Developmental Amnesia Research Articles

Anatomo-functional changes in neural substrates of cognitive memory in developmental amnesia: Insights from automated and manual Magnetic Resonance Imaging examinations.

Despite bilateral hippocampal damage dating to the perinatal or early childhood period and severely impaired episodic memory, patients with developmental amnesia continue to exhibit well-developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypothesize about the neural substrate that supports their remarkable capacity for encoding and retrieval of semantic memory. In particular, we need to assess whether the residual hippocampal tissue is involved in this preservation, or whether the surrounding cortical areas reorganize to rescue aspects of these critical cognitive memory processes after early injury. We used voxel-based morphometry (VBM) analysis, automatic (FreeSurfer) and manual segmentation to characterize structural changes in the brain of an exceptionally large cohort of 23 patients with developmental amnesia in comparison with 32 control subjects. Both the VBM and the FreeSurfer analyses revealed severe structural alterations in the hippocampus and thalamus of patients with developmental amnesia. Milder damage was found in the amygdala, caudate, and parahippocampal gyrus. Manual segmentation demonstrated differences in the degree of atrophy of the hippocampal subregions in patients. The level of atrophy in CA-DG subregions and subicular complex was more than 40%, while the atrophy of the uncus was moderate (-24%). Anatomo-functional correlations were observed between the volumes of residual hippocampal subregions in patients and selective aspects of their cognitive performance, viz, intelligence, working memory, and verbal and visuospatial recall. Our findings suggest that in patients with developmental amnesia, cognitive processing is compromised as a function of the extent of atrophy in hippocampal subregions. More severe hippocampal damage may be more likely to promote structural and/or functional reorganization in areas connected to the hippocampus. In this hypothesis, different levels of hippocampal function may be rescued following this variable reorganization. Our findings document not only the extent, but also the limits of circuit reorganization occurring in the young brain after early bilateral hippocampal damage.

Using recognition testing to support semantic learning in developmental amnesia

ABSTRACT Patients with developmental amnesia (DA) have suffered hippocampal damage in infancy and subsequently shown poor episodic memory, but good semantic memory. It is not clear how patients with DA learn semantic information in the presence of episodic amnesia. However, patients with DA show good recognition memory and it is possible that semantic learning may be supported by recognition. Building on previous work, we compared two methods for supporting semantic learning in DA; recognition-learning and recall-learning. In each condition, a patient with DA (aged 8 years) was presented with semantic information in animated videos. After each presentation of a video, learning was supported by an immediate memory test. Two videos were paired with a cued recall test. Another two videos were paired with a multiple-choice test to enable recognition-based learning. The outcome measure was semantic recall performance after a short delay of 30 min and a long delay of one week. Results showed a benefit of recognition-learning compared to recall-learning on cued recall in the patient with DA (76% vs. 35%). This finding indicates that young people with severe hippocampal damage can utilize recognition to support semantic learning. This has implications for the support of school-aged children with episodic memory difficulties.

Social cognition in developmental and adult-onset amnesia: a multiple case-control study

Memory disorders due to medial temporal lobe lesions are well documented, but studies on social cognition in patients with amnesia are rare. This study examined social cognitive functioning in three adult amnesic patients. We report on the neurocognitive and social cognitive profiles of two patients with developmental amnesia and a patient with adult-onset amnesia, all due to hypoxic events. All cases were compared to their individual IQ-matched control groups. Both cases with developmental amnesia showed notable deficits in tasks assessing emotion recognition and theory of mind. In comparison, the patient with adult-onset amnesia showed less severe and more circumscribed impairment in social cognition. Our findings suggest that social cognition is at serious risk in patients with amnesia. The deficits may be more pronounced in developmental amnesia with hippocampal lesions than in adult-onset amnesia. Our findings highlight the importance of examining social cognitive functions in patients with memory impairment to assess the need for therapeutic interventions and counselling of patients and their relatives.

Intact high-resolution working memory binding in a patient with developmental amnesia and selective hippocampal damage.

Debate continues regarding the possible role of the hippocampus across short‐term and working memory tasks. The current study examined the possibility of a hippocampal contribution to precise, high‐resolution cognition and conjunctive memory. We administered visual working memory tasks featuring a continuous response component to a well‐established developmental amnesic patient with relatively selective bilateral hippocampal damage (Jon) and healthy controls. The patient was able to produce highly accurate response judgments regarding conjunctions of color and orientation or color and location, using simultaneous or sequential presentation of stimuli, with no evidence of any impairment in working memory binding, categorical accuracy, or continuous precision. These findings indicate that hippocampal damage does not necessarily lead to deficits in high‐resolution cognitive performance, even when the damage is severe and bilateral.

When the brain, but not the person, remembers: Cortical reinstatement is modulated by retrieval goal in developmental amnesia

Developmental amnesia (DA) is associated with early hippocampal damage and subsequent episodic amnesia emerging in childhood alongside age-appropriate development of semantic knowledge. We employed fMRI to assess whether patients with DA show evidence of ‘cortical reinstatement’, a neural correlate of episodic memory, despite their amnesia. At study, 23 participants (5 patients) were presented with words overlaid on a scene or a scrambled image for later recognition. Scene reinstatement was indexed by scene memory effects (greater activity for previously presented words paired with a scene rather than scrambled images) that overlapped with scene perception effects. Patients with DA demonstrated scene reinstatement effects in the parahippocampal and retrosplenial cortex that were equivalent to those shown by healthy controls. Behaviourally, however, patients with DA showed markedly impaired scene memory. The data indicate that reinstatement can occur despite hippocampal damage, but that cortical reinstatement is insufficient to support accurate memory performance. Furthermore, scene reinstatement effects were diminished during a retrieval task in which scene information was not relevant for accurate responding, indicating that strategic mnemonic processes operate normally in DA. The data suggest that cortical reinstatement of trial-specific contextual information is decoupled from the experience of recollection in the presence of severe hippocampal atrophy.

A brief history of developmental amnesia

A brief history of developmental amnesia

Social cognition in an adult epilepsy patient with developmental amnesia

ABSTRACT Reports on social cognition in patients with developmental amnesia resulting from bilateral hippocampal lesions are rare, although the link between social cognition and temporal lobe structures is well established. We present the case of a 23-year-old male epilepsy patient, BM, with developmental amnesia due to perinatal cerebral hypoxia. The patient was examined with neuroimaging and neuropsychological methods and compared to IQ-matched patients with epilepsy to control for effects of epilepsy. In addition, we used a test battery that evaluates emotion recognition and theory of mind to study his social cognition abilities. Structural high-resolution magnetic resonance imaging showed bilateral hippocampal atrophy. The comparison to controls showed that, in addition to the well-documented memory disorders in developmental amnesia, BM showed remarkable deficits in 9 out of 17 social cognitive tasks assessing emotion recognition and theory of mind. In contrast, BM’s performance on tasks of executive functions was largely preserved. The relevance of deficits in social cognition for patients with developmental amnesia is discussed.

Representation of viewed and recalled film clips in patterns of brain activity in a person with developmental amnesia

As clear memories transport us back into the past, the brain also revives prior patterns of neural activity, a phenomenon known as neural reactivation. While growing evidence indicates a link between neural reactivation and typical variations in memory performance in healthy individuals, it is unclear how and to what extent reactivation is disrupted by a memory disorder. The current study characterizes neural reactivation in a case of amnesia using Multivoxel Pattern Analysis (MVPA). We tested NC, an individual with developmental amnesia linked to a diencephalic stroke, and 19 young adult controls on a functional magnetic resonance imaging (fMRI) task during which participants viewed and recalled short videos multiple times. An encoding classifier trained and tested to identify videos based on brain activity patterns elicited at perception revealed superior classification in NC. The enhanced consistency in stimulus representation we observed in NC at encoding was accompanied by an absence of multivariate repetition suppression, which occurred over repeated viewing in the controls. Another recall classifier trained and tested to identify videos during mental replay indicated normal levels of classification in NC, despite his poor memory for stimulus content. However, a cross-condition classifier trained on perception trials and tested on mental replay trials—a strict test of reactivation—revealed significantly poorer classification in NC. Thus, while NC's brain activity was consistent and stimulus-specific during mental replay, this specificity did not reflect the reactivation of patterns elicited at perception to the same extent as controls. Fittingly, we identified brain regions for which activity supported stimulus representation during mental replay to a greater extent in NC than in controls. This activity was not modeled on perception, suggesting that compensatory patterns of representation based on generic knowledge can support consistent mental constructs when memory is faulty. Our results reveal several ways in which amnesia impacts distributed patterns of stimulus representation during encoding and retrieval.

Dysmnésie développementale : un trouble neurodéveloppemental oublié

Introduction/objectiveMemory disorders in adults are common after cerebral stroke, brain tumor, or major neurocognitive disorder. But in childhood, these disorders are less described in scientific literature and are perhaps less frequent. Many studies have described long-term memory disorder after hypoxic–ischemic events (see articles from Vargha-Kadhem and colleagues). This disorder is named developmental amnesia because the origin of difficulties is identified. But in a few cases (4 cases described currently) causes are unknown despite the same memory disorders. This neurodevelopmental disorder could be named: developmental dysmnesia. So, the question is: is the prevalence of developmental dysmnesia in the general population really low or is this an under-diagnosis? Temple and Richardson (2006) stated prevalence at around 5–6%, but in fact neuropsychologists never diagnose developmental dysmnesia. MethodFrom literature review and description of two new cases which have have recently been identified (one with episodic dysmnesia and one with mixed dysmnesia), we postulate that developmental dysmnesia is an underdiagnosed neurodevelopmental disorder because of the presence of other developmental disorders such as ADHD, SLI… which become the tree that hides the forest; and because of low scholastic difficulties which are compensated for by more consequent personal effort. ConclusionLong-term memory can be perturbed in children without brain damage, which we have named developmental dysmnesia. We have demonstrated that many parameters generate few diagnostics of developmental dysmnesia which could be a neurodevelopmental disorder with the same prevalence as others. The diagnostic of memory disorder in children is difficult because complaints are not about memory, and/or scholastic difficulties are compensated. We have identified three types of developmental dysmnesia, based on the nature of the memory system that is disturbed: episodic dysmnesia, semantic dysmnesia and mixed dysmnesia (episodic and semantic memory disorders). Moreover, we could distinguish two sensorial modalities: verbal and/or visuo-spatial developmental dysmnesia. The systematic investigation of long-term memory problems in children with neurodevelopmental disorders (notably ADHD and dyslexia) must permit listing more cases of developmental dysmnesia in the future. We encourage all neuropsychologists and others professionals which working with children to assess long-term memory despite lack of complaints.

Refining understanding of working memory buffers through the construct of binding: Evidence from a single case informs theory and clinical practise

Binding operations carried out in working memory enable the integration of information from different sources during online performance. While available evidence suggests that working memory may involve distinct binding functions, whether or not they all involve the episodic buffer as a cognitive substrate remains unclear. Similarly, knowledge about the neural underpinnings of working memory buffers is limited, more specifically regarding the involvement of medial temporal lobe structures. In the present study, we report on the case of patient KA, with developmental amnesia and selective damage to the whole hippocampal system. We found that KA was unable to hold shape-colours associations (relational binding) in working memory. In contrast, he could hold integrated coloured shapes (conjunctive binding) in two different tasks. Otherwise, and as expected, KA was impaired on three relational memory tasks thought to depend on the hippocampus that are widely used in the early detection of Alzheimer's disease. Our results emphasize a dissociation between two binding processes within working memory, suggesting that the visuo-spatial sketchpad could support conjunctive binding, and may rely upon a large cortical network including sub-hippocampal structures. By contrast, we found evidence for a selective impairment of relational binding in working memory when the hippocampal system is compromised, suggesting that the long-term memory deficit observed in amnesic patients may be related to impaired short-term relational binding at encoding. Finally, these findings may inform research on the early detection of Alzheimer's disease as the preservation of conjunctive binding in KA is in sharp contrast with the impaired performance demonstrated very early in this disease.

Vingt ans d’amnésie développementale : quoi de neuf ?

In 1997, Faraneh Vargha-Khadem and her colleagues published a far-reaching paper describing for the first time three patients suffering from a new syndrome: developmental amnesia. Twenty years later, we propose here to establish a picture of today's knowledge about this syndrome. This pure amnesic syndrome is usually due to neonatal hypoxic/ischemic episodes resulting in brain lesions and notably in bilateral hippocampal atrophy. While some studies have aimed at providing a refined description of the neuropsychological profile of these patients, others considered them as a way of testing the hypothesis about normal functioning. The methods used and the main findings will be covered in the present article. We will focus in particular on the studies that investigated episodic memory disorders, their consequences on new semantic acquisition, on projection in the past and the future, or on the sense of identity. Brain damage associated with developmental amnesia will also be described, based on single cases and group studies. Finally, we will discuss the diagnosis of developmental amnesia and emphasize that this syndrome may be much more frequent than initially thought.

Hippocampal and diencephalic pathology in developmental amnesia

Developmental amnesia (DA) is a selective episodic memory disorder associated with hypoxia-induced bilateral hippocampal atrophy of early onset. Despite the systemic impact of hypoxia-ischaemia, the resulting brain damage was previously reported to be largely limited to the hippocampus. However, the thalamus and the mammillary bodies are parts of the hippocampal-diencephalic network and are therefore also at risk of injury following hypoxic-ischaemic events. Here, we report a neuroimaging investigation of diencephalic damage in a group of 18 patients with DA (age range 11–35 years), and an equal number of controls. Importantly, we uncovered a marked degree of atrophy in the mammillary bodies in two thirds of our patients. In addition, as a group, patients had mildly reduced thalamic volumes. The size of the anterior-mid thalamic (AMT) segment was correlated with patients' visual memory performance. Thus, in addition to the hippocampus, the diencephalic structures also appear to play a role in the patients' memory deficit.

Using fMRI to understand event construction in developmental amnesia

Recently, neuroimaging and patient-lesion methods have been combined to explain anomalies such as patients’ intact performance on tasks on which they would be predicted to perform poorly. In some cases, preserved performance has been attributed to activation of residual tissue within the damaged region. However, activation of remnant tissue can also occur in relation to impaired performance and, thus, may not necessarily correspond to successful recruitment. To constrain these neuroimaging interpretations, what is needed is a paradigm with closely matched conditions that yields intact and impaired performance in the same patient. We investigated this in H.C., an amnesic person with congenital abnormalities of the hippocampus and its connections, who was scanned during remembering and imagining, abilities known to depend on the hippocampus. Specifically, we examined whether differences in activation and/or functional connectivity would explain H.C.’s compromised ability to construct events relating to herself in autobiographical memory (SELF condition) and events relating to personally familiar others (FAMILIAR condition) versus her intact ability to construct events relating to unknown others (UNFAMILIAR condition). Despite behavioral dissociations in H.C., the pattern of activation and functional connectivity supporting her performance was strikingly similar to that of controls across conditions. Most notably, like controls, H.C. showed robust hippocampal activation and functional connectivity to the hippocampus, both when her performance was intact and impaired. Across all conditions, H.C. activated several extra-hippocampal regions to a greater extent than did controls, and modest differences were observed in functional connectivity between extra-hippocampal regions. Taken together, these findings urge caution when drawing conclusions about the functional integrity of a structurally compromised brain region even when it is activated and/or co-activated with other regions.

Object and spatial memory after neonatal perirhinal lesions in monkeys

The contribution of the perirhinal cortex (PRh) to recognition memory is well characterized in adults, yet the same lesions have limited effect on recognition of spatial locations. Here, we assessed whether the same outcomes will follow when perirhinal lesions are performed in infancy. Monkeys with neonatal perirhinal (Neo-PRh) lesions and control animals were tested in three operant recognition tasks as they reached adulthood: Delayed Nonmatching-to-Sample (DNMS) and Object Memory Span (OMS), measuring object recognition, and Spatial Memory Span (SMS), measuring recognition of spatial locations. Although Neo-PRh lesions did not impact acquisition of the DNMS rule, they did impair performance when the delays were extended from 30s to 600s. In contrast, the same neonatal lesions had no impact on either the object or spatial memory span tasks, suggesting that the lesions impacted the maintenance of information across longer delays and not memory capacity. Finally, the magnitude of recognition memory impairment after the Neo-PRh lesions was similar to that previously observed after adult-onset perirhinal lesions, indicating minimal, or no, functional compensation after the early PRh lesions. Overall, the results indicate that the PRh is a cortical structure that is important for the normal development of mechanisms supporting object recognition memory. Its contribution may be relevant to the memory impairment observed with human cases of temporal lobe epilepsy without hippocampal sclerosis, but not to the memory impairment found in developmental amnesia cases.

Patterns of preserved and impaired spatial memory in a case of developmental amnesia

The hippocampus is believed to have evolved to support allocentric spatial representations of environments as well as the details of personal episodes that occur within them, whereas other brain structures are believed to support complementary egocentric spatial representations. Studies of patients with adult-onset lesions lend support to these distinctions for newly encountered places but suggest that with time and/or experience, schematic aspects of environments can exist independent of the hippocampus. Less clear is the quality of spatial memories acquired in individuals with impaired episodic memory in the context of a hippocampal system that did not develop normally. Here we describe a detailed investigation of the integrity of spatial representations of environments navigated repeatedly over many years in the rare case of H.C., a person with congenital absence of the mammillary bodies and abnormal hippocampal and fornix development. H.C. and controls who had extensive experience navigating the residential and downtown areas known to H.C. were tested on mental navigation tasks that assess the identity, location, and spatial relations among landmarks, and the ability to represent routes. H.C. was able to represent distances and directions between familiar landmarks and provide accurate, though inefficient, route descriptions. However, difficulties producing detailed spatial features on maps and accurately ordering more than two landmarks that are in close proximity to one another along a route suggest a spatial representation that includes only coarse, schematic information that lacks coherence and that cannot be used flexibly. This pattern of performance is considered in the context of other areas of preservation and impairment exhibited by H.C. and suggests that the allocentric-egocentric dichotomy with respect to hippocampal and extended hippocampal system function may need to be reconsidered.

The role of relational binding in item memory: evidence from face recognition in a case of developmental amnesia.

Current theories state that the hippocampus is responsible for the formation of memory representations regarding relations, whereas extrahippocampal cortical regions support representations for single items. However, findings of impaired item memory in hippocampal amnesics suggest a more nuanced role for the hippocampus in item memory. The hippocampus may be necessary when the item elements need to be bound within and across episodes to form a lasting representation that can be used flexibly. The current investigation was designed to test this hypothesis in face recognition. H.C., an individual who developed with a compromised hippocampal system, and control participants incidentally studied individual faces that either varied in presentation viewpoint across study repetitions or remained in a fixed viewpoint across the study repetitions. Eye movements were recorded during encoding and participants then completed a surprise recognition memory test. H.C. demonstrated altered face viewing during encoding. Although the overall number of fixations made by H.C. was not significantly different from that of controls, the distribution of her viewing was primarily directed to the eye region. Critically, H.C. was significantly impaired in her ability to subsequently recognize faces studied from variable viewpoints, but demonstrated spared performance in recognizing faces she encoded from a fixed viewpoint, implicating a relationship between eye movement behavior in the service of a hippocampal binding function. These findings suggest that a compromised hippocampal system disrupts the ability to bind item features within and across study repetitions, ultimately disrupting recognition when it requires access to flexible relational representations.

Congenital absence of the mammillary bodies: A novel finding in a well-studied case of developmental amnesia

Individuals with developmental amnesia experience compromised development of episodic memory for details of personal life events, believed to relate to changes to the hippocampus after birth. Here we report the very rare discovery of aplasia of the mammillary bodies, hypogenesis of the fornix, and abnormal hippocampal shape and orientation in H.C., a well-documented case of selectively compromised episodic memory development who is the subject of numerous published empirical articles. These anatomical abnormalities are highly suggestive of disrupted extended hippocampal system development very early in gestation, despite an original diagnosis of developmental amnesia and assumed perinatal hypoxia. These findings provide a unique window into the normal function of the mammillary bodies, fornices, and related anterior nuclei of the thalamus bilaterally. The results also encourage re-examination of the pathological basis of developmental amnesia in other cases reported in the literature.

Hypoxia and inflammation in children with sickle cell disease: implications for hippocampal functioning and episodic memory.

Children with sickle cell disease (SCD) suffer from systemic processes (e.g., chronic anemia, recurrent hypoxic-ischemic events, chronic inflammation) that have been associated with neurocognitive impairment in a range of clinical populations, but which have been largely understudied in relation to specific domains of cognitive functioning in children with SCD. This review focuses on episodic memory, as the hippocampus may be especially vulnerable to the systemic processes associated with SCD. The first part of the paper outlines the pathophysiology of SCD and briefly reviews the extant literature on academic and cognitive functioning in children with SCD, emphasizing the dearth of research on episodic memory. Next, the complex systemic processes of hypoxia and inflammation associated with SCD are reviewed, along with research that has associated these processes with hippocampal damage and memory impairment. The paper concludes with suggestions for future research that are informed, in part, by the literature on developmental amnesia.

Deficits in egocentric-updating and spatial context memory in a case of developmental amnesia

Patients with developmental amnesia usually suffer from both episodic and spatial memory deficits. DM, a developmental amnesic, was impaired in her ability to process self-motion (i.e., idiothetic) information while her ability to process external stable landmarks (i.e., allothetic) was preserved when no self-motion processing was required. On a naturalistic and incidental episodic task, DM was severely and predictably impaired on both free and cued recall tasks. Interestingly, when cued, she was more impaired at recalling spatial context than factual or temporal information. Theoretical implications of that co-occurrence of deficits and those dissociations are discussed and testable cerebral hypothesis are proposed.

Scene construction in developmental amnesia: An fMRI study

Amnesic patients with bilateral hippocampal damage sustained in adulthood are generally unable to construct scenes in their imagination. By contrast, patients with developmental amnesia (DA), where hippocampal damage was acquired early in life, have preserved performance on this task, although the reason for this sparing is unclear. One possibility is that residual function in remnant hippocampal tissue is sufficient to support basic scene construction in DA. Such a situation was found in the one amnesic patient with adult-acquired hippocampal damage (P01) who could also construct scenes. Alternatively, DA patients’ scene construction might not depend on the hippocampus, perhaps being instead reliant on non-hippocampal regions and mediated by semantic knowledge. To adjudicate between these two possibilities, we examined scene construction during functional MRI (fMRI) in Jon, a well-characterised patient with DA who has previously been shown to have preserved scene construction. We found that when Jon constructed scenes he activated many of the regions known to be associated with imagining scenes in control participants including ventromedial prefrontal cortex, posterior cingulate, retrosplenial and posterior parietal cortices. Critically, however, activity was not increased in Jon's remnant hippocampal tissue. Direct comparisons with a group of control participants and patient P01, confirmed that they activated their right hippocampus more than Jon. Our results show that a type of non-hippocampal dependent scene construction is possible and occurs in DA, perhaps mediated by semantic memory, which does not appear to involve the vivid visualisation of imagined scenes.