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Background: Endocrine-disrupting chemicals (EDCs) have been linked to adverse health outcomes and prenatal exposure is known to impact infant and child development. However, few studies have assessed early developmental consequences of prenatal exposure to two common phenolic compounds, benzophenone-3 (BP-3) and triclosan (TCS)., Objective: We evaluated the relationship of prenatal exposure to BP-3 and TCS with infant cognition at 7.5 months via performance on a visual recognition memory (VRM) task., Methods: Drawing from the Illinois Kids Development Study (IKIDS) cohort, prenatal exposure to BP-3 and TCS was assessed in pools of five urine samples collected from each woman across pregnancy. Cognition was measured in 310 infants using a VRM task assessing information processing speed, attention, and recognition memory through infrared eye-tracking. Generalized linear regression estimated exposure-outcome associations, followed by stratification to investigate modification of associations by infant sex and stimulus set., Results: Sampled mothers were more likely to be white, college educated, and middle or high income relative to the US population. Mean chemical exposures were significantly higher than those of adult women in the NHANES cohort. In models adjusted for income, gestational age at birth, and testing age, prenatal BP-3 exposure was associated with an increase in run duration (average time spent looking at the stimuli before looking away) (β=0.0011, CI -0.0001:0.0022), indicating slower information processing speed, while TCS was associated with significantly longer time to familiarization (time to accrue a total of 20 seconds of looking time to the stimuli) (β=0.0686, CI 0.0203:0.1168, p<0.01), indicating poorer attention. Stratum-specific analyses isolated both effects to male infants who viewed the second of two stimulus sets., Conclusion: Higher prenatal exposure to triclosan was associated with poorer attention in infancy, while benzophenone-3 may be associated with slower information processing speed, particularly among males., Competing Interests: Declaration of Competing Interest ☐ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nicholas Cragoe reports financial support was provided by National Institutes of Health. Jenna Sprowles reports financial support was provided by National Institutes of Health. Megan L. Woodbury reports financial support was provided by National Institutes of Health. Salma Musaad reports financial support was provided by National Institutes of Health. Elizabeth Enright reports financial support was provided by National Institutes of Health. Andrea Aguiar reports financial support was provided by National Institutes of Health. Susan L. Schantz reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Phenols and parabens are two classes of high production volume chemicals that are used widely in consumer and personal care products and have been associated with reproductive harm and pregnancy complications, such as preeclampsia and gestational diabetes. However, studies examining their influence on maternal blood pressure and gestational hypertension are limited., Objectives: We investigated associations between individual phenols, parabens, and their mixture on maternal blood pressure measurements, including systolic and diastolic blood pressure (SBP and DBP) and hypertension during pregnancy (defined as stage 1 or 2 hypertension), among N = 1,433 Puerto Rico PROTECT study participants., Methods: We examined these relationships cross-sectionally at two time points during pregnancy (16-20 and 24-28 wks gestation) and longitudinally using linear mixed models (LMMs). Finally, we used quantile g-computation to examine the mixture effect on continuous (SBP, DBP) and binary (hypertension during pregnancy) blood pressure outcomes., Results: We observed a trend of higher odds of hypertension during pregnancy with exposure to multiple analytes and the overall mixture [including bisphenol A (BPA), bisphenol S (BPS), triclocarbon (TCC), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), methyl paraben (M-PB), propyl paraben (P-PB), butyl paraben (B-PB), and ethyl paraben (E-PB)], especially at 24-28 wk gestation, with an adjusted mixture odds ratio ( OR ) = 1.57 (95% CI: 1.03, 2.38). Lower SBP and higher DBP were also associated with individual analytes, with results from LMMs most consistent for methyl paraben (M-PB) or propyl paraben (P-PB) and increased DBP across pregnancy [adjusted M-PB β = 0.78 (95% CI: 0.17, 1.38) and adjusted P-PB β = 0.85 (95% CI: 0.19, 1.51)] and for BPA, which was associated with decreased SBP (adjusted β = - 0.57 ; 95% CI: - 1.09 , - 0.05 ). Consistent with other literature, we also found evidence of effect modification by fetal sex, with a strong inverse association observed between the overall exposure mixture and SBP at visit 1 among participants carrying female fetuses only., Conclusions: Our findings indicate that phenol and paraben exposure may collectively increase the risk of stage 1 or 2 hypertension during pregnancy, which has important implications for fetal and maternal health. https://doi.org/10.1289/EHP14008.

Background: Acetaminophen is the only analgesic considered safe for use throughout pregnancy. Recent studies suggest that use during pregnancy may be associated with poorer neurodevelopmental outcomes in children, but few have examined language development., Methods: The Illinois Kids Development Study is a prospective birth cohort in east-central Illinois. Between December 2013 and March 2020, 532 newborns were enrolled and had exposure data available. Participants reported the number of times they took acetaminophen six times across pregnancy. Language data were collected at 26.5-28.5 months using the MacArthur-Bates Communicative Development Inventories (CDI; n = 298), and 36-38 months using the Speech and Language Assessment Scale (SLAS; n = 254)., Results: Taking more acetaminophen during the second or third trimester was associated with marginally smaller vocabularies and shorter utterance length (M3L) at 26.5-28.5 months. More acetaminophen use during the third trimester was also associated with increased odds of M3L scores ≤25th percentile in male children. More use during the second or third trimester was associated with lower SLAS scores at 36-38 months. Third trimester use was specifically related to lower SLAS scores in male children., Conclusions: Higher prenatal acetaminophen use during pregnancy may be associated with poorer early language development., Impact: Taking more acetaminophen during pregnancy, particularly during the second and third trimesters, was associated with poorer scores on measures of language development when children were 26.5-28.5 and 36-38 months of age. Only male children had lower scores in analyses stratified by child sex. To our knowledge, this is the first study that has used a standardized measure of language development to assess the potential impact of prenatal exposure to acetaminophen on language development. This study adds to the growing body of literature suggesting that the potential impact of acetaminophen use during pregnancy on fetal neurodevelopment should be carefully evaluated., (© 2023. The Author(s).)

Importance: Unilateral spatial neglect (neglect) poststroke is disabling. It is critical that people with neglect are identified so that treatment can be provided to maximize independence. However, there is some evidence to suggest that existing assessments may not adequately measure neglect. It is unclear whether assessments also fail to identify people with neglect entirely., Objective: To determine whether there are stroke survivors who self-report neglect symptoms that are not detected by therapist-rated assessments and to compare self-report and therapist-ratings., Design: Cross-sectional study., Setting: U.S. university research center., Participants: Unilateral stroke survivors (N = 133)., Intervention: Not applicable., Outcomes and Measures: The Catherine Bergego Scale (CBS) was administered to participants and scored by a trained occupational therapist. The parallel self-evaluation anosognosia form was also administered to participants to self-report and rate neglect symptoms., Results: Forty-eight participants (36.1%) were classified as without neglect on the basis of therapist-rated total CBS scores, yet 30 (62.5%) of these 48 participants reported symptoms of neglect on the CBS self-evaluation anosognosia form. There was a significant difference (p < .001) between therapist-rated and self-rated total CBS scores., Conclusions and Relevance: Our results indicate that many stroke survivors report some level of disability associated with neglect yet do not meet the criteria to be classified as having neglect according to a commonly used therapist-rated performance-based measure. Plain-Language Summary: The findings of this study contribute to the evidence that existing assessments used by occupational therapists to measure performance-based neglect may not always detect neglect symptoms comprehensively in people poststroke. The finding also suggest that we may be missing neglect symptoms entirely. Occupational therapists should consider using various methods to assess for neglect, including patient self-report and comprehensive occupational profiles. Clinicians should also thoroughly screen all clients with stroke for neglect, regardless of lesion location., (Copyright © 2024 by the American Occupational Therapy Association, Inc.)

Oxidative stress has been identified as an important biological pathway leading to neurodevelopmental delay. However, studies assessing the effects of oxidative stress on cognitive outcomes during infancy, a critical period of neurodevelopment, are limited. Our analysis included a subset of those enrolled in the Illinois Kids Development Study (N = 144). Four oxidative stress biomarkers (8-isoprostane-PGF 2α , 2,3-dinor-5,6-dihydro-8-iso-PGF 2α , 2,3-dinor-8-iso-PGF 2α , and prostaglandin-F 2α ) were measured in second and third trimesters urine and were averaged. Infant cognition was measured using a visual recognition memory task consisting of five blocks, each with one familiarization trial (two identical stimuli) and two test trials (one familiar and one novel stimulus). Outcomes measured included average run duration (a measure of information processing speed), novelty preference (a measure of recognition memory), time to reach familiarization, and shift rate (measures of attention). Linear regression was used to estimate associations between individual oxidative stress biomarkers and each outcome. Increasing 8-isoprostane-PGF 2α , 2,3-dinor-8-iso-PGF 2α , and prostaglandin-F 2α were associated with a decrease in novelty preference (β = -0.02, 95% confidence interval [CI] = -0.03, 0.00; β = -0.02, 95% CI = -0.04, 0.00; β = -0.01, 95% CI = -0.02, 0.00, respectively), as well as a modest increase in shift rate. These findings suggest that oxidative stress may be associated with poorer recognition memory in early infancy., (© 2024 Wiley Periodicals LLC.)

Acetaminophen is currently the only analgesic considered safe for use throughout pregnancy, but recent studies indicate that prenatal exposure to acetaminophen may be related to poorer neurodevelopmental outcomes. Multiple studies have suggested that it may be associated with attention problems, but few have examined this association by trimester of exposure. The Illinois Kids Development Study is a prospective birth cohort located in east-central Illinois. Exposure data were collected between December 2013 and March 2020, and 535 newborns were enrolled during that period. Mothers reported the number of times they took acetaminophen at six time points across pregnancy. When children were 2, 3, and 4 years of age, caregivers completed the Child Behavior Checklist for ages 1.5-5 years (CBCL). Associations of acetaminophen use during pregnancy with scores on the Attention Problems and ADHD Problems syndrome scales, the Internalizing and Externalizing Behavior composite scales, and the Total Problems score were evaluated. Higher acetaminophen exposure during the second trimester of fetal development was associated with higher Attention Problems, ADHD Problems, Externalizing Behavior, and Total Problems scores at ages 2 and 3. Higher second trimester exposure was only associated with higher Externalizing Behavior and Total Problems scores at 4 years. Higher cumulative exposure across pregnancy was associated with higher Attention Problems and ADHD Problems scores at ages 2 and 3. Findings suggest that prenatal acetaminophen exposure, especially during the second trimester, may be related to problems with attention in early childhood., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Senior author serves on Neurotoxicology and Teratology Editorial Advisory Board - S.L.S., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to a wide array of adverse maternal and child health outcomes. However, studies examining PFAS in relation to offspring cognition have been inconclusive., Objective: We examined whether prenatal exposure to a mixture of PFAS was related to cognition in 7.5-month-old infants., Methods: Our analytic sample included participants enrolled in the Chemicals in Our Bodies (CIOB) and Illinois Kids Development Study (IKIDS) cohorts (N = 163). Seven PFAS were measured in 2nd trimester maternal serum samples and were detected in >65% of participants. Infant cognition was measured with a visual recognition memory task using an infrared eye tracker when infants were 7.5 months old. This task included familiarization trials where each infant was shown two identical faces and test trials where each infant was shown the familiar face paired with a novel face. In familiarization, we assessed average run duration (time looking at familiarization stimuli before looking away) as a measure of information processing speed, in addition to time to familiarization (time to reach 20 s of looking at stimuli) and shift rate (the number of times infants looked between stimuli), both as measures of attention. In test trials, we assessed novelty preference (proportion of time looking to the novel face) to measure recognition memory. Linear regression was used to estimate associations of individual PFAS with cognitive outcomes, while Bayesian kernel machine regression (BKMR) was used to estimate mixture effects., Results: In adjusted single-PFAS linear regression models, an interquartile range increase in PFNA, PFOA, PFOS, PFHxS, PFDeA, and PFUdA was associated with an increase in shift rate, reflecting better visual attention. Using BKMR, increasing quartiles of the PFAS mixture was similarly associated with a modest increase in shift rate. There were no significant associations between PFAS exposure and time to reach familiarization (another measure of attention), average run duration (information processing speed), or novelty preference (visual recognition memory)., Conclusion: In our study population, prenatal PFAS exposure was modestly associated with an increase in shift rate and was not strongly associated with any adverse cognitive outcomes in 7.5-month-old infants., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was supported by grants RD83543301 and RD83543401 from the United States Environmental Protection Agency Children's Environmental Health and Disease Prevention Research Center, P30 ES019776, P30 ES030284, P01 ES022841P01 ES022848 and R01ES02705 from the National Institute of Environmental Health Sciences, and UG3OD023272, UH3OD023272, and 5U2COD023375-05 from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) program. Stephanie Eick's participation was partially supported by the JPB Environmental Health Fellowship., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Implanted vagus nerve stimulation (VNS), when synchronized with post-stroke motor rehabilitation improves conventional motor rehabilitation training. A non-invasive VNS method known as transcutaneous auricular vagus nerves stimulation (taVNS) has emerged, which may mimic the effects of implanted VNS., Objective: To determine whether taVNS paired with motor rehabilitation improves post-stroke motor function, and whether synchronization with movement and amount of stimulation is critical to outcomes., Methods: We developed a closed-loop taVNS system for motor rehabilitation called motor activated auricular vagus nerve stimulation (MAAVNS) and conducted a randomized, double-blind, pilot trial investigating the use of MAAVNS to improve upper limb function in 20 stroke survivors. Participants attended 12 rehabilitation sessions over 4-weeks, and were assigned to a group that received either MAAVNS or active unpaired taVNS concurrently with task-specific training. Motor assessments were conducted at baseline, and weekly during rehabilitation training. Stimulation pulses were counted for both groups., Results: A total of 16 individuals completed the trial, and both MAAVNS (n = 9) and unpaired taVNS (n = 7) demonstrated improved Fugl-Meyer Assessment upper extremity scores (Mean ± SEM, MAAVNS: 5.00 ± 1.02, unpaired taVNS: 3.14 ± 0.63). MAAVNS demonstrated greater effect size (Cohen's d  = 0.63) compared to unpaired taVNS (Cohen's d  = 0.30). Furthermore, MAAVNS participants received significantly fewer stimulation pulses (Mean ± SEM, MAAVNS: 36 070 ± 3205) than the fixed 45 000 pulses unpaired taVNS participants received ( P  < .05)., Conclusion: This trial suggests stimulation timing likely matters, and that pairing taVNS with movements may be superior to an unpaired approach. Additionally, MAAVNS effect size is comparable to that of the implanted VNS approach.

Background: This study examined the relationship between prenatal maternal stress (PREMS) and non-nutritive suck (NNS) and tested its robustness across 2 demographically diverse populations., Methods: The study involved 2 prospective birth cohorts participating in the national Environmental influences on Child Health Outcomes (ECHO) Program: Illinois Kids Development Study (IKIDS) and ECHO Puerto Rico (ECHO-PROTECT). PREMS was measured during late pregnancy via the 10-item Perceived Stress Scale (PSS-10). NNS was sampled from 1- to 8-week-olds using a custom pacifier for ~5 min., Results: Overall, 237 mother-infant dyads completed this study. Despite several significant differences, including race/ethnicity, income, education, and PREMS levels, significant PREMS-NNS associations were found in the 2 cohorts. In adjusted linear regression models, higher PREMS, measured through PSS-10 total scores, related to fewer but longer NNS bursts per minute., Conclusions: A significant association was observed between PREMS and NNS across two diverse cohorts. This finding is important as it may enable the earlier detection of exposure-related deficits and, as a result, earlier intervention, which potentially can optimize outcomes. More research is needed to understand how NNS affects children's neurofunction and development., Impact: In this double-cohort study, we found that higher maternal perceived stress assessed in late pregnancy was significantly associated with fewer but longer sucking bursts in 1- to 8-week-old infants. This is the first study investigating the association between prenatal maternal stress (PREMS) and infant non-nutritive suck (NNS), an early indicator of central nervous system integrity. Non-nutritive suck is a potential marker of increased prenatal stress in diverse populations. Non-nutritive suck can potentially serve as an early indicator of exposure-related neuropsychological deficits allowing for earlier interventions and thus better prognoses., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objectives: To (1) examine the feasibility of combining lower extremity aerobic exercise (AEx) with a virtual reality (VR) upper extremity (UE) rehabilitation intervention and (2) provide an estimate of effect size for the combined intervention on UE function, aerobic capacity, and health-related quality of life., Design: Single-group feasibility trial., Setting: Research laboratory., Participants: Community-dwelling individuals with mild to moderate impairment of the UE at least 6 months post stroke (N=10; male, n=6; female n=4; mean age, 54 years)., Intervention: All participants received 18 sessions over a nominal 2-3 sessions per week schedule of a combined AEx and VR-UE rehabilitation intervention. During each session, participants completed 15 minutes of lower extremity AEx followed by playing a VR-UE rehabilitation game for approximately 20 minutes., Main Outcome Measures: Feasibility was evaluated by metrics of adherence, retention, treatment acceptability, data completeness, and adverse events. UE function, aerobic capacity (peak oxygen consumption [Vo 2 peak]), and quality of life were assessed with the Fugl-Meyer Assessment of Upper Extremity (FMA-UE), expired gas exchange analysis, and Stroke Impact Scale (SIS), respectively., Results: Adherence was 100%, and there were no withdrawals or losses to follow-up to report. Participants completed the intervention in 49±14 days. Cohen's d z effect size calculations indicated the intervention elicited medium effects on FMA-UE ( d z =0.50) and SIS memory domain ( d z =0.46) and large effects on absolute Vo 2 peak ( d z =1.46), relative Vo 2 peak ( d z =1.21), SIS strength ( d z =1.18), and SIS overall recovery domains ( d z =0.81)., Conclusions: Combining lower extremity AEx and VR-UE rehabilitation appears feasible in the clinical research setting. Fifteen minutes of lower extremity AEx performed at vigorous intensity appears to elicit clinically meaningful benefits in chronic stroke. Further examination of the combination of lower extremity AEx and VR-UE rehabilitation and its effects on physical function and quality of life is warranted.

Background: Post-stroke hand impairment is prevalent and persistent even after a full course of rehabilitation. Hand diminishes stroke survivors' abilities for activities of daily living and independence. One way to improve treatment efficacy is to augment therapy with peripheral sensory stimulation. Recently, a novel sensory stimulation, TheraBracelet, has been developed in which imperceptible vibration is applied during task practice through a wrist-worn device. The objective of this trial is to determine if combining TheraBracelet with hand task practice is superior to hand task practice alone., Methods: A double-blind randomized controlled trial will be used. Chronic stroke survivors will undergo a standardized hand task practice therapy program (3 days/week for 6 weeks) while wearing a device on the paretic wrist. The device will deliver TheraBracelet vibration for the treatment group and no vibration for the control group. The primary outcome is hand function measured by the Wolf Motor Function Test. Other outcomes include the Box and Block Test, Action Research Arm Test, upper extremity use in daily living, biomechanical measure of the sensorimotor grip control, and EEG-based neural communication., Discussion: This research will determine clinical utility of TheraBracelet to guide future translation. The TheraBracelet stimulation is delivered via a wrist-worn device, does not interfere with hand motion, and can be easily integrated into clinical practice. Enhancing hand function should substantially increase stroke survivors' independence and quality of life and reduce caregiver burden., Trial Registration: NCT04569123 . Registered on September 29, 2020., (© 2022. The Author(s).)

Background: Phthalates are endocrine disrupting chemicals that have been associated with adverse neurobehavior, but little is known about their influence on infant cognition., Methods: A visual recognition memory task was used to assess cognition in 244 7-8-month-old infants (121 females; 123 males) from a prospective cohort study. Phthalate metabolites were quantified in maternal urines pooled from across pregnancy. The task included familiarization trials (infant shown 2 identical faces) and test trials (infant shown the now familiar face paired with a novel one). Half of the infants saw one set of faces as familiar (set 1) and half saw the other set as familiar (set 2). During familiarization trials, average run duration (time looking at stimuli before looking away, measure of processing speed), and time to familiarization (time to reach 20 s looking at the stimuli, measure of attention) were assessed. During test trials, novelty preference (proportion of time looking at the novel face, measure of recognition memory) was assessed. Multivariable generalized linear models were used to assess associations of monoethyl phthalate (MEP), sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP), sum of di(isononyl) phthalate metabolites (ΣDINP), and sum of anti-androgenic phthalate metabolites (ΣAA) with each outcome., Results: Mothers were mostly white and college educated, and urine phthalate concentrations were similar to those in reproductive age women in the U.S., Population: All phthalate exposure biomarkers, except MEP, were associated with increases in average run duration. However, depending on the phthalate, associations were only in males or infants who saw the set 2 stimuli as familiar. Unexpectedly, ΣAA was associated with a shorter time to reach familiarization. Phthalate biomarkers also were associated with modest decrements in novelty preference, but these associations were nonsignificant., Conclusion: Prenatal exposure to phthalates may be related to slower information processing and poorer recognition memory in infants., (Published by Elsevier B.V.)

Objective: To evaluate the effect of intensive rehabilitation on the modified Rankin Scale (mRS), a measure of activities limitation commonly used in acute stroke studies, and to define the specific changes in body structure/function (motor impairment) most related to mRS gains., Methods: Patients were enrolled >90 days poststroke. Each was evaluated before and 30 days after a 6-week course of daily rehabilitation targeting the arm. Activity gains, measured using the mRS, were examined and compared to body structure/function gains, measured using the Fugl-Meyer (FM) motor scale. Additional analyses examined whether activity gains were more strongly related to specific body structure/function gains., Results: At baseline (160 ± 48 days poststroke), patients (n = 77) had median mRS score of 3 (interquartile range, 2-3), decreasing to 2 [2-3] 30 days posttherapy ( p < 0.0001). Similarly, the proportion of patients with mRS score ≤2 increased from 46.8% at baseline to 66.2% at 30 days posttherapy ( p = 0.015). These findings were accounted for by the mRS score decreasing in 24 (31.2%) patients. Patients with a treatment-related mRS score improvement, compared to those without, had similar overall motor gains (change in total FM score, p = 0.63). In exploratory analysis, improvement in several specific motor impairments, such as finger flexion and wrist circumduction, was significantly associated with higher likelihood of mRS decrease., Conclusions: Intensive arm motor therapy is associated with improved mRS in a substantial fraction (31.2%) of patients. Exploratory analysis suggests specific motor impairments that might underlie this finding and may be optimal targets for rehabilitation therapies that aim to reduce activities limitations., Clinical Trial: Clinicaltrials.gov identifier: NCT02360488., Classification of Evidence: This study provides Class III evidence that for patients >90 days poststroke with persistent arm motor deficits, intensive arm motor therapy improved mRS in a substantial fraction (31.2%) of patients., (© 2021 American Academy of Neurology.)

Objectives: To investigate the relationship between bimanual performance deficits measured using kinematics and callosum (CC) white matter changes that occur in people with chronic stroke., Design: Cross-sectional, observational study of participants with chronic stroke and age-matched controls., Setting: Recruitment and assessments occurred at a stroke recovery research center. Behavioral assessments were performed in a controlled laboratory setting. Magnetic resonance imaging scans were performed at the Center for Biomedical Imaging., Participants: Individuals were enrolled and completed the study (N=39; 21 participants with chronic stroke; 18 age-matched controls with at least 2 stroke risk factors)., Main Outcome Measures: Diffusion imaging metrics were obtained for each individual's CC and corticospinal tract (CST), including mean kurtosis (MK) and fractional anisotropy (FA). A battery of motor assessments, including bimanual kinematics, were collected from individuals while performing bimanual reaching., Results: Participants with stroke had lower FA and MK in the CST of the lesioned hemisphere when compared with the non-lesioned hemisphere. The FA and MK values in the CST were correlated with measures of unimanual hand performance. In addition, participants with stroke had significantly lower FA and MK in the CC than matched controls. CC diffusion metrics positively correlated with hand asymmetry and trunk displacement during bimanual performance, even when correcting for age and lesion volume., Conclusions: These data confirm previous studies that linked CST integrity to unimanual performance and provide new data demonstrating a link between CC integrity and both bimanual motor deficits and compensatory movements., (© 2020 The Authors.)

Importance: Many patients receive suboptimal rehabilitation therapy doses after stroke owing to limited access to therapists and difficulty with transportation, and their knowledge about stroke is often limited. Telehealth can potentially address these issues., Objectives: To determine whether treatment targeting arm movement delivered via a home-based telerehabilitation (TR) system has comparable efficacy with dose-matched, intensity-matched therapy delivered in a traditional in-clinic (IC) setting, and to examine whether this system has comparable efficacy for providing stroke education., Design, Setting, and Participants: In this randomized, assessor-blinded, noninferiority trial across 11 US sites, 124 patients who had experienced stroke 4 to 36 weeks prior and had arm motor deficits (Fugl-Meyer [FM] score, 22-56 of 66) were enrolled between September 18, 2015, and December 28, 2017, to receive telerehabilitation therapy in the home (TR group) or therapy at an outpatient rehabilitation therapy clinic (IC group). Primary efficacy analysis used the intent-to-treat population., Interventions: Participants received 36 sessions (70 minutes each) of arm motor therapy plus stroke education, with therapy intensity, duration, and frequency matched across groups., Main Outcomes and Measures: Change in FM score from baseline to 4 weeks after end of therapy and change in stroke knowledge from baseline to end of therapy., Results: A total of 124 participants (34 women and 90 men) had a mean (SD) age of 61 (14) years, a mean (SD) baseline FM score of 43 (8) points, and were enrolled a mean (SD) of 18.7 (8.9) weeks after experiencing a stroke. Among those treated, patients in the IC group were adherent to 33.6 of the 36 therapy sessions (93.3%) and patients in the TR group were adherent to 35.4 of the 36 assigned therapy sessions (98.3%). Patients in the IC group had a mean (SD) FM score change of 8.36 (7.04) points from baseline to 30 days after therapy (P < .001), while those in the TR group had a mean (SD) change of 7.86 (6.68) points (P < .001). The covariate-adjusted mean FM score change was 0.06 (95% CI, -2.14 to 2.26) points higher in the TR group (P = .96). The noninferiority margin was 2.47 and fell outside the 95% CI, indicating that TR is not inferior to IC therapy. Motor gains remained significant when patients enrolled early (<90 days) or late (≥90 days) after stroke were examined separately., Conclusions and Relevance: Activity-based training produced substantial gains in arm motor function regardless of whether it was provided via home-based telerehabilitation or traditional in-clinic rehabilitation. The findings of this study suggest that telerehabilitation has the potential to substantially increase access to rehabilitation therapy on a large scale., Trial Registration: ClinicalTrials.gov identifier: NCT02360488.

Importance: Along with growth in telerehabilitation, a concurrent need has arisen for standardized methods of tele-evaluation., Objective: To examine the feasibility of using the Kinect sensor in an objective, computerized clinical assessment of upper limb motor categories., Design: We developed a computerized Mallet classification using the Kinect sensor. Accuracy of computer scoring was assessed on the basis of reference scores determined collaboratively by multiple evaluators from reviewing video recording of movements. In addition, using the reference score, we assessed the accuracy of the typical clinical procedure in which scores were determined immediately on the basis of visual observation. The accuracy of the computer scores was compared with that of the typical clinical procedure., Setting: Research laboratory., Participants: Seven patients with stroke and 10 healthy adult participants. Healthy participants intentionally achieved predetermined scores., Outcomes and Measures: Accuracy of the computer scores in comparison with accuracy of the typical clinical procedure (immediate visual assessment)., Results: The computerized assessment placed participants' upper limb movements in motor categories as accurately as did typical clinical procedures., Conclusions and Relevance: Computerized clinical assessment using the Kinect sensor promises to facilitate tele-evaluation and complement telehealth applications., What This Article Adds: Computerized clinical assessment can enable patients to conduct evaluations remotely in their homes without therapists present., (Copyright © 2019 by the American Occupational Therapy Association, Inc.)

Background: Peripheral sensory stimulation has been used in conjunction with upper extremity movement therapy to increase therapy-induced motor gains in patients with stroke. The limitation is that existing sensory stimulation methods typically interfere with natural hand tasks and thus are administered prior to therapy, requiring patients' time commitment. To address this limitation, we developed TheraBracelet. This novel stimulation method provides subthreshold (ie, imperceptible) vibratory stimulation to the wrist and can be used during hand tasks/therapy without interfering with natural hand tasks., Objective: The objective was to determine the feasibility of using TheraBracelet during therapy to augment motor recovery after stroke., Design: The design was a triple-blinded pilot randomized controlled trial., Methods: Twelve chronic stroke survivors were assigned to the treatment or control group. All participants completed 2-hour task practice therapy sessions thrice weekly for 2 weeks. Both groups wore a small vibrator on the paretic wrist, which was turned on to provide TheraBracelet stimulation for the treatment group and turned off for the control group to provide sham stimulation. Outcome measures (Box and Block Test [BBT] and Wolf Motor Function Test [WMFT]) were obtained at baseline, 6 days after therapy, and at follow-up 19 days after therapy., Results: The intervention was feasible with no adverse events. The treatment group significantly improved their BBT scores after therapy and at follow-up compared with baseline, whereas the control group did not. For WMFT, the group × time interaction was short of achieving significance. Large effect sizes were obtained (BBT d = 1.43, WMFT d = 0.87). No indication of desensitization to TheraBracelet stimulation was observed., Limitations: The limitation was a small sample size., Conclusions: TheraBracelet could be a promising therapy adjuvant for upper extremity recovery after stroke., (© 2019 American Physical Therapy Association.)

Rasch keyforms can help interpret clinical assessment scores. The Action Research Arm Test (ARAT) is a commonly used assessment, yet no keyform currently exists. The aim is to provide a keyform for the ARAT and demonstrate how a clinician can use the keyform to design optimally challenging rehabilitation sessions. Secondary analysis of ARAT data ( n = 122) using confirmatory factor and Rasch analyses were used to examine the measurement properties and generate a keyform. The item standardized factor loadings were >0.40 (range = 0.82-0.96) and R 2 values were >.60 (range = .65-.96). All items exhibited adequate infit statistics with point measure correlations >.60 (range = .72-.97). Person reliability was .98, and person separation was 7.07. Item-difficulty measures ranged from -2.78 logits to 2.64 logits. The ARAT has strong measurement properties, and a keyform was provided. We showed how the keyform can be utilized by clinicians to interpret scores, set goals, and plan treatment.

Unilateral neglect (neglect) and anosognosia often co-occur post stroke. It is unknown whether anosognosia of neglect varies for different types of daily activities. The objective is to examine the frequency of anosognosia of neglect for items on the Catherine Bergego Scale (CBS) and to determine the level of agreement between participant/assessor item ratings and total scores. Secondary analysis of data was carried out. We conducted descriptive analyses and interrater reliability analyses (Cohen's kappa) to determine the level of agreement between assessor and participant item ratings. A paired t test was conducted to compare assessor and participant total scores. The frequency of anosognosia among items varied (29.2%-83.3%) and Kappa statistics ranged from -0.07 (no agreement) to 0.23 (fair agreement) for item ratings. There was a significant difference- t(36) = 3.02, p ≤ .01)-between assessor ( M = 8.0, SD = 5.2) and participant-rated ( M = 5.3, SD = 4.5) total CBS scores. Anosognosia is prevalent among those with neglect. Findings highlight the importance of assessing for anosognosia.

Objective: To investigate the measurement properties of the Functional Test of the Hemiparetic Upper Extremity (FTHUE) and examine how its score may or may not inform design of a rehabilitation program., Design: The FTHUE was recently used in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation randomized controlled trial. This circumstance provided the opportunity to examine the psychometric properties of the FTHUE as it pertains to contemporary poststroke rehabilitation and recovery models., Setting: Outpatient rehabilitation clinic., Participants: Participants (N=109; mean age, 61.2±13.5y; mean days poststroke, 46±20.3) with resultant hemiparesis in the upper extremity., Interventions: Not applicable., Main Outcome Measures: Dimensionality was examined with confirmatory factor analysis (CFA), and person and item measures were derived with Rasch item response analysis. Therapists' notes were also reviewed., Results: The CFA results support unidimensionality, and 16 of 17 items fit the Rasch model. The Rasch person separation (2.17) and item separation (4.50) indices, ability strata (3.22), person reliability (.82), and item reliability (.95) indicate good measurement properties. Item difficulties ranked from -6.46 to 3.43 logits; however, there was a substantial ceiling effect of person measures. Post hoc examination of therapists' written observations indicated that the scoring criteria are not sensitive to the movement strategy used for task completion., Conclusions: The FTHUE's item difficulty hierarchy indicated that scores adequately distinguished the ability to perform simple versus complex motor movements of functional tasks. However, the FTHUE scoring method did not allow inclusion of the type of movement strategy used to accomplish task items. Therefore, we suggest modifications to the FTHUE that would allow it to be used for collaborative treatment planning and align well with more contemporary perspectives on treatment theory., (Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: We determined whether various assessment tools detect neglect differently by administering a battery of assessments to people with stroke., Method: We conducted a case series study and administered five neglect assessments (paper-and-pencil, functional, virtual reality) to participants poststroke., Results: Twelve participants (6 men, 6 women) with stroke completed the assessment battery, which required approximately 2 hr to administer (over one to two sessions). All participants demonstrated neglect on three or more assessments. Functional assessments and the virtual reality assessment detected neglect more frequently than the paper-and-pencil assessments. Participants performed differently on the paper-and-pencil assessments and functional assessments., Conclusion: Because neglect is complex, detection may depend largely on the assessment administered., (Copyright © 2017 by the American Occupational Therapy Association, Inc.)

Objective: To test the feasibility of the Fugl-Meyer Assessment of the Upper Extremity "keyform," derived from Rasch analysis, as a method for systematically planning and progressing rehabilitation., Design: Feasibility study, single group design., Setting: University rehabilitation research laboratory., Participants: Participants (N=10; mean age, 59.70±9.96y; 24.1±30.54mo poststroke) with ischemic or hemorrhagic stroke >3 months prior, voluntarily shoulder flexion ≥30°, and simultaneous elbow extension ≥20°., Interventions: The keyform method defined initial rehabilitation targets (goals) and progressed the rehabilitation program after every third session. Targets were repetitively practiced within the context of client-selected functional tasks not in isolation., Main Outcome Measures: Feasibility was defined by subject's pain or fatigue, upper extremity motor function (Wolf Motor Function Test), and movement patterns (kinematics). Assessments were administered pre- and posttreatment and compared using paired t tests. Task-difficulty and patient-ability measures were calculated using Rasch analysis and compared using paired t tests (P<.05)., Results: Ten participants completed 9 sessions, 200 movement repetitions per session in <2 hours without pain or fatigue. Participants gained upper extremity motor function (Wolf Motor Function Test: pretreatment, 22.23±24.26s; posttreatment, 15.46±22.12s; P=.01), improved shoulder-elbow coordination (index of curvature: pretreatment, 1.30±0.15; posttreatment, 1.21±0.11; P=.01), and exhibited reduced trunk compensatory movement (trunk displacement: pretreatment, 133.97±74.15mm; posttreatment, 108.08±64.73mm; P=.02). Task-difficulty and patient-ability measures were not statistically different throughout the program (person-ability measures of 1.01±0.05, 1.64±0.45, and 2.22±0.65 logits and item-difficulty measures of 0.93±0.37, 1.70±0.20, and 2.06±0.24 logits at the 3 testing time points, respectively; P>.05)., Conclusions: The Fugl-Meyer Assessment of the Upper Extremity keyform is a feasible method to ensure that the difficulty of tasks practiced were well matched to initial and evolving levels of upper extremity motor ability., Competing Interests: There are no conflicts of interest, (Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine specific motor skills in premature infants, match those that correlate with standards tests of motor performance, and MRS measures of abnormal brain biochemistry., Methods: Prospective cohort study of preterm infants (n=22). Infant motor assessments were completed at term and 12 weeks corrected gestational age (CGA) using the Test of Infant Motor Performance (TIMP) and Bayley Scales of Infant and Toddler Development-III at 12 months CGA. Infants (n=12) received MRS scans at term CGA. Rasch analysis and MRS findings investigated TIMP items well targeted to high and low risk infants., Results: A 10 item subset of motor skill items correlated strongly with full 42-item TIMP at term and 12 week testing (r> 0.90, p< 0.001 for both), and with Bayley gross motor scores. MRS metabolites in basal ganglia correlated significantly with both TIMP and 10 item motor tests at term, while frontal white matter metabolites correlated with TIMP and 10 item tests at 12 weeks and Bayley motor scores., Conclusion: A short motor skill assessment may be representative of a longer standardized test and relate to brain metabolic function in key areas for motor movement and development. Validation of a shortened assessment may improve early identification of high-risk preterm infants.

Objectives: To define Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) cutoff scores that demarcate 1 level of upper extremity (UE) impairment from another, and describe motor behaviors for each category in terms of expected FMA-UE item performance., Design: Analysis of existing FMA-UE data., Setting: University research laboratory., Participants: Persons (N=512) 0 to 145 days poststroke, 42 to 90 years of age., Intervention: Not applicable., Main Outcome Measures: An item response Rasch analysis staging method was used to calculate cutoff scores, which were defined as the Rasch-Andrich threshold values of 2 criterion FMA-UE items derived from an analysis of this sample. The analysis enabled conversion of cutoff scores, in logit units, to FMA-UE points assessed on 30 FMA-UE voluntary movement items (60 possible points)., Results: The boundary between severe and moderate impairment was defined as -1.59 ± .27 logits or 19 ± 2 points; and between moderate and mild impairment was defined as 2.44 ± .27 logits or 47 ± 2 points. A description of expected performance in each impairment level shows that patients with severe impairment exhibited some distal movements, and patients with mild impairment had difficulties with some proximal movements., Conclusions: The cutoff scores, which link to a description of specific movements a patient can, can partially, and cannot perform, may enable formation of heterogeneous patient groups, advance efforts to identify specific movement therapy targets, and define treatment response in terms of specific movement that changed or did not change with therapy., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Standardized assessments are critical for advancing clinical rehabilitation, yet assessment scores often provide little information for rehabilitation treatment planning. A keyform recovery map is an innovative way for a therapist to record patient responses to standardized assessment items. The form enables a therapist to view the specific items that a patient can or cannot perform. This information can assist a therapist in tailoring treatments to a patient's individual ability level. We demonstrate how a keyform recovery map can be used to inform clinical treatment planning for individuals with stroke-related upper-limb motor impairment. A keyform map of poststroke upper-limb recovery defined by items of the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) was generated by a previously published Rasch analysis. Three individuals with stroke enrolled in a separate research study were randomly selected from each of the three impairment strata of the FMA-UE. Their performance on each item was displayed on the FMA-UE keyform. The forms directly connected qualitative descriptions of patients' motor ability to assessment measures, thereby suggesting appropriate shorter and longer term rehabilitation goals. This study demonstrates how measurement theory can be used to translate a standardized assessment into a useful, evidence-based tool for making clinical practice decisions.

Background: Poststroke reaching is characterized by excessive trunk motion and abnormal shoulder-elbow coordination. Little attention is typically given to arm-trunk kinematics during task practice. Preventing compensatory trunk motion during short-term practice immediately improves kinematics, but effects of longer-term practice are unknown., Objective: This study compared the effects of intensive task practice with and without trunk restraint on poststroke reaching kinematics and function., Methods: A total of 11 individuals with chronic stroke, baseline Fugl-Meyer Upper Extremity Assessment scores 26 to 54, were randomized to 2 constraint-therapy intervention groups. All participants wore a mitt on the unaffected hand for 90% of waking hours over 14 days and participated in 10 days/6 hours/day of supervised progressive task practice. During supervised sessions, one group trained with a trunk restraint (preventing anterior trunk motion) and one group did not. Tasks for the trunk-restraint group were located to afford repeated use of a shoulder flexion-elbow extension reaching pattern. Outcome measures included kinematics of unrestrained targeted reaching and tests of functional arm ability., Results: Posttraining, the trunk-restraint group demonstrated straighter reach trajectories (P=.000) and less trunk displacement (P=.001). The trunk-restraint group gained shoulder flexion (P=.006) and elbow extension (P=.022) voluntary ranges of motion, the nonrestraint group did not. Posttraining angle-angle plots illustrated that individuals from the trunk-restraint group transitioned from elbow flexion to elbow extension during mid-reach; individuals in the nonrestraint group retained pretraining movement strategies. Both groups gained functional arm ability (P<.05 all tests)., Conclusion: Intensive task practice structured to prevent compensatory trunk movements and promote shoulder flexion-elbow extension coordination may reinforce development of "normal" reaching kinematics.

Objective: To investigate the longitudinal stability of the Fugl-Meyer Assessment (FMA) of the upper-extremity item difficulties by using Rasch analysis., Design: Secondary analysis of existing data from a cohort longitudinal study of stroke recovery., Setting: University research center., Participants: A total of 377 people, ages 69.2+/-11.2 years, to whom the assessment was administered at 2 weeks and 6 months poststroke., Interventions: Not applicable., Main Outcome Measures: Differential item function analysis performed by using the Winsteps software program examined whether the item difficulty hierarchical order of a modified 30-item FMA for the upper extremity (reflex items removed) was invariant across 2 testing occasions., Results: Only 2 items (shoulder flexion to 180 degrees, movement with normal speed) showed large differences in test-retest item difficulty calibration. Item instability had no practical consequences on the longitudinal measurement of person ability., Conclusions: The 30-item assessment shows a longitudinally stable item difficulty order and is valid for measuring volitional arm motor ability over time.

Objective: Bilateral arm training with rhythmic auditory cueing (BATRAC) has been reported to be efficacious in promoting upper-extremity (UE) recovery in chronic stroke. We tested a modified form of BATRAC (modBATRAC) in a new group of participants with a condensed treatment regime to determine whether we could replicate these reported results., Methods: Fourteen subjects with chronic stroke completed 2 weeks of 2.25 hours per session, 4 sessions per week of modBATRAC., Results: No significant changes were observed in UE Fugl-Meyer or Wolf Motor Function Test scores. Subjects did report increased paretic UE use on the Motor Activity Log (mean change, 0.50; SD = 0.70)., Conclusions: The results of this study offer only partial support for the efficacy of modBATRAC. As in previous trials, modBATRAC facilitated increased use of the paretic arm, but unlike previous trials, it did not increase motor performance. These differences may reflect a more temporally condensed training schedule and less impaired patients.

Evidence indicates that experience-dependent cortical plasticity underlies post-stroke motor recovery of the impaired upper extremity. Motor skill learning in neurologically intact individuals is thought to involve the primary motor cortex, and the majority of studies in the animal literature have studied changes in the primary sensorimotor cortex with motor rehabilitation. Whether changes in engagement in the sensorimotor cortex occur in humans after stroke currently is an area of much interest. The present study conducted a meta-analysis on stroke studies examining changes in neural representations following therapy specifically targeting the upper extremity to determine if rehabilitation-related motor recovery is associated with neural plasticity in the sensorimotor cortex of the lesioned hemisphere. Twenty-eight studies investigating upper extremity neural representations (e.g., TMS, fMRI, PET, or SPECT) were identified, and 13 met inclusion criteria as upper extremity intervention training studies. Common outcome variables representing changes in the primary motor and sensorimotor cortices were used in calculating standardized effect sizes for each study. The primary fixed effects model meta-analysis revealed a large overall effect size (ES=0.84, S.D.=0.15, 95% CI=0.76-0.93). Moreover, a fail-safe analysis indicated that 42 null effect studies would be necessary to lower the overall effect size to an insignificant level. These results indicate that neural changes in the sensorimotor cortex of the lesioned hemisphere accompany functional paretic upper extremity motor gains achieved with targeted rehabilitation interventions.

Objective: To investigate the dimensionality and construct validity of the Fugl-Meyer Assessment of the upper extremity by using Rasch analysis., Design: Secondary analysis of pooled data from 2 existing datasets: a randomized therapeutic exercise clinical trial and a cohort longitudinal study of stroke recovery., Setting: University research center., Participants: A total of 512 subjects, ages 69.8+/-11.1 years, who were 0 to 145 days poststroke., Interventions: Not applicable., Main Outcome Measures: Dimensionality was examined with principal components analysis and Rasch item-fit statistics. The Rasch-derived item hierarchy was examined for consistency with the expected course of poststroke upper-extremity recovery suggested by the reflex-hierarchical conceptual model underlying the assessment., Results: Factor loadings and item infit statistics suggested that the 3 reflex items were empirically disconnected from other assessment items. The reflex items were removed. The modified 30-item assessment showed a unidimensional structure. The Rasch-item-difficulty order was not consistent with the expected item order., Conclusions: The items testing resting-state reflexes may threaten the assessment's dimensionality. With reflex items removed, the assessment is a unidimensional measure of volitional movement. The Rasch-generated item-difficulty order challenges the hierarchical structure implied by the instrument's underlying conceptual framework.