Proline and COMT Status Affect Visual Connectivity in Children with 22q11.2 Deletion Syndrome

Background Individuals with the 22q11.2 deletion syndrome (22q11DS) are at increased risk for schizophrenia and Autism Spectrum Disorders (ASDs). Given the prevalence of visual processing deficits in these three disorders, a causal relationship between genes in the deleted region of chromosome 22 and visual processing is likely. Therefore, 22q11DS may represent a unique model to understand the neurobiology of visual processing deficits related with ASD and psychosis. Methodology We measured Event-Related Potentials (ERPs) during a texture segregation task in 58 children with 22q11DS and 100 age-matched controls. The C1 component was used to index afferent activity of visual cortex area V1; the texture negativity wave provided a measure for the integrity of recurrent connections in the visual cortical system. COMT genotype and plasma proline levels were assessed in 22q11DS individuals. Principal Findings Children with 22q11DS showed enhanced feedforward activity starting from 70 ms after visual presentation. ERP activity related to visual feedback activity was reduced in the 22q11DS group, which was seen as less texture negativity around 150 ms post presentation. Within the 22q11DS group we further demonstrated an association between high plasma proline levels and aberrant feedback/feedforward ratios, which was moderated by the COMT158 genotype. Conclusions These findings confirm the presence of early visual processing deficits in 22q11DS. We discuss these in terms of dysfunctional synaptic plasticity in early visual processing areas, possibly associated with deviant dopaminergic and glutamatergic transmission. As such, our findings may serve as a promising biomarker related to the development of schizophrenia among 22q11DS individuals

Multisensory Integration and Attention in Autism Spectrum Disorder: Evidence from Event-Related Potentials

Successful integration of various simultaneously perceived perceptual signals is crucial for social behavior. Recent findings indicate that this multisensory integration (MSI) can be modulated by attention. Theories of Autism Spectrum Disorders (ASDs) suggest that MSI is affected in this population while it remains unclear to what extent this is related to impairments in attentional capacity. In the present study Event-related potentials (ERPs) following emotionally congruent and incongruent face-voice pairs were measured in 23 high-functioning, adult ASD individuals and 24 age- and IQ-matched controls. MSI was studied while the attention of the participants was manipulated. ERPs were measured at typical auditory and visual processing peaks, namely, P2 and N170. While controls showed MSI during divided attention and easy selective attention tasks, individuals with ASD showed MSI during easy selective attention tasks only. It was concluded that individuals with ASD are able to process multisensory emotional stimuli, but this is differently modulated by attention mechanisms in these participants, especially those associated with divided attention. This atypical interaction between attention and MSI is also relevant to treatment strategies, with training of multisensory attentional control possibly being more beneficial than conventional sensory integration therapy

Facial electromyographic responses to emotional information from faces and voices in individuals with pervasive developmental disorder.

Background: Despite extensive research, it is still debated whether impairments in social skills of individuals with pervasive developmental disorder (PDD) are related to specific deficits in the early processing of emotional information. We aimed to test both automatic processing of facial affect as well as the integration of auditory and visual emotion cues in individuals with PDD. Methods: In a group of high-functioning adult individuals with PDD and an age-and IQ-matched control group, we measured facial electromyography (EMG) following presentation of visual emotion stimuli (facial expressions) as well as the presentation of audiovisual emotion pairs (faces plus voices). This emotionally driven EMG activity is considered to be a direct correlate of automatic affect processing that is not under intentional control. Results: Our data clearly indicate that among individuals with PDD facial EMG activity is heightened in response to happy and fearful faces, and intact in response to audiovisual affective information. Conclusions: This study provides evidence for enhanced sensitivity to facial cues at the level of reflex-like emotional responses in individuals with PDD. Furthermore, the findings argue against impairments in crossmodal affect processing at this level of perception. However, given how little comparative work has been done in the area of multisensory perception, there is certainly need for further exploration

Event Related potentials.

<p>ERPs at P7 electrode to congruent visual – auditory fear (FF) and incongruent visual fear – auditory happy (FH) stimuli in the D₀, D₁ and D₂ conditions from the control group (above) and the ASD group (below). The arrows point to the N170 amplitudes.</p

Occipital-temporal N170 amplitudes.

<p>Left N170 amplitude differences (±SE) between stimulus conditions (FF - FH) show a lack of higher-order MSI in the D₀ condition for ASD individuals, while both groups show such an effect in the D₁ condition (* = p<.05).</p

Layout of the task.

<p>Attention was manipulated between AV blocks, and participants had to respond to a visual dot and auditory beep (D₀), a single digit ‘3’ (D₁), or when two digits together add up to 10 (D₂). Stimuli were presented concurrently during AV blocks and in isolation during unisensory blocks.</p

Frontal-central P2 amplitudes.

<p>Frontal-central P2 peaks are significantly larger (p<.001) to the sum of ERPs to unisensory stimuli (A+V) than to cross-modal (AV) stimuli under divided attention (D₀) and easy selective attention conditions (D₁) for both groups.</p

Feedback/feedforward ratio values.

<p>The association between proline and feedback/feedforward ratio is moderated by the <i>COMT</i>¹⁵⁸ genotype. The <i>COMT</i>^met subgroup is shown on the left, the <i>COMT</i>^val subgroup on the right. Ratio values were calculated by dividing texture negativity amplitudes by C1 amplitudes. The 22q11DS group was further split into ‘high proline’ and ‘low proline’ subgroups, by means of the group median plasma proline value of 257 µM. The control group feedback/feedforward ratio value was 1.9 (SE .24).</p

Event Related Potentials.

<p>ERPs at Oz electrode representing responses to checkerboards (red lines), homogeneous stimuli (blue lines) and difference waves (black lines). The upper graph represents the control group, the lower graph the 22q11DS group. Voltage maps indicate differential activity between both stimuli at the peak of Oz texture negativity.</p