Anne Uecker

Spatial locations gone awry: Object and spatial memory deficits in children with fetal alcohol syndrome

Hippocampus vulnerability following gestational alcohol exposure has been demonstrated neuroanatomically and behaviorally in animal models of fetal alcohol syndrome (FAS). There has been no similar demonstrations in humans. The Smith and Milner (1981) Memory for 16 Objects task has been used to explore the effects of right vs left temporal lobectomy with varying degrees of damage to the hippocampus. In the present experiment, this same task was administered to 15 children with FAS (mean age 10.03, S.D. = 2.33) and 15 control children (mean age 10.02, S.D. = 2.31). Similar to patients with right temporal lobectomies and a large excision to the hippocampus, children with FAS were able to perform immediate but not delayed object recall, had a general spatial memory deficit (P < 0.05), and significantly distorted the spatial array (P < 0.05). Although these results are consistent with an interpretation of hippocampal dysfunction, gestational alcohol exposure is known to result in a wide-ranging spectrum of neuropsychological deficits that vary in both extent and severity. Visuospatial deficits on the Beery test of Visuomotor Integration and Clock Drawing are suggestive of the other neural regions that may be involved in producing the behavioral deficits in children with FAS.

Preclinical memory decline in cognitively normal apolipoprotein E–ε4 homozygotes

Objective: To determine, in a cross-sectional evaluation of nondemented individuals, if age-related memory decline is influenced by apolipoprotein E (apoE) genotype. Background: The apoE-4 allele is an important risk factor for AD. PET in cognitively normal apoE-4 carriers (mean age, 56 years) shows reduced cerebral metabolism suggestive of very early AD that precedes clinically evident memory loss or MRI-based hippocampal atrophy. Methods: Tests of immediate and delayed recall (primary outcome measures) and other neuropsychological measures (secondary outcome measures) were given to three genetically defined groups of cognitively normal individuals (age, 49 to 69 years) including apoE-4 homozygotes (n = 25), apoE-4 heterozygotes (n = 25, all ε3/4), and apoE-4 noncarriers (n = 50). Groups were matched for age, gender, and educational background. Cross-sectional comparisons between the genetic subgroups of the relationship between age and test score were performed for each neuropsychological measure. Results: There were no intergroup differences in mean scores on any neuropsychological measure, but tests sensitive to immediate and delayed recall showed a significant negative correlation with age in the apoE-4 homozygote group relative to the noncarrier group. Conclusion: Consistent with previous neuropsychological studies of early AD, this cross-sectional study suggests that age-related memory decline occurs earlier in cognitively healthy apoE-4 homozygotes than in apoE-4 heterozygotes and noncarriers, and precedes clinically detectable AD.

Spatial but not object memory impairments in children with fetal alcohol syndrome.

Behavioral dissociations on tests of cognitive abilities are powerful tools that can help define the neuropsychology of developmentally disabling conditions. Animals gestationally exposed to alcohol demonstrate spatial (place) but not object (cue) memory impairments. Whether children with fetal alcohol syndrome demonstrate a similar dissociation has received little attention. In this experiment, 30 Native American children, 15 previously identified with fetal alcohol syndrome and 15 control children, were asked to recall places and objects in a task previously shown to be sensitive to memory skills in individuals with and without mental retardation. As in animal models, children with fetal alcohol syndrome demonstrated a spatial but not an object memory impairment. A possible role for the hippocampus was discussed.

Tracking Alzheimer's disease in transgenic mice using fluorodeoxyglucose autoradiography

While transgenic mice have great promise in the study of Alzheimers disease (AD), uncertainties remain about the extent to which they provide a model of the disorder or the best way to characterize disease progression. Using fluorodeoxyglucose (FDG) autoradiography, we found that transgenic mice over-expressing a mutant form of the human amyloid precursor protein have preferentially and progressively reduced activity in the posterior cingulate cortex and relatively spared activity in visual cortex, sensorimotor cortex, cerebellum and brain stem, a pattern previously demonstrated in FDG PET studies of persons with Alzheimers disease. Brain imaging of posterior cingulate activity could provide an indicator of AD in suitable animals, helping to clarify disease mechanisms and screen candidate treatments.

Effects of size and orientation change on hippocampal activation during episodic recognition: A PET study

TO determine whether physical match between studied and tested items influences blood flow increases in the hippocampal formation associated with recognition memory, positron emission tomography (PET) was used to measure changes in regional cerebral blood flow while healthy volunteers made old/new judgements about line drawings of objects. Some objects were tested in the same size and orientation as they had appeared earlier during the study phase of the experiment; other objects were tested in a different size or orientation than when they were studied. Blood flow increases in the vicinity of the hippocampal formation were observed in the same object condition compared with the size change and the orientation change conditions, even though recognition accuracy was affected significantly only by orientation change. Results add to previous findings suggesting that physical similarity between studied items and test cues may contribute to hippocampal activation during episodic retrieval.

Behavior and brain uptake of fluorodeoxyglucose in mature and aged C57BL/6 mice<

This paper describes regional brain energy metabolism, sensorimotor, and memory functions in mature (12 months) and old (24 months) C57BL/6 mice. Male mice were tested across a variety of sensorimotor procedures and in the Morris water maze before evaluating brain uptake of fluorodeoxyglucose (FDG) in the resting state. Mature mice outperformed older mice during the difficult sensorimotor and memory tasks, but not the easier tasks. This suggested that the greater sensorimotor and memory demands of a task compromised the performance of the older mice. This conclusion was consistent with the relative FDG uptake decreases found in regions mediating sensorimotor coordination (vestibular, cerebellar, ventral thalamic regions) and some limbic regions linked to memory (mammillary body, posterior cingulate, and piriform cortices). The inferior colliculus and flocculus had the greatest metabolism in mature mice, as shown by resting FDG uptake, and these regions showed the most marked hypometabolism in the older mice. The data also showed that the neurobehavioral correlative pattern in older mice was modified. In conclusion, brain regions with higher energy metabolism, and the behaviors to which they are related, were affected most greatly by aging in C57BL/6 mice-suggesting that these areas are more metabolically vulnerable to aging effects.

Mental rotation performance by learning disabled and down's syndrome children: A study of imaginal development

A mental rotation task was administered to 56 control (n = 22), learning‐disabled (LD; n = 24), and Downs syndrome (DS; n = 10) children. Each subject was asked to make a decision regarding the side on which a stick figure stimulus held a ball. Regression analyses were used to compare reaction time and accuracy scores among the groups. As predicted, reaction time scores from fastest to slowest were displayed by groups in the following order: control < LD < DS. Although control and LD subjects were more accurate in mental rotation perfonnance than DS subjects, the control subjects were only marginally better than the LD subjects (p < .06). Mental rotation presentations were further broken down into upright and rotated categories. The control group had quicker reaction times than the LD group in both of these categories. In accuracy analyses, the control group and the LD group performed similarly at the upright angles. However, at rotated angles there was a trend for the control group to be more accurate t...

Image manipulation and error estimation for MRI analysis

Manipulation of MRI images prior to volumetric analysis is a common practice that may unwittingly lead to errors in measurement. In this study, we examine the effects of two types of image manipulation: changes in the total number of slices used to obtain volume estimates (slice sampling rate) and image rotation. A phantom containing two regularly-shaped and two irregularly-shaped regions of interest (ROIs) was scanned using an SPGR sequence and 1-mm slices. Changes in slice sampling rate produced marked effects on volume estimation of irregularly-shaped ROls. Comparatively little error was associated with changes in slice sampling rates for regularly-shaped ROIs. In addition, there was an interaction between image rotation in non-orthogonal planes and slice sampling rate. The data suggests that the ability to detect anatomical effects may be influenced by an investigators choices concerning the number of slices included in a region of interest and image rotation when estimating volumes.

Neuropsychological Theories Associated with Learning Disorders

Although the term “learning disabilities” has been in existence for little over 25 years (Duane, 1991; Morrison & Siegel, 1991), the condition itself has aroused considerable interest for well over a century. Originally identified as congenital word blindness, learning disabilities and developmental dyslexia have long been suspected to be a result of a neural substrate located in the posterior left cerebral hemisphere (Satz, 1991). Observations such as anomalous hand preference, male predominance, and underachievement in subjects such as spelling have been consistently made since the turn of the century (Duane, 1991). A particularly persisting line of research has concerned the topic of language lateralization. Recent technological advances allow new approaches to an old problem.