Anna Rotarska-Jagiela

Neural synchrony and the development of cortical networks

Recent data indicate that the synchronisation of oscillatory activity is relevant for the development of cortical circuits as demonstrated by the involvement of neural synchrony in synaptic plasticity and changes in the frequency and synchronisation of neural oscillations during development. Analyses of resting-state and task-related neural synchrony indicate that gamma-oscillations emerge during early childhood and precise temporal coordination through neural synchrony continues to mature until early adulthood. The late maturation of neural synchrony is compatible with changes in the myelination of cortico-cortical connections and with late development of GABAergic neurotransmission. These findings highlight the role of neural synchrony for normal brain development as well as its potential importance for understanding neurodevelopmental disorders, such as autism spectrum disorders (ASDs) and schizophrenia.

Resting-state functional network correlates of psychotic symptoms in schizophrenia

Schizophrenia has been associated with aberrant intrinsic functional organization of the brain but the relationship of such deficits to psychopathology is unclear. In this study, we investigated associations between resting-state networks and individual psychopathology in sixteen patients with paranoid schizophrenia and sixteen matched healthy control participants. We estimated whole-brain functional connectivity of multiple networks using a combination of spatial independent component analysis and multiple regression analysis. Five networks (default-mode, left and right fronto-parietal, left fronto-temporal and auditory networks) were selected for analysis based on their involvement in neuropsychological models of psychosis. Between-group comparisons and correlations to psychopathology ratings were performed on both spatial (connectivity distributions) and temporal features (power-spectral densities of temporal frequencies below 0.06 Hz). Schizophrenia patients showed aberrant functional connectivity in the default-mode network, which correlated with severity of hallucinations and delusions, and decreased hemispheric separation of fronto-parietal activity, which correlated with disorganization symptoms. Furthermore, the severity of positive symptoms correlated with functional connectivity of fronto-temporal and auditory networks. Finally, default-mode and auditory networks showed increased spectral power of low frequency oscillations, which correlated with positive symptom severity. These results are in line with findings from studies that investigated the neural correlates of positive symptoms and suggest that psychopathology is associated with aberrant intrinsic organization of functional brain networks in schizophrenia.

The corpus callosum in schizophrenia-volume and connectivity changes affect specific regions

The corpus callosum (CC) is of great interest for pathophysiological models of schizophrenia. Volume and structural integrity of the CC have been examined by volumetric and diffusion tensor imaging (DTI) studies, but results were not consistent across methods or studies. A possible explanation may be varying methodologies and accuracy of measurements based on a single slice or small regions of interest. In addition, none of the studies examined volume and diffusion values in the same group of patients, and thus the relationship between these anatomical measures is not clear. We used an automatic algorithm to segment seven midline slices of the CC from DTI images. We compared volume and the DTI measures fractional anisotropy (FA) and mean diffusivity (MD) in the CC and its subdivisions in the schizophrenia patients and matched controls. Patients had decreased volume, decreased FA and increased MD of the whole CC. The important novel finding is, however, that not all regions were equally affected by anatomical changes. The results emphasize the importance of using different methods in evaluation of white matter (WM) in schizophrenia to avoid false negative findings. In addition, the measures were highly correlated with each other, implying a common pathological process influencing FA, MD and volume of the CC. Although we cannot rule out other mechanisms affecting volume, FA and MD, converging evidence from cytoarchitectonic and genetic studies suggests that WM changes observed in schizophrenia may involve disintegration of healthy, functional axons and strengthening of aberrant connections resulting in increased severity of clinical symptoms.

Reduced laterality as a trait marker of schizophrenia--evidence from structural and functional neuroimaging.

Laterality is a characteristic principle of the organization of the brain systems for language, and reduced hemispheric asymmetry has been considered a risk factor for schizophrenia. Here we sought support for the risk factor hypothesis by investigating whether reduced asymmetry of temporal lobe structure and function is also present in unaffected relatives. Sixteen schizophrenia patients, 16 age-matched first-degree relatives, and 15 healthy controls underwent high-resolution three-dimensional anatomical imaging and functional magnetic resonance imaging during auditory stimulation. Both the overall auditory cortex and planum temporale volumes and the lateralization to the left hemisphere were markedly reduced in patients. The decrease of lateralization correlated with increased severity of symptoms. In addition, both the overall functional activation in response to auditory stimulation and its asymmetry were reduced in the patients. Relatives had intermediate values between patients and controls on both structural and functional measures. This study provides added support for the idea that reduced hemispheric asymmetry is a biological risk factor for schizophrenia.

Interhemispheric hypoconnectivity in schizophrenia: Fiber integrity and volume differences of the corpus callosum in patients and unaffected relatives

Changes in hemispheric asymmetry and inter-hemispheric connectivity have been reported in schizophrenia. However, the genetic contribution to these alterations is still unclear. In the current study, we applied an automatic segmentation method to structural MRI and diffusion tensor imaging (DTI) data and examined volume and fiber integrity of the corpus callosum (CC), the main interhemispheric fiber tract, in 16 chronic schizophrenia (SZ) patients, matched first degree relatives and controls. SZ patients and relatives had smaller CC volumes than controls, particularly in the posterior genu, isthmus and splenium. Fractional anisotropy (FA), an indicator of fiber integrity, was reduced in patients and relatives in the whole CC, the inferior genu, the superior genu and the isthmus. Correspondingly, the mean diffusivity (MD) values of the whole CC and the isthmus were higher in patients and their unaffected relatives, indicating decreased compactness and increased intercellular space. Relatives had intermediate values in the volumetric and fiber integrity measurements between patients and controls. Lower CC volume and fiber integrity in SZ patients were associated with more severe auditory hallucinations. These results support the connectivity hypothesis of SZ (Friston, 1998) and particularly highlight the altered interhemispheric connectivity, which appears to be a genetic feature of SZ risk.

Imaging derived cortical thickness reduction in high-functioning autism: Key regions and temporal slope

Cortical thickness (CT) changes possibly contribute to the complex symptomatology of autism. The aberrant developmental trajectories underlying such differences in certain brain regions and their continuation in adulthood are a matter of intense debate. We studied 28 adults with high-functioning autism (HFA) and 28 control subjects matched for age, gender, IQ and handedness. A surface-based whole brain analysis utilizing FreeSurfer was employed to detect CT differences between the two diagnostic groups and to investigate the time course of age-related changes. Direct comparison with control subjects revealed thinner cortex in HFA in the posterior superior temporal sulcus (pSTS) of the left hemisphere. Considering the time course of CT development we found clusters around the pSTS and cuneus in the left and the paracentral lobule in the right hemisphere to be thinner in HFA with comparable age-related slopes in patients and controls. Conversely, we found clusters around the supramarginal gyrus and inferior parietal lobule (IPL) in the left and the precentral and postcentral gyrus in the right hemisphere to be thinner in HFA, but with different age-related slopes in patients and controls. In the latter regions CT showed a steady decrease in controls but no analogous thinning in HFA. CT analyses contribute in characterizing neuroanatomical correlates of HFA. Reduced CT is present in brain regions involved in social cognition. Furthermore, our results demonstrate that aberrant brain development leading to such differences is proceeding throughout adulthood. Discrepancies in prior morphometric studies may be induced by the complex time course of cortical changes.

Mental imagery vividness as a trait marker across the schizophrenia spectrum

We investigated the vividness of mental imagery and its possible relationship with the predisposition towards hallucinations in 52 schizophrenia (SZ) patients, 44 of their first-degree relatives (R) and two healthy control groups (high-schizotypy [CHS; n=24]; low-schizotypy [CLS; n=24]). We investigated phenomenological and cognitive trait markers of schizophrenia, including cognitive correlates of hallucinations and vividness of mental imagery, and the influence of individual psychopathology. Overall, scores on the mental imagery questionnaire (QMI [Sheehan, P.W., 1967. Reliability of a short test of imagery. Perceptual and Motor Skills 25, 744.]) suggested higher mental imagery vividness in first-degree relatives, high-schizotypy controls and patients, than in low-schizotypy controls. However, vividness of mental imagery was independent of predisposition towards hallucinations and cognitive test performance scores. These results suggest that vividness of mental imagery may be a trait marker across the schizophrenia spectrum. In addition we propose that imagery proneness is relatively independent of the individual psychopathology.

Association between Psychotic Symptoms and Cortical Thickness Reduction across the Schizophrenia Spectrum

The current study provides a complete magnetic resonance imaging (MRI) analysis of thickness throughout the cerebral cortical mantle in patients with schizophrenia (SZ) and rigorously screened and matched unaffected relatives and controls and an assessment of its relation to psychopathology and subjective cognitive function. We analyzed 3D-anatomical MRI data sets, obtained at 3 T, from 3 different subject groups: 25 SZ patients, 29 first-degree relatives, and 37 healthy control subjects. We computed whole-brain cortical thickness using the Freesurfer software and assessed group differences. We also acquired clinical and psychometric data. The results showed markedly reduced cortical thickness in SZ patients compared with controls, most notably in the frontal and temporal lobes, in the superior parietal lobe and several limbic areas, with intermediate levels of cortical thickness in relatives. In both patients and relatives, we found an association between subjective cognitive dysfunction and reduced thickness of frontal cortex, and predisposition toward hallucinations and reduced thickness of the superior temporal gyrus. Our findings suggest that changes in specific cortical areas may predispose to specific symptoms, as exemplified by the association between temporal cortex thinning and hallucinations.

Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development.

A fast B1-mapping method for the correction and normalization of magnetization transfer ratio maps at 3 T

In neuroimaging, there is increasing interest in magnetization transfer (MT) techniques which yield information about bound water protons. One of the main applications is the investigation of the myelin integrity in the central nervous system (CNS). However, several problems may arise, in particular at high magnetic field strengths: B1 inhomogeneities may yield deviations of the MT saturation angle and thus non-uniformities of the measured MT ratio (MTR). This effect can be corrected for but requires in general additional time consuming B1 mapping. Furthermore, increased values of the specific absorption rate (SAR) may require a reduction of the saturation angle for individual subjects, impairing comparability of results. In this work, a B1 mapping method based on magnetization-prepared FLASH with slice selective preparation and excitation pulses and correction for relaxation effects is presented, yielding B1 maps with whole brain coverage, an in-plane resolution of 4 mm, a slice thickness of 3 mm, and a clinically acceptable duration of 46 s. The method is tested both in vitro and in vivo and applied in a subsequent in vivo study to show that MTR values in human brain tissue depend approximately linearly on the preparation angle, with a slope similar to values reported for 1.5 T. Calibration data and B1 maps are applied to B1 inhomogeneity corrections of MTR maps. Subsequently, it is shown that B1-corrected MTR maps acquired at reduced preparation angles due to individual SAR restrictions can be normalized, allowing for a direct comparison with maps acquired at the full angle.