Principles of Integrated Cognitive Training for Executive Attention: Application to an Instrumental Skill.

One effective cognitive treatment is the rehabilitation of working memory (WM) using an integrated approach that targets the "executive attention" system. Recent neuroscientific literature has revealed that treatment efficacy depends on the presence of various features, such as adaptivity, empathy, customization, avoidance of automatism and stereotypies, and alertness activation. Over the last two decades, an Integrated Cognitive Training (ICT) protocol has been proposed and developed; ICT takes the above-mentioned features and existing literature into account, and has been used to promote the development of reading skills. ICT has been employed in several clinical settings and involves stimulation of a specific deteriorated system (e.g., reading) and the improvement of executive attention components, thus also increasing working memory capacity. In this context, we present two experiments. In Experiment 1, participants diagnosed with dyslexia (aged between 8 and 14 years) underwent two ICT sessions a week, with home supplements, for a duration of 7 months. The participants showed a significant improvement in the reading speed of text, words, and non-words, and in the reading accuracy of text and non-words. In Experiment 2, we replicated Experiment 1, but included a comparison between two groups (experimental group vs. control group) of young participants with diagnosis of dyslexia. The experimental group was subjected to 18 ICT sessions twice a week and with home supplements, using the same protocol as in Experiment 1. The control group was entrusted to the protocol of compensatory tools and dispense/helping procedures provided by the scholastic Personalized Educational Plan. After training, the experimental group gained about 0.5 syllables per second in text reading, and a marked decrease in error rate. The control group showed no significant improvement in reading skills after the same period. Moreover, the improvement observed in the experimental group remained stable 4 months after ICT had ended. The results of these two experiments support the efficacy of the integrated ICT protocol in improving reading skills in children with dyslexia and its sustained effect.

Spatial Stability of Functional Networks: A Measure to Assess the Robustness of Graph-Theoretical Metrics to Spatial Errors Related to Brain Parcellation.

There is growing interest in studying human brain connectivity and in modelling the brain functional structure as a network. Brain network creation requires parcellation of the cerebral cortex to define nodes. Parcellation might be affected by possible errors due to inter- and intra-subject variability as a consequence of brain structural and physiological characteristics and shape variations related to ageing and diseases, acquisition noise, and misregistration. These errors could induce a knock-on effect on network measure variability. The aim of this study was to investigate spatial stability, a measure of functional connectivity variations induced by parcellation errors. We simulated parcellation variability with random small spatial changes and evaluated its effects on twenty-seven graph-theoretical measures. The study included subjects from three public online datasets. Two brain parcellations were performed using FreeSurfer with geometric atlases. Starting from these, 100 new parcellations were created by increasing the area of 30% of parcels, reducing the area of neighbour parcels, with a rearrangement of vertices. fMRI data were filtered with linear regression, CompCor, and motion correction. Adjacency matrices were constructed with 0.1, 0.2, 0.3, and 0.4 thresholds. Differences in spatial stability between datasets, atlases, and threshold were evaluated. The higher spatial stability resulted for Characteristic-path-length, Density, Transitivity, and Closeness-centrality, and the lower spatial stability resulted for Bonacich and Katz. Multivariate analysis showed a significant effect of atlas, datasets, and thresholds. Katz and Bonacich centrality, which was subject to larger variations, can be considered an unconventional graph measure, poorly implemented in the clinical field and not yet investigated for reliability assessment. Spatial stability (SS) is affected by threshold, and it decreases with increasing threshold for several measures. Moreover, SS seems to depend on atlas choice and scanning parameters. Our study highlights the importance of paying close attention to possible parcellation-related spatial errors, which may affect the reliability of functional connectivity measures.

Robotic Technology in Pediatric Neurorehabilitation. A Pilot Study of Human Factors in an Italian Pediatric Hospital.

The introduction of robotic neurorehabilitation among the most recent technologies in pediatrics represents a new opportunity to treat pediatric patients. This study aims at evaluating the response of physiotherapists, patients and their parents to this new technology. The study considered the outcomes of technological innovation in physiotherapists (perception of the workload, satisfaction), as well as that in patients and their parents (quality of life, expectations, satisfaction) by comparing the answers to subjective questionnaires of those who made use of the new technology with those who used the traditional therapy. A total of 12 workers, 46 patients and 47 parents were enrolled in the study. Significant differences were recorded in the total workload score of physiotherapists who use the robotic technology compared with the traditional therapy (p < 0.001). Patients reported a higher quality of life and satisfaction after the use of the robotic neurorehabilitation therapy. The parents of patients undergoing the robotic therapy have moderately higher expectations and satisfaction than those undergoing the traditional therapy. In this pilot study, the robotic neurorehabilitation technique involved a significant increase in the patients' and parents' expectations. As it frequently happens in the introduction of new technologies, physiotherapists perceived a greater workload. Further studies are needed to verify the results achieved.

The Number Interval Position Effect (NIPE) in the mental bisection of numerical intervals might reflect the influence of the decimal-number system on the Gaussian representations of numerosities: A combined developmental and computational-modeling study.

Healthy adults show typical error biases when they mentally bisect number intervals without exact calculations. For a given number interval length, the bisection bias is in fact modulated by the position that the interval occupies within a ten. For intervals positioned at the beginning of tens the error bias is directed toward values that are higher than those of the true interval midpoint whereas for intervals at the end of tens the direction of the error bias is reversed toward values that are lower than that of the true midpoint (Doricchi et al., 2009; Rotondaro et al., 2015). This effect has been defined Number Interval Position Effect (NIPE). The NIPE recurs over consecutive tens and it is not found when intervals are bisected through exact calculations. For this reasons we have hypothesized that the NIPE reflects the influence that the habit of counting in tens has on the neural representations of numerosities that humans share with other species. Here, in a developmental study we demonstrate that children from preschool to fifth-grade display a NIPE that is comparable to that of healthy adults. Then, through a computational-modeling study we investigated whether the NIPE might reflect specific patterns in the Gaussian representations of numerosities that are found in the parietal and pre-frontal neuronal populations of macaque monkeys and that underlie approximate numerosity estimations also in humans. The findings of computational simulations suggest that the NIPE might reflect the influence that the learning and use of the decimal numerical system has on the phylogenetically and ontogenetically older representation of numerosities that humans share with other species. These changes in the representation of numerosities have an influence on approximate numerical estimations even when these, like in the case of the mental bisection of number intervals, are elicited by numerical symbols or words.

Time-frequency analyses of reaction times and theta/beta EEG ratio in pediatric patients with traumatic brain injury: A preliminary study.

PURPOSE: The literature on patients with attention deficit reports peculiar reaction time (RT) oscillation at very low frequencies (VLFO=0.06-0.2 Hz). The data were explained as default mode network (DMN) intrusion in goal-oriented activity. The present study investigates whether a pattern of recurrent lapses in attention can be detected in TBI patients and whether VLFO can be generalized to the sustained attention deficit, regardless of etiology. METHODS: Groups of pediatric TBIs and healthy controls performed four attentional tasks. RT and theta/beta timeseries were subjected to wavelet analyses. RESULTS: Significant high-power VLFOs were recorded in patient group performances but not in those of controls, both for RTs and theta/beta in all the tasks. CONCLUSION: This preliminary study suggests that central-midline theta/beta ratio could be considered a neurophysiological correlate of RT variability and that the general continuous goal-oriented activity can be cross-etiologically affected by recurrent lapses in attention regardless of the specific cognitive component involved.

Functional and Gait Assessment in Children and Adolescents Affected by Friedreich's Ataxia: A One-Year Longitudinal Study.

Friedreich's ataxia is the most common autosomal recessive form of neurodegenerative ataxia. We present a longitudinal study on the gait pattern of children and adolescents affected by Friedreich's ataxia using Gait Analysis and the Scale for the Assessment and Rating of Ataxia (SARA). We assessed the spectrum of changes over 12 months of the gait characteristics and the relationship between clinical and instrumental evaluations. We enrolled 11 genetically confirmed patients affected by Friedreich's ataxia in this study together with 13 normally developing age-matched subjects. Eight patients completed a 12-month follow-up under the same protocol. By comparing the gait parameters of Friedreich's ataxia with the control group, we found significant differences for some relevant indexes. In particular, the increased knee and ankle extension in stance revealed a peculiar biomechanical pattern, which correlated reliably with SARA Total, Gait and Sitting scores. The knee pattern showed its consistency also at the follow-up: Knee extension increased from 6.8±3.5° to -0.5±3.7° and was significantly correlated with the SARA total score. This feature anticipated the loss of the locomotor function in two patients. In conclusion, our findings demonstrate that the selective and segmental analysis of kinetic/kinematic features of ataxic gait, in particular the behavior of the knee, provides sensitive measures to detect specific longitudinal and functional alterations, more than the SARA scale, which however has proved to be a reliable and practical assessment tool. Functional outcomes measures integrated by instrumental evaluation increase their sensitivity, reliability and suitability for the follow-up of the disease progression and for the application in clinical trials and in rehabilitative programs.

The impact of vision on the dynamic characteristics of the gait: strategies in children with blindness.

Visually impaired persons present an atypical gait pattern characterized by slower walking speed, shorter stride length and longer time of stance. Three explanatory hypotheses have been advanced in the literature: balance deficit, lack of an anticipatory mechanisms and foot probing the ground. In the present study, we compared the three hypotheses by applying their predictions to gait analysis and posturography of blind children without neurological impairment and compared their performance with that of an age-matched control group. The gait analysis results documented that blind children presented reduced walking velocity and step length, increased step width and external rotation of the foot progression angle, reduced ground reaction force and ankle maximum angle, moment and power in late stance, increased head flexion, decreased thorax flexion and pelvis anteversion, compared with the control group. The posturographic analysis showed equal skill level between blind children and normally sighted children when they close their eyes. The results are consistent with only one of the three hypotheses: namely, they prove that blind children's gait is influenced only by the absence of visually driven anticipatory control mechanisms. Finally, rehabilitative recommendations for children with blindness are advanced in discussion.

Association between Attention and Heart Rate Fluctuations in Pathological Worriers.

Recent data suggests that several psychopathological conditions are associated with alterations in the variability of behavioral and physiological responses. Pathological worry, defined as the cognitive representation of a potential threat, has been associated with reduced variability of heart beat oscillations (i.e., decreased heart rate variability; HRV) and lapses of attention indexed by reaction times (RTs). Clinical populations with attention deficit show RTs oscillation around 0.05 and 0.01 Hz when performing a sustained attention task. We tested the hypothesis that people who are prone to worry do it in a predictable oscillating pattern revealed through recurrent lapses in attention and concomitant oscillating HRV. Sixty healthy young adults (50% women) were recruited: 30 exceeded the clinical cut-off on the Penn State Worry Questionnaire (PSWQ; High-Worry, HW); the remaining 30 constituted the Low-Worry (LW) group. After a diagnostic assessment, participants performed two 15-min sustained attention tasks, interspersed by a standardized worry-induction procedure. RTs, HRV and moods were assessed. The analyses of the frequency spectrum showed that the HW group presents a significant higher and constant peak of RTs oscillation around 0.01 Hz (period 100 s) after the induction of worry, in comparison with their baseline and with the LW group that was not responsive to the induction procedure. Physiologically, the induction significantly reduced high-frequency HRV and such reduction was associated with levels of self-reported worry. Results are coherent with the oscillatory nature of the default mode network (DMN) and further confirm an association between cognitive rigidity and autonomic nervous system inflexibility.

Test-retest reliability of graph metrics of resting state MRI functional brain networks: A review.

The employment of graph theory to analyze spontaneous fluctuations in resting state BOLD fMRI data has become a dominant theme in brain imaging studies and neuroscience. Analysis of resting state functional brain networks based on graph theory has proven to be a powerful tool to quantitatively characterize functional architecture of the brain and it has provided a new platform to explore the overall structure of local and global functional connectivity in the brain. Due to its increased use and possible expansion to clinical use, it is essential that the reliability of such a technique is very strongly assessed. In this review, we explore the outcome of recent studies in network reliability which apply graph theory to analyze connectome resting state networks. Therefore, we investigate which preprocessing steps may affect reproducibility the most. In order to investigate network reliability, we compared the test-retest (TRT) reliability of functional data of published neuroimaging studies with different preprocessing steps. In particular we tested influence of global signal regression, correlation metric choice, binary versus weighted link definition, frequency band selection and length of time-series. Statistical analysis shows that only frequency band selection and length of time-series seem to affect TRT reliability. Our results highlight the importance of the choice of the preprocessing steps to achieve more reproducible measurements.

Time to boundary function to assess upright stance in blind children.

The goal of this preliminary study was to assess the difference in postural stability between blind and sighted children using the Time to Boundary function (TtB). The experiment was conducted in twelve children (6-12 yrs), six of them had no visual impairment, and other six had congenital blindness. The participants stood on RotoBit force plate maintaining upright stance in static conditions. Each blind subject executed the task three times, each sighted subject executed the task six times, three with eyes closed (EC) and three with eyes open (EO). For all subjects each repetition lasted 30 s. The Centre of Pressure (CoP) coordinates, extracted directly from a force plate, are used to calculate four classical parameters (sway path, sway area, mean amplitude and mean frequency) and a predictive variable called Time to Boundary (TtB). The latter is the time it would take the CoP, given its instantaneous trajectory, to contact a stability boundary. Descriptive statistics were calculated for all parameters. Twoway ANOVA test was done considering the visual condition (EO, EC, BLIND) and the repetitions (RP) as a factor. In the first comparison (BLIND/EO) the results showed significant difference for all the parameters except for TtB. In the second comparison (BLIND/EC) the results showed significant difference only for TtB. In the third comparison (EO/EC) the results showed significant difference for all the calculated parameters. Therefore the TtB would be used to asses the postural control in children with blindness.

Developmental lag of visuospatial attention in Duchenne muscular dystrophy.

Children with Duchenne muscular dystrophy (DMD) present a specific deficit of voluntary attention but to date there has been no clear characterization of their attentional skills. The present study investigated the hypothesis that DMD patients present deficits of both voluntary and automatic visuospatial attention systems and that their performance could be equivalent to that of younger healthy males. Twenty males (mean age 10 years) with diagnosis of DMD, 20 age-matched healthy males (10 years 3 months) and 20 healthy younger males (7 years 6 months) were required to perform two visuospatial attention tasks: voluntary and automatic. In the voluntary task, the performance of the DMD group was significantly worse than that of the age-matched group, and equal to that of the younger controls. In the automatic attention task also, the performance of the DMD patients was less efficient than that of the age-matched controls and equal to that of the younger children. This study supports the previous report of voluntary attention deficit in DMD and extends the evidence to include also an automatic attention system deficit. The development level of attention in DMD patients is below that expected for their age and corresponds to a delay of about three years.

Brain network involved in visual processing of movement stimuli used in upper limb robotic training: an fMRI study.

BACKGROUND: The potential of robot-mediated therapy and virtual reality in neurorehabilitation is becoming of increasing importance. However, there is limited information, using neuroimaging, on the neural networks involved in training with these technologies. This study was intended to detect the brain network involved in the visual processing of movement during robotic training. The main aim was to investigate the existence of a common cerebral network able to assimilate biological (human upper limb) and non-biological (abstract object) movements, hence testing the suitability of the visual non-biological feedback provided by the InMotion2 Robot. METHODS: A visual functional Magnetic Resonance Imaging (fMRI) task was administered to 22 healthy subjects. The task required observation and retrieval of motor gestures and of the visual feedback used in robotic training. Functional activations of both biological and non-biological movements were examined to identify areas activated in both conditions, along with differential activity in upper limb vs. abstract object trials. Control of response was also tested by administering trials with congruent and incongruent reaching movements. RESULTS: The observation of upper limb and abstract object movements elicited similar patterns of activations according to a caudo-rostral pathway for the visual processing of movements (including specific areas of the occipital, temporal, parietal, and frontal lobes). Similarly, overlapping activations were found for the subsequent retrieval of the observed movement. Furthermore, activations of frontal cortical areas were associated with congruent trials more than with the incongruent ones. CONCLUSIONS: This study identified the neural pathway associated with visual processing of movement stimuli used in upper limb robot-mediated training and investigated the brain's ability to assimilate abstract object movements with human motor gestures. In both conditions, activations were elicited in cerebral areas involved in visual perception, sensory integration, recognition of movement, re-mapping on the somatosensory and motor cortex, storage in memory, and response control. Results from the congruent vs. incongruent trials revealed greater activity for the former condition than the latter in a network including cingulate cortex, right inferior and middle frontal gyrus that are involved in the go-signal and in decision control. Results on healthy subjects would suggest the appropriateness of an abstract visual feedback provided during motor training. The task contributes to highlight the potential of fMRI in improving the understanding of visual motor processes and may also be useful in detecting brain reorganisation during training.

Representation of grammatical properties of Italian verbs in the mental lexicon.

The present study focuses on the representation of verbs in the Italian mental lexicon and investigates some grammatical properties: inflectional class, mood, tense, and person. Two experiments based on free recall of single inflected forms are reported. The patterns of recall and error are taken as evidence for the grammatical and morphological information exploited in the access to the verb forms. The pattern of results provides support for the hypothesis that in the mental lexicon the information about conjugation and mood is an organizational criterion for the representation of verbal forms. An interaction between mood and conjugation, likely to arise from the difference in productivity between conjugations, is also observed.

Lexical representations of written nouns and verbs in Italian.

This study investigates the differences in the input representations of verbs and nouns in the Italian mental lexicon. One visual lexical decision experiment in which the stem homograph effect (Laudanna, Badecker, and Caramazza, 1989) was evaluated on noun and verb targets is reported. Strong inhibitory effects on verb targets preceded by stem homographs relative to nonhomographic word pairs were found. The effects on verb targets were also much more reliable than the effects on noun targets. The pattern of results provides support for the hypothesis that noun and verbs are differently represented in the orthographic input lexicon.