Do deficits in the magnocellular priming underlie visual derealization phenomena? Preliminary neurophysiological and self-report results in first-episode schizophrenia patients.

BACKGROUND: Early visual impairments probably partially caused by impaired interactions between magnocellular (M) and parvocellular (P) pathways (M priming deficit), and disturbances of basic self-awareness or self-disorders (SDs) are core features of schizophrenia. The relationships between these features have not yet been studied. We hypothesized that the M priming was impaired in first-episode patients and that this deficit was associated with visual aspects of SDs. AIM: To investigate early visual processing in a sample of first-episode schizophrenia patients and to explore the relationships between M and P functioning and visual aspects of SDs addressed by the Examination of Anomalous Self-Experience (EASE) interview. METHOD: Nine stimulating conditions were used to investigate M and P pathways and their interaction in a pattern reversal visually evoked potential (VEP) paradigm. N80 at mixed M- and P-conditions was used to investigate magnocellular priming. Generators were analyzed using source localization (Brain Electrical Source Analysis software: BESA). VEPs of nineteen first-episode schizophrenia patients were compared to those of twenty matched healthy controls by a bootstrap resample procedure. Visual aspects of SDs were analyzed through a factor analysis to separate symptom clusters of derealization phenomena. Thereafter, the associations between the main factors and the N80 component were explored using linear mixed models. RESULTS: Factor analyses separated two EASE factors ("distance to the world", and "intrusive world"). The N80 component was represented by a single dipole located in the occipital visual cortex. The bootstrap analysis yielded significant amplitude reductions and prolonged latencies in first-episode patients relative to controls in response to mixed M-P conditions, and normal amplitudes and latencies in response to isolated P- and M-biased stimulation. Exploratory analyses showed significant negative correlations between the N80 amplitude values at mixed M-P conditions and the EASE factor "distance to the world", i.e. relatively higher amplitudes in the patient group were associated with higher subjective perceived derealization ("distance to the world"). CONCLUSIONS: The early VEP component N80 evoked by mixed M-P conditions is assumed to be a correlate of M priming, and showed reduced amplitudes and longer latencies in first-episode patients. It probably reflects a hypoactivation of the M-pathway. The negative association between visual SDs (derealization phenomena characterized by visual experiences of being more distant to the world), and the M priming deficit was counterintuitive. It might indicate a dysregulated activity of the M-pathway in patients with SDs. Further research is needed to better understand this preliminary finding.

Evidence for a magnocellular disadvantage in early-onset schizophrenic patients: a source analysis of the N80 visual-evoked component.

BACKGROUND: Visual impairments in schizophrenia have been suggested to be partly caused by early processing deficits of the magnocellular (M) pathway. This might include disturbed interactions between the M and parvocellular (P) pathways and especially impaired M priming, which can disturb highlighting of relevant information. Such disorders may result from neurodevelopmental irregularities, which are assumed to be substantially involved in schizophrenia. This study sought to test the hypothesis that M priming is impaired in schizophrenia. In order to elucidate this neurodevelopmental aspect, we investigated patients with different ages of schizophrenia onset. This provided a useful design to integrate visual information processing in a neurodevelopmental model of schizophrenia. METHOD: Nine stimulus conditions were used to investigate the M- and P-pathways and their interaction in a pattern reversal VEP paradigm. N80 generators were analyzed using source localization (Brain Electrical Source Analysis software: BESA). Forty schizophrenia patients (early-onset=19; adult-onset=21) were compared with age- and gender-matched healthy controls (early-onset controls=19; adult-onset controls=21). Hypotheses were tested using a bootstrap resampling procedure. RESULTS: The N80 component was represented by a single dipole located in the occipital visual cortex. The bootstrap analysis yielded significant differences between early-onset schizophrenia patients and controls. We found lower amplitudes in response to mixed M-P conditions and normal amplitudes in response to isolated P- and M-biased stimulation. Concerning the latencies, significant differences were found between adult-onset subjects and their controls, with prolonged latencies for schizophrenia patients. CONCLUSIONS: The early VEP component N80 evoked by mixed M-P conditions is assumed to be a correlate of M priming and showed reduced amplitude in early-onset schizophrenic patients but not in adult-onset patients. These findings point towards an M priming deficit in early-onset patients and are compatible with a neurodevelopmental hypothesis of schizophrenia, probably reflecting asynchronies in brain maturational abnormalities occurring at different ages of illness onset.

Longitudinal assessment of response preparation and evaluation in migraine gives evidence for deviant maturation.

Evidence for deviant maturation of sensory processing in migraine has come recently from cross-sectional studies during childhood. Age-dependent development of response preparation and evaluation is characterized using a longitudinal design in school-aged migraine patients and controls in order to challenge the hypothesis of migraine as a maturation disorder. Forty-six children with migraine and 57 healthy controls aged 6-18 years were investigated and followed up 4 years later using a simple acoustic contingent negative variation (CNV) paradigm. Maturation in controls was characterized by increasing negativity of late and total CNV and stability of initial CNV (iCNV) and the motor postimperative negative variation (mPINV). Migraine patients showed a lack of development for late and total CNV and decreasing iCNV and mPINV negativity. This first longitudinal study confirms cross-sectional results of deviant CNV maturation in migraine. Altered maturation was not correlated with clinical improvement and may represent a vulnerability marker for migraine.

The topography of the scalp-recorded visual N700.

OBJECTIVE: To describe the topography of the N700 component of the scalp-recorded visual event-related potential (ERP) and to provide fundamental knowledge of the conditions under which it occurs. METHODS: We examined the time-course of visual ERP in response to the short (100ms) and prolonged (7s) presentation of simple salient visual stimuli separated by long interstimulus intervals employing high-resolution 64-channel DC-EEG. Current source density (CSD) mapping and spatio-temporal dipole source analysis were performed. RESULTS: CSD analysis revealed highly significant bilateral current sinks over occipito-temporal areas from about 450ms up to 1s after stimulus offset (visual N700). CSD topography and dipole source analysis suggested late prolonged activation of extrastriate visual areas which did not depend merely upon a stimulus offset response, afterimages or blinking, as confirmed by control conditions. CONCLUSIONS: Our findings provide basic knowledge about the time-course of sensory activation. We found that passive watching of rare salient short stimuli automatically evoked sustained activity in the extrastriate visual cortex up to 1s after stimulus offset. SIGNIFICANCE: Visual N700 provides a promising tool for important insights into the cortical mechanisms of stimulus post-processing. Its role in associative learning of temporally non-overlapping stimuli (automatic ultra-short-term sensory memory) should be explored.

Maturation of early visual processing investigated by a pattern-reversal habituation paradigm is altered in migraine.

Evidence for a disturbed maturation of information processing in migraine came recently from evoked and event-related potential studies during childhood. In adult migraineurs, deficient habituation is proposed as principal interictal abnormality and was found inter alia for Visual Evoked Potentials (VEPs). This study investigated response and habituation to pattern-reversal VEPs and its maturation in 102 children with primary headache (migraine with and without aura, tension-type headache) and 79 healthy controls from 6 to 18 years. A reduction of N180 latency from pre- to postpubertal age reflects maturation and was clearly present in controls but lessened in migraineurs. N180 latency was prolonged in migraineurs without aura from 12 years onwards. Habituation did not differ between groups. In conclusion, diminished N180 latency reduction with age in migraineurs gives further evidence that maturation of visual information processing is altered in migraine. Deficient habituation to pattern-reversal VEPs could not be confirmed during childhood migraine.

[Headache in children: also a problem for child and adolescent psychiatry? Pathogenesis, comorbidity, therapy]. / Kopfschmerzen bei Kindern: Auch ein kinder- und jugendpsychiatrisches Problem? Pathogenese, Komorbidität, Therapie.

Headache is a recurrent somatic complaint in childhood and adolescence. In recent decades headache prevalence has increased while the age of onset has decreased. In most cases headache can be categorized as migraine or tension-type headache without significant organic pathology, i.e. head trauma, structural lesion, etc. Diagnosis according to the criteria of the International Headache Society is based on subjective reports by patients and their parents. The basic tools of clinical assessment are history, physical examination and a headache diary. Laboratory tests, including electroencephalography and imaging studies should not, as a rule, be undertaken routinely. Pathophysiological models with an impact on therapeutic interventions will be discussed. Childhood headache is often treated inappropriately in daily practice despite the availability of various options (including environmental, drug, and psychological therapy). Psychological therapy (relaxation training, biofeedback, stress management, etc.) as well as medication can be applied for prophylaxis. Minimal therapeutic interventions have been shown to be equally effective in a remarkable number of patients. Chronic Headache shows relevant comorbidity with anxiety and depression and is associated with somatization and school disorders. A careful investigation and an adequate therapy of eventual psychiatric comorbidity is therefore strongly recommended.

Lack of age-dependent development of the contingent negative variation (CNV) in migraine children?

Increased negativity of contingent negative variation (CNV) in adult migraineurs is thought to reflect cortical hyperexcitability. CNV amplitude changes with age in healthy adults. Recently, evidence emerged that this might not be the case for migraineurs. Our study investigates age-dependency of CNV during childhood age. Seventy-six healthy controls and 61 children with migraine without aura (IHS code 1.1) between 6 and 18 years were examined using an acoustic S1-S2-CNV-paradigm with a 3-s inter-stimulus interval. The amplitude of the late component of CNV, as well as total CNV at the vertex (Cz according to the international 10-20 system), were significantly higher in migraineurs without aura than in controls. Healthy controls showed increasing amplitudes of CNV with age, whereas in migraine children without aura amplitudes did not change. Thus group differences were reduced during adolescence. Increased CNV negativity might reflect a biological vulnerability to migraine, rather than being a result of chronification. Migraineurs seem to lack age-dependent development of CNV also during early age, which supports the hypothesis of migraine as a maturation disorder.