Saber Sami

18F-AV-1451 positron emission tomography in Alzheimer's disease and progressive supranuclear palsy.

The extent to which the tau tracer [18F]AV-1451 can differentiate between tauopathies is unknown. By comparing patients with Alzheimer’s disease and progressive supranuclear palsy (PSP), Passamonti et al. show that [18F]AV-1451 displays greater specificity for Alzheimer-related tau pathology than PSP-related pathology. A machine learning algorithm correctly diagnosed 94% of cases.

Network-selective vulnerability of the human cerebellum to Alzheimer’s disease and frontotemporal dementia

SEE SCHMAHMANN DOI101093/BRAIN/AWW064 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Neurodegenerative diseases are associated with distinct and distributed patterns of atrophy in the cerebral cortex. Emerging evidence suggests that these atrophy patterns resemble intrinsic connectivity networks in the healthy brain, supporting the network-based degeneration framework where neuropathology spreads across connectivity networks. An intriguing yet untested possibility is that the cerebellar circuits, which share extensive connections with the cerebral cortex, could be selectively targeted by major neurodegenerative diseases. Here we examined the structural atrophy in the cerebellum across common types of neurodegenerative diseases, and characterized the functional connectivity patterns of these cerebellar atrophy regions. Our results showed that Alzheimers disease and frontotemporal dementia are associated with distinct and circumscribed atrophy in the cerebellum. These cerebellar atrophied regions share robust and selective intrinsic connectivity with the atrophied regions in the cerebral cortex. These findings for the first time demonstrated the selective vulnerability of the cerebellum to common neurodegenerative disease, extending the network-based degeneration framework to the cerebellum. Our work also has direct implications on the cerebellar contribution to the cognitive and affective processes that are compromised in neurodegeneration as well as the practice of using the cerebellum as reference region for ligand neuroimaging studies.

Atomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson’s Disease

Cognitive impairment is common in Parkinson’s disease (PD), but often not improved by dopaminergic treatment. New treatment strategies targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest (‘task-free’) provides the opportunity to examine the impact of a candidate drug on many of the brain networks that underpin cognition, while minimizing task-related performance confounds. We test this approach using atomoxetine, a selective noradrenaline reuptake inhibitor that modulates the prefrontal cortical activity and can facilitate some executive functions and response inhibition. Thirty-three patients with idiopathic PD underwent task-free fMRI. Patients were scanned twice in a double-blind, placebo-controlled crossover design, following either placebo or 40-mg oral atomoxetine. Seventy-six controls were scanned once without medication to provide normative data. Seed-based correlation analyses were used to measure changes in functional connectivity, with the right inferior frontal gyrus (IFG) a critical region for executive function. Patients on placebo had reduced connectivity relative to controls from right IFG to dorsal anterior cingulate cortex and to left IFG and dorsolateral prefrontal cortex. Atomoxetine increased connectivity from the right IFG to the dorsal anterior cingulate. In addition, the atomoxetine-induced change in connectivity from right IFG to dorsolateral prefrontal cortex was proportional to the change in verbal fluency, a simple index of executive function. The results support the hypothesis that atomoxetine may restore prefrontal networks related to executive functions. We suggest that task-free imaging can support translational pharmacological studies of new drug therapies and provide evidence for engagement of the relevant neurocognitive systems.

Cerebellar atrophy in neurodegeneration—a meta-analysis

Introduction The cerebellum has strong cortical and subcortical connectivity, but is rarely taken into account for clinical diagnosis in many neurodegenerative conditions, particularly in the absence of clinical ataxia. The current meta-analysis aims to assess patterns of cerebellar grey matter atrophy in seven neurodegenerative conditions (Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), progressive supranuclear palsy (MSP)). Methods We carried out a systematic search in PubMed (any date: 14 July 2016) and a hand search of references from pertinent articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The authors were contacted to provide missing coordinate data. Peer-reviewed studies with direct comparison of patient and control groups, and availability of coordinate data of grey matter cerebellar atrophy in patients were included. These coordinates were used in an anatomical likelihood estimation meta-analysis. Results Across 54 studies, clusters of cerebellar atrophy were found for AD, ALS, FTD, MSA, and PSP. Atrophy patterns were largely disease-specific, with overlap in certain areas of the cerebellar hemisphere, which showed marked atrophy in AD, ALS, FTD and PSP (Crus I/II), and MSA and PSP (lobules I–IV), respectively. Atrophy colocated with cerebellar areas implicated for motor (PSP, MSA) or cognitive symptoms (FTD, ALS, PSP) in the diseases. Discussion Our findings suggest that cerebellar changes are largely disease-specific and correspond to cortical or subcortical changes in neurodegenerative conditions. High clinical variability in PD and HD samples may explain the absence of findings for consistent grey matter loss across studies. Our results have clinical implications for diagnosis and cerebellar neuroimaging referencing approaches.

Neurophysiological signatures of Alzheimer’s disease and frontotemporal lobar degeneration: pathology versus phenotype

Sami et al. identify characteristic neurophysiological signatures of five neurodegenerative diseases, including two variants of Alzheimer’s disease and three forms of frontotemporal lobar degeneration. Disorders that share a common underlying pathology have a similar spectral signature of altered connectivity, regardless of phenotype.

Erratum: Atomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson’s Disease

Correction to: Neuropsychopharmacology advance online publication, 2 March 2016; doi:10.1038/npp.2016.18 Following the publication of this paper, the authors have changed the Funding and Disclosure section to read as follows: This work was funded by the Wellcome trust (103838), Parkinson’s UK, National Institute for Health Research’s Cambridge Biomedical Research Centre and the Medical Research Council (MC_US_A060_0016 and RG62761), and the James F McDonnell Foundation (21st century science initiative on Understanding Human Cognition).

Global Determinants of Navigation Ability

Human spatial ability is modulated by a number of factors, including age [1-3] and gender [4, 5]. Although a few studies showed that culture influences cognitive strategies [6-13], the interaction between these factors has never been globally assessed as this requires testing millions of people of all ages across many different countries in the world. Since countries vary in their geographical and cultural properties, we predicted that these variations give rise to an organized spatial distribution of cognition at a planetary-wide scale. To test this hypothesis, we developed a mobile-app-based cognitive task, measuring non-verbal spatial navigation ability in more than 2.5 million people and sampling populations in every nation state. We focused on spatial navigation due to its universal requirement across cultures. Using a clustering approach, we find that navigation ability is clustered into five distinct, yet geographically related, groups of countries. Specifically, the economic wealth of a nation was predictive of the average navigation ability of its inhabitants, and gender inequality was predictive of the size of performance difference between males and females. Thus, cognitive abilities, at least for spatial navigation, are clustered according to economic wealth and gender inequalities globally, which has significant implications for cross-cultural studies and multi-center clinical trials using cognitive testing.

Planetary-wide organization of human navigation ability

Human cognitive strategies vary across nations and cultures. However, it is unknown whether the cognitive strategies of nations are randomly distributed or whether groups of countries are clustered by similar cognitive profiles. Using a mobile-based virtual reality navigation task, we measured spatial navigation ability in more than 2.5 million people globally. Using a clustering approach, we find that navigation ability is not smoothly distributed globally but clustered into five distinct yet geographically related groups of countries. Furthermore, the economic wealth of a nation (Gross Domestic Product per capita) was predictive of the average navigation ability of its inhabitants and gender inequality (Gender Gap Index) was predictive of the size of performance difference between males and females. Thus, cognitive abilities, at least for spatial navigation, are clustered according to economic wealth and gender inequalities globally. This will not only inform cognitive assessment but also clinical assessment and educational approaches in the future.Countries vary in their geographical and cultural properties. We predicted that such variation impacts human cognition, resulting in an organized spatial distribution of cognition at a planetary-wide scale. To test this hypothesis we developed a mobile-app-based cognitive task, measuring non-verbal spatial navigation ability in more than 2.5 million people, sampling populations in every nation state. We focused on spatial navigation due to its universal requirement across cultures. Using a clustering approach, we find that navigation ability is clustered into five distinct, yet geographically related, groups of countries. Specifically, the economic wealth of a nation was predictive of the average navigation ability of its inhabitants, and gender inequality was predictive of the size of performance difference between males and females. Thus, cognitive abilities, at least for spatial navigation, are clustered according to economic wealth and gender inequalities globally, which has significant implications for cross-cultural studies and multi-centre clinical trials using cognitive testing.

Planetary-wide organization of human cognition

Human cognitive strategies vary across nations and cultures. However, it is unknown whether the cognitive strategies of nations are randomly distributed or whether groups of countries are clustered by similar cognitive profiles. Using a mobile-based virtual reality navigation task, we measured spatial navigation ability in more than 2.5 million people globally. Using a clustering approach, we find that navigation ability is not smoothly distributed globally but clustered into five distinct yet geographically related groups of countries. Furthermore, the economic wealth of a nation (Gross Domestic Product per capita) was predictive of the average navigation ability of its inhabitants and gender inequality (Gender Gap Index) was predictive of the size of performance difference between males and females. Thus, cognitive abilities, at least for spatial navigation, are clustered according to economic wealth and gender inequalities globally. This will not only inform cognitive assessment but also clinical assessment and educational approaches in the future.Countries vary in their geographical and cultural properties. We predicted that such variation impacts human cognition, resulting in an organized spatial distribution of cognition at a planetary-wide scale. To test this hypothesis we developed a mobile-app-based cognitive task, measuring non-verbal spatial navigation ability in more than 2.5 million people, sampling populations in every nation state. We focused on spatial navigation due to its universal requirement across cultures. Using a clustering approach, we find that navigation ability is clustered into five distinct, yet geographically related, groups of countries. Specifically, the economic wealth of a nation was predictive of the average navigation ability of its inhabitants, and gender inequality was predictive of the size of performance difference between males and females. Thus, cognitive abilities, at least for spatial navigation, are clustered according to economic wealth and gender inequalities globally, which has significant implications for cross-cultural studies and multi-centre clinical trials using cognitive testing.

Economic wealth and gender inequality shape the distribution of navigational ability in the world population

Human cognitive strategies vary across nations and cultures. However, it is unknown whether the cognitive strategies of nations are randomly distributed or whether groups of countries are clustered by similar cognitive profiles. Using a mobile-based virtual reality navigation task, we measured spatial navigation ability in more than 2.5 million people globally. Using a clustering approach, we find that navigation ability is not smoothly distributed globally but clustered into five distinct yet geographically related groups of countries. Furthermore, the economic wealth of a nation (Gross Domestic Product per capita) was predictive of the average navigation ability of its inhabitants and gender inequality (Gender Gap Index) was predictive of the size of performance difference between males and females. Thus, cognitive abilities, at least for spatial navigation, are clustered according to economic wealth and gender inequalities globally. This will not only inform cognitive assessment but also clinical assessment and educational approaches in the future.Countries vary in their geographical and cultural properties. We predicted that such variation impacts human cognition, resulting in an organized spatial distribution of cognition at a planetary-wide scale. To test this hypothesis we developed a mobile-app-based cognitive task, measuring non-verbal spatial navigation ability in more than 2.5 million people, sampling populations in every nation state. We focused on spatial navigation due to its universal requirement across cultures. Using a clustering approach, we find that navigation ability is clustered into five distinct, yet geographically related, groups of countries. Specifically, the economic wealth of a nation was predictive of the average navigation ability of its inhabitants, and gender inequality was predictive of the size of performance difference between males and females. Thus, cognitive abilities, at least for spatial navigation, are clustered according to economic wealth and gender inequalities globally, which has significant implications for cross-cultural studies and multi-centre clinical trials using cognitive testing.