Strategic retrieval processing and the impact of knowing when a memory was first created.

Retrieval orientation refers to a process where participants strategically alter how a memory cue is processed in response to different task demands. In the present study we explored whether retrieval orientation is influenced by knowing when an old stimulus was first encoded. Participants completed separate remember/know test blocks for old items from a recent delay (40min) and old items from a remote delay (48h). Manipulations at encoding ensured that performance levels were matched between these two blocks, thus avoiding confounds with differences in retrieval effort. Importantly, a third test block comprised old items from both delays randomly intermixed. As the nature of the old items varies unpredictably in the mixed block, it should not be possibly to adopt a specific retrieval orientation and the mixed block therefore acts as a control condition. Participants saw the words "mixed," "recent" or "remote" prior to each test block. Comparing ERPs from the recent and remote blocks permitted an investigation of whether participants alter their retrieval orientation in response to the specific length of the retention interval. Comparing ERPs from the pure (recent and remote) test blocks to ERPs from the mixed block permitted an investigation of whether delay information per se led to differences in retrieval strategy. Analysis of the ERP data found no differences between the recent and remote blocks. However, ERPs from these pure blocks were significantly less positive than ERPs from the mixed block from 200ms towards the end of the epoch. The findings suggest that the delay information was useful in a general sense and encouraged retrieval strategies distinct from those engaged in the mixed block. We speculate that such strategies might relate to whether or not the retrieval search is specific and constrained and/or whether processes that serve to reinstate the original encoding context are engaged.

Damage to the dorsomedial thalamic nucleus, central lateral intralaminar thalamic nucleus, and midline thalamic nuclei on the right-side impair executive function and attention under conditions of high demand but not low demand.

This study reports a patient, OG, with a unilateral right-sided thalamic lesion. High resolution 3T magnetic resonance imaging revealed damage to the parvicellular and magnocellular subdivisions of the dorsomedial thalamus (DMT), the central lateral intralaminar nucleus (also known as the paralamellar DMT), the paraventricular and the central medial midline thalamic nuclei. According to the neuropsychological literature, the DMT, the midline and intralaminar thalamic nuclei influence a wide array of cognitive functions by virtue of their modulatory influences on executive function and attention, and this is particularly indicated under conditions of low arousal or high cognitive demand. We explored this prediction in OG, and compared his performance on a range of low and high demand versions of tests that tapped executive function and attention to a group of 6 age- and IQ-matched controls. OG, without exception, significantly under performed on the high-demand attention and executive function tasks, but performed normally on the low-demand versions. These findings extend and refine current understanding of the effects of thalamic lesion on attention and executive function.

The electrophysiological correlates of recent and remote recollection.

Research using event related potentials (ERPs) to explore recognition memory has linked late parietal old/new effects to the recollection of episodic information. In the vast majority of these studies, the retrieval phase immediately follows encoding and consequently, very little is known about the ERP correlates of long term recollection. This is despite the fact that in other areas of the memory literature there is considerable interest in consolidation theories and the way episodic memory changes over time. The present study explored the idea that consolidation and forgetting processes operating over a moderate retention interval can alter the ERP markers of recollection memory. A remember/know test probed memory for stimuli studied either 15 minutes (recent memory) or 1 week (remote memory) prior to the test phase. Results revealed an attenuated late parietal effect for remote compared to recent remember responses, a finding that remained significant even when these recognition judgments were matched for reaction time. Experiments 2a and 2b identified characteristic differences between recent and remote recognition at the behavioural level. The 1 week delay produced an overall decline in recognition confidence and a dramatic loss of episodic detail. These behavioural changes are thought to underlie the ERP effects reported in the first experiment. The results highlight that although the neural basis of memory may exhibit significant changes as the length of the retention interval increases, it is important to consider the extent to which this is a direct effect of time or an indirect effect due to changes in memory quality, such as the amount of detail that can be recollected.

Change in background context disrupts performance on visual paired comparison following hippocampal damage.

The medial temporal lobe plays a critical role in recognition memory but, within the medial temporal lobe, the precise neural structures underlying recognition memory remain equivocal. In this study, visual paired comparison (VPC) was used to investigate recognition memory in a human patient (YR), who had a discrete lesion of the hippocampus, and a group of monkeys with neonatal hippocampal lesions, which included the dentate gyrus, and a portion of parahippocampal region. Participants were required to view a picture of an object on a coloured background. Immediately afterwards, this familiar object was shown again, this time paired with a novel object. All participants displayed a novelty preference, provided the background on which the objects were shown was the same as the one used during the learning phase. When the background of the familiar object was changed between initial familiarization and test, only the control subjects showed a novelty preference; the hippocampal-lesioned monkeys and patient YR showed null preference. The results are interpreted within Eichenbaum and Bunsey's [Eichenbaum, H., & Bunsey, M. (1995). On the binding of associations in memory: Clues from studies on the role of the hippocampal region in paired-associate learning. Current Directions in Psychological Science, 4, 19-23] proposal that the hippocampus facilitates the formation of a flexible representation of the elements that make up a stimulus whereas the parahippocampal region is involved in the formation of a fused representation.

The frequency and extent of mammillary body atrophy associated with surgical removal of a colloid cyst.

BACKGROUND AND PURPOSE: Patients who have had a colloid cyst removed from the third ventricle sometimes experience some difficulty with day-to-day memory. This study provided quantitative MR imaging volume measures of 1 structure potentially responsible for mnemonic problems, the mammillary bodies. Additional volume estimates in structures connected to the mammillary bodies sought to determine the specificity of any atrophy. MATERIALS AND METHODS: Volume estimates of the mammillary bodies were performed on 38 patients after surgical removal of colloid cysts and 20 control subjects by the application of stereologic volume-estimation techniques. For the mammillary body measures, 2 groups of MR images were assessed (0.8- and 1.0-mm section thickness) to compare the sensitivity of each imaging sequence for detecting any atrophy. Other structures associated with memory processes, such as the hippocampus and fornix, were also assessed quantitatively to determine whether there was a correlation between mammillary body damage and atrophy in connecting structures. RESULTS: Our investigations established the superiority of 0.8-mm-volume scans over standard isotropic 1.0-mm-thick-volume scans for mammillary body assessments. Comparisons with 20 age-matched controls revealed that patients with colloid cysts frequently showed significant mammillary body atrophy (mean volume of colloid cysts, 0.037 cm(3) right and 0.038 cm(3) left; control subjects, 0.069 cm(3) right and 0.067 cm(3) left). In fact, every patient had a mammillary body volume below the control mean, and the majority of patients had a volume decrease of >1 SD (82% right, 74% left). Mammillary body volumes correlated with fornix volumes in the same patient group. CONCLUSIONS: Our results reveal the frequent presence of mammillary body atrophy in patients with surgical removal of colloid cysts and indicate that this atrophy is partly due to a loss of temporal lobe projections in the fornix.

Two case studies illustrating how relatively selective hippocampal lesions in humans can have quite different effects on memory.

Two patients, with magnetic resonance imaging (MRI)-confirmed relatively selective hippocampal damage, showed distinct patterns of performance on tests of recall, item recognition, and associative recognition. Patient AC showed a mean bilateral volume reduction of the hippocampus of 28%, but displayed no memory deficit. Both recall and recognition memory were unimpaired. In contrast, patient PR, who showed a mean bilateral hippocampal volume reduction of 59%, was more consistently impaired on recall than recognition tests, although his recognition scores were highly variable. Patients AC and PR illustrate how variable the memory deficit following seemingly selective hippocampal damage can be in humans. They highlight the need for more sophisticated imaging in future studies if the human hippocampus' role in memory is to be fully identified.

Prose recall and amnesia: more implications for the episodic buffer.

Baddeley and Wilson [Baddeley, A. D., & Wilson, F. B. (2002). Prose recall and amnesia: implications for the structure of working memory. Neuropsychologia 40, 1737-1743.] have argued that their finding of a positive association between amnesics' immediate prose recall scores and their scores on measures of executive function and fluid intelligence supports the view that an episodic buffer exists. However, the pattern of data from amnesics tested in our laboratory presented some problems for this conceptualisation of the episodic buffer.

Item recognition is less impaired than recall and associative recognition in a patient with selective hippocampal damage.

This article explores the recall, item recognition, and associative recognition memory of patient B.E., whose pattern of retrograde amnesia was reported by Kapur and Brooks (1999; Hippocampus 9:1-8). Structural magnetic resonance imaging (MRI) has shown that B.E. has bilateral damage restricted to the hippocampus. The structural damage he had sustained was accompanied by bilateral hypoperfusion of the temporal lobe, revealed by positron emission tomography (PET), and which single photon emission computed tomography (SPECT) suggested was greater in the left than the right temporal lobe. B.E. showed a global anterograde amnesia for verbal material, but he displayed some sparing of nonverbal item recognition relative to nonverbal recall and associative recognition. His performance on an item recognition task that used the remember/know procedure and another that involved repetition of the test phase, to reduce the difference between the familiarity of the targets and foils, suggested that his relatively spared nonverbal item recognition may have been mainly supported by familiarity. This finding is consistent with the view that the anterior temporal lobe, including the perirhinal cortex, can support familiarity-based memory judgments (Brown and Bashir, 2002; Philos Trans R Soc Lond B 357:1083-1095). B.E.'s data also highlight the importance of functional as well as structural scan information for interpreting the pattern of memory deficits shown by patients with selective hippocampal structural lesions.

Associative recognition in a patient with selective hippocampal lesions and relatively normal item recognition.

Previous work (Mayes et al., Hippocampus 12:325-340, 2002) found that patient YR, who suffered a selective bilateral lesion to the hippocampus in 1986, showed relatively preserved verbal and visual item recognition memory in the face of clearly impaired verbal and visual recall. In this study, we found that YR's Yes/No as well as forced-choice recognition of both intra-item associations and associations between items of the same kind was as well preserved as her item recognition memory. In contrast, YR was clearly impaired, and more so than she was on the above kinds of recognition, at recognition of associations between different kinds of information. Thus, her recognition memory for associations between objects and their locations, words and their temporal positions, abstract visual items or words and their temporal order, animal pictures and names of professions, faces and voices, faces and spoken names, words and definitions, and pictures and sounds, was clearly impaired. Several of the different information associative recognition tests at which YR was impaired could be compared with related item or inter-item association recognition tests of similar difficulty that she performed relatively normally around the same time. It is suggested that YR's familiarity memory for items, intra-item associations, and associations between items of the same kind was mediated by her intact medial temporal lobe cortices and was preserved, whereas her hippocampally mediated recall/recollection of these kinds of information was impaired. It is also suggested that the components of associations between different kinds of information are represented in distinct neocortical regions and that initially they only converge for memory processing within the hippocampus. No familiarity memory may exist in normal subjects for such associations, and, if so, YR's often chance recognition occurred because of her severe recall/recollection deficit. Conflicting data and views are discussed, and the way in which recall as well as item and associative recognition need to be systematically explored in patients with apparently selective hippocampal lesions, in order to resolve existing conflicts, is outlined.

Visual paired comparison performance is impaired in a patient with selective hippocampal lesions and relatively intact item recognition.

In this study, we have examined visual recognition memory in a patient, YR, with discrete hippocampal damage who has shown normal or nearly normal item recognition over a large number of tests. We directly compared her performance as measured using a visual paired comparison task (VPC) with her performance on delayed matching to sample (DMS) tasks. We also investigated the effect of retention interval between familiarisation and test. YR shows good visual recognition with the DMS task up to 10 s after the familiarisation period, but only shows recognition with the VPC task for the shortest retention interval (0 s). Our results are consistent with the view that hippocampal damage disrupts recollection and recall, but not item familiarity memory.

Relative sparing of item recognition memory in a patient with adult-onset damage limited to the hippocampus.

There is disagreement about whether selective hippocampal lesions in humans cause clear item recognition as well as recall deficits. Whereas Reed and Squire (Behav Neurosci 1997;111:667-775) found that patients with adult-onset relatively selective hippocampal lesions showed clear item recognition deficits, Vargha-Khadem et al. (Science 1997;277: 376-380, Soc Neurosci Abstr 1998;24:1523) found that 3 patients who suffered selective hippocampal damage in early childhood showed clear recall deficits, but had relatively normal item recognition. Manns and Squire (Hippocampus 1999;9:495-499) argued, however, that item recognition may have been spared in these patients because the early onset of their pathology allowed compensatory mechanisms to develop. Therefore, to determine whether early lesion onset is critical for the relative sparing of item recognition and to determine whether its occurrence is influenced by task factors, we extensively examined item recognition in patient Y.R., who has pathology of adult-onset restricted to the hippocampus. Like the developmental cases, she showed clear free recall deficits on 34 tests, but her item recognition on 43 tests was relatively spared, and markedly less disrupted than her recall. Her item recognition performance relative to that of her controls was not significantly influenced by whether tests tapped visual or verbal materials, had a yes/no or forced-choice format, contained few or many items, had one or several foils per target item, used short or very long delays, or were difficult or easy for normal subjects. Interestingly, YR's bilateral hippocampal destruction was greater than at least 2 of the 3 patients of Manns and Squire (Hippocampus 1999;9:495-499). The possible reasons why item recognition differs across patients with relatively selective hippocampal damage of adult-onset and how the reasons that are truly critical can be best identified are discussed.

Under what conditions is recognition spared relative to recall after selective hippocampal damage in humans?

The claim that recognition memory is spared relative to recall after focal hippocampal damage has been disputed in the literature. We examined this claim by investigating object and object-location recall and recognition memory in a patient, YR, who has adult-onset selective hippocampal damage. Our aim was to identify the conditions under which recognition was spared relative to recall in this patient. She showed unimpaired forced-choice object recognition but clearly impaired recall, even when her control subjects found the object recognition task to be numerically harder than the object recall task. However, on two other recognition tests, YR's performance was not relatively spared. First, she was clearly impaired at an equivalently difficult yes/no object recognition task, but only when targets and foils were very similar. Second, YR was clearly impaired at forced-choice recognition of object-location associations. This impairment was also unrelated to difficulty because this task was no more difficult than the forced-choice object recognition task for control subjects. The clear impairment of yes/no, but not of forced-choice, object recognition after focal hippocampal damage, when targets and foils are very similar, is predicted by the neural network-based Complementary Learning Systems model of recognition. This model postulates that recognition is mediated by hippocampally dependent recollection and cortically dependent familiarity; thus hippocampal damage should not impair item familiarity. The model postulates that familiarity is ineffective when very similar targets and foils are shown one at a time and subjects have to identify which items are old (yes/no recognition). In contrast, familiarity is effective in discriminating which of similar targets and foils, seen together, is old (forced-choice recognition). Independent evidence from the remember/know procedure also indicates that YR's familiarity is normal. The Complementary Learning Systems model can also accommodate the clear impairment of forced-choice object-location recognition memory if it incorporates the view that the most complete convergence of spatial and object information, represented in different cortical regions, occurs in the hippocampus.

Differential involvement of the hippocampus and temporal lobe cortices in rapid and slow learning of new semantic information.

The present study examined the rapid and slow acquisition of new semantic information by two patients with differing brain pathology. A partial double dissociation was found between the patterns of new learning shown by these two patients. Rapid acquisition was impaired in a patient (YR) who had relatively selective hippocampal damage, but it was unimpaired in another patient (JL) who, according to structural MRI, had an intact hippocampus but damage to anterolateral temporal cortex accompanied by epileptic seizures. Slow acquisition was impaired in both patients, but was impaired to a much greater extent in JL. The dissociation suggests that the mechanisms underlying rapid and slow acquisition of new semantic information are at least partially separable. The findings indicate that rapid acquisition of semantic, as well as episodic information, is critically dependent on the hippocampus. However, they suggest that hippocampal processing is less important for the gradual acquisition of semantic information through repeated exposure, although it is probably necessary for normal levels of such learning to be achieved.

Amnesic syndrome and severe ataxia following the recreational use of 3,4-methylene-dioxymethamphetamine (MDMA, 'ecstasy') and other substances.

A 26-year-old woman suffered disseminated intravascular coagulation (DIC) and a brief respiratory arrest following recreational use of 3,4-methylene-dioxymethamphetamine (MDMA; 'ecstasy'), together with amyl nitrate, lysergic acid (LSD), cannabis and alcohol. She was left with residual cognitive and physical deficits, particularly severe anterograde memory disorder, mental slowness, severe ataxia and dysarthria. Follow-up investigations have shown that these have persisted, although there has been some improvement in verbal recognition memory and in social functioning. Magnetic resonance imaging and quantified positron emission tomography investigations have revealed: (i) severe cerebellar atrophy and hypometabolism accounting for the ataxia and dysarthria; (ii) thalamic, retrosplenial and left medial temporal hypometabolism to which the anterograde amnesia can be attributed; and (iii) some degree of fronto-temporal-parietal hypometabolism, possibly accounting for the cognitive slowness. The putative relationship of these abnormalities to the direct and indirect effects of MDMA toxicity, hypoxia and ischaemia is considered.

Exploring the neural bases of episodic and semantic memory: the role of structural and functional neuroimaging.

Exploration of the neural bases of episodic and semantic memory is best pursued through the combined examination of the effects of identified lesions on memory and functional neuroimaging of both normal people and patients when they engage in memory processing of various kinds. Both structural and functional neuroimaging acquisition and analysis techniques have developed rapidly and will continue to do so. This review briefly outlines the history of neuroimaging as it impacts on memory research. Next, what has been learned so far from lesion-based research is outlined with emphasis on areas of disagreement as well as agreement. What has been learned from functional neuroimaging, particularly emission tomography and functional magnetic resonance imaging, is then discussed, and some stress is placed on topics where the interpretation of imaging studies has so far been unclear. Finally, how functional and structural imaging techniques can be optimally used to help resolve three areas of disagreement in the lesion literature will be discussed. These disagreements concern what the hippocampus and perirhinal cortex contribute to memory; whether any form of priming depends on the medial temporal lobes; and whether remote episodic as well as semantic memories cease to depend on the medial temporal lobes. Although the discussion will show the value of imaging techniques, it will also emphasize some of the limitations of current neuroimaging studies.

Theories of episodic memory.

Theories of episodic memory need to specify the encoding (representing), storage, and retrieval processes that underlie this form of memory and indicate the brain regions that mediate these processes and how they do so. Representation and re-representation (retrieval) of the spatiotemporally linked series of scenes, which constitute an episode, are probably mediated primarily by those parts of the posterior neocortex that process perceptual and semantic information. However, some role of the frontal neocortex and medial temporal lobes in representing aspects of context and high-level visual object information at encoding and retrieval cannot currently be excluded. Nevertheless, it is widely believed that the frontal neocortex is mainly involved in coordinating episodic encoding and retrieval and that the medial temporal lobes store aspects of episodic information. Establishing where storage is located is very difficult and disagreement remains about the role of the posterior neocortex in episodic memory storage. One view is that this region stores all aspects of episodic memory ab initio for as long as memory lasts. This is compatible with evidence that the amygdala, basal forebrain, and midbrain modulate neocortical storage. Another view is that the posterior neocortex only gradually develops the ability to store some aspects of episodic information as a function of rehearsal over time and that this information is initially stored by the medial temporal lobes. A third view is that the posterior neocortex never stores these aspects of episodic information because the medial temporal lobes store them for as long as memory lasts in an increasingly redundant fashion. The last two views both postulate that the medial temporal lobes initially store contextual markers that serve to cohere featural information stored in the neocortex. Lesion and functional neuroimaging evidence still does not clearly distinguish between these views. Whether the feeling that an episodic memory is familiar depends on retrieving an association between a retrieved episode and this feeling, or by an attribution triggered by a priming process, is unclear. Evidence about whether the hippocampus and medial temporal lobe cortices play different roles in episodic memory is conflicting. Identifying similarities and differences between episodic memory and both semantic memory and priming will require careful componential analysis of episodic memory.

Remembering and knowing in a patient with preserved recognition and impaired recall.

ROB is a patient who has a severe deficit in recalling recently presented verbal material following rupture and repair of an anterior communicating artery aneurysm [Hanley JR, Davies ADM, Downes J, Mayes A. Cognitive Neuropsychology 1994;11:543-78; Hanley JR, Davies ADM. In: Parkin A, editor. Case Studies in the Neuropsychology of Memory. Hillsdale, NJ: Lawrence Erlbaum, 1997. p. 111-26]. Despite this, her performance on tests of recognition memory is comfortably within the normal range. In the present series of experiments, we investigated whether or not ROB's performance on tests of recognition memory might be associated with a disproportionately large number of correct decisions made on the basis of familiarity rather than contextual retrieval [e.g. Mandler G. Psychological Review 1980;87:252-71]. Contrary to this hypothesis, the results showed that ROB made a high proportion of remember decisions relative to know decisions in recognition [cf. Gardiner JM. Memory & Cognition 1988;16:309-13] and produced a high recollection score when conscious recollection and familiarity were placed in opposition to one another [cf. Jacoby LL, Woloshyn V, Kelley C. Journal of Experimental Psychology: General 1989;118:115-25.]. ROB's recognition memory performance therefore appears to be qualitatively as well as quantitatively similar to that found in the normal population. As ROB has suffered damage to both the fornix and the anterior thalamus, the results of the present study are consistent with the claim that damage to the extended hippocampal system has a much more severe effect on recall than on recognition [Aggleton JP, Shaw C. Neuropsychologia 1996;34:51-62; Aggleton JP, Saunders RC. Memory 1997;5:49-71]. The present results provide no support, however, for the additional suggestion [Aggleton JP, Brown MW. Behavioral and Brain Sciences 1999;22:425-56.] that the extended hippocampal system is necessary for recognition memory decisions that are based on contextual retrieval.

Aneurysmal SAH: cognitive outcome and structural damage after clipping or coiling.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) and surgical clipping of intracranial aneurysms are associated with substantial morbidity and mortality. OBJECTIVE: To compare cognitive outcome and structural damage in patients with aneurysmal SAH treated with surgical clipping or endovascular coiling. METHODS: Forty case-matched pairs of patients with aneurysmal SAH treated by surgical clipping or endovascular coiling were prospectively assessed by use of a battery of cognitive tests. Twenty-three case-matched pairs underwent MRI 1 year after the procedure. Matching was based on grade of SAH on admission, location of aneurysm, age, and premorbid IQ. RESULTS: Both groups were impaired in all cognitive domains when compared with age-matched healthy control subjects. Comparison of cognitive outcome between the two groups indicated an overall trend toward a poorer cognitive outcome in the surgical group, which achieved significance in four tests. MRI showed focal encephalomalacia exclusively in the surgical group. This group also had a significantly higher incidence of single or multiple small infarcts within the vascular territory of the aneurysm, but both groups had similar incidence of large infarcts and global ischemic damage. CONCLUSION: Endovascular treatment may cause less structural brain damage than surgery and have a more favorable cognitive outcome. However, cognitive outcome appears to be dictated primarily by the complications of SAH.

Effects of level of retrieval success on recall-related frontal and medial temporal lobe activations.

Brain dedicated single photon emission computed tomography (SPECT) was used to compare the neuroactivation produced by the cued recall of response words in a set of studied word pairs with that produced by the cued retrieval of words semantically related to unstudied stimulus words. Six of the 12 subjects scanned were extensively trained so as to have good memory of the studied pairs and the remaining six were minimally trained so as to have poor memory. When comparing episodic with semantic retrieval, the well-trained subjects showed significant left medial temporal lobe activation, which was also significantly greater than that shown by the poorly trained subjects, who failed to show significant medial temporal lobe activation. In contrast, the poorly trained subjects showed significant bilateral frontal lobe activation, which was significantly greater than that shown by the well-trained subjects who failed to show significant frontal lobe activation. The frontal activations occurred mainly in the dorsolateral region, but extended into the ventrolateral and, to a lesser extent, the frontal polar regions. It is argued that whereas the medial temporal lobe activation increased as the proportion of response words successfully recalled increased, the bilateral frontal lobe activation increased in proportion to retrieval effort, which was greater when learning had been less good.