Papers by Krestin Radonovich
Carolina Digital Repository (University of North Carolina at Chapel Hill), 2010
The purpose of this study was to investigate postural control in children with Autism Spectrum Di... more The purpose of this study was to investigate postural control in children with Autism Spectrum Disorders (ASD) during static and dynamic postural challenges. We evaluated postural sway during quiet standing and the center of pressure (COP) shift mechanism during gait initiation for thirteen children with ASD and twelve age matched typically developing (TD) children. Children with ASD produced 438% greater normalized mediolateral sway (p<0.05) and 104% greater normalized anteroposterior sway (p<0.05) than TD children. Consequently, normalized sway area was also significantly greater (p<0.05) in the group with ASD. Similarly, the maximum separation between the COP and center of mass (COM) during quiet stance was 100% greater in the anteroposterior direction (p<0.05) and 146% greater in the resultant direction (p<0.05) for children with ASD. No significant difference was observed in the mediolateral direction, in spite of the 123 % greater separation detected in children with ASD. During gait initiation, no group differences were detected in the posterior COP shift mechanism, suggesting the mechanism for generating forward momentum is intact. However, significantly smaller lateral COP shifts (p<0.05) were observed in children with ASD, suggesting instability or an alternative strategy for generating momentum in the mediolateral direction. These results help clarify some discrepancies in the literature, suggesting an impaired or immature control of posture, even under the most basic conditions when no afferent or sensory information have been removed or modified. Additionally, these findings provide new insight into dynamic balance in children with ASD.
Carolina Digital Repository (University of North Carolina at Chapel Hill), 2010
Restricted and repetitive behaviors in autism spectrum disorders have been conceptualized to refl... more Restricted and repetitive behaviors in autism spectrum disorders have been conceptualized to reflect impaired executive functions. In the present study, we investigated the performance of 6-17-year-old children with and without an autism spectrum disorder on a dimension-change card sort task that explicitly indicated sorting rules on every trial. Diagnostic groups did not differ in speed of responses after the first rule switch or in speed or accuracy on blocks with mixed versus single sort rules. However, performance of the ASD group was significantly slower and less accurate overall than the typically-developing group. Furthermore, within the ASD group, poorer DCCS task performance did not predict more severe autism symptoms. Implications for the executive dysfunction theory of autism are discussed.
JAMA Neurology
ImportanceThe association of fetal exposure to antiseizure medications (ASMs) with outcomes in ch... more ImportanceThe association of fetal exposure to antiseizure medications (ASMs) with outcomes in childhood are not well delineated.ObjectiveTo examine the association of fetal ASM exposure with subsequent adaptive, behavioral or emotional, and neurodevelopmental disorder outcomes at 2, 3, and 4.5 years of age.Design, Setting, and ParticipantsThe Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational cohort study conducted at 20 epilepsy centers in the US. A total of 456 pregnant women with epilepsy or without epilepsy were enrolled from December 19, 2012, to January 13, 2016. Children of enrolled women were followed up with formal assessments at 2, 3, 4.5, and 6 years of age. Statistical analysis took place from August 2022 to May 2023.ExposuresExposures included mother’s epilepsy status as well as mother’s ASM blood concentration in the third trimester (for children of women with epilepsy). Women with epilepsy were enrol...
Child Neuropsychology, Sep 1, 2004
Clinicians, parents, and teachers alike have noted that individuals with ADHD often have difficul... more Clinicians, parents, and teachers alike have noted that individuals with ADHD often have difficulties with &amp;amp;amp;amp;quot;time management,&amp;amp;amp;amp;quot; which has led some to suggest a primary deficit in time perception in ADHD. Previous studies have implicated the basal ganglia, cerebellum, and frontal lobes in time estimation and production, with each region purported to make different contributions to the processing and utilization of temporal information. Given the observed involvement of the frontal-subcortical networks in ADHD, we examined judgment of durations in children with ADHD (N = 27) and age- and gender-matched control subjects (N = 15). Two judgment tasks were administered: short duration (550 ms) and long duration (4 s). The two groups did not differ significantly in their judgments of short interval durations; however, subjects with ADHD performed more poorly when making judgments involving long intervals. The groups also did not differ on a judgment-of-pitch task, ruling out a generalized deficit in auditory discrimination. Selective impairment in making judgments involving long intervals is consistent with performance by patients with frontal lobe lesions and suggests that there is a deficiency in the utilization of temporal information in ADHD (possibly secondary to deficits in working memory and/or strategy utilization), rather than a problem involving a central timing mechanism.
Autism Research, May 25, 2016
Sensorimotor processing alterations are a growing focus in the assessment and treatment of Autism... more Sensorimotor processing alterations are a growing focus in the assessment and treatment of Autism Spectrum Disorders (ASD). The rotational vestibulo-ocular reflex (rVOR), which functions to maintain stable vision during head movements, is a sensorimotor system that may be useful in understanding such alterations and their underlying neurobiology. In this study, we assessed post-rotary nystagmus elicited by continuous whole body rotation among children with high-functioning ASD and typically developing children. Children with ASD exhibited increased rVOR gain, the ratio of eye velocity to head velocity, indicating a possible lack of cerebellar inhibitory input to brainstem vestibular nuclei in this population. The ASD group also showed less regular or periodic horizontal eye movements as indexed by greater variance accounted for by multiple higher frequency bandwidths as well as greater entropy scores compared to typically developing children. The decreased regularity or dysrhythmia in the temporal structure of nystagmus beats in children with ASD may be due to alterations in cerebellum and brainstem circuitry. These findings could potentially serve as a model to better understand the functional effects of differences in these brain structures in ASD.
Pediatric Rehabilitation, 2020
JAMA Neurology, 2022
Importance During pregnancy in women with epilepsy, lower blood concentrations of antiseizure med... more Importance During pregnancy in women with epilepsy, lower blood concentrations of antiseizure medications can have adverse clinical consequences. Objective To characterize pregnancy-associated concentration changes for several antiseizure medications among women with epilepsy. Design, Setting, and Participants Enrollment in this prospective, observational cohort study, Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), occurred from December 19, 2012, to February 11, 2016, at 20 US sites. Enrolled cohorts included pregnant women with epilepsy and nonpregnant control participants with epilepsy. Inclusion criteria were women aged 14 to 45 years, an intelligence quotient greater than 70 points, and, for the cohort of pregnant women, a fetal gestational age younger than 20 weeks. A total of 1087 women were assessed for eligibility; 397 were excluded and 230 declined. Data were analyzed from May 1, 2014, to June 30, 2021. Exposure Medication plasma concentrations in women taking monotherapy or in combination with noninteracting medications. The cohort of pregnant women was monitored through 9 months post partum, with similar time points for control participants. Main Outcomes and Measures Dose-normalized concentrations were calculated as total or unbound plasma medication concentrations divided by total daily dose. Phlebotomy was performed during 4 pregnancy study visits and 3 postpartum visits for the pregnant women and 7 visits over 18 months for control participants. The primary hypothesis was to test pregnancy changes of dose-normalized concentrations from nonpregnant postpartum samples compared with those of control participants. Results Of the 351 pregnant women and 109 control participants enrolled in MONEAD, 326 pregnant women (median [range] age, 29 [19-43] years) and 104 control participants (median [range] age, 29 [16-43] years) met eligibility criteria for this analysis. Compared with postpartum values, dose-normalized concentrations during pregnancy were decreased by up to 56.1% for lamotrigine (15.60 μg/L/mg to 6.85 μg/L/mg; P < .001), 36.8% for levetiracetam (11.33 μg/L/mg to 7.16 μg/L/mg; P < .001), 17.3% for carbamazepine (11.56 μg/L/mg to 7.97 μg/L/mg; P = .03), 32.6% for oxcarbazepine (11.55 μg/L/mg to 7.79 μg/L/mg; P < .001), 30.6% for unbound oxcarbazepine (6.15 μg/L/mg to 4.27 μg/L/mg; P < .001), 39.9% for lacosamide (26.14 μg/L/mg to 15.71 μg/L/mg; P < .001), and 29.8% for zonisamide (40.12 μg/L/mg to 28.15 μg/L/mg; P < .001). No significant changes occurred for unbound carbamazepine, carbamazepine-10,11-epoxide, and topiramate, although a decrease was observed for topiramate (29.83 μg/L/mg to 13.77 μg/L/mg; P = .18). Additionally, compared with dose-normalized concentrations from control participants, pregnancy dose-normalized median (SE) concentrations decreased significantly by week of gestational age: carbamazepine, -0.14 (0.06) μg/L/mg (P = .02); carbamazepine unbound, -0.04 (0.01) μg/L/mg (P = .01); lacosamide, -0.23 (0.07) μg/L/mg (P < .001); lamotrigine, -0.20 (0.02) μg/L/mg (P < .001); levetiracetam, -0.06 (0.03) μg/L/mg (P = .01); oxcarbazepine, -0.14 (0.04) μg/L/mg (P < .001); oxcarbazepine unbound, -0.11 (0.03) μg/L/mg (P < .001); and zonisamide, -0.53 (0.14) μg/L/mg (P < .001) except for topiramate (-0.35 [0.20] μg/L/mg per week) and carbamazepine-10,11-epoxide (0.02 [0.01] μg/L/mg). Conclusions and Relevance Study results suggest that therapeutic drug monitoring should begin early in pregnancy and that increasing doses of these anticonvulsants may be needed throughout the course of pregnancy.
Frontiers in Integrative Neuroscience, 2013
Restricted, repetitive behaviors (RRBs) are one of the core diagnostic criteria of autism spectru... more Restricted, repetitive behaviors (RRBs) are one of the core diagnostic criteria of autism spectrum disorders (ASD), and include simple repetitive motor behaviors and more complex cognitive behaviors, such as compulsions and restricted interests. In addition to the core symptoms, impaired movement is often observed in ASD. Research suggests that the postural system in individuals with ASD is immature and may never reach adult levels. RRBs have been related to postural sway in individuals with mental retardation. Our goals were to determine whether subjects with ASD had greater postural sway and whether RBS-R scores were related to the magnitude of postural sway. We compared the center of pressure (COP) sway area during quiet stance with scores on the Repetitive Behavior Scale-Revised (RBS-R) in children with ASD and typically developing (TD) controls ages 3-16. All subjects had Non-verbal IQ > 70. Subjects performed four quiet stance trials at a self-selected stance width for 20 s. Subjects with ASD had greater postural sway area compared to controls. Not surprisingly, subjects with ASD exhibited greater frequencies and intensities of RRBs overall and on all six subscales. Further, there was a positive correlation between postural sway area and presence of RRBs. Interestingly, results of the postural sway area for the ASD group suggests that roughly half of the ASD subjects scored comparable to TD controls, whereas the other half scored >2 SD worse. Motor impaired children did not have significantly worse IQ scores, but were younger and had more RRBs. Results support previous findings of relationships between RRBs and postural control. It appears that motor control impairments may characterize a subset of individuals with ASD. Better delineation of motor control abilities in individuals with ASD will be important to help explain variations of abilities in ASD, inform treatment, and guide examination of underlying neural involvement in this very diverse disorder.
Experimental and Clinical Psychopharmacology, 1998
Sixty-two individuals seeking treatment for marijuana dependence completed a comprehensive assess... more Sixty-two individuals seeking treatment for marijuana dependence completed a comprehensive assessment. Sociodemographics, substance use, psychosocial functioning, psychiatric symptoms, and medical status were compared with similar data collected from 70 treatment-seeking, cocaine-dependent individuals. Substantial psychosocial and psychiatric problems were observed in both groups. In general, the marijuana group reported substance-use histories and a range of impairment comparable with the cocaine group; however, they showed less severe dependence. The marijuana group was more ambivalent and less confident about stopping their marijuana use than the cocaine group was about stopping their cocaine use. These findings indicate that treatment-seeking, marijuana-dependent individuals exhibit substantial problems and that further efforts to develop effective treatments for this population are warranted.
Gait & Posture, 2014
Background: Postural control deficits in individuals with Autism Spectrum Disorders (ASD) are wid... more Background: Postural control deficits in individuals with Autism Spectrum Disorders (ASD) are widely acknowledged; however, the underlying biomechanical features of these deficits remain unknown. Nonlinear analyses provide insight into the nature of how movement is controlled and have the potential to provide new insight into the postural control abnormalities associated with ASD. The purpose of this study was to further investigate postural control deficits in children with ASD through linear and nonlinear analyses of center of pressure (COP) data. Methods: We evaluated COP data during quiet standing for 16 children with ASD and 17 age-matched typically developing (TD) children. The magnitude of COP fluctuations (COP ranges, velocity, and sway area) and complexity of postural control dynamics, quantified by multiscale entropy (MSE), were compared across groups. Results: Children with ASD displayed larger fluctuations in their COP data, observed in COP ranges (95.5% mediolaterally and 46.9% anteroposteriorly, p < 0.05 respectively) and COP sway area (885%, p < 0.05). Children with ASD also displayed less complexity in their COP data, observed in the MSE complexity index (C I ) (32.4% mediolaterally and 35.7% anteroposteriorly, p < 0.05 respectively). Conclusions: The present study successfully revealed that children with ASD have more repetitive patterns in their COP data, indicating a less complex control of posture, on multiple time scales, during quiet stance. These findings suggest a more regular or restricted control of posture and may be an initial step in linking postural instability to stereotypic behavior and the neurobiology of ASD.
Self-stimulatory behavior is one of the characteristics in children with autism spectrum disorder... more Self-stimulatory behavior is one of the characteristics in children with autism spectrum disorders (ASD). Self-stimulation causes repetitive and stereotypic behavior such as unusual ritualistic hand and body movement. Previous research suggests that these unusual movements in children with ASD may stem from one of the motor control deficits. Furthermore, this abnormal motor control ability manifests in impaired postural stability in children with ASD [1].
Journal of Consulting and Clinical Psychology, Dec 1, 2000
Http Dx Doi Org 10 1080 09297040490911104, Aug 9, 2010
This prospective, longitudinal study examined factors affecting intelligence and school readiness... more This prospective, longitudinal study examined factors affecting intelligence and school readiness in children 4-5 years of age with prenatal cocaine/opiate exposure. Intelligence and school readiness scores were not significantly different for the drug-exposed group (N = 104) than for unexposed, demographically matched controls (N = 35), although both groups scored slightly below average. Caregivers of drug-exposed children scored significantly lower in intelligence and reading achievement than caregivers of controls; both were below average. Caregiver reading scores accounted for the largest variance in both child intelligence and school readiness; for school readiness, birth weight also contributed but was less important in the model. Neither prenatal drug exposure nor continuing caregiver drug use was significant in the regression analyses. The relationship between child scores and caregiver reading achievement is consistent with studies showing the importance of a stimulating, supportive home environment, and suggests interventions to foster caregiver literacy skills and facilitate caregiver-child cognitive interactions such as reading to the child.
Child Neuropsychology, 2004
Child Neuropsychology, 2004
Autism research : official journal of the International Society for Autism Research, Jan 25, 2016
Sensorimotor processing alterations are a growing focus in the assessment and treatment of Autism... more Sensorimotor processing alterations are a growing focus in the assessment and treatment of Autism Spectrum Disorders (ASD). The rotational vestibulo-ocular reflex (rVOR), which functions to maintain stable vision during head movements, is a sensorimotor system that may be useful in understanding such alterations and their underlying neurobiology. In this study, we assessed post-rotary nystagmus elicited by continuous whole body rotation among children with high-functioning ASD and typically developing children. Children with ASD exhibited increased rVOR gain, the ratio of eye velocity to head velocity, indicating a possible lack of cerebellar inhibitory input to brainstem vestibular nuclei in this population. The ASD group also showed less regular or periodic horizontal eye movements as indexed by greater variance accounted for by multiple higher frequency bandwidths as well as greater entropy scores compared to typically developing children. The decreased regularity or dysrhythmia ...
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Papers by Krestin Radonovich