid: The neurobiology of attentional effort

Cited by 476 publications

References 174 publications

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Behavioral and Neural Effects of Nicotine on Visuospatial Attentional Reorienting in Non-Smoking Subjects

Detection of the Moderately Beneficial Cognitive Effects of Low-Dose Treatment with Haloperidol or Clozapine in an Animal Model of the Attentional Impairments of Schizophrenia

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