Invasive brain-computer interfaces hold promise to alleviate disabilities in individuals with neurologic injury, with fully implantable brain-computer interface systems expected to reach the clinic in the upcoming decade. Children with severe neurologic disabilities, like quadriplegic cerebral palsy or cervical spine trauma, could benefit from this technology. However, they have been excluded from clinical trials of intracortical brain-computer interface to date. In this manuscript, we discuss the ethical considerations related to the use of invasive brain-computer interface in children with severe neurologic disabilities. We first review the technical hardware and software considerations for the application of intracortical brain-computer interface in children. We then discuss ethical issues related to motor brain-computer interface use in pediatric neurosurgery. Finally, based on the input of a multidisciplinary panel of experts in fields related to brain-computer interface (functional and restorative neurosurgery, pediatric neurosurgery, mathematics and artificial intelligence research, neuroengineering, pediatric ethics, and pragmatic ethics), we then formulate initial recommendations regarding the clinical use of invasive brain-computer interfaces in children.

Introduction: To date, clinical trials of deep brain stimulation (DBS) for refractory chronic pain have yielded unsatisfying results. Recent evidence suggests that the posterior insula may represent a promising DBS target for this indication. Methods: We present a narrative review highlighting the theoretical basis of posterior insula DBS in patients with chronic pain. Results: Neuroanatomical studies identified the posterior insula as an important cortical relay center for pain and interoception. Intracranial neuronal recordings showed that the earliest response to painful laser stimulation occurs in the posterior insula. The posterior insula is one of the only regions in the brain whose low-frequency electrical stimulation can elicit painful sensations. Most chronic pain syndromes, such as fibromyalgia, had abnormal functional connectivity of the posterior insula on functional imaging. Finally, preliminary results indicated that high-frequency electrical stimulation of the posterior insula can acutely increase pain thresholds. Conclusion: In light of the converging evidence from neuroanatomical, brain lesion, neuroimaging, and intracranial recording and stimulation as well as non-invasive stimulation studies, it appears that the insula is a critical hub for central integration and processing of painful stimuli, whose high-frequency electrical stimulation has the potential to relieve patients from the sensory and affective burden of chronic pain.

Background: Amyloid-β positron emission tomography (PET) allows for in vivo detection of fibrillar amyloid plaques, a pathologic hallmark of Alzheimer’s disease (AD). However, amyloid-β PET interpretation is limited by the imperfect correlation between PET and autopsy, and the fact that it is positive in about 20% to 30% of cognitively normal individuals and non-AD dementias, especially when older or carrying the ε4 allele of apolipoprotein E (ApoE4). When facing a positive amyloid PET, clinicians have to evaluate the probability of a pathologic false positive as well as the probability of amyloid positivity being age-related, comorbid to a primary non-AD dementia (clinicopathologic false positive). These probabilities can be calculated to reach an evidence-based interpretation of amyloid-β. As literature review and calculations cannot be easily performed in the day-to-day clinic, we propose a clinician friendly, evidence-based Bayesian approach to the interpretation of amyloid-β PET results in the differential diagnosis of patients with cognitive impairment. Methods: We defined AD as a clinicopathologic entity in which amyloid-β is the primary cause of cognitive impairment. We systematically reviewed the literature to estimate the sensitivity and specificity of amyloid-β PET against neuropathologic examination. We inferred rates of clinicopathologic false positivity (non-AD dementia with comorbid amyloid) based on age-dependent and ApoE-dependent prevalence of amyloid positivity in normal individuals and AD patients provided in large meta-analyses published by the Amyloid Biomarker Study Group. We calculated positive predictive value (PPV) and negative predictive value (NPV) of amyloid-β PET, which are presented in a clinician-friendly table. Results: PPV of PET is highest in young ApoE4− patients with high pre-PET probability of AD. In older ApoE4+ patients with low pre-PET probability of AD, positive amyloid-β PET scans must be interpreted with caution. A negative amyloid-β PET makes a diagnosis of AD unlikely except in old patients with high pre-PET probability of AD. Conclusion: This evidence-based approach might provide guidance to clinicians and nuclear medicine physicians to interpret amyloid-β PET results for early and differential diagnosis of patients with progressive cognitive impairment.

Introduction: It is well known that some patients with Alz­heimer’s disease (AD) have atypical, nonamnestic presentations. While logopenic aphasia and posterior cortical atrophy are well-characterized atypical variants of AD, the behavioral/dysexecutive variant remains a controversial entity, lacking consensus regarding its distinctive clinical and imaging features. Methods: We present a case series of 8 patients with biomarker confirmation of AD (cerebrospinal fluid [CSF] analysis or amyloid positron emission tomography [PET]) and a progressive frontal syndrome, defined as prominent behavioral and/or executive deficits at initial presentation. We characterize the cohort based on clinical features, cognitive performance in 4 domains (memory, visuospatial, executive, and language) as well as behavior on the Dépistage Cognitif de Québec (DCQ), and regional brain metabolism using ¹⁸F-fluorodeoxyglucose PET (FDG-PET). We compare these features with 8 age-matched patients diagnosed with the behavioral variant of frontotemporal dementia (bvFTD) and 37 patients with typical amnestic AD. Results: Patients with the behavioral/dysexecutive variant of AD presented with early-onset (mean age: 59 years old) progressive executive and behavioral problems reminiscent of bvFTD, including disinhibition, loss of social conventions, and hyperorality. Patients scored higher on the Memory Index and lower on the Behavioral Index than patients with amnestic AD on the DCQ, yet they were indistinguishable from patients with bvFTD on each of the cognitive indices. Visual analysis of FDG-PET revealed half of patients with behavioral/dysexecutive AD presented with frontal hypometabolism suggestive of bvFTD and only 3/8 (37.5%) presented significant hypometabolism of the posterior cingulate cortex. Group-level analysis of FDG-PET data revealed that the most hypometabolic regions were the middle temporal, inferior temporal, and angular gyri in behavioral/dysexecutive AD and the inferior frontal gyrus, anterior cingulate cortex, caudate nucleus, and insula in bvFTD. Conclusion: The behavioral/dysexecutive variant of AD is a rare, atypical young-onset variant of AD defined clinically by early and prominent impairments in executive and behavioral domains. While behavioral/dysexecutive AD is hardly distinguishable from bvFTD using clinical and cognitive features alone, CSF biomarkers and temporoparietal hypometabolism help predict underlying pathology during life.