70 research outputs found
Basal ganglia correlates of fatigue in young adults
Although the prevalence of chronic fatigue is approximately 20% in healthy individuals, there are no studies of brain structure that elucidate the neural correlates of fatigue outside of clinical subjects. We hypothesized that fatigue without evidence of disease might be related to changes in the basal ganglia and prefrontal cortex and be implicated in fatigue with disease. We aimed to identify the white matter structures of fatigue in young subjects without disease using magnetic resonance imaging (MRI). Healthy young adults (n = 883; 489 males and 394 females) were recruited. As expected, the degrees of fatigue and motivation were associated with larger mean diffusivity (MD) in the right putamen, pallidus and caudate. Furthermore, the degree of physical activity was associated with a larger MD only in the right putamen. Accordingly, motivation was the best candidate for widespread basal ganglia, whereas physical activity might be the best candidate for the putamen. A plausible mechanism of fatigue may involve abnormal function of the motor system, as well as areas of the dopaminergic system in the basal ganglia that are associated with motivation and reward
An Imperfect Dopaminergic Error Signal Can Drive Temporal-Difference Learning
An open problem in the field of computational neuroscience is how to link synaptic plasticity to system-level learning. A promising framework in this context is temporal-difference (TD) learning. Experimental evidence that supports the hypothesis that the mammalian brain performs temporal-difference learning includes the resemblance of the phasic activity of the midbrain dopaminergic neurons to the TD error and the discovery that cortico-striatal synaptic plasticity is modulated by dopamine. However, as the phasic dopaminergic signal does not reproduce all the properties of the theoretical TD error, it is unclear whether it is capable of driving behavior adaptation in complex tasks. Here, we present a spiking temporal-difference learning model based on the actor-critic architecture. The model dynamically generates a dopaminergic signal with realistic firing rates and exploits this signal to modulate the plasticity of synapses as a third factor. The predictions of our proposed plasticity dynamics are in good agreement with experimental results with respect to dopamine, pre- and post-synaptic activity. An analytical mapping from the parameters of our proposed plasticity dynamics to those of the classical discrete-time TD algorithm reveals that the biological constraints of the dopaminergic signal entail a modified TD algorithm with self-adapting learning parameters and an adapting offset. We show that the neuronal network is able to learn a task with sparse positive rewards as fast as the corresponding classical discrete-time TD algorithm. However, the performance of the neuronal network is impaired with respect to the traditional algorithm on a task with both positive and negative rewards and breaks down entirely on a task with purely negative rewards. Our model demonstrates that the asymmetry of a realistic dopaminergic signal enables TD learning when learning is driven by positive rewards but not when driven by negative rewards
Multi-messenger observations of a binary neutron star merger
On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues
Autologous neural stem cell transplantation: A new treatment option for Parkinson's disease?
The clinical motor dysfunction in Parkinson s disease (PD) is primarily linked to the depletion of dopamine in the striatum consecutive to the loss of the large dopaminergic neurons in the substantia nigra. Despite intense investigations, no effective therapy is available to prevent the onset, or to halt the progression of the neuronal cell loss. Here, we hypothesize that autologous adult neural stem cells (NSCs) are an attractive source for cell therapy to treat PD. They overcome the ethical issues inherent to the use of human fetal tissue or embryonic stem cells. NSCs derived from adult tissue also open the possibility for autologous transplantation, where NSCs are taken out from the patient, expanded and differentiated in vitro and re-implanted back as dopaminergic precursor cells.link_to_subscribed_fulltex
Editorial: Combined EEG in research and diagnostics: Novel perspectives and improvements
A quantitative treatment to data from computer-supported collaboration: An ontological approach
Anatomy plays a fundamental role in supporting and shaping nervous system activity. The remarkable progress of computer processing power within the last two decades has enabled the generation of electronic databases of complete three-dimensional (3D) dendritic and axonal morphology for neuroanatomical studies. Several laboratories are freely posting their reconstructions online after result publication v.gr. NeuroMorpho.Org (Nat Rev Neurosci 7:318-324, 2006). These neuroanatomical archives represent a crucial resource to explore the relationship between structure and function in the brain (Front Neurosci 6:49, 2012). However, such 'Cartesian' descriptions bear little intuitive information for neuroscientists. Here, we developed a simple prototype of a MATLAB-based software tool to quantitatively describe the 3D neuronal structures from public repositories. The program imports neuronal reconstructions and quantifies statistical distributions of basic morphological parameters such as branch length, tortuosity, branch's genealogy and bifurcation angles. Using these morphological distributions, our algorithm can generate a set of virtual neurons readily usable for network simulations. " 2014 Ledderose et al.; licensee BioMed Central Ltd.",,,,,,"10.1186/1755-7682-7-6",,,"http://hdl.handle.net/20.500.12104/39131","http://www.scopus.com/inward/record.url?eid=2-s2.0-84894415440&partnerID=40&md5=3f51cef11f5d8f41ee67db718b4ac77
A software tool for the analysis of neuronal morphology data
Anatomy plays a fundamental role in supporting and shaping nervous system activity. The remarkable progress of computer processing power within the last two decades has enabled the generation of electronic databases of complete three-dimensional (3D) dendritic and axonal morphology for neuroanatomical studies. Several laboratories are freely posting their reconstructions online after result publication v.gr. NeuroMorpho.Org (Nat Rev Neurosci 7:318-324, 2006). These neuroanatomical archives represent a crucial resource to explore the relationship between structure and function in the brain (Front Neurosci 6:49, 2012). However, such 'Cartesian' descriptions bear little intuitive information for neuroscientists. Here, we developed a simple prototype of a MATLAB-based software tool to quantitatively describe the 3D neuronal structures from public repositories. The program imports neuronal reconstructions and quantifies statistical distributions of basic morphological parameters such as branch length, tortuosity, branch's genealogy and bifurcation angles. Using these morphological distributions, our algorithm can generate a set of virtual neurons readily usable for network simulations. © 2014 Ledderose et al.; licensee BioMed Central Ltd
- …