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The Hippocampus in Patients Treated With Electroconvulsive Therapy

Gabriele Ende, Dieter F. Braus, Sigrid Walter, Wolfgang Weber-Fahr, Fritz A. Henn
2000 Archives of General Psychiatry  
We monitored the effect of electroconvulsive therapy (ECT) on the nuclear magnetic resonancedetectable metabolites N-acetylaspartate, creatine and phosphocreatine, and choline-containing compounds in the hippocampus by means of hydrogen 1 magnetic resonance spectroscopic imaging. We hypothesized that if ECT-induced memory deterioration was associated with neuronal loss in the hippocampus, the N-acetylaspartate signal would decrease after ECT and any increased membrane turnover would result in
more » ... increase in the signal from choline-containing compounds. Methods: Seventeen patients received complete courses of ECT, during which repeated proton magnetic resonance spectroscopic imaging studies of the hippocampal region were performed. Individual changes during the course of ECT were compared with values obtained in 24 healthy control subjects and 6 patients remitted from major depression without ECT. Results: No changes in the hippocampal N-acetylaspartate signals were detected after ECT. A significant mean increase of 16% of the signal from choline-containing compounds after 5 or more ECT treatments was observed. Despite the mostly unilateral ECT application (14 of 17 patients), the increase in the choline-containing compound signal was observed bilaterally. Lactate or elevated lipid signals were not detected. All patients showed clinical amelioration of depression after ECT. Conclusions: Electroconvulsive therapy is not likely to induce hippocampal atrophy or cell death, which would be reflected by a decrease in the N-acetylaspartate signal. Compared with an age-matched control group, the choline-containing compounds signal in patients with a major depressive episode was significantly lower than normal, before ECT and normalized during ECT.
doi:10.1001/archpsyc.57.10.937 pmid:11015811 fatcat:tegih5q3dfbbjbqroom6q22dbm

Advantages and Challenges of Small Animal Magnetic Resonance Imaging as a Translational Tool

Carolin Hoyer, Natalia Gass, Wolfgang Weber-Fahr, Alexander Sartorius
2014 Neuropsychobiology  
DOI: 10.1159/000360859 Color version available onlineHoyer /Gass /Weber-Fahr /SartoriusNeuropsychobiology 2014;69:187-201 DOI: 10.1159/000360859  ...  The area under a metabolite reso-Hoyer /Gass /Weber-Fahr /Sartorius nance in the spectrum is proportional to the concentration of the metabolite within the measured volume.  ... 
doi:10.1159/000360859 pmid:24863537 fatcat:belz7e6dx5eyzorm7igkfdxg2u

Optogenetic fMRI in the mouse hippocampus: Hemodynamic response to brief glutamatergic stimuli

Philipp Lebhardt, Christian Clemm von Hohenberg, Wolfgang Weber-Fahr, Wolfgang Kelsch, Alexander Sartorius
2015 Journal of Cerebral Blood Flow and Metabolism  
The combination of optogenetics with functional magnetic resonance imaging is a promising tool to study the causal relationship between specific neuronal populations and global brain activity. We employed this technique to study the brain response to recruitment of glutamatergic neurons in the mouse hippocampus. The light-sensitive protein channelrhodopsin-2 was expressed in a-CamKII-positive glutamatergic neurons in the left hippocampus (N ¼ 10). Functional magnetic resonance imaging was
more » ... med during local laser stimulation, with stimulus duration of 1 second. The hemodynamic response to these stimuli was analyzed on a whole-brain level. In a secondary analysis, we examined the impact of the stimulation locus on the dorso-ventral axis within the hippocampal formation. The hemodynamic response in the mouse hippocampus had an earlier peak and a shorter duration compared to those observed in humans. Photostimulation was associated with significantly increased blood oxygen level-dependent signal in group statistics: bilaterally in the hippocampus, frontal lobe and septum, ipsilaterally in the nucleus accumbens and contralaterally in the striatum. More dorsal position of the laser fiber was associated with a stronger activation in projection regions (insular cortex and striatum). The characterization of brain-region-specific hemodynamic response functions may enable more precise interpretation of future functional magnetic resonance imaging experiments.
doi:10.1177/0271678x15606455 pmid:26661158 pmcid:PMC4794094 fatcat:xytsrqlgazelvmhn6j2phnzucm

Sensory Information Processing in Neuroleptic-Naive First-Episode Schizophrenic Patients

Dieter F. Braus, Wolfgang Weber-Fahr, Heike Tost, Matthias Ruf, Fritz A. Henn
2002 Archives of General Psychiatry  
Schizophrenic disorders are thought to involve widespread abnormalities in information processing. The present study used functional magnetic resonance imaging and a simple and robust paradigm that involved auditory and visual activation to examine basic sensory input circuits. Our aim was to determine which stages of the input processing network are disturbed in first-episode schizophrenic patients. Methods: Twelve neuroleptic-naive inpatients (paranoid subtype) were compared with 11 healthy
more » ... bjects by means of echo-planar functional magnetic resonance imaging. In a block design, the paradigm included the simultaneous presentation of a moving 6-Hz checkerboard and auditory stimuli in the form of drumbeats. The subjects were asked to simply look and listen.
doi:10.1001/archpsyc.59.8.696 pmid:12150645 fatcat:pdx2lsu4pzhk5mpxko2deufham

Cocaine addicted rats show reduced neural activity as revealed by manganese-enhanced MRI

Nazzareno Cannella, Alejandro Cosa-Linan, Tatiane Takahashi, Wolfgang Weber-Fahr, Rainer Spanagel
2020 Scientific Reports  
Cocaine addiction develops as a continuum from recreational to habitual and ultimately compulsive drug use. Cocaine addicts show reduced brain activity. However, it is not clear if this condition results from individual predisposing traits or is the result of chronic cocaine intake. A translational neuroimaging approach with an animal model distinguishing non-addict-like vs. addict-like animals may help overcome the limitations of clinical research by comparing controlled experimental
more » ... that are impossible to obtain in humans. Here we aimed to evaluate neuronal activity in freely moving rats by manganese enhanced magnetic resonance imaging in the 0/3crit model of cocaine addiction. We show that addict-like rats exhibit reduced neuronal activity compared to cocaine-naïve controls during the first week of abstinence. In contrast, cocaine-experienced non-addict-like rats maintained their brain activity at a level comparable to cocaine-naïve controls. We also evaluated brain activity during cocaine bingeing, finding a general reduction of brain activity in cocaine experienced rats independent of an addiction-like phenotype. These findings indicate that brain hypoactivity in cocaine addiction is associated with the development of compulsive use rather than the amount of cocaine consumed, and may be used as a potential biomarker for addiction that clearly distinguishes non-addict-like vs addict-like cocaine use.
doi:10.1038/s41598-020-76182-3 pmid:33168866 fatcat:fchq34ay7ve3lla7tirxyukv5a

Grey matter volume changes and corresponding cellular metrics identified in a longitudinal in vivo imaging approach [article]

Livia Asan, Claudia Falfan-Melgoza, Wolfgang Weber-Fahr, Carlo Beretta, Thomas Kuner, Johannes Knabbe
2019 bioRxiv   pre-print
Magnetic resonance imaging (MRI) of the brain combined with voxel-based morphometry (VBM) has revealed structural changes of grey and white matter in a range of neurological and psychiatric disorders. However, the cellular basis of volume changes observed with VBM has remained unclear. We devised an approach to systematically correlate changes in grey matter volume (GMV) with cellular composition. Mice were alternately examined with structural MRI and two-photon in vivo microscopy at three time
more » ... points, taking advantage of age-dependent changes in brain structure. We chose to image fluorescently labelled cell nuclei, because these can be readily imaged in large tissue volumes and allow inferences on several structural parameters: (1) the physical volume as determined from a subset of nuclei used to generate a geometrically defined space, (2) the number of cells, (3) the nearest neighbour distance measured between all nuclei as an indicator of cell clustering, and (4) the volume of the cell nuclei. Using this approach, we found that physical volume did not significantly correlate with GMV change, whereas mean nuclear volume was inversely correlated. When focusing on layers within the imaging volume, positive correlations of GMV were found with cell number near the cortical surface and nearest neighbour distance in deeper layers. Thus, the novel approach introduced here provided new insights into the factors underlying grey matter volume changes.
doi:10.1101/559765 fatcat:bsjzcafhijgxtiprrwabxfszse

Anti-Correlated Cortical Networks of Intrinsic Connectivity in the Rat Brain

Adam J. Schwarz, Natalia Gass, Alexander Sartorius, Celine Risterucci, Michael Spedding, Esther Schenker, Andreas Meyer-Lindenberg, Wolfgang Weber-Fahr
2013 Brain Connectivity  
In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that
more » ... are temporally anti-correlated with a midline "DMNlike" network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anticorrelation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans.
doi:10.1089/brain.2013.0168 pmid:23919836 pmcid:PMC3796325 fatcat:ibnoduobgngffl4lmj2fvrgio4

Aspartoacylase-LacZ Knockin Mice: An Engineered Model of Canavan Disease

Nadine Mersmann, Dmitri Tkachev, Ruth Jelinek, Philipp Thomas Röth, Wiebke Möbius, Torben Ruhwedel, Sabine Rühle, Wolfgang Weber-Fahr, Alexander Sartorius, Matthias Klugmann, Austin John Cooney
2011 PLoS ONE  
Canavan Disease (CD) is a recessive leukodystrophy caused by loss of function mutations in the gene encoding aspartoacylase (ASPA), an oligodendrocyte-enriched enzyme that hydrolyses N-acetylaspartate (NAA) to acetate and aspartate. The neurological phenotypes of different rodent models of CD vary considerably. Here we report on a novel targeted aspa mouse mutant expressing the bacterial b-Galactosidase (lacZ) gene under the control of the aspa regulatory elements. X-Gal staining in known ASPA
more » ... xpression domains confirms the integrity of the modified locus in heterozygous aspa lacZ-knockin (aspa lacZ/+ ) mice. In addition, abundant ASPA expression was detected in Schwann cells. Homozygous (aspa lacZ/lacZ ) mutants are ASPA-deficient, show CD-like histopathology and moderate neurological impairment with behavioural deficits that are more pronounced in aspa lacZ/lacZ males than females. Non-invasive ultrahigh field proton magnetic resonance spectroscopy revealed increased levels of NAA, myo-inositol and taurine in the aspa lacZ/lacZ brain. Spongy degeneration was prominent in hippocampus, thalamus, brain stem, and cerebellum, whereas white matter of optic nerve and corpus callosum was spared. Intracellular vacuolisation in astrocytes coincides with axonal swellings in cerebellum and brain stem of aspa lacZ/lacZ mutants indicating that astroglia may act as an osmolyte buffer in the aspadeficient CNS. In summary, the aspa lacZ mouse is an accurate model of CD and an important tool to identify novel aspects of its complex pathology.
doi:10.1371/journal.pone.0020336 pmid:21625469 pmcid:PMC3098885 fatcat:br3rakq7jjfhxau27oftqplrvm

Differences between ketamine's short-term and long-term effects on brain circuitry in depression

Natalia Gass, Robert Becker, Jonathan Reinwald, Alejandro Cosa-Linan, Markus Sack, Wolfgang Weber-Fahr, Barbara Vollmayr, Alexander Sartorius
2019 Translational Psychiatry  
Ketamine acts as a rapid clinical antidepressant at 25 min after injection with effects sustained for 7 days. As dissociative effects emerging acutely after injection are not entirely discernible from therapeutic action, we aimed to dissect the differences between short-term and long-term response to ketamine to elucidate potential imaging biomarkers of ketamine's antidepressant effect. We used a genetical model of depression, in which we bred depressed negative cognitive state (NC) and
more » ... essed positive cognitive state (PC) rat strains. Four parallel rat groups underwent stress-escape testing and a week later received either S-ketamine (12 NC, 13 PC) or saline (12 NC, 12 PC). We acquired resting-state functional magnetic resonance imaging time series before injection and at 30 min and 48 h after injection. Graph analysis was used to calculate brain network properties. We identified ketamine's distinct action over time in a qualitative manner. The rapid response entailed robust and strain-independent topological modifications in cognitive, sensory, emotion, and reward-related circuitry, including regions that exhibited correlation of connectivity metrics with depressive behavior, and which could explain ketamine's dissociative and antidepressant properties. At 48 h ketamine had mainly strain-specific action normalizing habenula, midline thalamus, and hippocampal connectivity measures in depressed rats. As these nodes mediate cognitive flexibility impaired in depression, action within this circuitry presumably reflects ketamine's procognitive effects induced only in depressed patients. This finding is especially valid, as our model represents cognitive aspects of depression. These empirically defined circuits explain ketamine's distinct action over time and might serve as translational imaging correlates of antidepressant response in preclinical testing.
doi:10.1038/s41398-019-0506-6 pmid:31253763 pmcid:PMC6599014 fatcat:yqb7drsonbeu5aae62wzeipgdy

Interactive tool to create adjustable anatomical atlases for mouse brain imaging

Markus Sack, Lei Zheng, Natalia Gass, Gabriele Ende, Alexander Sartorius, Wolfgang Weber-Fahr
2020 Magnetic Resonance Materials in Physics, Biology and Medicine  
Brain atlases are important research tools enabling researchers to focus their investigations on specific anatomically defined brain regions and are used in many MRI applications, e.g. in fMRI, morphometry, whole brain spectroscopy, et cetera. Despite their extensive use and numerous versions they usually consist of predefined rigid brain regions with a given level of detail often degrading them to a non-ideal tool in special research topics. To overcome this intrinsic weakness we present a
more » ... hical user interface application which allows researchers to easily create mouse brain atlases with an adjustable user-defined level of detail and coverage to match specific research questions.
doi:10.1007/s10334-020-00866-0 pmid:32696290 fatcat:xb5anwoleves7egoygj66pllvu

Hierarchical cross-scale analysis identifies parallel ventral striatal networks coding for dynamic and stabilized olfactory reward predictions [article]

Laurens Winkelmeier, Carla Filosa, Max Scheller, Renée Hartig, Markus Sack, Robert Becker, David Wolf, Jonathan Reinwald, Martin Fungisai Gerchen, Alexander Sartorius, Andreas Meyer-Lindenberg, Wolfgang Weber-Fahr (+3 others)
2021 bioRxiv   pre-print
Wolfgang Kelsch ( Materials Availability This study did not generate any new animal models nor reagents.  ... 
doi:10.1101/2021.02.22.432268 fatcat:fof724xncjh6blqntsxr26imne

Sub-Anesthetic Ketamine Modulates Intrinsic BOLD Connectivity Within the Hippocampal-Prefrontal Circuit in the Rat

Natalia Gass, Adam James Schwarz, Alexander Sartorius, Esther Schenker, Celine Risterucci, Michael Spedding, Lei Zheng, Andreas Meyer-Lindenberg, Wolfgang Weber-Fahr
2013 Neuropsychopharmacology  
Dysfunctional connectivity within the hippocampal-prefrontal circuit (HC-PFC) is associated with schizophrenia, major depression, and neurodegenerative disorders, and both the hippocampus and prefrontal cortex have dense populations of N-methyl-D-aspartate (NMDA) receptors. Ketamine, a potent NMDA receptor antagonist, is of substantial current interest as a mechanistic model of glutamatergic dysfunction in animal and human studies, a psychotomimetic agent and a rapidly acting antidepressant. In
more » ... this study, we sought to understand the modulatory effect of acute ketamine administration on functional connectivity in the HC-PFC system of the rat brain using resting-state fMRI. Sprague-Dawley rats in four parallel groups (N ¼ 9 per group) received either saline or one of three behaviorally relevant, sub-anesthetic doses of S-ketamine (5, 10, and 25 mg/kg, s.c.), and connectivity changes 15-and 30-min postinjection were studied. The strongest effects were dose-and exposure-dependent increases in functional connectivity within the prefrontal cortex and in anterior-posterior connections between the posterior hippocampus and retrosplenial cortex, and prefrontal regions. The increased prefrontal connectivity is consistent with ketamine-induced increases in HC-PFC electroencephalographic gamma band power, possibly reflecting a psychotomimetic aspect of ketamine's effect, and is contrary to the data from chronic schizophrenic patients suggesting that ketamine effect does not necessarily parallel the disease pattern but might rather reflect a hyperglutamatergic state. These findings may help to clarify the brain systems underlying different dose-dependent behavioral profiles of ketamine in the rat.
doi:10.1038/npp.2013.290 pmid:24136293 pmcid:PMC3924524 fatcat:fw54rjwkrfhjzblgvetfjp2j5i

Cortical Glutamate and GABA Changes During Early Abstinence in Alcohol Dependence and Their Associations With Benzodiazepine Medication

Guoying Wang, Wolfgang Weber-Fahr, Ulrich Frischknecht, Derik Hermann, Falk Kiefer, Gabriele Ende, Markus Sack
2021 Frontiers in Psychiatry  
In this report, we present cross-sectional and longitudinal findings from single-voxel MEGA-PRESS MRS of GABA as well as Glu, and Glu + glutamine (Glx) concentrations in the ACC of treatment-seeking alcohol-dependent patients (ADPs) during detoxification (first 2 weeks of abstinence). The focus of this study was to examine whether the amount of benzodiazepine administered to treat withdrawal symptoms was associated with longitudinal changes in Glu, Glx, and GABA. The tNAA levels served as an
more » ... ernal quality reference; in agreement with the vast majority of previous reports, these levels were initially decreased and normalized during the course of abstinence in ADPs. Our results on Glu and Glx support hyperglutamatergic functioning during alcohol withdrawal, by showing higher ACC Glu and Glx levels on the first day of detoxification in ADPs. Withdrawal severity is reflected in cumulative benzodiazepine requirements throughout the withdrawal period. The importance of withdrawal severity for the study of GABA and Glu changes in early abstinence is emphasized by the benzodiazepine-dependent Glu, Glx, and GABA changes observed during the course of abstinence.
doi:10.3389/fpsyt.2021.656468 pmid:34290627 pmcid:PMC8287125 fatcat:fgyhlk3iezd4zphvkwjnlmcg2y

3D RINEPT {1H}-31P CSI: A feasible approach for the study of membrane turnover in the human brain

Tim Wokrina, Marco Ulrich, Wolfgang Weber-Fahr, Gabriele Ende
2008 Magnetic Resonance in Medicine  
Introduction Phosphomonoesters (PME) and Phosphodiesters (PDE) are intermediates of membrane phospholipid turnover and thus phosphorous MRS studies of the human brain gain in importance in many brain diseases that involve membrane defects. The application of multinuclear techniques known from high-resolution MR spectroscopy are constricted by the low S/N at field strengths available for clinical routine (3 T or less) which lead to long measurement times and / or low spatial resolution. In
more » ... on, broad macromolecular contributions underlying the PME and PDE resonances complicate the determination of metabolite concentrations. The large chemical shifts of most 31 P metabolites prohibit the application of slice selection pulses or single voxel techniqes. Here a 3D spherical k-space encoding 31 P-CSI sequence is presented which incorporates heteronuclear polarization transfer editing (RINEPT) [1] . RINEPT has been previously proposed for in vivo brain studies [2, 3] . However, yet no spatial localization was obtained [2] or measurement times were extremely long [3] .
doi:10.1002/mrm.21588 pmid:18429015 fatcat:qtfggxgbora7nmw57csnl3e3s4

Lateral habenula perturbation reduces default-mode network connectivity in a rat model of depression

Christian Clemm von Hohenberg, Wolfgang Weber-Fahr, Philipp Lebhardt, Namasivayam Ravi, Urs Braun, Natalia Gass, Robert Becker, Markus Sack, Alejandro Cosa Linan, Martin Fungisai Gerchen, Jonathan Rochus Reinwald, Lars-Lennart Oettl (+4 others)
2018 Translational Psychiatry  
Hyperconnectivity of the default-mode network (DMN) is one of the most widely replicated neuroimaging findings in major depressive disorder (MDD). Further, there is growing evidence for a central role of the lateral habenula (LHb) in the pathophysiology of MDD. There is preliminary neuroimaging evidence linking LHb and the DMN, but no causal relationship has been shown to date. We combined optogenetics and functional magnetic resonance imaging (fMRI), to establish a causal relationship, using
more » ... animal model of treatment-resistant depression, namely Negative Cognitive State rats. First, an inhibitory light-sensitive ion channel was introduced into the LHb by viral transduction. Subsequently, laser stimulation was performed during fMRI acquisition on a 9.4 Tesla animal scanner. Neural activity and connectivity were assessed, before, during and after laser stimulation. We observed a connectivity decrease in the DMN following laser-induced LHb perturbation. Our data indicate a causal link between LHb downregulation and reduction in DMN connectivity. These findings may advance our mechanistic understanding of LHb inhibition, which had previously been identified as a promising therapeutic principle, especially for treatment-resistant depression.
doi:10.1038/s41398-018-0121-y pmid:29581421 pmcid:PMC5913319 fatcat:a3edolaxvbcf3bmc6oh4g7jtx4
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