Distributed attentional deficits in chronic methamphetamine abusers: Evidence from the Attentional Network Task (ANT)
Highlights
► We tested methamphetamine abusers and controls on an integrated attention task. ► The task measured attentional alertness, orienting, and conflict resolution. ► MA abusers displayed deficits in cognitive control and conflict resolution. ► These deficits may reflect a specific vulnerability in executive function.
Introduction
Addiction is a brain disease that involves dysfunction and morphological changes in the neural systems that regulate responsivity to reward and pleasure (Jentsch and Taylor, 1999, Kalivas and Volkow, 2005). In addicted individuals, the ability to refrain from activities that will result in negative consequences is often compromised due to changes in the neurobiology of the brain that govern decision-making and self-control (Jentsch & Taylor, 1999). It has been shown through elegant animal work (Cadet and Krasnova, 2009, Yamamoto et al., 2010) as well as neuroimaging studies of the addicted brain (Volkow, Fowler, & Wang, 2004) that neural changes occurring after long-term drug use are widely distributed, comprising multiple brain regions and diverse neurotransmitters (Kalivas and Volkow, 2005, Koob, 1998, Koob and Moal, 2006, Nestler and Malenka, 2004). Thus any investigations that delve into the behavioral sequelae of drug abuse should consider a network approach to the investigation of cognitive function.
One drug that has taken center stage in the global arena of substance abuse and addiction is methamphetamine (MA). In the past decade the use of the stimulant MA has increased in the general population, with worldwide abuse of amphetamines surpassing that of cocaine and opiates combined (Nations, 2004). It is now estimated that approximately 5% of the adult population in the United States have used MA on at least one occasion with worldwide use estimated to be 33 million users (Roehr, 2005). MA is known to damage the dopaminergic, serotonergic and glutamatergic systems (Davidson et al., 2001, Quinton and Yamamoto, 2006, Yamamoto and Bankson, 2005). The highly addictive nature of MA, as well as its neurotoxicity to the human brain that can produce clinical, physical and psychiatric symptoms, makes MA a major public and mental health concern in the 21st century.
Long-term MA abuse causes widespread damage to many brain regions including the striatum, prefrontal cortex, anterior cingulate cortex and amygdala (Davidson et al., 2005, Davidson et al., 2001). Such distributed damage may contribute to the broad range of cognitive deficits observed in MA dependent human subjects. Cognitive deficits have been observed in MA dependent individuals with increased performance deficits appearing on tasks that require the suppression of task irrelevant information (Kalechstein et al., 2003, Monterosso et al., 2005, Salo et al., 2008, Salo et al., 2007), decision-making (Paulus et al., 2003, Paulus et al., 2005), and working memory (Chang et al., 2002, McKetin and Mattick, 1997, McKetin and Mattick, 1998). In contrast, implicit tasks of cognitive function appear to be less affected (Salo et al., 2008, Salo et al., 2011). Although numerous studies have probed focused higher-level cognitive function in MA abusers, to the best of our knowledge, few have examined the interaction of basic bottom-up driven processes with more top-down behavioral regulation (Hoffman et al., 2006, Kalechstein et al., 2003, Monterosso et al., 2005, Monterosso et al., 2006, Monterosso et al., 2007, Nordahl et al., 2003, Paulus et al., 2003, Paulus et al., 2005, Salo et al., 2009, Salo et al., 2002, Salo et al., 2005, Salo et al., 2006, Salo et al., 2007, Simon et al., 2002a, Simon et al., 2002b, Simon et al., 2000). Given the fact that MA has widespread effects on the human brain it was of interest to study cognitive deficits in MA abusers using a task that measures a distributed network of attentional function, the Attentional Network Task (ANT).
The ANT is a validated test that measures multiple cognitive operations within a single paradigm and thus is a powerful tool for the investigation of how potential cognitive deficits following long-term MA abuse may interact with each other (Fan, McCandliss, Sommer, Raz, & Posner, 2002). Three attentional networks have been defined in both anatomical and functional terms (Posner and Fan, 2008, Posner and Petersen, 1990). These functions involve alerting, orienting, and executive attention. The ANT measures responses to unpredictably occurring non-spatial cues to test the alerting network, spatial cueing (Posner, 1980) to test the orienting network and attentional conflict (i.e., flanker interference) to test the executive network (Eriksen & Eriksen, 1974). Alerting refers to the tonic maintenance of attention over prolonged periods but also to engaging “bursts” of phasic attention under certain situations where extra attention is needed, such as in the ANT (Sturm & Willmes, 2001). Orienting refers to either the voluntary (endogenous or under conscious control) or reflexive (endogenous or captured by bottom-up attention capture) orienting of attention (Posner, 1980, Posner and Petersen, 1990). Executive control of attention refers to more complex operations such as detecting and resolving conflicts between different activated task sets (Botvinick et al., 2001, Bush et al., 2000, MacDonald et al., 2000).
It has been proposed that these processes are subserved by different anatomical brain networks (Fan, Byrne, Worden, Guise, McCandliss, Fossella, 2007). Alerting is thought to be subserved by the thalamus, frontal and parietal brain regions and is modulated by the midbrain locus coeruleus/norepinephrine system (Coull et al., 1996, Fan et al., 2002). Orienting is thought to be subserved by the frontal eye fields and parietal regions while the executive control network is thought to be subserved by the anterior cingulate cortex and frontal regions (Fan, McCandliss, Fossella, Flombaum, & Posner, 2005).
However recent behavioral evidence suggests that although these processes are distinct, they are also integrated and interact with each other (Fuentes & Campoy, 2008). For instance experimental data suggests that alerting inhibits and orienting enhances executive control (Callejas et al., 2005, Fuentes and Campoy, 2008). Functional MRI evidence also suggests that although the brain networks subserving each of these attention constructs are distinct, they also overlap to some degree (Fan et al., 2005). Fan and colleagues found that there was overlap in the thalamus and left fusiform between alerting and conflict but no overlap between conflict and orienting. Furthermore, alerting modulates activity in the executive control network (Fan, Kolster, Ghajar, Suh, Knight, Sarkar, 2007). Studies in participants with schizophrenia (Lopez et al., 2011), PTSD (Leskin & White, 2007) and in those who heavily use cannabis (Abdullaev, Posner, Nunnally, & Dishion, 2010) suggest impairments in the executive control network and conflict resolution.
The ANT is designed to evaluate alerting, orienting and executive control within a single 30-min testing session that can be easily performed (Fan et al., 2002). A published study with 40 normal adult subjects reported that the ANT produced reliable single subject estimates of each of these three functions (Fan et al., 2002). Reaction time (RT) measures obtained from the ANT can be used to quantify the processing efficiency within each of these networks (i.e., alerting, orienting and executive function) as well as potential interactions between the three systems (Callejas et al., 2004, Callejas et al., 2005). Recent studies have modified the ANT to further assess the interaction of alertness, orienting and executive function; some of them combining auditory and visual stimuli (Callejas et al., 2004, Callejas et al., 2005). The goal of the present study was to examine a range of attentional functions in long-term but currently abstinent MA abusers using a modified version of the ANT that contains both visual and auditory stimuli (Callejas et al., 2004).
Section snippets
Subjects
Two groups were studied: 30 MA-abusers and 22 non-substance abusing control subjects. The MA-abusing group was recruited from six substance abuse treatment centers (one inpatient clinic and five outpatient clinics) and met DSM-IV criteria for lifetime MA dependence determined from the Structured Clinical Interview (SCID) (First, Spitzer, Gibbon, & Williams, 1995). Random urine screens were performed at the referring sites as well as on-site oral toxicology screens on the day of testing.
Results
A main effect of group was observed (F(1, 50) = 12.64; p < 0.001) in that the MA abusers exhibited slower RTs across conditions (685 ms) compared to healthy non-substance using adults (584 ms). Statistically significant differences were also observed for each of the three main effects. Responses were faster in both groups for alerting trials (F(1, 50) = 103.42; p < 0.0001, d = 0.45), cued trials (F(2, 100) = 130.44; p < 0.0001, d = 0.48) and congruent trials (F(1, 50) = 333.90; p < 0.0001, d = 0.80). See Table 2.
Discussion
The results of this study suggest that attentional deficits following long-term MA abuse are most pronounced on tasks that tap into the executive system as measured by the flanker conflict component of the ANT. Although the ANT measures the alerting and orienting systems through target tones and spatial cueing, no group differences emerged on those measures. In contrast, in a task of spatial conflict using flanker stimuli, the MA dependent subjects were significantly slower on conditions in
Acknowledgment
This work was supported by DA021847 and DA0121847 to RS.
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