Scopus list of publications for August 20, 2023
Effectiveness assessment of repetitive transcranial alternating current stimulation with concurrent EEG and fNIRS measurement
(2023) Health Information Science and Systems, 11 (1), art. no. 35, .
Yang, D.a b , Ghafoor, U.a , Eggebrecht, A.T.b c , Hong, K.-S.a d
a School of Mechanical Engineering, Pusan National University, Busan, 46241, South Korea
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63100, United States
c Department of Biomedical Engineering, Washington University, St. Louis, MO 63130, United States
d Institute for Future, School of Automation, Qingdao University, Shandong, Qingdao, 266071, China
Abstract
Transcranial alternating current stimulation (tACS) exhibits the capability to interact with endogenous brain oscillations using an external low-intensity sinusoidal current and influences cerebral function. Despite its potential benefits, the physiological mechanisms and effectiveness of tACS are currently a subject of debate and disagreement. The aims of our study are to (i) evaluate the neurological and behavioral impact of tACS by conducting repetitive sham-controlled experiments and (ii) propose criteria to evaluate effectiveness, which can serve as a benchmark to determine optimal individual-based tACS protocols. In this study, 15 healthy adults participated in the experiment over two visiting: sham and tACS (i.e., 5 Hz, 1 mA). During each visit, we used multimodal recordings of the participants’ brain, including simultaneous electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS), along with a working memory (WM) score to quantify neurological effects and cognitive changes immediately after each repetitive sham/tACS session. Our results indicate increased WM scores, hemodynamic response strength, and EEG power in theta and delta bands both during and after the tACS period. Additionally, the observed effects do not increase with prolonged stimulation time, as the effects plateau towards the end of the experiment. In conclusion, our proposed closed-loop scheme offers a promising advance for evaluating the effectiveness of tACS during the stimulation session. Specifically, the assessment criteria use participant-specific brain-based signals along with a behavioral output. Moreover, we propose a feedback efficacy score that can aid in determining the optimal stimulation duration based on a participant-specific brain state, thereby preventing the risk of overstimulation. © 2023, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Author Keywords
Brain stimulation; Electroencephalography (EEG); Functional near-infrared spectroscopy (fNIRS); Hemodynamic response (HR); Transcranial alternating current stimulation (tACS); Working memory (WM)
Funding details
Ministry of Science, ICT and Future PlanningMSIPRS-2023–00207954
National Research Foundation of KoreaNRFNRF-2020R1A2B5B03096000
Document Type: Article
Publication Stage: Final
Source: Scopus
Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration
(2023) Life Science Alliance, 6 (11), .
Drieu, A.a b , Du, S.a b , Kipnis, M.c d e , Bosch, M.E.c d e , Herz, J.a b , Lee, C.c d e , Jiang, H.c d e , Manis, M.c d e , Ulrich, J.D.c d e , Kipnis, J.a b , Holtzman, D.M.c d e , Gratuze, M.c d e f
a https://ror.org/04cf69335 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
b https://ror.org/04cf69335 Center for Brain Immunology and Glia, Washington University School of Medicine, St. Louis, MO, United States
c https://ror.org/04cf69335 Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
d https://ror.org/04cf69335 Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
e https://ror.org/04cf69335 Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
f Aix-Marseille University, Marseille, France
Abstract
Parenchymal border macrophages (PBMs) reside close to the central nervous system parenchyma and regulate CSF flow dynamics. We recently demonstrated that PBMs provide a clearance pathway for amyloid-β peptide, which accumulates in the brain in Alzheimer’s disease (AD). Given the emerging role for PBMs in AD, we explored how tau pathology affects the CSF flow and the PBM populations in the PS19 mouse model of tau pathology. We demonstrated a reduction of CSF flow, and an increase in an MHCII+PBM subpopulation in PS19 mice compared with WT littermates. Consequently, we asked whether PBM dysfunction could exacerbate tau pathology and tau-mediated neurodegeneration. Pharmacological depletion of PBMs in PS19 mice led to an increase in tau pathology and tau-dependent neurodegeneration, which was independent of gliosis or aquaporin-4 depolarization, essential for the CSF-ISF exchange. Together, our results identify PBMs as novel cellular regulators of tau pathology and tau-mediated neurodegeneration. © 2023 Drieu et al.
Document Type: Article
Publication Stage: Final
Source: Scopus
Effect of Direction and Frequency of Skull Motion on Mechanical Vulnerability of the Human Brain
(2023) Journal of Biomechanical Engineering, 145 (11), .
Okamoto, R.J.a , Escarcega, J.D.b , Alshareef, A.c , Carass, A.d , Prince, J.L.d , Johnson, C.L.e , Bayly, P.V.b
a Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, MSC 1185-208-125, One Brookings Drive, St. Louis, MO 63130, United States
b Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63130, United States
c Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States
d Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD 21218, United States
e Department of Biomedical Engineering, University of Delaware, Newark, DE 19713
Abstract
Strain energy and kinetic energy in the human brain were estimated by magnetic resonance elastography (MRE) during harmonic excitation of the head, and compared to characterize the effect of loading direction and frequency on brain deformation. In brain MRE, shear waves are induced by external vibration of the skull and imaged by a modified MR imaging sequence; the resulting harmonic displacement fields are typically “inverted” to estimate mechanical properties, like stiffness or damping. However, measurements of tissue motion from MRE also illuminate key features of the response of the brain to skull loading. In this study, harmonic excitation was applied in two different directions and at five different frequencies from 20 to 90 Hz. Lateral loading induced primarily left-right head motion and rotation in the axial plane; occipital loading induced anterior-posterior head motion and rotation in the sagittal plane. The ratio of strain energy to kinetic energy (SE/KE) depended strongly on both direction and frequency. The ratio of SE/KE was approximately four times larger for lateral excitation than for occipital excitation and was largest at the lowest excitation frequencies studied. These results are consistent with clinical observations that suggest lateral impacts are more likely to cause injury than occipital or frontal impacts, and also with observations that the brain has low-frequency (∼10 Hz) natural modes of oscillation. The SE/KE ratio from brain MRE is potentially a simple and powerful dimensionless metric of brain vulnerability to deformation and injury. Copyright © 2023 by ASME.
Document Type: Article
Publication Stage: Final
Source: Scopus
Specialized late cingulo-opercular network activation elucidates the mechanisms underlying decisions about ambiguity
(2023) NeuroImage, 279, art. no. 120314, .
Pierce, J.E.a , Petro, N.M.b c , Clancy, E.d , Gratton, C.e , Petersen, S.E.f , Neta, M.a
a Center for Brain, Biology, and Behavior, University of Nebraska-Lincoln, Lincoln, NE, United States
b Institute for Human Neuroscience, Boys Town National Research Hospital, Boys Town, NE, United States
c Center for Pediatric Brain Health, Boys Town National Research Hospital, Boys Town, NE, United States
d Department of Psychology, University of Guelph, Guelph, ON, Canada
e Department of Psychology, Florida State University, Tallahassee, FL, United States
f Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Cortical task control networks, including the cingulo-opercular (CO) network play a key role in decision-making across a variety of functional domains. In particular, the CO network functions in a performance reporting capacity that supports successful task performance, especially in response to errors and ambiguity. In two studies testing the contribution of the CO network to ambiguity processing, we presented a valence bias task in which masked clearly and ambiguously valenced emotional expressions were slowly revealed over several seconds. This slow reveal task design provides a window into the decision-making mechanisms as they unfold over the course of a trial. In the main study, the slow reveal task was administered to 32 young adults in the fMRI environment and BOLD time courses were extracted from regions of interest in three control networks. In a follow-up study, the task was administered to a larger, online sample (n = 81) using a more extended slow reveal design with additional unmasking frames. Positive judgments of surprised faces were uniquely accompanied by slower response times and strong, late activation in the CO network. These results support the initial negativity hypothesis, which posits that the default response to ambiguity is negative and positive judgments are associated with a more effortful controlled process, and additionally suggest that this controlled process is mediated by the CO network. Moreover, ambiguous trials were characterized by a second CO response at the end of the trial, firmly placing CO function late in the decision-making process. © 2023
Author Keywords
Ambiguity; Cingulo-opercular network; Decision-making; Emotion; fMRI
Funding details
National Institutes of HealthNIHNIMH111640
Document Type: Article
Publication Stage: Final
Source: Scopus
Widespread frontoparietal fMRI activity is greatly affected by changes in criterion placement, not discriminability, during recognition memory and visual detection tests
(2023) NeuroImage, 279, art. no. 120307, .
Layher, E.a , Santander, T.a , Chakravarthula, P.b , Marinsek, N.c , Turner, B.O.d , Eckstein, M.P.a , Miller, M.B.a
a Department of Psychological and Brain Sciences, University of California, Santa Barbara, United States
b Department of Radiology, Washington University, St. Louis, United States
c Evidation Health, Inc., San Mateo, CA 94401, United States
d Wee Kim Wee School of Communication and Information, Nanyang Technological University, Singapore, Singapore
Abstract
Widespread frontoparietal activity is consistently observed in recognition memory tests that compare studied (“target”) versus unstudied (“nontarget”) responses. However, there are conflicting accounts that ascribe various aspects of frontoparietal activity to mnemonic evidence versus decisional processes. According to Signal Detection Theory, recognition judgments require individuals to decide whether the memory strength of an item exceeds an evidence threshold—the decision criterion—for reporting previously studied items. Yet, most fMRI studies fail to manipulate both memory strength and decision criteria, making it difficult to appropriately identify frontoparietal activity associated with each process. In the current experiment, we manipulated both discriminability and decision criteria across recognition memory and visual detection tests during fMRI scanning to assess how frontoparietal activity is affected by each manipulation. Our findings revealed that maintaining a conservative versus liberal decision criterion drastically affects frontoparietal activity in target versus nontarget response contrasts for both recognition memory and visual detection tests. However, manipulations of discriminability showed virtually no differences in frontoparietal activity in target versus nontarget response or item contrasts. Comparing across task domains, we observed similar modulations of frontoparietal activity across criterion conditions, though the recognition memory task revealed larger activations in both magnitude and spatial extent in these contrasts. Nonetheless, there appears to be some domain specificity in frontoparietal activity associated with the maintenance of a conservative versus liberal criterion. We propose that widespread frontoparietal activity observed in target versus nontarget contrasts is largely attributable to response bias where increased activity may reflect inhibition of a prepotent response, which differs depending on whether a person maintains a conservative versus liberal decision criterion. © 2023
Author Keywords
Criterion shifting; fMRI; Frontoparietal cortex; Recognition memory; Visual detection
Funding details
Army Research OfficeAROW911NF-19-2-0026
Institute for Collaborative BiotechnologiesICB
Document Type: Article
Publication Stage: Final
Source: Scopus
Gamma-band Intermuscular Connectivity Is Associated With Increased Neural Drive to Pelvic Floor Muscles in Women With Interstitial Cystitis/Bladder Pain Syndrome
(2023) The Journal of Urology, 210 (3), pp. 465-471.
Houston, M.a , Dias, N.a , Peng, Y.a , Spitznagle, T.b , Harris-Hayes, M.b , Lai, H.H.c , Zhang, Y.a
a Department of Biomedical Engineering, University of Houston, Houston, TX, United States
b Program in Physical Therapy, Washington University School of Medicine, St Louis, MO, United States
c Division of Urologic Surgery, Departments of Surgery and Anesthesiology, Washington University School of Medicine, St Louis, MO, United States
Abstract
PURPOSE: Interstitial cystitis/bladder pain syndrome patients can experience overactive pelvic floor muscle activity at rest. While the frequency power spectrum of pelvic floor muscle has briefly been explored, intermuscular connectivity of the pelvic floor muscle has yet to be studied, which may provide useful insight into the neurological component, ie, neural drive to muscles, in interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: High-density surface electromyography was collected from 15 female interstitial cystitis/bladder pain syndrome patients with pelvic floor tenderness and 15 urologically healthy female controls. Intermuscular connectivity was calculated across the maximally active locations of the left and right sides of the pelvic floor muscle as identified from the root mean squared amplitude at rest and compared with Student t tests for common sensorimotor rhythms involved in motor control: alpha (8-12 Hz), beta (13-30 Hz), and gamma (31-70 Hz) frequency bands. The root mean squared amplitudes at rest were also compared across groups. RESULTS: The resting root mean squared amplitude of the pelvic floor muscle was significantly greater in female interstitial cystitis/bladder pain syndrome patients compared to healthy female controls (P = .0046). The gamma-band intermuscular connectivity was significantly different between rest and pelvic floor muscle contraction (P = .0001) for healthy female controls, but not for female patients with interstitial cystitis/bladder pain syndrome (P = .1214). Both results indicate an elevated neural drive to pelvic floor muscle at rest in female interstitial cystitis/bladder pain syndrome patients. CONCLUSIONS: Gamma-band pelvic floor muscle connectivity in female interstitial cystitis/bladder pain syndrome patients is increased at rest. The results of this study may provide insight into the impaired neural drive to pelvic floor muscle implicated with interstitial cystitis/bladder pain syndrome.
Author Keywords
coordination; cystitis; electromyography; interstitial; pelvic floor
Document Type: Article
Publication Stage: Final
Source: Scopus
Entry receptor LDLRAD3 is required for Venezuelan equine encephalitis virus peripheral infection and neurotropism leading to pathogenesis in mice
(2023) Cell Reports, 42 (8), art. no. 112946, .
Kafai, N.M.a b , Janova, H.a , Cain, M.D.a , Alippe, Y.a , Muraro, S.a , Sariol, A.a , Elam-Noll, M.a , Klein, R.S.a b c , Diamond, M.S.a b d e
a Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
d Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, United States
e The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Venezuelan equine encephalitis virus (VEEV) is an encephalitic alphavirus responsible for epidemics of neurological disease across the Americas. Low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3) is a recently reported entry receptor for VEEV. Here, using wild-type and Ldlrad3-deficient mice, we define a critical role for LDLRAD3 in controlling steps in VEEV infection, pathogenesis, and neurotropism. Our analysis shows that LDLRAD3 is required for efficient VEEV infection and pathogenesis prior to and after central nervous system invasion. Ldlrad3-deficient mice survive intranasal and intracranial VEEV inoculation and show reduced infection of neurons in different brain regions. As LDLRAD3 is a determinant of pathogenesis and an entry receptor required for VEEV infection of neurons of the brain, receptor-targeted therapies may hold promise as countermeasures. © 2023 The Author(s)
Author Keywords
alphavirus, pathogenesis, receptor, tropism, brain, mice, animal model, infection, neuron; CP: Microbiology
Funding details
National Institutes of HealthNIHF30AI164842, R01AI14367, R01AI164653, T32 AI007172
Defense Threat Reduction AgencyDTRAW15QKN1691002
University of WashingtonUW
Vir Biotechnology
Document Type: Article
Publication Stage: Final
Source: Scopus
Rho enhancers play unexpectedly minor roles in Rhodopsin transcription and rod cell integrity
(2023) Scientific Reports, 13 (1), p. 12899.
Sun, C.a , Ruzycki, P.A.a b , Chen, S.a c
a Department of Ophthalmology and Visual Sciences, Washington University, Saint Louis, MO, USA
b Department of Genetics, Washington University, 660 South Euclid Avenue, MSC 8096-0006-11, Saint Louis, MO, 63110, USA
c Department of Developmental Biology, Washington University, 660 South Euclid Avenue, MSC 8096-0006-06, Saint Louis, MO, 63110, USA
Abstract
Enhancers function with a basal promoter to control the transcription of target genes. Enhancer regulatory activity is often studied using reporter-based transgene assays. However, unmatched results have been reported when selected enhancers are silenced in situ. In this study, using genomic deletion analysis in mice, we investigated the roles of two previously identified enhancers and the promoter of the Rho gene that codes for the visual pigment rhodopsin. The Rho gene is robustly expressed by rod photoreceptors of the retina, and essential for the subcellular structure and visual function of rod photoreceptors. Mutations in RHO cause severe vision loss in humans. We found that each Rho regulatory region can independently mediate local epigenomic changes, but only the promoter is absolutely required for establishing active Rho chromatin configuration and transcription and maintaining the cell integrity and function of rod photoreceptors. To our surprise, two Rho enhancers that enable strong promoter activation in reporter assays are largely dispensable for Rho expression in vivo. Only small and age-dependent impact is detectable when both enhancers are deleted. Our results demonstrate context-dependent roles of enhancers and highlight the importance of studying functions of cis-regulatory regions in the native genomic context. © 2023. Springer Nature Limited.
Document Type: Article
Publication Stage: Final
Source: Scopus
Sleep Behaviors, Genetic Predispositions, and Risk of Esophageal Cancer
(2023) Cancer Epidemiology Biomarkers and Prevention, 32 (8), pp. OF1-OF8.
Wang, X.a b , Tian, R.a b , Zong, X.a , Jeon, M.S.a c , Luo, J.a c , Colditz, G.A.a c , Wang, J.S.d , Tsilidis, K.K.e f , Ju, Y.-E.S.g h i , Govindan, R.c j , Puri, V.k , Cao, Y.a c d g
a Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
b Brown School, Washington University in St. Louis, St. Louis, MO, United States
c Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States
d Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
e Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
f Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
g Center on Biological Rhythms and Sleep (COBRAS), Washington University School of Medicine, St. Louis, MO, United States
h Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
i Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
j Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
k Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Risk factors contributing to more than 10-fold increase in esophageal cancer in the last 50 years remain underexplored. We aim to examine the associations of sleep behaviors with esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). Methods: We prospectively assessed the associations between sleep behaviors (chronotype, duration, daytime napping, daytime sleepiness, snoring, and insomnia) and EAC and ESCC risk in 393,114 participants in the UK Biobank (2006-2016). Participants with 0, 1, and ≥2 unhealthy behaviors, including sleep <6 or >9 h/d, daytime napping, and usual daytime sleepiness were classified as having a good, intermediate, and poor sleep. For EAC, we also examined interactions with polygenic risk score (PRS). Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: We documented 294 incident EAC and 95 ESCC. Sleep >9 h/d (HR, 2.05; 95% CI, 1.18-3.57) and sometimes daytime napping (HR, 1.36; 95% CI, 1.06-1.75) were individually associated with increased EAC risk. Compared with individuals with good sleep, those with intermediate sleep had a 47% (HR, 1.47; 95% CI, 1.13-1.91) increased EAC risk, and those with poor sleep showed an 87% (HR, 1.87; 95% CI, 1.24-2.82) higher risk (Ptrend < 0.001). The elevated risks for EAC were similar within strata of PRS (Pinteraction = 0.884). Evening chronotype was associated with elevated risk of ESCC diagnosed after 2 years of enrollment (HR, 2.79; 95% CI, 1.32-5.88). Conclusions: Unhealthy sleep behaviors were associated with an increased risk of EAC, independent of genetic risk. Impact: Sleep behaviors may serve as modifiable factors for the prevention of EAC. © 2023 American Association for Cancer Research.
Funding details
National Institutes of HealthNIHP30CA091842
Alvin J. Siteman Cancer Center
Document Type: Article
Publication Stage: Final
Source: Scopus
Personalized repetitive transcranial magnetic stimulation (prtms®) for post-traumatic stress disorder (ptsd) in military combat veterans
(2023) Heliyon, 9 (8), art. no. e18943, .
Makale, M.T.a , Abbasi, S.b , Nybo, C.c , Keifer, J.d , Christman, L.e , Fairchild, J.K.f g , Yesavage, J.f , Blum, K.h i j k , Gold, M.S.l , Baron, D.h , Cadet, J.L.m , Elman, I.n , Dennen, C.A.o , Murphy, K.T.p
a Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA 92093, United States
b Department of Electrical Engineering, University of Portland, Portland, OR 97203, United States
c CrossTx Inc., Bozeman, MT 59715, United States
d Brain Health Hawaii, Honolulu, HI 96816, United States
e StatKing Clinical Services, Fairfield, OH 45014, United States
f Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, United States
g Sierra Pacific Mental Illness Research, Education, and Clinical Center, VA Medical Center, Palo Alto, CA 94304, United States
h Division of Addiction Research & Education, Center for Sports, Exercise & Global Mental Health, Western University Health Sciences, Pomona, United States
i Department of Clinical Psychology and Addiction, Institute of Psychology, Faculty of Education and Psychology, Eötvös Loránd University, Hungary
j Department of Psychiatry, Wright University, Boonshoft School of Medicine, Dayton, OH, United States
k Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
l Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
m Molecular Neuropsychiatry Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, United States
n Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, United States
o Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA, United States
p PeakLogic Inc., Del Mar, CA 92130, United States
Abstract
Emerging data suggest that post-traumatic stress disorder (PTSD) arises from disrupted brain default mode network (DMN) activity manifested by dysregulated encephalogram (EEG) alpha oscillations. Hence, we pursued the treatment of combat veterans with PTSD (n = 185) using an expanded form of repetitive transcranial magnetic stimulation (rTMS) termed personalized-rTMS (PrTMS). In this treatment methodology spectral EEG based guidance is used to iteratively optimize symptom resolution via (1) stimulation of multiple motor sensory and frontal cortical sites at reduced power, and (2) adjustments of cortical treatment loci and stimulus frequency during treatment progression based on a proprietary frequency algorithm (PeakLogic, Inc. San Diego) identifying stimulation frequency in the DMN elements of the alpha oscillatory band. Following 4 – 6 weeks of PrTMS® therapy in addition to routine PTSD therapy, veterans exhibited significant clinical improvement accompanied by increased cortical alpha center frequency and alpha oscillatory synchronization. Full resolution of PTSD symptoms was attained in over 50% of patients. These data support DMN involvement in PTSD pathophysiology and suggest a role in therapeutic outcomes. Prospective, sham controlled PrTMS® trials may be warranted to validate our clinical findings and to examine the contribution of DMN targeting for novel preventive, diagnostic, and therapeutic strategies tailored to the unique needs of individual patients with both combat and non-combat PTSD. © 2023 The Authors
Author Keywords
Alpha oscillations; Automatic cognition; Contextual; Default mode network; EEG; Experience-based; Fast thinking; Implicit; Intuitive; Power spectrum; PTSD; PTSD checklist for DSM-5 (PCL-5); rTMS
Document Type: Article
Publication Stage: Final
Source: Scopus
White matter hyperintensity longitudinal morphometric analysis in association with Alzheimer disease
(2023) Alzheimer’s and Dementia, .
Strain, J.F.a , Phuah, C.-L.a b , Adeyemo, B.a , Cheng, K.a c , Womack, K.B.a , McCarthy, J.d , Goyal, M.e , Chen, Y.a , Sotiras, A.e f , An, H.e , Xiong, C.g , Scharf, A.h , Newsom-Stewart, C.i , Morris, J.C.a j , Benzinger, T.L.S.e j , Lee, J.-M.a c e , Ances, B.M.a c e j
a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, United States
c Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
d Department of Mathematics, Washington University School of Medicine, St. Louis, MO, United States
e Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
f Institute for Informatics, Washington University School of Medicine, St. Louis, MO, United States
g Division of Biostatics, Washington University School of Medicine, St. Louis, MO, United States
h Department of Biological Sciences, Missouri University for Science and Technology, Rolla, MO, United States
i Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
j Knight Alzheimer Disease Research Center, St. Louis, MO, United States
Abstract
INTRODUCTION: Vascular damage in Alzheimer’s disease (AD) has shown conflicting findings particularly when analyzing longitudinal data. We introduce white matter hyperintensity (WMH) longitudinal morphometric analysis (WLMA) that quantifies WMH expansion as the distance from lesion voxels to a region of interest boundary. METHODS: WMH segmentation maps were derived from 270 longitudinal fluid-attenuated inversion recovery (FLAIR) ADNI images. WLMA was performed on five data-driven WMH patterns with distinct spatial distributions. Amyloid accumulation was evaluated with WMH expansion across the five WMH patterns. RESULTS: The preclinical group had significantly greater expansion in the posterior ventricular WM compared to controls. Amyloid significantly associated with frontal WMH expansion primarily within AD individuals. WLMA outperformed WMH volume changes for classifying AD from controls primarily in periventricular and posterior WMH. DISCUSSION: These data support the concept that localized WMH expansion continues to proliferate with amyloid accumulation throughout the entirety of the disease in distinct spatial locations. © 2023 the Alzheimer’s Association.
Author Keywords
AD; longitudinal; preclinical; WLMA; WMH
Funding details
K23 NS110927, R01AG052550, R01AG057680, R01AG067103
National Institutes of HealthNIHU01 AG024904
U.S. Department of DefenseDODW81XWH‐12‐2‐0012
National Institute on AgingNIA
National Institute of Biomedical Imaging and BioengineeringNIBIB
Alzheimer’s AssociationAA
American Heart AssociationAHA19CDA34620004
Alzheimer’s Drug Discovery FoundationADDF
BiogenR01 AG053550
AbbVie
Alzheimer’s Disease Neuroimaging InitiativeADNI
BioClinica
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Lumbar punctures are safe in patients with ALS and have a risk profile similar to that in the non-ALS population
(2023) Muscle and Nerve, .
Kreple, C.J.a b , Gajagowni, S.c , Jockel-Balsaratti, J.a , Bucelli, R.C.a , Miller, T.M.a
a Department of Neurology, Washington University in St. Louis School of Medicine, Saint Louis, MO, United States
b Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
c University of Missouri School of Medicine, Columbia, MO, United States
Abstract
Introduction/Aims: Analysis of biofluids, especially cerebrospinal fluid (CSF), is critically important for amyotrophic lateral sclerosis (ALS) research. Collection of CSF is typically performed by lumbar puncture (LP). Previous studies have demonstrated the safety of LPs in patients with other neurodegenerative diseases, such as Alzheimer’s disease, although there are no published studies of the safety of LPs in patients with ALS. We performed a retrospective analysis of complications resulting from LPs. Methods: This is a retrospective study of LPs performed between 2015 and 2021 on a total of 233 participants (healthy controls [n = 63], ALS [n = 154], and disease controls [n = 16]) as part of clinical research studies at the Washington University ALS Center. We used bivariate logistical analyses looking for associations between participant characteristics and adverse events (AEs), and likelihood ratio tests were used for significance testing. Results: We found an overall AE rate of 21.03%. AEs included headache, back pain, vasovagal syncope, and severe headache requiring epidural blood patch. Participants with ALS were not more likely to experience post-LP AEs compared to controls (odds ratio [OR] 0.61 [0.32–1.18]). Post-LP headaches were significantly less likely in participants with ALS (OR 0.36 [0.15–0.83]). Discussion: Our findings demonstrate that LP is a safe procedure for participants with ALS, with a similar or lower rate of AEs than in participants without ALS. © 2023 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.
Author Keywords
amyotrophic lateral sclerosis; lumbar puncture
Funding details
National Institutes of HealthNIHR01NS078398, R01NS097816
ALS AssociationALSA
American Brain FoundationABF
University of WashingtonUW
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Adversity type and timing predict temporal summation of pain in African-American adults
(2023) Journal of Behavioral Medicine, .
Morris, M.C.a b k , Goodin, B.R.c d , Bruehl, S.b , Myers, H.e , Rao, U.f g , Karlson, C.a h , Huber, F.A.a , Nag, S.i , Carter, C.i , Kinney, K.a , Dickens, H.j
a Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, United States
b Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, United States
c Department of Psychology, University of Alabama at Birmingham, AL, Birmingham, United Kingdom
d Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, United States
e Department of Psychology, Vanderbilt University, Nashville, TN, United States
f Department of Psychiatry & Human Behavior and Center for the Neurobiology of Learning and Memory, University of California – Irvine, California, CA, United States
g Children’s Hospital of Orange County, Orange, CA, United States
h Department of Pediatrics, Hematology and Oncology, University of Mississippi Medical Center, Jackson, MS, United States
i Department of Biochemistry, Cancer Biology, Neuroscience & Pharmacology, Meharry Medical College, Nashville, TN, United States
j Department of Psychological Science, University of Arkansas, Fayetteville, AR, United States
k 2525 West End Ave, Nashville, TN 37206, United States
Abstract
African Americans are disproportionately exposed to adversity across the lifespan, which includes both stressful and traumatic events. Adversity, in turn, is associated with alterations in pain responsiveness. Racial differences in pain responsiveness among healthy adults are well established. However, the extent to which adversity type and timing are associated with alterations in pain responsiveness among healthy African-American adults is not well understood. The present study included 160 healthy African-American adults (98 women), ages 18 to 45. Outcome measures included pain tolerance and temporal summation of pain to evoked thermal pain. Composite scores were created for early-life adversity (childhood trauma, family adversity) and recent adversity (perceived stress, chronic stress burden). A measure of lifetime racial discrimination was also included. Higher levels of recent adversity were associated with higher temporal summation of pain, controlling for gender, age, and education. Neither early-life adversity nor lifetime racial discrimination were associated with temporal summation of pain. The present findings suggest that heightened temporal summation of pain among healthy African-American adults is associated with exposure to recent adversity events. Improved understanding of how recent adversity contributes to heightened temporal summation of pain in African Americans could help to mitigate racial disparities in pain experiences by identifying at-risk individuals who could benefit from early interventions. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Author Keywords
Adversity; African american; Discrimination; Pain tolerance; Temporal summation
Funding details
National Institutes of HealthNIHR01 MD016838, R01DA040966, R01HL164823, R01MD010757, R01MH108155, U54 MD007593, U54MD007586
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Cognition and education benefits of increased hemoglobin and blood oxygenation in children with sickle cell disease
(2023) PloS One, 18 (8), p. e0289642.
MacEwan, J.P.a , King, A.A.b , Nguyen, A.c , Mubayi, A.a , Agodoa, I.c , Smith-Whitley, K.c d
a Los Angeles, CA, United States
b Division of Pediatric Hematology/Oncology, Washington University and St. Louis Children’s Hospital, St. Louis, MO, United States
c Global Blood Therapeutics, Inc., South San Francisco, CA, United States
d Division of Hematology, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
Abstract
BACKGROUND: Among individuals with sickle cell disease (SCD), decreased hemoglobin is associated with lower oxygen saturation (SpO2) and increased risk of stroke, both of which are associated with lower intelligence quotient (IQ) scores. Thus, increasing hemoglobin and SpO2 in individuals with SCD may increase IQ and educational attainment. METHODS: A cohort simulation model was built to determine academic performance and educational attainment based on cognitive function (measured by IQ) of a pediatric SCD cohort randomly assigned to treatment and control groups. The model contained two key stages: childhood (<10 years) and adolescence (≥10 years). In stage 1, increased hemoglobin and increased SpO2 (assigned to the treatment group) were determinants of higher IQ, prevention of IQ deterioration over time. Increased hemoglobin was also a determinant of decreased stroke risk. In stage 2, improvement in adolescent IQ as a result of treatment was a determinant of academic performance. RESULTS: In a simulated cohort of 2000 children and adolescents with SCD (52.5% female, 50% treated), stroke incidence was predicted to be 44.4% lower among the treated group than the untreated group (4.5% versus 8.1%, respectively). The average IQ among the treated group was estimated to be 91.1 compared with 82.9 in the untreated group (a 9.9% difference; P<0.001). Finally, high school (≥12 years of education) completion rates were estimated to be 64.7% higher among the treated group: 76.1% of the treated group was projected to complete high school compared with 46.2% of the untreated group. CONCLUSIONS: Our model predicts that an average improvement in hemoglobin of 1.1 g/dL (11 g/L) among individuals with SCD may be associated with improved neurocognition and educational outcomes. These improvements may also generate benefits not captured by our model, including improved quality of life, employment, and income. Copyright: © 2023 MacEwan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Document Type: Article
Publication Stage: Final
Source: Scopus
Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease
(2023) Nature Medicine, .
Johnson, E.C.B.a b , Bian, S.c , Haque, R.U.a , Carter, E.K.a d , Watson, C.M.a b , Gordon, B.A.e , Ping, L.a b d , Duong, D.M.a d , Epstein, M.P.f , McDade, E.g , Barthélemy, N.R.g , Karch, C.M.h , Xiong, C.g i , Cruchaga, C.h , Perrin, R.J.g j , Wingo, A.P.a k l , Wingo, T.S.a b f , Chhatwal, J.P.m , Day, G.S.n , Noble, J.M.o , Berman, S.B.p , Martins, R.q , Graff-Radford, N.R.n , Schofield, P.R.r s , Ikeuchi, T.t , Mori, H.u , Levin, J.v , Farlow, M.w , Lah, J.J.a b , Haass, C.x y z , Jucker, M.aa ab , Morris, J.C.g , Benzinger, T.L.S.e , Roberts, B.R.a d , Bateman, R.J.g , Fagan, A.M.g , Seyfried, N.T.a b d , Levey, A.I.a b , Noble, J.M.o , Day, G.S.n , Graff-Radford, N.R.n , Voglein, J.v x , Allegri, R.ac , Mendez, P.C.ac , Surace, E.ad , Berman, S.B.ae af , Ikonomovic, S.ae , Nadkarni, N.ae ag , Lopera, F.ah , Ramirez, L.ah , Aguillon, D.ah , Leon, Y.ah , Ramos, C.ah , Alzate, D.ah , Baena, A.ah , Londono, N.ah , Moreno, S.ah , Laske, C.x ai aj , Kuder-Buletta, E.x , Graber-Sultan, S.x , Preische, O.x ai aj , Hofmann, A.x ai , Ikeuchi, T.t , Kasuga, K.ak , Niimi, Y.al , Ishii, K.am , Senda, M.an , Sanchez-Valle, R.ao , Rosa-Neto, P.ap , Fox, N.aq ar , Cash, D.aq ar , Lee, J.-H.as , Roh, J.H.as , Riddle, M.at , Menard, W.at , Bodge, C.at , Surti, M.at , Takada, L.T.au , Chhatwal, J.P.m , Sanchez-Gonzalez, V.J.av , Orozco-Barajas, M.av , Goate, A.aw , Renton, A.aw ax ay , Esposito, B.aw ay , Karch, C.M.h , Marsh, J.h , Cruchaga, C.h az , Fernandez, V.h az , Gordon, B.A.e , Fagan, A.M.g , Jerome, G.g , Herries, E.g , Llibre-Guerra, J.g , Johnson, E.C.B.a b , Seyfried, N.T.a b d , Schofield, P.R.r s , Brooks, W.r ba , Bechara, J.r , Bateman, R.J.g , Hassenstab, J.g bb , Perrin, R.J.g j , Franklin, E.j , Benzinger, T.L.S.e , Chen, A.e , Chen, C.e , Flores, S.e , Friedrichsen, N.e , Hantler, N.e , Hornbeck, R.e , Jarman, S.e , Keefe, S.e , Koudelis, D.e , Massoumzadeh, P.e , McCullough, A.e , McKay, N.e , Nicklaus, J.e , Pulizos, C.e , Wang, Q.e , Mishall, S.e , Sabaredzovic, E.e , Deng, E.e , Candela, M.e , Smith, H.e , Hobbs, D.e , Scott, J.e , Levin, J.v , Xiong, C.g i , Wang, P.i , Xu, X.i , Li, Y.i , Gremminger, E.i , Ma, Y.i , Bui, R.i , Lu, R.i , Ortiz, A.L.S.bc , Daniels, A.bd , Courtney, L.bd , Supnet-Bell, C.g , Xu, J.be , Ringman, J.bf , the Dominantly Inherited Alzheimer Networkbg
a Goizueta Alzheimer’s Disease Research Center, Emory University School of Medicine, Atlanta, GA, United States
b Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
c Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, United States
d Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, United States
e Mallinckrodt Institute of Radiology, Washington University in St Louis, St Louis, MO, United States
f Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, United States
g Department of Neurology, Washington University in St Louis, St Louis, MO, United States
h Department of Psychiatry, Washington University in St Louis, St Louis, MO, United States
i Division of Biostatistics, Washington University in St Louis, St Louis, MO, United States
j Department of Pathology and Immunology, Washington University in St Louis, St Louis, MO, United States
k Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, United States
l Division of Mental Health, Atlanta VA Medical Center, Atlanta, GA, United States
m Massachusetts General and Brigham & Women’s Hospitals, Harvard Medical School, Boston, MA, United States
n Department of Neurology, Mayo Clinic, Jacksonville, FL, United States
o Department of Neurology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, and GH Sergievsky Center, Columbia University Irving Medical Center, New York, NY, United States
p Departments of Neurology and Clinical and Translational Science, Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, United States
q Edith Cowan University, Perth, WA, Australia
r Neuroscience Research Australia, Sydney, NSW, Australia
s School of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia
t Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan
u Osaka Metropolitan University Medical School, Nagaoka Sutoku University, Nagaoka, Japan
v Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany
w Indiana University, Bloomington, IN, United States
x German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
y Metabolic Biochemistry, Biomedical Center (BMC), Ludwig-Maximilians University, Munich, Germany
z Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
aa Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
ab German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
ac Department of Cognitive Neurology, Institute for Neurological Research Fleni, Buenos Aires, Argentina
ad Department of Molecular Biology and Neuropathology, Institute for Neurological Research Fleni, Buenos Aires, Argentina
ae Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States
af Clinical and Translational Science, Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, United States
ag Department of Geriatric Medicine, University of Pittsburgh, Pittsburgh, PA, United States
ah Grupo de Neurociencias de Antioquia (GNA), Universidad de Antioquia, Medellín, Colombia
ai Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
aj Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
ak Brain Research Institute, Niigata University, Niigata, Japan
al The University of Tokyo Hospital Unit for Early and Exploratory Clinical Development, Tokyo, Japan
am Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
an Kobe City Medical Center General Hospital, Tokyo, Japan
ao Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Barcelona, Spain
ap McGill University, Montreal, QC, Canada
aq Dementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom
ar UK Dementia Research Institute at UCL, London, United Kingdom
as Korea University College of Medicine, Seoul, South Korea
at Butler Hospital, Warren Alpert School of Medicine, Brown University, Providence, RI, United States
au Hospital das Clinicas, University of São Paulo School of Medicine, São Paulo, Brazil
av Doctorado en Biociencias & Departamento de Clinicas, Centro Universitario de Los Altos, UDG, Tepatitlán de Morelos, Mexico
aw Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
ax Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
ay Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY, United States
az NeuroGenomics and Informatics Center, Washington University School of Medicine, St Louis, MO, United States
ba School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
bb Department of Psychological and Brain Sciences, Washington University in St Louis, St Louis, MO, United States
bc Mexico City, Mexico
bd Washington University School of Medicine in St Louis, St Louis, MO, United States
be Department of Radiology, Washington University in St Louis, St Louis, MO, United States
bf Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
Abstract
Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation of the amyloid-β (Aβ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)—are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of Aβ plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning six decades. SMOC1 and SPON1 proteins associated with Aβ plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers before symptom onset as well or better than Aβ and tau measures. Our results highlight the multifaceted landscape of AD pathophysiology and its temporal evolution. Such knowledge will be critical for developing precision therapeutic interventions and biomarkers for AD beyond those associated with Aβ and tau. © 2023, The Author(s).
Funding details
National Institute on AgingNIA
Alzheimer’s AssociationAASG-20-690363-DIAN
Alzheimer’s Disease Research Center, Emory UniversityADRCP30AG066511, U01AG061357
Fondation Brain Canada
Japan Agency for Medical Research and DevelopmentAMEDAMED 17929884, JP22dk0207049, P01AG003991, P01AG026276, P30 AG066444, U19 AG024904
Canadian Institutes of Health ResearchIRSC
Fonds de Recherche du Québec – SantéFRQS
Deutsche ForschungsgemeinschaftDFG390857198, HA1737/16-1, U19AG032438
Korea Health Industry Development InstituteKHIDI
Deutsches Zentrum für Neurodegenerative ErkrankungenDZNE
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Age-Specific Barriers and Facilitators to Research Participation Amongst African Americans in Observational Studies of Memory and Aging
(2023) Journal of Racial and Ethnic Health Disparities, .
Nissim, N.R.a , Fudge, M.R.a , Lachner, C.a b , Babulal, G.M.c , Allyse, M.A.d , Graff-Radford, N.R.a , Lucas, J.A.b , Day, G.S.a
a Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, United States
b Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL 32224, United States
c Washington University in St. Louis, Saint Louis, MO 63130, United States
d Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL 32224, United States
Abstract
Background: Black/African Americans experience a high burden of Alzheimer disease and related dementias yet are critically underrepresented in corresponding research. Understanding barriers and facilitators to research participation among younger and older African Americans is necessary to inform age-specific strategies to promote equity in studies of early- and late-onset neurodegenerative diseases. Study Design: Survey respondents (n = 240) rated barriers and facilitators of research participation. Age-specific differences were evaluated using nonparametric Kruskal–Wallis tests across respondents aged 18–44 years (n = 76), 45–64 years (n = 83), and ≥ 65 years (n = 81). Strategies to mitigate barriers and promote facilitators were further explored via community-based focus groups. Pooled frequency of common themes discussed in focus groups were evaluated and compared across different ages including ≥ 45 years, ≥ 65 years, and mixed ages ≥ 45 years. Results: Younger respondents (aged 18–44 and 45–64 years) expressed a greater need for flexibility in when, where, and how research testing takes place versus adults ≥ 65 years. Focus groups emphasized long-lasting consequences of systemic racism and the need to build and foster trust to resolve barriers and promote research engagement amongst African Americans. Discussion: Age-specific strategies are needed to increase engagement, address recruitment disparities, and promote retention of African American participants in memory and aging studies across the lifespan. © 2023, W. Montague Cobb-NMA Health Institute.
Author Keywords
African Americans; Alzheimer disease; Alzheimer disease-related dementia; Barriers; Facilitators; Research participation
Funding details
National Institutes of HealthNIHP30AG62677, U01AG057195, U01NS100620-6, U19AG032438, U19AG074879-1
National Institute on AgingNIAK23AG064029, R01AG067428, R01AG068183, R01AG074302
Alzheimer’s AssociationAA21–824473
BrightFocus FoundationBFFA2021142S
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Childhood Emotion Dysregulation Mediates the Relationship Between Preschool Emotion Labeling and Adolescent Depressive Symptoms
(2023) Emotion, .
Hollender, A.E.a , Elsayed, N.M.b , Vogel, A.C.c , Tillman, R.c , Barch, D.M.b , Luby, J.L.c , Gilbert, K.E.c
a Department of Psychology, Montclair State University, United States
b Department of Psychological and Brain Sciences, Washington University in St. Louis, United States
c Department of Psychiatry, Washington University School of Medicine, United States
Abstract
Deficits in emotion processing (e.g., emotion labeling and regulation) are widely implicated in depression risk. While prior literature documents these deficits in concurrence with depression, more research is needed to investigate emotion processing pathways of depression risk across development. The purpose of this study was to investigate if emotion processes (i.e., emotion labeling and emotion regulation/dysregulation) in early and middle childhood predict adolescent depressive symptom severity in a prospective sample. Data were analyzed from a longitudinal study of diverse preschoolers oversampled for depressive symptoms using measures of preschool emotion labeling of faces (i.e., Facial Affect Comprehension Evaluation), middle childhood emotion regulation and dysregulation (i.e., emotion regulation checklist), and adolescent depressive symptoms (i.e., PAPA, CAPA, and KSADS-PL diagnostic interviews). Multilevel models indicated that preschoolers with depression had similar development of emotion labeling in early childhood as peers. Mediation analyses revealed that deficits in preschool-aged anger and surprise labeling ability indirectly predicted higher adolescent depressive symptom severity through increased middle childhood emotion lability/negativity, not decreased emotion regulation. Adolescent depression may be predicted by an emotion processing pathway that spans from early childhood to adolescence, and findings may generalize to high risk for depression youth samples. Specifically, poor emotion labeling in early childhood may lead to increased childhood emotion lability/negativity, which increases the risk for adolescent depressive symptom severity. Findings may help identify specific emotion processing relations in childhood that increase the risk for depression and inform intervention aimed at improving preschoolers’ anger and surprise labeling. © 2023 American Psychological Association
Author Keywords
adolescence; depression; early childhood; emotion labeling; emotion regulation
Funding details
National Institute of Mental HealthNIMHK23MH115074, R01MH06769
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Everyday Emotion Regulation Goals, Motives, and Strategies in Current and Remitted Major Depressive Disorder: An Experience Sampling Study
(2023) Journal of Psychopathology and Clinical Science, .
Liu, D.Y., Springstein, T., Tuck, A.B., English, T., Thompson, R.J.
Department of Psychological and Brain Sciences, Washington University in St. Louis, United States
Abstract
People with major depressive disorder (MDD) report difficulties with emotion regulation (ER), particularly in habitual strategy use.We examined ER strategy use and other aspects of ER—desired emotional states (emotion goals) and reasons for ER (ER motives)—in current and remittedMDD. In a 2-week experience sampling study, adults with currentMDD (n= 48), remittedMDD (n=80), and healthy controls (n=87) reported their negative affect (NA) and positive affect (PA), emotion goals (frequency, direction), ER motives (hedonic, instrumental), and ER strategy use (social sharing, acceptance, savoring, reappraisal, suppression, distraction). Multilevel modeling and Bayes factors were used to assess differences and similarities across groups. Compared to the remitted MDD and control groups, the current MDD group regulated emotion more frequently in general but showed weakened associations between initiating regulation and momentary affect and reported different emotion goal directions. Although all groups mostly reported emotion goals to regulate prohedonically (decrease NA, increase or maintain PA), the current MDD group was the most likely to try to amplifyNA and PAsimultaneously. CurrentMDDand remittedMDDgroups endorsed hedonic motivesmore than controls, but the three groups did not differ in instrumental motives. The only group difference in ER strategy use was that the current MDD group used distraction more than controls. Most group differences in ER were between the current MDD group and controls, with the remitted MDD group and controls being quite similar. ER in current MDD is characterized by frequent regulation, weakened association between initiating regulation and momentary affect, increased hedonic-focused ER motives, and a greater use of distraction. © 2023 American Psychological Association
Author Keywords
emotion regulation; experience sampling; major depressive disorder; naturalistic approach; remitted depression
Funding details
Washington University in St. LouisWUSTL201709046
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Exploring hand and upper limb function in patients with inclusion body myositis (IBM)
(2023) Neuromuscular Disorders, .
Hunn, S.a , Alfano, L.b c , Seiffert, M.a , Weihl, C.C.a
a Washington University in St. Louis, 660 South Euclid Ave Campus Box 8111, St. Louis, MO 63110, United States
b Nationwide Children’s Hospital, 700 Children’s Dr., AB7036, Columbus, OH 43205, United States
c The Department of Pediatrics, The Ohio State University College of Medicine, 700 Children’s Dr, Columbus, OH 43205, United States
Abstract
Inclusion body myositis (IBM) is an inflammatory myopathy characterized by progressive weakness of knee extensors and finger flexors. Many patients lose independence with fine motor tasks; however, a gap remains as to how these deficits correlate with performance on functional outcome measures. We describe functional hand impairments as measured by performance-based outcome measures in a cross-sectional sample of 74 patients with IBM. Subjects completed a series of outcome measures (Functional Dexterity Test (FDT), Performance of the Upper Limb (PUL), and Sollerman Hand Function Test (SHFT)) alongside a collection of patient reported outcomes (PROs). Assessments were compared to standard IBM measurements, including grip strength and IBM Functional Rating Scale (IBMFRS). FDT and SHFT demonstrated significant correlations to grip (p<0.001; Spearman correlations r=0.48–0.70). Significant correlation was found between all functional outcome measures and IBMFRS (p<0.001; Spearman correlations r=0.51–0.77), as well as PRO Upper Extremity Scale for IBM (IBM-PRO) (p<0.05; Spearman correlations r=0.55–0.73). Non-ambulatory patients demonstrated significantly weaker grip (p<0.001), resulting in lower PUL scores and increased FDT completion times (p<0.001). Collectively, these assessments may provide insight to understanding functional limitations of the hands and potentially allow for more inclusive clinical trials with future validation of hand assessments in IBM. © 2023 The Author(s)
Author Keywords
Functional dexterity test; Grip strength; Hand weakness; Inclusion body myositis; Outcome measures; Patient reported outcome
Funding details
National Institutes of HealthNIHK24AR073317
Myositis AssociationTMA
Document Type: Article
Publication Stage: Article in Press
Source: Scopus