Extent of hippocampal atrophy predicts degree of deficit in recall.

Which specific memory functions are dependent on the hippocampus is still debated. The availability of a large cohort of patients who had sustained relatively selective hippocampal damage early in life enabled us to determine which type of mnemonic deficit showed a correlation with extent of hippocampal injury. We assessed our patient cohort on a test that provides measures of recognition and recall that are equated for difficulty and found that the patients' performance on the recall tests correlated significantly with their hippocampal volumes, whereas their performance on the equally difficult recognition tests did not and, indeed, was largely unaffected regardless of extent of hippocampal atrophy. The results provide new evidence in favor of the view that the hippocampus is essential for recall but not for recognition.

Virtual peer-delivered memory intervention: a single-case experimental design in an adolescent with chronic memory impairment.

BACKGROUND: Children and adolescents with chronic memory impairment may develop coping strategies that enable functioning, yet these often remain undetectable using traditional psychometric measures. Personalized intervention studies that promote the use of such strategies designed specifically for use by this young cohort are scarce. OBJECTIVE: To investigate the effect of a novel virtual reality peer-delivered memory intervention on the everyday functioning and well-being of SE, a 17-year-old female with a history of chronic verbal memory issues, impaired autobiographical event recall and elevated mood symptoms. RESEARCH DESIGN: A single-case ABA experimental design study was used to assess change. METHODS: Following initial baseline assessment using objective neuropsychological and subjective functional questionnaires and intervention training, case SE used the intervention daily for 3 weeks before repeating key outcome measures. RESULTS: Using non-overlap of all pairs and qualitative feedback analysis, the results revealed a significant increase in event recall and self-reported positive changes to levels of everyday functioning. CONCLUSION: Supporting autobiographical event recall and prospective memory via a virtual peer-delivered intervention may lead to reduction in cognitive load, and benefit overall well-being and everyday functioning.

Neonatal hypoxia, hippocampal atrophy, and memory impairment: evidence of a causal sequence.

Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life.

The emergence of age-dependent social cognitive deficits after generalized insult to the developing brain: a longitudinal prospective analysis using susceptibility-weighted imaging.

Childhood and adolescence are critical periods for maturation of neurobiological processes that underlie complex social and emotional behavior including Theory of Mind (ToM). While structural correlates of ToM are well described in adults, less is known about the anatomical regions subsuming these skills in the developing brain or the impact of cerebral insult on the acquisition and establishment of high-level social cognitive skills. This study aimed to examine the differential influence of age-at-insult and brain pathology on ToM in a sample of children and adolescents with traumatic brain injury (TBI). Children and adolescents with TBI (n = 112) were categorized according to timing of brain insult: (i) middle childhood (5-9 years; n = 41); (ii) late childhood (10-11 years; n = 39); and (iii) adolescence (12-15 years; n = 32) and group-matched for age, gender, and socioeconomic status to a typically developing (TD) control group (n = 43). Participants underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks postinjury and were assessed on a battery of ToM tasks at 6- and 24-months after injury. Results showed that for adolescents with TBI, social cognitive dysfunction at 6- and 24-months postinjury was associated with diffuse neuropathology and a greater number of lesions detected using SWI. In the late childhood TBI group, we found a time-dependent emergence of social cognitive impairment, linked to diffuse neuropathology. The middle childhood TBI group demonstrated performance unrelated to SWI pathology and comparable to TD controls. Findings indicate that the full extent of social cognitive deficits may not be realized until the associated skills reach maturity. Evidence for brain structure-function relationships suggests that the integrity of an anatomically distributed network of brain regions and their connections is necessary for the acquisition and establishment of high-level social cognitive skills.

Normative development of white matter tracts: similarities and differences in relation to age, gender, and intelligence.

The white matter of the brain undergoes a range of structural changes throughout development; from conception to birth, in infancy, and onwards through childhood and adolescence. Several studies have used diffusion magnetic resonance imaging (dMRI) to investigate these changes, but a consensus has not yet emerged on which white matter tracts undergo changes in the later stages of development or what the most important driving factors are behind these changes. In this study of typically developing 8- to 16-year-old children, we use a comprehensive data-driven approach based on principal components analysis to identify effects of age, gender, and brain volume on dMRI parameters, as well as their relative importance. We also show that secondary components of these parameters predict full-scale IQ, independently of the age- and gender-related effects. This overarching assessment of the common factors and gender differences in normal white matter tract development will help to advance understanding of this process in late childhood and adolescence.

Provoked confabulations in Alzheimer's disease.

Confabulation in Alzheimer's disease (AD) has been the subject of limited investigation. When studied, the phenomenon has been found to share characteristics with memory distortions produced by neurologically intact individuals. Previous studies that have investigated confabulation in AD have failed to take into account the characteristics of the disease and the presence of confabulations in the retrieval of recent autobiographical memory (ABM). The aim of this study was to develop a test that could investigate the tendency to confabulate in recent autobiographical memory that was specifically created for eliciting confabulatory behaviours in patients with AD. Four experiments have been carried out. In Experiment 1, AD patients who have yet to show confabulatory behaviour were compared to elderly adults. The results revealed that AD patients produced significantly more confabulations on the new test compared to elderly adults. Experiment 2 investigated if the results of the initial experiment were due to AD patients having limited working memory capacity that would lead to difficulties in performing the test compared with elderly adults as AD patients would be in a condition of memory overload. The results showed that even when compared with the performance of elderly individuals under memory overload condition, AD patients still produced more confabulations than elderly adults. Using a correlational approach Experiments 3 and 4 revealed that a high production of provoked confabulatory answers were associated with poor scores on personal episodic memory measures but not with other measures of cognitive functioning such as working memory and/or executive function.

Patterns of impairment in autobiographical memory in the degenerative dementias constrain models of memory.

Detailed study of the autobiographical memory (ABM) impairments seen in different forms of degenerative dementia, in particular Alzheimer's disease (AD) and semantic dementia (SD) can inform neuropsychological models of memory. A modified ABM questionnaire which allowed more detailed analysis of episodic and semantic ABM was used to study the pattern of deficits in patients with minimal to mild Alzheimer's disease (AD) and in two patients with mild and moderate semantic dementia (SD). The questionnaire tested both cued and free recall. A group of healthy elderly was also tested. AD patients differed from controls in all measures. There was no clear temporal gradient for episodic ABM, but a modest gradient was observed for semantic ABM. The mild SD patient performed at control level for episodic ABM but showed a deficit within the range of the AD patients for semantic ABM except for the most recent life period. In contrast the moderate SD patient was impaired within the range of the AD patients for both episodic and semantic ABM. The evidence for differential impairment of episodic and semantic ABM retrieval in AD and SD is interpreted as supporting the multiple trace model of memory.

Impairment on a self-ordered working memory task in patients with early-acquired hippocampal atrophy.

One of the features of both adult-onset and developmental forms of amnesia resulting from bilateral medial temporal lobe damage, or even from relatively selective damage to the hippocampus, is the sparing of working memory. Recently, however, a number of studies have reported deficits on working memory tasks in patients with damage to the hippocampus and in macaque monkeys with neonatal hippocampal lesions. These studies suggest that successful performance on working memory tasks with high memory load require the contribution of the hippocampus. Here we compared performance on a working memory task (the Self-ordered Pointing Task), between patients with early onset hippocampal damage and a group of healthy controls. Consistent with the findings in the monkeys with neonatal lesions, we found that the patients were impaired on the task, but only on blocks of trials with intermediate memory load. Importantly, only intermediate to high memory load blocks yielded significant correlations between task performance and hippocampal volume. Additionally, we found no evidence of proactive interference in either group, and no evidence of an effect of time since injury on performance. We discuss the role of the hippocampus and its interactions with the prefrontal cortex in serving working memory.

Sexual Dimorphism in White Matter Developmental Trajectories Using Tract-Based Spatial Statistics.

Increasing evidence is emerging for sexual dimorphism in the trajectory of white matter development in children assessed using volumetric magnetic resonance imaging (MRI) and more recently diffusion MRI. Recent studies using diffusion MRI have examined cohorts with a wide age range (typically between 5 and 30 years) showing focal regions of differential diffusivity and fractional anisotropy (FA) and have implicated puberty as a possible contributory factor. To further investigate possible dimorphic trajectories in a young cohort, presumably closer to the expected onset of puberty, we used tract-based spatial statistics to investigate diffusion metrics. The cohort consisted of 23 males and 30 females between the ages of 8 and 16 years. Differences in diffusion metrics were corrected for age, total brain volume, and full scale IQ. In contrast to previous studies showing focal differences between males and females, widespread sexually dimorphic trajectories in structural white matter development were observed. These differences were characterized by more advanced development in females compared to males indicated by lower mean diffusivity, radial and axial diffusivity, and higher FA in females. This difference appeared to be larger at lower ages (8-9 years) with diffusion measures from males and females tending to converge between 10 and 14 years of age. Males showed a steeper slope for age-diffusion metric correlations compared to females, who either did not correlate with age or correlated in fewer regions. Further studies are now warranted to determine the role of hormones on the observed differences, particularly in 8-9-year-old children.

Optic radiation structure and anatomy in the normally developing brain determined using diffusion MRI and tractography.

The optic radiation (OR) is a component of the visual system known to be myelin mature very early in life. Diffusion tensor imaging (DTI) and its unique ability to reconstruct the OR in vivo were used to study structural maturation through analysis of DTI metrics in a cohort of 90 children aged 5-18 years. As the OR is at risk of damage during epilepsy surgery, we measured its position relative to characteristic anatomical landmarks. Anatomical distances, DTI metrics and volume of the OR were investigated for age, gender and hemisphere effects. We observed changes in DTI metrics with age comparable to known trajectories in other white matter tracts. Left lateralization of DTI metrics was observed that showed a gender effect in lateralization. Sexual dimorphism of DTI metrics in the right hemisphere was also found. With respect to OR dimensions, volume was shown to be right lateralised and sexual dimorphism demonstrated for the extent of the left OR. The anatomical results presented for the OR have potentially important applications for neurosurgical planning.

Relationships between acute imaging biomarkers and theory of mind impairment in post-acute pediatric traumatic brain injury: A prospective analysis using susceptibility weighted imaging (SWI).

Theory of Mind (ToM) forms an integral component of socially skilled behavior, and is critical for attaining developmentally appropriate goals. The protracted development of ToM is mediated by increasing connectivity between regions of the anatomically distributed 'mentalizing network', and may be vulnerable to disruption from pediatric traumatic brain injury (TBI). The present study aimed to evaluate the post-acute effects of TBI on first-order ToM, and examine relations between ToM and both local and global indices of macrostructural damage detected using susceptibility-weighted imaging (SWI). 104 children and adolescents with TBI and 43 age-matched typically developing (TD) controls underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks post-injury and were assessed on cognitive ToM tasks at 6-months after injury. Compared to TD controls and children with mild-moderate injuries, children with severe TBI showed significantly poorer ToM. Moreover, impairments in ToM were related to diffuse neuropathology, and parietal lobe lesions. Our findings support the vulnerability of the immature social brain network to disruption from TBI, and suggest that global macrostructural damage commonly associated with traumatic axonal injury (TAI) may contribute to structural disconnection of anatomically distributed regions that underlie ToM. This study suggests that SWI may be a valuable imaging biomarker to predict outcome and recovery of social cognition after pediatric TBI.

Attentional control ten years post-childhood traumatic brain injury: the impact of lesion presence, location, and severity in adolescence and early adulthood.

The relationship between brain injury and attentional control (AC) long after a childhood traumatic brain injury (TBI) has received limited investigation. The aim of this article was to investigate the impact that lesion presence, location, and severity has on AC in a group of young persons who had sustained a moderate to severe TBI 10 years earlier during childhood. The participants in this study were a subset of a larger 10-year, follow-up assessment comprised of 31 persons in late adolescence and early adulthood (21 males), with a mean age at testing of 15.4 years (standard error 0.6; range 10.7-21.2 years). Analyses revealed that in regard to AC abilities, the presence of a lesion(s) appears to have a differential effect depending on the testing measure used. When using standardized testing with subtests of the TEA-ch, no differences in performance between those with and those without a lesion at 10 years post-TBI were found. On standardized behavioral measures such as parental reports of perceived AC (Behavior Rating Inventory of Executive Function), however, the presence of a lesion was found to have a detrimental effect on the ability to self-regulate and monitor behavior in late adolescence and the early stages of adulthood. We discuss these results and propose that there is a network of brain regions associated with AC, and generalized lesions have the greatest influence on such abilities.

The effect of hippocampal damage in children on recalling the past and imagining new experiences.

Compared to adults, relatively little is known about autobiographical memory and the ability to imagine fictitious and future scenarios in school-aged children, despite the importance of these functions for development and subsequent independent living. Even less is understood about the effect of early hippocampal damage on children's memory and imagination abilities. To bridge this gap, we devised a novel naturalistic autobiographical memory task that enabled us to formally assess the memory for recent autobiographical experiences in healthy school-aged children. Contemporaneous with the autobiographical memories being formed, the children also imagined and described fictitious scenarios. Having established the performance of healthy school-aged children on these tasks, we proceeded to make comparisons with children (n=21) who had experienced neonatal hypoxia/ischaemia, and consequent bilateral hippocampal damage. Our results showed that healthy children could recall autobiographical events, including spatiotemporal information and specific episodic details. By contrast, children who had experienced neonatal hypoxia/ischaemia had impaired recall, with the specific details of episodes being lost. Despite this significant memory deficit they were able to construct fictitious scenarios. This is in clear contrast to adults with hippocampal damage, who typically have impaired autobiographical memory and deficits in the construction of fictitious and future scenarios. We speculate that the paediatric patients' relatively intact semantic memory and/or some functionality in their residual hippocampi may underpin their scene construction ability.