Reduced prepulse inhibition in adolescents at risk for psychosis: a 2-year follow-up study.

BACKGROUND: Reduced prepulse inhibition (PPI) of the auditory startle reflex is a hallmark feature of attention-processing deficits in patients with schizophrenia and other psychotic disorders. Recent evidence suggests that these deficits may also be present before the onset of psychosis in individuals at ultra-high risk (UHR) and become progressively worse as psychosis develops. We conducted a longitudinal follow-up study to observe the development of PPI over time in UHR adolescents and healthy controls. METHODS: Two-year follow-up data of PPI measures were compared between UHR adolescents and a matched control group of typically developing individuals. RESULTS: We included 42 UHR adolescents and 32 matched controls in our study. Compared with controls, UHR individuals showed reduced PPI at both assessments. Clinical improvement in UHR individuals was associated with an increase in PPI parameters. LIMITATIONS: A developmental increase in startle magnitude partially confined the interpretation of the association between clinical status and PPI. Furthermore, post hoc analyses for UHR individuals who became psychotic between assessments had limited power owing to a low transition rate (14%). CONCLUSION: Deficits in PPI are present before the onset of psychosis and represent a stable vulnerability marker over time in UHR individuals. The magnitude of this marker may partially depend on the severity of clinical symptoms.

Audiovisual speech integration in pervasive developmental disorder: evidence from event-related potentials.

BACKGROUND: Integration of information from multiple sensory sources is an important prerequisite for successful social behavior, especially during face-to-face conversation. It has been suggested that communicative impairments among individuals with pervasive developmental disorders (PDD) might be caused by an inability to integrate synchronously presented visual and auditory cues. METHOD: We investigated audiovisual integration of speech stimuli among a group of high-functioning adult PDD individuals and age- and IQ-matched controls using electroencephalography, measuring both early pre-phonological, as well as late phonologically driven integration. RESULTS: Pre-phonological AV interactions are intact, while AV interactions corresponding to more complex phonological processes are impaired in individuals with PDD. CONCLUSIONS: The present findings argue for a pattern of impairments on tasks related to complex audiovisual integration combined with relative sparing of low-level integrational abilities. This combination may very well contribute to the communicative disabilities which are typical for the disorder.

Atypical processing of fearful face-voice pairs in Pervasive Developmental Disorder: an ERP study.

OBJECTIVE: An important premise for successful social-affective communication is rapid perception of visual and auditory emotional cues, as well as their multisensory integration (MSI). We investigated to what extent a deficit in recognition of emotions in individuals with Pervasive Developmental Disorder (PDD) may have its roots in abnormal MSI of emotional cues provided by the sight of a facial expression and an emotional tone of voice. METHODS: In twelve high-functioning, adult PDD individuals and thirteen age- and IQ-matched controls, (1) the processing of fearful faces was compared with that of happy faces; (2) MSI was assessed by characterizing the interaction effects of crossmodal presentation, using EEG. RESULTS: Increased P1 and N170 amplitudes were seen in response to fearful faces compared with happy faces in both groups. However, PDD individuals differed from healthy controls in MSI of fearful information from visual and auditory cues. CONCLUSIONS: Both groups show a similar pattern as concerns the early components of visual emotion processing, but there are anomalies in processing of fearful face-voice combinations in the PDD group. SIGNIFICANCE: Because of the importance of rapid MSI for social competence, MSI anomalies in PDD may be linked to the observed deficits in their emotional behavior.

Similar facial electromyographic responses to faces, voices, and body expressions.

Observing facial expressions automatically prompts imitation, as can be seen with facial electromyography. To investigate whether this reaction is driven by automatic mimicry or by recognition of the emotion displayed we recorded electromyograph responses to presentations of facial expressions, face-voice combinations and bodily expressions, which resulted from happy and fearful stimuli. We observed emotion-specific facial muscle activity (zygomaticus for happiness, corrugator for fear) for all three stimulus categories. This indicates that spontaneous facial expression is more akin to an emotional reaction than to facial mimicry and imitation of the seen face stimulus. We suggest that seeing a facial expression, an emotional body expression or hearing an emotional tone of voice all activate the affect program corresponding to the emotion displayed.

Reduced prepulse inhibition as an early vulnerability marker of the psychosis prodrome in adolescence.

BACKGROUND: The onset of psychosis is thought to be preceded by neurodevelopmental changes in the brain. However, the timing and nature of these changes have not been established. The aim of the present study was to determine whether three "classic" neurophysiological markers of schizophrenia are also characteristic of young adolescents (12-18 years) at ultra-high risk for psychosis (UHR). METHODS: 63 young UHR individuals and 68 typically developing, age-, sex- and IQ-matched controls were recruited for neurophysiological assessment. Data for P50 suppression, prepulse inhibition (PPI) and smooth pursuit eye movements (SPEM) were gathered and compared. RESULTS: UHR individuals showed reduced PPI compared to controls, which became more pronounced when controls were directly compared to medication-naive UHR individuals (N=39). There were no group differences in P50 or SPEM measures. CONCLUSIONS: These results suggest that PPI is a relatively early vulnerability marker, while changes in other neurophysiological measures may only be detected or affected later during the illness course. Antipsychotic and antidepressant medication may aid in elevating PPI levels and potentially have a neuroprotective effect.

More prolonged brain activity related to gaze cueing in schizophrenia.

OBJECTIVE: The ability to use the gaze direction of another person to guide attention is important for social functioning, but behavioral reports on this topic among individuals with schizophrenia are inconclusive. Event Related Potentials (ERPs) can very accurately pinpoint the shifting of attention, and can therefore shed more light on cueing abilities in schizophrenia. METHODS: ERPs were measured during two spatial attention tasks in 14 high-functioning, young adult schizophrenic individuals and 19 age- and IQ-matched controls. In one task neutral faces were used as cues, and in the other arrows. RESULTS: Speeded behavioral and ERP responses were found to validly cued targets compared with responses to invalidly cued targets in both groups. However, we found more prolonged cueing effects in the patient group in later stages of processing, indicated by enhanced validity effects of late ERP latencies to gaze cues but not to arrow cues. CONCLUSIONS: Our study provides evidence for normal attentional orienting at behavioral level and early cognitive processing, but more prolonged cognitive evaluation of gaze cues in young adults with schizophrenia. SIGNIFICANCE: Evidence from this study excludes a specific attentional orienting deficit from being a possible endophenotype for the disorder.

Psychophysiological markers of vulnerability to psychopathology in men with an extra X chromosome (XXY).

Studying genetically defined syndromes associated with increased risk for psychopathology may help in understanding neurodevelopmental mechanisms related to risk for psychopathology. Klinefelter syndrome (47,XXY) is one of the most common sex chromosomal aneuploidies (1 in 650 male births) and associated with increased vulnerability for psychopathology, including psychotic symptoms. Yet, it remains unknown whether this increased risk is associated with underlying psychophysiological mechanisms that are typically deficient in individuals with psychotic disorders. The present study assessed three "classic" psychophysiological markers of psychosis in Klinefelter syndrome (KS): smooth pursuit eye movements (SPEM), prepulse inhibition (PPI) and P50 suppression. Fourteen adults with KS and 15 non-clinical adults participated in the study. Data on SPEM (reflecting visuo-motor control) as well as PPI and P50 suppression (reflecting sensory gating) were collected. Dysfunctions in SPEM were observed in individuals with KS, with less smooth pursuit as expressed in lower position gain. Also, reduced sensory gating in individuals with KS was suggested by significantly reduced prepulse inhibition of the startle response (PPI) (effect size 1.6). No abnormalities were found in suppression of the P50 (effect size 0.6). We speculate that impairments in these psychophysiological mechanisms may reflect core brain dysfunctions that may also mediate the described increased vulnerability for psychotic symptoms in KS. Although speculative, such deficit specific, rather than disorder specific, psychophysiological dysfunctions in KS might convey vulnerability to other types of psychopathology as well. As KS already can be diagnosed prenatally, the predictive value of childhood impairments in prepulse inhibition and smooth pursuit for development of psychopathology later in life could be assessed. In sum, studying individuals with KS may prove to be an avenue of research leading to new hypotheses and insights into "at risk" pathways to psychopathology.

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.

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 COMT(158) 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.

Cross-sensory gating in schizophrenia and autism spectrum disorder: EEG evidence for impaired brain connectivity?

Autism spectrum disorders (ASD) and schizophrenia are both neurodevelopmental disorders that have extensively been associated with impairments in functional brain connectivity. Using a cross-sensory P50 suppression paradigm, this study investigated low-level audiovisual interactions on cortical EEG activation, which provides crucial information about functional integrity of connections between brain areas involved in cross-sensory processing in both disorders. Thirteen high functioning adult males with ASD, 13 high functioning adult males with schizophrenia, and 16 healthy adult males participated in the study. No differences in neither auditory nor cross-sensory P50 suppression were found between healthy controls and individuals with ASD. In schizophrenia, attenuated P50 responses to the first auditory stimulus indicated early auditory processing deficits. These results are in accordance with the notion that filtering deficits may be secondary to earlier sensory dysfunction. Also, atypical cross-sensory suppression was found, which implies that the cognitive impairments seen in schizophrenia may be due to deficits in the integrity of connections between brain areas involved in low-level cross-sensory processing.

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.