REVIEW | doi:10.20944/preprints202010.0065.v1
Subject: Biology, Anatomy & Morphology Keywords: Altruism; Basal ganglia; Dopamine; Emotion; Evolution; Plasticity; Social bonding
Online: 5 October 2020 (10:54:09 CEST)
In million years, under the pressure of natural selection, hominins acquired vocal learning, music, language, and intense cooperation, thanks to the efficacy of music in enhancing sociality. Thus, early in human evolution music became part of human life, a relevant activity, which required sophisticated perceptual and motor skills. It contributed to developing cultures and history, social bonding, and from the beginning of life strengthens the mother-baby relation while within the mother’s womb. Music existed in all known human cultures, although it varies in rhythmic and melodic complexity. It is art made of sounds capable of arousing emotions, evokes memories, engages multiple cognitive functions, and promotes attention, concentration, stimulates the imagination, creativity, and harmony of movement. Music and language share the same complex neural network. Music changes the chemistry of the brain activating the reward and prosocial systems, altruism, and allowing its use in therapy. This review explores "what" is music and illustrates the neural circuits that allow the production of music and language and those that transduce the sounds perceived by the ear, localize and archive them, allowing to recall them. Interestingly, songbirds share many commonalities with human music:, common neural pathways that shape vocal learning, and how they make sounds.
ARTICLE | doi:10.20944/preprints201811.0071.v1
Subject: Life Sciences, Other Keywords: basal angiosperms; chloroplast; comparative genomics; Nymphaeales; Nymphaeaceae; phylogenomics; water lily
Online: 2 November 2018 (16:20:31 CET)
The order Nymphaeales, consisting of three families with a record of eight genera, has gained significant interest from botanists probably due to its position as a basal-angiosperm. The phylogenetic relationships within the order have well been studied and resolved; however, a few controversial nodes still remain in the Nymphaeaceae including the position of the genus Nuphar. The position of the genus Nuphar and the monophyly of the Nymphaeaceae family remain uncertain. This study adds to the increasing number of completely sequenced plastid genomes of the Nymphaeales and applies large chloroplast gene data set in reconstructing the intergeneric relationships within the Nymphaeaceae. Five complete chloroplast genomes were newly generated, including a first one for the monotypic genus Euryale. Using a set of 66 protein coding genes from the chloroplast genomes of 17 taxa, the phylogenetic position of Nuphar was determined and a monophyletic Nymphaeaceae family was obtained with a convincing statistical support from both partitioned and unpartitioned data schemes. Although genomic comparative analyses revealed a high degree of synteny among the chloroplast genomes of the ancient angiosperms, key minor variations were evident particularly in the contraction/expansion of the Inverted Repeat regions and in RNA editing events. Genome structure, gene content and arrangement were highly conserved among the chloroplast genomes.
REVIEW | doi:10.20944/preprints202209.0146.v1
Subject: Life Sciences, Other Keywords: central obesity; waist circumference; physical activity; basal metabolic rate; body composition
Online: 12 September 2022 (11:36:37 CEST)
This article aims to systematically review the available evidence concerning the relationship between basal metabolism (BM), body composition (BC), and physical activity (PA) with central obesity. The search strategy was carried out using Web of Science, PubMed, Google Scholar, and SciELO following the PRISMA guidelines. The STROBE checklist and the Jadad scale for quality assessment were also used. A total of 1382 studies were initially identified being 25 publications eligible for systematic data extraction. Individual studies showed that adults with waist circumference (WC) above 88 cm in women and above 102 in men had a higher risk of metabolic alterations related to high absolute energy expenditure and less maximum oxygen consumption (VO2 max). Participants with central obesity presented a high percentage of body fat (BF%) between 30.6% and 41.6%. Most of the PA intervention studies reported reductions in WC between 1.3 and 5.8 cm. In conclusion, there is a direct relationship between the components of BM with central obesity and a direct association between central obesity and BF%. PA is a protective factor that needs to be promoted to reduce WC and control central obesity as a public health problem. PROSPERO ID registration: CRD42021232917.
ARTICLE | doi:10.20944/preprints201711.0136.v1
Subject: Earth Sciences, Environmental Sciences Keywords: diameter at breast height; basal area; frequency; density; important value index
Online: 21 November 2017 (03:43:54 CET)
Plants are an important feature of urban ecosystems which provide numerous environmental and ecosystem benefits such as defenses against noise and air pollution and conservation of biodiversity. The aim of this study was to investigate the structure and composition of urban vegetation in different urban habitats like roadsides, parks, gardens and playgrounds in Dhaka South City area. Stratified random sampling method was used in this study. A total of 221 plant species belonging to 63 families were identified and recorded. Among all plant species Swietenia macrophylla, Polyalthia longifolia, Cocos nucifera, Samanea saman, and Artocarpus heterophyllus are recorded as the most dominant. Most of the tree and shrub population were found between 6-9 m and 1-3m height classes whereas most of tree and shrub population were found in between 10-15cm dbh classes. Highest IVI was found for Swietenia macrophylla (193.22%) followed by Polyalthia longifolia (184.59%), Samanea saman (138.37%), Cocos nucifera (79.9%) and Delonix regia (68.27%) respectively. Average frequency, density, dbh and basal area were found 46.82%, 138.28 tree ha-1, 458.59 cm ha-1 and 12.33 m2 ha-1 respectively. Findings of this study reveals that structural attributes of plant represent quite young and still developing vegetation. This research will help to plan for future green infrastructure which will maintain ecosystem function, therefore, providing longer term benefits for the city dwellers.
ARTICLE | doi:10.20944/preprints202206.0376.v1
Subject: Biology, Other Keywords: effector proteins; genome-wide analysis; Ganoderma boninense; basal stem rot; genome architecture
Online: 28 June 2022 (04:59:14 CEST)
Ganoderma boninense is the major causal agent for the basal stem rot (BSR) disease in oil palm, causing the progressive rot of the basal part of the stem. Despite its prominence, key pathogenicity determinants for the aggressive nature of hemibiotrophic infection remain unknown. In this study, genome sequencing and annotation of G. boninense T10 were carried out using the Illumina sequencing platform and comparative genome analysis was performed with previously reported G. boninense strains (NJ3 and G3). The pan-secretome of G. boninense was constructed and comprised of 937 core orthogroups, 243 accessory orthogroups, and 84 strain-specific orthogroups. A set of core candidate effector proteins (CEPs) were found to be enriched with catalytic protein classified as the carbohydrate-active enzymes, hydrolases as well as non-catalytic proteins. Differential expression analysis revealed an upregulation of CEP genes which was linked to the suppression of PTI signaling cascade while the downregulation of CEP genes was linked to the inhibition of PTI by preventing host defense elicitation. Genome architecture analysis revealed the one-speed architecture of the G. boninense genome and the lack of preferential association of CEP genes to the transposable elements. The findings obtained from this study would aid in the characterization of pathogenicity determinants and molecular biomarkers of BSR disease.
REVIEW | doi:10.20944/preprints202201.0222.v1
Subject: Behavioral Sciences, Behavioral Neuroscience Keywords: Tics; Emotions; Basal ganglia; Tourette's syndrome; dopamine; HPA-axis; Premontory sensory phenomena
Online: 17 January 2022 (12:28:48 CET)
Tics can be associated with neurological disorders and are thought to be the result of dysfunctional basal ganglia pathways. In Tourette Syndrome (TS), excess dopamine in the striatum is thought to excite the thalamo-cortical circuits, producing tics. When external stressors activate the hypothalamic-pituitary-adrenal (HPA) axis, more dopamine is produced, furthering the excitation of tic-producing pathways. Emotional processing structures in the limbic are also activated during tics, providing further evidence of a possible emotional component in motor ticking behaviors. The purpose of the review is to better understand the relationship between emotional states and ticking behavior. We found support for the notion that premonitory-sensory phenomena (PSP), sensory stimulation, and other environmental stressors that impact the HPA-axis can influence tics through dopaminergic neurotransmission. Dopamine plays a vital role in cognition and motor control, and is an important neurotransmitter in the pathophysiology of other disorders such as obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD), which tend to be comorbid with ticking disorders and are thought to use similar pathways. It is concluded that there is an emotional component to ticking behaviors. Emotions primarily involving anxiety, tension, stress, and frustration have been associated with exacerbated tics, with PSP contributing to these feelings.
REVIEW | doi:10.20944/preprints202112.0119.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: resting state functional MRI; effective connectivity; dystonia; movement disorders; subcortical; basal ganglia
Online: 8 December 2021 (11:55:16 CET)
AbstractIn the evolving modern era of neuromodulation for movement disorders in adults and children, much progress has been made recently characterizing the human motor network (MN) with potentially important treatment implications. Herein is a focused review of relevant resting state fMRI functional and effective connectivity of the human motor network across the lifespan in health and disease. The goal is to examine how the transition from static functional to dynamic effective connectivity may be especially informative of network-targeted movement disorder therapies, with hopeful implications for children.Impact StatementWhile functional connectivity has elucidated much MN properties with relation to age, disease, and behavior, effective connectivity has been shown to be useful in MN-informed therapies in adults. Thus, effective connectivity may have potential to impact childhood movement disorder therapies, given the lower to no patient demand.
REVIEW | doi:10.20944/preprints201711.0096.v1
Subject: Biology, Other Keywords: Hedgehog signaling; skin; epidermis; hair follicle; development; homeostasis; basal cell carcinoma; signaling crosstalk
Online: 15 November 2017 (07:11:15 CET)
The epidermis is the outermost layer of skin and provides a protective barrier against environmental insults. It is a rapidly renewing tissue undergoing constant regeneration, maintained by several types of stem cells. Hedgehog (HH) ligands activate one of the fundamental signaling pathways that contribute to epidermal development, homeostasis and repair. The HH pathway interacts with other signal transduction pathways such as those activated by Wnt and bone morphogenetic protein. Furthermore, aberrant activation of HH signaling is associated with various tumors, including basal cell carcinoma. Therefore, an understanding of the regulatory mechanisms of the HH signaling pathway is important to elucidate fundamental mechanisms underlying both organogenesis and carcinogenesis. In this review, we discuss the role of the HH signaling pathway in skin development, homeostasis and basal cell carcinoma formation, providing an update of current knowledge in this field.
Subject: Life Sciences, Other Keywords: basal ganglia; dopamine; subthalamic nucleus; Parkinson's disease; brain learning; cholinergic interneurons; deep brain stimulation
Online: 31 May 2019 (11:24:42 CEST)
The basal ganglia (BG) are a central component of the brain, crucial to the initiation, execution and learning of adaptive actions. The BG are the major site of the action of dopamine. An important aspect of the BG architecture is the existence of two paths, direct and indirect, having different projection targets and dopamine receptor expression. To understand the BG, dopamine, and related disorders, it is imperative to understand the two paths. The standard account used in neuroscience research for decades posits that the role of the direct path is to support movements, while that of the indirect path is to suppress unselected or completed movements. This account is contradicted by converging evidence. Here, we explain why the arguments supporting the standard account are flawed, and present a new account, in which the role of the indirect path is completely opposite: to support automated execution. During acute events, the direct path allows coarse responses. These are refined by competition, and the resulting focused response is executed and learned by the indirect path, assisted by cholinergic interneurons and the subthalamic nucleus (STN). The new account allows a novel understanding of the symptoms of Parkinson's disease, in particular tremor and rigidity, and of its treatment by STN deep brain stimulation.
ARTICLE | doi:10.20944/preprints202008.0264.v1
Subject: Materials Science, General Materials Science Keywords: basal plane bending; homoepitaxial single-crystal diamond (SCD); high-resolution x-ray diffraction; growth temperature
Online: 11 August 2020 (10:14:27 CEST)
We report herein high-resolution x-ray diffraction measurements of basal plane bending of homoepitaxial single-crystal diamond (SCD). The results reveal that growth parameters such as temperature, growth time and basal plane bending of the substrate affect the basal plane bending of SCD. First, the basal plane bending of SCD depends mainly on the substrate itself. The basal plane bending of SCD becomes more severe with increasing basal plane bending of the substrate and this type of basal plane bending cannot be recovered. The SCD growth experiments show that the basal plane bending increases at high temperature and with increasing growth time. Finally, to understand the mechanism behind basal plane bending, we investigate the substrate-surface temperature distribution as a function of basal plane bending of SCD fabricated by chemical vapour deposition (CVD). This allows us to propose a bending model and understand the origin of basal plane bending. The results indicate that an uneven temperature distribution on the substrate surface is the main cause of the CVD diamond base-plane bending.
REVIEW | doi:10.20944/preprints202106.0448.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Parkinson’s disease; abnormal involuntary movements; dopaminergic signaling; basal ganglia; spiny projection neurons; neurotransmission; deep brain stimulation
Online: 16 June 2021 (14:17:30 CEST)
Levodopa remains the primary drug for controlling motor symptoms in Parkinson's disease through the whole course, but over time complications develop in the form of dyskinesias, which gradually become more frequent and severe. These abnormal, involuntary, hyperkinetic movements are mostly characteristic of the ON phase and reflect an excess of exogenous levodopa. They may also occur during OFF phase, or in both phases. Over the past 10 years, the issue of levodopa-induced dyskinesia has been the subject of research into both the substrate of this pathology and potential remedial strategies. The purpose of the present study was to review the results of recent research on the background and treatment of dyskinesia. To this end, databases were reviewed using a search strategy that included both relevant keywords related to the topic and appropriate filters to limit results to English-language literature published since 2010. Based on the selected papers, the current state of knowledge on morphological, functional, genetic, and clinical features of levodopa-induced dyskinesia, as well as pharmacological, genetic treatment and other therapies such as deep brain stimulation are described.
REVIEW | doi:10.20944/preprints202005.0488.v1
Subject: Keywords: striatal development; Huntington’s disease; spiny projection neurons; medium spiny neurons; neuronal excitability; striosomes; matrix; basal ganglia
Online: 31 May 2020 (18:20:17 CEST)
Huntington's disease (HD) is an inherited neurodegenerative disorder that usually starts during midlife with progressive alterations of motor and cognitive functions. The disease is caused by a CAG repeat expansion within the huntingtin gene leading to severe striatal neurodegeneration. Recent studies conducted on pre-HD children highlight early striatal developmental alterations starting as soon as 6 years old, the earliest age assessed. These findings, in line with data from mouse models of HD, raise the question of when during development do the first disease-related striatal alterations emerge or whether they contribute to the later appearance of the neurodegenerative features of the disease. In this review we will describe the different stages of striatal network development and then discuss recent evidence for its alterations in rodent models of the disease. We argue that a better understanding of the striatum’s development should help in assessing aberrant neurodevelopmental processes linked to the HD mutation.
ARTICLE | doi:10.20944/preprints201810.0314.v1
Subject: Life Sciences, Other Keywords: hepatitis B virus (HBV); cccDNA; basal core promoter; X promoter; single nucleotide polymorphisms; logo analyses; genotype alignments
Online: 15 October 2018 (13:03:06 CEST)
Over 250 million people are infected chronically with hepatitis B virus (HBV), the leading cause of liver cancer worldwide. HBV persists due in part to its compact, stable minichromosome, the covalently-closed, circular DNA (cccDNA), which resides in the hepatocytes’ nuclei. Current therapies target downstream replication products, however, a true virological cure will require targeting the cccDNA. Finding targets on such a small, compact genome is challenging. For HBV, to remain replication-competent, it needs to maintain nucleotide fidelity in key regions, such as the promoter regions, to ensure that it can continue to utilize the necessary host proteins. HBVdb (HBV database) is a repository of HBV sequences spanning all genotypes (A-H) amplified from clinical samples, and hence implying an extensive collection of replication-competent viruses. Here, we analyzed the HBV sequences from HBVdb using bioinformatics tools to comprehensively assess the HBV core and X promoter regions amongst the nearly 70,000 HBV sequences for highly-conserved nucleotides and variant frequencies. Notably, there is a high degree of nucleotide conservation within specific segments of these promoter regions highlighting their importance in potential host protein-viral interactions and thus the virus’ viability. Such findings may have key implications for designing antivirals to target these areas.
REVIEW | doi:10.20944/preprints202012.0129.v1
Subject: Biology, Anatomy & Morphology Keywords: oil palm; breeding; sustainability; certification; diseases; basal stem rot; phytophthora; climate change; modelling; supply chains; biodiesel; covid-19
Online: 7 December 2020 (08:50:30 CET)
Background Oil palm (OP), Elaeis guineensis , is by far the most important global oil crop, supplying about 40% of total traded vegetable oil. Palm oils are key dietary components consumed daily by over three billion people, mostly in Asia, and also have a wide range of important non-food uses including in cleansing and sanitising products. Main body Oil palm is a perennial crop with a >25-year life cycle and an exceptionally small land footprint compared to annual oilseed crops. Oil palm crops globally produce an annual 81 million tonnes (Mt) of oil from about 19 million hectares (Mha). In contrast, the second and third largest vegetable oil crops, soybean and rapeseed, yield a combined 84 Mt oil but occupy over 163 Mha of increasingly scarce arable land. Despite this advantage, oil palm has acquired a poor environmental reputation, especially in Europe and North America, although soybean planting is now responsible for more deforestation. Oil palm crops face other challenges in the 2020s. On the demand side, these include changing consumer purchasing habits, threats to global trade systems, and diminishing demand for liquid fuels as transport systems become increasingly electrified. On the supply side, major issues include stagnant yields in ageing plantations, sluggish replanting of improved varieties, labour shortages, diseases and climatic/ environmental threats. The latter include the increasing incidence of new and existing pests/diseases and a general lack of climatic resilience, especially relating to elevated temperatures and increasingly erratic rainfall patterns. This review surveys the oil palm sector in the 2020s and beyond, its major challenges and options for future progress. Conclusions Oil palm crops face many future challenges, including emerging threats from climate change and new pests and diseases, that require more effective international collaboration. Nevertheless, new breeding technologies are providing the promise of improvements, such as much higher yielding varieties, improved oil profiles, enhanced disease resistance and modified crop architecture to enable harvesting mechanisation. The industry also needs to redouble its efforts to engage with global consumers in a constructive dialogue aimed at addressing its image problem and explaining the many benefits of its products.
REVIEW | doi:10.20944/preprints202006.0050.v1
Subject: Behavioral Sciences, Other Keywords: competitive learning and memory functions; cognitive development; basal ganglia; medial temporal lobe; prefrontal cortex; model-based learning; model-free learning
Online: 5 June 2020 (14:10:15 CEST)
There has been a growing interest in incorporating psychological and neuroscientific knowledge about the development of cognitive functions in educational policies and academic practices. In this paper, we argue that the current knowledge about the interactions between these functions and their neurodevelopmental characteristics should also be considered in order to develop practices that could be better suited to pupils depending on their age. To facilitate this, we review current neuroscientific knowledge on the competitive interactions between two neural circuitry underlying distinct learning functions, their developmental trajectories and how they are linked to other functions such as cognitive control. The incorporation of this knowledge in education could help improve academic outcomes.
ARTICLE | doi:10.20944/preprints201806.0092.v1
Subject: Life Sciences, Other Keywords: Neuroscience; basal ganglia; cortical layers; cerebellum; habenula; inhibition; predictions; dopamine; serotonin; acetylcholine; opioids; mirror neurons; place cells; language; imagery; working memory
Online: 7 June 2018 (06:02:29 CEST)
Understanding brain function is one of the most important open problems in science today. At present, there is no concrete theory for how the brain works. Here, a theory is presented that provides a detailed mechanistic biological account of the brain’s capacities. Brain function is managed by a response (R) process that is structurally similar to the immune response, and shows anatomical and molecular specificity. Different R process stages utilize different cortical layers, hippocampus fields, basal ganglia paths, GABAergic interneurons, cerebellum paths, and molecular agents such as dopamine, serotonin and opioids. We show how the R process supports hierarchical action sequences, language and thought. The theory is supported by a large body of experimental evidence in many modalities, and accounts for virtually all of the major facts known about the brain at the system level.
ARTICLE | doi:10.20944/preprints201806.0020.v1
Subject: Medicine & Pharmacology, Dermatology Keywords: Annona muricata; apoptosis; basal cell carcinoma; cutaneous squamous cell carcinoma; graviola; Hedgehog signaling pathway; natural products chemistry; non-melanoma skin cancer
Online: 1 June 2018 (13:00:02 CEST)
Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; ii) induce G0/G1 cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iv) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs
REVIEW | doi:10.20944/preprints201705.0108.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: squamous cell carcinoma (SCC), Grainyhead-like 3 (Grhl3), interfollicular epidermis (IFE), supra-basal epidermis, involucrin (IVL), cancer-initiating cell (CIC), cancer stem cell (CSC).
Online: 12 May 2017 (18:15:31 CEST)
Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population as well as an economic load to the health care system, yet treatments of these preventable cancers remain ineffective. Although primary prevention is possible through minimising sunlight exposure, the World Health Organisation estimates that between 2 and 3 million new cases of NMSCs are diagnosed each year, accounting for 1 in 3 of all newly diagnosed cancers. Furthermore, studies have estimated there has been a 2-fold increase in the incidence of NMSCs between 1960s and 1980s. The increase in cases of NMSCs as well as the lack of effective treatments makes the need for novel therapeutic approaches all the more necessary. To rationally develop more targeted treatments for NMSCs, a better understanding of the cell of origin, in addition to the underlying pathophysiological mechanisms that govern the development of these cancers, is urgent. NMSCs are generally thought to arise from specific types of stem cells that become the source of clonal expansion of tumourigenic cells. Previous research on SCC has alluded to these stem cells being localised in the basal compartment of the skin, which ordinarily houses the progenitor cells that contribute towards wound healing and normal cell turnover of overlying epidermal skin layers. More recent research has suggested that commitment to differentiation, which requires exiting the basal, progenitor-cell compartment, is a reversible mechanism. Genetic modifications engage differentiated cells into dedifferentiation, converting them into cancer-initiating cells (CICs) and thereby promoting a tumourigenic environment. Here we explore the most recent developments in the understanding of skin SCC cell of origin, and discuss a case study illustrating the loss of the Grainy-head like 3 (GRHL3) transcription factor in suprabasal layers, which confers a tendency towards tumour development and thereby challenging the “stem cell” theory of tumourigenesis.
REVIEW | doi:10.20944/preprints201809.0281.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: axon guidance; growth cone; cytoskeleton; caspases; apoptosis; signal integration; basal level of caspase activity; death associated inhibitor of apoptosis; axon branching; Netrin; DCC; frazzled; slit; robo; Drosophila
Online: 16 September 2018 (09:43:52 CEST)
Navigating growth cones are exposed to multiple signals simultaneously and have to integrate competing cues into a coherent navigational response. Integration of guidance cues is traditionally thought to occur at the level of cytoskeletal dynamics. Drosophila studies indicate that cells exhibit a low level of continuous caspase protease activation, and that axon guidance cues can activate or suppress caspase activity. We base a model for axon guidance on these observations. By analogy with other systems in which caspase signaling has non-apoptotic functions, we propose that caspase signaling can either reinforce repulsion or negate attraction in response to external guidance cues by cleaving cytoskeletal proteins. Over the course of an entire trajectory, incorrectly navigating axons may pass the threshold for apoptosis and be eliminated, whereas axons making correct decisions will survive. These observations would also explain why neurotrophic factors can act as axon guidance cues and why axon guidance systems such as Slit/Robo signaling may act as tumor suppressors in cancer.
ARTICLE | doi:10.20944/preprints201805.0137.v1
Subject: Life Sciences, Other Keywords: neuroscience; thalamus; basal ganglia; cortical layers; hippocampus; cerebellum; habenula; claustrum; amygdala; inhibition; predictions; automaticity; dopamine; serotonin; acetylcholine; opioids; oxytocin; crh; glucocorticoids; cannabinoids; orexin; melanin-concentrating hormone; mirror neuron; place cells; grid cells; language; imagery; working memory; attention; consciousness; emotions
Online: 9 May 2018 (05:35:51 CEST)
Understanding brain function is one of the most important problems in human history. At present, there is no concrete theory for how the brain works. Here, a theory is presented that provides a detailed mechanistic biological account of the brain's capacities, including motor control, functional states, language, and thinking. Brain function is managed by a well-defined response (R) process that is generally similar to the process underlying the immune system. The R process is strongly reflected in the brain's anatomy, physiology, and external interactions. Different R process stages are supported by distinct excitatory networks located in different cortical layers, hippocampal fields, and bagal ganglia paths, by distinct coordination networks comprised of GABAergic interneurons, and by distinct molecular agents. The roles of norepinephrine, serotonin, dopamine and acetylcholine is to promote the alert, planning, goal-setting and execution R process modes, respectively. Opioids and oxytocin promote termination by success, failure, fight or run, while glucocorticoids and cannabinoids suppress acute responses to protect cells. The R process has two instances occurring at different time scales. The millisecond-scale Quax process implements the execution of hierarchical sequences of movements and thoughts, in which the selection of the next action is determined via interaction between top-down predictions and sensory inputs. The slower Need process controls the satisfaction of internal and external needs. The theory differs from the existing standard accounts in many of the major topics (e.g., the basal ganglia, dopamine, language), and shows how cognition results from biological processes.