Neural Computation, Multiple Realizability, and the Prospects for Mechanistic Explanation

Author(s):  
David M. Kaplan

There is an ongoing philosophical and scientific debate concerning the nature of computational explanation in the neurosciences. Recently, some have cited modeling work involving so-called canonical neural computations—standard computational modules that apply the same fundamental operations across multiple brain areas—as evidence that computational neuroscientists sometimes employ a distinctive explanatory scheme from that of mechanistic explanation. Because these neural computations can rely on diverse circuits and mechanisms, modeling the underlying mechanisms is supposed to be of limited explanatory value. I argue that these conclusions about computational explanations in neuroscience are mistaken, and rest upon a number of confusions about the proper scope of mechanistic explanation and the relevance of multiple realizability considerations. Once these confusions are resolved, the mechanistic character of computational explanations can once again be appreciated.

2020 ◽  
Author(s):  
Jafar Zamani ◽  
Ali Sadr ◽  
Amir-Homayoun Javadi

AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative disease that leads to anatomical atrophy, as evidenced by magnetic resonance imaging (MRI). Automated segmentation methods are developed to help with the segmentation of different brain areas. However, their reliability has yet to be fully investigated. To have a more comprehensive understanding of the distribution of changes in AD, as well as investigating the reliability of different segmentation methods, in this study we compared volumes of cortical and subcortical brain segments, using automated segmentation methods in more than 60 areas between AD and healthy controls (HC).MethodsA total of 44 MRI images (22 AD and 22 HC, 50% females) were taken from the minimal interval resonance imaging in Alzheimer’s disease (MIRIAD) dataset. HIPS, volBrain, CAT and BrainSuite segmentation methods were used for the subfields of hippocampus, and the rest of the brain.ResultsWhile HIPS, volBrain and CAT showed strong conformity with the past literature, BrainSuite misclassified several brain areas. Additionally, the volume of the brain areas that successfully discriminated between AD and HC showed a correlation with mini mental state examination (MMSE) scores. The two methods of volBrain and CAT showed a very strong correlation. These two methods, however, did not correlate with BrainSuite.ConclusionOur results showed that automated segmentation methods HIPS, volBrain and CAT can be used in the classification of AD and HC. This is an indication that such methods can be used to inform researchers and clinicians of underlying mechanisms and progression of AD.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247136
Author(s):  
Niels Chr. Hansen ◽  
Lindsey Reymore

The study of musical expertise illustrates how intense training in a specialized domain may instigate development of implicit skills. While absolute pitch, or the ability to identify musical pitches without external reference, is rare even in professional musicians and is understood to have a genetic component, anecdotal evidence and pilot data suggest that some musicians without traditional absolute pitch are nonetheless better able to name notes played on their musical instrument of expertise than notes played on less familiar instruments. We have previously termed this particular gain in absolute pitch identification ability “instrument-specific absolute pitch” (ISAP) and have proposed that this skill is related to learned instrument type-specific timbral and intonational idiosyncrasies and articulatory motor planning activated by the timbre of the instrument. In this Registered Report Protocol, we describe two experiments designed to investigate ISAP in professional oboists. Experiment 1 tests for ISAP ability by comparing oboists’ pitch identification accuracies for notes played on the oboe and on the piano. A subset of the participants from Experiment 1 who demonstrate this ability will be recruited for Experiment 2; the purpose of Experiment 2 is to test hypotheses concerning a mechanistic explanation for ISAP. The outcome of these experiments may provide support for the theory that some individuals have ISAP and that the underlying mechanisms of this ability may rely on the perception of subtle timbral/intonational idiosyncrasies and on articulatory motor planning developed through intensive long-term training. In general, this work will contribute to the understanding of specialized expertise, specifically of implicit abilities and biases that are not addressed directly in training, but that may yet develop through practice of a related skill set.


2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Christoph Lindemann ◽  
Joachim Ahlbeck ◽  
Sebastian H. Bitzenhofer ◽  
Ileana L. Hanganu-Opatz

Spindle oscillations have been described during early brain development and in the adult brain. Besides similarities in temporal patterns and involved brain areas, neonatal spindle bursts (NSBs) and adult sleep spindles (ASSs) show differences in their occurrence, spatial distribution, and underlying mechanisms. While NSBs have been proposed to coordinate the refinement of the maturating neuronal network, ASSs are associated with the implementation of acquired information within existing networks. Along with these functional differences, separate synaptic plasticity mechanisms seem to be recruited. Here, we review the generation of spindle oscillations in the developing and adult brain and discuss possible implications of their differences for synaptic plasticity. The first part of the review is dedicated to the generation and function of ASSs with a particular focus on their role in healthy and impaired neuronal networks. The second part overviews the present knowledge of spindle activity during development and the ability of NSBs to organize immature circuits. Studies linking abnormal maturation of brain wiring with neurological and neuropsychiatric disorders highlight the importance to better elucidate neonatal plasticity rules in future research.


2017 ◽  
Vol 114 (28) ◽  
pp. 7408-7413 ◽  
Author(s):  
Yan Jin ◽  
Yaohui Chen ◽  
Shimin Zhao ◽  
Kun-Liang Guan ◽  
Yuan Zhuang ◽  
...  

The involvement of host factors is critical to our understanding of underlying mechanisms of transposition and the applications of transposon-based technologies. Modified piggyBac (PB) is one of the most potent transposon systems in mammals. However, varying transposition efficiencies of PB among different cell lines have restricted its application. We discovered that the DNA–PK complex facilitates PB transposition by binding to PB transposase (PBase) and promoting paired-end complex formation. Mass spectrometry analysis and coimmunoprecipitation revealed physical interaction between PBase and the DNA–PK components Ku70, Ku80, and DNA-PKcs. Overexpression or knockdown of DNA–PK components enhances or suppresses PB transposition in tissue culture cells, respectively. Furthermore, germ-line transposition efficiency of PB is significantly reduced in Ku80 heterozygous mutant mice, confirming the role of DNA–PK in facilitating PB transposition in vivo. Fused dimer PBase can efficiently promote transposition. FRET experiments with tagged dimer PBase molecules indicated that DNA–PK promotes the paired-end complex formation of the PB transposon. These data provide a mechanistic explanation for the role of DNA–PK in facilitating PB transposition and suggest a transposition-promoting manipulation by enhancing the interaction of the PB ends. Consistent with this, deletions shortening the distance between the two PB ends, such as PB vectors with closer ends (PB-CE vectors), have a profound effect on transposition efficiency. Taken together, our study indicates that in addition to regulating DNA repair fidelity during transposition, DNA–PK also affects transposition efficiency by promoting paired-end complex formation. The approach of CE vectors provides a simple practical solution for designing efficient transposon vectors.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Minkang Kim ◽  
Jean Decety ◽  
Ling Wu ◽  
Soohyun Baek ◽  
Derek Sankey

AbstractOne means by which humans maintain social cooperation is through intervention in third-party transgressions, a behaviour observable from the early years of development. While it has been argued that pre-school age children’s intervention behaviour is driven by normative understandings, there is scepticism regarding this claim. There is also little consensus regarding the underlying mechanisms and motives that initially drive intervention behaviours in pre-school children. To elucidate the neural computations of moral norm violation associated with young children’s intervention into third-party transgression, forty-seven preschoolers (average age 53.92 months) participated in a study comprising of electroencephalographic (EEG) measurements, a live interaction experiment, and a parent survey about moral values. This study provides data indicating that early implicit evaluations, rather than late deliberative processes, are implicated in a child’s spontaneous intervention into third-party harm. Moreover, our findings suggest that parents’ values about justice influence their children’s early neural responses to third-party harm and their overt costly intervention behaviour.


2017 ◽  
Vol 37 (03) ◽  
pp. 202-207 ◽  
Author(s):  
Davit Manukyan ◽  
Nadine Müller-Calleja ◽  
Karl Lackner

SummaryThe antiphospholipid syndrome (APS) is characterized by venous and/or arterial thrombosis and severe pregnancy morbidity in presence of antiphospholipid antibodies (aPL). While there is compelling evidence that aPL cause the clinical manifestations of APS, the underlying mechanisms are still a matter of scientific debate. This is mainly related to the broad heterogeneity of aPL. There are three major types of aPL: The first one binds to (anionic) phospholipids, e.g. cardiolipin, in absence of other factors (cofactor independent aPL). The second type binds to phospholipids only in presence of protein cofactors, e.g. ß2-glycoprotein I (ß2GPI) (cofactor dependent aPL). The third type binds to cofactor proteins directly without need for phospholipids. It is widely believed that cofactor independent aPL (type 1) are associated with infections and, more importantly, non-pathogenic, while pathogenic aPL belong to the second and in particular to the third type. This view, in particular with regard to type 1 aPL, has not been undisputed and novel research data have shown that it is in fact untenable. We summarize the available data on the pathogenetic role of aPL and the implications for diagnosis of APS and future research.


2013 ◽  
Vol 25 (7) ◽  
pp. 1870-1890 ◽  
Author(s):  
Joel Kaardal ◽  
Jeffrey D. Fitzgerald ◽  
Michael J. Berry ◽  
Tatyana O. Sharpee

Current dimensionality-reduction methods can identify relevant subspaces for neural computations but do not favor one basis over the other within the relevant subspace. Finding the appropriate basis can simplify the description of the nonlinear computation with respect to the relevant variables, making it easier to elucidate the underlying neural computation and make hypotheses about the neural circuitry, giving rise to the observed responses. Part of the problem is that although some of the dimensionality reduction methods can identify many of the relevant dimensions, it is usually difficult to map out or interpret the nonlinear transformation with respect to more than a few relevant dimensions simultaneously without some simplifying assumptions. While recent approaches make it possible to create predictive models based on many relevant dimensions simultaneously, there still remains the need to relate such predictive models to the mechanistic descriptions of the operation of underlying neural circuitry. Here we demonstrate that transforming to a basis within the relevant subspace where the neural computation is best described by a given nonlinear function often makes it easier to interpret the computation and describe it with a small number of parameters. We refer to the corresponding basis as the functional basis, and illustrate the utility of such transformation in the context of logical OR and logical AND functions. We show that although dimensionality-reduction methods such as spike-triggered covariance are able to find a relevant subspace, they often produce dimensions that are difficult to interpret and do not correspond to a functional basis. The functional features can be found using a maximum likelihood approach. The results are illustrated using simulated neurons and recordings from retinal ganglion cells. The resulting features are uniquely defined and nonorthogonal, and they make it easier to relate computational and mechanistic models to each other.


2017 ◽  
Vol 85 (12) ◽  
Author(s):  
Aimin Wu ◽  
Piotr Tymoszuk ◽  
David Haschka ◽  
Simon Heeke ◽  
Stefanie Dichtl ◽  
...  

ABSTRACT Zinc sequestration by macrophages is considered a crucial host defense strategy against infection by the intracellular bacterium Salmonella enterica serovar Typhimurium. However, the underlying mechanisms remain elusive. In this study, we found that zinc favors pathogen survival within macrophages. Salmonella-hosting macrophages contained higher free zinc levels than did uninfected macrophages and cells that successfully eliminated bacteria, which was paralleled by the impaired production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in bacterium-harboring cells. A profound, zinc-mediated inhibition of NF-κB p65 transcriptional activity affecting the expression of the ROS- and RNS-forming enzymes phos47 and inducible nitric oxide synthase (iNOS) provided a mechanistic explanation for this phenomenon. Macrophages responded to infection by enhancing the expression of zinc-scavenging metallothioneins 1 and 2, whose genetic deletion caused increased free zinc levels, reduced ROS and RNS production, and increased the survival of Salmonella. Our data suggest that Salmonella invasion of macrophages results in a bacterium-driven increase in the intracellular zinc level, which weakens antimicrobial defense and the ability of macrophages to eradicate the pathogen. Thus, limitation of cytoplasmic zinc levels may help to control infection by intracellular bacteria.


2004 ◽  
Vol 13 (03) ◽  
pp. 669-689 ◽  
Author(s):  
LOTFI BEN ROMDHANE ◽  
BECHIR AYEB

In this work, we develop a neural model to solve causal reasoning problems (said also abduction) in the open, independent and incompatibility classes. We model the reasoning process by a single and global energy function using cooperative and competitive neural computation. The update rules of the distinct connections of the network are derived from its energy function using gradient descent techniques. Simulation results reveal a good performance of the model.


2015 ◽  
Vol 36 (3) ◽  
pp. 452-461 ◽  
Author(s):  
Laura Wiehle ◽  
Günter Raddatz ◽  
Tanja Musch ◽  
Meelad M. Dawlaty ◽  
Rudolf Jaenisch ◽  
...  

DNA methylation is a dynamic epigenetic modification with an important role in cell fate specification and reprogramming. The Ten eleven translocation (Tet) family of enzymes converts 5-methylcytosine to 5-hydroxymethylcytosine, which promotes passive DNA demethylation and functions as an intermediate in an active DNA demethylation process. Tet1/Tet2 double-knockout mice are characterized by developmental defects and epigenetic instability, suggesting a requirement for Tet-mediated DNA demethylation for the proper regulation of gene expression during differentiation. Here, we used whole-genome bisulfite and transcriptome sequencing to characterize the underlying mechanisms. Our results uncover the hypermethylation of DNA methylation canyons as the genomic key feature of Tet1/Tet2 double-knockout mouse embryonic fibroblasts. Canyon hypermethylation coincided with disturbed regulation of associated genes, suggesting a mechanistic explanation for the observed Tet-dependent differentiation defects. Based on these results, we propose an important regulatory role of Tet-dependent DNA demethylation for the maintenance of DNA methylation canyons, which prevents invasive DNA methylation and allows functional regulation of canyon-associated genes.


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