Dissociations in hippocampal and frontal contributions to episodic memory performance.

There is a general consensus that the hippocampus and adjacent structures are the primary anatomic substrate of episodic memory (Squire, 1998). The relationship between the hippocampus and memory has been borne out in numerous studies of patients with medial temporal damage due to surgery (Martin et al., 2002), vascular lesions (Ott & Saver, 1993), hypoxia (Yonelinas et al., 2002), Alzheimer’s disease (AD; Jack et al., 1999; Kramer et al., 2004; Mungas et al., 2001; Petersen et al., 2000), and other conditions (Kopelman et al., 2001). The frontal lobes also influence memory performance (Wheeler, Stuss, & Tulving, 1995). Although patients with frontal lobe lesions have a relatively well-preserved capacity to encode new information (Kopelman & Stanhope, 1997), memory performance can be affected because of deficits in executive skills such as planning and organization, response monitoring, inhibition of inappropriate responses, and memory for context (Kopelman, 2002). Deficits are often found on measures of free recall, delayed response, conditional learning, temporal order, autobiographical memory (Kopelman et al., 2003), and metamemory (Shimamura, 1995). Several investigators have suggested that frontal structures contribute to organizational aspects of memory at encoding and retrieval (Kapur et al., 1995; Moscovitch & Winocur, 1995; Tulving, Markowitsch, Kapur, Habib, & Houle, 1994) and thus are most evident on memory tasks that require active or strategic information processing (Petrides, 1995). For example, Alexander, Stuss, and Fansabedian (2003) reported that patients with focal frontal lesions exhibited poor implementation of subjective organization on a list-learning task. Incisa della Rocchetta and Milner (1993) also noted that the left frontal lobe is critical for strategic retrieval, and frontal structures help suppress potentially interfering items in verbal memory (Freedman & Cermak, 1986; Incisa della Rocchetta & Milner, 1993). The neuroanatomical mediators of recognition memory have been less well studied. Some investigators have suggested that the hippocampus is critical for recognition memory (Gron et al., 2003; Grunwald et al., 2003; Manns, Hopkins, Reed, Kitchener, & Squire, 2003; Reed & Squire, 1997), although some controversy remains (Aggleton & Shaw, 1996; Vargha-Khadem, Gadian, & Mishkin, 2001). The role of the frontal lobes in recognition memory is also unclear. Some aspects of recognition memory may be preserved in patients with frontal lobe damage (Janowsky, Shimamura, & Squire, 1989; Wheeler & Stuss, 2003). Other studies, however, have suggested that despite normal rates of recognition hits, frontal lobe injury may predispose toward making false-positive errors (Curran, Schacter, Norman, & Galluccio, 1997). Alexander et al. (2003) also showed that patients with left posterior dorsolateral lesions had a significantly elevated response bias that was associated with an increase in false-positive errors. This putative increase in response bias has been attributed to top-down controlled processes mediated by prefrontal cortex and may operate independently of memory accuracy (Swick & Knight, 1999). Taken together, these studies suggest different contributions of hippocampal and frontal structures to human memory performance, with the hippocampus critical for consolidation and retention, and frontal structures important for strategic processing and decision making. However, several issues remain unresolved. Much of the clinical literature is based on between-groups comparisons with focal lesion patients and may not assess the potential contributions of multiple brain regions. Therefore, the overarching goal of this study was to use quantitative MRI to delineate the contribution of multiple brain regions to different components of episodic memory by taking advantage of the variance in regional brain volumes found in patients with neurodegenerative diseases. Specifically, we examined the MRI predictors of both recall and recognition memory. We hypothesized that hippocampal volumes would be selectively associated with level of memory accuracy in recall and recognition, whereas frontal volumes would be selectively associated with more strategic or decision-making aspects of recall and recognition.