Veronika Schöpf

Orbitofrontal volume reductions during emotion recognition in patients with major depression.

BACKGROUND Major depressive disorder is associated with both structural and functional alterations in the emotion regulation network of the central nervous system. The relation between structural and functional changes is largely unknown. Therefore, we sought to determine the relation between structural differences and functional alterations during the recognition of emotional facial expressions. METHODS We examined 13 medication-free patients with major depression and 15 healthy controls by use of structural T1-weighted high-resolution magnetic resonance imaging (MRI) and functional MRI during 1 session. We set the statistical threshold for the analysis of imaging data to p < 0.001 (uncorrected). RESULTS As shown by voxel-based morphometry, depressed patients had reductions in orbitofrontal cortex volume and increases in cerebellar volume. Additionally, depressed patients showed increased activity during emotion recognition in the middle frontal cortex, caudate nucleus, precuneus and lingual gyrus. Within this cerebral network, the orbitofrontal volumes were negatively correlated in depressed patients but not in healthy controls with changes in blood oxygen level-dependent signal in the middle frontal gyrus, caudate nucleus, precuneus and supplementary motor area. LIMITATIONS Our results are limited by the relatively small sample size. CONCLUSIONS This combined functional and structural MRI study provides evidence that the orbitofrontal cortex is a key area in major depression and that structural changes result in functional alterations within the emotional circuit. Whether these alterations in the orbitofrontal cortex are also related to persistent emotional dysfunction in remitted mental states and, therefore, are related to the risk of depression needs further exploration.

Watching the fetal brain at 'rest'.

Functional magnetic resonance imaging (fMRI) has allowed insights into the spatiotemporal distribution of human brain networks. According to the neurophysiological property of the fetal brain to generate spontaneous activity, we aimed to determine the feasibility of investigating the maturation of intrinsic networks, beginning at gestational week 20 in healthy human fetuses by combining resting‐state fMRI and an analytical approach, independent component analysis (ICA).

Fully exploratory network ICA (FENICA) on resting-state fMRI data.

Independent component analysis (ICA) is one of the most valuable explorative methods for analyzing resting-state networks (RSNs) in fMRI, representing a data-driven approach that enables decomposition of high-dimensional data into discrete components. Extensions to a group-level suffer from the drawback of evaluating single-subject resting-state components of interest either using a predefined spatial template or via visual inspection. FENICA introduced in the context of group ICA methods is based solely on spatially consistency across subjects directly reflecting similar networks. Therefore, group data can be processed without further visual inspection of the single-subject components or the definition of a template (Schöpf et al., 2009). In this study FENICA was applied to fMRI resting-state data from 28 healthy subjects resulting in eight group RSNs. These RSNs resemble the spatial patterns of the following previously described networks: (1) visual network, (2) default mode network, (3) sensorimotor network, (4) dorsolateral prefrontal network, (5) temporal prefrontal network, (6) basal ganglia network, (7) auditory processing network, and (8) working memory network. This novel analysis approach for identifying spatially consistent networks across a group of subjects does not require manual or template-based selection of single-subject components and, therefore, offers a truly explorative procedure of assessing RSNs.

Model-free fMRI group analysis using FENICA.

Exploratory analysis of functional MRI data allows activation to be detected even if the time course differs from that which is expected. Independent Component Analysis (ICA) has emerged as a powerful approach, but current extensions to the analysis of group studies suffer from a number of drawbacks: they can be computationally demanding, results are dominated by technical and motion artefacts, and some methods require that time courses be the same for all subjects or that templates be defined to identify common components. We have developed a group ICA (gICA) method which is based on single-subject ICA decompositions and the assumption that the spatial distribution of signal changes in components which reflect activation is similar between subjects. This approach, which we have called Fully Exploratory Network Independent Component Analysis (FENICA), identifies group activation in two stages. ICA is performed on the single-subject level, then consistent components are identified via spatial correlation. Group activation maps are generated in a second-level GLM analysis. FENICA is applied to data from three studies employing a wide range of stimulus and presentation designs. These are an event-related motor task, a block-design cognition task and an event-related chemosensory experiment. In all cases, the group maps identified by FENICA as being the most consistent over subjects correspond to task activation. There is good agreement between FENICA results and regions identified in prior GLM-based studies. In the chemosensory task, additional regions are identified by FENICA and temporal concatenation ICA that we show is related to the stimulus, but exhibit a delayed response. FENICA is a fully exploratory method that allows activation to be identified without assumptions about temporal evolution, and isolates activation from other sources of signal fluctuation in fMRI. It has the advantage over other gICA methods that it is computationally undemanding, spotlights components relating to activation rather than artefacts, allows the use of familiar statistical thresholding through deployment of a higher level GLM analysis and can be applied to studies where the paradigm is different for all subjects.

Recovery of Olfactory Function Induces Neuroplasticity Effects in Patients with Smell Loss

The plasticity of brain function, especially reorganization after stroke or sensory loss, has been investigated extensively. Based upon its special characteristics, the olfactory system allows the investigation of functional networks in patients with smell loss, as it holds the unique ability to be activated by the sensorimotor act of sniffing, without the presentation of an odor. In the present study, subjects with chronic peripheral smell loss and healthy controls were investigated using functional magnetic resonance imaging (fMRI) to compare functional networks in one of the major olfactory areas before and after an olfactory training program. Data analysis revealed that olfactory training induced alterations in functional connectivity networks. Thus, olfactory training is capable of inducing neural reorganization processes. Furthermore, these findings provide evidence for the underlying neural mechanisms of olfactory training.

Magnetic resonance methods in fetal neurology

Fetal magnetic resonance imaging (MRI) has become an established clinical adjunct for the in-vivo evaluation of human brain development. Normal fetal brain maturation can be studied with MRI from the 18th week of gestation to term and relies primarily on T2-weighted sequences. Recently diffusion-weighted sequences have gained importance in the structural assessment of the fetal brain. Diffusion-weighted imaging provides quantitative information about water motion and tissue microstructure and has applications for both developmental and destructive brain processes. Advanced magnetic resonance techniques, such as spectroscopy, might be used to demonstrate metabolites that are involved in brain maturation, though their development is still in the early stages. Using fetal MRI in addition to prenatal ultrasound, morphological, metabolic, and functional assessment of the fetus can be achieved. The latter is not only based on observation of fetal movements as an indirect sign of activity of the fetal brain but also on direct visualization of fetal brain activity, adding a new component to fetal neurology. This article provides an overview of the MRI methods used for fetal neurologic evaluation, focusing on normal and abnormal early brain development.

Disrupted developmental organization of the structural connectome in fetuses with corpus callosum agenesis

Agenesis of the corpus callosum is a model disease for disrupted connectivity of the human brain, in which the pathological formation of interhemispheric fibers results in subtle to severe cognitive deficits. Postnatal studies suggest that the characteristic abnormal pathways in this pathology are compensatory structures that emerge via neural plasticity. We challenge this hypothesis and assume a globally different network organization of the structural interconnections already in the fetal acallosal brain. Twenty fetuses with isolated corpus callosum agenesis with or without associated malformations were enrolled and fiber connectivity among 90 brain regions was assessed using in utero diffusion tensor imaging and streamline tractography. Macroscopic scale connectomes were compared to 20 gestational age-matched normally developing fetuses with multiple granularity of network analysis. Gradually increasing connectivity strength and tract diffusion anisotropy during gestation were dominant in antero-posteriorly running paramedian and antero-laterally running aberrant pathways, and in short-range connections in the temporoparietal regions. In fetuses with associated abnormalities, more diffuse reduction of cortico-cortical and cortico-subcortical connectivity was observed than in cases with isolated callosal agenesis. The global organization of anatomical networks consisted of less segregated nodes in acallosal brains, and hubs of dense connectivity, such as the thalamus and cingulate cortex, showed reduced network centrality. Acallosal fetal brains show a globally altered connectivity network structure compared to normals. Besides the previously described Probst and sigmoid bundles, we revealed a prenatally differently organized macroconnectome, dominated by increased connectivity. These findings provide evidence that abnormal pathways are already present during at early stages of fetal brain development in the majority of cerebral white matter.

Altered likelihood of brain activation in attention and working memory networks in patients with multiple sclerosis: An ALE meta-analysis

Highlights • We conducted an ALE meta-analysis of fMRI studies investigating MS patients.• We included nine fMRI studies performing working memory/attention tasks.• Healthy controls showed higher activation in the IPL and the DLPFC.• For MS patients higher activation was obtained in the VLPFC.

Activation of Primary and Secondary Somatosensory Regions Following Tactile Stimulation of the Face

Background:Since the work of Penfield & Rasmussen it is well established that the human primary somatosensory cortex is organized somatotopically. However, the order of the representation of the face is still a matter of discussion, i.e., it is yet unclear whether the face is represented upside-down or vice versa in the somatosensory cortex.Material and Methods:In a functional magnetic resonance imaging study (n = 30), tactile stimuli to three different locations on each side of the face were applied using a pneumatic device. Locations of stimulation corresponded to the three branches of the trigeminal nerve (forehead, cheek, chin). To determine the representation of the face on primary and secondary somatosensory cortices, peak coordinates within these regions were analyzed subjectwise.Results:Contralateral activation of the primary somatosensory cortex following tactile stimulation of the face was found, whereas the secondary somatosensory cortices were activated bilaterally. However, differences between activation coordinates of different tactile stimuli applied to one side of the face were not statistically significant.Conclusion:Tactile stimulation of the face leads to contralateral activation of primary and bilateral activation of secondary somatosensory cortices. Using the authors’ methodological approach it was not possible to detect a somatotopic organization related to different facial areas.ZusammenfassungHintergrund:Seit Penfield & Rasmussen ist bekannt, dass der menschliche primäre somatosensorische Kortex somatotopisch organisiert ist. Die Reihenfolge dieser Repräsentation wird jedoch immer noch diskutiert, d.h., es ist nicht klar, ob das Gesicht in kraniokaudaler oder in kaudokranialer Reihenfolge repräsentiert ist.Material und Methodik:Mittels funktioneller Magnetresonanztomographie wurden an 30 Probanden taktile Stimuli an drei verschiedenen Orten auf jeder Seite des Gesichtes mit einem pneumatischen Gerät appliziert (Stirn, Wange, Kinn). Diese Orte korrespondierten mit den drei Ästen des N. trigeminus. Um die Repräsentation des Gesichts in primären und sekundären somatosensorischen Kortizes zu untersuchen, wurden Koordinaten lokaler Maxima probandenweise innerhalb dieser Regionen bestimmt.Ergebnisse:Es konnte eine kontralaterale Aktivierung des primären somatosensorischen Kortex bei taktiler Stimulation des Gesichts festgestellt werden. Der sekundäre somatosensorische Kortex war bilateral aktiviert. Die Unterschiede in den Aktivierungskoordinaten der verschiedenen taktilen Stimuli auf einer Seite des Gesichts waren jedoch nicht signifikant.Schlussfolgerung:Taktile Stimulation des Gesichts führt zu einer kontralateralen Aktivierung des primären und bilateralen Aktivierung des sekundären somatosensorischen Kortex. Mit der verwendeten Methodik konnte eine somatotopische Auflösung verschiedener Gesichtsareale nicht erreicht werden.

Kinetics of tumor size and peritumoral brain edema before, during, and after systemic therapy in recurrent WHO grade II or III meningioma

BACKGROUND The efficacy of systemic antineoplastic therapy on recurrent World Health Organization (WHO) grades II and III meningiomas is unclear. METHODS We performed a retrospective multicenter analysis of serial cranial MRI in patients with recurrent WHO II and III meningiomas treated with antineoplastic systemic therapies. Growth rates for tumor volume and diameter, as well as change rates for edema size, were calculated for all lesions. RESULTS We identified a total of 34 patients (23 atypical, 11 anaplastic meningiomas) with a total of 57 meningioma lesions who had been treated at 6 European institutions. Systemic therapies included bevacizumab, cytotoxic chemotherapy, somatostatin analogues, and tyrosine kinase inhibitors. Overall, tumor growth rates decreased during systemic therapy by 51% for tumor diameter and 14% for tumor volume growth rates compared with the period before initiation of systemic therapy. The most pronounced decrease in meningioma growth rates during systemic therapy was evident in patients treated with bevacizumab, with a reduction of 80% in diameter and 59% in volume growth. Furthermore, a decrease in size of peritumoral edema after initiation of systemic therapy was exclusively observed in patients treated with bevacizumab (-107%). CONCLUSIONS Our data indicate that systemic therapy may inhibit growth of recurrent WHO grades II and III meningiomas to some extent. In our small cohort, bevacizumab had the most pronounced inhibitory effect on tumor growth, as well as some anti-edematous activity. Prospective studies are needed to better define the role of medical therapies in this tumor type.