Publications by authors named "Timo Schmidt"

39 Publications

Altered states phenomena induced by visual flicker light stimulation.

PLoS One 2021 1;16(7):e0253779. Epub 2021 Jul 1.

Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany.

Flicker light stimulation can induce short-term alterations in consciousness including hallucinatory color perception and geometric patterns. In the study at hand, the subjective experiences during 3 Hz and 10 Hz stroboscopic light stimulation of the closed eyes were assessed. In a within-subjects design (N = 24), we applied the Positive and Negative Affect Schedule (mood state), time perception ratings, the Altered State of Consciousness Rating Scale, and the Phenomenology of Consciousness Inventory. Furthermore, we tested for effects of personality traits (NEO Five-Factor Inventory-2 and Tellegen Absorption Scale) on subjective experiences. Such systematic quantification improves replicability, facilitates comparisons between pharmacological and non-pharmacological techniques to induce altered states of consciousness, and is the prerequisite to study their underlying neuronal mechanisms. The resulting data showed that flicker light stimulation-induced states were characterized by vivid visual hallucinations of simple types, with effects strongest in the 10 Hz condition. Additionally, participants' personality trait of Absorption scores highly correlated with the experienced alterations in consciousness. Our data demonstrate that flicker light stimulation is capable of inducing visual effects with an intensity rated to be similar in strength to effects induced by psychedelic substances and thereby support the investigation of potentially shared underlying neuronal mechanisms.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253779PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248711PMC
July 2021

Short-term physical exercise impacts on the human holobiont obtained by a randomised intervention study.

BMC Microbiol 2021 Jun 2;21(1):162. Epub 2021 Jun 2.

Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University of Kiel, Rosalind-Franklin-Str. 12, 24105, Kiel, Germany.

Background: Human well-being has been linked to the composition and functional capacity of the intestinal microbiota. As regular exercise is known to improve human health, it is not surprising that exercise was previously described to positively modulate the gut microbiota, too. However, most previous studies mainly focused on either elite athletes or animal models. Thus, we conducted a randomised intervention study that focused on the effects of different types of training (endurance and strength) in previously physically inactive, healthy adults in comparison to controls that did not perform regular exercise. Overall study duration was ten weeks including six weeks of intervention period. In addition to 16S rRNA gene amplicon sequencing of longitudinally sampled faecal material of participants (six time points), detailed body composition measurements and analysis of blood samples (at baseline and after the intervention) were performed to obtain overall physiological changes within the intervention period. Activity tracker devices (wrist-band wearables) provided activity status and sleeping patterns of participants as well as exercise intensity and heart measurements.

Results: Different biometric responses between endurance and strength activities were identified, such as a significant increase of lymphocytes and decrease of mean corpuscular haemoglobin concentration (MCHC) only within the strength intervention group. In the endurance group, we observed a significant reduction in hip circumference and an increase in physical working capacity (PWC). Though a large variation of microbiota changes were observed between individuals of the same group, we did not find specific collective alterations in the endurance nor the strength groups, arguing for microbiome variations specific to individuals, and therefore, were not captured in our analysis.

Conclusions: We could show that different types of exercise have distinct but moderate effects on the overall physiology of humans and very distinct microbial changes in the gut. The observed overall changes during the intervention highlight the importance of physical activity on well-being. Future studies should investigate the effect of exercise on a longer timescale, investigate different training intensities and consider high-resolution shotgun metagenomics technology.

Trial Registration: DRKS, DRKS00015873 . Registered 12 December 2018; Retrospectively registered.
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http://dx.doi.org/10.1186/s12866-021-02214-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170780PMC
June 2021

Dipolar-stabilized first and second-order antiskyrmions in ferrimagnetic multilayers.

Nat Commun 2021 May 10;12(1):2611. Epub 2021 May 10.

Institute of Physics, University of Augsburg, Augsburg, Germany.

Skyrmions and antiskyrmions are topologically protected spin structures with opposite vorticities. Particularly in coexisting phases, these two types of magnetic quasi-particles may show fascinating physics and potential for spintronic devices. While skyrmions are observed in a wide range of materials, until now antiskyrmions were exclusive to materials with D symmetry. In this work, we show first and second-order antiskyrmions stabilized by magnetic dipole-dipole interaction in Fe/Gd-based multilayers. We modify the magnetic properties of the multilayers by Ir insertion layers. Using Lorentz transmission electron microscopy imaging, we observe coexisting antiskyrmions, Bloch skyrmions, and type-2 bubbles and determine the range of material properties and magnetic fields where the different spin objects form and dissipate. We perform micromagnetic simulations to obtain more insight into the studied system and conclude that the reduction of saturation magnetization and uniaxial magnetic anisotropy leads to the existence of this zoo of different spin objects and that they are primarily stabilized by dipolar interaction.
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http://dx.doi.org/10.1038/s41467-021-22600-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110839PMC
May 2021

Representation of visual numerosity information during working memory in humans: An fMRI decoding study.

Hum Brain Mapp 2021 Jun 11;42(9):2778-2789. Epub 2021 Mar 11.

Neurocomputation and Neuroimaging Unit (NNU), Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany.

Both animal and human studies on numerosity have shown the importance of the parietal cortex for numerosity processing. However, most studies have focused on the perceptual processing of numerosity. Still, it is unclear how and where numerosity information is coded when this information is retained during a working memory delay phase. Such temporal storage could be realized by the same structures as perceptual processes, or be transformed to a more abstract representation, potentially involving prefrontal regions. FMRI decoding studies allow the identification of brain areas that exhibit multi-voxel activation patterns specific to the content of working memory. Here, we used an assumption-free searchlight-decoding approach to test where numerosity-specific codes can be found during a 12 s retention period. Participants (n = 24) performed a retro-cue delayed match-to-sample task, in which numerosity information was presented as visual dot arrays. We found mnemonic numerosity-specific activation in the right lateral portion of the intraparietal sulcus; an area well-known for perceptual processing of numerosity. The applied retro-cue design dissociated working memory delay activity from perceptual processes and showed that the intraparietal sulcus also maintained working memory representation independent of perception.
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http://dx.doi.org/10.1002/hbm.25402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127141PMC
June 2021

Dose-response relationships of psilocybin-induced subjective experiences in humans.

J Psychopharmacol 2021 Apr 4;35(4):384-397. Epub 2021 Mar 4.

Psychotropic Substances Research Group, Charité Universitätsmedizin, Berlin, Germany.

Background: Psilocybin is the psychoactive component in mushrooms ('magic mushrooms'). Whether and how the quality of the psilocybin-induced experience might mediate beneficial health outcomes is currently under investigation, for example, in therapeutic applications. However, to date, no meta-analysis has investigated the dose-dependency of subjective experiences across available studies.

Aim: Establishing dose-response relationships of the subjective experiences induced by psilocybin in healthy study participants and a comparison of patient groups.

Method: We applied a linear meta-regression approach, based on the robust variance estimation framework, to obtain linear dose-response relationship estimates on questionnaire ratings after oral psilocybin administration. Data were obtained from the Altered States Database, which contains data extracted from MEDLINE-listed journal articles that used standardized and validated questionnaires: the Altered States of Consciousness Rating Scale, the Mystical Experience Questionnaire and the Hallucinogen Rating Scale.

Results: Psilocybin dose positively correlated with ratings on most factors and scales, mainly those referring to perceptual alterations and positively experienced ego dissolution. Measures referring to challenging experiences exhibited small effects and were barely modulated by dose.

Conclusion: Psilocybin intensified almost all characteristics of altered states of consciousness assessed with the given questionnaires. Because subjective experiences are not only determined by dose, but also by individual and environmental factors, the results may only apply to controlled laboratory experiments and not to recreational use. This paper may serve as a general literature citation for the use of psilocybin in experimental and clinical research, to compare expected and observed subjective experiences.
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http://dx.doi.org/10.1177/0269881121992676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058832PMC
April 2021

Connected to the spirit of the frog: An Internet-based survey on Kambô, the secretion of the Amazonian Giant Maki Frog (): Motivations for use, settings and subjective experiences.

J Psychopharmacol 2021 Apr 4;35(4):421-436. Epub 2021 Mar 4.

Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.

Background/aim: Kambô is a name for the secretion of the Giant Maki Frog (), which has been used by indigenous cultures from the Amazonas basin and has recently become popular in alternative healing circles in Western countries, with a certain overlap with psychedelic self-exploration.

Methods: We carried out an online-based survey in English (54.92%) and German investigating motivations for using Kambô, settings in which rituals take place, and subjective experiences during and after the application.

Results: Participants ( = 386, mean age: 38.08 years, (standard deviation = 9.95)) were well-educated individuals with an increased lifetime prevalence of the use of ayahuasca (67.88%). A plethora of motivations for using Kambô was reported, including general healing, detoxification and spiritual growth. Acute effects included severe physical reactions and mild psychoactive effects, most surprisingly, the feeling of being connected to the frog's spirit (41.97%), whereas predominantly positive persisting psychological effects were reported. Few participants reported long-lasting physical (2.85%) or mental (1.81%) health problems which they attributed to Kambô. Of the participants, 87.31% reported an increase in personal well-being or life satisfaction, and 64.26% considered Kambô to have been at least of 'very much' spiritual significance for their lives.

Conclusions: The majority of users claimed beneficial effects including more health-orientated behaviors, whereas only very few participants complained about new health problems which they ascribed to Kambô. In retrospect, Kambô was given a high personal and spiritual significance by many participants. Additional research is needed to determine in how far reported effects are modulated by setting and subjective expectations.
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http://dx.doi.org/10.1177/0269881121991554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058834PMC
April 2021

Acute and subacute psychoactive effects of Kambô, the secretion of the Amazonian Giant Maki Frog (Phyllomedusa bicolor): retrospective reports.

Sci Rep 2020 12 9;10(1):21544. Epub 2020 Dec 9.

Research Group Psychotropic Substances, Psychiatric University Clinic at Hospital St. Hedwig, Charité Universitätsmedizin Berlin, Berlin, Germany.

Kambô, the secretion of the Amazonian Giant Leaf Frog (Phyllomedusa bicolor) contains a plethora of bioactive peptides and was originally used by indigenous communities from the Amazon basin as medicine for improving hunting capacities. In the last 20 years, Kambô has spread to Western urban healing circles. To date it is still controversial whether the acute effects of Kambô include alterations of consciousness similar to known psychoactive substance like serotonergic psychedelics. Here we retrospectively assessed psychological effects of Kambô in a sample of anonymous users (n = 22, mean age: 39 years, ± 8.5; 45.5% female), administering standardized questionnaires for the assessment of altered states of consciousness (ASC), including the Altered States of Consciousness Rating Scale, the Phenomenology of Consciousness Inventory (PCI), the Mystical Experience Questionnaire (MEQ), the Challenging Experience Questionnaire (CEQ) for acute effects and the Persisting Effects Questionnaire (PEQ) and a scale assessing connectedness for subacute effects. The intensity of retrospectively reported acute psychological effects remained on a mild to moderate level, with no psychedelic-type distortions of perception or thinking. Conversely, persisting effects were predominantly described as positive and pleasant, revealing high scores on measures of personal and spiritual significance.
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http://dx.doi.org/10.1038/s41598-020-78527-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725827PMC
December 2020

The multimodal Ganzfeld-induced altered state of consciousness induces decreased thalamo-cortical coupling.

Sci Rep 2020 10 29;10(1):18686. Epub 2020 Oct 29.

Neurocomputation and Neuroimaging Unit (NNU), Department of Education and Psychology, Freie Universität Berlin, Habelschwerdter Allee 45, 14195, Berlin, Germany.

Different pharmacologic agents have been used to investigate the neuronal underpinnings of alterations in consciousness states, such as psychedelic substances. Special attention has been drawn to the role of thalamic filtering of cortical input. Here, we investigate the neuronal mechanisms underlying an altered state of consciousness (ASC) induced by a non-pharmacological procedure. During fMRI scanning, N = 19 human participants were exposed to multimodal Ganzfeld stimulation, a technique of perceptual deprivation where participants are exposed to intense, unstructured, homogenous visual and auditory stimulation. Compared to pre- and post-resting-state scans, the Ganzfeld data displayed a progressive decoupling of the thalamus from the cortex. Furthermore, the Ganzfeld-induced ASC was characterized by increased eigenvector centrality in core regions of the default mode network (DMN). Together, these findings can be interpreted as an imbalance of sensory bottom-up signaling and internally-generated top-down signaling. This imbalance is antithetical to psychedelic-induced ASCs, where increased thalamo-cortical coupling and reduced DMN activity were observed.
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http://dx.doi.org/10.1038/s41598-020-75019-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596232PMC
October 2020

Rehearsal of tactile working memory: Premotor cortex recruits two dissociable neuronal content representations.

Hum Brain Mapp 2021 01 3;42(1):245-258. Epub 2020 Oct 3.

Neurocomputation and Neuroimaging Unit (NNU), Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany.

Recent working memory (WM) research has focused on identifying brain regions that retain different types of mental content. Only few neuroimaging studies have explored the mechanism of attention-based refreshing, which is a type of rehearsal and is thought to implement the dynamic components of WM allowing for update of WM contents. Here, we took advantage of the distinct coding properties of the superior parietal lobe (SPL), which retains spatial layout information, and the right inferior frontal gyrus (IFG), which retains frequency information of vibrotactile stimuli during tactile WM. In an fMRI delayed match-to-sample task, participants had to internally rehearse sequences of spatial layouts or vibratory frequencies. Our results replicate the dissociation of SPL and IFG for the retention of layout and frequency information in terms of activation differences between conditions. Additionally, we found strong premotor cortex (PMC) activation during rehearsal of either stimulus type. To explore interactions between these regions we used dynamic causal modeling and found that activation within the network was best explained by a model that allows the PMC to drive activity in the SPL and IFG during rehearsal. This effect was content-specific, meaning that the PMC showed stronger influence on the SPL during pattern rehearsal and stronger influence on the IFG during frequency rehearsal. In line with previously established PMC contributions to sequence processing, our results suggest that it acts as a content-independent area that flexibly recruits content-specific regions to bring a WM item into the focus of attention during the rehearsal of tactile stimulus sequences.
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http://dx.doi.org/10.1002/hbm.25220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721226PMC
January 2021

Intraparietal sulcus maintains working memory representations of somatosensory categories in an adaptive, context-dependent manner.

Neuroimage 2020 11 11;221:117146. Epub 2020 Jul 11.

Neurocomputation and Neuroimaging Unit, Freie Universität Berlin, Habelschwerdter Allee 45, Berlin, 14195, Germany; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Luisenstraße 56, Berlin, 10117, Germany. Electronic address:

Working memory (WM) representations are generally known to be influenced by task demands, but it is not clear whether this extends to the somatosensory domain. One way to investigate the influence of task demands is with categorization paradigms, wherein either a single stimulus or an associated category is maintained in WM. In the somatosensory modality, category representations have been identified in the premotor cortex (PMC) and the intraparietal sulcus (IPS). In this study we used multivariate-pattern-analysis with human fMRI data to investigate whether the WM representations in the PMC, IPS or other regions are influenced by changing task demands. We ensured the task-dependent, categorical WM information was decorrelated from stimulus features by (1) teaching participants arbitrary, non-rule based stimulus groupings and (2) contrasting identical pairs of stimuli across experimental conditions, where either a single stimulus or the associated group was maintained in WM. Importantly, we also decoupled the decision and motor output from the WM representations. With these experimental manipulations, we were able to pinpoint stimulus-specific WM information to the left frontal and parietal cortices and context-dependent, group-specific WM information to the left IPS. By showing that grouped stimuli are represented more similarly in the Group condition than in the Stimulus condition, free from stimulus and motor output confounds, we provide novel evidence for the adaptive nature of somatosensory WM representations in the IPS with changing task-demands.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117146DOI Listing
November 2020

Parametric Representation of Tactile Numerosity in Working Memory.

eNeuro 2020 Jan/Feb;7(1). Epub 2020 Feb 7.

Neurocomputation and Neuroimaging Unit (NNU), Department of Education and Psychology, Freie Universität Berlin, 14195 Berlin, Germany.

Estimated numerosity perception is processed in an approximate number system (ANS) that resembles the perception of a continuous magnitude. The ANS consists of a right lateralized frontoparietal network comprising the lateral prefrontal cortex (LPFC) and the intraparietal sulcus. Although the ANS has been extensively investigated, only a few studies have focused on the mental representation of retained numerosity estimates. Specifically, the underlying mechanisms of estimated numerosity working memory (WM) is unclear. Besides numerosities, as another form of abstract quantity, vibrotactile WM studies provide initial evidence that the right LPFC takes a central role in maintaining magnitudes. In the present fMRI multivariate pattern analysis study, we designed a delayed match-to-numerosity paradigm to test what brain regions retain approximate numerosity memoranda. In line with parametric WM results, our study found numerosity-specific WM representations in the right LPFC as well as in the supplementary motor area and the left premotor cortex extending into the superior frontal gyrus, thus bridging the gap in abstract quantity WM literature.
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http://dx.doi.org/10.1523/ENEURO.0090-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029184PMC
May 2021

Neural basis of somatosensory target detection independent of uncertainty, relevance, and reports.

Elife 2019 03 29;8. Epub 2019 Mar 29.

Neurocomputation and Neuroimaging Unit, Freie Universität Berlin, Berlin, Germany.

Research on somatosensory awareness has yielded highly diverse findings with putative neural correlates ranging from activity within somatosensory cortex to activation of widely distributed frontoparietal networks. Divergent results from previous studies may reside in cognitive processes that often coincide with stimulus awareness in experimental settings. To scrutinise the specific relevance of regions implied in the target detection network, we used functional magnetic resonance imaging (n = 27) on a novel somatosensory detection task that explicitly controls for stimulus uncertainty, behavioural relevance, overt reports, and motor responses. Using Bayesian Model Selection, we show that responses reflecting target detection are restricted to secondary somatosensory cortex, whereas activity in insular, cingulate, and motor regions is best explained in terms of stimulus uncertainty and overt reports. Our results emphasise the role of sensory-specific cortex for the emergence of perceptual awareness and dissect the contribution of the frontoparietal network to classical detection tasks.
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http://dx.doi.org/10.7554/eLife.43410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440741PMC
March 2019

The Somatotopy of Mental Tactile Imagery.

Front Hum Neurosci 2019 18;13:10. Epub 2019 Feb 18.

Neurocomputation and Neuroimaging Unit, Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany.

To what degree mental imagery (MI) bears on the same neuronal processes as perception has been a central question in the neurophysiological study of imagery. Sensory-recruitment models suggest that imagery of sensory material heavily relies on the involvement of sensory cortices. Empirical evidence mainly stems from the study of visual imagery and suggests that it depends on the mentally imagined material whether hierarchically lower regions are recruited. However, evidence from other modalities is necessary to infer generalized principles. In this fMRI study we used the somatotopic organization of the primary somatosensory cortex (SI) to test in how far MI of tactile sensations activates topographically sensory brain areas. Participants ( = 19) either perceived or imagined vibrotactile stimuli on their left or right thumbs or big toes. The direct comparison to a corresponding perception condition revealed that SI was somatotopically recruited during imagery. While stimulus driven bottom-up processing induced activity throughout all SI subareas, i.e., BA1, BA3a, BA3b, and BA2 defined by probabilistic cytoarchitectonic maps, top-down recruitment during imagery was limited to the hierarchically highest subarea BA2.
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http://dx.doi.org/10.3389/fnhum.2019.00010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387936PMC
February 2019

Neuronal correlates of label facilitated tactile perception.

Sci Rep 2019 02 7;9(1):1606. Epub 2019 Feb 7.

Brain Language Laboratory, Department of Philosophy and Humanities, WE4, Freie Universität Berlin, 14195, Berlin, Germany.

It is a long-standing question in neurolinguistics, to what extent language can have a causal effect on perception. A recent behavioural study reported that participants improved their discrimination ability of Braille-like tactile stimuli after one week of implicit association training with language stimuli being co-presented redundantly with the tactile stimuli. In that experiment subjects were exposed twice a day for 1 h to the joint presentation of tactile stimuli presented to the fingertip and auditorily presented pseudowords. Their discrimination ability improved only for those tactile stimuli that were consistently paired with pseudowords, but not for those that were discordantly paired with different pseudowords. Thereby, a causal effect of verbal labels on tactile perception has been demonstrated under controlled laboratory conditions. This raises the question as to what the neuronal mechanisms underlying this implicit learning effect are. Here, we present fMRI data collected before and after the aforementioned behavioral learning to test for changes in brain connectivity as the underlying mechanism of the observed behavioral effects. The comparison of pre- and post-training revealed a language-driven increase in connectivity strength between auditory and secondary somatosensory cortex and the hippocampus as an association-learning related region.
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http://dx.doi.org/10.1038/s41598-018-37877-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367477PMC
February 2019

The Ganzfeld experience-A stably inducible altered state of consciousness: Effects of different auditory homogenizations.

Psych J 2019 Mar 4;8(1):66-81. Epub 2019 Jan 4.

Institute of Cognitive Science, Osnabrück University, Osnabrück, Germany.

In the Ganzfeld technique, the visual and auditory perceptual fields are homogenized. After a short exposure to completely unstructured sensory input, participants transit into an altered state of consciousness. Visual homogenization is typically accomplished by a combination of goggles and bright light; auditory homogenization is accomplished by the presentation of unstructured auditory noise via headphones. The induced state is phenomenologically similar to a transition state between wakefulness and sleep, characterized by alterations in attentiveness, perception, and awareness, as well as by a compressed sense of time. Due to these replicable features of the Ganzfeld-induced state, it can be used within empirical research on the neuronal underpinnings of altered states phenomena. After a historic overview, here, we present data from a study on the stability of the subjectively experienced effects induced under different auditory homogenization conditions. In a fully randomized within-subject design (n = 24), we tested for the effects of three different auditory noise conditions: (1) violet, (2) white, and (3) brown noise. The combination of a standardized psychometric assessment, ratings on subjective time perception, as well as open reports prove the Ganzfeld-induced effects as being stable and effects within each participant as highly replicable, and therefore well suited for experimental purposes. Finally, the subjective experiences elucidated by the Ganzfeld technique are discussed within the framework of predictive coding and how changes in the interaction of top-down and bottom-up brain mechanisms could lead to the observed phenomenology.
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http://dx.doi.org/10.1002/pchj.262DOI Listing
March 2019

Content-specific codes of parametric auditory working memory in humans.

Neuroimage 2018 12 11;183:254-262. Epub 2018 Aug 11.

Neurocomputation and Neuroimaging Unit (NNU), Department of Education and Psychology, Freie Universität Berlin, 14195 Berlin, Germany; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, 10099 Berlin, Germany.

Brain activity in frontal regions has been found to represent frequency information with a parametric code during working memory delay phases. The mental representation of frequencies has furthermore been shown to be modality independent in non-human primate electrophysiology and human EEG studies, suggesting frontal regions encoding quantitative information in a supramodal manner. A recent fMRI study using multivariate pattern analysis (MVPA) supports an overlapping multimodal network for the maintenance of visual and tactile frequency information over frontal and parietal brain regions. The present study extends the investigation of working memory representation of frequency information to the auditory domain. To this aim, we used MVPA on fMRI data recorded during an auditory frequency maintenance task. A support vector regression analysis revealed working memory information in auditory association areas and, consistent with earlier findings of parametric working memory, in a frontoparietal network. A direct comparison to an analogous dataset of vibrotactile parametric working memory revealed an overlap of information coding in prefrontal regions, particularly in the right inferior frontal gyrus. Therefore, our findings indicate that the prefrontal cortex represents frequency-specific working memory content irrespective of the modality as has been now also revealed for the auditory modality.
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http://dx.doi.org/10.1016/j.neuroimage.2018.08.024DOI Listing
December 2018

Synthesis and Biological Activity of Tetrameric Ribitol Phosphate Fragments of Staphylococcus aureus Wall Teichoic Acid.

Org Lett 2018 08 20;20(15):4449-4452. Epub 2018 Jul 20.

Department of Chemistry , KAIST , Daejeon , 34141 , Korea.

A systematically designed and synthesized ribitol phosphate (RboP) oligomer using a series of building blocks, which make up the wall teichoic acid (WTA) of S. aureus, is presented. Based on the use of a solution-phase phosphodiester synthesis, a library of ribitol phosphate tetramers, decorated with d-alanine and N-acetylglucosamine (GlcNAc), were generated. The synthesized RboP tetramers showed increased cytokine levels in mice in a subcutaneous air pouch model.
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http://dx.doi.org/10.1021/acs.orglett.8b01725DOI Listing
August 2018

The Altered States Database: Psychometric Data of Altered States of Consciousness.

Front Psychol 2018 2;9:1028. Epub 2018 Jul 2.

Institute of Cognitive Science, University of Osnabrück, Osnabrück, Germany.

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http://dx.doi.org/10.3389/fpsyg.2018.01028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036510PMC
July 2018

Brain regions that retain the spatial layout of tactile stimuli during working memory - A 'tactospatial sketchpad'?

Neuroimage 2018 09 31;178:531-539. Epub 2018 May 31.

Neurocomputation and Neuroimaging Unit (NNU), Department of Education and Psychology, Freie Universität Berlin, 14195, Berlin, Germany. Electronic address:

Working memory (WM) studies have been essential for ascertaining how the brain flexibly handles mentally represented information in the absence of sensory stimulation. Most studies on the memory of sensory stimulus features have focused, however, on the visual domain. Here, we report a human WM study in the tactile modality where participants had to memorize the spatial layout of patterned Braille-like stimuli presented to the index finger. We used a whole-brain searchlight approach in combination with multi-voxel pattern analysis (MVPA) to investigate tactile WM representations without a priori assumptions about which brain regions code tactospatial information. Our analysis revealed that posterior and parietal cortices, as well as premotor regions, retained information across the twelve-second delay phase. Interestingly, parts of this brain network were previously shown to also contain information of visuospatial WM. Also, by specifically testing somatosensory regions for WM representations, we observed content-specific activation patterns in primary somatosensory cortex (SI). Our findings demonstrate that tactile WM depends on a distributed network of brain regions in analogy to the representation of visuospatial information.
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http://dx.doi.org/10.1016/j.neuroimage.2018.05.076DOI Listing
September 2018

Verbal labels facilitate tactile perception.

Cognition 2018 02 23;171:172-179. Epub 2017 Nov 23.

Brain Language Laboratory, Department of Philosophy and Humanities, WE4, Freie Universität Berlin, 14195 Berlin, Germany; Berlin School of Mind and Brain, Humboldt Universität zu Berlin, 10099 Berlin, Germany; Einstein Center for Neurosciences Berlin, 10117 Berlin, Germany.

One of the key statements of linguistic relativity is that language has a causal effect on perception. Although much previous research has addressed such putative language perception causality, no firm proof is available thus far which demonstrates that verbal labels help or otherwise influence perceptual processes. Here, we tested the hypothesis of language perception causality by using novel, minimally-different tactile-patterned stimuli applied to the finger, which initially could not be discriminated by our participants. By combining novel verbal pseudoword- and novel tactile-patterned stimuli in an implicit learning experiment, we show a language-induced facilitation in tactile-patterned stimulus discrimination. After one week of intensive yet implicit learning of tactile stimuli in the presence of irrelevant consistent verbal labels, participants demonstrated significant discrimination improvement. In contrast, the same participants showed no improvement in discriminating tactile-patterned stimuli that had been learnt in the context of variable linguistic stimuli. These results show that specific mental links between verbal labels and perceptual information brought about by their correlated presentation enable one to better discriminate said sensory information (and build percepts).
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http://dx.doi.org/10.1016/j.cognition.2017.10.010DOI Listing
February 2018

Genetic profiling and surface proteome analysis of human atrial stromal cells and rat ventricular epicardium-derived cells reveals novel insights into their cardiogenic potential.

Stem Cell Res 2017 12 7;25:183-190. Epub 2017 Nov 7.

Department of Molecular Cardiology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. Electronic address:

Epicardium-derived cells (EPDC) and atrial stromal cells (ASC) display cardio-regenerative potential, but the molecular details are still unexplored. Signals which induce activation, migration and differentiation of these cells are largely unknown. Here we have isolated rat ventricular EPDC and rat/human ASC and performed genetic and proteomic profiling. EPDC and ASC expressed epicardial/mesenchymal markers (WT-1, Tbx18, CD73, CD90, CD44, CD105), cardiac markers (Gata4, Tbx5, troponin T) and also contained phosphocreatine. We used cell surface biotinylation to isolate plasma membrane proteins of rEPDC and hASC, Nano-liquid chromatography with subsequent mass spectrometry and bioinformatics analysis identified 396 rat and 239 human plasma membrane proteins with 149 overlapping proteins. Functional GO-term analysis revealed several significantly enriched categories related to extracellular matrix (ECM), cell migration/differentiation, immunology or angiogenesis. We identified receptors for ephrin and growth factors (IGF, PDGF, EGF, anthrax toxin) known to be involved in cardiac repair and regeneration. Functional category enrichment identified clusters around integrins, PI3K/Akt-signaling and various cardiomyopathies. Our study indicates that EPDC and ASC have a similar molecular phenotype related to cardiac healing/regeneration. The cell surface proteome repository will help to further unravel the molecular details of their cardio-regenerative potential and their role in cardiac diseases.
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http://dx.doi.org/10.1016/j.scr.2017.11.006DOI Listing
December 2017

Overlapping frontoparietal networks for tactile and visual parametric working memory representations.

Neuroimage 2018 02 28;166:325-334. Epub 2017 Oct 28.

Neurocomputation and Neuroimaging Unit (NNU), Department of Education and Psychology, Freie Universität Berlin, Habelschwerdter Allee 45, 14195 Berlin, Germany; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099 Berlin, Germany; Bernstein Center for Computational Neuroscience Berlin, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099 Berlin, Germany.

Previous working memory (WM) research based on non-human primate electrophysiology and human EEG has shown that frontal brain regions maintain frequencies of flutter stimulation across different sensory modalities by means of a supramodal parametric WM code. These findings imply that frontal regions encode the memorized frequencies in a sensory-unspecific, quantitative format. Here, we explored which brain regions maintain information about frequencies provided by different sensory modalities at the level of activity pattern across fMRI voxel populations. Moreover, we sought evidence for a supramodal multivariate WM representation. Participants maintained the same set of frequencies of tactile vibration and visual flicker for a 6 s WM delay in a frequency discrimination task. A support vector regression model for multivariate pattern analysis was applied. We observed that sensory cortices were only selective for memoranda of their corresponding modalities, while frontoparietal regions exhibited distinguishable activity patterns to memorized frequencies regardless of sensory modality. A common multivariate code was not evident in our data. Collectively, we show that mnemonic representations for stimulus frequencies are maintained throughout the cortical hierarchy, in line with the suggested transformation of information across different representational formats. Although evidence for a supramodal multivariate code is absent, our findings underpin the generalized role of the frontoparietal cortex for maintaining quantitative information across sensory modalities.
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http://dx.doi.org/10.1016/j.neuroimage.2017.10.059DOI Listing
February 2018

Content-Specific Codes of Parametric Vibrotactile Working Memory in Humans.

J Neurosci 2017 10 11;37(40):9771-9777. Epub 2017 Sep 11.

Neurocomputation and Neuroimaging Unit, Department of Education and Psychology, Freie Universität Berlin, 14195 Berlin, Germany.

To understand how the brain handles mentally represented information flexibly in the absence of sensory stimulation, working memory (WM) studies have been essential. A seminal finding in monkey research is that neurons in the prefrontal cortex (PFC) retain stimulus-specific information when vibrotactile frequencies were memorized. A direct mapping between monkey studies and human research is still controversial. Although oscillatory signatures, in terms of frequency-dependent parametric beta-band modulation, have been observed recently in human EEG studies, the content specificity of these representations in terms of multivariate pattern analysis has not yet been shown. Here, we used fMRI in combination with multivariate classification techniques to determine which brain regions retain information during WM. In a retro-cue delayed-match-to-sample task, human subjects memorized the frequency of vibrotactile stimulation over a 12 s delay phase. Using an assumption-free whole-brain searchlight approach, we tested with support vector regression which brain regions exhibited multivariate parametric WM codes of the maintained frequencies during the WM delay. Interestingly, our analysis revealed an overlap with regions previously identified in monkeys composed of bilateral premotor cortices, supplementary motor area, and the right inferior frontal gyrus as part of the PFC. Therefore, our results establish a link between the WM codes found in monkeys and those in humans and emphasize the importance of the PFC for information maintenance during WM also in humans. Working memory (WM) research in monkeys has identified a network of regions, including prefrontal regions, to code stimulus-specific information when vibrotactile frequencies are memorized. Here, we performed an fMRI study during which human subjects had to memorize vibratory frequencies in parallel to previous monkey research. Using an assumption-free, whole-brain searchlight decoding approach, we identified for the first time regions in the human brain that exhibit multivariate patterns of activity to code the vibratory frequency parametrically during WM. Our results parallel previous monkey findings and show that the supplementary motor area, premotor, and the right prefrontal cortex are involved in vibrotactile WM coding in humans.
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http://dx.doi.org/10.1523/JNEUROSCI.1167-17.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596612PMC
October 2017

[Psychotherapy with Adjuvant use of Serotonergic Psychoactive Substances: Possibilities and Challenges].

Fortschr Neurol Psychiatr 2017 Jul 2;85(7):383-392. Epub 2017 Aug 2.

Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Psychiatrie und Psychotherapie, Hamburg.

 Recently, scientific interest in the therapeutic potential of serotonergic and psilocybin hallucinogens (psychedelics) such as lysergic acid diethylamide (LSD) and entactogens like 3,4-methylendioxymethamphetamine (MDMA) within the framework of psychotherapy has resumed. The present article provides an overview on the current evidence on substance-assisted psychotherapy with these substances.  A selective search was carried out in the PubMed and Cochrane Library including studies investigating the clinical use of serotonergic psychoactive substances since 2000.  Studies were found investigating the following indications: alcohol (LSD and psilocybin) and tobacco addiction (psilocybin), anxiety and depression in patients suffering from life-threatening somatic illness (LSD and psilocybin), obsessive-compulsive disorder (OCD) (psilocybin), treatment-resistant major depression (psilocybin), and posttraumatic stress disorder (PTSD) (MDMA).  Substance use disorders, PTSD and anxiety and depression in patients suffering from life-threatening somatic illness belong to the indications with the best evidence for substance-assisted psychotherapy with serotonergic psychoactive agents. To date, studies indicate efficacy and relatively good tolerability. Further studies are needed to determine whether these substances may represent suitable and effective treatment options for some treatment-resistant psychiatric disorders in the future.
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http://dx.doi.org/10.1055/s-0043-103085DOI Listing
July 2017

Generation and characterization of two iPSC lines from human epicardium-derived cells.

Stem Cell Res 2017 04 24;20:50-53. Epub 2017 Feb 24.

Department of Molecular Cardiology, Medical Faculty, Heinrich Heine University, 40225 Duesseldorf, Germany. Electronic address:

Human epicardium-derived cells (EPDC) were reprogrammed to generate two iPSC lines, MCDU1i-EPDC and MCDU2i-EPDC, by nucleofection of episomal-based plasmids expressing the reprogramming factors OCT4, SOX2, KLF4, c-MYC, NANOG and LIN28. Pluripotency was confirmed in vitro by immunofluorescence analysis and embryoid body formation. The iPSC lines and the human embryonic stem cell line H1 show a Pearson correlation co-efficient of 0.951 (MCDU1i-EPDC) and 0.937 (MCDU2i-EPDC) as assessed by comparative transcriptome profiling.
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http://dx.doi.org/10.1016/j.scr.2017.02.007DOI Listing
April 2017

CD73-derived adenosine and tenascin-C control cytokine production by epicardium-derived cells formed after myocardial infarction.

FASEB J 2017 07 31;31(7):3040-3053. Epub 2017 Mar 31.

Department of Molecular Cardiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany;

Epicardium-derived cells (EPDCs) play a fundamental role in embryonic cardiac development and are reactivated in the adult heart in response to myocardial infarction (MI). In this study, EPDCs from post-MI rat hearts highly expressed the ectoenzyme CD73 and secreted the profibrotic matricellular protein tenascin-C (TNC). CD73 on EPDCs extensively generated adenosine from both extracellular ATP and NAD. This in turn stimulated the release of additional nucleotides from a Brefeldin A-sensitive intracellular pool adenosine-AR signaling, forming a positive-feedback loop. AR activation, in addition, strongly promoted the release of major regulatory cytokines, such as IL-6, IL-11, and VEGF. TNC was found to stimulate EPDC migration and, together with ATP-P2XR signaling, to activate inflammasomes in EPDCs TLR4. Our results demonstrate that EPDCs are an important source of various proinflammatory factors in the post-MI heart controlled by purinergic and TNC signaling.-Hesse, J., Leberling, S., Boden, E., Friebe, D., Schmidt, T., Ding, Z., Dieterich, P., Deussen, A., Roderigo, C., Rose, C. R., Floss, D. M., Scheller, J., Schrader, J. CD73-derived adenosine and tenascin-C control cytokine production by epicardium-derived cells formed after myocardial infarction.
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http://dx.doi.org/10.1096/fj.201601307RDOI Listing
July 2017

To drink or not to drink: Harmful drinking is associated with hyperactivation of reward areas rather than hypoactivation of control areas in men.

J Psychiatry Neurosci 2016 04;41(3):E24-36

From the Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany (Stuke, Gutwinski, Wiers, Gröpper, Parnack, Gawron, Attar, Spengler, Walter, Heinz, Bermpohl); the Berlin School of Mind and Brain, Humboldt University Berlin, Berlin, Germany (Gutwinski, Wiers, Walter, Heinz, Bermpohl); and the Neurocomputation and Neuroimaging Unit (NNU), Department of Education and Psychology, Free University Berlin, Berlin, Germany (Schmidt).

Background: The maintenance of harmful alcohol use can be considered a reiterated decision in favour of alcohol in concrete drinking occasions. These decisions are often made despite an intention to quit or reduce alcohol consumption. We tested if a hyperactive reward system and/or an impaired cognitive control system contribute to such unfavourable decision-making.

Methods: In this fMRI study, men with modest to harmful drinking behaviour, which was measured using the Alcohol Use Disorders Identification Test (AUDIT), repeatedly made decisions between alcoholic and nonalcoholic drinks. Based on prior individual ratings, decision pairs were created with an alcoholic decision option considered more desirable but less beneficial by the participant. By correlating AUDIT scores with brain activation during decision-making, we determined areas explicitly related to pro-alcohol decisions in men with greater drinking severity.

Results: Thirty-eight men participated in our study. Behaviourally, we found a positive correlation between AUDIT scores and the number of decisions for desired alcoholic drinks compared with beneficial nonalcoholic drinks. The fMRI results show that AUDIT scores were positively associated with activation in areas associated with reward and motivation processing (i.e., ventral striatum, amygdala, medial prefrontal cortex) during decisions favouring a desired, nonbeneficial alcoholic drink. Conversely, we did not find hypoactivation in areas associated with self-control (dorsolateral prefrontal cortex). These effects were not present when participants chose a desired, nonbenefical, nonalcoholic drink.

Limitations: The men participating in our study had to be abstinent and would potentially consume an alcoholic drink at the end of the experiment. Hence, we did not define manifest alcohol dependence as an inclusion criterion and instead focused on less severely affected individuals.

Conclusion: Our results indicate that with growing drinking severity, decisions for alcoholic drinks are associated with increasing activity in reward-associated neural systems, rather than decreasing activity in self-control-associated systems.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4853213PMC
http://dx.doi.org/10.1503/jpn.150203DOI Listing
April 2016

Peak experiences and the afterglow phenomenon: when and how do therapeutic effects of hallucinogens depend on psychedelic experiences?

J Psychopharmacol 2015 Mar 9;29(3):241-53. Epub 2015 Feb 9.

Clinic for Psychiatry and Psychotherapy, Charité University Medicine, Berlin, Germany Department for Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Interest in the therapeutic potential of psychedelic substances has recently resumed. During an early phase of human psychedelic research, their therapeutic application in different pathologies had been suggested, and the first evidence for efficacy was provided. The range of recent clinical applications of psychedelics spans from cluster headaches and obsessive-compulsive disorder to addiction and the treatment of fear and anxiety in patients suffering from terminal illness, indicating potentially different therapeutic mechanisms. A variety of approaches in psychotherapy emphasize subjective experiences, such as so-called peak experiences or afterglow phenomena, as differentially mediating therapeutic action. This review aims to re-evaluate earlier and recent concepts of how psychedelic substances may exert beneficial effects. After a short outline of neurophenomenological aspects, we discuss different approaches to how psychedelics are used in psychotherapy. Finally, we summarize evidence for the relationship between subjective experiences and therapeutic success. While the distinction between pharmacological and psychological action obviously cannot be clear-cut, they do appear to contribute differently from each other when their effects are compared with regard to pathologies.
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http://dx.doi.org/10.1177/0269881114568040DOI Listing
March 2015

Evaluation of a new mist-chamber bioreactor for biotechnological applications.

Biotechnol Bioeng 2015 Jun 17;112(6):1155-64. Epub 2015 Apr 17.

Institut für Technische Chemie der Leibniz Universität Hannover, Callinstr. 5, D-30167, Hannover, Germany.

In this article we describe the development, the characterization and the evaluation of a novel bioreactor type for the cultivation of different pro- and eukaryotic cell-systems: the mist-chamber bioreactor. This innovative bioreactor meets the demand of cultivation systems for shear stress sensitive cells with high requirements for gas supply. Within the mist-chamber bioreactor the cells are cultivated inside an aerosol of vaporized medium generated by ultrasonic vaporization. In contrast to many established bioreactor systems the mist-chamber bioreactor offers an environment with an excellent gas supply without any impeller or gas bubble induced shear stress. A mist-chamber bioreactor prototype has been manufactured and characterized during this work. In the technical and chemical characterization we evaluated the vaporization process, resulting in a vaporization performance of 32 mL/h at working conditions. On this basis we calculated a biomass of 1.4 g (S. cerevisiae, qs  = 3.45 × 10-3 mol/g/h) and 3.4 g (Aspergillus niger, qs  = 1.33 × 10-3 mol/g/h) where the growth rate becomes limited by transport processes. Additionally, we determined a homogenous cultivation area to a height of 3 cm giving a total volume of 0.45 L for the cultivation. Medium components were examined according to their stability during vaporization with the result that all components are stable for at least 5 days. After the technical characterization we demonstrated the feasibility to cultivate S. cerevisiae and F. velupites in the mist-chamber bioreactor. The results demonstrated that the mist-chamber bioreactor is able to transport a sufficient amount of nutrients consistently to the cell samples and offers an excellent oxygen supply without any shear stress inducing aeration. Furthermore we successfully cultivated F. velupites in a solid state cultivation in a long term experiment. The data indicate that the new bioreactor concept can contribute to improve various fermentations and cell culture processes depending on the cultured cell types.
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http://dx.doi.org/10.1002/bit.25523DOI Listing
June 2015

Imaging tactile imagery: changes in brain connectivity support perceptual grounding of mental images in primary sensory cortices.

Neuroimage 2014 Sep 13;98:216-24. Epub 2014 May 13.

Neurocomputation and Neuroimaging Unit (NNU), Department of Education and Psychology, Freie Universität Berlin, 14195 Berlin, Germany; Bernstein Center for Computational Neuroscience, 10115 Berlin, Germany; Max Planck Institute for Human Development, Center for Adaptive Rationality (ARC), 14195 Berlin, Germany.

Constructing mental representations in the absence of sensory stimulation is a fundamental ability of the human mind and has been investigated in numerous brain imaging studies. However, it is still unclear how brain areas facilitating mental construction processes interact with brain regions related to specific sensory representations. In this fMRI study subjects formed mental representations of tactile stimuli either from memory (imagery) or from presentation of actual corresponding vibrotactile patterned stimuli. First our analysis addressed the question of whether tactile imagery recruits primary somatosensory cortex (SI), because the activation of early perceptual areas is classically interpreted as perceptual grounding of the mental image. We also tested whether a network, referred to as 'core construction system', is involved in the generation of mental representations in the somatosensory domain. In fact, we observed imagery-induced activation of SI. We further found support for the notion of a modality independent construction network with the retrosplenial cortices and the precuneus as core components, which were supplemented with the left inferior frontal gyrus (IFG). Finally, psychophysiological interaction (PPI) analyses revealed robust imagery-modulated changes in the connectivity of these construction related areas, which suggests that they orchestrate the assembly of an abstract mental representation. Interestingly, we found increased coupling between prefrontal cortex (left IFG) and SI during mental imagery, indicating the augmentation of an abstract mental representation by reactivating perceptually grounded sensory details.
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http://dx.doi.org/10.1016/j.neuroimage.2014.05.014DOI Listing
September 2014