Patterns of regional cerebellar atrophy in genetic frontotemporal dementia

BACKGROUND: Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder with a strong genetic component. The cerebellum has not traditionally been felt to be involved in FTD but recent research has suggested a potential role. METHODS: We investigated the volumetry of the cerebellum and its subregions in a cohort of 44 patients with genetic FTD (20 MAPT, 7 GRN, and 17 C9orf72 mutation carriers) compared with 18 cognitively normal controls. All groups were matched for age and gender. On volumetric T1-weighted magnetic resonance brain images we used an atlas propagation and label fusion strategy of the Diedrichsen cerebellar atlas to automatically extract subregions including the cerebellar lobules, the vermis and the deep nuclei. RESULTS: The global cerebellar volume was significantly smaller in C9orf72 carriers (mean (SD): 99989 (8939) mm(3)) compared with controls (108136 (7407) mm(3)). However, no significant differences were seen in the MAPT and GRN carriers compared with controls (104191 (6491) mm(3) and 107883 (6205) mm(3) respectively). Investigating the individual subregions, C9orf72 carriers had a significantly lower volume than controls in lobule VIIa-Crus I (15% smaller, p < 0.0005), whilst MAPT mutation carriers had a significantly lower vermal volume (10% smaller, p = 0.001) than controls. All cerebellar subregion volumes were preserved in GRN carriers compared with controls. CONCLUSION: There appears to be a differential pattern of cerebellar atrophy in the major genetic forms of FTD, being relatively spared in GRN, localized to the lobule VIIa-Crus I in the superior-posterior region of the cerebellum in C9orf72, the area connected via the thalamus to the prefrontal cortex and involved in cognitive function, and localized to the vermis in MAPT, the 'limbic cerebellum' involved in emotional processing

Basal forebrain atrophy in frontotemporal dementia

Background: The basal forebrain is a subcortical structure that plays an important role in learning, attention, and memory. Despite the known subcortical involvement in frontotemporal dementia (FTD), there is little research into the role of the basal forebrain in this disease. We aimed to investigate differences in basal forebrain volumes between clinical, genetic, and pathological diagnoses of FTD. / Methods: 356 patients with FTD were recruited from the UCL Dementia Research Centre and matched on age and gender with 83 cognitively normal controls. All subjects had a T1-weighted MR scan suitable for analysis. Basal forebrain volumes were calculated using the Geodesic Information Flow (GIF) parcellation method and were compared between clinical (148 bvFTD, 82 svPPA, 103 nfvPPA, 14 PPA-NOS, 9 FTD-MND), genetic (24 MAPT, 15 GRN, 26 C9orf72) and pathological groups (28 tau, 3 FUS, 35 TDP-43) and controls. A subanalysis was also performed comparing pathological subgroups of tau (11 Pick's disease, 6 FTDP-17, 7 CBD, 4 PSP) and TDP-43 (12 type A, 2 type B, 21 type C). / Results: All clinical subtypes of FTD showed significantly smaller volumes than controls (p≤ 0.010, ANCOVA), with svPPA (10% volumetric difference) and bvFTD (9%) displaying the smallest volumes. Reduced basal forebrain volumes were also seen in MAPT mutations (18%, p<0.0005) and in individuals with pathologically confirmed FTDP-17 (17%), Pick's disease (12%), and TDP-43 type C (8%) (p<0.001). / Conclusion: Involvement of the basal forebrain is a common feature in FTD, although the extent of volume reduction differs between clinical, genetic, and pathological diagnoses. Tauopathies, particularly those with MAPT mutations, had the smallest volumes. However, atrophy was also seen in those with TDP-43 type C pathology (most of whom have svPPA clinically). This suggests that the basal forebrain is vulnerable to multiple types of FTD-associated protein inclusions

Radiation from a D-dimensional collision of shock waves: first order perturbation theory

We study the spacetime obtained by superimposing two equal Aichelburg-Sexl shock waves in D dimensions traveling, head-on, in opposite directions. Considering the collision in a boosted frame, one shock becomes stronger than the other, and a perturbative framework to compute the metric in the future of the collision is setup. The geometry is given, in first order perturbation theory, as an integral solution, in terms of initial data on the null surface where the strong shock has support. We then extract the radiation emitted in the collision by using a D-dimensional generalisation of the Landau-Lifschitz pseudo-tensor and compute the percentage of the initial centre of mass energy epsilon emitted as gravitational waves. In D=4 we find epsilon=25.0%, in agreement with the result of D'Eath and Payne. As D increases, this percentage increases monotonically, reaching 40.0% in D=10. Our result is always within the bound obtained from apparent horizons by Penrose, in D=4, yielding 29.3%, and Eardley and Giddings, in D> 4, which also increases monotonically with dimension, reaching 41.2% in D=10. We also present the wave forms and provide a physical interpretation for the observed peaks, in terms of the null generators of the shocks.Comment: 27 pages, 11 figures; v2 some corrections, including D dependent factor in epsilon; matches version accepted in JHE

Patterns of progressive atrophy vary with age in Alzheimer's disease patients

Age is not only the greatest risk factor for Alzheimer's disease (AD) but also a key modifier of disease presentation and progression. Here, we investigate how longitudinal atrophy patterns vary with age in mild cognitive impairment (MCI) and AD. Data comprised serial longitudinal 1.5-T magnetic resonance imaging scans from 153 AD, 339 MCI, and 191 control subjects. Voxel-wise maps of longitudinal volume change were obtained and aligned across subjects. Local volume change was then modeled in terms of diagnostic group and an interaction between group and age, adjusted for total intracranial volume, white-matter hyperintensity volume, and apolipoprotein E genotype. Results were significant at p < 0.05 with family-wise error correction for multiple comparisons. An age-by-group interaction revealed that younger AD patients had significantly faster atrophy rates in the bilateral precuneus, parietal, and superior temporal lobes. These results suggest younger AD patients have predominantly posterior progressive atrophy, unexplained by white-matter hyperintensity, apolipoprotein E, or total intracranial volume. Clinical trials may benefit from adapting outcome measures for patient groups with lower average ages, to capture progressive atrophy in posterior cortices

Distributions of charged massive scalars and fermions from evaporating higher-dimensional black holes

A detailed numerical analysis is performed to obtain the Hawking spectrum for charged, massive brane scalars and fermions on the approximate background of a brane charged rotating higher-dimensional black hole constructed in arXiv:0907.5107. We formulate the problem in terms of a "spinor-like" first order system of differential wave equations not only for fermions, but for scalars as well and integrate it numerically. Flux spectra are presented for non-zero mass, charge and rotation, confirming and extending previous results based on analytic approximations. In particular we describe an inverted charge splitting at low energies, which is not present in four or five dimensions and increases with the number of extra dimensions. This provides another signature of the evaporation of higher-dimensional black holes in TeV scale gravity scenarios.Comment: 19 pages, 6 figures, minor typos corrected, 1 page added with a discussion on higher spins, added reference

Attention wins over sensory attenuation in a sound detection task

'Sensory attenuation', i.e., reduced neural responses to self-induced compared to externally generated stimuli, is a well-established phenomenon. However, very few studies directly compared sensory attenuation with attention effect, which leads to increased neural responses. In this study, we brought sensory attenuation and attention together in a behavioural auditory detection task, where both effects were quantitatively measured and compared. The classic auditory attention effect of facilitating detection performance was replicated. When attention and sensory attenuation were both present, attentional facilitation decreased but remained significant. The results are discussed in the light of current theories of sensory attenuation

Critical Trapped Surfaces Formation in the Collision of Ultrarelativistic Charges in (A)dS

We study the formation of marginally trapped surfaces in the head-on collision of two ultrarelativistic charges in $(A)dS$ space-time. The metric of ultrarelativistic charged particles in $(A)dS$ is obtained by boosting Reissner-Nordstr\"om $(A)dS$ space-time to the speed of light. We show that formation of trapped surfaces on the past light cone is only possible when charge is below certain critical - situation similar to the collision of two ultrarelativistic charges in Minkowski space-time. This critical value depends on the energy of colliding particles and the value of a cosmological constant. There is richer structure of critical domains in $dS$ case. In this case already for chargeless particles there is a critical value of the cosmological constant only below which trapped surfaces formation is possible. Appearance of arbitrary small nonzero charge significantly changes the physical picture. Critical effect which has been observed in the neutral case does not take place more. If the value of the charge is not very large solution to the equation on trapped surface exists for any values of cosmological radius and energy density of shock waves. Increasing of the charge leads to decrease of the trapped surface area, and at some critical point the formation of trapped surfaces of the type mentioned above becomes impossible.Comment: 30 pages, Latex, 7 figures, Refs. added and typos correcte

The Expanded mtDNA Phylogeny of the Franco-Cantabrian Region Upholds the Pre-Neolithic Genetic Substrate of Basques

The European genetic landscape has been shaped by several human migrations occurred since Paleolithic times. The accumulation of archaeological records and the concordance of different lines of genetic evidence during the last two decades have triggered an interesting debate concerning the role of ancient settlers from the Franco-Cantabrian region in the postglacial resettlement of Europe. Among the Franco-Cantabrian populations, Basques are regarded as one of the oldest and more intriguing human groups of Europe. Recent data on complete mitochondrial DNA genomes focused on macrohaplogroup R0 revealed that Basques harbor some autochthonous lineages, suggesting a genetic continuity since pre-Neolithic times. However, excluding haplogroup H, the most representative lineage of macrohaplogroup R0, the majority of maternal lineages of this area remains virtually unexplored, so that further refinement of the mtDNA phylogeny based on analyses at the highest level of resolution is crucial for a better understanding of the European prehistory. We thus explored the maternal ancestry of 548 autochthonous individuals from various Franco-Cantabrian populations and sequenced 76 mitogenomes of the most representative lineages. Interestingly, we identified three mtDNA haplogroups, U5b1f, J1c5c1 and V22, that proved to be representative of Franco-Cantabria, notably of the Basque population. The seclusion and diversity of these female genetic lineages support a local origin in the Franco-Cantabrian area during the Mesolithic of southwestern Europe, ∼10,000 years before present (YBP), with signals of expansions at ∼3,500 YBP. These findings provide robust evidence of a partial genetic continuity between contemporary autochthonous populations from the Franco-Cantabrian region, specifically the Basques, and Paleolithic/Mesolithic hunter-gatherer groups. Furthermore, our results raise the current proportion (≈15%) of the Franco-Cantabrian maternal gene pool with a putative pre-Neolithic origin to ≈35%, further supporting the notion of a predominant Paleolithic genetic substrate in extant European populations