Discriminating between neurofibromatosis-1 and typically developing children by means of multimodal MRI and multivariate analyses.

Neurofibromatosis Type 1 leads to brain anomalies involving both gray and white matter. The extent and granularity of these anomalies, together with their possible impact on brain activity, is still unknown. In this multicentric cross-sectional study we submitted a sample of 42 typically developing and 38 neurofibromatosis-1 children to a multimodal MRI assessment including T1, diffusion weighted and resting state functional sequences. We used a pipeline involving several features selection steps coupled with multivariate statistical analysis (supporting vector machine) to discriminate between the two groups while having interpretable models. We used MRI indexes measuring macro (gray matter volume) and microstructural (fractional anisotropy, mean diffusivity) characteristics of the brain, as well as indexes of brain activity (fractional amplitude of low frequency fluctuations) and connectivity (local and global correlation) at rest. We found that structural indexes could discriminate between the two groups, with the mean diffusivity leading to performance as high as the combination of all structural indexes combined (accuracy = 0.86), while functional indexes had worse performances. The MRI signature of NF1 brain pathology is a combination of gray and white matter abnormalities, as measured with gray matter volume, fractional anisotropy, and mean diffusivity.

Mu-oscillation changes related to the development of anticipatory postural control in children and adolescents.

Anticipatory postural adjustments (APAs) cancel the destabilizing effects of movement on posture. Across development, the maturation of APAs is characterized by an accurate adjustment of the timing parameters of electromyographic (EMG) response. The study aimed at investigating the maturation of cortical oscillations involved in the improvement of APAs efficiency. Thirty-six healthy participants (8-16 yr) performed the bimanual load-lifting task in which subjects are instructed to lift a load, placed on the left forearm, with the right hand. EMG data were acquired over the biceps brachii on the postural arm to the determine EMG response onset. Electroencephalographic signals were analyzed in the time-frequency domain by convolution with complex Gaussian Morlet wavelets. Electrophysiological signature of APAs in children and adolescents consisted of a mu-rhythm desynchronization over the sensorimotor cortex contralateral to the postural arm. Across development, the mu-rhythm desynchronization was characterized by a progressive shift forward of the onset of the desynchronization, lower amplitude, and velocity. These changes occurred along with an alteration of the timing of the EMG response, as shown by an earlier onset of the flexor inhibition with increasing age. The maturational changes in the Mu-oscillations might sustain the development of APAs. A possible role of the Mu-oscillation in the generation of postural command is discussed. NEW & NOTEWORTHY Across development, our study showed a progressive shift forward of the parameters of the mu-rhythm desynchronization. These changes occurred along with an alteration of the timing parameters of the electromyographic response, as shown by an earlier onset of the flexor inhibition with increasing age. The progressive development of APAs during childhood and adolescence might therefore be sustained by maturational electrophysiological changes that include mu-rhythm oscillation modifications in the postural sensorimotor cortex.

Protracted Development of the Proprioceptive Brain Network During and Beyond Adolescence.

Proprioceptive processing is important for appropriate motor control, providing error-feedback and internal representation of movement for adjusting the motor command. Although proprioceptive functioning improves during childhood and adolescence, we still have few clues about how the proprioceptive brain network develops. Here, we investigated developmental changes in the functional organization of this network in early adolescents (n = 18, 12 ± 1 years), late adolescents (n = 18, 15 ± 1), and young adults (n = 18, 32 ± 4), by examining task-evoked univariate activity and patterns of functional connectivity (FC) associated with seeds placed in cortical (supramarginal gyrus) and subcortical (dorsal rostral putamen) regions. We found that although the network is already well established in early adolescence both in terms of topology and functioning principles (e.g., long-distance communication and economy in wiring cost), it is still undergoing refinement during adolescence, including a shift from diffuse to focal FC and a decreased FC strength. This developmental effect was particularly pronounced for fronto-striatal connections. Furthermore, changes in FC features continued beyond adolescence, although to a much lower extent. Altogether, these findings point to a protracted developmental time course for the proprioceptive network, which breaks with the relatively early functional maturation often associated with sensorimotor networks.

Boosted activation of right inferior frontoparietal network: a basis for illusory movement awareness.

The feeling of illusory movement is considered important in the study of human behavior because it is deeply related to motor consciousness. However, the neural basis underlying the illusion of movement remains to be understood. Following optimal vibratory stimulation of muscle tendon, certain subjects experience illusory movements while others do not. In the present fMRI study, we sought to uncover the neural basis of illusory movement awareness by contrasting a posteriori these two types of subjects. Examining fMRI data using leave-one-subject-out general linear models and region of interest analyses, we found that a non-limb-specific associative network, including the opercular part of the right inferior frontal gyrus and the right inferior parietal lobule, was more active in subjects with illusions. On the other hand, levels of activation in other brain areas involved in kinaesthetic processing were rather similar between the two subsamples of subjects. These results suggest that activation of the right inferior frontoparietal areas, once passed a certain threshold, forms the basis of illusory movements. This is consistent with the global neuronal workspace hypothesis that associates conscious processing with surges of frontoparietal activity.

Developmental dyslexia, developmental coordination disorder and comorbidity discrimination using multimodal structural and functional neuroimaging.

Developmental dyslexia (DD) and developmental coordination disorder (DCD) are two common neurodevelopmental disorders with a high co-occurrence rate. This led several authors to postulate that the two disorders share, at least partially, similar neural underpinning. However, even though several studies examined brain differences between typically developing (TD) children and children with either DD or DCD, no previous study directly compared DD, DCD and children with both disorders (COM) using neuroimaging. We acquired structural and resting-state functional MRI images of 136 children (TD = 42, DD = 45, DCD = 20, COM = 29). Difference between TD children and the other groups was assessed using univariate analysis of structural indexes including grey and white matter volumes and functional indexes quantifying activity (fraction of the amplitude of the low frequency fluctuations), local and global connectivity. Regional differences in structural and functional brain indexes were then used to train machine learning models to discriminate among DD, DCD and COM and to find the most discriminant regions. While no imaging index alone discriminated between the three groups, grouping grey and white matter volumes (structural model) or activity, local and global connectivity (functional model) made possible to discriminate among the DD, DCD and COM groups. The most important discrimination was obtained using the functional model, with regions in the cerebellum and the temporal lobe being the most discriminant for DCD and DD children, respectively. Results further showed that children with both DD and DCD have subtle but identifiable brain differences that can only be captured using several imaging indexes pertaining to both brain structure and function.

Does visual experience influence arm proprioception and its lateralization? Evidence from passive matching performance in congenitally-blind and sighted adults.

In humans, body segments' position and movement can be estimated from multiple senses such as vision and proprioception. It has been suggested that vision and proprioception can influence each other and that upper-limb proprioception is asymmetrical, with proprioception of the non-dominant arm being more accurate and/or precise than proprioception of the dominant arm. However, the mechanisms underlying the lateralization of proprioceptive perception are not yet understood. Here we tested the hypothesis that early visual experience influences the lateralization of arm proprioceptive perception by comparing 8 congenitally-blind and 8 matched, sighted right-handed adults. Their proprioceptive perception was assessed at the elbow and wrist joints of both arms using an ipsilateral passive matching task. Results support and extend the view that proprioceptive precision is better at the non-dominant arm for blindfolded sighted individuals. While this finding was rather systematic across sighted individuals, proprioceptive precision of congenitally-blind individuals was not lateralized as systematically, suggesting that lack of visual experience during ontogenesis influences the lateralization of arm proprioception.

Phoneme Representation and Articulatory Impairment: Insights from Adults with Comorbid Motor Coordination Disorder and Dyslexia.

Phonemic processing skills are impaired both in children and adults with dyslexia. Since phoneme representation development is based on articulatory gestures, it is likely that these gestures influence oral reading-related skills as assessed through phonemic awareness tasks. In our study, fifty-two young dyslexic adults, with and without motor impairment, and fifty-nine skilled readers performed reading, phonemic awareness, and articulatory tasks. The two dyslexic groups exhibited slower articulatory rates than skilled readers and the comorbid dyslexic group presenting with an additional difficulty in respiratory control (reduced speech proportion and increased pause duration). Two versions of the phoneme awareness task (PAT) with pseudoword strings were administered: a classical version under time pressure and a delayed version in which access to phonemic representations and articulatory programs was facilitated. The two groups with dyslexia were outperformed by the control group in both versions. Although the two groups with dyslexia performed equally well on the classical PAT, the comorbid group performed significantly less efficiently on the delayed PAT, suggesting an additional contribution of articulatory impairment in the task for this group. Overall, our results suggest that impaired phoneme representations in dyslexia may be explained, at least partially, by articulatory deficits affecting access to them.

Specific Learning Disorder in Children and Adolescents, a Scoping Review on Motor Impairments and Their Potential Impacts.

Mastering motor skills is important for children to achieve functional mobility and participate in daily activities. Some studies have identified that students with specific learning disorders (SLD) could have impaired motor skills; however, this postulate and the potential impacts remain unclear. The purpose of the scoping review was to evaluate if SLD children have motor impairments and examine the possible factors that could interfere with this assumption. The sub-objective was to investigate the state of knowledge on the lifestyle behavior and physical fitness of participants with SLD and to discuss possible links with their motor skills. Our scoping review included preregistration numbers and the redaction conformed with the PRISMA guidelines. A total of 34 studies published between 1990 and 2022 were identified. The results of our scoping review reflected that students with SLD have poorer motor skills than their peers. These motor impairments are exacerbated by the complexity of the motor activities and the presence of comorbidities. These results support our sub-objective and highlight the link between motor impairments and the sedentary lifestyle behavior of SLDs. This could lead to deteriorating health and motor skills due to a lack of motor experience, meaning that this is not necessarily a comorbidity. This evidence emphasizes the importance of systematic clinical motor assessments and physical activity adaptations.

A sensorimotor representation impairment in dyslexic adults: A specific profile of comorbidy.

Sensorimotor disorders have been frequently reported in children and adults with dyslexia over the past 30 years. The present study aimed to determine the impact of sensorimotor comorbidity risks in dyslexia by investigating the functional links between phonological and sensorimotor representations in young dyslexic adults. Using 52 dyslexic participants and 58 normo-readers, we investigated whether the underlying phonological deficit, which is reported in the literature, was associated with a general impairment of sensorimotor representations of articulatory and bodily actions. Internal action representations were explored through motor imagery tasks, consisting of measuring and comparing the durations of performed or imagined actions chosen from their current repertoire of daily life activities. To detect sensorimotor deficits, all participants completed the extended version of the M-ABC 2, as a reference test. We found sensorimotor impairments in 27% of the young adult dyslexics, then considered as sensorimotor comorbid, as opposed to much less in the normo-reader group (5%). While motor slowdown, reflecting motor difficulty, was present in all dyslexic adults, motor imagery performance was impacted only in the specific dyslexic subgroup with sensorimotor impairments. Moreover, in contrast with slowness, only the comorbid subgroup showed an increased variability in execution durations. The present study highlights the importance of the quality of perception-action coupling, questions the relevance of investigating sensorimotor impairment profiles beyond phonological deficits and provides new arguments supporting the perspective of multiple deficits approaches in dyslexia.

Neurodevelopment of Posture-movement Coordination from Late Childhood to Adulthood as Assessed From Bimanual Load-lifting Task: An Event-related Potential Study.

In a bimanual task, proprioception provides information about position and movement of upper arms. Developmental studies showed improvement of proprioceptive accuracy and timing adjustments of muscular events from childhood to adulthood in bimanual tasks. However, the cortical maturational changes related to bimanual coordination is not fully understood. The aim of this study was to investigate cortical correlates underlying motor planning and upper limb stabilization performance at left (C3) and right (C4) sensorimotor cortices using event-related potential (ERP) analyses. We recruited 46 participants divided into four groups (12 children: 8-10 years, 13 early adolescents: 11-13 years, 11 late adolescents: 14-16 years and 10 young adults: 20-35 years). Participants performed a bimanual load-lifting task, where the left postural arm supported the load and the right motor arm lifted the load. Maximal amplitude of elbow rotation (MA%) of the postural arm, reaction time (RT) and EMG activity of biceps brachii bilaterally were computed. Laplacian-transformed ERPs of the electroencephalographic (EEG) signal response-locked to motor arm biceps EMG activity onset were analyzed over C3 and C4. We found a developmental effect for behavioral and EEG data denoted by significant decrease of MA% and RT with age, earlier inhibition of the biceps brachii of the postural arm in adults and earlier EEG activation/inhibition onset at C3/C4. Amplitude of the negative wave at C4 was higher in children and early adolescents compared to the other groups. In conclusion, we found a maturational process in cortical correlates related to motor planning and upper limb stabilization performance with interhemispheric lateralization appearing during adolescence. Findings may serve documenting bimanual performance in children with neurodevelopmental disorders.

Anticipatory postural adjustments in a bimanual load-lifting task in children with developmental coordination disorder.

AIM: Postural control is a fundamental component of action in which deficits have been shown to contribute to motor difficulties in children with developmental coordination disorder (DCD). The purpose of this study was to examine anticipatory postural adjustments (APAs) in children with DCD in a bimanual load-lifting task. METHOD: Sixteen children with reported motor problems (two females, 14 males; mean age 9 y; SD 2 y) and 16 typically developing, age-matched children (six females, 10 males; mean age 9 y; SD 2 y) took part in the study. The task required the children to maintain a stable elbow angle, despite imposed or voluntary unloading of the forearm. APAs were assessed using electromyography and kinematics analysis. RESULTS: Although children with DCD could compensate for the consequences of unloading, the results demonstrated that APAs were less efficient in children with DCD than in typically developing children. A positive and significant coefficient of regression between the flexor inhibition latency and the postural stabilization was only found in typically developing children. INTERPRETATION: The impaired fine-tuning of the muscle contribution and the poor stabilization performances demonstrate poor predictive modelling in DCD.

Coordination between posture and phonation in vocal effort behavior.

BACKGROUND: Postural correlates of vocal effort are rarely described in the literature, while they are extensively dealt with in speech therapy. OBJECTIVES: This study aims at determining whether body movement is a side effect of vocal effort or an integral part of communication effort behavior. The answer to this question is mainly based on correlations between posture and phonation. METHOD: Twenty healthy subjects participated in this study. They had to communicate with a listener under 3 conditions requiring different levels of vocal effort. RESULTS: The vocal parameters increased and confirmed that the subjects had made a vocal effort. The kinematic parameters (amplitude and duration of body movement) increased with vocal effort. Lastly, vocal and kinematic characteristics were significantly correlated. CONCLUSION: The close correlation of posture with vocal production shows that movement is not a mere consequence of vocal effort. Posture and voice are coordinated in communication behavior, and each body segment plays its specific role in the vocal effort behavior.

Intrinsic Cortico-Subcortical Functional Connectivity in Developmental Dyslexia and Developmental Coordination Disorder.

Developmental dyslexia (DD) and developmental coordination disorder (DCD) are distinct diagnostic disorders. However, they also frequently co-occur and may share a common etiology. It was proposed conceptually a neural network framework that explains differences and commonalities between DD and DCD through impairments of distinct or intertwined cortico-subcortical connectivity pathways. The present study addressed this issue by exploring intrinsic cortico-striatal and cortico-cerebellar functional connectivity in a large (n = 136) resting-state fMRI cohort study of 8-12-year-old children with typical development and with DD and/or DCD. We delineated a set of cortico-subcortical functional circuits believed to be associated with the brain's main functions (visual, somatomotor, dorsal attention, ventral attention, limbic, frontoparietal control, and default-mode). Next, we assessed, using general linear and multiple kernel models, whether and which circuits distinguished between the groups. Findings revealed that somatomotor cortico-cerebellar and frontoparietal cortico-striatal circuits are affected in the presence of DCD, including abnormalities in cortico-cerebellar connections targeting motor-related regions and cortico-striatal connections mapping onto posterior parietal cortex. Thus, DCD but not DD may be considered as an impairment of cortico-subcortical functional circuits.

Are morphological and structural MRI characteristics related to specific cognitive impairments in neurofibromatosis type 1 (NF1) children?

INTRODUCTION: NF1 children have cognitive disorders, especially in executive functions, visuospatial, and language domains, the pathophysiological mechanisms of which are still poorly understood. MATERIALS AND METHODS: A correlation study was performed from neuropsychological assessments and brain MRIs of 38 NF1 patients and 42 controls, all right-handed, aged 8-12 years and matched in age and gender. The most discriminating neuropsychological tests were selected to assess their visuospatial, metaphonological and visuospatial working memory abilities. The MRI analyses focused on the presence and location of Unidentified Bright Objects (UBOs) (1), volume analysis (2) and diffusion analysis (fractional anisotropy and mean diffusivity) (3) of the regions of interest including subcortical structures and posterior fossa, as well as shape analysis of subcortical structures (4). The level of attention, intelligence quotient, age and gender of the patients were taken into account in the statistical analysis. Then, we studied how diffusion and volumes parameters were associated with neuropsychological characteristics in NF1 children. RESULTS: NF1 children present different brain imaging characteristics compared to the control such as (1) UBOs in 68%, (2) enlarged total intracranial volume, involving all subcortical structures, especially thalamus, (3) increased MD and decreased FA in thalamus, corpus callosum and hippocampus. These alterations are diffuse, without shape involvement. In NF1 group, brain microstructure is all the more altered that volumes are enlarged. However, we fail to find a link between these brain characteristics and neurocognitive scores. CONCLUSION: While NF1 patients have obvious pathological brain characteristics, the neuronal substrates of their cognitive deficits are still not fully understood, perhaps due to complex and multiple pathophysiological mechanisms underlying this disorder, as suggested by the heterogeneity observed in our study. However, our results are compatible with an interpretation of NF1 as a diffuse white matter disease.

Sequential activation of axial muscles during different forms of rhythmic behavior in man.

In humans, studies of back muscle activity have mainly addressed the functioning of lumbar muscles during postural adjustments or rhythmic activity, including locomotor tasks. The present study investigated how back muscles are activated along the spine during rhythmical activities in order to gain insights into spinal neuronal organization. Electromyographic recordings of back muscles were performed at various trunk levels, and changes occurring in burst amplitudes and phase relationships were analyzed. Subjects performed several rhythmic behaviors: forward walking (FW), backward walking (BW), amble walking (where the subjects moved their arms in phase with the ipsilateral leg), walking on hands and knees (HK) and walking on hands with the knees on the edge of a treadmill (Hand). In a final task, the subjects were standing and were asked to swing (Swing) only their arms as if they were walking. It was found that axial trunk muscles are sequentially activated by a motor command running along the spinal cord (which we term "motor waves") during various types of locomotion or other rhythmic motor tasks. The bursting pattern recorded under these conditions can be classified into three categories: (1) double-burst rhythmic activity in a descending (i.e., with a rostro-caudal propagation) motor wave during FW, BW and HK conditions; (2) double-burst rhythmic activity with a stationary motor wave (i.e., occurring in a single phase along the trunk) during the 'amble' walk condition; (3) monophasic rhythmic activity with an ascending (i.e., with a caudo-rostral propagation) motor wave during the Swing and Hands conditions. Our results suggest that the networks responsible for the axial propagation of motor activity during locomotion may correspond to those observed in invertebrates or lower vertebrates, and thus may have been partly phylogenetically conserved. Such an organization could support the dynamic control of posture by ensuring fluent movement during locomotion.

Feedforward motor control in developmental dyslexia and developmental coordination disorder: Does comorbidity matter?

BACKGROUND AND AIM: Feedforward and online controls are two facets of predictive motor control from internal models, which is suspected to be impaired in learning disorders. We examined whether the feedforward component is affected in children (8-12 years) with developmental dyslexia (DD) and/or with developmental coordination disorder (DCD) compared to typically developing (TD) children. METHODS: Children underwent a bimanual unloading paradigm during which a load supported to one arm, the postural arm, was either unexpectedly unloaded by a computer or voluntary unloaded by the subject with the other arm. RESULTS: All children showed a better stabilization (lower flexion) of the postural arm and an earlier inhibition of the arm flexors during voluntary unloading, indicating anticipation of unloading. Between-group comparisons of kinematics and electromyographic activity of the postural arm revealed that the difference during voluntary unloading was between DD-DCD children and the other groups, with the former showing a delayed inhibition of the flexor muscles. CONCLUSION: Deficit of the feedforward component of motor control may particularly apply to comorbid subtypes, here the DD-DCD subtype. The development of a comprehensive framework for motor performance deficits in children with learning disorders will be achieved only by dissociating key components of motor prediction and focusing on subtypes and comorbidities.

Brain network connectivity associated with anticipatory postural control in children and adults.

Internal models provide a coherent framework for understanding motor behavior. Examples for the use of internal models include anticipatory postural adjustments (APAs), where the individual anticipates and cancels out the destabilizing effect of movement on body posture. Yet little is known about the functional changes in the brain supporting the development of APAs. Here, we addressed this issue by relating individual differences in APAs as assessed during bimanual load lifting to interindividual variation in brain network interactions at rest. We showed that the strength of the connectivity between three main canonical brain networks, namely the cingulo-opercular, the fronto-parietal and the somatosensory-motor networks, is an index of the ability to implement APAs from late childhood (9- to 11-year-old children). We also found an effect of age on the relationship between APAs and coupling strength between these networks, consistent with the notion that APAs are near but not yet fully mature in children. We discuss the implications of these findings for our understanding of learning disorders with impairment in predictive motor control.

Dual-task study of cognitive and postural interference in 7-year-olds and adults.

The study examined, in children aged 7 and adults, the postural control when a cognitive task (modified Stroop) of varying level of difficulty is executed simultaneously. Postural difficulty also varied (with or without vibrations of the ankle joint). We hypothesized that children's performance was more affected than adults', when the difficulty of the cognitive and postural tasks increased. Results (i) demonstrated that the presence of a concurrent cognitive task affected postural sway at all ages; (ii) confirmed that the interference between mental activity and postural control can be attributed mainly to general capacity limitations and (iii) showed a degradation of the postural criteria in children but not of the cognitive ones, when the postural condition was constraining.

Drifting while stepping in place in old adults: Association of self-motion perception with reference frame reliance and ground optic flow sensitivity.

Optic flow provides visual self-motion information and is shown to modulate gait and provoke postural reactions. We have previously reported an increased reliance on the visual, as opposed to the somatosensory-based egocentric, frame of reference (FoR) for spatial orientation with age. In this study, we evaluated FoR reliance for self-motion perception with respect to the ground surface. We examined how effects of ground optic flow direction on posture may be enhanced by an intermittent podal contact with the ground, and reliance on the visual FoR and aging. Young, middle-aged and old adults stood quietly (QS) or stepped in place (SIP) for 30s under static stimulation, approaching and receding optic flow on the ground and a control condition. We calculated center of pressure (COP) translation and optic flow sensitivity was defined as the ratio of COP translation velocity over absolute optic flow velocity: the visual self-motion quotient (VSQ). COP translation was more influenced by receding flow during QS and by approaching flow during SIP. In addition, old adults drifted forward while SIP without any imposed visual stimulation. Approaching flow limited this natural drift and receding flow enhanced it, as indicated by the VSQ. The VSQ appears to be a motor index of reliance on the visual FoR during SIP and is associated with greater reliance on the visual and reduced reliance on the egocentric FoR. Exploitation of the egocentric FoR for self-motion perception with respect to the ground surface is compromised by age and associated with greater sensitivity to optic flow.

Gravity Cues Embedded in the Kinematics of Human Motion Are Detected in Form-from-Motion Areas of the Visual System and in Motor-Related Areas.

The present study investigated the cortical areas engaged in the perception of graviceptive information embedded in biological motion (BM). To this end, functional magnetic resonance imaging was used to assess the cortical areas active during the observation of human movements performed under normogravity and microgravity (parabolic flight). Movements were defined by motion cues alone using point-light displays. We found that gravity modulated the activation of a restricted set of regions of the network subtending BM perception, including form-from-motion areas of the visual system (kinetic occipital region, lingual gyrus, cuneus) and motor-related areas (primary motor and somatosensory cortices). These findings suggest that compliance of observed movements with normal gravity was carried out by mapping them onto the observer's motor system and by extracting their overall form from local motion of the moving light points. We propose that judgment on graviceptive information embedded in BM can be established based on motor resonance and visual familiarity mechanisms and not necessarily by accessing the internal model of gravitational motion stored in the vestibular cortex.