Mapping grip force to motor networks.

There is ongoing debate about the role of cortical and subcortical brain areas in force modulation. In a whole-brain approach, we sought to investigate the anatomical basis of grip force whilst acknowledging interindividual differences in connectivity patterns. We tested if brain lesion mapping in patients with unilateral motor deficits can inform whole-brain structural connectivity analysis in healthy controls to uncover the networks underlying grip force. Using magnetic resonance imaging (MRI) and whole-brain voxel-based morphometry in chronic stroke patients (n=55) and healthy controls (n=67), we identified the brain regions in both grey and white matter significantly associated with grip force strength. The resulting statistical parametric maps (SPMs) provided seed areas for whole-brain structural covariance analysis in a large-scale community dwelling cohort (n=977) that included beyond volume estimates, parameter maps sensitive to myelin, iron and tissue water content. The SPMs showed symmetrical bilateral clusters of correlation between upper limb motor performance, basal ganglia, posterior insula and cortico-spinal tract. The covariance analysis with the seed areas derived from the SPMs demonstrated a widespread anatomical pattern of brain volume and tissue properties, including both cortical, subcortical nodes of motor networks and sensorimotor areas projections. We interpret our covariance findings as a biological signature of brain networks implicated in grip force. The data-driven definition of seed areas obtained from chronic stroke patients showed overlapping structural covariance patterns within cortico-subcortical motor networks across different tissue property estimates. This cumulative evidence lends face validity of our findings and their biological plausibility

The metaphysics of mental files

There is much to be said for a diachronic or interpersonal individuation of singular modes of presentation (MOPs) in terms of a criterion of epistemic transparency between thought tokens. This way of individuating MOPs has been discussed recently within the mental files framework, though the issues discussed here arise for all theories that individuate MOPs in terms of relations among tokens. All such theories face objections concerning apparent failures of the transitivity of the ‘same MOP’ relation. For mental files, these transitivity failures most obviously occur because mental files can merge or undergo fission. In this paper I argue that this problem is easily resolved once mental files are properly construed as continuants, whose metaphysics is analogous to that of persons or physical objects. All continuants can undergo fission or fusion, leading to similar transitivity problems, but there are well-established theories of persistence that accommodate this. I suggest that, in particular, the stage theory best suits the purposes of a continuant theory of MOPs.PostprintPeer reviewe

Executive deficits are related to the inferior frontal junction in early dementia

Executive functions describe a wide variety of higher order cognitive processes that allow the flexible modification of thought and behaviour in response to changing cognitive or environmental contexts. Their impairment is common in neurodegenerative disorders. Executive deficits negatively affect everyday activities and hamper the ability to cope with other deficits, such as memory impairment in Alzheimer's disease or behavioural disorders in frontotemporal lobar degeneration. Our study aimed to characterize the neural correlates of executive functions by relating respective deficits to regional hypometabolism in early dementia. Executive functions were assessed with two classical tests, the Stroop and semantic fluency test and various subtests of the behavioural assessment of the dysexecutive syndrome test battery capturing essential aspects of executive abilities relevant to daily living. Impairments in executive functions were correlated with reductions in brain glucose utilization as measured by [18F]fluorodeoxyglucose positron emission tomography and analysed voxelwise using statistical parametric mapping in 54 subjects with early dementia, mainly Alzheimer's disease and frontotemporal lobar degeneration, and its prodromal stages: subjective and mild cognitive impairment. Although the analysis revealed task-specific frontoparietal networks, it consistently showed that hypometabolism in one region in the left lateral prefrontal cortex—the inferior frontal junction area—was related to performance in the various neuropsychological tests. This brain region has recently been related to the three component processes of cognitive control—working memory, task switching and inhibitory control. Group comparisons additionally showed hypometabolism in this area in Alzheimer's disease and frontotemporal lobar degeneration. Our study underlines the importance of the inferior frontal junction area for cognitive control in general and for executive deficits in early dementia

Three-dimensional flux states as a model for the pseudogap phase of transition metal oxides

We propose that the pseudogap state observed in the transition metal oxides can be explained by a three-dimensional flux state, which exhibits spontaneously generated currents in its ground state due to electron-electron correlations. We compare the energy of the flux state to other classes of mean field states, and find that it is stabilized over a wide range of $t$ and $\delta$. The signature of the state will be peaks in the neutron diffraction spectra, the location and intensity of which are presented. The dependence of the pseudogap in the optical conductivity is calculated based on the parameters in the model.Comment: submitted to Phys. Rev. B on January 8, 200

Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems

Aside to clinical changes, behavioral variant frontotemporal dementia (bvFTD) is characterized by progressive structural and functional alterations in frontal and temporal regions. We examined if there is a selective vulnerability of specific neurotransmitter systems in bvFTD by evaluating the link between disease-related functional alterations and the spatial distribution of specific neurotransmitter systems and their underlying gene expression levels.Maps of fractional amplitude of low frequency fluctuations (fALFF) were derived as a measure of local activity from resting-state functional magnetic resonance imaging for 52 bvFTD patients (mean age = 61.5 ± 10.0 years; 14 female) and 22 healthy controls (HC) (mean age = 63.6 ± 11.9 years; 13 female). We tested if alterations of fALFF in patients co-localize with the non-pathological distribution of specific neurotransmitter systems and their coding mRNA gene expression. Further, we evaluated if the strength of co-localization is associated with the observed clinical symptoms.Patients displayed significantly reduced fALFF in fronto-temporal and fronto-parietal regions. These alterations co-localized with the distribution of serotonin (5-HT1b, 5-HT2a), dopamine (D2), and γ-aminobutyric acid (GABAa) receptors, the norepinephrine transporter (NET), and their encoding mRNA gene expression. The strength of co-localization with D2 and NET was associated with cognitive symptoms and disease severity of bvFTD.Local brain functional activity reductions in bvFTD followed the distribution of specific neurotransmitter systems indicating a selective vulnerability. These findings provide novel insight into the disease mechanisms underlying functional alterations. Our data-driven method opens the road to generate new hypotheses for pharmacological interventions in neurodegenerative diseases even beyond bvFTD

Increased serum NSE and S100B indicate neuronal and glial alterations in subjects under 71 years with mild neurocognitive disorder/mild cognitive impairment

Background: Mild cognitive impairment (MCI) is considered a pre-stage of different dementia syndromes. Despite diagnostic criteria refined by DSM-5 and a new term for MCI - "mild neurocognitive disorder" (mild NCD) - this diagnosis is still based on clinical criteria.Methods: To link mild NCD to the underlying pathophysiology we assessed the degree of white matter hyperintensities (WMH) in the brain and peripheral biomarkers for neuronal integrity (neuron-specific enolase, NSE), plasticity (brain-derived neurotrophic factor, BDNF), and glial function (S100B) in 158 community-dwelling subjects with mild NCD and 82 healthy controls. All participants (63-79 years old) were selected from the Leipzig-population-based study of adults (LIFE).Results: Serum S100B levels were increased in mild NCD in comparison to controls (p = 0.007). Serum NSE levels were also increased but remained non-significant after Bonferroni-Holm correction (p = 0.04). Furthermore, age by group interaction was significant for S100B. In an age-stratified sub-analysis, NSE and S100B were higher in younger subjects with mild NCD below 71 years of age. Some effects were inconsistent after controlling for potentially confounding factors. The discriminatory power of the two biomarkers NSE and S100B was insufficient to establish a pathologic threshold for mild NCD. In subjects with mild NCD, WMH load correlated with serum NSE levels (r = 0.20, p = 0.01), independently of age.Conclusion: Our findings might indicate the presence of neuronal (NSE) and glial (S100B) injury in mild NCD. Future studies need to investigate whether younger subjects with mild NCD with increased biomarker levels are at risk of developing major NCD