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Ronald M. Harper

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5 papers
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5

YNICL Journal 2018 Journal Article

Regional cortical thickness changes accompanying generalized tonic-clonic seizures

  • Jennifer A. Ogren
  • Raghav Tripathi
  • Paul M. Macey
  • Rajesh Kumar
  • John M. Stern
  • Dawn S. Eliashiv
  • Luke A. Allen
  • Beate Diehl

Objective: Generalized tonic-clonic seizures are accompanied by cardiovascular and respiratory sequelae that threaten survival. The frequency of these seizures is a major risk factor for sudden unexpected death in epilepsy (SUDEP), a leading cause of untimely death in epilepsy. The circumstances accompanying such fatal events suggest a cardiovascular or respiratory failure induced by unknown neural processes rather than an inherent cardiac or lung deficiency. Certain cortical regions, especially the insular, cingulate, and orbitofrontal cortices, are key structures that integrate sensory input and influence diencephalic and brainstem regions regulating blood pressure, cardiac rhythm, and respiration; output from those cortical regions compromised by epilepsy-associated injury may lead to cardiorespiratory dysregulation. The aim here was to assess changes in cortical integrity, reflected as cortical thickness, relative to healthy controls. Cortical alterations in areas that influence cardiorespiratory action could contribute to SUDEP mechanisms. Methods: < 0.05 corrected). Results: Increased cortical thickness appeared in post-central gyri, insula, and subgenual, anterior, posterior, and isthmus cingulate cortices. Post-central gyri increases were greater in females, while males showed more extensive cingulate increases. Frontal and temporal cortex, lateral orbitofrontal, frontal pole, and lateral parietal and occipital cortices showed thinning. The extents of thickness changes were sex- and hemisphere-dependent, with only males exhibiting right-sided and posterior cingulate thickening, while females showed only left lateral orbitofrontal thinning. Regional cortical thickness showed modest correlations with seizure frequency, but not epilepsy duration. Significance: Cortical thickening and thinning occur in patients with generalized tonic-clonic seizures, in cardiovascular and somatosensory areas, with extent of changes sex- and hemisphere-dependent. The data show injury in key autonomic and respiratory cortical areas, which may contribute to dysfunctional cardiorespiratory patterns during seizures, as well as to longer-term SUDEP risk.

YNICL Journal 2018 Journal Article

Sex-specific hippocampus volume changes in obstructive sleep apnea

  • Paul M. Macey
  • Janani P. Prasad
  • Jennifer A. Ogren
  • Ammar S. Moiyadi
  • Ravi S. Aysola
  • Rajesh Kumar
  • Frisca L. Yan-Go
  • Mary A. Woo

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 ± SD: 46.3 ± 8.8 years; mean AHI ± SD: 34.1 ± 21.5 events/h;50 male) and 59 healthy age-matched control (46.8 ± 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 ± 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.

YNICL Journal 2014 Journal Article

Brain putamen volume changes in newly-diagnosed patients with obstructive sleep apnea

  • Rajesh Kumar
  • Salar Farahvar
  • Jennifer A. Ogren
  • Paul M. Macey
  • Paul M. Thompson
  • Mary A. Woo
  • Frisca L. Yan-Go
  • Ronald M. Harper

Obstructive sleep apnea (OSA) is accompanied by cognitive, motor, autonomic, learning, and affective abnormalities. The putamen serves several of these functions, especially motor and autonomic behaviors, but whether global and specific sub-regions of that structure are damaged is unclear. We assessed global and regional putamen volumes in 43 recently-diagnosed, treatment-naïve OSA (age, 46.4 ± 8.8 years; 31 male) and 61 control subjects (47.6 ± 8.8 years; 39 male) using high-resolution T1-weighted images collected with a 3.0-Tesla MRI scanner. Global putamen volumes were calculated, and group differences evaluated with independent samples t-tests, as well as with analysis of covariance (covariates; age, gender, and total intracranial volume). Regional differences between groups were visualized with 3D surface morphometry-based group ratio maps. OSA subjects showed significantly higher global putamen volumes, relative to controls. Regional analyses showed putamen areas with increased and decreased tissue volumes in OSA relative to control subjects, including increases in caudal, mid-dorsal, mid-ventral portions, and ventral regions, while areas with decreased volumes appeared in rostral, mid-dorsal, medial-caudal, and mid-ventral sites. Global putamen volumes were significantly higher in the OSA subjects, but local sites showed both higher and lower volumes. The appearance of localized volume alterations points to differential hypoxic or perfusion action on glia and other tissues within the structure, and may reflect a stage in progression of injury in these newly-diagnosed patients toward the overall volume loss found in patients with chronic OSA. The regional changes may underlie some of the specific deficits in motor, autonomic, and neuropsychologic functions in OSA.