Corticospinal neuron subpopulation-specific developmental genes prospectively indicate mature segmentally specific axon projection targeting.

For precise motor control, distinct subpopulations of corticospinal neurons (CSN) must extend axons to distinct spinal segments, from proximal targets in the brainstem and cervical cord to distal targets in thoracic and lumbar spinal segments. We find that developing CSN subpopulations exhibit striking axon targeting specificity in spinal white matter, which establishes the foundation for durable specificity of adult corticospinal circuitry. Employing developmental retrograde and anterograde labeling, and their distinct neocortical locations, we purified developing CSN subpopulations using fluorescence-activated cell sorting to identify genes differentially expressed between bulbar-cervical and thoracolumbar-projecting CSN subpopulations at critical developmental times. These segmentally distinct CSN subpopulations are molecularly distinct from the earliest stages of axon extension, enabling prospective identification even before eventual axon targeting decisions are evident in the spinal cord. This molecular delineation extends beyond simple spatial separation of these subpopulations in the cortex. Together, these results identify candidate molecular controls over segmentally specific corticospinal axon projection targeting.

Does paternal methamphetamine exposure affect the behavior of rat offspring during development and in adulthood?

Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic and worldwide. Previous studies have demonstrated the adverse effects of maternal drug abuse. However, the father's contribution as a parent and donor of the half genetic information is unclear. The present study aimed to examine the effect of paternal MA exposure on behavioral development and locomotor activity in rat offspring. MA was administrated subcutaneously for 30 days at a dose of 5 mg/kg to adult male rats. The impact of paternal MA exposure on rat pups was investigated using behavioral tests during development and locomotor activity tests in adulthood. Prior to testing, adult offspring were exposed to an acute challenge dose of MA (1 mg/kg) to examine the possible sensitizing effect of the paternal treatment. Our results found no significant differences in behavioral development or locomotor activity in adulthood of offspring linked to paternal MA application. These results differ from the effects induced by maternal MA application. Further, our results demonstrated a significant increase in locomotor activity on the Laboras test after acute MA application. When comparing sex differences, females showed more activity than males in adulthood, whereas males were more active during development.

Increased wiring cost during development is driven by long-range cortical, but not subcortical connections.

The brain undergoes a protracted, metabolically expensive maturation process from childhood to adulthood. Therefore, it is crucial to understand how network cost is distributed among different brain systems as the brain matures. To address this issue, here we examined developmental changes in wiring cost and brain network topology using resting-state functional magnetic resonance imaging (rsfMRI) data longitudinally collected in awake rats from the juvenile age to adulthood. We found that the wiring cost increased in the vast majority of cortical connections but decreased in most subcortico-subcortical connections. Importantly, the developmental increase in wiring cost was dominantly driven by long-range cortical, but not subcortical connections, which was consistent with more pronounced increase in network integration in the cortical network. These results collectively indicate that there is a non-uniform distribution of network cost as the brain matures, and network resource is dominantly consumed for the development of the cortex, but not subcortex from the juvenile age to adulthood.

Changes in Neuronal Density of the Sensorimotor Cortex and Neurodevelopmental Behaviour in Neonatal Mice with Kaolin-Induced Hydrocephalus.

INTRODUCTION: Hydrocephalus is a disorder in which the circulation of cerebrospinal fluid is altered in a manner that leads to its accumulation in the ventricles and subarachnoid space. Its impact on the neuronal density and networks in the overlying cerebral cortex in a time-dependent neonatal hydrocephalic process is largely unknown. We hypothesize that hydrocephalus will affect the cytoarchitecture of the cerebral cortical mantle of neonatal hydrocephalic mice, which will in turn modify sensorimotor processing and neurobehaviour. OBJECTIVE: The purpose of this study is to probe the effect of hydrocephalus on 3 developmental milestones (surface righting reflex, cliff avoidance reflex, and negative geotaxis) and on cortical neuronal densities in neonatal hydrocephalic mice. METHODS: Hydrocephalus was induced in 1-day-old mice by intracisternal injection of sterile kaolin suspension. The pups were tested for reflex development and sensorimotor ability using surface righting reflex (PND 5, 7, and 9), cliff avoidance (PND 6), and negative geotaxis (PND 10 and 12) prior to their sacrifice on PND 7, 14, and 21. Neuronal density and cortical thickness in the sensorimotor cortex were evaluated using atlas-based segmentation of the neocortex and boundary definition in 4-µm paraffin-embedded histological sections with hematoxylin and eosin as well as cresyl violet stains. RESULTS: Surface righting and cliff avoidance activities were significantly impaired in hydrocephalic pups but no statistically significant difference was observed in negative geotaxis in both experimental and control pups. The neuronal density of the sensorimotor cortex was significantly higher in hydrocephalic mice than in age-matched controls on PND 14 and 21 (373.20 ± 21.54 × 10-6 µm2 vs. 157.70 ± 21.88 × 10-6 µm2; 230.0 ± 44.1 × 10-6 µm2 vs. 129.60 ± 3.72 × 10-6 µm2, respectively; p < 0.05). This was accompanied by reduction in the cortical thickness (µm) in the hydrocephalic mice on PND 7 (2,409 ± 43.37 vs. 3,752 ± 65.74, p < 0.05), PND 14 (2,035 ± 322.10 vs. 4,273 ± 67.26, p < 0.05), and PND 21 (1,676 ± 33.90 vs. 4,945 ± 81.79, p < 0.05) compared to controls. CONCLUSION: In this murine model of neonatal hydrocephalus, the quantitative changes in the cortical neuronal population may play a role in the observed changes in neurobehavioural findings.

Exaggerated cortical representation of speech in older listeners: mutual information analysis.

Aging is associated with an exaggerated representation of the speech envelope in auditory cortex. The relationship between this age-related exaggerated response and a listener's ability to understand speech in noise remains an open question. Here, information-theory-based analysis methods are applied to magnetoencephalography recordings of human listeners, investigating their cortical responses to continuous speech, using the novel nonlinear measure of phase-locked mutual information between the speech stimuli and cortical responses. The cortex of older listeners shows an exaggerated level of mutual information, compared with younger listeners, for both attended and unattended speakers. The mutual information peaks for several distinct latencies: early (∼50 ms), middle (∼100 ms), and late (∼200 ms). For the late component, the neural enhancement of attended over unattended speech is affected by stimulus signal-to-noise ratio, but the direction of this dependency is reversed by aging. Critically, in older listeners and for the same late component, greater cortical exaggeration is correlated with decreased behavioral inhibitory control. This negative correlation also carries over to speech intelligibility in noise, where greater cortical exaggeration in older listeners is correlated with worse speech intelligibility scores. Finally, an age-related lateralization difference is also seen for the ∼100 ms latency peaks, where older listeners show a bilateral response compared with younger listeners' right lateralization. Thus, this information-theory-based analysis provides new, and less coarse-grained, results regarding age-related change in auditory cortical speech processing, and its correlation with cognitive measures, compared with related linear measures.NEW & NOTEWORTHY Cortical representations of natural speech are investigated using a novel nonlinear approach based on mutual information. Cortical responses, phase-locked to the speech envelope, show an exaggerated level of mutual information associated with aging, appearing at several distinct latencies (∼50, ∼100, and ∼200 ms). Critically, for older listeners only, the ∼200 ms latency response components are correlated with specific behavioral measures, including behavioral inhibition and speech comprehension.

A pilot study assessing reliability and age-related differences in corticomuscular and intramuscular coherence in ankle dorsiflexors during walking.

Corticomuscular (CMC) and intramuscular (intraMC) coherence represent measures of corticospinal interaction. Both CMC and intraMC can be assessed during human locomotion tasks, for example, while walking. Corticospinal control of gait can deteriorate during the aging process and CMC and intraMC may represent an important monitoring means. However, it is unclear whether such assessments represent a reliable tool when performed during walking in an ecologically valid scenario and whether age-related differences may occur. Wireless surface electroencephalography and electromyography were employed in a pilot study with young and old adults during overground walking in two separate sessions. CMC and intraMC analyses were performed in the gathered beta and lower gamma frequencies (i.e., 13-40 Hz). Significant log-transformed coherence area was tested for intersessions test-retest reliability by determining intraclass correlation coefficient (ICC), yielding to low reliability in CMC in both younger and older adults. intraMC exclusively showed low reliability in the older adults, whereas intraMC in the younger adults revealed similar values as previously reported: test-retest reliability [ICC (95% CI): 0.44 (-0.23, 0.87); SEM: 0.46; MDC: 1.28; MDC%: 103; Hedge's g (95% CI): 0.54 (-0.13, 1.57)]. Significant differences between the age groups were observed in intraMC by either comparing the two groups with the first test [Hedge's g (95% CI): 1.55 (0.85, 2.15); p-value: .006] or with the retest data [Hedge's g (95% CI): 2.24 (0.73, 3.70); p-value: .005]. Notwithstanding the small sample size investigated, intraMC seems a moderately reliable assessment in younger adults. The further development and use of this measure in practical settings to infer corticospinal interaction in human locomotion in clinical practice is warranted and should help to refine the analysis. This necessitates involving larger sample sizes as well as including a wider number of lower limb muscles. Moreover, further research seems warranted by the observed differences in modulation mechanisms of corticospinal control of gait as ascertained by intraMC between the age groups.

Impact of prenatal hypoxia on the development and behavior of the rat offspring.

The healthy development of the fetus depends on the exact course of pregnancy and delivery. Therefore, prenatal hypoxia remains between the greatest threats to the developing fetus. Our study aimed to assess the impact of prenatal hypoxia on postnatal development and behavior of the rats, whose mothers were exposed to hypoxia (10.5 % O2) during a critical period of brain development on GD20 for 12 h. This prenatal insult resulted in a delay of sensorimotor development of hypoxic pups compared to the control group. Hypoxic pups also had lowered postnatal weight which in males persisted up to adulthood. In adulthood, hypoxic males showed anxiety-like behavior in the OF, higher sucrose preference, and lower levels of grimace scale (reflecting the degree of negative emotions) in the immobilization chamber compared to the control group. Moreover, hypoxic animals showed hyperactivity in EPM and LD tests, and hypoxic females had reduced sociability compared to the control group. In conclusion, our results indicate a possible relationship between prenatal hypoxia and changes in sociability, activity, and impaired emotion regulation in ADHD, ASD, or anxiety disorders. The fact that changes in observed parameters are manifested mostly in males confirms that male sex is more sensitive to prenatal insults.

Modular segregation of task-dependent brain networks contributes to the development of executive function in children.

Executive function (EF) refers as to a set of high-level cognitive abilities that are critical to many aspects of daily life. Despite its importance in human daily life, the neural networks responsible for the development of EF in childhood are not well understood. The present study thus aimed to examine the development of task-dependent brain network organization and its relationship to age-related improvements in EF. To address this issue, we recruited eighty-eight Chinese children ranging in age from 7 to 12 years old, and collected their functional magnetic resonance imaging (fMRI) data when they performed an EF task. By utilizing graph theory, we found that the task-dependent brain network modules became increasingly segregated with age. Specifically, the intra-module connections within the default-mode network (DMN), frontal-parietal network (FPN) and sensorimotor network (SMN) increased significantly with age. In contrast, the inter-module connections of the visual network to both the FPN/SMN decreased significantly with age. Most importantly, modular segregation of the FPN significantly mediated the relationship between age and EF performance. These findings add to our growing understanding of how development changes in task-dependent brain network organization support vast behavioral improvements in EF observed during childhood.

End-state comfort effect in manipulative motor actions of typical and atypical children: a systematic review / Estado de conforto final de ações motoras manipulativas de crianças típicas e atípicas: revisão sistemática / Estado de confort final de acciones motoras manipuladoras de niños típicos y atípicos: revisión sistemática

ABSTRACT This study aimed to make a systematic review of scientific articles on the planning of manual motor actions of typical and atypical children. To do so, a search of articles published between 1996 and 2017 was done on PubMed, LILACS, Science Direct, and SciElo databases. Original articles in English and Portuguese evaluating the planning of motor actions in typical and atypical children performing manual tasks were selected. For the analysis, the population age, number of children, type of task, main results, site of study and impact of the journal were considered. From the eighteen articles found, twelve were about typical children (from nine months old to twenty years old) and six about atypical children (from three to fourteen years old) diagnosed with autism, hemiplegic cerebral palsy, and developmental coordination disorders. In nine- to ten-year-old typical children, the planning ability of manual motor actions develops over the time and is similar to that of an adult. The atypical children showed motor planning ability lower than that of the typical children, and determining the age when this planning ability is acquired was not possible.

RESUMO O objetivo desse estudo foi realizar uma revisão sistemática de artigos científicos sobre o planejamento de ações motoras manuais de crianças típicas e atípicas. Para isso, foi feita uma busca de artigos publicados entre 1996 e 2017 nas bases de dados PubMed, Lilacs, Science Direct e SciELO. Foram incluídos artigos originais em língua inglesa e portuguesa, que avaliaram o planejamento de ações motoras em crianças típicas e atípicas por meio de tarefas manuais. Para a análise dos artigos, considerou-se a população, a faixa etária, o número de crianças, o tipo de tarefa, os principais resultados, o local de realização do estudo e o fator de impacto da revista. Ao todo, foram encontrados 18 artigos, sendo 12 com crianças típicas (9 meses a 20 anos de idade), e 6 com crianças atípicas (3 a 14 anos) diagnosticadas com autismo, paralisia cerebral hemiplégica e transtornos de déficit de coordenação. Nas crianças típicas, observa-se que a capacidade de planejamento de ações motoras manuais se desenvolve ao longo do tempo e se assemelha a de um adulto entre os 9 e 10 anos de idade. As crianças atípicas apresentaram capacidade de planejamento motor inferior à das crianças típicas e não foi possível determinar a idade em que essa habilidade de planejamento é estabelecida.

RESUMEN El objetivo de este estudio fue realizar una revisión sistemática de artículos científicos sobre la planificación de acciones motoras manuales de niños típicos y atípicos. Para ello, se realizó una búsqueda de artículos publicados entre 1996 y 2017 en las bases de datos PubMed, Lilacs, Science Direct y SciELO. Se incluyeron artículos originales en inglés y portugués que evaluaron la planificación de acciones motoras en niños típicos y atípicos a través de tareas manuales. Para el análisis de los artículos, se consideró la población, el grupo de edad, el número de niños, el tipo de tarea, los principales resultados, el lugar de realización del estudio y el factor de impacto de la revista. En total, se encontraron 18 artículos, 12 con niños típicos (9 meses a 20 años) y 6 con niños atípicos (3 a 14 años) diagnosticados con autismo, parálisis cerebral hemipléjica y trastornos de déficit de coordinación. En los niños típicos, se observa que la capacidad de planificación de acciones motoras manuales se desarrolla a lo largo del tiempo y entre los 9 y 10 años se asemeja a la de un adulto. Los niños atípicos presentaron una capacidad de planificación de motores inferior a la de los niños típicos y no fue posible determinar la edad en que se estableció esta capacidad de planificación.

Changes of functional response in sensorimotor cortex of preterm and full-term infants during the first year: An fNIRS study.

BACKGROUND: Motor impairments are frequently associated with preterm birth and interfere in acquisition of essential skills to global development. Using Near Infrared Spectroscopy (NIRS), the study of neural correlates of motor development in early stages of life are feasible in an ecological assessment. AIMS: To evaluate changes in cortical activity in response to a sensorimotor stimulation in preterm and full-term infants at 6 and 12 months of age. STUDY DESIGN: A longitudinal study was conducted with 22 infants (12 preterm and 10 full-term). Hemodynamic activity during sensorimotor task (8 blocks of 8 s of vibration applied to infant's right hand) was measured by Functional Near Infrared Spectroscopy (fNIRS). The optical probe consisted of 84 channels positioned according to the international 10-20 system coordinates, covering the frontal (38 channels), parietal (16 channels), temporal (22 channels) and occipital (8 channels) lobes of both hemispheres. RESULTS: Preterm and full-term infants exhibited differences of location of the activation as well on the hemodynamic response in both the evaluated age groups. CONCLUSIONS: Group differences in activation of sensorimotor cortex observed in this study demonstrate the potential of fNIRS application for preterm evaluation of motor development in children. Overall, the present work contributes to our understanding of cortical activation of cerebral motor skills spanning early ages in preterm-born children.

The development of functional and directed corticomuscular connectivity during tonic ankle muscle contraction across childhood and adolescence.

In adults, oscillatory activity in the sensorimotor cortex is coherent with contralateral muscle activity at beta frequencies (15-35 Hz) during tonic contraction. This functional coupling reflects the involvement of the sensorimotor cortex, the corticospinal pathway, and likely also ascending sensory feedback in the task at hand. However, little is known about the developmental trajectory of task-related corticomuscular connectivity relating to the voluntary control of the ankle muscles. To address this, we recorded electroencephalography (EEG) from the vertex (Cz) and electromyography (EMG) from ankle muscles (proximal and distal anterior tibial, TA; soleus, SOL; gastrocnemius medialis, GM) in 33 participants aged 7-23 yr during tonic dorsi- and plantar flexion requiring precise maintenance of a submaximal torque level. Coherence was calculated for Cz-TA, Cz-SOL, TA-TA, and SOL-GM signal pairs. We found strong, positive associations between age and beta band coherence for Cz-TA, Cz-SOL, and TA-TA, suggesting that oscillatory corticomuscular connectivity is strengthened during childhood development and adolescence. Directionality analysis indicated that the primary interaction underlying this age-related increase was in the descending direction. In addition, performance during dorsi- and plantar flexion tasks was positively associated with age, indicating more precise control of the ankle joint in older participants. Performance was also positively associated with beta band coherence, suggesting that participants with greater coherence also exhibited greater precision. We propose that these results indicate an age-related increase in oscillatory corticospinal input to the ankle muscle motoneuron pools during childhood development and adolescence, with possible implications for maturation of precision force control. Within the theoretical framework of predictive coding, we suggest that our results may reflect an age-related increase in reliance on feedforward control as the developing nervous system becomes better at predicting the sensory consequences of movement. These findings may contribute to the development of novel intervention strategies targeting improved sensorimotor control in children and adolescents with central motor disorders.

Toddlers show sensorimotor activity during auditory verb processing.

Language that describes actions, for instance verbs, can help to predict future actions of conspecifics in social interactions. Language and action are therefore interrelated. This interrelation has been described on a behavioral level for adults and toddlers. Furthermore, in adults, the sensorimotor system is involved in this interrelation. However, little is known about the early interrelation on the neural level at the onset of verb acquisition. In the present study, we examined the role of the sensorimotor system during the processing of acoustically presented verbs that describe dynamic actions and visually presented actions in toddlers, who are in the earliest stage of expressive language development. The activity of the sensorimotor system, in particular the suppression of the mu rhythm, was measured by means of electroencephalography (EEG). Results showed a significant suppression of the mu rhythm during both the processing of action verbs and observed actions, but not during the processing of pseudoverbs. This suggests that the sensorimotor system is already involved in the processing of action and language early in life.

Maternal exposure to TCDD during gestation advanced sensory-motor development, but induced impairments of spatial learning and memory in adult male rat offspring.

2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) is an endocrine disrupting chemical (EDC) with high persistency. Even a low amount can pass the placental barrier during gestational exposure. Exposure to TCDD exposure can impair the development of the nervous system in children, leading to impaired learning ability in later-life. But the changes in neurobehavioral developments in infancy and childhood caused by TCDD are unknown. Pregnant Sprague-Dawley rats were given a consecutive daily dose of TCDD (200 or 800 ng/day/kg) or an equivalent volume of vehicle by gavage on gestational days 8-14 (GD 8-14) as the prenatal TCDD exposure model. In the offspring, early neurobehavioral development was assessed at postnatal day 5 (PND5) and eye-opening was monitored from PND10 onwards. Adult male offspring was tested by Morris Water Maze for spatial memory and learning ability evaluation. Hippocampus Nissl's staining and astrocyte GFAP immunohistochemistry were used to evaluate the activity of astrocytes. The results of the behavioral tests showed that gestational TCDD exposure induced premature motor activity and earlier eyes-opening, but lead to serious deficits of spatial memory and learning ability in the adult male offspring. Morphology and number of neurons in the hippocampus CA1 region was not affected, while the activity of astrocytes in the same region was significantly reduced. These data indicate that perinatal TCDD exposure induced premature neurobehavioral development but impaired the spatial learning and memory in adult male rat offspring. The decreased activity of astrocytes in the hippocampus may play a role in these adverse effects.

Neuromuscular determinants of slip-induced falls and recoveries in older adults.

Is there a neuromuscular basis for falls? If so, it may provide new insight into falls and their assessment and treatment. We hypothesized that falls and recoveries from a laboratory-induced slip would be characterized by differences in multimuscle coordination patterns. Using muscle synergy analysis, we identified different multimuscle coordination patterns between older adults who fell and those who recovered from a laboratory-induced "feet-forward" slip. Participants who fell recruited fewer muscle synergies than participants who recovered. This suggests that a fall may result from recruitment of an inadequate number of muscle synergies to produce the necessary mechanical functions required to maintain balance. Participants who fell also recruited different muscle synergies, including one with high levels of coactivity consistent with a startle-like response. These differences in multimuscle coordination between slip outcomes were not accompanied by differences in slip difficulty or gait kinematics before or during the slip response. The differences in neuromuscular control may therefore reflect differences in sensorimotor control rather than kinematic constraints imposed by the slip, or the musculoskeletal system. Further research is required to test the robustness of these results and their interpretation with respect to additional mechanical variables (e.g., joint torques, ground reaction forces), responses to other fall types (e.g., trips), and within rather than between individuals. NEW & NOTEWORTHY Do falls and recoveries possess distinct neuromuscular features? We identified differences in neuromuscular control between older adults who fell and those who recovered from a "feet-forward" slip. Differences in neuromuscular control were not accompanied by differences in gait or slip kinematics before or during the slip response, suggesting differences in sensorimotor control rather than kinematics dictated the observed differences in neuromuscular control. An analysis of additional mechanical variables is required to confirm this interpretation.

Somatotopic Mapping of the Developing Sensorimotor Cortex in the Preterm Human Brain.

In the mature mammalian brain, the primary somatosensory and motor cortices are known to be spatially organized such that neural activity relating to specific body parts can be somatopically mapped onto an anatomical "homunculus". This organization creates an internal body representation which is fundamental for precise motor control, spatial awareness and social interaction. Although it is unknown when this organization develops in humans, animal studies suggest that it may emerge even before the time of normal birth. We therefore characterized the somatotopic organization of the primary sensorimotor cortices using functional MRI and a set of custom-made robotic tools in 35 healthy preterm infants aged from 31 + 6 to 36 + 3 weeks postmenstrual age. Functional responses induced by somatosensory stimulation of the wrists, ankles, and mouth had a distinct spatial organization as seen in the characteristic mature homunculus map. In comparison to the ankle, activation related to wrist stimulation was significantly larger and more commonly involved additional areas including the supplementary motor area and ipsilateral sensorimotor cortex. These results are in keeping with early intrinsic determination of a somatotopic map within the primary sensorimotor cortices. This may explain why acquired brain injury in this region during the preterm period cannot be compensated for by cortical reorganization and therefore can lead to long-lasting motor and sensory impairment.

Self-reported sex differences in high-functioning adults with autism: a meta-analysis.

Background: Sex differences in autistic symptomatology are believed to contribute to the mis- and missed diagnosis of many girls and women with an autism spectrum condition (ASC). Whilst recent years have seen the emergence of clinical and empirical reports delineating the profile of young autistic girls, recognition of sex differences in symptomatology in adulthood is far more limited. Methods: We chose here to focus on symptomatology as reported using a screening instrument, the Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R). In a meta-analysis, we pooled and analysed RAADS-R data from a number of experimental groups. Analysis of variance (ANOVA) searched for the presence of main effects of Sex and Diagnosis and for interactions between these factors in our sample of autistic and non-autistic adults. Results: In social relatedness and circumscribed interests, main effects of Diagnosis revealed that as expected, autistic adults reported significantly greater lifetime prevalence of symptoms in these domains; an effect of Sex, in circumscribed interests, also suggested that males generally reported more prevalent symptoms than females. An interaction of Sex and Diagnosis in language symptomatology revealed that a normative sex difference in language difficulties was attenuated in autism. An interaction of Sex and Diagnosis in the sensorimotor domain revealed the opposite picture: a lack of sex differences between typically developing men and women and a greater prevalence of sensorimotor symptoms in autistic women than autistic men. Conclusions: We discuss the literature on childhood sex differences in relation to those which emerged in our adult sample. Where childhood sex differences fail to persist in adulthood, several interpretations exist, and we discuss, for example, an inherent sampling bias that may mean that only autistic women most similar to the male presentation are diagnosed. The finding that sensorimotor symptomatology is more highly reported by autistic women is a finding requiring objective confirmation, given its potential importance in diagnosis.

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.

Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development.

Neuronal synapse formation and remodeling are essential to central nervous system (CNS) development and are dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this affects CNS synapses is largely unknown. Here, we show that the interleukin-1 family cytokine interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.

Bayesian optimal adaptation explains age-related human sensorimotor changes.

The brain uses information from different sensory systems to guide motor behavior, and aging is associated with simultaneous decline in the quality of sensory information provided to the brain and deterioration in motor control. Correlations between age-dependent decline in sensory anatomical structures and behavior have been demonstrated in many sensorimotor systems, and it has recently been suggested that a Bayesian framework could explain these relationships. Here we show that age-dependent changes in a human sensorimotor reflex, the vestibuloocular reflex, are explained by a Bayesian optimal adaptation in the brain occurring in response to death of motion-sensing hair cells. Specifically, we found that the temporal dynamics of the reflex as a function of age emerge from ( r = 0.93, P < 0.001) a Kalman filter model that determines the optimal behavioral output when the sensory signal-to-noise characteristics are degraded by death of the transducers. These findings demonstrate that the aging brain is capable of generating the ideal and statistically optimal behavioral response when provided with deteriorating sensory information. While the Bayesian framework has been shown to be a general neural principle for multimodal sensory integration and dynamic sensory estimation, these findings provide evidence of longitudinal Bayesian processing over the human life span. These results illuminate how the aging brain strives to optimize motor behavior when faced with deterioration in the peripheral and central nervous systems and have implications in the field of vestibular and balance disorders, as they will likely provide guidance for physical therapy and for prosthetic aids that aim to reduce falls in the elderly. NEW & NOTEWORTHY We showed that age-dependent changes in the vestibuloocular reflex are explained by a Bayesian optimal adaptation in the brain that occurs in response to age-dependent sensory anatomical changes. This demonstrates that the brain can longitudinally respond to age-related sensory loss in an ideal and statistically optimal way. This has implications for understanding and treating vestibular disorders caused by aging and provides insight into the structure-function relationship during aging.

Network Supervision of Adult Experience and Learning Dependent Sensory Cortical Plasticity.

The brain is capable of remodeling throughout life. The sensory cortices provide a useful preparation for studying neuroplasticity both during development and thereafter. In adulthood, sensory cortices change in the cortical area activated by behaviorally relevant stimuli, by the strength of response within that activated area, and by the temporal profiles of those responses. Evidence supports forms of unsupervised, reinforcement, and fully supervised network learning rules. Studies on experience-dependent plasticity have mostly not controlled for learning, and they find support for unsupervised learning mechanisms. Changes occur with greatest ease in neurons containing α-CamKII, which are pyramidal neurons in layers II/III and layers V/VI. These changes use synaptic mechanisms including long term depression. Synaptic strengthening at NMDA-containing synapses does occur, but its weak association with activity suggests other factors also initiate changes. Studies that control learning find support of reinforcement learning rules and limited evidence of other forms of supervised learning. Behaviorally associating a stimulus with reinforcement leads to a strengthening of cortical response strength and enlarging of response area with poor selectivity. Associating a stimulus with omission of reinforcement leads to a selective weakening of responses. In some preparations in which these associations are not as clearly made, neurons with the most informative discharges are relatively stronger after training. Studies analyzing the temporal profile of responses associated with omission of reward, or of plasticity in studies with different discriminanda but statistically matched stimuli, support the existence of limited supervised network learning. © 2017 American Physiological Society. Compr Physiol 7:977-1008, 2017.