Transient brain activity dynamics discriminate levels of consciousness during anesthesia.

The awake mammalian brain is functionally organized in terms of large-scale distributed networks that are constantly interacting. Loss of consciousness might disrupt this temporal organization leaving patients unresponsive. We hypothesize that characterizing brain activity in terms of transient events may provide a signature of consciousness. For this, we analyze temporal dynamics of spatiotemporally overlapping functional networks obtained from fMRI transient activity across different anesthetics and levels of anesthesia. We first show a striking homology in spatial organization of networks between monkeys and humans, indicating cross-species similarities in resting-state fMRI structure. We then track how network organization shifts under different anesthesia conditions in macaque monkeys. While the spatial aspect of the networks is preserved, their temporal dynamics are highly affected by anesthesia. Networks express for longer durations and co-activate in an anesthetic-specific configuration. Additionally, hierarchical brain organization is disrupted with a consciousness-level-signature role of the default mode network. In conclusion, large-scale brain network temporal dynamics capture differences in anesthetic-specific consciousness-level, paving the way towards a clinical translation of these cortical signature.

Supraspinal control of motoneurons after paralysis enabled by spinal cord stimulation.

Spinal cord stimulation (SCS) restores motor control after spinal cord injury (SCI) and stroke. This evidence led to the hypothesis that SCS facilitates residual supraspinal inputs to spinal motoneurons. Instead, here we show that SCS does not facilitate residual supraspinal inputs but directly triggers motoneurons action potentials. However, supraspinal inputs can shape SCS-mediated activity, mimicking volitional control of motoneuron firing. Specifically, by combining simulations, intraspinal electrophysiology in monkeys and single motor unit recordings in humans with motor paralysis, we found that residual supraspinal inputs transform subthreshold SCS-induced excitatory postsynaptic potentials into suprathreshold events. We then demonstrated that only a restricted set of stimulation parameters enables volitional control of motoneuron firing and that lesion severity further restricts the set of effective parameters. Our results explain the facilitation of voluntary motor control during SCS while predicting the limitations of this neurotechnology in cases of severe loss of supraspinal axons.

Epidural stimulation of the cervical spinal cord for post-stroke upper-limb paresis.

Cerebral strokes can disrupt descending commands from motor cortical areas to the spinal cord, which can result in permanent motor deficits of the arm and hand. However, below the lesion, the spinal circuits that control movement remain intact and could be targeted by neurotechnologies to restore movement. Here we report results from two participants in a first-in-human study using electrical stimulation of cervical spinal circuits to facilitate arm and hand motor control in chronic post-stroke hemiparesis ( NCT04512690 ). Participants were implanted for 29 d with two linear leads in the dorsolateral epidural space targeting spinal roots C3 to T1 to increase excitation of arm and hand motoneurons. We found that continuous stimulation through selected contacts improved strength (for example, grip force +40% SCS01; +108% SCS02), kinematics (for example, +30% to +40% speed) and functional movements, thereby enabling participants to perform movements that they could not perform without spinal cord stimulation. Both participants retained some of these improvements even without stimulation and no serious adverse events were reported. While we cannot conclusively evaluate safety and efficacy from two participants, our data provide promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke.

SUPRASPINAL CONTROL OF MOTONEURONS AFTER PARALYSIS ENABLED BY SPINAL CORD STIMULATION.

Spinal cord stimulation (SCS) restores motor control after spinal cord injury (SCI) and stroke. This evidence led to the hypothesis that SCS facilitates residual supraspinal inputs to spinal motoneurons. Instead, here we show that SCS does not facilitate residual supraspinal inputs but directly triggers motoneurons action potentials. However, supraspinal inputs can shape SCS-mediated activity, mimicking volitional control of motoneuron firing. Specifically, by combining simulations, intraspinal electrophysiology in monkeys and single motor unit recordings in humans with motor paralysis, we found that residual supraspinal inputs transform subthreshold SCS-induced excitatory postsynaptic potentials into suprathreshold events. We then demonstrated that only a restricted set of stimulation parameters enables volitional control of motoneuron firing and that lesion severity further restricts the set of effective parameters. Our results explain the facilitation of voluntary motor control during SCS while predicting the limitations of this neurotechnology in cases of severe loss of supraspinal axons.

Real-time brain-machine interface in non-human primates achieves high-velocity prosthetic finger movements using a shallow feedforward neural network decoder.

Despite the rapid progress and interest in brain-machine interfaces that restore motor function, the performance of prosthetic fingers and limbs has yet to mimic native function. The algorithm that converts brain signals to a control signal for the prosthetic device is one of the limitations in achieving rapid and realistic finger movements. To achieve more realistic finger movements, we developed a shallow feed-forward neural network to decode real-time two-degree-of-freedom finger movements in two adult male rhesus macaques. Using a two-step training method, a recalibrated feedback intention-trained (ReFIT) neural network is introduced to further improve performance. In 7 days of testing across two animals, neural network decoders, with higher-velocity and more natural appearing finger movements, achieved a 36% increase in throughput over the ReFIT Kalman filter, which represents the current standard. The neural network decoders introduced herein demonstrate real-time decoding of continuous movements at a level superior to the current state-of-the-art and could provide a starting point to using neural networks for the development of more naturalistic brain-controlled prostheses.

Locally Affine Diffeomorphic Surface Registration and Its Application to Surgical Planning of Fronto-Orbital Advancement.

Metopic craniosynostosis is a condition caused by the premature fusion of the metopic cranial suture. If untreated, it can result into brain growth restriction, increased intra-cranial pressure, visual impairment, and cognitive delay. Fronto-orbital advancement is the widely accepted surgical approach to correct cranial shape abnormalities in patients with metopic craniosynostosis, but the outcome of the surgery remains very dependent on the expertise of the surgeon because of the lack of objective and personalized cranial shape metrics to target during the intervention. We propose in this paper a locally affine diffeomorphic surface registration framework to create an optimal interventional plan personalized to each patient. Our method calculates the optimal surgical plan by minimizing cranial shape abnormalities, which are quantified using objective metrics based on a normative model of cranial shapes built from 198 healthy cases. It is guided by clinical osteotomy templates for fronto-orbital advancement, and it automatically calculates how much and in which direction each bone piece needs to be translated, rotated, and/or bent. Our locally affine framework models separately the transformation of each bone piece while ensuring the consistency of the global transformation. We used our method to calculate the optimal surgical plan for 23 patients, obtaining a significant reduction of malformations (p < 0.001) between 40.38% and 50.85% in the simulated outcome of the surgery using different osteotomy templates. In addition, malformation values were within healthy ranges (p > 0.01).

Cranial ultrasound-based prediction of post hemorrhagic hydrocephalus outcome in premature neonates with intraventricular hemorrhage.

Premature neonates with intraventricular hemorrhage (IVH) followed by post hemorrhagic hydrocephalus (PHH) are at high risk for brain injury. Cranial ultrasound (CUS) is used for monitoring of premature neonates during the first weeks after birth to identify IVH and follow the progression to PHH. However, the lack of a standardized method for CUS evaluation has led to significant variability in decision making regarding treatment. We propose a quantitative imaging tool for the evaluation of PHH on CUS for premature neonates based on morphological features of the cerebral ventricles. We retrospectively studied 64 extremely premature neonates born less than 29 weeks gestational age, less than 1,500 grams weight at birth, admitted to our center within two weeks of life, and diagnosed with different grades of IVH. We extracted morphological features of the lateral ventricles from CUS imaging using image analysis techniques to compare neonates who needed a temporizing intervention to treat PHH to the ones who did not. From the original set of features, an optimal ranking was obtained based on linear support vector machine. A subset of features was subsequently selected that maximizes the overall accuracy level. Regarding whether or not there was a need for temporizing intervention, we predicted the outcome of PHH with an improved accuracy level of 84%, compared to the 76% rate obtained by linear manual measurement. The proposed imaging tool allowed us to establish a quantitative method for PHH evaluation on CUS in extremely premature neonates with IVH. Further studies will help standardize the evaluation of CUS in those neonates to institute treatments earlier and improve outcomes.

Intracranial Volume Quantification from 3D Photography.

3D photography offers non-invasive, radiation-free, and anesthetic-free evaluation of craniofacial morphology. However, intracranial volume (ICV) quantification is not possible with current non-invasive imaging systems in order to evaluate brain development in children with cranial pathology. The aim of this study is to develop an automated, radiation-free framework to estimate ICV. Pairs of computed tomography (CT) images and 3D photographs were aligned using registration. We used the real ICV calculated from the CTs and the head volumes from their corresponding 3D photographs to create a regression model. Then, a template 3D photograph was selected as a reference from the data, and a set of landmarks defining the cranial vault were detected automatically on that template. Given the 3D photograph of a new patient, it was registered to the template to estimate the cranial vault area. After obtaining the head volume, the regression model was then used to estimate the ICV. Experiments showed that our volume regression model predicted ICV from head volumes with an average error of 5.81 ± 3.07% and a correlation (R2) of 0.96. We also demonstrated that our automated framework quantified ICV from 3D photography with an average error of 7.02 ± 7.76%, a correlation (R2) of 0.94, and an average estimation error for the position of the cranial base landmarks of 11.39 ± 4.3mm.

Locally affine diffeomorphic surface registration for planning of metopic craniosynostosis surgery.

The outcome of cranial vault reconstruction for the surgical treatment of craniosynostosis heavily depends on the surgeon's expertise because of the lack of an objective target shape. We introduce a surface-based diffeomorphic registration framework to create the optimal post-surgical cranial shape during craniosynostosis treatment. Our framework estimates and labels where each bone piece needs to be cut using a reference template. Then, it calculates how much each bone piece needs to be translated and in which direction, using the closest normal shape from a multi-atlas as a reference. With our locally affine approach, the method also allows for bone bending, modeling independently the transformation of each bone piece while ensuring the consistency of the global transformation. We evaluated the optimal plan for 15 patients with metopic craniosynostosis. Our results showed that the automated surgical planning creates cranial shapes with a reduction in cranial malformations of 51.43% and curvature discrepancies of 35.09%, which are the two indices proposed in the literature to quantify cranial deformities objectively. In addition, the cranial shapes created were within healthy ranges.