When you focus your attention on specific stimuli found in your environment you are engaging in the?

Sustained attention

Sustained attention refers to maintaining vigilance, or tonic alertness, over time and has been associated with a cingulo-opercular network (Sadaghiani and D’Esposito, 2015) as well as dorsolateral PFC and inferior parietal lobe, particularly in the right hemisphere (Sarter et al., 2001). However, a recent study demonstrated that sustained attention ability is predicted by whole-brain functional connectivity during rest and that only 27% of high sustained attention network edges were located within frontoparietal regions (Rosenberg et al., 2015). Thus, additional research is necessary to elucidate the neuroanatomic substrate associated with sustained attention.

Previous studies of selective attention in aging yield conflicting reports that have hindered a definitive conclusion regarding the effects of age on sustained attention (for reviews, see Davies and Parasuraman, 1982; Giambra, 1993). Because sustained attention is typically assessed via paradigms that require participants to either respond to infrequent targets or withhold responses to infrequent targets, some of this heterogeneity may stem from differential contributions of top-down and bottom-up processes between tasks (Staub et al., 2013). Aside from task-based differences, several other factors may help account for this heterogeneity, particularly age, motivation, and task difficulty. Regarding age, equivalence in sustained attention performance between younger and older adults has been observed when the older adult population is aged 50–69 years (Berardi et al., 2001; Carriere et al., 2010). Yet, in older adults aged 70 + years, deficient sustained attention is more consistently observed (Parasuraman and Giambra, 1991; Filley and Cullum, 1994; Mani et al., 2005). In addition to age, motivation is known to affect sustained attention ability (Oken et al., 2006; Esterman et al., 2016), and older adults have reported higher motivation and less mind wandering than younger adults during sustained attention tasks, which may help maintain equivalent performance (Staub et al., 2014). Finally, differences in sustained attention have also been reported under increased perceptual demands, such that age-equivalence may be observed with low perceptual demands but age-related declines become apparent as perceptual demands increase, thereby increasing task difficulty (Parasuraman et al., 1989; Mouloua and Parasuraman, 1995). Together, accounting for age, motivation, and task difficulty helps reconcile many of the disparate findings in the literature on sustained attention and aging.

It is worthwhile to note that, with increasing demands on sustained attention, older adults may retain accuracy at the expense of response time (Thomson and Hasher, 2017), suggesting a differential strategy in aging (Staub et al., 2015). In support of this, an impressive study with more than 10,000 participants assessed both strategy and sustained attention ability across the life span and demonstrated that increased age is associated with a more conservative strategy and lower sustained attention ability (Fortenbaugh et al., 2015). Therefore, it may be hypothesized that older adults compensate for sustained attention declines by adopting a more conservative approach that minimizes performance decrements. However, additional research will be required to test this hypothesis.

Unfortunately, there is limited research assessing age-related differences in the neural mechanisms underlying sustained attention. Studies using the attention network task have shown age-related declines in the ability to capitalize on alerting cues (Gamboz et al., 2010; Kaufman et al., 2016) (but also see Zhou et al., 2011), which may index sustained attention (Oken et al., 2006). Because the alerting attention network has been associated with PFC, parietal, and thalamic regions (Fan et al., 2005), this could indicate age-related declines in sustained attention may stem from deficiencies in these areas. Research using a change detection (delay match to sample) task corroborates the idea that impaired sustained attention in aging may be due to altered PFC function (Chao and Knight, 1997). Nonetheless, additional research is required to better characterize the anatomic and physiological changes in aging that underlie sustained attention ability.

Sustained attention is fundamental to multiple cognitive domains, so it is not surprising that sustained attention ability can differentiate healthy aging from mild cognitive impairment (López Pérez-Díaz et al., 2013). Moreover, deficits in sustained attention are associated with frailty in older adults (i.e., low gait speed, low grip strength, low physical activity, weight loss, exhaustion) (O’Halloran et al., 2014). Thus, assessments of sustained attention ability may serve to identify various pathologic changes in aging.

In summary, sustained attention ability is highly heterogeneous in the aged population, but accounting for age, motivation, and task difficulty may help predict when age-related deficits are observed. Although additional research is necessary to understand the anatomic and neurophysiological changes associated with age-related declines in sustained attention, current evidence points to a deficient cingulo-opercular network and other PFC and parietal regions. Because sustained attention is fundamental to multiple cognitive domains and is associated with physical frailty, it may serve to differentiate healthy from pathologic aging. However, sustained attention research is limited and much work remains before strong conclusions may be drawn regarding the effects of age on sustained attention ability.

Sustained attention

Sustained attention indicates the ability to sustain attention over time in specific goal-directed behaviors. Patients with TBI are particularly impaired at maintaining consistent attention because of primary (neuropathology) or secondary (fatigue, sleep disorders, or depression) factors (Stuss et al., 1989; Whyte et al., 1995). Although several studies have investigated the effect of TBI on sustained attention (Serino et al., 2006; Whyte et al., 2006), it is still unclear if TBI causes sustained attention impairments. Early studies on sustained attention involved relatively long tasks (> 10 minutes) to examine time-on-task effects. These studies focused on vigilance decrement and performance variability across time. These tasks required continuous responses to targets and nontargets or responses only to infrequent targets. The findings of these studies were mixed; several reported no evidence of sustained attention deficits (Spikman et al., 1996; Serino et al., 2006) while other studies reported significant deficits (Whyte et al., 1995). The inconsistency of the results may be due to methodological differences across studies or to the measures used to investigate sustained attention.

Impairments to sustained attention after TBI may depend on the areas damaged during injury. Lesion studies with TBI patients suggested the frontoparietal network play a role in sustained attention (Rueckert and Grafman, 1996; Malhotra et al., 2009). TBI patients with lesions to the frontal and parietal lobes showed longer reactions times and missed more targets than healthy matched controls in simple reaction time tasks.

Other studies have also investigated the effect of secondary factors, such as fatigue, on sustained attention deficits, using the Psychomotor Vigilance Task (PVT) (Dinges and Powell, 1985). Patients with TBI showed significant deficits during the PVT, such as slow reaction time and increased response variability, when compared to healthy controls. Distribution analyses indicated that the deficits were likely due to general cognitive slowing. In addition, self-reported fatigue effected overall attention performance (Sinclair et al., 2013). The PVT has shown its effectiveness in detecting sustained attention deficits after TBI.

Effects of Arousal on Novelty Detection

If sustained attention can facilitate processing speed in habituation tasks, how does sustained attention relate to novelty detection and memory? To manipulate arousal, experimenters often expose the infant to a highly salient stimulus, such as a movie clip. Images of the to-be-remembered object are then interspersed with the presentation of the movie clip, and HR is recorded. These types of studies have found that sustained attention during presentation of the to-be-remembered object is related to greater novelty preferences at test. In fact, exposure to a stimulus for just 5 or 6 s during sustained attention results in novelty preferences at test. Furthermore, infants are more likely to show a novelty preference at test when they are ‘tested’ during the sustained-attention phase; if in the attention in contrast termination phase, infants tend to look equally long at the novel and familiar stimulus. Combined, the results of these studies indicate that sustained attention, or increased arousal, facilitates the infant’s ability to acquire information about a stimulus, resulting in faster habituation and enhanced novelty detection at test.

VI Conclusions

Sustained attention represents a fundamental component of the cognitive capacities of humans. Aberrations in the ability to properly monitor significant sources of information rapidly develop into major cognitive impairments. Human neuropsychological and functional imaging studies have indicated frontoparietal areas, particularly in the right hemisphere, as being prominently involved in the mediation of sustained attention or vigilance. Animal experimental evidence strongly supports the basal forebrain corticopetal cholinergic projection as a major component of the neuronal circuits mediating sustained attention performance. Future research will test the prediction that sustained attention performance-associated increases in cortical acetylcholine release mediate the activation of the anterior attention system and, in parallel, sensory cortical areas, and that the interactions between the direct effects of acetylcholine in sensory regions and the top-down modulation of sensory processing by the anterior attention system are required for proper sustained attention performance. Furthermore, hypotheses suggesting that aberrations in the integrity or afferent regulation of corticopetal cholinergic systems mediate the alterations in sustained attention as they contribute to schizophrenia, dementia, as well as other disorders, require investigations in humans, particularly using PET combined with radiotracers for markers for cholinergic transmission and muscarinic and nicotinic receptor function, as well as the generation of valid animal models on the long-term attentional effects of changes in cortical cholinergic inputs. Such studies will also clarify the significance of the hypothesis that the right frontoparietal circuits dominate over left cortical areas in the mediation of sustained attention performance.

Given the close theoretical relationships between different aspects of attention (sustained, selective, and divided), it should not be surprising that the available data from neuropsychological, functional imaging, and animal experimental studies suggest extensive overlaps in the circuits mediating different aspects of attention. For research purposes, it is important to maintain clear definitions of the aspects of attention studied. However, with respect to real-life performance, and to the underlying brain mechanisms, those differentiations may turn out to be of more limited significance. Monitoring a particular source of information requires the selection of such a source and the rejection of competing sources and also the allocation of processing resources to this task. Obviously, such tasks cannot be performed without mnemonic processing, taxing additional executive functions. Likewise, impairments in attention are difficult to conceive as remaining restricted to a particular aspect of attention, and suggestions for such specific impairments in patients have overly relied on dissociations in performance on standardized tests. Thus, the current reductional attempts to determine the neuronal circuits mediating specific aspects of attentional functions represent a first step toward a more comprehensive understanding of the multiple circuits that allow us to effectively attend to our environment and our cognitive operations.

II. SUSTAINED ATTENTION

Sustained attention or vigilance is measured in continuous performance-type (CPT) tasks that require constant monitoring of the situation at hand. Vigilance tasks usually entail a consistent decrement in performance (i.e., a lengthening of reaction times and decrease in signal detection) with increasing time on task. Typically, sustained attention tasks fall short of the typical definitions of vigilance, but nevertheless require sustained effort to perform adequately. In one basic form of the CPT, the subject is presented with a series of letters or numbers (usually presented on a computer screen) and is asked to respond only to a certain character (the letter X, for example), which appears infrequently. In another, working memory version of the task, the individual is asked to respond to a certain character only if it is immediately preceded by a cue character (i.e., the person responds to the letter X only if the letter A immediately precedes it) (Rosvold et al., 1956).

In animals, it is quite difficult to dissociate so-called vigilance decrements in response latencies from general satiety or reduction in motivation, as the animal generally performs for a prolonged period and, thus, has been similarly rewarded for prior performance, perhaps to the point of satiety. Satiety effects can, however, be dissociated in well-designed tasks, by examining trials completed and latencies to collect food reward.

The five-choice serial reaction time task (5CSRT) is one such task that has been used extensively in the study of the neural mechanisms underlying visuospatial sustained attention in the rat (see Robbins, 2002, for a history and review of the task). At its core, this task has both continuous performance and spatial elements. The basic task requires the animal to scan a horizontal array of five nose-poke apertures in the rear of an operant chamber and respond to a brief flash of light (0.5 second) presented randomly behind one of the apertures. Responding correctly to the illuminated hole produces a food pellet in the magazine situated at the front of the chamber. Responding to an incorrect (non-illuminated) hole (commission error) or failing to respond within a prescribed time limit after stimulus presentation (omission error) results in a 5-second “time-out” punishment period, as does responding within the intertrial interval, prior to stimulus presentation (premature response). Effects of distractor stimuli (interpolated bursts of white noise) index attentional selectivity; and making the target stimuli temporally unpredictable or stimulus degradation (e.g., decreases in stimulus duration or stimulus intensity) taxes additional attentional resources. As the task requires inhibition of premature responses, it involves primarily the “anterior attentional network” including the rat frontal cortex.

Another test of visual sustained attention, which requires a forced choice between two levers (“yes” and “no”) to detect a signal, has been used to measure a vigilance decrement (McGaughy and Sarter, 1995; Sarter et al., 2001). However, although this task usefully allows a signal detection analysis, the decrement does not usually occur in untreated animals. This paradigm has also been modified to study attention divided across modality (auditory and visual). Briefly, in this variant, rats are trained consecutively in visual and auditory conditional discrimination tasks before being required to perform both discriminations in the same trial block. A “frontoparietal” task, it presumably taps both attentional networks. Disadvantages of two-lever tasks include side and other response biases that make a purely attentional interpretation of performance difficult, especially when studying drugs such as the psychostimulants, which can have response-altering effects without altering attentional mechanisms per se.

2.4.1 Sustained attention to response task (SART)

Sustained attention was assessed using a modified version of the SART (Robertson et al., 1997). During the task, single digits (0 through 9) were continuously presented on screen one at a time for 250 ms, with each digit followed by an inter-trial-interval of 900 ms during which a fixation cross was presented. Participants were instructed to refrain from pressing the spacebar to the number 3 (target) and to press the spacebar for all other digits (non-targets) while emphasizing both accuracy and speed. Stimuli were presented in black font on a gray screen, and responses were recorded during the stimulus display or the inter-trial interval. Targets comprised 5% of trials, non-targets comprised 90% of trials, and probe questions comprised the remaining 5% of trials. Trial order was quasi-randomized so that targets were always separated by at least one other non-target digit.

Participants responded to two consecutive probe questions, which were randomly dispersed throughout the task, in order to assess spontaneous episodes of mind wandering (MW). The first probe (Probe 1) asked, “Where was your attention focused just before the probe?” with participants responding using a 6-point Likert scale ranging from 1 (on task) to 6 (off task). The second probe (Probe 2) asked, “How aware were you of where your attention was?” with participants responding from 1 (aware) to 6 (unaware). The questions were displayed until a response was provided.

After a 163-trial practice block, participants completed two experimental blocks which consisted of a total of 519 non-targets, 27 targets, and 28 sets of probes. Results from the practice block were not included in the analyses. SART outcomes included task accuracy, reaction time variability, and subjective probe responses. Accuracy was indexed by A′, a nonparametric measure of detection sensitivity. A′ yields a composite of hits (correctly withholding a response to target trials) and false alarms (incorrectly withholding a response to non-target trials) while allowing for the difference in frequency between target and non-target trials (see Stanislaw and Todorov, 1999, for calculations). Reaction time variability was assessed using the intra-individual coefficient of variation (ICV), which was calculated as the standard deviation RT of correct non-target trials divided by the mean RT of correct non-target trials (i.e., for each participant: standard deviation RT/mean RT). Greater ICV reflects more variation in response time, and prior research has suggested ICV may be a valid index of MW (Bastian and Sackur, 2013; Seli et al., 2013). Subjective probe responses were assessed using the mean of probe ratings, separately for each probe question.

1 SUSTAINED ATTENTION TASKS

Sustained attention refers to the ability to maintain attentional focus on relevant stimuli with repeated presentation over extended periods. Vigilance tasks are the prototypic procedure used for measuring sustained attention. Vigilance procedures vary in form but generally have several features in common. A stimulus (the signal or target) that controls some response is presented aperiodically and infrequently relative to background stimulus conditions (“noise”). The background stimulus conditions may be constant, such as white noise, or composed of discrete presentations of nontarget or distracter stimuli that are usually similar to the target (e.g., different spoken words or visual letters). Discriminative stimuli or signals may be of short duration or otherwise difficult to discriminate from background conditions, but above-discrimination thresholds and reliably responded to under nonvigilance conditions. The task is continuous over a prolonged session (usually 1–2 hr) and responding does not affect the probability of stimulus presentations. Measures of stimulus control can be accuracy (percentage of stimulus presentations that produce responses) and/or reaction time/latency to respond to the “target” stimulus. In addition, the number of responses made in the absence of the stimulus is measured.

The robust result of vigilance studies is a reliable decrement in the proportion of stimuli that produce reporting responses and/or in the speed of responding to S + as a function of time in the session. The magnitude and rapidity of these decrements are said to measure the capacity to sustain focused attention, or “attention span.” The decrement has been demonstrated to occur sooner as a function of neuropsychiatric impairment, aging, and MR (e.g., Warm & Berch, 1985).

Procedural variables also determine the course of sustained attention. Factors that increase the rapidity and magnitude of the decrement are a difficult targetnoise discrimination, a conditional versus a simple discrimination, high-frequency distracters and targets (e.g., 40 vs. 12 stimuli per min), and rare target events. Extreme values of these parameters can produce significant decreases in stimulus control within the first 5 min of the session, even after extended practice (Parasuraman & Giambra, 1991).

Various vigilance tasks have been used to assess cognitive side effects of psychotropic and antiepileptic medications in clinical and normal populations of adults and children of normal IQ (see reviews by Novelly et al., 1986; Rapport & Kelly, 1991; Wittenborn, 1978). Aman (1991) noted that these are the most extensively used procedures in pediatric psychopharmacology. The task typically used is the continuous performance task (CPT). Two general versions of this task have been used, one requiring simple successive discrimination and the other adding a requirement for conditional control. In the former, the subjects must respond to a single S + that is presented less frequently than one or more S–’s. For example, the letter X is the target with other letters as distracters. In the conditional version, the target stimulus functions as an S + only if it has been preceded by a specified stimulus. For example, the letter X is the S +, but only if preceded by the letter A; otherwise, X is an S–.

The literature contains little information on vigilance tasks in general in subjects functioning below the mild level of MR (see Warm & Berch, 1985, for a review). Moreover, we found no study of subjects with MR on the effects of drugs on sustained attention, per se. Although the CPT has been used, the studies have used short duration sessions and have not focused on performance decrements across the session. Short duration sessions are likely to reduce the sensitivity of the procedure to drug effects.

Studies using the CPT in short duration sessions do give some indication of the range of subjects who can perform the task with little training (usually with instruction). In a procedural review, Aman (1991) noted that few subjects with IQs below 40 or 50 could perform the task. Because continuous attention tasks have been widely used in the drug literature on normally capable subjects, it seems wise to fully develop their use in studies of subjects with MR.

The range of possible subjects can be increased by using training procedures that do not rely on verbal instructions. Procedures for training successive discrimination, such as stimulus fading, are applicable (for options, see Lancioni & Smeets, 1986; Spradlin, Locke, & Fulton, 1969; Stoddard & Mcllvane, 1989; Terrace, 1963). In addition, explicit reinforcement procedures will be necessary to maintain responding over long duration sessions in people who are not responsive to instructions (Baron & Galizio, 1983). For example, Perryman, Halcomb, and Landers (1981), studied subjects with mild MR in a 68-min simple-discrimination CPT. Response-contingent reinforcement completely eliminated the across-session performance decrement shown under no-feedback conditions. This raises important issues about the use of these procedures. The effects of reinforcement, feedback, and repeated practice on sustaining attention in people with MR are largely unexplored. Further development of these tasks with subjects functioning across a range of mental ages is required before these procedures can be used as drug baselines.

Continuous Performance Tests

Sustained attention as a cognitive process was first introduced during World War II when military personnel were required to monitor radar to detect enemy signals (Mackworth, 1948). This idea led to the creation of CPTs to examine sustained attention in a clinical setting. The CPT as a clinical tool has been in use since the 1950s (Rosvold, Mirsky, Sarason, Bransome, & Beck, 1956); however, CPTs were originally designed to study traumatic brain injury in children and adults. It was not until the 1970s that CPTs were utilized to examine attention in individuals with attention dysregulation (Kupletz & Richardson, 1978). As technology progressed, so did the CPTs, leading to tests designed to be administered on a personal computer or specialized machines. As CPTs advanced, scores for other domains besides sustained attention began to be incorporated into CPT output. CPTs today are designed to assess inattention, impulsivity, sustained attention, and vigilance. Four commonly utilized CPTs include the Conners Continuous Performance Test—3rd Edition (CPT-3; Conners, 2015), the Test of Variables of Attention (TOVA), the Integrated Visual and Auditory Continuous Performance Test (IVA+Plus), and the GDS. These tests, in addition to the GDS, are administered via a computerized software program. The tools necessary to administer the tests include a computer, keyboard, and mouse. A primary difference among the tests includes the modality in which the target stimuli are presented (e.g., auditory, visual, auditory and visual).

There are hundreds of studies that examine different types of CPTs and the role they can play in the diagnosis of ADHD in children and adults. Studies have examined the correlation between reported behavioral symptoms of ADHD and performance on CPT, the CPTs ability to differentiate between an ADHD group and a typical group, and the CPTs ability to differentiate an ADHD group from another clinical group.

Several studies have examined the relationship between performance on the CPT and behavior rating scales. In an early study examining CPTs as a diagnostic tool for children with ADHD, Klee and Garfinkle (1983) administered a CPT test to 51 children in an inpatient hospital. They found that the CPT significantly correlated with other psychological measures as well as with parent and teacher rating scales that specifically address inattention. Epstein et al. (2003) examined the relationship between CPT performance and the 18 ADHD criteria according to the DSM-IV-TR. They found that “CPT performance measures demonstrated significant relationships to ADHD symptoms” (p. 543). Specifically, they reported that commission errors and mean reaction time were strongly related to a constellation of ADHD symptom criteria. Other studies comparing CPT performance to behavior rating scales have also found significant correlations between CPT outcome variables and behaviors associated with ADHD (Murphy, 2007; Raggio, Rhodes, & Whitten, 1999).

While some studies have found a significant relationship between rating scales and CPTs as previously noted, others have found little to no significant correlations between them. Bodnar, Prahme, Cutting, Denckla, and Mahone (2007) researched the relationship between parent ratings and performance-based measures, including the CPT. In their two studies, they found that the Behavior Rating Inventory of Executive Function inhibition scale did not strongly correlate with the CPT-II or the TOVA. In another study, Kallitsoglou (2013) examined the relationship between factors assessed by a CPT and teacher rating scales. The author concluded that there was not a strong correlation between CPT outcomes and teacher’s ratings of children’s inattention and hyperactivity in the classroom setting. Several other studies have found nonsignificant relationships between behavior rating scales and continuous performance tests (Naglieri, Goldstein, Delauder, & Schwebach, 2005; Sims & Lonigan, 2012). The mixed results of CPT studies adds further support that, while a CPT can add valuable information to a comprehensive evaluation, results should be considered with all available information when making diagnostic decisions.

In terms of differentiating ADHD groups from typical peers, a meta-analysis of 47 between group studies by Huang-Pollock, Karalunas, Tam, and Moore (2012) found that children with ADHD committed more errors and demonstrated slower or more variable reaction times. While this meta-analysis supports the use of CPTs to differentiate individuals with ADHD from those without the diagnosis, other studies have found that CPTs alone does not differentiate groups (Corkum & Siegel, 1993; Schachar, Logan, Wachsmuth, & Chajczyk, 1988; Werry, Elkind, & Reeves, 1987). In addition, some studies have found that CPTs are less useful when trying to make a differential diagnosis between other clinical subgroups (Barkley, DuPaul, & McMurray, 1990; Koriath, Gualtieri, Van Bourgondien, Quade, & Werry, 1985). Of particular interest for this chapter, many studies have found that the CPT does not reliably discriminate between children with ADHD and children with reading disabilities. Specifically, children with reading disabilities also tend to perform poorly on CPTs (McGee, Clark, & Symons, 2000; Eliason & Richman, 1987; Tarnowski, Prinz, & Nay, 1986). While the research is mixed, it appears that the CPT can be useful in distinguishing clinical groups from nonclinical groups, but is not specific in differentiating those with only ADHD.

Preliminary research has also examined the use of the CPT as a mobile application for a cellular phone. For example, SnappyApp is a CPT application for the phone that takes into account both responding and the movement of the person completing a given task. Movement is measured through the accelerometer and gyroscope sensors in the phone. The data provide information on the amount of physical activity of the participant while completing the task (Young, Craven, Groom, & Crowe, 2014). Infrared movement analysis is also utilized in combination with some CPT paradigms in order to gather additional information for a more objective approach to diagnosis (Reh et al., 2013; Teicher, Ito, Glod, & Barber, 1996). Teicher and colleagues utilized an infrared movement analysis system to track head movements of children while they completed a CPT task for the research study. They found that boys with ADHD moved their heads 2.3 times more frequently than children without ADHD, demonstrating that boys with ADHD fidget more than their peers without the diagnosis. This preliminary research on technological advances with CPTs is promising.

Attentional Deficits Resulting From Nicotine Withdrawal in Humans

Sustained attention or vigilance refers to the process that facilitates the ability to discriminate between relevant (target) stimuli and irrelevant distractors (non-target stimuli) (Sarter & Paolone, 2011). There are numerous behavioral tasks available to objectively measure sustained attention in humans. The most widely used test for assaying attention in clinical trials is the Continuous Performance Test (CPT), an umbrella term for a variety of tasks where the common denominator is that they all require a subject to respond to certain target stimuli, but withhold from responding to specified non-target stimuli (eg, when the letter “X” appears in the X-CPT). Some versions are more complex, requiring a sequence of target alphanumeric numbers to appear, such as in the Rapid Visual Information Processing test [RVIP (Lawrence, Ross, Hoffmann, Garavan, & Stein, 2003)]. Irrespective of the version and its complexity, however, all CPTs require responses to target stimuli and the inhibition of responding from non-target stimuli.

Many CPT versions have been used to measure attentive performance of people during smoking abstinence. For example, both male and female adults abstinent from smoking for 17, but not 5 h, made more omission errors and reacted slower in the Connors’ CPT (Harrison, Coppola, & McKee, 2009). In adolescent children, however, no change in performance was observed on two CPT versions after 24 h of abstinence (Jacobsen et al., 2005). In other studies, overnight abstinence resulted in reduced correct responses and increased response time variability in adults performing the CPT (Myers, Taylor, Moolchan, & Heishman, 2008), but no change in discriminability (d-prime), a calculated measure reflecting attention, in the Connors’ CPT (Ashare & Hawk, 2012). A more thorough longitudinal examination importantly demonstrated that inhibitory control as measured by CPT commission errors predicted relapse at 1 and 3 months after quitting [see Fig. 2.1; (Powell, Dawkins, West, Powell, & Pickering, 2010)]. A slower reaction time on the RVIP task was observed as quickly as 30 min after smoking cessation (Hendricks, Ditre, Drobes, & Brandon, 2006). Hence, it is clear that adults undergoing smoking abstinence demonstrate impaired attentional performance as measured by CPTs and CPT-like tasks, aspects of which predict smoking relapse.

Other indirect support for nicotine withdrawal causing attentional deficits comes from studies demonstrating that nicotinic treatments attenuate these deficits. Wesnes and Warburton demonstrated decades ago the potential for nicotine to improve attention, specifically so in individuals that are undergoing withdrawal (Wesnes & Warburton, 1983; Wesnes, Warburton, & Matz, 1983). More recent studies support these initial findings demonstrating that following overnight cigarette abstinence, nicotine replacement therapy improved the number of target responses compared to placebo in the Conners CPT and RVIP (Atzori, Lemmonds, Kotler, Durcan, & Boyle, 2008; Myers et al., 2008). Such nicotine replacement therapy also improved attention (as measured by d-prime) compared to placebo in an identical pair version of the CPT (Dawkins, Powell, West, Powell, & Pickering, 2007). Transdermal nicotine also increased attentional measures in female smokers performing the CPT (Poltavski, Petros, & Holm, 2012) and alcohol-dependent individuals compared to placebo (Boissoneault, Gilbertson, Prather, & Nixon, 2011). These studies provided sufficient evidence that more selective treatments targeting specific nicotinic acetylcholine receptor (nAChR) subunits might provide alleviation of attentional deficits without the need to utilize the prototypical nAChR ligand nicotine.

Other nicotinic agents have demonstrated efficacy at blocking smoking withdrawal–induced inattention in humans. The full α7 and partial α4β2 nAChR agonist varenicline increased the number of correct responses and reduced reaction times compared with placebo following 72 h of abstinence (Patterson et al., 2009). Varenicline also improved reaction times during the Connors’ CPT following overnight abstinence (Ashare & McKee, 2012). The weak norepinephrine/dopamine reuptake inhibitor and α3β4 nAChR antagonist buproprion (Bondarev, Bondareva, Young, & Glennon, 2003; Foley, DeSanty, & Kast, 2006) also alleviated withdrawal-induced inattention (Perkins, Karelitz, Jao, Gur, & Lerman, 2013). Other studies have also demonstrated nicotinic agents can improve attention, especially during periods of withdrawal (Dawkins et al., 2007). Although some differences in findings have been reported, these differences are likely a result of altered abstinence duration protocols and specific task parameters (Ashare, Falcone, et al., 2014). Importantly, nAChR agents and dopaminergic agents can alleviate withdrawal-induced inattention.

In addition to nicotine-induced improvement in attention in subjects undergoing nicotine withdrawal, nicotine-induced improved attention has also been observed in nonsmoking healthy adults. These improvements were driven by increased target responding (Levin et al., 1998) and/or reduced commission errors (Myers, Taylor, Salmeron, Waters, & Heishman, 2013) in the CPT. This nicotine-induced enhancement in attention drove theories that the high rate of smoking in psychiatric patients is for self-medication purposes, a self-driven attempt to improve their cognitive functioning (Evans & Drobes, 2009). This point is of importance because various mentally ill patients exhibit attentional deficits, with reduced cognition in general being closely linked to functional outcome (Green, 2006). Hence, many researchers have attempted to understand the neural mechanisms underlying such attentional deficits in psychiatric patients to develop procognitive treatments. Subsequently, nAChRs have become an important target for procognitive enhancement in psychiatric disorders (Bidwell, McClernon, & Kollins, 2011; Demeter & Sarter, 2013; Martin et al., 2007; Young & Geyer, 2013), in part given the overlap of attentional deficits and improvements associated with nicotine use already described.

3.1 PET and fMRI

These techniques measure hemodynamic response and have a good spatial resolution (∼4 mm) but poor temporal resolution (several seconds). Cabeza and Nyberg (2000) provide a valuable review of imaging during cognition. In general, these studies display bilateral activations that contrast with the asymmetric effect of lateralized lesions.