Dual Cross-Linked Stimuli-Responsive Alginate-Based Hydrogels.

Sodium alginate with different molecular weights (55, 170, and 320 kg mol-1) were chemically modified by grafting methacrylic moieties onto the hydroxyl groups of the alginate backbone. The methacrylation was optimized to obtain different degrees of modification. Chemically cross-linked hydrogels were obtained following UV-light irradiation in the presence of a photoinitiator. The swelling behavior and the mechanical properties were observed to depend on both the degree of methacrylation and the alginate molecular weight. Due to the chain entanglement present in high-viscosity sodium alginate, lower degrees of modification were required to tune the hydrogel properties. Moreover, in the presence of Ca2+, secondary cross-linking was introduced by the coordination of the alginate guluronate moieties with the Ca2+ ions. The addition of this secondary cross-linking caused fast volume shrinkage and a reinforcement of the mechanical properties. The secondary cross-linking was reversible, and the hydrogels regained their original shape for at least three cycles. Additionally, the dual cross-linked network can be used to induce adhesion between hydrogels and serve as a building block for self-folding actuators.

Writing letters in two graphic systems: Behavioral and neural correlates in Latin-Arabic biscripters.

Biscriptuality is the ability to read and write using two scripts. Despite the increasing number of biscripters, this phenomenon remains poorly understood. Here, we focused on investigating graphomotor processing in French-Arabic biscripters. We chose the French and Arabic alphabets because they have comparable visuospatial complexity and linguistic features, but differ dramatically in their graphomotor characteristics. In a first experiment we describe the graphomotor features of the two alphabets and showed that while Arabic and Latin letters are produced with the same velocity and fluency, Arabic letters require more pen lifts, contain more right-to-left strokes and clockwise curves, and take longer to write than Latin letters. These results suggest that Arabic and Latin letters are produced via different motor patterns. In a second experiment we used functional magnetic resonance imaging to ask whether writing the two scripts relies upon partially distinct or fully overlapping neural networks, and whether the elements of the previously described handwriting network are recruited to the same extent by the two scripts. We found that both scripts engaged the so-called "writing network", but that within the network, Arabic letters recruited the left superior parietal lobule (SPL) and the left primary motor cortex (M1) more strongly than Latin letters. Both regions have previously been identified as holding scale-invariant representations of letter trajectories. Arabic and Latin letters also activated distinct regions that do not belong to the writing network. Complementary analyses indicate that the differences observed between scripts at the neural level could be driven by the specific graphomotor features of each script. Overall, our results indicate that particular features of the practiced scripts can lead to different motor organization at both the behavioral and brain levels in biscripters.

The Neurological Basis of Developmental Dyslexia and Related Disorders: A Reappraisal of the Temporal Hypothesis, Twenty Years on.

In a now-classic article published a couple of decades ago (Brain, 2000; 123: 2373-2399), I proposed an "extended temporal processing deficit hypothesis of dyslexia", suggesting that a deficit in temporal processing could explain not only language-related peculiarities usually noticed in dyslexic children, but also a wider range of symptoms related to impaired processing of time in general. In the present review paper, I will revisit this "historical" hypothesis both in the light of a new clinical perspective, including the central yet poorly explained notion of comorbidity, and also taking a new look at the most recent experimental work, mainly focusing on brain imaging data. First, consistent with daily clinical practice, I propose to distinguish three groups of children who fail to learn to read, of fairly equal occurrence, who share the same initial presentation (difficulty in mastering the rules of grapheme-phoneme correspondence) but with differing associated signs and/or comorbid conditions (language disorders in the first group, attentional deficits in the second one, and motor coordination problems in the last one), thus suggesting, at least in part, potentially different triggering mechanisms. It is then suggested, in the light of brain imaging information available to date, that the three main clinical presentations/associations of cognitive impairments that compromise reading skills acquisition correspond to three distinct patterns of miswiring or "disconnectivity" in specific brain networks which have in common their involvement in the process of learning and their heavy reliance on temporal features of information processing. With reference to the classic temporal processing deficit of dyslexia and to recent evidence of an inability of the dyslexic brain to achieve adequate coupling of oscillatory brain activity to the temporal features of external events, a general model is proposed according to which a common mechanism of temporal uncoupling between various disconnected-and/or mis-wired-processors may account for distinct forms of specific learning disorders, with reading impairment being a more or less constant feature. Finally, the potential therapeutic implications of such a view are considered, with special emphasis on methods seeking to enhance cross-modal connectivity between separate brain systems, including those using rhythmic and musical training in dyslexic patients.

The handwriting brain in middle childhood.

While the brain network supporting handwriting has previously been defined in adults, its organization in children has never been investigated. We compared the handwriting network of 23 adults and 42 children (8- to 11-year-old). Participants were instructed to write the alphabet, the days of the week, and to draw loops while being scanned. The handwriting network previously described in adults (five key regions: left dorsal premotor cortex, superior parietal lobule (SPL), fusiform and inferior frontal gyri, and right cerebellum) was also strongly activated in children. The right precentral gyrus and the right anterior cerebellum were more strongly activated in adults than in children, while the left fusiform gyrus (FuG) was more strongly activated in children than in adults. Finally, we found that, contrary to adults, children recruited prefrontal regions to complete the writing task. This constitutes the first comparative investigation of the neural correlates of writing in children and adults. Our results suggest that the network supporting handwriting is already established in middle childhood. They also highlight the major role of prefrontal regions in learning this complex skill and the importance of right precentral regions and cerebellum in the performance of automated handwriting.

Developmental dyslexia: A new look at clinical features and brain mechanisms.

Developmental dyslexia is the commonest "specific learning disorder" (DSM-5) or "developmental learning disorder with impairment in reading" (ICD-11). This impairment in reading acquisition is related to a defect in the installation of cognitive precursors necessary to master the grapheme-phoneme conversion. Its origin is largely genetic, but many environmental factors seem capable of modulating symptom intensity. Three types of presentation, roughly equal in occurrence, are useful to distinguish according to the associated disorders (language, attentional, and/or motor coordination), thus suggesting, at least in part, potentially different mechanisms at their origin. In adolescence and adulthood the clinical presentation tends to bear a more uniform pattern, covering a large range of severity depending on each person's ability to compensate for their deficit. Research has demonstrated dysfunction of specific brain areas during reading-related tasks (using fMRI), essentially in the left cerebral hemisphere, but also atypical patterns of connectivity (using diffusion imaging), further supplemented by functional connectivity studies at rest. The current therapeutic recommendations emphasize the need for multidisciplinary care, giving priority, depending on the clinical form, to the language, psychomotor, or neuropsychologic aspects of rehabilitation. Various training methods whose effectiveness has been scientifically tested are reviewed, emphasizing those exploiting the hypothesis of a lack of intermodal connectivity between separate cognitive systems.

Music Training Positively Influences the Preattentive Perception of Voice Onset Time in Children with Dyslexia: A Longitudinal Study.

Previous results showed a positive influence of music training on linguistic abilities at both attentive and preattentive levels. Here, we investigate whether six months of active music training is more efficient than painting training to improve the preattentive processing of phonological parameters based on durations that are often impaired in children with developmental dyslexia (DD). Results were also compared to a control group of Typically Developing (TD) children matched on reading age. We used a Test-Training-Retest procedure and analysed the Mismatch Negativity (MMN) and the N1 and N250 components of the Event-Related Potentials to syllables that differed in Voice Onset Time (VOT), vowel duration, and vowel frequency. Results were clear-cut in showing a normalization of the preattentive processing of VOT in children with DD after music training but not after painting training. They also revealed increased N250 amplitude to duration deviant stimuli in children with DD after music but not painting training, and no training effect on the preattentive processing of frequency. These findings are discussed in view of recent theories of dyslexia pointing to deficits in processing the temporal structure of speech. They clearly encourage the use of active music training for the rehabilitation of children with language impairments.

The impact of spelling regularity on handwriting production: A coupled fMRI and kinematics study.

Current models of writing assume that the orthographic processes involved in spelling retrieval and the motor processes involved in the control of the hand are independent. This view has been challenged by behavioral studies, which showed that the linguistic features of words impact motor execution during handwriting. We designed an experiment coupling functional magnetic resonance imaging and kinematic recordings during a writing to dictation task. Participants wrote orthographically regular and irregular words. The presence of an irregularity impacts both the initiation of the movement and its fine motor execution. At the brain level, the left inferior frontal and fusiform gyri, two regions belonging to the core of the written language system, were found to be sensitive to the presence of an irregularity and to its position in the word during writing execution. Moreover, the left superior parietal lobule, the left superior frontal gyrus and the right cerebellum, three motor-related regions, displayed a stronger response to irregular than regular words. These results constitute direct evidence that orthographic and motor processes occur in a continuous and interactive fashion during writing.

Music and Dyslexia: A New Musical Training Method to Improve Reading and Related Disorders.

Numerous arguments in the recent neuroscientific literature support the use of musical training as a therapeutic tool among the arsenal already available to therapists and educators for treating children with dyslexia. In the present study, we tested the efficacy of a specially-designed Cognitivo-Musical Training (CMT) method based upon three principles: (1) music-language analogies: training dyslexics with music could contribute to improve brain circuits which are common to music and language processes; (2) the temporal and rhythmic features of music, which could exert a positive effect on the multiple dimensions of the "temporal deficit" characteristic of some types of dyslexia; and (3) cross-modal integration, based on converging evidence of impaired connectivity between brain regions in dyslexia and related disorders. Accordingly, we developed a series of musical exercises involving jointly and simultaneously sensory (visual, auditory, somatosensory) and motor systems, with special emphasis on rhythmic perception and production in addition to intensive training of various features of the musical auditory signal. Two separate studies were carried out, one in which dyslexic children received intensive musical exercises concentrated over 18 h during 3 consecutive days, and the other in which the 18 h of musical training were spread over 6 weeks. Both studies showed significant improvements in some untrained, linguistic and non-linguistic variables. The first one yielded significant improvement in categorical perception and auditory perception of temporal components of speech. The second study revealed additional improvements in auditory attention, phonological awareness (syllable fusion), reading abilities, and repetition of pseudo-words. Importantly, most improvements persisted after an untrained period of 6 weeks. These results provide new additional arguments for using music as part of systematic therapeutic and instructional practice for dyslexic children.

Dyslexia.

Developmental dyslexia (DD) is a specific and persistent disability affecting the acquisition of written language. Prevalence is estimated to be between 5% and 17% of school-aged children; it therefore represents a major public health issue. Neurological in origin, its causes are unknown, although there is a clear genetic component. Diagnosis rests upon the use of standardized tests and tools to assess reading and spelling, as well as phonological skills. The importance of early diagnosis cannot be overemphasized and much current research is focusing on screening and prediction, particularly through use of objective imaging techniques (e.g., EEG/MEG), which have implicated cortical abnormalities in central auditory processing (Giraud et al., 2005, 2008). Remediation should be intensive, begin as early as possible, and be tailored to the individual. Phonics based treatments are most effective and several variants, incorporating temporal auditory, articulatory, or multisensory training exercises, have been developed or proposed. Clinical improvements in phonological skills and reading with such treatments have been shown to correlate with changes in the brains of dyslexic children in several functional imaging studies.

Constructing a minimum phylogenetic network from a dense triplet set.

For a given set L of species and a set T of triplets on L, we seek to construct a phylogenetic network which is consistent with T i.e. which represents all triplets of T. The level of a network is defined as the maximum number of hybrid vertices in its biconnected components. When T is dense, there exist polynomial time algorithms to construct level-0,1 and 2 networks (Aho et al., 1981; Jansson, Nguyen and Sung, 2006; Jansson and Sung, 2006; Iersel et al., 2009). For higher levels, partial answers were obtained in the paper by Iersel and Kelk (2008), with a polynomial time algorithm for simple networks. In this paper, we detail the first complete answer for the general case, solving a problem proposed in Jansson and Sung (2006) and Iersel et al. (2009). For any k fixed, it is possible to construct a level-k network having the minimum number of hybrid vertices and consistent with T, if there is any, in time O(T(k+1)n([4k/3]+1)).

Deficit in the preattentive processing of syllabic duration and VOT in children with dyslexia.

The aim of this experiment was to examine the preattentive processing of syllables in 9-11-year-old children with dyslexia and matched controls using the Mismatch Negativity (MMN), an auditory Event-Related brain potential (ERP) related to preattentive discrimination. Children were presented with a sequence of syllables that included standards (the syllable "Ba") and deviants in vowel frequency, vowel duration and Voice Onset Time (VOT) that were either close to or far from the standard (Small and Large deviants). No between-group differences were found for frequency deviants. However, whilst normal-reading children showed larger MMNs to Large than to Small deviants in vowel duration and VOT, no such deviance size effect was found in children with dyslexia. These results are taken to indicate that the preattentive processing of vowel duration and VOT is impaired in children with dyslexia, with no impairment in the processing of vowel frequency deviants. By revealing processing deficits of both duration and VOT deviants, these results suggest a strong link between acoustical and phonological processing.

Combined auditory and articulatory training improves phonological deficit in children with dyslexia.

A group of 19 children with dyslexia aged 7 years 2 months to 10 years 9 months were selected from a clinical sample and tested using a large neuropsychological battery in order to specify the severity and subtype of dyslexia as well as the presence of comorbid conditions. Thereafter, they received a standardised training of 6 weeks of daily auditory exercises aimed at reinforcing explicit and implicit phonological awareness. Ten participants also received specific training of the sensory-motor aspects of articulatory production of individual phonemes during the first 3 weeks of auditory training, whereas the remaining received the same specific training during the last 3 weeks of auditory training. Repetition, phonological awareness, reading and spelling were assessed before the first session, between the two sessions and after the second session. Results confirm the overall efficiency of intensive phonological training, even with exclusively auditory material. The main outcome of this study is a significant improvement of phonology and non-word reading specifically during the periods where the two methods were associated, suggesting a significant contribution of articulatory training to the observed improvement. Finally performance to a motor tapping task proved to be one of the best predictors of training efficiency while comorbid co-ordination or attention deficit did not interfere. Results are interpreted with reference to current theories about mechanisms underlying dyslexia.

Behavioural and event-related potentials evidence for pitch discrimination deficits in dyslexic children: improvement after intensive phonic intervention.

Although it is commonly accepted that dyslexic children have auditory phonological deficits, the precise nature of these deficits remains unclear. This study examines potential pitch processing deficit in dyslexic children, and recovery after specific training, by measuring event-related brain potentials (ERPs) and behavioural responses to pitch manipulations within natural speech. In two experimental sessions, separated by 6 weeks of training, 10 dyslexic children, aged 9-12, were compared to reading age-matched controls, using sentences from children's books. The pitch of the sentence's final words was parametrically manipulated (either congruous, weakly or strongly incongruous). While dyslexics followed a training focused on phonological awareness and grapheme-to-phoneme conversion, controls followed a non-auditory training. Before training, controls outperformed dyslexic children in the detection of the strong pitch incongruity. Moreover, while strong pitch incongruities were associated with increased late positivity (P300 component) in controls, no such pattern was found in dyslexics. Most importantly, pitch discrimination performance was significantly improved, and the amplitude of the late positivity to the strong pitch incongruity enhanced, for dyslexics after a relatively brief period of training, so that their pattern of response more closely resemble those of controls.

Athymhormia and disorders of motivation in Basal Ganglia disease.

The author proposes a general model of human motivation as a separate function at the interface between emotion and action, which can be ascribed to subcortical circuits that are mainly centered on a subset of the basal ganglia and on their limbic connections. It is argued that the long-standing historical understatement of the notion of motivation in neurology is not only due to the complexity of the issue, which has proven hard to disentangle from other domains of dysfunction, but also to the persistence of some misleading conceptual orientations in the way neurologists have considered the brain mechanisms of goal-directed action, torn between a nonspecific "activation" view and an exclusively cognitive conception of motivation. How combining early clinical intuitions of some psychiatrists, careful clinical observations of neurological patients, and data derived from experimental studies in animals provide the basis for a coherent model of human motivation and its specific impairment in clinical neurology is explained. Clinical implications that can be drawn from such a model for some neuropsychiatric conditions are proposed.

Rewiring the dyslexic brain.

Overcoming learning disorders is now becoming a realistic goal for neuroscientists and therapists. Seven years after their twin papers in Science suggesting the efficacy of intensive auditory training in children with language learning impairment, the Tallal-Merzenich team now report convincing evidence of just what such training programs can change in these children's brain. With the help of functional imaging, they demonstrate significant reorganization in both hemispheres after only eight weeks of daily training.

[Semiology of behavioral disorders caused by cerebral injury]. / Sémiologie des troubles du comportement par lésion cérébrale.

Behavioural and emotional changes, often referred to as pseudo-psychiatric symptoms, vary according to lesional sites. The study of different types of frontal syndromes provide the largest part of this chapter, including depression and pseudo-depression, mania, emotional indifference, anosognosia, desinhibition. Temporal lobe syndromes are less frequent, at the exception of various consequences of temporal lobe epilepsy. The Klüver and Bucy syndrome is classical but fortunately rare. The French literature as recently emphasised a special syndrome associating loss of motivation, lack of spontaneous mental activity and reduced emotionality (athymhormic syndrome) specifically associated to bilateral basal ganglia lesions. Finally, the syndrome of alexithymia, often considered but a personality trait may also appear as a consequence of callosal lesions.

Phonological training in children with dyslexia using temporally modified speech: a three-step pilot investigation.

Three separate studies were successively carried out to investigate the usefulness of intensively training children with dyslexia with daily exercizes based on the temporal processing theory of dyslexia, according to which these children would be specifically unable to process brief and rapidly changing auditory stimuli. The speech modification, similar for the three studies, was close to that proposed by Merzenich et al. (1996) and Tallal et al. (1996), including both artificial slowing of natural speech stimuli and amplification of brief, unstable portions of the speech signal. In the first study, 12 children, aged 10-12 years, received either such modified speech or normal speech for 1 h a day, 5 days a week, over 5 weeks, and they were assessed on phonological tasks before, during and after training. A significant advantage for the modified speech group was found both in pre-post-training improvement and in day-to-day progression on phonological performance. In a second study, 29 children with dyslexia, aged 5-12, received a similar training, but for only 15 min a day, 7 days a week, over 6 weeks, part at the speech therapist office, part in their own homes. The finding of comparable improvement in a more 'natural' environment and in children over a wider age range indicates both the efficacy and feasibility of the method in usual clinical practice. However, this study also showed that one of four children did not improve as expected, prompting a third study where 23 other children underwent specific tasks presumably exploring various aspects of temporal processing in order to find predictors of training efficacy. A 'temporal order judgement' (TOJ) task was found best correlated with post-training improvement, suggesting that one use this task for selecting the best candidates for temporo-phonological training. Moreover, such correlation provided further argument in favour of the temporal deficit theory of dyslexia, not only by showing a link between a purely temporal task and ultimate phonological performance, but also by demonstrating that TOJ performance itself improves after phonological training. Finally, and taken together, these studies provide further justification for a rational, indication-based temporo-phonological treatment of dyslexia. Possible neural substrates of the relevant mechanisms are discussed in the light of recent experimental and brain-imaging studies.

Interhemispheric sensorimotor integration in pointing movements: a study on dyslexic adults.

In addition to reading disorders, numerous deficits have been found to be associated with dyslexia, suggesting that various neurological factors might be involved in its etiology. In the present study, we focused on three of the deficits which have been thought to accompany and to a certain extent, to explain dyslexia: an abnormal pattern of hemispheric asymmetry, abnormal hemispheric communication, and abnormal motor control. The aim of the present study was to determine whether adults with reading difficulties perform differently from control subjects in a visuo-manual pointing task, in which the subject was required to point with the right or the left hand to targets appearing to the right or left of a central fixation point. A total of 14 dyslexic adults and 14 control adults participated in this experiment. Motor control was assessed based on the time taken to perform the pointing task, hemispheric asymmetry in terms of the inter-hand differences in the reaction and movement times, and hemispheric communication based on the interhemispheric transfer time under crossed conditions, where the hand and the target were not on the same side. The results showed that neither hemispheric asymmetry nor interhemispheric transfer differed between dyslexic and control adults. However, the dyslexics were significantly slower when performing the pointing task. These results are in agreement with the hypothesis that dyslexia may involve a mild motor deficit.

Temporal processing and phonological impairment in dyslexia: effect of phoneme lengthening on order judgment of two consonants.

The evidence of supporting phonological deficit as a cause of developmental dyslexia has been accumulating rapidly over the past 2 decades, yet the exact mechanisms underlying this deficit remain controversial. Some authors assume that a temporal processing deficit is the source of the phonological disorder observed in dyslexic children. Others maintain that the phonological deficit in dyslexia is basically linguistic, not acoustic, in nature. Three experiments were conducted and tested the impact of the temporal alteration and the impact of complex syllabic structure on consonant order judgments. Thirteen phonological dyslexics (age 10-13) and 10 controls matched for chronologial age were compared on a Temporal Order Judgment (TOJ) task using the succession of two consonants (/p/ /s/) within a cluster. In order to test the possible relevance of the temporal deficit hypothesis, the task also included two additional conditions where either the two stimuli were artificially slowed or two phonological structures were opposed (CCV and CVCV). As expected, the TOJ performance was significantly poorer in dyslexics than in controls. Moreover, in the "slowed speech" condition dyslexics' performance improved to reach the normal controls' level, whereas manipulating the phonological structure complexity provided no significant improvement. Finally dyslexics' performances, especially on the slowed condition, were found correlated with several tests of phonological processing. These results lend support to the general temporal deficit theory of dyslexia.

An electrophysiological study of dyslexic and control adults in a sentence reading task.

Event-related potentials and cued-recall performance were used to compare dyslexic and control adult subjects. Sentences that ended either congruously or incongruously were presented visually, one word at a time, at fast (stimulus-onset-asynchrony (SOA)=100 ms) or slow (SOA=700 ms) rates of presentation. Results revealed (1) a large effect of presentation rate that started with the N1-P2 components and lasted for the entire recording period, (2) larger N400 components for dyslexic than control subjects, at slow presentation rates, to both congruous and incongruous endings and (3) a large ERPs difference related to memory (Dm effect) that did not differentiate controls from dyslexics but was larger at slow than at fast rates of presentation. These findings indicate that the reading impairment observed in the present group of adult dyslexics is more likely to result from difficulties integrating the meaning of words within a sentence context than from pure sensory processing deficits.