In addition, the findings of Kuhl et al. The current study involved two Phases. Phase 1 extends the ERP results of Kuhl et al. Phase 2 builds upon the results of Phase 1, investigating the consequences of the neural response to words at age 2 years in a prospective longitudinal study. In Phase 2, we evaluate the predictive power of the more typical ERP response to words in children with ASD identified in Phase 1 in terms of future linguistic, cognitive, and adaptive function in the full group of children with ASD.
In brief, Phase 1 studies the relationship between word processing and concurrent social function. Phase 2 builds on the results of Phase 1, evaluating the predictive power of a more typical neural response to words on later linguistic, cognitive, and adaptive function.
The ERP word paradigm examines responses to known, unknown, and backward words and has produced stable patterns of response from TD children across laboratories [18] — [23]. Collectively, these studies show that the pattern of ERP response to known and unknown words follows a specific developmental time course related to age and language proficiency.
Mills, Coffey-Corina and Neville [18] , [19] separated TD children between 13 and 20 months of age into subgroups based on parental reports of word comprehension and word production. They demonstrated that the overall characteristics of the ERP response to known and unknown words differ with age and with language proficiency. In the youngest and least proficient children, significant differences in ERP responses to known and unknown words are broadly and bilaterally distributed.
With increasing age, and with increasing language ability at a given age, significant differences in ERP responses to known and unknown words are limited to the temporal and parietal regions of the left hemisphere [18] , [19]. Mills and colleagues [18] , [19] also evaluated ERPs to a complex auditory signal i.
They interpreted the developmental pattern of results as evidence that the functional organization of language-relevant brain systems becomes progressively more specialized with increasing language abilities, and is specific to differences in word meaning—not simply a differential response to words and complex auditory stimuli. The pattern of developmental change over time shown by Mills and her colleagues has been replicated [20] and extended in investigations of known words and phonetically similar nonsense words [20] , known words and novel words just learned by toddlers [21] , known and unknown words in bilingual populations [22] , and known and unknown words in late talkers up to age 30 months [23].
All studies report the same pattern of ERP response to known and unknown words as a function of age and language proficiency, supporting the interpretation that language proficiency, and not age or brain structure maturation, accounts for the signature changes in language-relevant brain activity from broadly and bilaterally distributed to focal brain activity limited to the left temporal and parietal regions.
In the current study, Phase 1 tested the hypothesis that the ERP pattern of results in response to words in TD children and in two groups of children with ASD classified dichotomously on a social variable would reveal the same group and subgroup effects we had previously seen with speech syllables [10].
In other words, we expected that children with ASD who had less severe social symptoms would produce ERP responses to words resembling the TD controls, while affected children with more severe social symptoms would produce a very different pattern. Phase 2 depended upon the results of Phase 1. We reasoned that if the results of Phase 1 produced the expected group and subgroup effects—showing that affected children with less severe social symptoms produce an ERP response to words resembling the TD controls—Phase 2 would examine the predictive power of the defining characteristic of that more typical ERP response to words in terms of future language, cognitive, and adaptive function in the full group of children with ASD.
Phase 2 was motivated by studies conducted across laboratories in TD children which show future language is predicted by both ERP brain measures of early speech processing [24] — [27] and behavioral measures of early speech processing [28] — [33]. For example, the response to speech syllables at 7 months of age predicts the speed of language growth to 30 months of age [24] , and also predicts measures of reading readiness at the age of 5 years [28] , [29].
Given that research in TD children shows that neural measures of speech processing provide valid indicators of language growth, we reasoned that the use of neural measures to characterize language processing in children with ASD would provide a highly sensitive index of the brain functions underlying language learning, which would in turn provide an excellent predictor of functional outcomes in these children.
Phase 1 of the current study investigated children with ASD at enrollment in an intervention study at 2 years of age Time 1 [34] , employing an ERP measure of word processing with a documented developmental pattern in TD children, as well as a concurrent measure of severity of social symptoms.
Following Kuhl et al. Phase 2 of the current study investigated the potential for the defining characteristic of this neural response to words in 2-year-old children with ASD to, in turn, serve as an early brain indicator of functional outcome in the areas of language, cognition, and adaptive behavior 2 years later at the end of the experimental intervention when children were 4 years old Time 2 [34] , and 4 years later when children were 6 years old Time 3.
The paper reports data from human subjects, and ethical approval was obtained from the University of Washington Human Subjects Division. Written informed consent was obtained from parents or legal guardians of all participants according to the principles explained in the Declaration of Helsinki, and the rights of these participants were protected. Participants were recruited from local parent advocacy groups, Washington State Department of Developmental Disabilities, clinics, hospitals and the University of Washington Communications Studies Participant Pool.
Children with ASD in the present study were drawn from a larger group of children enrolled in a previously reported randomized, controlled trial that demonstrated the efficacy of the Early Start Denver Model ESDM as a developmental behavioral intervention ClinicalTrials. The inclusion criteria were: age below 30 months at entry, meeting criteria for autistic disorder on the Toddler Autism Diagnostic Interview [35] , meeting criteria for autism or ASD on the Autism Diagnostic Observation Schedule [36] , a clinical diagnosis based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition DSM-IV criteria [37] using all available information, residing within 30 minutes of the University of Washington, and willingness to participate in a 2-year intervention.
See Dawson et al. Data were collected from children with ASD at enrollment in the clinical trial Time 1 , at the end of the 2-year intervention phase Time 2 , and in a follow up study conducted 2 years after the completion of the intervention portion of the clinical trial Time 3.
These children were between 1. Affected children with usable ERP data did not differ from affected children without usable ERP data in terms of age, gender, diagnostic measures or standardized measures of receptive language cognitive ability, or adaptive behavior at Time 1.
Children with ASD were divided into subgroups based on a median split of their social scores on the Autism Diagnostic Observation Schedule ADOS [36] to investigate the relationship between ERPs to words and severity of social symptoms: those exhibiting more severe social symptoms and those exhibiting less severe social symptoms.
Subgroups did not differ significantly in chronological age. Although children exhibiting more severe social symptoms had lower mean scores on standardized behavioral measures of language, cognitive ability, and adaptive function, these differences were marginally significant for language measures, and were not significant for cognitive ability and adaptive behavior Table 1.
Families of 22 of the 24 children with ASD agreed to participate in the clinical trial following randomized assignment to intensive intervention groups. These 22 children with ASD returned for diagnostic testing when they were at least 33 months old, and all retained the diagnostic status as described above.
Two participants withdrew during the 2-year intervention period 1 female before Time 2 data collection, and one male participant did not return for the follow up study at Time 3. Twenty TD children were enrolled as control subjects for this study. Families reported no speech, language, hearing or other developmental problems in the participants or in their siblings. Diagnostic and standardized behavioral measures were not collected from the TD control group.
Known words were early acquired nouns selected from the MacArthur Communicative Development Inventory norming study [38]. Unknown words were low frequency words matched for number of syllables and were similar in phonological form to known words.
As in previous ERP word studies in young children [18] , [19] , [22] , [23] , we prepared a large pool of candidate known words naturally spoken by a female voice; digitized at 16 bits, 44 kHz sampling rate; and loudness balanced.
Individualized lists were determined for each child during the week before ERP testing based on parental report. Parents completed a questionnaire, indicating whether each potential known word was 1 produced, or 2 comprehended.
For children with ASD, we began with a standard list and then substituted additional words to insure that each word was comprehended by the child, and to maximize the inclusion of produced words on the individualized list. However, children were recruited and scheduled to meet the needs of the randomized controlled trial which prevented one to one matching. Frequency of presentation of specific known and unknown words was similar among the 3 groups affected children with more severe social symptoms, affected children with less severe social symptoms, and TD controls , with intergroup word frequency correlations ranging from.
EEG was collected continuously from 20 electrode sites using the standard International 10—20 system. Participants wore an elastic Electro-cap, and data were acquired using SAI amplifiers, band pass filtered at. The left mastoid served as reference. Participants listened passively while sitting on their parent's lap, watching an assistant playing quietly with toys while a silent child-oriented video was displayed on a monitor behind the assistant.
Stimuli were presented from two speakers placed on either side of the video monitor, approximately 4 feet in front of the participant. Words were presented at 65—67 dBA. The inter-stimulus interval was ms, onset to onset. All data were processed off-line, using epochs of ms pre-stimulus and ms post-stimulus onset.
Trials exceeding the threshold of positive or negative microvolts were rejected. In addition, hand editing was performed to ensure data were free of eye movements, muscle artifact and drift. Finally, individual subject averages were filtered using a low pass filter with a cut off of 25 Hz. The average number of trials per word-type was Individual and grand mean ERPs were examined to determine the most appropriate interval consistent with that found to be sensitive to differences in word type by Mills and colleagues [18] — [23].
Standardized measures of receptive language, cognitive ability, and adaptive behavior were administered to children with ASD at three time points: at enrollment in the intervention study Time 1 , 2 years later at the end of the experimental intervention Time 2 , and 4 years later in a follow up study Time 3.
TD controls did not complete standardized behavioral measures. The standardized measures of receptive language and cognitive ability used in the intervention study had age range limitations requiring different standardized measures for these domains in the follow up study at Time 3. In addition, not all participants at Time 3 completed all behavioral measures: 18 participants completed the standardized measure of receptive language, 19 participants completed the standardized measure of cognitive ability, and 15 participants completed the standardized measure of adaptive behavior.
Specific standardized tests at each time point are listed in Table 2. Intercorrelations among standardized behavioral measures of receptive language, cognitive ability, and adaptive behavior were significant at each time point; significant among behavioral measures at Time 1 and Time 2 using the same standardized tests for cognitive ability and adaptive behavior; and significant among all behavioral measures at Time 2 and Time 3, using different standardized tests of cognitive ability and receptive language.
However, intercorrelations among behavioral measures at Time 1 and Time 3 are not significant, indicating a decline in association over time that is unrelated to the specific standardized tests Table 3.
Variability also increased from Time 1 to Time 3 as evidenced by increased standard deviations and range of scores Table 4. Families of 22 of the 24 children with useable ERP data agreed to participate in the clinical trial and were randomly assigned to one of two intensive treatment groups as part of the clinical trial.
In addition, parents reported an additional Families assigned to the Community Intervention CI treatment group were referred to local providers for interventions commonly available in the community, and reported an average of 9. Although the random assignment did not consider availability of usable ERP data or the subgroup based on the severity of social symptoms, the group of children with ASD who had usable ERP data were evenly divided into the two treatment groups: 11 3 female, 6 with more severe social symptoms were assigned to the ESDM experimental intervention group, 11 3 female, 5 with more severe social symptoms were assigned to the CI treatment group, and 2 1 female, 1 with more severe social symptoms declined to participate in the randomized intervention see [34] for detailed information.
Nor did they differ significantly on these measures from children without usable ERP data assigned to their respective treatment groups.
In addition, toddlers with useable Time 1 ERP exhibited the same significant treatment effects on primary outcome measures i. Phase 1 examined whether the ERP response to words in 2-year-old children with ASD who were classified on a social measure and compared to TD controls produced group and subgroup effects similar to those previously observed in a study using speech syllables [10]. We hypothesized that the pattern of ERP brain responses to known and unknown words in children with ASD exhibiting less severe impairments in social function would resemble those of TD controls.
Note that ASD is characterized by deficits in social and linguistic function, and we hypothesized that affected children with ASD would be similar to TD children in the current study, but not that they would be indistinguishable from TD controls. Data were analyzed in the same manner as previous ERP word studies of TD children [18] — [23] employing repeated measures ANOVA and planned comparisons at all individual electrode sites measured.
The between subjects factor divided children with ASD based on severity of social symptoms using a median split, just as previous studies divided TD children based on various measures of language proficiency using a median split or percentile rankings [18] — [23]. Greenhouse- Geisser corrections were applied when appropriate and partial eta-squared was calculated for main effects and interactions.
Planned comparisons were reported as significant at the. Since all participants processed backward words in a similar way, consistent with previous research, further analyses were conducted with a two level within subjects word-type factor i. This three-way interaction reflects group differences in the response to known words. Previous work conducted planned comparisons at multiple electrode sites and reported significant differences in ERP response to known and unknown words in the temporal and parietal regions of the left hemisphere with increasing age and with increasing language ability at a given age [18] , [19].
The current study employed the standard International 10—20 electrode array without custom arrangements of electrode sites. Planned comparisons at each electrode site in the current study revealed that TD children exhibited results consistent with the previously reported signature focal negativity for known words in the left hemisphere. Taken together, these results indicate a link between the overall pattern of brain response to known words and social function in very young children with ASD: children with less severe social symptoms resemble TD controls, while those with more severe social symptoms show a clearly atypical brain response.
A TD 2-year-olds exhibit a focal response with significant differences between known and unknown words only at the left temporal electrode site T3, B children with ASD exhibiting less severe social symptoms show a more typical ERP pattern with a focal response that is significant only at the left parietal electrode site P3, C affected children exhibiting more severe social symptoms show a more diffuse response in the right hemisphere.
In contrast, affected children exhibiting more severe social symptoms show a more diffuse response with significant word-type effects at 2 right hemisphere electrode sites. Since the median split analysis yielded a relationship between severity of social symptoms and the overall pattern of ERP response across two word-types and 10 electrode sites, we did not anticipate significant associations between ERP mean amplitudes to known or unknown words at individual electrode site and the ADOS social total.
However, there is a significant association between the signature focal negativity for known words at the P3 electrode site, when compared to the overall negativity across all electrode sites, and severity of social symptoms. We calculated the average difference between known and unknown words across all electrode sites, and then subtracted that average from the difference between known and unknown words at P3.
Our results thus show significant relationships between a measure of severity of social symptoms in children with ASD ADOS social total and our ERP measure of word processing, consistent with our hypothesis of an association between linguistic and social function.
In Phase 1 of the current study, word stimuli were used to test 2-year-old children with ASD who were categorized into two groups based on social function, and comparisons were made with TD controls. As predicted, children with ASD who exhibit less severe social symptoms show a pattern of ERP response that resembles TD controls — a focal response in the left hemisphere, with one difference.
This could potentially indicate a difference in the source of brain activation in response to known words in the two groups. However, ERP methods are not sufficiently sensitive to fully explore this possibility, and we are currently using more sophisticated neuroimaging methods magnetoencephalography, or MEG in our laboratory to compare children with ASD and TD controls, which will allow the sources of brain activity to be more accurately localized in both groups.
Children with ASD exhibiting more severe social symptoms show an atypical ERP response to word stimuli, one that is more diffuse and in the right hemisphere, consistent with frequent reports of right hemisphere dominance in ASD, which in turn has been associated with both language impairment [44] and better language outcomes [45] see [46] for a general review. Nor does it resemble the broad, bilateral response shown in very young TD children [18] , [19] , which is also seen in older TD children with low productive vocabularies [23].
These results confirm an association between the pattern of ERP responses to word stimuli and social function in children with ASD. The group and subgroup effects are similar to those of our earlier study using an ERP syllable discrimination paradigm in older 3—4 year old children with ASD [10].
The results support the theoretical hypothesis that linguistic development, both in TD children and in children with ASD, is closely linked to social development see [15] , [17].
The link between language learning and social processing will be considered in the General Discussion. Phase 1 of the current study revealed that the pattern of ERP response to known and unknown words in affected children exhibiting less severe social symptoms resembled that of TD controls—a focal response with enhanced negativity to known vs.
In addition, the significant group level differences between affected children exhibiting less severe social symptoms and TD controls on one hand, and affected children exhibiting more severe social symptoms on the other, was shown in Phase 1 to be due to the processing of known words. Phase 2 of the current study builds on these results, investigating the predictive power of the ERP response to known words at the P3 electrode site Time 1 ERP in the full group of children with ASD on later linguistic, cognitive, and adaptive function.
We hypothesized that this defining characteristic of the more typical ERP response to words observed in children with ASD who exhibit less severe social symptoms i. The results of Phase 2 strongly support the hypothesis that brain responses to words in children with ASD at enrollment Time 1 predict outcome measures 2 and 4 years later when the children are 4 and 6 years of age.
Standardized behavioral measures of receptive language, cognitive ability, and adaptive function were collected at enrollment Time 1 , 2 years later at the end of the experimental intervention Time 2 , and 4 years later in a follow up study Time 3. The scatterplots in Figure 2 show the relationships between Time 1 ERP shown on the x-axis and measures of receptive language, cognitive ability, and adaptive function at Time 1, Time 2, and Time 3.
The measures of receptive language, cognitive ability, and adaptive behavior are expressed as norm-referenced standard scores and are plotted on the y-axis using the same scale across scatterplots. Constructing the x- and y-axes in this manner allows comparison of each child uniquely identified by Time 1 ERP mean amplitude on the x-axis to other children in his or her age group, and allows comparison of each child's standard scores on the same scale across time and standardized tests.
Ohio law also required the court to sentence Jeffrey to consecutive prison terms based on the conviction for failure to comply with the order or signal of a police officer.
Padden imposed a year driver's license suspension and ordered Jeffrey to pay court costs, although no fine was imposed. Jeffrey was given 70 days credit for time served since his arrest on Jan. In court Monday, Jeffrey admitted he told State Highway Patrol Trooper Adam Masinelli that officers would have to shoot and kill him after initially being stopped for a traffic violation.
Masinelli and other law enforcement pursued Jeffrey south at approximately 65 mph until he allegedly accelerated to mph upon approaching a spike strip deployed by a trooper.
More: Ohio man arrested after pursuit, stand-off on I I wanted to flip my car to hurt myself and I jerked the steering wheel after hitting the spikes, but it just spun on the road.
The vehicle slid off the right side of I and came to rest in a wooded area along the highway where Jeffrey refused to exit the car while surrounded by troopers and sheriff's deputies from Guernsey and Noble counties. After crashing, Jeffrey consumed a significant amount of pills before finally exiting the vehicle some time later. But instead of surrendering, Jeffrey emerged brandishing a knife and held authorities at bay until a Taser was eventually used to gain control of him approximately three hours after the crash.
Guernsey County Assistant Prosecuting Attorney Kent Biegler and defense attorney Matthew Mollica asked Paden to suspend the maximum four-year sentence in favor of community control sanctions Monday. Both attorneys cited Jeffrey's lengthy mental health history and the need for treatment as reasons for the request. He didn't try to assault the officers.
He had knives that he held out trying to get them to shoot him. Biegler and Mollica praised Patrol Lt. Melanie Appleman for taking control of the scene and preventing Jeffrey from being harmed.
Mollica told Padden his client is better because he is taking his medication and attending mental health counseling appointments. Give him a chance. Jeffrey said he started drinking alcohol at age 6 and smoking marijuana with his mother at age 7.
He was removed from his home at age 11 after allegedly being sexually assaulted by his father, according to court testimony.
He was reportedly in and out of multiple foster homes and group homes over the next several years. Following the arrest, Mollica filed a motion seeking a competency evaluation and filed a not guilty by reason of insanity plea on March 4. Daniel Hrinko of the Forensic Diagnostic Center of Region 9 determined Jeffrey was competent to stand trial following an evaluation, according to report revealed during a competency hearing on May More: Judge: Ohio man competent to stand trial.
An initial indictment of felonious assault, a second-degree felony, returned by a grand jury on Feb. A sentencing hearing slated for Oct.
Jeffrey was incarcerated in the Belmont County Jail at the time of the sentencing hearing, but was released after pleading no contest to the fourth-degree misdemeanor offense. He was sentenced in Belmont County Western Court to 30 days in jail with four days credit for time served and 26 days suspended. Kelly M. Lise G. Mischa B. Glenn G Jacob G Rusty D 1.
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