Bilateral Damage Research Articles

A Patient With Psychotic Disorder Following Traumatic Brain Injury With Bilateral Frontal Lobe Damage

A Patient With Psychotic Disorder Following Traumatic Brain Injury With Bilateral Frontal Lobe Damage

Risk factors for development of postoperative cerebellar mutism syndrome in children after medulloblastoma surgery.

OBJECTIVE Postoperative cerebellar mutism syndrome (pCMS) occurs in 7%-50% of children after cerebellar tumor surgery. Typical features include a latent onset of 1-2 days after surgery, transient mutism, emotional lability, and a wide variety of motor and neurobehavioral abnormalities. Sequelae of this syndrome usually persist long term. The principal causal factor is bilateral surgical damage (regardless of tumor location) to any component of the proximal efferent cerebellar pathway, which leads to temporary dysfunction of cerebral cortical regions as a result of diaschisis. Tumor type, cerebellar midline location, and brainstem involvement are risk factors for pCMS that have been identified repeatedly, but they do not explain its latent onset. Ambiguous or negative results for other factors, such as hydrocephalus, postoperative meningitis, length of vermian incision, and tumor size, have been reached. The aim of this study was to identify perioperative clinical, radiological, and laboratory factors that also increase risk for the development of pCMS. The focus was on factors that might explain the delayed onset of pCMS and thus might provide a time window for taking precautionary measures to prevent pCMS or reduce its severity. The study was focused specifically on children who had undergone surgery for medulloblastoma. METHODS In this single-center retrospective cohort study, the authors included 71 children with medulloblastoma, 28 of whom developed pCMS after primary resection. Clinical and laboratory data were collected prospectively and analyzed systematically. Variables were included for univariate and multivariate analysis. RESULTS Univariate regression analysis revealed 7 variables that had a significant influence on pCMS onset, namely, tumor size, maximum tumor diameter > 5 cm, tumor infiltration or compression of the brainstem, significantly larger decreases in hemoglobin (p = 0.010) and hematocrit (p = 0.003) in the pCMS group after surgery than in the no-pCMS group, significantly more reported incidents of severe bleeding in the tumor bed during surgery in the pCMS group, preoperative hydrocephalus, and a mean body temperature rise of 0.5°C in the first 4 days after surgery in the pCMS group. Multiple regression analysis revealed that tumor size, tumor infiltration into or compression of the brainstem, and higher mean body temperature in the first 4 postoperative days were independent and highly significant predictors for pCMS. CONCLUSIONS The authors confirmed earlier findings that tumor-associated preoperative conditions, such as a maximum tumor diameter ≥ 5 cm and infiltration into or compression of the brainstem, are associated with a higher risk for the development of pCMS. Most importantly, the authors found that a 0.5°C higher mean body temperature in the first 4 postoperative days increased the odds ratio for the development of pCMS almost 5-fold. These data suggest that an important focus for the prevention of pCMS in children who have undergone medulloblastoma surgery might be rigorous maintenance of normothermia as standard care after surgery.

Literature review. Noninvasive fungal rhinosinusitis

AbstractFungus ball (FB) of the paranasal sinuses has a distinctive clinicopathological presentation. The disease occurs more frequently in elderly patients and has a female preponderance. Classically, it involves only one paranasal sinus in more than 90% of the cases, most commonly the maxillary sinus. Imaging characteristics (calcifications and / or erosion of the inner wall of the sinus visible on CT) and histopathological ones (luminal aggregation of fungal hyphae) confirm the diagnosis.Allergic fungal rhinosinusitis (AFRS) usually occurs in younger, immunocompetent patients, with a history of atopy, including allergic rhinitis and / or asthma, or a long clinical picture of chronic rhinosinusitis (CRS), refractory to antibiotic treatment. Nasal polyps (NP) are present in almost all patients, while extra-sinusal complications are described only in some of them. Usually, there is involvement of several sinuses, as well as bilateral damage. The definitive diagnosis is confirmed only by examining surgical specimens - the characteristic appearance of eosinophilic mucin is the most reliable indicator of AFRS.

Impaired peripheral reaching and on-line corrections in patient DF: Optic ataxia with visual form agnosia

An influential model of vision suggests the presence of two visual streams within the brain: a dorsal occipito-parietal stream which mediates action and a ventral occipito-temporal stream which mediates perception. One of the cornerstones of this model is DF, a patient with visual form agnosia following bilateral ventral stream lesions. Despite her inability to identify and distinguish visual stimuli, DF can still use visual information to control her hand actions towards these stimuli. These observations have been widely interpreted as demonstrating a double dissociation from optic ataxia, a condition observed after bilateral dorsal stream damage in which patients are unable to act towards objects that they can recognize. In Experiment 1, we investigated how patient DF performed on the classical diagnostic task for optic ataxia, reaching in central and peripheral vision. We replicated recent findings that DF is remarkably inaccurate when reaching to peripheral targets, but not when reaching in free vision. In addition we present new evidence that her peripheral reaching errors follow the optic ataxia pattern increasing with target eccentricity and being biased towards fixation. In Experiments 2 and 3, for the first time we examined DF's on-line control of reaching using a double-step paradigm in fixation-controlled and free-vision versions of the task. DF was impaired when performing fast on-line corrections on all conditions tested, similarly to optic ataxia patients. Our findings question the long-standing assumption that DF's dorsal visual stream is functionally intact and that her on-line visuomotor control is spared. In contrast, in addition to visual form agnosia, DF also has visuomotor symptoms of optic ataxia which are most likely explained by bilateral damage to the superior parietal-occipital cortex (SPOC). We thus conclude that patient DF can no longer be considered as an appropriate single-case model for testing the neural basis of perception and action dissociations.

Texture segmentation without human V4

ABSTRACTTexture segmentation, or second-order segmentation, is a rapid perceptual process, allowing object and surface boundaries to be effortlessly detected. It is currently unclear whether this is achieved in early cortical areas or whether it necessitates the region referred to as human V4. The present report presents a single case study of patient MS, whose bilateral occipitotemporal damage includes the putative human V4 area, yet whose early visual cortex is spared. As shown in these experiments, MS can accurately locate a target defined by an orientation contrast to its background, even with considerable orientation noise. Importantly, his performance was significantly reduced when the texture edges were masked by black borders (thus preventing edge-based segmentation), indicating that he retains a functional edge-based texture segmentation process. Additionally, when the sign of the orientation contrast was reversed at a temporal frequency of 12.5 Hz, MS could nonetheless detect the contours defined by the orientation contrast despite being unable to judge whether the surfaces either side of the contrast were the same or not. This reveals that MS’s early visual cortex is sufficient for the intact phase-insensitive component of texture segmentation. Human area V4, therefore, is not necessary for texture segmentation.

Akinetic mutism and the story of David

ABSTRACTFollowing a description about the characteristics of akinetic mutism (AM) and how it differs from locked-in syndrome (LIS) and a disorder of consciousness (DOC), we present the case of David, a 71-year-old man with AM. David sustained a stroke following a middle cerebral artery (MCA) thrombus. A CT scan at the time detected old ischaemic infarcts affecting the right frontal lobe, the left occipital lobe and the left parietal lobe so David had bilateral brain damage. Initially thought to have a DOC, further neuropsychological assessments administered when David had improved a little, resulted in the diagnosis of AM. Although David spoke little, when he did speak, his words and phrases were well articulated, grammatical and with appropriate intonation. He was alert and visually aware and he was not paralysed. We discuss whether the diagnosis was correct and address the difficulties in assessing such patients.

Morphological, structural, and functional alterations of the prefrontal cortex and the basolateral amygdala after early lesion of the rat mediodorsal thalamus.

Early postnatal damage to the mediodorsal thalamus (MD) produces deficits in cognition and behavior believed to be associated with early prefrontal cortical maldevelopment. We assessed the role of MD afferents during development on the morphological and functional maturation of the prefrontal cortex (PFC) and the basolateral amygdala (BLA). Sprague-Dawley rat pups (n = 56) received a bilateral electrolytic lesion of the MD or a MD Sham lesion on postnatal day 4. 7weeks later, all rats were tested in anxiety-related and cognitive paradigms using the elevated plus maze and novel object recognition tests. Following behavioral testing (P70), rats were killed and the baseline expression of C-Fos protein and the number of GABAergic neurons were evaluated in the PFC and the BLA. The dendritic morphology and spine density in the PFC using Golgi-Cox staining was also evaluated. Adult rats with early postnatal bilateral MD damage exhibited disrupted recognition memory and increased anxiety-like behaviors. The lesion also caused a significant diminution of C-Fos immunolabeling and an increase of the number of GABAergic neurons in the PFC. In the BLA, the number of GABAergic neurons was significantly reduced, associated with an increase in C-Fos immunolabeling. Furthermore, in the PFC the lesion induced a significant reduction in dendritic branching and spine density. Our data are consistent with the hypothesis that the MD plays a role in the development of the PFC and, therefore, may be a good animal model to investigate cognitive symptoms associated with schizophrenia.

A Lesion-Proof Brain? Multidimensional Sensorimotor, Cognitive, and Socio-Affective Preservation Despite Extensive Damage in a Stroke Patient.

In this study, we report an unusual case of mutidimensional sensorimotor, cognitive, and socio-affective preservation in an adult with extensive, acquired bilateral brain damage. At age 43, patient CG sustained a cerebral hemorrhage and a few months later, she suffered a second (ischemic) stroke. As a result, she exhibited extensive damage of the right hemisphere (including frontal, temporal, parietal, and occipital regions), left Sylvian and striatal areas, bilateral portions of the insula and the amygdala, and the splenium. However, against all probability, she was unimpaired across a host of cognitive domains, including executive functions, attention, memory, language, sensory perception (e.g., taste recognition and intensity discrimination), emotional processing (e.g., experiencing of positive and negative emotions), and social cognition skills (prosody recognition, theory of mind, facial emotion recognition, and emotional evaluation). Her functional integrity was further confirmed through neurological examination and contextualized observation of her performance in real-life tasks. In sum, CG's case resists straightforward classifications, as the extent and distribution of her lesions would typically produce pervasive, multidimensional deficits. We discuss the rarity of this patient against the backdrop of other reports of atypical cognitive preservation, expound the limitations of several potential accounts, and highlight the challenges that the case poses for current theories of brain organization and resilience.

Deciding what is possible and impossible following hippocampal damage in humans.

ABSTRACTThere is currently much debate about whether the precise role of the hippocampus in scene processing is predominantly constructive, perceptual, or mnemonic. Here, we developed a novel experimental paradigm designed to control for general perceptual and mnemonic demands, thus enabling us to specifically vary the requirement for constructive processing. We tested the ability of patients with selective bilateral hippocampal damage and matched control participants to detect either semantic (e.g., an elephant with butterflies for ears) or constructive (e.g., an endless staircase) violations in realistic images of scenes. Thus, scenes could be semantically or constructively ‘possible’ or ‘impossible’. Importantly, general perceptual and memory requirements were similar for both types of scene. We found that the patients performed comparably to control participants when deciding whether scenes were semantically possible or impossible, but were selectively impaired at judging if scenes were constructively possible or impossible. Post‐task debriefing indicated that control participants constructed flexible mental representations of the scenes in order to make constructive judgements, whereas the patients were more constrained and typically focused on specific fragments of the scenes, with little indication of having constructed internal scene models. These results suggest that one contribution the hippocampus makes to scene processing is to construct internal representations of spatially coherent scenes, which may be vital for modelling the world during both perception and memory recall. © 2016 The Authors. Hippocampus Published by Wiley Periodicals, Inc.

The possibilities for the restoration of the laryngeal function: the current state-of-the-art

The restoration of the functional competence of the larynx following bilateral laryngeal nerve damage and vocal fold paralysis is a serious challenge for the surgeon that has thus far no satisfactory solution. Physiological re-innervation that occurs naturally with time is non-selective and, in the majority of the cases, leads to synkinesis. Laryngeal pacing achieved with the application of the implantable microchips appears to be a promising approach. The animal experiments have demonstrated the possibility of successful restoration of all the functions of the larynx by means of laryngeal pacing but simultaneously revealed a number of technical issues that have to be addressed if the further progress in this field is to be achieved including the choice of the proper materials for implantation, solution of problems pertaining to the neuromuscular mapping during pacer implantation, etc.). The results of the first prospective clinical trial involving the human patients gave evidence suggesting that the laryngeal electrostimulation technology is both safe and efficient. Nevertheless, further investigations and modification of the method are needed before it can be recommended for the wider application in the routine clinical practice.

A Patient With Psychotic Disorder Following Traumatic Brain Injury With Bilateral Frontal Lobe Damage

A Patient With Psychotic Disorder Following Traumatic Brain Injury With Bilateral Frontal Lobe Damage

Functional modulation of contralateral bias in early and object-selective areas after stroke of the occipital ventral cortices

Object agnosia is a rare symptom, occurring mainly after bilateral damage of the ventral visual cortex. Most patients suffering from unilateral ventral lesions are clinically non-agnosic. Here, we studied the effect of unilateral occipito-temporal lesions on object categorization and its underlying neural correlates in visual areas. Thirteen non-agnosic stroke patients and twelve control subjects performed an event-related rapid object categorization task in the fMRI scanner where images were presented either to the left or to the right of a fixed point. Eight patients had intact central visual fields within at least 10° eccentricity while five patients showed an incomplete hemianopia. Patients made more errors than controls for both contra- and ipsilesional presentation, meaning that object categorization was impaired bilaterally in both patient groups. The activity in cortical visual areas is usually higher when a stimulus is presented contralaterally compared to presented ipsilaterally (contralateral bias). A region of interest analysis of early visual (V1–V4) and object-selective areas (lateral occipital complex, LOC; fusiform face area, FFA; and parahippocampal place area, PPA) revealed that the lesioned-hemisphere of patients showed reduced contralateral bias in early visual areas and LOC. In contrast, literally no contralateral bias in FFA and PPA was found. These findings indicate disturbed processing in the lesioned hemisphere, which might be related to the processing of visually presented objects. Thus, unilateral occipito-temporal damage leads to altered contralateral bias in the lesioned hemisphere, which might be the cause of impaired categorization performance in both visual hemifields in clinically non-agnosic patients. We conclude that both hemispheres need to be functionally intact for unimpaired object processing.

Hippocampal Damage Increases Deontological Responses during Moral Decision Making.

Complex moral decision making is associated with the ventromedial prefrontal cortex (vmPFC) in humans, and damage to this region significantly increases the frequency of utilitarian judgments. Since the vmPFC has strong anatomical and functional links with the hippocampus, here we asked how patients with selective bilateral hippocampal damage would derive moral decisions on a classic moral dilemmas paradigm. We found that the patients approved of the utilitarian options significantly less often than control participants, favoring instead deontological responses—rejecting actions that harm even one person. Thus, patients with hippocampal damage have a strikingly opposite approach to moral decision making than vmPFC-lesioned patients. Skin-conductance data collected during the task showed increased emotional arousal in the hippocampal-damaged patients and they stated that their moral decisions were based on emotional instinct. By contrast, control participants made moral decisions based on the integration of an adverse emotional response to harming others, visualization of the consequences of one's action, and the rational re-evaluation of future benefits. This integration may be disturbed in patients with either hippocampal or vmPFC damage. Hippocampal lesions decreased the ability to visualize a scenario and its future consequences, which seemed to render the adverse emotional response overwhelmingly dominant. In patients with vmPFC damage, visualization might also be reduced alongside an inability to detect the adverse emotional response, leaving only the utilitarian option open. Overall, these results provide insights into the processes involved in moral decision making and highlight the complementary roles played by two closely connected brain regions.SIGNIFICANCE STATEMENT The ventromedial prefrontal cortex (vmPFC) is closely associated with the ability to make complex moral judgements. When this area is damaged, patients become more utilitarian (the ends justify the means) and have decreased emotional arousal during moral decision making. The vmPFC is closely connected with another brain region—the hippocampus. In this study we found that patients with selective bilateral hippocampal damage show a strikingly opposite response pattern to those with vmPFC damage when making moral judgements. They rejected harmful actions of any kind (thus their responses were deontological) and showed increased emotional arousal. These results provide new insights into the processes involved in moral decision making and highlight the complementary roles played by two closely connected brain regions.

Selective lesion of the hippocampus increases the differentiation of immature neurons in the monkey amygdala

A large population of immature neurons is present in the ventromedial portion of the adult primate amygdala, a region that receives substantial direct projections from the hippocampal formation. Here, we show the effects of neonatal (n = 8) and adult (n = 6) hippocampal lesions on the populations of mature and immature neurons in the paralaminar, lateral, and basal nuclei of the adult monkey amygdala. Compared with unoperated controls (n = 7), the number of mature neurons was about 70% higher in the paralaminar nucleus of neonate- and adult-lesioned monkeys, and 40% higher in the lateral and basal nuclei of neonate-lesioned monkeys. The number of immature neurons in the paralaminar nucleus was 40% higher in neonate-lesioned monkeys and 30% lower in adult-lesioned monkeys. Similar changes in neuron numbers were also found in two monkeys with nonexperimental, selective, bilateral hippocampal damage. These changes in neuron numbers following hippocampal lesions appear to reflect the differentiation of immature neurons present in the paralaminar nucleus. After adult lesions, the differentiation of immature neurons was essentially restricted to the paralaminar nucleus and was associated with a decrease in the population of immature neurons. In contrast, after neonatal lesions, the differentiation of immature neurons involved the paralaminar, lateral, and basal nuclei. It was associated with an increase in the population of immature neurons in the paralaminar nucleus. Such lesion-induced neuronal plasticity sheds new light on potential mechanisms that may facilitate functional recovery following focal brain injury.

Residual perception of biological motion in cortical blindness

From birth, the human visual system shows a remarkable sensitivity for perceiving biological motion. This visual ability relies on a distributed network of brain regions and can be preserved even after damage of high-level ventral visual areas. However, it remains unknown whether this critical biological skill can withstand the loss of vision following bilateral striate damage. To address this question, we tested the categorization of human and animal biological motion in BC, a rare case of cortical blindness after anoxia-induced bilateral striate damage. The severity of his impairment, encompassing various aspects of vision (i.e., color, shape, face, and object recognition) and causing blind-like behavior, contrasts with a residual ability to process motion. We presented BC with static or dynamic point-light displays (PLDs) of human or animal walkers. These stimuli were presented either individually, or in pairs in two alternative forced choice (2AFC) tasks. When confronted with individual PLDs, the patient was unable to categorize the stimuli, irrespective of whether they were static or dynamic. In the 2AFC task, BC exhibited appropriate eye movements towards diagnostic information, but performed at chance level with static PLDs, in stark contrast to his ability to efficiently categorize dynamic biological agents. This striking ability to categorize biological motion provided top-down information is important for at least two reasons. Firstly, it emphasizes the importance of assessing patients’ (visual) abilities across a range of task constraints, which can reveal potential residual abilities that may in turn represent a key feature for patient rehabilitation. Finally, our findings reinforce the view that the neural network processing biological motion can efficiently operate despite severely impaired low-level vision, positing our natural predisposition for processing dynamicity in biological agents as a robust feature of human vision.

Whiplash trauma to the vestibular system: What effect does whiplash have on the ear?

Introduction Dizziness after traumatic acceleration/deceleration injury is well-known and the complaints voiced by these patients are similar to those of many non-trauma patients referred with vestibular sounding complaints. Patients often deny spinning but voice “non-traditional” complaints of imbalance, subtle boat like feelings and nausea. These complaints may arise because of otolithic damage from the trauma. It is traditionally thought that most vestibular pathology is unilateral and our concern is that trauma patients may have suffered bilateral damage due to the mechanism of the injury. We felt the need to document this. Pathology in these patients is important to define, as bilateral pathology is more of a challenge to compensate for. Material and methods We assess patients with computerized dynamic posturography in our tertiary care diagnostic unit, but we also carry out vestibular-evoked myogenic potential (VEMP) assessment which can document and quantify otolithic pathology. Posturography, OVEMP and CVEMP results were compared in 25 whiplash trauma patients with an age and sex matched group of non-trauma patients with spontaneous vestibular disease. Results We examined both groups of patients with respect to CVEMP and OVEMP abnormalities. Posturography results were not different between the two groups but there was a statistically higher OVEMP abnormality rate in the trauma group when compared to the vestibular non-trauma patients. The meaning of this will be discussed. Discussion–conclusion We will be discussing the findings in our two groups of patients. It is important to document the pathology in these patients as being vestibular, as immediate activation with “goal directed” activities in the patient with vestibular pathology is extremely important. Our concern is patients may be diagnosed with “post concussion syndrome”; the treatment for this is complete rest.

Electrophysiological correlates of visual binding errors after bilateral parietal damage

Illusory conjunctions (e.g. the confusion between the shape of one stimulus with the color of another stimulus) are the most dramatic expression of binding failures in vision. Under brief exposure or when attention is diverted illusory conjunctions may be observed in healthy participants, but they only represent a real-life problem for patients with parietal damage. However, it is unclear whether such failures reflect the impairment of early or late stages of visual processing. Here, we examined the time-course of visual processing using evoked potential measures in a patient with bilateral damage to the posterior parietal cortex presenting prominent binding failures. The patient was asked to identify colored letters that were briefly flashed to the left or right hemifield. When only one item was presented she adequately identified color or shape of left and right letters. In contrast, when presentation was bilateral she either identified the correct right shape-color combination and missed the item in the left hemifield (extinction) or combined incorrectly the right shape with the left color (illusory conjunction). Evoked potential analyses revealed a specific electrophysiological signature of illusory conjunctions, starting ∼105ms after stimulus onset over the right frontal cortex. These findings indicate that binding errors reflect failures of early stages of attentional filtering relying on the integrity of the posterior parietal cortex.

The role of parieto-temporal connectivity in pure neglect dyslexia

The initial stages of reading are characterised by parallel and effortless access to letters constituting a word. Neglect dyslexia is an acquired reading disorder characterised by omission or substitution of the initial or the final letters of words. Rarely, the disorder appears in a'pure’ form that is, without other signs of spatial neglect. Neglect dyslexia is linked to damage involving the inferior parietal lobe and regions of the temporal lobe, but the precise anatomical basis of the pure form of the disorder is unknown. Here, we show that pure neglect dyslexia is associated with decreased structural connectivity between the inferior parietal and lateral temporal lobe. We examined patient DM, who following bilateral occipito-parietal damage presented left neglect dyslexia together with right visual field loss, but no signs of spatial neglect. DM's reading errors were affected by word length and were much more frequent for pseudowords than for existing words. Most errors were omissions or substitutions of the first or second letter, and the spatial distribution of errors was similar for stimuli presented left or right of fixation. The brain lesions of DM comprised the inferior and superior parietal lobule as well as the cuneus and precuneus of the left hemisphere, and the angular gyrus and lateral occipital cortex of the right hemisphere. Diffusion tensor imaging revealed bilateral decrease of fibre tracts connecting the inferior parietal lobule with the superior and middle temporal cortex. These findings suggest that parieto-temporal connections play a significant role for the deployment of attention within words during reading.

Structural correlates of apathy in Alzheimer's disease: a multimodal MRI study.

Apathy is one of the most frequent symptoms of dementia, whose underlying neurobiology is not well understood. The objective was to analyze the correlations of apathy and its dimensions with gray and white matter damage in the brain of patients with advanced Alzheimer's disease (AD). The setting of the study was at the Alzheimer Center Reina Sofía Foundation Research Unit. Participants include 37 nursing home patients with moderate to severe AD, 78.4% were women, and mean Standard Deviation (SD) age is 82.7 (5.8). Several measurements were taken: severe mini-mental state examination and Global Deterioration Scale for cognitive and functional status, Neuropsychiatric Inventory for behavioral problems, and Apathy In Dementia-Nursing Home Version Scale for apathy, including total score and subscores of emotional blunting, deficit of thinking, and cognitive inertia. 3T magnetic resonance imaging measures (voxel-based morphometry, fluid-attenuated inversion recovery, and diffusion tensor imaging) were also conducted. Moderate levels of apathy (mean Apathy In Dementia-Nursing Home Version Scale: 31.1 ± 18.5) were found. Bilateral damage to the corpus callosum and internal capsule was associated with apathy severity (cluster size 2435, p < 0.0005, family-wise error [FWE]-corrected). A smaller and more anteriorly located region of the right internal capsule and corpus callosum was associated with higher emotional blunting (cluster size 334, p < 0.0005, FWE-corrected). Ischemic damage in the right periventricular frontal region was associated with higher deficit of thinking (cluster size 3805, p < 0.005, FWE-corrected). Brain damage related to apathy may have different features in the advanced stages of AD and differs between the three apathy dimensions. Besides atrophy, brain connectivity and vascular lesions are relevant in the study of apathy, especially in the more severe stages of dementia. Further magnetic resonance imaging studies should include multimodal techniques. Copyright © 2016 John Wiley & Sons, Ltd.

Scenes, Spaces, and Memory Traces

The hippocampus is one of the most closely scrutinized brain structures in neuroscience. While traditionally associated with memory and spatial cognition, in more recent years it has also been linked with other functions, including aspects of perception and imagining fictitious and future scenes. Efforts continue apace to understand how the hippocampus plays such an apparently wide-ranging role. Here we consider recent developments in the field and in particular studies of patients with bilateral hippocampal damage. We outline some key findings, how they have subsequently been challenged, and consider how to reconcile the disparities that are at the heart of current lively debates in the hippocampal literature.