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Brain and Cognition 58 (2005) 1–8

Introduction

Neuropsychology of timing and time perception

Warren H. Meck*

Department of Psychological and Brain Sciences, Genome Sciences Research Building II, 3rd Floor, 103 Research Drive,

Box 91050, Duke University, Durham, NC 27708, United States

Accepted 16 September 2004Available online 18 November 2004

Abstract

Interval timing in the range of milliseconds to minutes is affected in a variety of neurological and psychiatric populations involv-ing disruption of the frontal cortex, hippocampus, basal ganglia, and cerebellum. Our understanding of these distortions in timingand time perception are aided by the analysis of the sources of variance attributable to clock, memory, decision, and motor-controlprocesses. The conclusion is that the representation of time depends on the integration of multiple neural systems that can be fruit-fully studied in selected patient populations.� 2004 Elsevier Inc. All rights reserved.

Subjective or psychological time is the internal expe-rience of how fast time is passing, or how much time haspassed since the occurrence of some event. The ability toestimate objective or physical time has been shown to bea robust and stable function, varying only with severepsychiatric disorders, brain pathology, or pharmacolog-ical/toxicological challenges (e.g., Meck, 1996, 2003;Paule et al., 1999). Subjective time estimation requiresthe participant to use an internal clock in order to mea-sure objective time without the benefit of cues fromexternal clocks. Because of the difficulty in localizingthis ‘‘internal clock’’ within the brain the discipline oftiming and time perception has struggled to define itsown identity and to separate itself from the study ofother cognitive processes such as attention and memory.The concern has been that interval timing in the secondsto minutes range may be derivative from these othercognitive processes and may not possess its own definingcharacteristics or neural substrate (see Grimm, Wid-mann, & Schroger, 2004; Macar, 2003; Zakay & Block,1997). Fortunately, interval timing is becoming recog-nized as a fundamental component of cognition due tothe recent identification of brain mechanisms specialized

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doi:10.1016/j.bandc.2004.09.004

* Fax: +1 919 660 5626.E-mail address: meck@psych.duke.edu.

for the encoding of stimulus duration (e.g., Coull, Vidal,Nazarian, & Macar, 2004; Gibbon, Malapani, Dale, &Gallistel, 1997; Harrington et al., 2004; Hazeltine, Hel-muth, & Ivry, 1997; Hinton, 2003; Hinton & Meck,1997, 2004; Ivry, 1996; Leon & Shadlen, 2003; Lewis& Miall, 2003a, 2003b; Lustig, Matell, & Meck, 2004;Matell & Meck, 2000, 2004; Meck & Benson, 2002; Pas-tor, Day, Macaluso, Friston, & Frackowlak, 2004; Pou-thas, 2003; Rammsayer, 1997; Rao, Mayer, &Harrington, 2001; Spencer, Zelaznik, Diedrichsen, &Ivry, 2003) and because of the identification of inter-val-timing dysfunctions in a variety of neurologicaland psychiatric disorders as well as in normal aging(e.g., Barkely, Murphy, & Bush, 2001; Elvevag et al.,2004; Harrington & Haaland, 1999; Harrington, Haa-land, & Knight, 1998; Levin et al., 1996; Lustig, 2003;Lustig & Meck, 2001; Malapani, Deweer, & Gibbon,2002; Malapani & Rakitin, 2003; Malapani et al.,1998; Meck, 2003; Meck & Benson, 2002; Papagno, Al-legra, & Cardaci, 2004; Pouthas & Perbal, 2004; Wimp-ory, Nicholas, & Nash, 2002).

Numerous studies have examined abnormal timeexperience and time estimation in depressive patients(e.g., Blewett, 1992; Kitamura & Kumar, 1984; Kuhs,Hermann, Kammer, & Tolle, 1991; Melges & Fou-gerousse, 1966; Mundt, Richter, van Hees, & Stumpf,

Fig. 1. A diagram of the cortico-striatal and cortico-cerebellar circuitsthought to be involved in the interval-timing and motor-controlcomponents of procedural learning that are dysfunctional in schizo-phrenia (see Doyon et al., 2003; Kumari et al., 2002). Full colored linesrepresent excitatory input to various areas. Dashed lines and blacklines represent inhibitory input to areas. MTL, medial temporal lobe;GPE, globus pallidus external capsule; GPI, globus pallidus internalcapsule; SNC, substantia nigra pars compacta; PN, pontine nuclei; IO,inferior olive; Red N, red nucleus; Ret N, reticular nucleus; VN,vestibular nuclei; VLm, ventrolateral medial thalamic nucleus; VLo,ventrolateral thalamic nucleus—oral division; and VL c/x, ventrolat-eral thalamic nucleus—caudal and area x divisions.

2 W.H. Meck / Brain and Cognition 58 (2005) 1–8

1998; Munzel, Gendner, Steinberg, & Raith, 1988; Rich-ter & Benzenhofer, 1985; Sevigny, Everett, & Grondin,2003). In one example, Elsass, Mellerup, Rafaelsen,and Theilgaard (1979) reported that time estimates var-ied between lithium-treated bipolar patients and un-treated controls. This work has since been advancedby Tysk (1984) and Bschor et al. (2004) who have alsoreported that time estimation can vary with clinical statein bipolar disorders. In spite of the large number of pa-tients tested, much more systematic research needs to bedirected toward this issue in order to permit a distinctionamong attention, clock speed, and memory explanationsof changes in timing behavior (see Gibbon & Church,1990; Gibbon, Church, & Meck, 1984; Meck, 1983,1996; Penney, Holder, & Meck, 1996).

Rammsayer (1990) reported poorer time discrimina-tion among schizophrenic and dysthymic patients thanhealthy controls and inferred differences in clock ratebetween these groups. Administration of the anti-psy-chotic agent haloperidol to healthy normal participantsproduced timing effects that implicate the dopaminergicsystem in the control of clock speed in the millisecondsand seconds ranges (Rammsayer, 1999). Subsequentneuroimaging studies revealed procedural learning andtiming specific differences in schizophrenia mediated bycortico-striatal as well as cortico-cerebellar dysfunction(e.g., Kumari et al., 2002; Volz, Nenadic, Gaser, &Rammsayer, 2001). The primary cortico-striatal andcortico-cerebellar pathways relevant to these intervaltiming and neuroimaging data are illustrated in Fig. 1.

There is ample reason to believe that humans andother animals have a well-developed time sense in theseconds-to-minutes range. Humans are excellent atinterval timing and sequencing, they can make fine tem-poral discriminations and are sensitive to small pertur-bations in rhythm and musical structure (e.g., Epstein,1989; Janata & Grafton, 2003; McAuley & Jones,2003; Naatanen, Syssoeva, & Takegata, 2004). Estimat-ing time intervals is an important adaptive skill, vital formaking predictions and for motor control (e.g., Died-richsen, Ivry, & Pressing, 2003; Ivry, 1996; Ivry & Rich-ardson, 2002; Spencer et al., 2003). Evolutionarily, timeestimations in the seconds-to-minutes range are impor-tant for making predictions about one�s environment,for example, about the appearance of predators or prey(e.g., Bateson, 2003; Gallistel & Gibbon, 2000). Millisec-ond time estimations are important for motor controland for rapid sequencing of cognitive operations, suchas updating working memory and language processing(e.g., Justus & Ivry, 2001; Lustig et al., 2004; Meck &Benson, 2002; Schirmer, 2004).

Although certain aspects of language are unique andhighly specialized, its evolution has not been so selectivethat neural systems have been appropriated at theexpense of other cognitive processes (Schirmer, 2004;Ullman, 2004). In fact, it appears that language shares

temporal-lobe structures in order to store word-specificknowledge and activates frontal, basal ganglia, parietal,and cerebellar networks in order to provide grammaticalstructure for the various combinations of lexical itemsused in discourse. The important aspect of this ‘‘dual-use’’ strategy is that many of these same brain structuresunderlie the more general-purpose functions of declara-tive, procedural, and working memory as well as motorlearning, set-switching, attention, and interval timing(see Lustig et al., 2004; Meck & Benson, 2002). Perhapsnot too surprisingly, there has been some controversy interms of identifying those brain structures that are crit-ical for language just as there has been controversy indetermining the precise contributions of frontal-striataland cerebellar circuits to timing and time perception(see Diedrichsen et al., 2003; Gibbon et al., 1997; Har-rington, Lee, Boyd, Rapcsak, & Knight, 2004; Ivry,1996; Malapani, Dubois, Rancurel, & Gibbon, 1998;Meck, 2003; Spencer et al., 2003). One major source of

W.H. Meck / Brain and Cognition 58 (2005) 1–8 3

agreement, however, is that motor control and its asso-ciated variance can be separated from the perceptual as-pects of interval timing, thus defining a specializedprocess that has been referred to as the ‘‘internal clock.’’Consequently, although there may be disagreement as towhether the internal clock takes the form of an oscillatoror hourglass (see Pashler, 2001) there is substantialagreement that a specialized timing system exists—muchlike the language system described by Ullman (2004).

Recently, an integrative model of timing and timeperception has been proposed in which two parallel sys-tems are required in order to account for the full rangeof durations resolved by the ‘‘internal clock’’ (Santama-ria, 2002; see also Madison, 2001). This model includes abottom-up system for timing in the milliseconds range—considered important for motor coordination and com-puted by the cerebellum. The other component involvesa top–down system for timing in the seconds to minutesrange—considered important for temporal estimationand computed by frontal-striatal circuits that are ableto concatenate smaller intervals generated locally or bythe cerebellum. To evaluate this model, Santamaria(2002) simulated a neural network of cerebellar activitythat represented the millisecond timing system. Con-trary to the initial predictions of nonlinearity in the out-put of this network, simulations indicated that timingerror increased linearly as a function of interval length,but drift in the variability of the model�s output showeda systematic nonlinearity (see Crystal, 2003). It was alsopredicted that transfer of timing between different effec-tor systems (e.g., left and right hands) would be minimaldue to motor-specific interval learning by the cerebel-lum. In contrast, model simulations provided evidencefor transfer of timing between hands indicating an unex-pected robustness of the frontal networks and a surpris-ing degree of independence from the cerebellum. Oneconclusion that can be drawn from this type of analysisis that frontal-striatal circuits are apparently able to re-scale durations in a proportional manner and compen-sate for error differences generated by the cerebellum.This type of ‘‘scalar’’ representation of intervals (seeGibbon & Church, 1990; Gibbon et al., 1984; Malapani& Fairhurst, 2002) may contribute to the observedtransfer among different effector systems by allowingfor the encoding of duration in a less motor-specificfashion and establishes a manner in which different tim-ing systems (e.g., cerebellum and basal ganglia) caninteract across a wider range of durations (e.g., millisec-onds to hours).

A classic case study of the neuropsychology of timingand time perception comes from the renowned individ-ual H.M., who underwent a bilateral medial temporallobe (MTL) resection that resulted in a severe memoryloss following surgery (Richards, 1973). When H.M.was required to reproduce durations ranging between 1and 300 s he demonstrated reasonably accurate timing

for durations <20 s, but systematic underestimation fordurations >20 s. Eisler and Eisler (2001) fit a power-function model to these reproduction data and deter-mined that H.M.�s psychophysical function showed adistinct break, dividing the function into a lower andan upper segment. The conclusion was that the hippo-campus and other temporal lobe structures are involvedin the maintenance of task instructions in short-termmemory, but that once accumulated, clock readings areretained in the absence of normal temporal lobe func-tion. Despite this and other extremely interesting casestudies (e.g., Perbal, Pouthas, & Van der Linden,2000), much remains to be determined about the neuro-psychology of interval timing. Some of the main goals ofthe field of timing and time perception are to determinehow brain lesions, neurodegenerative disease states,pharmacological treatments, and normal aging contrib-ute to changes in the speed of internal clock and/or mem-ory storage processes (Gibbon et al., 1997; Malapaniet al., 1998; Meck, 1983, 1996; Pouthas & Perbal, 2004).

The observation of hemispheric asymmetries in theeffects of MTL resection on timing and time perceptionhas renewed interest in the lateralization of temporalprocessing. For example, patients with right MTL resec-tions often exhibit impairments in the precision of theirtiming abilities that are associated with the underestima-tion of retrospective duration and little or no change inthe accuracy of prospective timing. In contrast, patientswith left MTL resections have been shown to exhibiteither no impairments or an improvement in the preci-sion of their timing abilities that may be accompaniedby an ability to correct underestimations in retrospectivetime judgments as well as a persistent overestimation/underproduction of prospective duration (e.g., Drane,Lee, Loring, & Meador, 1999; Vidalaki, Ho, Bradshaw,& Szabadi, 1999). These observations are of particularinterest given the recent findings that hippocampal andstriatal systems can interact competitively such thatdamage to one system can lead to facilitation in theother (e.g., Poldrack & Packard, 2003). This ‘‘see-saw’’effect may be explained by a number of factors, includ-ing direct anatomical projections from the MTL to areasof the dorsal striatum that have been shown to beimportant for interval timing as illustrated in Fig. 2(Matell, Meck, & Nicolelis, 2003; Sorensen & Witter,1983). Furthermore, animal studies have indicated thatlesions to the hippocampus can result in increased dopa-minergic transmission in the portions of the striatum towhich the hippocampus projects (e.g., Lipska, Jaskiw,Chrapusta, Karoum, & Weinberger, 1992) thereby pro-ducing long-term alterations in the accuracy and preci-sion of interval timing in the seconds-to-minutes range(e.g., Buhusi, Mocanu, & Meck, 2004; Meck, 1988;Meck, Church, & Olton, 1984; Meck, Church, Wenk,& Olton, 1987; Olton, Meck, & Church, 1987; Olton,Wenk, Church, & Meck, 1988).

Fig. 3. Percent maximum response rate in the peak-interval procedure plottediagnosed with attention deficit disorder (ADD) trained at two criterion time(25 and 100%). The top panel shows performance at these two criterion timesand the bottom panel shows performance in a medicated state (NicPost). Se

Fig. 2. Outline of the neurotransmitter systems and cortico-striatal/hippocampal circuitry proposed to mediate timing and time perceptionin the seconds-to-minutes range. Descriptions of these anatomicalconnections and how cortico-striatal coincidence detection and result-ing thalamo-cortical feedback results in the temporal control ofbehavior is provided by Xiao and Barbas (2004) and Matell and Meck(2000, 2004), respectively. Ach, acetylcholine; Glu, glutamate; SP,substance P; Enk, enkephalin; GABA, c-aminobutyric acid; DA,dopamine; D1, dopamine D1 receptor subtype; D2, dopamine D2receptor subtype; GPE, globus pallidus external capsule; GPI, globuspallidus internal capsule; SNC, substantia nigra pars compacta; SNR,substantia nigra pars reticulata; and STN, subthalamic nucleus.

4 W.H. Meck / Brain and Cognition 58 (2005) 1–8

An intriguing example of the neuropharmacologicalbasis of interval timing is illustrated by the resultsobtained from an adult participant diagnosed withattentional-deficit disorder (ADD). This patient�s repro-duction of 7- and 17-s signal durations while performinga peak-interval procedure are displayed in Fig. 3 (seeLevin et al., 1996, 1998; Lustig & Meck, 2005; Rakitinet al., 1998 for procedural details). The top panel dis-plays percent maximum response rate for the participantin an unmedicated state (NicPre) plotted as a function ofthe 7- and 17-s criteria. In this procedure, a blue squarepresented on a computer monitor is transformed to ma-genta at the appropriate criterion time during fixed-timetraining trials. Thereafter, participants are requested toreproduce the temporal criterion for a sequence of testtrials after which a distribution of their responses is plot-ted on a relative timescale at the completion of the trialduring the inter-trial interval (ITI). This ITI feedback isdisplayed on the computer monitor and provides theparticipant with information concerning the relativeaccuracy and precision of their timing behavior on thepreceding trial. ITI feedback can be randomly presentedfollowing a fixed proportion of trials (in this case 25 and100%). As can be seen in the top panel of the figure,when the participant is provided with ITI feedback on100% of the trials the PI functions are centered at thecorrect times showing excellent accuracy of the repro-

d as a function of signal duration for a single adult participant (ALB)s (7 and 17 s) under two conditions of intertrial interval (ITI) feedbackunder the two ITI feedback conditions in an unmedicated state (NicPre)e Levin et al. (1996, 1998) for additional procedural details.

W.H. Meck / Brain and Cognition 58 (2005) 1–8 5

duced intervals. In contrast, when ITI feedback is pro-vided on only 25% of the trials a proportional rightwardshift is observed in the timing of the 7- and 17-s inter-vals, reflecting a discrepancy in the accuracy of temporalreproductions that is not observed in normal partici-pants (e.g., Lustig & Meck, 2005; Rakitin et al., 1998).This rightward shift is accompanied by a broadeningof the PI functions indicating a decrease in temporalprecision with lower levels of feedback. Both of thesefindings are consistent with a slowing of the internalclock as a function of the probability of feedback andmay be the result of a deficit in attention mediated theflickering of a mode switch that gates pulses from apacemaker into an accumulator (e.g., Lustig, 2003; Lus-tig & Meck, 2005; Meck & Benson, 2002; Penney, 2003;Penney, Allan, Meck, & Gibbon, 1998; Penney, Gibbon,& Meck, 2000). Interestingly, the bottom panel indicatesthat when the participant is given a stimulant drug (e.g.,7 mg/day transdermal nicotine skin patch) that increasesdopamine levels in the brain during the NicPost condi-tion the effects of 25% ITI feedback are enhanced andproduce levels of temporal accuracy and precision thatare equivalent to the 100% ITI feedback condition inboth the medicated and unmedicated states. These re-sults suggest an equivalence of the ITI feedback effectsand the types of pharmacological stimulation providedto ADD patients by drugs such as nicotine and methyl-phenidate (see Levin et al., 1996, 1998). These findingsalso support the proposal that deficits in attention canlead to the underestimation of signal durations in amanner consistent with a slowing of an internal clockthat is sensitive to dopaminergic manipulations whetherthey are produced by behavioral (ITI feedback) or phar-macological means (see Buhusi, 2003; Buhusi & Meck,2002).

In the papers that follow in this special issue of Brainand Cognition on the ‘‘Neuropsychology of Timing andTime Perception,’’ the contributing authors explore thecharacteristics of the interval-timing system as it is per-turbed by dopaminergic antagonists and feedback (Lus-tig & Meck, 2005), normal aging (Rakitin, Stern, &Malapani, 2005), Parkinson�s disease (Perbal et al.,2005; Jurkowski, Stepp, & Hackley, 2004; Spencer &Ivry, 2005), unilateral and focal lesions of the basal gan-glia (Aparicio, Diedrichsen, & Ivry, 2005; Shin, Apari-cio, & Ivry, 2004), cerebellar lesions (Spencer & Ivry,2005), schizophrenia and/or its associated risk factors(e.g., Brown et al., 2005; Penney, Meck, Roberts, Gib-bon, & Erlenmeyer-Kimling, 2005), MTL resection(Melgire et al., 2005), as well as hemispheric differencesin temporal processing (Grondin & Girard, 2005) andthe effects of musical expertise on timing and time per-ception (Ehrle & Samson, 2005).

Without question, there is still much to be learnedabout how modifications in the neural systems that sup-port interval timing contribute to cognitive dysfunction.

Nevertheless, the neuropsychological evidence presentedhere from a variety of subject populations arguesstrongly for one or more dedicated timekeeping mecha-nisms that involve the integration of cortical circuitswith the basal ganglia, cerebellum, and hippocampusin order to support temporal cognition and motor skilllearning across a broad range of stimulus contexts andtimescales (see Doyon, Penhune, & Ungerleider, 2003;Gibbon et al., 1997).

Acknowledgments

The author is very grateful to Sid Segalowitz for hisinvitation to edit this special issue on the ‘‘Neuropsy-chology of Timing and Time Perception’’ and for hiscontinued support and patience throughout all phasesof production. Inspiration for this volume also camefrom the organizers of TENNET XV, Montreal, Can-ada, June 24–26, 2004 with special thanks to SimonGrondin for assembling an excellent symposium onthe ‘‘Neural Bases of Timing and Time Perception.’’

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