Listener effort quantifies clinically meaningful progression of dysarthria in people living with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motor neuron disease that causes progressive muscle weakness. Progressive bulbar dysfunction causes dysarthria and thus social isolation, reducing quality of life. The Everything ALS Speech Study obtained longitudinal clinical information and speech recordings from 292 participants. In a subset of 120 participants, we measured speaking rate (SR) and listener effort (LE), a measure of dysarthria severity rated by speech pathologists from recordings. LE intra- and inter-rater reliability was very high (ICC 0.88 to 0.92). LE correlated with other measures of dysarthria at baseline. LE changed over time in participants with ALS (slope 0.77 pts/month; p<0.001) but not controls (slope 0.005 pts/month; p=0.807). The slope of LE progression was similar in all participants with ALS who had bulbar dysfunction at baseline, regardless of ALS site of onset. LE could be a remotely collected clinically meaningful clinical outcome assessment for ALS clinical trials.

The Long and Winding Road to Real-Life Experiments: Remote Assessment of Executive Functions with Computerized Games-Results from 8 Years of Naturalistic Interventions.

Mate Marote is an open-access cognitive training software aimed at children between 4 and 8 years old. It consists of a set of computerized games specifically tailored to train and evaluate Executive Functions (EF), a class of processes critical for purposeful, goal-directed behavior, including working memory, planning, flexibility, and inhibitory control. Since 2008, several studies were performed with this software at children's own schools in interventions supervised in-person by cognitive scientists. After 2015, we incorporated naturalistic, yet controlled, interventions with children's own teachers' help. The platform includes a battery of standardized tests, disguised as games, to assess children's EF. The main question that emerges is whether the results, obtained with these traditional tasks but conducted without the presence of researchers, are comparable to those widely reported in the literature, that were obtained in more supervised settings. In this study, we were able to replicate the expected difficulty and age effects in at least one of the analyzed dependent variables of each employed test. We also report important discrepancies between the expected and the observed response time patterns, specifically for time-constrained tasks. We hereby discuss the benefits and setbacks of a new possible strategy for this type of assessment in naturalistic settings. We conclude that this battery of established EF tasks adapted for its remote usage is appropriate to measure the expected mental processes in naturalistic settings, enriching opportunities to upscale cognitive training interventions at schools. These types of tools can constitute a concerted strategy to bring together educational neuroscience research and real-life practice.

Assessing robustness and generalization of a deep neural network for brain MS lesion segmentation on real-world data.

OBJECTIVES: Evaluate the performance of a deep learning (DL)-based model for multiple sclerosis (MS) lesion segmentation and compare it to other DL and non-DL algorithms. METHODS: This ambispective, multicenter study assessed the performance of a DL-based model for MS lesion segmentation and compared it to alternative DL- and non-DL-based methods. Models were tested on internal (n = 20) and external (n = 18) datasets from Latin America, and on an external dataset from Europe (n = 49). We also examined robustness by rescanning six patients (n = 6) from our MS clinical cohort. Moreover, we studied inter-human annotator agreement and discussed our findings in light of these results. Performance and robustness were assessed using intraclass correlation coefficient (ICC), Dice coefficient (DC), and coefficient of variation (CV). RESULTS: Inter-human ICC ranged from 0.89 to 0.95, while spatial agreement among annotators showed a median DC of 0.63. Using expert manual segmentations as ground truth, our DL model achieved a median DC of 0.73 on the internal, 0.66 on the external, and 0.70 on the challenge datasets. The performance of our DL model exceeded that of the alternative algorithms on all datasets. In the robustness experiment, our DL model also achieved higher DC (ranging from 0.82 to 0.90) and lower CV (ranging from 0.7 to 7.9%) when compared to the alternative methods. CONCLUSION: Our DL-based model outperformed alternative methods for brain MS lesion segmentation. The model also proved to generalize well on unseen data and has a robust performance and low processing times both on real-world and challenge-based data. CLINICAL RELEVANCE STATEMENT: Our DL-based model demonstrated superior performance in accurately segmenting brain MS lesions compared to alternative methods, indicating its potential for clinical application with improved accuracy, robustness, and efficiency. KEY POINTS: • Automated lesion load quantification in MS patients is valuable; however, more accurate methods are still necessary. • A novel deep learning model outperformed alternative MS lesion segmentation methods on multisite datasets. • Deep learning models are particularly suitable for MS lesion segmentation in clinical scenarios.

Neural Bases of Predictions During Natural Reading of Known Statements: An Electroencephalography and Eye Movements Co-registration Study.

Predictions of incoming words performed during reading have an impact on how the reader moves their eyes and on the electrical brain potentials. Eye tracking (ET) experiments show that less predictable words are fixated for longer periods of times. Electroencephalography (EEG) experiments show that these words elicit a more negative potential around 400 ms (N400) after the word onset when reading one word at a time (foveated reading). Nevertheless, there was no N400 potential during the foveated reading of previously known sentences (memory-encoded), which suggests that the prediction of words from memory-encoded sentences is based on different mechanisms than predictions performed on common sentences. Here, we performed an ET-EEG co-registration experiment where participants read common and memory-encoded sentences. Our results show that the N400 potential disappear when the reader recognises the sentence. Furthermore, time-frequency analyses show a larger alpha lateralisation and a beta power increase for memory-encoded sentences. This suggests a more distributed attention and an active maintenance of the cognitive set, in concordance to the predictive coding framework.

Expanding horizons of cross-linguistic research on reading: The Multilingual Eye-movement Corpus (MECO).

Scientific studies of language behavior need to grapple with a large diversity of languages in the world and, for reading, a further variability in writing systems. Yet, the ability to form meaningful theories of reading is contingent on the availability of cross-linguistic behavioral data. This paper offers new insights into aspects of reading behavior that are shared and those that vary systematically across languages through an investigation of eye-tracking data from 13 languages recorded during text reading. We begin with reporting a bibliometric analysis of eye-tracking studies showing that the current empirical base is insufficient for cross-linguistic comparisons. We respond to this empirical lacuna by presenting the Multilingual Eye-Movement Corpus (MECO), the product of an international multi-lab collaboration. We examine which behavioral indices differentiate between reading in written languages, and which measures are stable across languages. One of the findings is that readers of different languages vary considerably in their skipping rate (i.e., the likelihood of not fixating on a word even once) and that this variability is explained by cross-linguistic differences in word length distributions. In contrast, if readers do not skip a word, they tend to spend a similar average time viewing it. We outline the implications of these findings for theories of reading. We also describe prospective uses of the publicly available MECO data, and its further development plans.

Information Structure and Word Order Canonicity in the Comprehension of Spanish Texts: An Eye-Tracking Study.

Word order alternation has been described as one of the most productive information structure markers and discourse organizers across languages. Psycholinguistic evidence has shown that word order is a crucial cue for argument interpretation. Previous studies about Spanish sentence comprehension have shown greater difficulty to parse sentences that present a word order that does not respect the order of participants of the verb's lexico-semantic structure, irrespective to whether the sentences follow the canonical word order of the language or not. This difficulty has been accounted as the cognitive cost related to the miscomputation of prominence status of the argument that precedes the verb. Nonetheless, the authors only analyzed the use of alternative word orders in isolated sentences, leaving aside the pragmatic motivation of word order alternation. By means of an eye-tracking task, the current study provides further evidence about the role of information structure for the comprehension of sentences with alternative word order and verb type, and sheds light on the interaction between syntax, semantics and pragmatics. We analyzed both "early" and "late" eye-movement measures as well as accuracy and response times to comprehension questions. Results showed an overall influence of information structure reflected in a modulation of late eye-movement measures as well as offline measures like total reading time and questions response time. However, effects related to the miscomputation of prominence status did not fade away when sentences were preceded by a context that led to non-canonical word order of constituents, showing that prominence computation is a core mechanism for argument interpretation, even in sentences preceded by context.

Brain folding shapes the branching pattern of the middle cerebral artery.

The folds of the brain offer a particular challenge for the subarachnoid vascular grid. The primitive blood vessels that occupy this space, when the brain is flat, have to adapt to an everchanging geometry while constructing an efficient network. Surprisingly, the result is a non-redundant arterial system easily challenged by acute occlusions. Here, we generalize the optimal network building principles of a flat surface growing into a folded configuration and generate an ideal middle cerebral artery (MCA) configuration that can be directly compared with the normal brain anatomy. We then describe how the Sylvian fissure (the fold in which the MCA is buried) is formed during development and use our findings to account for the differences between the ideal and the actual shaping pattern of the MCA. Our results reveal that folding dynamics condition the development of arterial anastomosis yielding a network without loops and poor response to acute occlusions.

Motor representations underlie the reading of unfamiliar letter combinations.

Silent reading is a cognitive operation that produces verbal content with no vocal output. One relevant question is the extent to which this verbal content is processed as overt speech in the brain. To address this, we acquired sound, eye trajectories and lips' dynamics during the reading of consonant-consonant-vowel (CCV) combinations which are infrequent in the language. We found that the duration of the first fixations on the CCVs during silent reading correlate with the duration of the transitions between consonants when the CCVs are actually uttered. With the aid of an articulatory model of the vocal system, we show that transitions measure the articulatory effort required to produce the CCVs. This means that first fixations during silent reading are lengthened when the CCVs require a greater laryngeal and/or articulatory effort to be pronounced. Our results support that a speech motor code is used for the recognition of infrequent text strings during silent reading.

Human and computer estimations of Predictability of words in written language.

When we read printed text, we are continuously predicting upcoming words to integrate information and guide future eye movements. Thus, the Predictability of a given word has become one of the most important variables when explaining human behaviour and information processing during reading. In parallel, the Natural Language Processing (NLP) field evolved by developing a wide variety of applications. Here, we show that using different word embeddings techniques (like Latent Semantic Analysis, Word2Vec, and FastText) and N-gram-based language models we were able to estimate how humans predict words (cloze-task Predictability) and how to better understand eye movements in long Spanish texts. Both types of models partially captured aspects of predictability. On the one hand, our N-gram model performed well when added as a replacement for the cloze-task Predictability of the fixated word. On the other hand, word embeddings were useful to mimic Predictability of the following word. Our study joins efforts from neurolinguistic and NLP fields to understand human information processing during reading to potentially improve NLP algorithms.

Fading of collective attention shapes the evolution of linguistic variants.

Language change involves the competition between alternative linguistic forms. The spontaneous evolution of these forms typically results in monotonic growths or decays, such as in winner-take-all attractor behaviors. In the case of the Spanish past subjunctive, the spontaneous evolution of its two competing forms (ending in -ra and -se) was perturbed by the appearance of the Royal Spanish Academy in 1713, which enforced the spelling of both forms as perfectly interchangeable variants, at a moment in which the -ra form was predominant. Time series extracted from a massive corpus of books reveal that this regulation in fact produced a transient renewed interest for the old form -se which, once faded, left the -ra again as the dominant form up to the present day. We show that time series are successfully explained by a two-dimensional linear model that integrates an imitative and a novelty component. The model reveals that the temporal scale over which collective attention fades is in inverse proportion to the verb frequency. The integration of the two basic mechanisms of imitation and attention to novelty allows us to understand diverse competing objects, with lifetimes that range from hours for memes and news to decades for verbs, suggesting the existence of a general mechanism underlying cultural evolution.

Predicting Known Sentences: Neural Basis of Proverb Reading Using Non-parametric Statistical Testing and Mixed-Effects Models.

Predictions of future events play an important role in daily activities, such as visual search, listening, or reading. They allow us to plan future actions and to anticipate their outcomes. Reading, a natural, commonly studied behavior, could shed light over the brain processes that underlie those prediction mechanisms. We hypothesized that different mechanisms must lead predictions along common sentences and proverbs. The former ones are more based on semantic and syntactic cues, and the last ones are almost purely based on long-term memory. Here we show that the modulation of the N400 by Cloze-Task Predictability is strongly present in common sentences, but not in proverbs. Moreover, we present a novel combination of linear mixed models to account for multiple variables, and a cluster-based permutation procedure to control for multiple comparisons. Our results suggest that different prediction mechanisms are present during reading.

Language, gesture, and judgment: Children's paths to abstract geometry.

As infants, children are sensitive to geometry when recognizing objects or navigating through rooms; however, explicit knowledge of geometry develops slowly and may be unstable even in adults. How can geometric concepts be both so accessible and so elusive? To examine how implicit and explicit geometric concepts develop, the current study assessed, in 132 children (3-8 years old) while they played a simple geometric judgment task, three distinctive channels: children's choices during the game as well as the language and gestures they used to justify and accompany their choices. Results showed that, for certain geometric properties, children chose the correct card even if they could not express with words (or gestures) why they had made this choice. Furthermore, other geometric concepts were expressed and supported by gestures prior to their articulation in either choices or speech. These findings reveal that gestures and behavioral choices may reflect implicit knowledge and serve as a foundation for the development of geometric reasoning. Altogether, our results suggest that language alone might not be enough for expressing and organizing geometric concepts and that children pursue multiple paths to overcome its limitations, a finding with potential implications for primary education in mathematics.

Vocal effort modulates the motor planning of short speech structures.

Speech requires programming the sequence of vocal gestures that produce the sounds of words. Here we explored the timing of this program by asking our participants to pronounce, as quickly as possible, a sequence of consonant-consonant-vowel (CCV) structures appearing on screen. We measured the delay between visual presentation and voice onset. In the case of plosive consonants, produced by sharp and well defined movements of the vocal tract, we found that delays are positively correlated with the duration of the transition between consonants. We then used a battery of statistical tests and mathematical vocal models to show that delays reflect the motor planning of CCVs and transitions are proxy indicators of the vocal effort needed to produce them. These results support that the effort required to produce the sequence of movements of a vocal gesture modulates the onset of the motor plan.

Pupillary dynamics reveal computational cost in sentence planning.

This study investigated the computational cost associated with grammatical planning in sentence production. We measured people's pupillary responses as they produced spoken descriptions of depicted events. We manipulated the syntactic structure of the target by training subjects to use different types of sentences following a colour cue. The results showed higher increase in pupil size for the production of passive and object dislocated sentences than for active canonical subject-verb-object sentences, indicating that more cognitive effort is associated with more complex noncanonical thematic order. We also manipulated the time at which the cue that triggered structure-building processes was presented. Differential increase in pupil diameter for more complex sentences was shown to rise earlier as the colour cue was presented earlier, suggesting that the observed pupillary changes are due to differential demands in relatively independent structure-building processes during grammatical planning. Task-evoked pupillary responses provide a reliable measure to study the cognitive processes involved in sentence production.

Far transfer to language and math of a short software-based gaming intervention.

Executive functions (EF) in children can be trained, but it remains unknown whether training-related benefits elicit far transfer to real-life situations. Here, we investigate whether a set of computerized games might yield near and far transfer on an experimental and an active control group of low-SES otherwise typically developing 6-y-olds in a 3-mo pretest-training-posttest design that was ecologically deployed (at school). The intervention elicits transfer to some (but not all) facets of executive function. These changes cascade to real-world measures of school performance. The intervention equalizes academic outcomes across children who regularly attend school and those who do not because of social and familiar circumstances.

Freedom and rules in human sequential performance: a refractory period in eye-hand coordination.

In action sequences, the eyes and hands ought to be coordinated in precise ways. The mechanisms governing the architecture of encoding and action of several effectors remain unknown. Here we study hand and eye movements in a sequential task in which letters have to be typed while they move down through the screen. We observe a strict refractory period of about 200 ms between the initiation of manual and eye movements. Subjects do not initiate a saccade just after typing and do not type just after making the saccade. This refractory period is observed ubiquitously in every subject and in each step of the sequential task, even when keystrokes and saccades correspond to different items of the sequence-for instance when a subject types a letter that has been gazed at in a preceding fixation. These results extend classic findings of dual-task paradigms, of a bottleneck tightly locked to the response selection process, to unbounded serial routines. Interestingly, while the bottleneck is seemingly inevitable, better performing subjects can adopt a strategy to minimize the cost of the bottleneck, overlapping the refractory period with the encoding of the next item in the sequence.

Choosing in freedom or forced to choose? Introspective blindness to psychological forcing in stage-magic.

We investigated an individual ability to identify whether choices were made freely or forced by external parameters. We capitalized on magical setups where the notion of psychological forcing constitutes a well trodden path. In live stage magic, a magician guessed cards from spectators while inquiring how freely they thought they had made the choice. Our data showed a marked blindness in the introspection of free choice. Spectators assigned comparable ratings when choosing the card that the magician deliberately forced them compared to any other card, even in classical forcing, where the magician literally handles a card to the participant This observation was paralleled by a laboratory experiment where we observed modest changes in subjective reports by factors with drastic effect in choice. Pupil dilatation, which is known to tag slow cognitive events related to memory and attention, constitutes an efficient fingerprint to index subjective and objective aspects of choice.

Extension of mental preparation positively affects motor imagery as compared to motor execution: a functional near-infrared spectroscopy study.

Motor imagery (MI) is widely used to study cognitive action control. Although, the neural simulation theory assumes that MI and motor execution (ME) share many common features, the extent of similarity and whether it spreads into the preparation phase is still under investigation. Here we asked, whether an extension of physiological mental preparation has a comparable effect on MI and ME. Data were recorded using wireless functional near-infrared spectroscopy (fNIRS) in a two-stage task design where subjects were cued with or without preparatory stimuli to either execute or imagine complex sequential thumb-finger tasks. The main finding is that the extended mental preparation has a significant positive effect on oxy-hemoglobin (∆[O(2)Hb]) in response to MI, which is proportionally larger as that found in response to ME. Furthermore, fNIRS was capable to discriminate within each task whether it was preceded by preparatory stimuli or not. Transition from mental preparation to actual performance (ME or MI) was reflected by a dip of the fNIRS signal presumably related to underlying cortical processes changing between preparation and task performance. Statistically significant main effects of 'Preparation' and 'Task' showed that ∆[O(2)Hb] during preparation was preparation-specific, i.e., positively affected by the presence of preparatory stimuli, whereas during task performance ∆[O(2)Hb] was both preparation- and task-specific, i.e., additionally affected by the task mode. These results are particularly appealing from a practical point of view for making use of MI in neuroscientific applications. Especially neurorehabilitation and neural interfaces may benefit from utilizing positive interactions between mental preparation and MI performance.

Understanding inverse oxygenation responses during motor imagery: a functional near-infrared spectroscopy study.

Motor imagery (MI) is described as the mental rehearsal of voluntary movements. We used wireless functional near-infrared spectroscopy (fNIRS) recorded over secondary motor areas during performance of MI and motor execution (ME) in 11 healthy subjects, who either executed or imagined two drawing tasks differing in shape and frequency, i.e. simple (circle, 0.2 Hz) and complex (curved shape, 0.333 Hz). At the group level, results showed that fNIRS is capable of discriminating between the task mode, i.e. MI vs. ME, and the task complexity, i.e. simple vs. complex. At the single-subject level, we observed inverse oxygenation responses, i.e. a decrease in Δ[O(2) Hb] and/or increase in Δ[HHb]. These inverse responses only occurred during MI tasks and were highly correlated, in the first place, with task mode, and secondly with task complexity. Inverse Δ[O(2) Hb] responses are likely to reflect individual differences in performance-related signals and may contribute to the commonly observed inter-subject variability in fNIRS measurements. As MI is now widely used as a mental task in neurorehabilitative applications, the resulting oxygenation pattern may be of use for future developments. For this programme to be successful it is crucial to determine the sources of inter-subject variability. Our study presents a first effort in this direction, indicating that MI-related inverse Δ[O(2) Hb] responses are correlated, first, with task mode and, secondly, with task complexity.

Looking at Breakout: urgency and predictability direct eye events.

We investigated the organization of eye-movement classes in a natural and dynamical setup. To mimic the goals and objectives of the natural world in a controlled environment, we studied eye-movements while participants played Breakout, an old Atari game which remains surprisingly entertaining, often addictive, in spite of its graphic and structural simplicity. Our results show that eye-movement dynamics can be explained in terms of simple principles of moments of prediction and urgency of action. We observed a consistent anticipatory behavior (gaze was directed ahead of ball trajectory) except during the moment in which the ball bounced either in the walls, or in the paddle. At these moments, we observed a refractory period during which there are no blinks and saccades. Saccade delay caused the gaze to fall behind the ball. This pattern is consistent with a model by which participants postpone saccades at the bounces while predicting the ball trajectory and subsequently make a catch-up saccade directed to a position which anticipates ball trajectory. During bounces, trajectories were smooth and curved interpolating the V-shape function of the ball with minimal acceleration. These results pave the path to understand the taxonomy of eye-movements on natural configurations in which stimuli and goals switch dynamically in time.