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A wireless brain–spine interface is presented that enables macaques with a spinal cord injury to regain locomotor movements of a paralysed leg. Locomotion restored after spinal cord injury in a primate Grégoire Courtine and colleagues show that a fully implantable, wireless brain–spine interface can be used to improve locomotion after a unilateral spinal lesion in monkeys without training. The authors implanted monkeys with an electrode array in the leg area of the motor cortex and a stimulator in the lumbar spinal cord, enabling real-time decoding and stimulation. Decoded activity from the motor cortex was used to stimulate 'hotspot' locations in the lumbar spinal cord that control hindlimb flexion and extension during locomotion. Stimulating these hotspots enhanced flexion and extension of the target muscles during locomotion in intact monkeys and restored weight-bearing locomotion of the paralysed leg in monkeys with a unilateral spinal cord lesion six days after the injury. This proof-of-principle study shows that a similar system may improve or restore locomotion in people with spinal cord injury. Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces 1 , 2 , 3 have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis 1 , 4 . Theoretically, this strategy could also restore control over leg muscle activity for walking 5 . However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges 6 , 7 . Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion 8 , 9 , 10 . Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain–spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys ( Macaca mulatta ) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain–spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain–spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain–spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.

People with late-stage Parkinson’s disease (PD) often suffer from debilitating locomotor deficits that are resistant to currently available therapies. To alleviate these deficits, we developed a neuroprosthesis operating in closed loop that targets the dorsal root entry zones innervating lumbosacral segments to reproduce the natural spatiotemporal activation of the lumbosacral spinal cord during walking. We first developed this neuroprosthesis in a non-human primate model that replicates locomotor deficits due to PD. This neuroprosthesis not only alleviated locomotor deficits but also restored skilled walking in this model. We then implanted the neuroprosthesis in a 62-year-old male with a 30-year history of PD who presented with severe gait impairments and frequent falls that were medically refractory to currently available therapies. We found that the neuroprosthesis interacted synergistically with deep brain stimulation of the subthalamic nucleus and dopaminergic replacement therapies to alleviate asymmetry and promote longer steps, improve balance and reduce freezing of gait. This neuroprosthesis opens new perspectives to reduce the severity of locomotor deficits in people with PD. A spinal cord neuroprosthesis targeting leg motor neurons in real time improves walking and reduces freezing of gait in non-human primate models and in one individual with advanced Parkinson’s disease.

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces1–3 have directly linked cortical activity to electrical stimulation of muscles, which have restored grasping abilities after hand paralysis1,4. Theoretically, this strategy could also restore control over leg muscle activity for walking5. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges6,7. Recently, we showed in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion8–10. Here, we interfaced leg motor cortex activity with epidural electrical stimulation protocols to establish a brain–spinal interface that alleviated gait deficits after a spinal cord injury in nonhuman primates. Rhesus monkeys were implanted with an intracortical microelectrode array into the leg area of motor cortex; and a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain–spinal interface in intact monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain–spinal interface restored weight-bearing locomotion of the paralyzed leg on a treadmill and overground. The implantable components integrated in the brain–spinal interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.

Background Many patients have mixed feelings about end-of-life care, even when facing life-limiting conditions. Motivational interviewing might be useful for supporting patients in evoking reasons for advance care planning. This study aimed to examine the effects of an advance care planning program adopting motivational interviewing among palliative care patients. Methods A two-arm parallel randomized controlled trial was conducted between January 2018 and December 2019 in the palliative care clinics of two hospitals. Adult patients who were newly referred to palliative care services, with a score of 60 or higher in the Palliative Performance Scale and mentally competent, were eligible for the study. While all participants received palliative care as usual care, those in the intervention group also received the advance care planning program through three home visits. The primary outcome was the readiness to discuss and document end-of-life care decisions, and the secondary outcomes included decisional conflict, perceived stress, and quality of life. Results A total of 204 participants (mean [SD] age, 74.9 [10.8]; 64.7% male; 80.4% cancer) were recruited. Generalized estimating equation analyses showed a significant improvement in readiness for advance care planning behaviors in the intervention group compared with the control group at 3 months post-allocation (group-by-time interaction, appointing proxy: β  = 0.80; 95% CI, 0.25–1.35; p  = .005; discussing with family: β  = 0.76; 95% CI, 0.22–1.31; p  = .006; discussing with medical doctors: β  = 0.86; 95% CI, 0.30–1.42; p  = .003; documenting: β  = 0.89; 95% CI, 0.36–1.41; p  < .001). The proportions of signing advance directives and placing a do-not-attempt cardiopulmonary resuscitation order were significantly higher in the intervention group, with a relative risk of 3.43 (95% CI, 1.55–7.60) and 1.16 (95% CI, 1.04–1.28), respectively. The intervention group reported greater improvements in social support and value of life than the control group immediately after the intervention. Significant improvements in decisional conflicts and perceived stress were noted in both groups. Conclusions Motivational interviewing was effective in supporting patients to resolve ambivalence regarding end-of-life care, thereby increasing their readiness for discussing and documenting their care choices. Trial registration ClinicalTrials.gov Identifier: NCT04162912 (Registered on 14/11//2019).

To investigate (1) the effects of indoor incense burning upon cognition over 3 years; (2) the associations between indoor incense burning with the brain’s structure and functional connectivity of the default mode network (DMN); and (3) the interactions between indoor incense burning and vascular disease markers upon cognitive functions. Community older adults without stroke or dementia were recruited (n = 515). Indoor incense use was self-reported as having burnt incense at home ≥ weekly basis over the past 5 years. Detailed neuropsychological battery was administered at baseline (n = 227) and the Montreal Cognitive Assessment at baseline and year 3 (n = 515). MRI structural measures and functional connectivity of the DMN were recorded at baseline. Demographic and vascular risk factors and levels of outdoor pollutants were treated as covariates. Indoor incense burning was associated with reduced performance across multiple cognitive domains at baseline and year 3 as well as decreased connectivity in the DMN. It interacted with diabetes mellitus, hyperlipidemia and white matter hyperintensities to predict poorer cognitive performance. Indoor incense burning is (1) associated with poorer cognitive performance over 3 years; (2) related to decreased brain connectivity; and (3) it interacts with vascular disease to predispose poor cognitive performance.