Biomedical subjects

Mary A Woo

Publications and source records attributed to Mary A Woo.

17 recordsLinked to original sources

PubMed2006

Elevated mean diffusivity in widespread brain regions in congenital central hypoventilation syndrome.

PURPOSE: To investigate whether mean diffusivity (MD) values are altered in brain areas underlying cardiovascular and respiratory control in congenital central hypoventilation syndrome (CCHS). MATERIALS AND METHODS: Conventional and diffusion tensor imaging were performed in 15 CCHS and 30 control subjects, using a 3.0-Tesla MRI unit. Mean diffusivity maps were calculated from diffusion-weighted images, spatially normalized, smoothed, and compared between groups using analysis of covariance at each voxel with age as covariate. Global mean MD values of gray and white matter were determined in individual subjects and compared between groups and with age. RESULTS: Increased MD values appeared in CCHS over control subjects within multiple areas influencing breathing and cardiovascular control, including the midbrain, pons, and dorsal and ventral medulla. Other altered sites included cerebellar cortex and deep nuclei, basal ganglia, basal forebrain, and temporal and frontal cortices. Global mean MD values for gray and white matter did not differ between groups; however, gray matter MD values significantly increased with age (P < 0.02) in CCHS patients only. CONCLUSION: Increased MD values suggest regional alterations or injury; affected areas include brainstem sites classically associated with autonomic and respiratory control. Other altered regions mediate additional physiological characteristics impaired in CCHS.

Adolescent↗

PubMed2005

Regional brain response patterns to Cheyne-Stokes breathing.

Cheyne-Stokes breathing (CSB) results from impaired integration of sensory information with respiratory motor output; however, regions mediating the disturbed control are unknown. We examined functional magnetic resonance imaging signals during CSB within sleep to determine affected areas. Two male patients with severe obstructive sleep apnea were scanned while asleep over multiple sessions during which they exhibited CSB. Significant signal increases coincident with apneic periods emerged bilaterally in the cerebellar cortex, hippocampus, mediodorsal thalamus, frontal cortex and precentral gyrus. Signals declined bilaterally in the anterior cingulate cortex and postcentral gyrus. The reduced activation in primary sensory cortex and increased signals prior to breathing onset in the motor cortex are consistent with loss of sensory stimulation by airflow, and with anticipatory action of the motor cortex prior to initiation of breathing. Hippocampal and anterior cingulate cortex participation likely reflect previously-demonstrated roles for initiating inspiratory efforts and resolving sensory information and motor action, respectively.

Adult↗

PubMed2005

Neuroanatomic deficits in congenital central hypoventilation syndrome.

Congenital Central Hypoventilation Syndrome (CCHS) patients exhibit compromised autonomic regulation, reduced breathing drive during sleep, diminished ventilatory responses to chemoreceptor stimulation, and diminished air hunger perception. The syndrome provides an opportunity to partition neural processes regulating breathing and cardiovascular action. No obvious lesions appear with conventional magnetic resonance imaging; however, T2 relaxometry procedures can detect reduced cell or fiber density or diminished myelination not found with routine evaluation. High-resolution T1, proton density, and T2-weighted brain images were collected from 12 patients and 28 age- and gender-matched controls. Voxel-by-voxel T2 maps were generated from the proton density and T2-weighted images and evaluated by voxel-based-relaxometry procedures. Normalized and smoothed T2 maps were compared between groups using analysis of covariance at each voxel, with age and ventricle size included as covariates. Patients showed damaged or maldeveloped tissue, principally right-sided, including white matter from the level of the anterior cingulate cortex caudally to the level of the posterior cingulate and laterally to the posterior superior temporal cortex. Portions of the posterior, mid, and anterior cingulate, as well as the internal capsule, putamen, and globus pallidus and basal forebrain extending to the anterior and medial thalamus were affected. Deficits in the cingulum bundle and mid-hippocampus and ventral prefrontal cortex appeared, as well as the right cerebellar cortex and deep nuclei. Neuroanatomic deficiencies in limbic structures suggest a structural basis for reduced air hunger perception, thermoregulatory and autonomic deficiencies in the syndrome, while cerebellar deficits may also contribute to breathing and cardiovascular dysregulation.

Adolescent↗

PubMed2005

Inspiratory loading elicits aberrant fMRI signal changes in obstructive sleep apnea.

We hypothesized that neural processes mediating deficient sensory and autonomic regulatory mechanisms in obstructive sleep apnea (OSA) would be revealed by responses to inspiratory loading in brain regions regulating sensory and motor control. Functional magnetic resonance imaging (fMRI) signals and physiologic changes were assessed during baseline and inspiratory loading in 7 OSA patients and 11 controls, all male and medication-free. Heart rate increases to inspiratory loading began earlier and load pressures were achieved later in OSA patients. Comparable fMRI changes emerged in multiple brain regions in both groups, including limbic, cerebellar, midbrain, and primary motor cortex. However, in OSA subjects, altered signals appeared in primary sensory thalamus and sensory cortex, supplementary motor cortex, cerebellar cortex and deep nuclei, cingulate, medial temporal, and insular cortices, right hippocampus, and midbrain. Signal delays occurred in basal ganglia. We conclude that areas mediating sensory and autonomic processes, and motor timing, are affected in OSA; many of these areas overlap regions of previously demonstrated gray matter loss.

Adult↗

PubMed2005

Aberrant neural responses to cold pressor challenges in congenital central hypoventilation syndrome.

Patients with congenital central hypoventilation syndrome (CCHS), a condition characterized by impaired ventilatory responses to chemoreceptor stimulation, do not show the normal increase in respiratory rate and respiratory-related heart rate variation to cold forehead stimulation, a challenge that bypasses central chemoreceptors. We hypothesized that a forehead cold pressor challenge would reveal abnormal neural response patterns, as assessed by functional magnetic resonance imaging, in brain regions that are responsible for the integration of cold afferent stimulation with respiratory and cardiovascular output in patients with CCHS. Primary sensory thalamic and cortical areas for the forehead showed diminished responses in 13 patients with CCHS (ventilator dependent during sleep but not waking, no Hirschsprung's disease) compared with 14 control subjects, despite initial signal changes in the cortex being similar in both groups. Cerebellar cortex and deep nuclei; basal ganglia; and middle to posterior cingulate, insular, frontal, and temporal cortices showed reduced signal rises in patients with CCHS. Areas within the frontal and anterior cingulate cortices exhibited marked signal declines in control subjects but little change in patients with CCHS. No response occurred in either group in the dorsal medulla, but medial and ventral medullary areas showed enhanced signals in patients with CCHS. The cold pressor stimulation did not recruit dorsal medullary sites that would be affected by PHOX2B (a mutation of which is associated with the syndrome) expression in either group but demonstrated deficient cerebellar and medial medullary influences that, by action on rostral sites, may underlie the loss of respiratory responses.

Adolescent↗

PubMed2005

FMRI responses to hyperoxia in congenital central hypoventilation syndrome.

Congenital Central Hypoventilation Syndrome (CCHS) patients show partial retention of peripheral chemoreception despite impaired ventilatory responses to CO2 and hypoxia. The condition allows examination of central responses to hyperoxia, which minimizes afferent traffic from peripheral chemoreceptors. We used functional magnetic resonance imaging to assess blood oxygen level-dependent signals over the brain during a baseline and subsequent 2-min hyperoxia (100% O2) period in 14 CCHS and 15 control subjects. After partitioning gray matter and correcting for global effects, the images were analyzed using volume-of-interest time trends followed by repeated-measures ANOVA and conventional cluster analyses. Respiratory rates initially (first 20 s) fell in CCHS, but rose in control subjects; CCHS heart rate increased in the first minute, and then decreased in the second minute, as in controls, but with muted rise and extent of decline. Multiple sites within the cerebellum, midbrain, and pons responded similarly to the challenge in both groups. Response patterns differed early in the right amygdala, paralleling initial respiratory pattern deficits, and late in the right insula, concomitant with cardiac rate differences. Signals also differed between groups in the medial and anterior cingulate, hippocampus, head of caudate, and lentiform nuclei, as well as pontine and midbrain structures and regions within the superior temporal and inferior frontal cortical gyri. The findings emphasize that structures that can alter respiratory timing, such as the amygdala, and modulate sympathetic outflow, such as the right insula, are deficient in CCHS. Medullary and pontine areas targeted by PHOX2B expression are also affected.

Adolescent↗

PubMed2005

Functional abnormalities in brain areas that mediate autonomic nervous system control in advanced heart failure.

BACKGROUND: Heart failure patients show substantial gray matter loss in brain areas that mediate autonomic control. Those injuries may lead to the aberrant autonomic patterns found in the syndrome. The purpose of this study was to determine if functional responses in the brain to an autonomic challenge would differ from normal patterns and would appear in areas of previously-demonstrated gray matter loss. METHODS AND RESULTS: We subjected 6 heart failure patients (left ventricular ejection fraction 0.15 +/- 0.08; age 49 +/- 12 years) and 16 controls (age 48 +/- 11 years) to a forehead cold pressor challenge that would enhance sympathetic outflow and assessed functional magnetic resonance image signals over the entire brain during a 54-second baseline and 90-second challenge. Application of the cold stimulus elicited aberrant responses in the anterior and posterior hypothalamus, bilateral amygdala, hippocampus, cerebellar cortex, insular cortex, mid/posterior cingulate cortex, right ventral frontal cortex, and temporal and frontal cortices. Many of the areas neighbored or overlaid regions of previously demonstrated gray matter damage. Both classical autonomic control regions, as well as brain areas modulating these sites showed deficient responses, some of which appeared to be of an overdampened or underdampened nature. CONCLUSION: The findings suggest that the earlier demonstrated changes in brain structure in heart failure result in aberrant functional neural responses; these dysfunctions may contribute to progression of the pathology in heart failure.

Adult↗

PubMed2004

Temporal trends of cardiac and respiratory responses to ventilatory challenges in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) patients exhibit respiratory deficits to ventilatory challenges, diminished breathing drive during sleep, and reduction of respiratory-related heart rate variation, but at least partially preserved peripheral chemoreception. We hypothesized that integration of afferent activity with respiratory motor output is deficient in CCHS, rather than chemoreceptor failure, and that examination of trends in heart and breathing rates and variabilities following ventilatory challenges may clarify the deficient mechanisms. Twelve children with CCHS and 12 age- and gender-matched control cases were subjected to hyperoxic hypercapnic, poikylocapnic hypoxic, and hyperoxic challenges while supine. Heart and respiratory rates and variabilities during 60-s baseline and 120-s challenge periods were assessed. Hypoxia and hypercapnia enhanced breathing rate in control subjects; in CCHS cases, the rise differed during hypercapnia and did not occur to hypoxia. Hyperoxia showed initial transient patterns in breathing rate that differed between groups. A heart rate increase to hypoxia and late decline to hyperoxia were muted in CCHS patients. In hypercapnia, heart rate followed similar rising patterns in both groups. Overall CCHS heart rate variability was lower in baseline and challenge periods, principally due to diminished respiratory-related variation, especially during hypercapnia. No heart rate variability group differences emerged in hypoxia, and only a late increase for CCHS cases developed in hyperoxia. The findings indicate retention of aspects of chemoreceptor sensitivity in CCHS cases. The heart rate alterations to ventilatory challenges suggest specific compensatory responses of a slower nature remain intact in CCHS, whereas other rapidly changing components are deficient.

Adolescent↗

PubMed2004

Effects of a home walking exercise program on functional status and symptoms in heart failure.

BACKGROUND: Hospital-based exercise programs using a bicycle ergometer or a combination of exercise modalities have shown positive benefits in heart failure, but may not be readily accessible to many patients. Thus, we sought to evaluate the effects of a 12-week home walking exercise program on functional status and symptoms in patients with heart failure. METHODS: A randomized controlled trial comparing a 12-week progressive home walking exercise program (n = 42) to a "usual activity" control group (n = 37) was conducted in patients with heart failure (78 [99%] male; mean age 62.6 +/- 10.6 years; ejection fraction 27% +/- 8.8%; 63 [80%] New York Heart Association class II; 15[20%] New York Heart Association class III-IV) from a Veterans Affairs medical center and a university-affiliated medical center. Functional status (peak oxygen consumption via cardiopulmonary exercise testing, 6-minute walk test, the Heart Failure Functional Status Inventory), and symptoms (Dyspnea-Fatigue Index score with a postglobal rating of symptoms) were measured at baseline and 12 weeks. RESULTS: No adverse events related to exercise training occurred. Overall mean compliance to training was 74 +/- 37%. Peak oxygen consumption and the Heart Failure Functional Status Inventory were unchanged with training. Compared to the usual activity group, the training group had significantly longer walking distances measured by the 6-minute walk test (1264 +/- 255 vs 1337 +/- 272 feet, P =.001), and improved postglobal rating of symptoms (P =.03). CONCLUSION: In patients with heart failure, a progressive home walking exercise program is acceptable, increases walking distance, and decreases global rating of symptoms.

Aged↗

PubMed2003

Global BOLD MRI changes to ventilatory challenges in congenital central hypoventilation syndrome.

We evaluated global blood oxygen level dependent (BOLD) signal changes in gray and white matter in 14 congenital central hypoventilation syndrome (CCHS) and 14 control subjects. One baseline image series with room air and three series with 30 s room air followed by 120 s hypercapnia (5% CO2/95% O2), hypoxia (15% O2/85% N2) or hyperoxia (100% O2) were collected. Hypercapnia and hyperoxia raised, and hypoxia lowered gray and white matter global signal in both groups, with smaller changes in white matter. Signal changes in CCHS cases were lower than control subjects for hypercapnia in gray and white matter, slightly more-enhanced in hypoxia, and, except for initial transient responses, were nearly comparable during hyperoxia. Initial signal rate or pattern changes emerged in all three challenges in gray or white matter in control, but not CCHS cases. Neural or vascular mechanisms mediate perfusion differently in CCHS; the aberrant initial transient responses may reflect deficiencies in rapidly-varying physiologic interactions in the syndrome.

Adolescent↗

PubMed2003

Regional brain gray matter loss in heart failure.

Heart failure (HF) patients exhibit enhanced sympathetic tone, aberrant responses to blood pressure challenges, and sleep-related breathing disorders, suggesting that the syndrome is accompanied by central neural deficits. We assessed regional gray matter volumes over the entire brain in nine HF patients (51 +/- 10 yr; left ventricular ejection fraction 0.27 +/- 0.06; six men) and 27 healthy controls (46 +/- 12 yr; 22 men) using T1-weighted magnetic resonance imaging to evaluate potential neural damage. Regional volumes were evaluated by using voxel-based morphometry while controlling for age, gender, and handedness. HF patients showed significant and largely lateralized gray matter loss in autonomic and respiratory-related areas as well as regions not classically associated with such control, including the insula and basal ganglia, right cingulate gyrus, parahippocampal/fusiform gyrus, dorsal midbrain extending to the posterior and medial thalamus, ventral and superior lateral frontal cortex, bilateral cerebellar quadrangular lobules and right fastigial and neighboring nuclei, and bilateral deep parietal and lateral parietal-occipital cortex. Areas of gray matter loss may contribute to inappropriate cognitive, autonomic, and breathing regulation in HF.

Adult↗

PubMed2003

fMRI responses to cold pressor challenges in control and obstructive sleep apnea subjects.

Obstructive sleep apnea (OSA) patients exhibit altered sympathetic outflow, which may reveal mechanisms underlying the syndrome. We used functional MRI (fMRI) in 16 control and 10 OSA subjects who were free of cardiovascular or mood-altering drugs to examine neural responses to a forehead cold pressor challenge, which elicits respiratory slowing, bradycardia, and enhanced sympathetic outflow. The magnitude of cold-induced bradycardia was smaller, and respiratory slowing showed greater intersubject variability and reached a nadir later in OSA patients. Both groups showed similar signal changes to cold stimulation in multiple brain sites. However, signal increases emerged in OSA over controls in anterior and posterior cingulate and cerebellar and frontal cortex, whereas signals markedly declined in the ventral thalamus, hippocampus, and insula rather than rising as in controls. Anomalous responses often paralleled changes in breathing and heart rate. Medullary, midbrain areas and lentiform and cerebellar dentate nuclei also showed lower signals in OSA cases. Cold pressor physiological responses are modified in OSA and may result from both diminished and exaggerated responses in multiple brain structures.

Adult↗

PubMed2003

Sleep disturbance symptoms in patients with heart failure.

Sleep disturbances have a major impact on physical functioning, emotional well-being, and quality of life, but are not well described in patients with heart failure (HF). Eighty-four HF patients completed a sleep survey and provided demographic and clinical data. Seventy percent of the patients were male with a mean age of 54 years and a mean left ventricular ejection fraction of 22%. Forty-seven patients (56%) reported trouble sleeping and one-third used sleeping medication. The most frequently reported problems were inability to sleep flat (51%), restless sleep (44%), trouble falling asleep (40%), and awakening early (39%). Using logistic regression, physiological variables were tested as predictors of sleep disturbance. Severity of HF, age, gender, etiology, obesity, smoking, and use of beta-blockers were not predictors of sleep disturbance. HF patients experience significant sleep disturbances, which are not predicted by severity of symptoms or clinical status. Problems with sleep are an important component of a clinical assessment in this vulnerable population.

Cardiac Output, Low↗

PubMed2002

Brain morphology associated with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by repeated occurrences of hypoxic, hypercapnic, and transient blood pressure elevation episodes that may damage or alter neural structures. Underdeveloped structures or pre-existing damage in brain areas may also contribute to the genesis of the syndrome. Brain morphology in 21 patients with OSA and in 21 control subjects was assessed using high-resolution T1-weighted magnetic resonance imaging. Three-dimensional brain images were obtained with voxels of approximately 1 mm3. Images were spatially normalized and segmented into gray matter, white matter, and cerebrospinal fluid. For each segment, regional volumetric differences were determined relative to age, handedness, and group (patients with OSA versus control subjects), using voxel-based morphometry, with OSA effects weighted by disease severity. A significant age effect on total gray matter was found in control subjects but not in patients with OSA. Diminished regional and often unilateral gray matter loss was apparent in multiple sites of the brain in patients with OSA, including the frontal and parietal cortex, temporal lobe, anterior cingulate, hippocampus, and cerebellum. Unilateral loss in well-perfused structures suggests onset of neural deficits early in the OSA syndrome. The gray matter loss occurs within sites involved in motor regulation of the upper airway as well as in areas contributing to cognitive function.

Adult↗

PubMed2002

Neural responses during Valsalva maneuvers in obstructive sleep apnea syndrome.

The repetitive upper airway muscle atonic episodes and cardiovascular sequelae of obstructive sleep apnea (OSA) suggest dysfunction of specific neural sites that integrate afferent airway signals with autonomic and somatic outflow. We determined neural responses to the Valsalva maneuver by using functional magnetic resonance imaging. Images were collected during a baseline and three Valsalva maneuvers in 8 drug-free OSA patients and 15 controls. Multiple cortical, midbrain, pontine, and medullary regions in both groups showed intensity changes correlated to airway pressure. In OSA subjects, the left inferior parietal cortex, superior temporal gyrus, posterior insular cortex, cerebellar cortex, fastigial nucleus, and hippocampus showed attenuated signal changes compared with controls. Enhanced responses emerged in the left lateral precentral gyrus, left anterior cingulate, and superior frontal cortex of OSA patients. The anterior cingulate, cerebellar cortex, and posterior insula exhibited altered response timing patterns between control and OSA subjects. The response patterns in OSA subjects suggest deficits in particular neural pathways that normally mediate the Valsalva maneuver and compensatory actions in other structures.

Adult↗

PubMed2002

Normal fluctuations in pulmonary artery pressures and cardiac output in patients with severe left ventricular dysfunction.

BACKGROUND: One barrier to accurate interpretation of changes in hemodynamic pressures and cardiac output is lack of data about what constitutes a normal fluctuation. Few investigators have examined normal fluctuations in these parameters and none have done so in patients with left ventricular dysfunction. AIMS: To describe normal fluctuations in pulmonary artery pressures and cardiac output in patients with left ventricular dysfunction. METHODS: Hemodynamically stable advanced heart failure patients (N=39; 55+/-6 years old; 62% male) with left ventricular dysfunction (mean ejection fraction 22+/-5%) were studied. Cardiac output and pulmonary artery pressures were measured every 15 min for 2 h. RESULTS: Mean+/-standard deviation fluctuations were as follows: pulmonary artery systolic pressure=7+/-4 mmHg; pulmonary artery diastolic pressure=6+/-3 mmHg; pulmonary capillary wedge pressure=5+/-3 mmHg; cardiac output=0.7+/-0.3 l/min. The coefficient of variation for fluctuations in pulmonary artery systolic pressure was 6.7%, in pulmonary artery diastolic pressure was 9.3%, in pulmonary capillary wedge pressure was 9.2%, and in cardiac output was 7.2%. CONCLUSIONS: Values that vary <8% for pulmonary artery systolic pressure, <11% for pulmonary artery diastolic pressure, <12% for pulmonary capillary wedge pressure, and <9% for cardiac output from baseline represent normal fluctuations in these parameters in patients with left ventricular dysfunction.

Blood Pressure↗

PubMed2002

Brain responses associated with the Valsalva maneuver revealed by functional magnetic resonance imaging.

The Valsalva maneuver, a test frequently used to evaluate autonomic function, recruits discrete neural sites. The time courses of neural recruitment relative to accompanying cardiovascular and breathing patterns are unknown. We examined functional magnetic resonance imaging signal changes within the brain to repeated Valsalva maneuvers and correlated these changes with physiological trends. In 12 healthy subjects (age, 30-58 yr), a series of 25 volumes (20 gradient echo echo-planar image slices per volume) was collected using a 1.5-Tesla scanner during a 60-s baseline and 90-s challenge period consisting of three Valsalva maneuvers. Regions of interest were examined for signal intensity changes over baseline and challenge conditions in cardiorespiratory-related regions. In addition, whole brain correlations between signal intensity and heart rate and airway load pressure were performed on a voxel-by-voxel basis. Significant signal changes, correlated with the time course of load pressure and heart rate, emerged within multiple areas, including the amygdala and hippocampus, insular and lateral frontal cortices, dorsal pons, dorsal medulla, lentiform nucleus, and fastigial and dentate nuclei of the cerebellum. Signal intensities peaked early in the Valsalva maneuver within the hippocampus and amygdala, later within the dorsal medulla, pons and midbrain, and deep cerebellar nuclei, and last within the lentiform nuclei and the lateral prefrontal cortex. The ventral pontine signals increased during the challenge, but not in a fashion correlated to load pressure or heart rate. Sites showing little or no correlation included the vermis and medial prefrontal cortex. These data suggest an initiating component arising in rostral brain areas, a later contribution from cerebellar nuclei, basal ganglia, and lateral prefrontal cortex, and a role for the ventral pons in mediating longer term processes.

Adult↗