Data Driven Classification Using fMRI Network Measures: Application to Schizophrenia

Using classification to identify biomarkers for various brain disorders has become a common practice among the functional MR imaging community. Typical classification pipeline includes taking the time series, extracting features from them, and using them to classify a set of patients and healthy controls. The most informative features are then presented as novel biomarkers. In this paper, we compared the results of single and double cross validation schemes on a cohort of 170 subjects with schizophrenia and healthy control subjects. We used graph theoretic measures as our features, comparing the use of functional and anatomical atlases to define nodes and the effect of prewhitening to remove autocorrelation trends. We found that double cross validation resulted in a 20% decrease in classification performance compared to single cross validation. The anatomical atlas resulted in higher classification results. Prewhitening resulted in a 10% boost in classification performance. Overall, a classification performance of 80% was obtained with a double-cross validation scheme using prewhitened time series and an anatomical brain atlas. However, reproducibility of classification within subjects across scans was surprisingly low and comparable to across subject classification rates, indicating that subject state during the short scan significantly influences the estimated features and classification performance

Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia

We employed multi-electrode array recording to evaluate the influence of NMDA receptors (NMDAR) on spike-timing dynamics in prefrontal networks of monkeys as they performed a cognitive control task measuring specific deficits in schizophrenia. Systemic, periodic administration of an NMDAR antagonist (phencyclidine) reduced the prevalence and strength of synchronous (0-lag) spike correlation in simultaneously recorded neuron pairs. We employed transfer entropy analysis to measure effective connectivity between prefrontal neurons at lags consistent with monosynaptic interactions and found that effective connectivity was persistently reduced following exposure to the NMDAR antagonist. These results suggest that a disruption of spike timing and effective connectivity might be interrelated factors in pathogenesis, supporting an activity-dependent disconnection theory of schizophrenia. In this theory, disruption of NMDAR synaptic function leads to dys-regulated timing of action potentials in prefrontal networks, accelerating synaptic disconnection through a spike-timing-dependent mechanism

Controversies in epilepsy: Debates held during the Fourth International Workshop on Seizure Prediction

Debates on six controversial topics were held during the Fourth International Workshop on Seizure Prediction (IWSP4) convened in Kansas City, KS, USA, July 4–7, 2009. The topics were (1) Ictogenesis: Focus versus Network? (2) Spikes and Seizures: Step-relatives or Siblings? (3) Ictogenesis: A Result of Hyposynchrony? (4) Can Focal Seizures Be Caused by Excessive Inhibition? (5) Do High-Frequency Oscillations Provide Relevant Independent Information? (6) Phase Synchronization: Is It Worthwhile as Measured? This article, written by the IWSP4 organizing committee and the debaters, summarizes the arguments presented during the debates

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Dynamic control of modeled tonic-clonic seizure states with closed-loop stimulation

Seizure control using deep brain stimulation (DBS) provides an alternative therapy to patients with intractable and drug resistant epilepsy. This paper presents novel DBS stimulus protocols to disrupt seizures. Two protocols are presented: open-loop stimulation and a closed-loop feedback system utilizing measured firing rates to adjust stimulus frequency. Stimulation suppression is demonstrated in a computational model using 3000 excitatory Morris-Lecar model neurons connected with depressing synapses. Cells are connected using second order network topology to simulate network topologies measured in cortical networks. The network spontaneously switches from tonic to clonic as synaptic strengths and tonic input to the neurons decreases. To this model we add periodic stimulation pulses to simulate DBS. Periodic forcing can synchronize or desynchronize an oscillating population of neurons, depending on the stimulus frequency and amplitude. Therefore, it is possible to either extend or truncate the tonic or clonic phases of the seizure. Stimuli applied at the firing rate of the neuron generally synchronize the population while stimuli slightly slower than the firing rate prevent synchronization. We present an adaptive stimulation algorithm that measures the firing rate of a neuron and adjusts the stimulus to maintain a relative stimulus frequency to firing frequency and demonstrate it in a computational model of a tonic-clonic seizure. This adaptive algorithm can affect the duration of the tonic phase using much smaller stimulus amplitudes than the open-loop control

Bayesian adaptive dual control of deep brain stimulation in a computational model of Parkinson's disease.

In this paper, we present a novel Bayesian adaptive dual controller (ADC) for autonomously programming deep brain stimulation devices. We evaluated the Bayesian ADC's performance in the context of reducing beta power in a computational model of Parkinson's disease, in which it was tasked with finding the set of stimulation parameters which optimally reduced beta power as fast as possible. Here, the Bayesian ADC has dual goals: (a) to minimize beta power by exploiting the best parameters found so far, and (b) to explore the space to find better parameters, thus allowing for better control in the future. The Bayesian ADC is composed of two parts: an inner parameterized feedback stimulator and an outer parameter adjustment loop. The inner loop operates on a short time scale, delivering stimulus based upon the phase and power of the beta oscillation. The outer loop operates on a long time scale, observing the effects of the stimulation parameters and using Bayesian optimization to intelligently select new parameters to minimize the beta power. We show that the Bayesian ADC can efficiently optimize stimulation parameters, and is superior to other optimization algorithms. The Bayesian ADC provides a robust and general framework for tuning stimulation parameters, can be adapted to use any feedback signal, and is applicable across diseases and stimulator designs

Optimal Entrainment of Heterogeneous Noisy Neurons

We develop a methodology to design a stimulus optimized to entrain nonlinear, noisy limit cycle oscillators with uncertain properties. Conditions are derived which guarantee that the stimulus will entrain the oscillators despite these uncertainties. Using these conditions, we develop an energy optimal control strategy to design an efficient entraining stimulus and apply it to numerical models of noisy phase oscillators and to in vitro hippocampal neurons. In both instances, the optimal stimuli outperform other similar but suboptimal entraining stimuli. Because this control strategy explicitly accounts for both noise and inherent uncertainty of model parameters, it could have experimental relevance to neural circuits where robust spike timing plays an important role