Brain health INnovation Diplomacy: a model binding diverse disciplines to manage the promise and perils of technological innovation.

BACKGROUND: Brain health diplomacy aims to influence the global policy environment for brain health (i.e. dementia, depression, and other mind/brain disorders) and bridges the disciplines of global brain health, international affairs, management, law, and economics. Determinants of brain health include educational attainment, diet, access to health care, physical activity, social support, and environmental exposures, as well as chronic brain disorders and treatment. Global challenges associated with these determinants include large-scale conflicts and consequent mass migration, chemical contaminants, air quality, socioeconomic status, climate change, and global population aging. Given the rapidly advancing technological innovations impacting brain health, it is paramount to optimize the benefits and mitigate the drawbacks of such technologies. OBJECTIVE: We propose a working model of Brain health INnovation Diplomacy (BIND). METHODS: We prepared a selective review using literature searches of studies pertaining to brain health technological innovation and diplomacy. RESULTS: BIND aims to improve global brain health outcomes by leveraging technological innovation, entrepreneurship, and innovation diplomacy. It acknowledges the key role that technology, entrepreneurship, and digitization play and will increasingly play in the future of brain health for individuals and societies alike. It strengthens the positive role of novel solutions, recognizes and works to manage both real and potential risks of digital platforms. It is recognition of the political, ethical, cultural, and economic influences that brain health technological innovation and entrepreneurship can have. CONCLUSIONS: By creating a framework for BIND, we can use this to ensure a systematic model for the use of technology to optimize brain health.

How the brain learns how few are "many": An fMRI study of the flexibility of quantifier semantics.

Previous work has shown that the meaning of a quantifier such as "many" or "few" depends in part on quantity. However, the meaning of a quantifier may vary depending on the context, e.g. in the case of common entities such as "many ants" (perhaps several thousands) compared to endangered species such as "many pandas" (perhaps a dozen). In a recent study (Heim et al., 2015 Front. Psychol.) we demonstrated that the relative meaning of "many" and "few" may be changed experimentally. In a truth value judgment task, displays with 40% of circles in a named color initially had a low probability of being labeled "many". After a training phase, the likelihood of acceptance 40% as "many" increased. Moreover, the semantic learning effect also generalized to the related quantifier "few" which had not been mentioned in the training phase. Thus, fewer 40% arrays were considered "few." In the present study, we tested the hypothesis that this semantic adaptation effect was supported by cytoarchitectonic Brodmann area (BA) 45 in Broca's region which may contribute to semantic evaluation in the context of language and quantification. In an event-related fMRI study, 17 healthy volunteers performed the same paradigm as in the previous behavioral study. We found a relative signal increase when comparing the critical, trained proportion to untrained proportions. This specific effect was found in left BA 45 for the trained quantifier "many", and in left BA 44 for both quantifiers, reflecting the semantic adjustment for the untrained but related quantifier "few." These findings demonstrate the neural basis for processing the flexible meaning of a quantifier, and illustrate the neuroanatomical structures that contribute to variable meanings that can be associated with a word when used in different contexts.

Transplanted glial restricted precursor cells improve neurobehavioral and neuropathological outcomes in a mouse model of neonatal white matter injury despite limited cell survival.

OBJECTIVE: Neonatal white matter injury (NWMI) is the leading cause of cerebral palsy and other neurocognitive deficits in prematurely-born children, and no restorative therapies exist. Our objective was to determine the fate and effect of glial restricted precursor cell (GRP) transplantation in an ischemic mouse model of NWMI. METHODS: Neonatal CD-1 mice underwent unilateral carotid artery ligation on postnatal-Day 5 (P5). At P22, intracallosal injections of either enhanced green fluorescent protein (eGFP) + GRPs or saline were performed in control and ligated mice. Neurobehavioral and postmortem studies were performed at 4 and 8 weeks post-transplantation. RESULTS: GRP survival was comparable at 1 month but significantly lower at 2 months post-transplantation in NWMI mice compared with unligated controls. Surviving cells showed better migration capability in controls; however, the differentiation capacity of transplanted cells was similar in control and NWMI. Saline-treated NWMI mice showed significantly altered response in startle amplitude and prepulse inhibition (PPI) paradigms compared with unligated controls, while these behavioral tests were completely normal in GRP-transplanted animals. Similarly, there was significant increase in hemispheric myelin basic protein density, along with significant decrease in pathologic axonal staining in cell-treated NWMI mice compared with saline-treated NWMI animals. INTERPRETATION: The reduced long-term survival and migration of transplanted GRPs in an ischemia-induced NWMI model suggests that neonatal ischemia leads to long-lasting detrimental effects on oligodendroglia even months after the initial insult. Despite limited GRP-survival, behavioral, and neuropathological outcomes were improved after GRP-transplantation. Our results suggest that exogenous GRPs improve myelination through trophic effects in addition to differentiation into mature oligodendrocytes.

Promoting Tech Transfer Between Space and Global Mental Health.

INTRODUCTION: Numerous issues in mental health benefit from technological innovation. An example involves the mental health challenges of long-duration spaceflight (such as a Mars mission), including prolonged confinement, microgravity, and different sunlight exposure lengths. Persisting on Earth are global mental health challenges stemming from disease burdens, limited interview-based diagnostic systems, trial-and-error treatment approaches, and suboptimal access. There is potential for cross-pollinating solutions between these seemingly disparate challenges using a range of emerging technologies such as sensors, omics, and big data. In this review, we highlight the bidirectional value of mental health technology transfer aimed to address issues both on Earth and in space.METHODS: We prepared a systematic review of studies pertaining to mental health technological innovation and space medicine.RESULTS: For Earth mental health technologies translatable to long-duration space missions, we cite several example technologies, including device-based psychotherapy and social support, conversational agents aka chatbots, and nutritional and physical activity focused mental health. Space technologies translatable to Earth mental health include remote sensing devices, global navigation satellite systems, satellite communications, chronotherapies, and nutritional advances.DISCUSSION: There is a rich history of space technologies informing Earth technological trends, including general health care on Earth, and vice versa. To avoid the traditional happenstance approach that results in delays, missed opportunities, and increased cost, and to improve outcomes for both Earth and space utilization of these technologies, we propose increased dialogue and training opportunities to enhance innovation and outcomes.Chang DD, Storch EA, Black L, Berk M, Pellis N, Lavretsky H, Sutton J, Ternes K, Shepanek M, Smith E, Abbott R, Eyre HA. Promoting tech transfer between space and global mental health. Aerosp Med Hum Perform. 2020; 91(9):737745.

18F-Flortaucipir PET/MRI Correlations in Nonamnestic and Amnestic Variants of Alzheimer Disease.

Nonamnestic Alzheimer disease (AD) variants, including posterior cortical atrophy and the logopenic variant of primary progressive aphasia, differ from amnestic AD in distributions of tau aggregates and neurodegeneration. We evaluated whether 18F-flortaucipir (also called 18F-AV-1451) PET, targeting tau aggregates, detects these differences, and we compared the results with MRI measures of gray matter (GM) atrophy. Methods: Five subjects with posterior cortical atrophy, 4 subjects with the logopenic variant of primary progressive aphasia, 6 age-matched patients with AD, and 6 control subjects underwent 18F-flortaucipir PET and MRI. SUV ratios and GM volumes were compared using regional and voxel-based methods. Results: The subgroups showed the expected 18F-flortaucipir-binding patterns. Group effect sizes were generally stronger with 18F-flortaucipir PET than with MRI volumes. There were moderate-to-high correlations between regional GM atrophy and 18F-flortaucipir uptake. 18F-flortaucipir binding and GM atrophy correlated similarly to cognitive test performance. Conclusion:18F-flortaucipir binding corresponds to the expected neurodegeneration patterns in nonamnestic AD, with potential for earlier detection of pathology than is possible with MRI atrophy measures.

Dissociation of quantifiers and object nouns in speech in focal neurodegenerative disease.

Quantifiers such as many and some are thought to depend in part on the conceptual representation of number knowledge, while object nouns such as cookie and boy appear to depend in part on visual feature knowledge associated with object concepts. Further, number knowledge is associated with a frontal-parietal network while object knowledge is related in part to anterior and ventral portions of the temporal lobe. We examined the cognitive and anatomic basis for the spontaneous speech production of quantifiers and object nouns in non-aphasic patients with focal neurodegenerative disease associated with corticobasal syndrome (CBS, n=33), behavioral variant frontotemporal degeneration (bvFTD, n=54), and semantic variant primary progressive aphasia (svPPA, n=19). We recorded a semi-structured speech sample elicited from patients and healthy seniors (n=27) during description of the Cookie Theft scene. We observed a dissociation: CBS and bvFTD were significantly impaired in the production of quantifiers but not object nouns, while svPPA were significantly impaired in the production of object nouns but not quantifiers. MRI analysis revealed that quantifier production deficits in CBS and bvFTD were associated with disease in a frontal-parietal network important for number knowledge, while impaired production of object nouns in all patient groups was related to disease in inferior temporal regions important for representations of visual feature knowledge of objects. These findings imply that partially dissociable representations in semantic memory may underlie different segments of the lexicon.

Cognitive reserve in frontotemporal degeneration: Neuroanatomic and neuropsychological evidence.

OBJECTIVE: To evaluate if cognitive reserve (CR) contributes to interindividual differences in frontal gray matter density (GMD) and executive impairment that underlie heterogeneity in the disease course of confirmed frontotemporal lobar degeneration (FTLD) pathology. METHODS: Fifty-five patients with autopsy confirmation or a pathogenic mutation consistent with underlying tau (FTLD-tau) or TDP-43 (FTLD-TDP) pathology and 90 demographically comparable healthy controls were assessed with T1 MRI and neuropsychological measures (Mini-Mental State Examination, letter fluency, forward digit span, Rey complex figure, and Boston Naming Test). CR was indexed using a composite measure of education and occupation. We used t tests to identify reduced GMD in patients with FTLD relative to controls, regression analyses to relate reduced GMD to CR index, and correlations to relate regions of GMD associated with CR to performance on neuropsychological measures. RESULTS: Patients with FTLD demonstrated impairment on neuropsychological measures. Patients with FTLD exhibited reduced bilateral frontotemporal GMD relative to controls, consistent with the known anatomic distribution of FTLD pathology. Higher CR index was associated with superior letter fluency and with GMD in right dorsolateral prefrontal cortex, orbitofrontal cortex, rostral frontal cortex, and inferior frontal gyrus. Furthermore, we found that higher GMD in frontal regions associated with CR was associated with superior letter fluency. CONCLUSIONS: Executive control and verbal ability assessed by letter fluency in FTLD is mediated in part by CR and frontal GMD. The identification of factors influencing cognitive and anatomic heterogeneity in FTLD suggests that CR should be considered in symptom detection, prognosis, and treatment.

Estimating frontal and parietal involvement in cognitive estimation: a study of focal neurodegenerative diseases.

We often estimate an unknown value based on available relevant information, a process known as cognitive estimation. In this study, we assess the cognitive and neuroanatomic basis for quantitative estimation by examining deficits in patients with focal neurodegenerative disease in frontal and parietal cortex. Executive function and number knowledge are key components in cognitive estimation. Prefrontal cortex has been implicated in multilevel reasoning and planning processes, and parietal cortex has been associated with number knowledge required for such estimations. We administered the Biber cognitive estimation test (BCET) to assess cognitive estimation in 22 patients with prefrontal disease due to behavioral variant frontotemporal dementia (bvFTD), to 17 patients with parietal disease due to corticobasal syndrome (CBS) or posterior cortical atrophy (PCA) and 11 patients with mild cognitive impairment (MCI). Both bvFTD and CBS/PCA patients had significantly more difficulty with cognitive estimation than controls. MCI were not impaired on BCET relative to controls. Regression analyses related BCET performance to gray matter atrophy in right lateral prefrontal and orbital frontal cortices in bvFTD, and to atrophy in right inferior parietal cortex, right insula, and fusiform cortices in CBS/PCA. These results are consistent with the hypothesis that a frontal-parietal network plays a crucial role in cognitive estimation.