Reversible Cation-Selective Attachment and Self-Assembly of Human Tau on Supported Brain Lipid Membranes.

Misfolding and aggregation of the neuronal, microtubule-associated protein tau is involved in the pathogenesis of Alzheimer's disease and tauopathies. It has been proposed that neuronal membranes could play a role in tau release, internalization, and aggregation and that tau aggregates could exert toxicity via membrane permeabilization. Whether and how tau interacts with lipid membranes remains a matter of discussion.

The differentiated networks related to essential tremor onset and its amplitude modulation after alcohol intake.

The dysregulation of endogenous rhythms within brain networks have been implicated in a broad range of motor and non-motor pathologies. Essential tremor (ET), classically the purview of a single aberrant pacemaker, has recently become associated with network-level dysfunction across multiple brain regions. Specifically, it has been suggested that motor cortex constitutes an important node in a tremor-generating network involving the cerebellum.

In vivo bioluminescence imaging of vascular remodeling after stroke.

Thrombolysis remains the only beneficial therapy for ischemic stroke, but is restricted to a short therapeutic window following the infarct. Currently research is focusing on spontaneous regenerative processes during the sub-acute and chronic phase. Angiogenesis, the formation of new blood vessels from pre-existing ones, was observed in stroke patients, correlates with longer survival and positively affects the formation of new neurons.

An age-related shift of resting-state functional connectivity of the subthalamic nucleus: a potential mechanism for compensating motor performance decline in older adults.

Healthy aging is associated with decline in basic motor functioning and higher motor control. Here, we investigated age-related differences in the brain-wide functional connectivity (FC) pattern of the subthalamic nucleus (STN), which plays an important role in motor response control. As earlier studies revealed functional coupling between STN and basal ganglia, which both are known to influence the conservativeness of motor responses on a superordinate level, we tested the hypothesis that STN FC with the striatum becomes dysbalanced with age.

Objects tell us what action we can expect: dissociating brain areas for retrieval and exploitation of action knowledge during action observation in fMRI.

Objects are reminiscent of actions often performed with them:knife and apple remind us on peeling the apple or cutting it. Mnemonic representations of object-related actions (action codes) evoked by the sight of an object may constrain and hence facilitate recognition of unrolling actions. The present fMRI study investigated if and how action codes influence brain activation during action observation.

Neural correlates of sensorimotor gating: a metabolic positron emission tomography study in awake rats.

Impaired sensorimotor gating occurs in neuropsychiatric disorders such as schizophrenia and can be measured using the prepulse inhibition (PPI) paradigm of the acoustic startle response. This assay is frequently used to validate animal models of neuropsychiatric disorders and to explore the therapeutic potential of new drugs. The underlying neural network of PPI has been extensively studied with invasive methods and genetic modifications.

Dissociating dynamic probability and predictability in observed actions-an fMRI study.

The present fMRI study investigated whether human observers spontaneously exploit the statistical structure underlying continuous action sequences. In particular, we tested whether two different statistical properties can be distinguished with regard to their neural correlates: an action step's predictability and its probability. To assess these properties we used measures from information theory.

Obesity promotes liver carcinogenesis via Mcl-1 stabilization independent of IL-6Rα signaling.

Obesity increases the incidence of hepatocellular carcinoma (HCC) development in part through the activation of obesity-associated proinflammatory signaling. Here, we show that in lean mice, abrogation of IL-6Rα signaling protects against diethylnitrosamine (DEN)-induced HCC development. HCC protection occurs via Mcl-1 destabilization, thus promoting hepatocyte apoptosis.

Cerebellar networks with basal ganglia: feasibility for tracking cerebello-pallidal and subthalamo-cerebellar projections in the human brain.

Neuroanatomical studies using transneuronal virus tracers in macaque monkeys recently demonstrated that substantial interactions exist between basal ganglia and the cerebellum. To what extent these interactions are present in the human brain remains unclear; however, these connections are thought to provide an important framework for understanding cerebellar contributions to the manifestation of basal ganglia disorders, especially with respect to tremor genesis in movement disorders such as Parkinson's disease. Here, we tested the feasibility of assessing these connections in vivo and non-invasively in the human brain with diffusion magnetic resonance imaging and tractography.

Cascade of tau toxicity in inducible hippocampal brain slices and prevention by aggregation inhibitors.

Mislocalization and aggregation of the axonal protein tau are hallmarks of Alzheimer's disease and other tauopathies. Here, we studied the relationship between tau aggregation, loss of spines and neurons, and reversibility by aggregation inhibitors. To this end we established an in vitro model of tauopathy based on regulatable transgenic hippocampal organotypic slice cultures prepared from mice expressing proaggregant Tau repeat domain with mutation ΔK280 (Tau(RD)ΔK).

Error awareness and the error-related negativity: evaluating the first decade of evidence.

From its discovery in the early 1990s until this day, the error-related negativity (ERN) remains the most widely investigated electrophysiological index of cortical error processing. When researchers began addressing the electrophysiology of subjective error awareness more than a decade ago, the role of the ERN, alongside the subsequently occurring error positivity (Pe), was an obvious locus of attention. However, the first two studies explicitly addressing the role of error-related event-related brain potentials (ERPs) would already set the tone for what still remains a controversy today: in contrast to the clear-cut findings that link the amplitude of the Pe to error awareness, the association between ERN amplitude and error awareness is vastly unclear.

Cutting edge: Inhibition of IL-6 trans-signaling protects from malaria-induced lethality in mice.

Circulating IL-6 levels correlate with the severity of blood-stage malaria in humans and mouse models, but the impact of IL-6 classic signaling through membrane IL-6Rα, as well as IL-6 trans-signaling through soluble IL-6Rα, on the outcome of malaria has remained unknown. In this study, we created IL-6Rα-deficient mice that exhibit a 50% survival of otherwise lethal blood-stage malaria of the genus Plasmodium chabaudi. Inducing IL-6 trans-signaling by injection of mouse recombinant soluble IL-6Rα in IL-6Rα-deficient mice restores the lethal outcome to malaria infection.

Conflict Processing in the Rat Brain: Behavioral Analysis and Functional μPET Imaging Using [F]Fluorodeoxyglucose.

Conflicts in spatial stimulus-response tasks occur when the task-relevant feature of a stimulus implies a response toward a certain location which does not match the location of stimulus presentation. This conflict leads to increased error rates and longer reaction times, which has been termed Simon effect. A model of dual route processing (automatic and intentional) of stimulus features has been proposed, predicting response conflicts if the two routes are incongruent.

Hierarchical information-based clustering for connectivity-based cortex parcellation.

One of the most promising avenues for compiling connectivity data originates from the notion that individual brain regions maintain individual connectivity profiles; the functional repertoire of a cortical area ("the functional fingerprint") is closely related to its anatomical connections ("the connectional fingerprint") and, hence, a segregated cortical area may be characterized by a highly coherent connectivity pattern. Diffusion tractography can be used to identify borders between such cortical areas. Each cortical area is defined based upon a unique probabilistic tractogram and such a tractogram is representative of a group of tractograms, thereby forming the cortical area.

Caudate nucleus signals for breaches of expectation in a movement observation paradigm.

The striatum has been established as a carrier of reward-related prediction errors. This prediction error signal concerns the difference between how much reward was predicted and how much reward is gained. However, it remains to be established whether general breaches of expectation, i.

Masked auditory feedback affects speech motor learning of a plosive duration contrast.

Adult speakers have developed precise forward models of articulation for their native language and seem to rely less on auditory sensory feedback. However, for learning of the production of new speech sounds, auditory perception provides a corrective signal for motor control. We assessed adult German speakers' speech motor learning capacity in the absence of auditory feedback but with clear somatosensory information.

Dynamic causal modeling of cortical activity from the acute to the chronic stage after stroke.

Functional neuroimaging studies frequently demonstrated that stroke patients show bilateral activity in motor and premotor areas during movements of the paretic hand in contrast to a more lateralized activation observed in healthy subjects. Moreover, a few studies modeling functional or effective connectivity reported performance-related changes in the motor network after stroke. Here, we investigated the temporal evolution of intra- and interhemispheric (dys-) connectivity during motor recovery from the acute to the early chronic phase post-stroke.

Modulating cortical connectivity in stroke patients by rTMS assessed with fMRI and dynamic causal modeling.

Data derived from transcranial magnetic stimulation (TMS) studies suggest that transcallosal inhibition mechanisms between the primary motor cortex of both hemispheres may contribute to the reduced motor performance of stroke patients. We here investigated the potential of modulating pathological interactions between cortical motor areas by means of repetitive TMS using functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM). Eleven subacute stroke patients were scanned 1-3 months after symptom onset while performing whole hand fist closure movements.