Biomedical subjects

K Boone

Publications and source records attributed to K Boone.

At least 19 recordsLinked to original sources

PubMed2002

Utility of clinical criteria in differentiating frontotemporal lobar degeneration (FTLD) from AD.

OBJECTIVE: To assess the ability of the current diagnostic criteria for frontotemporal lobar degeneration (FTLD) to differentiate FTLD from AD. METHODS: Thirty cases with autopsy-proven FTLD and 30 cases of AD, matched for Mini-Mental State Examination score, were identified from the clinical databases of three dementia subspecialty centers, and their charts were reviewed for the presence of clinical features described in the current criteria for FTLD. The proportion of patients with each clinical feature at the first clinical presentation was compared across groups. RESULTS: A significantly larger proportion of patients with FTLD showed behavioral abnormalities, particularly social and personal conduct disorders and emotional blunting, than patients with AD. Few differences in language features were seen between the groups, and many of the language features detailed in the criteria were found in only a small proportion of patients. In both groups, many patients showed neuropsychological abnormalities, except for perceptual difficulties, which were present in many patients with AD but only in a few patients with FTLD. Extrapyramidal motor symptoms were more likely to be present in FTLD. Logistic regression revealed that five features-social conduct disorders, hyperorality, akinesia, absence of amnesia, and the absence of a perceptual disorder-correctly classified 93% of patients with FTLD and 97% of patients with AD. CONCLUSION: A combination of behavioral, neuropsychological, and physical findings is most useful in distinguishing FTLD from AD. Future studies should be directed at establishing more objective methods of identifying these clinical features.

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PubMed2001

Neuroanatomy of the self: evidence from patients with frontotemporal dementia.

OBJECTIVE: To evaluate the frequency and types of change in "self" seen in frontotemporal dementia (FTD) and to determine the relative involvement of the nondominant and dominant frontal and temporal brain regions in FTD patients with or without changes in a sense of self using neuropsychology tests and neuroimaging. BACKGROUND: The self has been defined as "the total, essential, or particular being of a person" involving "the essential qualities distinguishing one person from another." Some suggest that the frontal lobes play a dominant role in maintaining the self. FTD affects anterior frontal and temporal areas and can be associated with a loss of self. METHODS: Seventy-two consecutive FTD patients were evaluated with neuropsychiatric, neuropsychologic, and behavioral measures. Patients were imaged with MRI and SPECT. Charts were reviewed by a social psychologist to determine patients who exhibited a dramatic change in their self as defined by changes in political, social, or religious values. The brain areas with the most severe atrophy or hypoperfusion on neuroimaging were noted. RESULTS: Seven of 72 patients exhibited a dramatic change in self. In six of the seven, the selective dysfunction involved the nondominant frontal region. In contrast, only one of the other 65 patients without selective nondominant frontal dysfunction showed a change in self. CONCLUSIONS: FTD patients with asymmetric loss of function in the nondominant frontal lobe often exhibit a diminished maintenance of previously learned self-concepts despite intact memory and language. Normal nondominant frontal function is important for the maintenance of the self.

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PubMed2000

Functional correlates of musical and visual ability in frontotemporal dementia.

BACKGROUND: The emergence of new skills in the setting of dementia suggests that loss of function in one brain area can release new functions elsewhere. AIMS: To characterise 12 patients with frontotemporal dementia (FTD) who acquired, or sustained, new musical or visual abilities despite progression of their dementia. METHOD: Twelve patients with FTD who acquired or maintained musical or artistic ability were compared with 46 patients with FTD in whom new or sustained ability was absent. RESULTS: The group with musical or visual ability performed better on visual, but worse on verbal tasks than did the other patients with FTD. Nine had asymmetrical left anterior dysfunction. Nine showed the temporal lobe variant of FTD. CONCLUSION: Loss of function in the left anterior temporal lobe may lead to facilitation of artistic or musical skills. Patients with the left-sided temporal lobe variant of FTD offer an unexpected window into the neurological mediation of visual and musical talents.

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PubMed2000

Molecular, biochemical and functional analysis of a novel and developmentally important fibrillar collagen (Hcol-I) in hydra.

The body wall of hydra (a member of the phylum Cnidaria) is structurally reduced to an epithelial bilayer with an intervening extracellular matrix (ECM). Previous studies have established that cell-ECM interactions are important for morphogenesis and cell differentiation in this simple metazoan. The ECM of hydra is particularly interesting because it represents a primordial form of matrix. Despite progress in our understanding of hydra ECM, we still know little about the nature of hydra collagens. In the current study we provide a molecular, biochemical and functional analysis of a hydra fibrillar collagen that has similarity to vertebrate type I and type II collagens. This fibrillar collagen has been named hydra collagen-I (Hcol-I) because of its structure and because it is the first ECM collagen to be identified in hydra. It represents a novel member of the collagen family. Similar to vertebrate type I and II collagens, Hcol-I contains an N-terminal propeptide-like domain, a triple helical domain containing typical Gly-X-Y repeats and a C-terminal propeptide domain. The overall identity to vertebrate fibrillar collagens is about 30%, while the identity of the C-terminal propeptide domain is 50%. Because the N-terminal propeptide domain is retained after post-translational processing, Hcol-I does not form thick fibers as seen in vertebrates. This was confirmed using transmission electron microscopy to study rotary shadow images of purified Hcol-I. In addition, absence of crucial lysine residues and an overall reduction in proline content, results in reduced crosslinking of fibrils and increased flexibility of the molecule, respectively. These structural changes in Hcol-I help to explain the flexible properties of hydra ECM. Immunocytochemical studies indicate that Hcol-I forms the 10 nm fibrils that comprise the majority of molecules in the central fibrous zone of hydra ECM. The central fibrous zone resides between the two subepithelial zones where hydra laminin is localized. While previous studies have shown that basal lamina components like laminin are expressed by the endoderm, in situ hybridisation studies show that Hcol-I mRNA expression is restricted to the ectoderm. Hcol-I expression is upregulated during head regeneration, and antisense studies using thio-oligonucleotides demonstrated that blocking the translation of Hcol-I leads to a reversible inhibition of head morphogenesis during this regenerative process. Taken in total, the data presented in this study indicate that Hcol-I is required for morphogensis in hydra and represents a novel fibrillar collagen whose structural characteristics help to explain the unique biophysical properties of hydra ECM. Interestingly, the structure of Hcol-I mimics what is seen in Ehlers-Danlos syndrome type VII in humans; an inherited pathological condition that leads to joint and skin abnormalities. Hcol-I therefore illustrates an adaptive trait in which the normal physiological situation in hydra translates into a pathological condition in humans.

Amino Acid Sequence↗

PubMed1998

Klinefelter's syndrome as a model of anomalous cerebral laterality: testing gene dosage in the X chromosome pseudoautosomal region using a DNA microarray.

Consistent handedness and language laterality are two of the most striking behavioral and cognitive asymmetries observed in humans. Alterations in the typical pattern of cerebral laterality, termed "anomalous dominance," is observed in left-handers and some patients with verbal learning disabilities. We undertook the study of a genetically distinct group of subjects, XXY males (Klinefelter's syndrome; KS), who demonstrate anomalous dominance in a variety of testing paradigms in order to begin to elucidate the molecular basis of anomalous dominance in this population. KS subjects manifest specific verbal learning disability, evidence of altered functional laterality for phonologic processing, and an increase in left-handedness when measured by skill. It is proposed that an alteration in gene dosage in the pseudoautosomal region (PAR) of the sex chromosomes is the most likely explanation for anomalous dominance in these patients. This is especially intriguing in light of previously described genetic models of cerebral laterality that suggest a contributing locus in the PAR, or adjacent high homology regions of the X chromosome. We have developed an ordered DNA microarray covering the X chromosome PAR at high resolution for hybridization with two-color fluorescently labeled probes. We demonstrate the ability to detect changes in hybridization signal that will facilitate efficient large-scale screening of this region for alterations in gene dosage associated with features of anomalous dominance and other cognitive or behavioral phenotypes.

Case-Control Studies↗

PubMed1998

Emergence of artistic talent in frontotemporal dementia.

OBJECTIVE: To describe the clinical, neuropsychological, and imaging features of five patients with frontotemporal dementia (FTD) who acquired new artistic skills in the setting of dementia. BACKGROUND: Creativity in the setting of dementia has recently been reported. We describe five patients who became visual artists in the setting of FTD. METHODS: Sixty-nine FTD patients were interviewed regarding visual abilities. Five became artists in the early stages of FTD. Their history, artistic process, neuropsychology, and anatomy are described. RESULTS: On SPECT or pathology, four of the five patients had the temporal variant of FTD in which anterior temporal lobes are involved but the dorsolateral frontal cortex is spared. Visual skills were spared but language and social skills were devastated. CONCLUSIONS: Loss of function in the anterior temporal lobes may lead to the "facilitation" of artistic skills. Patients with the temporal lobe variant of FTD offer a window into creativity.

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PubMed1998

Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria.

OBJECTIVE: To improve clinical recognition and provide research diagnostic criteria for three clinical syndromes associated with frontotemporal lobar degeneration. METHODS: Consensus criteria for the three prototypic syndromes-frontotemporal dementia, progressive nonfluent aphasia, and semantic dementia-were developed by members of an international workshop on frontotemporal lobar degeneration. These criteria build on earlier published clinical diagnostic guidelines for frontotemporal dementia produced by some of the workshop members. RESULTS: The consensus criteria specify core and supportive features for each of the three prototypic clinical syndromes and provide broad inclusion and exclusion criteria for the generic entity of frontotemporal lobar degeneration. The criteria are presented in lists, and operational definitions for features are provided in the text. CONCLUSIONS: The criteria ought to provide the foundation for research work into the neuropsychology, neuropathology, genetics, molecular biology, and epidemiology of these important clinical disorders that account for a substantial proportion of cases of primary degenerative dementia occurring before the age of 65 years.

Dementia↗

PubMed1997

The temporal variant of frontotemporal dementia.

Frontotemporal dementia is a dementia syndrome with diverse clinical characteristics. Based upon clinical parameters and single photon emission computed tomography, we identified 47 frontotemporal dementia subjects. In 10 of these 47 the primary site of brain dysfunction was anterior temporal and orbital-frontal with other frontal regions relatively spared. In this temporal lobe variant (TLV) of frontotemporal dementia, five of the subjects had more severe left-sided, and five had more right-sided, hypoperfusion. The clinical, neuropsychological and neuropsychiatric features of predominantly left-sided (LTLV) and right-sided (RTLV) TLV subjects are discussed and contrasted with more frontal presentations of frontotemporal dementia. In LTLV, aphasia was usually the first and most severe clinical abnormality RTLV patients presented with behavioural disorders characterized by irritability, impulsiveness, bizarre alterations in dress, limited and fixed ideas, decreased facial expression and increased visual alertness. These findings suggest that: (i) frontotemporal dementia is clinically heterogeneous with bitemporal and inferior frontal lobe dysfunction contributing to the clinical presentation; (ii) behavioural disturbance and aphasia are the most prominent features of predominantly temporal subtypes of frontotemporal dementia; (iii) the right and left anterior temporal regions may mediate different behavioural functions. The results of this study suggests that TLV offers a valuable source of information concerning the behavioural disorders seen with combined anterior temporal and inferior frontal lobe dysfunction.

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PubMed1997

A study of the Lund-Manchester research criteria for frontotemporal dementia: clinical and single-photon emission CT correlations.

We evaluated the Lund-Manchester research criteria (LMRC) for frontotemporal dementia (FTD). With single-photon emission CT, we diagnosed 30 patients with FTD. These patients were compared with 30 with a research diagnosis of Alzheimer's disease (AD). We scored every patient on each LMRC item and compared the two groups. A discriminant function showed that loss of personal awareness, hyperorality, stereotyped and perseverative behavior, progressive reduction of speech, and preserved spatial orientation differentiated 100% of FTD and AD subjects. Items relating to affect and physical findings were not different in FTD versus AD. Loss of personal awareness, eating, perseverative behavior, and reduction of speech are the LMRC items that most clearly differentiate FTD from AD.

Alzheimer Disease↗

PubMed1995

Experimental validation of a novel reconstruction algorithm for electrical impedance tomography based on backprojection of Lagrange multipliers.

A novel approach to image reconstruction for electrical impedance tomography (EIT) has been developed. It is based on a constrained optimization technique for the reconstruction of difference resistivity images without finite-element modelling. It solves the inverse problem by optimizing a cost function under constraints, in the form of normalized boundary potentials. Its application to the neighboring data collection method is presented here. Mathematical models are developed according to specified criteria. These express the reconstructed image in terms of one-dimensional Lagrange multiplier functions. The reconstruction problem becomes one of estimating these functions from normalized boundary potentials. This model is based on a cost criterion of the minimization of the variance between the reconstructed and the true resistivity distributions. The algorithm was tested on data collected in a cylindrical saline-filled tank. A polyacrylamide rod was placed in various positions with or without a peripheral plaster of Paris ring in place. This was intended to resemble the conditions during EIT of epileptic seizures recorded with scalp or cortical electrodes in the human head. One advantage of this approach is that compensation for non-uniform initial conditions may be made, as this is a significant problem in imaging cerebral activity through the skull.

Algorithms↗

PubMed1994

Imaging of cortical spreading depression by EIT: implications for localization of epileptic foci.

Severe epileptics may require curative neurosurgery. Sometimes focus localization requires recording with electrodes inserted deep into the brain, which may cause death or permanent neurological damage. Since epileptic seizures are associated with marked changes in cerebral impedance, we propose that EIT with sub-dural electrodes (inserted between the brain and skull) could provide a superior and less dangerous method for the localization of epileptic foci. The purpose of these experiments was to determine whether EIT could be used to localize the origin of seizure activity. In terms of impedance characteristics, an appropriate model is cortical spreading depression in the animal brain. Six rabbits were anaesthetized and paralysed and the brain exposed. EIT images and DC potentials were recorded from an array of 16 electrodes on the brain during cortical spreading depression induced by DC stimulus. Cortical spreading depression could be localized by EIT with an accuracy of 8.7% +/- 6.4% (mean +/- SD) of electrode array diameter. The errors in localization appeared to be distributed randomly. In a phantom of similar geometry, the error was 5% after correction for a systematic component. Results are sufficiently encouraging that we intend to extend this study to human patients.

Animals↗

PubMed1994

Agenesis of corpus callosum and dementia of the Alzheimer's type: a review and case report.

This paper describes a previously sufficiently functioning 57 year old man who presented with a recent onset of frontal behaviour. Partial agenesis of corpus callosum was an incidental finding on a computerized tomography scan. The EEG was within normal limits and neuropsychological testing did not reveal any interhemispheric disconnection. A SPECT-Scan revealed bilateral hypoperfusion, consistent with Alzheimer's dementia. Normal functioning up to 50 years of age and a later manifestation of Alzheimer's disease along with agenesis of carpus callosum is of clinical interest as such an association has not been published.

Agenesis of Corpus Callosum↗

PubMed1993

Cerebral abnormalities in myotonic dystrophy. Cerebral blood flow, magnetic resonance imaging, and neuropsychological tests.

OBJECTIVE: To study cerebral abnormalities in myotonic dystrophy (MD) and determine the different patterns of cerebral function in patients with MD with maternal (mMD) vs paternal (pMD) inheritance. DESIGN: Patients with MD and normal controls were studied with neuropsychological testing, magnetic resonance imaging, and single photon emission computed tomography. SETTING: Studies were done at Harbor-UCLA Medical Center, Torrance, Calif. PATIENTS AND OTHER PARTICIPANTS: Twenty-two consecutive-patients with MD, 11 of whom had pMD and eight mMD, and 10 normal controls were studied. Diagnoses were made on the basis of family history, electromyography, and clinical examinations. Normal subjects in the same age distribution were studied for comparisons. RESULTS: We found significantly lower neuropsychological performance and cerebral blood flow in the patients with MD compared with the controls. Patients with mMD had statistically lower scores on IQ tests and more extensive cerebral hypoperfusion when compared with those with pMD. Changes in cerebral blood flow were most severe in the frontal and temporoparietal association cortex. Cerebral blood blow measures strongly correlated with IQ. CONCLUSIONS: Patients with mMD had earlier onset of disease and lower IQs than the pMD group. The pattern of cerebral perfusion in the mMD group was consistent with a diffuse brain injury, while cerebral perfusion in pMD showed more minor changes. These findings emphasize the cognitive differences between mMD and pMD.

Adolescent↗

PubMed1993

Neuropsychological deficits in abstinent cocaine abusers: preliminary findings after two weeks of abstinence.

Sixteen subjects hospitalized for treatment of cocaine dependence were administered a battery of neuropsychological tests within 72 h of last cocaine use and again approximately 2 weeks later. Twenty-one non-cocaine using control subjects, matched for age, gender, ethnicity and education, also received neuropsychological testing. Abstinence from mood altering substances during the 2-week study period was verified for both groups on three occasions using quantitative urine analysis. The results suggest that recent cocaine use is associated with impairment in memory, visuospatial abilities, and concentration during the acute phase of withdrawal, independent of withdrawal-related depression. Furthermore, many of these deficits appear to persist at least 2 weeks beyond cessation of cocaine use.

Adult↗

PubMed1992

Cardiac stimulator for the study of refractory period control using current pulses of programmable duration and shape.

A programmable current stimulator has been developed that allows unipolar current pulses of complex shape, long duration and high current to be generated. The stimulator conforms to the safety requirements for devices connected directly to the heart. It incorporates additional safety features to prevent unintended current being delivered, even under fault conditions. The stimulator has been used to investigate the effects of long duration current pulses on the refractory period of cardiac tissue. The flexibility of the device suggests that it may well have uses in other fields of electrophysiology.

Electric Stimulation↗

PubMed1991

Major depressives' and dysthmics' performance on the Wisconsin Card Sorting Test.

Despite awareness that depression may affect performance on commonly used neuropsychological tests, little research has been conducted on the relative impact of severity and type of depression on higher problem-solving ability. Major depressives (n = 13), dysthymics (n = 17), and non-psychiatric comparison subjects (n = 18) were administered the Wisconsin Card Sorting Test (WCST). Although diagnostic category was related only marginally to some WCST measures after controlling for intellectual function, depressive symptom severity emerged as an independent predictor of Total Errors, Perseverative Responses, and Failure to Maintain Set. These findings lend support to the suggestion that neuropsychological test batteries should include assessment for depression and suggest that even relatively mild depression may affect WCST scores.

Attention↗

PubMed1991

Right-hemisphere language dominance in temporal lobe epilepsy: clinical and neuropsychological correlates.

Prior to and following temporal lobe surgery, patients with right-hemisphere language dominance and focal left temporal lobe epilepsy (RHLD-LTLSz) were compared to right-handed patients with left-hemisphere language dominance and either left temporal lobe epilepsy (LHLD-LTLSz) or right temporal lobe epilepsy (LHLD-RTLSz). The group of RHLD-LTLSz patients had a more consistent history of brain involvement before the age of 5 years and had a higher seizure frequency rating than did either LHLD patient group. Cognitively, RHLD-LTLSz patients did not show significant deficits in psychometric intellectural scores. In addition, they did not demonstrate comparable degrees of verbal memory loss as found either pre- or postoperatively in LHLD-LTLSz patients. The right-handed RHLD-LTLSz and the right-handed LHLD-LTLSz groups both appeared to exhibit bilaterally depressed fine-motor coordination. The left-handed RHLD-LTLSz patients did not show the same motor deficiencies. These latter findings suggest that hemispheric dominance for bilateral motor control may exist independent of language dominance, but not independent of handedness.

Adolescent↗

PubMed1991

Frontal lobe degeneration: clinical, neuropsychological, and SPECT characteristics.

The clinical, neuropsychological, and cerebral blood flow characteristics of eight patients with frontal lobe degeneration (FLD) were studied. Social withdrawal and behavioral disinhibition were the earliest and most common clinical presentations, and psychiatric symptoms typically preceded the onset of dementia by several years. Neuropsychological testing showed selective impairment of frontal and memory tasks with relative sparing of attention, language, and visuospatial skills. Single-photon emission computerized tomography demonstrated frontal and temporal hypoperfusion with relative sparing of parietal and occipital blood flow. Previous studies suggest that the neuropathologic findings in patients with FLD are varied; some demonstrate frontal gliosis, neuronal loss, and Pick bodies while others show only gliosis and neuronal loss.

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