Brain Injury, August 2008; 22(9): 697–704

Prefrontal cortex involvement in the event-based

prospective memory: Evidence from patients with lesions

in the prefrontal cortex

HUAI-DONG CHENG1, KAI WANG1, CHUN-HUA XI1, CHAO-SHI NIU2,& XIAN-MING FU2

1Neuropsychology Laboratory, Institute of Neurology and Department of Neurology, The First Hospital of Anhui

Medical University, Heifei, PR China and 2Department of Neurosurgery, Anhui Province Hospital, Heifei, PR China

(Received 20 March 2008; accepted 7 June 2008)

AbstractPrimary objective: The aim of the present study was to investigate the event-based prospective memory (EBPM) and time-based prospective memory (TBPM) in patients with lesion in prefrontal cortex (PFC) and test the hypothesis that theprefrontal cortex is involved in the prospective memory (PM) network.Research design: The performance of patients with lesion in PFC (n¼ 30) was compared with that of a demographicallymatched control group (n¼ 30).Methods and procedures: A neuropsychological battery of tests including EBPM and TBPM tasks were administered to bothgroups.Main outcome and results: The group with lesion in PFC were significantly impaired in EBPM, but insignificantly impaired inTBPM tasks. There was no difference in performance of EBPM and TBPM tasks between the patients with lesion in the leftand the right PFC.Conclusions: These results suggest that the patients with lesion in PFC were impaired in EBPM, but not in TBPM, implyingthat EBPM and TBPM may have different neural substrates. It is possible that PFC is more selectively involved in EBPM,but less in TBPM.

Keywords: Prospective memory, prefrontal cortex, neural substrate, neuropsychology

Introduction

The memory process needed most in everyday life isnot forgetting something but forgetting to do some-thing at an appropriate time in the future [1, 2]. Thisaspect of memory has been termed prospectivememory (PM), i.e. remembering to perform anintended action after a delay [3]. Prospectivememory failures are quite common and mayconstitute 50–70% of memory failures occurring ineveryday life [4]. Despite its importance, knowledgeof cerebral mechanisms involved in prospectivememory has remained scanty, Prospective memory

is a multi-step cognitive process and may involve anumber of processing stages: forming an intention,maintaining the intention in memory over an intervalwhile being engaged in another (or ongoing) task,executing the intended action at the appropriatemoment and evaluating the outcome [5].Prospective memory purported to depend upon theintegrity of multiple cognitive abilities associatedwith the frontal cortex.

Although prefrontal cortex (PFC) involvement inthe memory domain is well-documented [6–9], thespecific functions the frontal lobes have in prospec-tive memory are still unclear. Most studies on the

Correspondence: Kai Wang, Department of Neurology, The First Hospital of Anhui Medical University, 218 Jixi Road Hefei, Anhui Province, 230022,PR China. E-mail: wangkai1964@126.com

ISSN 0269–9052 print/ISSN 1362–301X online � 2008 Informa Healthcare USA, Inc.DOI: 10.1080/02699050802263035

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memory impairment of patients with lesion in theprefrontal cortex have focused on retrospectivememory (RM) [6, 8] and prospective memory hasrarely been reported. Retrospective memory ismemory for past events, such as remembering whatyou did yesterday or remembering the words from alist learned in an experiment. On the other hand,prospective memory is memory for actions to beperformed in the future [10], such as rememberingto post a letter as you pass the postbox orremembering an appointment at 5 pm. One has toperform many activities based on prospectivememory in everyday life and its decline may lead tosubstantial disability. Without prospective memory,one could not carry out an intended future actionwithout continuous verbal rehearsal of the intentionuntil the appropriate time (or context) occurred.Relative to retrospective memory, prospectivememory is believed to be more dependent oninternal control mechanisms [11].

In this way, prospective memory functions serve tobind together complex goal-directed behaviouralsequences and enable a person to carry out theirplans and wishes in a meaningful order and at theappropriate time. Patients with neurological injurywho have lost this ability demonstrate the impor-tance of prospective memory to everyday lifecompetency. Despite high intelligence quotient(IQ) and no problems with language, perception orretrospective memory, they are nevertheless severelyimpaired in everyday life [12]. Knight [13] describedthat prospective memory involves both the ‘what’knowledge of declarative memory and the planningabilities of executive functions. Executive functionsrefer to the mental processes needed for theelaboration of adaptive behaviour in response tonew challenging environmental situations, whichinclude the processing of relevant information, thegeneration of new concepts or mental sets, problem-solving and planning abilities. Some of theseprocesses have been reported to be disturbed inpatients with lesion in the prefrontal cortex [14],while planning ability to realize delayed intention,which is necessary for successful prospectivememory, has rarely been investigated. Einstein andMcDaniel [15] proposed an important distinctionbetween event-based and time-based prospectivememory. Event-based prospective memory(EBPM) is remembering to perform an actionwhen some external event occurs, such as remem-bering to give a message to a friend when you meetthe friend. Time-based prospective memory(TBPM) is remembering to perform an action at acertain time, such as remembering to attend ameeting at 10 am. Einstein and McDaniel [16]also pointed out that prospective memory containstwo components: a retrospective component and a

prospective component. The retrospective compo-nent is remembering what action has to beperformed and when it has to be performed andthe prospective component is remembering to per-form the action when the appropriate event or timeoccurs. For example, in remembering to give amessage to a friend, the retrospective component isremembering the message and the friend to whom itis to be given. The prospective component isremembering to perform this action when one seesthe friend. Einstein et al [17] have argued that thissecond component, which seems not to be present inmost laboratory tests of retrospective memory, istypically accomplished through spontaneous remem-bering. That is, successful prospective memoryrequires that the occurrence of the appropriateevent or time activates the memory without thebenefit of a specific external prompt to initiate acontrolled search of memory at the time ofremembering.

In a number of previous studies, impairments ofprospective memory have been well observed inpatients with ageing [10, 18] or dementia [19–21].These data, however, lacked strict neuroanatomicalcorrelations. Despite a lot of neuroimaging studiessuch as functional magnetic resonance imaging(fMRI) or positron emission tomography (PET)found prefrontal cortex activations in relation to aprospective memory task [1, 22–26], evidence frompatients with lesions in the prefrontal cortex isrelatively small. The aim of the present study is toelucidate the precise neural basis involved inprospective memory by using a neuropsychologicaltests in the patients with lesion in PFC. This studyinvestigated event-based and time-based prospectivememory in patients with lesion in PFC usingprospective memory tasks analogous to those ofEinstein and colleagues [15, 17].

Methods

Participants

Thirty patients with lesions in the prefrontal cortexand 30 healthy control participants who gaveinformed consent were included in this study. The30 patients with lesions in the prefrontal cortex wereall in-hospital patients in the Department ofNeurology of The First Hospital of Anhui MedicalUniversity or the Department of Neurosurgery ofAnhui Province Hospital and there was no psychia-tric histories, no history of other neurological illnessor brain injury in any patient. Patients had focalprefrontal cortex lesions secondary to stroke, menin-goma or neurogliocytoma and were in stableneurological condition at the time of testing.Patients in the Department of Neurosurgery were

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all tested before they underwent surgical procedures.None of the patients showed significant languageimpairment that would have interfered with taskperformance. CT and/or MRI data, which identifiedthe site of lesion, were available for all patients.Lesions in the prefrontal cortex of 14 patients wereon the right, 15 patients on the left and one patienton both sides. Two patients who had damageextending outside the frontal cortex were excluded.The Mini-Mental State Examination (MMSE) wasadministered to all patients and only those whoscored 24 of 30 or above were included in this study.The patients with lesiond in the prefrontal cortexgroup included 18 men and 12 women. The averageage was 41.5 years, ranging from 27–55 years.

The control group included 19 men and11 women who were matched to patients in ageand education level, with no history of neurologicalor psychiatric disorder. They were staff of The FirstHospital of Anhui Medical University, family mem-bers of patients or students of Anhui MedicalUniversity. The average education level of thecontrol group was 11.6 years, ranging from 8–15years. The average age of the control group was 36.8years, ranging from 22–51 years. MMSE was alsoadministered to them and only those who scored 24of 30 or above were included in this study.

Neuropsychological background tests

A comprehensive battery of tests was administered toassess general cognitive and memory functions: theMMSE and Wechsler Adult Intelligence Scale-Revised Chinese (WAIS-RC) to measure globalcognitive function, the Verbal fluency test (VFT),in which subjects or participants were asked togenerate as many names, belonging to animals orvehicles, as possible in 1 minute, to measure frontallobe functions, and Digit span (DS) to measureworking memory.

Event-based prospective memory task

The participant was initially instructed that theyshould tap the desk whenever the two words whichbelong to animals (target events) appeared duringthe subsequent tasks and also that they should telltheir telephone number after the test finished with-out any mention. Next the participant was given aword selection task in which the target events for theprospective task were embedded. The task consistedof 32 question cards. On each card, 12 Chinesewords were printed. Ten of the 12 words belonged toone category and the remaining two words belongedto another category. The participant was told toselect the two words that belonged to a category thatdiffered from the other 10 words. The experimenterpresented each card to the participants, who were

then instructed to answer verbally at their own pace.The target events for the prospective memory taskoccurred on the 6th, 11th, 16th, 21st, 25th and 31stcard of the word selection task. After the wordselection task, the participant should remember tospeak out their telephone number and the partici-pant was also asked to recall the animal words.

A prospective memory (EBPM) and a retro-spective memory (RM1) score were recorded,respectively, for correct response during the test.The maximum score of EBPM is 8. One point wasgiven for each correct response to a target event(total six target events), while 0 was given for anincorrect response and 2 was given for rememberingto tell their telephone number after the test.The retrospective memory score (RM1) refers tothe participant’s performance on recalling animalwords after the word selection task; 1 was given foreach correct recalling of an animal word (maximumscore 12).

Time-based prospective memory task

The participant was instructed that they should tapthe desk after each 5 minutes had elapsed during theupcoming test (i.e. to remember to tap the deskexactly at the time points of 5, 10 and 15 minutes,respectively, after the test). Participants wereallowed to use a digital clock to check the time. Toexclude any visible external cue, the digital clock(the clock was set to display 0 hour 0 min 0 s at thebeginning) was located 1 metre away behind theparticipant’s right shoulder and the participantsmight turn their head to the clock when theymanaged to check the time during the test. Afterthe clock was started, the participant was shown 100cards one by one, on each of which 12 arabicnumerals were printed. The participant was requiredto select the biggest and the smallest number foreach card and the test did not stop until the digitalclock indicated 17 minutes. The participants wereexpected to recall check the time and tap the desk atthe each time point.

A prospective memory (TBPM) score and aretrospective memory (RM2) score were recorded,respectively, for correct response. The maximumscore of TBPM is 6. Each exactly punctual responseat time point (from 10 seconds before to 10 secondsafter the target time) were given a score of 2 andnearly punctual response (from 30 seconds before to30 seconds after the target time) were given a scoreof 1. The retrospective memory (RM2) score refersto the participants’ performance on recalling thetime when tapping the desk after the numberselection task. A score of 2 was given for correctrecalling each time point when tapping the desk(maximum score 6).

Evidence from patients with lesions in the prefrontal cortex 699

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For both groups, 15 participants performed theevent-based prospective memory task first and theother 15 participants performed the time-basedprospective memory task first.

Statistical analysis

Performance on the event-based and time-basedprospective memory tasks and retrospective memorytasks in patients with lesions in the prefrontal cortexand control groups were compared by analysis ofT test. Performance on the event-based andtime-based prospective memory tasks between theleft and right PFC patients were achieved usingMann-Whitney U-test. Results were consideredsignificant if p50.05.

Results

Background neuropsychological evaluation

In Table I, scores on the neuropsychological testsadministered to both groups are presented. There isno significant difference between patients andcontrols on WAIS-RC, MMSE or DS (p40.05).The performance of patients with lesions in theprefrontal cortex was significantly poorer than that ofthe control group on the VFT (p50.01).

Event-based prospective memory task

In Table II and Figure 1, the means and standarddeviations for the performance of EBPM arepresented for the two groups. The result shows thesignificant difference between the performance ofpatients and controls. The event-based prospectivememory score of the patients with lesions in theprefrontal cortex (1.47�1.07) was significantlylower than that of the control group (6.00� 1.91)(t¼�11.322, p50.01).

Time-based prospective memory task

In Table II and Figure 1, the means and standarddeviations for the performance of TBPM arepresented for the two groups. There was nosignificant difference between the control andpatients with lesions in the prefrontal cortex in thetime-based prospective memory score (t¼�1.972,p40.05).

Table I. Demographics data and neuropsychological tests scores and SD of the patients with lesions in the prefrontalcortex and the control group.

Patients with lesions in the PFC Normal controls

n 30 30Age (years) 41.50� 13.16 36.77� 14.14Gender 18 f/12 m 19 f/11 mEducation level (years) 10.77� 3.14 11.57� 3.32Handedness 30 R/0 L 28 R/2 LWechsler Adult Intelligence Scale-Revised

Chinese (WAIS-RC)103� 8.6 105� 7.2

Word fluency test (VFT) 8.20� 2.31* 10.97� 2.39The Mini-Mental State Examination (MMSE) 28.83� 1.21 29.27� 0.94Digital Span (DS) 5.97� 1.10 6.33� 0.96

*T-test, p50.01.

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Figure 1. Mean prospective memory scores of the control groupand the patients with lesion in PFC on the event-based and time-based prospective memory tasks. PFC: the patients with lesion inPFC, Normal: Normal controls, EBPM: event-based prospectivememory, TBPM: time-based prospective memory.

Table II. The performance of the control group and the patientswith lesions in the prefrontal cortex on event- or time-basedprospective memory.

Patients with lesionsin the PFC (n¼ 30)

Normalcontrols (n¼ 30)

EBPM 1.47� 1.07* 6.00� 1.91TBPM 4.77� 1.17 5.30� 0.92

*T-test, p50.01.

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Event- and time-based prospective memory in

the left and right prefrontal cortex

In Table III, the means and standard deviations forthe performance of EBPM and TBPM are presentedfor the left and right sub-groups in patients withlesions in the prefrontal cortex. There was nodifference in performance of EBPM and TBPMtasks between the left and the right prefrontal cortex.

Retrospective memory task

In Table IV, the means and standard deviations forthe performance of retrospective memory task arepresented for the two groups. There was nosignificant difference between the control and thepatients with lesions in the prefrontal cortex inretrospective memory tasks.

Discussion

The present study shows that the patients withlesions in the prefrontal cortex performed poorly onthe event-based prospective memory task, butperformed normally on the time-based prospectivememory task. There is a current consensus amongstinvestigators that at least some of the processeswhich are critical to realizing delayed intentions aresupported by brain structures located in the pre-frontal cortex and related structures [6, 8, 12, 15].As expected, the main findings of the presentexperiment confirmed the view from previous

neuroimaging reports that the prefrontal cortex islikely to be of central importance to event-basedprospective memory [1, 22–26]. For example,Okuda et al. [1] reported activation in the left frontalpole, as well as right dorsolateral and ventrolateralprefrontal cortex, when participants rememberedand acted upon a list of target words relative toperforming an ongoing routine activity (word repeti-tion). Activation in the frontal pole bilaterally wasalso found by Burgess et al. [23] across several event-based prospective memory tasks. Recently, denOuden et al. [25] reported activation in lateralPFC, associated with keeping an intention in mindwhile performing an ongoing task responding toquestions about intentions and actions; Simons et al.[26] have suggested that differential components ofprospective memory (cue identification and inten-tion retrieval) share some common neural basis inthe anterior prefrontal cortex. All of this neuroima-ging evidence has shown repeatedly that PFC have arole in the maintenance and realization of delayedintentions that are triggered by event cues (i.e. event-based prospective memory). The cerebral organiza-tion of the processes associated with the use of timecues (i.e. time-based prospective memory) hashowever received little attention in the literature.Some evidence indicates differential involvement ofregions of the prefrontal cortex in time- and event-based prospective memory [22].

The present research provides further evidence forthe involvement of the prefrontal cortex in event-based prospective memory, but less involvement intime-based prospective memory. It indicates thatEBPM is likely to be particularly sensitive to theeffects of lesions in PFC. This neuropsychologicalstudy strongly suggests that further investigation isneeded to clarify the similarities and differencesbetween the two forms of prospective memory.

Event-based prospective memory

The advent of functional neuroimaging techniquessuch as positron emission tomography (PET) hasallowed investigators to examine the functionalneuroanatomy of prospective memory [1, 22–24].These studies have examined changes in regionalcerebral blood flow (rCBF) during event-basedprospective memory tasks and shown significantrCBF changes in the rostral prefrontal cortex,situated in the most anterior part of the frontallobes (consisting of the superior frontal gyrus, part ofthe middle frontal gyrus and the medial frontal lobe).The present study provides further evidence for theinvolvement of the rostral prefrontal cortex in event-based prospective memory. On the event-basedprospective memory task, the prospective memoryscore of the patients with lesions in the prefrontal

Table IV. The performance of the patients with lesions in theprefrontal cortex and control groups on retrospective memory.

Patients with lesionsin the PFC (n¼ 30)

Normalcontrols (n¼ 30) p-value*

RM1 6.43� 1.43 6.97� 1.77 NSRM2 4.87� 1.36 5.13� 1.14 NS

RM1 is the retrospective memory score during the event-basedprospective memory. RM2 is the retrospective memory scoreduring the time-based prospective memory. *T-test. NS,not significant.

Table III. The performance of the patients with lesions in the leftor right prefrontal cortex on event- and time-based prospectivememory.

LPFC (n¼ 15) RPFC (n¼14) p-value*

EBPM 1.40�1.12 1.64� 1.01 NSTBPM 4.60�1.06 4.86� 1.29 NS

LPFC is the patients with lesions in the left prefrontal cortex,RPFC is the patients with lesions in the right prefrontal cortex.*Mann-Whitney U-test. NS, not significant.

Evidence from patients with lesions in the prefrontal cortex 701

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cortex was significantly lower than that of the controlgroup, but there was no significance in retrospectivememory between the control group and the patientswith lesions in the prefrontal cortex. Einstein andMcDaniel [15] had reported that there wereprospective and retrospective component in event-based prospective memory and also pointed out thatthe retrospective component of prospective memorytasks seemed to be identical to the ability that isevaluated by retrospective memory tasks. Thus, theimpairment of event-based prospective memory inthe patients with lesions in the prefrontal cortex wasattributable mainly to impairment of the prospectivecomponent. The retrospective memory of patientswith lesions in the prefrontal cortex has beenreported to be impaired [27]. However, the deficitin retrospective memory in the patients with lesionsin the prefrontal cortex is generally mild and theretrospective component of the task was quite simplein this study. These may be the reasons why thepatients with lesions in the prefrontal cortex did notshow significant impairment on the retrospectivecomponent. Lezak [28] mentioned that the retro-spective memory of patients with frontal lobedamage may be comparatively intact, but that theyare unable to carry out previously decided uponactivities at designated times or places.The prospective component is an essential part ofprospective memory [15, 16]. Several authors[29, 30] have mentioned that the prefrontal cortexplays a critical part in the prospective component ofprospective memory. Shimamura et al. [31]described that the frontal lobe plays an importantpart in self-initiated retrieval of information inprospective memory. A recent study [22] usingPET demonstrated activations relating to prospec-tive memory in the prefrontal cortices. Impairedevent-based prospective memory evidence was alsofound in other patients with prefrontal lobe dysfunc-tion such as Parkinson’s disease [32], Korsakoffs[33] and schizophrenia [34, 35]. Taken together, it ispossible that the impaired prospective component ofevent-based prospective memory found in this studyarises from the patients with lesions in the prefrontalcortex.

Time-based prospective memory

Time-based prospective memory is remembering toperform an action at a certain time. Previous studieshave shown a significant age-related decline on thetime-based task [17–19]. However, the functionalneuroanatomy of time-based prospective memoryhas received relatively little attention in previousliterature. Therefore it is not known whether the twoprospective memory tasks make differential demandsupon the prefrontal cortex. Okuda et al. [36] had

reported preliminary results regarding PETactivations during a time-based prospectivememory task. The rCBF increases common to thetime- and event-based tasks were observed in thefrontal and medial temporal regions. Some otherstudies have shown better performance on time-based rather than event-based prospective memorytasks in patients with cerebrovascular stroke [37] andParkinson’s disease [32]. Consistent with theseinvestigations, the present study found that thepatients with lesions in the prefrontal cortex andcontrol groups differed unsignificantly on the time-based prospective memory task. This indicates thatthe time-based prospective memory task in thepatients with lesions in the prefrontal cortex waspreserved. This may be because the nature of theprospective component of the time-based prospec-tive memory task was essentially different from thatof the event-based prospective memory task. In thetime-based prospective memory task, there was noobvious external cue and the participants had toremember on their own to monitor the passage oftime and to initiate the action. According to thetime-based prospective memory task, successfulremembering is critically dependent on monitoringor checking the time during a critical period.Einstein et al. [17] investigated the relations betweenclock checking frequency and time-based prospec-tive memory performance. They found that clockchecking frequency, especially clock checking closeto the target time, highly correlated with time-basedprospective memory performance, with higher clockchecking associated with faster responding. Thus,the prospective component of the time-based pro-spective memory task was heavily dependent onclock checking or time monitoring behaviour andthese may be involved in some other brain areaswhich are related to time perception. Burgess et al.[23] reported that prospective memory-related acti-vation was also seen in a number of areas outside thePFC such as inferior parietal regions, precuneus andthalamus. Whether the time-based prospectivememory is selectively involved in these areas mustdepend on further neuroimaging and neuropsycho-logical investigation.

Why were the patients with lesions in theprefrontal cortex impaired on the event-basedprospective memory task, but not on the time-based prospective memory task? Okuda et al. [36]investigated localized brain activations in relation toan event-based prospective memory task usingpositron emission tomography and concluded thatretaining the intention of future behaviour in theevent-based prospective memory tasks was mediatedby the right ventrolateral prefrontal region and theleft frontal pole. On the other hand, Harrington et al.[38] suggested that a neural network composed of

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the right inferior parietal cortex to the rightmiddle and superior frontal gyri plays a crucial partin the temporal monitoring process in timeperception tasks. These findings suggest that pro-spective memory components of event-based andtime-based prospective memory tasks may bemediated by different neural networks and dissocia-tion in prospective memory impairment in patientswith lesions in the prefrontal cortex may beattributable to selective impairment of these neuralnetworks.

Finally, there are two limitations worthy ofdiscussion. The first is the lack of within-hemispherecomparisons of the prefrontal cortex. Future inves-tigations may include more patients with lesions inPFC and examine the difference between sub-regiongroups, such as anterior, dorsolateral and ventrolat-eral PFC. It is also necessary to compare thepatients’ performance with that of brain damagedcontrols to make sure that EBPM deficit is aconsequence of a specific functional deficit of PFCrather than a more general result of’ brain damage.The second limitation for discussion is the difficultyof excluding confounds to the present results whichcan be taken as evidence of ‘dissociation’ infunctions between EBPM and TBPM. Althoughthere were multiple aetiological factors on patientswith lesions in the prefrontal cortex and the durationof brain lesion may be different, the primaryobjective of the investigation, however, was todetermine if persons with PFC injury can lead to achange in prospective memory. So, one will start byexcluding these factors that must be of littlesignificance. However, given these caveats and thelimitations of the present research and the primitiveexperimental procedures, the data here are probablyas strong an indicator of double dissociation betweenthe EBPM and TBPM as might be expected fromprevious neuroimaging studies.

Acknowledgements

This research was supported by the National NaturalScience Foundation of China (3067070), NationalBasic Research Program of China (2005CB522800),Distinguished Youth Science Grants (04043071)and Natural Science Grants of Anhui, China(01043602, 2004kj192zd). The authors are gratefulto the members of the Department of Neurosurgeryof Anhui Province Hospital and the Department ofNeurology of The First Hospital of Anhui MedicalUniversity for their participation in and assistancewith the study. We would like to thank Chao-shi Niuand Xian-ming Fu for their helpful comments on anearlier draft of this paper.

Declaration of interest: The authors report noconflicts of interest. The authors alone are respon-sible for the content and writing of the paper.

References

1. Okuda J, Fujii T, Yamadori A, et al. Participation of theprefrontal cortices in prospective memory: Evidence from aPET study in humans. Neuroscience Letters 1998;253:127–130.

2. Smith G, Della Sala S, Logie RH, Maylor EA. Prospectiveand retrospective memory in normal ageing and dementia:A questionnaire study. Memory 2000;8:311–321.

3. Meacham JA, Singer J. Incentive effects in prospectiveremembering. Journal of Psychology 1977;97:191–197.

4. Kvavilashvili L, Messer DJ, Ebdon P. Prospective memory inchildren: The effects of age and task interruption.Developmental Psychology 2001;7:418–443.

5. Ellis J, Milne A. Retrieval cue specificity and the realization ofdelayed intentions. Quarterly Journal of ExperimentalPsychology (A): Human Experimental Psychology 1996;49:862–887.

6. Randy L, Buckner WM, Kelley SE, Petersen SE. Frontalcortex contributes to human memory formation. NatureNeuroscience 1999;2:311–314.

7. Miller EK. The prefrontal cortex and cognitive control.Nature Reviews Neuroscience 2000;1:59–65.

8. Fletcher PC, Henson RN. Frontal lobes and human memoryinsights from functional neuroimaging. Brain 2001;124:849–881.

9. West R, Krompinger J. Neural correlates of prospective andretrospective memory. Neuropsychologia 2005;43:418–433.

10. Henry JD, MacLeod MS, Phillips LH, Crawford JR.A metaanalytic review of prospective memory and aging.Psychology and Aging 2004;19:27–39.

11. Craik FIM. A functional account of age differences inmemory. In: Klix F, Hagendorf H, editors. Humanmemory and cognitive capabilities: Mechanisms and perfor-mances. Amsterdam: Elsevier–North-Holland; 1986.pp 409–422.

12. Burgess PW. Strategy application disorder: The role of thefrontal lobes in human multitasking. Psychological Research2000;63:279–288.

13. Knight RG. Prospective memory in aging and neurodegen-erative disease. In: Troster AI, editor. Memory in neurode-generative disease: Biological, cognitive, and clinicalperspectives. Cambridge: Cambridge University Press;1998. pp 172–183.

14. Miller EK. The prefrontal cortex: Complex neural propertiesfor complex behavior. Neuron 1999;22:15–17.

15. Einstein GO, McDaniel MA. Normal aging and prospectivememory. Journal of Experimental Psychology: Learning,Memory, and Cognition 1990;16:717–726.

16. Einstein GO, McDaniel MA. Retrieval processes in prospec-tive memory: Theoretical approaches and some new empiri-cal findings. In: Brandimonte M, Einstein GO, McDanielMA, editors. Prospective memory: Theory and applications.Mahwah: Erlbaum; 1996. pp 115–141.

17. Einstein GO, McDaniel MA, Richardson SL, Guynn MJ,Cunfer AR. Aging and prospective memory: Examining theinfluences of self-initiated retrieval processes. Journal ofExperimental Psychology: Learning, Memory, andCognition 1995;21:996–1007.

18. Zollig J, West R, Martin M, Altgassen M, Lemke U,Kliegel M. Neural correlates of prospective memory acrossthe lifespan. Neuropsychologia 2007;45:3299–3314.

Evidence from patients with lesions in the prefrontal cortex 703

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om b

y U

nive

rsita

t de

Gir

ona

on 1

1/18

/14

For

pers

onal

use

onl

y.

19. Maylor EA, Smith G, Della SS, et al. Prospective andretrospective memory in normal aging and dementia: Anexperimental study. Memory and Cognition 2002;30:871–884.

20. Jones S, Livner A, Backman L. Patterns of prospective andretrospective memory impairment in preclinical Alzheimer’sdisease. Neuropsychology 2006;20:144–152.

21. Huppert FA, Beardsall L. Prospective memory impair-ment as an early indicator of dementia. Journal ofClinical and Experimental Neuropsychology 1993;15:805–821.

22. Okuda J, Fujii T, Ohtake H, et al. Differential involvement ofregions of rostral prefrontal cortex (Brodmann area 10) intime- and event-based prospective memory. InternationalJournal of Psychophysiology 2007;64:233–246.

23. Burgess PW, Quayle A, Frith CD. Brain regions involved inprospective memory as determined by positron emissiontomography. Neuropsychologia 2001;39:545–555.

24. Burgess PW, Scott SK, Frith CD. The role of the rostralfrontal cortex (area 10) in prospective memory: A lateralversus medial dissociation. Neuropsychologia 2003;41:439–453.

25. den Ouden HEM, Frith U, Frith C, Blakemore SJ. Thinkingabout intentions. NeuroImage 2005;28:787–796.

26. Simons JS, Scholvinck M, Gilbert SJ, Frith CD, Burgess PW.Differential components of prospective memory? Evidencefrom fMRI. Neuropsychologia 2006;44:1388–1397.

27. Vallesia A, Shallicea T. Prefrontal involvement in sourcememory: An electrophysiological investigation of accountsconcerning confidence and accuracy. Brain Research2006;1124:111–125.

28. Lezak MD. Neuropsychological assessment. 3rd ed.New York: Oxford University Press; 1995. p 33.

29. Stuss DT, Benson DF. The frontal lobes. New York: RavenPress; 1986. pp 180–193.

30. Cockburn J. Task interruption in prospective memory:A frontal lobe function? Cortex 1995;31:87–89.

31. Shimamura AP, Janowsky JS, Squire LR. What is the role offrontal lobe damage in memory disorders? In: Levin HS,Eisenberg HM, Benton AL, editors. Frontal lobe functionand dysfunction. New York: Oxford University Press; 1991.pp 173–195.

32. Katai S, Maruyama T, Hashimoto T, et al. Event based andtime based prospective memory in Parkinson’s disease.Journal of Neurology, Neurosurgery, and Psychiatry2003;74:704–709.

33. Brunfaut E, Vanoverberghe V, d‘Ydewalle G. Prospectiveremembering of korsakoffs and alcoholics as a function of theprospective-memory and on-going tasks. Neuropsychologia2000;38:975–984.

34. Shum D, Ungvari GS, Tang WK, et al. Performance ofschizophrenia patients on time-, event-, and activity-basedprospective memory tasks. Schizophrenia Bulletin 2004;30:693–701.

35. Henry JD, Rendell PG, Kliegel M, et al. Prospective memoryin schizophrenia: Primary or secondary impairment?Schizophrenia Research 2007;95:179–185.

36. Okuda J, Fujii T, Ohtake H, et al. Thinking of the future andpast: The roles of the frontal pole and the medial temporallobes. NeuroImage 2003;19:1369–1380.

37. Brooks BM, Rose FD, Potter J, et al. Assessing strokepatients’ prospective memory using virtual reality. BrainInjury 2004;18:391–401.

38. Harrington DL, Haaland KY, Knight RT. Cortical networksunderlying mechanisms of time perception. Journal ofNeuroscience 1998;18:1085–1095.

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