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There is a striking sex bias in the prevalence and severity of autism spectrum disorder (ASD) with 80% of diagnoses occurring in males. Because the molecular etiology of ASD is likely combinatorial, including interactions across multiple genetic and environmental factors, it is difficult to investigate the physiological mechanisms driving sex-specific differences. Loss of function mutations in TSC1 result in dysregulated mTORC1 signaling and underlie a multi-system disorder known as tuberous sclerosis (TSC). Interestingly, more than 50% of individuals diagnosed with TSC are also diagnosed with ASD, making TSC mutations one of the most prevalent monogenic causes of ASD. Mice harboring targeted deletion of Tsc1 selectively in cerebellar Purkinje neurons, referred to here as Tsc1mut/mut , have multiple ASD-linked behavioral impairments, including deficits in social interactions, motor coordination, and vocalizations. However, these ASD-linked behavioral deficits have only been investigated using male Tsc1mut/mut animals. Here, we used cohorts of male and female Tsc1mut/mut animals to determine if behavioral impairments, previously identified in this model, are similar across sex. Specifically, we measured balance and motor coordination and social interaction behaviors in two age groups across sex. We determined balance and motor coordination deficits are similar in male and female Tsc1mut/mut mice, and that deficits in the firing of Tsc1mut/mut Purkinje neurons located in the cerebellar vermis are also similar across sex. However, impairments in social approach behavior were found to be significantly more severe in Tsc1mut/mut males compared to females. These results indicate the selective deletion of Tsc1 in Purkinje neurons differentially impairs cerebellar circuits based on sex. [ABSTRACT FROM AUTHOR]

Introduction: Physical fitness is associated with health-related quality of life, especially among youth. Although schools play an important role in promoting children's physical activity, in Italy the lack of qualified physical education teachers in primary schools may be compromising children's achievement of recommended levels of physical activity. Methods: To test that possibility, we measured the physical fitness of 170 children (i.e., 79 boys and 91 girls) 6-10 years old in two schools in Cadore, Veneto, in northeast Italy, using the Physical Fitness Test, a tool developed in Norway and previously used among children there and in Lithuania. Teachers in Italy also assessed their students' physical fitness, and their rankings were correlated with the children's test results. The test battery included nine elements: a standing broad jump, hopping 7 m on both feet, hopping 7 m on one foot, throwing a tennis ball, pushing a medicine ball, climbing wall bars, a 10 × 5 m shuttle run, a 20 m run, and a 6 min Cooper test. Results: Test scores generally increased with age and more steeply among boys than girls, and boys outperformed girls on most items. Children in Italy performed similarly to children in Norway but outperformed ones in Lithuania on nearly every item across sex and age groups. The correlation between teachers' predictions and the actual test results was rather low for boys (.538, p <.001) and even lower for girls (.360, p <.001). Discussion: Data revealed similar results in physical fitness between the three countries, albeit with some differences for individual items. However, primary school teachers in Italy assessed physical fitness rather poorly, possibly due to their lack of specific academic training in physical education and thus limited perception of physical fitness compared with academically trained physical education teachers. Last, because the procedure for categorizing children by age may significantly affect the results and subsequent between-group comparisons, researchers comparing children in different age groups should report their procedures for categorizing age. [ABSTRACT FROM AUTHOR]

There is a striking sex bias in the prevalence and severity of autism spectrum disorder (ASD) with 80% of diagnoses occurring in males. Because the molecular etiology of ASD is likely combinatorial, including interactions across multiple genetic and environmental factors, it is difficult to investigate the physiological mechanisms driving sex-specific differences. Loss of function mutations in TSC1 result in dysregulated mTORC1 signaling and underlie a multi-system disorder known as tuberous sclerosis (TSC). Interestingly, more than 50% of individuals diagnosed with TSC are also diagnosed with ASD, making TSC mutations one of the most prevalent monogenic causes of ASD. Mice harboring targeted deletion of Tsc1 selectively in cerebellar Purkinje neurons, referred to here as Tsc1mut/mut, have multiple ASD-linked behavioral impairments, including deficits in social interactions, motor coordination, and vocalizations. However, these ASD-linked behavioral deficits have only been investigated using male Tsc1mut/mut animals. Here, we used cohorts of male and female Tsc1mut/mut animals to determine if behavioral impairments, previously identified in this model, are similar across sex. Specifically, we measured balance and motor coordination and social interaction behaviors in two age groups across sex. We determined balance and motor coordination deficits are similar in male and female Tsc1mut/mut mice, and that deficits in the firing of Tsc1mut/mut Purkinje neurons located in the cerebellar vermis are also similar across sex. However, impairments in social approach behavior were found to be significantly more severe in Tsc1mut/mut males compared to females. These results indicate the selective deletion of Tsc1 in Purkinje neurons differentially impairs cerebellar circuits based on sex.

IntroductionPhysical fitness is associated with health-related quality of life, especially among youth. Although schools play an important role in promoting children's physical activity, in Italy the lack of qualified physical education teachers in primary schools may be compromising children's achievement of recommended levels of physical activity.MethodsTo test that possibility, we measured the physical fitness of 170 children (i.e., 79 boys and 91 girls) 6-10 years old in two schools in Cadore, Veneto, in northeast Italy, using the Physical Fitness Test, a tool developed in Norway and previously used among children there and in Lithuania. Teachers in Italy also assessed their students' physical fitness, and their rankings were correlated with the children's test results. The test battery included nine elements: a standing broad jump, hopping 7 m on both feet, hopping 7 m on one foot, throwing a tennis ball, pushing a medicine ball, climbing wall bars, a 10 × 5 m shuttle run, a 20 m run, and a 6 min Cooper test.ResultsTest scores generally increased with age and more steeply among boys than girls, and boys outperformed girls on most items. Children in Italy performed similarly to children in Norway but outperformed ones in Lithuania on nearly every item across sex and age groups. The correlation between teachers' predictions and the actual test results was rather low for boys (.538, p

Purposes: First, to examine the relationship between primary school children's academic achievement and healthy lifestyle habits. Second, to evaluate the effectiveness of two different 5-month physical education interventions (traditional physical education vs. coordinative physical education) on children's academic achievement. Third, to examine whether variations of anthropometric variables, fitness level, gross motor coordination, physical activity level, sedentary time, attentional performance, fruit and vegetable consumption, meal frequency and type of physical education intervention could predict children's academic achievement variations. Methods: Before and after the intervention, Italian language and mathematics skills, anthropometric variables (weight, height, body fat percentage, BMI), physical fitness (aerobic fitness, muscular strength, flexibility), gross motor coordination, attentional performance (processing speed, concentration performance, performance accuracy, attentional and inhibitory control), physical activity level, sedentary time and eating habits (meal frequency, fruit and vegetable consumption) were assessed in 161 Italian primary school children, randomly assigned to a traditional physical education group or to a coordinative physical education group. Results: Physical activity level, gross motor coordination and aerobic fitness moderately predicted mathematics skill (R² = 17%). Moreover, physical activity level, aerobic fitness and muscular strength moderately predicted Italian language skill (R² = 21%). Intervention type differently affected academic achievement. Specifically, Italian language and mathematics skills significantly improved only after traditional intervention. Fruit consumption increase was positively associated with the improvement in academic achievement. Coordinative physical education intervention was associated with a lower probability of improvement in Italian language and mathematical skills. Conclusion: Motor ability and lifestyle habits may have a positive influence on academic achievement in children. Unexpectedly, traditional physical education intervention resulted to be more effective on both Italian language and mathematical skills. [ABSTRACT FROM AUTHOR]

Background: Motor coordination difficulties could contribute to social communication deficits in autistic children. However, the exploration of the mechanism implicated in these claims has been limited by the lack of potential confounders such as executive function (EF). Methods: We investigated the role that EF plays in the relationship between motor coordination and social communication in a school-aged autistic population via a structural model in a statistically robust manner. The results of questionnaires, including the Developmental Coordination Disorder questionnaire, the Behavior Rating Inventory of Executive Function, and the Social Responsiveness Scale, were collected to measure motor coordination, social communication deficits, and EF. Results: A total of 182 autistic children (7.61±1.31 years, 87.9% boys) were included in the final analysis. In the model with EF as a mediator, the total effect (β=-0.599, P<0.001) and the direct effect (β=-0.331, P =0.003) of motor coordination function on social communication were both significant among autistic children without intellectual disability (ID), as were indirect effects through EF (β=-0.268, P<0.001). Conclusion: EF partially mediates the motor coordination and social communication correlation among autistic children. We suggest that motor coordination should be included in the routine evaluation of autistic surveillance and rehabilitation procedures. [ABSTRACT FROM AUTHOR]

Background: Existing research underscores the positive influence of consistent physical activity, fitness, and motor coordination on school-aged children’s cognitive and academic performance. However, a gap exists in fully understanding this relationship among preschoolers, a critical age group where the development of cognitive functions is significant. The study aims to expand upon existing evidence that connects motor and cognitive development by examining the correlation between specific motor coordination and physical fitness skills and the development of constructive and conceptual thinking in preschool-aged children. Methods: Data from 56 children aged 4–5 years (mean age 4.5 ± 0.36y), comprising 30 girls and 26 boys, participated in this study. We assessed muscular strength (via standing long jump, wall toss test, flexibility), agility (4 × 5 m shuttle), cardiorespiratory fitness (20 m pacer test), and motor coordination (lateral jumping, platform shifting). Cognitive abilities were measured using the IDS-P. Results: Linear regression models showed that significant predictors of constructive thinking scores were observed solely for flexibility (p = 0.02) and shifting platforms (p = 0.01). Notably, flexibility exhibited a negative relationship (β = −1.68). In the context of conceptual thinking, significant predictors (p < 0.05) included standing long jump (p = 0.01), jumping laterally (p = 0.005), shifting platforms (p = 0.001), throwing (p = 0.02). Conclusion: Coordination-demanding activities seem to be related considerably to conceptual thinking in preschoolers. Integrating such motor activities into preschool curricula that demand cognitive engagement can positively influence the development of cognitive functions. [ABSTRACT FROM AUTHOR]

Pigs can be an important model for preclinical biological research, including neurological diseases such as Alcohol Use Disorder. Such research often involves longitudinal assessment of changes in motor coordination as the disease or disorder progresses. Current motor coordination tests in pigs are derived from behavioral assessments in rodents and lack critical aspects of face and construct validity. While such tests may permit for the comparison of experimental results to rodents, a lack of validation studies of such tests in the pig itself may preclude the drawing of meaningful conclusions. To address this knowledge gap, an apparatus modeled after a horizontally placed ladder and where the height of the rungs could be adjusted was developed. The protocol that was employed within the apparatus mimicked the walk and turn test of the human standardized field sobriety test. Here, five Sinclair miniature pigs were trained to cross the horizontally placed ladder, starting at a rung height of six inches and decreasing to three inches in one-inch increments. It was demonstrated that pigs can reliably learn to cross the ladder, with few errors, under baseline/unimpaired conditions. These animals were then involved in a voluntary consumption of ethanol study where animals were longitudinally evaluated for motor coordination changes at baseline, 2.5, 5, 7.5, and 10% ethanol concentrations subsequently to consuming ethanol. Consistent with our predictions, relative to baseline performance, motor incoordination increased as voluntary consumption of escalating concentrations of ethanol increased. Together these data highlight that the horizontal ladder test (HLT) test protocol is a novel, optimized and reliable test for evaluating motor coordination as well as changes in motor coordination in pigs. [ABSTRACT FROM AUTHOR]

The current study aims to provide an in-depth analysis and extension of the Environmental Stress Hypothesis (ESH) framework, focusing on the complex interplay between poor motor skills and internalising problems like anxiety and depression. Using an integrative research review methodology, this study synthesises findings from 38 articles, both empirical and theoretical, building upon previous foundational works. The hypothesis posits that poor motor skills serve as a primary stressor, leading to internalising problems through various secondary stressors. A rigorous comparison of data was conducted, considering study design, findings, and methodologies—while exploring variables such as age, sex, and comorbidities. The study also enhances the ESH framework by including intrapersonal stressors and introducing resource buffers, including optimism and familial support as additional influencing factors. This multi-level approach yields a more nuanced and comprehensive ESH framework, highlighting the need for future studies to consider variables that intersect across multiple domains and how the relationship between poor motor skills and internalising problems may vary across different life stages.

PurposesFirst, to examine the relationship between primary school children’s academic achievement and healthy lifestyle habits. Second, to evaluate the effectiveness of two different 5-month physical education interventions (traditional physical education vs. coordinative physical education) on children’s academic achievement. Third, to examine whether variations of anthropometric variables, fitness level, gross motor coordination, physical activity level, sedentary time, attentional performance, fruit and vegetable consumption, meal frequency and type of physical education intervention could predict children’s academic achievement variations.MethodsBefore and after the intervention, Italian language and mathematics skills, anthropometric variables (weight, height, body fat percentage, BMI), physical fitness (aerobic fitness, muscular strength, flexibility), gross motor coordination, attentional performance (processing speed, concentration performance, performance accuracy, attentional and inhibitory control), physical activity level, sedentary time and eating habits (meal frequency, fruit and vegetable consumption) were assessed in 161 Italian primary school children, randomly assigned to a traditional physical education group or to a coordinative physical education group.ResultsPhysical activity level, gross motor coordination and aerobic fitness moderately predicted mathematics skill (R2 = 17%). Moreover, physical activity level, aerobic fitness and muscular strength moderately predicted Italian language skill (R2 = 21%). Intervention type differently affected academic achievement. Specifically, Italian language and mathematics skills significantly improved only after traditional intervention. Fruit consumption increase was positively associated with the improvement in academic achievement. Coordinative physical education intervention was associated with a lower probability of improvement in Italian language and mathematical skills.ConclusionMotor ability and lifestyle habits may have a positive influence on academic achievement in children. Unexpectedly, traditional physical education intervention resulted to be more effective on both Italian language and mathematical skills.

BackgroundExisting research underscores the positive influence of consistent physical activity, fitness, and motor coordination on school-aged children’s cognitive and academic performance. However, a gap exists in fully understanding this relationship among preschoolers, a critical age group where the development of cognitive functions is significant. The study aims to expand upon existing evidence that connects motor and cognitive development by examining the correlation between specific motor coordination and physical fitness skills and the development of constructive and conceptual thinking in preschool-aged children.MethodsData from 56 children aged 4–5 years (mean age 4.5 ± 0.36y), comprising 30 girls and 26 boys, participated in this study. We assessed muscular strength (via standing long jump, wall toss test, flexibility), agility (4 × 5 m shuttle), cardiorespiratory fitness (20 m pacer test), and motor coordination (lateral jumping, platform shifting). Cognitive abilities were measured using the IDS-P.ResultsLinear regression models showed that significant predictors of constructive thinking scores were observed solely for flexibility (p = 0.02) and shifting platforms (p = 0.01). Notably, flexibility exhibited a negative relationship (β = −1.68). In the context of conceptual thinking, significant predictors (p

The ability to finely control our movement is key to achieving many of the educational milestones and life-skills we develop throughout our lives. Despite the centrality of coordination to early development, there is a vast gap in our understanding of the underlying biology. Like most complex traits, both genetics and environment influence motor coordination, however, the specific genes, early environmental risk factors and molecular pathways are unknown. Previous studies have shown that about 5% of school-age children experience unexplained difficulties with motor coordination. These children are said to have Developmental Coordination Disorder (DCD). For children with DCD, these motor coordination difficulties significantly impact their everyday life and learning. DCD is associated with poorer academic achievement, reduced quality of life, it can constrain career opportunities and increase the risk of mental health issues in adulthood. Despite the high prevalence of coordination difficulties, many children remain undiagnosed by healthcare professionals. Compounding under-diagnosis in the clinic, research into the etiology of DCD is severely underrepresented in the literature. Here we present the first genome-wide association study to examine the genetic basis of early motor coordination in the context of motor difficulties. Using data from the Avon Longitudinal Study of Parents and Children we generate a derived measure of motor coordination from four components of the Movement Assessment Battery for Children, providing an overall measure of coordination across the full range of ability. We perform the first genome-wide association analysis focused on motor coordination (N = 4542). No single nucleotide polymorphisms (SNPs) met the threshold for genomewide significance, however, 59 SNPs showed suggestive associations. Three regions contained multiple suggestively associated SNPs, within five preliminary candidate genes: IQSEC1, LRCC1, SYNJ2B2, ADAM20, and ADAM21. Association to the gene IQSEC1 suggests a potential link to axon guidance and dendritic projection processes as a potential underlying mechanism of motor coordination difficulties. This represents an interesting potential mechanism, and whilst further validation is essential, it generates a direct window into the biology of motor coordination difficulties. This research has identified potential biological drivers of DCD, a first step towards understanding this common, yet neglected neurodevelopmental disorder. [ABSTRACT FROM AUTHOR]

The mechanisms underlying bimanual coordination have not yet been fully elucidated. Here, we evaluated the clinical features of bimanual movement impairment in a patient following surgery for a frontal lobe tumor. The patient was an 80-year-old man who had undergone subtotal tumor resection for a tumor in the right superior frontal gyrus. Histological examination of the resected specimen led to the diagnosis of malignant lymphoma of the diffuse large B-cell type, and the patient subsequently received high-dose methotrexate-based chemotherapy. Postoperatively, the patient had difficulty with bimanual movement, and on the 5th postoperative day we found that the impairment could not be attributed to weakness. Temporal changes in the characteristics of manual movements were analyzed. Bimanual diadochokinesis (opening/closing of the hands, pronation/supination of the forearms, and sequential finger movements) was more disturbed than unilateral movements; in-phase movements were more severely impaired than anti-phase movements. Bimanual movement performance was better when cued using an auditory metronome. On the 15th postoperative day, movements improved. The present observations show that in addition to the disturbance of anti-phase bimanual movements, resection of the frontal lobe involving the supplementary motor area (SMA) and premotor cortex (PMC) can cause transient impairment of in-phase bimanual diadochokinesis, which can be more severe than the impairment of anti-phase movements. The effect of auditory cueing on bimanual skills may be useful in the diagnosis of anatomical localization of the superior frontal gyrus and functional localization of the SMA and PMC and in rehabilitation of patients with brain tumors, as in the case of degenerative movement disorders. [ABSTRACT FROM AUTHOR]

AimThis study investigated minor impairments in neurological, sensorimotor, and neuropsychological functioning in extremely preterm-born (EPT) children compared to term-born children. The aim was to explore the most affected domains and to visualize their co-occurrences in relationship maps.MethodsA prospective cohort of 56 EPT children (35 boys) and 37 term-born controls (19 boys) were assessed at a median age of 6 years 7 months with Touwen Neurological Examination, Movement Assessment Battery for Children, 2nd edition (MABC-2), Sensory Integration and Praxis Test (SIPT), and a Developmental Neuropsychological Assessment, 2nd edition (NEPSY-II). Altogether 20 test domains were used to illustrate the frequency of impaired test performances with a bar chart profile and to construct relationship maps of co-occurring impairments.ResultsThe EPT children were more likely to perform inferiorly compared to the term-born controls across all assessments, with a wider variance and more co-occurring impairments. When aggregating all impaired test domains, 45% of the EPT children had more impaired domains than any term-born child (more than five domains, p

Spinal cord injury (SCI) induces neurological deficits associated with longterm functional impairments. Since the current treatments remain ineffective, novel therapeutic options are needed. Besides its effect on bipolar mood disorder, lithium was reported to have neuroprotective activity in different neurodegenerative conditions, including SCI. In SCI, the effects of lithium on long-term neurological recovery and neuroplasticity have not been assessed. We herein investigated the effects of intraperitoneally administered lithium chloride (LiCl) on motor coordination recovery, electromyography (EMG) responses, histopathological injury and remodeling, and axonal plasticity in mice exposed to spinal cord transection. At a dose of 0.2, but not 2.0 mmol/kg, LiCl enhanced motor coordination and locomotor activity starting at 28 days post-injury (dpi), as assessed by a set of behavioral tests. Following electrical stimulation proximal to the hemitransection, LiCl at 0.2 mmol/kg decreased the latency and increased the amplitude of EMG responses in the denervated hindlimb at 56 dpi. Functional recovery was associated with reduced gray and white matter atrophy rostral and caudal to the hemitransection, increased neuronal survival and reduced astrogliosis in the dorsal and ventral horns caudal to the hemitransection, and increased regeneration of long-distance axons proximal and distal to the lesion site in mice receiving 0.2 mmol/kg, but not 2 mmol/kg LiCl, as assessed by histochemical and immunohistochemical studies combined with anterograde tract tracing. Our results indicate that LiCl induces long-term neurological recovery and neuroplasticity following SCI. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to investigate the arm--forearm coordination of both the injured and uninjured UL of TBPI subjects. Methods: TBPI participants (n = 13) and controls (n = 10) matched in age, gender, and anthropometric characteristics were recruited. Kinematics from the shoulder, elbow, wrist, and index finger markers were collected, while upstanding participants transported a cup to their mouth and returned the UL to a starting position. The UL coordination was measured through the relative phase (RP) between arm and forearm phase angles and analyzed as a function of the hand kinematics. Results: For all participants, the hand transport had a shorter time to peak velocity (p < 0.01) compared to the return. Also, for the control and the uninjured TBPI UL, the RP showed a coordination pattern that favored forearm movements in the peak velocity of the transport phase (p < 0.001). TBPI participants' injured UL showed a longer movement duration in comparison to controls (p < 0.05), but no di erences in peak velocity, time to peak velocity, and trajectory length, indicating preserved hand kinematics. The RP of the injured UL revealed altered coordination in favor of armmovements compared to controls and the uninjured UL (p < 0.001). Finally, TBPI participants' uninjured UL showed altered control of arm and forearm phase angles during the deceleration of hand movements compared to controls (p < 0.05). Conclusion: These results suggest that UL coordination is reorganized after a TBPI so as to preserve hand kinematics. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) induces neurological deficits associated with long-term functional impairments. Since the current treatments remain ineffective, novel therapeutic options are needed. Besides its effect on bipolar mood disorder, lithium was reported to have neuroprotective activity in different neurodegenerative conditions, including SCI. In SCI, the effects of lithium on long-term neurological recovery and neuroplasticity have not been assessed. We herein investigated the effects of intraperitoneally administered lithium chloride (LiCl) on motor coordination recovery, electromyography (EMG) responses, histopathological injury and remodeling, and axonal plasticity in mice exposed to spinal cord transection. At a dose of 0.2, but not 2.0 mmol/kg, LiCl enhanced motor coordination and locomotor activity starting at 28 days post-injury (dpi), as assessed by a set of behavioral tests. Following electrical stimulation proximal to the hemitransection, LiCl at 0.2 mmol/kg decreased the latency and increased the amplitude of EMG responses in the denervated hindlimb at 56 dpi. Functional recovery was associated with reduced gray and white matter atrophy rostral and caudal to the hemitransection, increased neuronal survival and reduced astrogliosis in the dorsal and ventral horns caudal to the hemitransection, and increased regeneration of long-distance axons proximal and distal to the lesion site in mice receiving 0.2 mmol/kg, but not 2 mmol/kg LiCl, as assessed by histochemical and immunohistochemical studies combined with anterograde tract tracing. Our results indicate that LiCl induces long-term neurological recovery and neuroplasticity following SCI.

The correlation between the performance of coordination movement and brain activity is still not fully understood. The current study aimed to identify activated brain regions and brain network connectivity changes for several coordinated finger movements with different difficulty levels and to correlate the brain hemodynamics and connectivity with kinematic performance. Methods: Twenty-one right-dominant-handed subjects were recruited and asked to complete circular motions of single and bilateral fingers in the same direction (in-phase, IP) and in opposite directions (anti-phase, AP) on a plane. Kinematic data including radius and angular velocity at each task and synchronized blood oxygen concentration data using functional near-infrared spectroscopy (fNIRS) were recorded covering six brain regions including the prefrontal cortex, motor cortex, and occipital lobes. A general linear model was used to locate activated brain regions, and changes compared with baseline in blood oxygen concentration were used to evaluate the degree of brain region activation. Small-world properties, clustering coefficients, and efficiency were used to measure information interaction in brain activity during the movement. Result: It was found that the radius error of the dominant hand was significantly lower than that of the non-dominant hand (p < 0.001) in both clockwise and counterclockwise movements. The fNIRS results confirmed that the contralateral brain region was activated during single finger movement and the dominant motor area was activated in IP movement, while both motor areas were activated simultaneously in AP movement. The 1hbo were weakly correlated with radius errors (p = 0.002). Brain information interaction in IP movement was significantly larger than that from AP movement in the brain network (p < 0.02) in the right prefrontal cortex. Brain activity in the right motor cortex reduces motor performance (p < 0.001), while the right prefrontal cortex region promotes it (p < 0.05). Conclusion: Our results suggest there was a significant correlation between motion performance and brain activation level, as well as between motion deviation and brain functional connectivity. The findings may provide a basis for further exploration of the operation of complex brain networks. [ABSTRACT FROM AUTHOR]

Cancer induced bone pain (CIBP) occurs in patients with advanced osteosarcoma or metastasized bone tumors that can negatively affects the patient's quality of life. However, motor impairment in CIBP is still understudied. To improve the quality of life of patients with CIBP, the study of CIBP induced movement impairment is of particular importance. Here, we presented a model of metastatic cancer induced bone pain caused by an allograft of Lewis lung cancer cells. In this method, we injected Lewis lung cancer cells into the femoral medulla cavity and recorded the pain behavior and motor behavior after CIBP surgery. We observed enhanced pain after the initial surgery. Interestingly, we found the latency on rotarod was significantly reduced concomitant with tumor growth and pain. This result indicated that the motor coordination and balance were severely impaired in CIBP. We also found the pain and motor behavioral differences in models that severed the patellar ligament vs. maintaining the patellar ligament. These findings provide a novel clue for further investigating the mechanisms responsible for the generation and development of CIBP. [ABSTRACT FROM AUTHOR]

The expression of circadian clock genes, either centrally or in the periphery, has been shown to play an integral role in the control of behavior. Brain region-specific downregulation of clock genes revealed behavioral phenotypes associated with neuropsychiatric disorders and neurodegenerative disease. The specific function of the clock genes as well as the underlying mechanisms that contribute to the observed phenotypes, however, are not yet fully understood. We assessed anxiety- and depressive-like behavior and motor functions in male and female mice with a conditional ablation of Bmal1 or Per2 from medium spiny neurons (MSNs) of the striatum as well as mice lacking one copy of Gpr88. Whereas the conditional knockout of Bmal1 and Per2 had mild effects on affective behaviors, a pronounced effect on motor functions was found in Bmal1 knockout mice. Subsequent investigation revealed an attenuated response of Bmal1 knockout mice to dopamine receptor type 1 agonist treatment, independently of the expression of targets of the dopamine signaling pathway or mitochondrial respiration in MSNs. The study thus suggests a potential interaction of Bmal1 within the direct dopamine signaling pathway, which may provide the link to a shared, MSN-dependent mechanism regulating affective behavior and motor function in mice. [ABSTRACT FROM AUTHOR]

Assessment of motor competence (MC) is crucial to finding deficiencies in children's motor development. Because of the need to ensure validity, reliability, and feasibility, the selection of contemporary testing batteries is a difficult task. Many papers report the validity of the KTK test in describing MC in school aged children. KTK consists of 4 four separate items: walking back, jumping sideways, moving sideways, and hopping for height. Some authors suggested the use of a short version of KTK that includes 3 items excluding one subtest: hopping for height. This study aimed to evaluate the effectiveness of short versions of Körperkoordinationstest für Kinder (KTK). A sample of 2,231 participants (boys: n=1,188; girls: n = 1,043; age range: 6–12 years) were recruited from Italian schools between January 2019 and February 2020 and they performed the complete version of KTK. Stepwise linear regression was performed on the dataset to evaluate the ideal number of variables to describe the KTK short form version. Data for both the sexes and all ages indicated that considering the item combinations of each short version, the highest R squares were obtained in those that included exactly the deleted subtest (ranging from 0.881–0.979). The adoption of a short form does not seem to provide a fully satisfactory condition for measuring MC in children 6–12 years.

Research suggests a relationship between sensory processing, motor skills and quality of life (QOL) in a variety of clinical populations of adults and children. There have been no studies which investigated the relationship of childhood sensory processing and integration and related motor performance (sensori-motor) patterns identified using an Ayres Sensory Integration® (ASI) frame of reference and later QOL of those children as adults. This longitudinal follow-up study examined this relationship. Adult QOL was also examined in relation to current adult sensori-motor patterns. Fifty-three adults who received occupational therapy services as children, were identified as having sensori-motor difficulties at that time and completed a sensory history and a quality-of-life measure as adults participated. Measures included the OTA the Koomar Center Sensory History (SXHX), Adult/Adolescent Sensory History (ASH), and the World Health Organization Quality of Life-Brief (WHOQOL-BREF). MANCOVA found that Total childhood sensori-motor scores had a small relationship to Physical Health QOL as adults that approached significance. Pearson Correlations found that adults with childhood sensori-motor challenges who report sensori-motor challenges as adults had a moderate significant relationship among overall sensori-motor functioning and Physical Health (r = −0.56, p = 0.018). Visual (r = −0.76, p = 0.001), movement (vestibular; r = −0.48, p = 0.042) and tactile processing (r = −0.63, p = 0.008) had moderate to large significant relationships with Physical Health. Visual processing (r = −0.54, p = 0.024) was also significantly related to Psychological Health. Motor Coordination trended to significance for Physical Health (r = −0.42) and Psychological Health (r = −0.41). Conversely, adults who reported typical sensori-motor scores as adults, despite childhood sensori-motor challenges, had a good QOL. Furthermore, similar to previous research, there was a relationship between current visual, movement (vestibular) and tactile (touch) sensory processing and adult Physical and Psychological Health. A multivariate linear regression found Sensory Discrimination and Modulation accounted for one-quarter of the variance in QOL in adults with only Discrimination being statistically significant. Therefore, it is important to consider childhood sensori-motor function as well as adult functioning when examining QOL. Further, heretofore unexamined Sensory Discrimination was found to play a role in adult QOL.

Cancer induced bone pain (CIBP) occurs in patients with advanced osteosarcoma or metastasized bone tumors that can negatively affects the patient's quality of life. However, motor impairment in CIBP is still understudied. To improve the quality of life of patients with CIBP, the study of CIBP induced movement impairment is of particular importance. Here, we presented a model of metastatic cancer induced bone pain caused by an allograft of Lewis lung cancer cells. In this method, we injected Lewis lung cancer cells into the femoral medulla cavity and recorded the pain behavior and motor behavior after CIBP surgery. We observed enhanced pain after the initial surgery. Interestingly, we found the latency on rotarod was significantly reduced concomitant with tumor growth and pain. This result indicated that the motor coordination and balance were severely impaired in CIBP. We also found the pain and motor behavioral differences in models that severed the patellar ligament vs. maintaining the patellar ligament. These findings provide a novel clue for further investigating the mechanisms responsible for the generation and development of CIBP.

The expression of circadian clock genes, either centrally or in the periphery, has been shown to play an integral role in the control of behavior. Brain region-specific downregulation of clock genes revealed behavioral phenotypes associated with neuropsychiatric disorders and neurodegenerative disease. The specific function of the clock genes as well as the underlying mechanisms that contribute to the observed phenotypes, however, are not yet fully understood. We assessed anxiety- and depressive-like behavior and motor functions in male and female mice with a conditional ablation of Bmal1 or Per2 from medium spiny neurons (MSNs) of the striatum as well as mice lacking one copy of Gpr88. Whereas the conditional knockout of Bmal1 and Per2 had mild effects on affective behaviors, a pronounced effect on motor functions was found in Bmal1 knockout mice. Subsequent investigation revealed an attenuated response of Bmal1 knockout mice to dopamine receptor type 1 agonist treatment, independently of the expression of targets of the dopamine signaling pathway or mitochondrial respiration in MSNs. The study thus suggests a potential interaction of Bmal1 within the direct dopamine signaling pathway, which may provide the link to a shared, MSN-dependent mechanism regulating affective behavior and motor function in mice.

Although numerous evidences reported a negative correlation between motor coordination (MC) and overweight/obesity in children and adolescents, the interrelationship between age, gender, and weight status is still debatable. Hence, the aim of this cross-sectional study was to examine the association between MC and weight status according to age and gender across childhood and early adolescence in a large sample of Italian elementary and middle school students. A number of 1961 Italian school students (1,026 boys, 935 girls) was stratified in three consecutive age groups (6–7, 8–10, and 11–13 years) and four weight status categories (underweight, normal weight, overweight, and obese) according to Cole's body mass index (BMI) cut-off points for children. MC performance was assessed measuring motor quotient (MQ) with the Körperkoordinationstest für Kinder (KTK). Results showed significantly lower MQ levels in children in overweight (OW) and with obesity (OB) in both sexes for all age groups than peers in normal weight (NW), except in 6–7-year-old boys. Girls in OW and with OB had similar MQ levels across all age groups, while younger boys in OW and with OB showed higher MQ levels than older ones (p < 0.05). The 6–7-year-old boys showed better MQ levels than girls peers in NW, OW, and with OB, while 8–10-year-old boys in underweight (UW), NW, and OW; and 11–13-year-old boys only in NW (p < 0.05). No interaction effect was found between age, gender, and weight status on MQ levels. These outcomes showed the negative impact of higher weight status on MC performance according to age and gender, pointing out the importance of planning targeted motor programs that consider these variables to improve MC performance.

The ability to finely control our movement is key to achieving many of the educational milestones and life-skills we develop throughout our lives. Despite the centrality of coordination to early development, there is a vast gap in our understanding of the underlying biology. Like most complex traits, both genetics and environment influence motor coordination, however, the specific genes, early environmental risk factors and molecular pathways are unknown. Previous studies have shown that about 5% of school-age children experience unexplained difficulties with motor coordination. These children are said to have Developmental Coordination Disorder (DCD). For children with DCD, these motor coordination difficulties significantly impact their everyday life and learning. DCD is associated with poorer academic achievement, reduced quality of life, it can constrain career opportunities and increase the risk of mental health issues in adulthood. Despite the high prevalence of coordination difficulties, many children remain undiagnosed by healthcare professionals. Compounding under-diagnosis in the clinic, research into the etiology of DCD is severely underrepresented in the literature. Here we present the first genome-wide association study to examine the genetic basis of early motor coordination in the context of motor difficulties. Using data from the Avon Longitudinal Study of Parents and Children we generate a derived measure of motor coordination from four components of the Movement Assessment Battery for Children, providing an overall measure of coordination across the full range of ability. We perform the first genome-wide association analysis focused on motor coordination (N = 4542). No single nucleotide polymorphisms (SNPs) met the threshold for genome-wide significance, however, 59 SNPs showed suggestive associations. Three regions contained multiple suggestively associated SNPs, within five preliminary candidate genes: IQSEC1 , LRCC1 , SYNJ2B2 , ADAM20 , and ADAM21. Association to the gene IQSEC1 suggests a potential link to axon guidance and dendritic projection processes as a potential underlying mechanism of motor coordination difficulties. This represents an interesting potential mechanism, and whilst further validation is essential, it generates a direct window into the biology of motor coordination difficulties. This research has identified potential biological drivers of DCD, a first step towards understanding this common, yet neglected neurodevelopmental disorder. [ABSTRACT FROM AUTHOR]

Learning to drive is a significant event for the transition to adulthood and delay or avoidance may have social, practical, and psychological implications. For those with Developmental Coordination Disorder (DCD/Dyspraxia), driving presents a considerable challenge, and the literature shows that there are differences in driving ability between individuals with and without DCD. The aim of the current research is to further our understanding of the mechanisms underlying the driving experiences of individuals with DCD. Nineteen participants with DCD (10 drivers and 9 non-drivers) and 36 controls (17 drivers and 19 non-drivers) aged 18–57 years took part in this study. Participants completed standardized tests, questionnaires and a driving simulation task designed to measure speed, road positioning, and rate of change of steering in three conditions with increasing perceptual complexity. Results indicate that behaviors for all participants changed as the perceptual demands of the task increased. However, drivers with DCD were more affected than all other groups, driving more slowly, and driving further to the right. These findings illustrate how the impact of both internal and external constraints negatively affect the success of the driving task for individuals with DCD compared to their TD peers.

Background: Primary familial brain calcification (PFBC, OMIM#213600), also known as Fahr's disease, is a rare autosomal dominant or recessive neurodegenerative disorder characterized by bilateral and symmetrical microvascular calcifications affecting multiple brain regions, particularly the basal ganglia (globus pallidus, caudate nucleus, and putamen) and thalamus. The most common clinical manifestations include cognitive impairment, neuropsychiatric signs, and movement disorders. Loss-of-function mutations in SLC20A2 are the major genetic causes of PFBC. Objective: This study aimed to investigate whether Slc20a2 knockout mice could recapitulate the dynamic processes and patterns of brain calcification and neurological symptoms in patients with PFBC. We comprehensively evaluated brain calcifications and PFBC-related behavioral abnormalities in Slc20a2 -deficient mice. Methods: Brain calcifications were analyzed using classic calcium-phosphate staining methods. The Morris water maze, Y-maze, and fear conditioning paradigms were used to evaluate long-term spatial learning memory, working memory, and episodic memory, respectively. Sensorimotor gating was mainly assessed using the prepulse inhibition of the startle reflex program. Spontaneous locomotor activity and motor coordination abilities were evaluated using the spontaneous activity chamber, cylinder test, accelerating rotor-rod, and narrowing balance beam tests. Results: Slc20a2 homozygous knockout (Slc20a2 -HO) mice showed congenital and global developmental delay, lean body mass, skeletal malformation, and a high proportion of unilateral or bilateral eye defects. Brain calcifications were detected in the hypothalamus, ventral thalamus, and midbrain early at postnatal day 80 in Slc20a2 -HO mice, but were seldom found in Slc20a2 heterozygous knockout (Slc20a2 -HE) mice, even at extremely old age. Slc20a2 -HO mice exhibited spatial learning memory impairments and sensorimotor gating deficits while exhibiting normal working and episodic memories. The general locomotor activity, motor balance, and coordination abilities were not statistically different between Slc20a2 -HO and wild-type mice after adjusting for body weight, which was a major confounding factor in our motor function evaluations. Conclusion: The human PFBC-related phenotypes were highly similar to those in Slc20a2 -HO mice. Therefore, Slc20a2 -HO mice might be suitable for the future evaluation of neuropharmacological intervention strategies targeting cognitive and neuropsychiatric impairments. [ABSTRACT FROM AUTHOR]

Learning to drive is a significant event for the transition to adulthood and delay or avoidance may have social, practical, and psychological implications. For those with Developmental Coordination Disorder (DCD/Dyspraxia), driving presents a considerable challenge, and the literature shows that there are differences in driving ability between individuals with and without DCD. The aim of the current research is to further our understanding of the mechanisms underlying the driving experiences of individuals with DCD. Nineteen participants with DCD (10 drivers and 9 non-drivers) and 36 controls (17 drivers and 19 non-drivers) aged 18–57 years took part in this study. Participants completed standardized tests, questionnaires and a driving simulation task designed to measure speed, road positioning, and rate of change of steering in three conditions with increasing perceptual complexity. Results indicate that behaviors for all participants changed as the perceptual demands of the task increased. However, drivers with DCD were more affected than all other groups, driving more slowly, and driving further to the right. These findings illustrate how the impact of both internal and external constraints negatively affect the success of the driving task for individuals with DCD compared to their TD peers. [ABSTRACT FROM AUTHOR]

The frontal aslant tract (FAT) is a recently identified white matter tract connecting the supplementary motor complex and lateral superior frontal gyrus to the inferior frontal gyrus. Advancements in neuroimaging and refinements to anatomical dissection techniques of the human brain white matter contributed to the recent description of the FAT anatomical and functional connectivity and its role in the pathogenesis of several neurological, psychiatric, and neurosurgical disorders. Through the application of diffusion tractography and intraoperative electrical brain stimulation, the FAT was shown to have a role in speech and language functions (verbal fluency, initiation and inhibition of speech, sentence production, and lexical decision), working memory, visual–motor activities, orofacial movements, social community tasks, attention, and music processing. Microstructural alterations of the FAT have also been associated with neurological disorders, such as primary progressive aphasia, post-stroke aphasia, stuttering, Foix–Chavany–Marie syndrome, social communication deficit in autism spectrum disorders, and attention–deficit hyperactivity disorder. We provide a systematic review of the current literature about the FAT anatomical connectivity and functional roles. Specifically, the aim of the present study relies on providing an overview for practical neurosurgical applications for the pre-operative, intra-operative, and post-operative assessment of patients with brain tumors located around and within the FAT. Moreover, some useful tests are suggested for the neurosurgical evaluation of FAT integrity to plan a safer surgery and to reduce post-operative deficits.

Senescence-accelerated mouse prone 8 (SAMP8) is an animal model of age-related central nervous system (CNS) disorders. Although SAMP8 shows deficits in learning, memory, and emotion, its motor coordination has not been clarified. We have recently reported that DGKγ-regulated PKCγ activity is important for cerebellar motor coordination. However, involvement of the functional correlation between the kinases in age-related motor dyscoordination still remains unknown. Therefore, we have investigated the motor coordination in SAMP8 and involvement of the functional correlation between DGKγ and PKCγ in the age-related motor dyscoordination. Although 6 weeks old SAMP8 showed equivalent motor coordination with control mice (SAMR1) in the rotarod test, 24 weeks old SAMP8 exhibited significantly less latency in the rotarod test and more frequent slips in the beam test compared to the age-matched SAMR1. Furthermore, 24 weeks old SAMP8 showed the higher locomotor activity in open field test and Y-maze test. Western blotting revealed that DGKγ expression decreased in the cerebellum of 24 weeks old SAMP8, while PKCγ was upregulated. These results suggest that SAMP8 is a useful model of age-related motor dysfunction and that the DGKγ-regulated PKCγ activity is involved in the age-related motor dyscoordination.

Chronic exposure to a high-fat diet (HFD) may predispose individuals to neuropathologies and behavioral deficits. The objective of this study was to determine the temporal effects of a HFD on weight gain, behavioral deficits, and dopamine changes in young mice. One-month old C57BL/6J male and female mice were fed either a control diet (containing 10% calories from fat) or a HFD (containing 45% of calories from fat) for 5 months. Physiological measures such as food consumption, body weight, blood glucose, and behaviors such as motor activity, sensorimotor integration, and anxiety-like behaviors were evaluated monthly. Dopamine (DA), dopamine receptor D2 (DRD2), and dopamine transporter (DT) protein expression levels were measured in the midbrain after 5 months of dietary exposure. Results showed that body weight was significantly greater in the HFD-exposed group compared to the control-group at the end of the 4th month, while food consumption was similar in both groups. For behavioral effects, the HFD group exhibited a significant decrease in motor activity in the open field test after 3 months, and rearing frequency after 4 months of dietary exposure. The HFD group also showed deficits in sensorimotor integration after 3 months. Specifically, chronic HFD exposure increased contact time and time to remove the first adhesive tape in the adhesive-tape removal test (p < 0.05). Furthermore, the HFD group showed significant deficits in balance/coordination compared to the control group after 4 months of dietary exposure using the beam traverse test, and increased anxiety-like behavior tested by both the open field and light/dark box tests (p < 0.05). Neurochemical measurements showed that HFD-exposed mice had significantly higher midbrain DA and DRD2 protein levels compared to the control group after 5 months of dietary exposure (p < 0.05). These results indicate that the impact of HFD on the C57BL/6J mouse strain began at the 3rd month of dietary exposure. Behavioral deficits occurred at a similar time point as increased body weight, at about 3–4 months. Overall, this study provides a critical understanding on how HFD-induced changes in weight gain and behavioral deficits in this strain occur over time. The behavioral changes support the idea that changes also occurred in neurochemical pathways such as dopamine dysregulation.

Kinematic synergies (kSYN) provide an approach to quantify the covariation of joint motions and to explain the mechanisms underlying human motor behavior. A low-dimensional control strategy by means of the activation of a moderate number of kSYN would simplify the performance of complex motor tasks. The purpose of this study was to examine similarities between the kSYN of varying locomotion tasks: straight-line walking, walking a 90° spin turn and walking upstairs. Task-specific kSYN were extracted from full body kinematic recordings of 13 participants by principal component analysis. The first five kSYN accounting for most of the variance within each task were selected for further analysis following previous studies. The similarities between the kSYN of the three different locomotion tasks were quantified by calculating cosine similarities (SIM), as a vector-based similarity measure ranging from 0 (no similarity) to 1 (high similarity), between absolute principal component loading vectors. A SIM between two kSYN > 0.8 was interpreted as highly similar. Two to three highly similar kSYN were identified when comparing two individual tasks with each other. One kSYN, primarily characterized by anteversion and retroversion of the arms and legs, were found to be similar in all three tasks. Additional kSYN that occurred between individual tasks reflected mainly an upwards/downwards movement of the body or a countercyclical knee flexion/extension. The results demonstrate that the three investigated locomotion tasks are characterized by kSYN and that certain kSYN repeatedly occur across the three locomotion tasks. PCA yields kSYN which are in descent order according to their amount of total variance accounted for. Referring to the placing of a kSYN within the order as priorization, we found a change in priorization of repeatedly occurring kSYN across the individual tasks. The findings support the idea that movements can be efficiently performed through a flexible combination of a lower number of control-relevant variables.

The frontal aslant tract (FAT) is a recently identified white matter tract connecting the supplementary motor complex and lateral superior frontal gyrus to the inferior frontal gyrus. Advancements in neuroimaging and refinements to anatomical dissection techniques of the human brain white matter contributed to the recent description of the FAT anatomical and functional connectivity and its role in the pathogenesis of several neurological, psychiatric, and neurosurgical disorders. Through the application of diffusion tractography and intraoperative electrical brain stimulation, the FAT was shown to have a role in speech and language functions (verbal fluency, initiation and inhibition of speech, sentence production, and lexical decision), working memory, visual–motor activities, orofacial movements, social community tasks, attention, and music processing. Microstructural alterations of the FAT have also been associated with neurological disorders, such as primary progressive aphasia, post-stroke aphasia, stuttering, Foix–Chavany–Marie syndrome, social communication deficit in autism spectrum disorders, and attention–deficit hyperactivity disorder. We provide a systematic review of the current literature about the FAT anatomical connectivity and functional roles. Specifically, the aim of the present study relies on providing an overview for practical neurosurgical applications for the pre-operative, intra-operative, and post-operative assessment of patients with brain tumors located around and within the FAT. Moreover, some useful tests are suggested for the neurosurgical evaluation of FAT integrity to plan a safer surgery and to reduce post-operative deficits. [ABSTRACT FROM AUTHOR]

Senescence-accelerated mouse prone 8 (SAMP8) is an animal model of age-related central nervous system (CNS) disorders. Although SAMP8 shows deficits in learning, memory, and emotion, its motor coordination has not been clarified. We have recently reported that DGKγ-regulated PKCγ activity is important for cerebellar motor coordination. However, involvement of the functional correlation between the kinases in age-related motor dyscoordination still remains unknown. Therefore, we have investigated the motor coordination in SAMP8 and involvement of the functional correlation between DGKγ and PKCγ in the age-related motor dyscoordination. Although 6 weeks old SAMP8 showed equivalent motor coordination with control mice (SAMR1) in the rotarod test, 24 weeks old SAMP8 exhibited significantly less latency in the rotarod test and more frequent slips in the beam test compared to the age-matched SAMR1. Furthermore, 24 weeks old SAMP8 showed the higher locomotor activity in open field test and Y-maze test. Western blotting revealed that DGKγ expression decreased in the cerebellum of 24 weeks old SAMP8, while PKCγ was upregulated. These results suggest that SAMP8 is a useful model of age-related motor dysfunction and that the DGKγ-regulated PKCγ activity is involved in the age-related motor dyscoordination. [ABSTRACT FROM AUTHOR]

In this study, we performed a comprehensive behavioral and anatomical analysis of the Missing in Metastasis (Mtss1/MIM) knockout (KO) mouse brain. We also analyzed the expression of MIM in different brain regions at different ages. MIM is an I-BAR containing membrane curving protein, shown to be involved in dendritic spine initiation and dendritic branching in Purkinje cells in the cerebellum. Behavioral analysis of MIM KO mice revealed defects in both learning and reverse-learning, alterations in anxiety levels and reduced dominant behavior, and confirmed the previously described deficiency in motor coordination and pre-pulse inhibition. Anatomically, we observed enlarged brain ventricles and decreased cortical volume. Although MIM expression was relatively low in hippocampus after early development, hippocampal pyramidal neurons exhibited reduced density of thin and stubby dendritic spines. Learning deficiencies can be connected to all detected anatomical changes. Both behavioral and anatomical findings are typical for schizophrenia mouse models.

Background: Developmental coordination disorder (DCD) and attention-deficit hyperactivity disorder (ADHD) are highly comorbid in children. There is evidence linking second hand smoke (SHS) exposure in utero to ADHD; however, it's relation to DCD is unknown. The purpose of this study was to examine the effect of SHS exposure in utero in children with and without DCD.Methods: This study was a cross-sectional examination of 122 children from the District School Board of Niagara (72 males, 50 females, Mage = 12.9 years) who were part of a larger, prospective cohort study. Participants were assessed for motor proficiency and intelligence and were screened for symptoms of ADHD using the Bruininks-Oseretsky Test of Motor Proficiency-Short Form, the Kaufman Brief Intelligence Inventory, 2nd edition, and the Conners' Parent Rating Scales-Revised: Short Form, respectively. Parent questionnaires were used to determine SHS exposure in utero as either yes or no. Multinomial logistic regression was used to examine the relationship between SHS exposure and DCD risk.Results: Children exposed to SHS in utero were significantly more likely to be at high risk for DCD than children who were not (OR = 3.33, p = 0.004), and children exposed to SHS in utero were more likely to be at moderate risk for DCD in the presence (OR = 3.57, p = 0.025) or absence of ADHD (OR = 2.38, p = 0.042). However, statistical adjustment for birth weight, socioeconomic status, age, and sex reduced this effect to non-significance in the moderate risk group.Conclusion: Results suggest exposure to SHS during pregnancy increases the chances of a child developing high risk DCD. While SHS exposure may increase DCD risk with and without ADHD, this effect may be explained by covariates and confounding factors. Further study is needed to examine the mechanisms linking SHS exposure in utero to motor coordination problems in children.

Movement coordination depends on directing our limbs to the right place and in the right time. Movement science can study this central requirement in the Fitts task that asks participants to touch each of two targets in alternation, as accurately and as fast as they can. The Fitts task is an experimental attempt to focus on how the movement system balances its attention to speed and to accuracy. This balance in the Fitts task exhibits a hierarchical organization according to which finer details (e.g., kinematics of single sweeps from one target to the other) change with relatively broader constraints of task parameters (e.g., distance between targets and width of targets). The present work seeks to test the hypothesis that this hierarchical organization of movement coordination reflects a multifractal tensegrity in which non-linear interactions across scale support stability. We collected movement series data during a easy variant of the Fitts task to apply just such a multifractal analysis with surrogate comparison to allow clearer test of non-linear interactions across scale. Furthermore, we test the role of visual feedback both in potential and in fact, i.e., by manipulating both whether experimenters instructed participants that they might potentially have to close their eyes during the task and whether participants actually closed their eyes halfway through the task. We predict that (1) non-linear interactions across scales in hand movement series will produce variability that will actually stabilize aiming in the Fitts task, reducing standard deviation of target contacts; (2) non-linear interactions across scales in head sway will stabilize aiming following the actual closing eyes; and (3) non-linear interactions across scales in head sway and in hand movements will interact to support stabilizing effects of expectation about closing eyes. In sum, this work attempts to make the case that the multifractal-tensegrity hypothesis supports more accurate aiming behavior in the Fitts task.

In this study, we performed a comprehensive behavioral and anatomical analysis of the Missing in Metastasis (Mtss1/MIM) knockout (KO) mouse brain. We also analyzed the expression of MIM in different brain regions at different ages. MIM is an I-BAR containing membrane curving protein, shown to be involved in dendritic spine initiation and dendritic branching in Purkinje cells in the cerebellum. Behavioral analysis of MIM KO mice revealed defects in both learning and reverse-learning, alterations in anxiety levels and reduced dominant behavior, and confirmed the previously described deficiency in motor coordination and pre-pulse inhibition. Anatomically, we observed enlarged brain ventricles and decreased cortical volume. Although MIM expression was relatively low in hippocampus after early development, hippocampal pyramidal neurons exhibited reduced density of thin and stubby dendritic spines. Learning deficiencies can be connected to all detected anatomical changes. Both behavioral and anatomical findings are typical for schizophrenia mouse models. [ABSTRACT FROM AUTHOR]

Movement coordination depends on directing our limbs to the right place and in the right time. Movement science can study this central requirement in the Fitts task that asks participants to touch each of two targets in alternation, as accurately and as fast as they can. The Fitts task is an experimental attempt to focus on how the movement system balances its attention to speed and to accuracy. This balance in the Fitts task exhibits a hierarchical organization according to which finer details (e.g., kinematics of single sweeps from one target to the other) change with relatively broader constraints of task parameters (e.g., distance between targets and width of targets). The present work seeks to test the hypothesis that this hierarchical organization of movement coordination reflects a multifractal tensegrity in which non-linear interactions across scale support stability. We collected movement series data during a easy variant of the Fitts task to apply just such a multifractal analysis with surrogate comparison to allow clearer test of non-linear interactions across scale. Furthermore, we test the role of visual feedback both in potential and in fact, i.e., by manipulating both whether experimenters instructed participants that they might potentially have to close their eyes during the task and whether participants actually closed their eyes halfway through the task. We predict that (1) non-linear interactions across scales in hand movement series will produce variability that will actually stabilize aiming in the Fitts task, reducing standard deviation of target contacts; (2) non-linear interactions across scales in head sway will stabilize aiming following the actual closing eyes; and (3) non-linear interactions across scales in head sway and in hand movements will interact to support stabilizing effects of expectation about closing eyes. In sum, this work attempts to make the case that the multifractal-tensegrity hypothesis supports more accurate aiming behavior in the Fitts task. [ABSTRACT FROM AUTHOR]

Altered neuronal connectivity has been implicated in the pathophysiology of Autism Spectrum Disorder (ASD). SLIT/ROBO signaling plays an important role in developmental processes of neuronal connectivity, including axon guidance, neuronal migration, and axonal and dendritic branching. Genetic evidence supports that SLIT3, one of the genes encoding SLITs, is associated with ASD. Yet the causal link between SLIT3 mutation and autism symptoms has not been examined. Here we assessed ASD-associated behaviors in Slit3 knockout (KO) mice. Our data showed that Slit3-KO mice exhibited reduced marble burying behaviors but normal social behaviors. In addition, Slit3-KO mice displayed hypolocomotion in the open field test and impaired motor coordination in the rotarod test. Anxiety-like behaviors were mainly observed in female KO mice assessed by three types of behavioral tests, namely, the open field test, elevated plus maze test, and light/dark box test. No differences were observed between KO and wildtype mice in recognition memory in the novel object recognition test or depression-like behavior in the tail suspension test. Taken together, loss of Slit3 may result in disrupted neural circuits related to motor function and increased anxiety-like states, which are co-occurring symptoms in ASD.

Background: Impairments in imitation abilities have been commonly described in children with autism spectrum disorder (ASD). How motricity in interpersonal coordination impacts imitation, during long lasting semi-ecological conditions, has not been carefully investigated.Methods: Eighty-five children and adolescents (39 controls with typical development, TD; 29 patients with ASD; 17 patients with developmental coordination disorder, DCD), aged 6 to 20 years, participated to a behavioral paradigm in which participants, standing and moving, interacted with a virtual tightrope walker standing and moving as well. During the protocol, we measured automatically and continuously bodily postures and movements from RGB sensor recording to assess participants' behavioral imitation.Results: We show that (1) interpersonal synchronization (as evidenced by the synchrony between the participant's and the tightrope walker's bars) and (2) motor coordination (as evidenced by the synchrony between the participant's bar and its own head axis) increased with age and were more impaired in patients with ASD. Also, motor control as evidenced by the movement angle standard deviations of participants' bar and head were significantly impaired in ASD compared to TD or DCD.Conclusion: Interpersonal synchronization and motor coordination during ecological interaction show both subtle impairment in children with ASD as compared to children with TD or DCD. These results questioned how motricity mature in terms of motor control and proprioception in children with ASD.

Methadone is used as a substitution drug for the treatment of opioid dependence and chronic pain. Despite its widespread use and availability, there is a serious concern with respect to the relative safety of methadone. The purpose of this study was to characterize how acute methadone overdose affects the cognitive and motor performance of naïve healthy rats. The methadone overdose was induced by administering an acute toxic dose of methadone (15 mg/kg; ip; the equivalent dose of 80% of LD50) to adolescent rats. Resuscitation using a ventilator pump along with a single dose of naloxone (2 mg/kg; ip) was administered following the occurrence of apnea. The animals which were successfully resuscitated divided randomly into three apnea groups that evaluated either on day 1, 5, or 10 post-resuscitation (M/N-Day 1, M/N-Day 5, and M/N-Day 10 groups) in the Y-maze and novel object memory recognition tasks as well as pole and rotarod tests. The data revealed that a single toxic dose of methadone had an adverse effect on spontaneous behavior. In addition, Recognition memory impairment was observed in the M/N-Day 1, 5, and 10 groups after methadone-induced apnea. Further, descending time in the M/N-Day 5 group increased significantly in comparison with its respective Saline control group. The overall results indicate that acute methadone-overdose-induced apnea produced delay-dependent cognitive and motor impairment. We suggest that methadone poisoning should be considered as a possible cause of delayed neurological disorders, which might be transient, in some types of memory or motor performance in naïve healthy rats.

School-aged children with developmental coordination disorder (DCD) are at greater risk for physical inactivity, lower global self-worth, and internalizing problems, such as depression and anxiety. Based on the environmental stress hypothesis (ESH), recent research has shown that physical inactivity and lower global self-worth sequentially mediate the relationship between DCD and internalizing problems, suggesting that DCD leads to lower levels of physical activity, which in turn leads to lower levels of global self-worth, and ultimately, a greater amount of internalizing problems. However, physical activity and global self-worth may also buffer (i.e., moderate) the adverse effect of DCD on internalizing problems. To date, this has yet to be tested. Participants were 1206 children aged 12–14 years [611 boys, 79 with probable DCD (pDCD)]. All children received assessments of motor coordination, physical activity, global self-worth, and internalizing problems. Children with pDCD were less physically active, had lower self-worth, and experienced more internalizing problems compared to typically developing (TD) children (p’s < 0.05). Furthermore, the moderated moderating effect (three-way interaction) of physical activity and global self-worth was also evident (p < 0.05), indicating that internalizing problems in both TD and pDCD groups decreased with concurrent increases in physical activity and global self-worth. Importantly, when compared to TD children, increases in physical activity and global self-worth were associated with a greater reduction in internalizing problems among children with pDCD. The findings support several pathways in the ESH and highlight that, in addition to improving motor skills, interventions should also target both physical activity and global self-worth to mitigate potential mental health issues for children with motor difficulties.

Parkinson’s disease (PD) is a neurodegenerative disorder of unknown etiology. The main treatment of PD consists of medication with dopamine-based drugs, which palliate the symptoms but may produce adverse effects after chronic administration. Accordingly, there is a need to develop novel neuroprotective therapies. Several studies suggest that omega-3 polyunsaturated fatty acids (n-3 PUFA) might provide protection against brain damage. Here, we studied several experimental models of PD, using striatal neuronal cultures, striatal slices, and mice, to assess the neuroprotective effects of docosahexaenoic acid (DHA), the main n-3 PUFA in the brain, administered in its triglyceride form (TG-DHA). Hence, we determined the beneficial effects of TG-DHA on neural viability following 6-hydroxydopamine (6-OHDA)-induced neurotoxicity, a well-established PD model. We also implemented a novel mouse behavioral test, the beam walking test, to finely assess mouse motor skills following dopaminergic denervation. This test showed potential as a useful behavioral tool to assess novel PD treatments. Our results indicated that TG-DHA-mediated neuroprotection was independent of the net incorporation of PUFA into the striatum, thus suggesting a tight control of brain lipid homeostasis both in normal and pathological conditions.

Although studies have investigated the role of gamma-aminobutyric acid (GABA)ergic signaling in rodent neural development and behaviors relevant to autism, behavioral ontogeny, as underlain by the changes in GABAergic system, is poorly characterized in different brain regions. Here, we employed a valproic acid (VPA) rat model of autism to investigate the autism-like behaviors and GABAergic glutamic acid decarboxylase 67 (GAD67) expression underlying these altered behaviors in multiple brain areas at different developmental stages from birth to adulthood. We found that VPA-treated rats exhibited behavioral abnormalities relevant to autism, including delayed nervous reflex development, altered motor coordination, delayed sensory development, autistic-like and anxiety behaviors and impaired spatial learning and memory. We also found that VPA rats had the decreased expression of GAD67 in the hippocampus (HC) and cerebellum from childhood to adulthood, while decreased GAD67 expression of the temporal cortex (TC) was only observed in adulthood. Conversely, GAD67 expression was increased in the prefrontal cortex (PFC) from adolescence to adulthood. The dysregulated GAD67 expression could alter the excitatory-inhibitory balance in the cerebral cortex, HC and cerebellum. Our findings indicate an impaired GABAergic system could be a major etiological factor occurring in the cerebral cortex, HC and cerebellum of human cases of autism, which suggests enhancement of GABA signaling would be a promising therapeutic target for its treatment.

How do robots learn to perform motor tasks in a specific condition and apply what they have learned in a new condition? This paper proposes a framework for motor coordination acquisition of a robot drawing straight lines within a part of the workspace. Then, it addresses transferring the acquired coordination into another area of the workspace while performing the same task. Motor patterns are generated by a Central Pattern Generator (CPG) model. The motor coordination for a given task is acquired by using a multi-objective optimization method that adjusts the CPGs' parameters involved in the coordination. To transfer the acquired motor coordination to the whole workspace we employed (1) a Self-Organizing Map that represents the end-effector coordination in the Cartesian space, and (2) an estimation method based on Inverse Distance Weighting that estimates the motor program parameters for each SOM neuron. After learning, the robot generalizes the acquired motor program along the SOM network. It is able therefore to draw lines from any point in the 2D workspace and with different orientations. Aside from the obvious distinctiveness of the proposed framework from those based on inverse kinematics typically leading to a point-to-point drawing, our approach also permits of transferring the motor program throughout the workspace.

In daily life, humans frequently engage in object-directed joint actions, be it carrying a table together or jointly pulling a rope. When two or more individuals control an object together, they may distribute control by performing complementary actions, e.g., when two people hold a table at opposite ends. Alternatively, several individuals may execute control in a redundant manner by performing the same actions, e.g., when jointly pulling a rope in the same direction. Previous research has investigated whether dyads can outperform individuals in tasks where control is either distributed or redundant. The aim of the present review is to integrate findings for these two types of joint control to determine common principles and explain differing results. In sum, we find that when control is distributed, individuals tend to outperform dyads or attain similar performance levels. For redundant control, conversely, dyads have been shown to outperform individuals. We suggest that these differences can be explained by the possibility to freely divide control: Having the option to exercise control redundantly allows co-actors to coordinate individual contributions in line with individual capabilities, enabling them to maximize the benefit of the available skills in the group. In contrast, this freedom to adopt and adapt customized coordination strategies is not available when the distribution of control is determined from the outset.