Research into the mechanisms underlying neuromodulation by tES using in-vivo animal models is key to overcoming experimental limitations in humans and essential to building a detailed understanding of the in-vivo consequences of tES. Insights from such animal models are needed to develop targeted and effective therapeutic applications of non-invasive brain stimulation in humans. The sheer difference in scale and geometry between animal models and the human brain contributes to the complexity of designing and interpreting animal studies. Here, we introduce EFMouse, a toolbox that extends previous approaches to model intracranial electric fields and generate predictions that can be tested with in-vivo recordings in mice. Novel functionality includes the ability to capture typical surgical approaches in the mouse (e.g., cranial recording windows), the placement of stimulation electrodes anywhere in or on the animal, and novel ways to report field predictions, including some refined measures of focality and direction homogeneity, and quantification based on regions defined in the Allen Mouse Brain Atlas. Although the EFMouse toolbox is generally applicable to planning and designing tES studies in mice, we illustrate its use by posing questions about transcranial direct current stimulation (tDCS) experiments with the goal of targeting the left visual cortex of the mouse. The EFMouse toolbox is publicly available at https://github.com/klabhub/EFMouse.

A central goal of neuroscience is to understand how function-relevant brain activations are generated. Here we test the hypothesis that function-relevant brain activations are generated primarily by distributed network flows. We focused on visual processing in human cortex, given the long-standing literature supporting the functional relevance of brain activations in visual cortex regions exhibiting visual category selectivity. We began by using fMRI data from N = 352 human participants to identify category-specific responses in visual cortex for images of faces, places, body parts, and tools. We then systematically tested the hypothesis that distributed network flows can generate these localized visual category selective responses. This was accomplished using a recently developed approach for simulating - in a highly empirically constrained manner - the generation of task-evoked brain activations by modeling activity flowing over intrinsic brain connections. We next tested refinements to our hypothesis, focusing on how stimulus-driven network interactions initialized in V1 generate downstream visual category selectivity. We found evidence that network flows directly from V1 were sufficient for generating visual category selectivity, but that additional, globally distributed (whole-cortex) network flows increased category selectivity further. Using null network architectures we also found that each region's unique intrinsic "connectivity fingerprint" was key to the generation of category selectivity. These results generalized across regions associated with all four visual categories tested (bodies, faces, places, and tools), and provide evidence that the human brain's intrinsic network organization plays a prominent role in the generation of functionally relevant, localized responses.

Learning graphical conditional independence structures is an important machine learning problem and a cornerstone of causal discovery. However, the accuracy and execution time of learning algorithms generally struggle to scale to problems with hundreds of highly connected variables---for instance, recovering brain networks from fMRI data. We introduce the best order score search (BOSS) and grow-shrink trees (GSTs) for learning directed acyclic graphs (DAGs) in this paradigm. BOSS greedily searches over permutations of variables, using GSTs to construct and score DAGs from permutations. GSTs efficiently cache scores to eliminate redundant calculations. BOSS achieves state-of-the-art performance in accuracy and execution time, comparing favorably to a variety of combinatorial and gradient-based learning algorithms under a broad range of conditions. To demonstrate its practicality, we apply BOSS to two sets of resting-state fMRI data: simulated data with pseudo-empirical noise distributions derived from randomized empirical fMRI cortical signals and clinical data from 3T fMRI scans processed into cortical parcels. BOSS is available for use within the TETRAD project which includes Python and R wrappers.

It is commonplace to encounter heterogeneous or nonstationary data, of which the underlying generating process changes across domains or over time. Such a distribution shift feature presents both challenges and opportunities for causal discovery. In this paper, we develop a framework for causal discovery from such data, called Constraint-based causal Discovery from heterogeneous/NOnstationary Data (CD-NOD), to find causal skeleton and directions and estimate the properties of mechanism changes. First, we propose an enhanced constraint-based procedure to detect variables whose local mechanisms change and recover the skeleton of the causal structure over observed variables. Second, we present a method to determine causal orientations by making use of independent changes in the data distribution implied by the underlying causal model, benefiting from information carried by changing distributions. After learning the causal structure, next, we investigate how to efficiently estimate the “driving force” of the nonstationarity of a causal mechanism. That is, we aim to extract from data a low-dimensional representation of changes. The proposed methods are nonparametric, with no hard restrictions on data distributions and causal mechanisms, and do not rely on window segmentation. Furthermore, we find that data heterogeneity benefits causal structure identification even with particular types of confounders. Finally, we show the connection between heterogeneity/nonstationarity and soft intervention in causal discovery. Experimental results on various synthetic and real-world data sets (task-fMRI and stock market data) are presented to demonstrate the efficacy of the proposed methods.

We address two important issues in causal discovery from nonstationary or heterogeneous data, where parameters associated with a causal structure may change over time or across data sets. First, we investigate how to efficiently estimate the "driving force" of the nonstationarity of a causal mechanism. That is, given a causal mechanism that varies over time or across data sets and whose qualitative structure is known, we aim to extract from data a low-dimensional and interpretable representation of the main components of the changes. For this purpose we develop a novel kernel embedding of nonstationary conditional distributions that does not rely on sliding windows. Second, the embedding also leads to a measure of dependence between the changes of causal modules that can be used to determine the directions of many causal arrows. We demonstrate the power of our methods with experiments on both synthetic and real data.