Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules

Peer reviewe

Where in the brain do internally generated and externally presented visual information interact?

Conscious experiences normally result from the flow of external input into our sensory systems. However, we can also create conscious percepts independently of sensory stimulation. These internally generated percepts are referred to as mental images, and they have many similarities with real visual percepts. Consequently, mental imagery is often referred to as "seeing in the mind's eye". While the neural basis of imagery has been widely studied, the interaction between internal and external sources of visual information has received little interest. Here we examined this question by using fMRI to record brain activity of healthy human volunteers while they were performing visual imagery that was distracted with a concurrent presentation of a visual stimulus. Multivariate pattern analysis (MVPA) was used to identify the brain basis of this interaction. Visual imagery was reflected in several brain areas in ventral temporal, lateral occipitotemporal, and posterior frontal cortices, with a left-hemisphere dominance. The key finding was that imagery content representations in the left lateral occipitotemporal cortex were disrupted when a visual distractor was presented during imagery. Our results thus demonstrate that the representations of internal and external visual information interact in brain areas associated with the encoding of visual objects and shapes.Peer reviewe

Emotional speech synchronizes brains across listeners and engages large-scale dynamic brain networks

Speech provides a powerful means for sharing emotions. Here we implement novel intersubject phase synchronization and whole-brain dynamic connectivity measures to show that networks of brain areas become synchronized across participants who are listening to emotional episodes in spoken narratives. Twenty participants' hemodynamic brain activity was measured with functional magnetic resonance imaging (fMRI) while they listened to 45-s narratives describing unpleasant, neutral, and pleasant events spoken in neutral voice. After scanning, participants listened to the narratives again and rated continuously their feelings of pleasantness–unpleasantness (valence) and of arousal–calmness. Instantaneous intersubject phase synchronization (ISPS) measures were computed to derive both multi-subject voxel-wise similarity measures of hemodynamic activity and inter-area functional dynamic connectivity (seed-based phase synchronization, SBPS). Valence and arousal time series were subsequently used to predict the ISPS and SBPS time series. High arousal was associated with increased ISPS in the auditory cortices and in Broca's area, and negative valence was associated with enhanced ISPS in the thalamus, anterior cingulate, lateral prefrontal, and orbitofrontal cortices. Negative valence affected functional connectivity of fronto-parietal, limbic (insula, cingulum) and fronto-opercular circuitries, and positive arousal affected the connectivity of the striatum, amygdala, thalamus, cerebellum, and dorsal frontal cortex. Positive valence and negative arousal had markedly smaller effects. We propose that high arousal synchronizes the listeners' sound-processing and speech-comprehension networks, whereas negative valence synchronizes circuitries supporting emotional and self-referential processing.Peer reviewe

Exposure Bias and State Matching in Recurrent Neural Network Virtual Analog Models

Virtual analog (VA) modeling using neural networks (NNs) has great potential for rapidly producing high-fidelity models. Recurrent neural networks (RNNs) are especially appealing for VA due to their connection with discrete nodal analysis. Furthermore, VA models based on NNs can be trained efficiently by directly exposing them to the circuit states in a gray-box fashion. However, exposure to ground truth information during training can leave the models susceptible to error accumulation in a free-running mode, also known as “exposure bias” in machine learning literature. This paper presents a unified framework for treating the previously proposed state trajectory network (STN) and gated recurrent unit (GRU) networks as special cases of discrete nodal analysis. We propose a novel circuit state-matching mechanism for the GRU and experimentally compare the previously mentioned networks for their performance in state matching, during training, and in exposure bias, during inference. Experimental results from modeling a diode clipper show that all the tested models exhibit some exposure bias, which can be mitigated by truncated backpropagation through time. Furthermore, the proposed state matching mechanism improves the GRU modeling performance of an overdrive pedal and a phaser pedal, especially in the presence of external modulation, apparent in a phaser circuit.Peer reviewe

Reproducibility of importance extraction methods in neural network based fMRI classification

Recent advances in machine learning allow faster training, improved performance and increased interpretability of classification techniques. Consequently, their application in neuroscience is rapidly increasing. While classification approaches have proved useful in functional magnetic resonance imaging (fMRI) studies, there are concerns regarding extraction, reproducibility and visualization of brain regions that contribute most significantly to the classification. We addressed these issues using an fMRI classification scheme based on neural networks and compared a set of methods for extraction of category-related voxel importances in three simulated and two empirical datasets. The simulation data revealed that the proposed scheme successfully detects spatially distributed and overlapping activation patterns upon successful classification. Application of the proposed classification scheme to two previously published empirical fMRI datasets revealed robust importance maps that extensively overlap with univariate maps but also provide complementary information. Our results demonstrate increased statistical power of importance maps compared to univariate approaches for both detection of overlapping patterns and patterns with weak univariate information.Peer reviewe

Discrete Neural Signatures of Basic Emotions

Categorical models of emotions posit neurally and physiologically distinct human basic emotions. We tested this assumption by using multivariate pattern analysis (MVPA) to classify brain activity patterns of 6 basic emotions (disgust, fear, happiness, sadness, anger, and surprise) in 3 experiments. Emotions were induced with short movies or mental imagery during functional magnetic resonance imaging. MVPA accurately classified emotions induced by both methods, and the classification generalized from one induction condition to another and across individuals. Brain regions contributing most to the classification accuracy included medial and inferior lateral prefrontal cortices, frontal pole, precentral and postcentral gyri, precuneus, and posterior cingulate cortex. Thus, specific neural signatures across these regions hold representations of different emotional states in multimodal fashion, independently of how the emotions are induced. Similarity of subjective experiences between emotions was associated with similarity of neural patterns for the same emotions, suggesting a direct link between activity in these brain regions and the subjective emotional experience