A P300 Based Cognitive Assessment Battery for Severely Motor-impaired and Overtly Non-responsive Patients

Diagnosing disorders of consciousness (DOC) is notoriously difficult, with estimates of misdiagnosis rates as high as 40%. Moreover, recent studies have demonstrated that patients who do not show signs of volitional motor responses can exhibit preserved command following detected by functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Although these patients clearly retain some cognitive abilities, lack of consistent motor responses makes administration of standard neuropsychological tests impossible. Consequently, the extent of their cognitive function is unknown. In the current study, we developed and validated a P300b event related potential (ERP) neuropsychological battery in healthy participants to assess components of executive function without requiring motor output. First, participants were instructed to attend to a target auditory stimulus. P300b responses to attended relative to unattended stimuli were used as a neural proxy for detecting command following. To assess working memory capacity we adapted a digit span test to use a similar P300b response mechanism. Finally, reasoning was assessed by adapting a verbal reasoning task in the same manner. At the group level, and in a large majority of participants at the single-participant level, accurate performance could be detected using the P300b ERP, validating the potential utility of the battery. Additionally, the normalized magnitude of the P300b predicted individual differences in performance, but only when a suitable level of variability between participants was present. A post hoc Monte Carlo analysis was conducted to examine the necessary time required to conduct the battery as well as the interaction between time and performance in determining statistically significant performance. At 100% accuracy, a mean time of five minutes was required to achieve a significant result, with time increasing as a function of decreasing performance. These results demonstrate that covert control of attention, as measured by the P300b ERP, can be used to assess command following, working memory and reasoning abilities with a high degree of reliabilit

GrassPlot v. 2.00 – first update on the database of multi-scale plant diversity in Palaearctic grasslands

Abstract: GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). Following a previous Long Database Report (Dengler et al. 2018, Phyto- coenologia 48, 331–347), we provide here the first update on content and functionality of GrassPlot. The current version (GrassPlot v. 2.00) contains a total of 190,673 plots of different grain sizes across 28,171 independent plots, with 4,654 nested-plot series including at least four grain sizes. The database has improved its content as well as its functionality, including addition and harmonization of header data (land use, information on nestedness, structure and ecology) and preparation of species composition data. Currently, GrassPlot data are intensively used for broad-scale analyses of different aspects of alpha and beta diversity in grassland ecosystems

Prion-like domain mutations in hnRNPs cause multisystem proteinopathy and ALS

Summary Algorithms designed to identify canonical yeast prions predict that ~250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbor a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here, we define pathogenic mutations in PrLDs of hnRNPA2/B1 and hnRNPA1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and a case of familial ALS. Wild-type hnRNPA2 and hnRNPA1 display an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a ‘steric zipper’ motif in the PrLD, which accelerates formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Importantly, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant ‘steric zipper’ motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs must be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone

Stochastic Resonance Modulates Neural Synchronization within and between Cortical Sources

Neural synchronization is a mechanism whereby functionally specific brain regions establish transient networks for perception, cognition, and action. Direct addition of weak noise (fast random fluctuations) to various neural systems enhances synchronization through the mechanism of stochastic resonance (SR). Moreover, SR also occurs in human perception, cognition, and action. Perception, cognition, and action are closely correlated with, and may depend upon, synchronized oscillations within specialized brain networks. We tested the hypothesis that SR-mediated neural synchronization occurs within and between functionally relevant brain areas and thus could be responsible for behavioral SR. We measured the 40-Hz transient response of the human auditory cortex to brief pure tones. This response arises when the ongoing, random-phase, 40-Hz activity of a group of tuned neurons in the auditory cortex becomes synchronized in response to the onset of an above-threshold sound at its “preferred” frequency. We presented a stream of near-threshold standard sounds in various levels of added broadband noise and measured subjects' 40-Hz response to the standards in a deviant-detection paradigm using high-density EEG. We used independent component analysis and dipole fitting to locate neural sources of the 40-Hz response in bilateral auditory cortex, left posterior cingulate cortex and left superior frontal gyrus. We found that added noise enhanced the 40-Hz response in all these areas. Moreover, added noise also increased the synchronization between these regions in alpha and gamma frequency bands both during and after the 40-Hz response. Our results demonstrate neural SR in several functionally specific brain regions, including areas not traditionally thought to contribute to the auditory 40-Hz transient response. In addition, we demonstrated SR in the synchronization between these brain regions. Thus, both intra- and inter-regional synchronization of neural activity are facilitated by the addition of moderate amounts of random noise. Because the noise levels in the brain fluctuate with arousal system activity, particularly across sleep-wake cycles, optimal neural noise levels, and thus SR, could be involved in optimizing the formation of task-relevant brain networks at several scales under normal conditions

Preclinical Targeting of the Type I Insulin-Like Growth Factor Receptor in Adrenocortical Carcinoma

Context: Drug therapy for adrenocortical carcinoma (ACC), a rare and lethal malignancy, is largely empirical and ineffective. New treatments directed at molecular targets critical to the pathophysiology of ACC may prove more efficacious