Dissociable contributions of the mid-ventrolateral frontal cortex and the medial temporal lobe system to human memory

Abstract

Although the prefrontal cortex and regions of the medial temporal lobe are commonly co-activated in neuroimaging studies, their precise respective contributions to human memory remain unclear. In this event-related fMRI study, conditions requiring volunteers to simply look at pictures of abstract art were compared with conditions in which they were explicitly instructed to remember similar stimuli for later recognition. Looking, with no explicit instruction to remember, was associated with significant increases in signal intensity in the medial temporal lobe in 19 of the 20 volunteers scanned, but not in a region of the mid-ventrolateral prefrontal cortex that has previously been implicated in memory encoding and retrieval. Behavioral data collected outside the scanner on the same task revealed that recognition of these stimuli was, however, above chance. When the task instructions were changed to encourage the volunteers to remember the stimuli, significant increases in signal intensity were observed bilaterally, in the mid-ventrolateral frontal cortex, but there was no concomitant increase within the medial temporal lobe region. Moreover, behavioral data collected outside the scanner confirmed that recognition of these stimuli was significantly improved relative to the ‘just look’ trials. These results suggest that the mid-ventrolateral frontal cortex and the medial temporal lobe region make dissociable contributions to human memory that correspond closely to ‘top–down’ and ‘bottom–up’ notions of cognitive control, respectively.

Introduction

For many years, it has been known that medial temporal lobe damage in humans produces profound memory impairments, while patients with frontal lobe lesions often perform normally on many standard tests of memory (Lee et al., 2000a, Petrides, 1994). The pattern that has emerged from functional neuroimaging studies in healthy volunteers is quite different, with increases in activity reported in medial temporal and frontal lobe areas during many different memory tasks (Buckner et al., 1995, Buckner et al., 1999, Fletcher and Henson, 2001, Lee et al., 2000a). One region that has been consistently activated is the mid-ventrolateral frontal cortex which, in humans, lies below the inferior frontal sulcus and includes Brodmann areas 45 and 47 (Brodmann, 1909). Activity in this region has been reported during spatial, verbal and pattern working memory tasks (Owen et al., 1996a, Owen et al., 2000, Stern et al., 2000) but also during episodic memory tests of encoding and retrieval (Fletcher et al., 1998, Lee et al., 2000b, Owen et al., 1996b). The medial temporal lobe structures, including the hippocampus, are also frequently activated during tests of both episodic (Ryan et al., 2001, Schacter et al., 1999) and working memory (Cabeza et al., 2002, Monk et al., 2002, Ranganath and D'Esposito, 2001, Stern et al., 1996). In short, while individual studies have reported memory-related activity in the medial temporal lobe system or the mid-ventrolateral frontal cortex, the picture emerging from the imaging literature as a whole is of frequent co-activation across the two regions (Buckner et al., 1999).

In neuropsychological studies, medial temporal lobe damage frequently impairs simple recognition memory performance, even when the vaguest sense of familiarity should be sufficient to generate a correct response (Owen et al., 1995, Wheeler et al., 1995). Frontal lobe patients are generally unimpaired on such tasks but have difficulties when internally generated intentions or goals are required to generate a response (Lee et al., 2000a, Petrides and Milner, 1982, Wheeler et al., 1995). Such evidence suggests that an important factor for understanding the functional relationship between the mid-ventrolateral frontal cortex and the medial temporal lobe system may be the extent to which a volunteer explicitly intends to remember or retrieve a given stimulus and the changes in attentional control that may be consequent upon such an intention. The role of intention has been investigated previously in memory by comparing intentional encoding tasks with so-called ‘incidental’ memory tasks (Buckner et al., 2001, Stark and Okado, 2003, Wagner et al., 1998, Otten et al., 2001, Fletcher et al., 2003), although in both cases, activity in the mid-ventrolateral frontal cortex has been reported. However, in many incidental tasks, an intention is still involved, but it is directed away from explicit memorization (e.g., to judging whether words are in uppercase or lowercase letters; Buckner et al., 2000, Buckner et al., 2001).

In this study, event-related functional magnetic resonance imaging (fMRI) was used to explicitly test the hypothesis that mid-ventrolateral frontal cortex activity, but not medial temporal lobe activity, will vary according to the degree to which the intention to encode or retrieve information is modulated by a prior instruction cue, all other factors being held constant. Volunteers were instructed on random trials either to just look at pictures of abstract art or to try and remember them for later test. Recognition was examined by asking, on random trials, whether they remembered seeing specific pictures previously. In a fourth condition, volunteers were instructed to passively re-view stimuli shown previously. It was predicted that medial temporal lobe activity would be observed during all experimental conditions when compared to rest, while activity in the mid-ventrolateral frontal cortex would only be observed when volunteers specifically intended to remember or retrieve the stimuli following a specific instruction to do so.