Life space assessment and falls in older adults with multiple sclerosis.

BACKGROUND/OBJECTIVE: Falls research in older adults with MS (OAMS) is scarce, and no studies have reported on the association between life-space mobility and falls in this group. Herein, we hypothesized that higher baseline life-space scores would be associated with reduced odds of reporting falls during follow-up, and explored whether the association differed by MS subtype (progressive vs. relapsing-remitting). METHODS: OAMS (n = 91, mean age = 64.7 ± 4.3ys, %female = 66.9,%progressive MS = 30.7) completed the University of Alabama at Birmingham Life-Space-Assessment (UAB-LSA) scale and reported falls during a structured monthly telephone interview during follow-up (mean = 16.39 ± 11.44 months). General Estimated Equations (GEE) models were utilized to determine whether UAB-LSA scores predicted falls during follow-up. RESULTS: GEE models revealed that higher UAB-LSA scores were associated with a significant reduction in the odds of falling during follow-up (OR = 0.69, p = 0.012, 95 %CI = 0.51 to 0.92). Stratified analyses revealed that this association was significant in progressive (OR = 0.57, p = 0.004, 95 %CI = 0.39 to 0.84), but not relapsing-remitting (OR = 0.93, p = 0.779, 95 %CI = 0.57 to 1.53) MS. CONCLUSION: Higher life-space mobility was associated with lower odds of falling among OAMS with progressive subtype. The UAB-LSA may complement existing mobility measures for predicting fall risk.

Brain control of dual-task walking can be improved in aging and neurological disease.

The peak prevalence of multiple sclerosis has shifted into older age groups, but co-occurring and possibly synergistic motoric and cognitive declines in this patient population are poorly understood. Dual-task-walking performance, subserved by the prefrontal cortex, and compromised in multiple sclerosis and aging, predicts health outcomes. Whether acute practice can improve dual-task walking performance and prefrontal cortex hemodynamic response efficiency in multiple sclerosis has not been reported. To address this gap in the literature, the current study examined task- and practice-related effects on dual-task-walking and associated brain activation in older adults with multiple sclerosis and controls. Multiple sclerosis (n = 94, mean age = 64.76 ± 4.19 years) and control (n = 104, mean age = 68.18 ± 7.01 years) participants were tested under three experimental conditions (dual-task-walk, single-task-walk, and single-task-alpha) administered over three repeated counterbalanced trials. Functional near-infrared-spectroscopy was used to evaluate task- and practice-related changes in prefrontal cortex oxygenated hemoglobin. Gait and cognitive performances declined, and prefrontal cortex oxygenated hemoglobin was higher in dual compared to both single task conditions in both groups. Gait and cognitive performances improved over trials in both groups. There were greater declines over trials in oxygenated hemoglobin in dual-task-walk compared to single-task-walk in both groups. Among controls, but not multiple sclerosis participants, declines over trials in oxygenated hemoglobin were greater in dual-task-walk compared to single-task-alpha. Dual-task walking and associated prefrontal cortex activation efficiency improved during a single session, but improvement in neural resource utilization, although significant, was attenuated in multiple sclerosis participants. These findings suggest encouraging brain adaptability in aging and neurological disease.

Cortical thickness moderates intraindividual variability in prefrontal cortex activation patterns of older adults during walking.

OBJECTIVE: Increased intraindividual variability (IIV) in behavioral and cognitive performance is a risk factor for adverse outcomes but research concerning hemodynamic signal IIV is limited. Cortical thinning occurs during aging and is associated with cognitive decline. Dual-task walking (DTW) performance in older adults has been related to cognition and neural integrity. We examined the hypothesis that reduced cortical thickness would be associated with greater increases in IIV in prefrontal cortex oxygenated hemoglobin (HbO2) from single tasks to DTW in healthy older adults while adjusting for behavioral performance. METHOD: Participants were 55 healthy community-dwelling older adults (mean age = 74.84, standard deviation (SD) = 4.97). Structural MRI was used to quantify cortical thickness. Functional near-infrared spectroscopy (fNIRS) was used to assess changes in prefrontal cortex HbO2 during walking. HbO2 IIV was operationalized as the SD of HbO2 observations assessed during the first 30 seconds of each task. Linear mixed models were used to examine the moderation effect of cortical thickness throughout the cortex on HbO2 IIV across task conditions. RESULTS: Analyses revealed that thinner cortex in several regions was associated with greater increases in HbO2 IIV from the single tasks to DTW (ps < .02). CONCLUSIONS: Consistent with neural inefficiency, reduced cortical thickness in the PFC and throughout the cerebral cortex was associated with increases in HbO2 IIV from the single tasks to DTW without behavioral benefit. Reduced cortical thickness and greater IIV of prefrontal cortex HbO2 during DTW may be further investigated as risk factors for developing mobility impairments in aging.

Caudate volume and symptoms of apathy in older adults with multiple sclerosis.

BACKGROUND: Apathy is common in multiple sclerosis (MS) and neurological disease, but its presence and underlying brain mechanisms in older adults with MS (OAMS) have not been evaluated. OBJECTIVE: Examine apathy and its association with caudate nuclei volume in OAMS and controls. We hypothesized that compared to controls, OAMS would demonstrate: a) greater apathy; b) stronger associations between apathy and caudate nuclei volumes. METHODS: OAMS (n = 67, mean age = 64.55 ± 3.89) and controls (n = 74, mean age = 69.04 ± 6.32) underwent brain MRI, cognitive assessment, psychological, and motoric testing. Apathy was assessed through the apathy subscale of the 30-item Geriatric Depression Scale. RESULTS: OAMS reported greater apathy compared to controls (ß = 0.281, p = 0.004). Adjusted moderation analyses revealed a significantly stronger association between caudate volume and apathy (left: B = -1.156, p = 0.039, right: B = -1.163, p = 0.040) among OAMS compared to controls. Conditional effects revealed that in adjusted models, lower volume of both the left (b = -0.882, p = 0.037) and right (b = -0.891, p = 0.038) caudate nuclei was significantly associated with greater apathy only among OAMS. CONCLUSION: Caudate nuclei, which are susceptible to adverse MS effects and implicated in mediating cognitive and motor function, may influence the presence and severity of apathy in OAMS.

Differential Associations of Mobility With Fronto-Striatal Integrity and Lesion Load in Older Adults With and Without Multiple Sclerosis.

BACKGROUND: Mobility impairment is common in older persons with multiple sclerosis (MS), and further compounded by general age-related mobility decline but its underlying brain substrates are poorly understood. OBJECTIVE: Examine fronto-striatal white matter (WM) integrity and lesion load as imaging correlates of mobility outcomes in older persons with and without MS. METHODS: Fifty-one older MS patients (age 64.9 ± 3.7 years, 29 women) and 50 healthy, matched controls (66.2 ± 3.2 years, 24 women), participated in the study, which included physical and cognitive test batteries and 3T MRI imaging session. Primary imaging measures were fractional anisotropy (FA) and WM lesion load. The relationship between mobility impairment, defined using a validated short physical performance battery cutoff score, and neuroimaging measures was assessed with stratified logistic regression models. FA was extracted from six fronto-striatal circuits (left/right): dorsal striatum (dStr)-to-anterior dorsolateral prefrontal cortex (aDLPFC), dStr-to-posterior DLPFC, and ventral striatum (vStr)-to-ventromedial prefrontal cortex (VMPFC). RESULTS: Mobility impairment was significantly associated with lower FA in two circuits, left dStr-aDLPFC (P = .003) and left vStr-VMPFC (P = .004), in healthy controls but not in MS patients (P > .20), for fully adjusted regression models. Conversely, in MS patients but not in healthy controls, mobility impairment was significantly associated with greater lesion volume (P < .02). CONCLUSIONS: Comparing older persons with and without MS, we provide compelling evidence of a double dissociation between the presence of mobility impairment and two neuroimaging markers of white matter integrity, fronto-striatal fractional anisotropy, and whole brain lesion load.

Gray matter volume and within-task verbal fluency performance among older adults.

The current study examined the relationship between gray matter volume (GMV) and rate of word generation over the course of three consecutive 20-sec intervals in 60-sec letter and category verbal fluency (VF) tasks. Attenuated rate of within-person word generation in VF provides incremental information beyond total scores and predicts increased risk of incident Mild Cognitive Impairment (MCI). No studies to date, however, have determined the structural neural substrates underlying word generation rate in VF. Participants were 70 community-residing adults ≥ 65 years, who completed the letter and category VF tasks and a 3 T structural MRI scan. Linear mixed effects models (LMEMs) were used to determine the moderating effect of GMV on word generation rate. Whole brain voxel-wise LMEMs, adjusted for age, gender, education, Wide-Range Achievement Test - reading subtest score (WRAT3), and global health score, were run using permutation methods to correct for multiple comparisons. Lower GMV, primarily in frontal regions (superior frontal, rostral middle frontal, frontal pole, medial orbitofrontal, and pars orbitalis), were related to attenuated word generation rate, especially for letter VF. We propose that lower frontal GMV underlies inefficient executive word search processes reflected by attenuated word generation slope in letter VF amongst older adults.

Individual reserve in aging and neurological disease.

BACKGROUND AND OBJECTIVE: Cognitive and physical functions correlate and delineate aging and disease trajectories. Whereas cognitive reserve (CR) is well-established, physical reserve (PR) is poorly understood. We, therefore, developed and evaluated a novel and more comprehensive construct, individual reserve (IR), comprised of residual-derived CR and PR in older adults with and without multiple sclerosis (MS). We hypothesized that: (a) CR and PR would be positively correlated; (b) low CR, PR, and IR would be associated with worse study outcomes; (c) associations of brain atrophy with study outcomes would be stronger in lower compared to higher IR due to compensatory mechanisms conferred by the latter. METHODS: Older adults with MS (n = 66, mean age = 64.48 ± 3.84 years) and controls (n = 66, mean age = 68.20 ± 6.09 years), underwent brain MRI, cognitive assessment, and motoric testing. We regressed the repeatable battery for the assessment of neuropsychological status and short physical performance battery on brain pathology and socio-demographic confounders to derive independent residual CR and PR measures, respectively. We combined CR and PR to define a 4-level IR variable. The oral symbol digit modalities test (SDMT) and timed-25-foot-walk-test (T25FW) served as outcome measures. RESULTS: CR and PR were positively correlated. Low CR, PR and IR were associated with worse SDMT and T25FW performances. Reduced left thalamic volume, a marker of brain atrophy, was associated with poor SDMT and T25FW performances only in individuals with low IR. The presence of MS moderated associations between IR and T25FW performance. CONCLUSION: IR is a novel construct comprised of cognitive and physical dimensions representing collective within-person reserve capacities.

Cortical thickness and hippocampal volume in adolescent children with obstructive sleep apnea.

STUDY OBJECTIVES: Intermittent hypoxia and sleep fragmentation due to obstructive sleep apnea (OSA) may contribute to oxidative tissue damage and apoptotic neuronal cell death, inflammation, and intracellular edema in the brain. We examined whether OSA in overweight and obese adolescent children is associated with cortical thickness and hippocampal structure compared to overweight and obese controls and whether OSA severity is associated with measures of brain integrity. METHODS: We calculated cortical thickness and hippocampal subfield volumes from T1-weighted images of 45 controls (age 15.43 ±â€…1.73 years, 21 male) and 53 adolescent children with OSA (age 15.26 ±â€…1.63 years, 32 male) to investigate the association of childhood OSA with the alteration of cortical structure and hippocampal subfield structural changes. In addition, we investigated the correlation between OSA severity and cortical thickness or hippocampal subfield volume using Pearson's correlation analysis. RESULTS: We found cortical thinning in the right superior parietal area of adolescent children with OSA (cluster size 32.29 mm2, cluster-wise corrected p-value = .030) that was negatively correlated with apnea-hypopnea index (AHI) (R=-0.27, p-value = .009) and arousal index (R=-0.25, p-value = .014). In addition, the volume of the right subiculum-head area of the hippocampus of adolescent children with OSA was larger than controls (0.19 ±â€…0.02 ml vs. 0.18 ±â€…0.02 ml, ß = 13.79, false discovery rate corrected p-value = .044), and it was positively correlated with AHI (R = 0.23, p-value = .026) and arousal index (R = 0.31, p-value = .002). CONCLUSIONS: Our findings provide evidence for OSA-associated brain structure alterations in adolescent children prior to the onset of treatment that likely have important implications for timely intervention and continued monitoring of health outcomes.

Altered cortical structure network in children with obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by recurrent airway collapse during sleep, resulting in intermittent hypoxia and sleep fragmentation that may contribute to alternations in brain structure and function. We hypothesized that OSA in children reorganizes and alters cortical structure, which can cause changes in cortical thickness correlation between brain regions across subjects. METHODS: We constructed cortical structure networks based on cortical thickness measurements from 41 controls (age 15.54 ±â€…1.66 years, male 19) and 50 children with OSA (age 15.32 ±â€…1.65 years, male 29). The global (clustering coefficient [CC], path length, and small-worldness) and regional (nodal betweenness centrality, NBC) network properties and hub region distributions were examined between groups. RESULTS: We found increased CCs in OSA compared to controls across a wide range of network densities (p-value < .05) and lower NBC area under the curve in left caudal anterior cingulate, left caudal middle frontal, left fusiform, left transverse temporal, right pars opercularis, and right precentral gyri (p-value < .05). In addition, while most of the hub regions were the same between groups, the OSA group had fewer hub regions and a different hub distribution compared to controls. CONCLUSIONS: Our findings suggest that children with OSA exhibit altered global and regional network characteristics compared to healthy controls. Our approach to the investigation of cortical structure in children with OSA could prove useful in understanding the etiology of OSA-related brain functional disorders.

Automatic upper airway segmentation in static and dynamic MRI via anatomy-guided convolutional neural networks.

PURPOSE: Upper airway segmentation on MR images is a prerequisite step for quantitatively studying the anatomical structure and function of the upper airway and surrounding tissues. However, the complex variability of intensity and shape of anatomical structures and different modes of image acquisition commonly used in this application makes automatic upper airway segmentation challenging. In this paper, we develop and test a comprehensive deep learning-based segmentation system for use on MR images to address this problem. MATERIALS AND METHODS: In our study, both static and dynamic MRI data sets are utilized, including 58 axial static 3D MRI studies, 22 mid-retropalatal dynamic 2D MRI studies, 21 mid-retroglossal dynamic 2D MRI studies, 36 mid-sagittal dynamic 2D MRI studies, and 23 isotropic dynamic 3D MRI studies, involving a total of 160 subjects and over 20 000 MRI slices. Samples of static and 2D dynamic MRI data sets were randomly divided into training, validation, and test sets by an approximate ratio of 5:2:3. Considering that the variability of annotation data among 3D dynamic MRIs was greater than for other MRI data sets, we increased the ratio of training data for these data to improve the robustness of the model. We designed a unified framework consisting of the following procedures. For static MRI, a generalized region-of-interest (GROI) strategy is applied to localize the partitions of nasal cavity and other portions of upper airway in axial data sets as two separate subobjects. Subsequently, the two subobjects are segmented by two separate 2D U-Nets. The two segmentation results are combined as the whole upper airway structure. The GROI strategy is also applied to other MRI modes. To minimize false-positive and false-negative rates in the segmentation results, we employed a novel loss function based explicitly on these rates to train the segmentation networks. An inter-reader study is conducted to test the performance of our system in comparison to human variability in ground truth (GT) segmentation of these challenging structures. RESULTS: The proposed approach yielded mean Dice coefficients of 0.84±0.03, 0.89±0.13, 0.84±0.07, and 0.86±0.05 for static 3D MRI, mid-retropalatal/mid-retroglossal 2D dynamic MRI, mid-sagittal 2D dynamic MRI, and isotropic dynamic 3D MRI, respectively. The quantitative results show excellent agreement with manual delineation results. The inter-reader study results demonstrate that the segmentation performance of our approach is statistically indistinguishable from manual segmentations considering the inter-reader variability in GT. CONCLUSIONS: The proposed method can be utilized for routine upper airway segmentation from static and dynamic MR images with high accuracy and efficiency. The proposed approach has the potential to be employed in other dynamic MRI-related applications, such as lung or heart segmentation.

Cognitive Reserve Moderates the Efficiency of Prefrontal Cortex Activation Patterns of Gait in Older Adults.

BACKGROUND: Cognitive reserve (CR) protects against cognitive decline, but whether CR influences the efficiency of cortical control of gait has not been reported. The current study addressed this important gap in the literature. Specifically, we determined the role of CR in moderating the efficiency of functional near-infrared spectroscopy (fNIRS)-derived oxygenated hemoglobin (HbO2) in the prefrontal cortex (PFC) assessed during active walking. We hypothesized that higher CR would be associated with more efficient brain activation patterns. METHODS: Participants were 55 (mean age = 74.84; %female = 49.1) older adults who underwent the combined walking/fNIRS protocol and had magnetic resonance imaging data. We used an established dual-task walking paradigm that consisted of 3 task conditions: single-task walk (STW), single-task alpha (STA, cognitive task), and dual-task walk (DTW). Using the residual approach, CR was derived from a word-reading test score by removing variance accounted for by sociodemographic variables, tests of current cognitive functions, and a measure of structural brain integrity. RESULTS: CR moderated the change in fNIRS-derived HbO2 in the PFC across tasks. Higher CR was associated with smaller increases in fNIRS-derived HbO2 from the single tasks to dual-task walking (CR × DTW compared with STW: estimate = 0.183; p < .001; CR × DTW compared with STA: estimate = 0.257; p < .001). The moderation effect of CR remained significant when adjusting for multiple covariates and concurrent moderation effects of measures of gait performance, current cognitive functions, and structural integrity of the brain. CONCLUSION: The current study provided first evidence that higher CR was associated with better neural efficiency of walking in older adults.

Prefrontal cortex activation during dual-task walking in older adults is moderated by thickness of several cortical regions.

Dual tasking, a defined facet of executive control processes, is subserved, in part, by the prefrontal cortex (PFC). Previous functional near-infrared spectroscopy (fNIRS) studies revealed elevated PFC oxygenated hemoglobin (HbO2) under Dual-Task-Walk (DTW) compared to Single-Task Walk (STW) conditions. Based on the concept of neural inefficiency (i.e., greater activation coupled with similar or worse performance), we hypothesized that decreased cortical thickness across multiple brain regions would be associated with greater HbO2 increases from STW to DTW. Participants were 55 healthy community-dwelling older adults, whose cortical thickness was measured via MRI. HbO2 levels in the PFC, measured via fNIRS, were assessed during active walking under STW and DTW conditions. Statistical analyses were adjusted for demographics and behavioral performance. Linear mixed-effects models revealed that the increase in HbO2 from STW to DTW was moderated by cortical thickness in several regions. Specifically, thinner cortex in specific regions of the frontal, parietal, temporal, and occipital lobes, cingulate cortex, and insula was associated with greater increases in HbO2 levels from single to dual-task walking. In conclusion, participants with thinner cortex in regions implicated in higher order control of walking employed greater neural resources, as measured by increased HbO2, in the PFC during DTW, without demonstrating benefits to behavioral performance. To our knowledge, this is the first study to examine cortical thickness as a marker of neural inefficiency during active walking.

Upper airway effective compliance during wakefulness and sleep in obese adolescents studied via two-dimensional dynamic MRI and semiautomated image segmentation.

Novel biomarkers of upper airway biomechanics may improve diagnosis of obstructive sleep apnea syndrome (OSAS). Upper airway effective compliance (EC), the slope of cross-sectional area versus pressure estimated using computational fluid dynamics (CFD), correlates with apnea-hypopnea index (AHI) and critical closing pressure (Pcrit). The study objectives are to develop a fast, simplified method for estimating EC using dynamic MRI and physiological measurements and to explore the hypothesis that OSAS severity correlates with mechanical compliance during wakefulness and sleep. Five obese children with OSAS and five control subjects with obesity aged 12-17 yr underwent anterior rhinomanometry, polysomnography, and dynamic MRI with synchronized airflow measurement during wakefulness and sleep. Airway cross section in retropalatal and retroglossal section images was segmented using a novel semiautomated method that uses optimized singular value decomposition (SVD) image filtering and k-means clustering combined with morphological operations. Pressure was estimated using rhinomanometry Rohrer's coefficients and flow rate, and EC was calculated from the area-pressure slope during five normal breaths. Correlations between apnea-hypopnea index (AHI), EC, and cross-sectional area (CSA) change were calculated using Spearman's rank correlation. The semiautomated method efficiently segmented the airway with average Dice Coefficient above 89% compared with expert manual segmentation. AHI correlated positively with EC at the retroglossal site during sleep (rs = 0.74, P = 0.014) and with change of EC from wake to sleep at the retroglossal site (rs = 0.77, P = 0.01). CSA change alone did not correlate significantly with AHI. EC, a mechanical biomarker which includes both CSA change and pressure variation, is a potential diagnostic biomarker for studying and managing OSAS.NEW & NOTEWORTHY This study investigated the dynamics of the upper airway at retropalatal and retroglossal sites during wakefulness and sleep by evaluating the effective compliance (EC) of each site and its correlation with apnea-hypopnea index (AHI) using novel semiautomated image processing. AHI correlated significantly with retroglossal EC during sleep and change of retroglossal EC from wake to sleep. The results suggest EC as a promising noninvasive diagnostic marker for estimating the mechanical properties of various upper airway regions in patients with OSAS.

Effect of sleep on upper airway dynamics in obese adolescents with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: The biomechanical basis of obstructive sleep apnea syndrome (OSAS) may influence upper airway dynamics. In this study, we investigate dynamic changes during respiration in wakefulness and sleep in obese adolescents with and without OSAS. METHODS: Respiratory-gated dynamic magnetic resonance imaging (MRI) at the retropalatal and retroglossal regions was performed with simultaneous measurement of SpO2 and nasal-oral mask airflow and pressure. Airway cross-sectional area (CSA) was determined using AMIRA. Percent change in CSA was calculated from five continuous tidal breaths in states of wakefulness and sleep. Mixed effects models were used to evaluate interactions between group (OSAS/control), site (retropalatal/retroglossal), and stage (wake/sleep). RESULTS: We studied 24 children with OSAS (mean age 15.49 ± 2.00 years, mean apnea-hypopnea index [AHI] 16.53 ± 8.72 events/h) and 19 controls (mean age 14.86 ± 1.75 years, mean AHI 2.12 ± 1.69 events/h). Groups were similar in age, sex, height, weight, and BMI Z-score. Participants with OSAS had a 48.17% greater increase in percent change of airway CSA during sleep than controls (p < 0.0001), while there was no difference between groups during wakefulness (p = 0.6589). Additionally, participants with OSAS had a 48.80% increase in percent change of airway CSA during sleep as compared with wakefulness (p < 0.0001), whereas no such relationship was observed in controls (p = 0.5513). CONCLUSIONS: This study demonstrates significant effects of sleep on upper airway dynamics in obese children with OSAS. Dynamic MRI with physiological data can potentially provide further insight into the biomechanical basis of OSAS and assist in more effective management.

Multi-modal neuroimaging of dual-task walking: Structural MRI and fNIRS analysis reveals prefrontal grey matter volume moderation of brain activation in older adults.

It has been well established over the last two decades that walking is not merely an automatic, motoric activity; it also utilizes executive function circuits, which play an increasingly important role in walking for older people and those with mobility and cognitive deficits. Dual-task walking, such as walking while performing a cognitive task, is a necessary skill for everyday functioning, and has been shown to activate prefrontal lobe areas in healthy older people. Another well-established point in healthy aging is the loss of grey matter, and in particular loss of frontal lobe grey matter volume. However, the relationship between increased frontal lobe activity during dual-task walking and loss of frontal grey matter in healthy aging remains unknown. In the current study, we combined oxygenated hemoglobin (HbO2) data from functional near-infrared spectroscopy (fNIRS), taken during dual-task walking, with structural MRI volumetrics in a cohort of healthy older subjects to identify this relationship. We studied fifty-five relatively healthy, older participants (≥65 years) during two separate sessions: fNIRS to measure HbO2 changes between single-task (i.e., normal walking) and dual-task walking-while-talking, and high-resolution, structural MRI to measure frontal lobe grey matter volumes. Linear mixed effects modeling was utilized to determine the moderation effect of grey matter volume on the change in prefrontal oxygenated hemoglobin between the two walking tasks, while controlling for covariates including task performance. We found a highly significant interaction effect between frontal grey matter volume and task on HbO2 levels (p < 0.0001). Specifically, increased HbO2 levels during dual-task compared to single-task walking were associated with reduced frontal grey matter volume. Regional analysis identified bilateral superior and rostral middle gyri as the primary areas driving these results. The findings provide support for the concept of neural inefficiency: in the absence of behavioral gains, grey matter loss in relatively healthy, older individuals leads to over-activation of frontal lobe during a cognitively demanding walking task with established clinical and predictive utility.

Moderating Effect of White Matter Integrity on Brain Activation During Dual-Task Walking in Older Adults.

Using multimodal neuroimaging methods, the current study was designed to examine the relationship between white matter microstructural integrity (WMI) and changes in prefrontal cortex (PFC) oxygenated hemoglobin (HbO2) during active walking in older adults. Consistent with neural inefficiency, we hypothesized that worse WMI would be associated with a greater increase in PFC HbO2 from single to dual-task walking in the context of worse or similar gait performance. Fifty-five cognitively healthy older adults (mean age = 74.76 years, 49% women) underwent diffusion tensor imaging (DTI) to derive a whole-brain measure of fractional anisotropy (FA) and functional Near Infrared Spectroscopy (fNIRS), which measured PFC HbO2 during walking tasks. Gait velocity was assessed using an instrumented walkway. A linear mixed effects model revealed that HbO2 levels increased from single to dual-task walking (P < 0.01) given the greater cognitive demands inherent in the latter condition. Moreover, WMI moderated the effect of dual tasking on PFC HbO2 (P < 0.05). Specifically, worse WMI was associated with a larger increase in PFC HbO2 levels from single to dual-task walking in the context of similar gait velocity. Results suggest that compromised WMI may be a mechanism underlying inefficient brain response to cognitive demands of locomotion.

Biomechanics of the soft-palate in sleep apnea patients with polycystic ovarian syndrome.

Highly compliant tissue supporting the pharynx and low muscle tone enhance the possibility of upper airway occlusion in children with obstructive sleep apnea (OSA). The present study describes subject-specific computational modeling of flow-induced velopharyngeal narrowing in a female child with polycystic ovarian syndrome (PCOS) with OSA and a non-OSA control. Anatomically accurate three-dimensional geometries of the upper airway and soft-palate were reconstructed for both subjects using magnetic resonance (MR) images. A fluid-structure interaction (FSI) shape registration analysis was performed using subject-specific values of flow rate to iteratively compute the biomechanical properties of the soft-palate. The optimized shear modulus for the control was 38 percent higher than the corresponding value for the OSA patient. The proposed computational FSI model was then employed for planning surgical treatment for the apneic subject. A virtual surgery comprising of a combined adenoidectomy, palatoplasty and genioglossus advancement was performed to estimate the resulting post-operative patterns of airflow and tissue displacement. Maximum flow velocity and velopharyngeal resistance decreased by 80 percent and 66 percent respectively following surgery. Post-operative flow-induced forces on the anterior and posterior faces of the soft-palate were equilibrated and the resulting magnitude of tissue displacement was 63 percent lower compared to the pre-operative case. Results from this pilot study indicate that FSI computational modeling can be employed to characterize the mechanical properties of pharyngeal tissue and evaluate the effectiveness of various upper airway surgeries prior to their application.

Diffusion tensor imaging and ventricle volume quantification in patients with chronic shunt-treated hydrocephalus: a matched case-control study.

OBJECTIVEThe object of this study was to use diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) to characterize the long-term effects of hydrocephalus and shunting on white matter integrity and to investigate the relationship of ventricular size and alterations in white matter integrity with headache and quality-of-life outcome measures.METHODSPatients with shunt-treated hydrocephalus and age- and sex-matched healthy controls were recruited into the study and underwent anatomical and DTI imaging on a 3-T MRI scanner. All patients were clinically stable, had undergone CSF shunt placement before 2 years of age, and had a documented history of complaints of headaches. Outcome was scored based on the Headache Disability Inventory and the Hydrocephalus Outcome Questionnaire. Fractional anisotropy (FA) and other DTI-based measures (axial, radial, and mean diffusivity; AD, RD, and MD, respectively) were extracted in the corpus callosum and internal capsule with manual region-of-interest delineation and in other regions with TBSS. Paired t-tests, corrected with a 5% false discovery rate, were used to identify regions with significant differences between patients and controls. Within the patient group, linear regression models were used to investigate the relationship between FA or ventricular volume and outcome, as well as the effect of shunt-related covariates.RESULTSTwenty-one hydrocephalus patients and 21 matched controls completed the study, and their data were used in the final analysis. The authors found significantly lower FA for patients than for controls in 20 of the 48 regions, mostly posterior white matter structures, in periventricular as well as more distal tracts. Of these 20 regions, 17 demonstrated increased RD, while only 5 showed increased MD and 3 showed decreased AD. No areas of increased FA were observed. Higher FA in specific periventricular white matter tracts, tending toward FA in controls, was associated with increased ventricular size, as well as improved clinical outcome.CONCLUSIONSThe study shows that TBSS-based DTI is a sensitive technique for elucidating changes in white matter structures due to hydrocephalus and chronic CSF shunting and provides preliminary evidence that DTI may be a valuable tool for tailoring shunt procedures to monitor ventricular size following shunting and achieve optimal outcome, as well as for guiding the development of alternate therapies for hydrocephalus.

The Effects of Obstructive Sleep Apnea Syndrome on the Dentate Gyrus and Learning and Memory in Children.

Obstructive sleep apnea syndrome (OSAS) is associated with intermittent hypoxia and sleep loss. In children, impairments of cognitive function are important manifestations, but the underlying pathology is unknown. We hypothesized that OSAS would affect the dentate gyrus, a hippocampal subdivision essential to neurogenesis and cognition, and that this impact would further affect cognitive function in children. In children with OSAS (n = 11) and control subjects (n = 12; age and sex matched), we performed diffusion tensor imaging and structural MRI, polysomnography, and neuropsychological assessments. We found that OSAS was associated with decreased mean diffusivity of the left dentate gyrus (p = 0.002; false discovery rate corrected; adjusting for sex, age, and body mass index), showing a large effect size (partial η2 = 0.491), but not with any other structural measures across the brain. Decreased dentate gyrus mean diffusivity correlated with a higher apnea hypopnea index (Spearman's r = -0.50, p = 0.008) and a greater arousal index (r = -0.44, p = 0.017). OSAS did not significantly affect neuropsychological measures (p values >0.5); however, a lower verbal learning score correlated with lower dentate gyrus mean diffusivity (r = 0.54, p = 0.004). Path analysis demonstrated that dentate gyrus mean diffusivity mediates the impact of OSAS on verbal learning capacity. Finally, the diagnostic accuracy of a regression model based on dentate gyrus mean diffusivity reached 85.8% (cross validated). This study demonstrates a likely pathway of effects of OSAS on neurocognitive function in children, as well as potential utility of the dentate gyrus mean diffusivity as an early marker of brain pathology in children with OSAS.SIGNIFICANCE STATEMENT In this study we investigate the relationships between dentate gyrus structure, hippocampus-dependent cognition, and obstructive sleep apnea syndrome (OSAS). We demonstrate lower mean diffusivity of the dentate gyrus in children with OSAS, which correlates with a lower verbal learning and memory score. This study provides new evidence of disrupted microstructure of the dentate gyrus in children with OSAS that may help explain some of the neurocognitive deficits described in these children.

Computational fluid dynamics upper airway effective compliance, critical closing pressure, and obstructive sleep apnea severity in obese adolescent girls.

Obstructive sleep apnea syndrome (OSAS) is associated with anatomical abnormalities restricting upper airway size and functional factors decreasing pharyngeal dilator activity in sleep. In this study we hypothesized that OSAS is also associated with altered pharyngeal mechanical compliance during wakefulness. Five OSAS and six control obese girls between 14 and 18 years of age were studied. All underwent polysomnography, critical closing pressure (Pcrit) studies, and dynamic MRI of the upper airway during awake tidal breathing. Effective airway compliance was defined as the slope of cross-sectional area vs. average pressure between maximum inspiration and maximum expiration along the pharyngeal airway. Pharyngeal pressure fields were calculated by using image-based computational fluid dynamics and nasal resistance. Spearman correlations were calculated to test associations between apnea-hypopnea index (AHI), Pcrit, and airway compliance. Effective compliances in the nasopharynx (CNP) and velopharynx (CVP) were lower and negative in OSAS compared with controls: -4.4 vs. 1.9 (mm2/cmH2O, P = 0.012) and -2.1 vs. 3.9 (mm2/cmH2O, P = 0.021), respectively, suggesting a strong phasic pharyngeal dilator activity during inspiration in OSAS compared with controls. For all subjects, CNP and AHI correlated negatively (rS = -0.69, P = 0.02), and passive Pcrit correlated with CNP (rS = -0.76, P = 0.006) and with AHI (rS = 0.86, P = 0.0006). Pharyngeal mechanics obtained during wakefulness could be used to characterize subjects with OSAS. Moreover, negative effective compliance during wakefulness and its correlation to AHI and Pcrit suggest that phasic dilator activity of the upper pharynx compensates for negative pressure loads in these subjects.