Interpretable surface-based detection of focal cortical dysplasias: a Multi-centre Epilepsy Lesion Detection study.

One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted 'gold-standard' subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy.

Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia: A MELD study.

OBJECTIVE: Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome. METHODS: The MELD (Multi-centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging-based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom. RESULTS: FCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%. SIGNIFICANCE: FCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data-driven atlases and predictive models are essential for evidence-based, precision medicine and risk counseling in epilepsy.

Association of Outcomes with Model-Based Indices of Cerebral Autoregulation After Pediatric Traumatic Brain Injury.

BACKGROUND: We investigated whether model-based indices of cerebral autoregulation (CA) are associated with outcomes after pediatric traumatic brain injury. METHODS: This was a retrospective analysis of a prospective clinical database of 56 pediatric patients with traumatic brain injury undergoing intracranial pressure monitoring. CA indices were calculated, including pressure reactivity index (PRx), wavelet pressure reactivity index (wPRx), pulse amplitude index (PAx), and correlation coefficient between intracranial pressure pulse amplitude and cerebral perfusion pressure (RAC). Each CA index was used to compute optimal cerebral perfusion pressure (CPP). Time of CPP below lower limit of autoregulation (LLA) or above upper limit of autoregulation (ULA) were computed for each index. Demographic, physiologic, and neuroimaging data were collected. Primary outcome was determined using Pediatric Glasgow Outcome Scale Extended (GOSE-Peds) at 12 months, with higher scores being suggestive of unfavorable outcome. Univariate and multiple linear regression with guided stepwise variable selection was used to find combinations of risk factors that can best explain the variability of GOSE-Peds scores, and the best fit model was applied to the age strata. We hypothesized that higher GOSE-Peds scores were associated with higher CA values and more time below LLA or above ULA for each index. RESULTS: At the univariate level, CPP, dose of intracranial hypertension, PRx, PAx, wPRx, RAC, percent time more than ULA derived for PAx, and percent time less than LLA derived for PRx, PAx, wPRx, and RAC were all associated with GOSE-Peds scores. The best subset model selection on all pediatric patients identified that when accounting for CPP, increased dose of intracranial hypertension and percent time less than LLA derived for wPRx were independently associated with higher GOSE-Peds scores. Age stratification of the best fit model identified that in children less than 2 years of age or 8 years of age or more, percent time less than LLA derived for wPRx represented the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and dose of intracranial hypertension. For children 2 years or younger to less than 8 years of age, dose of intracranial hypertension was identified as the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and percent time less than LLA derived for wPRx. CONCLUSIONS: Increased dose of intracranial hypertension, PRx, wPRx, PAx, and RAC values and increased percentage time less than LLA based on PRx, wPRx, PAx, and RAC are associated with higher GOSE-Peds scores, suggestive of unfavorable outcome. Reducing intracranial hypertension and maintaining CPP more than LLA based on wPRx may improve outcomes and warrants prospective investigation.

Multimodal Assessment of Cerebral Autoregulation and Autonomic Function After Pediatric Cerebral Arteriovenous Malformation Rupture.

BACKGROUND: Management after cerebral arteriovenous malformation (AVM) rupture aims toward preventing hemorrhagic expansion while maintaining cerebral perfusion to avoid secondary injury. We investigated associations of model-based indices of cerebral autoregulation (CA) and autonomic function (AF) with outcomes after pediatric cerebral AVM rupture. METHODS: Multimodal neurologic monitoring data from the initial 3 days after cerebral AVM rupture were retrospectively analyzed in children (< 18 years). AF indices included standard deviation of heart rate (HRsd), root-mean-square of successive differences in heart rate (HRrmssd), low-high frequency ratio (LHF), and baroreflex sensitivity (BRS). CA indices include pressure reactivity index (PRx), wavelet pressure reactivity indices (wPRx and wPRx-thr), pulse amplitude index (PAx), and correlation coefficient between intracranial pressure pulse amplitude and cerebral perfusion pressure (RAC). Percent time of cerebral perfusion pressure (CPP) below lower limits of autoregulation (LLA) was also computed for each CA index. Primary outcomes were determined using Pediatric Glasgow Outcome Score Extended-Pediatrics (GOSE-PEDs) at 12 months and acquired epilepsy. Association of biomarkers with outcomes was investigated using linear regression, Wilcoxon signed-rank, or Chi-square. RESULTS: Fourteen children were analyzed. Lower AF indices were associated with poor outcomes (BRS [p = 0.04], HRsd [p = 0.04], and HRrmssd [p = 0.00]; and acquired epilepsy (LHF [p = 0.027]). Higher CA indices were associated with poor outcomes (PRx [p = 0.00], wPRx [p = 0.00], and wPRx-thr [p = 0.01]), and acquired epilepsy (PRx [p = 0.02] and wPRx [p = 0.00]). Increased time below LLA was associated with poor outcome (percent time below LLA based on PRx [p = 0.00], PAx [p = 0.04], wPRx-thr [p = 0.03], and RAC [p = 0.01]; and acquired epilepsy (PRx [p = 0.00], PAx [p = 0.00], wPRx-thr [p = 0.03], and RAC [p = 0.01]). CONCLUSIONS: After pediatric cerebral AVM rupture, poor outcomes are associated with AF and CA when applying various neurophysiologic model-based indices. Prospective work is needed to assess these indices of CA and AF in clinical decision support.

Intracranial Electroencephalography in Pediatric Severe Traumatic Brain Injury.

OBJECTIVES: Electroencephalography is used in neurocritical care for detection of seizures and assessment of cortical function. Due to limited resolution from scalp electroencephalography, important abnormalities may not be readily detectable. We aimed to identify whether intracranial electroencephalography allows for improved methods of monitoring cortical function in children with severe traumatic brain injury. DESIGN: This is a retrospective cohort study from a prospectively collected clinical database. We investigated the occurrence rate of epileptiform abnormalities detected on intracranial electroencephalography when compared with scalp electroencephalography. We also investigated the strength of association of quantitative electroencephalographic parameters and cerebral perfusion pressure between both intracranial and scalp electroencephalography. SETTING: This is a single-institution study performed in the Phoenix Children's Hospital PICU. PATIENTS: Eleven children with severe traumatic brain injury requiring invasive neuromonitoring underwent implantation of a six-contact intracranial electrode as well as continuous surface electroencephalography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Visual detection of epileptiform abnormalities was performed by pediatric epileptologists. Association of intracranial and scalp electroencephalography total power, alpha percentage, and alpha-delta power ratio to cerebral perfusion pressure was performed using univariate dynamic structural equations modeling. Demographic data were assessed by retrospective analysis. Intracranial and scalp electroencephalography was performed in 11 children. Three of 11 children had observed epileptiform abnormalities on intracranial electroencephalography. Two patients had epileptiform abnormalities identified exclusively on intracranial electroencephalography, and one patient had seizures initiating on intracranial electroencephalography before arising on scalp electroencephalography. Identification of epileptiform abnormalities was associated with subsequent identification of stroke or malignant cerebral edema. We observed statistically significant positive associations between intracranial alpha-delta power ratio to cerebral perfusion pressure in nine of 11 patients with increased strength of association on intracranial compared with scalp recordings. CONCLUSIONS: These findings suggest that intracranial electroencephalography may be useful for detection of secondary insult development in children with traumatic brain injury.

Subcentimeter epilepsy surgery targets by resting state functional magnetic resonance imaging can improve outcomes in hypothalamic hamartoma.

OBJECTIVE: The purpose of this study is to investigate the outcomes of epilepsy surgery targeting the subcentimeter-sized resting state functional magnetic resonance imaging (rs-fMRI) epileptogenic onset zone (EZ) in hypothalamic hamartoma (HH). METHODS: Fifty-one children with HH-related intractable epilepsy received anatomical MRI-guided stereotactic laser ablation (SLA) procedures. Fifteen of these children were control subjects (CS) not guided by rs-fMRI. Thirty-six had been preoperatively guided by rs-fMRI (RS) to determine EZs, which were subsequently targeted by SLA. The primary outcome measure for the study was a predetermined goal of 30% reduction in seizure frequency and improvement in class I Engel outcomes 1 year postoperatively. Quantitative and qualitative volumetric analyses of total HH and ablated tissue were also assessed. RESULTS: In the RS group, the EZ target within the HH was ablated with high accuracy (>87.5% of target ablated in 83% of subjects). There was no difference between the groups in percentage of ablated hamartoma volume (P = 0.137). Overall seizure reduction was higher in the rs-fMRI group: 85% RS versus 49% CS (P = 0.0006, adjusted). The Engel Epilepsy Surgery Outcome Scale demonstrated significant differences in those with freedom from disabling seizures (class I), 92% RS versus 47% CS, a 45% improvement (P = 0.001). Compared to prior studies, there was improvement in class I outcomes (92% vs 76%-81%). No postoperative morbidity or mortality occurred. SIGNIFICANCE: For the first time, surgical SLA targeting of subcentimeter-sized EZs, located by rs-fMRI, guided surgery for intractable epilepsy. Our outcomes demonstrated the highest seizure freedom rate without surgical complications and are a significant improvement over prior reports. The approach improved freedom from seizures by 45% compared to conventional ablation, regardless of hamartoma size or anatomical classification. This technique showed the same or reduced morbidity (0%) compared to recent non-rs-fMRI-guided SLA studies with as high as 20% permanent significant morbidity.

Altered modulation of sensorimotor rhythms with chronic paralysis.

After paralysis, the disconnection between the cortex and its peripheral targets leads to neuroplasticity throughout the nervous system. However, it is unclear how chronic paralysis specifically impacts cortical oscillations associated with attempted movement of impaired limbs. We hypothesized that µ- (8-13 Hz) and ß- (15-30 Hz) event-related desynchronization (ERD) would be less modulated for individuals with hand paralysis due to cervical spinal cord injury (SCI). To test this, we compared the modulation of ERD from magnetoencephalography (MEG) during attempted and imagined grasping performed by participants with cervical SCI (n = 12) and able-bodied controls (n = 13). Seven participants with tetraplegia were able to generate some electromyography (EMG) activity during attempted grasping, whereas the other five were not. The peak and area of ERD were significantly decreased for individuals without volitional muscle activity when they attempted to grasp compared with able-bodied subjects and participants with SCI,with some residual EMG activity. However, no significant differences were found between subject groups during mentally simulated tasks (i.e., motor imagery) where no muscle activity or somatosensory consequences were expected. These findings suggest that individuals who are unable to produce muscle activity are capable of generating ERD when attempting to move, but the characteristics of this ERD are altered. However, for people who maintain volitional muscle activity after SCI, there are no significant differences in ERD characteristics compared with able-bodied controls. These results provide evidence that ERD is dependent on the level of intact muscle activity after SCI.NEW & NOTEWORTHY Source space MEG was used to investigate sensorimotor cortical oscillations in individuals with SCI. This study provides evidence that individuals with cervical SCI exhibit decreased ERD when they attempt to grasp if they are incapable of generating muscle activity. However, there were no significant differences in ERD between paralyzed and able-bodied participants during motor imagery. These results have important implications for the design and evaluation of new therapies, such as motor imagery and neurofeedback interventions.

MEG-based neurofeedback for hand rehabilitation.

BACKGROUND: Providing neurofeedback (NF) of motor-related brain activity in a biologically-relevant and intuitive way could maximize the utility of a brain-computer interface (BCI) for promoting therapeutic plasticity. We present a BCI capable of providing intuitive and direct control of a video-based grasp. METHODS: Utilizing magnetoencephalography's (MEG) high temporal and spatial resolution, we recorded sensorimotor rhythms (SMR) that were modulated by grasp or rest intentions. SMR modulation controlled the grasp aperture of a stop motion video of a human hand. The displayed hand grasp position was driven incrementally towards a closed or opened state and subjects were required to hold the targeted position for a time that was adjusted to change the task difficulty. RESULTS: We demonstrated that three individuals with complete hand paralysis due to spinal cord injury (SCI) were able to maintain brain-control of closing and opening a virtual hand with an average of 63 % success which was significantly above the average chance rate of 19 %. This level of performance was achieved without pre-training and less than 4 min of calibration. In addition, successful grasp targets were reached in 1.96 ± 0.15 s. Subjects performed 200 brain-controlled trials in approximately 30 min excluding breaks. Two of the three participants showed a significant improvement in SMR indicating that they had learned to change their brain activity within a single session of NF. CONCLUSIONS: This study demonstrated the utility of a MEG-based BCI system to provide realistic, efficient, and focused NF to individuals with paralysis with the goal of using NF to induce neuroplasticity.

A roadmap for implanting microelectrode arrays to evoke tactile sensations through intracortical microstimulation.

Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays. In five participants with cervical spinal cord injury, across two study locations, this procedure successfully enabled ICMS-evoked sensations localized to at least the first four digits of the hand. The imaging and planning procedures developed through this clinical trial provide a roadmap for other brain-computer interface studies to ensure successful placement of stimulation electrodes.

Speaking and cognitive distractions during EEG-based brain control of a virtual neuroprosthesis-arm.

BACKGROUND: Brain-computer interface (BCI) systems have been developed to provide paralyzed individuals the ability to command the movements of an assistive device using only their brain activity. BCI systems are typically tested in a controlled laboratory environment were the user is focused solely on the brain-control task. However, for practical use in everyday life people must be able to use their brain-controlled device while mentally engaged with the cognitive responsibilities of daily activities and while compensating for any inherent dynamics of the device itself. BCIs that use electroencephalography (EEG) for movement control are often assumed to require significant mental effort, thus preventing users from thinking about anything else while using their BCI. This study tested the impact of cognitive load as well as speaking on the ability to use an EEG-based BCI. FINDINGS: Six participants controlled the two-dimensional (2D) movements of a simulated neuroprosthesis-arm under three different levels of cognitive distraction. The two higher cognitive load conditions also required simultaneously speaking during BCI use. On average, movement performance declined during higher levels of cognitive distraction, but only by a limited amount. Movement completion time increased by 7.2%, the percentage of targets successfully acquired declined by 11%, and path efficiency declined by 8.6%. Only the decline in percentage of targets acquired and path efficiency were statistically significant (p < 0.05). CONCLUSION: People who have relatively good movement control of an EEG-based BCI may be able to speak and perform other cognitively engaging activities with only a minor drop in BCI-control performance.

Neuroprosthetic technology for individuals with spinal cord injury.

CONTEXT: Spinal cord injury (SCI) results in a loss of function and sensation below the level of the lesion. Neuroprosthetic technology has been developed to help restore motor and autonomic functions as well as to provide sensory feedback. FINDINGS: This paper provides an overview of neuroprosthetic technology that aims to address the priorities for functional restoration as defined by individuals with SCI. We describe neuroprostheses that are in various stages of preclinical development, clinical testing, and commercialization including functional electrical stimulators, epidural and intraspinal microstimulation, bladder neuroprosthesis, and cortical stimulation for restoring sensation. We also discuss neural recording technologies that may provide command or feedback signals for neuroprosthetic devices. CONCLUSION/CLINICAL RELEVANCE: Neuroprostheses have begun to address the priorities of individuals with SCI, although there remains room for improvement. In addition to continued technological improvements, closing the loop between the technology and the user may help provide intuitive device control with high levels of performance.

Quantitative Electroencephalography After Pediatric Anterior Circulation Stroke.

OBJECTIVE: Regional differences were investigated in quantitative EEG (QEEG) characteristics and associations of QEEG to hemodynamics after pediatric acute stroke. METHODS: Quantitative EEG was analyzed, including power in delta, theta, alpha, and beta bands, alpha-delta power ratio, total power, and spectral edge frequency from 11 children with unilateral, anterior circulation strokes during the first 24 hours of continuous EEG recording. Differences between injured and uninjured hemispheres were assessed using multivariate dynamic structural equations modeling. Dynamic structural equations modeling was applied to six children with hemorrhagic stroke undergoing arterial blood pressure, heart rate, and cerebral oximetry monitoring to investigate associations between hemodynamics with QEEG adjacent to anterior circulation regions. RESULTS: All patients with acute ischemic stroke ( n = 5) had lower alpha and beta power and spectral edge frequency on injured compared with uninjured regions. This was not consistent after hemorrhagic stroke ( n = 6). All hemorrhagic stroke patients demonstrated negative association of total power with arterial blood pressure within injured regions. No consistency was observed for direction or strength of association in other QEEG measures to arterial blood pressure nor were such consistent relationships observed for any QEEG measure studied in relation to heart rate or cerebral oximetry. CONCLUSIONS: After pediatric anterior circulation acute ischemic stroke, reduced spectral edge frequency and alpha and beta power can be observed on injured as compared with noninjured regions. After pediatric anterior circulation hemorrhagic stroke, total power can be negatively associated with arterial blood pressure within injured regions. Larger studies are needed to understand conditions in which QEEG patterns manifest and relate to hemodynamics and brain penumbra.

Case Study: Mapping Evoked Fields in Primary Motor and Sensory Areas via Magnetoencephalography in Tetraplegia.

Devices interfacing with the brain through implantation in cortical or subcortical structures have great potential for restoration and rehabilitation in patients with sensory or motor dysfunction. Typical implantation surgeries are planned based on maps of brain activity generated from intact function. However, mapping brain activity for planning implantation surgeries is challenging in the target population due to abnormal residual function and, increasingly often, existing MRI-incompatible implanted hardware. Here, we present methods and results for mapping impaired somatosensory and motor function in an individual with paralysis and an existing brain-computer interface (BCI) device. Magnetoencephalography (MEG) was used to directly map the neural activity evoked during transcutaneous electrical stimulation and attempted movement of the impaired hand. Evoked fields were found to align with the expected anatomy and somatotopic organization. This approach may be valuable for guiding implants in other applications, such as cortical stimulation for pain and to improve implant targeting to help reduce the craniotomy size.

Treatment Timing, EEG, Neuroimaging, and Outcomes After Acute Necrotizing Encephalopathy in Children.

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a rare condition associated with rapid progression to coma and high incidence of morbidity and mortality. METHODS: Clinical, electroencephalographic (EEG), and brain magnetic resonance imaging (MRI) characteristics and immunomodulatory therapy timing were retrospectively analyzed in children with ANE. ANE severity scores (ANE-SS) and MRI scores were also assessed. The associations of patient characteristics with 6-month modified Rankin scale (mRS) and length of hospitalization were determined using either univariate linear regression or one-way analysis of variance. RESULTS: 7 children were retrospectively evaluated. Normal EEG sleep spindles (P = .024) and early treatment (R2 = .57, P = .030) were associated with improved outcomes (ie, decreased mRS). Higher ANE-SS (R2 = .79, P = .011), higher age (R2 = .62, P = .038), and presence of brainstem lesions (P = .015) were associated with longer length of hospitalization. Other patient characteristics were not significantly associated with mRS or length of hospitalization. CONCLUSION: Early immunomodulatory therapy and normal sleep spindles are associated with better functional outcome in children with ANE.

Transdermal Electrical Neuromodulation for Anxiety and Sleep Problems in High-Functioning Autism Spectrum Disorder: Feasibility and Preliminary Findings.

BACKGROUND: Autism spectrum disorder (ASD) is associated with anxiety and sleep problems. We investigated transdermal electrical neuromodulation (TEN) of the cervical nerves in the neck as a safe, effective, comfortable and non-pharmacological therapy for decreasing anxiety and enhancing sleep quality in ASD. METHODS: In this blinded, sham-controlled study, seven adolescents and young adults with high-functioning ASD underwent five consecutive treatment days, one day of the sham followed by four days of subthreshold TEN for 20 min. Anxiety-provoking cognitive tasks were performed after the sham/TEN. Measures of autonomic nervous system activity, including saliva α-amylase and cortisol, electrodermal activity, and heart rate variability, were collected from six participants. RESULTS: Self-rated and caretaker-rated measures of anxiety were significantly improved with TEN treatment as compared to the sham, with effect sizes ranging from medium to large depending on the rating scale. Sleep scores from caretaker questionnaires also improved, but not significantly. Performance on two of the three anxiety-provoking cognitive tasks and heart rate variability significantly improved with TEN stimulation as compared to the sham. Four of the seven (57%) participants were responders, defined as a ≥ 30% improvement in self-reported anxiety. Salivary α-amylase decreased with more TEN sessions and decreased from the beginning to the end of the session on TEN days for responders. TEN was well-tolerated without significant adverse events. CONCLUSIONS: This study provides preliminary evidence that TEN is well-tolerated in individuals with ASD and can improve anxiety.

Effects of MEG-based neurofeedback for hand rehabilitation after tetraplegia: preliminary findings in cortical modulations and grip strength.

OBJECTIVE: Neurofeedback (NF) trains people to volitionally modulate their cortical activity to affect a behavioral outcome. We evaluated the feasibility of using NF to improve hand function after chronic cervical-level spinal cord injury (SCI) using biologically-relevant visual feedback of motor-related brain activity and an intuitive control scheme. APPROACH: The NF system acquired magnetoencephalography (MEG) data in real-time to provide feedback of event-related desynchronization (ERD) measured over the sensorimotor cortex during attempted hand grasping. During brain control, stronger ERD resulting from attempted grasping drove the virtual hand towards a more closed grasp, while less ERD drove the hand more open. MAIN RESULTS: Eight individuals with partial or complete hand impairment due to chronic SCI controlled the NF to perform a grasping task that increased in difficulty as the participants achieved success. During their first NF session, participants achieved an average success rate of 63.7 ± 6.4% (chance level of 13.9%). After as few as one intervention session, four of the seven individuals evaluated for ERD changes had significantly strengthened ERD and three of the four participants with measurable grip strength prior to NF had increased grip strength. Interestingly, both individuals who participated in a longer-term study (i.e. >8 NF sessions) had improved grip strength and significantly strengthened ERD. SIGNIFICANCE: This study demonstrates that MEG-based NF training can change brain activity in individuals with hand impairment due to SCI and has the potential to induce acute changes in grip strength. Future studies will evaluate whether neuroplasticity induced with long term NF can improve hand function for those with moderate impairment.

Shift in electrocorticography electrode locations after surgical implantation in children.

Interpreting electrocorticography (ECoG) in the context of neuroimaging requires that multimodal information be integrated accurately. However, the implantation of ECoG electrodes can shift the brain impacting the spatial interpretation of electrode locations in the context of pre-implant imaging. We characterized the amount of shift in ECoG electrode locations immediately after implant in a pediatric population. Electrode-shift was quantified as the difference in the electrode locations immediately after surgery (via post-operation CT) compared to the brain surface before the operation (pre-implant T1 MRI). A total of 1140 ECoG contracts were assessed across 18 patients ranging from 3 to 19 (12.1 ± 4.8) years of age who underwent intracranial monitoring in preparation for epilepsy resection surgery. Patients had an average of 63 channels assessed with an average of 5.64 ± 3.27 mm shift from the pre-implant brain surface within 24 h of implant. This shift significantly increased with estimated intracranial volume, but not age. Shift also varied significantly depending of the lobe the contact was over; where contacts on the temporal and frontal lobe had less shift than the parietal. Furthermore, contacts on strips had significantly less shift than those on grids. The shift in the brain surface due to ECoG implantation could lead to a misinterpretation of contact location particularly in patients with larger intracranial volume and for grid contacts over the parietal lobes.

Resting-state functional MRI connectivity impact on epilepsy surgery plan and surgical candidacy: prospective clinical work.

OBJECTIVE: The authors' goal was to prospectively quantify the impact of resting-state functional MRI (rs-fMRI) on pediatric epilepsy surgery planning. METHODS: Fifty-one consecutive patients (3 months to 20 years old) with intractable epilepsy underwent rs-fMRI for presurgical evaluation. The team reviewed the following available diagnostic data: video-electroencephalography (n = 51), structural MRI (n = 51), FDG-PET (n = 42), magnetoencephalography (n = 5), and neuropsychological testing (n = 51) results to formulate an initial surgery plan blinded to the rs-fMRI findings. Subsequent to this discussion, the connectivity results were revealed and final recommendations were established. Changes between pre- and post-rs-fMRI treatment plans were determined, and changes in surgery recommendation were compared using McNemar's test. RESULTS: Resting-state fMRI was successfully performed in 50 (98%) of 51 cases and changed the seizure onset zone localization in 44 (88%) of 50 patients. The connectivity results prompted 6 additional studies, eliminated the ordering of 11 further diagnostic studies, and changed the intracranial monitoring plan in 10 cases. The connectivity results significantly altered surgery planning with the addition of 13 surgeries, but it did not eliminate planned surgeries (p = 0.003). Among the 38 epilepsy surgeries performed, the final surgical approach changed due to rs-fMRI findings in 22 cases (58%), including 8 (28%) of 29 in which extraoperative direct electrical stimulation mapping was averted. CONCLUSIONS: This study demonstrates the impact of rs-fMRI connectivity results on the decision-making for pediatric epilepsy surgery by providing new information about the location of eloquent cortex and the seizure onset zone. Additionally, connectivity results may increase the proportion of patients considered eligible for surgery while optimizing the need for further testing.

Approaches to Multimodality Monitoring in Pediatric Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children. Improved methods of monitoring real-time cerebral physiology are needed to better understand when secondary brain injury develops and what treatment strategies may alleviate or prevent such injury. In this review, we discuss emerging technologies that exist to better understand intracranial pressure (ICP), cerebral blood flow, metabolism, oxygenation and electrical activity. We also discuss approaches to integrating these data as part of a multimodality monitoring strategy to improve patient care.

Clinical trials for pediatric traumatic brain injury: definition of insanity?

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children both in the United States and throughout the world. Despite valiant efforts and multiple clinical trials completed over the last few decades, there are no high-level recommendations for pediatric TBI available in current guidelines. In this review, the authors explore key findings from the major pediatric clinical trials in children with TBI that have shaped present-day recommendations and the insights gained from them. The authors also offer a perspective on potential efforts to improve the efficacy of future clinical trials in children following TBI.