ترغب بنشر مسار تعليمي؟ اضغط هنا

A mathematical model of reward and executive circuitry in obsessive compulsive disorde

73   0   0.0 ( 0 )
 نشر من قبل Anca Radulescu
 تاريخ النشر 2015
  مجال البحث علم الأحياء
والبحث باللغة English




اسأل ChatGPT حول البحث

The neuronal circuit that controls obsessive and compulsive behaviors involves a complex network of brain regions (some with known involvement in reward processing). Among these are cortical regions, the striatum and the thalamus (which compose the CSTC pathway), limbic areas such as the amygdala and the hippocampus, and well as dopamine pathways. Abnormal dynamic behavior in this brain network is a hallmark feature of patients with increased anxiety and motor activity, like the ones affected by OCD. There is currently no clear understanding of precisely what mechanisms generates these behaviors. We attempt to investigate a collection of connectivity hypotheses of OCD by means of a computational model of the brain circuitry that governs reward and motion execution. Mathematically, we use methods from ordinary differential equations and continuous time dynamical systems. We use classical analytical methods as well as computational approaches to study phenomena in the phase plane (e.g., behavior of the systems solutions when given certain initial conditions) and in the parameter space (e.g., sensitive dependence of initial conditions). We find that different obsessive-compulsive subtypes may correspond to different abnormalities in the network connectivity profiles. We suggest that it is combinations of parameters (connectivity strengths between regions), rather the than the value of any one parameter taken independently, that provides the best basis for predicting behavior, and for understanding the heterogeneity of the illness.



قيم البحث

اقرأ أيضاً

Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2-3 percent. Recently, brain activity in the resting state is gathering attention as a new means of exploring altered functional connectivity in psychi atric disorders. Although previous resting-state functional magnetic resonance imaging studies investigated neurobiological abnormalities of patients with OCD, there are concerns that should be addressed. One concern is the validity of the hypothesis employed. Most studies used seed-based analysis of the fronto-striatal circuit, despite the potential for abnormalities in other regions. A hypothesis-free study is a promising approach in such a case, while it requires researchers to handle a dataset with large dimensions. Another concern is the reliability of biomarkers derived from a single dataset, which may be influenced by cohort-specific features. Here, by employing a recently developed machine-learning algorithm to avoid these concerns, we identified the first OCD biomarker that is generalized to an external dataset. We also demonstrated that the functional connectivities that contributed to the classification were widely distributed rather than locally constrained. Our generalizable classifier has the potential not only to deepen our understanding of the abnormal neural substrates of OCD but also to find use in clinical applications.
The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates numerous physiological processes. Disruptions in the activity of the HPA axis are correlated with many stress-related diseases such as post-traumatic stress disor der (PTSD) and major depressive disorder. In this paper, we characterize normal and diseased states of the HPA axis as basins of attraction of a dynamical system describing the inhibition of peptide hormones such as corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) by circulating glucocorticoids such as cortisol (CORT). In addition to including key physiological features such as ultradian oscillations in cortisol levels and self-upregulation of CRH neuron activity, our model distinguishes the relatively slow process of cortisol-mediated CRH biosynthesis from rapid trans-synaptic effects that regulate the CRH secretion process. Crucially, we find that the slow regulation mechanism mediates external stress-driven transitions between the stable states in novel, intensity, duration, and timing-dependent ways. These results indicate that the timing of traumatic events may be an important factor in determining if and how patients will exhibit hallmarks of stress disorders. Our model also suggests a mechanism whereby exposure therapy of stress disorders such as PTSD may act to normalize downstream dysregulation of the HPA axis.
A strong preference for novelty emerges in infancy and is prevalent across the animal kingdom. When incorporated into reinforcement-based machine learning algorithms, visual novelty can act as an intrinsic reward signal that vastly increases the effi ciency of exploration and expedites learning, particularly in situations where external rewards are difficult to obtain. Here we review parallels between recent developments in novelty-driven machine learning algorithms and our understanding of how visual novelty is computed and signaled in the primate brain. We propose that in the visual system, novelty representations are not configured with the principal goal of detecting novel objects, but rather with the broader goal of flexibly generalizing novelty information across different states in the service of driving novelty-based learning.
81 - Li Zhaoping , Alex Lewis , 2004
We analyze the dynamics of the neural circuit of the lamprey central pattern generator (CPG). This analysis provides insights into how neural interactions form oscillators and enable spontaneous oscillations in a network of damped oscillators, which were not apparent in previous simulations or abstract phase oscillator models. We also show how the different behaviour regimes (characterized by phase and amplitude relationships between oscillators) of forward/backward swimming, and turning, can be controlled using the neural connection strengths and external inputs.
Edge-centric functional connectivity (eFC) has recently been proposed to characterise the finest time resolution on the FC dynamics without the concomitant assumptions of sliding-window approaches. Here, we lay the mathematical foundations for the ed ge-centric analysis and examine its main findings from a quantitative perspective. The proposed framework provides a theoretical explanation for the observed occurrence of high-amplitude edge cofluctuations across datasets and clarifies why a few large events drive the node-centric FC (nFC). Our exposition also constitutes a critique of the edge-centric approach as currently applied to functional MRI (fMRI) time series. The central argument is that the existing findings based on edge time series can be derived from the static nFC under a null hypothesis that only accounts for the observed static spatial correlations and not the temporal ones. Challenging our analytic predictions against fMRI data from the Human Connectome Project confirms that the nFC is sufficient to replicate the eFC matrix, the edge communities, the large cofluctuations, and the corresponding brain activity mode. We conclude that the temporal structure of the edge time series has not so far been exploited sufficiently and encourage further work to explore features that cannot be explained by the presented static null model.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا