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 these850 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 inter￾Acquisition 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 memory￾most 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