Karen R. Dobkins

Recurrence risk for autism spectrum disorders: A baby siblings research consortium study

OBJECTIVE: The recurrence risk of autism spectrum disorders (ASD) is estimated to be between 3% and 10%, but previous research was limited by small sample sizes and biases related to ascertainment, reporting, and stoppage factors. This study used prospective methods to obtain an updated estimate of sibling recurrence risk for ASD. METHODS: A prospective longitudinal study of infants at risk for ASD was conducted by a multisite international network, the Baby Siblings Research Consortium. Infants (n = 664) with an older biological sibling with ASD were followed from early in life to 36 months, when they were classified as having or not having ASD. An ASD classification required surpassing the cutoff of the Autism Diagnostic Observation Schedule and receiving a clinical diagnosis from an expert clinician. RESULTS: A total of 18.7% of the infants developed ASD. Infant gender and the presence of >1 older affected sibling were significant predictors of ASD outcome, and there was an almost threefold increase in risk for male subjects and an additional twofold increase in risk if there was >1 older affected sibling. The age of the infant at study enrollment, the gender and functioning level of the infants older sibling, and other demographic factors did not predict ASD outcome. CONCLUSIONS: The sibling recurrence rate of ASD is higher than suggested by previous estimates. The size of the current sample and prospective nature of data collection minimized many limitations of previous studies of sibling recurrence. Clinical implications, including genetic counseling, are discussed.

Clinical Assessment and Management of Toddlers With Suspected Autism Spectrum Disorder: Insights From Studies of High-Risk Infants

With increased public awareness of the early signs and recent American Academy of Pediatrics recommendations that all 18- and 24-month-olds be screened for autism spectrum disorders, there is an increasing need for diagnostic assessment of very young children. However, unique challenges exist in applying current diagnostic guidelines for autism spectrum disorders to children under the age of 2 years. In this article, we address challenges related to early detection, diagnosis, and treatment of autism spectrum disorders in this age group. We provide a comprehensive review of findings from recent studies on the early development of children with autism spectrum disorders, summarizing current knowledge on early signs of autism spectrum disorders, the screening properties of early detection tools, and current best practice for diagnostic assessment of autism spectrum disorders before 2 years of age. We also outline principles of effective intervention for children under the age of 2 with suspected/confirmed autism spectrum disorders. It is hoped that ongoing studies will provide an even stronger foundation for evidence-based diagnostic and intervention approaches for this critically important age group.

Decreased levels of protein kinase C in Alzheimer brain

Protein kinase C (PK-C) levels were determined using [3H]phorbol-12,13-dibutyrate (PDB) binding and the in vitro phosphorylation of histone H I (III-S), in autopsied human frontal cortex of age- and postmortem time-matched normal and Alzheimer patients. PK-C levels in Alzheimer particulate fractions determined by both methods were about 50% of those in controls. PK-C levels in Alzheimer cytosol fractions were not significantly different from those in controls. In a parallel study, we measured the phosphorylation of a Mr 86,000 protein (P86), the major protein kinase C substrate in the cytosol fraction prepared from Alzheimer frontal cortex, and found it to be reduced to 43% of that in control brains. This reduction in P86 protein phosphorylation compared to controls was not detected in brain samples prepared from demented patients without Alzheimers disease. We considered 3 extraneous factors (postmortem delay, age and sex) which may have affected the extent of P86 phosphorylation and concluded that the reduced P86 phosphorylation in the Alzheimer samples is not due to any of them. Reduced PK-C levels and Mr 86,000 protein phosphorylation may reflect a biochemical deficit related specifically to the pathogenesis of Alzheimers disease.

Comparing the Effects of Auditory Deprivation and Sign Language within the Auditory and Visual Cortex

To investigate neural plasticity resulting from early auditory deprivation and use of American Sign Language, we measured responses to visual stimuli in deaf signers, hearing signers, and hearing nonsigners using functional magnetic resonance imaging. We examined compensatory hypertrophy (changes in the responsivity/size of visual cortical areas) and cross-modal plasticity (changes in auditory cortex responses to visual stimuli). We measured the volume of early visual areas (V1, V2, V3, V4, and MT+). We also measured the amplitude of responses within these areas, and within the auditory cortex, to a peripheral visual motion stimulus that was attended or ignored. We found no major differences between deaf and hearing subjects in the size or responsivity of early visual areas. In contrast, within the auditory cortex, motion stimuli evoked significant responses in deaf subjects, but not in hearing subjects, in a region of the right auditory cortex corresponding to Brodmanns areas 41, 42, and 22. This hemispheric selectivity may be due to a predisposition for the right auditory cortex to process motion; earlier studies report a right hemisphere bias for auditory motion in hearing subjects. Visual responses within the auditory cortex of deaf subjects were stronger for attended than ignored stimuli, suggesting top-down processes. Hearing signers did not show visual responses in the auditory cortex, indicating that cross-modal plasticity can be attributed to auditory deprivation rather than sign language experience. The largest effects of auditory deprivation occurred within the auditory cortex rather than the visual cortex, suggesting that the absence of normal input is necessary for large-scale cortical reorganization to occur.

Atypical face versus object processing and hemispheric asymmetries in 10-month-old infants at risk for autism.

BACKGROUND Previous studies have documented atypicalities in face/object processing in children and adults with autism spectrum disorders (ASDs). To investigate whether such atypicalities may reflect a genetically mediated risk factor present early in development, we measured face/object processing in 10-month-old high-risk infants who carry some of the genes associated with ASD because they have an older sibling diagnosed with the disorder. METHODS We employed event-related potentials (ERPs) to measure cortical responses to pictures of faces and objects, the objects being toys. Latencies and amplitudes of four ERP components (P100, N290, P400, and Nc) were compared between 20 high-risk infants and 20 low-risk control subjects (infants with no family history of ASD). RESULTS Responses to faces versus objects differed between high- and low-risk infants for the latencies of the N290 and P400. Differences were driven by faster responses to faces than objects in low-risk, but not high-risk, infants (P400) and, conversely, faster responses to objects than faces in high-risk, but not low-risk, infants (N290). Object responses were also faster in high-risk than low-risk infants (both N290 and P400). Left versus right hemisphere responses also differed between high- and low-risk infants for the amplitudes of the P100, N290, and P400; collapsed across faces/objects, low-risk, but not high-risk, infants exhibited hemisphere asymmetries. CONCLUSIONS Genetic risk for ASD is associated with atypical face versus object processing and an atypical lack of hemispheric asymmetry early in life. These atypicalities might contribute to development of the disorder.

The Effects of Spatial Attention on Motion Processing in Deaf Signers, Hearing Signers, and Hearing Nonsigners

Visual abilities in deaf individuals may be altered as a result of auditory deprivation and/or because the deaf rely heavily on a sign language (American Sign Language, or ASL). In this study, we asked whether attentional abilities of deaf subjects are altered. Using a direction of motion discrimination task in the periphery, we investigated three aspects of spatial attention: orienting of attention, divided attention, and selective attention. To separate influences of auditory deprivation and sign language experience, we compared three subject groups: deaf and hearing native signers of ASL and hearing nonsigners. To investigate the ability to orient attention, we compared motion thresholds obtained with and without a valid spatial precue, with the notion that subjects orient to the stimulus prior to its appearance when a precue is presented. Results suggest a slight advantage for deaf subjects in the ability to orient spatial attention. To investigate divided attention, we compared motion thresholds obtained when a single motion target was presented to thresholds obtained when the motion target was presented among confusable distractors. The effect of adding distractors was found to be identical across subject groups, suggesting that attentional capacity is not altered in deaf subjects. Finally, to investigate selective attention, we compared performance for a single, cued motion target with that of a cued motion target presented among distractors. Here, deaf, but not hearing, subjects performed better when the motion target was presented among distractors than when it was presented alone, suggesting that deaf subjects are more affected by the presence of distractors. In sum, our results suggest that attentional orienting and selective attention are altered in the deaf and that these effects are most likely due to auditory deprivation as opposed to sign language experience.

Visual contrast sensitivity in deaf versus hearing populations: exploring the perceptual consequences of auditory deprivation and experience with a visual language.

Early deafness in humans provides a unique opportunity to examine the perceptual consequences of altered sensory experience. In particular, visual perception in the deaf may be altered as a result of their auditory deprivation and/or because the deaf rely heavily upon a visual language (American Sign Language, or ASL, in the US). Recently, we found that deaf, but not hearing, subjects exhibit a right visual field/left hemisphere advantage on a low-level direction of motion task, a finding that has been attributed to the deafs experience with ASL [Psychol. Sci. 10 (1999) 256; Brain Res. 405 (1987) 268]. In order to determine whether this visual field asymmetry generalizes to other low-level visual functions, in this study we measured contrast sensitivity in deaf and hearing subjects to moving stimuli over a range of speeds (0.125-64 degrees /s). We hypothesized that if ASL use drives differences between hearing and deaf subjects, such differences may occur over a restricted range of speeds most commonly found in ASL. In addition, we tested a third group, hearing native signers who learned ASL early from their deaf parents, to further assess whether potential differences between groups results from ASL use. These experiments reveal no overall differences in contrast sensitivity, nor differences in visual field asymmetries, across subject groups at any speed tested. Thus, differences previously observed between deaf and hearing subjects for discriminating the direction of moving stimuli do not generalize to contrast sensitivity for moving stimuli, a result that has implications for the neural level at which plastic changes occur in the visual system of deaf subjects.

Visual Field Asymmetries for Motion Processing in Deaf and Hearing Signers

Recently, we reported a strong right visual field/left hemisphere advantage for motion processing in deaf signers and a slight reverse asymmetry in hearing nonsigners (Bosworth & Dobkins, 1999). This visual field asymmetry in deaf signers may be due to auditory deprivation or to experience with a visual-manual language, American Sign Language (ASL). In order to separate these two possible sources, in this study we added a third group, hearing native signers, who have normal hearing and have learned ASL from their deaf parents. As in our previous study, subjects performed a direction-of-motion discrimination task at different locations across the visual field. In addition to investigating differences in left vs right visual field asymmetries across subject groups, we also asked whether performance differences exist for superior vs inferior visual fields and peripheral vs central visual fields. Replicating our previous study, a robust right visual field advantage was observed in deaf signers, but not in hearing nonsigners. Like deaf signers, hearing signers also exhibited a strong right visual field advantage, suggesting that this effect is related to experience with sign language. These results suggest that perceptual processes required for the acquisition and comprehension of language (motion processing in the case of ASL) are recruited by the left, language-dominant, hemisphere. Deaf subjects also exhibited an inferior visual field advantage that was significantly larger than that observed in either hearing group. In addition, there was a trend for deaf subjects to perform relatively better on peripheral than on central stimuli, while both hearing groups showed the reverse pattern. Because deaf signers differed from hearing signers and nonsigners along these domains, the inferior and peripheral visual field advantages observed in deaf subjects is presumably related to auditory deprivation. Finally, these visual field asymmetries were not modulated by attention for any subject group, suggesting they are a result of sensory, and not attentional, factors.

Left-Hemisphere Dominance for Motion Processing in Deaf Signers

Evidence from neurophysiological studies in animals as well as humans has demonstrated robust changes in neural organization and function following early-onset sensory deprivation. Unfortunately, the perceptual consequences of these changes remain largely unexplored. The study of deaf individuals who have been auditorily deprived since birth and who rely on a visual language (i.e., American Sign Language, ASL) for communication affords a unique opportunity to investigate the degree to which perception in the remaining, intact senses (e.g., vision) is modified as a result of altered sensory and language experience. We studied visual motion perception in deaf individuals and compared their performance with that of hearing subjects. Thresholds and reaction times were obtained for a motion discrimination task, in both central and peripheral vision. Although deaf and hearing subjects had comparable absolute scores on this task, a robust and intriguing difference was found regarding relative performance for left-visual-field (LVF) versus right-visual-field (RVF) stimuli: Whereas hearing subjects exhibited a slight LVF advantage, the deaf exhibited a strong RVF advantage. Thus, for deaf subjects, the left hemisphere may be specialized for motion processing. These results suggest that perceptual processes required for the acquisition and comprehension of language (motion processing, in the case of ASL) are recruited (or “captured”) by the left, language-dominant hemisphere.

Infant temporal contrast sensitivity functions (tCSFs) mature earlier for luminance than for chromatic stimuli: evidence for precocious magnocellular development?

In order to investigate the development of luminance and chromatic temporal contrast sensitivity functions (tCSFs), we obtained chromatic and luminance contrast thresholds from individual 3- and 4-month old infants, and compared them to previously obtained functions in adults. Stimuli were moving sinusoidal gratings of 0.27 cyc/deg, presented at one of five temporal frequencies: 1.0, 2.1, 4.2, 9.4 or 19 Hz (corresponding speeds: 3.8, 7.7, 15, 34, 69 deg/s). Previous studies, including our own, have shown that adult tCSFs are bandpass for luminance stimuli (peaking at 5-10 Hz), yet lowpass for chromatic stimuli (sensitivity falling at > 2 Hz), and that the two functions cross one another near 4-5 Hz when plotted in terms of cone contrast. In the present study, we find that the shapes and peaks of the luminance tCSF in both 3- and 4-months-olds appear quite similar to those of adults. By contrast, chromatic tCSFs in infants are markedly different from those of adults. In agreement with our earlier report (Dobkins, K. R., Lia, B., & Teller, D. Y. (1997). Vision Research, 37(19), 2699-2716), the chromatic function in 3-month-olds is rather flat, lacking the sharp high temporal frequency fall-off characteristic of the adult function. In addition, the luminance tCSF in 3-month-olds is elevated above the chromatic tCSF, and the two functions do not exhibit an adult-like cross-over within the range of temporal frequencies tested. By 4 months of age, substantial development of chromatic contrast sensitivity takes place at the lowest temporal frequencies. Although still immature, the 4-month-old chromatic tCSF has begun to adopt a more adult-like shape. In addition, similar to adults, luminance and chromatic tCSFs in 4-month-olds cross one another near 5 Hz. In adults, magnocellular (M) and parvocellular (P) pathways are thought to underlie the bandpass luminance and lowpass chromatic tCSF, respectively (e.g. Lee, B. B., Pokorny, J., Smith, V. C., Martin, P. R., & Valberg, A. (1990). Journal of the Optical Society of America (a), 7(12), 2223-2236). Based on this correspondence between psychophysical and neural responses in adults, our results suggest that the relatively slow development of the chromatic tCSF in infants may reflect immature chromatic responses in the P pathway and/or reliance on chromatic responses originating in the M pathway.