Preventing a Thought from Coming to Mind Elicits Increased Right Frontal Beta Just as Stopping Action Does.

In the stop-signal task, an electrophysiological signature of action-stopping is increased early right frontal beta band power for successful vs. failed stop trials. Here we tested whether the requirement to stop an unwanted thought from coming to mind also elicits this signature. We recorded scalp EEG during a Think/No-Think task and a subsequent stop signal task in 42 participants. In the Think/No-Think task, participants first learned word pairs. In a second phase, they received the left-hand word as a reminder and were cued either to retrieve the associated right-hand word ("Think") or to stop retrieval ("No-Think"). At the end of each trial, participants reported whether they had experienced an intrusion of the associated memory. Finally, they received the left-hand reminder word and were asked to recall its associated target. Behaviorally, there was worse final recall for items in the No-Think condition, and decreased intrusions with practice for No-Think trials. For EEG, we reproduced increased early right frontal beta power for successful vs. failed action stopping. Critically, No-Think trials also elicited increased early right frontal beta power and this was stronger for trials without intrusion. These results suggest that preventing a thought from coming to mind also recruits fast prefrontal stopping

Lattice dynamics and vibrational spectra of the orthorhombic, tetragonal and cubic phases of methylammonium lead iodide

The hybrid halide perovskite CH3NH3PbI3 exhibits a complex structural behaviour, with successive transitions between orthorhombic, tetragonal and cubic polymorphs at ca. 165 K and 327 K. Herein we report first-principles lattice dynamics (phonon spectrum) for each phase of CH3NH3PbI3. The equilibrium structures compare well to solutions of temperature-dependent powder neutron diffraction. By following the normal modes we calculate infrared and Raman intensities of the vibrations, and compare them to the measurement of a single crystal where the Raman laser is controlled to avoid degradation of the sample. Despite a clear separation in energy between low frequency modes associated with the inorganic PbI3 network and high-frequency modes of the organic CH3NH3+ cation, significant coupling between them is found, which emphasises the interplay between molecular orientation and the corner-sharing octahedral networks in the structural transformations. Soft modes are found at the boundary of the Brillouin zone of the cubic phase, consistent with displacive instabilities and anharmonicity involving tilting of the PbI6 octahedra around room temperature.Comment: 9 pages, 4 figure

Intracranial EEG reveals a time- and frequency-specific role for the right inferior frontal gyrus and primary motor cortex in stopping initiated responses.

Inappropriate response tendencies may be stopped via a specific fronto/basal ganglia/primary motor cortical network. We sought to characterize the functional role of two regions in this putative stopping network, the right inferior frontal gyrus (IFG) and the primary motor cortex (M1), using electocorticography from subdural electrodes in four patients while they performed a stop-signal task. On each trial, a motor response was initiated, and on a minority of trials a stop signal instructed the patient to try to stop the response. For each patient, there was a greater right IFG response in the beta frequency band ( approximately 16 Hz) for successful versus unsuccessful stop trials. This finding adds to evidence for a functional network for stopping because changes in beta frequency activity have also been observed in the basal ganglia in association with behavioral stopping. In addition, the right IFG response occurred 100-250 ms after the stop signal, a time range consistent with a putative inhibitory control process rather than with stop-signal processing or feedback regarding success. A downstream target of inhibitory control is M1. In each patient, there was alpha/beta band desynchronization in M1 for stop trials. However, the degree of desynchronization in M1 was less for successfully than unsuccessfully stopped trials. This reduced desynchronization on successful stop trials could relate to increased GABA inhibition in M1. Together with other findings, the results suggest that behavioral stopping is implemented via synchronized activity in the beta frequency band in a right IFG/basal ganglia network, with downstream effects on M1

One-year changes in brain microstructure differentiate preclinical Huntington's disease stages.

OBJECTIVE: To determine whether brain imaging markers of tissue microstructure can detect the effect of disease progression across the preclinical stages of Huntington's disease. METHODS: Longitudinal microstructural changes in diffusion imaging metrics (mean diffusivity and fractional anisotropy) were investigated in participants with presymptomatic Huntington's disease (N = 35) stratified into three preclinical subgroups according to their estimated time until onset of symptoms, compared with age- and gender-matched healthy controls (N = 19) over a 1y period. RESULTS: Significant differences were found over the four groups in change of mean diffusivity in the posterior basal ganglia and the splenium of the corpus callosum. This overall effect was driven by significant differences between the group far-from-onset (FAR) of symptoms and the groups midway- (MID) and near-the-onset (NEAR) of symptoms. In particular, an initial decrease of mean diffusivity in the FAR group was followed by a subsequent increase in groups closer to onset of symptoms. The seemingly counter-intuitive decrease of mean diffusivity in the group furthest from onset of symptoms might be an early indicator of neuroinflammatory process preceding the neurodegenerative phase. In contrast, the only clinical measure that was able to capture a difference in 1y changes between the preclinical stages was the UHDRS confidence in motor score. CONCLUSIONS: With sensitivity to longitudinal changes in brain microstructure within and between preclinical stages, and potential differential response to distinct pathophysiological mechanisms, diffusion imaging is a promising state marker for monitoring treatment response and identifying the optimal therapeutic window of opportunity in preclinical Huntington's disease

Surprise disrupts cognition via a fronto-basal ganglia suppressive mechanism

Surprising events markedly affect behaviour and cognition, yet the underlying mechanism is unclear. Surprise recruits a brain mechanism that globally suppresses motor activity, ostensibly via the subthalamic nucleus (STN) of the basal ganglia. Here, we tested whether this suppressive mechanism extends beyond skeletomotor suppression and also affects cognition (here, verbal working memory, WM). We recorded scalp-EEG (electrophysiology) in healthy participants and STN local field potentials in Parkinson's patients during a task in which surprise disrupted WM. For scalp-EEG, surprising events engage the same independent neural signal component that indexes action stopping in a stop-signal task. Importantly, the degree of this recruitment mediates surprise-related WM decrements. Intracranially, STN activity is also increased post surprise, especially when WM is interrupted. These results suggest that surprise interrupts cognition via the same fronto-basal ganglia mechanism that interrupts action. This motivates a new neural theory of how cognition is interrupted, and how distraction arises after surprising events

Sociology Back to the Publics

This article is a reading of the `new sociology' that is mainly identified with the works of C. Wright Mills and Alvin Gouldner. Its main argument is that during the past 40 years the new sociology gave back a public face to sociology. This distinguishes it from the `old sociology' that had not been able to free itself from `private' social values. It is argued that Mills' power elite and Gouldner's coming crisis theses provided the foundation for a common enterprise among many `new sociologists' to develop a critical and public sociology that would seek to shape what Mills called the `democratic society of publics'.`New sociologists' share a critique of modern societies, namely, that though most modern societies have formal democracies, a substantial democratic social structure of publics is often lacking, due to the erosion of the public sphere by private values

Oscillatory cAMP signaling rapidly alters H3K4 methylation

receptors (GPCRs) alter H3K4 methylation via oscillatory intracellular cAMP. Activation of Gs-coupled receptors caused a rapid decrease of H3K4me3 by elevating cAMP, whereas stimulation of Gi-coupled receptors increased H3K4me3 by diminishing cAMP. H3K4me3 gradually recovered towards baseline levels after the removal of GPCR ligands, indicating that H3K4me3 oscillates in tandem with GPCR activation. cAMP increased intracellular labile Fe(II), the cofactor for histone demethylases, through a non-canonical cAMP target—Rap guanine nucleotide exchange factor-2 (RapGEF2), which subsequently enhanced endosome acidification and Fe(II) release from the endosome via vacuolar H+-ATPase assembly. Removing Fe(III) from the media blocked intracellular Fe(II) elevation after stimulation of Gs-coupled receptors. Iron chelators and inhibition of KDM5 demethylases abolished cAMP-mediated H3K4me3 demethylation. Taken together, these results suggest a novel function of cAMP signaling in modulating histone demethylation through labile Fe(II)

Manganese causes neurotoxic iron accumulation via translational repression of Amyloid Precursor Protein (APP) and H-Ferritin

For more than 150 years, it is known that occupational overexposure of manganese (Mn) causes movement disorders resembling Parkinson's disease (PD) and PD‐like syndromes. However, the mechanisms of Mn toxicity are still poorly understood. Here, we demonstrate that Mn dose‐ and time‐dependently blocks the protein translation of amyloid precursor protein (APP) and heavy‐chain Ferritin (H‐Ferritin), both iron homeostatic proteins with neuroprotective features. APP and H‐Ferritin are post‐transcriptionally regulated by iron responsive proteins, which bind to homologous iron responsive elements (IREs) located in the 5′‐untranslated regions (5′‐UTRs) within their mRNA transcripts. Using reporter assays, we demonstrate that Mn exposure repressed the 5′‐UTR‐activity of APP and H‐Ferritin, presumably via increased iron responsive proteins‐iron responsive elements binding, ultimately blocking their protein translation. Using two specific Fe2+‐specific probes (RhoNox‐1 and IP‐1) and ion chromatography inductively coupled plasma mass spectrometry (IC‐ICP‐MS), we show that loss of the protective axis of APP and H‐Ferritin resulted in unchecked accumulation of redox‐active ferrous iron (Fe2+) fueling neurotoxic oxidative stress. Enforced APP expression partially attenuated Mn‐induced generation of cellular and lipid reactive oxygen species and neurotoxicity. Lastly, we could validate the Mn‐mediated suppression of APP and H‐Ferritin in two rodent in vivo models (C57BL6/N mice and RjHan:SD rats) mimicking acute and chronic Mn exposure. Together, these results suggest that Mn‐induced neurotoxicity is partly attributable to the translational inhibition of APP and H‐Ferritin resulting in impaired iron metabolism and exacerbated neurotoxic oxidative stress