Altered Visuospatial Processing in Schizophrenia: An Event-related Potential Microstate Analysis Comparing Patients with and without Hallucinations with Healthy Controls.

Patients with schizophrenia present with various symptoms related to different domains. Abnormalities of auditory and visual perception are parts of a more general problem. Nevertheless, the relationship between the lifetime history of auditory verbal hallucination (AVH), one of the most prevalent symptoms in schizophrenia, and visuospatial deficits remains unclear. This study aimed to investigate differences in hemispheric involvement and visuospatial processing between healthy controls (HCs) and schizophrenia patients with and without AVHs. HCs (N = 20), schizophrenia patients with AVH (AVH group, N = 16), and schizophrenia patients without hallucinations (NH group, N = 10) participated in a 4-choice reaction task with lateralized stimuli. An event-related potential (ERP)-microstate approach was used to analyze ERP differences between the conditions and groups. The schizophrenia patients without hallucinations had slower responses than the HCs. An early visual N1 contralateral to stimulation side was prominent in all groups of participants but with decreased amplitude in the patients with schizophrenia, especially in the AVH group over the right hemisphere. The amplitude of P3b, a cognitive evaluation component, was also decreased in schizophrenia. Compared to AVH and HC groups, the patients in the NH group had altered microstate patterns: P3b was replaced by a novelty component, P3a. Although the difference between both patient groups was only based on the presence of AVHs, our findings indicated that patients had specific visuospatial deficits associated with a lifetime history of hallucinations: patients with AVHs showed early visual component alterations in the right hemisphere, and those without AVHs had more prominent visuospatial impairment.

Early- and late-latency gamma auditory steady-state response in schizophrenia during closed eyes: Does hallucination status matter?

OBJECTIVES: Auditory steady-state responses are larger in patients experiencing auditory verbal hallucinations (AVH) than in never hallucinating subjects (NH) when recorded with open eyes. Compensatory effects were shown for schizophrenic patients when recorded with closed eyes. This effect has not been evaluated in respect to hallucination status. METHODS: Gamma responses to 40Hz stimulation were recorded in 15AVH patients, 25 healthy controls and 11NH patients with closed eyes. Mean and peak evoked amplitude and phase-locking index, peak time and maximal frequency were extracted for early- and late-latency responses and compared between groups. RESULTS: Phase-locking of early, but not late-latency gamma was diminished in schizophrenic patients independently on hallucination status. Peak entrainment time was delayed in hallucinating patients. Magnitude and frequency of early-latency response correlated to negative symptoms. CONCLUSIONS: In AVH patients, entrainment at gamma frequency was "normal" when eyes were closed. In contrast to never hallucinating subjects, entrainment to stimulation was delayed in AVH. The early-latency gamma response, standing for early sensory stimulus processing, on the contrary, was impaired in SZ irrespective of prevalence of hallucinations and was not modulated by subjects' general state; however its magnitude might be related to the expression of negative symptomatology. SIGNIFICANCE: Evaluation of auditory entrainment in both open eyes and closed eyes conditions is informative. Frequency and timing information of both early-latency and late-latency responses helps to uncover different aspects of impairment in schizophrenia patients.

Reaction Time in a Visual 4-Choice Reaction Time Task: ERP Effects of Motor Preparation and Hemispheric Involvement.

Reaction time (RT), the most common measure of CNS efficiency, shows intra- and inter-individual variability. This may be accounted for by hemispheric specialization, individual neuroanatomy, and transient functional fluctuations between trials. To explore RT on these three levels, ERPs were measured in a visual 4-choice RT task with lateralized stimuli (left lateral, left middle, right middle, and right lateral) in 28 healthy right-handed subjects. We analyzed behavioral data, ERP microstates (MS), N1 and P3 components, and trial-by-trial variance. Across subjects, the N1 component was contralateral to the stimulation side. N1-MSs were stronger over the left hemisphere, and middle stimulation evoked stronger activation than lateral stimulation in both hemispheres. The P3 was larger for the right visual field stimulation. RTs were shorter for the right visual hemifield stimulation/right hand responses. Within subjects, covariance analysis of single trial ERPs with RTs showed consistent lateralized predictors of RT over the motor cortex (MC) in the 112-248 ms interval. Decreased RTs were related to negativity over the MC contralateral to the stimulation side, an effect that could be interpreted as the lateralized readiness potential (LRP), and which was strongest for right side stimulation. The covariance analysis linking individual mean RTs and individual mean ERPs showed a frontal negativity and an occipital positivity correlating with decreased RTs in the 212-232 ms interval. We concluded that a particular RT is a composite measure that depends on the appropriateness of the motor preparation to a particular response and on stimulus lateralization that selectively involves a particular hemisphere.

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations.

BACKGROUND: Cerebral dysfunction occurring in mental disorders can show metabolic disturbances which are limited to circumscribed brain areas. Auditory hallucinations have been shown to be related to defined cortical areas linked to specific language functions. Here, we investigated if the study of metabolic changes in auditory hallucinations requires a functional rather than an anatomical definition of their location and size to allow a reliable investigation by magnetic resonance spectroscopy (MRS). METHODS: Schizophrenia patients with (AH; n=12) and without hallucinations (NH; n=8) and healthy controls (HC; n=11) underwent a verbal fluency task in functional MRI (fMRI) to functionally define Broca's and Wernicke's areas. Left and right Heschl's gyri were defined anatomically. RESULTS: The mean distances in native space between the fMRI-defined regions and a corresponding anatomically defined area were 12.4±6.1 mm (range: 2.7-36.1 mm) for Broca's area and 16.8±6.2 mm (range: 4.5-26.4 mm) for Wernicke's area, respectively. Hence, the spatial variance was of similar extent as the size of the investigated regions. Splitting the investigations into a single voxel examination in the frontal brain and a spectroscopic imaging part for the more homogeneous field areas led to good spectral quality for almost all spectra. In Broca's area, there was a significant group effect (p=0.03) with lower levels of N-acetyl-aspartate (NAA) in NH compared to HC (p=0.02). There were positive associations of NAA levels in the left Heschl's gyrus with total (p=0.03) and negative (p=0.006) PANSS scores. In Broca's area, there was a negative association of myo-inositol levels with total PANSS scores (p=0.008). CONCLUSION: This study supports the neurodegenerative hypothesis of schizophrenia only in a frontal region whereas the results obtained from temporal regions are in contrast to the majority of previous studies. Future research should test the hypothesis raised by this study that a functional definition of language regions is needed if neurochemical imbalances are expected to be restricted to functional foci.

Alterations of white matter integrity related to the season of birth in schizophrenia: a DTI study.

In schizophrenia there is a consistent epidemiological finding of a birth excess in winter and spring. Season of birth is thought to act as a proxy indicator for harmful environmental factors during foetal maturation. There is evidence that prenatal exposure to harmful environmental factors may trigger pathologic processes in the neurodevelopment, which subsequently increase the risk of schizophrenia. Since brain white matter alterations have repeatedly been found in schizophrenia, the objective of this study was to investigate whether white matter integrity was related to the season of birth in patients with schizophrenia. Thirty-four patients with schizophrenia and 33 healthy controls underwent diffusion tensor imaging. Differences in the fractional anisotropy maps of schizophrenia patients and healthy controls born in different seasons were analysed with tract-based spatial statistics. A significant main effect of season of birth and an interaction of group and season of birth showed that patients born in summer had significantly lower fractional anisotropy in widespread white matter regions than those born in the remainder of the year. Additionally, later age of schizophrenia onset was found in patients born in winter months. The current findings indicate a relationship of season of birth and white matter alterations in schizophrenia and consequently support the neurodevelopmental hypothesis of early pathological mechanisms in schizophrenia.

Is gamma band EEG synchronization reduced during auditory driving in schizophrenia patients with auditory verbal hallucinations?

Auditory verbal hallucinations (AVH) in schizophrenia patients assumingly result from a state inadequate activation of the primary auditory system. We tested brain responsiveness to auditory stimulation in healthy controls (n=26), and in schizophrenia patients that frequently (n=18) or never (n=11) experienced AVH. Responsiveness was assessed by driving the EEG with click-tones at 20, 30 and 40Hz. We compared stimulus induced EEG changes between groups using spectral amplitude maps and a global measure of phase-locking (GFS). As expected, the 40Hz stimulation elicited the strongest changes. However, while controls and non-hallucinators increased 40Hz EEG activity during stimulation, a left-lateralized decrease was observed in the hallucinators. These differences were significant (p=.02). As expected, GFS increased during stimulation in controls (p=.08) and non-hallucinating patients (p=.06), which was significant when combining the two groups (p=.01). In contrast, GFS decreased with stimulation in hallucinating patients (p=0.13), resulting in a significantly different GFS response when comparing subjects with and without AVH (p<.01). Our data suggests that normally, 40Hz stimulation leads to the activation of a synchronized network representing the sensory input, but in hallucinating patients, the same stimulation partly disrupts ongoing activity in this network.

Possible dysregulation of cortical plasticity in auditory verbal hallucinations-A cortical thickness study in schizophrenia.

INTRODUCTION: Investigations of gray matter changes in relation with auditory verbal hallucinations (AVH) have reported conflicting results. Assuming that alterations in gray matter might be related to certain symptoms in schizophrenia this study aimed to investigate changes in cortical thickness specific to AVH. It was hypothesized that schizophrenia patients suffering from persistent AVH would show significant differences in cortical thickness in regions involved in language-production and perception when compared to schizophrenia patients which had never experienced any hallucinations. METHODS: Using cortical thickness analysis the present study investigated ten schizophrenic patients suffering from AVH, ten non-hallucinating schizophrenic patients, and ten healthy control subjects. Anatomical data were acquired on a 3 T MRI system, transformed into standard space and cortically aligned to investigate local differences in whole brain cortical thickness between the two patient groups. Based on this comparison, brain regions with alterations specific for the patients with AVH were identified and then used as regions of interest to compare both patient groups to the healthy subjects respectively. RESULTS: Hallucinating patients showed gray matter reductions in the dominant hemisphere predominantly in sensory language areas relevant for speech processing. Increased cortical thickness was found in regions related to self-monitoring. CONCLUSIONS: Gray matter reductions in chronic schizophrenic patients may be the sequel of synaptic derangement or disease-related deregulation of language circuits. In order to clarify the ambiguous information processing additional demands might be put on cortical structures responsible for self-monitoring processes leading to changes in cortical thickness in the sense of neural plasticity.