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"Trenerry, Max R."
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Regional variation in cerebral oxygen metabolism during acute severe hypoxia with temporary cognitive impairment
2025
•Hypoxia impairs inhibitory control and sustained attention during the Go/No-Go task.•A modified Davis model for normoxia-hypoxia differences estimates CMRO2 changes.•Regional CMRO2 reductions reveal significant heterogeneity across brain networks.•Attention and executive frontoparietal networks exhibited the largest CMRO2 reductions.•Adaptive prioritization of brain networks explains cognitive impairments in hypoxia.
Acute exposure to severe hypoxia impairs cognitive performance, yet the integrated brain mechanisms underlying this temporary decline remain unclear. This study examined regional variations in cerebral oxygen metabolism during acute hypoxia and their relationship to cognitive impairment. Eleven young, healthy participants (26.5 ± 4.5 years old) performed the Go/No-Go task during two sessions, each of which includes three minutes of hypoxia (FiO2 = 7.7 %). Cerebral blood flow (CBF) was assessed using pCASL MRI in one session, while blood-oxygen-level-dependent (BOLD) signals were acquired in another. Fractional changes in CBF (δCBF) and BOLD (δBOLD) were combined using a modified Davis model, adjusted for physiological differences between normoxia and acute and severe hypoxia, to calculate the fractional change in cerebral metabolic rate of oxygen (δCMRO2). Group-level z-normalized δCMRO2 maps revealed significant regional heterogeneity, with most pronounced reductions in areas associated with the dorsal and ventral attention networks and executive frontoparietal networks. These regions exhibited δCMRO2 reductions exceeding the hemispheric average (-9.6 ± 7.9 %) and were associated with increased commission errors during the Go/No-Go task, reflecting impaired inhibitory control and sustained attention. This study highlights the brain's adaptive prioritization of certain networks under oxygen deprivation, providing insights into the physiological mechanisms underlying hypoxia-induced cognitive impairments. These findings enhance our understanding of how acute hypoxia affects brain function, emphasizing the importance of network-specific adaptations in maintaining cognitive performance during oxygen deprivation.
Journal Article
Autoimmune Dementia: Clinical Course and Predictors of Immunotherapy Response
by
Flanagan, Eoin P.
,
Drubach, Daniel A.
,
Lennon, Vanda A.
in
Autoimmunity - immunology
,
Biological and medical sciences
,
Care and treatment
2010
To define the diagnostic characteristics and predictors of treatment response in patients with suspected autoimmune dementia.
Between January 1, 2002, and January 1, 2009, 72 consecutive patients received immunotherapy for suspected autoimmune dementia. Their baseline clinical, radiologic, and serologic characteristics were reviewed and compared between patients who were responsive to immunotherapy and those who were not. Patients were classified as responders if the treating physician had reported improvement after immunotherapy (documented in 80% by the Kokmen Short Test of Mental Status, neuropsychological testing, or both).
Initial immunotherapeutic regimens included methylprednisolone in 56 patients (78%), prednisone in 12 patients (17%), dexamethasone in 2 patients (3%), intravenous immune globulin in 1 patient (1%), and plasma exchange in 1 patient (1%). Forty-six patients (64%) improved, most in the first week of treatment. Thirty-five percent of these immunotherapy responders were initially diagnosed as having a neurodegenerative or prion disorder. Pretreatment and posttreatment neuropsychological score comparisons revealed improvement in almost all cognitive domains, most notably learning and memory. Radiologic or electroencephalographic improvements were reported in 22 (56%) of 39 patients. Immunotherapy responsiveness was predicted by a subacute onset (
P<.001), fluctuating course (
P<.001), tremor (
P=.007), shorter delay to treatment (
P=.005), seropositivity for a cation channel complex autoantibody (
P=.01; neuronal voltage-gated potassium channel more than calcium channel or neuronal acetylcholine receptor), and elevated cerebrospinal fluid protein (>100 mg/dL) or pleocytosis (
P=.02). Of 26 immunotherapy-responsive patients followed up for more than 1 year, 20 (77%) relapsed after discontinuing immunotherapy.
Identification of clinical and serologic clues to an autoimmune dementia allows early initiation of immunotherapy, and maintenance if needed, thus favoring an optimal outcome.
Journal Article
Sporadic leucodystrophy with neuroaxonal spheroids: persistence of DWI changes and neurocognitive profiles: a case study
by
Pittock, Sean J
,
Krecke, Karl
,
Mateen, Farrah J
in
Axons - pathology
,
Behavioural disorder
,
Biological and medical sciences
2010
Leucodystrophy with neuroaxonal spheroids (LNS) is rare. There have been fewer than 10 sporadic cases reported, all occurring in the fourth to sixth decades of life. Previously unreported diffusion weighted imaging (DWI) changes on brain imaging in LNS are described as well as the first neurocognitive profile of this disorder in a 24-year-old woman. Neuropsychological testing demonstrated a global cognitive decline, with deficits most representative of a frontal-subcortical dementia. Bright DWI and corresponding dark apparent diffusion coefficient changes were initially mistaken for acute cerebral infarction but then persisted for 19 weeks. Biopsy of a bright DWI lesion showed no evidence of vascular disease and confirmed this rare diagnosis. Given the number of patients with the diagnosis of cerebrovascular disease, supported by DWI findings, we propose other milder cases of LNS may be overlooked.
Journal Article
Differential neuropsychological test sensitivity to left temporal lobe epilepsy
by
WESTERVELD, MICHAEL
,
CHELUNE, GORDON
,
BOWDEN, STEPHEN C.
in
Adult
,
Anterior temporal lobectomy
,
Case-Control Studies
2008
We examined the sensitivity of the Rey Auditory Verbal Learning Test (AVLT), California Verbal Learning Test (CVLT), Boston Naming Test (BNT), and Multilingual Aphasia Examination Visual Naming subtest (MAE VN) to lateralized temporal lobe epilepsy (TLE) in patients who subsequently underwent anterior temporal lobectomy. For the AVLT (n = 189), left TLE patients performed more poorly than their right TLE counterparts [left TLE = 42.9 (10.6), right TLE = 47.7 (9.9); p < .002 (Cohen's d = .47)]. Although statistically significant, the CVLT group difference (n = 212) was of a smaller magnitude [left LTE = 40.7 (11.1), right TLE = 43.8 (9.9); (p < .03, Cohen's d = .29)] than the AVLT. Group differences were also present for both measures of confrontation naming ability [BNT: left LTE = 43.1 (8.9), right TLE = 48.1 (8.9); p < .001 (Cohen's d = .56); MAE VN: left TLE = 42.2, right TLE = 45.6, p = .02 (Cohen's d = .36)]. When these data were modeled in independent logistic regression analyses, the AVLT and BNT both significantly predicted side of seizure focus, although the positive likelihood ratios were modest. In the subset of 108 patients receiving both BNT and AVLT, the AVLT was the only significant predictor of seizure laterality, suggesting individual patient variability regarding whether naming or memory testing may be more sensitive to lateralized TLE. (JINS, 2008, 14, 394–400.)
Journal Article
Brain functional connectivity initiates structured reorganization at a critical oxygen threshold during hypoxia
2025
The human brain dynamically adapts to hypoxia, a reduction in oxygen essential for metabolism. The brain's adaptive response to hypoxia, however, remains unclear. We investigated dynamic functional connectivity (FC) in healthy adults under acute hypoxia (FiO
= 7.7%, 11.8%) using BOLD fMRI, physiological monitoring (PetO
, PetCO
, SpO
), and a Go/No-Go task. Principal component analysis identified a hypoxia-responsive FC component involving 400 cerebral parcels. This component emerged with a critical drop in PetO
(~53 mmHg), preceding changes in SpO
, BOLD signals, and behavior. These FC changes were network-specific and centered on the default mode network (DMN), which selectively synchronized with other high-level cognitive networks. In contrast, visual networks remained stable and segregated from the DMN. These results suggest that the brain proactively reorganizes its functional architecture in anticipation of oxygen decline, rather than in response to it. FC-based markers may offer early indicators of vulnerability in neurological or neurodegenerative conditions.
Journal Article
The Mayo Clinic Cohort Study of Personality and Aging: Design and Sampling, Reliability and Validity of Instruments, and Baseline Description
2006
We established a historical cohort of 7,216 subjects who completed the Minnesota Multiphasic Personality Inventory (MMPI) at the Mayo Clinic from 1962 through 1965 for research (not clinical indication), and who resided within a 120-mile radius centered in Rochester, Minnesota. We describe here the overall cohort design and sampling, we report results concerning reliability and validity, and we describe age and sex patterns at baseline for four MMPI scores of primary interest (depression, anxiety, social introversion, and negativity). Subjects excluded from the cohort because of missing data had MMPI scores similar to subjects included (after appropriate rescaling). A cut-off specific for age and sex at the 75th percentile of the distribution of raw scores was valid compared with the traditional clinical cut-off (T scores plus one standard deviation). Baseline scores for all four scales were higher in women than in men at all ages (all p < 0.0001). Depression and social introversion scores showed an increasing trend with age in both sexes (Spearman rank correlation, rho = 0.05 and 0.08, respectively, p < 0.0001 for both). Baseline scores on the anxiety scale showed a decreasing trend with age in both sexes (rho = –0.06, p < 0.0001). Negativity scores remained relatively stable with age in both sexes (rho = 0.03, p = 0.01). We found a high correlation between the anxiety score and the negativity score (rho = 0.90, p < 0.0001) even after the exclusion of overlapping items (rho = 0.68, p < 0.0001). This newly established historical cohort study provides opportunities to test hypotheses regarding the link between personality and aging, aging-related diseases, and overall mortality.
Journal Article
Toward Integrating Cognitive Neuroscience: One Method Deserves Another
2008
Methods in Mind. Carl Senior, Tamara Russell, and Michael S. Gazzaniga (Eds.). 2006. Cambridge, MA: The MIT Press, 394 pp., $55.00 (HB) In the preface of Methods in Mind, the editors express their intent to provide a text that integrates different cognitive neuroscience methods. The chapter authors were given the lofty charge of describing their method of choice, considering the method's strengths and limitations, and how other methods might be integrated. By-and-large, the editors have achieved their goal.
Book Review