Cerebellar Transcranial Direct Current Stimulation Applied over Multiple Days Does Not Enhance Motor Learning of a Complex Overhand Throwing Task in Young Adults.

Cerebellar transcranial direct current stimulation (tDCS) enhances motor skill and learning in relatively simple motor tasks, but it is unclear if c-tDCS can improve motor performance in complex motor tasks. The purpose of this study was to determine the influence of c-tDCS applied over multiple days on motor learning in a complex overhand throwing task. In a double-blind, randomized, between-subjects, SHAM-controlled, experimental design, 30 young adults were assigned to either a c-tDCS or a SHAM group. Participants completed three identical experiments on consecutive days that involved overhand throwing in a pre-test block, five practice blocks with concurrent c-tDCS, and a post-test block. Overhand throwing endpoint accuracy was quantified as the endpoint error. The first dorsal interosseous muscle motor evoked potential (MEP) amplitude elicited by transcranial magnetic stimulation was used to quantify primary motor cortex (M1) excitability modulations via c-tDCS. Endpoint error significantly decreased over the 3 days of practice, but the magnitude of decrease was not significantly different between the c-tDCS and SHAM group. Similarly, MEP amplitude slightly increased from the pre-tests to the post-tests, but these increases did not differ between groups. These results indicate that multi-day c-tDCS does not improve motor learning in an overhand throwing task or increase M1 excitability.

Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity.

BACKGROUND: Classic psychedelics, such as psilocybin and LSD, and other serotonin 2A receptor (5-HT2AR) agonists evoke acute alterations in perception and cognition. Altered thalamocortical connectivity has been hypothesized to underlie these effects, which is supported by some functional MRI (fMRI) studies. These studies have treated the thalamus as a unitary structure, despite known differential 5-HT2AR expression and functional specificity of different intrathalamic nuclei. Independent Component Analysis (ICA) has been previously used to identify reliable group-level functional subdivisions of the thalamus from resting-state fMRI (rsfMRI) data. We build on these efforts with a novel data-maximizing ICA-based approach to examine psilocybin-induced changes in intrathalamic functional organization and thalamocortical connectivity in individual participants. METHODS: Baseline rsfMRI data (n=38) from healthy individuals with a long-term meditation practice was utilized to generate a statistical template of thalamic functional subdivisions. This template was then applied in a novel ICA-based analysis of the acute effects of psilocybin on intra- and extra-thalamic functional organization and connectivity in follow-up scans from a subset of the same individuals (n=18). We examined correlations with subjective reports of drug effect and compared with a previously reported analytic approach (treating the thalamus as a single functional unit). RESULTS: Several intrathalamic components showed significant psilocybin-induced alterations in spatial organization, with effects of psilocybin largely localized to the mediodorsal and pulvinar nuclei. The magnitude of changes in individual participants correlated with reported subjective effects. These components demonstrated predominant decreases in thalamocortical connectivity, largely with visual and default mode networks. Analysis in which the thalamus is treated as a singular unitary structure showed an overall numerical increase in thalamocortical connectivity, consistent with previous literature using this approach, but this increase did not reach statistical significance. CONCLUSIONS: We utilized a novel analytic approach to discover psilocybin-induced changes in intra- and extra-thalamic functional organization and connectivity of intrathalamic nuclei and cortical networks known to express the 5-HT2AR. These changes were not observed using whole-thalamus analyses, suggesting that psilocybin may cause widespread but modest increases in thalamocortical connectivity that are offset by strong focal decreases in functionally relevant intrathalamic nuclei.

Accounting for motion in resting-state fMRI: What part of the spectrum are we characterizing in autism spectrum disorder?

The exclusion of high-motion participants can reduce the impact of motion in functional Magnetic Resonance Imaging (fMRI) data. However, the exclusion of high-motion participants may change the distribution of clinically relevant variables in the study sample, and the resulting sample may not be representative of the population. Our goals are two-fold: 1) to document the biases introduced by common motion exclusion practices in functional connectivity research and 2) to introduce a framework to address these biases by treating excluded scans as a missing data problem. We use a study of autism spectrum disorder in children without an intellectual disability to illustrate the problem and the potential solution. We aggregated data from 545 children (8-13 years old) who participated in resting-state fMRI studies at Kennedy Krieger Institute (173 autistic and 372 typically developing) between 2007 and 2020. We found that autistic children were more likely to be excluded than typically developing children, with 28.5% and 16.1% of autistic and typically developing children excluded, respectively, using a lenient criterion and 81.0% and 60.1% with a stricter criterion. The resulting sample of autistic children with usable data tended to be older, have milder social deficits, better motor control, and higher intellectual ability than the original sample. These measures were also related to functional connectivity strength among children with usable data. This suggests that the generalizability of previous studies reporting naïve analyses (i.e., based only on participants with usable data) may be limited by the selection of older children with less severe clinical profiles because these children are better able to remain still during an rs-fMRI scan. We adapt doubly robust targeted minimum loss based estimation with an ensemble of machine learning algorithms to address these data losses and the resulting biases. The proposed approach selects more edges that differ in functional connectivity between autistic and typically developing children than the naïve approach, supporting this as a promising solution to improve the study of heterogeneous populations in which motion is common.

Moving Toward Understanding Autism: Visual-Motor Integration, Imitation, and Social Skill Development.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a behavioral phenotype characterized by impaired development of social-communicative skills and excessive repetitive and stereotyped behaviors. Despite high phenotypic heterogeneity in ASD, a meaningful subpopulation of children with ASD (∼90%) show significant general motor impairment. More focused studies on the nature of motor impairment in ASD reveal that children with ASD are particularly impaired on tasks such as ball catching and motor imitation that require efficient visual-motor integration (VMI). Motor computational approaches also provide evidence for VMI impairment showing that children with ASD form internal sensorimotor representations that bias proprioceptive over visual feedback. Impaired integration of visual information to form internal representations of others' and the external world may explain observed impairments on VMI tasks and motor imitation of others. Motor imitation is crucial for acquiring both social and motor skills, and impaired imitation skill may contribute to the observed core behavioral phenotype of ASD. The current review examines evidence supporting VMI impairment as a core feature of ASD that may contribute to both impaired motor imitation and social-communicative skill development. We propose that understanding the neurobiological mechanisms underlying VMI impairment in ASD may be key to discovery of therapeutics to address disability in children and adults with ASD.

A Data Driven Approach Reveals That Anomalous Motor System Connectivity is Associated With the Severity of Core Autism Symptoms.

This study examined whether disruptions in connectivity involving regions critical for learning, planning, and executing movements are relevant to core autism symptoms. Spatially constrained ICA was performed using resting-state fMRI from 419 children (autism spectrum disorder (ASD) = 105; typically developing (TD) = 314) to identify functional motor subdivisions. Comparing the spatial organization of each subdivision between groups, we found voxels that contributed significantly less to the right posterior cerebellar component in children with ASD versus TD (P <0.001). Next, we examined the effect of diagnosis on right posterior cerebellar connectivity with all other motor subdivisions. The model was significant (P = 0.014) revealing that right posterior cerebellar connectivity with bilateral dorsomedial primary motor cortex was, on average, stronger in children with ASD, while right posterior cerebellar connectivity with left-inferior parietal lobule (IPL), bilateral dorsolateral premotor cortex, and supplementary motor area was stronger in TD children (all P ≤0.02). We observed a diagnosis-by-connectivity interaction such that for children with ASD, elevated social-communicative and excessive repetitive-behavior symptom severity were both associated with right posterior cerebellar-left-IPL hypoconnectivity (P ≤0.001). Right posterior cerebellar and left-IPL are strongly implicated in visuomotor processing with dysfunction in this circuit possibly leading to anomalous development of skills, such as motor imitation, that are crucial for effective social-communication. LAY SUMMARY: This study examines whether communication between various brain regions involved in the control of movement are disrupted in children with autism spectrum disorder (ASD). We show communication between the right posterior cerebellum and left IPL, a circuit important for efficient visual-motor integration, is disrupted in children with ASD and associated with the severity of ASD symptoms. These results may explain observations of visual-motor integration impairments in children with ASD that are associated with ASD symptom severity.

Children with Autism Spectrum Disorder Show Impairments During Dynamic Versus Static Grip-force Tracking.

Impairments in visuomotor integration (VMI) may contribute to anomalous development of motor, as well as social-communicative, skills in children with autism spectrum disorder (ASD). However, it is relatively unknown whether VMI impairments are specific to children with ASD versus children with other neurodevelopmental disorders. As such, this study addressed the hypothesis that children with ASD, but not those in other clinical control groups, would show greater deficits in high-VMI dynamic grip-force tracking versus low-VMI static presentation. Seventy-nine children, aged 7-17 years, participated: 22 children with ASD, 17 children with fetal alcohol spectrum disorder (FASD), 18 children with Attention-Deficit Hyperactivity Disorder (ADHD), and 22 typically developing (TD) children. Two grip-force tracking conditions were examined: (1) a low-VMI condition (static visual target) and (2) a high-VMI condition (dynamic visual target). Low-frequency force oscillations <0.5 Hz during the visuomotor task were also examined. Two-way ANCOVAs were used to examine group x VMI and group x frequency effects (α = 0.05). Children with ASD showed a difficulty, above that seen in the ADHD/FASD groups, tracking dynamic, but not static, visual stimuli as compared to TD children. Low-frequency force oscillations <0.25 Hz were also significantly greater in the ASD versus the TD group. This study is the first to report VMI deficits during dynamic versus static grip-force tracking and increased proportion of force oscillations <0.25 Hz during visuomotor tracking in the ASD versus TD group. Dynamic VMI impairments may be a core psychophysiologic feature that could contribute to impaired development of motor and social-communicative skills in ASD. LAY SUMMARY: Children with autism spectrum disorder (ASD) show difficulties using dynamic visual stimuli to guide their own movements compared to their typically developing (TD) peers. It is unknown whether children without a diagnosis of ASD, but with other neurological disorders, show similar difficulties processing dynamic visual stimuli. In this study, we showed that children with ASD show a difficulty using dynamic, but not static, visual stimuli to guide movement that may explain atypical development of motor and social skills.

A comparison of two techniques for center of pressure measurements.

INTRODUCTION: Force platforms and pressure-measuring insoles are the most common tools used for measuring center of pressure. Earlier studies to assess these instruments suffered from limited sample sizes or an inadequate range of participant foot sizes. The purpose of this study was to propose new methods to extract and calculate comparably accurate center of pressure for the Kistler® force platform and Medilogic® insoles. METHODS: Center of pressure data were collected from 65 participants wearing pressure-measuring insoles (six different sizes). Participants walked over consecutive force platforms for three trials while wearing pressure-measuring insoles within socks. Onset force thresholds and center of pressure segment length thresholds were used to determine accurate center of pressure path length and width. A single step for each foot and trial was extracted from both instruments. RESULTS: A strong correlation was observed between instruments in center of pressure length (4.12 ± 6.72% difference, r = 0.74). Center of pressure width varied and was weakly correlated (-7.04 ± 4.48% difference, r = 0.11). CONCLUSIONS: The results indicate that both instruments can measure center of pressure path length consistently and with comparable accuracy (differences < 10%). There were differences between instruments in measuring center of pressure path width, which were attributed to the limited number of sensors across the width of the insoles.

Electronic measurement of plantar contact area during walking using an adaptive thresholding method for Medilogic® pressure-measuring insoles.

BACKGROUND: Pressure-measuring insoles have the potential to measure plantar contact area (PA) during walking. However, they are not widely used for this purpose because of the need for a reliable process that can convert the insole output into PA. The purposes of this study were to: (1) develop an adaptive-threshold method for pressure-measuring insoles that can improve the accuracy of the PA measurements during walking, and (2) experimentally assess the accuracy and generalizability of this method. METHODS: A sample of 42 healthy, ambulatory, young adults (age=24.3±3.2years, mass=67.2±16.9kg, height=1.63±0.08m) completed 10 trials walking on an elevated walkway while wearing Medilogic® pressure-measuring insoles (sizes 35-45). A total of six insole sizes were considered. Insole data were converted to PA using three unique adaptive-thresholds that were based on percentages of the maximum sum of digital values (MSDV) during an analyzed step. Three values were considered: 0.1%, 0.2%, and 0.3% of the MSDV. Additionally, a fixed-threshold, which is typically used to estimate PA, was assessed. These two techniques, applied to the insole worn on the left foot, were compared with PA obtained from high-resolution reference footprints obtained from optical pedography of the right foot and processed using digital image processing algorithms. An assumption of PA symmetry between the left (insole) and right (barefoot) feet was made and comparisons were conducted over the entire stance phase of walking. The generalizability of the algorithm was assessed by comparing PA errors from insoles with respect to the optical pedography results based on insole size criteria. RESULTS: The adaptive-thresholds of 0.1%, 0.2%, and 0.3% of MSDV produced mean errors of 7.31±17.44%, -8.62±15.01%, and -20.45±14.18%, respectively. Using the 2-digital value fixed-threshold produced a mean error of 20.88±22.44%. The best performing adaptive-threshold varied among insole sizes. CONCLUSION: It was observed that the fixed-threshold technique produced large magnitudes of errors. The proposed adaptive-thresholds of 0.1% and 0.2% of the MSDV reduced PA error to ±10% during walking. The adaptive-threshold method consistently reduced PA error vs. the fixed-threshold for each insole size.

Concurrent Validity of an Automated Footprint Detection Algorithm to Measure Plantar Contact Area During Walking.

BACKGROUND: Monitoring footprints during walking can lead to better identification of foot structure and abnormalities. Current techniques for footprint measurements are either static or dynamic, with low resolution. This work presents an approach to monitor the plantar contact area when walking using high-speed videography. METHODS: Footprint images were collected by asking the participants to walk across a custom-built acrylic walkway with a high-resolution digital camera placed directly underneath the walkway. This study proposes an automated footprint identification algorithm (Automatic Identification Algorithm) to measure the footprint throughout the stance phase of walking. This algorithm used coloration of the plantar tissue that was in contact with the acrylic walkway to distinguish the plantar contact area from other regions of the foot that were not in contact. RESULTS: The intraclass correlation coefficient (ICC) demonstrated strong agreement between the proposed automated approach and the gold standard manual method (ICC = 0.939). Strong agreement between the two methods also was found for each phase of stance (ICC > 0.78). CONCLUSIONS: The proposed automated footprint detection technique identified the plantar contact area during walking with strong agreement with a manual gold standard method. This is the first study to demonstrate the concurrent validity of an automated identification algorithm to measure the plantar contact area during walking.

Gastrocnemius fascicle and achilles tendon length at the end of the eccentric phase in a single and multiple countermovement hop.

The purpose of this investigation was to compare fascicle and tendon length of the gastrocnemius at the end of the eccentric phase during a hop utilizing a single countermovement (sCM) versus multiple countermovement (mCM1, mCM2, mCM3) strategy. Seventeen healthy males performed nine hopping trials of sCM and nine trials of mCM. Ankle and knee joint angle and lower leg length from videography and muscle ultrasound were used to calculate muscle-tendon unit (MTU), fascicle and tendon length. Sacral marker data was used to determine hopping height. Force- and displacement-time curves were utilized to calculate work. Muscle activity of the lateral and medial gastrocnemius was also measured. Fascicle length was significantly shorter (mCM3: 6.2 ±â€¯1.5 cm, sCM: 7.3 ±â€¯2.0 cm) and tendon length was significantly longer (mCM3: 36.5 ±â€¯3.6 cm, sCM: 35.5 ±â€¯3.8 cm) at the end of the eccentric phase in mCM3 in comparison to sCM. Maximal hopping height (mCM: 14.6 ±â€¯3.1 cm, sCM: 13.1 ±â€¯2.5 cm), eccentric phase gastrocnemius muscle activity (mCM medial gastrocnemius: 0.10 ±â€¯0.03 mV, mCM lateral gastrocnemius: 0.08 ±â€¯0.04 mV, sCM medial gastrocnemius: 0.07 ±â€¯0.03 mV, sCM lateral gastrocnemius: 0.05 ±â€¯0.04 mV), and both eccentric (mCM3: 46.6 ±â€¯19.4 J, sCM: 38.5 ±â€¯15.9 J) and concentric work (mCM3: 87.6 ±â€¯26.5 J, sCM: 80.9 ±â€¯27.6 J) were significantly higher for mCM3 compared to sCM. The results indicate that a multiple countermovement hop strategy results in shorter fascicle length and longer tendon length at the end of the eccentric phase. In addition, greater eccentric phase muscle activity during the third countermovement (mCM3) in comparison to a single countermovement hop (sCM) was observed. A multiple countermovement strategy appears to result in higher hopping height and greater work done in both the eccentric and concentric phase indicating possible contribution of stored-elastic energy from the tendon.

Assessing the validity of pressure-measuring insoles in quantifying gait variables.

INTRODUCTION: Pressure-measuring insoles can provide a portable alternative to existing gait analysis tools. However, there is disagreement among researchers on their accuracy and the appropriate calibration methods. The purposes of this study were to (1) determine the validity of pressure-measuring insoles for calculating stance time and support-phase impulse during walking using two calibration procedures, and (2) examine the effect of insole size on the results. METHODS: Data were collected from 39 participants (23.5 ± 3.24 yrs, 66.7 ± 17.5 kg, 1.64 ± 0.09 m), each wearing appropriately sized insoles as they walked over two consecutive force platforms. Two calibration methods were evaluated: (1) manufacturer's recommendation, and (2) a participant weight-based approach. Qualitative and quantitative evaluations were conducted. RESULTS: The results indicated that the insoles measured longer stance times than the force platform (differences are less than 10%). Both calibration methods resulted in inaccurate impulse values (differences are 30 and 50% for the two calibration methods, respectively). The results showed that when using the first calibration method, impulse values depended on insole size. The second calibration consistently underestimated the impulse. CONCLUSIONS: It was concluded that while the insoles provide acceptable qualitative representation of the gait, the two studied calibration methods may lead to a misleading quantitative assessment.

Physiological and Biomechanical Responses to Prolonged Heavy Load Carriage During Level Treadmill Walking in Females.

Heavy load carriage has been identified as a main contributing factor to the high incidence of overuse injuries in soldiers. Peak vertical ground reaction force (VGRFMAX) and maximal vertical loading rates (VLRMAX) may increase during heavy prolonged load carriage with the development of muscular fatigue and reduced shock attenuation capabilities. The objectives of the current study were (1) to examine physiological and biomechanical changes that occur during a prolonged heavy load carriage task, and (2) to examine if this task induces neuromuscular fatigue and changes in muscle architecture. Eight inexperienced female participants walked on an instrumented treadmill carrying operational loads for 60 minutes at 5.4 km·h-1. Oxygen consumption ( V ˙ O 2 ), heart rate, rating of perceived exertion (RPE), trunk lean angle, and ground reaction forces were recorded continuously during task. Maximal force and in-vivo muscle architecture were assessed pre- and posttask. Significant increases were observed for VGRFMAX, VLRMAX, trunk lean angle, [Formula: see text], heart rate, and RPE during the task. Increased vastus lateralis fascicle length and decreased maximal force production were also observed posttask. Prolonged heavy load carriage, in an inexperienced population carrying operational loads, results in progressive increases in ground reaction force parameters that have been associated with overuse injury.

Medial gastrocnemius muscle-tendon interaction and architecture change during exhaustive hopping exercise.

BACKGROUND: Previous literature has shown in vivo changes in muscle-tendon interaction during exhaustive stretch-shortening cycle (SSC) exercise. It is unclear whether these changes in muscle-tendon length during exhaustive SSC exercise are associated with changes in mechanical efficiency (ME). The purpose of the study was to investigate whether changes in platarflexor contractile component (CC) length, tendon length, and changes in plantarflexor muscle activity could explain reduction in ME during exhaustive SSC exercise. METHODS: Eight males participated in an exhaustive hopping task to fatigue. Mechanical work and energy expenditure were calculated at different time-points during the hopping task. Furthermore, hopping kinetics and kinematics, medial gastrocnemius (MG) muscle activity, and in vivo ultrasound of the MG were also collected at different time-points throughout the hopping task. RESULTS: ME did not change during the hopping protocol despite shorter tendon and longer CC lengths as subjects approached exhaustion. Percent decreases in pennation angle and muscle thickness were most strongly correlated to time to exhaustion (r=0.94, p⩽0.05; r=0.87, p⩽0.05; respectively). Percent changes in CC length change and pennation angle were strongly correlated to percent decrease in maximal voluntary isometric plantarflexion (MVIP) force (r=-0.71, p⩽0.04; r=0.70, p⩽0.05; respectively). Braking/push-off EMG ratio increased from initial pre-fatigue values to all other time points showing neuromuscular adaptations to altered muscle lengths. CONCLUSION: Findings from the current study suggest that changes in CC and tendon lengths occur during repetitive hopping to exhaustion, with the amount change strongly related to time to exhaustion. ME of hopping remained unchanged in the presence of altered CC and tendon lengths.