Improving Cutaneous Wound Healing in Diabetic Mice Using Naturally Derived Tissue-Engineered Biological Dressings Produced under Serum-Free Conditions.

Long-term diabetes often leads to chronic wounds refractory to treatment. Cell-based therapies are actively investigated to enhance cutaneous healing. Various cell types are available to produce biological dressings, such as adipose-derived stem/stromal cells (ASCs), an attractive cell source considering their abundancy, accessibility, and therapeutic secretome. In this study, we produced human ASC-based dressings under a serum-free culture system using the self-assembly approach of tissue engineering. The dressings were applied every 4 days to full-thickness 8-mm splinted skin wounds created on the back of polygenic diabetic NONcNZO10/LtJ mice and streptozotocin-induced diabetic K14-H2B-GFP mice. Global wound closure kinetics evaluated macroscopically showed accelerated wound closure in both murine models, especially for NONcNZO10/LtJ; the treated group reaching 98.7% ± 2.3% global closure compared to 76.4% ± 11.8% for the untreated group on day 20 (p=0.0002). Histological analyses revealed that treated wounds exhibited healed skin of better quality with a well-differentiated epidermis and a more organized, homogeneous, and 1.6-fold thicker granulation tissue. Neovascularization, assessed by CD31 labeling, was 2.5-fold higher for the NONcNZO10/LtJ treated wounds. We thus describe the beneficial impact on wound healing of biologically active ASC-based dressings produced under an entirely serum-free production system facilitating clinical translation.

Resting-state Functional Connectivity of the Motor and Cognitive Areas is Preserved in Masters Athletes.

Aging is characterized by a decline in physical and cognitive functions, often resulting in decreased quality of life. Physical activity has been suggested to potentially slow down various aspects of the aging process, a theory that has been supported by studies of Masters Athletes (MA). For example, MA usually have better cognitive and physical functions than age-matched sedentary and healthy older adults (OA), making them a valuable model to gain insights into mechanisms that promote physical and cognitive function with aging. The purpose of this study was to identify differences in resting-state functional connectivity (rs-FC) of motor and cognitive regions between MA and OA and determine if these differences in the resting brain are associated with differences in cognitive and physical performance between groups. Fifteen MA (9 males) and 12 age-matched OA (six males) were included. rs-FC images were compared to identify significant between-groups differences in brain connectivity. There was higher connectivity between the cognitive and motor networks for the OA group, whereas the MA group had stronger connectivity between different regions within the same network, both for the cognitive and the motor networks. These results are in line with the literature suggesting that aging reduces the segregation between functional networks and causes regions within the same network to be less strongly connected. High-level physical activity practiced by the MA most likely contributes to attenuating aging-related changes in brain functional connectivity, preserving clearer boundaries between different functional networks, which may ultimately favor maintenance of efficient cognitive and sensorimotor processing.

Reorganization of Brain Resting-state Functional Connectivity Following 14 Days of Elbow Immobilization in Young Females.

Limb immobilization is known to cause significant decreases in muscle strength and muscle mass as early as two days following the onset of immobilization. However, the decline in strength surpasses the decline in muscle mass, suggesting that factors in addition to muscle loss, such as neuroplasticity, contribute to the decrease in force production. However, little is known regarding immobilization-induced neural changes, although sensorimotor regions seem to be the most affected. The present study aimed to determine whether brain functional organization is altered following 14 days of unilateral elbow immobilization. Functional organization was quantified using resting-state functional connectivity, a measure of the synchronicity of the spontaneous discharge of different brain regions at rest. Data was obtained from twelve healthy young females before and after completing the immobilization period. A seed-to-voxel analysis was performed using seeds associated with cortical, subcortical, and cerebellar sensorimotor regions of the brain. The results showed changes predominantly involving cerebellar connectivity. For example, the immobilization period caused a decrease in connectivity between the motor cerebellar region of the immobilized arm and the left temporal lobe, and an increase between the same cerebellar region and the supplementary motor area. Overall, changes in connectivity occurred in regions typically associated with error detection and motor learning, suggesting a potential functional reorganization of the brain within 14 days of elbow immobilization.

The Effect of Different Types of Exercise on Sleep Quality and Architecture in Parkinson Disease: A Single-Blinded Randomized Clinical Trial Protocol.

OBJECTIVES: The purpose of this trial is to (1) determine the best exercise modality to improve sleep quality and sleep architecture in people with Parkinson disease (PD); (2) investigate whether exercise-induced improvements in sleep mediate enhancements in motor and cognitive function as well as other non-motor symptoms of PD; and (3) explore if changes in systemic inflammation after exercise mediate improvements in sleep. METHODS: This is a multi-site, superiority, single-blinded randomized controlled trial. One hundred fifty persons with PD and sleep problems will be recruited and randomly allocated into 4 intervention arms. Participants will be allocated into 12 weeks of either cardiovascular training, resistance training, multimodal training, or a waiting list control intervention. Assessments will be conducted at baseline, immediately after each intervention, and 8 weeks after each intervention by blinded assessors. Objective sleep quality and sleep architecture will be measured with polysomnography and electroencephalography. Motor and cognitive function will be assessed with the Unified PD Rating Scale and the Scale for Outcomes in PD-Cognition, respectively. Subjective sleep quality, fatigue, psychosocial functioning, and quality of life will be assessed with questionnaires. The concentration of inflammatory biomarkers in blood serum will be assessed with enzyme-linked immunosorbent assays. IMPACT: This study will investigate the effect of different types of exercise on sleep quality and architecture in PD, exploring interactions between changes in sleep quality and architecture with motor and cognitive function and other non-motor symptoms of the disease as well as mechanistic interactions between systemic inflammation and sleep. The results will provide important practical information to guide physical therapists and other rehabilitation professionals in the selection of exercise and the design of more personalized exercise-based treatments aimed at optimizing sleep, motor, and cognitive function in people with PD.

Upregulation of the parietal cortex improves freezing of gait in Parkinson's disease.

BACKGROUND The posterior parietal cortex (PPC) is a key brain area for visuospatial processing and locomotion. It has been repetitively shown to be involved in the neural correlates of freezing of gait (FOG), a common symptom of Parkinson's disease (PD). However, current neuroimaging modalities do not allow to precisely determine the role of the PPC during real FOG episodes. OBJECTIVES The purpose of this study was to modulate the PPC cortical excitability using repetitive transcranial magnetic stimulation (rTMS) to determine whether the PPC contributes to FOG or compensates for dysfunctional neural networks to reduce FOG. METHODS Fourteen participants with PD who experience freezing took part in a proof of principle study consisting of three experimental sessions targeting the PPC with inhibitory, excitatory, and sham rTMS. Objective FOG outcomes and cortical excitability measurements were acquired before and after each stimulation protocol. RESULTS Increasing PPC excitability resulted in significantly fewer freezing episodes and percent time frozen during a FOG-provoking task. This reduction in FOG most likely emerged from the trend in PPC inhibiting the lower leg motor cortex excitability. CONCLUSION Our results suggest that the recruitment of the PPC is linked to less FOG, providing support for the beneficial role of the PPC upregulation in preventing FOG. This could potentially be linked to a reduction of the cortical input burden on the basal ganglia prior to FOG. Excitatory rTMS interventions targeting the PPC may have the potential to reduce FOG.

Motor Memory Consolidation Deficits in Parkinson's Disease: A Systematic Review with Meta-Analysis.

BACKGROUND: The ability to encode and consolidate motor memories is essential for persons with Parkinson's disease (PD), who usually experience a progressive loss of motor function. Deficits in memory encoding, usually expressed as poorer rates of skill improvement during motor practice, have been reported in these patients. Whether motor memory consolidation (i.e., motor skill retention) is also impaired is unknown. OBJECTIVE: To determine whether motor memory consolidation is impaired in PD compared to neurologically intact individuals. METHODS: We conducted a pre-registered systematic review (PROSPERO: CRD42020222433) following PRISMA guidelines that included 46 studies. RESULTS: Meta-analyses revealed that persons with PD have deficits in retaining motor skills (SMD = -0.17; 95% CI = -0.32, -0.02; p = 0.0225). However, these deficits are task-specific, affecting sensory motor (SMD = -0.31; 95% CI -0.47, -0.15; p = 0.0002) and visuomotor adaptation (SMD = -1.55; 95% CI = -2.32, -0.79; p = 0.0001) tasks, but not sequential fine motor (SMD = 0.17; 95% CI = -0.05, 0.39; p = 0.1292) and gross motor tasks (SMD = 0.04; 95% CI = -0.25, 0.33; p = 0.7771). Importantly, deficits became non-significant when augmented feedback during practice was provided, and additional motor practice sessions reduced deficits in sensory motor tasks. Meta-regression analyses confirmed that deficits were independent of performance during encoding, as well as disease duration and severity. CONCLUSION: Our results align with the neurodegenerative models of PD progression and motor learning frameworks and emphasize the importance of developing targeted interventions to enhance motor memory consolidation in PD.

Levodopa alters resting-state functional connectivity more selectively in Parkinson's disease with freezing of gait.

Freezing of gait (FOG) is a debilitating motor symptom of Parkinson's disease (PD). Although PD dopaminergic medication (L-DOPA) seems to generally reduce FOG severity, its effect on neural mechanisms of FOG remains to be determined. The purpose of this study was to quantify the effect of L-DOPA on brain resting-state functional connectivity in individuals with FOG. Functional magnetic resonance imaging was acquired at rest in 30 individuals living with PD (15 freezers) in the ON- and OFF- medication state. A seed-to-voxel analysis was performed with seeds in the bilateral basal ganglia nuclei, the thalamus and the mesencephalic locomotor region. In freezers, medication-state contrasts revealed numerous changes in resting-state functional connectivity, not modulated by L-DOPA in non-freezers. In freezers, L-DOPA increased the functional connectivity between the seeds and regions including the posterior parietal, the posterior cingulate, the motor and the medial prefrontal cortices. Comparisons with non-freezers revealed that L-DOPA generally normalizes brain functional connectivity to non-freezers levels but can also increase functional connectivity, possibly compensating for dysfunctional networks in freezers. Our findings suggest that L-DOPA could contribute to a better sensorimotor, attentional, response inhibition and limbic processing to prevent FOG when triggers are encountered but could also contribute to FOG by interfering with the processing capacity of the striatum. This study shows that levodopa taken to control PD symptoms induces changes in functional connectivity at rest, in freezers only. Increases (green) in functional connectivity of GPe, GPi, putamen and thalamus with cognitive, sensorimotor and limbic cortical regions of the Interference model (blue) was observed. Our results suggest that levodopa can normalize connections similar to non-freezers or increases connectivity to compensate for dysfunctional networks.

A case of eruptive xanthomas associated with pregnancy unmasking a G188E heterozygous mutation of the lipoprotein lipase gene: A case report.

A case of eruptive xanthomas with exceptionally high levels of blood triglycerides without any complication during pregnancy is reported. Eruptive xanthomas may develop in the setting of severe hypertriglyceridemia. Clinically, patients present with small and smooth papules with a characteristic yellow hue. The condition can also be associated with morbid systemic complications. Estrogen replacement therapy is a known cause of secondary hypertriglyceridemia. Estrogen increase in pregnancy is associated with a physiologic elevation of blood triglycerides in order to provide sufficient nutrition for the fetus. However, in the setting of primary dyslipidemia, severe hypertriglyceridemia can occur. The case presented here was explained by a partial primary lipoprotein lipase deficiency with a heterozygous G188E mutation of the LPL gene. The delivery by induced labor and the introduction of fenofibrate led to a rapid decrease of triglycerides and a resolution of cutaneous lesions without any complication for the patient or her baby.

Differential Effects of Speech and Language Therapy and rTMS in Chronic Versus Subacute Post-stroke Aphasia: Results of the NORTHSTAR-CA Trial.

BACKGROUND & OBJECTIVE: Contralesional 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the right pars triangularis combined with speech-language therapy (SLT) has shown positive results on the recovery of naming in subacute (5-45 days) post-stroke aphasia. NORTHSTAR-CA is an extension of the previously reported NORTHSTAR trial to chronic aphasia (>6 months post-stroke) designed to compare the effectiveness of the same rTMS protocol in both phases. METHODS: Sixty-seven patients with left middle cerebral artery infarcts (28 chronic, 39 subacute) were recruited (01-2014 to 07-2019) and randomized to receive rTMS (N = 34) or sham stimulation (N = 33) with SLT for 10 days. Primary outcome variables were Z-score changes in naming, semantic fluency and comprehension tests and adverse event frequency. Intention-to-treat analyses tested between-group effects at days 1 and 30 post-treatment. Chronic and subacute results were compared. RESULTS: Adverse events were rare, mild, and did not differ between groups. Language outcomes improved significantly in all groups irrespective of treatment and recovery phase. At 30-day follow-up, there was a significant interaction of stimulation and recovery phase on naming recovery (P <.001). Naming recovery with rTMS was larger in subacute (Mdn = 1.91/IQR = .77) than chronic patients (Mdn = .15/IQR = 1.68/P = .015). There was no significant rTMS effect in the chronic aphasia group. CONCLUSIONS: The addition of rTMS to SLT led to significant supplemental gains in naming recovery in the subacute phase only. While this needs confirmation in larger studies, our results clarify neuromodulatory vs training-induced effects and indicate a possible window of opportunity for contralesional inhibitory stimulation interventions in post-stroke aphasia. NORTHSTAR TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02020421.

Analysis of Human Head Motion and Robotic Compensation for PET Imaging Studies.

Functional medical imaging systems can provide insights into brain activity during various tasks, but most current imaging systems are bulky devices that are not compatible with many human movements. Our motivating application is to perform Positron Emission Tomography (PET) imaging of subjects during sitting, upright standing and locomotion studies on a treadmill. The proposed long-term solution is to construct a robotic system that can support an imaging system surrounding the subject's head, and then move the system to accommodate natural motion. This paper presents the first steps toward this approach, which are to analyze human head motion, determine initial design parameters for the robotic system, and verify the concept in simulation.

Potential Non-invasive Brain Stimulation Targets to Alleviate Freezing of Gait in Parkinson's Disease.

Freezing of gait (FOG) is a common motor symptom in Parkinson's disease (PD). Although FOG reduces quality of life, affects mobility and increases the risk of falls, there are little to no effective treatments to alleviate FOG. Non-invasive brain stimulation (NIBS) has recently yielded attention as a potential treatment to reduce FOG symptoms however, stimulation parameters and protocols remain inconsistent and require further research. Specifically, targets for stimulation require careful review. Thus, with current neuroimaging and neuro-electrophysiological evidence, we consider potential cortical targets thought to be involved in the pathophysiology of FOG according to the Interference model, and within reach of NIBS. We note that the primary motor cortex, the supplementary motor area and the dorsolateral prefrontal cortex have already drawn attention as NIBS targets for FOG, but based on neuroimaging evidence the premotor cortex, the medial prefrontal cortex, the cerebellum, and more particularly, the posterior parietal cortex should be considered as potential regions for stimulation. We also discuss different methodological considerations, such as stimulation type, medication state, and hemisphere to target, and future perspectives for NIBS protocols in FOG.

Identification of Predictors of Abnormal Calcium, Magnesium and Phosphorus Blood Levels in the Emergency Department: A Retrospective Cohort Study.

PURPOSE: With rising healthcare costs limiting access to care, the judicious use of diagnostic tests has become a critical issue for many jurisdictions. Calcium, magnesium and phosphorus serum levels are regularly performed tests in the emergency department, but their clinical relevance have come into question. Authors sought to determine risk factors that could predict abnormal calcium, magnesium and phosphorus serum levels, as well as identify patients who may need corrective interventions. METHODS: A retrospective cohort study was conducted in two academic hospitals in Québec City. Demographic and clinical characteristics of 1008 patients who had serum calcium and/or magnesium and/or phosphorus levels drawn by an emergency physician were collected. Multivariate logistic regression models were fitted to obtain adjusted odds ratios for each risk factor for abnormal calcium or magnesium or phosphorus blood levels, and for a required intervention. RESULTS: Among patients for whom calcium, magnesium and phosphorus were tested in the Emergency Department, the most significant risk factors (OR>2) for electrolytic abnormality were as follows: hypocalcemia - respiratory distress, diuretics (excluding loop and thiazide), anti-neoplastic medication, long QTc, chronic kidney disease (CKD); hypercalcemia - bone pain, vitamin D, hallucinations; hypomagnesemia - diabetes, corticosteroids; hypermagnesemia - poor extremity perfusion, CKD, furosemide; hypophosphatemia - seizure; hyperphosphatemia - phosphate-binders, CKD, peripheral vascular atherosclerotic disease. Of all patients tested, 3.4% received a corrective intervention initiated by the emergency physician. Predictors of intervention on an electrolyte abnormality include poor peripheral perfusion, nausea and chronic obstructive pulmonary disease (COPD). CONCLUSION: Emergency physicians can potentially reduce the unnecessary testing of calcium, magnesium and phosphorus blood levels by targeting patients with high-acuity conditions or chronic comorbidities such as CKD, diabetes and COPD.

Canadian Platform for Trials in Noninvasive Brain Stimulation (CanStim) Consensus Recommendations for Repetitive Transcranial Magnetic Stimulation in Upper Extremity Motor Stroke Rehabilitation Trials.

Objective. To develop consensus recommendations for the use of repetitive transcranial magnetic stimulation (rTMS) as an adjunct intervention for upper extremity motor recovery in stroke rehabilitation clinical trials. Participants. The Canadian Platform for Trials in Non-Invasive Brain Stimulation (CanStim) convened a multidisciplinary team of clinicians and researchers from institutions across Canada to form the CanStim Consensus Expert Working Group. Consensus Process. Four consensus themes were identified: (1) patient population, (2) rehabilitation interventions, (3) outcome measures, and (4) stimulation parameters. Theme leaders conducted comprehensive evidence reviews for each theme, and during a 2-day Consensus Meeting, the Expert Working Group used a weighted dot-voting consensus procedure to achieve consensus on recommendations for the use of rTMS as an adjunct intervention in motor stroke recovery rehabilitation clinical trials. Results. Based on best available evidence, consensus was achieved for recommendations identifying the target poststroke population, rehabilitation intervention, objective and subjective outcomes, and specific rTMS parameters for rehabilitation trials evaluating the efficacy of rTMS as an adjunct therapy for upper extremity motor stroke recovery. Conclusions. The establishment of the CanStim platform and development of these consensus recommendations is a first step toward the translation of noninvasive brain stimulation technologies from the laboratory to clinic to enhance stroke recovery.

Understanding Human Neural Control of Short-term Gait Adaptation to the Split-belt Treadmill.

Many studies of split-belt treadmill adaptation have been focused on the biomechanical changes that occur in response to walking on belts at different speeds. This process of adaptation, and the ensuing aftereffects that are present when participants return to typical treadmill walking, have inspired the potential use of the split-belt treadmill as a rehabilitation tool. However, a full systematic review of the current split-belt treadmill literature has not yet been published to consolidate what is known about how the human central nervous system (CNS) controls adaptation to this type of symmetry perturbation. A systematic literature search identified 55 studies that investigated the neural control of human gait adaptation to a split-belt treadmill. Studies of infants and manipulated sensory feedback in healthy adults suggest that the initial gait adjustments to split-belt walking are reliant on proprioceptive feedback to inform central pattern generators to modify lower limb muscle activation patterns appropriately. Simultaneously, this literature suggested that proprioceptive and visual feedback inform supraspinal centres for motor planning and motor output to adapt and store a new and efficient gait pattern to walk on belts at different speeds. However, evidence from participants with brain injury (post-stroke, cerebellar lesions) suggest that injury impedes, but does not completely take away, the ability to adjust and adapt aspects of the gait pattern to split-belts. The model proposed from this review provides the overarching roles of the CNS in the adaptation process, specifically in short-term, and potential sites of focus within the human CNS for future rehabilitation-based work.

Non-invasive brain stimulation as add-on therapy for subacute post-stroke aphasia: a randomized trial (NORTHSTAR).

INTRODUCTION: Non-invasive brain stimulation (NIBS) with speech therapy might improve recovery from post-stroke aphasia. This three-armed sham-controlled blinded prospective proof-of-concept study tested 1 Hz subthreshold repetitive transcranial magnetic stimulation (rTMS) and 2-mA cathodal transcranial direct current stimulation (ctDCS) on the right pars triangularis in subacute post-stroke aphasia. PATIENTS AND METHODS: Sixty-three patients with left middle cerebral artery infarcts were recruited in five hospitals (Canada/United States/Germany, 01-2014/03-2018) and randomized to receive rTMS (N = 20), ctDCS (N = 24) or sham stimulation (N = 19) with ST for 10 days. Primary outcome variables were Z-score changes in naming, semantic fluency and comprehension tests and adverse event frequency. Secondary outcome variable was the percent change in the Unified Aphasia Score. Intention-to-treat analyses tested between-group effects at days 1 and 30 post-treatment with a pre-planned subgroup analysis for lesion location (affecting Broca's area or not). RESULTS: Naming was significantly improved by rTMS (median = 1.91/interquartile range = 0.77/p = .01) at 30 days versus ctDCS (median = 1.11/interquartile range = 1.51) and sham stimulation (median = 1.02/interquartile range = 1.71). All other primary results were non-significant. The rTMS effect was driven by the patient subgroup with intact Broca's area where NIBS tended to improve UnAS (median = 33.2%/interquartile range = 46.7%/p = .062) versus sham stimulation (median = 12.5%/interquartile range = 7.9%) at day 30. Conversely, in patients with infarcted Broca's area, UnAS tended to improve more with sham stimulation (median = 75.0%/interquartile range = 86.9%/p = .053) versus NIBS (median = 12.7%/interquartile range = 31.7).Conclusion: We found a delayed positive effect of low-frequency rTMS targeting the right pars triangularis on the recovery of naming performance in subacute post-stroke aphasia. This intervention may be beneficial only in patients with morphologically intact Broca's area.

Does dual task placement and duration affect split-belt treadmill adaptation?

BACKGROUND: Dual tasking during prolonged split-belt adaptation (10-15 min) has shown to slow the adaptation process and prolong aftereffects. Therefore, dual tasks during split-belt adaptation are being explored for their potential in gait symmetry rehabilitation. However, the ideal paradigm configuration it is still not clear. RESEARCH QUESTION: To determine whether split-belt adaptation and ensuing aftereffects are altered by dual task placement, specifically looking at onset of split-belt adaptation or later part way through Adaptation (Experiment 1) and dual task duration (Experiment 2). METHODS: Healthy young adults (n = 40) performed 5 min of tied-belt walking, followed by 14 min of split-belts (Adaptation, 1:3 ratio) and 5 min of de-adaptation (both belts at same speed) to assess after effects (Post-Adaptation). Experiment 1: To assess the effects of dual task placement, an auditory version of an n-back task was presented during the first 8 min or last 8 min of Adaptation. Experiment 2: To assess the effects of dual task duration, the cognitive task was presented during the entire split-belt Adaptation phase (14 min) or during four 2-minute bouts (8 min). Cognitive task accuracy, dual support symmetry, and rates of adaptation and de-adaptation were compared. RESULTS: When both the onset of the auditory cognitive task and the onset of Adaptation (split-belts) occurred simultaneously, participants prioritized split-belt adaptation and in doing so, cognitive task accuracy was reduced (Experiment 1). By prioritizing gait symmetry over cognitive performance, there were no differences in dual support symmetry adaptation (magnitude, variability or rate of Adaptation/De-adaptation) regardless of cognitive task placement or duration (Experiment 2). SIGNIFICANCE: We believe the early portion of split-belt treadmill adaptation to be a cognitive interference period. These results support future work exploring the use of dual task in a rehabilitation setting with more complicated motor-cognitive dual task paradigms during this key period.

Abnormal Muscle Activity and Variability Before, During, and After the Occurrence of Freezing in Parkinson's Disease.

Freezing of gait (FOG) is often experienced in advanced stages of Parkinson's disease (PD) and can lead to an increased risk of falls. Although spatiotemporal characteristics of FOG are well-described, their underlying neuromuscular mechanisms remain poorly understood. Several studies have demonstrated an abnormal activation of distal muscles of the lower limb and coordination impairments during gait in people with PD (pwPD). However, few have investigated how various characteristics of electromyograms (EMGs) change before, during and after a freezing episode (FE). Our objective was to quantify changes in proximal and distal leg muscle activity associated with FEs. In this study, 12 pwPD, confirmed as freezers, performed a repetitive stepping-in-place task used to elicit FE. Surface EMGs were collected from proximal [rectus femoris and biceps femoris (BF)] and distal [tibialis anterior (TA) and gastrocnemius medialis (GM)] muscles. Data epochs of 500 ms were extracted from EMG time series at four different periods: baseline, 2 s before a FE, during a FE, and 2 s after a FE. For each epoch, EMG amplitude [root-mean-square (RMS)], variability [coefficient of variation (CoV)], and inter-muscle functional connectivity (mutual information) were quantified. Results from the analysis of 21 FEs show a significant main effect of Period for EMG amplitude in bilateral TA and in the least affected GM (p < 0.01), with decreased activation before freezing that remained low during and after the FE. On the other hand, a main effect of Period was also found in bilateral BF muscles (p < 0.01) but with increased activation before freezing that was generally sustained during and after FE. Main effects of Period were also found for all measures of variability, except for the least affected GM, showing reduced variability during the FE that returned to baseline in all muscles except both TA. Moreover, an increase in functional connectivity between the least affected distal muscles was seen before the FE. Our findings confirm that many characteristics of EMG patterns of both distal and proximal leg muscles change throughout periods of a FE, suggesting both impairment and adaptive strategies from proximal muscles.

Changes in Resting-State Functional Connectivity Related to Freezing of Gait in Parkinson's Disease.

Freezing of gait (FOG) is a common motor symptom in Parkinson's disease (PD) thought to arise from the dysfunctional cortico-basal ganglia-thalamic circuity. The purpose of this study was to assess the changes in brain resting-state functional connectivity (rs-FC) of subcortical structures comprising the cortico-basal ganglia-thalamic circuity in individuals with PD with and without FOG. Resting-state functional magnetic resonance imaging was acquired in 27 individuals with idiopathic PD (14 with FOG and 13 without FOG). A seed-to-voxel analysis was performed with the seeds in the bilateral basal ganglia nuclei, thalamus, and pedunculopontine nucleus. Between-group differences in rs-FC revealed that the bilateral thalamus and globus pallidus external were significantly more connected with visual areas in PD with FOG compared to PD without FOG. In addition, PD with FOG had increased connectivity between the left putamen and retrosplenial cortex as well as with the cerebellum. Our findings suggest an increased connectivity at rest of subcortical and cortical regions involved in sensory and visuospatial processing that may be compensating for sensorimotor deficits in FOG. This increased connectivity may contribute to the hypothesized overload in the cortico-basal ganglia-thalamic circuity processing capacity, which may ultimately result in FOG occurrence.

Adjusting gait step-by-step: Brain activation during split-belt treadmill walking.

When walking on a split-belt treadmill, where each leg is driven at a different speed, a temporary change is made to the typical steady-state walking pattern. The exact ways in which the brain controls these temporary changes to walking are still unknown. Ten young adults (23±3y) walked on a split-belt treadmill for 30 min on 2 separate occasions: tied-belt control with both belts at comfortable walking speed, and continuous adjustment where speed ratio between belts changed every 15 seconds. 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET) imaging measured whole brain glucose metabolism distribution, or activation, during each treadmill walking condition. The continuous adjustment condition, compared to the tied-belt control, was associated with increased activity of supplementary motor areas (SMA), posterior parietal cortex (PPC), anterior cingulate cortex and anterior lateral cerebellum, and decreased activity of posterior cingulate and medial prefrontal cortex. In addition, peak activation of the PPC, SMA and PFC were correlated with cadence and temporal gait variability. We propose that a "fine-tuning" network for human locomotion exists which includes brain areas for sensorimotor integration, motor planning and goal directed attention. These findings suggest that distinct regions govern the inherent flexibility of the human locomotor plan to maintain a successful and adjustable walking pattern.

The effects of dual-tasking on temporal gait adaptation and de-adaptation to the split-belt treadmill in older adults.

BACKGROUND: It has been well established that with aging, walking becomes more challenging when dividing attention towards other tasks (i.e. dual-tasks) and when adapting walking to environmental demands. Although these gait-related features are believed to contribute to an increased risk of falling in older adults, little is known about the interplay between dual-tasking and gait adaptation. OBJECTIVE: To investigate whether the rate and variability of temporal gait adaptation to a split-belt treadmill and ensuing aftereffects are altered by dual-tasking in healthy older adults. METHODS: Split-belt walking was assessed in 28 healthy older adults (mean age 69 years) who were free of any ongoing medical conditions affecting gait. Participants adapted their walking pattern to a split-belt treadmill at a 2:1 speed ratio (10 min) followed by 3 min of de-adaptation (both belts at the same speed) to assess aftereffects. Half of the participants performed an intermittent dual-task (auditory cognitive task) during the adaptation period, whereas the other half completed the adaptation period as a single task. Double support symmetry magnitude and variability were used to compare group differences in rate of adaptation to the split-belt condition and retention of aftereffects during de-adaptation. RESULTS: During adaptation, the presence of a dual-task slowed the rate of adaptation to the split-belts and was characterized by greater variability in the dual-task group compared to the single-task group. During the first minute of de-adaptation, both groups similarly decreased their double support asymmetry towards baseline performance. Still, the dual-task group had a significant decrease in asymmetry during the end of de-adaptation and spent less steps within baseline performance during the entire de-adaptation period compared to the single-task group (35% vs 50%). CONCLUSION: Dual-tasking led to slower and more variable temporal gait adaptation to the split-belt treadmill and larger variability during de-adaptation. Our findings indicate that in older adults, gait adaptation is affected by a competing cognitive task and highlights the importance of being aware of the influence of dual-task on short-term learning when developing rehabilitation programs for cognitive-motor interference.