Semantic organization

In general, FL patients use fewer strategies than healthy controls to work with memory (e.g., Gershberg & Shimamura, 1995). One strategy that is normally quite beneficial involves organization of study materials with respect to semantics or meaning (Bousfield, 1953; Mandler, 1967; Tulving, 1962). The frontal lobes seem to be especially important for such organization during encoding. Hirst and Volpe (1988) examined this phenomenon in a small group of frontal patients. Participants were asked to memorize two sets of words for later recall: one set contained unrelated words, and the other contained categories of related words, randomly intermixed with one another (plant names, occupations, etc.). Healthy controls showed much better memory for the categorizeable words than the unrelated ones, whereas frontal patients showed no benefit. In another version of the task, Hirst and Volpe gave participants a set of categorizeable words to study, along with detailed instructions on how to organize them. These instructions did not confer any additional benefit on the controls, but helped the frontal patients improve substantially. Incisa della Rocchetta and Milner (1993) and Gershberg and Shimamura (1995) reported similar findings, although both emphasized that FL damage impairs organization and strategy implementation during encoding and retrieval (see also Baldo et al., 2002; but see Alexander et al., 2003; Stuss et al., 1994). Taken together, these findings suggest that FL patients are capable of organizing materials and benefiting from this in memory, although they fail to do so spontaneously. This may be especially true when the lesion encroaches on dorsolateral frontal cortex (Baldo et al., 2002; but see Alexander et al., 2003), consistent with the function assigned to this region in the various models.

Clinical evaluation and real world performance. The main way to assess the influence of semantic organization on episodic memory in the clinic is by using a verbal memory test, such as the California Verbal Learning Test (CVLT-II; Delis et al., 2000), and examining indices of semantic clustering during the initial learning trials. Patients with focal FL lesions obtained lower scores on the CVLT-II semantic clustering measure in comparison to normal controls in Baldo et al.'s (2002) report, although neither Stuss et al. (1994) nor Alexander et al. (2003) found any regional differences for this measure. Related information can be obtained when testing nonverbal memory, such as memory for the Rey-Osterreith Complex Figure (1941). Detailed scoring systems (e.g., Boston Qualitative Scoring System; Stern et al., 1999) can provide information about how well organized copying is (e.g., shows good planning and little fragmentation).

A deficit in organizing materials along semantic lines may have some impact on FL lesion patients in the real world, although there appears to be little research on this question. For instance, it is conceivable that patients may have greater difficulty recalling a shopping list (which is essentially what the CVLT-II is) or any other material where organizational principles are helpful, such as in studying any subject or complex set of instructions or procedures. Autobiographical memory also may be impaired if patients are less able to organize and create connections among life experiences, or even in encoding and recounting an extended, complex episode, such as a long conversation, a busy day, a vacation, or a movie or play one had just seen. On the whole, however, this may not be the most debilitating memory problem faced by FL patients. Furthermore, the Hirst and Volpe (1988) results suggest that if such memory problems are apparent in real life, organizing stimuli for patients, or providing explicit instructions for them to do so on their own, will aid them greatly. A similar conclusion was reached by Incisa della Rocchetta and Milner (1993), who reported that even though FL patients had trouble recalling the words on their experimental task, they showed relatively good recall of prose passages from the Wechsler Memory Scale Logical Memory subtest (Wechsler, 1997). The authors argued that the prose passages required less self-initiated organization on the part of subjects. These studies indicate that supplying external organization can help, at least if the material is relatively simple and the organizing principles are obvious, such as they are in a list of semantically related items, which is rarely the case for real-world episodes. As yet, there are few tests of real world memory to examine the effects of frontal damage or dysfunction (discussed later).

Contextual information

The frontal lobes may be especially important for remembering the context within which information was acquired. For example, frontal patients are usually impaired in memory for the sequence or temporal order in which items occur, even when memory for the items themselves is intact (Butters et al., 1994; Johnson et al., 1997; Kesner et al., 1994; Mangels, 1997; Parkin et al., 1988; Shimamura et al., 1990; Swain et al., 1998). Dorsolateral FL regions may be particularly important for these operations (Kopelman et al., 1997; Milner et al., 1991), as many of the models outlined in the introduction suggest. Functional neuroimaging data fit with this idea, although it is unclear whether one hemisphere is more critical than the other, or whether left and right hemispheres make material-specific contributions (e.g., Cabeza et al., 1997b, 2000; Dobbins et al., 2002; Fan et al., 2003; Nolde et al., 1998; Nyberg et al., 1996; Slotnick et al., 2003).

FL impairments in temporal order memory are not inevitable. They can be overcome if subject-performed tasks (SPTs) are employed during encoding. For instance, McAndrews and Milner (1991) had FL patients and controls either say the name of objects presented during study or perform a predetermined action for each (e.g., squeeze a sponge). On a subsequent test of memory for the order in which the objects had been presented, FL patients were reliably impaired in the naming condition, but performed the same as controls in the action condition (see Butters et al., 1994, for similar findings). McAndrews and Milner suggested that subject-performed tasks create more distinctive encoding of events, by providing extra cues (e.g., motor cues) with which to retrieve object-order information.

Another example of impaired memory for context concerns source, which can consist of various types (location, perceptual attributes, surrounding information, etc.). When FL patients are exposed to information from more than one source within a session (e.g., seeing some words and hearing others, or hearing different sentences from different experimenters), they are usually able to remember the content itself, but are impaired when asked about the source (e.g., Janowsky et al., 1989a; Johnson et al., 1997; Schacter et al., 1984; Shimamura & Squire, 1987, 1991; cf. Thaiss & Petrides, 2003). Glisky and colleagues (1995) reported analogous findings in older adults who were characterized preexperimentally on the basis of their frontal lobe function using neuropsychological tests. The experimenters presented sentences spoken by one of two voices (sources) to the older adults, and found that better memory for source was related to higher FL function.

Recently, however, Glisky and colleagues (2001) showed that the source memory deficit associated with poor FL function can be reduced or eliminated. By instructing participants to think about the relation between content and source during study (e.g., by asking “How well do this voice and sentence go together?”), the experimenters eliminated the usual source memory impairment in older people with mild FL dysfunction. These older people may be less likely to attend to contextual information spontaneously, and/or link context with content, but the deficit apparently can be overcome by changing task instructions. Such a study deserves to be extended to focal FL lesion patients.

Clinical evaluation and real world performance. Taken together, the temporal order and source memory studies indicate that FL patients' memory problems are attributable, at least in part, to poor attentional control or selection and organization of information at encoding. Unfortunately, there are few standardized clinical measures with appropriate norms for the evaluation of context memory. There are, however, tests that measure memory for two similar sets of information (e.g., both the CVLT-II and Wechsler Memory Scale–III [WMS-III] Word Lists contain two lists of words, WMS-III Logical Memory contains two stories). Intrusions of words or details from one list or story when subjects are trying to remember those from the other may be a good indicator of impaired memory for temporal order. Indeed, patients with focal FL lesions are more likely than control participants to intrude words from a distractor list during yes/no recognition (Baldo et al., 2002).

One limiting factor for clinical use is that these tests do not have normative data for these specific types of intrusions. Moreover, they examine memory for just one kind of context, and use only verbal materials, and so it might be an idea to adapt some of the experimental tasks outlined above for clinical testing. After all, memory for when an event occurred or from whom one learned a fact is important for functioning in the real world, allowing patients to answer questions like “Did I take my pill before or after lunch?” or “Did I read that fact in the New York Times or the National Enquirer?” (Senkfor & Van Petten, 1998).

The few studies that exist suggest that problems remembering context are not restricted to the laboratory. For example, Davidson et al. (2005) asked FL lesion patients about what they knew about the terrorist attacks in the United States on September 11th, 2001, and the source of this information. The patients appeared to have normal knowledge of what happened on September 11th, but were impaired when asked about the source. Similarly, Shimamura and colleagues (1990) had FL patients organize historical events into chronological order, and found that the patients were impaired, despite the fact that their knowledge about the events appeared normal. Some researchers have argued that poor temporal context memory may underlie other problems, including confabulation (see Schnider, 2001), though Moscovitch and Gilboa (Gilboa, 2005; Gilboa & Moscovitch, 2002; Moscovitch, 1994; Moscovitch & Melo, 1997) consider the deficits in temporal order and confabulation to be symptoms of impairment to more fundamental processes, such as search, evaluation, and “felt rightness” associated with strategic retrieval.

It thus might be fruitful to develop real-world tests of memory for context to probe for these deficits, and if they exist, to try to overcome them. For example, the Shimamura et al. (1990) historical events task could easily be used to examine whether a patient has a retrograde temporal ordering impairment. An analogous task involving recent events could be developed to test for an anterograde deficit, although it would have to be updated every few months. Memory for source could be probed by initially presenting stimuli in different modalities (e.g., seeing some words and hearing others), to determine whether a patient has disproportionately poor source memory.

The experimental data outlined earlier suggest that FL patients' context memory deficits can be minimized if information is more richly and distinctively encoded (in temporal order memory), or if patients are encouraged to link content and context information (in source memory). A subject-performed task or attentional manipulation could easily be included in a clinical assessment of context memory. Furthermore, as far as we are aware, no one has tried to adapt either of these paradigms outside of the laboratory, to see if FL patients' memory problems can be attenuated in the real world. It seems that this would be a worthwhile endeavor. Of course, there may be limitations on how far the beneficial effects of such manipulations can generalize. For example, in Butters and colleagues' (1994) replication of the McAndrews and Milner (1991) study, they included a condition in which subjects merely imagined performing a task with each studied object, but this did not ameliorate FL patients performance. As well, the Shimamura et al. (1990) historical events data suggest that the temporal ordering deficit is not based only on encoding, and cannot be ameliorated entirely by encoding strategies (because the patients encoded these events when they were healthy). Providing appropriate cues or organizational strategies at retrieval may thus prove useful too.

Effects of cuing

Retrieval of previously learned information can be tested by using free recall, cued recall, or recognition. Free recall arguably makes the greatest demands on self-initiated strategic processing, whereas the cuing inherent in cued recall and recognition decreases the need for strategic processing. Surprisingly, there have been few studies in which recall and recognition have been compared in the same FL patients, and when they have, the findings have been mixed (e.g., Alexander et al., 2003; Baldo et al., 2002; Kopelman & Stanhope, 1998; Stuss et al., 1994). A recent meta-analysis (Wheeler et al., 1995) suggested that free recall was most likely to produce memory deficits in FL patients (i.e., in 80% of reviewed studies), and recognition was least likely (i.e., in only 8% of reviewed studies). Cued recall was intermediate in producing memory deficits in these patients (i.e., in 50% of studies). Note, however, that for many of the studies in that review, recall was for organized materials, whereas recognition was for unorganized materials, so whether there is truly a difference between recall and recognition is still not clear. Neuroimaging studies with healthy participants have shown increased activation in anterior regions (among others) during cued recall in comparison to recognition of word pairs (e.g., Cabeza et al., 1997a, 1997c), although as Shallice (2003) notes, it is challenging to compare lesion with function imaging data because of the different assumptions inherent to each method. Thus, although the FLs appear to be important for episodic memory tasks regardless of the procedure used for retrieval, they may be especially important for free recall. Based on the theories of frontal function, one would expect that the regions likely to be activated more during recall than recognition include right dorsolateral and left ventrolateral cortex, although there are too few studies and too much variability to determine whether this prediction is consistent with the results of the neuroimaging findings (for a brief discussion, see Fletcher & Henson, 2001).

This recall/recognition dissociation may provide additional insight into how different memory processes are dependent on the FLs. For example, dual-process theories of memory distinguish between recollection (controlled retrieval of item-specific or contextual information) and familiarity (the mere sense that an item is old; e.g., Jacoby, 1991; Mandler, 1980; Tulving, 1983; for a review, see Gardiner & Richardson-Klavehn, 2000). Although the definitions of recollection and familiarity are contentious, some theorists have suggested that recall relies more heavily on recollection, whereas recognition depends on both but can often (but not always) be performed on the basis of familiarity alone (see Mandler, 1980). There is some neuropsychological and neuroimaging evidence that the FLs may be more involved in recollection than familiarity (e.g., Davidson & Glisky, 2002; Henson et al., 1999; Wheeler & Stuss, 2003). Although some recent neuroimaging studies have additionally found activity in frontal regions that is correlated with familiarity (e.g., Ranganath et al., 2000, 2004; Yonelinas et al., 2005), the implications are unclear. Neuroimaging data on whether the frontal lobes are differentially involved in familiarity versus recollection may be confounded with the degree of confidence participants have in their decisions. When recollection is associated with highly confident decisions, and familiarity with relatively less confident decisions, then regions of frontal cortex associated with evaluation, such as the dorsolateral aspects, will show greater activation for the latter (Henson et al., 1999; 2000; but see Yonelinas et al., 2005).

Clinical evaluation and real world performance. Many standardized clinical memory tests use both recall and recognition, including the CVLT-II, WMS-III subtests (Logical Memory, Paired Associates, Word Lists, Visual Reproduction), Kaplan-Baycrest Neurocognitive Assessment memory tasks (Word Lists and Complex Figure; Leach et al., 2000), and the Doors and People test (Baddeley et al., 1994). Although most of these tests do not provide normative data specifically on the difference between recall and recognition, separate norms are provided for each measure, allowing the clinician to judge whether there are meaningful differences between recall and recognition in a patient.

This relative difficulty with free recall as opposed to recognition has obvious implications for compensating for everyday memory problems of FL patients. These patients may be better able to answer questions that rely on recognition (e.g., “Did you talk to your sister on the telephone yesterday?”) rather than on recall (e.g., “Who did you talk to on the telephone yesterday?”). Providing organization at encoding (Gershberg & Shimamura, 1995; Incisa della Rocchetta & Milner, 1993) or giving cues in the form of notes or reminders should also decrease the demands on strategic search at retrieval.

Given the difficulty that FL patients have when presented with insufficient cues, it would be useful to develop a self-cuing retrieval strategy for everyday life. Most mnemonics (such as the method of loci) essentially provide a framework of cuing, but the problem is that one has to use the framework at encoding for it to be effective at retrieval. Can there be some procedure designed to help people cue themselves at retrieval without also engaging in some stilted methods of encoding? At present, there seem to be few studies concerning this question. Yet even if one could devise a good retrieval strategy, it might be difficult to train patients to implement it. In order to use a retrieval strategy in a sophisticated, flexible way, a patient would need (at a minimum) to (1) recognize there is a problem, (2) retrieve the appropriate strategy, (3) initiate and maintain it, (4) evaluate the result, and (5) switch to a new strategy if he or she recognizes that the current one is ineffective. Performing this series of operations requires good monitoring, metamemory, and inhibition—the very processes with which FL patients have difficulty (see Burgess et al., 2000). Nevertheless, research in the rehabilitation of executive function and problem-solving is currently in its infancy (see Turner & Levine, 2004), and so, if in the future, FL patients can be taught to implement other sorts of problem-solving strategies, perhaps they can be taught to do so for memory as well.

Liberal response bias

Although FL patients have fewer difficulties with recognition than recall, there are aspects of recognition that appear to be abnormal. For example, on a yes-no recognition memory test, people are shown a mix of previously seen items and new ones, and have to discriminate the old from the new. A person endorsing more of the new items (false alarms) relative to the old ones (hits) is said to have a more liberal response bias. Persons with MTL damage usually have a reduced hit rate, but show normal (or conservative) response bias. In contrast, FL damage may have little effect on hit rate, but can lead to an elevated false alarm rate, suggesting more liberal bias (e.g., Swick & Knight, 1999; but see Verfaellie et al., 2004). Frontal patients are especially susceptible to producing false alarms when the foils are perceptually or conceptually similar to targets (Baldo et al., 2002; Melo et al., 1999; Schacter et al., 1996). There may be some regional, and hemispheric, specialization within FL with regard to false alarms. For example, when Rapcsak and colleagues (2001) divided FL patients into those with unilateral left versus right hemisphere damage, the right frontal group was more liberal on a face memory task than the left frontal and control groups (compare to Alexander et al., 2003, who reported abnormal bias for verbal materials in left frontal patients).

The studies outlined earlier concern large groups of FL patients, who usually show a small but significant shift in bias, but there are single cases that are more extreme. Rapcsak and colleagues have reported several patients with right FL damage who show pathologically high false recognition rates, across a variety of stimuli. Most of these patients also show false recognition of information in the retrograde domain, suggesting a retrieval deficit. In one study, Rapcsak et al. (1999) examined whether changing retrieval instructions could attenuate false recognition. They administered a face recognition task, in which famous and nonfamous faces were presented, and subjects were asked to endorse only the famous ones. The FL patients showed normal memory for the famous faces, but pathologically high false recognition of the nonfamous ones. The investigators then administered a similar task, but this time they changed the instructions during the test, asking participants only to endorse a face if they could state the name, occupation, or other identifying information for it. Giving these extra instructions had little effect on controls but led to a dramatic improvement in the patients, presumably by encouraging them to be more cautious, and/or make an endorsement based on more detailed information (i.e., using “recollection” rather than mere “familiarity” or “gist;” Jacoby, 1991; Mandler, 1980).

Schacter and colleagues (1996) made a similar argument in describing B.G., a right FL lesion patient who also showed pathological false alarming. The authors found that when foils were conceptually similar to targets (e.g., members of the same category), B.G. was very likely to false alarm to the foils, but when they were not similar, B.G.'s false alarm rate fell greatly. Note, however, that Parkin and colleagues (1999) reported a similar patient, but argued that his deficit involved faulty encoding. It could be that some patients are liberal due to poor encoding (e.g., impoverished, general coding of items) and others due to poor retrieval (e.g., abnormal bias and/or confidence), and this may depend on the hemisphere or frontal region damaged. Although many of the models mentioned at the outset describe criterion setting as a function of prefrontal cortex (e.g., Henson et al., 2000), Moscovitch and Winocur's (2002) is the only one which considers these biases explicitly by assigning criterion-setting and automatic monitoring functions to the ventromedial and frontopolar regions, respectively, with damage to them leading to changes in negative and positive biases, respectively. Thus, damage to ventromedial prefrontal cortex can lead to acceptance of false information typical of confabulation, and damage to frontopolar regions can lead to impairment in endorsing true memories or imbuing them with a sense of self-relatedness and recollection (for further discussion see Moscovitch & Winocur, 2002).

Clinical evaluation and real world performance. Some clinical memory measures include yes-no recognition, but the most popular of these uses only verbal stimuli (the CVLT-II), and liberal bias could be a material-specific problem (cf. Alexander et al., 2003; Rapcsak et al., 2001). The WMS-III has a yes-no face recognition subtest, but does not include normative data for false alarms or a criterion measure. The ideal clinical measure would compare yes-no to forced-choice recognition across verbal and nonverbal stimuli, because the latter may be easier for FL patients.

In the real world, it is currently unclear what proportion of FL patients have major problems resulting from a liberal bias in recognition, but there are at least a few cases that do. A good example is described by Ward and colleagues (1999). This patient would approach strangers on the street, asking if they were personal acquaintances or television stars, because they seemed so familiar to him. This spurious sense of familiarity might cause FL patients to be more vulnerable to scams and exploitation in the real world, where they might be more likely to believe what is told to them because it seems familiar (Jacoby, 1999). Harassment or other inappropriate social interactions may also be a concern. Fortunately, even in more extreme cases, encouraging patients to use a more conservative response criterion, or to search their memory carefully before making a decision, may help reduce false alarm rates greatly (as in Rapcsak et al., 1999; Schacter et al., 1996; but see Parkin et al., 1999).

Confabulation

Confabulation (or “honest lying;” Moscovitch, 1989; for recent reviews, see Gilboa & Moscovitch, 2002; Johnson et al., 2000), describes the phenomenon in which patients retrieve information that is untrue, accompanied by a strong feeling that it is true, and are unaware of any discrepancy, and usually of any memory impairment at all. Confabulation is most common in autobiographical memory, although it can be evoked in other domains, including semantics or general knowledge (Moscovitch & Melo, 1997). Many theorists have dichotomized confabulations (albeit, using different nomenclatures and criteria) into those that are severe (e.g., bizarre, spontaneous, persistent, frequent, etc.) versus those that are mild (e.g., realistic, provoked, momentary, rare, etc.), although a comprehensive taxonomy of confabulation has yet to be established.

The most parsimonious explanation of confabulation attributes it to a retrieval deficit, because patients often confabulate regarding memories acquired long before brain damage. In separate reviews of the literature, Gilboa and Moscovitch (2002) and Johnson et al. (2000) found that ventromedial FL regions (in either hemisphere) were most often implicated in confabulation, consistent with the function ascribed to this region in various models. Although basal forebrain damage (as in cases of anterior communicating artery aneurysm; AcoA) is common in confabulating patients, it does not always lead to confabulation, and may not be necessary to produce it. When confabulation resolves over time, it does so in a gradual and seemingly spontaneous manner, and does not necessarily improve at the same rate as other memory abilities (see Gilboa & Moscovitch, 2002).

Clinical evaluation and real world performance. Confabulation may be difficult to detect in the clinic, because we often take patients at their word, and do not seek corroboration of their reports unless we suspect a need. Although confabulation is associated with poor memory and executive function, the literature suggests these correlations are not very strong. Spontaneous or fantastic confabulations may be easier to spot than mild ones (simply because they are implausible, inconsistent, or bizarre), but mild ones may also cause problems in daily functioning. Two published methods may aid in documenting confabulation in the clinic. Dalla Barba (1993) has designed a series of questions to which most normal people would answer “I don't know” (e.g., “What did you have for lunch on March 12, 1998?”). As well, Moscovitch and Melo (1997) used a cue-word procedure and found that confabulations could be elicited for both personal and semantic information. Another good way to detect confabulation is by asking both the patient and a relative or friend about a few of the patient's life experiences, and seeing how the two reports square with one another.

Despite its rarity, confabulation can have severe real-life consequences. As stated earlier, it is usually accompanied by unawareness of deficit. If there is no reason for a patient to think he is confabulating, there is no reason for him not to act according to his memory. Few reports of rehabilitation or management of confabulation exist in the literature, possibly because it is so difficult. Asking the patient to use a stricter criterion at retrieval, or to reason through a series of logical steps to see that his confabulation cannot be true, may do little to convince him, especially in the long run (see Moscovitch, 1989). Burgess and McNeil (1999), however, did report a successful case of rehabilitation of an AcoA patient who would try to leave his house each morning for a nonexistent job. The authors had the patient keep a diary of his daily experiences, and trained him to check it at the beginning of each day to convince himself that he had not been working recently, and had nothing scheduled for the day. Of course, this method may not be successful with every patient. Confabulation may have multiple possible causes, for example, faulty memory search, decision-making, or temporal context memory (Burgess & Shallice, 1996; Moscovitch & Melo, 1997; Schnider, 2001; for reviews of models, see Gilboa & Moscovitch, 2002; Johnson et al., 2000). If so, different rehabilitation strategies may work with different patients.