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Nishant Sinha

Publications and source records attributed to Nishant Sinha.

22 records · Page 2Linked to original sources

Personalised network modelling in epilepsy

Epilepsy is a disorder characterised by spontaneous, recurrent seizures. Both local and network abnormalities have been associated with epilepsy, and the exact processes generating seizures are thought to be heterogeneous and patient-specific. Due to the heterogeneity, treatments such as surgery and medication are not always effective in achieving full seizure control and choosing the best treatment for the individual patient can be challenging. Predictive models constrained by the patient's own data therefore offer the potential to assist in clinical decision making. In this chapter, we describe how personalised patient-derived networks from structural or functional connectivity can be incorporated into predictive models. We focus specifically on dynamical systems models which are composed of differential equations capable of simulating brain activity over time. Here we review recent studies which have used these models, constrained by patient data, to make personalised patient-specific predictions about seizure features (such as propagation patterns) or treatment outcomes (such as the success of surgical resection). Finally, we suggest future research directions for patient-specific network models in epilepsy, including their application to integrate information from multiple modalities, to predict long-term disease evolution, and to account for within-subject variability for treatment.

q-bio.NC↗

Computer modelling of connectivity change suggests epileptogenesis mechanisms in idiopathic generalised epilepsy

Patients with idiopathic generalised epilepsy (IGE) typically have normal conventional magnetic resonance imaging (MRI), hence MRI based diagnosis is challenging. Anatomical abnormalities underlying brain dysfunctions in IGE are unclear and their relation to the pathomechanisms of epileptogenesis is poorly understood. In this study, we applied connectometry, an advanced quantitative neuroimaging technique for investigating localised changes in white-matter tissue. Analysing white matter structures of 32 subjects we incorporated our findings in a computational model of seizure dynamics to suggest a plausible mechanism of epileptogenesis. Patients with IGE have significant bilateral alterations in major white-matter fascicles. In the cingulum, fornix, and superior longitudinal fasciculus, tract integrity is compromised, whereas in specific parts of tracts between thalamus and the precentral gyrus, tract integrity is enhanced in patients. Combining these alterations in a logistic regression model, we computed the decision boundary that discriminated patients and controls. The computational model, informed with the findings on the tract abnormalities, specifically highlighted the importance of enhanced cortico-reticular connections along with impaired cortico-cortical connections in inducing pathological seizure-like dynamics. We emphasise taking directionality of brain connectivity into consideration towards understanding the pathological mechanisms; this is possible by combining neuroimaging and computational modelling. Our imaging evidence of structural alterations suggest the loss of cortico-cortical and enhancement of cortico-thalamic fibre integrity in IGE. We further suggest that impaired connectivity from cortical regions to the thalamic reticular nucleus offers a therapeutic target for selectively modifying the brain circuit for reversing the mechanisms leading to epileptogenesis.

q-bio.NC↗

The impact of epilepsy surgery on the structural connectome and its relation to outcome

Temporal lobe surgical resection brings seizure remission in up to 80% of patients, with long-term complete seizure freedom in 41%. However, it is unclear how surgery impacts on the structural white matter network, and how the network changes relate to seizure outcome. We used white matter fibre tractography on preoperative diffusion MRI to generate a structural white matter network, and postoperative T1-weighted MRI to retrospectively infer the impact of surgical resection on this network. We then applied graph theory and machine learning to investigate the properties of change between the preoperative and predicted postoperative networks. Temporal lobe surgery had a modest impact on global network efficiency, despite the disruption caused. This was due to alternative shortest paths in the network leading to widespread increases in betweenness centrality post-surgery. Measurements of network change could retrospectively predict seizure outcomes with 79% accuracy and 65% specificity, which is twice as high as the empirical distribution. Fifteen connections which changed due to surgery were identified as useful for prediction of outcome, eight of which connected to the ipsilateral temporal pole. Our results suggest that the use of network change metrics may have clinical value for predicting seizure outcome. This approach could be used to prospectively predict outcomes given a suggested resection mask using preoperative data only.

q-bio.NC↗

An Executable Sequential Specification for Spark Aggregation

Spark is a new promising platform for scalable data-parallel computation. It provides several high-level application programming interfaces (APIs) to perform parallel data aggregation. Since execution of parallel aggregation in Spark is inherently non-deterministic, a natural requirement for Spark programs is to give the same result for any execution on the same data set. We present PureSpark, an executable formal Haskell specification for Spark aggregate combinators. Our specification allows us to deduce the precise condition for deterministic outcomes from Spark aggregation. We report case studies analyzing deterministic outcomes and correctness of Spark programs.

cs.DC↗