Chris M. Bird

The hippocampus and memory: insights from spatial processing

The hippocampus appears to be crucial for long-term episodic memory, yet its precise role remains elusive. Electrophysiological studies in rodents offer a useful starting point for developing models of hippocampal processing in the spatial domain. Here we review one such model that points to an essential role for the hippocampus in the construction of mental images. We explain how this neural-level mechanistic account addresses some of the current controversies in the field, such as the role of the hippocampus in imagery and short-term memory, and discuss its broader implications for the neural bases of episodic memory.

Recollection and familiarity in dense hippocampal amnesia: a case study

In the amnesia literature, disagreement exists over whether anterograde amnesia involves recollective-based recognition processes and/or familiarity-based ones depending on whether the anatomical damage is restricted to the hippocampus or also involves adjacent areas, particularly the entorhinal and perirhinal cortices. So far, few patients with well documented anatomical lesions and detailed assessment of recollective and recognition performance have been described. We report a comprehensive neuroanatomical assessment and detailed investigation of the anterograde memory functions of a previously described severe amnesic patient (VC). The results of four previously published neuroradiological investigations (resting PET, qualitative MRIs, volumetric MRI and functional MRI) together with the results of two new investigations (voxel-based morphometry and magnetic resonance spectroscopy) are presented. The consistent finding across these different qualitative and quantitative examinations of VCs brain has shown that there is primarily structural and functional abnormality located selectively in the hippocampus bilaterally. Marked impairments in both verbal and non-verbal recall and recognition standardized memory tests were documented in the context of VCs intact cognitive profile and normal semantic memory. The results of five new experimental recognition memory tests tapping recollection and familiarity using verbal, topographical (buildings and landscapes) and unknown human faces memoranda revealed striking differential effects according to the type of stimuli used. A receiver operating characteristic analysis revealed that VCs recollective- and familiarity-based recognition processes were well preserved for unknown human faces. In contrast, recollective-based recognition for verbal and topographical material was at floor. Familiarity-based recognition was also impaired, significantly below controls for verbal and buildings memoranda and quite weak, although not reaching significance, for landscapes. These data suggest that the hippocampus is involved in recollective processes of verbal and topographical stimuli. It also plays an appreciable role in familiarity processes for these stimuli. However, recollection and familiarity of human faces appear not to depend on this region.

Visual neglect after right posterior cerebral artery infarction

Objectives: To investigate the characteristics and neuroanatomical correlates of visual neglect after right-sided posterior cerebral artery (PCA) infarction. Methods: 15 patients with acute PCA strokes were screened for the presence of neglect on a comprehensive battery of cognitive tests. Extra tests of visual perception were also carried out on six patients. To establish which areas were critically associated with neglect, the lesions of patients with and without neglect were compared. Results: Neglect of varying severity was documented in 8 patients. In addition, higher-order visual perception was impaired in 5 of the 6 patients. Neglect was critically associated with damage to an area of white matter in the occipital lobe corresponding to a white matter tract connecting the parahippocampal gyrus with the angular gyrus of the parietal lobe. Lesions of the thalamus or splenium of the corpus callosum did not appear necessary or sufficient to cause neglect, but may mediate its severity in these patients. Conclusions: PCA stroke can result in visual neglect. Interruption of the white matter fibres connecting the parahippocampal gyrus to the angular gyrus may be important in determining whether a patient will manifest neglect.

Anterior Hippocampus and Goal-Directed Spatial Decision Making

Planning spatial paths through our environment is an important part of everyday life and is supported by a neural system including the hippocampus and prefrontal cortex. Here we investigated the precise functional roles of the components of this system in humans by using fMRI as participants performed a simple goal-directed route-planning task. Participants had to choose the shorter of two routes to a goal in a visual scene that might contain a barrier blocking the most direct route, requiring a detour, or might be obscured by a curtain, requiring memory for the scene. The participants start position was varied to parametrically manipulate their proximity to the goal and the difference in length of the two routes. Activity in medial prefrontal cortex, precuneus, and left posterior parietal cortex was associated with detour planning, regardless of difficulty, whereas activity in parahippocampal gyrus was associated with remembering the spatial layout of the visual scene. Activity in bilateral anterior hippocampal formation showed a strong increase the closer the start position was to the goal, together with medial prefrontal, medial and posterior parietal cortices. Our results are consistent with computational models in which goal proximity is used to guide subsequent navigation and with the association of anterior hippocampal areas with nonspatial functions such as arousal and reward expectancy. They illustrate how spatial and nonspatial functions combine within the anterior hippocampus, and how these functions interact with parahippocampal, parietal, and prefrontal areas in decision making and mnemonic function.

Topographical Short-Term Memory Differentiates Alzheimer's Disease From Frontotemporal Lobar Degeneration

We used a recently developed test of spatial memory—the Four Mountains Test—to investigate the core cognitive processes underpinning topographical disorientation in patients with amnestic mild cognitive impairment (a‐MCI) and mild Alzheimers disease (AD). Performance of these clinical groups was compared with age‐matched controls, patients with frontotemporal lobar degeneration (FTLD), and patients with subjective memory impairments. We investigated the perception (concurrent match‐to‐sample) and short‐term retention (2‐s delayed match‐to‐sample) of the configuration of topographical features in computer‐generated landscapes shown from different viewpoints. Thirty‐one patients were tested (7 AD, 6 a‐MCI, 7 temporal variant FTLD, 5 frontal variant FTLD, 6 subjective memory impairment) and 25 age‐ and gender‐matched controls. Brain MRI was available for 27 patients; medial temporal lobe atrophy was assessed using a visual rating scale. Patients with a‐MCI or mild AD were impaired on topographical short‐term memory, but not perception. No other group differences were found on the topographical subtests. Notably, patients with temporal variants of FTLD performed normally, regardless of the laterality of damage. Subtests for the perception and retention of nonspatial aspects of the landscapes (weather conditions, seasonal and daily variations in lighting and color) were poor at differentiating the patient groups. These results indicate a core deficit in representing topographical layout, even for very short durations, within the context of more general long‐term memory impairments found in AD, and suggest that this function is particularly sensitive to the earliest stages of the disease.

Establishing the Boundaries: The Hippocampal Contribution to Imagining Scenes

When we visualize scenes, either from our own past or invented, we impose a viewpoint for our “minds eye” and we experience the resulting image as spatially coherent from that viewpoint. The hippocampus has been implicated in this process, but its precise contribution is unknown. We tested a specific hypothesis based on the spatial firing properties of neurons in the hippocampal formation of rats, that this region supports the construction of spatially coherent mental images by representing the locations of the environmental boundaries surrounding our viewpoint. Using functional magnetic resonance imaging, we show that hippocampal activation increases parametrically with the number of enclosing boundaries in the imagined scene. In contrast, hippocampal activity is not modulated by a nonspatial manipulation of scene complexity nor to increasing difficulty of imagining the scenes in general. Our findings identify a specific computational role for the hippocampus in mental imagery and episodic recollection.

Amnesia and the hippocampus.

Purpose of reviewLong-term memory impairments have great medical significance and a considerable health and economic burden. Understanding their cognitive and neuroanatomical underpinnings is of crucial importance. Severe amnesia is usually observed following bilateral hippocampal pathology. This review addresses the precise role of the hippocampus and related medial temporal lobe structures in amnesia. Recent findingsDisagreements exist over whether, following selective hippocampal damage: retrograde amnesia for episodic memories is temporally limited or extensive and ungraded; anterograde amnesia involves both recollective and familiarity processes. It is accepted that material specific impairments follow unilateral medial temporal lobe damage, with verbal and nonverbal memory lateralized to left or right, respectively. Memory for unknown faces, however, may not depend on the hippocampus. Pharmacological studies in animals, with some extension to humans, highlight promising future therapeutic interventions targeting synaptic plasticity modulation. SummaryDespite considerable progress, some issues remain unresolved. The available evidence favours the view, however, that the hippocampus, in conjunction with other cortical areas, is critical for the retrieval of remote episodic memories and for both recollection and familiarity anterograde memory processes. There are as yet no effective pharmacological treatments for medial temporal lobe amnesia, but various rehabilitative techniques may be useful.

Lost and found: bespoke memory testing for Alzheimer's disease and semantic dementia.

The neural network activated during Topographical Memory (TM) tasks in controls overlaps with the earliest affected regions in Alzheimers disease (AD) but not with those of Semantic Dementia (SD). This suggests that clinical TM tests could be more bespoke to neural dysfunction in early AD and therefore more sensitive and specific. We hypothesized that TM impairment would be characteristic of AD but not of SD making it useful both for early diagnosis and differential diagnosis. TM was assessed in 69 patients (22 mild AD, 15 SD, 32 with mild cognitive impairment (MCI)) and 35 controls, using three tasks: the four mountains test and two novel tests in a virtual town (the Virtual Route Learning Test (VRLT) and the Heading Orientation Test). AD patients were impaired on all TM tasks. The VRLT was the most discriminatory; had the highest correlation with caregiver reports of navigation problems; and correlated strongly with memory, attention/executive function, and to a lesser degree, visuospatial ability. In contrast, SD patients performed well on the TM battery only becoming abnormal with very advanced dementia and performance correlated exclusively with attention/executive function. The VRLT achieved 95% sensitivity and 94% specificity in discriminating AD patients from controls; at the same cutoff, 70% of MCI patients were impaired. When combined with either naming performance or global dementia severity, there was complete separation of AD from SD. The VRLT is ecologically valid, highly sensitive to early AD, and useful in discriminating AD from the non-Alzheimer dementia, SD.

The Hippocampus Supports Recognition Memory for Familiar Words but Not Unfamiliar Faces

Bilateral damage to the human hippocampus profoundly impairs the ability to form long-term, consciously accessible memories, producing a classic amnesic syndrome. However, the effect of hippocampal damage on our ability to recognize items via a feeling of familiarity is hotly disputed. Dual-process theory predicts no effect, whereas declarative memory theory predicts impairment of all types of recognition memory. Here, we demonstrate a striking material specificity in the effect of focal hippocampal damage: Recognition memory is impaired for words but intact for faces. The latter finding is incompatible with declarative memory theory, whereas the former constrains dual-process theory by revealing the limitations of postulated extrahippocampal familiarity-based processes. We suggest that the hippocampus boosts recognition of well-known stimuli (high-frequency words) by activating pre-experimental associations that enrich the context of their presentation. By contrast, recognition memory for some kinds of previously unfamiliar stimuli (unfamiliar faces) may be supported by extrahippocampal familiarity-based processes, at least over short intervals.

Consolidation of Complex Events via Reinstatement in Posterior Cingulate Cortex

It is well-established that active rehearsal increases the efficacy of memory consolidation. It is also known that complex events are interpreted with reference to prior knowledge. However, comparatively little attention has been given to the neural underpinnings of these effects. In healthy adults humans, we investigated the impact of effortful, active rehearsal on memory for events by showing people several short video clips and then asking them to recall these clips, either aloud (Experiment 1) or silently while in an MRI scanner (Experiment 2). In both experiments, actively rehearsed clips were remembered in far greater detail than unrehearsed clips when tested a week later. In Experiment 1, highly similar descriptions of events were produced across retrieval trials, suggesting a degree of semanticization of the memories had taken place. In Experiment 2, spatial patterns of BOLD signal in medial temporal and posterior midline regions were correlated when encoding and rehearsing the same video. Moreover, the strength of this correlation in the posterior cingulate predicted the amount of information subsequently recalled. This is likely to reflect a strengthening of the representation of the videos content. We argue that these representations combine both new episodic information and stored semantic knowledge (or “schemas”). We therefore suggest that posterior midline structures aid consolidation by reinstating and strengthening the associations between episodic details and more generic schematic information. This leads to the creation of coherent memory representations of lifelike, complex events that are resistant to forgetting, but somewhat inflexible and semantic-like in nature. SIGNIFICANCE STATEMENT Memories are strengthened via consolidation. We investigated memory for lifelike events using video clips and showed that rehearsing their content dramatically boosts memory consolidation. Using MRI scanning, we measured patterns of brain activity while watching the videos and showed that, in a network of brain regions, similar patterns of brain activity are reinstated when rehearsing the same videos. Within the posterior cingulate, the strength of reinstatement predicted how well the videos were remembered a week later. The findings extend our knowledge of the brain regions important for creating long-lasting memories for complex, lifelike events.