Ultrafast photogeneration of a metal-organic nitrene from 1,1'-diazidoferrocene.

Ferrocene and its derivatives have fascinated chemists for more than 70 years, not least due to the analogies with the properties of benzene. Despite these similarities, the obvious difference between benzene and ferrocene is the presence of an iron ion and hence the availability of d-orbitals for properties and reactivity. Phenylnitrene with its rich photochemistry can be considered an analogue of nitrenoferrocene. As with most organic and inorganic nitrenes, nitrenoferrocene can be obtained by irradiating the azide precursor. We study the photophysical and photochemical processes of dinitrogen release from 1,1'-diazidoferrocene to form 1-azido-1'-nitrenoferrocene with UV-pump-mid-IR-probe transient absorption spectroscopy and time-dependent density functional theory calculations including spin-orbit coupling. An intermediate with a bent azide moiety is identified that is pre-organised for dinitrogen release via a low-lying transition state. The photochemical decay paths on the singlet and triplet surfaces including the importance of spin-orbit coupling are discussed. We compare our findings with the processes discussed for photochemical dinitrogen activation and highlight implications for the photochemistry of azides more generally.

Photoinduced Metallonitrene Formation by N2 Elimination from Azide Diradical Ligands.

Transition-metal nitrides/nitrenes are highly promising reagents for catalytic nitrogen-atom-transfer reactivity. They are typically prepared in situ upon optically induced N2 elimination from azido precursors. A full exploitation of their catalytic potential, however, requires in-depth knowledge of the primary photo-induced processes and the structural/electronic factors mediating the N2 loss with birth of the terminal metal-nitrogen core. Using femtosecond infrared spectroscopy, we elucidate here the primary molecular-level mechanisms responsible for the formation of a unique platinum(II) nitrene with a triplet ground state from a closed-shell platinum(II) azide precursor. The spectroscopic data in combination with quantum-chemical calculations provide compelling evidence that product formation requires the initial occupation of a singlet excited state with an anionic azide diradical ligand that is bound to a low-spin d8 -configured PtII ion. Subsequent intersystem crossing generates the Pt-bound triplet azide diradical, which smoothly evolves into the triplet nitrene via N2 loss in a near barrierless adiabatic dissociation. Our data highlight the importance of the productive, N2 -releasing state possessing azide ππ* character as a design principle for accessing efficient N-atom-transfer catalysts.

Metacognitive sensitivity and symptoms of mental disorder: A systematic review and meta-analysis.

Introduction: Metacognition is a term used to refer to cognition about cognitive processes. In this systematic review and meta-analysis, we reviewed studies that investigated the relationship between experimentally measured objective metacognitive sensitivity and diverse symptoms of mental disorder. In these studies, metacognitive sensitivity is operationalized as the correspondence between the accuracy of task performance and reported confidence therein. Methods: A literature search was conducted across four databases and studies were selected for review based on predefined eligibility criteria. Twenty studies were included in the review and separate meta-analyses were conducted for psychotic and non-psychotic categories of psychiatric symptoms. Results: A significant reduction (medium effect size) in metacognitive sensitivity was found in individuals with psychosis-related symptoms of mental disorder compared to healthy control groups, but no significant difference was found for individuals with non-psychotic symptoms. It should be noted though, that fewer studies were available for the latter group. Sub-group analysis found no evidence that the effect of metacognitive impairment depended on whether perceptual or non-perceptual experimental tasks were employed. Discussion: These findings are discussed in relation to other conceptualizations of metacognition and the role reduced metacognitive sensitivity may play in forms of mental disorder.

Discovery of potent and selective HER2 inhibitors with efficacy against HER2 exon 20 insertion-driven tumors, which preserve wild-type EGFR signaling.

Oncogenic alterations in human epidermal growth factor receptor 2 (HER2) occur in approximately 2% of patients with non-small cell lung cancer and predominantly affect the tyrosine kinase domain and cluster in exon 20 of the ERBB2 gene. Most clinical-grade tyrosine kinase inhibitors are limited by either insufficient selectivity against wild-type (WT) epidermal growth factor receptor (EGFR), which is a major cause of dose-limiting toxicity or by potency against HER2 exon 20 mutant variants. Here we report the discovery of covalent tyrosine kinase inhibitors that potently inhibit HER2 exon 20 mutants while sparing WT EGFR, which reduce tumor cell survival and proliferation in vitro and result in regressions in preclinical xenograft models of HER2 exon 20 mutant non-small cell lung cancer, concomitant with inhibition of downstream HER2 signaling. Our results suggest that HER2 exon 20 insertion-driven tumors can be effectively treated by a potent and highly selective HER2 inhibitor while sparing WT EGFR, paving the way for clinical translation.

Can the causal role of brain oscillations be studied through rhythmic brain stimulation?

Many studies have investigated the causal relevance of brain oscillations using rhythmic stimulation, either through direct-brain or sensory stimulation. Yet, how intrinsic rhythms interact with the externally generated rhythm is largely unknown. We presented a flickered (60 Hz) visual grating or its correspondent unflickered stimulus in a psychophysical change detection task during simultaneous magnetoencephalography recordings to humans to test the effect of visual entrainment on induced gamma oscillations. Notably, we generally observed the coexistence of the broadband induced gamma rhythm with the entrained flicker rhythm (reliably measured in each participant), with the peak frequency of the induced response remaining unaltered in approximately half of participants-relatively independently of their native frequency. However, flicker increased broadband induced gamma power, and this was stronger in participants with a native frequency closer to the flicker frequency (resonance) and led to strong phase entrainment. Presence of flicker did not change behavior itself but profoundly altered brain behavior correlates across the sample: While broadband induced gamma oscillations correlated with reaction times for unflickered stimuli (as known previously), for the flicker, the amplitude of the entrained flicker rhythm (but no more the induced oscillation) correlated with reaction times. This, however, strongly depended on whether a participant's peak frequency shifted to the entrained rhythm. Our results suggests that rhythmic brain stimulation leads to a coexistence of two partially independent oscillations with heterogeneous effects across participants on the downstream relevance of these rhythms for behavior. This may explain the inconsistency of findings related to external entrainment of brain oscillations and poses further questions toward causal manipulations of brain oscillations in general.

Coral: a web-based visual analysis tool for creating and characterizing cohorts.

SUMMARY: A main task in computational cancer analysis is the identification of patient subgroups (i.e. cohorts) based on metadata attributes (patient stratification) or genomic markers of response (biomarkers). Coral is a web-based cohort analysis tool that is designed to support this task: Users can interactively create and refine cohorts, which can then be compared, characterized and inspected down to the level of single items. Coral visualizes the evolution of cohorts and also provides intuitive access to prevalence information. Furthermore, findings can be stored, shared and reproduced via the integrated session management. Coral is pre-loaded with data from over 128 000 samples from the AACR Project GENIE, the Cancer Genome Atlas and the Cell Line Encyclopedia. AVAILABILITY AND IMPLEMENTATION: Coral is publicly available at https://coral.caleydoapp.org. The source code is released at https://github.com/Caleydo/coral. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Solid-phase microextraction (SPME) for determination of geosmin and 2-methylisoborneol in volatile emissions from soil disturbance.

A method is described here for the concentration and determination of geosmin and 2-methylisoborneol (2-MIB) from the gaseous phase, with translation to field collection and quantification from soil disturbances in situ. The method is based on the use of solid-phase microextraction (SPME) fibers for adsorption of volatile chemicals from the vapor phase, followed by desorption into a gas chromatograph-mass spectrometer (GC-MS) for analysis. The use of a SPME fiber allows simple introduction to the GC-MS without further sample preparation. Several fiber sorbent types were studied and the 50/30 µm DVB/CAR/PDMS was the best performer to maximize the detected peak areas of both analytes combined. Factors such as extraction temperature and time along with desorption temperature and time were explored with respect to analyte recovery. An extraction temperature of 30 °C for 10 min, with a desorption temperature of 230 °C for 4 min was best for the simultaneous analysis of both geosmin and 2-MIB without complete loss of either one. The developed method was used successfully to measure geosmin and 2-MIB emission from just above disturbed and undisturbed soils, indicating that this method detects both compounds readily from atmospheric samples. Both geosmin and 2-MIB were present as background concentrations in the open air, while disturbed soils emitted much higher concentrations of both compounds. Surprisingly, 2-MIB was always detected at higher concentrations than geosmin, indicating that a focus on its detection may be more useful for soil emission monitoring and more sensitive to low levels of soil disturbance.

Fathering behavior, attachment, and engagement in childcare predict testosterone and cortisol.

The present study examined testosterone (T) and cortisol (Cort) in fathers engaged with caregiving. We collected saliva samples in the mornings and evenings of two consecutive days in 150 fathers of 1- to 5-year-old children. Fathers completed questionnaires on socioeconomic status, family structure and life, sleep characteristics and body mass index (BMI), and reported on their engagement in childcare. Fathers used smartphone-based experience sampling throughout 1 week to sample ongoing activities with their children, including times of supervision, joint play, rough-and-tumble play, and cuddling episodes. External observers rated father-child attachment during a home visit. We began by testing for widely characterized covariates of T and excluded seasonal variations and known predictors associated with lowered T, such as older fathers and those with multiple and young children, lower BMI, shorter sleep duration, and sexual activity before sampling. Most interestingly, however, fathers' engagement in childcare and attachment to the child appeared more pronounced the greater the diurnal decline in T. Cuddling predicted a similar negative association, whereas joint play and rough-and-tumble play (RTP) showed enhancing effects on declining T. Interestingly, all fathering behaviors (except RTP) were positively related to lower Cort. In contrast, supervision was ineffective on both Cort and T.

Individual differences in theta-band oscillations in a spatial memory network revealed by electroencephalography predict rapid place learning.

Spatial memory has been closely related to the medial temporal lobe and theta oscillations are thought to play a key role. However, it remains difficult to investigate medial temporal lobe activation related to spatial memory with non-invasive electrophysiological methods in humans. Here, we combined the virtual delayed-matching-to-place task, reverse-translated from the watermaze delayed-matching-to-place task in rats, with high-density electroencephalography recordings. Healthy young volunteers performed this computerised task in a virtual circular arena, which contained a hidden target whose location moved to a new place every four trials, allowing the assessment of rapid memory formation. Using behavioural measures as predictor variables for source reconstructed frequency-specific electroencephalography power, we found that inter-individual differences in 'search preference' during 'probe trials', a measure of one-trial place learning known from rodent studies to be particularly hippocampus-dependent, correlated predominantly with distinct theta-band oscillations (approximately 7 Hz), particularly in the right temporal lobe, the right striatum and inferior occipital cortex or cerebellum. This pattern was found during both encoding and retrieval/expression, but not in control analyses and could not be explained by motor confounds. Alpha-activity in sensorimotor and parietal cortex contralateral to the hand used for navigation also correlated (inversely) with search preference. This latter finding likely reflects movement-related factors associated with task performance, as well as a frequency difference in (ongoing) alpha-rhythm for high-performers versus low-performers that may contribute to these results indirectly. Relating inter-individual differences in ongoing brain activity to behaviour in a continuous rapid place-learning task that is suitable for a variety of populations, we could demonstrate that memory-related theta-band activity in temporal lobe can be measured with electroencephalography recordings. This approach holds great potential for further studies investigating the interactions within this network during encoding and retrieval, as well as neuromodulatory impacts and age-related changes.

Frequency- and state-dependent effects of hippocampal neural disinhibition on hippocampal local field potential oscillations in anesthetized rats.

Reduced inhibitory GABA function, so-called neural disinhibition, has been implicated in cognitive disorders, including schizophrenia and age-related cognitive decline. We previously showed in rats that hippocampal disinhibition by local microinfusion of the GABA-A receptor antagonist picrotoxin disrupted memory and attention and enhanced hippocampal multi-unit burst firing recorded around the infusion site under isoflurane anesthesia. Here, we analyzed the hippocampal local field potential (LFP) recorded alongside the multi-unit data. We predicted frequency-specific LFP changes, based on previous studies implicating GABA in hippocampal oscillations, with the weight of evidence suggesting that disinhibition would facilitate theta and disrupt gamma oscillations. Using a new semi-automated method based on the kurtosis of the LFP peak-amplitude distribution as well as on amplitude envelope thresholding, we separated three distinct hippocampal LFP states under isoflurane anesthesia: "burst" and "suppression" states-high-amplitude LFP spike bursts and the interspersed low-amplitudeperiods-and a medium-amplitude "continuous" state. The burst state showed greater overall power than suppression and continuous states and higher relative delta/theta power, but lower relative beta/gamma power. The burst state also showed reduced functional connectivity across the hippocampal recording area, especially around theta and beta frequencies. Overall neuronal firing was higher in the burst than the other two states, whereas the proportion of burst firing was higher in burst and continuous states than the suppression state. Disinhibition caused state- and frequency-dependent LFP changes, tending to increase power at lower frequencies (<20 Hz), but to decrease power and connectivity at higher frequencies (>20 Hz) in burst and suppression states. The disinhibition-induced enhancement of multi-unit bursting was also state-dependent, tending to be more pronounced in burst and suppression states than the continuous state. Overall, we characterized three distinct hippocampal LFP states in isoflurane-anesthetized rats. Disinhibition changed hippocampal LFP oscillations in a state- and frequency-dependent way. Moreover, the disinhibition-induced enhancement of multi-unit bursting was also LFP state-dependent.

Case Report: Afatinib Treatment in a Patient With NSCLC Harboring a Rare EGFR Exon 20 Mutation.

Unlike most other primary epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), exon 20 insertions, comprising approximately 4% to 10% of all EGFR mutations, are generally considered to be resistant to EGFR tyrosine kinase inhibitors (TKIs). However, EGFR exon 20 insertions are structurally and pharmacologically heterogeneous, with variability in their position and size having implications for response to different EGFR TKIs. The second-generation ErbB family blocker, afatinib, is approved for the first-line treatment of EGFR mutation-positive NSCLC and has been shown to have a broad inhibitory profile against common and uncommon EGFR mutations. Here, we describe a patient with bilateral multifocal lung adenocarcinoma harboring a very rare EGFR exon 20 insertion (c.2317_2319dup3; p.H773dup), who has been receiving treatment with afatinib for 4.5 years. To our knowledge, this is the first report describing long-term benefit for a patient treated with afatinib with this rare exon 20 insertion. We are aware of two further cases with this rare EGFR mutation. One patient, also reported here, has early-stage lung adenocarcinoma and has not yet received systemic therapy for NSCLC. The other patient received afatinib in the context of a global compassionate use program and had progressive disease. Our findings may be of clinical relevance for patients carrying tumors with this rare mutation as epidemiological evidence suggests that p.H773dup may function as a driver mutation in NSCLC. Together with previous preclinical and clinical evidence for the activity of afatinib against certain EGFR exon 20 insertions, these findings warrant further investigation.

Toward an automatic preoperative pipeline for image-guided temporal bone surgery.

PURPOSE: Minimally invasive surgery is often built upon a time-consuming preoperative step consisting of segmentation and trajectory planning. At the temporal bone, a complete automation of these two tasks might lead to faster interventions and more reproducible results, benefiting clinical workflow and patient health. METHODS: We propose an automatic segmentation and trajectory planning pipeline for image-guided interventions at the temporal bone. For segmentation, we use a shape regularized deep learning approach that is capable of automatically detecting even the cluttered tiny structures specific for this anatomy. We then perform trajectory planning for both linear and nonlinear interventions on these automatically segmented risk structures. RESULTS: We evaluate the usability of segmentation algorithms for planning access canals to the cochlea and the internal auditory canal on 24 CT data sets of real patients. Our new approach achieves similar results to the existing semiautomatic method in terms of Dice but provides more accurate organ shapes for the subsequent trajectory planning step. The source code of the algorithms is publicly available. CONCLUSION: Automatic segmentation and trajectory planning for various clinical procedures at the temporal bone are feasible. The proposed automatic pipeline leads to an efficient and unbiased workflow for preoperative planning.

Increased peripheral levels of TARC/CCL17 in first episode psychosis patients.

BACKGROUND: Evidence for a link between the pathophysiology of schizophrenia and the immune system is mounting. Altered levels of chemokines in plasma have previously been reported in patients with schizophrenia under antipsychotic medication. Here we aimed to study both peripheral and central chemokine levels in drug-naïve or short-time medicated first episode psychosis (FEP) patients. METHOD: We analyzed nine chemokines in plasma and CSF from 41 FEP patients and 22 healthy controls using electrochemiluminescence assay. RESULTS: In plasma four chemokines; TARC/CCL17, eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 and in CSF one chemokine; IP-10/CXCL10 showed reliable detection in >50% of the cases. FEP patients displayed increased levels of TARC/CCL17 in plasma compared to healthy controls, 89.6 (IQR 66.2-125.8) pg/mL compared to 48.6 (IQR 28.0-71.7) pg/mL (p = 0.001). The difference was not attributed to confounding factors. Plasma TARC/CCL17 was not associated with PANSS, CGI or GAF scores, neither with cognitive functions. The chemokines eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 in plasma and IP-10/CXCL10 in CSF did not differ between FEP patients and controls. CONCLUSION: In line with a previous study showing that chronic patients with schizophrenia display increased plasma TARC/CCL17 levels, we here found an elevation in FEP patients suggesting a role of TARC/CCL17 in early stages of schizophrenia. The exact mechanism of this involvement is still unknown and future longitudinal studies as well as studies of central and peripheral chemokine levels would be of great interest.

Relationships Between Neuronal Oscillatory Amplitude and Dynamic Functional Connectivity.

Event-related fluctuations of neural oscillatory amplitude are reported widely in the context of cognitive processing and are typically interpreted as a marker of brain "activity". However, the precise nature of these effects remains unclear; in particular, whether such fluctuations reflect local dynamics, integration between regions, or both, is unknown. Here, using magnetoencephalography, we show that movement induced oscillatory modulation is associated with transient connectivity between sensorimotor regions. Further, in resting-state data, we demonstrate a significant association between oscillatory modulation and dynamic connectivity. A confound with such empirical measurements is that increased amplitude necessarily means increased signal-to-noise ratio (SNR): this means that the question of whether amplitude and connectivity are genuinely coupled, or whether increased connectivity is observed purely due to increased SNR is unanswered. Here, we counter this problem by analogy with computational models which show that, in the presence of global network coupling and local multistability, the link between oscillatory modulation and long-range connectivity is a natural consequence of neural networks. Our results provide evidence for the notion that connectivity is mediated by neural oscillations, and suggest that time-frequency spectrograms are not merely a description of local synchrony but also reflect fluctuations in long-range connectivity.

Altered Nucleus Basalis Connectivity Predicts Treatment Response in Mild Cognitive Impairment.

Purpose To determine whether functional connectivity (FC) mapping of nucleus basalis of Meynert (NBM) cholinergic network (hereafter, NBM FC) could provide a biomarker of central cholinergic deficits with predictive potential for response to cholinesterase inhibitor (ChEI) treatment. Materials and Methods The Alzheimer's Disease Neuroimaging Initiative (ADNI) was approved by the institutional review boards of all participating sites. All participants and their representatives gave written informed consent prior to data collection. NBM FC was examined in 33 healthy control participants, 102 patients with mild cognitive impairment (MCI), and 33 patients with AD by using resting-state functional MRI data from the ADNI database. NBM FC was compared between groups before and after 6 months of ChEI treatment in MCI. Associations between baseline NBM FC and baseline cognitive performance as well as cognitive outcomes after treatment were investigated. Results Compared with the healthy control group, NBM FC was decreased in patients with untreated MCI and increased in patients with AD treated with ChEI (corrected P ˂ .05). Global cognition (Alzheimer's Disease Assessment Scale-Cognitive subscale score) was associated with NBM FC (r = -0.349; P ˂ .001). NBM FC was higher 6 months after ChEI compared with before ChEI in treated MCI (corrected P ˂ .05), but did not change at 6 months in patients with untreated MCI (corrected P ˂ .05). Baseline NBM FC in MCI strongly predicted cognitive outcomes 6 months after ChEI (R2 = 0.458; P = .001). Conclusion Functional dissociation of the nucleus basalis of Meynert from a cortical network may explain the cognitive deficits in dementia and allow for the selection of individuals who are more likely to respond to cholinesterase inhibitors at early disease stages. © RSNA, 2018 Online supplemental material is available for this article.

Output-oriented analysis of the wet mechanical processing of polyolefin-rich waste for feedstock recycling.

In recent years, an increasing number of studies have revealed that plastics and their components (e.g. plasticisers) pose an environmental risk. However, it is hard to imagine how our industrialised society could do without these materials, since the fields of application are manifold. One possible approach to tackle this mounting problem is the implementation of a comprehensive and well-functioning collection and recycling system. An international comparison shows that only a small proportion of the total plastics in circulation is collected and recycled. The investigations conducted under the present research project, 'Plastic Reborn', focused on both identification and analysis of the discharge paths of polyolefin-rich waste streams, under the Austrian waste management system. Another objective was determining the utilisation potential of the output fractions of these polyolefin-rich waste streams, generated from a wet mechanical processing pilot plant. Experiments have shown that the polyolefins are successfully separated from the waste streams and that a total polyolefin potential of 429,000 t y-1 remains unexploited in the Austrian waste management system. Thus, these separated plastic fractions can make a significant contribution to the implementation of the European Circular Economy Directive. The residual fractions meet the legal and company-specific requirements for their use as solid recovered fuels in co-combustion plants.

Discovery of Novel Spiro[3H-indole-3,2'-pyrrolidin]-2(1H)-one Compounds as Chemically Stable and Orally Active Inhibitors of the MDM2-p53 Interaction.

Scaffold modification based on Wang's pioneering MDM2-p53 inhibitors led to novel, chemically stable spiro-oxindole compounds bearing a spiro[3H-indole-3,2'-pyrrolidin]-2(1H)-one scaffold that are not prone to epimerization as observed for the initial spiro[3H-indole-3,3'-pyrrolidin]-2(1H)-one scaffold. Further structure-based optimization inspired by natural product architectures led to a complex fused ring system ideally suited to bind to the MDM2 protein and to interrupt its protein-protein interaction (PPI) with TP53. The compounds are highly selective and show in vivo efficacy in a SJSA-1 xenograft model even when given as a single dose as demonstrated for 4-[(3S,3'S,3'aS,5'R,6'aS)-6-chloro-3'-(3-chloro-2-fluorophenyl)-1'-(cyclopropylmethyl)-2-oxo-1,2,3',3'a,4',5',6',6'a-octahydro-1'H-spiro[indole-3,2'-pyrrolo[3,2-b]pyrrole]-5'-yl]benzoic acid (BI-0252).

Modulation of post-movement beta rebound by contraction force and rate of force development.

Movement induced modulation of the beta rhythm is one of the most robust neural oscillatory phenomena in the brain. In the preparation and execution phases of movement, a loss in beta amplitude is observed [movement related beta decrease (MRBD)]. This is followed by a rebound above baseline on movement cessation [post movement beta rebound (PMBR)]. These effects have been measured widely, and recent work suggests that they may have significant importance. Specifically, they have potential to form the basis of biomarkers for disease, and have been used in neuroscience applications ranging from brain computer interfaces to markers of neural plasticity. However, despite the robust nature of both MRBD and PMBR, the phenomena themselves are poorly understood. In this study, we characterise MRBD and PMBR during a carefully controlled isometric wrist flexion paradigm, isolating two fundamental movement parameters; force output, and the rate of force development (RFD). Our results show that neither altered force output nor RFD has a significant effect on MRBD. In contrast, PMBR was altered by both parameters. Higher force output results in greater PMBR amplitude, and greater RFD results in a PMBR which is higher in amplitude and shorter in duration. These findings demonstrate that careful control of movement parameters can systematically change PMBR. Further, for temporally protracted movements, the PMBR can be over 7 s in duration. This means accurate control of movement and judicious selection of paradigm parameters are critical in future clinical and basic neuroscientific studies of sensorimotor beta oscillations. Hum Brain Mapp 37:2493-2511, 2016. © 2016 Wiley Periodicals, Inc.

Dynamic causal modelling of eye movements during pursuit: Confirming precision-encoding in V1 using MEG.

This paper shows that it is possible to estimate the subjective precision (inverse variance) of Bayesian beliefs during oculomotor pursuit. Subjects viewed a sinusoidal target, with or without random fluctuations in its motion. Eye trajectories and magnetoencephalographic (MEG) data were recorded concurrently. The target was periodically occluded, such that its reappearance caused a visual evoked response field (ERF). Dynamic causal modelling (DCM) was used to fit models of eye trajectories and the ERFs. The DCM for pursuit was based on predictive coding and active inference, and predicts subjects' eye movements based on their (subjective) Bayesian beliefs about target (and eye) motion. The precisions of these hierarchical beliefs can be inferred from behavioural (pursuit) data. The DCM for MEG data used an established biophysical model of neuronal activity that includes parameters for the gain of superficial pyramidal cells, which is thought to encode precision at the neuronal level. Previous studies (using DCM of pursuit data) suggest that noisy target motion increases subjective precision at the sensory level: i.e., subjects attend more to the target's sensory attributes. We compared (noisy motion-induced) changes in the synaptic gain based on the modelling of MEG data to changes in subjective precision estimated using the pursuit data. We demonstrate that imprecise target motion increases the gain of superficial pyramidal cells in V1 (across subjects). Furthermore, increases in sensory precision - inferred by our behavioural DCM - correlate with the increase in gain in V1, across subjects. This is a step towards a fully integrated model of brain computations, cortical responses and behaviour that may provide a useful clinical tool in conditions like schizophrenia.

Causal evidence that intrinsic beta-frequency is relevant for enhanced signal propagation in the motor system as shown through rhythmic TMS.

Correlative evidence provides support for the idea that brain oscillations underpin neural computations. Recent work using rhythmic stimulation techniques in humans provide causal evidence but the interactions of these external signals with intrinsic rhythmicity remain unclear. Here, we show that sensorimotor cortex follows externally applied rhythmic TMS (rTMS) stimulation in the beta-band but that the elicited responses are strongest at the intrinsic individual beta peak frequency. While these entrainment effects are of short duration, even subthreshold rTMS pulses propagate through the network and elicit significant cortico-spinal coupling, particularly when stimulated at the individual beta-frequency. Our results show that externally enforced rhythmicity interacts with intrinsic brain rhythms such that the individual peak frequency determines the effect of rTMS. The observed downstream spinal effect at the resonance frequency provides evidence for the causal role of brain rhythms for signal propagation.