Srinivasa Chakravarthy

Motor symptoms in Parkinson's disease: A unified framework.

Parkinsons disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (akinesia and bradykinesia, tremor and rigidity), PD patients show additional motor deficits, including: gait disturbance, impaired handwriting, grip force and speech deficits, among others. Some of these motor symptoms (e.g., deficits of gait, speech, and handwriting) have similar clinical profiles, neural substrates, and respond similarly to dopaminergic medication and deep brain stimulation (DBS). Here, we provide an extensive review of the clinical characteristics and neural substrates of each of these motor symptoms, to highlight precisely how PD and its medical and surgical treatments impact motor symptoms. In conclusion, we offer a unified framework for understanding the range of motor symptoms in PD. We argue that various motor symptoms in PD reflect dysfunction of neural structures responsible for action selection, motor sequencing, and coordination and execution of movement.

Systems biological approach on neurological disorders: a novel molecular connectivity to aging and psychiatric diseases

BackgroundSystems biological approach of molecular connectivity map has reached to a great interest to understand the gene functional similarities between the diseases. In this study, we developed a computational framework to build molecular connectivity maps by integrating mutated and differentially expressed genes of neurological and psychiatric diseases to determine its relationship with aging.ResultsThe systematic large-scale analyses of 124 human diseases create three classes of molecular connectivity maps. First, molecular interaction of disease protein network generates 3632 proteins with 6172 interactions, which determines the common genes/proteins between diseases. Second, Disease-disease network includes 4845 positively scored disease-disease relationships. The comparison of these disease-disease pairs with Medical Subject Headings (MeSH) classification tree suggests 25% of the disease-disease pairs were in same disease area. The remaining can be a novel disease-disease relationship based on gene/protein similarity. Inclusion of aging genes set showed 79 neurological and 20 psychiatric diseases have the strong association with aging. Thirdand lastly, a curated disease biomarker network was created by relating the proteins/genes in specific disease contexts, such analysis showed 73 markers for 24 diseases. Further, the overall quality of the results was achieved by a series of statistical methods, to avoid insignificant data in biological networks.ConclusionsThis study improves the understanding of the complex interactions that occur between neurological and psychiatric diseases with aging, which lead to determine the diagnostic markers. Also, the disease-disease association results could be helpful to determine the symptom relationships between neurological and psychiatric diseases. Together, our study presents many research opportunities in post-genomic biomarkers development.

XML standard for Indic online handwritten database

This article proposes an improved XML standard for storing online handwritten data in Indian languages. This standard has evolved over a period of two years, and is currently being used by the Consortium for online handwritten recognition of Indian languages, for annotating about 100,000 handwritten words in each of six Indian languages, namely, Tamil, Kannada, Telugu, Malayalam, Hindi and Bangla. In order that the huge amount of data that is being collected is useable by the future researchers, it is preferable that the data is stored in a format that is unambiguous and easy to read. The uniqueness of this refined standard is that it gives quality labels at different levels to the data, and has provision to annotate all the peculiarities of writing the script of the various Indian languages included in the current consortium project. The current format allows the use of automated and semi-automated annotation tools.

A Complete OCR System for Tamil Magazine Documents

We present a complete optical character recognition (OCR) system for Tamil magazines/documents. All the standard elements of OCR process like de-skewing, preprocessing, segmentation, character recognition, and reconstruction are implemented. Experience with OCR problems teaches that for most subtasks of OCR, there is no single technique that gives perfect results for every type of document image. We exploit the ability of neural networks to learn from experience in solving the problems of segmentation and character recognition. Text segmentation of Tamil newsprint poses a new challenge owing to its italic-like font type; problems that arise in recognition of touching and close characters are discussed. Character recognition efficiency varied from 94 to 97% for this type of font. The grouping of blocks into logical units and the determination of reading order within each logical unit helped us in reconstructing automatically the document image in an editable format.

Interrelations between cognitive dysfunction and motor symptoms of Parkinson's disease: behavioral and neural studies.

Abstract Parkinson’s disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (tremor, bradykinesia/akinesia, and rigidity), PD patients also show other motor deficits, including gait disturbance, speech deficits, and impaired handwriting. However, along with these key motor symptoms, PD patients also experience cognitive deficits in attention, executive function, working memory, and learning. Recent evidence suggests that these motor and cognitive deficits of PD are not completely dissociable, as aspects of cognitive dysfunction can impact motor performance in PD. In this article, we provide a review of behavioral and neural studies on the associations between motor symptoms and cognitive deficits in PD, specifically akinesia/bradykinesia, tremor, gait, handwriting, precision grip, and speech production. This review paves the way for providing a framework for understanding how treatment of cognitive dysfunction, for example cognitive rehabilitation programs, may in turn influence the motor symptoms of PD.

A system for offline character recognition using auto-encoder networks

We present a technique of using Deep Neural Networks (DNNs) for offline character recognition of Telugu characters. We construct DNNs by stacking Auto-encoders that are trained in a greedy layer-wise fashion in an unsupervised manner. We then perform supervised fine-tuning to train the entire network. We provide results on Consonant and Vowel Modifier Datasets using two and three hidden layer DNNs. We also construct an ensemble classifier to increase the classification performance further. We observe 94.25% accuracy for the two hidden layer network on Consonant data and 94.1% on Vowel Modifier Dataset which increases to 95.4% for Consonant and 94.8% for Vowel Modifier Dataset after combining classifiers to form an ensemble classifier of 4 different two hidden layer networks.

An oscillatory neural network model for birdsong learning and generation

We present a model of bird song production in which the motor control pathway is modeled by a trainable network of oscillators and the Anterior Forebrain Pathway (AFP) is modeled as a stochastic system. We hypothesize 1) that the songbird learns only evaluations of songs during the sensory phase; 2) that the AFP plays a role analogous to the Explorer, a key component in Reinforcement Learning (RL); 3) the motor pathway learns the song by combining the evaluations (Value information) stored from the sensory phase, and the exploratory inputs from the AFP in a temporal stage-wise manner. Model performance from real birdsong samples is presented

The many facets of dopamine: Toward an integrative theory of the role of dopamine in managing the body's energy resources

In neuroscience literature, dopamine is often considered as a pleasure chemical of the brain. Dopaminergic neurons respond to rewarding stimuli which include primary rewards like opioids or food, or more abstract forms of reward like cash rewards or pictures of pretty faces. It is this reward-related aspect of dopamine, particularly its association with reward prediction error, that is highlighted by a large class of computational models of dopamine signaling. Dopamine is also a neuromodulator, controlling synaptic plasticity in several cortical and subcortical areas. But dopamines influence is not limited to the nervous system; its effects are also found in other physiological systems, particularly the circulatory system. Importantly, dopamine agonists have been used as a drug to control blood pressure. Is there a theoretical, conceptual connection that reconciles dopamines effects in the nervous system with those in the circulatory system? This perspective article integrates the diverse physiological roles of dopamine and provides a simple theoretical framework arguing that its reward related function regulates the processes of energy consumption and acquisition in the body. We conclude by suggesting that energy-related book-keeping of the body at the physiological level is the common motif that links the many facets of dopamine and its functions.

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 leads to a positive outcome, while the other leads to a negative outcome. 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. The model is cast at three levels of abstraction: 1) a two-dimensional dynamical system model, 2) a phenomenological basal ganglia model, 3) a detailed network model of basal ganglia. 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. In addition to constraint induced movement therapy (CIMT), the model performs both unimanual and bimanual reaching tasks and the simulation results are in congruence with the experiment conducted by Rose et al (2004). Based on our study on the effect of lesion size on arm performance, we hypothesize that the effectiveness of a therapy could greatly depend on this factor. 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.