Deficits In Motor Performance Research Articles

Deficits in basal and evoked striatal dopamine release following alpha-synuclein preformed fibril injection: An in vivo microdialysis study.

Parkinson's disease (PD) is characterized by the accumulation of misfolded alpha-synuclein (α-syn) protein, forming intraneuronal Lewy body (LB) inclusions. The α-syn preformed fibril (PFF) model of PD recapitulates α-syn aggregation, progressive nigrostriatal degeneration and motor dysfunction; however, little is known about the time course of PFF-induced alterations in basal and evoked dopamine (DA). In vivo microdialysis is well suited for identifying small changes in neurotransmitter levels over extended periods. In the present study, adult male Fischer 344 rats received unilateral, intrastriatal injections of either α-syn PFFs or phosphate-buffered saline (PBS). At 4 or 8 months post-injection (p.i.), animals underwent in vivo microdialysis to evaluate basal extracellular striatal DA and metabolite levels, local KCl-evoked striatal DA release and the effects of systemic levodopa (l-DOPA). Post-mortem analysis demonstrated equivalent PFF-induced reductions in tyrosine hydroxylase (TH) immunoreactive nigral neurons (~50%) and striatal TH (~20%) at both time points. Compared with reduction in striatal TH, reduction in striatal dopamine transporter (DAT) was more pronounced and progressed between the 4- and 8-month p.i. intervals (36%➔46%). Significant PFF-induced deficits in basal and evoked striatal DA, as well as deficits in motor performance, were not observed until 8 months p.i. Responses to l-DOPA did not differ regardless of PBS or PFF treatment. These results suggest that basal and evoked striatal DA are maintained for several months following PFF injection, with loss of both associated with motor dysfunction. Our studies provide insight into the time course and magnitude of PFF-induced extracellular dopaminergic deficits in the striatum.

Gross motor proficiency deficits among children and adolescents post posterior fossa brain tumor removal vs. traumatic brain injury in the chronic phase of recovery: a cross-sectional study.

Acquired brain injury (ABI) is a prevalent diagnosis in pediatric rehabilitation. Gross motor skills are often affected by ABI and limit the ability to participate in various physical activities. However, as ABI injury location is diverse, children and adolescents (youth) with localized ABI, such as ABI in the posterior fossa (ABI-PF) may present unique and different motor disabilities than youth with ABI on account of traumatic brain injury (TBI). The aims of the study were: (1) to compare gross motor deficits in youth with TBI vs. ABI-PF; and (2) to compare two methods on scoring BOT2 to determine which is better for identifying motor deficits. Participated in this study youth with TBI (N = 50) and ABI-PF (N = 30). Participants were tested on Bruininks-Oseretsky Test of Motor Proficiency-2nd Edition (BOT2) Upper-Limb Coordination, Balance, Strength, Running Speed and Agility, and Bilateral-Coordination subtests. Motor performance deficits were established using two-standard deviations (2SD) and age-equivalent methods. Between-group differences were assessed via independent t-tests and receiver operating characteristic curves (ROC). According to the 2SD method, motor deficits in the ABI-PF group ranged from 20% to 66.66%, whereas in the TBI group 8%-16%. According to the age-equivalent method, in the TBI and ABI-PF groups 40%-66.0% and 46.66%-76.66% of the youth presented motor deficits, respectively. Moreover, ROC analysis showed that motor performance deficits of both groups in all sub-scales except for Bilateral Coordination differed enough to result in medium area under the curve. Motor deficits post-pediatric ABI are prevalent. In comparison to the TBI group, deficits are greater in the ABI-PF group. Moreover, compared to the 2SD method, the extent of motor deficiency is greater in the age-equivalent method. Therefore, using the later might provide a more valid classification of deficits in gross motor proficiency for youth post-ABI.

RELAÇÃO ENTRE O PERFIL COGNITIVO E MOTOR EM INDIVÍDUOS COM SÍNDROME DE DOWN POR MEIO DA EXECUÇÃO DE TAREFA VIRTUAL

The objective of the study was to verify if there is a relationship between the cognitive and motor profile in individuals with Down Syndrome (DS). Cross-sectional study (CAAE:58089622.5.0000.5515), with 27 individuals, 15 from the SD Group with a mean age of 17.5±5.5 years, and 12 from the Control Group, with a mean age of 19.1±5.2 years, evaluated by the Mini Mental State Examination (MMSE) and MoveHero software (to analyze the motor profile), the Borg Scale was also used. The SD group had a statistically significant MMSE score when compared to the Control group (p<0.001). Post-hoc comparisons showed that the SD Group had a greater EA in MoveHero (p= 0.008) and the SD Group had an increase in HR from rest to the end of the activity (p= 0.050). Thus, it can be concluded that individuals with down syndrome have a greater motor performance deficit, under the influence of the cognitive profile.

Motor performance and functional connectivity between the posterior cingulate cortex and supplementary motor cortex in bipolar and unipolar depression.

Although implicated in unsuccessful treatment, psychomotor deficits and their neurobiological underpinnings in bipolar (BD) and unipolar (UD) depression remain poorly investigated. Here, we hypothesized that motor performance deficits in depressed patients would relate to basal functional coupling of the hand primary motor cortex (M1) and the posterior cingulate cortex (PCC) with the supplementary motor area (SMA). We performed a longitudinal, naturalistic study in BD, UD and matched healthy controls comprising of two resting-state functional MRI measurements five weeks apart and accompanying assessments of motor performance using a finger tapping task (FTT). A subject-specific seed-based analysis describing functional connectivity between PCC-SMA as well as M1-SMA was conducted. The basal relationships with motor performance were investigated using linear regression models and all measures were compared across groups. Performance in FTT was impaired in BD in comparison to HC in both sessions. Behavioral performance across groups correlated significantly with resting state functional coupling of PCC-SMA, but not of M1-SMA regions. This relationship was partially reflected in a reduced PCC-SMA connectivity in BD vs HC in the second session. Exploratory evaluation of large-scale networks coupling (SMN-DMN) exhibited no correlation to motor performance. Our results shed new light on the association between the degree of disruption in the SMA-PCC anticorrelation and the level of motor impairment in BD.

Inhibiting cholinergic signalling in the cerebellar interpositus nucleus impairs motor behaviour.

The role of neuromodulators in the cerebellum is not well understood. In particular, the behavioural significance of the cholinergic system in the cerebellum is unknown. To investigate the importance of cerebellar cholinergic signalling in behaviour, we infused acetylcholine receptor antagonists, scopolamine and mecamylamine, bilaterally into the rat cerebellum (centred on interpositus nucleus) and observed the motor effects through a battery of behavioural tests. These tests included unrewarded behaviour during open field exploration and a horizontal ladder walking task and reward-based beam walking and pellet reaching tasks. Infusion of a mix of the antagonists did not impair motor learning in the horizontal ladder walking or the reaching task but reduced spontaneous movement during open field exploration, impaired coordination during beam walking and ladder walking, led to fewer reaches in the pellet reaching task, slowed goal-directed reaching behaviour and reduced reward pellet consumption in a free access to food task. Infusion of the muscarinic antagonist scopolamine on its own resulted in deficits in motor performance and a reduction in the number of reward pellets consumed in the free access to food task. By contrast, infusion of the nicotinic antagonist mecamylamine on its own had no significant effect on any task, except beam walking traversal time, which was reduced. Together, these data suggest that acetylcholine in the cerebellar interpositus nucleus is important for the execution and coordination of voluntary movements mainly via muscarinic receptor signalling, especially in relation to reward-related behaviour.

Modified mouse model of repeated mild traumatic brain injury through a thinned-skull window and fluid percussion.

Mild traumatic brain injury (mTBI) is a clinically highly heterogeneous neurological disorder, none of the existing animal models can replicate the entire sequelae. This study aimed to develop a modified closed head injury (CHI) model of repeated mTBI (rmTBI) for investigating Ca2+ fluctuations of the affected neural network, the alternations of electrophysiology, and behavioral dysfunctions. The transcranial Ca2+ study protocol includes AAV-GCaMP6s infection in the right motor cortex, thinned-skull preparation, and two-photon laser scanning microscopy (TPLSM) imaging. The CHI rmTBI model is fabricated using the thinned-skull site and applying 2.0 atm fluid percussion with 48-h interval. The neurological dysfunction, minor motor performance, evident mood, spatial working, and reference deficits we found in this study mimic the clinically relevant syndromes after mTBI. Besides, our study revealed that there was a trend of transition from Ca2+ singlepeak to multipeak and plateau, and the total Ca2+ activities of multipeaks and plateaus (p < .001 vs. pre-rmTBI value) were significantly increased in ipsilateral layer 2/3 motor neurons after rm TBI. In parallel, there is a low-frequency power shift from delta to theta band (p < .01 vs. control) in the ipsilateral layer 2/3 of motor cortex of the rmTBI mice, and the overall firing rates significantly increased (p < .01 vs. control). Moreover, rmTBI causes slight cortical and hippocampal neuron damage and possibly induces neurogenesis in the dentate gyrus (DG). The alternations of Ca2+ and electrophysiological characteristics in layer 2/3 neuronal network, histopathological changes, and possible neurogenesis may play concertedly and partially contribute to the functional outcome post-rmTBI.

White matter and neurochemical mechanisms underlying age-related differences in motor processing speed

Aging is associated with changes in the central nervous system and leads to reduced life quality. Here, we investigated the age-related differences in the CNS underlying motor performance deficits using magnetic resonance spectroscopy and diffusion MRI. MRS measured N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) concentrations in the sensorimotor and occipital cortex, whereas dMRI quantified apparent fiber density (FD) in the same voxels to evaluate white matter microstructural organization. We found that aging was associated with increased reaction time and reduced FD and NAA concentration in the sensorimotor voxel. Both FD and NAA mediated the association between age and reaction time. The NAA concentration was found to mediate the association between age and FD in the sensorimotor voxel. We propose that the age-related decrease in NAA concentration may result in reduced axonal fiber density in the sensorimotor cortex which may ultimately account for the response slowness of older participants.

Efficacy of a Task-Oriented Intervention for Children with a Dual Diagnosis of Specific Learning Disabilities and Developmental Coordination Disorder: A Pilot Study.

Task-oriented approaches are recommended for children with developmental coordination disorder (DCD) to address deficits in motor performance and reduce activity limitations. Although this approach is used in several settings, the efficacy of these approaches in children with in dual-diagnosis of specific learning disabilities (SLD) and DCD is less widely known. This study aims to determine the effect of a group-based intervention based on neuromotor task training (NTT) principles on the motor performance of children aged 6-10 years with SLD/DCD. A pre-post-test controlled study design was conducted in children with a primary diagnosis of specific learning disabilities (SLD). DCD status was confirmed based on clinical assessment. Children scoring ≤16th percentile on the Motor Assessment Battery for Children 2nd Edition (MABC-2), who also presented with a functional motor problem, according to the MABC checklist were considered as having DCD. Children were allocated to the NTT intervention group based on teachers' perceived notion of need and received two 45-60 min training sessions per week for nine weeks. Children allocated to the usual care (UC) group, received their planned occupational therapy and physical education. The MABC-2 was used to assess changes in motor performance. Our numbers confirm that it is crucial to identify the presence of motor coordination difficulties in children who have been diagnosed with SLD. A task-oriented training program based on NTT principles, presented in small groups, has a positive effect on the motor performance in learners with neurodevelopmental disorders and this effect was larger than in the usual care group. Although using a small group format in children with multiple neurodevelopmental disorders may be challenging for the therapists, it may be a way of delivering services to children in schools for special education. Children with DCD plus LSD show improvement in their motor skills by performing group-based NTT in the school environment. Group-based NTT shows a significant improvement in the TSS score of the MABC-2 compared to usual care. Children with DCD plus SLD show equal effect sizes after NTT intervention as DCD without SLD.

Late-life depression and frailty-Epidemiological, clinical and neurobiological associations

Depression is the most common mental disorder in older adults and is influenced by age-related processes. Frailty is awell-established clinical expression of ageing that implies astate of increased vulnerability to stressor events as well as increased risks of disability, hospitalization and death. Neurobiological findings will disentangle the comorbidity of frailty and depression and may inform future management of depression in old age. This narrative review provides an overview of the comorbidity of late-life depression and frailty, with afocus on neuroscientific findings that are organized within the research domain criteria (RDoC) framework. More than one third of old people with depression are affected by frailty, which results in more chronic depression and in poorer efficacy and tolerability of antidepressant medication. Depression and frailty share motivational and psychomotor characteristics, particularly apathy, decreased physical activity and fatigue. In patients with frailty, altered activity of the supplementary motor cortex is associated with motor performance deficits. Patients with late-life depression and apathy are characterized by abnormal structure and altered functional connectivity of the reward network and the salience network, along with altered functional connectivity of these networks with premotor brain areas. Identifying frailty in older adults with depression is relevant for prognostic assessment and treatment. Abetter understanding of the neuronal mechanisms of comorbidity will provide potential targets for future personalized therapeutic interventions.

Deletion of the voltage-gated calcium channel, CaV 1.3, causes deficits in motor performance and associative learning.

L-type voltage-gated calcium channels are important regulators of neuronal activity and are widely expressed throughout the brain. One of the major L-type voltage-gated calcium channel isoforms in the brain is CaV 1.3. Mice lacking CaV 1.3 are reported to have impairments in fear conditioning and depressive-like behaviors, which have been linked to CaV 1.3 function in the hippocampus and amygdala. Genetic variation in CaV 1.3 has been linked to a variety of psychiatric disorders, including autism and schizophrenia, which are associated with altered motor learning, associative learning and social function. Here, we explored whether CaV 1.3 plays a role in these behaviors. We found that CaV 1.3 knockout mice have deficits in rotarod learning despite normal locomotor function. Deletion of CaV 1.3 is also associated with impaired gait adaptation and associative learning on the Erasmus Ladder. We did not observe any impairments in CaV 1.3 knockout mice on assays of anxiety-like, depression-like or social preference behaviors. Our results suggest an important role for CaV 1.3 in neural circuits involved in motor learning and concur with previous data showing its involvement in associative learning.

C57BL/6 Background Attenuates mHTT Toxicity in the Striatum of YAC128 Mice.

Mouse models are frequently used to study Huntington’s disease (HD). The onset and severity of neuronal and behavioral pathologies vary greatly between HD mouse models, which results from different huntingtin expression levels and different CAG repeat length. HD pathology appears to depend also on the strain background of mouse models. Thus, behavioral deficits of HD mice are more severe in the FVB than in the C57BL/6 background. Alterations in medium spiny neuron (MSN) morphology and function have been well documented in young YAC128 mice in the FVB background. Here, we tested the relevance of strain background for mutant huntingtin (mHTT) toxicity on the cellular level by investigating HD pathologies in YAC128 mice in the C57BL/6 background (YAC128/BL6). Morphology, spine density, synapse function and membrane properties were not or only subtly altered in MSNs of 12-month-old YAC128/BL6 mice. Despite the mild cellular phenotype, YAC128/BL6 mice showed deficits in motor performance. More pronounced alterations in MSN function were found in the HdhQ150 mouse model in the C57BL/6 background (HdhQ150/BL6). Consistent with the differences in HD pathology, the number of inclusion bodies was considerably lower in YAC128/BL6 mice than HdhQ150/BL6 mice. This study highlights the relevance of strain background for mHTT toxicity in HD mouse models.

Immunisation with UB-312 in the Thy1SNCA mouse prevents motor performance deficits and oligomeric \u03b1-synuclein accumulation in the brain and gut

Alpha synuclein has a key role in the pathogenesis of Parkinson’s disease (PD), Dementia with Lewy Bodies (LBD) and Multiple System Atrophy (MSA). Immunotherapies aiming at neutralising toxic αSyn species are being investigated in the clinic as potential disease modifying therapies for PD and other synucleinopathies. In this study, the effects of active immunisation against αSyn with the UB-312 vaccine were investigated in the Thy1SNCA/15 mouse model of PD. Young transgenic and wild-type mice received an immunisation regimen over a period of 6 weeks, then observed for an additional 9 weeks. Behavioural assessment was conducted before immunisation and at 15 weeks after the first dose. UB-312 immunisation prevented the development of motor impairment in the wire test and challenging beam test, which was associated with reduced levels of αSyn oligomers in the cerebral cortex, hippocampus and striatum of Thy1SNCA/15 mice. UB-312 immunotherapy resulted in a significant reduction of theαSyn load in the colon, accompanied by a reduction in enteric glial cell reactivity in the colonic ganglia. Our results demonstrate that immunisation with UB-312 prevents functional deficits and both central and peripheral pathology in Thy1SNCA/15 mice.

Insights into motor performance deficits after stroke: an automated and refined analysis of the lower-extremity motor coordination test (LEMOCOT)

BackgroundThe lower-extremity motor coordination test (LEMOCOT) is a performance-based measure used to assess motor coordination deficits after stroke. We aimed to automatically quantify performance on the LEMOCOT and to extract additional performance parameters based on error analysis in persons with stroke (PwS) and healthy controls. We also aimed to explore whether these parameters provide additional information regarding motor control deficit that is not captured by the traditional LEMOCOT score. In addition, the associations between the LEMOCOT score, parameters of error and performance-based measures of lower-extremity impairment and gait were tested.MethodsTwenty PwS (age: 62 ± 11.8 years, time after stroke onset: 84 ± 83 days; lower extremity Fugl-Meyer: 30.2 ± 3.7) and 20 healthy controls (age: 42 ± 15.8 years) participated in this cross-sectional exploratory study. Participants were instructed to move their big toe as fast and accurately as possible between targets marked on an electronic mat equipped with force sensors (Zebris FDM-T, 60 Hz). We extracted the contact surface area of each touch, from which the endpoint location, the center of pressure (COP), and the distance between them were computed. In addition, the absolute and variable error were calculated.ResultsPwS touched the targets with greater foot surface and demonstrated a greater distance between the endpoint location and the location of the COP. After controlling for the number of in-target touches, greater absolute and variable errors of the endpoint were observed in the paretic leg than in the non-paretic leg and the legs of controls. Also, the COP variable error differentiated between the paretic, non-paretic, and control legs and this parameter was independent of in-target counts. Negative correlations with moderate effect size were found between the Fugl Meyer assessment and the error parameters.ConclusionsPwS demonstrated lower performance in all outcome measures than did controls. Several parameters of error indicated differences between legs (paretic leg, non-paretic leg and controls) and were independent of in-target touch counts, suggesting they may reflect motor deficits that are not identified by the traditional LEMOCOT score.

Cholecystokinin 1 receptor activation restores normal mTORC1 signaling and is protective to Purkinje cells of SCA mice.

SUMMARYSpinocerebellar ataxias (SCAs) are a group of genetic diseases characterized by progressive ataxia and neurodegeneration, often in cerebellar Purkinje neurons. A SCA1 mouse model, Pcp2-ATXN1[30Q]D776, has severe ataxia in absence of progressive Purkinje neuron degeneration and death. Previous RNA-seq analyses identify cerebellar upregulation of the peptide hormone cholecystokinin (Cck) in Pcp2-ATXN1[30Q]D776 mice. Importantly, absence of Cck1 receptor (Cck1R) in Pcp2-ATXN1[30Q]D776 mice confers a progressive disease with Purkinje neuron death. Administration of a Cck1R agonist, A71623, to Pcp2-ATXN1[30Q] D776;Cck−/− and Pcp2-AXTN1[82Q] mice dampens Purkinje neuron pathology and associated deficits in motor performance. In addition, A71623 administration improves motor performance of Pcp2-ATXN2[127Q] SCA2 mice. Moreover, the Cck1R agonist A71623 corrects mTORC1 signaling and improves expression of calbindin in cerebella of AXTN1[82Q] and ATXN2[127Q] mice. These results indicate that manipulation of the Cck-Cck1R pathway is a potential therapeutic target for treatment of diseases involving Purkinje neuron degeneration.

Effects of an Intervention for Promoting Basic Motor Competencies in Middle Childhood.

The development of motor competencies is necessary for participation in the culture of sport, exercise, and physical activity, which in turn supports the development of a healthy lifestyle. A lack of physical activity in childhood and deficits in motor performance emphasize the relevance of interventions for promoting basic motor competencies. However, there are research desiderata with regard to such interventions. This article describes an intervention program for promoting basic motor competencies in middle childhood (around 6 to 10 years of age). The intervention was investigated in a longitudinal study from June 2019 to January 2020 (n = 200; 58% girls, M = 8.84 years, SD = 0.63) at three primary schools. The intervention was conducted once a week in physical education (PE). The comparison group participated in regular PE. The intervention showed significant effects on basic motor competencies in object movement but not in self-movement. The results demonstrate that positive effects on basic motor competencies can be achieved with the help of a relatively simple intervention. Further longitudinal studies are desirable as a means of substantiating the results and developing evidence-based concepts to support children in their development in the best possible way.

Cognitive Load Impairs Time to Initiate and Complete Shooting Tasks in ROTC Members.

Multitasking typically requires an individual to simultaneously process cognitive information while performing a motor task. Cognitive motor interference (CMi) is encountered when cognitive challenges negatively impact motor task performance. Military personnel encounter cognitively taxing situations, especially during combat or other tactical performance scenarios, which may lead to injury or motor performance deficits (i.e., shooting inaccuracy, delayed stimulus-response time, and slowed movement speed). The purpose of the current study was to develop four cognitive motor shooting paradigms to determine the effects of cognitive load on shooting performance in healthy Reserve Officers' Training Corps (ROTC) cadets. Thirty-two healthy collegiate ROTC members (24 male and 8 female; 20.47 ± 1.24 years, 174.95 ± 10.58 cm, and 77.99 ± 13.90 kg) were recruited to complete four simulated shooting tasks with additional "motor" challenge (180° turn, gait, weighted, and unweighted landing) and with and without a "cognitive" decision-making challenge requiring response selection and inhibition to both auditory and visual stimuli, totaling eight multi-task cognitive motor shooting conditions. The current study was approved by the university's Institutional Review Board. Task initiation (seconds), task completion (seconds), and number of misses were calculated to determine marksmanship efficiency and accuracy. For each task, a multivariate repeated-measures analysis of variance (ANOVA) was conducted for the combined dependent variables. If the overall multivariate repeated-measures ANOVA was significant, follow-up univariate ANOVAs were conducted for each dependent variable. Alpha was set at α = 0.05 for all analyses. Task initiation increased for the cognitive condition for the 180° turn (4.29 ± 1.22 seconds baseline, 5.09 ± 1.39 seconds cognitive; P < .05), gait (2.76 ± .60 seconds baseline, 3.93 ± .62 seconds cognitive; P < .05), unweighted (1.27 ± .57 seconds baseline, 3.39 ± .63 seconds cognitive; P < .05), and weighted landing (1.46 ± .72 seconds baseline, 3.35 ± .60 seconds cognitive; P < .05). Task completion time increased for the cognitive condition for the 180° turn (3.48 ± 1.53 seconds baseline, 4.85 ± 1.24 seconds cognitive; P < .05), gait (7.84 ± 2.07 seconds baseline, 9.23 ± 1.76 seconds cognitive; P < .05), unweighted (5.98 ± 1.55 seconds baseline, 7.45 ± 1.51 seconds cognitive; P < .05), and weighted landing (6.09 ± 1.42 seconds baseline, 7.25 ± 1.79 seconds cognitive; P < .05). There were no statistically significant differences in the number of misses for any of the tasks between conditions (P > .05). The addition of a cognitive load increased both task initiation and task completion times during cognitive motor simulated shooting. Adding cognitive loads to tactical performance tasks can result in CMi and negatively impact tactical performance. Thus, consideration for additional cognitive challenges into training may be warranted to reduce the potential CMi effect on tactical performance.

Fractional Anisotropy in Selected, Motor-Related White Matter Tracts and Its Cross-Sectional and Longitudinal Associations With Motor Function in Healthy Older Adults.

BackgroundWhile it is well-known that deficits in motor performance and brain structural connectivity occur in the course of healthy aging, it is still unclear if and how these changes are related to each other. While some cross-sectional studies suggest that white matter (WM) microstructure is positively associated with motor function in healthy older adults, more evidence is needed. Moreover, longitudinal data is required to estimate whether similar associations can be found between trajectories of change in WM microstructure and motor function. The current study addresses this gap by investigating age-associations and longitudinal changes in WM microstructure and motor function, and the cross-sectional (level-level) and longitudinal (level-change, change-change) association between these two domains.MethodWe used multiple-occasion data (covering 4 years) from a large sample (N = 231) of healthy older adults from the Longitudinal Healthy Aging Brain (LHAB) database. To measure WM microstructure, we used diffusion-weighted imaging data to compute mean FA in three selected WM tracts [forceps minor (FMIN); superior longitudinal fasciculus (SLF); corticospinal tract (CST)]. Motor function was measured via two motor speed tests (grooved pegboard, finger tapping) and one motor strength test (grip force test), separately for the left and the right hand. The statistical analysis was conducted with longitudinal growth curve models in the structural equation modeling framework.ResultsThe results revealed longitudinal decline and negative cross-sectional age-associations for mean WM FA in the FMIN and SLF, and for motor function in all tests, with a higher vulnerability for left than right hand motor performance. Regarding cross-domain associations, we found a significant positive level-level correlation among mean WM FA in the FMIN with motor speed. Mean FA in SLF and CST was not correlated with motor performance measures, and none of the level-change or change-change associations were significant. Overall, our results (a) provide important insights into aging-related changes of fine motor abilities and FA in selected white matter tracts associated with motor control, (b) support previous cross-sectional work showing that neural control of movement in older adults also involves brain structures outside the core motor system and (c) align with the idea that, in healthy aging, compensatory mechanisms may be in place and longer time delays may be needed to reveal level-change or change-change associations.

The Association among Autistic Traits, Interactional Synchrony and Typical Pattern of Motor Planning and Execution in Neurotypical Individuals

Autism spectrum disorder (ASD) is characterized by deficits in interactional synchrony and motor performance, but little is known about the association between them. The current study investigated the association among aberrant interactional synchrony (as measured by interactors’ symmetry in the form of the hand at each time-point along movement’s execution), motor functioning and the level of Autistic traits. In this study, autistic traits were evaluated by the Autistic Spectrum Quotient (AQ). Two tasks were used: (1) an interactional synchrony task where participants and the research assistant were instructed to move their hands together; and (2) a motor planning task which allows for continuous monitoring of natural hand movements. Pearson correlation analysis indicated a significant association between lower communication skills (i.e., higher AQ communication scores) and lower intentional synchrony rates. In addition, lower communication skills were found associated with typical patterns of motor planning and execution characterized by shorter time to start the movement and higher value of max speed. Mediator analyses supported the notion that aberrant intentional synchrony in individuals with low communication skills is partially mediated through typical patterns of motor planning and execution. These results suggest typical patterns of motor functions may account for intentional synchrony difficulties.

Characterization of a Mouse Model of Alzheimer's Disease Expressing Aβ4-42 and Human Mutant Tau.

The relationship between the two most prominent neuropathological hallmarks of Alzheimer’s Disease (AD), extracellular amyloid-β (Aβ) deposits and intracellular accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFT), remains at present not fully understood. A large body of evidence places Aβ upstream in the cascade of pathological events, triggering NFTs formation and the subsequent neuron loss. Extracellular Aβ deposits were indeed causative of an increased tau phosphorylation and accumulation in several transgenic models but the contribution of soluble Aβ peptides is still controversial. Among the different Aβ variants, the N-terminally truncated peptide Aβ4–42 is among the most abundant. To understand whether soluble Aβ4–42 peptides impact the onset or extent of tau pathology, we have crossed the homozygous Tg4–42 mouse model of AD, exclusively expressing Aβ4–42 peptides, with the PS19 (P301S) tau transgenic model. Behavioral assessment showed that the resulting double-transgenic line presented a partial worsening of motor performance and spatial memory deficits in the aged group. While an increased loss of distal CA1 pyramidal neurons was detected in young mice, no significant alterations in hippocampal tau phosphorylation were observed in immunohistochemical analyses.

Manganese exacerbated chronic khat-induced neurological deficits, inflammation and organ toxicity in a mouse model

This study sought to determine whether chronic exposure to khat (Catha Edulis, Forsk) increases the vulnerability to the toxic effects of manganese (Mn2+), when co-exposed. Three (3)-week-old forty (40) Swiss albino mice were randomly divided into four groups (n = 10). The various groups received khat and manganese separately or both. The experiment was conducted for 132 days to mimic chronic exposure to khat, with manganese administration in the last twelve days. Khat-induced neurological deficits were markedly pronounced on co-exposure with manganese. Notably, deficits in motor performance, touch escape and aggression were deepened by manganese. Co-exposure (khat + Mn2+) induced more profound changes in hematological indices such as suppression of RBCs, low hematocrit and hemoglobin levels. Manganese enhanced khat-induced depletion of a very powerful antioxidant, glutathione (GSH) in the brain, liver, heart and lung tissues. Exposure to khat and/or manganese led to significant elevations in the pro-inflammatory cytokines—tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-ϒ), with a concomitant suppression of the anti-inflammatory cytokine and interleukin 10 (IL-10). Similarly, there was enhanced suppression of IL-10 following co-exposure (khat + Mn). Khat-induced hepatotoxicity and nephrotoxicity were exacerbated by co-exposure. In conclusion, acute exposure to manganese appears to aggravate neurological deficits and other multiple organ toxicities driven by chronic exposure to khat.