ABSTRACT
BACKGROUND: Implantable brain-computer interfaces (BCIs), functioning as motor neuroprostheses, have the potential to restore voluntary motor impulses to control digital devices and improve functional independence in patients with severe paralysis due to brain, spinal cord, peripheral nerve or muscle dysfunction. However, reports to date have had limited clinical translation. METHODS: Two participants with amyotrophic lateral sclerosis (ALS) underwent implant in a single-arm, open-label, prospective, early feasibility study. Using a minimally invasive neurointervention procedure, a novel endovascular Stentrode BCI was implanted in the superior sagittal sinus adjacent to primary motor cortex. The participants undertook machine-learning-assisted training to use wirelessly transmitted electrocorticography signal associated with attempted movements to control multiple mouse-click actions, including zoom and left-click. Used in combination with an eye-tracker for cursor navigation, participants achieved Windows 10 operating system control to conduct instrumental activities of daily living (IADL) tasks. RESULTS: Unsupervised home use commenced from day 86 onwards for participant 1, and day 71 for participant 2. Participant 1 achieved a typing task average click selection accuracy of 92.63% (100.00%, 87.50%-100.00%) (trial mean (median, Q1-Q3)) at a rate of 13.81 (13.44, 10.96-16.09) correct characters per minute (CCPM) with predictive text disabled. Participant 2 achieved an average click selection accuracy of 93.18% (100.00%, 88.19%-100.00%) at 20.10 (17.73, 12.27-26.50) CCPM. Completion of IADL tasks including text messaging, online shopping and managing finances independently was demonstrated in both participants. CONCLUSION: We describe the first-in-human experience of a minimally invasive, fully implanted, wireless, ambulatory motor neuroprosthesis using an endovascular stent-electrode array to transmit electrocorticography signals from the motor cortex for multiple command control of digital devices in two participants with flaccid upper limb paralysis.
Subject(s)
Activities of Daily Living , Brain-Computer Interfaces , Implantable Neurostimulators , Motor Cortex/physiology , Paralysis/therapy , Severity of Illness Index , Activities of Daily Living/psychology , Aged , Brain-Computer Interfaces/psychology , Feasibility Studies , Female , Humans , Imaging, Three-Dimensional/methods , Male , Middle Aged , Motor Cortex/diagnostic imaging , Paralysis/diagnostic imaging , Paralysis/physiopathology , Prospective StudiesABSTRACT
Although the pig is an accepted model species for human digestive physiology, no previous study of the pig gastric mucosa and gastric enteroendocrine cells has investigated the parallels between pig and human. In this study, we have investigated markers for each of the classes of gastric endocrine cells, gastrin, ghrelin, somatostatin, 5-hydroxytryptamine, histidine decarboxylase, and PYY cells in pig stomach. The lining of the proximal stomach consisted of a collar of stratified squamous epithelium surrounded by gastric cardiac glands in the fundus. This differs considerably from human that has only a narrow band of cardiac glands at its entrance, surrounded by a fundic mucosa consisting of oxyntic glands. However, the linings of the corpus and antrum are similar in pig and human. Likewise, the endocrine cell types are similar and similarly distributed in the two species. As in human, gastrin cells were almost exclusively in the antrum, ghrelin cells were most abundant in the oxyntic mucosa and PYY cells were rare. In the pig, 70% of enterochromaffin-like (ECL) cells in the antrum and 95% in the fundus contained 5-hydroxytryptamine (5-HT), higher proportions than in human. Unlike the enteroendocrine of the small intestine, most gastric enteroendocrine cells (EEC) did not contain colocalised hormones. This is similar to human and other species. We conclude that the pig stomach has substantial similarity to human, except that the pig has a protective lining at its entrance that may reflect the difference between a pig diet with hard abrasive components and the soft foods consumed by humans.