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BackgroundStroke is a debilitating disease affecting millions of people worldwide. Despite the survival rate has significantly increased over the years, many stroke survivors are left with severe impairments impacting their quality of life. Rehabilitation programs have proved to be successful in improving the recovery process. However, a reliable model of sensorimotor recovery and a clear identification of predictive markers of rehabilitation-induced recovery are still needed. This article introduces the cross-modality protocols designed to investigate the rehabilitation treatment’s effect in a group of stroke survivors.Methods/designA total of 75 stroke patients, admitted at the IRCCS San Camillo rehabilitation Hospital in Venice (Italy), will be included in this study. Here, we describe the rehabilitation programs, clinical, neuropsychological, and physiological/imaging [including electroencephalography (EEG), transcranial magnetic stimulation (TMS), and magnetic resonance imaging (MRI) techniques] protocols set up for this study. Blood collection for the characterization of predictive biological biomarkers will also be taken. Measures derived from data acquired will be used as candidate predictors of motor recovery.Discussion/summaryThe integration of cutting-edge physiological and imaging techniques, with clinical and cognitive assessment, dose of rehabilitation and biological variables will provide a unique opportunity to define a predictive model of recovery in stroke patients. Taken together, the data acquired in this project will help to define a model of rehabilitation induced sensorimotor recovery, with the final aim of developing personalized treatments promoting the greatest chance of recovery of the compromised functions.

The authors investigate the influence of brain injury (strokes) on the criticality of neural dynamics using directly measured connectomes and whole-brain models. They show that lesions engender a sub-critical state that recovers over time in parallel with behavior.

Andrea Zangrossi et al. analyze individual variability in eye movements when healthy participants view images of natural scenes. Their results suggest that eye movement patterns can be summarized by three principle components, and depend more on subjects’ intrinsic characteristics than the visual contents of the scene.

Abstract Multivariate prediction of human behavior from resting state data is gaining increasing popularity in the neuroimaging community, with far-reaching translational implications in neurology and psychiatry. However, the high dimensionality of neuroimaging data increases the risk of overfitting, calling for the use of dimensionality reduction methods to build robust predictive models. In this work, we assess the ability of four well-known dimensionality reduction techniques to extract relevant features from resting state functional connectivity matrices of stroke patients, which are then used to build a predictive model of the associated deficits based on cross-validated regularized regression. In particular, we investigated the prediction ability over different neuropsychological scores referring to language, verbal memory, and spatial memory domains. Principal Component Analysis (PCA) and Independent Component Analysis (ICA) were the two best methods at extracting representative features, followed by Dictionary Learning (DL) and Non-Negative Matrix Factorization (NNMF). Consistent with these results, features extracted by PCA and ICA were found to be the best predictors of the neuropsychological scores across all the considered cognitive domains. For each feature extraction method, we also examined the impact of the regularization method, model complexity (in terms of number of features that entered in the model) and quality of the maps that display predictive edges in the resting state networks. We conclude that PCA-based models, especially when combined with L1 (LASSO) regularization, provide optimal balance between prediction accuracy, model complexity, and interpretability.

Abstract Individuals with Down syndrome (DS) present reduced basic numerical skills, which have a negative impact on everyday numeracy and mathematical learning. Here, we evaluated the efficacy of the adaptive (non-commercial) computerized game “The Number Race” in improving basic numerical skills in children with DS. The experimental group (EG; N = 30, M age-in-months 118, range 70–149) completed a training playing with “The Number Race”, whereas children in the control group (CG; N = 31, M age-in-months 138, range 76–207) worked with software aiming at improving their reading skills. The training lasted 10 weeks with two weekly sessions of 20–30 min each. We assessed both groups’ numerical and reading skills before and immediately after the end of the training, as well as at a 3-months follow-up. We found weak evidence for post-training groups differences in terms of overall numeracy score. However, the EG displayed substantial improvements in specific numerical skills and in mental calculation, which were maintained over time, and no improvement in reading. Conversely, the CG showed improvements in their reading skills as well as in number skills but to a lesser extent compared to the EG. Overall, “The Number Race” appears as a suitable tool to improve some aspects of numeracy in DS.

Abstract Numerosity perception is thought to be foundational to mathematical learning, but its computational bases are strongly debated. Some investigators argue that humans are endowed with a specialized system supporting numerical representations; others argue that visual numerosity is estimated using continuous magnitudes, such as density or area, which usually co-vary with number. Here we reconcile these contrasting perspectives by testing deep neural networks on the same numerosity comparison task that was administered to human participants, using a stimulus space that allows the precise measurement of the contribution of non-numerical features. Our model accurately simulates the psychophysics of numerosity perception and the associated developmental changes: discrimination is driven by numerosity, but non-numerical features also have a significant impact, especially early during development. Representational similarity analysis further highlights that both numerosity and continuous magnitudes are spontaneously encoded in deep networks even when no task has to be carried out, suggesting that numerosity is a major, salient property of our visual environment.

The number of elements in a small set of items is appraised in a fast and exact manner, a phenomenon called subitizing. In contrast, humans provide imprecise responses when comparing larger numerosities, with decreasing precision as the number of elements increases. Estimation is thought to rely on a dedicated system for the approximate representation of numerosity. While previous behavioral and neuroimaging studies associate subitizing to a domain-general system related to object tracking and identification, the nature of small numerosity processing is still debated. We investigated the neural processing of numerosity across subitizing and estimation ranges by examining electrophysiological activity during the memory retention period in a delayed numerical match-to-sample task. We also assessed potential differences in the neural signature of numerical magnitude in a fully non-symbolic or cross-format comparison. In line with behavioral performance, we observed modulation of parietal-occipital neural activity as a function of numerosity that differed in two ranges, with distinctive neural signatures of small numerosities showing clear similarities with those observed in visuospatial working memory tasks. We also found differences in neural activity related to numerical information in anticipation of single vs. cross-format comparison, suggesting a top-down modulation of numerical processing. Finally, behavioral results revealed enhanced performance in the mixed-format conditions and a significant correlation between task performance and symbolic mathematical skills. Overall, we provide evidence for distinct mechanisms related to small and large numerosity and differences in numerical encoding based on task demands.

Embodied and grounded cognition theories state that cognitive processing is built upon sensorimotor systems. In the context of numerical cognition, support to this framework comes from the interactions between numerical processing and the hand actions of reaching and grasping documented in skilled adults. Accordingly, mechanisms for the processing of object size and location during reach and grasp actions might scaffold the development of mental representations of numerical magnitude. The present study exploited motor adaptation to test the hypothesis of a functional overlap between neurocognitive mechanisms of hand action and numerical processing. Participants performed repetitive grasping of an object, repetitive pointing, repetitive tapping, or passive viewing. Subsequently, they performed a symbolic number comparison task. Importantly, hand action and number comparison were functionally and temporally dissociated, thereby minimizing context-based effects. Results showed that executing the action of pointing slowed down the responses in number comparison. Moreover, the typical distance effect (faster responses for numbers far from the reference as compared to close ones) was not observed for small numbers after pointing, while it was enhanced by grasping. These findings confirm the functional link between hand action and numerical processing, and suggest new hypotheses on the role of pointing as a meaningful gesture in the development and embodiment of numerical skills.

The rehabilitation of motor deficits following stroke relies on both sensorimotor and cognitive abilities, thereby involving large-scale brain networks. However, few studies have investigated the integration between motor and cognitive domains, as well as its neuroanatomical basis. In this retrospective study, upper limb motor responsiveness to technology-based rehabilitation was examined in a sample of 29 stroke patients (18 with right and 11 with left brain damage). Pretreatment sensorimotor and attentional abilities were found to influence motor recovery. Training responsiveness increased as a function of the severity of motor deficits, whereas spared attentional abilities, especially visuospatial attention, supported motor improvements. Neuroanatomical analysis of structural lesions and white matter disconnections showed that the poststroke motor performance was associated with putamen, insula, corticospinal tract, and frontoparietal connectivity. Motor rehabilitation outcome was mainly associated with the superior longitudinal fasciculus and partial involvement of the corpus callosum. The latter findings support the hypothesis that motor recovery engages large-scale brain networks that involve cognitive abilities and provides insight into stroke rehabilitation strategies.

Contemporary neuroscience has embraced network science and dynamical systems to study the complex and self-organized structure of the human brain. Despite the developments in non-invasive neuroimaging techniques, a full understanding of the directed interactions in whole brain networks, referred to as effective connectivity, as well as their role in the emergent brain dynamics is still lacking. The main reason is that estimating brain connectivity requires solving a formidable large-scale inverse problem from indirect and noisy measurements. Building on the dynamic causal modelling framework, the present study offers a novel method for estimating whole-brain effective connectivity from resting-state functional magnetic resonance data. To this purpose sparse estimation methods are adapted to infer the parameters of our novel model, which is based on a linearized, region-specific haemodynamic response function. The resulting algorithm, referred to as sparse DCM, is shown to compare favorably with state-of-the art methods when tested on both synthetic and real data. We also provide a graph-theoretical analysis on the whole-brain effective connectivity estimated using data from a cohort of healthy individuals, which reveals properties such as asymmetry in the connectivity structure as well as the different roles of brain areas in favoring segregation or integration.

One of the most rapidly advancing areas of deep learning research aims at creating models that learn to disentangle the latent factors of variation from a data distribution. However, modeling joint probability mass functions is usually prohibitive, which motivates the use of conditional models assuming that some information is given as input. In the domain of numerical cognition, deep learning architectures have successfully demonstrated that approximate numerosity representations can emerge in multi-layer networks that build latent representations of a set of images with a varying number of items. However, existing models have focused on tasks requiring to conditionally estimate numerosity information from a given image. Here, we focus on a set of much more challenging tasks, which require to conditionally generate synthetic images containing a given number of items. We show that attention-based architectures operating at the pixel level can learn to produce well-formed images approximately containing a specific number of items, even when the target numerosity was not present in the training distribution.

English serves as today’s lingua franca, a role not eased by the inconsistency of its orthography. Indeed, monolingual readers of more consistent orthographies such as Italian or German learn to read more quickly than monolingual English readers. Here, we assessed whether long-lasting bilingualism would mitigate orthography-specific differences in reading speed and whether the order in which orthographies with a different regularity are learned matters. We studied high-proficiency Italian-English and English-Italian bilinguals, with at least 20 years of intensive daily exposure to the second language and its orthography and we simulated sequential learning of the two orthographies with the CDP++ connectionist model of reading. We found that group differences in reading speed were comparatively bigger with Italian stimuli than with English stimuli. Furthermore, only Italian bilinguals took advantage of a blocked presentation of Italian stimuli compared to when stimuli from both languages were presented in mixed order, suggesting a greater ability to keep language-specific orthographic representations segregated. These findings demonstrate orthographic constraints on bilingual reading, whereby the level of consistency of the first learned orthography affects later learning and performance on a second orthography. The computer simulations were consistent with these conclusions.

Stroke causes behavioral deficits in multiple cognitive domains and there is a growing interest in predicting patient performance from neuroimaging data using machine learning techniques. Here, we investigated a deep learning approach based on convolutional neural networks (CNNs) for predicting the severity of language disorder from 3D lesion images from magnetic resonance imaging (MRI) in a heterogeneous sample of stroke patients. CNN performance was compared to that of conventional (shallow) machine learning methods, including ridge regression (RR) on the images’ principal components and support vector regression. We also devised a hybrid method based on re-using CNN’s high-level features as additional input to the RR model. Predictive accuracy of the four different methods was further investigated in relation to the size of the training set and the level of redundancy across lesion images in the dataset, which was evaluated in terms of location and topological properties of the lesions. The Hybrid model achieved the best performance in most cases, thereby suggesting that the high-level features extracted by CNNs are complementary to principal component analysis features and improve the model’s predictive accuracy. Moreover, our analyses indicate that both the size of training data and image redundancy are critical factors in determining the accuracy of a computational model in predicting behavioral outcome from the structural brain imaging data of stroke patients.

Unilateral brain damage following stroke frequently hampers the processing of contralesional space. Whether and how it also affects the processing of stimuli appearing on the same side of the lesion is still poorly understood. Three main alternative hypotheses have been proposed, namely that ipsilesional processing is functionally (i) hyperefficient, (ii) impaired, or (iii) spared. Here, we investigated ipsilesional space awareness through a computerized paradigm that exploits a manipulation of concurrent information processing demands (i.e., multitasking). Twelve chronic right-hemisphere stroke patients with a total lack of awareness for the contralesional side of space were administered a task that required the spatial monitoring of two locations within the ipsilesional hemispace. Targets were presented immediately to the right of a central fixation point (3° eccentricity), or farther to the right toward the screen edge (17° eccentricity), or on both locations. Response to target position occurred either in isolation or while performing a concurrent visual or auditory task. Results showed that most errors occurred when two targets were simultaneously presented and patients were faced with additional task demands (in the visual or auditory modalities). In the context of concurrent visual load, ipsilesional targets presented at the rightmost location were omitted more frequently than those presented closer to fixation. This pattern qualifies ipsilesional processing in right-hemisphere stroke patients as functionally impaired, arguing against the notion of ipsilesional hyperperformance, especially when under visual load.

The ability to compare the numerical magnitude of symbolic numbers represents a milestone in the development of numerical skills. However, it remains unclear how basic numerical abilities contribute to the understanding of symbolic magnitude and whether the impact of these abilities may vary when symbolic numbers are presented as number words (e.g., “six vs. eight”) vs. Arabic numbers (e.g., 6 vs. 8). In the present study on preschool children, we show that comparison of number words is related to cardinality knowledge whereas the comparison of Arabic digits is related to both cardinality knowledge and the ability to spatially map numbers. We conclude that comparison of symbolic numbers in preschool children relies on multiple numerical skills and representations, which can be differentially weighted depending on the presentation format. In particular, the spatial arrangement of digits on the number line seems to scaffold the development of a “spatial route” to understanding the exact magnitude of numerals.