Objective Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow‐up. Unfortunately, the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three‐dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image‐based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE. Methods This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively. Results Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic‐clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome. Significance LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control.

Objective To identify features of ablations and trajectories that correlate with optimal seizure control and minimize the risk of neurocognitive deficits in patients undergoing laser interstitial thermal therapy (LiTT) for mesiotemporal epilepsy (mTLE). Methods Clinical and radiographic data were reviewed from a prospectively maintained database of all patients undergoing LiTT for the treatment of mTLE at the University of Miami Hospital. Standard pre- and post-operative evaluations, including contrast-enhanced MRI and neuropsychological testing, were performed in all patients. Laser trajectory and ablation volumes were computed both by manual tracing of mesiotemporal structures and by non-rigid registration of ablation cavities to a common reference system based on 7T MRI data. Results Among 23 patients with at least one-year follow-up, 15 (65%) were free of disabling seizures since the time of their surgery. Sparing of mesial hippocampal head was significantly correlated with persistent disabling seizures (p = 0.01). A lateral trajectory through the hippocampus showed a trend for poor seizure outcome (p = 0.08). Comparison of baseline and postoperative neurocognitive testing revealed areas of both improvement and worsening, which were not associated with ablation volume or trajectory. Significance At one-year follow-up, LiTT appears to be a safe and effective tool for the treatment of mTLE, though a longer follow-up period is necessary to confirm these observations. Better understanding of the impact of ablation volume and location could potentially fine-tune this technique to improve seizure freedom rates and associated neurological and cognitive changes.

Although chronic vagus nerve stimulation (VNS) is an established treatment for medically-intractable childhood epilepsy, there is considerable heterogeneity in seizure response and little data are available to pre-operatively identify patients who may benefit from treatment. Since the therapeutic effect of VNS may be mediated by afferent projections to the thalamus, we tested the hypothesis that intrinsic thalamocortical connectivity is associated with seizure response following chronic VNS in children with epilepsy. Twenty-one children (ages 5–21 years) with medically-intractable epilepsy underwent resting-state fMRI prior to implantation of VNS. Ten received sedation, while 11 did not. Whole brain connectivity to thalamic regions of interest was performed. Multivariate generalized linear models were used to correlate resting-state data with seizure outcomes, while adjusting for age and sedation status. A supervised support vector machine (SVM) algorithm was used to classify response to chronic VNS on the basis of intrinsic connectivity. Of the 21 subjects, 11 (52%) had 50% or greater improvement in seizure control after VNS. Enhanced connectivity of the thalami to the anterior cingulate cortex (ACC) and left insula was associated with greater VNS efficacy. Within our test cohort, SVM correctly classified response to chronic VNS with 86% accuracy. In an external cohort of 8 children, the predictive model correctly classified the seizure response with 88% accuracy. We find that enhanced intrinsic connectivity within thalamocortical circuitry is associated with seizure response following VNS. These results encourage the study of intrinsic connectivity to inform neural network-based, personalized treatment decisions for children with intractable epilepsy.

An exoskeleton reveals that walking humans adapt to changes in step length and height by maximizing locomotor stability.

No abstract

Humans respond to mechanical perturbations that affect their gait by changing their motor control strategy. previous work indicates that adaptation during gait is context dependent, and perturbations altering long-term stability are compensated for even at the cost of higher energy expenditure. However, it is unclear if gait adaptation is driven by unilateral or bilateral mechanisms, and what the roles of feedback and feedforward control are in the generation of compensatory responses. Here, we used a robot-based adaptation paradigm to investigate if feedback/feedforward and unilateral/ bilateral contributions to locomotor adaptation are also context dependent in healthy adults. A robot was used to induce two opposite unilateral mechanical perturbations affecting the step length over multiple gait cycles. electromyographic signals were collected and analyzed to determine how muscle synergies change in response to perturbations. The results unraveled different unilateral modulation dynamics of the muscle-synergy activations during adaptation, characterized by the combination of a slow-progressive feedforward process and a fast-reactive feedback-driven process. the relative unilateral contributions of the two processes to motor-output adjustments, however, depended on which perturbation was delivered. overall, these observations provide evidence that, in humans, both descending and afferent drives project onto the same spinal interneuronal networks that encode locomotor muscle synergies. Humans have the ability to modify their motor plan in response to changes in the walking environment, a phenomenon referred to as locomotor adaptation 1. The study of locomotor adaption has been pursued to improve our understanding of the organization of human locomotor circuits, given the inapplicability, in humans, of the invasive techniques employed in animal models. As a case in point, studies in the lamprey, frog, turtle and cat have consistently shown that locomotor control is accomplished by rhythmic activations of lower-level spinal circuits that regulate the activities of fixed neuromuscular modules 2-6. It has been debated if such modules exist in humans 7 , and if they encode the relative levels of activation across muscles 8 , the temporal relations among the activations of muscle groups 9 , or involve more complex structures 10,11. A study on adaptation during forward/backward walking on a split-belt treadmill has provided evidence that human locomotion is controlled by leg-specific and forward/backward-specific independent networks 12. These observations are compatible with a two-level organization of spinal central pattern generator (CPG) circuits where the higher level regulates the

No abstract

No abstract