David E. Warren

Hippocampal amnesia impairs all manner of relational memory

Relational memory theory holds that the hippocampus supports, and amnesia following hippocampal damage impairs, memory for all manner of relations. Unfortunately, many studies of hippocampal-dependent memory have either examined only a single type of relational memory or conflated multiple kinds of relations. The experiments reported here employed a procedure in which each of several kinds of relational memory (spatial, associative, and sequential) could be tested separately using the same materials. In Experiment 1, performance of amnesic patients with medial temporal lobe (MTL) damage was assessed on memory for the three types of relations as well as for items. Compared to the performance of matched comparison participants, amnesic patients were impaired on all three relational tasks. But for those patients whose MTL damage was limited to the hippocampus, performance was relatively preserved on item memory as compared to relational memory, although still lower than that of comparison participants. In Experiment 2, study exposure was reduced for comparison participants, matching their item memory to the amnesic patients in Experiment 1. Relational memory performance of comparison subjects was well above amnesic patient levels, showing the disproportionate dependence of all three relational memory performances on the integrity of the hippocampus. Correlational analyses of the various task performances of comparison participants and of college-age participants showed that our measures of item memory were not influenced significantly by memory for associations among the items.

Worth a Glance: Using Eye Movements to Investigate the Cognitive Neuroscience of Memory

Results of several investigations indicate that eye movements can reveal memory for elements of previous experience. These effects of memory on eye movement behavior can emerge very rapidly, changing the efficiency and even the nature of visual processing without appealing to verbal reports and without requiring conscious recollection. This aspect of eye movement based memory investigations is particularly useful when eye movement methods are used with special populations (e.g., young children, elderly individuals, and patients with severe amnesia), and also permits use of comparable paradigms in animals and humans, helping to bridge different memory literatures and permitting cross-species generalizations. Unique characteristics of eye movement methods have produced findings that challenge long-held views about the nature of memory, its organization in the brain, and its failures in special populations. Recently, eye movement methods have been successfully combined with neuroimaging techniques such as fMRI, single-unit recording, and magnetoencephalography, permitting more sophisticated investigations of memory. Ultimately, combined use of eye-tracking with neuropsychological and neuroimaging methods promises to provide a more comprehensive account of brain–behavior relationships and adheres to the “converging evidence” approach to cognitive neuroscience.

Network measures predict neuropsychological outcome after brain injury

Significance Thought depends on the brain, and cognitive neuroscience has shown that different sets of brain regions (systems) support different cognitive abilities. We hypothesized that complex cognition might be especially supported by hub brain locations that participate in many such systems. We studied neurological patients with focal brain lesions, and found that damage to hub locations produced much greater cognitive impairment than damage to other locations. This work may improve the understanding of outcomes of brain injuries (from, e.g., stroke, resection, or trauma) and help inform prognosis and rehabilitation efforts. Hubs are network components that hold positions of high importance for network function. Previous research has identified hubs in human brain networks derived from neuroimaging data; however, there is little consensus on the localization of such hubs. Moreover, direct evidence regarding the role of various proposed hubs in network function (e.g., cognition) is scarce. Regions of the default mode network (DMN) have been frequently identified as “cortical hubs” of brain networks. On theoretical grounds, we have argued against some of the methods used to identify these hubs and have advocated alternative approaches that identify different regions of cortex as hubs. Our framework predicts that our proposed hub locations may play influential roles in multiple aspects of cognition, and, in contrast, that hubs identified via other methods (including salient regions in the DMN) might not exert such broad influence. Here we used a neuropsychological approach to directly test these predictions by studying long-term cognitive and behavioral outcomes in 30 patients, 19 with focal lesions to six “target” hubs identified by our approaches (high system density and participation coefficient) and 11 with focal lesions to two “control” hubs (high degree centrality). In support of our predictions, we found that damage to target locations produced severe and widespread cognitive deficits, whereas damage to control locations produced more circumscribed deficits. These findings support our interpretation of how neuroimaging-derived network measures relate to cognition and augment classic neuroanatomically based predictions about cognitive and behavioral outcomes after focal brain injury.

Spontaneous revisitation during visual exploration as a link among strategic behavior, learning, and the hippocampus.

Effective exploratory behaviors involve continuous updating of sensory sampling to optimize the efficacy of information gathering. Despite some work on this issue in animals, little information exists regarding the cognitive or neural mechanisms for this sort of behavioral optimization in humans. Here we examined a visual exploration phenomenon that occurred when human subjects studying an array of objects spontaneously looked “backward” in their scanning paths to view recently seen objects again. This “spontaneous revisitation” of recently viewed objects was associated with enhanced hippocampal activity and superior subsequent memory performance in healthy participants, but occurred only rarely in amnesic patients with severe damage to the hippocampus. These findings demonstrate the necessity of the hippocampus not just in the aspects of long-term memory with which it has been associated previously, but also in the short-term adaptive control of behavior. Functional neuroimaging showed hippocampal engagement occurring in conjunction with frontocerebellar circuits, thereby revealing some of the larger brain circuitry essential for the strategic deployment of information-seeking behaviors that optimize learning.

The Eyes Know Eye Movements as a Veridical Index of Memory

In two experiments, we examined whether observers’ eye movements distinguish studied faces from highly similar novel faces. Participants’ eye movements were monitored while they viewed three-face displays. Target-present displays contained a studied face and two morphed faces that were visually similar to it; target-absent displays contained three morphed faces that were visually similar to a studied, but not tested, face. On each trial in a test session, participants were instructed to choose the studied face if it was present or a random face if it was not and then to indicate whether the chosen face was studied. Whereas manipulating visual similarity in target-absent displays influenced the rate of false endorsements of nonstudied items as studied, eye movements proved impervious to this manipulation. Studied faces were viewed disproportionately from 1,000 to 2,000 ms after display onset and from 1,000 to 500 ms before explicit identification. Early viewing also distinguished studied faces from faces incorrectly endorsed as studied. Our findings show that eye movements provide a relatively pure index of past experience that is uninfluenced by explicit response strategies, and suggest that eye movement measures may be of practical use in applied settings.

False recall is reduced by damage to the ventromedial prefrontal cortex: implications for understanding the neural correlates of schematic memory.

Schematic memory, or contextual knowledge derived from experience (Bartlett, 1932), benefits memory function by enhancing retention and speeding learning of related information (Bransford and Johnson, 1972; Tse et al., 2007). However, schematic memory can also promote memory errors, producing false memories. One demonstration is the “false memory effect” of the Deese–Roediger–McDermott (DRM) paradigm (Roediger and McDermott, 1995): studying words that fit a common schema (e.g., cold, blizzard, winter) often produces memory for a nonstudied word (e.g., snow). We propose that frontal lobe regions that contribute to complex decision-making processes by weighting various alternatives, such as ventromedial prefrontal cortex (vmPFC), may also contribute to memory processes by weighting the influence of schematic knowledge. We investigated the role of human vmPFC in false memory by combining a neuropsychological approach with the DRM task. Patients with vmPFC lesions (n = 7) and healthy comparison participants (n = 14) studied word lists that excluded a common associate (the critical item). Recall and recognition tests revealed expected high levels of false recall and recognition of critical items by healthy participants. In contrast, vmPFC patients showed consistently reduced false recall, with significantly fewer intrusions of critical items. False recognition was also marginally reduced among vmPFC patients. Our findings suggest that vmPFC increases the influence of schematically congruent memories, a contribution that may be related to the role of the vmPFC in decision making. These novel neuropsychological results highlight a role for the vmPFC as part of a memory network including the medial temporal lobes and hippocampus (Andrews-Hanna et al., 2010).

Hiding in plain view: Lesions of the medial temporal lobe impair online representation

The hippocampus is necessary for the normal formation of enduring declarative memories, but its role in cognitive processes spanning short intervals is less well understood. Within the last decade, several reports have described modest behavioral deficits in medial temporal lobe (MTL)‐lesion patients when they perform tasks that do not seem likely to rely on enduring memory. An intriguing but sparsely‐tested implication of such results is that the MTL is involved in the online representation of information, possibly of an associative/relational nature, irrespective of delay. We administered several tests that simultaneously presented all information necessary for accurate responses to a group of MTL‐lesion patients with severe declarative memory deficits but otherwise normal cognition, and to matched brain‐damaged and healthy comparison participants. MTL‐lesion patients performed less well than either comparison group in the Hooper Visual Organization Test, and several patients performed outside the normal range on the Overlapping Figures Test. A novel follow‐up borrowing characteristics of the Overlapping Figures Test revealed impaired identification of novel items by MTL‐lesion patients when target items were obscured by distracters, and two additional novel tests of fragmented object identification further implicated the hippocampus/MTL in the integration of information across very brief intervals. These findings suggest that MTL structures including the hippocampus contribute similarly to cognition irrespective of timescale.

Medial temporal lobe damage impairs representation of simple stimuli

Medial temporal lobe (MTL) damage in humans is typically thought to produce a circumscribed impairment in the acquisition of new enduring memories, but recent reports have documented deficits even in short-term maintenance. We examined possible maintenance deficits in a population of MTL amnesics, with the goal of characterizing their impairments as either representational drift or outright loss of representation over time. Patients and healthy comparisons performed a visual search task in which the similarity of various lures to a target was varied parametrically. Stimuli were simple shapes varying along one of several visual dimensions. The task was performed in two conditions, one presenting a sample target simultaneously with the search array and the other imposing a delay between sample and array. Eye-movement data collected during search revealed that the duration of fixations to items varied with lure-target similarity for all participants, i.e., fixations were longer for items more similar to the target. In the simultaneous condition, patients and comparisons exhibited an equivalent effect of similarity on fixation durations. However, imposing a delay modulated the effect differently for the two groups: in comparisons, fixation duration to similar items was exaggerated; in patients, the original effect was diminished. These findings indicate that MTL lesions subtly impair short-term maintenance of even simple stimuli, with performance reflecting not the complete loss of the maintained representation but rather a degradation or progressive drift of the representation over time.

Not so fast: Hippocampal amnesia slows word learning despite successful fast mapping

The human hippocampus is widely believed to be necessary for the rapid acquisition of new declarative relational memories. However, processes supporting on‐line inferential word use (“fast mapping”) may also exercise a dissociable learning mechanism and permit rapid word learning without the hippocampus (Sharon et al. (2011) Proc Natl Acad Sci USA 108:1146–1151). We investigated fast mapping in severely amnesic patients with hippocampal damage (N = 4), mildly amnesic patients (N = 6), and healthy comparison participants (N = 10) using on‐line measures (eye movements) that reflected ongoing processing. All participants studied unique word‐picture associations in two encoding conditions. In the explicit‐encoding condition, uncommon items were paired with their names (e.g., “This is a numbat.”). In the fast mapping study condition, participants heard an instruction using a novel word (e.g., “Click on the numbat.”) while two items were presented (an uncommon target such as a numbat, and a common distracter such as a dog). All groups performed fast mapping well at study, and on‐line eye movement measures did not reveal group differences. However, while comparison participants showed robust word learning irrespective of encoding condition, severely amnesic patients showed no evidence of learning after fast mapping or explicit encoding on any behavioral or eye‐movement measure. Mildly amnesic patients showed some learning, but performance was unaffected by encoding condition. The findings are consistent with the following propositions: the hippocampus is not essential for on‐line fast mapping of novel words; but is necessary for the rapid learning of arbitrary relational information irrespective of encoding conditions.

The Hippocampus Uses Information Just Encountered to Guide Efficient Ongoing Behavior

Adaptive ongoing behavior requires using immediate sensory input to guide upcoming actions. Using a novel paradigm with volitional exploration of visuo‐spatial scenes, we revealed novel deficits among hippocampal amnesic patients in effective spatial exploration of scenes, indicated by less‐systematic exploration patterns than those of healthy comparison subjects. The disorganized exploration by amnesic patients occurred despite successful retention of individual object locations across the entire exploration period, indicating that exploration impairments were not secondary to rapid decay of scene information. These exploration deficits suggest that amnesic patients are impaired in integrating memory for recent actions, which may include information such as locations just visited and scene content, to plan immediately forthcoming actions. Using a novel task that measured the on‐line links between sensory input and behavior, we observed the critical role of the hippocampus in modulating ongoing behavior.