Biomedical subjects

K M Thomas

Publications and source records attributed to K M Thomas.

At least 19 recordsLinked to original sources

PubMed2002

The effect of preceding context on inhibition: an event-related fMRI study.

In this study we combined event-related fMRI with a parametric manipulation of the go nogo paradigm to examine the effect of preceding context on inhibitory processes. Nogo trials were preceded by either 1, 3, or 5 go trials and then compared to one another. Two distinct patterns of activation were associated with behavioral inhibition: First, the ventral prefrontal cortex, cingulate gyrus, and superior parietal regions showed a context effect with an increase in MR signal to nogo trials with increasing number of preceding go trials. Second, anterior regions in the supplementary and premotor cortex showed an increase in MR signal on the nogo condition after 5 preceding go trials, but not after only 1 or 3. A model using the BOLD response in our data was used to verify that the effect of context was not an artifact of the randomization scheme used in the design.

Adult↗

PubMed2001

Adsorption dynamics of gases and vapors on the nanoporous metal organic framework material Ni2(4,4'-bipyridine)3(NO3)4: guest modification of host sorption behavior.

This study combines measurements of the thermodynamics and kinetics of guest sorption with powder X-ray diffraction measurements of the nanoporous metal organic framework adsorbent (host) at different adsorptive (guest) loadings. The adsorption characteristics of nitrogen, argon, carbon dioxide, nitrous oxide and ethanol and methanol vapors on Ni2(4,4'-bipyridine)3(NO3)4 were studied over a range of temperatures as a function of pressure. Isotherm steps were observed for both carbon dioxide and nitrous oxide adsorption at approximately 10-20% of the total pore volume and at approximately 70% of total pore volume for methanol adsorption. The adsorption kinetics obey a linear driving force (LDF) mass transfer model for adsorption at low surface coverage. At high surface coverage, both methanol and ethanol adsorption follow a combined barrier resistance/diffusion model. The rates of adsorption in the region of both the carbon dioxide and methanol isotherm steps were significantly slower than those observed either before or after the step. X-ray diffraction studies at various methanol loadings showed that the host structure disordered initially but underwent a structural change in the region of the isotherm step. These isotherm steps are ascribed to discrete structural changes in the host adsorbent that are induced by adsorption on different sites. Isotherm steps were not observed for ethanol adsorption, which followed a Langmuir isotherm. Previous X-ray crystallography studies have shown that all the sites are equivalent for ethanol adsorption on Ni2(4,4'-bipyridine)3(NO3)4, with the host structure undergoing a scissoring motion and the space group remaining unchanged during adsorption. The activation energies and preexponential factors for methanol and ethanol adsorption were calculated for each pressure increment at which the linear driving force model was obeyed. There was a good correlation between activation energy and ln(preexponential factor), indicating a compensation effect. The results are discussed in terms of reversible adsorbate/adsorbent (guest/host) structural changes and interactions and the adsorption mechanism. The paper contains the first evidence of specific interactions between guests and functional groups leading to structural change in flexible porous coordination polymer frameworks.

Journal Article↗

PubMed2001

Amygdala response to facial expressions in children and adults.

BACKGROUND: The amygdala plays a central role in the human response to affective or emotionally charged stimuli, particularly fear-producing stimuli. We examined the specificity of the amygdala response to facial expressions in adults and children. METHODS: Six adults and 12 children were scanned in a 1.5-T scanner during passive viewing of fearful and neutral faces using an EPI BOLD sequence. All scans were registered to a reference brain, and analyses of variance were conducted on the pooled data to examine interactions with age and gender. RESULTS: Overall, we observed predominantly left amygdala and substantia innominata activity during the presentation of nonmasked fearful faces relative to fixation, and a decrease in activation in these regions with repeated exposure to the faces. Adults showed increased left amygdala activity for fearful faces relative to neutral faces. This pattern was not observed in the children who showed greater amygdala activity with neutral faces than with fearful faces. For the children, there was an interaction of gender and condition whereby boys but not girls showed less activity with repeated exposure to the fearful faces. CONCLUSIONS: This is the first study to examine developmental differences in the amygdala response to facial expressions using functional magnetic resonance imaging.

Adult↗

PubMed2001

Amygdala response to fearful faces in anxious and depressed children.

BACKGROUND: Alterations in amygdala function have been implicated in the pathophysiological characteristics of adult anxiety and depressive disorders. Studies with healthy adults and children, as well as with adults who have amygdala lesions, have found facial expressions of emotion to be useful probes of amygdala activity. Our study examined the amygdala response to fearful and neutral facial expressions in healthy, anxious, and depressed children. We hypothesized that children with anxiety and depression may show atypical amygdala responses to emotional stimuli. METHODS: Twelve children (8-16 years of age) with generalized anxiety or panic disorder and 12 healthy comparison children underwent noninvasive functional magnetic resonance imaging while viewing photographs of fearful and neutral facial expressions. In a second comparison, 5 girls with major depressive disorder were compared with 5 anxious and 5 healthy girls from the previous sample. RESULTS: Children with anxiety disorders showed an exaggerated amygdala response to fearful faces compared with healthy children, whereas depressed children showed a blunted amygdala response to these faces. In addition, the magnitude of the amygdala's signal change between fearful and neutral faces was positively correlated with the severity of everyday anxiety symptoms. CONCLUSIONS: Our results suggest that amygdala function is affected in both anxiety and depression during childhood and adolescence. Moreover, this disruption appears to be specific to the child's own rating of everyday anxiety.

Adolescent↗

PubMed2001

Sensitivity of prefrontal cortex to changes in target probability: a functional MRI study.

Electrophysiological studies suggest sensitivity of the prefrontal cortex to changes in the probability of an event. The purpose of this study was to determine if subregions of the prefrontal cortex respond differentially to changes in target probabilities using functional magnetic resonance imaging (fMRI). Ten right-handed adults were scanned using a gradient-echo, echo planar imaging sequence during performance of an oddball paradigm. Subjects were instructed to respond to any letter but "X". The frequency of targets (i.e., any letter but X) varied across trials. The results showed that dorsal prefrontal regions were active during infrequent events and ventral prefrontal regions were active during frequent events. Further, we observed an inverse relation between the dorsal and ventral prefrontal regions such that when activity in dorsal prefrontal regions increased, activity in ventral prefrontal regions decreased, and vice versa. This finding may index competing cognitive processes or capacity limitations. Most importantly, these findings taken as a whole suggest that any simple theory of prefrontal cortex function must take into account the sensitivity of this region to changes in target probability.

Adolescent↗

PubMed2001

Serial reaction time learning in preschool- and school-age children.

Visuomotor sequence learning was assessed in 4- to 10-year-old children using a serial reaction time (SRT) task with both random and sequenced trials. One-half of the children received exposure to the sequence prior to performing the reaction time (RT) task. In Experiment 1, 7- and 10-year-old children demonstrated sequence-specific decreases in RT. As in the adult SRT literature, participants with explicit awareness of the sequence at the end of the session showed larger sequence-specific reaction time decrements than those without explicit awareness. Contrary to expectation, preexposure to the sequence did not reliably predict the level of awareness attained. Results from Experiment 2 indicate that 4-year-olds also demonstrate significant sequence learning on a variant of the SRT task. This article provides preliminary data regarding developmental changes in sequential learning and the development and use of implicit and explicit knowledge. Age-related differences emerged primarily in explicit rather than implicit knowledge.

Age Factors↗

PubMed2001

Is all sexual harassment viewed the same? Mock juror decisions in same- and cross-gender cases.

Given recent court decisions, there is a need to investigate less common forms of sexual harassment, including women harassing men and same-gender harassment. The present study was a 2 (harasser gender) x 2 (target gender) x 2 (participant gender) factorial design in which 408 mock jurors made decisions in a hostile work environment case. Women harassing men were more likely to be found guilty than were men harassing women, and harassers in same-gender cases were more likely to be found guilty and were perceived more negatively than harassers in cross-gender cases. Participant gender differences were found in cross-gender, but not same-gender, conditions. Results suggest that the gender composition of the harasser and target may be an extralegal factor influencing managerial and juror decision making.

Adult↗

PubMed2000

Dissociation of response conflict, attentional selection, and expectancy with functional magnetic resonance imaging.

Two different attentional networks have been associated with visuospatial attention and conflict resolution. In most situations either one of the two networks is active or both are increased in activity together. By using functional magnetic resonance imaging and a flanker task, we show conditions in which one network (anterior attention system) is increased in activity whereas the other (visuospatial attention system) is reduced, showing that attentional conflict and selection are separate aspects of attention. Further, we distinguish between neural systems involved in different forms of conflict. Specifically, we dissociate patterns of activity in the basal ganglia and insula cortex during simple violations in expectancies (i.e., sudden changes in the frequency of an event) from patterns of activity in the anterior attention system specifically correlated with response conflict as evidenced by longer response latencies and more errors. These data provide a systems-level approach in understanding integrated attentional networks.

Adult↗

PubMed2000

A pilot study of amygdala volumes in pediatric generalized anxiety disorder.

BACKGROUND: The neurodevelopment of childhood anxiety disorders is not well understood. Basic research has implicated the amygdala and circuits related to these nuclei as being central to several aspects of fear and fear-related behaviors in animals. METHODS: Magnetic resonance imaging was used to measure amygdala volumes and comparison brain regions in 12 child and adolescent subjects with generalized anxiety disorder and 24 comparison subjects. Groups were matched on age, sex, height, and handedness and were also similar on measures of weight, socioeconomic status, and full scale IQ. RESULTS: Right and total amygdala volumes were significantly larger in generalized anxiety disorder subjects. Intracranial, cerebral, cerebral gray and white matter, temporal lobe, hippocampal, and basal ganglia volumes and measures of the midsagittal area of the corpus callosum did not differ between groups. CONCLUSIONS: Although these data are preliminary and from a small sample, the results are consistent with a line of thinking that alterations in the structure and function of the amygdala may be associated with pediatric generalized anxiety disorder.

Adolescent↗

PubMed2000

Structural and functional brain development and its relation to cognitive development.

Despite significant gains in the fields of pediatric neuroimaging and developmental neurobiology, surprisingly little is known about the developing human brain or the neural bases of cognitive development. This paper addresses MRI studies of structural and functional changes in the developing human brain and their relation to changes in cognitive processes over the first few decades of human life. Based on post-mortem and pediatric neuroimaging studies published to date, the prefrontal cortex appears to be one of the last brain regions to mature. Given the prolonged physiological development and organization of the prefrontal cortex during childhood, tasks believed to involve this region are ideal for investigating the neural bases of cognitive development. A number of normative pediatric fMRI studies examining prefrontal cortical activity in children during memory and attention tasks are reported. These studies, while largely limited to the domain of prefrontal functioning and its development, lend support for continued development of attention and memory both behaviorally and physiologically throughout childhood and adolescence. Specifically, the magnitude of activity observed in these studies was greater and more diffuse in children relative to adults. These findings are consistent with the view that increasing cognitive capacity during childhood may coincide with a gradual loss rather than formation of new synapses and presumably a strengthening of remaining synaptic connections. It is clear that innovative methods like fMRI together with MRI-based morphometry and nonhuman primate studies will transform our current understanding of human brain development and its relation to behavioral development.

Adolescent↗

PubMed2000

Functional neuroanatomy of spatial working memory in children.

Functional magnetic resonance imaging (fMRI) was used to examine spatial working memory in 8- to 11-year-old children tested under three conditions. In the visual condition, children were asked to examine the location of a dot on a screen. In the motor condition, children were instructed to push a button that corresponded to the location of a dot presented on a screen. In the memory condition, children were asked to remember the location of a dot presented 1 or 2 trials previously. Subtracting the activation of the motor condition from the memory condition revealed activity in the dorsal aspects of the prefrontal cortex and in the posterior parietal and anterior cingulate cortex. These findings were also obtained in the analysis of the memory minus visual conditions except that motor cortex activation was also observed. These findings parallel those reported in comparable studies of adults and suggest that fMRI may be a useful means of examining function-structure relations in developmental populations.

Adult↗

PubMed2000

Neurophysiologic evaluation of auditory recognition memory in healthy newborn infants and infants of diabetic mothers.

OBJECTIVES: We evaluated the integrity of neural pathways for auditory recognition memory in normal newborn infants (n = 32) and infants of diabetic mothers (IDMs, n = 25). IDMs are at risk for fetal metabolic abnormalities that potentially damage recognition memory pathways. We hypothesized that newborn IDMs would have recognition memory deficits that would be correlated with later cognitive development. STUDY DESIGN: Recognition memory was assessed with event-related potentials (ERPs). Neonatal ERPs elicited by the maternal voice were compared with those elicited by a stranger's voice. The Bayley Scales of Infant Development were administered at 1 year of age. RESULTS: Infants in both the control and IDM groups demonstrated recognition of the maternal voice, but their ERP patterns differed. Both groups demonstrated increased amplitude and latency for the "P2" peak elicited by the maternal voice compared with the stranger's voice. In the control group the stranger's voice also elicited a negative slow wave, which was attenuated in the IDMs. The negative slow wave correlated significantly with the 1-year Mental Developmental Index. CONCLUSIONS: The presence of a specific neonatal ERP pattern indicated better 1-year cognitive development in infants in the control and IDM groups. ERPs from IDMs demonstrated subtle evidence of recognition memory impairments.

Analysis of Variance↗

PubMed2000

Neurocognitive sequelae of infants of diabetic mothers.

On the basis of animal models, it was hypothesized that infants of diabetic mothers (IDMs) would be at risk for suffering damage to the hippocampus primarily because of fetal iron deficiency, chronic hypoxia, and hypoglycemia. This, in turn, may result in impairments in recognition memory at a young age. To test this model, the memory of 6-month-old IDMs and control infants was evaluated with electrophysiological (event-related potential [ERP]) and behavioral (looking time) measures. At 12 months, the Bayley Scales of Infant Development was administered. Our ERP measures showed robust evidence consistent with memory deficits in the IDMs. In contrast, the looking time measures and the Bayley exam failed to distinguish between the groups. From these results it was concluded that the ERP, but not the behavioral, measures are able to detect, in an at-risk population, deficits in recognition memory that are thought to be mediated by damage to the hippocampus.

Cognition Disorders↗

PubMed1999

Upregulation of lysyl oxidase in vascular smooth muscle cells by cAMP: role for adenosine receptor activation.

Lysyl oxidase (LO) is a key participant in the accumulation of insoluble fibers of elastin and collagen by virtue of its role in the initiation of the covalent cross-linkages between and within individual molecules comprising these fibers. In view of the essential role played by LO in the accumulation of the fibrotic components of occlusive arterial lesions in atherosclerosis, identification of the signaling molecules which can affect the expression of the LO gene in vascular smooth muscle is of considerable interest. In the present report, we describe evidence for the role of the second messenger, cAMP, in the modulation of the levels of LO in vascular smooth muscle cells. Elevated intracellular cAMP induces the transcription of the LO gene, as revealed by Northern blot analysis and nuclear run on assays. Transient transfection experiments performed with the wild-type LO promoter and with this promoter mutated at a consensus CREB site, located within the region -100 to -93 base pairs relative to the start of transcription, indicate that cAMP-induced transcriptional activation is partially due to the presence of this CREB site within the promoter. Activation of stimulatory adenosine receptors in vascular smooth muscle cells with 5'-N-ethylcarboxamido adenosine (NECA) increases cAMP, LO mRNA, and enzyme activity. These findings point to the importance of cAMP signaling, potentially initiated by a variety of physiological agents, in the upregulation of LO expression in vascular smooth muscle cells.

Adenosine-5'-(N-ethylcarboxamide)↗

PubMed1999

A developmental functional MRI study of spatial working memory.

Functional magnetic resonance imaging (fMRI) was used to examine patterns of cortical activity in children during performance of a spatial working memory task. Six children (8-10 years) and six adults (19-26 years) searched a linear array of four boxes for the appearance of a dot. In the visual blocks, participants made no response. In the motor blocks, participants were instructed to indicate the location of the dot on each trial using a button-press response. In the working memory blocks, participants were instructed to indicate at which location the dot had appeared 1 or 2 trials previously. Both children and adults showed activity in the left precentral and postcentral gyri, as well as the right cerebellum for the motor condition as compared to the visual condition. Comparison of the memory and motor conditions revealed reliable activity in the right superior frontal gyrus (BA 8), right dorsolateral prefrontal cortex (BA 10/46), right superior parietal cortex, and bilateral inferior parietal cortex for both adults and children. These results suggest that spatial working memory tasks activate very similar cortical regions for school-age children and adults. The findings differ from previous imaging studies of nonspatial working memory tasks in that the prefrontal activations observed in the current work tend to be more dorsal. Results are discussed in light of the significant behavioral performance differences observed between child and adult participants.

Adult↗

PubMed1998

Degradation and repair of elastic fibers in rat lung interstitial fibroblast cultures.

BACKGROUND: Evidence from in vitro and in vivo studies indicates that damaged elastic fibers can be repaired. METHODS: Lipid interstitial pulmonary fibroblasts were cultured for 6 weeks. Cultures were then exposed to 25 microg of porcine pancreatic elastase and fixed in pairs (control, elastase-treated) immediately after exposure and at 1, 2, 3, 4, 7, 10, 14, and 22 days for ultrastructural examination. Elastin was also analyzed biochemically for resistance to hot alkali, an indicator of repair. Steady-state levels of tropoelastin and lysyl oxidase mRNA at 2, 4, and 7 days after elastase treatment were determined by Northern blot analysis. RESULTS: Immediately after exposure to elastase, damaged elastic fibers exhibited a frayed, porous appearance and a granular texture. Through day 4, fibers showed no evidence of repair. By day 7, the granular texture of damaged fibers was no longer evident and a gradual filling-in of porous areas appeared to be taking place. By 22 days, elastic fibers were indistinguishable from elastic fibers in control cultures. The ultrastructural changes were paralleled by changes in hot alkali resistance. Through day 4, there was no change in the level of hot alkali resistant elastin. Between day 4 and day 7, resistance to hot alkali increased sharply and continued to increase at a slower rate, reaching 84% of the control level by day 22. Steady-state levels of tropoelastin and lysyl oxidase mRNA showed no increase over control levels at 2, 4, and 7 days after elastase treatment. CONCLUSIONS: Elastic fibers synthesized by lipid interstitial pulmonary fibroblasts in culture were repaired after damage by elastase. This type of repair may have relevance to the prevention of pathological conditions, such as emphysema.

Animals↗

PubMed1998

Delayed recognition memory in infants and adults as revealed by event-related potentials.

The present study sought to compare adult and infant ERP responses in analogous tests of visual recognition memory. Adults were tested under two test conditions, in which they were given either explicit instructions to respond to a previously-seen stimulus, or no instructions. Testing in both conditions took place after either a 1- or 5-min delay between familiarization and test. Eight-month-old infants were tested under the same 'passive' (no instruction) conditions as adults. ERP morphology differed across age groups. Adults evinced a P300 that was larger under 'active' as compared to 'passive' test conditions, and a late positive slow wave response that was greater to novel than familiar stimuli. There was no evidence in infants of a P300, although infants did demonstrate a late positive slow wave that was greater to familiar than to novel stimuli. Parallels between the infant and adult findings are discussed and in particular, whether the infant slow wave response is the precursor to the adult P300.

Adolescent↗

PubMed1997

Localization and activity of lysyl oxidase within nuclei of fibrogenic cells.

Lysyl oxidase (EC 1.4.3.13) oxidizes peptidyl lysine to peptidyl aldehyde residues within collagen and elastin, thus initiating formation of the covalent cross-linkages that insolubilize these extracellular proteins. Recent findings raise the possibility that this enzyme may also function intracellularly. The present study provides evidence by immunocytochemical confocal microscopy, Western blot analysis, enzyme assays, and chemical analyses for lysyl oxidase reaction products that this enzyme is present and active within rat vascular smooth muscle cell nuclei. Confocal microscopy indicates its presence within nuclei of 3T3 fibroblasts, as well.

Amino Acid Sequence↗