Liver-Directed Locoregional Therapies for Neuroendocrine Liver Metastases: Recent Advances and Management.

Neuroendocrine tumors (NETs) are a heterogeneous class of cancers, predominately occurring in the gastroenteropancreatic system, which pose a growing health concern with a significant rise in incidence over the past four decades. Emerging from neuroendocrine cells, these tumors often elicit paraneoplastic syndromes such as carcinoid syndrome, which can manifest as a constellation of symptoms significantly impacting patients' quality of life. The prognosis of NETs is influenced by their tendency for metastasis, especially in cases involving the liver, where the estimated 5-year survival is between 20 and 40%. Although surgical resection remains the preferred curative option, challenges emerge in cases of neuroendocrine tumors with liver metastasis (NELM) with multifocal lobar involvement, and many patients may not meet the criteria for surgery. Thus, minimally invasive and non-surgical treatments, such as locoregional therapies, have surfaced. Overall, these approaches aim to prioritize symptom relief and aid in overall tumor control. This review examines locoregional therapies, encompassing catheter-driven procedures, ablative techniques, and radioembolization therapies. These interventions play a pivotal role in enhancing progression-free survival and managing hormonal symptoms, contributing to the dynamic landscape of evolving NELM treatment. This review meticulously explores each modality, presenting the current state of the literature on their utilization and efficacy in addressing NELM.

Organization of sensorimotor activity in anterior cruciate ligament reconstructed individuals: an fMRI conjunction analysis.

Introduction: Anterior cruciate ligament reconstruction (ACLR) is characterized by persistent involved limb functional deficits that persist for years despite rehabilitation. Previous research provides evidence of both peripheral and central nervous system adaptations following ACLR. However, no study has compared functional organization of the brain for involved limb motor control relative to the uninvolved limb and healthy controls. The purpose of this study was to examine sensorimotor cortex and cerebellar functional activity overlap and non-overlap during a knee motor control task between groups (ACLR and control), and to determine cortical organization of involved and uninvolved limb movement between groups. Methods: Eighteen participants with left knee ACLR and 18 control participants performed a knee flexion/extension motor control task during functional magnetic resonance imaging (fMRI). A conjunction analysis was conducted to determine the degree of overlap in brain activity for involved and uninvolved limb knee motor control between groups. Results: The ACLR group had a statistically higher mean percent signal change in the sensorimotor cortex for the involved > uninvolved contrast compared to the control group. Brain activity between groups statistically overlapped in sensorimotor regions of the cortex and cerebellum for both group contrasts: involved > uninvolved and uninvolved > involved. Relative to the control group, the ACLR group uniquely activated superior parietal regions (precuneus, lateral occipital cortex) for involved limb motor control. Additionally, for involved limb motor control, the ACLR group displayed a medial and superior shift in peak voxel location in frontal regions; for parietal regions, the ACLR group had a more posterior and superior peak voxel location relative to the control group. Conclusion: ACLR may result in unique activation of the sensorimotor cortex via a cortically driven sensory integration strategy to maintain involved limb motor control. The ACLR group's unique brain activity was independent of strength, self-reported knee function, and time from surgery.

Recent Advances in Image-Guided Locoregional Therapies for Primary Liver Tumors.

Primary liver cancer is the leading cause of cancer-related deaths worldwide. with incidences predicted to rise over the next several decades. Locoregional therapies, such as radiofrequency or microwave ablation, are described as image-guided percutaneous procedures, which offer either a curative intent for early-stage hepatocellular carcinoma or bridging/downstaging for surgical resection or transplantation. Catheter-driven locoregional therapies, such as transarterial chemoembolization and radioembolization, induce tumor hypoxia, can be palliative, and improve survival for early-to-intermediate hepatocellular carcinoma and unresectable intrahepatic cholangiocarcinoma. Herein, we provide a comprehensive overview of the antineoplastic mechanisms underpinning locoregional therapies, different treatment approaches, and the current state of the literature for the efficacy of locoregional therapies for primary liver cancer. We also discuss emerging advancements, such as the adjuvant use of immunotherapies and molecular targeting agents with locoregional therapy, for the treatment of primary liver cancer.

Brain activity associated with quadriceps strength deficits after anterior cruciate ligament reconstruction.

Prolonged treatment resistant quadriceps weakness after anterior cruciate ligament reconstruction (ACL-R) contributes to re-injury risk, poor patient outcomes, and earlier development of osteoarthritis. The origin of post-injury weakness is in part neurological in nature, but it is unknown whether regional brain activity is related to clinical metrics of quadriceps weakness. Thus, the purpose of this investigation was to better understand the neural contributions to quadriceps weakness after injury by evaluating the relationship between brain activity for a quadriceps-dominated knee task (repeated cycles of unilateral knee flexion/extension from 45° to 0°), , and strength asymmetry in individuals returned to activity after ACL-R. Forty-four participants were recruited (22 with unilateral ACL reconstruction; 22 controls) and peak isokinetic knee extensor torque was assessed at 60°/s to calculate quadriceps limb symmetry index (Q-LSI, ratio of involved/uninvolved limb). Correlations were used to determine the relationship of mean % signal change within key sensorimotor brain regions and Q-LSI. Brain activity was also evaluated group wise based on clinical recommendations for strength (Q-LSI < 90%, n = 12; Q-LSI ≥ 90%, n = 10; controls, all n = 22 Q-LSI ≥ 90%). Lower Q-LSI was related to increased activity in the contralateral premotor cortex and lingual gyrus (p < .05). Those who did not meet clinical recommendations for strength demonstrated greater lingual gyrus activity compared to those who met clinical recommendations Q-LSI ≥ 90 and healthy controls (p < 0.05). Asymmetrically weak ACL-R patients displayed greater cortical activity than patients with no underlying asymmetry and healthy controls.

Combining Neurocognitive and Functional Tests to Improve Return-to-Sport Decisions Following ACL Reconstruction.

SYNOPSIS: Neuroplasticity after anterior cruciate ligament (ACL) injury alters how the nervous system generates movement and maintains dynamic joint stability. The postinjury neuroplasticity can cause neural compensations that increase reliance on neurocognition. Return-to-sport testing quantifies physical function but fails to detect important neural compensations. To assess for neural compensations in a clinical setting, we recommend evaluating athletes' neurocognitive reliance by augmenting return-to-sport testing with combined neurocognitive and motor dual-task challenges. In this Viewpoint, we (1) share the latest evidence related to ACL injury neuroplasticity and (2) share simple principles and new assessments with preliminary data to improve return-to-sport decisions following ACL reconstruction. J Orthop Sports Phys Ther 2023;53(8):1-5. Epub: 16 May 2023. doi:10.2519/jospt.2023.11489.

Cognitive Load Influences Drop Jump Landing Mechanics During Cognitive-Motor-Simulated Shooting.

INTRODUCTION: Military duties require immense cognitive-motor multitasks that may predispose soldiers to musculoskeletal injury. Most cognitive challenges performed in the research laboratory are not tactical athlete specific, limiting generalizability and transferability to in-field scenarios. The purpose of this study was to determine the impact of a cognitive-motor multitask (forward drop jump landing while simultaneously performing simulated shooting) on knee kinetics and kinematics. METHODS: Twenty-four healthy collegiate Reserve Officer's Training Corps members (18 males and 6 females, 20.42 ± 1.28 years, 174.54 ± 10.69 cm, 78.11 ± 14.96 kg) volunteered, and knee kinetics and kinematics were assessed between baseline and cognitive-loaded conditions. Repeated measures ANOVAs were conducted for each dependent variable with the within-subject factor of condition (baseline vs. cognitive load). RESULTS: Univariate ANOVAs indicated that knee flexion angle at initial contact (IC) (decreased 6.07°; d = 3.14), knee flexion displacement (increased 6.78°; d = 1.30), knee abduction angle at IC (increased 2.3°; d = 1.46), peak knee abduction angle (increased 3.04°; d = 0.77), and peak vertical ground reaction force (increased 0.81 N/kg; d = 2.13) were significant between conditions (P < .001). Therefore, cognitive load resulted in decreased knee flexion and increased knee abduction angle at IC and greater peak vertical ground reaction force, all factors commonly associated with knee injury risk. Peak knee flexion angle and knee abduction displacement were not significant between conditions (P > .05). CONCLUSIONS: Cognitive challenge induced knee landing biomechanics commonly associated with injury risk. Injury risk screening or return-to-training or duty assessments in military personnel might consider both baseline and cognitive conditions.

Salvage locoregional therapies for recurrent hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide. Despite the advent of screening efforts and algorithms to stratify patients into appropriate treatment strategies, recurrence rates remain high. In contrast to first-line treatment for HCC, which relies on several factors, including clinical staging, tumor burden, and liver function, there is no consensus or general treatment recommendations for recurrent HCC (R-HCC). Locoregional therapies include a spectrum of minimally invasive liver-directed treatments which can be used as either curative or neoadjuvant therapy for HCC. Herein, we provide a comprehensive review of recent evidence using salvage loco-regional therapies for R-HCC after failed curative-intent.

The relationship between drop vertical jump action-observation brain activity and kinesiophobia after anterior cruciate ligament reconstruction: A cross-sectional fMRI study.

BACKGROUND: Injury and reconstruction of anterior cruciate ligament (ACL) result in central nervous system alteration to control the muscles around the knee joint. Most individuals with ACL reconstruction (ACLR) experience kinesiophobia which can prevent them from returning to activity and is associated with negative outcomes after ACLR. However, it is unknown if kinesiophobia alters brain activity after ACL injury. OBJECTIVES: To compare brain activity between an ACLR group and matched uninjured controls during an action-observation drop vertical jump (AO-DVJ) paradigm and to explore the association between kinesiophobia and brain activity in the ACLR group. METHODS: This cross-sectional study enrolled 26 individuals, 13 with ACLR (5 males and 8 females, 20.62 ± 1.93 years, 1.71 ± 0.1 m, 68.42 ± 14.75 kg) and 13 matched uninjured controls (5 males and 8 females, 22.92 ± 3.17 years, 1.74 ± 0.10 m, 70.48 ± 15.38 kg). Individuals were matched on sex and activity level. Participants completed the Tampa Scale of Kinesiophobia-11 (TSK-11) to evaluate the level of movement-related fear. To assay the brain activity associated with a functional movement, the current study employed an action-observation/motor imagery paradigm during functional magnetic resonance imaging (fMRI). RESULTS: The ACLR group had lower brain activity in the right ventrolateral prefrontal cortex relative to the uninjured control group. Brain activity of the left cerebellum Crus I and Crus II, the right cerebellum lobule IX, amygdala, middle temporal gyrus, and temporal pole were positively correlated with TSK-11 scores in the ACLR group. CONCLUSION: Brain activity for the AO-DVJ paradigm was different between the ACLR group and uninjured controls. Secondly, in participants with ACLR, there was a positive relationship between TSK-11 scores and activity in brain areas engaged in fear and cognitive processes during the AO-DVJ paradigm.

Neural Correlates of Self-Reported Knee Function in Individuals After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is a common knee injury among athletes and physically active adults. Despite surgical reconstruction and extensive rehabilitation, reinjuries are common and disability levels are high, even years after therapy and return to activity. Prolonged knee dysfunction may result in part from unresolved neuromuscular deficits of the surrounding joint musculature in response to injury. Indeed, "upstream" neurological adaptations occurring after injury may explain these persistent functional deficits. Despite evidence for injury consequences extending beyond the joint to the nervous system, the link between neurophysiological impairments and patient-reported measures of knee function remains unclear. HYPOTHESIS: Patterns of brain activation for knee control are related to measures of patient-reported knee function in individuals after ACL reconstruction (ACL-R). STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: In this multicenter, cross-sectional study, participants with unilateral ACL-R (n = 25; 10 men, 15 women) underwent task-based functional magnetic resonance imaging testing. Participants performed repeated cycles of open-chain knee flexion/extension. Neural activation patterns during the movement task were quantified using blood oxygen level-dependent (BOLD) signals. Regions of interest were generated using the Juelich Histological Brain Atlas. Pearson product-moment correlations were used to determine the relationship between mean BOLD signal within each brain region and self-reported knee function level, as measured by the International Knee Documentation Committee index. Partial correlations were also calculated after controlling for time from surgery and sex. RESULTS: Patient-reported knee function was positively and moderately correlated with the ipsilateral secondary somatosensory cortex (r = 0.57, P = 0.005) and the ipsilateral supplementary motor area (r = 0.51, P = 0.01). CONCLUSION: Increased ipsilateral secondary sensorimotor cortical activity is related to higher perceived knee function. CLINICAL RELEVANCE: Central nervous system mechanisms for knee control are related to subjective levels of knee function after ACL-R. Increased neural activity may reflect central neuroplastic strategies to preserve knee functionality after traumatic injury.

Preliminary brain-behavioral neural correlates of anterior cruciate ligament injury risk landing biomechanics using a novel bilateral leg press neuroimaging paradigm.

Anterior cruciate ligament (ACL) injury risk reduction strategies primarily focus on biomechanical factors related to frontal plane knee motion and loading. Although central nervous system processing has emerged as a contributor to injury risk, brain activity associated with the resultant ACL injury-risk biomechanics is limited. Thus, the purposes of this preliminary study were to determine the relationship between bilateral motor control brain activity and injury risk biomechanics and isolate differences in brain activity for those who demonstrate high versus low ACL injury risk. Thirty-one high school female athletes completed a novel, multi-joint leg press during brain functional magnetic resonance imaging (fMRI) to characterize bilateral motor control brain activity. Athletes also completed an established biomechanical assessment of ACL injury risk biomechanics within a 3D motion analysis laboratory. Knee abduction moments during landing were modelled as a covariate of interest within the fMRI analyses to identify directional relationships with brain activity and an injury-risk group classification analysis, based on established knee abduction moment cut-points. Greater landing knee abduction moments were associated with greater lingual gyrus, intracalcarine cortex, posterior cingulate cortex and precuneus activity when performing the bilateral leg press (all z > 3.1, p < .05; multiple comparison corrected). In the follow-up injury-risk classification analysis, those classified as high ACL injury-risk had greater activity in the lingual gyrus, parietal cortex and bilateral primary and secondary motor cortices relative to those classified as low ACL injury-risk (all z > 3.1, p < .05; multiple comparison corrected). In young female athletes, elevated brain activity for bilateral leg motor control in regions that integrate sensory, spatial, and attentional information were related to ACL injury-risk landing biomechanics. These data implicate crossmodal visual and proprioceptive integration brain activity and knee spatial awareness as potential neurotherapeutic targets to optimize ACL injury-risk reduction strategies.

Preliminary Report on the Train the Brain Project, Part II: Neuroplasticity of Augmented Neuromuscular Training and Improved Injury-Risk Biomechanics.

CONTEXT: Neuromuscular training (NMT) facilitates the acquisition of new movement patterns that reduce the anterior cruciate ligament injury risk. However, the neural mechanisms underlying these changes are unknown. OBJECTIVE: To determine the relationship between brain activation and biomechanical changes after NMT with biofeedback. DESIGN: Cohort study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty female high school soccer athletes, with 10 in an augmented NMT group and 10 in a control (no training) group. MAIN OUTCOME MEASURE(S): Ten participants completed 6 weeks of NMT augmented with real-time biofeedback to reduce knee injury-risk movements, and 10 participants pursued no training. Augmented neuromuscular training (aNMT) was implemented with visual biofeedback that responded in real time to injury-risk biomechanical variables. A drop vertical jump with 3-dimensional motion capture was used to assess injury-risk neuromuscular changes before and after the 6-week intervention. Brain-activation changes were measured using functional magnetic resonance imaging during unilateral knee and multijoint motor tasks. RESULTS: After aNMT, sensory (precuneus), visual-spatial (lingual gyrus), and motor-planning (premotor) brain activity increased for knee-specific movement; sensorimotor cortex activity for multijoint movement decreased. The knee-abduction moment during landing also decreased (4.66 ± 5.45 newton meters; P = .02; Hedges g = 0.82) in the aNMT group but did not change in the control group (P > .05). The training-induced increased brain activity with isolated knee movement was associated with decreases in knee-abduction moment (r = 0.67; P = .036) and sensorimotor cortex activity for multijoint movement (r = 0.87; P = .001). No change in brain activity was observed in the control group (P > .05). CONCLUSIONS: The relationship between neural changes observed across tasks and reduced knee abduction suggests that aNMT facilitated recruitment of sensory integration centers to support reduced injury-risk mechanics and improve sensorimotor neural efficiency for multijoint control. Further research is warranted to determine if this training-related multimodal neuroplasticity enhances neuromuscular control during more complex sport-specific activities.

Preliminary Report on the Train the Brain Project, Part I: Sensorimotor Neural Correlates of Anterior Cruciate Ligament Injury Risk Biomechanics.

CONTEXT: Anterior cruciate ligament injury commonly occurs via noncontact motor coordination errors that result in excessive multiplanar loading during athletic movements. Preventing motor coordination errors requires neural sensorimotor integration activity to support knee-joint neuromuscular control, but the underlying neural mechanisms driving injury-risk motor control are not well understood. OBJECTIVE: To evaluate brain activity differences for knee sensorimotor control between athletes with high or low injury-risk mechanics. DESIGN: Case-control study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Of 38 female high school soccer players screened, 10 were selected for analysis based on magnetic resonance imaging compliance, injury-risk classification via 3-dimensional biomechanics during a drop vertical jump, and matching criteria to complete neuroimaging during knee motor tasks. MAIN OUTCOME MEASURE(S): Peak knee-abduction moment during landing was used for group allocation into the high (≥21.74 newton meters [Nm], n = 9) or low (≤10.6 Nm, n = 11) injury-risk classification (n = 11 uncategorized, n = 7 who were not compliant with magnetic resonance imaging). Ten participants (5 high risk, 5 low risk) with adequate data were matched and compared across 2 neuroimaging paradigms: unilateral knee-joint control and unilateral multijoint leg press against resistance. RESULTS: Athletes with high injury-risk biomechanics had less neural activity in 1 sensory-motor cluster for isolated knee-joint control (precuneus, peak Z score = 4.14, P ≤ .01, 788 voxels) and greater brain activity for the multijoint leg press in 2 cognitive-motor clusters: the frontal cortex (peak Z score = 4.71, P < .01, 1602 voxels) and posterior cingulate gyrus (peak Z score = 4.43, P < .01, 725 voxels) relative to the low injury-risk group. CONCLUSIONS: The high injury-risk group's lower relative engagement of neural sensory resources controlling the knee joint may elevate demand on cognitive motor resources to control loaded multijoint action. The neural activity profile in the high injury-risk group may manifest as a breakdown in neuromuscular coordination, resulting in elevated knee-abduction moments during landing.

The effects of virtual reality immersion on drop landing mechanics.

Virtual reality (VR) can be used to alter the environment and challenge sensory calibration which rehabilitation and return-to-sport testing lack. The purpose was to establish how VR manipulation of the environment changes knee landing biomechanics. Twenty-nine healthy active adults (22 males; 20.52 ± 1.21 years; 1.75 ± 0.09 m; 78.34 ± 14.33 kg) were recruited. Three drop landing trials (31 cm height box) were performed for three conditions: eyes-open (EO), eyes-closed (EC), and VR, consisting of a head-mounted display of a 360° photo of a steep man-made edge or drop. Knee kinematics and kinetics were evaluated using 3D motion capture. The VR condition significantly increased Landing Error Score System errors relative to EO (1.28 ± 0.20, p < 0.001) and EC (0.98 ± 0.22, p < 0.001) and increased vertical ground reaction force relative to EO (0.41 ± 0.09 N·bw-1, p < 0.001) and EC (0.34 ± 0.07 N·bw-1, p < 0.001). The VR condition had less knee flexion at initial contact compared to EO (4.39 ± 0.75°, p = 0.001) and EC (1.83 ± 0.63°, p = 0.021). The VR condition had more knee abduction at initial contact compared to EO (0.71 ± 0.24°, p = 0.002) and EC (0.69 ± 0.22°, p = 0.002) and increased knee abduction at maximum flexion compared to EO (2.01 ± 0.58°, p = 0.026). Landing in VR increased injury risk landing biomechanics, indicating that VR may option to incorporate into return-to-play or injury risk assessment.

Visual cognition associated with knee proprioception, time to stability, and sensory integration neural activity after ACL reconstruction.

Visual cognitive ability has previously been associated with anterior cruciate ligament injury and injury risk biomechanics in healthy athletes. Neuroimaging reports have identified increased neural activity in regions corresponding to visual-spatial processing, sensory integration, and visual cognition in individuals after anterior cruciate ligament reconstruction (ACLR), indicating potential neural compensatory strategies for motor control. However, it remains unclear whether there is a relationship between visual cognition, neural activity, and metrics of neuromuscular ability after ACLR. The purpose of this study was to (1) evaluate the relationship between visual cognitive function and measurements of neuromuscular control (proprioception and time to stability [TTS]), isokinetic strength, and subjective function, and (2) examine the neural correlates of visual cognition between ACLR (n = 16; time since surgery 41.4 ± 33.0 months) and demographically similar controls (n = 15). Visual cognition was assessed by the ImPACT visual motor and visual memory subscales. Outcome variables of proprioception to target knee angle 20°, landing TTS, strength, and subjective function were compared between groups, and visual cognition was correlated within groups to determine the relationship between visual cognition and outcome variables controlled for time from surgery (ACLR group). The control group had better IKDC scores and strength. Visual memory and visual motor ability were negatively associated with proprioception error (r = -0.63) and TTS (r = -0.61), respectively, in the ACLR group but not controls. Visual cognition was associated with increased neural activity in the precuneus and posterior cingulate cortex in the ACLR group but not control participants. These data suggest the neural strategy in which ACLR participants maintain proprioception and stability varies, and may depend on visual cognition and sensory integration neural activity.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Visual Perturbation to Enhance Return to Sport Rehabilitation after Anterior Cruciate Ligament Injury: A Clinical Commentary.

Anterior cruciate ligament (ACL) tears are common traumatic knee injuries causing joint instability, quadriceps muscle weakness and impaired motor coordination. The neuromuscular consequences of injury are not limited to the joint and surrounding musculature, but may modulate central nervous system reorganization. Neuroimaging data suggest patients with ACL injuries may require greater levels of visual-motor and neurocognitive processing activity to sustain lower limb control relative to healthy matched counterparts. Therapy currently fails to adequately address these nuanced consequences of ACL injury, which likely contributes to impaired neuromuscular control when visually or cognitively challenged and high rates of re-injury. This gap in rehabilitation may be filled by visual perturbation training, which may reweight sensory neural processing toward proprioception and reduce the dependency on vision to perform lower extremity motor tasks and/or increase visuomotor processing efficiency. This clinical commentary details a novel approach to supplement the current standard of care for ACL injury by incorporating stroboscopic glasses with key motor learning principles customized to target visual and cognitive dependence for motor control after ACL injury. LEVEL OF EVIDENCE: 5.

Rupture, reconstruction, and rehabilitation: A multi-disciplinary review of mechanisms for central nervous system adaptations following anterior cruciate ligament injury.

BACKGROUND: Despite surgical reconstruction and extensive rehabilitation, persistent quadriceps inhibition, gait asymmetry, and functional impairment remain prevalent in patients after anterior cruciate ligament (ACL) injury. A combination of reports have suggested underlying central nervous system adaptations in those after injury govern long-term neuromuscular impairments. The classic assumption has been to attribute neurophysiologic deficits to components of injury, but other factors across the continuum of care (e.g. surgery, perioperative analgesia, and rehabilitative strategies) have been largely overlooked. OBJECTIVE: This review provides a multidisciplinary perspective to 1) provide a narrative review of studies reporting neuroplasticity following ACL injury in order to inform clinicians of the current state of literature and 2) provide a mechanistic framework of neurophysiologic deficits with potential clinical implications across all phases of injury and recovery (injury, surgery, and rehabilitation) RESULTS: Studies using a variety of neurophysiologic modalities have demonstrated peripheral and central nervous system adaptations in those with prior ACL injury. Longitudinal investigations suggest neurophysiologic changes at spinal-reflexive and corticospinal pathways follow a unique timecourse across injury, surgery, and rehabilitation. CONCLUSION: Clinicians should consider the unique injury, surgery, anesthesia, and rehabilitation on central nervous system adaptations. Therapeutic strategies across the continuum of care may be beneficial to mitigate maladaptive neuroplasticity in those after ACL injury.

Is impaired dopaminergic function associated with mobility capacity in older adults?

The capacity to move is essential for independence and declines with age. Slow movement speed, in particular, is strongly associated with negative health outcomes. Prior research on mobility (herein defined as movement slowness) and aging has largely focused on musculoskeletal mechanisms and processes. More recent work has provided growing evidence for a significant role of the nervous system in contributing to reduced mobility in older adults. In this article, we report four pieces of complementary evidence from behavioral, genetic, and neuroimaging experiments that, we believe, provide theoretical support for the assertion that the basal ganglia and its dopaminergic function are responsible, in part, for age-related reductions in mobility. We report four a posteriori findings from an existing dataset: (1) slower central activation of ballistic force development is associated with worse mobility among older adults; (2) older adults with the Val/Met intermediate catecholamine-O-methyl-transferase (COMT) genotype involved in dopamine degradation exhibit greater mobility than their homozygous counterparts; (3) there are moderate relationships between performance times from a series of lower and upper extremity tasks supporting the notion that movement speed in older adults is a trait-like attribute; and (4) there is a relationship of functional connectivity within the medial orbofrontal (mOFC) cortico-striatal network and measures of mobility, suggesting that a potential neural mechanism for impaired mobility with aging is the deterioration of the integrity of key regions within the mOFC cortico-striatal network. These findings align with recent basic and clinical science work suggesting that the basal ganglia and its dopaminergic function are mechanistically linked to age-related reductions in mobility capacity.

Neural activity for hip-knee control in those with anterior cruciate ligament reconstruction: A task-based functional connectivity analysis.

Anterior cruciate ligament injury may induce neurophysiological changes for sensorimotor control. Neuroimaging investigations have revealed unique brain activity patterns for knee movement following injury, indicating potential neural mechanisms underlying aberrant neuromuscular control that may contribute to heightened risk of secondary injury, altered movement patterns and poor patient outcomes. However, neuroimaging paradigms thus far have been limited to single joint, single motion knee tasks. Therefore, we sought to overcome prior limitations to understand the effects of injury on neural control of lower extremity movement by employing a multi-joint motor paradigm and determining differences in neural activity between ACL-reconstructed (ACLr) individuals relative to healthy matched controls. Fifteen patients with left anterior cruciate ligament reconstruction and fifteen matched healthy controls participated in this study. Neural activity was examined using functional magnetic resonance imaging during a block-designed knee-hip movement paradigm (similar to a supine heel-slide). Participants for each group were monitored and task performance was controlled via a metronome to ensure the same spatial-temporal parameters. We observed that those with ACL reconstruction displayed increased activation within the intracalcarine cortex, lingual gyrus, occipital fusiform gyrus, lateral occipital cortex, angular gyrus, and superior parietal lobule relative to controls. A follow-up task-based functional connectivity analyses using seed regions identified from the group analysis revealed connectivity among fronto-insular-temporal and sensorimotor regions within the ACLr participants. The results of this fMRI investigation suggest ACLr individuals require increased activity and connectivity in areas responsible for visual-spatial cognition and orientation, and attention for hip and knee motor control.

Neural Correlates of Knee Extension and Flexion Force Control: A Kinetically-Instrumented Neuroimaging Study.

Background: The regulation of muscle force is a vital aspect of sensorimotor control, requiring intricate neural processes. While neural activity associated with upper extremity force control has been documented, extrapolation to lower extremity force control is limited. Knowledge of how the brain regulates force control for knee extension and flexion may provide insights as to how pathology or intervention impacts central control of movement. Objectives: To develop and implement a neuroimaging-compatible force control paradigm for knee extension and flexion. Methods: A magnetic resonance imaging (MRI) safe load cell was used in a customized apparatus to quantify force (N) during neuroimaging (Philips Achieva 3T). Visual biofeedback and a target sinusoidal wave that fluctuated between 0 and 5 N was provided via an MRI-safe virtual reality display. Fifteen right leg dominant female participants (age = 20.3 ± 1.2 years, height = 1.6 ± 0.10 m, weight = 64.8 ± 6.4 kg) completed a knee extension and flexion force matching paradigm during neuroimaging. The force-matching error was calculated based on the difference between the visual target and actual performance. Brain activation patterns were calculated and associated with force-matching error and the difference between quadriceps and hamstring force-matching tasks were evaluated with a mixed-effects model (z > 3.1, p < 0.05, cluster corrected). Results: Knee extension and flexion force-matching tasks increased BOLD signal among cerebellar, sensorimotor, and visual-processing regions. Increased knee extension force-matching error was associated with greater right frontal cortex and left parietal cortex activity and reduced left lingual gyrus activity. Increased knee flexion force-matching error was associated with reduced left frontal and right parietal region activity. Knee flexion force control increased bilateral premotor, secondary somatosensory, and right anterior temporal activity relative to knee extension. The force-matching error was not statistically different between tasks. Conclusion: Lower extremity force control results in unique activation strategies depending on if engaging knee extension or flexion, with knee flexion requiring increased neural activity (BOLD signal) for the same level of force and no difference in relative error. These fMRI compatible force control paradigms allow precise behavioral quantification of motor performance concurrent with brain activity for lower extremity sensorimotor function and may serve as a method for future research to investigate how pathologies affect lower extremity neuromuscular function.