Recognition and perception of emotions in juvenile myoclonic epilepsy.

OBJECTIVE: Perception and recognition of emotions are fundamental prerequisites of human life. Patients with juvenile myoclonic epilepsy (JME) may have emotional and behavioral impairments that might influence socially desirable interactions. We aimed to investigate perception and recognition of emotions in patients with JME by means of neuropsychological tests and functional magnetic resonance imaging (fMRI). METHODS: Sixty-five patients with JME (median age = 27 years, interquartile range [IQR] = 23-34) were prospectively recruited at the Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria. Patients were compared to 68 healthy controls (median age = 24 years, IQR = 21-31), matched for sex, age, and education. All study participants underwent the Networks of Emotion Processing test battery (NEmo), an fMRI paradigm of "dynamic fearful faces," a structured interview for psychiatric and personality disorders, and comprehensive neuropsychological testing. RESULTS: JME patients versus healthy controls demonstrated significant deficits in emotion recognition in facial and verbal tasks of all emotions, especially fear. fMRI revealed decreased amygdala activation in JME patients as compared to healthy controls. Patients were at a higher risk of experiencing psychiatric disorders as compared to healthy controls. Cognitive evaluation revealed impaired attentional and executive functioning, namely psychomotor speed, tonic alertness, divided attention, mental flexibility, and inhibition of automated reactions. Duration of epilepsy correlated negatively with parallel prosodic and facial emotion recognition in NEmo. Deficits in emotion recognition were not associated with psychiatric comorbidities, impaired attention and executive functions, types of seizures, and treatment. SIGNIFICANCE: This prospective study demonstrated that as compared to healthy subjects, patients with JME had significant deficits in recognition and perception of emotions as shown by neuropsychological tests and fMRI. The results of this study may have importance for psychological/psychotherapeutic interventions in the management of patients with JME.

Identification of the Actin-Binding Region and Binding to Host Plant Apple Actin of Immunodominant Transmembrane Protein of 'Candidatus Phytoplasma mali'.

'Candidatus Phytoplasma mali' ('Ca. P. mali') has only one major membrane protein, the immunodominant membrane protein (Imp), which is regarded as being close to the ancestor of all phytoplasma immunodominant membrane proteins. Imp binds to actin and possibly facilitates its movement in the plant or insect host cells. However, protein sequences of Imp are quite diverse among phytoplasma species, thus resulting in difficulties in identifying conserved domains across species. In this work, we compare Imp protein sequences of 'Ca. P. mali' strain PM19 (Imp-PM19) with Imp of different strains of 'Ca. P. mali' and identify its actin-binding domain. Moreover, we show that Imp binds to the actin of apple (Malus x domestica), which is the host plant of 'Ca. P. mali'. Using molecular and scanning force spectroscopy analysis, we find that the actin-binding domain of Imp-PM19 contains a highly positively charged amino acid cluster. Our result could allow investigating a possible correlation between Imp variants and the infectivity of the corresponding 'Ca. P. mali' isolates.

Neural processing of vision and language in kindergarten is associated with prereading skills and predicts future literacy.

The main objective of this longitudinal study was to investigate the neural predictors of reading acquisition. For this purpose, we followed a sample of 54 children from the end of kindergarten to the end of second grade. Preliterate children were tested for visual symbol (checkerboards, houses, faces, written words) and auditory language processing (spoken words) using a passive functional magnetic resonance imaging paradigm. To examine brain-behavior relationships, we also tested cognitive-linguistic prereading skills at kindergarten age and reading performance of 48 of the same children 2 years later. Face-selective response in the bilateral fusiform gyrus was positively associated with rapid automatized naming (RAN). Response to both spoken and written words at preliterate age was negatively associated with RAN in the dorsal temporo-parietal language system. Longitudinally, neural response to faces in the ventral stream predicted future reading fluency. Here, stronger neural activity in inferior and middle temporal gyri at kindergarten age was associated with higher reading performance. Our results suggest that interindividual differences in the neural system of language and reading affect literacy acquisition and thus might serve as a marker for successful reading acquisition in preliterate children.

Do Words Stink? Neural Reuse as a Principle for Understanding Emotions in Reading.

How do we understand the emotional content of written words? Here, we investigate the hypothesis that written words that carry emotions are processed through phylogenetically ancient neural circuits that are involved in the processing of the very same emotions in nonlanguage contexts. This hypothesis was tested with respect to disgust. In an fMRI experiment, it was found that the same region of the left anterior insula responded whether people observed facial expressions of disgust or whether they read words with disgusting content. In a follow-up experiment, it was found that repetitive TMS over the left insula in comparison with a control site interfered with the processing of disgust words to a greater extent than with the processing of neutral words. Together, the results support the hypothesis that the affective processes we experience when reading rely on the reuse of phylogenetically ancient brain structures that process basic emotions in other domains and species.

A simple method to estimate the isoelectric point of modified Tomato bushy stunt virus (TBSV) particles.

We present a simple method to estimate the isoelectric point (pI) of Tomato Bushy Stunt particles. We demonstrate that the combination of agarose gels with different pH buffers can be used to electrophorese the virus particles and their migration patterns can be compared. This method allows us to estimate the pI of the virus particles (wild type, wt, and genetically modified particles) and to monitor the effect of the pI of modified peptide side chains of the viral capsid subunit on the pI of the whole virus particle.

Emotions in reading: Dissociation of happiness and positivity.

The hierarchical emotion model proposed by Panksepp (1998) predicts that affective processing will rely on three functionally and neuroanatomically distinct levels, engaging subcortical networks (primary level), the limbic system (secondary level), and the neocortex (tertiary level). In the present fMRI study, we manipulated happiness and positivity, which are assumed to rely on secondary- and tertiary-level processes, respectively, to test these assumptions in a word recognition task. In accordance with the model predictions, evidence for a double dissociation was found in the brain activation patterns: Secondary-level processes engaged parts of the limbic system-specifically, the right hemispheric amygdala. Tertiary-level processes, in contrast, relied predominantly on frontal neocortical structures such as the left inferior frontal and medial frontal gyri. These results are interpreted as support for Panksepp's (1998) model and as an indicator of a semantic foundation of affective dimensions.

Fixation-related FMRI analysis in the domain of reading research: using self-paced eye movements as markers for hemodynamic brain responses during visual letter string processing.

The present study investigated the feasibility of using self-paced eye movements during reading (measured by an eye tracker) as markers for calculating hemodynamic brain responses measured by functional magnetic resonance imaging (fMRI). Specifically, we were interested in whether the fixation-related fMRI analysis approach was sensitive enough to detect activation differences between reading material (words and pseudowords) and nonreading material (line and unfamiliar Hebrew strings). Reliable reading-related activation was identified in left hemisphere superior temporal, middle temporal, and occipito-temporal regions including the visual word form area (VWFA). The results of the present study are encouraging insofar as fixation-related analysis could be used in future fMRI studies to clarify some of the inconsistent findings in the literature regarding the VWFA. Our study is the first step in investigating specific visual word recognition processes during self-paced natural sentence reading via simultaneous eye tracking and fMRI, thus aiming at an ecologically valid measurement of reading processes. We provided the proof of concept and methodological framework for the analysis of fixation-related fMRI activation in the domain of reading research.

A dual-route cascaded model of reading by deaf adults: evidence for grapheme to viseme conversion.

There is an ongoing debate whether deaf individuals access phonology when reading, and if so, what impact the ability to access phonology might have on reading achievement. However, the debate so far has been theoretically unspecific on two accounts: (a) the phonological units deaf individuals may have of oral language have not been specified and (b) there seem to be no explicit cognitive models specifying how phonology and other factors operate in reading by deaf individuals. We propose that deaf individuals have representations of the sublexical structure of oral-aural language which are based on mouth shapes and that these sublexical units are activated during reading by deaf individuals. We specify the sublexical units of deaf German readers as 11 "visemes" and incorporate the viseme set into a working model of single-word reading by deaf adults based on the dual-route cascaded model of reading aloud by Coltheart, Rastle, Perry, Langdon, and Ziegler (2001. DRC: A dual route cascaded model of visual word recognition and reading aloud. Psychological Review, 108, 204-256. doi: 10.1037//0033-295x.108.1.204). We assessed the indirect route of this model by investigating the "pseudo-homoviseme" effect using a lexical decision task in deaf German reading adults. We found a main effect of pseudo-homovisemy, suggesting that at least some deaf individuals do automatically access sublexical structure during single-word reading.

Beyond Destabilizing Activity of SAP11-like Effector of Candidatus Phytoplasma mali Strain PM19.

It was shown that the SAP11 effector of different Candidatus Phytoplasma can destabilize some TEOSINE BRANCHES/CYCLOIDEA/PROLIFERATING CELL FACTORs (TCPs), resulting in plant phenotypes such as witches' broom and crinkled leaves. Some SAP11 exclusively localize in the nucleus, while the others localize in the cytoplasm and the nucleus. The SAP11-like effector of Candidatus Phytoplasma mali strain PM19 (SAP11PM19) localizes in both compartments of plant cells. We show here that SAP11PM19 can destabilize TCPs in both the nucleus and the cytoplasm. However, expression of SAP11PM19 exclusively in the nucleus resulted in the disappearance of leaf phenotypes while still showing the witches' broom phenotype. Moreover, we show that SAP11PM19 can not only destabilize TCPs but also relocalizes these proteins in the nucleus. Interestingly, three different transgenic Nicotiana species expressing SAP11PM19 show all the same witches' broom phenotype but different leaf phenotypes. A possible mechanism of SAP11-TCP interaction is discussed.

Structural gray matter features and behavioral preliterate skills predict future literacy - A machine learning approach.

When children learn to read, their neural system undergoes major changes to become responsive to print. There seem to be nuanced interindividual differences in the neurostructural anatomy of regions that later become integral parts of the reading network. These differences might affect literacy acquisition and, in some cases, might result in developmental disorders like dyslexia. Consequently, the main objective of this longitudinal study was to investigate those interindividual differences in gray matter morphology that might facilitate or hamper future reading acquisition. We used a machine learning approach to examine to what extent gray matter macrostructural features and cognitive-linguistic skills measured before formal literacy teaching could predict literacy 2 years later. Forty-two native German-speaking children underwent T1-weighted magnetic resonance imaging and psychometric testing at the end of kindergarten. They were tested again 2 years later to assess their literacy skills. A leave-one-out cross-validated machine-learning regression approach was applied to identify the best predictors of future literacy based on cognitive-linguistic preliterate behavioral skills and cortical measures in a priori selected areas of the future reading network. With surprisingly high accuracy, future literacy was predicted, predominantly based on gray matter volume in the left occipito-temporal cortex and local gyrification in the left insular, inferior frontal, and supramarginal gyri. Furthermore, phonological awareness significantly predicted future literacy. In sum, the results indicate that the brain morphology of the large-scale reading network at a preliterate age can predict how well children learn to read.

Emotional Word Processing in Patients With Juvenile Myoclonic Epilepsy.

Objective: According to Panksepp's hierarchical emotion model, emotion processing relies on three functionally and neuroanatomically distinct levels. These levels comprise subcortical networks (primary level), the limbic system (secondary level), and the neocortex (tertiary level) and are suggested to serve differential emotional processing. We aimed to validate and extend previous evidence of discrete and dimensional emotion processing in patient with juvenile myoclonic epilepsy (JME). Methods: We recorded brain activity of patients with JME and healthy controls in response to lexical decisions to words reflecting the discrete emotion fear and the affective dimension negativity previously suggested to rely on different brain regions and to reflect different levels of processing. In all study participants, we tested verbal cognitive functions, as well as the relationship of psychiatric conditions, seizure types and duration of epilepsy and emotional word processing. Results: In support of the hierarchical emotion model, we found an interaction of discrete emotion and affective dimensional processing in the right amygdala likely to reflect secondary level processing. Brain activity related to affective dimensional processing was found in the right inferior frontal gyrus and is suggested to reflect tertiary level processing. Psychiatric conditions, type of seizure nor mono- vs. polytherapy and duration of epilepsy within patients did not have any effect on the processing of emotional words. In addition, no differences in brain activity or response times between patients and controls were observed, despite neuropsychological testing revealed slightly decreased verbal intelligence, verbal fluency and reading speed in patients with JME. Significance: These results were interpreted to be in line with the hierarchical emotion model and to highlight the amygdala's role in processing biologically relevant stimuli, as well as to suggest a semantic foundation of affective dimensional processing in prefrontal cortex. A lack of differences in brain activity of patients with JME and healthy controls in response to the emotional content of words could point to unaffected implicit emotion processing in patients with JME.

The Effect of the Anticipated Nuclear Localization Sequence of 'Candidatus Phytoplasma mali' SAP11-like Protein on Localization of the Protein and Destabilization of TCP Transcription Factor.

SAP11 is an effector protein that has been identified in various phytoplasma species. It localizes in the plant nucleus and can bind and destabilize TEOSINE BRANCHES/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factors. Although SAP11 of different phytoplasma species share similar activities, their protein sequences differ greatly. Here, we demonstrate that the SAP11-like protein of 'Candidatus Phytoplasma mali' ('Ca. P. mali') strain PM19 localizes into the plant nucleus without requiring the anticipated nuclear localization sequence (NLS). We show that the protein induces crinkled leaves and siliques, and witches' broom symptoms, in transgenic Arabidopsis thaliana (A. thaliana) plants and binds to six members of class I and all members of class II TCP transcription factors of A. thaliana in yeast two-hybrid assays. We also identified a 17 amino acid stretch previously predicted to be a nuclear localization sequence that is important for the binding of some of the TCPs, which results in a crinkled leaf and silique phenotype in transgenic A. thaliana. Moreover, we provide evidence that the SAP11-like protein has a destabilizing effect on some TCPs in vivo.

Anticipating trajectories of exponential growth.

Humans grossly underestimate exponential growth, but are at the same time overconfident in their (poor) judgement. The so-called 'exponential growth bias' is of new relevance in the context of COVID-19, because it explains why humans have fundamental difficulties to grasp the magnitude of a spreading epidemic. Here, we addressed the question, whether logarithmic scaling and contextual framing of epidemiological data affect the anticipation of exponential growth. Our findings show that underestimations were most pronounced when growth curves were linearly scaled and framed in the context of a more advanced epidemic progression. For logarithmic scaling, estimates were much more accurate, on target for growth rates around 31%, and not affected by contextual framing. We conclude that the logarithmic depiction is conducive for detecting exponential growth during an early phase as well as resurgences of exponential growth.

Pseudohomophone effects provide evidence of early lexico-phonological processing in visual word recognition.

Previous research using event-related brain potentials (ERPs) suggested that phonological processing in visual word recognition occurs rather late, typically after semantic or syntactic processing. Here, we show that phonological activation in visual word recognition can be observed much earlier. Using a lexical decision task, we show that ERPs to pseudohomophones (PsHs) (e.g., ROZE) differed from well-matched spelling controls (e.g., ROFE) as early as 150 ms (P150) after stimulus onset. The PsH effect occurred as early as the word frequency effect suggesting that phonological activation occurs early enough to influence lexical access. Low-resolution electromagnetic tomography analysis (LORETA) revealed that left temporoparietal and right frontotemporal areas are the likely brain regions associated with the processing of phonological information at the lexical level. Altogether, the results show that phonological processes are activated early in visual word recognition and play an important role in lexical access.

A model-guided dissociation between subcortical and cortical contributions to word recognition.

Neurocognitive studies of visual word recognition have provided information about brain activity correlated with orthographic processing. Some of these studies related the orthographic neighborhood density of letter strings to the amount of hypothetical global lexical activity (GLA) in the brain as simulated by computational models of word recognition. To further investigate this issue, we used GLA of words and nonwords from the multiple read-out model of visual word recognition (MROM) and related this activity to neural correlates of orthographic processing in the brain by using functional magnetic resonance imaging (fMRI). Words and nonwords elicited linear effects in the cortex with increasing BOLD responses for decreasing values of GLA. In addition, words showed increasing linear BOLD responses for increasing GLA values in subcortical regions comprising the hippocampus, globus pallidus and caudate nucleus. We propose that these regions are involved in the matching of orthographic input onto representations in long-term memory. The results speak to a potential involvement of the basal ganglia in visual word recognition with globus pallidus and caudate nucleus activity potentially reflecting maintenance of orthographic input in working memory supporting the matching of the input onto stored representations by selection of appropriate lexical candidates and the inhibition of orthographically similar but non-matching candidates.

Conflict monitoring engages the mediofrontal cortex during nonword processing.

The current study investigated the role played by conflict monitoring in a lexical-decision task involving competing word representations, using event-related potentials. We extended the multiple read-out model (Grainger and Jacobs, 1996), a connectionist model of word recognition, to quantify conflict by means of Hopfield Energy, which is defined as the sum of the products of all orthographic word node pair activations within the artificial mental lexicon of this model. With increasing conflict levels in nonwords, a late negativity increased in amplitude (400-600 ms) accompanied by activation of the anterior cingulate cortex and the medial frontal gyrus. The simulated conflict predicted the amplitudes associated with this mediofrontal conflict-monitoring network on an item level, and is consistent with the conflict-monitoring theory.

Same Same But Different: Processing Words in the Aging Brain.

Reading is not only one of the most appreciated leisure activities of the elderly but it clearly helps older people to maintain functional independence, which has a significant impact on life quality. Yet, very little is known about how aging affects the neural circuits of the processes that underlie skilled reading. Therefore, the aim of the present study was to systematically investigate the neural correlates of sublexical, orthographic, phonological and lexico-semantic processing in the aging brain. Using functional magnetic resonance imaging, we recorded brain activity of younger (N = 20; 22-35 years) and older (N = 38; 65-76 years) adults during letter identification, lexical decision, phonological decision and semantic categorization. Older and younger adults recruited an identical set of reading-related brain regions suggesting that the general architecture of the reading network is preserved across the lifespan. However, we also observed age-related differences in brain activity in the subcomponents of the reading network. Age-related differences were most prominent during phonological and orthographic processing possibly due to a failure of older adults to inhibit non-optimal reading strategies. Neural effects of aging were also observed outside reading-related circuits, especially in frontal midline regions. These regions might be involved because of their important role in memory, attention and executive control functions and their potential role in resting-state networks.

Delivery of Hairpin RNAs and Small RNAs Into Woody and Herbaceous Plants by Trunk Injection and Petiole Absorption.

Since its discovery, RNA interference has been widely used in crop protection. Recently, transgene-free procedures that were based on exogenous application of RNA molecules having the capacity to trigger RNAi in planta have been reported. Yet, efficient delivery of such RNA molecules to plants and particularly to trees poses major technical challenges. Here, we describe simple methods for efficient delivery of hairpin RNAs (hpRNAs) and small interfering RNAs (siRNAs) to Malus domestica, Vitis vinifera, and Nicotiana benthamiana that are based on trunk injection and/or petiole absorption. The applied RNA molecules were efficiently taken up and systemically transported. In apical leaves, the RNA was already detectable 1 day post-application (dpa) and could be detected at least up to 10 dpa, depending on the method of application. Confocal microscopy revealed that the uptaken and systemically transported RNA molecules were strictly restricted to the xylem and apoplast which may illustrate why the applied hpRNAs were not processed into siRNAs by plant DICER-LIKE (DCL) endonucleases. These innovative methods may have great impact in pest management against chewing and/or xylem sap-feeding vectors and eukaryotic pathogens that reside in the xylem.

Welcome to the real world: validating fixation-related brain potentials for ecologically valid settings.

Exploration of the real world usually expresses itself through a perceptual behaviour that is complex and adaptive -- an interplay between external visual and internal cognitive states. However, up to now, the measurement of electrophysiological correlates of cognitive processes has been limited to situations, in which the experimental setting confined visual exploration to the mere reception of a strict serial order of events. Here we show -- exemplified by the well known old/new effect in the domain of visual word recognition -- that an alternative approach that utilizes brain potentials corresponding to eye fixations during free exploration reveals effects as reliable as conventional event-related brain potentials.

Neurofunctionally dissecting the reading system in children.

The reading system can be broken down into four basic subcomponents in charge of prelexical, orthographic, phonological, and lexico-semantic processes. These processes need to jointly work together to become a fluent and efficient reader. Using functional magnetic resonance imaging (fMRI), we systematically analyzed differences in neural activation patterns of these four basic subcomponents in children (N=41, 9-13 years) using tasks specifically tapping each component (letter identification, orthographic decision, phonological decision, and semantic categorization). Regions of interest (ROI) were selected based on a meta-analysis of child reading and included the left ventral occipito-temporal cortex (vOT), left posterior parietal cortex (PPC), left inferior frontal gyrus (IFG), and bilateral supplementary motor area (SMA). Compared to a visual baseline task, enhanced activation in vOT and IFG was observed for all tasks with very little differences between tasks. Activity in the dorsal PPC system was confined to prelexical and phonological processing. Activity in the SMA was found in orthographic, phonological, and lexico-semantic tasks. Our results are consistent with the idea of an early engagement of the vOT accompanied by executive control functions in the frontal system, including the bilateral SMA.