In 1936, Jacobsen first demonstrated that lesions of the PFC of primates impair performance of the delayed-response working memory task and this finding has been replicated by numerous investigators (see Funahashi and Kubota, 1994 for review). However, there has been considerable difficulty in understanding the nature of this deficit. Working memory and short-term memory have been related theoretically, and therefore there has been a lasting tendency to view working memory processes mediated by the PFC simply as short-term memory processes. There is considerable evidence against the idea that the PFC subserves simply short-term memory processing.
First, short-term memory loss is generally not a result of selective PFC damage (Petrides, 1996). Patients with PFC damage show no deficits on traditional short-term memory tasks of recognition or recall, and such patients have a normal digit span and are unimpaired in the memory component of intelligence tests (Hebb, 1939, 1977; Stuss and Benson, 1986; Petrides, 1989; D'Esposito and Postle, 1999; Manes et al., 2002). Moreover, primates with PFC lesions perform normally on recognition memory tasks, delayed matching to sample tasks, and delayed object alternation tasks (Passingham, 1975; Bachevalier and Mishkin, 1986; Petrides, 1995, 2000a) that require short-term memory.
Consistent with the role of the PFC in working memory, PFC lesions affect the monitoring and manipulation of information in short-term memory. A classic demonstration of monitoring in memory is the self- ordered pointing task whereby different arrangements of stimuli are presented on each trial and the subject must choose a different stimulus until all are chosen (Petrides and Milner, 1982; Petrides, 1995). In this task, attention must be directed both to the stimulus under consideration as well as other stimuli in memory. Performance on this task is severely impaired by dorsolateral PFC lesions. Likewise the dorsolateral PFC is activated during the feedback portion of sorting tasks when current information must be related to earlier events (Monchi et al., 2001). PFC lesions also impair the ability to use memory to plan events in everyday life or plan responses on laboratory tasks (Shallice, 1982; Shallice and Burges, 1996; Robbins, 1996). PFC patients are particularly impaired on a modified version of the traditional Tower of London task that requires subjects to plan the moves from a starting state to a ‘goal’ configuration set by the experimenter (Robbins, 1996; Owen et al., 1990, 1995, 1996; Manes et al., 2002). In this way, the subject must plan moves internally by maintaining and comparing information about the initial, transition, and goal states in short-term memory. Thus, the deficit seen with patients with PFC damage is the result of an inability to monitor and manipulate information in memory, rather than the ability to actually hold the information in memory.
The distinction between the role of the PFC in working, as opposed to
short-term, memory is made especially clear when one examines the effects
of PFC lesions on tasks requiring response flexibility. On such tasks, PFC patients commit repeated errors that they are consciously aware of and that they can report, but cannot use to update behavior (Milner, 1963; Konow and Pribram, 1970). A classic example of this is observed in PFC patients with the Wisconsin Card Sorting task (Milner, 1963). This task requires subjects to formulate a card sorting strategy based on feedback from an experimenter. PFC-damaged patients are able to deduce, remember, and verbalize the correct sorting strategy to the experimenter, but are unable to
alter their sorting strategy based on this knowledge. As a result, they perseverate in their initial response strategy, unable to shift to a strategy they know to be correct. Primates with lesions of the PFC also perseverate on their initial response strategy during performance of the analogous “A-not- B” task (Diamond and Goldman-Rakic, 1989). In the “A-not-B” task, primates must learn that one of two spatially distinct wells initially contains food while the other does not. After training, the well containing food is switched. Normal animals quickly go to the newly baited food well, while lesioned animals continue to revisit a previously rewarded spatial location, indicating that they had specific knowledge about the spatial location where food was presented previously, yet they could not use this knowledge to update their behavior. In contrast, primates with hippocampal damage perform normally at short delays (2-15s) but at 30s delays respond randomly on this task, not exhibiting the “AB error pattern” but rather alternating their responses between correct and incorrect food wells (Diamond et al., 1989). This indicates an anatomical dissociation between the retention of spatial- reward contingencies (at >15s intervals) and the ability to use this knowledge to guide behavior (working memory), with the former involving hippocampal regions and the latter involving the PFC.
According to Petrides (1994, 1995, 1996, 2000a), the PFC may act alone or in concert with other brain regions to guide working memory under different conditions. He has suggested that ventrolateral regions of the PFC are involved in the active organization of behavior based on the retrieval of information from posterior association corticies while dorsolateral regions are involved in holding information for monitoring and manipulation in accordance with willed actions. Based on this hypothesis, information may be retained within the PFC or in other brain regions but the critical function of the dorsolateral PFC relates to the ability to monitor, manipulate and use information to guide thought or action, i.e. working memory.