Heart failure-induced brain myelin changes and differences between sexes.

Heart failure (HF) leads to brain injury in autonomic, respiratory, mood, and cognitive control sites, revealed as tissue volume loss, altered metabolites, and impaired diffusion tissue properties. The extent of myelin changes in HF and variations within sexes are unclear. Our aim was to examine regional brain subcortical and white matter myelin integrity in HF patients over control subjects, as well as differences between sexes using T1- and T2-weighted clinical images. We acquired T1- and T2-weighted images from 63 HF patients and 129 controls using a 3.0-Tesla MRI scanner. Using T1- and T2-weighted images, ratio maps were computed, normalized to a common space, smoothed, and compared between groups (ANCOVA; covariates: age and sex; SPM12, false discovery rate, p < .010), as well as between male versus female HF (ANCOVA; covariate: age; SPM12, uncorrected p < .005). Multiple brain areas in HF showed decreased myelin integrity, including the amygdala, hippocampus, cingulate, insula, cerebellum, prefrontal cortices, and multiple white matter areas, compared to controls. Female HF patients showed more brain injuries in the parietal, prefrontal and frontal, hippocampus, amygdala, pons, cerebellar, insula, and corpus callosum compared to male HF patients. HF subjects showed compromised subcortical and white matter myelin integrity, especially in sites regulating autonomic, respiratory, mood, and cognition, with more changes in females over males. These findings provide a structural basis for the enhanced symptoms identified in female over male HF patients with similar disease severity.

Brain Changes Linked to Cognitive Symptomatology in Homeless Youth.

Youth impacted by homelessness experience diminished cognition due to a variety of reasons including mental health symptoms, alcohol and substance use, and adverse childhood experiences. However, the status of specific brain regions which could impact important cognitive functions in homeless youth remains unclear. In this pilot comparative and correlational study, a series of demographic, psychological, cognitive assessments, and brain magnetic resonance imaging were performed in 10 male youth experiencing homelessness and 9 age-matched healthy male controls (age range: 18-25 years). Participants experiencing homelessness had significantly decreased regional brain gray matter tissue in comparison to the controls. Moreover, there were strong inverse correlations between the brain regions classically associated with executive decision-making (prefrontal cortices), depression (insular lobes), and conflict resolution (anterior cingulate), and the level of the symptoms detected by their questionnaires.

Brain regional homogeneity changes after short-term positive airway pressure treatment in patients with obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) reveal functional changes in brain sites involved in autonomic, cognitive, and mood regulations. However, it is unclear whether these brain changes reverse with short-term positive airway pressure (PAP) treatment. Our aim was to examine brain functional changes in response to 3-months of PAP treatment using regional homogeneity (ReHo) measures, where increased and decreased ReHo value indicates hyper- and hypo-local neural activities, respectively, and considered as functional deficits. We collected brain magnetic resonance imaging data as well as mood, cognitive, and sleep variables from 17 treatment-naïve OSA at baseline and after 3-months of PAP treatment and 25 age- and gender-matched healthy controls. Whole-brain ReHo maps were calculated and compared between OSA and controls and OSA subjects before and after PAP treatment. At baseline, treatment-naïve OSA subjects showed higher ReHo in the bilateral thalamus, putamen, postcentral gyrus, paracentral lobule, supplementary motor area, and right insula, and lower ReHo in the frontal and parietal cortices, compared to controls. After 3-months of PAP treatment, abnormal sleep and mood scores decreased significantly to normal levels. ReHo decreased in the autonomic and somatosensory control areas, including the thalamus, putamen, postcentral gyrus, and insula, and increased in the cognitive and affective regulatory parietal regions. The normalized ReHo was correlated with improved sleep quality and reduced anxiety symptoms. These findings suggest that 3-months of PAP use can improve sleep, mood issues, and partly recover brain activities, however, longer PAP treatment may be required to fully and permanently reverse brain functional deficits.

Reduced hippocampal volumes and memory deficits in adolescents with single ventricle heart disease.

INTRODUCTION: Adolescents with single ventricle congenital heart disease (SVHD) show functional deficits, particularly in memory and mood regulation. Hippocampi are key brain structures that regulate mood and memory; however, their tissue integrity in SVHD is unclear. Our study aim is to evaluate hippocampal volumes and their associations with memory, anxiety, and mood scores in adolescents with SVHD compared to healthy controls. METHODS: We collected brain magnetic resonance imaging data from 25 SVHD (age 15.9 ± 1.2 years; 15 male) and 38 controls (16.0 ± 1.1 years; 19 male) and assessed memory (Wide Range Assessment of Memory and Learning 2, WRAML2), anxiety (Beck Anxiety Inventory, BAI), and mood (Patient Health Questionnaire 9, PHQ-9) functions. Both left and right hippocampi were outlined and global volumes, as well as three-dimensional surfaces were compared between groups using ANCOVA and associations with cognitive and behavioral scores with partial correlations (covariates: age and total brain volume). RESULTS: The SVHD group showed significantly higher BAI (p = .001) and PHQ-9 (p < .001) scores, indicating anxiety and depression symptoms and significantly reduced WRAML2 scores (p < .001), suggesting memory deficits compared with controls. SVHD group had significantly reduced right global hippocampal volumes (p = .036) compared with controls, but not the left (p = .114). Right hippocampal volume reductions were localized in the CA1, CA4, subiculum, and dentate gyrus. Positive correlations emerged between WRAML2 scores and left (r = 0.32, p = .01) and right (r = 0.28, p = .03) hippocampal volumes, but BAI and PHQ-9 did not show significant correlations. CONCLUSION: Adolescents with SVHD show reduced hippocampal volumes, localized in several sites (CA1, CA4, subiculum, and dentate gyrus), which are associated with memory deficits. The findings indicate the need to explore ways to improve memory to optimize academic achievement and ability for self-care in the condition.

Poor Sleep Quality Linked to Decreased Brain Gray Matter Density in Adults with Type 2 Diabetes.

BACKGROUND: Poor sleep is common in adults with Type 2 Diabetes Mellitus (T2DM), which may contribute to brain tissue changes. However, the impact of sleep quality on brain tissue in T2DM individuals is unclear. We aimed to evaluate differential sleep quality with brain changes, and brain tissue integrity in T2DM patients. METHODS: Data were collected from 34 patients with T2DM and included sleep quality (assessed by the Pittsburgh Sleep Quality Index [PSQI], and high-resolution T1-weighted brain images using a 3.0-Tesla MRI scanner. Gray matter density (GMD) maps were compared between subjects with good vs poor sleep quality as assessed by PSQI (covariates: age, sex, BMI). RESULTS: Of 34 T2DM patients, 17 showed poor sleep quality. Multiple brain sites, including the hippocampus, cerebellum, prefrontal, amygdala, thalamus, hypothalamus, insula, cingulate, and temporal areas, showed reduced gray matter in T2DM patients with poor sleep quality over patients with good sleep quality. Negative associations emerged between PSQI scores and gray matter density in multiple areas. CONCLUSIONS: T2DM patients with poor sleep quality show brain tissue changes in sites involved in sleep regulation. Findings indicate that improving sleep may help mitigate brain tissue damage, and thus, improve brain function in T2DM patients.

Caudate nuclei volume alterations and cognition and mood dysfunctions in adolescents with single ventricle heart disease.

Adolescents with single ventricle heart disease (SVHD) exhibit mood and cognitive deficits, which may result from injury to the basal ganglia structures, including the caudate nuclei. However, the integrity of the caudate in SVHD adolescents is unclear. Our aim was to examine the global and regional caudate volumes, and evaluate the relationships between caudate volumes and cognitive and mood scores in SVHD and healthy adolescents. We acquired two high-resolution T1-weighted images from 23 SVHD and 37 controls using a 3.0-Tesla MRI scanner, as well as assessed mood (Patient Health Questionnaire-9 [PHQ-9]; Beck Anxiety Inventory [BAI]) and cognition (Montreal Cognitive Assessment [MoCA]; Wide Range Assessment of Memory and Learning-2; General Memory Index [GMI]) functions. Both left and right caudate nuclei were outlined, which were then used to calculate and compare volumes between groups using ANCOVA (covariates: age, gender, and head-size), as well as perform 3D surface morphometry. Partial correlations (covariates: age, gender, and head-size) were used to examine associations between caudate volumes, cognition, and mood scores in SVHD and controls. SVHD subjects showed significantly higher PHQ-9 and BAI scores, indicating more depressive and anxiety symptoms, as well as reduced GMI scores, suggesting impaired cognition, compared to controls. SVHD patients showed significantly reduced caudate volumes (left, 3,198.8 ± 490.1 vs. 3,605.0 ± 480.4 mm3 , p < 0.004; right, 3,162.1 ± 475.4 vs. 3,504.8 ± 465.9 mm3 , p < 0.011) over controls, and changes were localized in the rostral, mid-dorsolateral, and caudal areas. Significant negative correlations emerged between caudate volumes with PHQ-9 and BAI scores and positive correlations with GMI and MoCA scores in SVHD and controls. SVHD adolescents show significantly reduced caudate volumes, especially in sites that have projections to regulate mood and cognition, which may result from developmental and/or hypoxia-/ischemia-induced processes.

Regional Brain Gray Matter Changes in Patients with Type 2 Diabetes Mellitus.

Patients with Type 2 diabetes mellitus (T2DM) show cognitive and mood impairment, indicating potential for brain injury in regions that control these functions. However, brain tissue integrity in cognition, anxiety, and depression regulatory sites, and their associations with these functional deficits in T2DM subjects remain unclear. We examined gray matter (GM) changes in 34 T2DM and 88 control subjects using high-resolution T1-weighted images, collected from a 3.0-Tesla magnetic resonance imaging scanner, and assessed anxiety [Beck Anxiety Inventory], depressive symptoms [Beck Depression Inventory-II], and cognition [Montreal Cognitive Assessment]. We also investigated relationships between GM status of cognitive and mood control sites and these scores in T2DM. Significantly increased anxiety (p = 0.003) and depression (p = 0.001), and reduced cognition (p = 0.002) appeared in T2DM over controls. Decreased GM volumes appeared in several regions in T2DM patients, including the prefrontal, hippocampus, amygdala, insular, cingulate, cerebellum, caudate, basal-forebrain, and thalamus areas (p < 0.01). GM volumes were significantly associated with anxiety (r = -0.456,p = 0.009), depression (r = -0.465,p = 0.01), and cognition (r = 0.455,p = 0.009) scores in regions associated with those regulations (prefrontal cortices, hippocampus, para hippocampus, amygdala, insula, cingulate, caudate, thalamus, and cerebellum) in T2DM patients. Patients with T2DM show brain damage in regions that are involved in cognition, anxiety, and depression control, and these tissue alterations are associated with functional deficits. The findings indicate that mood and cognitive deficits in T2DM patients has brain structural basis in the condition.

Prefrontal cortex brain damage and glycemic control in patients with type 2 diabetes.

BACKGROUND: This study examined brain tissue integrity in sites that controls cognition (prefrontal cortices; PFC) and its relationships to glycemic outcomes in adults with type 2 diabetes mellitus (T2DM). METHODS: We examined 28 T2DM patients (median age 57.1 years; median body mass index [BMI] 30.6 kg/m2 ;11 males) and 47 healthy controls (median age 55.0 years; median BMI 25.8 kg/m2 ; 29 males) for cognition (Montreal Cognitive Assessment [MoCA]), glycemic control (hemoglobin A1c [HbA1c]), and PFC tissue status via brain magnetic resonance imaging (MRI). High-resolution T1-weighted images were collected using a 3.0-Tesla MRI scanner, and PFC tissue changes (tissue density) were examined with voxel-based morphometry procedures. RESULTS: Reduced PFC density values were observed in T2DM patients compared to controls (left, 0.41 ± 0.02 mm3 /voxel vs 0.44 ± 0.02 mm3 /voxel, P < 0.001; right, 0.41 ± 0.03 mm3 /voxel vs 0.45 ± 0.02 mm3 /voxel, P < 0.001). PFC density values were positively correlated with cognition; left PFC region (r = 0.53, P = 0.005) and right PFC region (r = 0.56, P = 0.003), with age and sex as covariates. Significant negative correlations were found between PFC densities and HbA1c values; left PFC region (r = -0.39, P = 0.049) and right PFC region (r = -0.48, P = 0.01), with age and sex as covariates. CONCLUSIONS: T2DM patients showed PFC brain tissue damage, which is associated with cognitive deficits and poor glycemic control. Further research is needed to identify causal relationships between HbA1c, cognition, and brain changes in T2DM and to evaluate the impact of interventions to prevent brain tissue injury or neuroregeneration in this high-risk patient population, to eventually preserve or enhance cognition and improve glucose outcomes.

Reduced brain mammillary body volumes and memory deficits in adolescents who have undergone the Fontan procedure.

BACKGROUND: Adolescents with single ventricle heart disease (SVHD) who have undergone the Fontan procedure show cognitive/memory deficits. Mammillary bodies are key brain sites that regulate memory; however, their integrity in SVHD is unclear. We evaluated mammillary body (MB) volumes and their associations with cognitive/memory scores in SVHD and controls. METHODS: Brain MRI data were collected from 63 adolescents (25 SVHD; 38 controls) using a 3.0-Tesla MRI scanner. Cognition and memory were assessed using Montreal Cognitive Assessment (MoCA) and Wide Range Assessment of Memory and Learning 2. MB volumes were calculated and compared between groups (ANCOVA, covariates: age, sex, and total brain volume [TBV]). Partial correlations and linear regression were performed to examine associations between volumes and cognitive scores (covariates: age, sex, and TBV). RESULTS: SVHD group showed significantly lower MoCA and WRAML2 scores over controls. MB volumes were significantly reduced in SVHD over controls. After controlling for age, sex, and TBV, MB volumes correlated with MoCA and delayed memory recall scores in SVHD and controls. CONCLUSION: Adolescents with SVHD show reduced MB volumes associated with cognitive/memory deficits. Potential mechanisms of volume losses may include developmental and/or hypoxic/ischemic-induced processes. Providers should screen for cognitive deficits and explore possible interventions to improve memory.

Heart Failure Self-care Associated With Brain Injury in Executive Control Regions.

BACKGROUND: Inadequate self-care is linked to poor health outcomes in heart failure (HF). Self-care depends on decision-making abilities, but links between self-care and brain injury to executive decision-making regulatory areas (prefrontal cortices) are unclear. OBJECTIVE: We investigated the relationships between HF self-care and status of prefrontal cortices. METHODS: Magnetic resonance imaging-based diffusion tensor imaging was performed in 21 patients with HF (age, 53.8 ± 7.9 years; 15 men; left ventricular ejection fraction, 25.1% ± 6.1%), and self-care and executive function were measured with the Self-care of Heart Failure Index (SCHFI) and Trail Making Test B. Using diffusion tensor imaging data, mean diffusivity (MD) maps were calculated and region-of-interest analyses were performed on the left and right prefrontal brain areas. Statistical analyses consisted of partial correlations (covariates, age, and gender). RESULTS: The mean ± SD SCHFI scores were 70.78 ± 11.37 for maintenance, 70 ± 17.32 for management, and 74.91 ± 15.76 for confidence. The mean ± SD Trail Making Test B score was 90.2 ± 73.3 seconds. The mean ± SD MD values (higher values indicate tissue injury) of the left and right prefrontal cortices were 1.46 ± 0.16 (×10 mm/s) and 1.44 ± 0.14 (×10 mm/s), respectively. Significant negative correlations emerged between prefrontal MD values and SCHFI maintenance (left/right, r = -0.64/-0.70; P < .003) and SCHFI management (r = -0.93/-0.86; P < .003). Significant positive correlations were observed between prefrontal MD values and Trail Making Test B (r = 0.71/0.74; P < .001). A nonsignificant correlation emerged between prefrontal MD values and SCHFI confidence scores. CONCLUSIONS: Brain tissue integrity in executive function regulatory regions is associated with HF self-care for maintenance and management. The findings indicate that protection and brain injury repair in executive control areas may improve HF self-care.

Aberrant Brain Functional Connectivity Dynamic Responses to the Valsalva Maneuver in Heart Failure.

BACKGROUND: Patients with heart failure (HF) show abnormal autonomic activities, which may stem from altered functional connectivity (FC) between different brain sites. METHODS AND RESULTS: We evaluate insular and cerebellar FC with other brain areas, before, during, and after the Valsalva challenge, with functional magnetic resonance imaging in 35 HF and 35 control subjects. Significant insular FC emerged with striatum, thalamus, and anterior cingulate. While left and right cerebellar cortices showed significant FC with each other constituting the cerebellum network, the insula and cerebellum networks showed significant negative FC with each other at baseline, challenge, and recovery phases. The challenge induced increased FC within the insula and the cerebellum networks in both HF and controls. However, patients with HF showed more increased insular network FC, but less enhanced cerebellar FC. During the recovery phase, the negative FC between the insular network and cerebellum enhanced significantly in controls, but not in HF. Lower left ventricle ejection fraction was correlated with lower insula network FC, and impaired negative FC between cerebellum and the insula network in HF. CONCLUSIONS: Increased insular FC in patients with HF might contribute to exaggerated sympathetic tone. While impaired cerebellar FC and diminished negative interactions between cerebellum and insular systems may indicate impaired parasympathetic functions in HF.

Altered brain diffusion tensor imaging indices in adolescents with the Fontan palliation.

PURPOSE: Single ventricle heart disease (SVHD) patients show injury in brain sites that regulate autonomic, mood, and cognitive functions. However, the nature (acute or chronic changes) and extent of brain injury in SVHD are unclear. Our aim was to examine regional brain tissue damage in SVHD over controls using DTI-based mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) procedures. METHODS: We collected two DTI series (3.0-T MRI), mood and cognitive data, from 27 SVHD and 35 control adolescents. Whole-brain MD, AD, RD, and FA maps were calculated from each series, realigned and averaged, normalized to a common space, smoothed, and compared between groups using ANCOVA (covariates, age and sex; false discovery rate, p < 0.05). Region-of-interest analyses were performed to calculate MD, AD, RD, and FA values for magnitude assessment between groups. RESULTS: SVHD patients showed impaired mood and cognitive functions over healthy adolescents. Multiple brain sites in SVHD showed increased MD values, including the insula, caudate, cingulate, hypothalamus, thalamus, medial prefrontal and frontal cortices, parahippocampal gyrus, hippocampus, precentral gyrus, amygdala, cerebellum, corpus callosum, basal forebrain, mammillary bodies, internal capsule, midbrain, fornix, and occipital, parietal, and temporal cortices, indicating chronic tissue changes. Similar areas showed either increased AD or RD values, with RD changes more enhanced over AD in SVHD compared to controls. Few brain regions emerged with increased or decreased FA values in SVHD patients over controls. CONCLUSION: SVHD adolescents, more than a decade from their last surgical procedure, show widespread brain abnormalities in autonomic, mood, and cognitive regulatory areas. These findings indicate that brain injury is in a chronic stage in SVHD with predominantly myelin changes that may result from previous hypoxia/ischemia- or developmental-induced processes.

Sex-specific hippocampus volume changes in obstructive sleep apnea.

Introduction: Obstructive sleep apnea (OSA) patients show hippocampal-related autonomic and neurological symptoms, including impaired memory and depression, which differ by sex, and are mediated in distinct hippocampal subfields. Determining sites and extent of hippocampal sub-regional injury in OSA could reveal localized structural damage linked with OSA symptoms. Methods: High-resolution T1-weighted images were collected from 66 newly-diagnosed, untreated OSA (mean age ±â€¯SD: 46.3 ±â€¯8.8 years; mean AHI ±â€¯SD: 34.1 ±â€¯21.5 events/h;50 male) and 59 healthy age-matched control (46.8 ±â€¯9.0 years;38 male) participants. We added age-matched controls with T1-weighted scans from two datasets (IXI, OASIS-MRI), for 979 controls total (426 male/46.5 ±â€¯9.9 years). We segmented the hippocampus and analyzed surface structure with "FSL FIRST" software, scaling volumes for brain size, and evaluated group differences with ANCOVA (covariates: total-intracranial-volume, sex; P < .05, corrected). Results: In OSA relative to controls, the hippocampus showed small areas larger volume bilaterally in CA1 (surface displacement ≤0.56 mm), subiculum, and uncus, and smaller volume in right posterior CA3/dentate (≥ - 0.23 mm). OSA vs. control males showed higher bilateral volume (≤0.61 mm) throughout CA1 and subiculum, extending to head and tail, with greater right-sided increases; lower bilateral volumes (≥ - 0.45 mm) appeared in mid- and posterior-CA3/dentate. OSA vs control females showed only right-sided effects, with increased CA1 and subiculum/uncus volumes (≤0.67 mm), and decreased posterior CA3/dentate volumes (≥ - 0.52 mm). Unlike males, OSA females showed volume decreases in the right hippocampus head and tail. Conclusions: The hippocampus shows lateralized and sex-specific, OSA-related regional volume differences, which may contribute to sex-related expression of symptoms in the sleep disorder. Volume increases suggest inflammation and glial activation, whereas volume decreases suggest long-lasting neuronal injury; both processes may contribute to dysfunction in OSA.

Brain structural changes associated with aberrant functional responses to the Valsalva maneuver in heart failure.

Heart failure (HF) patients show inability to regulate autonomic functions in response to autonomic challenges. The autonomic deficits may stem from brain tissue injury in central autonomic regulatory areas, resulting from ischemic and hypoxic processes accompanying the condition. However, the direct evaluation of correlations between brain structural injury and functional timing and magnitude of neural signal patterns within affected areas, which may lead to impaired autonomic outflow, is unclear. In this study, we evaluate neural responses to the Valsalva maneuver with blood oxygen level-dependent functional magnetic resonance imaging in 29 HF patients and 35 control subjects and brain structural changes using diffusion tensor imaging-based mean diffusivity in a subsample of 19 HF and 24 control subjects. HF showed decreased neural activation in multiple autonomic and motor control areas, including cerebellum cortices, vermis, left insular, left putamen, and bilateral postcentral gyrus. Structural brain changes emerged in similar autonomic, as well as cognitive and mood regulation areas. Functional MRI responses in cerebellum and insula in HF subjects are delayed or decreased in magnitude to the challenge. The impaired functional responses of insular and cerebellar sites are correlated with the severity of tissue changes. These results indicate that the functions of insular and cerebellar regions, sites that are involved in autonomic regulation, are compromised, and that autonomic deficits in these areas have brain structural basis for impaired functions. Our study enhanced our understanding of brain structural and functional alterations underlying impaired autonomic regulations in HF subjects.

Altered resting-state hippocampal and caudate functional networks in patients with obstructive sleep apnea.

INTRODUCTION: Brain structural injury and metabolic deficits in the hippocampus and caudate nuclei may contribute to cognitive and emotional deficits found in obstructive sleep apnea (OSA) patients. If such contributions exist, resting-state interactions of these subcortical sites with cortical areas mediating affective symptoms and cognition should be disturbed. Our aim was to examine resting-state functional connectivity (FC) of the hippocampus and caudate to other brain areas in OSA relative to control subjects, and to relate these changes to mood and neuropsychological scores. METHODS: We acquired resting-state functional magnetic resonance imaging (fMRI) data from 70 OSA and 89 healthy controls using a 3.0-Tesla magnetic resonance imaging scanner, and assessed psychological and behavioral functions, as well as sleep issues. After standard fMRI data preprocessing, FC maps were generated for bilateral hippocampi and caudate nuclei, and compared between groups (ANCOVA; covariates, age and gender). RESULTS: Obstructive sleep apnea subjects showed significantly higher levels of anxiety and depressive symptoms over healthy controls. In OSA subjects, the hippocampus showed disrupted FC with the thalamus, para-hippocampal gyrus, medial and superior temporal gyrus, insula, and posterior cingulate cortex. Left and right caudate nuclei showed impaired FC with the bilateral inferior frontal gyrus and right angular gyrus. In addition, altered limbic-striatal-cortical FC in OSA showed relationships with behavioral and neuropsychological variables. CONCLUSIONS: The compromised hippocampal-cortical FC in OSA may underlie depression and anxious mood levels in OSA, while impaired caudate-cortical FC may indicate deficits in reward processing and cognition. These findings provide insights into the neural mechanisms underlying the comorbidity of mood and cognitive deficits in OSA.

Obstructive sleep apnea and cortical thickness in females and males.

INTRODUCTION: Obstructive sleep apnea (OSA) affects approximately 10% of adults, and alters brain gray and white matter. Psychological and physiological symptoms of the disorder are sex-specific, perhaps related to greater injury occurs in female than male patients in white matter. Our objective was to identify influences of OSA separated by sex on cortical gray matter. METHODS: We assessed cortical thickness in 48 mild-severe OSA patients (mean age±std[range] = 46.5±9.0[30.8-62.7] years; apnea-hypopnea index = 32.6±21.1[6-102] events/hour; 12 female, 36 male; OSA severity: 5 mild, 18 moderate, 25 severe) and 62 controls (mean age = 47.7±8.9[30.9-65.8] years; 22 female, 40 male). All OSA patients were recently-diagnosed via polysomnography, and control subjects screened and a subset assessed with sleep studies. We used high-resolution magnetic resonance imaging to identify OSA-related cortical thinning, based on a model with condition and sex as independent variables. OSA and OSA-by-sex interaction effects were assessed (P<0.05, corrected for multiple comparisons). RESULTS: Multiple regions of reduced cortical thickness appeared bilaterally in the superior frontal lobe in female OSA vs. all other groups. Significant thinning within the pre- and post-central gyri and the superior temporal gyrus, extending into the insula, appeared between the general OSA populations vs. control subjects. No areas showed increased thickness in OSA vs. controls or positive female OSA interaction effects. CONCLUSIONS: Reduced cortical thickness likely represents tissue atrophy from long term injury, including death of neurons and supporting glia from repeated intermittent hypoxic exposure in OSA, although disease comordities may also contribute to thinning. Lack of polysomnography in all control subjects means results may be confounded by undiagnosed OSA. The greater cortical injury in cognitive areas of female OSA patients may underlie enhanced symptoms in that group. The thinning associated with OSA in male and females OSA patients may contribute to autonomic dysregulation and impaired upper airway sensori-motor function.

Validation of time to task performance assessment method in simulation: A comparative design study.

BACKGROUND: There is a lack of objective and valid measures for assessing nursing clinical competence which could adversely impact patient safety. Therefore, we evaluated an objective assessment of clinical competence, Time to Task (ability to perform specific, critical nursing care activities within 5 min), and compared it to two subjective measures, (Lasater Clinical Judgement Rubric [LCJR] and common "pass/fail" assessment). DESIGN/METHODS: Using a prospective, "Known Groups" (Expert vs. Novice nurses) comparative design, Expert nurses (ICU nurses with >5 years of ICU experience) and Novice nurses (senior prelicensure nursing students) participated individually in a simulation of a patient in decompensated heart failure. Fourteen nursing instructors or preceptors, blinded to group assignment, reviewed 28 simulation videos (15 Expert and 13 Novice) and scored them using the LCJR and pass/fail assessments. Time to Task assessment was scored based on time thresholds for specific nursing actions prospectively set by an expert clinical panel. Statistical analysis consisted of Medians Test and sensitivity and specificity analyses. RESULTS: The LCJR total score was significantly different between Experts and Novices (p < 0.01) and revealed adequate sensitivity (ability to correctly identify "Expert" nurses; 0.72) but had a low specificity (ability to correctly identify "Novice" nurses; 0.40). For the subjective measure 'pass/fail', sensitivity was high (0.90) but specificity was low (0.47). The Time to Task measure had statistical significance between Expert and Novice groups (p < 0.01) and sensitivity (0.80) and specificity (0.85) were good. CONCLUSION: Commonly used subjective measures of clinical nursing competence have difficulties with achieving acceptable specificity. However, an objective measure, Time to Task, had good sensitivity and specificity in differentiating between groups. While more than one assessment instrument should be used to determine nurse competency, an objective measure, such as Time to Task, warrants further study.

Brain abnormalities in cognition, anxiety, and depression regulatory regions in adolescents with single ventricle heart disease.

BACKGROUND: Single ventricle heart disease (SVHD) adolescents show cognitive impairments and anxiety and depressive symptoms, indicating the possibility of brain injury in regions that control these functions. However, brain tissue integrity in cognition, anxiety, and depression regulatory sites in SVHD remains unclear. We examined brain tissue changes in SVHD compared to controls using T2-relaxometry procedures, which measure free water content and show tissue injury. METHODS: Proton-density and T2-weighted images, using a 3.0-Tesla MRI, as well as anxiety (Beck anxiety inventory [BAI]), depressive symptoms (patient health questionnaire-9 [PHQ-9]), and cognition (wide range assessment of memory and learning 2 [WRAML2] and Montreal cognitive assessment [MoCA]) data were collected from 20 SVHD (age: 15.8 ± 1.1 years, male/female: 11/9) and 36 controls (age: 16.0 ± 1.1 years, male/female: 19/17). Whole-brain T2-relaxation maps were calculated, normalized to a common space, smoothed, and compared between groups and sexes (analysis of covariance; covariates: age, sex; p < 0.001). RESULTS: SVHD subjects showed significantly increased BAI and PHQ-9 and reduced MoCA and WRAML2 scores over controls. Several brain regions in SVHD showed increased T2-relaxation values (chronic injury), including the cingulate, and insula, hippocampus/para-hippocampal gyrus, thalamus, hypothalamus, amygdala, frontal white matter, corpus callosum, brainstem, and cerebellar areas. Decreased T2-relaxation values (acute injury) emerged in a few regions, including the prefrontal and cerebellar cortices in SVHD over controls. In addition, male SVHD showed more brain changes over female SVHD. CONCLUSIONS: Adolescents with SVHD showed significant brain injury with variable male-female differences in areas that control cognition, anxiety, and depression, which may contribute to functional deficits found in the condition.

Regional brain gray matter changes in adolescents with single ventricle heart disease.

Adolescents with single ventricle heart disease (SVHD) show autonomic, mood, and cognitive deficits, indicating aberrations in brain areas that regulate these functions. However, the gray matter integrity in autonomic, mood, and cognitive control sites is unclear. We examined regional brain gray matter changes, using high-resolution T1-weighted images (3.0-T magnetic resonance scanner) with voxel based morphometry procedures, as well as mood and cognitive functions in SVHD (n=18; age, 15.7±1.1years; male, 10) and controls (n=31; age, 16.0±1.1years; male, 17). High-resolution T1-weighted images were realigned, gray matter tissue type partitioned, normalized to a common space, smoothed, and compared between groups (analysis of covariance; covariates, age and gender). The mood and cognitive scores were compared between groups using independent samples t-tests. SVHD subjects showed significantly altered mood and cognitive functions over controls. Significantly reduced gray matter emerged in multiple brain areas, including the thalamus, caudate nuclei, putamen, insula, prefrontal, post-central and precentral gyrus, occipital gyrus, para-hippocampal gyrus, temporal gyrus, and cerebellar sites in SVHD over controls. SVHD subjects show compromised gray matter integrity in autonomic, mood and cognitive control sites. The findings indicate that frequent deficits found in SVHD subjects have a brain structural basis in the condition.