Janine M. Cooper

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

Highlights ► Children with bilateral hippocampal damage are impaired at recalling past events. ► They are intact at imagining fictitious experiences. ► This contrasts with adult amnesic patients who are impaired at both. ► Hippocampal damage affects memory differently depending on when in life it occurs.

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 Alzheimers 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 Alzheimers 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.

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.

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 cohorts 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.

Provoked confabulations in Alzheimer's disease

Confabulation in Alzheimers 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.

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. Hum Brain Mapp 36:1677–1691, 2015.

The Young Everest Study: preliminary report of changes in sleep and cerebral blood flow velocity during slow ascent to altitude in unacclimatised children

Background Cerebral blood flow velocity (CBFV) and sleep physiology in healthy children exposed to hypoxia and hypocarbia are under-researched. Aim To investigate associations between sleep variables, daytime end-tidal carbon dioxide (EtCO2) and CBFV in children during high-altitude ascent. Methods Vital signs, overnight cardiorespiratory sleep studies and transcranial Doppler were undertaken in nine children (aged 6–13 years) at low altitude (130 m), and then at moderate (1300 m) and high (3500 m) altitude during a 5-day ascent. Results Daytime (130 m: 98%; 3500 m: 90%, p=0.004) and mean (130 m: 97%, 1300 m: 94%, 3500: 87%, p=0.0005) and minimum (130 m: 92%, 1300 m: 84%, 3500 m: 79%, p=0.0005) overnight pulse oximetry oxyhaemoglobin saturation decreased, and the number of central apnoeas increased at altitude (130 m: 0.2/h, 1300 m: 1.2/h, 3500 m: 3.5/h, p=0.2), correlating inversely with EtCO2 (R2 130 m: 0.78; 3500 m: 0.45). Periodic breathing occurred for median (IQR) 0.0 (0; 0.3)% (130 m) and 0.2 (0; 1.2)% (3500 m) of total sleep time. At 3500 m compared with 130 m, there were increases in middle (MCA) (mean (SD) left 29.2 (42.3)%, p=0.053; right 9.9 (12)%, p=0.037) and anterior cerebral (ACA) (left 65.2 (69)%, p=0.024; right 109 (179)%; p=0.025) but not posterior or basilar CBFV. The right MCA CBFV increase at 3500 m was predicted by baseline CBFV and change in daytime SpO2 and EtCO2 at 3500 m (R2 0.92); these associations were not seen on the left. Conclusions This preliminary report suggests that sleep physiology is disturbed in children even with slow ascent to altitude. The regional variations in CBFV and their association with hypoxia and hypocapnia require further investigation.

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

Abstract 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.

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.

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

Highlights • Patients with early onset hippocampal damage were impaired on a working memory task.• Impairment was evident only on those trials when memory load was intermediate.• Hippocampal volume correlated with behaviour when memory load was intermediate/high.• Patients showed no proactive interference.• Patients showed no effect of age at injury on performance.