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ABSTRACT: White matter integrity changes with age, with the extent of variation dependent on attributes such as sex and oligodendrocyte health. Quantification of myelin and axonal integrity in healthy people would provide normative values necessary to determine pathology-related tissue characteristics with normal-aging and gender. We assessed white matter integrity with diffusion tensor imaging-based axial and radial diffusivity procedures (3.0-Tesla magnetic resonance imaging), which measure water diffusion parallel and perpendicular to axonal bundles, indicating axonal and myelin status, respectively, using region-of-interest (ROI) analyses, in 34 healthy adults (age, 46.5±6.0 years, 19 male). Sex differences in diffusion values were assessed with two-sample t-tests, and diffusion changes with age using Pearson's correlations; whole-brain effect sizes were examined with voxel-based procedures. Multiple brain areas showed increased axial and radial diffusivity values reflecting declines in axonal and myelin integrity with age, especially in mid-hippocampal and posterior thalamic areas. However, axonal and myelin integrity increased in insular and occipital cortex projections with maturity. Females showed reduced fiber and myelin integrity in substantially more structures than males, and included limbic, basal ganglia, pontine, and cerebellar sites. A minority of structures, confined to cerebellar, temporal, and frontal cortices, showed reduced fiber and myelin integrity with age in males over females. Whole-brain effect sizes in diffusion values between sexes and age-related changes showed findings parallel to ROI analyses. The structural differences mandate partitioning of sex and age in adult white matter pathology assessment, and likely contribute to sex-based physiological and behavioral dysfunction in aging and in multiple pathologies.
Brain research 03/2013; · 2.46 Impact Factor
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ABSTRACT: Heart failure (HF) patients exhibit depression and executive function impairments that contribute to HF mortality. Using specialized magnetic resonance imaging (MRI) analysis procedures, brain changes appear in areas regulating these functions (mammillary bodies, hippocampi, and frontal cortex). However, specialized MRI procedures are not part of standard clinical assessment for HF (which is usually a visual evaluation), and it is unclear whether visual MRI examination can detect changes in these structures.
Using brain MRI, we visually examined the mammillary bodies and frontal cortex for global and hippocampi for global and regional tissue changes in 17 HF and 50 control subjects. Significantly global changes emerged in the right mammillary body (HF 1.18 ± 1.13 vs control 0.52 ± 0.74; P = .024), right hippocampus (HF 1.53 ± 0.94 vs control 0.80 ± 0.86; P = .005), and left frontal cortex (HF 1.76 ± 1.03 vs control 1.24 ± 0.77; P = .034). Comparison of the visual method with specialized MRI techniques corroborates right hippocampal and left frontal cortical, but not mammillary body, tissue changes.
Visual examination of brain MRI can detect damage in HF in areas regulating depression and executive function, including the right hippocampus and left frontal cortex. Visual MRI assessment in HF may facilitate evaluation of injury to these structures and the assessment of the impact of potential treatments for this damage.
Journal of cardiac failure 02/2013; 19(2):94-100. · 3.25 Impact Factor
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ABSTRACT: Obstructive sleep apnea (OSA) is a common and progressive disorder accompanied by severe cardiovascular and neuropsychological sequelae, presumably induced by brain injury resulting from the intermittent hypoxia and cardiovascular processes accompanying the syndrome. However, whether the predominant brain tissue pathology is acute or chronic in newly-diagnosed, untreated OSA subjects is unclear; this assessment is essential for revealing pathological processes. Diffusion tensor imaging (DTI)-based mean diffusivity (MD) procedures can detect and differentiate acute from chronic pathology and may be useful to reveal processes in the condition. We collected four DTI series from 23 newly-diagnosed, treatment-naïve OSA and 23 control subjects, using a 3.0-Tesla magnetic resonance imaging scanner. Mean diffusivity maps were calculated from each series, realigned, averaged, normalized to a common space, and smoothed. Global brain MD values for each subject were calculated using normalized MD maps and a global brain mask. Mean global brain MD values and smoothed MD maps were compared between groups by using analysis of covariance (covariate: age). Mean global brain MD values were significantly reduced in OSA compared with controls (P = 0.01). Multiple brain sites in OSA, including medullary, cerebellar, basal ganglia, prefrontal and frontal, limbic, insular, cingulum bundle, external capsule, corpus callosum, temporal, occipital, and corona radiata regions showed reduced regional MD values compared with controls. The results suggest that global brain MD values are significantly reduced in OSA, with certain regional sites especially affected, presumably a consequence of axonal, glial, and other cell changes in those areas. The findings likely represent acute pathological processes in newly-diagnosed OSA subjects.
Journal of Neuroscience Research 06/2012; 90(10):2043-52. · 2.74 Impact Factor
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ABSTRACT: Human patient simulation (HPS) is becoming a popular teaching method in nursing education globally and is believed to enhance both knowledge and critical thinking. OBJECTIVE: While there is evidence that HPS improves knowledge, there is no objective nursing data to support HPS impact on critical thinking. Therefore, we studied knowledge and critical thinking before and after HPS in prelicensure nursing students and attempted to identify the predictors of higher critical thinking scores. METHODS: Using a one-group, quasi-experimental, pre-test post-test design, 154 prelicensure nursing students (age 25.7±6.7; gender=87.7% female) from 3 schools were studied at the same point in their curriculum using a high-fidelity simulation. Pre- and post-HPS assessments of knowledge, critical thinking, and self-efficacy were done as well as assessments for demographics and learning style. RESULTS: There was a mean improvement in knowledge scores of 6.5 points (P<0.001), showing evidence of learning. However, there was no statistically significant change in the critical thinking scores. A logistic regression with 10 covariates revealed three variables to be predictors of higher critical thinking scores: greater "age" (P=0.01), baseline "knowledge" (P=0.04) and a low self-efficacy score ("not at all confident") in "baseline self-efficacy in managing a patient's fluid levels" (P=.05). CONCLUSION: This study reveals that gains in knowledge with HPS do not equate to changes in critical thinking. It does expose the variables of older age, higher baseline knowledge and low self-efficacy in "managing a patient's fluid levels" as being predictive of higher critical thinking ability. Further study is warranted to determine the effect of repeated or sequential simulations (dosing) and timing after the HPS experience on critical thinking gains.
Nurse education today 05/2012; · 0.91 Impact Factor
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ABSTRACT: Heart failure (HF) patients show an inability to regulate autonomic functions, a characteristic which is associated with increased mortality. These autonomic deficits may stem from earlier demonstrated injury to central autonomic regulatory areas, providing a structural basis for the autonomic abnormalities. However, knowledge of structural injury provides insufficient insights into timing and magnitude of signal patterns within affected areas which lead to impaired autonomic outflow. Among damaged brain areas, cerebellar sites are key for timely coordination of sympathetic and parasympathetic attributes, and for dampening extremes of hypotension and hypertension induced by other injured sites, including hypothalamic and limbic areas. We collected functional magnetic resonance imaging (fMRI) signals in cerebellar and limbic areas to characterize amplitude and timing patterns of neural responses to the Valsalva maneuver, an autonomic challenge that elicits sequential sympathetic and parasympathetic responses, in 16 HF patients and 33 control subjects. HF patients showed distorted fMRI signal patterns during the challenge period in the cerebellar vermis, left cerebellar crus II, and left insula, whereas the right crus II and insula, and bilateral amygdalae showed normal patterns. However, all structures, except the left crus II, showed altered responses in HF during the recovery period. Crus II patterns reflected a failure of HF subjects to demonstrate the normal lateralized responses, while in the insula, HF subjects exhibited abnormal left-right patterns, relative to controls. The abnormal timing and response patterns in these injured areas critical for autonomic regulation likely contribute to the enhanced sympathetic outflow and autonomic dysfunction characteristic of HF.
The Cerebellum 02/2012; · 3.21 Impact Factor
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ABSTRACT: Determining insular functional topography is essential for assessing autonomic consequences of neural injury. We examined that topography in the five major insular cortex gyri to three autonomic challenges, the Valsalva, hand grip, and foot cold pressor, using functional magnetic resonance imaging (fMRI) procedures. Fifty-seven healthy subjects (age ± std: 47 ± 9 years) performed four 18 s Valsalva maneuvers (30 mm Hg load pressure), four hand grip challenges (16 s at 80% effort), and a foot cold pressor (60 s, 4°C), with fMRI scans recorded every 2 s. Signal trends were compared across gyri using repeated measures ANOVA. Significantly (P<0.05) higher signals in left anterior versus posterior gyri appeared during Valsalva strain, and in the first 4 s of recovery. The right anterior gyri showed sustained higher signals up to 2 s post-challenge, relative to posterior gyri, with sub-gyral differentiation. Left anterior gyri signals were higher than posterior areas during the hand grip challenge. All right anterior gyri showed increased signals over posterior up to 12 s post-challenge, with decline in the most-anterior gyrus from 10 to 24 s during recovery. The left three anterior gyri showed relatively lower signals only during the 90 s recovery of the cold pressor, while the two most-anterior right gyri signals increased only during the stimulus. More-differentiated representation of autonomic signals appear in the anterior right insula for the Valsalva maneuver, a bilateral, more-posterior signal representation for hand grip, and preferentially right-sided, anterior-posterior representation for the cold pressor. The functional organization of the insular cortex is gyri-specific to unique autonomic challenges.
Autonomic neuroscience: basic & clinical 02/2012; 168(1-2):72-81. · 1.82 Impact Factor
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ABSTRACT: Patients with congenital central hypoventilation syndrome (CCHS) show brain injury in areas that control chemosensory, autonomic, motor, cognitive, and emotion functions, which are deficient in the condition. Many of these abnormal characteristics are present from the neonatal period; however, it is unclear whether tissue injury underlying the characteristics progressively worsens with time. We hypothesized that several brain areas in subjects with CCHS would show increased gray matter volume loss over time.
We collected high-resolution T1-weighted images twice (4 years apart) from seven subjects with CCHS (age at first study, 16.1 ± 2.7 years; four males) and three control subjects (15.9 ± 2.1 years; three males) using a 3.0-Tesla magnetic resonance imaging (MRI) scanner, and evaluated regional gray matter volume changes with voxel-based morphometry (VBM) procedures.
Multiple brain sites in CCHS, including frontal, prefrontal, insular, and cingulate cortices; caudate nuclei and putamen; ventral temporal and parietal cortices; and cerebellar cortices showed significantly reduced gray matter volume over time. Only limited brain areas, including sensory, temporal, and medullary regions, emerged with increased gray matter at the later age.
Patients with CCHS show reduced gray matter volume with age progression in autonomic, respiratory, and cognitive regulatory areas, an outcome that may contribute to deterioration of functions found in the syndrome with increasing age.
Pediatric Research 02/2012; 71(6):701-6. · 2.70 Impact Factor
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ABSTRACT: To determine normal T2-relaxation values from different brain areas in healthy adults, assess age-related T2-relaxation changes in those sites, and evaluate potential gender-related T2-relaxation value differences.
We performed proton-density and T2-weighted imaging in 60 healthy adults (male: 38, age range = 31-64 years, mean age ± SD = 46.1 ± 9.3 years; female: 22, age range = 37-66 years, mean age ± SD = 49.5 ± 8.3 years), using a 3.0 Tesla MRI scanner. T2-relaxation values were calculated voxel-by-voxel from proton-density and T2-weighted images, and whole-brain T2-relaxation maps were constructed and normalized to a common space. A set of regions-of-interest were outlined within the basal ganglia, limbic, frontal, parietal, temporal, occipital, thalamic, hypothalamic, cerebellar, and pontine regions using mean background images derived from normalized and averaged T2-weighted images of all individuals, and regional T2-relaxation values were determined from these regions-of-interest and normalized T2-relaxation maps. Pearson's correlations were calculated between T2-relaxation values and age, and male-female differences evaluated with independent-samples t-tests.
T2-relaxation values typically increased with age in multiple brain sites; only a few regions showed declines, including the putamen and ventral pons. Sex-related differences in T2-relaxation values appeared in basal ganglia, frontal, temporal, occipital, and cerebellar regions; males showed higher values over females in these sites.
Establishment of normative adult T2-relaxation values over different brain areas, with age and sex as co-factors, offers baseline values against which disease-related tissue changes can be assessed.
Journal of Magnetic Resonance Imaging 02/2012; 35(2):300-8. · 2.70 Impact Factor
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ABSTRACT: Females with obstructive sleep apnea (OSA) show different psychological and physiological symptoms from males, which may be associated with sex-related variations in neural injury occurring with the disorder. To determine whether male- or female-specific brain injury is present in OSA, we assessed influences of sex on white matter changes in the condition.
Two-group factorial.
University medical center.
80 subjects total, with newly diagnosed, untreated OSA groups of 10 female (age mean ± SE: 52.6 ± 2.4 years, AHI 22.5 ± 4.1 events/h) and 20 male (age 48.9 ± 1.7, AHI 25.5 ± 2.9) patients, and 20 female (age 50.3 ± 1.7) and 30 male (age 49.2 ± 1.4) healthy control subjects.
None.
Brain fiber integrity was assessed with fractional anisotropy (FA), a diffusion tensor imaging-derived measure. Sleep quality, daytime sleepiness, depression, and anxiety were assessed with questionnaires. We identified regions of differing injury in male versus female OSA patients by assessing brain regions with significant interaction effects of OSA and sex on FA. Areas of sex-specific, OSA-related FA reductions appeared in females relative to males, including in the bilateral cingulum bundle adjacent to the mid hippocampus, right stria terminalis near the amygdala, prefrontal and posterior-parietal white matter, corpus callosum, and left superior cerebellar peduncle. Females with OSA showed higher daytime sleepiness, anxiety and depression levels, and reduced sleep quality.
Sex differences in white matter structural integrity appeared in OSA patients, with females more affected than males. These female-specific structural changes may contribute to or derive from neuropsychological and physiological symptom differences between sexes. CITATION: Macey PM; Kumar R; Yan-Go FL; Woo MA; Harper RM. Sex differences in white matter alterations accompanying obstructive sleep apnea. SLEEP 2012;35(12):1603-1613.
Sleep 01/2012; 35(12):1603-13. · 5.05 Impact Factor
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ABSTRACT: Central hypoventilation syndrome (CHS) is a rare condition characterized by hypoventilation during sleep, reduced ventilatory responsiveness to CO(2) and O(2), impaired perception of air hunger, and autonomic abnormalities. Neural impairments accompany the condition, including structural injury, impaired cerebral autoregulation, and dysfunctional autonomic control. The hypoventilation may induce cortical hypoxic injury, additional to consequences of maldevelopment from PHOX2B mutations present in most CHS subjects. We assessed cortical injury in clinically diagnosed CHS using high-resolution magnetic resonance imaging scans, collected from 14 CHS (mean age ± standard deviation [SD] 17.7 ± 5.0 years; 6 female) and 29 control (mean age ± SD, 17.9 ± 4.3 years; 12 female) subjects. We measured group differences in mean cortical thickness and age-thickness correlations using FreeSurfer software, accounting for age and sex (0.1 false discovery rate). Reduced thickness in CHS appeared in the dorsomedial frontal cortex and anterior cingulate; medial prefrontal, parietal, and posterior cingulate cortices; the insular cortex; anterior and lateral temporal lobes; and mid- and accessory motor strips. Normal age-related cortical thinning in multiple regions did not appear in CHS. The cortical thinning may contribute to CHS cardiovascular and memory deficits and may impair affect and perception of breathlessness. Extensive axonal injury in CHS is paralleled by reduced cortical tissue and absence of normal developmental patterns.
Cerebral Cortex 09/2011; 22(8):1728-37. · 6.54 Impact Factor
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ABSTRACT: The developing human brain shows rapid myelination and axonal changes during childhood, adolescence, and early adulthood, requiring successive evaluations to determine normative values for potential pathological assessment. Fiber characteristics can be examined by axial and radial diffusivity procedures, which measure water diffusion parallel and perpendicular to axons and show primarily axonal status and myelin changes, respectively. Such measures are lacking from widespread sites for the developing brain. Diffusion tensor imaging data were acquired from 30 healthy subjects (age 17.7 ± 4.6 years, range 8-24 years, body mass index 21.5 ± 4.5 kg/m(2), 18 males) using a 3.0-Tesla MRI scanner. Diffusion tensors were calculated, principal eigenvalues determined, and axial and radial diffusivity maps calculated and normalized to a common space. A set of regions of interest was outlined from widespread brain areas within rostral, thalamic, hypothalamic, cerebellar, and pontine regions, and average diffusivity values were calculated using normalized diffusivity maps and these regions of interest masks. Age-related changes were assessed with Pearson's correlations, and gender differences evaluated with Student's t-tests. Axial and radial diffusivity values declined with age in the majority of brain areas, except for midhippocampus, where axial diffusivity values correlated positively with age. Gender differences emerged within putamen, thalamic, hypothalamic, cerebellar, limbic, temporal, and other cortical sites. Documentation of normal axial and radial diffusivity values will help assess disease-related tissue changes. Axial and radial diffusivities change with age,with fiber structure and organization differing between sexes in several brain areas. The findings may underlie gender-based functional characteristics, and mandate partitioning age- and gender-related changes during developmental brain pathology evaluation.
Journal of Neuroscience Research 09/2011; 90(2):346-55. · 2.74 Impact Factor
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ABSTRACT: Although gray matter injury appears in heart failure (HF) patients, the presence, extent, and nature of axonal injury impacting on cardiovascular regulation and other functions is unclear. We performed diffusion tensor imaging (3.0-Tesla magnetic resonance imaging scanner) in 16 HF and 26 control subjects, and assessed whole-brain water diffusion parallel (axial diffusivity; axonal status) and perpendicular (radial diffusivity; myelin changes) to fibers. Regions with increased axial diffusivity only, indicating impaired axonal integrity, emerged in cardiovascular, hedonic, and pain regulatory areas, including basal forebrain, hypothalamic and limbic projections through the medial forebrain bundle and raphe magnus projections to the medulla and cerebellum. Other fiber paths between sites implicated in cognition, including limbic, basal-ganglia, thalamic, internal capsule, and corpus callosum were also altered. Sites with increased radial diffusivity only, indicating myelin breakdown, appeared in the corpus callosum, cingulate, and temporal, parietal, occipital, and frontal regions. Both higher axial and radial diffusivity, indicating loss of tissue integrity, appeared in parietal and occipital lobes, limbic regions, insula, internal capsule, cerebellum, and dorsolateral medulla. Axons and myelin are altered in HF, likely resulting from ischemic/hypoxic processes acting chronically and sub-acutely, respectively. The alterations would contribute to the multiple autonomic and neuropsychological symptoms found in HF.
Journal of the neurological sciences 05/2011; 307(1-2):106-13. · 2.32 Impact Factor
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ABSTRACT: Heart failure (HF) is accompanied by diminished cognitive, motor, learning, emotional, and planning deficits, which are associated with increased morbidity and mortality. A basal ganglia structure, the putamen, serves many functions that are affected in HF, but its global or localized structural integrity is unknown. Our aim was to evaluate global and regional putamen volume differences in HF over control subjects.
We collected two high-resolution T1-weighted scans from 16 HF patients (age, 54.1 ± 8.3 years; 12 males; left ventricular ejection fraction, 27.8 ± 6.8%) and 32 control subjects (52.4 ± 7.3 years; 24 males) using a 3.0 T magnetic resonance imaging scanner. After realigning, averaging, and reorienting the T1-weighted volumes into a common space, the structures were manually outlined, tracings were normalized for head size, volumes calculated, and surface models generated. Demographic data were compared between groups with χ(2) and independent samples t-tests, global putamen volumes were evaluated using independent samples t-tests, and regional differences were examined with surface morphometry. No significant differences in age or sex appeared between groups, but body mass index differed significantly (P = 0.008). Heart failure patients showed significantly lower left (controls vs. HF; 4842.1 ± 740.0 vs. 4224.1 ± 894.4 mm(3), P = 0.014) and right (4769.3 ± 651.9 vs. 4193.7 ± 876.2 mm(3), P = 0.014) global putamen volumes than controls, with localized reductions in bilateral rostral, mid-dorsal, and medial-caudal regions (left, P < 0.003; right, P < 0.0002).
Putamen structures showed global and localized volume reductions in HF over controls. The localized volume losses suggest deficits in motor and neuropsychological functions, which are evident in HF subjects, and may be due to hypoxic and ischaemic processes targeting these areas.
European Journal of Heart Failure 03/2011; 13(6):651-5. · 4.90 Impact Factor
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ABSTRACT: Nurse educators strive to engage students in an active learning process. Human patient simulation (HPS) may provide an interactive learning experience for nursing students. However, the current literature and research published on HPS is restricted and lacks objective evidence supporting this educational method in prelicensure nursing education. Studies with large numbers of participants and clearly defined, objective, and validated data collection methods are rare. Despite the lack of empirical evidence for HPS, many are embracing a technology and form of education in which the efficacy is still in question. This article reviews the current research in the areas of HPS value perceptions and studies of HPS impact on knowledge and knowledge transfer among nurses.
Journal of Nursing Education 02/2011; 50(2):65-72. · 0.86 Impact Factor
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ABSTRACT: Brain tissue changes accompany multiple neurodegenerative and developmental conditions in adolescents. Complex processes that occur in the developing brain with disease can be evaluated accurately only against normal aging processes. Normal developmental changes in different brain areas alter tissue water content, which can be assessed by magnetic resonance (MR) T2 relaxometry. We acquired proton-density (PD) and T2-weighted images from 31 subjects (mean age±S.D., 17.4±4.9 years; 18 male), using a 3.0-T MR imaging scanner. Voxel-by-voxel T2-relaxation values were calculated, and whole-brain T2-relaxation maps constructed and normalized to a common space template. We created a set of regions of interest (ROIs) over cortical gray and white matter, basal ganglia, amygdala, thalamic, hypothalamic, pontine and cerebellar sites, with sizes of ROIs varying from 12 to 243 mm(3); regional T2-relaxation values were determined from these ROIs and normalized T2-relaxation maps. Correlations between R2 (1/T2) values in these sites and age were assessed with Pearson's correlation procedures, and gender differences in regional T2-relaxation values were evaluated with independent-samples t tests. Several brain regions, but not all, showed principally positive correlations between R2 values and age; negative correlations emerged in the cerebellar peduncles. No significant differences in T2-relaxation values emerged between males and females for those areas, except for the mid pons and left occipital white matter; males showed higher T2-relaxation values over females. The findings indicate that T2-relaxation values vary with development between brain structures, and emphasize the need to correct for such age-related effects during any determination of potential changes from control values.
Magnetic Resonance Imaging 10/2010; 29(2):185-93. · 1.99 Impact Factor
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ABSTRACT: Autonomic dysfunction, mood disturbances, and memory deficits appear in pediatric and adult heart failure (HF). Brain areas controlling these functions show injury in adult HF patients, many of whom have comorbid cerebrovascular disease. We examined whether similar brain pathology develops in pediatric subjects without such comorbidities. In this study, high-resolution T1 brain magnetic resonance images were collected from seven severe HF subjects age (age 8-18 years [mean 13]; left ventricular shortening 9 to 19% [median 14%]) and seven age-matched healthy controls (age 8-18 years [mean 13]). After segmentation into gray matter (GM), white matter, and cerebrospinal fluid (CSF), regional volume loss between groups was determined by voxel-based morphometry. GM volume loss appeared on all HF scans, but ischemic changes and infarcts were absent. HF subjects showed greater CSF volume than controls (mean ± SD 0.30 ± 0.04 vs. 0.25 ± 0.04 l, P = 0.03), but total intracranial volume was identical (1.39 ± 0.11 vs. 1.39 ± 0.09 l, P = NS). Regional GM volume reduction appeared in the right and left posterior hippocampus, bilateral mid-insulae, and the superior medial frontal gyrus and mid-cingulate cortex of HF subjects (threshold P < 0.001). No volume-loss sites appeared in control brains. We conclude that pediatric HF patients show brain GM loss in areas similar to those of adult HF subjects. Substantial changes emerged in sites that regulate autonomic function as well as mood, personality and short-term memory. In the absence of thromboembolic disease and many comorbid conditions found in adult HF patients, pediatric HF patients show significant, focal GM volume loss, which may coincide with the multiple neurologic and psychological changes observed in patients with HF.
Pediatric Cardiology 10/2010; 31(7):969-76. · 1.30 Impact Factor
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Sleep Medicine 06/2010; 11(6):589-90. · 3.40 Impact Factor
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ABSTRACT: Brain injury underlying the state-related loss of ventilatory drive, autonomic, cognitive, and affective deficits in congenital central hypoventilation syndrome (CCHS) patients appears throughout the brain, as demonstrated by magnetic resonance (MR) T2 relaxometry and mean diffusivity studies. However, neither MR measure is optimal to describe types of axonal injury essential for assessing neural interactions responsible for CCHS characteristics. To evaluate axonal integrity and partition the nature of tissue damage (axonal vs. myelin injury) in CCHS, we measured water diffusion parallel (axial diffusivity) and perpendicular (radial diffusivity) to rostral brain fibers, indicative of axonal and myelin changes, respectively, with diffusion tensor imaging (DTI). We performed DTI in 12 CCHS (age 18.5 + or - 4.9 years, 7 male) and 30 control (17.7 + or - 4.6 years, 18 male) subjects, using a 3.0-Tesla MR imaging scanner. Axial and radial diffusivity maps were calculated, spatially normalized, smoothed, and compared between groups (analysis of covariance; covariates, age and gender). Significantly increased radial diffusivity, primarily indicative of myelin injury, emerged in fibers of the corona radiata, internal capsule, corpus callosum, hippocampus through the fornix, cingulum bundle, and temporal and parietal lobes. Increased axial diffusivity, suggestive of axonal injury, appeared in fibers of the internal capsule, thalamus, corona radiata, and occipital and temporal lobes. Multiple brain regions showed both higher axial and radial diffusivity, indicative of loss of tissue integrity with a combination of myelin and axonal injury, including basal ganglia, bed nucleus, and limbic, occipital, and temporal areas. The processes underlying injury are unclear, but likely stem from both hypoxic and developmental processes.
Journal of Neuroscience Research 03/2010; 88(10):2146-54. · 2.74 Impact Factor
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ABSTRACT: Congenital central hypoventilation syndrome (CCHS) patients show significant autonomic dysfunction in addition to the well-described loss of breathing drive during sleep. Some characteristics, for example, syncope, may stem from delayed sympathetic outflow to the vasculature; other symptoms, including profuse sweating, may derive from overall enhanced sympathetic output. The dysregulation suggests significant alterations to autonomic regulatory brain areas. Murine models of the genetic mutations present in the human CCHS condition indicate brainstem autonomic nuclei are targeted; however, the broad range of symptoms suggests more widespread alterations. We used functional magnetic resonance imaging (fMRI) to assess neural response patterns to the Valsalva maneuver, an autonomic challenge eliciting a sequence of sympathetic and parasympathetic actions, in nine CCHS and 25 control subjects. CCHS patients showed diminished and time-lagged heart rate responses to the Valsalva maneuver, and muted fMRI signal responses across multiple brain areas. During the positive pressure phase of the Valsalva maneuver, CCHS responses were muted, but were less so in recovery phases. In rostral structures, including the amygdala and hippocampus, the normal declining patterns were replaced by increasing trends or more modest declines. Earlier onset responses appeared in the hypothalamus, midbrain, raphé pallidus, and left rostral ventrolateral medulla. Phase-lagged responses appeared in cerebellar pyramis and anterior cingulate cortex. The time-distorted and muted central responses to autonomic challenges likely underlie the exaggerated sympathetic action and autonomic dyscontrol in CCHS, impairing cerebral autoregulation, possibly exacerbating neural injury, and enhancing the potential for cardiac arrhythmia.
Neuroscience 03/2010; 167(4):1249-56. · 3.38 Impact Factor
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ABSTRACT: Obstructive sleep apnea (OSA) occurs in at least 10% of the population, and leads to higher morbidity and mortality; however, relationships between OSA severity and sleep or psychological symptoms are unclear. Existing studies include samples with wide-ranging comorbidities, so we assessed relationships between severity of OSA and common sleep and psychological disturbances in recently diagnosed OSA patients with minimal co-morbidities. We studied 49 newly diagnosed, untreated OSA patients without major co-morbidities such as mental illness, cardiovascular disease, or stroke; subjects were not using psychoactive medications or tobacco (mean +/- std age: 46.8+/-9.1 years; apnea/hyponea index [AHI]: 32.1+/-20.5 events/hour; female/male: 12/37; weight <125 kg). We evaluated relationships between the AHI and daytime sleepiness (Epworth Sleepiness Scale; ESS), sleep quality (Pittsburg Sleep Quality Index; PSQI), depressive symptoms (Beck Depression Inventory-II; BDI), and anxiety symptoms (Beck Anxiety Inventory; BAI), as well as sex and body mass index (BMI). AHI was similar in females and males. Mean levels of all symptoms were above normal thresholds, but AHI was not correlated with age, ESS, PSQI, BDI, or BAI; only BMI was correlated with OSA severity. No differences in mean AHI appeared when subjects were grouped by normal versus elevated values of ESS, PSQI, BDI, or BAI. Consistent with other studies, a strong link between OSA severity and psychological symptoms did not appear in these newly diagnosed patients, suggesting that mechanisms additional to the number and frequency of hypoxic events and arousals occurring with apneas contribute to adverse health effects in OSA. OSA patients presenting with mild or moderate severity, and no major co-morbidities will not necessarily have low levels of sleep or psychological disturbances.
PLoS ONE 01/2010; 5(4):e10211. · 4.09 Impact Factor
