A lateralized motor network in order to understand adaptation to visuomotor rotation.

Objective.The functional asymmetry between the two brain hemispheres in language and spatial processing is well documented. However, a description of difference in control between the two hemispheres in motor function is not well established. Our primary objective in this study was to examine the distribution of control in the motor hierarchy and its variation across hemispheres.Approach.We developed a computation model termed the bilateral control network and implemented the same in a neural network framework to be used to replicate certain experimental results. The network consists of a simple arm model capable of making movements in 2D space and a motor hierarchy with separate elements coding target location, estimated position of arm, direction, and distance to be moved by the arm, and the motor command sent to the arm. The main assumption made here is the division of direction and distance coding between the two hemispheres with distance coded in the non-dominant and direction coded in the dominant hemisphere.Main results.With this assumption, the network was able to show main results observed in visuomotor adaptation studies. Importantly it showed decrease in error exhibited by the untrained arm while the other arm underwent training compared to the corresponding naïve arm's performance-transfer of motor learning from trained to the untrained arm. It also showed how this varied depending on the performance variable used-with distance as the measure, the non-dominant arm showed transfer and with direction, dominant arm showed transfer.Significance.Our results indicate the possibility of shared control between the two hemispheres. If indeed found true, this result could have major significance in motor rehabilitation as treatment strategies will need to be designed in order to account for this and can no longer be confined to the arm contralateral to the affected hemisphere.

A phenomenological model of whole brain dynamics using a network of neural oscillators with power-coupling.

We present a general, trainable oscillatory neural network as a large-scale model of brain dynamics. The model has a cascade of two stages - an oscillatory stage and a complex-valued feedforward stage - for modelling the relationship between structural connectivity and functional connectivity from neuroimaging data under resting brain conditions. Earlier works of large-scale brain dynamics that used Hopf oscillators used linear coupling of oscillators. A distinctive feature of the proposed model employs a novel form of coupling known as power coupling. Oscillatory networks based on power coupling can accurately model arbitrary multi-dimensional signals. Training the lateral connections in the oscillator layer is done by a modified form of Hebbian learning, whereas a variation of the complex backpropagation algorithm does training in the second stage. The proposed model can not only model the empirical functional connectivity with remarkable accuracy (correlation coefficient between simulated and empirical functional connectivity- 0.99) but also identify default mode network regions. In addition, we also inspected how structural loss in the brain can cause significant aberration in simulated functional connectivity and functional connectivity dynamics; and how it can be restored with optimized model parameters by an in silico perturbational study.

A deep network-based model of hippocampal memory functions under normal and Alzheimer's disease conditions.

We present a deep network-based model of the associative memory functions of the hippocampus. The proposed network architecture has two key modules: (1) an autoencoder module which represents the forward and backward projections of the cortico-hippocampal projections and (2) a module that computes familiarity of the stimulus and implements hill-climbing over the familiarity which represents the dynamics of the loops within the hippocampus. The proposed network is used in two simulation studies. In the first part of the study, the network is used to simulate image pattern completion by autoassociation under normal conditions. In the second part of the study, the proposed network is extended to a heteroassociative memory and is used to simulate picture naming task in normal and Alzheimer's disease (AD) conditions. The network is trained on pictures and names of digits from 0 to 9. The encoder layer of the network is partly damaged to simulate AD conditions. As in case of AD patients, under moderate damage condition, the network recalls superordinate words ("odd" instead of "nine"). Under severe damage conditions, the network shows a null response ("I don't know"). Neurobiological plausibility of the model is extensively discussed.

Modeling the development of cortical responses in primate dorsal ("where") pathway to optic flow using hierarchical neural field models.

Although there is a plethora of modeling literature dedicated to the object recognition processes of the ventral ("what") pathway of primate visual systems, modeling studies on the motion-sensitive regions like the Medial superior temporal area (MST) of the dorsal ("where") pathway are relatively scarce. Neurons in the MST area of the macaque monkey respond selectively to different types of optic flow sequences such as radial and rotational flows. We present three models that are designed to simulate the computation of optic flow performed by the MST neurons. Model-1 and model-2 each composed of three stages: Direction Selective Mosaic Network (DSMN), Cell Plane Network (CPNW) or the Hebbian Network (HBNW), and the Optic flow network (OF). The three stages roughly correspond to V1-MT-MST areas, respectively, in the primate motion pathway. Both these models are trained stage by stage using a biologically plausible variation of Hebbian rule. The simulation results show that, neurons in model-1 and model-2 (that are trained on translational, radial, and rotational sequences) develop responses that could account for MSTd cell properties found neurobiologically. On the other hand, model-3 consists of the Velocity Selective Mosaic Network (VSMN) followed by a convolutional neural network (CNN) which is trained on radial and rotational sequences using a supervised backpropagation algorithm. The quantitative comparison of response similarity matrices (RSMs), made out of convolution layer and last hidden layer responses, show that model-3 neuron responses are consistent with the idea of functional hierarchy in the macaque motion pathway. These results also suggest that the deep learning models could offer a computationally elegant and biologically plausible solution to simulate the development of cortical responses of the primate motion pathway.

The development of bi-directionally coupled self-organizing neurovascular networks captures orientation-selective neural and hemodynamic cortical responses.

Networks of neurons are the primary substrate of information processing. Conversely, blood vessels in the brain are generally viewed to have physiological functions unrelated to information processing, such as the timely supply of oxygen, and other nutrients to the neural tissue. However, recent studies have shown that cerebral microvessels, like neurons, exhibit tuned responses to sensory stimuli. Tuned neural responses to sensory stimuli may be enhanced with experience-dependent Hebbian plasticity and other forms of learning. Hence, it is possible that the microvascular network might also be subject to some form of competitive learning rules during early postnatal development such that its fine-scale structure becomes optimized for metabolic delivery to a given neural micro-architecture. To explore the possibility of adaptive lateral interactions and tuned responses in cerebral microvessels, we modelled the cortical neurovascular network by interconnecting two laterally connected self-organizing networks. The afferent and lateral connections of the neural and vascular networks were defined by trainable weights. By varying the topology of lateral connectivity in the vascular network layer, we observed that the partial correspondence of feature selectivity between neural and hemodynamic responses could be explained by lateral coupling across local blood vessels such that the central domain receives an excitatory drive of more blood flow and a distal surrounding region where blood flow is reduced. Critically, our simulations suggest a new role for feedback from the vascular to the neural network because the radius of vascular perfusion determines whether the cortical neural map develops into a clustered vs. salt-and-pepper organization.

A generalized reinforcement learning based deep neural network agent model for diverse cognitive constructs.

Human cognition is characterized by a wide range of capabilities including goal-oriented selective attention, distractor suppression, decision making, response inhibition, and working memory. Much research has focused on studying these individual components of cognition in isolation, whereas in several translational applications for cognitive impairment, multiple cognitive functions are altered in a given individual. Hence it is important to study multiple cognitive abilities in the same subject or, in computational terms, model them using a single model. To this end, we propose a unified, reinforcement learning-based agent model comprising of systems for representation, memory, value computation and exploration. We successfully modeled the aforementioned cognitive tasks and show how individual performance can be mapped to model meta-parameters. This model has the potential to serve as a proxy for cognitively impaired conditions, and can be used as a clinical testbench on which therapeutic interventions can be simulated first before delivering to human subjects.

BIAS-3D: Brain inspired attentional search model fashioned after what and where/how pathways for target search in 3D environment.

We propose a brain inspired attentional search model for target search in a 3D environment, which has two separate channels-one for the object classification, analogous to the "what" pathway in the human visual system, and the other for prediction of the next location of the camera, analogous to the "where" pathway. To evaluate the proposed model, we generated 3D Cluttered Cube datasets that consist of an image on one vertical face, and clutter or background images on the other faces. The camera goes around each cube on a circular orbit and determines the identity of the image pasted on the face. The images pasted on the cube faces were drawn from: MNIST handwriting digit, QuickDraw, and RGB MNIST handwriting digit datasets. The attentional input of three concentric cropped windows resembling the high-resolution central fovea and low-resolution periphery of the retina, flows through a Classifier Network and a Camera Motion Network. The Classifier Network classifies the current view into one of the target classes or the clutter. The Camera Motion Network predicts the camera's next position on the orbit (varying the azimuthal angle or "θ"). Here the camera performs one of three actions: move right, move left, or do not move. The Camera-Position Network adds the camera's current position (θ) into the higher features level of the Classifier Network and the Camera Motion Network. The Camera Motion Network is trained using Q-learning where the reward is 1 if the classifier network gives the correct classification, otherwise 0. Total loss is computed by adding the mean square loss of temporal difference and cross entropy loss. Then the model is trained end-to-end by backpropagating the total loss using Adam optimizer. Results on two grayscale image datasets and one RGB image dataset show that the proposed model is successfully able to discover the desired search pattern to find the target face on the cube, and also classify the target face accurately.

Interaction of network and rehabilitation therapy parameters in defining recovery after stroke in a Bilateral Neural Network.

BACKGROUND: Restoring movement after hemiparesis caused by stroke is an ongoing challenge in the field of rehabilitation. With several therapies in use, there is no definitive prescription that optimally maps parameters of rehabilitation with patient condition. Recovery gets further complicated once patients enter chronic phase. In this paper, we propose a rehabilitation framework based on computational modeling, capable of mapping patient characteristics to parameters of rehabilitation therapy. METHOD: To build such a system, we used a simple convolutional neural network capable of performing bilateral reaching movements in 3D space using stereovision. The network was designed to have bilateral symmetry to reflect the bilaterality of the cerebral hemispheres with the two halves joined by cross-connections. This network was then modified according to 3 chosen patient characteristics-lesion size, stage of recovery (acute or chronic) and structural integrity of cross-connections (analogous to Corpus Callosum). Similarly, 3 parameters were used to define rehabilitation paradigms-movement complexity (Exploratory vs Stereotypic), hand selection mode (move only affected arm, CIMT vs move both arms, BMT), and extent of plasticity (local vs global). For each stroke condition, performance under each setting of the rehabilitation parameters was measured and results were analyzed to find the corresponding optimal rehabilitation protocol. RESULTS: Upon analysis, we found that regardless of patient characteristics network showed better recovery when high complexity movements were used and no significant difference was found between the two hand selection modes. Contrary to these two parameters, optimal extent of plasticity was influenced by patient characteristics. For acute stroke, global plasticity is preferred only for larger lesions. However, for chronic, plasticity varies with structural integrity of cross-connections. Under high integrity, chronic prefers global plasticity regardless of lesion size, but with low integrity local plasticity is preferred. CONCLUSION: Clinically translating the results obtained, optimal recovery may be observed when paretic arm explores the available workspace irrespective of the hand selection mode adopted. However, the extent of plasticity to be used depends on characteristics of the patient mainly stage of stroke and structural integrity. By using systems as developed in this study and modifying rehabilitation paradigms accordingly it is expected post-stroke recovery can be maximized.

Modeling the tonotopic map using a two-dimensional array of neural oscillators.

We present a model of a tonotopic map known as the Oscillatory Tonotopic Self-Organizing Map (OTSOM). It is a 2-dimensional, self-organizing array of Hopf oscillators, capable of performing a Fourier-like decomposition of the input signal. While the rows in the map encode the input phase, the columns encode frequency. Although Hopf oscillators exhibit resonance to a sinusoidal signal when there is a frequency match, there is no obvious way to also achieve phase tuning. We propose a simple method by which a pair of Hopf oscillators, unilaterally coupled through a coupling scheme termed as modified power coupling, can exhibit tuning to the phase offset of sinusoidal forcing input. The training of OTSOM is performed in 2 stages: while the frequency tuning is adapted in Stage 1, phase tuning is adapted in Stage 2. Earlier tonotopic map models have modeled frequency as an abstract parameter unconnected to any oscillation. By contrast, in OTSOM, frequency tuning emerges as a natural outcome of an underlying resonant process. The OTSOM model can possibly be regarded as an approximation of the tonotopic map found in the primary auditory cortices of mammals, particularly exemplified in the studies of echolocating bats.

The Influence of Neural Activity and Neural Cytoarchitecture on Cerebrovascular Arborization: A Computational Model.

Normal functioning of the brain relies on a continual and efficient delivery of energy by a vast network of cerebral blood vessels. The bidirectional coupling between neurons and blood vessels consists of vasodilatory energy demand signals from neurons to blood vessels, and the retrograde flow of energy substrates from the vessels to neurons, which fuel neural firing, growth and other housekeeping activities in the neurons. Recent works indicate that, in addition to the functional coupling observed in the adult brain, the interdependence between the neural and vascular networks begins at the embryonic stage, and continues into subsequent developmental stages. The proposed Vascular Arborization Model (VAM) captures the effect of neural cytoarchitecture and neural activity on vascular arborization. The VAM describes three important stages of vascular tree growth: (i) The prenatal growth phase, where the vascular arborization depends on the cytoarchitecture of neurons and non-neural cells, (ii) the post-natal growth phase during which the further arborization of the vasculature depends on neural activity in addition to neural cytoarchitecture, and (iii) the settling phase, where the fully grown vascular tree repositions its vascular branch points or nodes to ensure minimum path length and wire length. The vasculature growth depicted by VAM captures structural characteristics like vascular volume density, radii, mean distance to proximal neurons in the cortex. VAM-grown vasculature agrees with the experimental observation that the neural densities do not covary with the vascular density along the depth of the cortex but predicts a high correlation between neural areal density and microvascular density when compared over a global scale (across animals and regions). To explore the influence of neural activity on vascular arborization, the VAM was used to grow the vasculature in neonatal rat whisker barrel cortex under two conditions: (i) Control, where the whiskers were intact and (ii) Lesioned, where one row of whiskers was cauterized. The model captures a significant reduction in vascular branch density in lesioned animals compared to control animals, concurring with experimental observation.

A Multi-Scale Computational Model of Levodopa-Induced Toxicity in Parkinson's Disease.

Parkinson's disease (PD) is caused by the progressive loss of dopaminergic cells in substantia nigra pars compacta (SNc). The root cause of this cell loss in PD is still not decisively elucidated. A recent line of thinking has traced the cause of PD neurodegeneration to metabolic deficiency. Levodopa (L-DOPA), a precursor of dopamine, used as a symptom-relieving treatment for PD, leads to positive and negative outcomes. Several researchers inferred that L-DOPA might be harmful to SNc cells due to oxidative stress. The role of L-DOPA in the course of the PD pathogenesis is still debatable. We hypothesize that energy deficiency can lead to L-DOPA-induced toxicity in two ways: by promoting dopamine-induced oxidative stress and by exacerbating excitotoxicity in SNc. We present a systems-level computational model of SNc-striatum, which will help us understand the mechanism behind neurodegeneration postulated above and provide insights into developing disease-modifying therapeutics. It was observed that SNc terminals are more vulnerable to energy deficiency than SNc somas. During L-DOPA therapy, it was observed that higher L-DOPA dosage results in increased loss of terminals in SNc. It was also observed that co-administration of L-DOPA and glutathione (antioxidant) evades L-DOPA-induced toxicity in SNc neurons. Our proposed model of the SNc-striatum system is the first of its kind, where SNc neurons were modeled at a biophysical level, and striatal neurons were modeled at a spiking level. We show that our proposed model was able to capture L-DOPA-induced toxicity in SNc, caused by energy deficiency.

A Network Architecture for Bidirectional Neurovascular Coupling in Rat Whisker Barrel Cortex.

Neurovascular coupling is typically considered as a master-slave relationship between the neurons and the cerebral vessels: the neurons demand energy which the vessels supply in the form of glucose and oxygen. In the recent past, both theoretical and experimental studies have suggested that the neurovascular coupling is a bidirectional system, a loop that includes a feedback signal from the vessels influencing neural firing and plasticity. An integrated model of bidirectionally connected neural network and the vascular network is hence required to understand the relationship between the informational and metabolic aspects of neural dynamics. In this study, we present a computational model of the bidirectional neurovascular system in the whisker barrel cortex and study the effect of such coupling on neural activity and plasticity as manifest in the whisker barrel map formation. In this model, a biologically plausible self-organizing network model of rate coded, dynamic neurons is nourished by a network of vessels modeled using the biophysical properties of blood vessels. The neural layer which is designed to simulate the whisker barrel cortex of rat transmits vasodilatory signals to the vessels. The feedback from the vessels is in the form of available oxygen for oxidative metabolism whose end result is the adenosine triphosphate (ATP) necessary to fuel neural firing. The model captures the effect of the feedback from the vascular network on the neuronal map formation in the whisker barrel model under normal and pathological (Hypoxia and Hypoxia-Ischemia) conditions.

Artificial neurovascular network (ANVN) to study the accuracy vs. efficiency trade-off in an energy dependent neural network.

Artificial feedforward neural networks perform a wide variety of classification and function approximation tasks with high accuracy. Unlike their artificial counterparts, biological neural networks require a supply of adequate energy delivered to single neurons by a network of cerebral microvessels. Since energy is a limited resource, a natural question is whether the cerebrovascular network is capable of ensuring maximum performance of the neural network while consuming minimum energy? Should the cerebrovascular network also be trained, along with the neural network, to achieve such an optimum? In order to answer the above questions in a simplified modeling setting, we constructed an Artificial Neurovascular Network (ANVN) comprising a multilayered perceptron (MLP) connected to a vascular tree structure. The root node of the vascular tree structure is connected to an energy source, and the terminal nodes of the vascular tree supply energy to the hidden neurons of the MLP. The energy delivered by the terminal vascular nodes to the hidden neurons determines the biases of the hidden neurons. The "weights" on the branches of the vascular tree depict the energy distribution from the parent node to the child nodes. The vascular weights are updated by a kind of "backpropagation" of the energy demand error generated by the hidden neurons. We observed that higher performance was achieved at lower energy levels when the vascular network was also trained along with the neural network. This indicates that the vascular network needs to be trained to ensure efficient neural performance. We observed that below a certain network size, the energetic dynamics of the network in the per capita energy consumption vs. classification accuracy space approaches a fixed-point attractor for various initial conditions. Once the number of hidden neurons increases beyond a threshold, the fixed point appears to vanish, giving place to a line of attractors. The model also showed that when there is a limited resource, the energy consumption of neurons is strongly correlated to their individual contribution to the network's performance.

A Complex-Valued Oscillatory Neural Network for Storage and Retrieval of Multidimensional Aperiodic Signals.

Recurrent neural networks with associative memory properties are typically based on fixed-point dynamics, which is fundamentally distinct from the oscillatory dynamics of the brain. There have been proposals for oscillatory associative memories, but here too, in the majority of cases, only binary patterns are stored as oscillatory states in the network. Oscillatory neural network models typically operate at a single/common frequency. At multiple frequencies, even a pair of oscillators with real coupling exhibits rich dynamics of Arnold tongues, not easily harnessed to achieve reliable memory storage and retrieval. Since real brain dynamics comprises of a wide range of spectral components, there is a need for oscillatory neural network models that operate at multiple frequencies. We propose an oscillatory neural network that can model multiple time series simultaneously by performing a Fourier-like decomposition of the signals. We show that these enhanced properties of a network of Hopf oscillators become possible by operating in the complex-variable domain. In this model, the single neural oscillator is modeled as a Hopf oscillator, with adaptive frequency and dynamics described over the complex domain. We propose a novel form of coupling, dubbed "power coupling," between complex Hopf oscillators. With power coupling, expressed naturally only in the complex-variable domain, it is possible to achieve stable (normalized) phase relationships in a network of multifrequency oscillators. Network connections are trained either by Hebb-like learning or by delta rule, adapted to the complex domain. The network is capable of modeling N-channel electroencephalogram time series with high accuracy and shows the potential as an effective model of large-scale brain dynamics.

Influence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration.

Parkinson's disease (PD) is the second most prominent neurodegenerative disease around the world. Although it is known that PD is caused by the loss of dopaminergic cells in substantia nigra pars compacta (SNc), the decisive cause of this inexorable cell loss is not clearly elucidated. We hypothesize that "Energy deficiency at a sub-cellular/cellular/systems level can be a common underlying cause for SNc cell loss in PD." Here, we propose a comprehensive computational model of SNc cell, which helps us to understand the pathophysiology of neurodegeneration at the subcellular level in PD. The aim of the study is to see how deficits in the supply of energy substrates (glucose and oxygen) lead to a deficit in adenosine triphosphate (ATP). The study also aims to show that deficits in ATP are the common factor underlying the molecular-level pathological changes, including alpha-synuclein aggregation, reactive oxygen species formation, calcium elevation, and dopamine dysfunction. The model suggests that hypoglycemia plays a more crucial role in leading to ATP deficits than hypoxia. We believe that the proposed model provides an integrated modeling framework to understand the neurodegenerative processes underlying PD.

A Multiscale, Systems-Level, Neuropharmacological Model of Cortico-Basal Ganglia System for Arm Reaching Under Normal, Parkinsonian, and Levodopa Medication Conditions.

In order to understand the link between substantia nigra pars compacta (SNc) cell loss and Parkinson's disease (PD) symptoms, we developed a multiscale computational model that can replicate the symptoms at the behavioural level by incorporating the key cellular and molecular mechanisms underlying PD pathology. There is a modelling tradition that links dopamine to reward and uses reinforcement learning (RL) concepts to model the basal ganglia. In our model, we replace the abstract representations of reward with the realistic variable of extracellular DA released by a network of SNc cells and incorporate it in the RL-based behavioural model, which simulates the arm reaching task. Our results successfully replicated the impact of SNc cell loss and levodopa (L-DOPA) medication on reaching performance. It also shows the side effects of medication, such as wearing off and peak dosage dyskinesias. The model demonstrates how differential dopaminergic axonal degeneration in basal ganglia results in various cardinal symptoms of PD. It was able to predict the optimum L-DOPA medication dosage for varying degrees of cell loss. The proposed model has a potential clinical application where drug dosage can be optimised as per patient characteristics.

A Multi-Scale Computational Model of Excitotoxic Loss of Dopaminergic Cells in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in substantia nigra pars compacta (SNc). Although the exact cause of cell death is not clear, the hypothesis that metabolic deficiency is a key factor has been gaining attention in recent years. In the present study, we investigated this hypothesis using a multi-scale computational model of the subsystem of the basal ganglia comprising the subthalamic nucleus (STN), globus pallidus externa (GPe), and SNc. The proposed model is a multiscale model in that interaction among the three nuclei are simulated using more abstract Izhikevich neuron models, while the molecular pathways involved in cell death of SNc neurons are simulated in terms of detailed chemical kinetics. Simulation results obtained from the proposed model showed that energy deficiencies occurring at cellular and network levels could precipitate the excitotoxic loss of SNc neurons in PD. At the subcellular level, the models show how calcium elevation leads to apoptosis of SNc neurons. The therapeutic effects of several neuroprotective interventions are also simulated in the model. From neuroprotective studies, it was clear that glutamate inhibition and apoptotic signal blocker therapies were able to halt the progression of SNc cell loss when compared to other therapeutic interventions, which only slowed down the progression of SNc cell loss.

Neurodegenerative Diseases - Is Metabolic Deficiency the Root Cause?

Neurodegenerative diseases, including Alzheimer, Parkinson, Huntington, and amyotrophic lateral sclerosis, are a prominent class of neurological diseases currently without a cure. They are characterized by an inexorable loss of a specific type of neurons. The selective vulnerability of specific neuronal clusters (typically a subcortical cluster) in the early stages, followed by the spread of the disease to higher cortical areas, is a typical pattern of disease progression. Neurodegenerative diseases share a range of molecular and cellular pathologies, including protein aggregation, mitochondrial dysfunction, glutamate toxicity, calcium load, proteolytic stress, oxidative stress, neuroinflammation, and aging, which contribute to neuronal death. Efforts to treat these diseases are often limited by the fact that they tend to address any one of the above pathological changes while ignoring others. Lack of clarity regarding a possible root cause that underlies all the above pathologies poses a significant challenge. In search of an integrative theory for neurodegenerative pathology, we hypothesize that metabolic deficiency in certain vulnerable neuronal clusters is the common underlying thread that links many dimensions of the disease. The current review aims to present an outline of such an integrative theory. We present a new perspective of neurodegenerative diseases as metabolic disorders at molecular, cellular, and systems levels. This helps to understand a common underlying mechanism of the many facets of the disease and may lead to more promising disease-modifying therapeutic interventions. Here, we briefly discuss the selective metabolic vulnerability of specific neuronal clusters and also the involvement of glia and vascular dysfunctions. Any failure in satisfaction of the metabolic demand by the neurons triggers a chain of events that precipitate various manifestations of neurodegenerative pathology.

Bipolar oscillations between positive and negative mood states in a computational model of Basal Ganglia.

Bipolar disorder is characterized by mood swings-oscillations between manic and depressive states. The swings (oscillations) mark the length of an episode in a patient's mood cycle (period), and can vary from hours to years. The proposed modeling study uses decision making framework to investigate the role of basal ganglia network in generating bipolar oscillations. In this model, the basal ganglia system performs a two-arm bandit task in which one of the arms (action responses) leads to a positive outcome, while the other leads to a negative outcome. We explore the dynamics of key reward and risk related parameters in the system while the model agent receives various outcomes. Particularly, we study the system using a model that represents the fast dynamics of decision making, and a module to capture the slow dynamics that describe the variation of some meta-parameters of fast dynamics over long time scales. The model is cast at three levels of abstraction: (1) a two-dimensional dynamical system model, that is a simple two variable model capable of showing bistability for rewarding and punitive outcomes; (2) a phenomenological basal ganglia model, to extend the implications from the reduced model to a cortico-basal ganglia setup; (3) a detailed network model of basal ganglia, that incorporates detailed cellular level models for a more realistic understanding. In healthy conditions, the model chooses positive action and avoids negative one, whereas under bipolar conditions, the model exhibits slow oscillations in its choice of positive or negative outcomes, reminiscent of bipolar oscillations. Phase-plane analyses on the simple reduced dynamical system with two variables reveal the essential parameters that generate pathological 'bipolar-like' oscillations. Phenomenological and network models of the basal ganglia extend that logic, and interpret bipolar oscillations in terms of the activity of dopaminergic and serotonergic projections on the cortico-basal ganglia network dynamics. The network's dysfunction, specifically in terms of reward and risk sensitivity, is shown to be responsible for the pathological bipolar oscillations. The study proposes a computational model that explores the effects of impaired serotonergic neuromodulation on the dynamics of the cortico basal ganglia network, and relates this impairment to abstract mood states (manic and depressive episodes) and oscillations of bipolar disorder.

A Cortico- Basal Ganglia Model for choosing an optimal rehabilitation strategy in Hemiparetic Stroke.

To facilitate the selection of an optimal therapy for a stroke patient with upper extremity hemiparesis, we propose a cortico-basal ganglia model capable of performing reaching tasks under normal and stroke conditions. The model contains two hemispherical systems, each organized into an outer sensory-motor cortical loop and an inner basal ganglia (BG) loop, controlling their respective hands. The model is trained to simulate two therapeutic approaches: the constraint induced movement therapy (CIMT) in which the intact is arrested, and Bimanual Reaching in which the movements of the intact arm are found to aid the affected arm. Which of these apparently mutually conflicting approaches is right for a given patient? Based on our study on the effect of lesion size on arm performance, we hypothesize that the choice of the therapy depends on the lesion size. Whereas bimanual reaching is more suitable for smaller lesion size, CIMT is preferred in case of larger lesion sizes. By virtue of the model's ability to capture the experimental results effectively, we believe that it can serve as a benchmark for the development and testing of various rehabilitation strategies for stroke.