《认知神经科学》课程教学资源（参考文献）[Fletcher, P. C., & Henson, R. N. A.（2001）]Frontal lobes and human memory - Insights from functional neuroimaging..pdf

Brain (2001), 124, 849–881 INVITED REVIEW Frontal lobes and human memory Insights from functional neuroimaging P. C. Fletcher1 and R. N. A. Henson2 1Research Department of Psychiatry, Cambridge University, Correspondence to: P. C. Fletcher, Box 189, Research Addenbrooke’s Hospital, Cambridge and 2Wellcome Department of Psychiatry, Cambridge University, Department of Cognitive Neurology and Institute of Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK Cognitive Neuroscience, University College London, UK E-mail: pcf22@cam.ac.uk Summary The new functional neuroimaging techniques, PET and lateral, dorsolateral and anterior—that are consistently functional MRI (fMRI), offer sufficient experimental activated in these studies, and attribute these activations flexibility and spatial resolution to explore the functional to the updating/maintenance of information, the selection/ neuroanatomical bases of different memory stages and manipulation/monitoring of that information, and the processes. They have had a particular impact on our selection of processes/subgoals, respectively. We also understanding of the role of the frontal cortex in memory acknowledge a number of empirical inconsistencies assoprocessing. We review the insights that have been gained, ciated with this synthesis, and suggest possible reasons and attempt a synthesis of the findings from functional for these. More generally, we predict that the resolution imaging studies of working memory, encoding in episodic of questions concerning the functional neuroanatomical memory and retrieval from episodic memory. Though subdivisions of the frontal cortex will ultimately depend on these different aspects of memory have usually been a fuller cognitive psychological fractionation of memory studied in isolation, we suggest that there is sufficient control processes, an enterprise that will be guided and convergence with respect to frontal activations to make tested by experimentation. We expect that the neurosuch a synthesis worthwhile. We concentrate in particular imaging techniques will provide an important part of this on three regions of the lateral frontal cortex—ventro- enterprise. Keywords: frontal; memory; functional MRI; PET Abbreviations: AFC anterior frontal cortex; DLFC dorsolateral frontal cortex; ERP event-related potential; FC frontal cortex; fMRI functional MRI; HERA hemispheric encoding–retrieval asymmetry; LTM long-term memory; VLFC ventrolateral frontal cortex; WM working memory Introduction PET and functional MRI (fMRI) have demonstrated consistent specialization might not exist within FC. We believe this activations of the frontal cortex (FC) in a number of memory approach will prove more fruitful than attempting to define tasks. Interpretations of these activations vary widely, how- a general and abstract function for FC as a whole. Ultimately ever, as do their precise locations within FC. In this article, however, the validity of this level of functional specialization we review these findings and offer a new interpretation that is best judged by its success in explaining extant neuroimaging takes heed of the broad anatomical variation of activations and neuropsychological data. within FC. Neuroimaging offers a number of advantages over Our main hypothesis is that functional specialization, neuropsychology with regard to understanding the functional within the context of memory-related processes, exists across parcellation of FC. First, neuropsychological studies deal at least three anatomically distinct frontal regions. This with lesions that often differ markedly in size and location principle of functional–anatomical specialization has proved across different patients. PET and in particular fMRI offer a remarkably successful in, for example, the study of the visual more precise spatial characterization of functional cortex, and we see no a priori reason why analogous differentiation across FC. Secondly, the memory deficits © Oxford University Press 2001

850 P.C.Fletcher and R.N.A.Henson produced by frontal lesions tend to be subtle,and it is likely only meaningful to the extent that the psychological theory that the sorts of memory processes subserved by FC are of task performance is accurate.A specific example of this upstre of observe haviours (Burg isthe assumption that a task manipulation changes behavioural performance with varving degrees of frontal mediation and compensatory strategies.Functional neuro 1996:Donders,1969)is particularly relevant to simple ctive methods of analysing imaging data,in whicl of rol)is subtr memory process.For example,they can examine separately another task that is assumed to differ only in the single psychological process of interest.The difference between the on mad wo ta sks may in to function inde endently of other brain systems with which measures aone)This is why the activations cannot be evaluated without but no m may b h。 er a regi .This pro cquisition of whole-hrain im lated ved by FC tio of spatially distributed functional networks of activity Moreove analytical techniques have been developed tha allow the cha on connectivity others const but do so witho cha ha ions rather than the stimuli). (e.g the 1997) It is important to raise this problem -that neuroimaging I acti vation obs are only context of 0 subjects show onta I activation in ass tion with recogn re discussed in the Conclusions section).This is b au ing et al. Rugg et c e recent neurom ng nndi that such tasks may be performed relatively ontext of specific theories In the final section.howeve normally even in the face of widespread frontal damage.On possibility is that such activations are theoretical note also thet the pproa ontain important additional information about the wa 000).When the Talairach of activation healthy subjects perform the task.If so. the failure of naxima these authors found a ural m res region that asks.but failed to ind evidence for discrepancies between functional imaging and neuropsycho of the maxima within these regions.Our approach begins logical data may point to flaws in our cognitive models o with prior,anatomically defined regions and. while accepting asks are pert mance is me the functional imaging techniques rather than,as has beer unt emeroes from diff ntial activations of these re suggested,a weaknes We propose to distinguish be een activatio use imaging to addre nctiona regi y state of e nfined to the lateral understanding of the types of processes subserved by FC.In they are the regions most commonly activated in memory- most functional neuroimaging experiments,changes in the elated tasks.DLFC con of pon tal gyrus E the to a specific psychological process sedly isolated hy the fron olar area lying anterior to the anteriormost extent the task manipulation.The pattern of brain activity is therefore of the inferior frontal gyrus (Fig.1).We make these

850 P. C. Fletcher and R. N. A. Henson produced by frontal lesions tend to be subtle, and it is likely only meaningful to the extent that the psychological theory that the sorts of memory processes subserved by FC are of task performance is accurate. A specific example of this some distance ‘upstream’ of observed behaviours (Burgess, problem is the assumption that a task manipulation changes 1997). Patients may, for example, achieve comparable only a single cognitive process, leaving other processes behavioural performance with varying degrees of frontal unaffected. This assumption of ‘pure insertion’ (Friston et al., mediation and compensatory strategies. Functional neuro- 1996; Donders, 1969) is particularly relevant to simple imaging offers the possibility of detecting differences in the subtractive methods of analysing imaging data, in which strategies that subjects or patients employ. Thirdly, functional mean brain activity during the performance of one task (the neuroimaging techniques can elucidate different stages of a control) is subtracted from that during the performance of memory process. For example, they can examine separately another task that is assumed to differ only in the single the encoding and retrieval of memories, a dissociation that psychological process of interest. The difference between the cannot be made with confidence from anterograde memory two tasks may in fact be accompanied by numerous cognitive deficits following frontal lobe lesions. Finally, FC is unlikely changes (which may not be evident from behavioural to function independently of other brain systems with which measures alone). This is why the ‘activations’ reported it interacts (Fuster, 1997). Neuropsychological study can by neuroimaging experiments cannot be evaluated without show whether a region is necessary for a given task, but not reference to the control task. This problem may be particularly usually the broader system of which that region forms a part. relevant to the relatively high-level (non-automatic) and interAcquisition of whole-brain images enables the characteriza- related processes generally believed to be subserved by FC. tion of spatially distributed functional networks of activity. Isolating such processes requires experimental manipulations Moreover, analytical techniques have been developed that that not only engage each of them to different degrees while allow the characterization of the effective connectivity holding the others constant, but do so without changing between different brain regions during task performance lower-level (e.g. perceptual) processes (e.g. changing the (McIntosh and Gonzales-Lima, 1994; Bu¨chel and Friston, instructions rather than the stimuli). 1997). It is important to raise this problem—that neuroimaging It has been suggested that a regional activation observed ‘activations’ are only interpretable in the context of a in functional imaging tells us little about the necessity of particular theory of task performance and often with respect that region for task performance (Price and Friston, 1999; to a specific control—at the outset of this review (other Fletcher, 2000). For example, a number of studies of healthy problems associated with current neuroimaging experiments subjects show frontal activation in association with recogni- are discussed in the Conclusions section). This is because we tion memory (e.g. Tulving et al., 1994b; Rugg et al., 1996) describe and organize recent neuroimaging findings initially in while neuropsychological studies (e.g. Stuss et al., 1994) terms of one or more conventional labels and within the have indicated that such tasks may be performed relatively context of specific theories. In the final section, however, we normally even in the face of widespread frontal damage. One offer a re-evaluation of the prominent findings within a possibility is that such activations are epiphenomenal, in the modified theoretical framework. We note also that our sense that they are not directly task-related. A more interesting approach differs from formal meta-analyses, such as that possibility, however, is that the functional imaging data recently performed by Duncan and Owen (Duncan and Owen, contain important additional information about the way 2000). When plotting the Talairach coordinates of activation healthy subjects perform the task. If so, the failure of maxima from a number of studies, these authors found a behavioural measures to distinguish between the performance subset of lateral and dorsomedial FC regions that were of a task in patients and in controls may indicate a limitation commonly activated across a range of different cognitive or insensitivity in the behavioural measures. That is, tasks, but failed to find evidence for functional segregation discrepancies between functional imaging and neuropsycho- of the maxima within these regions. Our approach begins logical data may point to flaws in our cognitive models of with prior, anatomically defined regions and, while accepting how tasks are performed and how performance is measured. some errors in the attribution of functional activations to In this sense, such discrepancies may represent a strength of these regions, examines whether a consistent theoretical the functional imaging techniques rather than, as has been account emerges from differential activations of these regions. suggested, a weakness. We propose to distinguish between activations occurring The use of functional imaging to address functional in the following FC regions: ventrolateral FC (VLFC), specialization within FC is, however, problematic. The most dorsolateral FC (DLFC) and anterior FC (AFC). We chose fundamental problem lies in the rudimentary state of current these regions, confined to the lateral aspect of FC, because understanding of the types of processes subserved by FC. In they are the regions most commonly activated in memorymost functional neuroimaging experiments, changes in the related tasks. DLFC consists of the area lying superior to the haemodynamic response of a region are correlated with a inferior frontal gyrus and VLFC to the area below it, i.e. the manipulation of the subject’s task. This change is attributed inferior frontal gyrus. AFC is defined more arbitrarily as to a specific psychological process supposedly isolated by the frontopolar area lying anterior to the anteriormost extent the task manipulation. The pattern of brain activity is therefore of the inferior frontal gyrus (Fig. 1). We make these

Frontal lobes and human memory 851 Fig. 1 Left-sided view of human brain showing our working subdivisions of lateral FC. The border between VLFC and DLFC is marked by the inferior frontal sulcus. The posterior border of AFC is marked by a line drawn vertically at the anterior edge of the inferior frontal gyrus. distinctions (in addition to the left–right lateralization of the we cannot be certain of the precise relationship between regions) with due consideration of the imperfect spatial connectivity and macroanatomical landmarks, and we refrain resolution of the techniques, of the enormous anatomical from further speculation. Finally, we confine our review to variability among subjects, and of the likelihood that, studies of groups of young, healthy individuals. ultimately, these broad areas will themselves be shown to be The nature of the contribution of the frontal lobe to functionally subdivided. The rationale behind this division memory is clouded by the division of the experimental is, on the one hand, an attempt to acknowledge the limited literature into two broad fields: working memory (WM), the spatial information provided by group studies (particularly ability to maintain information temporarily over periods of with PET) and, on the other hand, to avoid treating clearly seconds, and long-term memory (LTM), the ability to retain separate regional responses as undifferentiated ‘frontal’ information for much longer periods. While there are good activations. Our particular subdivisions are based on existing reasons for distinguishing between these two types of memfunctional imaging data rather than microstructural findings, ory, it is also likely that considerable overlap exists between although they may be considered to provide some clues to the frontally mediated processes involved in each. Many the underlying anatomy. Thus, VLFC corresponds loosely imaging studies of encoding and retrieval in LTM, for to Brodmann areas 44, 45 and 47, DLFC to areas 9 and 46 example, are likely to entail maintaining and manipulating and AFC to areas 8 and 10. It is our intention, however, to information in WM. Conversely, information maintained in avoid relying upon the uncertain and inconsistent relationship WM may be encoded into LTM. It is interesting, therefore, between macroscopic sulcal/gyral features (onto which the that similar FC dissociations of function have been proposed PET and fMRI activations are mapped) and the boundaries in both LTM and WM imaging studies, and yet these of the Brodmann areas (Roland et al., 1997; Zilles et al., findings, with certain exceptions (Wagner, 1999), are not 1997). Amunts and colleagues, for example, noted a 10-fold often considered together. Nonetheless, a convenient way to difference in the size of Broca’s area across a group of introduce the evidence is to consider each field separately, 10 individuals, the microscopic boundaries bearing little before subsequently discussing how they may converge. consistent relationship to macroscopic landmarks (Amunts We therefore address the patterns of memory-related FC et al., 1999). Caution must therefore be exercised in relating activation in two stages. First, we consider interpretations of macro- to microanatomy, and we will avoid the use of FC activations offered by researchers within each domain Brodmann’s definitions. The chosen subdivisions are also (WM, LTM encoding, LTM retrieval). Secondly, in the likely to reflect differences in patterns of connectivity concluding section, we attempt a more general interpretation (Passingham, 1993; Fuster, 1997). Once more, however, that extends to FC activations across the different domains

P.C.Fletcher and R.N.A.Henson Frontal function in working memory tasks The term 'working memory'is ger rally used to refer to the currently maintain ability to maintain information on-line,often in the service as he onitoring and h her-level planning of a particular be illustrated or goa ever,the term has diffe om often used to describe the ability of an animal to remembe simply require that the subject decides whether a prob a stimulus for a short period after it is removed (in orde matches one of a set to perform e.g.delayed matching-to-sample tasks).In th cognitive stimulus at a time fror ature.on th the set presented previously.such that,over trials,every sources of information are order to perform timulus has been selected once (without repetition). Thi requires that the wo perspectives etore consi revious responses.According to ol stigation eas a sel tent with thi defici tasks but not typi ally on delayed-matchin Perspectives from animal studies:domain in patients which typical lly include (Petrides nal specializ 98 19 0).Fur theories. These theories co entrate in r particular on dis with DLFC lesions w re imnaired on simple verhal o sociations between ventral and dorsal regions of lateral FC span tasks that require only maintenance of a stimulus on-line ry. hou ymanipula on)(D'Esposito oppo Moreover,the fo mainte prec n the is 0 largely on electrophysio tical recordings and is 3 imnle spatial delaved r sponse tasks or only in more comple extension of the object-spatial (what'versus'where)visua situations,such as self-ordering tasks.Nonetheless,we will n posterior regions(Mishkin ompare the e two genera theories for their ability to accoun ore spec n and the imaging dat The data are i from the human psychological literature. on WM e dorsal to the principal sulcus code for r spatial information al. 1993 gene tial VLEC-DLEC distinction refects all com Perspectives from human cognitive psychology: WM:the'attentional,memorial and response control mechan multiple-component models isms'(Goldman-Rakic 1998).That is,there is no suggestio hich th 194 nerate develoned to account for a range of different wM functions The altemative,process-specific theory proposes that the from temporary maintenance of a single stimulus to the e the type of nipulation of multiple types of inform ratine on that material (Pe Shiffrin.1968).which acted simply as ag derives mainly from animal lesion data (Petrides,1994)and perception and LTM,to a multicomponent system in which has been extende to human lesion data (Petride a number of subsidiary 'slave'systems are coordinated by a wen et e ding to this th nmo centra ex The ave systen tion in WM.This infommation may have been perccived limited-capacity.material-specific stors.concemed with the recently or retrieved from LTM.DLFC.however.supports maintenance of verbal and visuospatial material respectively

852 P. C. Fletcher and R. N. A. Henson Frontal function in working memory tasks more complex processes operating on information that is The term ‘working memory’ is generally used to refer to the currently maintained in WM. These include processes such ability to maintain information on-line, often in the service as monitoring and higher-level planning. of a particular task or goal. However, the term has different The process-specific distinction can be illustrated by connotations in different fields. In the animal literature, it is comparing two types of WM task. ‘Delayed matching tasks’ often used to describe the ability of an animal to remember simply require that the subject decides whether a probe a stimulus for a short period after it is removed (in order stimulus matches one of a set of stimuli held in WM. This task requires maintenance only. In ‘self-ordered tasks’, to perform e.g. delayed matching-to-sample tasks). In the cognitive psychological literature, on the other hand, WM however, the subject must select one stimulus at a time from frequently refers to a mental workspace in which multiple the set presented previously, such that, over trials, every stimulus has been selected once (without repetition). This sources of information are manipulated in order to perform complex problem-solving tasks. We begin by introducing the requires that the subject not only selects stimuli from a set background to these two perspectives, before considering maintained in WM but also updates and monitors the set of recent imaging studies that have attempted to synthesize ideas previous responses. According to Petrides and colleagues, a delayed matching task would engage VLFC, whereas a self- from these traditionally quite distinct fields of investigation. ordering task would engage DLFC. Consistent with this view, DLFC lesions in primates produce deficits on self-ordering tasks but not typically on delayed-matching tasks (Petrides, Perspectives from animal studies: domain- 1995). Self-ordering deficits are also seen following frontal versus process-specific theories lesions in patients, which typically include DLFC (Petrides Two competing ideas concerning functional specialization and Milner, 1982; Owen et al., 1990). Furthermore, a review of FC in WM are ‘domain-specific’ and ‘process-specific’ by D’Esposito and Postle found no evidence that patients theories. These theories concentrate in particular on dis- with DLFC lesions were impaired on simple verbal or spatial sociations between ventral and dorsal regions of lateral FC. span tasks that require only maintenance of a stimulus on-line According to the domain-specific theory, FC is the primary (without any manipulation) (D’Esposito and Postle, 1999). site of WM processes and different regions within FC process Though often placed in opposition, the domain-specific different types of information (Goldman-Rakic, 1987, 1998). and process-specific theories are not necessarily incompatible. Specifically, VLFC is believed to be responsible for the FC may be functionally dissociable according to both the maintenance of stimulus form (object information), whereas type of material and the type of process. Moreover, the DLFC is believed to be responsible for the maintenance of precise site of lesions in the primate DLFC (e.g. Brodmann stimulus location (spatial information). This theory is based areas 9 or 46) can affect whether impairments are seen in largely on electrophysiological recordings and is an simple spatial delayed response tasks or only in more complex extension of the object–spatial (‘what’ versus ‘where’) visual situations, such as self-ordering tasks. Nonetheless, we will processing streams found in posterior regions (Mishkin et al., compare these two general theories for their ability to account 1983). More specifically, Wilson and colleagues found that for the human imaging data. The data are introduced later, FC cells ventral to the principal sulcus code for object after considering an alternative perspective on WM deriving information during a delay, whereas frontal cells within and from the human psychological literature. dorsal to the principal sulcus code for spatial information during a delay (Wilson et al., 1993). More generally, Goldman-Rakic and colleagues suggested that the object– Perspectives from human cognitive psychology: spatial VLFC–DLFC distinction reflects all components of WM: the ‘attentional, memorial and response control mechan- multiple-component models isms’ (Goldman-Rakic, 1998). That is, there is no suggestion Baddeley and Hitch’s theoretical model of WM function of specialization for different WM processes across FC, only (Baddeley and Hitch, 1974) has been highly influential in specialization for the domains over which these processes framing functional neuroimaging studies. This model was operate. developed to account for a range of different WM functions, The alternative, process-specific theory proposes that the from temporary maintenance of a single stimulus to the difference between VLFC and DLFC lies not in the type of manipulation of multiple types of information. It evolved from material being maintained but in the type of processes earlier conceptions of a single short-term buffer (Atkinson and operating on that material (Petrides, 1994, 1995). This theory Shiffrin, 1968), which acted simply as a gateway between derives mainly from animal lesion data (Petrides, 1994) and perception and LTM, to a multicomponent system in which has been extended to human lesion data (Petrides and Milner, a number of subsidiary ‘slave’ systems are coordinated by a 1982; Owen et al., 1990). According to this theory, VLFC common ‘central executive’. The slave systems, the supports processes that transfer, maintain and match informa- ‘phonological loop’ and ‘visuospatial scratch-pad’, are tion in WM. This information may have been perceived limited-capacity, material-specific stores, concerned with the recently or retrieved from LTM. DLFC, however, supports maintenance of verbal and visuospatial material respectively

Frontal lobes and human memory 853 age an n et c nents of distinguished a phond logical store' verbal WM.Paulesu and colleagues (Paulesu) control process'(Baddeley,1986).Verbal material is assu compared a verbal Sternberg task with a control task in enter the p store wher ymed with a target by (subvocal)rehearsal via the articulatory control process omparison revealed left inferior parietal activation but no The proposal of a 'visual cache'and an 'inner scribe (L0g1 995)repre ents an istinctior FCcivatioRAwhandcoleaguescompared2backn age-rehearsa (Fig.2D)with a continuous subvocal repetition taskwithno bdsof WM that cmploy storage requirement(Awh er al..1996).Again,activation of pariet ved. bu nd in the left inferior p of distraction).This would correspond to use of the slave store,which was engaged in the memory tasks,and the left systems of the WM model.Manipulation refers to the VLFC in subvocal articulatory rehearsal,which was assumed of th is bein the WM model.We ng mainte Early imaging studies of such tasks have tended to support the neuropsychological evidence Maintenance of spatial and object ial Both have hee ma of s to the left for verbal material and to the right for spa and object information.In a study using a spatial Ste hav task (Fig.2B).activations were seen in everal een the ject of more recent in to th 10 03 thus relevant to the domain versus process-specific parietal cortex,right dorsal debate outlined above. cortex and right VLFC.(The FC activations resulting from ompa the h its Maintenance of verbal infor A common test of maintenance in WM is the Sternberg task and (Fig.2).Subjects are presented with a'memory set' spatial material are made.)Smith and colleagues re typically three which a n ren ved dings in V15 -and right-late lized the probe stimulus was one of the stimuli in the memory set. To isolate brain areas involved in maintenance from tho involved in perceptual or m ta the 20 pes (o contrasted against those obtained in a control task in which the memory set and probe item are presented simultaneously lateralized pari etal cortex, any mem 24S por ated with two abstract sha and hemisphere regions,including parietal,dorsal premotor and after a 3-s delay,a single probe shape prompting a yes-no 1996).Similar regions test of the task was to decide were y when the the p one of th e In the te non-verbalizable symbols (Fig.2A and C)(Paulest WM.the task was to decide whether the probe matched one et al 1993).This left hemisphere network of the VLFC f the memory set in its location (regardless of its shape) parietal and motor areas (plus right cerebellum)is a consistent The regions mon active in the object task than in the spatial

Frontal lobes and human memory 853 An important distinction within the slave systems of the finding in studies of maintenance in verbal WM (Smith and WM model is between passive storage and active rehearsal. Jonides, 1997; Henson et al., 2000b). In the case of the phonological loop, for example, Baddeley To distinguish the storage and rehearsal components of distinguished a ‘phonological store’ from an ‘articulatory verbal WM, Paulesu and colleagues (Paulesu et al., 1993) control process’ (Baddeley, 1986). Verbal material is assumed compared a verbal Sternberg task with a control task in to enter the phonological store, where it is vulnerable to which subjects judged whether letters rhymed with a target interference and/or rapid decay over time. The rapid decay letter [a task that is believed to require the same articulatory of material in the phonological store can be offset, however, processes as those used in rehearsal (Besner, 1987)]. This by (subvocal) rehearsal via the articulatory control process. comparison revealed left inferior parietal activation but no The proposal of a ‘visual cache’ and an ‘inner scribe’ (Logie, FC activation. Awh and colleagues compared a 2-back task 1995) represents an analogous storage–rehearsal distinction (in which a positive response is required whenever the current within the visuospatial scratchpad. stimulus matches the stimulus presented two trials previously) For the purpose of this review, we make a coarse distinction (Fig. 2D) with a continuous subvocal repetition task with no between imaging studies of WM that employ maintenance storage requirement (Awh et al., 1996). Again, activation of tasks and those that employ manipulation tasks. Maintenance the inferior parietal cortex was observed, but no difference refers to the process of keeping information in mind in the in FC activation was seen. Both studies therefore implicate absence of an external stimulus (and perhaps in the presence the left inferior parietal cortex as the locus of a phonological of distraction). This would correspond to use of the slave store, which was engaged in the memory tasks, and the left systems of the WM model. Manipulation refers to the VLFC in subvocal articulatory rehearsal, which was assumed reorganization of the information that is being maintained, to be engaged in both memory and control tasks and therefore and would correspond to the use of the central executive in not observed in the subtractions. the WM model. We begin by considering maintenance tasks. Early imaging studies of such tasks have tended to support the neuropsychological evidence for a role of posterior Maintenance of spatial and object information regions in the passive storage of material and of posterior Imaging studies of WM using non-verbal material have FC in the rehearsal of material. Both have been lateralized focused on differences between the maintenance of spatial to the left for verbal material and to the right for spatial and object information. In a study using a spatial Sternberg material. We then consider manipulation tasks. These have task (Fig. 2B), activations were seen in several right been the subject of more recent imaging studies which have hemisphere regions, broadly homologous to those seen in focused on dissociations between VLFC and DLFC and are verbal maintenance tasks (Jonides et al., 1993). These thus relevant to the domain-specific versus process-specific included the right parietal cortex, right dorsal premotor debate outlined above. cortex and right VLFC. (The FC activations resulting from comparison of the Sternberg task with its control are sometimes bilateral for both verbal and spatial material. Maintenance of verbal information However, the left–right verbal–spatial lateralization is A common test of maintenance in WM is the Sternberg task normally clearer when direct comparisons of verbal and (Fig. 2). Subjects are presented with a ‘memory set’ of spatial material are made.) Smith and colleagues reported typically three to nine stimuli, which are then removed for similar findings in a direct comparison of visuospatial and several seconds before the appearance of a single probe verbal Sternberg tasks, the networks of parietal, dorsal stimulus. The goal of the subject is to decide whether or not premotor and VLFC regions being left- and right-lateralized the probe stimulus was one of the stimuli in the memory set. for verbal and spatial tasks, respectively (Smith et al., 1996). To isolate brain areas involved in maintenance from those Smith and Jonides used an object version of the Sternberg involved in perceptual or motor components of the task, task that tested memory for abstract shapes (for which spatial functional images obtained during the Sternberg task can be location was irrelevant) (Fig. 2C) (Smith and Jonides, 1995a). contrasted against those obtained in a control task in which This task produced activations that were predominantly leftthe memory set and probe item are presented simultaneously, lateralized, including the inferior parietal cortex, inferior alleviating any memory requirement. Using a verbal Sternberg temporal cortex and left VLFC. In a direct comparison of task in which the stimuli were letters (Fig. 2A), Awh and object and spatial maintenance (Smith and Jonides, 1995b), colleagues reported significant activations in several left participants were presented with two abstract shapes and, hemisphere regions, including parietal, dorsal premotor and after a 3-s delay, a single probe shape prompting a yes–no ventral premotor/VLFC (Awh et al., 1996). Similar regions response. In the test of object WM, the task was to decide were implicated by Paulesu and colleagues when they whether the probe matched one of the memory set in shape compared two Sternberg tasks, one using letters and one (regardless of its location on the screen). In the test of spatial using non-verbalizable symbols (Fig. 2A and C) (Paulesu WM, the task was to decide whether the probe matched one et al., 1993). This left hemisphere network of the VLFC, of the memory set in its location (regardless of its shape). parietal and motor areas (plus right cerebellum) is a consistent The regions more active in the object task than in the spatial