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    • Samii Amir
    • 2019
    • World Neurosurgery
    • Can intraoperative magnetic resonance imaging be helpful in the surgical resection of parasellar meningiomas ?
    • <p>Objective: The surgery of parasellar meningiomas is crucial. There are only a few reports of the use of intraoperative magnetic resonance imaging (iMRI) for resection of these lesions. We discuss the safety and usefulness of this technique in achieving the planned surgical goal and analyze patients' outcomes. Methods: Nineteen cases of parasellar meningioma were treated in our institution using iMRI. We classified the tumors according to their primary location: tuberculum sellae, clinoidal, and cavernous sinus meningiomas. We evaluated the history of previous surgery, outcome, residual (if present) tumor volume, degree of resection, achievement of the surgical goal, and number of iMRI scans. Results: The preoperative surgical goal was achieved in all patients. In 7 of 19 patients, (37%) further tumor resection was performed after the first iMRI scan. Regarding the cavernous sinus group, the surgical resection was continued after the first iMRI in 56% of patients, obtaining substantial additional volume reduction. No complications were found related to the use of iMRI scan. Conclusions: iMRI has been effective in safely increasing the extent of parasellar meningioma resection mainly for recurrent and invasive tumors. Its usefulness has been seen mostly in cavernous sinus lesions, in which it allowed the further safe resection in 56% of cases. Moreover, this tool was particularly useful in recurrent or residual meningiomas with extension in extracranial compartments.</p>
    • http://www.scopus.com/inward/record.url?scp=85072075078&partnerID=8YFLogxK
    • Samii Amir
    • 2019
    • World Neurosurgery
    • Intraoperative resting state functional connectivity and resting state networks in patients with intracerebral lesions
    • <p>OBJECTIVE: To evaluate the functional connectivity (FC) and resting-state networks (RSNs) in patients under anesthesia operated for resection of intracerebral lesions.</p><p>METHODS: We performed intraoperative resting-state functional magnetic resonance imaging (irs-fMRI) in 24 patients under anesthesia before and after lesion resection. Correlation matrices were established for each session (a total 48 of sessions). We analyzed the changes in overall FC and in FC of the healthy and operated hemispheres between the first and second sessions. We tested the correlation between changes in FC and clinical outcomes and the duration, rate, and total dosage of anesthesia. We also performed a group analysis to detect topographic changes in RSNs in patients under anesthesia. A single-subject analysis was performed to detect clinically relevant RSNs in each patient.</p><p>RESULTS: FC decreased significantly in the second session, as did interhemispheric connectivity. The decrease in the pathological hemisphere was significant and significantly greater than the decrease in the intrahemispheric connectivity of the healthy hemisphere. The change in FC was not correlated with clinical outcome or with the duration, rate, or dosage of anesthesia. Group analysis showed topographic changes in RSNs, especially in high-level networks such as default mode and salience networks. Identification of clinically relevant networks was also possible.</p><p>CONCLUSIONS: FC and RSNs could be identified under anesthesia and used for extended brain mapping. Further studies are needed to optimize the depth of hypnosis to stabilize FC between sessions.</p>
    • Frank Angenstein, Frank Angenstein
    • 2019
    • NeuroImage
    • The role of ongoing neuronal activity for baseline and stimulus-induced BOLD signals in the rat hippocampus
    • <p>To understand how ongoing neuronal activity affects baseline BOLD signals, neuronal and resultant fMRI responses were simultaneously recorded in the right hippocampus of male rats during continuous low-frequency (2 or 4 Hz) pulse stimulation of the right perforant pathway. Despite continuously increased neuronal activity, BOLD signals only transiently increased in the hippocampus and subsequently returned to either the initial level (2 Hz) or even to a consistently lower level (4 Hz). Whereas the initially transient increase in BOLD signals coincided with an increased spiking of granule cells, the subsequent reduction of BOLD signals was independent of granule cell spiking activity but coincided with persistent inhibition of granule cell excitability, i.e., with reduced postsynaptic activity and prolonged population spike latency. The decline in BOLD signals occurred in the presence of an elevated local cerebral blood volume (CBV), thus the reduction of granule cell excitability is attended by high oxygen consumption. When previous or current stimulations lessen baseline BOLD signals, subsequent short stimulation periods only elicited attenuated BOLD responses, even when actual spiking activity of granule cells was similar. Thus, the quality of stimulus-induced BOLD responses critically depends on the current existing inhibitory activity, which closely relates to baseline BOLD signals. Thus, a meaningful interpretation of stimulus-induced BOLD responses should consider slowly developing variations in baseline BOLD signals; therefore, baseline correction tools should be cautiously used for fMRI data analysis.</p>
    • http://www.scopus.com/inward/record.url?scp=85070886138&partnerID=8YFLogxK
    • Frank Angenstein, Detlef Balschun, Frank Angenstein
    • 2019
    • NeuroImage
    • 347-356
    • Low frequency pulse stimulation of Schaffer collaterals in Trpm4<sup>−/−</sup> knockout rats differently affects baseline BOLD signals in target regions of the right hippocampus but not BOLD responses at the site of stimulation
    • <p>Electrical stimulation of right Schaffer collateral in Trpm4<sup>−/−</sup> knockout and wild type rats were used to study the role of Trpm4 channels for signal processing in the hippocampal formation. Stimulation induced neuronal activity was simultaneously monitored in the CA1 region by in vivo extracellular field recordings and in the entire brain by BOLD fMRI measurements. In wild type and Trpm4<sup>−/−</sup> knockout rats, consecutive 5 Hz pulse trains elicited similar neuronal responses in the CA1 region and similar BOLD responses in the stimulated right hippocampus. Stimulus-related positive BOLD responses were also found in the left dorsal hippocampus. In contrast to the right dorsal hippocampus, baseline BOLD signals in the left hippocampus significantly decreased during consecutive stimulation trains. Similarly, slowly developing significant declines in baseline BOLD signals, in absence of any positive BOLD responses, were also observed in the right entorhinal, right piriform cortex, right basolateral amygdala and right dorsal striatum whereas baseline BOLD signals remained almost stable in the corresponding left regions. Furthermore, significant declines in baseline BOLD signals were found in the prefrontal cortex and prelimbic/infralimbic cortex. Because significant baseline BOLD declines were only observed in target regions of the right dorsal hippocampus, it might reflect functional connectivity between these regions. In all observed regions the decline in baseline BOLD signals was significantly delayed and less pronounced in Trpm4<sup>−/−</sup> knockout rats when compared to wild type rats. Thus, either Trpm4 channels are involved in mediating these baseline BOLD shifts or functional connectivity of the hippocampus is impaired in Trpm4<sup>−/−</sup> knockout rats.</p>
    • http://www.scopus.com/inward/record.url?scp=85058635497&partnerID=8YFLogxK
    • Hans-Jochen Heinze, Hans Jochen Heinze
    • 2019
    • Respiratory medicine
    • 116-121
    • Dyspnea in amyotrophic lateral sclerosis
    • <p>BACKGROUND: Dyspnea is a cardinal but often underestimated symptom in amyotrophic lateral sclerosis (ALS). The newly developed Dyspnea-ALS-Scale (DALS-15) is highly relevant for therapeutic decisions because dyspnea is a separate criterion to consider noninvasive ventilation (NIV) in ALS. In comparison to the limited effects of neuroprotective compounds, NIV has the greatest impact on survival and improves quality of life.</p><p>OBJECTIVE: To investigate whether dyspnea corresponds to parameters of respiratory status mainly used in clinical neurological practice. We also investigated if the DALS-15 could help identify patients for consideration of NIV in whom neither spirometry nor blood gas parameters indicate the need for NIV (forced vital capacity (FVC) &lt; 50% or probable &lt;75%, pCO2 ≥45  mmHg).</p><p>METHODS: Seventy ALS patients with dyspnea according to the DALS-15 obtained blood gas analysis and spirometry (FVC in sitting and supine positions). The supine decline in FVC was calculated.</p><p>RESULTS: There was no linear relationship between dyspnea and spirometry as well as blood gases. 83% of our patients had an upright FVC still greater than 50% and no daytime hypercapnia.</p><p>CONCLUSIONS: Our study clearly shows that dyspnea can occur independently of objective indicators of respiratory impairment like spirometry or blood gases. Hence, the DALS-15 covers another aspect of respiratory impairment than these tests and refers to the subjective component of respiratory impairment. It detects dyspnea in a considerable proportion of patients in whom NIV should thus be considered although their spirometric and blood gas results do not point towards NIV. The DALS-15 therefore may help to improve the stratification of patients with respiratory impairment for more efficient symptom management and timely coordination of care.</p>
    • http://www.scopus.com/inward/record.url?scp=85067581056&partnerID=8YFLogxK
    • Hans-Jochen Heinze, Jürgen Voges, Hans Jochen Heinze
    • 2019
    • Journal of Clinical Medicine
    • 9
    • Deep Brain Stimulation of the Subthalamic Nucleus Selectively Modulates Emotion Recognition of Facial Stimuli in Parkinson's Patients
    • <p>: Background: Diminished emotion recognition is a known symptom in Parkinson (PD) patients and subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to further deteriorate the processing of especially negative emotions. While emotion recognition generally refers to both, implicit and explicit processing, demonstrations of DBS-influences on implicit processing are sparse. In the present study, we assessed the impact of STN-DBS on explicit and implicit processing for emotional stimuli.</p><p>METHODS: Under STN-DBS ON and OFF, fourteen PD patients performed an implicit as well as an explicit emotional processing task. To assess implicit emotional processing, patients were tested with a lexical decision task (LTD) combined with an affective priming paradigm, which provides emotional content through the facial eye region. To assess explicit emotional processing, patients additionally explicitly rated the emotional status of eyes and words used in the implicit task.</p><p>RESULTS: DBS affected explicit emotional processing more than implicit processing with a more pronounced effect on error rates than on reaction speed. STN-DBS generally worsened implicit and explicit processing for disgust stimulus material but improved explicit processing of fear stimuli.</p><p>CONCLUSIONS: This is the first study demonstrating influences of STN-DBS on explicit and implicit emotion processing in PD patients. While STN stimulation impeded the processing of disgust stimuli, it improved explicit discrimination of fear stimuli.</p>
    • Hans-Jochen Heinze, Hans Jochen Heinze
    • 2019
    • Health and Quality of Life Outcomes
    • 1
    • The Dyspnea-ALS-Scale (DALS-15) optimizes individual treatment in patients with amyotrophic lateral sclerosis (ALS) suffering from dyspnea
    • <p>BACKGROUND: Dyspnea is frequent in amyotrophic lateral sclerosis (ALS) and one of the most bothersome symptoms. The recently developed Dyspnea-ALS-Scale (DALS-15) is a disease-specific patient-reported outcome to detect and quantify dyspnea.</p><p>OBJECTIVES: To analyze in a case-based approach the diagnostic and clinical implications and the benefit of the DALS-15 for individual patients in daily clinical routine.</p><p>METHODS: Dyspnea was assessed by the 15-item comprising DALS-15 in two patients with ALS. Spirometry was performed and blood gases were analyzed. Results were evaluated in the clinical context of the respective patients.</p><p>RESULTS: In one patient the presence of dyspnea detected by the DALS-15 indicated noninvasive ventilation (NIV) although forced vital capacity (FVC) and blood gas analysis were well preserved. After NIV implementation, the DALS-15 was helpful to determine the patient's need for medication, the timing of NIV titration and the adaptation of NIV sessions. In another patient, who was anarthric and no longer able to perform spirometry due to severe bulbar impairment, the DALS-15 allowed a standardized assessment of dyspnea-related distress independently of bulbar dysfunction.</p><p>CONCLUSION: The DALS-15 provides a deeper insight into the respiratory status of individual patients. It helps to diagnose respiratory impairment in patients in whom NIV should be considered although FVC and blood gas results do not reveal indication for NIV. It is also valuable for the guidance of patients in later stages of respiratory impairment when NIV is already implemented, and in patients with severe bulbar dysfunction. The DALS-15 can improve specific symptom management and coordination of care and therefore has the potential to optimize individual treatment in ALS patients with dyspnea.</p>
    • Hans-Jochen Heinze, Hans Jochen Heinze, Jürgen Voges, Janet Hausmann
    • 2019
    • Journal of NeuroEngineering and Rehabilitation
    • 1
    • Long-term outcomes of semi-implantable functional electrical stimulation for central drop foot
    • <p>Background: Central drop foot is a common problem in patients with stroke or multiple sclerosis (MS). For decades, it has been treated with orthotic devices, keeping the ankle in a fixed position. It has been shown recently that semi-implantable functional electrical stimulation (siFES) of the peroneal nerve can lead to a greater gait velocity increase than orthotic devices immediately after being switched on. Little is known, however, about long-term outcomes over 12 months, and the relationship between quality of life (QoL) and gait speed using siFES has never been reported applying a validated tool. We provide here a report of short (3 months) and long-term (12 months) outcomes for gait speed and QoL. Methods: Forty-five consecutive patients (91% chronic stroke, 9% MS) with central drop foot received siFES (Actigait®). A 10 m walking test was carried out on day 1 of stimulation (T1), in stimulation ON and OFF conditions, and repeated after 3 (T2) and 12 (T3) months. A 36-item Short Form questionnaire was applied at all three time points. Results: We found a main effect of stimulation on both maximum (p &lt; 0.001) and comfortable gait velocity (p &lt; 0.001) and a main effect of time (p = 0.015) only on maximum gait velocity. There were no significant interactions. Mean maximum gait velocity across the three assessment time points was 0.13 m/s greater with stimulation ON than OFF, and mean comfortable gait velocity was 0.083 m/s faster with stimulation ON than OFF. The increase in maximum gait velocity over time was 0.096 m/s, with post hoc testing revealing a significant increase from T1 to T2 (p = 0.012), which was maintained but not significantly further increased at T3. QoL scores showed a main effect of time (p &lt; 0.001), with post hoc testing revealing an increase from T1 to T2 (p &lt; 0.001), which was maintained at T3 (p &lt; 0.001). Finally, overall absolute QoL scores correlated with the absolute maximum and comfortable gait speeds at T2 and T3, and the increase in overall QoL scores correlated with the increase in comfortable gait velocity from T1 to T3. Pain was reduced at T2 (p &lt; 0.001) and was independent of gait speed but correlated with overall QoL (p &lt; 0.001). Conclusions: Peroneal siFES increased maximal and comfortable gait velocity and QoL, with the greatest increase in both over the first three months, which was maintained at one year, suggesting that 3 months is an adequate follow-up time. Pain after 3 months correlated with QoL and was independent of gait velocity, suggesting pain as an independent outcome measure in siFES for drop foot.</p>
    • http://www.scopus.com/inward/record.url?scp=85067258864&partnerID=8YFLogxK
    • Christoph Reichert, Hermann Hinrichs, Amr Farahat, Christoph Reichert
    • 2019
    • Journal of Neural Engineering
    • 6
    • Convolutional neural networks for decoding of covert attention focus and saliency maps for EEG feature visualization
    • <p>OBJECTIVE: Convolutional neural networks (CNNs) have proven successful as function approximators and have therefore been used for classification problems including electroencephalography (EEG) signal decoding for brain-computer interfaces (BCI). Artificial neural networks, however, are considered black boxes, because they usually have thousands of parameters, making interpretation of their internal processes challenging. Here we systematically evaluate the use of CNNs for EEG signal decoding and investigate a method for visualizing the CNN model decision process.</p><p>APPROACH: We developed a CNN model to decode the covert focus of attention from EEG event-related potentials during object selection. We compared the CNN and the commonly used linear discriminant analysis (LDA) classifier performance, applied to datasets with different dimensionality, and analyzed transfer learning capacity. Moreover, we validated the impact of single model components by systematically altering the model. Furthermore, we investigated the use of saliency maps as a tool for visualizing the spatial and temporal features driving the model output.</p><p>MAIN RESULTS: The CNN model and the LDA classifier achieved comparable accuracy on the lower-dimensional dataset, but CNN exceeded LDA performance significantly on the higher-dimensional dataset (without hypothesis-driven preprocessing), achieving an average decoding accuracy of 90.7% (chance level = 8.3%). Parallel convolutions, tanh or ELU activation functions, and dropout regularization proved valuable for model performance, whereas the sequential convolutions, ReLU activation function, and batch normalization components, reduced accuracy or yielded no significant difference. Saliency maps revealed meaningful features, displaying the typical spatial distribution and latency of the P300 component expected during this task.</p><p>SIGNIFICANCE: Following systematic evaluation, we provide recommendations for when and how to use CNN models in EEG decoding. Moreover, we propose a new approach for investigating the neural correlates of a cognitive task by training CNN models on raw high-dimensional EEG data and utilizing saliency maps for relevant feature extraction.</p>
    • Mircea Ariel Schoenfeld
    • 2019
    • NeuroImage
    • Cortical, subcortical and spinal neural correlates of slackline training-induced balance performance improvements
    • <p>Humans develop posture and balance control during childhood. Interestingly, adults can also learn to master new complex balance tasks, but the underlying neural mechanisms are not fully understood yet. Here, we combined broad scale brain connectivity fMRI at rest and spinal excitability measurements during movement. Six weeks of slackline training improved the capability to walk on a slackline which was paralleled by functional connectivity changes in brain regions associated with posture and balance control and by task-specific changes of spinal excitability. Importantly, the performance of trainees was not better than control participants in a different, untrained balance task. In conclusion, slackline training induced large-scale neuroplasticity which solely transferred into highly task specific performance improvements.</p>
    • http://www.scopus.com/inward/record.url?scp=85073652470&partnerID=8YFLogxK
    • Björn Schott, B. Schott
    • 2019
    • Neuroscience
    • 20-29
    • Reduced Hippocampal Neurogenesis in Mice Deficient in Apoptosis Repressor with Caspase Recruitment Domain (ARC)
    • <p>In the adult hippocampal dentate gyrus (DG), the majority of newly generated cells are eliminated by apoptotic mechanisms. The apoptosis repressor with caspase recruitment domain (ARC), encoded by the Nol3 gene, is a potent and multifunctional death repressor that inhibits both death receptor and mitochondrial apoptotic signaling. The aim of the present study was to parse the role of ARC in the development of new granule cell neurons. Nol3 gene expression as revealed by in situ hybridization is present in the entire dentate granule cell layer. Moreover, a comparison of Nol3 expression between FACS-sorted Sox2-positive neural stem cells and Doublecortin (DCX)-positive immature neurons demonstrates upregulation of Nol3 during neurogenesis. Using ARC-deficient mice, we show that proliferation and survival of BrdU birth-dated cells are strongly reduced in the absence of ARC while neuronal-glial fate choice is not affected. Both the number of DCX-positive cells and the number of calretinin (CR)-positive immature postmitotic neurons are reduced in the hippocampus of ARC <sup>−/−</sup> mice. ARC knockout is not associated with increased numbers of microglia or with microglia activation. However, hippocampal brain-derived neurotrophic factor (BDNF) protein content is significantly increased in ARC <sup>−/−</sup> mice, possibly representing a compensatory response. Collectively, our results suggest that ARC plays a critical cell-autonomous role in preventing cell death during adult granule cell neogenesis. </p>
    • http://www.scopus.com/inward/record.url?scp=85070389647&partnerID=8YFLogxK
    • Björn Schott, B. Schott
    • 2019
    • Pharmacopsychiatry
    • Hippocampal Dysfunction in Schizophrenia and Aberrant Hippocampal Synaptic Plasticity in Rodent Model Psychosis
    • <p>Schizophrenia is a complex, heterogeneous psychiatric disorder that affects about 1% of the global population. Hippocampal dysfunction has been linked to both cognitive deficits and positive symptoms in schizophrenia. Here, we briefly review current findings on disrupted hippocampal processing from a clinical perspective before concentrating on preclinical studies of aberrant hippocampal synaptic plasticity using the N-methyl-D-aspartate receptor hypofunction model of psychosis and related findings from genetic models. Taken together, the results put the case for maladaptive hippocampal synaptic plasticity and its extrinsic connections as mechanistic underpinnings of cognitive impairments in schizophrenia.</p>
    • Björn Schott, Timothy French, B. Schott
    • 2019
    • Journal of Neuroinflammation
    • 1
    • Neuronal impairment following chronic Toxoplasma gondii infection is aggravated by intestinal nematode challenge in an IFN-γ-dependent manner
    • <p>BACKGROUND: It has become increasingly evident that the immune and nervous systems are closely intertwined, relying on one another during regular homeostatic conditions. Prolonged states of imbalance between neural and immune homeostasis, such as chronic neuroinflammation, are associated with a higher risk for neural damage. Toxoplasma gondii is a highly successful neurotropic parasite causing persistent subclinical neuroinflammation, which is associated with psychiatric and neurodegenerative disorders. Little is known, however, by what means neuroinflammation and the associated neural impairment can be modulated by peripheral inflammatory processes.</p><p>METHODS: Expression of immune and synapse-associated genes was assessed via quantitative real-time PCR to investigate how T. gondii infection-induced chronic neuroinflammation and associated neuronal alterations can be reshaped by a subsequent acute intestinal nematode co-infection. Immune cell subsets were characterized via flow cytometry in the brain of infected mice. Sulfadiazine and interferon-γ-neutralizing antibody were applied to subdue neuroinflammation.</p><p>RESULTS: Neuroinflammation induced by T. gondii infection of mice was associated with increased microglia activation, recruitment of immune cells into the brain exhibiting Th1 effector functions, and enhanced production of Th1 and pro-inflammatory molecules (IFN-γ, iNOS, IL-12, TNF, IL-6, and IL-1β) following co-infection with Heligmosomoides polygyrus. The accelerated cerebral Th1 immune response resulted in enhanced T. gondii removal but exacerbated the inflammation-related decrease of synapse-associated gene expression. Synaptic proteins EAAT2 and GABAAα1, which are involved in the excitation/inhibition balance in the CNS, were affected in particular. These synaptic alterations were partially recovered by reducing neuroinflammation indirectly via antiparasitic treatment and especially by application of IFN-γ-neutralizing antibody. Impaired iNOS expression following IFN-γ neutralization directly affected EAAT2 and GABAAα1 signaling, thus contributing to the microglial regulation of neurons. Besides, reduced CD36, TREM2, and C1qa gene expression points toward inflammation induced synaptic pruning as a fundamental mechanism.</p><p>CONCLUSION: Our results suggest that neuroimmune responses following chronic T. gondii infection can be modulated by acute enteric nematode co-infection. While consecutive co-infection promotes parasite elimination in the CNS, it also adversely affects gene expression of synaptic proteins, via an IFN-γ-dependent manner.</p>
    • Martin Walter, Viola Borchardt
    • 2019
    • Scientific Reports
    • 1
    • Alterations in Brain Structure and Amplitude of Low-frequency after 8 weeks of Mindfulness Meditation Training in Meditation-Naïve Subjects
    • <p>Increasing neuroimaging evidence suggests that mindfulness meditation expertise is related to different functional and structural configurations of the default mode network (DMN), the salience network (SN) and the executive network at rest. However, longitudinal studies observing resting network plasticity effects in brains of novices who started to practice meditation are scarce and generally related to one dimension, such as structural or functional effects. The purpose of this study was to investigate structural and functional brain network changes (e.g. DMN) after 40 days of mindfulness meditation training in novices and set these in the context of potentially altered depression symptomatology and anxiety. We found overlapping structural and functional effects in precuneus, a posterior DMN region, where cortical thickness increased and low-frequency amplitudes (ALFF) decreased, while decreased ALFF in left precuneus/posterior cingulate cortex correlates with the reduction of (CES-D) depression scores. In conclusion, regional overlapping of structural and functional changes in precuneus may capture different components of the complex changes of mindfulness meditation training.</p>
    • http://www.scopus.com/inward/record.url?scp=85069936643&partnerID=8YFLogxK
    • Martin Walter, Vanessa Teckentrup, Viola Borchardt, Claus Tempelmann
    • 2019
    • NeuroImage
    • 414-424
    • The anterior insula channels prefrontal expectancy signals during affective processing
    • <p>Expectancy shapes our perception of impending events. Although such an interplay between cognitive and affective processes is often impaired in mental disorders, it is not well understood how top-down expectancy signals modulate future affect. We therefore track the information flow in the brain during cognitive and affective processing segregated in time using task-specific cross-correlations. Participants in two independent fMRI studies (N1 = 37 &amp; N2 = 55) were instructed to imagine a situation with affective content as indicated by a cue, which was then followed by an emotional picture congruent with expectancy. To correct for intrinsic covariance of brain function, we calculate resting-state cross-correlations analogous to the task. First, using factorial modeling of delta cross-correlations (task-rest) of the first study, we find that the magnitude of expectancy signals in the anterior insula cortex (AIC) modulates the BOLD response to emotional pictures in the anterior cingulate and dorsomedial prefrontal cortex in opposite directions. Second, using hierarchical linear modeling of lagged connectivity, we demonstrate that expectancy signals in the AIC indeed foreshadow this opposing pattern in the prefrontal cortex. Third, we replicate the results in the second study using a higher temporal resolution, showing that our task-specific cross-correlation approach robustly uncovers the dynamics of information flow. We conclude that the AIC arbitrates the recruitment of distinct prefrontal networks during cued picture processing according to triggered expectations. Taken together, our study provides new insights into neuronal pathways channeling cognition and affect within well-defined brain networks. Better understanding of such dynamics could lead to new applications tracking aberrant information processing in mental disorders.</p>
    • http://www.scopus.com/inward/record.url?scp=85068527628&partnerID=8YFLogxK
    • Martin Walter, Lejla Colic
    • 2019
    • Frontiers in Neuroscience
    • Interaction of Sex and Age on the Dissociative Effects of Ketamine Action in Young Healthy Participants
    • <p>Ketamine is a drug that reduces depressive and elicits schizophrenia-like symptoms in humans. However, it is largely unexplored whether women and men differ with respect to ketamine-action and whether age contributes to drug-effects. In this study we assessed dissociative symptoms via the Clinician Administered Dissociative States Scale (CADSS) in a total of 69 healthy subjects aged between 18 and 30 years (early adulthood) after ketamine or placebo infusion. Dissociative symptoms were generally increased only in the ketamine group post-infusion. Specifically, within the ketamine group, men reported significantly more depersonalization and amnestic symptoms than women. Furthermore, with rising age only men were less affected overall with respect to dissociative symptoms. This suggests a sex-specific protective effect of higher age which may be due to delayed brain maturation in men compared to women. We conclude that it is crucial to include sex and age in studies of drug effects in general and of ketamine-action in specific to tailor more efficient psychiatric treatments. Clinical Trial Registration: EU Clinical Trials Register (EudraCT), trial number: 2010-023414-31.</p>
    • http://www.scopus.com/inward/record.url?scp=85068499136&partnerID=8YFLogxK
    • Martin Walter, Lejla Colic
    • 2019
    • Psychological Medicine
    • Impaired cognitive self-awareness mediates the association between alexithymia and excitation/inhibition balance in the pgACC
    • <p>BackgroundPrevious research showed that automatic emotion regulation is associated with activation of subcortical areas and subsequent feedforward processes to cortical areas. In contrast, cognitive awareness of emotions is mediated by negative feedback from cortical to subcortical areas. Pregenual anterior cingulate cortex (pgACC) is essential in the modulation of both affect and alexithymia. We considered the interplay between these two mechanisms in the pgACC and their relationship with alexithymia.MethodIn 68 healthy participants (30 women, age = 26.15 ± 4.22) we tested associations of emotion processing and alexithymia with excitation/inhibition (E/I) balance represented as glutamate (Glu)/GABA in the pgACC measured via magnetic resonance spectroscopy in 7 T.ResultsAlexithymia was positively correlated with the Glu/GABA ratio (N = 41, p = 0.0393). Further, cognitive self-awareness showed an association with Glu/GABA (N = 52, p = 0.003), which was driven by a correlation with GABA. In contrast, emotion regulation was only correlated with glutamate levels in the pgACC (N = 49, p = 0.008).ConclusionOur results corroborate the importance of the pgACC as a mediating region of alexithymia, reflected in an altered E/I balance. Furthermore, we could specify that this altered balance is linked to a GABA-related modulation of cognitive self-awareness of emotions.</p>
    • http://www.scopus.com/inward/record.url?scp=85069464451&partnerID=8YFLogxK
    • Martin Walter
    • 2019
    • Journal of Affective Disorders
    • 133-143
    • Neuroimaging insights into the link between depression and Insomnia
    • <p>BACKGROUND: Insomnia is a common symptom of Major Depressive Disorder (MDD) and genome-wide association studies pointed to their strong genetic association. Although the prevalence of insomnia symptoms in MDD is noticeable and evidence supports their strong bidirectional association, the number of available neuroimaging findings on patients of MDD with insomnia symptoms is limited. However, such neuroimaging studies could verily improve our understanding of their shared pathophysiology and advance corresponding theories.</p><p>METHODS: Based on the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guideline, we have conducted a literature search using PubMed, EMBASE, and Scopus databases and systematically explored 640 studies using various neuroimaging modalities in MDD patients with different degrees of insomnia symptoms.</p><p>RESULTS: Despite inconsistencies, current findings from eight studies suggested structural and functional disturbances in several brain regions including the amygdala, prefrontal cortex and anterior cingulate cortex and insula. The aberrant functional connectivity within and between the main hubs of the salience and default mode networks could potentially yield new insights into the link between MDD and insomnia, which needs further assessment.</p><p>LIMITATIONS: The number of studies reviewed herein is limited. The applied methods for assessing structural and functional neural mechanisms of insomnia and depression were variable.</p><p>CONCLUSION: Neuroimaging methods demonstrated the overlapping underlying neural mechanisms between MDD and insomnia. Future studies may facilitate better understanding of their pathophysiology to allow development of specific treatment.</p>
    • http://www.scopus.com/inward/record.url?scp=85070207849&partnerID=8YFLogxK
    • Martin Walter, Lejla Colic, Anton R Lord, Oliver Speck
    • 2019
    • Biological psychiatry: Cognitive neuroscience and neuroimaging
    • Rostral Anterior Cingulate Glutamine/Glutamate Disbalance in Major Depressive Disorder Depends on Symptom Severity
    • <p>BACKGROUND: Patients with major depressive disorder (MDD) show glutamatergic deficits in the ventral anterior cingulate cortex. The glutamine/glutamate (Gln/Glu) ratio was proposed to be connected to glutamatergic cycling, which is hypothesized to be dysregulated in MDD. As an indicator of regional metabolite status, this ratio might be a robust state marker sensitive to clinical heterogeneity.</p><p>METHODS: Thirty-two MDD patients (mean age 40.88 ± 13.66 years, 19 women) and control subjects (mean age 33.09 ± 8.24 years, 19 women) were compared for pregenual anterior cingulate cortex levels of Gln/Glu, Gln/total creatine (tCr), Glu/tCr, and gamma-aminobutyric acid/tCr as determined by high-field magnetic resonance spectroscopy. We tested if symptom severity (Hamilton Depression Rating Scale) and anhedonia (Snaith-Hamilton Pleasure Scale) influence the relation of metabolites to clinical symptoms.</p><p>RESULTS: MDD patients showed higher Gln/Glu. This was driven by marginally higher Gln/tCr and nonsignificantly lower Glu/tCr. Groups defined by severity moderated relationship between Gln/Glu and the Hamilton Depression Rating Scale. Moreover, severe cases differed from both control subjects and moderate cases. Groups defined by the Snaith-Hamilton Pleasure Scale also displayed differential relationship between Gln/Glu and levels of anhedonia, predominantly driven by Gln/tCr.</p><p>CONCLUSIONS: We elaborate previous accounts of metabolite deficits in the anterior cingulate cortex toward increased Gln/Glu. There is a moderated relationship between severity and the ratio, which suggests consideration of different mechanisms or disease state for the respective subgroups in future studies.</p>
    • http://www.scopus.com/inward/record.url?scp=85067129279&partnerID=8YFLogxK
    • Martin Walter, Viola Borchardt
    • 2019
    • Journal of Abnormal Psychology
    • 5
    • 453-464
    • Empathy in pedophilia and sexual offending against children
    • <p>Empathy is regarded as dynamic risk factor of child sexual offending. However, empathy research in the context of child sexual abuse suffers from various problems. First, prior studies failed to differentiate between pedophilic and nonpedophilic sexual offenders. Second, there is no distinction made between cognitive and affective empathy. Third, cognitive and affective empathy toward emotional states of specific age groups (children and adults) has not been adequately addressed. The current study tackles these shortcomings investigating offending and nonoffending pedophiles and multiple aspects of empathy using self-reports and objective behavioral measures. Participants included 85 pedophilic men who committed hands-on child sexual offenses (PCSO), 72 pedophilic men who never committed hands-on child sexual offenses (P+CSO), and 128 nonoffending teleiophilic male controls (TC). Several affective and cognitive aspects of empathy were assessed using the Multifaceted Empathy Test (MET) and the Interpersonal Reactivity Index (IRI). Whereas in self-reports (IRI) PCSO scored lower than TC (P+CSO intermediate) in cognitive perspective-taking abilities, a performance-based measure (MET) revealed evidence for a better differentiation of emotional states in P+CSO as compared with PCSO (TC intermediate). In addition, PCSO and P+CSO showed significantly higher affective resonance while observing children (MET), which was paralleled by higher self-reported levels of personal distress in social situations (IRI). The results indicate evidence for higher general affective empathic resonance to children in pedophilic men but superior cognitive empathy abilities in nonoffending pedophiles only, which may act as a protective factor in the prevention of sexual offending. Together, these findings underline the importance of accounting for multiple facets of empathy when targeting pedophilia and child sexual offending.</p>
    • http://www.scopus.com/inward/record.url?scp=85065118984&partnerID=8YFLogxK
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