856 P.C.Fletcher and R.N.A.Hensor VLFC.Though this was not the FC region that might have to detect which digit was omitted,the same bilateral DLFC DLCthisd on the bas of the above ee th activation was observed (Petrides er al..1993b) re (Baddeley as well as condition. forming to any rule or pattern.Tasks like these involve no only internal monitoring of previous responses (as in self but also The use of eventa clated fMRI to distinguish transient and random ke sustained effects in wM tasks is clearly an important method pressing was compared with reactive.stimulus-driven key ological advance.and one that is likely to prove valuable in pressing(Frith et al. 1991).Jahanshahi and colleagues apart pen on anc ma on when ra technique to isolate brain regionsre nsive during the s at higher of WM trials (see also (ahanshahi e) (D'Eposi whe for ex with a sea of fiv indices of random s or the ation rate orting the letters.followed by either a 'forward or an'alphabetize instruction.After a d ented tha are required by,but not related to,random generation and h as ih gen ney.a com osition denoted by the ce of fiv stimuli from much lar sets.The ve task ters were maintained in the (original)forward order (in requires generation without repetition of.for example.as Oin th the s).or five lette ge alpha of five as the latter additional manipulation GpTcntoncWtaceiestoaidgeaernlion(eg ordering).Both VLFC resp sive durin en a subject is require to gene rate as many animals a del D sho may by the consistent with the ecific FC modelo left di fC activation when letter fluency was compared with Petride these word repetition () are invo CO rable only DL and the evi Ge Dual asks task m tasks simulta rated withoutr tition one at a tim y 1986)mo e This task has been explored in neuropsychological (Petride between information appropriate for one or other task.patient and Milner.1982 and neur maging studies Petrides with frontal lesions may be disproportiona es er a 199 ersus singl Dowell er a durins contro task in which participants res nded WM.D'Esposito and collea exte nally produced stim h participants performed two brain activit tasks concurrently with ab was ting the atial totatio task and a semantic iude nt task roduced lateralization of manipulation ses in visuos patial wm ignificant activation of DLFC when performed alone:only s),DLFC activation as bi they were combir activa of did ed was significant bilate not dep activation w when an extemally ordered condition was tested in which omhined hecause a second exneriment in which perform participants listened to a random sequence of digits in orde ance of the rotation task was impaired by decreasing the856 P. C. Fletcher and R. N. A. Henson VLFC. Though this was not the FC region that might have to detect which digit was omitted, the same bilateral DLFC been expected on the basis of the above studies (i.e. the activation was observed (Petrides et al., 1993b). DLFC), this experiment illustrates the opportunity afforded A related task is random number generation (Baddeley, by event-related studies to dissociate FC processes by time 1966), in which numbers must be generated without con￾as well as condition. forming to any rule or pattern. Tasks like these involve not only internal monitoring of previous responses (as in self￾ordering tasks), but also inhibition of prepotent responses Reordering tasks and well-learned routines. Frith and colleagues reported The use of event-related fMRI to distinguish transient and bilateral DLFC activations when generative, random key sustained effects in WM tasks is clearly an important method- pressing was compared with reactive, stimulus-driven key ological advance, and one that is likely to prove valuable in pressing (Frith et al., 1991). Jahanshahi and colleagues teasing apart perception and maintenance, and maintenance observed left DLFC activation when random number genera￾and manipulation. D’Esposito and colleagues have used this tion was compared with counting, and this activity was technique to isolate brain regions responsive during the negatively related to indices of randomness at higher genera￾presentation, delay and probe phases of WM trials (see also tion rates (Jahanshahi et al., 2000). Interestingly, VLFC Courtney et al., 1997). D’Esposito and colleagues (D’Esposito activation was also seen when random number generation et al., 1999) and Postle and colleagues (Postle et al., 1999), was compared with counting, but did not correlate with for example, presented subjects with a sequence of five indices of randomness or the generation rate, supporting the letters, followed by either a ‘forward’ or an ‘alphabetize’ proposal that this region is involved in maintenance processes instruction. After a delay of 8 s, a probe was presented that that are required by, but not related to, random generation. consisted of a letter and a digit (Fig. 2E). The subject’s task Other generation tasks, such as verbal fluency, a common was to indicate whether the probe letter would appear in the clinical test of frontal lobe damage, involve the selection of position denoted by the probe digit if the sequence of five stimuli from much larger sets. The verbal fluency task letters were maintained in the (original) forward order (in requires generation without repetition of, for example, as the ‘forward’ trials), or if the five letters were rearranged many animal names (category fluency) or words beginning into alphabetical order (in the ‘alphabetize’ trials). The former with a specified letter (letter fluency) as possible in a short trials require only the maintenance of five letters in order, period of time. This task involves not only monitoring but whereas the latter trials require additional manipulation (i.e. also the development of new strategies to aid generation (e.g. reordering). Both VLFC and DLFC were responsive during when a subject is required to generate as many animals as the delay period, but DLFC showed a greater response they can, they may begin by thinking of pets, then safari during the alphabetize trials (bilaterally in all cases). Though animals, etc.). The PET study of Frith and colleagues found broadly consistent with the process-specific FC model of left DLFC activation when letter fluency was compared with Petrides and colleagues, these studies suggest a nested word repetition (Frith et al., 1991). organization in which both VLFC and DLFC are involved Considerable evidence thus exists for a role of DLFC, on in maintenance, but only DLFC is additionally involved in the left for verbal and the right for visuospatial information, manipulation. in the manipulation processes necessary for generation tasks. Generation tasks Dual tasks In the self-ordering task mentioned earlier, stimuli must be Performing two tasks simultaneously makes demands on generated without repetition, one at a time, from a finite set. WM (Baddeley, 1986), most probably reflecting the switching This task has been explored in neuropsychological (Petrides between information appropriate for one or other task. Patients and Milner, 1982) and neuroimaging studies. Petrides and with frontal lesions may be disproportionately impaired in colleagues (Petrides et al., 1993a, b) compared brain activity dual-task versus single-task performance (McDowell et al., during the performance of a self-ordering task with activity 1997), again suggesting a frontal role in these aspects of during a control task in which participants responded to WM. D’Esposito and colleagues compared brain activity externally produced stimuli, without the requirement to order when participants performed two tasks concurrently with their own responses. When abstract figures were used, the the brain activity when each task was performed alone self-ordering task produced greater activation in right DLFC, (D’Esposito et al., 1995). Neither of the two tasks, a as predicted (Petrides et al., 1993a), supporting the right spatial rotation task and a semantic judgement task, produced lateralization of manipulation processes in visuospatial WM. significant activation of DLFC when performed alone; only With verbal stimuli (digits), DLFC activation was bilateral when they were combined was significant bilateral activation (Petrides et al., 1993b). This FC activation did not depend of this area observed. This activation was unlikely to be due solely on the self-generated nature of the ordering task: simply to the impaired performance of both tasks when when an externally ordered condition was tested in which combined, because a second experiment in which perform￾participants listened to a random sequence of digits in order ance of the rotation task was impaired by decreasing the