Liste der Publikationen

Filtern

Filter zurücksetzen
    • Samii Amir
    • 2019
    • World Neurosurgery
    • Prognostic significance of preoperative geometric changes in the internal acoustic canal for hearing preservation in vestibular schwannoma surgery
    • <p>Objective: This study focused on the changes in the internal acoustic canal (IAC) caused by vestibular schwannomas (VSs) and their prognostic significance for postoperative hearing outcome. Methods: A total of 125 consecutive cases of VS were included. We used a neuronavigation software to perform the following measurements on both the tumor side and healthy side: volume of the IAC (VIAC), maximal diameter of the IAC (DIAC), and length of the IAC (LIAC). A statistical analysis was realized using Spearman correlation to test the correlation of the morphometric measure of the IAC and postoperative hearing. Multivariate analysis was performed to test the impact of measurements of the IAC and preoperative hearing on postoperative hearing. Results: The mean VIAC on the tumor side and on the healthy side was 0.271 and 0.169 cm <sup>3</sup>, respectively. The mean DIAC was 9.438 mm on the tumor side and 7.034 mm contralateral. The correlations tests showed significant correlations of both postoperative hearing deficit and degree of hearing loss with 1) VIAC on the tumor side, 2) difference between VIAC on the tumor side and healthy side, 3) DIAC on the tumor side, and 4) difference between the DIAC on the tumor side and healthy side. The multivariate analysis showed significant impact of the DIAC (P = 0.01) and preoperative hearing status (P = 0.02) on postoperative hearing. Conclusions: Enlargement of the VIAC and DIAC are negative prognostic factors for hearing preservation. Reasons may be long-standing compression of the auditory nerve and an increased vulnerability of the inner ear structures during the drilling of the IAC. </p>
    • http://www.scopus.com/inward/record.url?scp=85072598215&partnerID=8YFLogxK
    • Andreas Heinz, Gunter Schumann
    • 2019
    • Nature Human Behaviour
    • Identification of neurobehavioural symptom groups based on shared brain mechanisms
    • <p>Most psychopathological disorders develop in adolescence. The biological basis for this development is poorly understood. To enhance diagnostic characterization and develop improved targeted interventions, it is critical to identify behavioural symptom groups that share neural substrates. We ran analyses to find relationships between behavioural symptoms and neuroimaging measures of brain structure and function in adolescence. We found two symptom groups, consisting of anxiety/depression and executive dysfunction symptoms, respectively, that correlated with distinct sets of brain regions and inter-regional connections, measured by structural and functional neuroimaging modalities. We found that the neural correlates of these symptom groups were present before behavioural symptoms had developed. These neural correlates showed case-control differences in corresponding psychiatric disorders, depression and attention deficit hyperactivity disorder in independent clinical samples. By characterizing behavioural symptom groups based on shared neural mechanisms, our results provide a framework for developing a classification system for psychiatric illness that is based on quantitative neurobehavioural measures.</p>
    • Michael R. Kreutz
    • 2019
    • PLoS ONE
    • 2
    • The primate-specific peptide Y-P30 regulates morphological maturation of neocortical dendritic spines
    • <p>The 30-amino acid peptide Y-P30 corresponds to the N-terminus of the primate-specific, sweat gland-derived dermcidin prepropeptide. Previous work has revealed that Y-P30 enhances the interaction of pleiotrophin and syndecans-2/3, and thus represents a natural ligand to study this signaling pathway. In immature neurons, Y-P30 activates the c-Src and p42/44 ERK kinase pathway, increases the amount of F-actin in axonal growth cones, and promotes neuronal survival, cell migration and axonal elongation. The action of Y-P30 on axonal growth requires syndecan-3 and heparan sulfate side chains. Whether Y-P30 has the potential to influence dendrites and dendritic protrusions has not been explored. The latter is suggested by the observations that syndecan-2 expression increases during postnatal development, that syndecan-2 becomes enriched in dendritic spines, and that overexpression of syndecan-2 in immature neurons results in a premature morphological maturation of dendritic spines. Here, analysing rat cortical pyramidal and non-pyramidal neurons in organotypic cultures, we show that Y-P30 does not alter the development of the dendritic arborization patterns. However, Y-P30 treatment decreases the density of apical, but not basal dendritic protrusions at the expense of the filopodia. Analysis of spine morphology revealed an unchanged mushroom/stubby-to-thin spine ratio and a shortening of the longest decile of dendritic protrusions. Whole-cell recordings from cortical principal neurons in dissociated cultures grown in the presence of Y-P30 demonstrated a decrease in the frequency of glutamatergic mEPSCs. Despite these differences in protrusion morphology and synaptic transmission, the latter likely attributable to presynaptic effects, calcium event rate and amplitude recorded in pyramidal neurons in organotypic cultures were not altered by Y-P30 treatment. Together, our data suggest that Y-P30 has the capacity to decelerate spinogenesis and to promote morphological, but not synaptic, maturation of dendritic protrusions.</p>
    • http://www.scopus.com/inward/record.url?scp=85061544091&partnerID=8YFLogxK
    • KG Reymann, Ulrich H. Schroeder
    • 2019
    • Journal of Pharmacology and Experimental Therapeutics
    • The novel phosphodiesterase 9A inhibitor BI 409306 increases cyclic guanosine monophosphate levels in the brain, promotes synaptic plasticity and enhances memory function in rodents
    • <p>N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) is an established cellular model underlying learning and memory, and involves intracellular signaling mediated by the second messenger cyclic guanosine monophosphate (cGMP). As phosphodiesterase (PDE)9A selectively hydrolyses cGMP in areas of the brain related to cognition, PDE9A inhibitors may improve cognitive function by enhancing NMDA receptor-dependent LTP. This study aimed to pharmacologically characterize BI 409306, a novel PDE9A inhibitor, using in vitro assays and in vivo determination of cGMP levels in the brain. Further, the effects of BI 409306 on synaptic plasticity evaluated by LTP in ex vivo hippocampal slices, and on cognitive performance in rodents were also investigated. In vitro assays demonstrated that BI 409306 is a potent and selective inhibitor of PDE9A with a mean (standard deviation) concentration at half-maximal inhibition (IC50) of 65 (11) nM. BI 409306 increased cGMP levels in rat prefrontal cortex and cerebrospinal fluid, and attenuated a reduction in mouse striatum cGMP induced by the NMDA receptor antagonist MK 801. In ex vivo rat brain slices, BI 409306 enhanced LTP induced by both weak and strong tetanic stimulation. Treatment of mice with BI 409306 reversed MK 801-induced working memory deficits in a T maze spontaneous alternation task, and improved long term memory in an object recognition task. These findings suggest that BI 409306 is a potent and selective inhibitor of PDE9A. BI 409306 shows target engagement by increasing cGMP levels in brain, facilitates synaptic plasticity as demonstrated by enhancement of hippocampal LTP, and improves episodic and working memory function in rodents. SIGNIFICANCE STATEMENT: This pre-clinical study demonstrates that BI 409306 is a potent and selective PDE9A inhibitor in rodents. Treatment with BI 409306 increased brain cGMP levels, promoted long-term potentiation, and improved episodic and working memory performance in rodents. These findings support a role for PDE9A in synaptic plasticity and cognition. The potential benefits of BI 409306 are currently being investigated in clinical trials.</p>
    • Michael R. Kreutz
    • 2019
    • 567-581
    • Tryptophan Scanning Mutagenesis of EF-Hand Motifs
    • <p>Ca2+ regulation in living systems occurs via specific structural alterations, subtle or drastic, in the Ca2+-binding domains of sensor proteins. Sensor proteins perform designated nonredundant roles within the dense network of Ca2+-binding proteins. A detailed understanding of the structural changes in calcium sensor proteins due to Ca2+ spikes that vary spatially, temporally, and in magnitude would provide better insights into the mechanism of Ca2+ sensing. This chapter describes a method to study various stages during apo to the holo transition of Ca2+-binding proteins by Trp-mediated scanning of individual EF-hand motifs. We describe the applicability of this procedure to caldendrin, which is a neuronal Ca2+-binding protein and to integrin-binding protein. Tryptophan mutants of full-length caldendrin were designed to reveal local structural changes in each EF-hand of the protein. This method, referred to as "EF-hand scanning tryptophan mutagenesis," not only allows the identification of canonical and noncanonical EF-hands using very low concentrations of protein but also enables visualization of the hierarchical filling of Ca2+ into the canonical EF-hands.</p>
    • http://www.scopus.com/inward/record.url?scp=85060911324&partnerID=8YFLogxK
    • André Brechmann, Norman Peitek, Norman Peitek, André Brechmann
    • 2019
    • Communications of the ACM
    • Studying Programming in the Neuroage: Just a Crazy Idea?
    • André Brechmann, Nicole Angenstein, André Brechmann
    • 2019
    • Human Brain Mapping
    • The impact of task difficulty on the lateralization of processing in the human auditory cortex
    • <p>Perception of complex auditory stimuli like speech requires the simultaneous processing of different fundamental acoustic parameters. The contribution of left and right auditory cortex (AC) in the processing of these parameters differs. In addition, activity within the AC can vary positively or negatively with task performance depending on the type of task. This might affect the allocation of processing to the left and right AC. Here we studied with functional magnetic resonance imaging the impact of task difficulty on the degree of involvement of the left and right AC in two tasks that have previously been shown to differ in hemispheric involvement: categorization and sequential comparison of the direction of frequency modulations (FM). Task difficulty was manipulated by changing the speed of modulation and by that the frequency range covered by the FM. To study the impact of task-difficulty despite covarying the stimulus parameters, we utilized the contralateral noise procedure that allows comparing AC activation unconfounded by bottom-up driven activity. The easiest conditions confirmed the known right AC involvement during the categorization task and the left AC involvement during the comparison task. The involvement of the right AC increased with increasing task difficulty for both tasks presumably due to the common task component of categorizing FM direction. The involvement of left AC varied with task difficulty depending on the task. Thus, task difficulty has a strong impact on lateralized processing in AC. This connection must be taken into account when interpreting future results on lateralized processing in the AC.</p>
    • http://www.scopus.com/inward/record.url?scp=85071325953&partnerID=8YFLogxK
    • André Brechmann, Norman Peitek, Norman Peitek, André Brechmann
    • 2019
    • 126-129
    • CodersMUSE: Multi-Modal Data Exploration of Program-Comprehension Experiments
    • <p>Program comprehension is a central cognitive process in programming. It has been in the focus of researchers for decades, but is still not thoroughly unraveled. Multi-modal psycho-physiological and neurobiological measurement methods have proved successful to gain a more holistic understanding of program comprehension. However, there is no proper tool support that lets researchers explore synchronized, conjoint multi-modal data, specifically designed for the needs in program-comprehension research. In this paper, we present CodersMUSE, a prototype implementation that aims to satisfy this crucial need.</p>
    • http://www.scopus.com/inward/record.url?scp=85072331223&partnerID=8YFLogxK
    • Alessandro-Dario Confettura, Rahul Kaushik, Michael R. Kreutz
    • 2019
    • Frontiers in Aging Neuroscience
    • Traditional Japanese Herbal Medicine Yokukansan Targets Distinct but Overlapping Mechanisms in Aged Mice and in the 5xFAD Mouse Model of Alzheimer's Disease
    • <p>Yokukansan (YKS) is a traditional Japanese herbal medicine that has been used in humans for the treatment of several neurological conditions, such as age-related anxiety and behavioral and psychological symptoms (BPSD) related to multiple forms of dementia, including Alzheimer's disease (AD). However, the cellular and molecular mechanisms targeted by YKS in the brain are not completely understood. Here, we compared the efficacy of YKS in ameliorating the age- and early-onset familial AD-related behavioral and cellular defects in two groups of animals: 18- to 22-month-old C57BL6/J wild-type mice and 6- to 9-month-old 5xFAD mice, as a transgenic mouse model of this form of AD. Animals were fed food pellets that contained YKS or vehicle. After 1-2 months of YKS treatment, we evaluated the cognitive improvements in both the aged and 5xFAD transgenic mice, and their brain tissues were further investigated to assess the molecular and cellular changes that occurred following YKS intake. Our results show that both the aged and 5xFAD mice exhibited impaired behavioral performance in novel object recognition and contextual fear conditioning (CFC) tasks, which was significantly improved by YKS. Further analyses of the brain tissue from these animals indicated that in aged mice, this improvement was associated with a reduction in astrogliosis, microglia activation and downregulation of the extracellular matrix (ECM), whereas in 5xFAD mice, none of these mechanisms were evident. These results show the differential action of YKS in healthy aged and 5xFAD mice. However, both aged and 5xFAD YKS-treated mice showed increased neuroprotective signaling through protein kinase B/Akt as the common mode of action. Our data suggest that YKS may impart its beneficial effects through Akt signaling in both 5xFAD mice and aged mice, with multiple additional mechanisms potentially contributing to its beneficial effects in aged animals.</p>
    • Camilla Fusi, Jennifer Mundhenk, Jennifer Mundhenk, Camilla Fusi, Michael R. Kreutz
    • 2019
    • Frontiers in Molecular Neuroscience
    • Caldendrin and Calneurons-EF-Hand CaM-Like Calcium Sensors With Unique Features and Specialized Neuronal Functions
    • <p>The calmodulin (CaM)-like Ca2+-sensor proteins caldendrin, calneuron-1 and -2 are members of the neuronal calcium-binding protein (nCaBP)-family, a family that evolved relatively late during vertebrate evolution. All three proteins are abundant in brain but show a strikingly different subcellular localization. Whereas caldendrin is enriched in the postsynaptic density (PSD), calneuron-1 and -2 accumulate at the trans-Golgi-network (TGN). Caldendrin exhibit a unique bipartite structure with a basic and proline-rich N-terminus while calneurons are the only EF-Hand CaM-like transmembrane proteins. These uncommon structural features come along with highly specialized functions of calneurons in Golgi-to-plasma-membrane trafficking and for caldendrin in actin-remodeling in dendritic spine synapses. In this review article, we will provide a synthesis of available data on the structure and biophysical properties of all three proteins. We will then discuss their cellular function with special emphasis on synaptic neurotransmission. Finally, we will summarize the evidence for a role of these proteins in neuropsychiatric disorders.</p>
    • http://www.scopus.com/inward/record.url?scp=85064213862&partnerID=8YFLogxK
    • Hans-Jochen Heinze, Julia Steinhardt, Jürgen Voges, Hans Jochen Heinze
    • 2019
    • Parkinsonism and Related Disorders
    • Cerebello-striatal interaction mediates effects of subthalamic nucleus deep brain stimulation in Parkinson's disease
    • <p>BACKGROUND: In Parkinson's disease (PD), dopamine replacement therapy (DRT) enhances the effective connectivity of the prefrontal cortex (PFC) and supplementary motor area (SMA). The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) go beyond DRT effects including highly beneficial tremor suppression.</p><p>OBJECTIVES: Here, we aimed to determine DBS-related changes of a motor network using resting state fMRI in PD patients with chronic STN DBS.</p><p>METHODS: In a repeated-measurement design, 26 medicated PD patients (60.9 years (SD 8.9)) were investigated using resting state fMRI while bipolar STN stimulation was (i) active or (ii) switched off, and dynamic causal modelling was subsequently performed.</p><p>RESULTS: DBS improved the MDS-UPDRS-III score by 26.4% (DBS ON/Med ON vs. DBS OFF/Med ON). Active stimulation resulted in an increased effective connectivity from cerebellum to putamen (p = 0.00118). In addition, there was a stronger coupling from PFC to cerebellum (p = 0.021), as well as from cerebellum to SMA (p = 0.043) on an uncorrected level. Coupling strength from PFC to cerebellum correlated with the DBS-related change of the resting tremor subscore (r = 0.54, p = 0.031). Self-connections increased as a function of DBS in the right PFC, PMC, SMA, M1, thalamus and left cerebellum.</p><p>CONCLUSIONS: DBS-related improvement of Parkinsonian signs appears to be driven by an interaction between the cerebellum and the putamen. Resting tremor suppression may be related to an enhanced prefronto-cerebellar network. Activation of the mesial premotor loop (PFC-SMA) as seen in DRT may thus be secondary due to the primary modulation of cerebellar networks.</p>
    • http://www.scopus.com/inward/record.url?scp=85071699595&partnerID=8YFLogxK
    • Hermann Hinrichs, Michael Scholz
    • 2019
    • Clinical Neurophysiology
    • 11
    • 2076-2087
    • Assessment of the technical usability and efficacy of a new portable dry-electrode EEG recorder
    • <p>OBJECTIVES: The HOME project is intended to provide evidence of diagnostic and therapeutic yield of a patient-controlled EEG home-monitoring for neurological outpatients.</p><p>METHODS: This study evaluated the technical and practical usability and efficacy of a new portable dry-electrode EEG recorder in comparison to conventional EEG devices based on technical assessments and inter-rater comparisons of EEG record examinations of office-based practitioners and two experienced neurologists.</p><p>RESULTS: The technical assessment was based on channel-wise comparisons of band power values derived from power spectra as observed in two recording modalities. Slight yet significant differences were observed only in the Delta-frequency band (1.5-4 Hz). The fraction of automatically detected artifact segments was larger in the new portable recordings than in conventional recordings (20% vs. 11%, median). Overall, 93% of raters' stated diagnostic findings gathered from conventional devices were concordant with stated diagnostic findings gathered from the new portable device.</p><p>CONCLUSION: The new EEG device was shown to have technical comparability to and a high concordance rate of diagnostic findings with conventional EEG devices.</p><p>SIGNIFICANCE: The new portable dry-electrode EEG device is suitable to meet the HOME projects' goal of establishing a patient-controlled EEG home-monitoring in the routine care of neurological outpatients.</p><p>TRIAL REGISTRATION: DRKS DRKS00012685. Registered 09 August 2017, retrospectively registered.</p>
    • http://www.scopus.com/inward/record.url?scp=85072276427&partnerID=8YFLogxK
    • Jens-Max Hopf
    • 2019
    • Brain Sciences
    • 9
    • High Working Memory Capacity at the Cost of Precision?
    • <p>Working memory capacity (WMC) varies tremendously among individuals. Here, we investigate the possibility that subjects with high WMC use this limited resource more efficiently by reducing the precision with which they store information in demanding tasks. Task difficulty was increased by (a) presenting more objects to be memorized, (b) informing subjects only after the encoding phase about the relevant objects, and (c) delivering distracting features at retrieval. Precision was assessed by means of a continuous delayed-estimation task, in which object features had to be estimated from memory. High WMC subjects did not show a stronger drop in precision in difficult tasks. Instead, a positive correlation between precision and general WMC emerged. These findings suggest that high WMC subjects do not necessarily trade in quantity for quality when forming working memory (WM) representations under increasing demand. Instead, they seem to be able to devote more cognitive resources to support WM storage.</p>
    • http://www.scopus.com/inward/record.url?scp=85073275318&partnerID=8YFLogxK
    • Jens-Max Hopf, Mircea Ariel Schoenfeld, Sarah E Donohue, Steffi Weinhold, Rodrigo Quian Quiroga
    • 2019
    • PLoS ONE
    • 1
    • A neural hallmark of auditory implicit learning is altered in older adults
    • <p>Temporal regularities in the environment are often learned implicitly. In an auditory target-detection paradigm using EEG, Jongsma and colleagues (2006) showed that the neural response to these implicit regularities results in a reduction of the P3-N2 complex. Here, we utilized the same paradigm, this time in both young and old participants, to determine if this EEG signature of implicit learning was altered with age. Behaviorally, both groups of participants showed similar benefits for the presence of temporal regularity, with faster and more accurate responses given when the auditory targets were presented in a temporally regular vs. random pattern. In the brain, the younger adults showed the expected decrease in amplitude of this complex for regular compared to irregular trials. Older adults, in contrast, showed no difference in the amplitude of the P3-N2 complex between the irregular and regular condition. These data suggest that, although auditory implicit learning may be behaviorally spared in aging, older adults are not using the same neural substrates as younger adults to achieve this.</p>
    • http://www.scopus.com/inward/record.url?scp=85060789636&partnerID=8YFLogxK
    • Reinhard König, Aida Hajizadeh, Artur Matysiak, Aida Hajizadeh, Artur Matysiak, Patrick J C May, Reinhard König
    • 2019
    • Biological Cybernetics
    • 3
    • 321-345
    • Explaining event-related fields by a mechanistic model encapsulating the anatomical structure of auditory cortex
    • <p>Event-related fields of the magnetoencephalogram are triggered by sensory stimuli and appear as a series of waves extending hundreds of milliseconds after stimulus onset. They reflect the processing of the stimulus in cortex and have a highly subject-specific morphology. However, we still have an incomplete picture of how event-related fields are generated, what the various waves signify, and why they are so subject-specific. Here, we focus on this problem through the lens of a computational model which describes auditory cortex in terms of interconnected cortical columns as part of hierarchically placed fields of the core, belt, and parabelt areas. We develop an analytical approach arriving at solutions to the system dynamics in terms of normal modes: damped harmonic oscillators emerging out of the coupled excitation and inhibition in the system. Each normal mode is a global feature which depends on the anatomical structure of the entire auditory cortex. Further, normal modes are fundamental dynamical building blocks, in that the activity of each cortical column represents a combination of all normal modes. This approach allows us to replicate a typical auditory event-related response as a weighted sum of the single-column activities. Our work offers an alternative to the view that the event-related field arises out of spatially discrete, local generators. Rather, there is only a single generator process distributed over the entire network of the auditory cortex. We present predictions for testing to what degree subject-specificity is due to cross-subject variations in dynamical parameters rather than in the cortical surface morphology.</p>
    • http://www.scopus.com/inward/record.url?scp=85062629758&partnerID=8YFLogxK
    • Jing Ma, Jing Ma
    • 2019
    • Shengtai Xuebao/ Acta Ecologica Sinica
    • 13
    • 4966-4974
    • The effects of family groups on individual foraging behavior in reed voles (Microtus fortis)
    • <p>Herbivorous mammals benefit from foraging in family groups through the sharing of vigilance information and the dilution of the individual risks of being preyed upon; however, interference competition may reduce their intake rates. To evaluate the effects of family foraging on the individual foraging behavior of reed voles (Microtus fortis), the behavioral sequences and parameters of the voles' foraging on concentrated homogenous food patches consisting of fresh crabgrass leaves (Digitaria sanguinalis) were measured. The results showed that there is no significant difference in foraging behavior between female and male among family groups; however compared to a lone individual, individuals in family groups had significantly shortened foraging decision times, but markedly reduced intake rates. Analyses showed that, compared with the lone individual, the foraging interruption times of individuals increased significantly in family groups, but their intake rates declined significantly as a result of the greater amount of time spent on searching for adjacent food items. Analyses of the individual vigilance time showed that interference competition triggered by others individuals in family groups significantly increased the proportion of vigilance time spent on scanning, staring, and sniffing. While the proportion of vigilance time spent on upright scanning and listening decreased for individuals in family groups, the interruption times of individuals didnot decrease significantly. These results revealed that the interference competition among individuals in family groups triggered variations in the parameters of the foraging behavior of the reed voles, increasing their foraging interruption times and decreasing their intake rates.</p>
    • http://www.scopus.com/inward/record.url?scp=85069446276&partnerID=8YFLogxK
    • Norman Peitek, Norman Peitek
    • 2019
    • 154-164
    • Indentation: Simply a Matter of Style or Support for Program Comprehension?
    • <p>An early study showed that indentation is not a matter of style, but provides actual support for program comprehension. In this paper, we present a non-exact replication of this study. Our aim is to provide empirical evidence for the suggested level of indentation made by many style guides. Following Miara and others, we also included the perceived difficulty, and we extended the original design to gain additional insights into the influence of indentation on visual effort by employing an eye-tracker. In the course of our study, we asked 22 participants to calculate the output of Java code snippets with different levels of indentation, while we recorded their gaze behavior. We did not find any indication that the indentation levels affect program comprehension or visual effort, so we could not replicate the findings of Miara and others. Nevertheless, our modernization of the original experiment design is a promising starting point for future studies in this field.</p>
    • http://www.scopus.com/inward/record.url?scp=85072335696&partnerID=8YFLogxK
    • Martin Walter
    • 2019
    • Journal of Affective Disorders
    • 205-212
    • A preliminary study of anti-suicidal efficacy of repeated ketamine infusions in depression with suicidal ideation
    • <p>Background: Suicide is a tremendous public health crisis and is demanded urgent intervention. Previous studies found that ketamine intervention could rapidly reduce suicidal ideation in depression. However, the comparatively study in Chinese population remains absence. The current study aims to assess the anti-suicidal efficacy of repeated ketamine infusions for Chinese depressed suicidal patients, especially distinguish between low suicidal ideation (SI) group and high SI group. Methods: Eighty-six unipolar and bipolar depressive patients with current suicidal ideation received six ketamine infusions during a 12-day period. Hamilton Depression Rating Scale (HAMD) and Beck Scale for Suicide Ideation (SSI) was measured at baseline, 4 h and 24 h after each infusion, and two-week naturalistically follow-up. Results: Forty-nine (57.0%) patients relief of suicidal ideation after first infusion and 56 (65.1%) after six infusions. Anti-suicidal response rate in low SI group were higher than high SI group, and anti-suicidal response at 4 h after first infusion was significant predictor of response at 24 h after sixth infusion. Furthermore, at 24 h after the sixth infusion, correlation between changes in suicidal ideation and depression was 0.23, accounting for 7.4% in the variance of suicidal ideation change. Limitation: The major limitation of this study was that lack of a placebo or other control group limits the interpretation of efficacy. Conclusions: We confirmed that six repeated ketamine infusions for Chinese suicidal depressed patients were effective in generating a rapid response of suicidal ideation, especially low SI achieved more benefits from ketamine infusions.</p>
    • http://www.scopus.com/inward/record.url?scp=85063407145&partnerID=8YFLogxK
    • Martin Walter
    • 2019
    • Progress in Neuro-Psychopharmacology and Biological Psychiatry
    • The role of NMDA receptor in neurobiology and treatment of major depressive disorder
    • <p>There is accumulating evidence demonstrating that dysfunction of glutamatergic neurotransmission, particularly via N-methyl-d-aspartate (NMDA) receptors, is involved in the pathophysiology of major depressive disorder (MDD). Several studies have revealed an altered expression of NMDA receptor subtypes and impaired NMDA receptor-mediated intracellular signaling pathways in brain circuits of patients with MDD. Clinical studies have demonstrated that NMDA receptor antagonists, particularly ketamine, have rapid antidepressant effects in treatment-resistant depression, however, neurobiological mechanisms are not completely understood. Growing body of evidence suggest that signal transduction pathways involved in synaptic plasticity play critical role in molecular mechanisms underlying rapidly acting antidepressant properties of ketamine and other NMDAR antagonists in MDD. Discovering the molecular mechanisms underlying the unique antidepressant actions of ketamine will facilitate the development of novel fast acting antidepressants which lack undesirable effects of ketamine. This review provides a critical examination of the NMDA receptor involvement in the neurobiology of MDD including analyses of alterations in NMDA receptor subtypes and their interactive signaling cascades revealed by postmortem studies. Furthermore, to elucidate mechanisms underlying rapid-acting antidepressant properties of NMDA receptor antagonists we discussed their effects on the neuroplasticity, mostly based on signaling systems involved in synaptic plasticity of mood-related neurocircuitries.</p>
    • http://www.scopus.com/inward/record.url?scp=85067500241&partnerID=8YFLogxK
    • Martin Walter, Lejla Colic, Viola Borchardt
    • 2019
    • Frontiers in Behavioral Neuroscience
    • Glutamate in Salience Network Predicts BOLD Response in Default Mode Network During Salience Processing
    • <p>Background: Brain investigations identified salience network (SN) comprising the dorsal Anterior Cingulate Cortex (dACC) and the Anterior Insula (AI). Magnetic resonance spectroscopy (MRS) studies revealed the link between the glutamate concentration in the ACC and alterations in attentional scope. Hence, we investigated whether glutamate concentration in the dACC modulates brain response during salience processing. Methods: Twenty-seven healthy subjects (12♀, 15♁) provided both STEAM MRS at 7T measuring glutamate concentrations in the dACC as well as a functional magnetic resonance imaging (fMRI) task to study the influence on content-related salience processing and expectedness. Salience was modulated for both sexual and non-sexual emotional photos in either expected or unexpected situations. Correlation between MRS and task fMRI was investigated by performing regression analyses controlling for age, gender, and gray matter partial volume. Results/Conclusion: During picture processing, the extent of deactivation in the Posterior Cingulate Cortex (PCC) was attenuated by two different salience attributions: sexual content and unexpectedness of emotional content. Our results indicate that stimulus inherent salience induces an attenuation of the deactivation in PCC, which is in turn balanced by higher level of glutamate in the dACC.</p>
    • http://www.scopus.com/inward/record.url?scp=85073683646&partnerID=8YFLogxK
Diese Seite teilen: