Neuroökonomie = (Neuroeconomics): Neuronale Mechanismen ökonomischer Entscheidungen

Ökonomische Entscheidungen sind ebenso wie alltägliche Entscheidungen von der Aktivität von Hirnregionen abhängig, die zur Kontrolle verschiedener Teilschritte der Entscheidung beitragen. Aktivierung und Desaktivierung dieser Hirnregionen können mit Hilfe moderner bildgebender Verfahren, wie z.B. der funktionellen Magnet-Resonanz-Tomographie (fMRI) dargestellt werden. Die vorliegende Publikation gibt einen Überblick über das interdisziplinäre wissenschaftliche Arbeitsgebiet der „Neuroökonomie“ – einem jungen Forschungsfeld der Neurowissenschaften. Dieser Überblick ist auf sieben Hauptaspekte ökonomischer und finanzieller Entscheidungen fokusiert: 1. In welcher Weise werden ökonomische Parameter wie Wert und Nutzen einer Belohnung, Gewinn oder Verlust, Risiko und Ungewissheit in spezifischen Hirnregionen abgebildet? 2. In welcher spezifischen Weise tragen anatomisch definierte Areale des Gehirns zum Entscheidungsprozess bei? 3. In welcher Weise sind die Entscheidungsprozesse durch Läsion entscheidungsrelevanter Areale des Gehirns gestört? 4. In welcher Weise sind Hirnregionen, die an den Prozessen der Entscheidung beteiligt sind, miteinander vernetzt, um durch Interaktion die Entscheidung herbeizuführen? 5. In welcher Weise ist der Entscheidungsprozess von Persönlichkeitseigenschaften, von genetischen Variationen neuronaler Funktionen und von physiologischer Regulation, z.B. durch Hormone bestimmt? 6. In welcher Weise hängt der Entscheidungsprozess vom sozialen und kulturellen Umfeld des Entscheiders ab? 7. Auf welche Weise werden bei unvollständiger Information über die Optionen der Entscheidung Heuristiken oder Intuitionen genutzt, und in welcher Weise sind Entscheidungen durch Biases beeinflussbar? Der zentrale Teil dieser Publikation gibt einen zusammenfassenden Überblick (review) über die Ergebnisse neuroökonomischer Studien, die die fMRI-Technik nutzen (bis Juni 2010).

Cerebro-corticale und subcorticale Prozessierung vestibulärer Informationen im intakten und lädierten System der Ratte (Micro-PET-Studie)

In dieser Studie wurde anhand des Modells der Ratte das Gleichgewichtssystem auf cerebro-corticaler Ebene untersucht, und das Verhalten des Gehirns nach akuten sowie chronischen Ausfällen mit funktioneller Bildgebung untersucht. rnMit der Positronen-Emissions-Tomographie (PET) kann die Metabolismusrate bestimmter Gehirnareale gemessen werden. Narkotisierte Tiere wurden unter galvanischer vestibulärer Stimulation im PET gemessen und die Ergebnisse wurden mit Kontrollstimulations-Messungen verglichen. Es konnten verschiedene Areale, die eine erhöhte Stoffwechselaktivität aufwiesen, ermittelt werden. Dazu gehören der somatosensorische und der insuläre Cortex, Teile des auditorischen Cortexes, der anteriore cinguläre sowie der entorhinale Cortex. Subcorticale Strukturen wie der Hippocampus, die Amygdala sowie die latero-dorsalen thalamischen Kerne wiesen ebenfalls erhöhten Stoffwechsel unter vestibulärer Stimulation auf. rnBei dieser PET-Studie handelt es sich um die erste funktionell-bildgebende Studie, die Verarbeitung vestibulärer Informationen bei Ratten in vivo darstellt. Die anatomische Verbindung der gefundenen Areale wurde mit anterograden und retrograden neuronalen Tracings unterstützt. rnDarüber hinaus wurde markiertes Gewebe, welches die Verbindung zwischen thalamischen und cerebro-corticalen Kernen der vestibulären Verschaltung aufweist, immunhistochemisch auf dessen Neurotransmission hin untersucht. Das katecholaminergen und dem opioidergen System wurde untersucht. Eine Beteiligung katecholaminerger Transmitter konnte nicht nachgewiesen werden. Neurone im somatosensorischen Cortex, die positiv auf einen Opioid-Rezeptor-Antikörper getestet wurden erhalten anterograd markierte Terminale aus dem thalamischen Kern LDDM, der mittels der PET als vestibulär identifiziert werden konnte. rnBasierend auf den Ergebnissen der ersten bildgebenden Studie wurde in einer zweiten funktionell-bildgebenden Studie die zentral-vestibuläre Verschaltung unterbrochen, indem relevante thalamische Kerngebiete (LDDM, LDVL) elektrolytisch zerstört wurden. Die Stoffwechselaktivität wurde anschließend bei diesen Tieren an verschiedenen Zeitpunkten nach der Läsion im PET unter vestibulärer Stimulation gemessen. Die Stoffwechselaktivität dieser Tiere wurde mit der Stoffwechselaktivität von Kontroll-Tieren verglichen. rnBei dieser Studie wurde zum ersten Mal, mittels funktioneller Bildgebung gezeigt, welche Bereiche des Gehirns nach akuter und chronischer Läsion des vestibulären Systems an Kompensationsmechanismen beteiligt sind. Alle Gehirnareale, die in verschiedenen Zeitfenstern (1, 3, 7 und 20 Tage nach Läsion) erhöhten Metabolismus aufweisen, sind Teil der vestibulären Verschaltung. Es handelt sich dabei um Areale der Okulomotorik und des räumlichen Gedächtnisses: das Postsubiculum, den Colliculus superior, das mediale Corpus geniculatum, den entorhinalen Cortex sowie die Zona incerta.rn

Involvement of the opioid system and BDNF in neuroplastic alterations occurring in neuropathic pain conditions

Chronic pain affects one in five adults, reducing quality of life and increasing risk of developing co-morbidities such as depression. Neuropathic pain results by lesions to the nervous system that alter its structure and function leading to spontaneous pain and amplified responses to noxious and innocuous stimuli. The Opioid System is probably the most important system involved in control of nociceptive transmission. Dynorphin and nociceptin systems have been suggested key mediators of some neuropathic pain aspects. An important role also for BDNF has been recently suggested since its involvement in the peripheral and central sensitization phenomena is known. We studied neuroplastic alterations occurring in chronic pain in mice subjected to the chronic constriction injury (CCI). We investigated gene expression alterations of both BDNF and Opioid System at spinal level at different intervals of time. A transient upregulation of pBDNF and pDYN was observed in spinal cord, while increasing upregulation of ppN/OFQ was found in the DRGs of injured mice. Development of neuropathic behavioral signs has been observed in ICR/CD-1 and BDNF+/+ mice, subjected to CCI. A different development of these signs was observed in BDNF+/-. We also studied gene expression changes of investigated systems in different brain areas fourteen days after surgery. We found pBDNF, pDYN, pKOP, ppN/OFQ and pNOP gene expression alterations in several areas of CCI mice. In the same brain regions we also determined bioactive nociceptin peptide levels, and elevated N/OFQ levels were observed in the amygdala area. Histone modifications studies have been performed in BDNF and DYN gene promoters of CCI animal spinal cord showing selected alterations in pDYN gene promoter. In addition, a preliminary characterization of the innovative NOP-EGFP mice was performed. Overall, our results could be useful to understand which and how neuropeptidergic systems are involved in neuroplastic mechanism occurring in neuropathic pain.

Alterations of white matter integrity related to motor activity in schizophrenia

Altered structural connectivity is a key finding in schizophrenia, but the meaning of white matter alterations for behavior is rarely studied. In healthy subjects, motor activity correlated with white matter integrity in motor tracts. To explore the relation of motor activity and fractional anisotropy (FA) in schizophrenia, we investigated 19 schizophrenia patients and 24 healthy control subjects using Diffusion Tensor Imaging (DTI) and actigraphy on the same day. Schizophrenia patients had lower activity levels (AL). In both groups linear relations of AL and FA were detected in several brain regions. Schizophrenia patients had lower FA values in prefrontal and left temporal clusters. Furthermore, using a general linear model, we found linear negative associations of FA and AL underneath the right supplemental motor area (SMA), the right precentral gyrus and posterior cingulum in patients. This effect within the SMA was not seen in controls. This association in schizophrenia patients may contribute to the well known dysfunctions of motor control. Thus, structural disconnectivity could lead to disturbed motor behavior in schizophrenia.

The Bern psychopathology scale for the assessment of system-specific psychotic symptoms

The translation from psychiatric core symptoms to brain functions and vice versa is a largely unresolved issue. In particular, the search for disorders of single brain regions explaining classical symptoms has not yielded the expected results. Based on the assumption that the psychopathology of psychosis is related to a functional imbalance of higher-order brain systems, the authors focused on three specific candidate brain circuitries, namely the language, and limbic and motor systems. These domains are of particular interest for understanding the disastrous communication breakdown during psychotic disorders. Core symptoms of psychosis were mapped on these domains by shaping their definitions in order to match the related brain functions. The resulting psychopathological assessment scale was tested for interrater reliability and internal consistency in a group of 168 psychotic patients. The items of the scale were reliable and a principal component analysis (PCA) was best explained by a solution resembling the three candidate systems. Based on the results, the scale was optimized as an instrument to identify patient subgroups characterized by a prevailing dysfunction of one or more of these systems. In conclusion, the scale is apt to distinguish symptom domains related to the activity of defined brain systems. PCA showed a certain degree of independence of the system-specific symptom clusters within the patient group, indicating relative subgroups of psychosis. The scale is understood as a research instrument to investigate psychoses based on a system-oriented approach. Possible immediate advantages in the clinical application of the understanding of psychoses related to system-specific symptom domains are also discussed.

Frontal areas contribute to reduced global coordination of resting-state gamma activities in drug-naïve patients with schizophrenia

Schizophrenia has been postulated to involve impaired neuronal cooperation in large-scale neural networks, including cortico-cortical circuitry. Alterations in gamma band oscillations have attracted a great deal of interest as they appear to represent a pathophysiological process of cortical dysfunction in schizophrenia. Gamma band oscillations reflect local cortical activities, and the synchronization of these activities among spatially distributed cortical areas has been suggested to play a central role in the formation of networks. To assess global coordination across spatially distributed brain regions, Omega complexity (OC) in multichannel EEG was proposed. Using OC, we investigated global coordination of resting-state EEG activities in both gamma (30–50 Hz) and below-gamma (1.5–30 Hz) bands in drug-naïve patients with schizophrenia and investigated the effects of neuroleptic treatment. We found that gamma band OC was significantly higher in drug-naïve patients with schizophrenia compared to control subjects and that a right frontal electrode (F3) contributed significantly to the higher OC. After neuroleptic treatment, reductions in the contribution of frontal electrodes to global OC in both bands correlated with the improvement of schizophrenia symptomatology. The present study suggests that frontal brain processes in schizophrenia were less coordinated with activity in the remaining brain. In addition, beneficial effects of neuroleptic treatment were accompanied by improvement of brain coordination predominantly due to changes in frontal regions. Our study provides new evidence of improper intrinsic brain integration in schizophrenia by investigating the resting-state gamma band activity.

Investigating human audio-visual object perception with a combination of hypothesis-generating and hypothesis-testing fMRI analysis tools

Primate multisensory object perception involves distributed brain regions. To investigate the network character of these regions of the human brain, we applied data-driven group spatial independent component analysis (ICA) to a functional magnetic resonance imaging (fMRI) data set acquired during a passive audio-visual (AV) experiment with common object stimuli. We labeled three group-level independent component (IC) maps as auditory (A), visual (V), and AV, based on their spatial layouts and activation time courses. The overlap between these IC maps served as definition of a distributed network of multisensory candidate regions including superior temporal, ventral occipito-temporal, posterior parietal and prefrontal regions. During an independent second fMRI experiment, we explicitly tested their involvement in AV integration. Activations in nine out of these twelve regions met the max-criterion (A < AV > V) for multisensory integration. Comparison of this approach with a general linear model-based region-of-interest definition revealed its complementary value for multisensory neuroimaging. In conclusion, we estimated functional networks of uni- and multisensory functional connectivity from one dataset and validated their functional roles in an independent dataset. These findings demonstrate the particular value of ICA for multisensory neuroimaging research and using independent datasets to test hypotheses generated from a data-driven analysis.

Semantic network disconnection in formal thought disorder

Structural and functional findings in schizophrenic patients with formal thought disorder (FTD) show abnormalities within left-side semantic areas. The present study investigate the network function of the involved brain regions as a function of FTD severity.

Neuropathogenesis of naturally occurring encephalitis caused by Listeria monocytogenes in ruminants

Listeriosis is a serious food-borne disease with increasing frequency in humans and ruminants. Despite the facts that in both hosts, listeriosis can occur as rhombencephalitis and ruminants are a reservoir of Listeria monocytogenes (LM) strains pathogenic for humans, little work has been done on the pathogenesis in ruminants. This study investigates the neuropathogenesis of listeric encephalitis in over 200 natural cases in cattle, sheep and goats by analyzing anatomical distribution, severity, bacterial load and temporal evolution of the lesions. Our results suggest that LM gains access to the brainstem of all three species via axonal migration not only along the trigeminal nerve, but also along other nerves. The ensuing encephalitis does not remain restricted to the brainstem. Rather, LM spreads further from the brainstem into rostral brain regions likely by intracerebral axonal migration. Significant differences in severity of the lesions and bacterial load were found between cattle and small ruminants, which may be caused by species-specific properties of antibacterial immune responses. As histopathological lesions of human rhombencephalitis caused by LM strongly resemble those of ruminants, the disease likely has a similar pathogenesis in both hosts.

Development of a morphometric magnetic resonance image parameter suitable for distinguishing between normal dogs and dogs with cerebellar atrophy

Neurodegenerative diseases affect the cerebellum of numerous dog breeds. Although subjective, magnetic resonance (MR) imaging has been used to detect cerebellar atrophy in these diseases, but there are few data available on the normal size range of the cerebellum relative to other brain regions. The purpose of this study was to determine whether the size of the cerebellum maintains a consistent ratio with other brain regions in different ages and breeds of normal dogs and to define a measurement that can be used to identify cerebellar atrophy on MR images. Images from 52 normal and 13 dogs with cerebellar degenerative diseases were obtained. Volume and mid-sagittal cross-sectional area of the forebrain, brainstem, and cerebellum were calculated for each normal dog and compared between different breeds and ages as absolute and relative values. The ratio of the cerebellum to total brain and of the brainstem to cerebellum mid-sagittal cross-sectional area was compared between normal and affected dogs and the sensitivity and specificity of these ratios at distinguishing normal from affected dogs was calculated. The percentage of the brain occupied by the cerebellum in diverse dog breeds between 1 and 5 years of age was not significantly different, and cerebellar size did not change with increasing age. Using a cut off of 89%, the ratio between the brainstem and cerebellum mid-sagittal cross-sectional area could be used successfully to differentiate affected from unaffected dogs with a sensitivity and specificity of 100%, making this ratio an effective tool for identifying cerebellar atrophy on MR images.

Time course based artifact identification for independent components of resting-state FMRI

In functional magnetic resonance imaging (fMRI) coherent oscillations of the blood oxygen level-dependent (BOLD) signal can be detected. These arise when brain regions respond to external stimuli or are activated by tasks. The same networks have been characterized during wakeful rest when functional connectivity of the human brain is organized in generic resting-state networks (RSN). Alterations of RSN emerge as neurobiological markers of pathological conditions such as altered mental state. In single-subject fMRI data the coherent components can be identified by blind source separation of the pre-processed BOLD data using spatial independent component analysis (ICA) and related approaches. The resulting maps may represent physiological RSNs or may be due to various artifacts. In this methodological study, we propose a conceptually simple and fully automatic time course based filtering procedure to detect obvious artifacts in the ICA output for resting-state fMRI. The filter is trained on six and tested on 29 healthy subjects, yielding mean filter accuracy, sensitivity and specificity of 0.80, 0.82, and 0.75 in out-of-sample tests. To estimate the impact of clearly artifactual single-subject components on group resting-state studies we analyze unfiltered and filtered output with a second level ICA procedure. Although the automated filter does not reach performance values of visual analysis by human raters, we propose that resting-state compatible analysis of ICA time courses could be very useful to complement the existing map or task/event oriented artifact classification algorithms.

Age, sex, and performance influence the visuospatial working memory network in childhood

This study describes the influence of age, sex, and working memory (WM) performance on the visuospatial WM network. Thirty-nine healthy children (7-12 years) completed a dot location functional magnetic resonance imaging (fMRI) task. Percent signal change measured the intensity and laterality indices measured the asymmetry of activation in frontal and parietal brain regions. Old children showed greater intensity of activation in parietal regions than young children but no differences in lateralization were observed. Intensity of activation was similar across sex and WM performance groups. Girls and high WM performers showed more right-sided lateralization of parietal regions than boys and low WM performers.

Examining the gateway to the limbic system with diffusion tensor imaging: the perforant pathway in dementia

Current treatments for Alzheimer's disease (AD) are only able to slow the progression of mental deterioration, making early and reliable diagnosis an essential part of any promising therapeutic strategy. In the initial stages of AD, the first neuropathological alterations occur in the perforant pathway (PP), a large neuronal fiber tract located at the entrance to the limbic system. However, to date, there is no sensitive diagnostic tool for performing in vivo assessments of this structure. In the present bimodal magnetic resonance imaging (MRI) study, we examined 10 elderly controls, 10 subjects suffering from mild cognitive impairment (MCI), and 10 AD patients in order to evaluate the sensitivity of diffusion tensor imaging (DTI), a new MRI technique, for detecting changes in the PP. Furthermore, the diagnostic explanatory power of DTI data of the PP should be compared to high-resolution MRI volumetry and intervoxel coherences (COH) of the hippocampus and the entorhinal cortex, two limbic regions also involved in the pathophysiology of early AD. DTI revealed a marked decrease in COH values in the PP region of MCI (right side: 26%, left side: 29%, as compared to controls) and AD patients (right side: 37%, left side: 43%, as compared to controls). Reductions in COH values of the PP region were significantly correlated with cognitive impairment. DTI data of the PP zone were the only parameter differing significantly between control subjects and MCI patients, while the volumetric measures and the COH values of the hippocampus and the entorhinal cortex did not. DTI of medial temporal brain regions is a promising non-invasive tool for the in vivo diagnosis of the early/preclinical stages of AD.

Increased sensitivity in mapping task demand in visuospatial processing using reaction-time-dependent hemodynamic response predictors in rapid event-related fMRI

Searching for the neural correlates of visuospatial processing using functional magnetic resonance imaging (fMRI) is usually done in an event-related framework of cognitive subtraction, applying a paradigm comprising visuospatial cognitive components and a corresponding control task. Besides methodological caveats of the cognitive subtraction approach, the standard general linear model with fixed hemodynamic response predictors bears the risk of being underspecified. It does not take into account the variability of the blood oxygen level-dependent signal response due to variable task demand and performance on the level of each single trial. This underspecification may result in reduced sensitivity regarding the identification of task-related brain regions. In a rapid event-related fMRI study, we used an extended general linear model including single-trial reaction-time-dependent hemodynamic response predictors for the analysis of an angle discrimination task. In addition to the already known regions in superior and inferior parietal lobule, mapping the reaction-time-dependent hemodynamic response predictor revealed a more specific network including task demand-dependent regions not being detectable using the cognitive subtraction method, such as bilateral caudate nucleus and insula, right inferior frontal gyrus and left precentral gyrus.

Spastin in the human and mouse central nervous system with special reference to its expression in the hippocampus of mouse pilocarpine model of status epilepticus and temporal lobe epilepsy

In the present in situ hybridization and immunocytochemical studies in the mouse central nervous system (CNS), a strong expression of spastin mRNA and protein was found in Purkinje cells and dentate nucleus in the cerebellum, in hippocampal principal cells and hilar neurons, in amygdala, substantia nigra, striatum, in the motor nuclei of the cranial nerves and in different layers of the cerebral cortex except piriform and entorhinal cortices where only neurons in layer II were strongly stained. Spastin protein and mRNA were weakly expressed in most of the thalamic nuclei. In selected human brain regions such as the cerebral cortex, cerebellum, hippocampus, amygdala, substania nigra and striatum, similar results were obtained. Electron microscopy showed spastin immunopositive staining in the cytoplasma, dendrites, axon terminals and nucleus. In the mouse pilocarpine model of status epilepticus and subsequent temporal lobe epilepsy, spastin expression disappeared in hilar neurons as early as at 2h during pilocarpine induced status epilepticus, and never recovered. At 7 days and 2 months after pilocarpine induced status epilepticus, spastin expression was down-regulated in granule cells in the dentate gyrus, but induced expression was found in reactive astrocytes. The demonstration of widespread distribution of spastin in functionally different brain regions in the present study may provide neuroanatomical basis to explain why different neurological, psychological disorders and cognitive impairment occur in patients with spastin mutation. Down-regulation or loss of spastin expression in hilar neurons may be related to their degeneration and may therefore initiate epileptogenetic events, leading to temporal lobe epilepsy.