Attention Deficit Hyperactivity Disorder (ADHD) is characterized by age-inappropriate levels of inattention, impulsivity, and hyperactivity [1
]. The most heavily cited theoretical account of ADHD claims that "the essential impairment in ADHD is a deficit involving response inhibition" [2
]. Inhibition, according to Barkley's theory, comprises three processes: (a) Inhibiting the initiation
of responses that have been reinforced in the past but that are currently inappropriate; for example, restraining from playing in classroom; (b) Discontinuing ongoing
responses that are no longer functional, as when loud talking is halted at the beginning of a lecture; (c) Initiation and maintenance of behaviors that compete
with the proscribed response, as opening a conversation could distract from the temptation to skip lines, or to respond aggressively. According to this theory [2
], deficits in response inhibition yield the executive functioning profile that characterizes ADHD. Most current models of ADHD regularly compare their claims against those of the executive functions model, whether or not they subscribe to it [3
The ability to inhibit reinforced responses is widely studied using the Differential Reinforcement of Low rates (DRL) preparation in both humans [8
] and animals [14
]. In DRL, a response (pressing a button or a lever) is reinforced only after a specified interval has elapsed since the last response. Premature responses are often labeled impulsive
. The opposite of impulsivity, self control, is typically measured as efficiency
: the proportion of inter-response times (IRT) longer than the target interval. It is important to note that efficiency does not differentiate between IRTs that are just longer than the target interval from those much longer; such very long lapses may result from task delinquency rather than self-control, and, by decreasing the rate of reinforcement, are themselves a source of inefficiency.
The relation between DRL efficiency and ADHD is unclear. Gordon [9
] found that 6–8 year old boys rated as hyperactive by their teachers were less efficient in DRL with a 6-s target interval (DRL 6 s) than was a control group. Mancebo [19
] found similar results using DRL 5 s. With sufficient training, however, children with ADHD in Mancebo's study acquired behavioral strategies that brought their performance up to the level of control children (see also [20
]). In contrast, Daugherty and Quay [11
], and Avila and colleagues [12
] did not find a correlation between DRL efficiency and ratings of ADHD symptoms in school-age children. Despite these disagreements, Gordon's procedure is widely used for diagnosing impulsivity in ADHD [21
Assays of impulsivity based on DRL in the Spontaneously Hypertensive Rat (SHR), an animal model of ADHD, have also been problematic. Bull and colleagues [22
] showed that SHR were more efficient than Sprague-Dawley (CD) rats in DRL 60 s, suggesting that SHR were less
impulsive than a conventional laboratory strain of rats – if indeed inefficiency is a valid measure of impulsivity. Using DRL 72 s, van den Bergh and colleagues [23
] concluded that Wistar (WST) rats, another conventional laboratory strain, were not more efficient than SHR. Furthermore, these authors did not observe significant improvements in SHR performance when the rats were administered methylphenidate, a drug shown to enhance inhibitory control of ADHD patients [24
]. Using a modified version of DRL which controlled for rate of reinforcement, Sagvolden and Berger [26
] found that SHR responded more than WKY, but it is unclear whether or not the mean waiting time was substantially shorter for SHR than for WKY.
There are various potential explanations for the failure to detect impulsivity in SHR using DRL. It is possible that SHR do not display the kind of impulsivity that characterizes ADHD, despite analogous performance of SHR and children with ADHD in other behavioral tasks [27
]. Another possibility is that the DRL task does not elicit ADHD-related impulsivity, as suggested by some reports [11
]. In this paper we consider two alternative accounts of performance in DRL. Both accounts are consistent with the characterization of SHR as a valid animal model of ADHD, and with evidence that response-withholding tasks like DRL tap into ADHD-related impulsivity.
Impulsivity and incentive motivation in DRL
Failure to detect abnormal levels of impulsivity in SHR may be related to the sensitivity of DRL performance to incentive motivation [30
]: A subject that is not motivated to complete the DRL task may engage in other activities, producing longer IRTs that would be wrongly attributed to self control. With very long target times, such as those used by Bull et al. [22
] and van den Bergh et al. [23
], it is possible that successful performance is a result of periodic desertion of the task due to flagging motivation, rather than controlled waiting associated with self-control. Failure to detect abnormal impulsivity in SHR using DRL may be due to SHR's reduced motivation for the incentive relative to control strains – more frequent desertion of the waiting task may have been wrongly interpreted as more controlled waiting.
To isolate impulsivity from motivation, we propose to complement measures obtained from DRL with those obtained from a lever-holding task (LHT). In LHT, releasing a lever or button is reinforced only if it had been pressed longer than a specified interval; early releases restart the clock but are not reinforced. Variations of LHT have been used as a timing task in animals [31
In LHT and DRL, reinforcement is contingent on emitting a response (lever or button press in DRL; lever or button release in LHT) after withholding it for a minimum time. Both tasks differ in what subjects are required to do between responses: Waiting activities in LHT are restricted to those that keep the switch depressed, whereas in DRL they are anything other than pressing the switch. Like short IRTs in DRL, short response durations in LHT are deemed impulsive. Supporting this characterization of LHT inefficiency, Baldwin and colleagues [33
] demonstrated that methylphenidate reduces the variability of response durations and the frequency of very short durations in children with ADHD.
As the case for DRL, the interpretation of LHT performance is not without confounds. A subject exposed to LHT contingencies may produce shorter "impulsive" response durations because of reduced motivation or poor motor control, not because of an impulsive tendency to release the lever early. Conversely, reduced motivation and poor motor control are unlikely to contribute to shorter IRTs in DRL: Smaller rewards yield longer IRTs in rats and pigeons [30
]. Longer "self-controlled" IRTs in DRL may result from low motivation to complete the task. Conversely, reduced motivation is unlikely to result in longer response durations in LHT. Thus, demonstration of impulsivity in both
LHT and DRL cannot be attributed to motor impairment or enhanced motivation. Some studies have taken advantage of the complementary nature of LHT and DRL to interpret the behavioral effects of drugs in rats [34
] and to evaluate timing in children [37
], as is our strategy here.
Efficiency and peak deviation
A second hypothesis concerning the failure to detect impulsivity in SHR using DRL derives from the use of DRL "efficiency" as an (inverse) measure of impulsivity. Efficiency is typically inferred from the proportion of responses that exceed the target interval. Efficiency measures are intuitive and descriptive, but do not take full advantage of the data for drawing inferences, as would a truly efficient model of the behavior. A change in efficiency indicates that the distribution of IRTs changed, but it does not tell us precisely how it changed [38
]. Four responses spaced just under the target interval followed by a reinforced response are given the same efficiency score (20%) as a burst of 4 closely spaced responses followed by a reinforced response; yet the former performance is more inefficient in most senses of that term. Moreover, despite having the same efficiency score, responses that are spaced almost right would score better in most measures of timing than a burst of responses would. DRL efficiency ignores much of the information contained in performance, some of which may be critical to distinguish levels of impulsivity across strains of rats.
Richards and colleagues [38
] suggested an analytic technique that might characterize DRL performance using more information than is provided by efficiency measures. Their peak deviation analysis
identifies deviations in the IRT distribution from a random process, defined as one in which interval terminations occur randomly with constant probability. A constant-rate random process entails a negative exponential distribution of IRTs. In DRL, very short IRTs ("bursts") and IRTs around the target interval ("peak") are typically much more frequent than expected from a constant-rate random process. Using this analysis, van den Bergh [23
] showed that bursts tended to be more frequent and peak IRTs tended to be shorter in SHR than in Wistar (WST); these tendencies, however, did not reach statistical significance.
Peak deviation analysis may reveal differences in DRL performance between SHR and control strains, but it is unclear how these differences should be linked to impulsivity. In the following analysis we develop a plausible behavioral mechanism for both DRL and LHT performance, and test it against data collected from SHR and two other strains. Some of the model parameters are directly related to the ability of rats to inhibit responses, and thus provide a measure of impulsivity. We then evaluate differences in these parameters across strains and reconcile our conclusions with prior data reported on SHR impulsivity.