Concurrent- and After-Effects of Medial Temporal Lobe Stimulation on Directed Information Flow to and from Prefrontal and Parietal Cortices during Memory Formation.

Electrical stimulation of the medial temporal lobe (MTL) has the potential to uncover causal circuit mechanisms underlying memory function. However, little is known about how MTL stimulation alters information flow with frontoparietal cortical regions implicated in episodic memory. We used intracranial EEG recordings from humans (14 participants, 10 females) to investigate how MTL stimulation alters directed information flow between MTL and PFC and between MTL and posterior parietal cortex (PPC). Participants performed a verbal episodic memory task during which they were presented with words and asked to recall them after a delay of ∼20 s; 50 Hz stimulation was applied to MTL electrodes on selected trials during memory encoding. Directed information flow was examined using phase transfer entropy. Behaviorally, we observed that MTL stimulation reduced memory recall. MTL stimulation decreased top-down PFC→MTL directed information flow during both memory encoding and subsequent memory recall, revealing aftereffects more than 20 s after end of stimulation. Stimulation suppressed top-down PFC→MTL influences to a greater extent than PPC→MTL. Finally, MTL→PFC information flow on stimulation trials was significantly lower for successful, compared with unsuccessful, memory recall; in contrast, MTL→ventral PPC information flow was higher for successful, compared with unsuccessful, memory recall. Together, these results demonstrate that the effects of MTL stimulation are behaviorally, regionally, and directionally specific, that MTL stimulation selectively impairs directional signaling with PFC, and that causal MTL-ventral PPC circuits support successful memory recall. Findings provide new insights into dynamic casual circuits underling episodic memory and their modulation by MTL stimulation.SIGNIFICANCE STATEMENT The medial temporal lobe (MTL) and its interactions with prefrontal and parietal cortices (PFC and PPC) play a critical role in human memory. Dysfunctional MTL-PFC and MTL-PPC circuits are prominent in psychiatric and neurologic disorders, including Alzheimer's disease and schizophrenia. Brain stimulation has emerged as a potential mechanism for enhancing memory and cognitive functions, but the underlying neurophysiological mechanisms and dynamic causal circuitry underlying bottom-up and top-down signaling involving the MTL are unknown. Here, we use intracranial EEG recordings to investigate the effects of MTL stimulation on causal signaling in key episodic memory circuits linking the MTL with PFC and PPC. Our findings have implications for translational applications aimed at realizing the promise of brain stimulation-based treatment of memory disorders.

Causalized Convergent Cross Mapping and Its Implementation in Causality Analysis.

Rooted in dynamic systems theory, convergent cross mapping (CCM) has attracted increased attention recently due to its capability in detecting linear and nonlinear causal coupling in both random and deterministic settings. One limitation with CCM is that it uses both past and future values to predict the current value, which is inconsistent with the widely accepted definition of causality, where it is assumed that the future values of one process cannot influence the past of another. To overcome this obstacle, in our previous research, we introduced the concept of causalized convergent cross mapping (cCCM), where future values are no longer used to predict the current value. In this paper, we focus on the implementation of cCCM in causality analysis. More specifically, we demonstrate the effectiveness of cCCM in identifying both linear and nonlinear causal coupling in various settings through a large number of examples, including Gaussian random variables with additive noise, sinusoidal waveforms, autoregressive models, stochastic processes with a dominant spectral component embedded in noise, deterministic chaotic maps, and systems with memory, as well as experimental fMRI data. In particular, we analyze the impact of shadow manifold construction on the performance of cCCM and provide detailed guidelines on how to configure the key parameters of cCCM in different applications. Overall, our analysis indicates that cCCM is a promising and easy-to-implement tool for causality analysis in a wide spectrum of applications.

Information Rates for Channels with Fading, Side Information and Adaptive Codewords.

Generalized mutual information (GMI) is used to compute achievable rates for fading channels with various types of channel state information at the transmitter (CSIT) and receiver (CSIR). The GMI is based on variations of auxiliary channel models with additive white Gaussian noise (AWGN) and circularly-symmetric complex Gaussian inputs. One variation uses reverse channel models with minimum mean square error (MMSE) estimates that give the largest rates but are challenging to optimize. A second variation uses forward channel models with linear MMSE estimates that are easier to optimize. Both model classes are applied to channels where the receiver is unaware of the CSIT and for which adaptive codewords achieve capacity. The forward model inputs are chosen as linear functions of the adaptive codeword's entries to simplify the analysis. For scalar channels, the maximum GMI is then achieved by a conventional codebook, where the amplitude and phase of each channel symbol are modified based on the CSIT. The GMI increases by partitioning the channel output alphabet and using a different auxiliary model for each partition subset. The partitioning also helps to determine the capacity scaling at high and low signal-to-noise ratios. A class of power control policies is described for partial CSIR, including a MMSE policy for full CSIT. Several examples of fading channels with AWGN illustrate the theory, focusing on on-off fading and Rayleigh fading. The capacity results generalize to block fading channels with in-block feedback, including capacity expressions in terms of mutual and directed information.

Feed-forward information and zero-lag synchronization in the sensory thalamocortical circuit are modulated during stimulus perception.

The direction of functional information flow in the sensory thalamocortical circuit may play a role in stimulus perception, but, surprisingly, this process is poorly understood. We addressed this problem by evaluating a directional information measure between simultaneously recorded neurons from somatosensory thalamus (ventral posterolateral nucleus, VPL) and somatosensory cortex (S1) sharing the same cutaneous receptive field while monkeys judged the presence or absence of a tactile stimulus. During stimulus presence, feed-forward information (VPL → S1) increased as a function of the stimulus amplitude, while pure feed-back information (S1 → VPL) was unaffected. In parallel, zero-lag interaction emerged with increasing stimulus amplitude, reflecting externally driven thalamocortical synchronization during stimulus processing. Furthermore, VPL → S1 information decreased during error trials. Also, VPL → S1 and zero-lag interaction decreased when monkeys were not required to report the stimulus presence. These findings provide evidence that both the direction of information flow and the instant synchronization in the sensory thalamocortical circuit play a role in stimulus perception.

Directed Data-Processing Inequalities for Systems with Feedback.

We present novel data-processing inequalities relating the mutual information and the directed information in systems with feedback. The internal deterministic blocks within such systems are restricted only to be causal mappings, but are allowed to be non-linear and time varying, and randomized by their own external random input, can yield any stochastic mapping. These randomized blocks can for example represent source encoders, decoders, or even communication channels. Moreover, the involved signals can be arbitrarily distributed. Our first main result relates mutual and directed information and can be interpreted as a law of conservation of information flow. Our second main result is a pair of data-processing inequalities (one the conditional version of the other) between nested pairs of random sequences entirely within the closed loop. Our third main result introduces and characterizes the notion of in-the-loop (ITL) transmission rate for channel coding scenarios in which the messages are internal to the loop. Interestingly, in this case the conventional notions of transmission rate associated with the entropy of the messages and of channel capacity based on maximizing the mutual information between the messages and the output turn out to be inadequate. Instead, as we show, the ITL transmission rate is the unique notion of rate for which a channel code attains zero error probability if and only if such an ITL rate does not exceed the corresponding directed information rate from messages to decoded messages. We apply our data-processing inequalities to show that the supremum of achievable (in the usual channel coding sense) ITL transmission rates is upper bounded by the supremum of the directed information rate across the communication channel. Moreover, we present an example in which this upper bound is attained. Finally, we further illustrate the applicability of our results by discussing how they make possible the generalization of two fundamental inequalities known in networked control literature.

Neural Estimator of Information for Time-Series Data with Dependency.

Novel approaches to estimate information measures using neural networks are well-celebrated in recent years both in the information theory and machine learning communities. These neural-based estimators are shown to converge to the true values when estimating mutual information and conditional mutual information using independent samples. However, if the samples in the dataset are not independent, the consistency of these estimators requires further investigation. This is of particular interest for a more complex measure such as the directed information, which is pivotal in characterizing causality and is meaningful over time-dependent variables. The extension of the convergence proof for such cases is not trivial and demands further assumptions on the data. In this paper, we show that our neural estimator for conditional mutual information is consistent when the dataset is generated with samples of a stationary and ergodic source. In other words, we show that our information estimator using neural networks converges asymptotically to the true value with probability one. Besides universal functional approximation of neural networks, a core lemma to show the convergence is Birkhoff's ergodic theorem. Additionally, we use the technique to estimate directed information and demonstrate the effectiveness of our approach in simulations.

Inferring neuronal network functional connectivity with directed information.

A major challenge in neuroscience is to develop effective tools that infer the circuit connectivity from large-scale recordings of neuronal activity patterns. In this study, context tree maximizing (CTM) was used to estimate directed information (DI), which measures causal influences among neural spike trains in order to infer putative synaptic connections. In contrast to existing methods, the method presented here is data driven and can readily identify both linear and nonlinear relations between neurons. This CTM-DI method reliably identified circuit structures underlying simulations of realistic conductance-based networks. It also inferred circuit properties from voltage-sensitive dye recordings of the buccal ganglion of Aplysia. This method can be applied to other large-scale recordings as well. It offers a systematic tool to map network connectivity and to track changes in network structure such as synaptic strengths as well as the degrees of connectivity of individual neurons, which in turn could provide insights into how modifications produced by learning are distributed in a neural network.NEW & NOTEWORTHY This study brings together the techniques of voltage-sensitive dye recording and information theory to infer the functional connectome of the feeding central pattern generating network of Aplysia. In contrast to current statistical approaches, the inference method developed in this study is data driven and validated by conductance-based model circuits, can distinguish excitatory and inhibitory connections, is robust against synaptic plasticity, and is capable of detecting network structures that mediate motor patterns.

Analysis of Respiratory Sinus Arrhythmia and Directed Information Flow between Brain and Body Indicate Different Management Strategies of fMRI-Related Anxiety.

BACKGROUND: Respiratory sinus arrhythmia (RSA) denotes decrease of cardiac beat-to-beat intervals (RRI) during inspiration and RRI increase during expiration, but an inverse pattern (termed negative RSA) was also found in healthy humans with elevated anxiety. It was detected using wave-by-wave analysis of cardiorespiratory rhythms and was considered to reflect a strategy of anxiety management involving the activation of a neural pacemaker. Results were consistent with slow breathing, but contained uncertainty at normal breathing rates (0.2-0.4 Hz). OBJECTIVES AND METHODS: We combined wave-by-wave analysis and directed information flow analysis to obtain information on anxiety management at higher breathing rates. We analyzed cardiorespiratory rhythms and blood oxygen level-dependent (BOLD) signals from the brainstem and cortex in 10 healthy fMRI participants with elevated anxiety. RESULTS: Three subjects with slow respiratory, RRI, and neural BOLD oscillations showed 57 ± 26% negative RSA and significant anxiety reduction by 54 ± 9%. Six participants with breathing rate of ~0.3 Hz showed 41 ± 16% negative RSA and weaker anxiety reduction. They presented significant information flow from RRI to respiration and from the middle frontal cortex to the brainstem, which may result from respiration-entrained brain oscillations, indicating another anxiety management strategy. CONCLUSIONS: The two analytical approaches applied here indicate at least two different anxiety management strategies in healthy subjects.

Physician-directed information prescription service. A scoping review.

OBJECTIVE: This scoping review aims to identify and map the characteristics of research studies, types, delivery methods, and team members of physician-directed information prescription services. METHODS: Following the PRISMA-ScR checklist, a systematic search was performed on Web of Science, Scopus, Library, Information Science & Technology Abstracts (LISTA), and PubMed/Medline from 1990 to 2021. RESULTS: 37 studies were included in the final analysis. Five types of providing information prescription were recognized: typical, oral, web-based, electronic, and mixed methods. Physicians, nurses, and librarians were the most agreed-upon professionals in information prescription delivery teams. The steps of prescribing information were needs assessment, content production, information evaluation, prescribing information, follow-up, and documentation. DISCUSSION: This review presents a synthesis of the process of information prescription. It is suggested to determine the effective information prescription type, provide methods and develop the service according to patients' preferences and characteristics. PRACTICE IMPLICATIONS: Results of this study can be used to identify the challenges, the competent individuals, roles, and steps of information prescription service, as well as design and develop the protocol, model, and flowchart of it.

Regional identification of information flow termination of electrohysterographic signals: Towards understanding human uterine electrical propagation.

BACKGROUND AND OBJECTIVE: The uterine electrohysterogram (EHG) contains important information about electrical signal propagation which may be useful to monitor and predict the progress of pregnancy towards parturition. Directed information processing has the potential to be of use in studying EHG recordings. However, so far, there is no directed information-based estimation scheme that has been applied to investigating the propagation of human EHG recordings. To realize this, the approach of directed information and its reliability and adaptability should be scientifically studied. METHODS: We demonstrated an estimation scheme of directed information to identify the spatiotemporal relationship between the recording channels of EHG signal and assess the algorithm reliability initially using simulated data. Further, a regional identification of information flow termination (RIIFT) approach was developed and applied for the first time to extant multichannel EHG signals to reveal the terminal zone of propagation of the electrical activity associated with uterine contraction. RIIFT operates by estimating the pairwise directed information between neighboring EHG channels and identifying the location where there is the strongest inward flow of information. The method was then applied to publicly-available experimental data obtained from pregnant women with the use of electrodes arranged in a 4-by-4 grid. RESULTS: Our results are consistent with the suggestions from the previous studies with the added identification of preferential sites of excitation termination - within the estimated area, the direction of surface action potential propagation towards the medial axis of uterus during contraction was discovered for 72.15% of the total cases, demonstrating that our RIIFT method is a potential tool to investigate EHG propagation for advancing our understanding human uterine excitability. CONCLUSIONS: We developed a new approach and applied it to multichannel human EHG recordings to investigate the electrical signal propagation involved in uterine contraction. This provides an important platform for future studies to fill knowledge gaps in the spatiotemporal patterns of electrical excitation of the human uterus.

NetDI: Methodology Elucidating the Role of Power and Dynamical Brain Network Features That Underpin Word Production.

Canonical language models describe eloquent function as the product of a series of cognitive processes, typically characterized by the independent activation profiles of focal brain regions. In contrast, more recent work has suggested that the interactions between these regions, the cortical networks of language, are critical for understanding speech production. We investigated the cortical basis of picture naming (PN) with human intracranial electrocorticography (ECoG) recordings and direct cortical stimulation (DCS), adjudicating between two competing hypotheses: are task-specific cognitive functions discretely computed within well-localized brain regions or rather by distributed networks? The time resolution of ECoG allows direct comparison of intraregional activation measures [high gamma (h γ ) power] with graph theoretic measures of interregional dynamics. We developed an analysis framework, network dynamics using directed information (NetDI), using information and graph theoretic tools to reveal spatiotemporal dynamics at multiple scales: coarse, intermediate, and fine. Our analysis found novel relationships between the power profiles and network measures during the task. Furthermore, validation using DCS indicates that such network parameters combined with hγ power are more predictive than hγ power alone, for identifying critical language regions in the brain. NetDI reveals a high-dimensional space of network dynamics supporting cortical language function, and to account for disruptions to language function observed after neurosurgical resection, traumatic injury, and degenerative disease.

Inferring functional connectivity through graphical directed information.

Objective. Accurate inference of functional connectivity is critical for understanding brain function. Previous methods have limited ability distinguishing between direct and indirect connections because of inadequate scaling with dimensionality. This poor scaling performance reduces the number of nodes that can be included in conditioning. Our goal was to provide a technique that scales better and thereby enables minimization of indirect connections.Approach. Our major contribution is a powerful model-free framework, graphical directed information (GDI), that enables pairwise directed functional connections to be conditioned on the activity of substantially more nodes in a network, producing a more accurate graph of functional connectivity that reduces indirect connections. The key technology enabling this advancement is a recent advance in the estimation of mutual information (MI), which relies on multilayer perceptrons and exploiting an alternative representation of the Kullback-Leibler divergence definition of MI. Our second major contribution is the application of this technique to both discretely valued and continuously valued time series.Main results. GDI correctly inferred the circuitry of arbitrary Gaussian, nonlinear, and conductance-based networks. Furthermore, GDI inferred many of the connections of a model of a central pattern generator circuit inAplysia, while also reducing many indirect connections.Significance. GDI is a general and model-free technique that can be used on a variety of scales and data types to provide accurate direct connectivity graphs and addresses the critical issue of indirect connections in neural data analysis.

Visual Experience-Dependent Oscillations and Underlying Circuit Connectivity Changes Are Impaired in Fmr1 KO Mice.

Fragile X syndrome (FX), the most common inherited form of autism and intellectual disability, is a condition associated with visual perceptual learning deficits. We recently discovered that perceptual experience can encode visual familiarity via persistent low-frequency oscillations in the mouse primary visual cortex (V1). Here, we combine this paradigm with a multifaceted experimental approach to identify neurophysiological impairments of these oscillations in FX mice. Extracellular recordings reveal shorter durations, lower power, and lower frequencies of peak oscillatory activity in FX mice. Directed information analysis of extracellularly recorded spikes reveals differences in functional connectivity from multiple layers in FX mice after the perceptual experience. Channelrhodopsin-2 assisted circuit mapping (CRACM) reveals increased synaptic strength from L5 pyramidal onto L4 fast-spiking cells after experience in wild-type (WT), but not FX, mice. These results suggest differential encoding of visual stimulus familiarity in FX via persistent oscillations and identify circuit connections that may underlie these changes.

Are all data useful? Inferring causality to predict flows across sewer and drainage systems using directed information and boosted regression trees.

As more sensor data become available across urban water systems, it is often unclear which of these new measurements are actually useful and how they can be efficiently ingested to improve predictions. We present a data-driven approach for modeling and predicting flows across combined sewer and drainage systems, which fuses sensor measurements with output of a large numerical simulation model. Rather than adjusting the structure and parameters of the numerical model, as is commonly done when new data become available, our approach instead learns causal relationships between the numerically-modeled outputs, distributed rainfall measurements, and measured flows. By treating an existing numerical model - even one that may be outdated - as just another data stream, we illustrate how to automatically select and combine features that best explain flows for any given location. This allows for new sensor measurements to be rapidly fused with existing knowledge of the system without requiring recalibration of the underlying physics. Our approach, based on Directed Information (DI) and Boosted Regression Trees (BRT), is evaluated by fusing measurements across nearly 30 rain gages, 15 flow locations, and the outputs of a numerical sewer model in the city of Detroit, Michigan: one of the largest combined sewer systems in the world. The results illustrate that the Boosted Regression Trees provide skillful predictions of flow, especially when compared to an existing numerical model. The innovation of this paper is the use of the Directed Information step, which selects only those inputs that are causal with measurements at locations of interest. Better predictions are achieved when the Directed Information step is used because it reduces overfitting during the training phase of the predictive algorithm. In the age of "big water data", this finding highlights the importance of screening all available data sources before using them as inputs to data-driven models, since more may not always be better. We discuss the generalizability of the case study and the requirements of transferring the approach to other systems.