Sustaining and recovering attentional performance requires interactions between the brain’s motivation and attention systems. The first experiment demonstrated that in rats performing a sustained attention task (SAT), presentation of a distractor (dSAT) augmented performance-associated increases in cholinergic neurotransmission in prefrontal cortex (PFC). Because stimulation of NMDA receptors in the shell of the nucleus accumbens (NAC) activates PFC cholinergic neurotransmission, a second experiment demonstrated that bilateral infusions of NMDA into the NAC shell, but not core, improved dSAT-performance to levels observed in the absence of a distractor. A third experiment demonstrated that removal of prefrontal or posterior parietal cholinergic inputs, by intra-cortical infusions of the cholinotoxin 192 IgG saporin, attenuated the beneficial effects of NMDA on dSAT perfomance. Mesolimbic activation of cholinergic projections to the cortex benefits the cognitive control of attentional performance by enhancing the detection of cues and the filtering of distractors.

Substantial gains have been made on the neurobiology of attention from systems neuroscience work in animal models and human cognitive neuroscience. However, the integration of rodent-based research on the specific neurotransmitter systems that subserve attention with the results from human behavioral and neuroimaging studies has been hampered by the lack of tasks that validly assess attention in both species. To address this issue, an operant sustained attention task that has been extensively used in research on the neurobiology of attention in rats was re-designed and validated for use in humans. Although humans showed better performance overall, the two species showed similar effects of several attention-related variables, including the introduction of distractor-related challenge. This task provides a useful tool for integrative, cross-species research, and may help to determine how specific neurotransmitter systems contribute to the hemodynamic changes observed in human functional neuroimaging experiments.Keywords sustained attention; rat; human; distraction; cross-species Animal models play a critical role in research designed to determine the neuronal bases of cognition and behavior. In particular, animal research provides a degree of experimental control and precision not usually feasible in studies using human subjects, as well as avenues for manipulating and monitoring specific neurotransmitter and receptor systems. Attempts to use evidence from animal-based research to inform the design and interpretation of human studies inherently assume that different species draw on similar cognitive processes to perform tasks that are similar in terms of face validity. However, this assumption has been rarely tested, limiting the potential benefits of direct cross-utilization of evidence. Perhaps as a result, treatment approaches for cognitive disorders that are based on animal research frequently fail to translate into clinical efficacy (e.g., Sarter, 2004Sarter, ,2006. This paper describes a set of studies designed to address this issue by characterizing human performance in a task (McGaughy & Sarter, 1995) that has been extensively used in rat research to determine the role of the cholinergic system in sustained attention and in responding to challenging situations that require the intentional, top-down control of attention (for review see Sarter, Hasselmo, Bruno, & Givens, 2005). Here, we compare rat and human performance patterns on the sustained attention task (SAT) under standard conditions and under distraction * Corresponding author: E-mail: clustig@umich.edu NIH Public Access Author ManuscriptNeuropsychology. Author manuscript; available in PMC 2009 July 2. Published in final edited form as:Neuropsychology. 2008 November ; 22(6): 787-799. doi:10.1037/a0013712. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript (dSAT). Our main focus is on the distraction condition, which in rats has been biologically linked to increased acetylcholine efflux and theoretically linked to an i...

Maintaining attention and performance over time is an essential part of many activities, and effortful cognitive control is required to avoid vigilance decrements and interference from distraction. Regions at or near right middle frontal gyrus (Brodmann’s area (BA) 9), as well as in other prefrontal and parietal areas, are often activated in studies of sustained attention (e.g., Cabeza & Nyberg, 2000; Kim et al., 2006; Lim et al., 2010). This activation has often been interpreted as representing the engagement of cognitive control processes. However, such studies are typically implemented at one level of task difficulty, without an experimental manipulation of control demands. The present study used the distractor condition sustained attention task (dSAT), which has been used extensively in animals to determine the role of neuromodulator systems in attentional performance, to test the hypotheses that BA 9 is sensitive to changes in the demand for cognitive control and that this sensitivity reflects an increased engagement of attentional effort. Continuous arterial spin labeling (ASL) was used to measure neural activity in sixteen healthy, young adults performing a sustained attention task under standard conditions and under a distraction condition that provided an experimental manipulation of demands on cognitive control. The distractor impaired behavioral performance and increased activation in right middle frontal gyrus. Larger increases in right middle frontal gyrus activity were associated with greater behavioral vulnerability to the distractor. These findings indicate that while right middle frontal gyrus regions are sensitive to demands for attentional effort and control, they may not be sufficient to maintain performance under challenge. In addition, they demonstrate the sensitivity of ASL methods to variations in task demands, and suggest that the dSAT may be a useful tool for translational cross-species and clinical research.

Both the passage of time and external distraction make it difficult to keep attention on the task at hand. We tested the hypothesis that time-on-task and external distraction pose independent challenges to attention, and that the brain’s cholinergic system selectively modulates our ability to resist distraction. Participants with a polymorphism limiting cholinergic capacity (Ile89Val variant (rs1013940) of the choline transporter gene SLC5A7) and matched controls completed self-report measures of attention and a laboratory task that measured decrements in sustained attention with and without distraction. We found evidence that distraction and time-on-task effects are independent and that the cholinergic system is strongly linked to greater vulnerability to distraction. Ile89Val participants reported more distraction during everyday life than controls, and their task performance was more severely impacted by the presence of an ecologically valid video distractor (similar to a television playing in the background). These results are the first to demonstrate a specific impairment in cognitive control associated with the Ile89Val polymorphism, and add to behavioral and cognitive neuroscience studies indicating the cholinergic system’s critical role in overcoming distraction.

Given the information overload often imparted to human cognitive-processing systems, suppression of irrelevant and distracting information is essential for successful behavior. Using a hybrid block/event-related fMRI design, we characterized proactive and reactive brain mechanisms for filtering distracting stimuli. Participants performed a flanker task, discriminating the direction of a target arrow in the presence versus absence of congruent or incongruent flanking distracting arrows during either Pure blocks (distracters always absent) or Mixed blocks (distracters on 80% of trials). Each Mixed block had either 20% or 60% incongruent trials. Activations in the dorsal frontoparietal attention network during Mixed versus Pure blocks evidenced proactive (blockwise) recruitment of a distraction-filtering mechanism. Sustained activations in right middle frontal gyrus during 60% Incongruent blocks correlated positively with behavioral indices of distraction-filtering (slowing when distractersmightoccur)andnegativelywithdistraction-relatedbehavioralcosts(incongruentvscongruenttrials),suggestingaroleincoordinating proactive filtering of potential distracters. Event-related analyses showed that incongruent trials elicited greater reactive activations in 20% (vs 60%) Incongruent blocks for counteracting distraction and conflict, including in the insula and anterior cingulate. Context-related effects in occipitoparietal cortex consisted of greater target-evoked activations for distracter-absent trials (central-target-only) in Mixed versus Pure blocks, suggesting enhanced attentional engagement. Functional-localizer analyses in V1/V2/V3 revealed less distracter-processing activity in 60% (vs 20%) Incongruent blocks, presumably reflecting tonic suppression by proactive filtering mechanisms. These results delineate brain mechanisms underlying proactive and reactive filtering of distraction and conflict, and how they are orchestrated depending on distraction probability, thereby aiding task performance.