Timing deficits in attention-deficit/hyperactivity disorder (ADHD): Evidence from neurocognitive and neuroimaging studies
Highlights
► ADHD patients show deficits in motor timing, perceptual timing and temporal foresight. ► ADHD patients show impairments in fronto-striato-parieto-cerebellar timing networks. ► Temporal abnormalities in ADHD interact with inattention and behavioural impulsivity.
Introduction
Timing refers to the ability to deal with the temporal domain in behaviour, such as the adjustment of behaviour to specific timeframes, the ability to perceive and estimate time intervals, and the ability to consider future consequences of behaviour in order to make use of temporal foresight for inter-temporal choices. Timing functions are therefore commonly subcategorised into motor timing (i.e., adjustment of behaviour or motor responses to externally or internally defined timeframes, typically measured in the range of milliseconds and seconds), perceptual timing (i.e., time estimation and discrimination, also measured in intervals of milliseconds and seconds), and temporal foresight or inter-temporal bridging (considering future outcomes to make present choices, typically comprising longer intervals of days to years) (Rubia, 2006, Rubia and Smith, 2004). For instance, accurate motor timing is needed to execute action at an optimal moment, such as hitting a tennis ball when it is not too close or too far. Perceptual timing is required to estimate the duration of events, such as whether you have enough time to reach a drop-shot ball. Temporal foresight is needed to estimate future implications of immediate actions, such as playing too hard might result in a back pain next morning. Despite obvious differences, all three timing functions are closely intertwined in order to provide the most adaptive behaviour, and they might even share the same underlying neural mechanisms (Rubia, 2006, Wiener et al., 2010). Due to evidence for differences in neural networks involved based on the duration of processed intervals, in particular differences between timing processes that occur within milliseconds and longer durations of seconds and more, another common subcategorisation has been made between sub-second and supra-second timing functions (Lewis and Miall, 2003a, Lewis and Miall, 2003b, Rubia, 2006, Wiener et al., 2010). This differentiation takes also into account that sub-second timing processes typically rely less on other cognitive functions that are necessary for longer interval timing functions, such as attention to time, working memory and cognitive control functions. For this review, we will use the first subcategorisation, i.e., the distinction between motor timing, perceptual timing, and temporal foresight (for a more detailed description of different timing functions and tasks, see Section 2), but throughout the review we will point out the temporal domains that are being discussed.
Timing functions are associated with diverse functions such as perception of phoneme duration (Liberman et al., 1961), verbal skills (Stanford & Barratt, 1996), expressive performance of music (Repp, 1995), time perspective and future planning (Teuscher & Mitchell, 2011), gross and fine motor skills (Bartscherer & Dole, 2005), and emotional intelligence (Stolarski, Bitner, & Zimbardo, 2011). There are several basic cognitive functions that are closely interlinked with timing functions, in particular attention and working memory (Pouthas & Perbal, 2004). Attention to time is crucial to estimate time or to adjust motor responses to externally determined time intervals (Rubia, 2006, Wiener et al., 2010), whereas working memory is necessary to hold temporal information online, which is particularly relevant for the temporal reproduction of time intervals or for inter-temporal decision making (Dutke, 2005, Hinson et al., 2003).
Developmental research shows that some perceptual timing tasks such as temporal bisection can be carried out already at a very early stage of life, possibly relying on implicit sensory learning. For instance, infants as young as 4 month old were able to be trained to discriminate whether intervals between standard durations of 0.5 s and 1.5 s were closer to the shorter or the longer standard (Provasi et al., 2011), demonstrating that neurocognitive capabilities for making comparative judgements regarding varying duration of sensory stimuli are present in the infant brain. However, their temporal performance was marked by a large number of random responses. In general, however, children have a limited abstract sense of time until late childhood, e.g., they tend to confuse time with distance (Siegler & Richards, 1979), and there is consistent evidence that the timing functions, i.e., motor timing, perceptual timing and temporal foresight, continue to develop until adolescence and even mid-adulthood (Christakou, Brammer, & Rubia, 2011; Drake, Jones, & Baruch, 2000; Droit-Volet & Wearden, 2001; Fischer & Hartnegg, 2004; McAuley, Riess-Jones, Holub, Johnston, & Miller, 2006; Rozek, Wessman, & Gorman, 1977; Smith et al., 2011; Steinberg et al., 2009; for a recent review, see Allman, Pelphrey and Meck (2012)). For example, performance of motor tapping in the milliseconds range was shown to improve throughout the life-span in 305 participants between 4 and 95 years, e.g., the average free tapping tempo decreased progressively from the age of 4 until the age of 75 and later (McAuley et al., 2006). Regarding perceptual timing tasks in the milliseconds range, discrimination of auditory tempo improves from the age of 4 to 10 and further (Drake et al., 2000) and detection of brief temporal gaps of silence changes significantly from 7 to 19 years of age (Fischer & Hartnegg, 2004). A similar improvement in the accuracy of perceptual timing from childhood to adolescence and adulthood has been reported in a number of studies that probed perception of longer supra-second durations (for a review, see Block, Zakay, & Hancock, 1999). Droit-Volet and Wearden (2001) tested 3, 5 and 8 year old children and found an age-dependent improvement of performance in a temporal bisection task within a range of several seconds, while Rozek et al. (1977) found a similar improvement in a task requiring reproduction of a 1 min interval. With respect to temporal foresight as measured in delay discounting tasks, which typically probe much longer time intervals from 1 day up to several years, better performance has been shown in older adolescents relative to children and in adults relative to adolescents (Christakou et al., 2011, Scheres et al., 2006, Steinberg et al., 2009).
People with impulsive disorders typically show deficits in temporal processing. Impulsiveness is defined as a premature, impatient, delay-aversed, non-reflected and immediacy-bound response style, where actions are executed before all available information and the future consequences are being considered (Rubia, 2002, Rubia et al., 2009a). As can be observed from the above provided definition of impulsiveness, temporal processes appear to be underlying many of its features, such as abnormalities in motor timing (response prematurity), in subjective time sense (impatience and delay-aversion, suggesting that the passage of time is subjectively more insufferable and possibly elongated for impulsive than reflective personalities) and in temporal foresight (unreflected behaviour and not considering future consequences of one’s acts, suggesting temporal myopia). In fact, impulsive disorders have typically been associated with deficits in timing functions, including attention deficit/hyperactivity disorder (ADHD), bipolar disorder, borderline personality disorder, and alcohol and substance abuse (Rubia et al., 2009a). However, also other psychiatric disorders have been associated with abnormal timing processes (for a review, see Allman & Meck, 2012), such as autism spectrum disorder (Falter and Noreika, 2011, Falter et al., 2012 in pressPlease provide an update for Ref. “Falter, Noreika, Wearden, and Bailey (2012)”.) or depression (Gil & Droit-Volet, 2009).
ADHD is considered the disorder of impulsiveness per excellence. ADHD is one of the most common neurodevelopmental psychiatric disorders, presenting about 5% of the population (Polanczyk et al., 2007) and persisting in about 65% into adulthood (Biedermann et al., 2006). ADHD is defined in the DSM-IV by persistent patterns of age-inappropriate inattention, hyperactivity and impulsivity whereby impulsiveness is considered the core feature (DSM-IV-TR, 2000). Based on the predominant primary symptom pattern, three ADHD subtypes are currently being distinguished: the most common inattentive-hyperactive impulsive combined type, and the lesser occurring predominantly inattentive and predominantly hyperactive-impulsive types.
Neuropsychological studies have shown that ADHD patients have consistent deficits in executive functions, defined as functions that are necessary for mature adult goal-directed behaviour, such as set-shifting and set maintenance, attention control (sustained and selective attention), interference and motor inhibition, planning, decision making, temporal foresight and working memory (Stuss & Alexander, 2000). It should be noted that we use the wider definition of executive functions that includes attention control functions as well as specific aspects of temporal processing such as temporal foresight because they are underlying other goal-directed behaviours, such as planning. The most prominent deficits in executive functions in ADHD are in tasks of motor response inhibition, working memory and sustained attention (Cubillo et al., 2012, Rubia, 2011, Willcutt et al., 2005). However, there is also consistent evidence that ADHD patients have cognitive deficits in the timing domain, including impairments in motor timing, time perception and temporal foresight (Rubia et al., 2009a, Toplak et al., 2006). Furthermore, there is emerging evidence that ADHD patients have abnormalities in the underlying neurofunctional networks that mediate these timing functions (Rubia et al., 2009a). Despite converging evidence for neurocognitive deficits in timing functions in ADHD, this cognitive domain is still relatively neglected and omitted from recent reviews of the cognitive abnormalities in ADHD.
The aim of this review is therefore (1) to provide a focused summary of the neurocognitive evidence regarding deficits in timing functions in individuals with ADHD, (2) to review the evidence for the neurofunctional basis of such impairments in ADHD from functional neuroimaging studies, and (3) to initiate a closer integration of ADHD studies of timing with the cognitive neuroscience literature on the brain basis of temporal functions. An overview of the evidence on the interactions between timing functions and other cognitive functions and behavioural traits will show that timing deficits are independent but associated with behavioural as well as cognitive measures of impulsivity and inattention, supporting the proposal that impaired timing plays a fundamental role in the disorder.
Section snippets
Motor timing
Motor timing refers to the temporal organisation of motor behaviour, which is typically measured by free tapping, sensorimotor synchronisation, and rhythm reproduction tasks. In free tapping experiments, participants are instructed to tap their finger in a freely chosen regular rhythm. Sensorimotor synchronisation (also called cued synchronisation) experiments require participants to tap with their finger in synchrony with regularly presented sensory stimuli (e.g., flashing visual or auditory
Sub-second intervals
Regarding neural mechanisms of different timing functions in healthy individuals, sensorimotor synchronisation of sub-second intervals is associated with activation of the dorsolateral prefrontal cortex (DLPFC) (Jantzen et al., 2007, Lewis et al., 2004, Rubia et al., 1998, Rubia et al., 2000), the inferior frontal cortex (IFC) (Jantzen et al., 2007, Rao et al., 1997), medial frontal cortex (MFC) (Jantzen et al., 2004, Jantzen et al., 2005, Oullier et al., 2005), and the supplementary motor
Motor timing
Motor timing has been investigated in individuals with ADHD using tasks of free tapping (Rubia et al., 1999a, Rubia et al., 2003, Tiffin-Richards et al., 2004), cued and uncued sensorimotor synchronisation (Ben-Pazi et al., 2003, Ben-Pazi et al., 2006, Gilden and Marusich, 2009, Pitcher et al., 2002, Rubia et al., 1999a, Rubia et al., 2003, Tiffin-Richards et al., 2004, Toplak and Tannock, 2005b, Zelaznik et al., 2012), rhythm reproduction (Tiffin-Richards et al., 2004), and sensorimotor
Timing and general intelligence
The link between IQ and abnormal timing functions in ADHD, as reviewed in Section 4, is not suprising given that measures of perceptual timing vary with IQ scores (Wearden, Wearden, & Rabbitt, 1997), and that IQ tends to be lower in individuals with ADHD than in the age-matched typical controls (Bridgett and Walker, 2006, Kuntsi et al., 2004). Indeed, such a link has been demonstrated in perceptual timing and temporal foresight studies, including duration reproduction (Smith et al., 2002,
Neural mechanisms of timing abnormalities in ADHD
Considering that there is consistent evidence for deficits in ADHD patients in a range of timing processes it is surprising that relatively few fMRI studies in ADHD have focused on these functions (see Table 4 and Fig. 2).
Methylphenidate modulation of timing functions in ADHD
It is well-established that the basal ganglia have an important role in timing functions (Riecker et al., 2003, Meck, 1996, Nenadic et al., 2003, Rubia, 2006, Rubia and Smith, 2004, Tanaka et al., 2004, Wiener et al., 2010), which are known to be mediated at least in part by dopamine, a neurotransmitter produced in the substantia nigra pars compacta, and the key neurotransmitter innervating the frontal-basal ganglia systems. Dopamine and its agonists have been shown to have an important role in
Timing and diagnostic subtypes of ADHD
Several studies investigated potential differences in timing functions between diagnostic subtypes of ADHD (Barkley et al., 2001a, Huang et al., 2012, McInerney and Kerns, 2003, Radonovich and Mostofsky, 2004, Toplak et al., 2003). Two of these studies found that only children with the ADHD impulsive-hyperactive and inattentive-combined subtype but not those with inattentive symptoms only were more impaired than controls in their variability of duration reproduction errors (McInerney & Kerns,
Comorbidities and timing deficits
Comorbidities are likely to have an impact on timing functions in ADHD, as they also impact other functions (Rubia, 2011). Individuals with ADHD frequently have comorbid disorders, most commonly conduct disorder (CD), oppositional defiant disorder (ODD), dyslexia, and anxiety, all of which may have a unique contribution to timing abnormalities. Only few studies, however, assessed a possible influence of comorbidities on timing abnormalities in ADHD. Several studies tested for differences in
ADHD familial associations and timing deficits
Several studies have indicated that timing functions might be associated with a family history of ADHD, which opens an intriguing prospect to frame timing abnormalities as an endophenotype of ADHD. Two studies showed familial effects in a duration reproduction task with ADHD patients with a family history being more impaired than those without a family history (Huang et al., 2012) and non-affected siblings of individuals with ADHD having lower reproduction accuracy than typical controls (
General discussion
The present synthesis of neurocognitive and neuroimaging studies of timing functions in ADHD provides consistent evidence that ADHD is associated with both cognitive as well as neurofunctional deficits in a remarkably wide range of timing functions, including motor timing, perceptual timing, and temporal foresight. Neurocognitively, the most investigated and consistent deficits are in sensorimotor synchronisation, duration discrimination, duration reproduction, and delay discounting tasks.
Acknowledgments
The study was supported by a European Cooperation in Science and Technology (COST) action on Time in Mental Activity (TIMELY; TD0904). Individually, VN was supported by the Academy of Finland and the Signe and Ane Gyllenberg Foundation.
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