Biomedical subjects

Ira Driscoll

Publications and source records attributed to Ira Driscoll.

13 recordsLinked to original sources

PubMed2006

Impact of Alzheimer's pathology on cognitive trajectories in nondemented elderly.

OBJECTIVE: Some individuals who are asymptomatic for dementia while alive have substantial Alzheimer's disease (AD) neuropathology at autopsy. We investigated whether cognitive trajectories differ between clinically normal elderly individuals with and without AD neuropathology and how they compare with trajectories of clinically impaired individuals before dementia diagnosis. METHODS: Eighty-one elderly participants in the Baltimore Longitudinal Study of Aging (BLSA) were followed prospectively with neurological and neuropsychological assessments before autopsy evaluation at death. Trajectories of cognitive change were estimated for a number of domains using cognitive data before a clinical diagnosis of dementia. RESULTS: Clinically normal elderly individuals with and without AD-type neuropathology have similar cognitive trajectories across different cognitive domains. In contrast, individuals with mild cognitive impairment/AD show steeper rates of longitudinal decline in several aspects of cognition compared with clinically normal elderly individuals regardless of whether the latter have AD neuropathology. Moreover, the cognitive differences between impaired and unimpaired groups can be detected years before a diagnosis of dementia. INTERPRETATION: Clinically normal individuals with and without AD neuropathology do not differ in rates of cognitive decline across a number of cognitive domains. Understanding the factors that protect some individuals with AD pathology from cognitive impairment may contribute to the maintenance of cognitive health in the elderly.

Aged↗

PubMed2006

FGF-2-induced cell proliferation stimulates anatomical, neurophysiological and functional recovery from neonatal motor cortex injury.

Infant rats treated with basic fibroblast growth factor-2 (FGF-2) after postnatal day (P)10 motor cortical injury, show functional improvement in adulthood relative to those that do not receive FGF-2. In this study we used a combination of behavioural, immunohistochemical, electrophysiological, electron microscopic and teratological approaches to investigate possible mechanisms by which FGF-2 may influence functional recovery. We show that subcutaneous injections of FGF-2 following bilateral lesions to the motor cortex at P10 in the rat leads to filling of the lesion area with migrating neuroblasts and cycling cells. We assessed the functionality of this tissue in adulthood, and show that cells from the filled region spontaneously fire and form synapses. Behavioural analysis shows enhanced motor performance in the FGF-2-treated lesion rats in comparison to vehicle-treated lesion rats, and this improvement is reversed by removal of the tissue from the previously lesioned area or by blocking cortical regeneration by embryonic treatment with bromodeoxyuridine (BrdU). The results show that FGF-2 stimulates filling of the lesion cavity with cells after neonatal motor cortex lesions, that the new tissue has anatomical and physiological properties similar to control tissue, and that the filled region supports motor behaviour.

Animals↗

PubMed2005

Seahorse wins all races: hippocampus participates in both linear and non-linear visual discrimination learning.

Consistent with configural/conjunctive theories of the hippocampus, we report that rats trained on the non-linear transverse patterning discrimination problem (A+ versus B-, B+ versus C-, and C+ versus A) displayed retrograde amnesia when the hippocampus was later damaged. They also failed to relearn the solution to this problem. Damage to the hippocampus following training also produced retrograde amnesia in rats trained on a set of elemental discrimination problems (A+ versus B-, C+ versus D-, and E+ versus F-) that could be solved based on the associative strengths of the individual choice cues. However, in contrast to transverse patterning, rats easily relearned and retained these elemental problems and learned a new set of elemental problems after the damage. These results support two theoretical conclusions: (a) elemental discriminations can be learned by both a system that depends on the hippocampus and a system that does not require the hippocampus, and (b) in the intact animal these two systems competitively interact with the hippocampal-dependent system inhibiting memory formation by the extra-hippocampal system.

Animals↗

PubMed2005

Differential contributions of hippocampus, amygdala and perirhinal cortex to recognition of novel objects, contextual stimuli and stimulus relationships.

This study examined contributions of the hippocampus, amygdala and perirhinal cortex to memory. Rats performed a cover task, and changes to stimulus identity or relationships were used to test incidental memory. Rats with hippocampal damage showed deficient responses to relationship changes, but demonstrated knowledge of the position and identity of the target object. They over-focused on the most predictive stimuli, and failed to acquire associations including surrounding cues. Rats with amygdala damage responded to changes involving distal stimuli, and showed deficient responses to novel objects and object relationships. These rats may be highly reliant on relational representations, resulting in a reduced salience for individual novel stimuli. Rats with perirhinal damaged responded to novel stimulus relationships and distal cues, but showed deficient responses to novel objects, suggesting that changes in identity had reduced salience. Implications for declarative and conjunctive hippocampal theories are discussed.

Amygdala↗

PubMed2005

A quantitative comparison of synaptic density following perfusion versus immersion fixation in the rat cerebral cortex.

The main objective of the present study was to perform an unbiased comparison of immersion vs. perfusion techniques to assess whether we could use the former to quantify synapses through electron microscopy (EM). Using the immersion technique is ideally suited for instances in which the specimen under study could not be perfused under the standard EM protocol. Our results suggest that, despite suboptimal qualitative results, fixation by immersion allows for adequate quantification of synapses.

Animals↗

PubMed2005

Virtual navigation in humans: the impact of age, sex, and hormones on place learning.

Certain cognitive processes, including spatial ability, decline with normal aging. Spatial ability is also a cognitive domain with robust sex differences typically favoring males. However, tests of spatial ability do not seem to measure a homogeneous class of processes. For many, mentally matching rotated three-dimensional images is the gold standard for measuring spatial cognition in humans, while the Morris water task (MWT) is a preferred method in the domain of nonhuman animal research. The MWT is sensitive to hippocampal damage, a structure critical for normal learning and memory and often implicated in age-related cognitive decline. A computerized (virtual) version of the MWT (VMWT) appears to require and engage human hippocampal circuitry, and has proven useful in studying sex differences and testing spatial learning theories. In Experiment 1, we tested participants (20-90 years of age) in the VMWT and compared their performance to that on the Vandenberg Mental Rotation Test. We report an age-related deficit in performance on both tasks. In Experiment 2, we tested young (age 20-39) and elderly (age >60) participants in the VMWT and correlated their performance to the circulating levels of testosterone and cortisol. Our findings indicate that the persistence of male spatial advantage may be related to circulating testosterone, but not cortisol levels, and independent of generalized age-related cognitive decline.

Adult↗

PubMed2005

Apolipoprotein E and prospective memory in normally aging adults.

The epsilon4 allele of apolipoprotein E (APOE) is an established risk factor for Alzheimer's disease, despite uncertainty as to its effect on cognitive function in normal aging. Some evidence suggests poor episodic memory and executive functioning in epsilon4 allele carriers. Prospective memory has been overlooked in investigations of the relationship between APOE and cognition. The authors used a laboratory paradigm to examine the relationship between prospective memory and APOE status in healthy elderly adults, and they varied the association (high vs. low) between a target word and a response word. The authors found a significant deficit in prospective memory for epsilon4 allele carriers but no effect of association in either group. The results suggest the deficit was due to failure of the prospective component of the task.

Aged↗

PubMed2005

The aging hippocampus: navigating between rat and human experiments.

Aging is associated with impairments in certain aspects of cognition, especially learning and memory. The hippocampus is a structure intimately involved with certain aspects of learning and memory, and is especially vulnerable to the course of aging. Recent findings, primarily from cognitive, magnetic resonance imaging, and magnetic resonance spectroscopy studies, but also briefly physiology and neurogenesis work, are reviewed. Evidence suggests that age-related impairment of hippocampus-dependent cognition is associated with changes on various levels of investigation in both humans and non-human animals. Also, the emphasis is placed on tasks and techniques that can be used to test both non-human and human animals in an attempt to bridge the gulf between the vast bodies of knowledge about the hippocampus in different species. To the extent that changes with normal aging are understood, they may aid in diagnosis, prevention, and/or treatment of age-related learning and memory deficits in both normal and pathological aging. In addition, studies of the aging hippocampus may have a side-effect in leading to a better understanding of the mechanisms that underlie learning and memory in general.

Aging↗

PubMed2004

Reduced area of the corpus callosum in posttraumatic stress disorder.

Magnetic resonance imaging (MRI) studies have revealed decreases in the mid-sagittal area of the corpus callosum (CC) in pediatric posttraumatic stress disorder (PTSD), but at present no data are available in adult PTSD patients. We have previously reported decreased whole-brain white matter (WM) volume in adults with PTSD and now report corpus callosum area from the same sample. MRI was used to obtain whole-brain images in 12 adult patients with PTSD and 10 matched controls. Total parenchyma (white matter plus gray matter [GM]) volume, mid-sagittal area of the CC and seven sub-regions of this structure were calculated. In PTSD patients, the total CC area, absolute and normalized to total brain parenchyma, was smaller compared with control values. Several absolute and normalized CC sub-regions were also smaller in PTSD patients: genu (region 2), mid-body (region 5) and isthmus (region 6). There was also a trend for the anterior mid-body (area 4) to be smaller in PTSD patients. No differences were found in the rostrum (region 1), rostral body (region 3) or splenium (region 7). Adult patients with PTSD had decreased CC area after correcting for total brain tissue, indicating that these differences are not attributable to generalized white matter atrophy. These findings are similar to previous results in children with PTSD and suggest specific changes in the CC.

Adult↗

PubMed2004

Damage to the hippocampal formation does not disrupt representational flexibility as measured by a novelty transfer test.

Rats were trained on a set of visual discrimination problems (A+B-, C+D-, E+F-). The choice stimuli were then recombined to create novel combination tests (A+D-, C+F-, E+B-). Rats with damage to the hippocampus showed perfect transfer on these tests, always choosing A, C, and E, but were not able to learn the spatial location of the platform, indicating that damage to the hippocampus was functional. These results question the generality of H. Eichenbaum, P. Mathews, and N. J. Cohen's (1989) findings and the theoretical claim that choice behavior with novel combinations is based on inferential-like hippocampus-dependent processes (H. Eichenbaum, 1992). They are consistent with the view that simple associative processes guide choice behavior in animals with hippocampal damage that are confronted with novel combinations.

Animals↗

PubMed2003

The aging hippocampus: cognitive, biochemical and structural findings.

Aging is often accompanied by learning and memory problems, many of which resemble deficits associated with hippocampal damage. Studies of aging in nonhuman animals have demonstrated hippocampus-related memory decline, and point to a possible locus for impairments associated with normal and pathological aging in humans. Two well-characterized hippocampus-dependent tasks in nonhuman animal literature are the Morris water task (MWT) and the transverse patterning discrimination task (TPDT). We employed the virtual MWT and the TPDT to assess hippocampus-dependent cognition in humans. Magnetic resonance imaging and proton magnetic resonance spectroscopy were employed to measure hippocampal volume and neurochemistry respectively. Age-related deficits were observed in performance on both hippocampus-dependent tasks. This pattern of impairment was accompanied by decreased hippocampal NAA/Cre ratios and volume, both of which imply neuronal loss and/or decrease in neuronal density. Collectively, our results suggest that hippocampus undergoes structural and biochemical changes with normal aging and that these changes may represent an important component of age-related deterioration in hippocampus-dependent cognition.

Adult↗

PubMed2002

Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder.

BACKGROUND: Reduced hippocampal volumes in posttraumatic stress disorder (PTSD) patients are thought to reflect specific changes of this structure. Previous magnetic resonance imaging (MRI) studies have not consistently examined indices of overall brain atrophy, therefore it cannot be completely ruled out that hippocampal changes are explained by whole-brain atrophy. The purpose of this study was to assess hippocampal and whole-brain volume in civilian PTSD. METHODS: Twelve subjects with PTSD and 10 control subjects underwent brain MRI. Hippocampal volumes were visually quantified using a computerized volumetric program. Whole-brain volumes were obtained with automated k-means-based segmentation. RESULTS: No differences were found in intracranial volumes (ICV). Subjects with PTSD had higher cerebrospinal fluid (CSF)/ICV ratios and lower white matter/ICV ratios, consistent with generalized white matter (WM) atrophy. The effect of age on CSF/ICV was more pronounced in the PTSD group. Subjects with PTSD had smaller absolute and normalized bilateral hippocampal volumes. These differences persisted after adjusting for lifetime weeks of alcohol intoxication. Posttraumatic stress disorder and depression scores correlated negatively with left hippocampal volume, but PTSD scores were a better predictor of hippocampal volumes. CONCLUSIONS: Our results replicate previous findings of reduced hippocampal volume in PTSD but also suggest independent, generalized, white matter atrophy.

Adult↗

PubMed2002

Human place learning in a virtual Morris water task: some important constraints on the flexibility of place navigation.

We investigated human place learning in a computerized version of the Morris water task (VMWT) under comparable conditions to those employed by Sutherland et al. (Sutherland et al. Psychobiology, 1987;15:48-57) with rats. Participants viewed a computer-generated environment and were trained to locate a hidden goal in one half of a circular pool (region 1). The opportunity to navigate in and view cues from region 2 was systematically varied during training. Participants were then started from region 2 to assess transfer. Accurate transfer performance was dependent upon prior experience viewing distal cues from region 2 while on a trajectory to the goal, a finding we interpret as inconsistent with the automatic formation and modification of a cognitive map (O'Keefe J, Nadel L. The Hippocampus as a cognitive map. Oxford, UK: Clarendon Press, 1978). Additionally, the transfer data reported here closely match the data obtained by Sutherland et al. with rats suggesting some generality in the principles involved in place learning.

Acoustic Stimulation↗