One dimensional approximations of neuronal dynamics reveal computational strategy.

The relationship between neuronal activity and computations embodied by it remains an open question. We develop a novel methodology that condenses observed neuronal activity into a quantitatively accurate, simple, and interpretable model and validate it on diverse systems and scales from single neurons in C. elegans to fMRI in humans. The model treats neuronal activity as collections of interlocking 1-dimensional trajectories. Despite their simplicity, these models accurately predict future neuronal activity and future decisions made by human participants. Moreover, the structure formed by interconnected trajectories-a scaffold-is closely related to the computational strategy of the system. We use these scaffolds to compare the computational strategy of primates and artificial systems trained on the same task to identify specific conditions under which the artificial agent learns the same strategy as the primate. The computational strategy extracted using our methodology predicts specific errors on novel stimuli. These results show that our methodology is a powerful tool for studying the relationship between computation and neuronal activity across diverse systems.

SuperSegger: robust image segmentation, analysis and lineage tracking of bacterial cells.

Many quantitative cell biology questions require fast yet reliable automated image segmentation to identify and link cells from frame-to-frame, and characterize the cell morphology and fluorescence. We present SuperSegger, an automated MATLAB-based image processing package well-suited to quantitative analysis of high-throughput live-cell fluorescence microscopy of bacterial cells. SuperSegger incorporates machine-learning algorithms to optimize cellular boundaries and automated error resolution to reliably link cells from frame-to-frame. Unlike existing packages, it can reliably segment microcolonies with many cells, facilitating the analysis of cell-cycle dynamics in bacteria as well as cell-contact mediated phenomena. This package has a range of built-in capabilities for characterizing bacterial cells, including the identification of cell division events, mother, daughter and neighbouring cells, and computing statistics on cellular fluorescence, the location and intensity of fluorescent foci. SuperSegger provides a variety of postprocessing data visualization tools for single cell and population level analysis, such as histograms, kymographs, frame mosaics, movies and consensus images. Finally, we demonstrate the power of the package by analyzing lag phase growth with single cell resolution.

Attractor dynamics with activity-dependent plasticity capture human working memory across time scales.

Most cognitive functions require the brain to maintain immediately preceding stimuli in working memory. Here, using a human working memory task with multiple delays, we test the hypothesis that working memories are stored in a discrete set of stable neuronal activity configurations called attractors. We show that while discrete attractor dynamics can approximate working memory on a single time scale, they fail to generalize across multiple timescales. This failure occurs because at longer delay intervals the responses contain more information about the stimuli than can be stored in a discrete attractor model. We present a modeling approach that combines discrete attractor dynamics with activity-dependent plasticity. This model successfully generalizes across all timescales and correctly predicts intertrial interactions. Thus, our findings suggest that discrete attractor dynamics are insufficient to model working memory and that activity-dependent plasticity improves durability of information storage in attractor systems.

A neural signature of social support mitigates negative emotion.

Social support can mitigate the impact of distressing events. Such stress buffering elicits activity in many brain regions, but it remains unclear (1) whether this activity constitutes a stable brain signature, and (2) whether brain activity can predict buffering across people. Here, we developed a neural signature that predicted social buffering of negative emotion in response to real life stressors. During neuroimaging, participants (n = 95) responded to stressful autobiographical memories either naturally, or by imagining a conversation with a peer. Using supervised dimensionality reduction and machine learning techniques, we identified a spatio-temporal neural signature that distinguished between these two trials. Activation of this signature was associated with less negative affect across trials, and people who most activated the signature reported more supportive social connections and lower loneliness outside the lab. Together, this work provides a behaviorally relevant neurophysiological marker for social support that underlies stress buffering.

Enriching adult male rats prior to traumatic brain injury does not attenuate neurobehavioral or histological deficits.

Environmental enrichment (EE) confers significant increases in neurobehavioral and cognitive recovery and decreases histological damage in various models of traumatic brain injury (TBI). However, despite EE's pervasiveness, little is known regarding its prophylactic potential. Thus, the goal of the current study was to determine whether enriching rats prior to a controlled cortical impact exerts protection as evidenced by attenuated injury-induced neurobehavioral and histological deficits relative to rats without prior EE. The hypothesis was that enrichment prior to TBI would be protective. After two weeks of EE or standard (STD) housing, anesthetized adult male rats received either a controlled cortical impact (2.8 mm deformation at 4 m/s) or sham injury and then were placed in EE or STD conditions. Motor (beam-walk) and cognitive (spatial learning) performance were assessed on post-operative days 1-5 and 14-18, respectively. Cortical lesion volume was quantified on day 21. The group that was housed in STD conditions before TBI and received post-injury EE performed significantly better in motor, cognitive, and histological outcomes vs. both groups in STD conditions regardless of whether having received pre-injury EE or not (p < 0.05). That no differences in any endpoint were revealed between the two STD-housed groups after TBI suggests that enriching rats prior to TBI does not attenuate neurobehavioral or histological deficits and therefore does not support the hypothesis.

Visual evoked feedforward-feedback traveling waves organize neural activity across the cortical hierarchy in mice.

Sensory processing is distributed among many brain regions that interact via feedforward and feedback signaling. Neuronal oscillations have been shown to mediate intercortical feedforward and feedback interactions. Yet, the macroscopic structure of the multitude of such oscillations remains unclear. Here, we show that simple visual stimuli reliably evoke two traveling waves with spatial wavelengths that cover much of the cerebral hemisphere in awake mice. 30-50 Hz feedforward waves arise in primary visual cortex (V1) and propagate rostrally, while 3-6 Hz feedback waves originate in the association cortex and flow caudally. The phase of the feedback wave modulates the amplitude of the feedforward wave and synchronizes firing between V1 and parietal cortex. Altogether, these results provide direct experimental evidence that visual evoked traveling waves percolate through the cerebral cortex and coordinate neuronal activity across broadly distributed networks mediating visual processing.

A quantitative model of conserved macroscopic dynamics predicts future motor commands.

In simple organisms such as Caenorhabditis elegans, whole brain imaging has been performed. Here, we use such recordings to model the nervous system. Our model uses neuronal activity to predict expected time of future motor commands up to 30 s prior to the event. These motor commands control locomotion. Predictions are valid for individuals not used in model construction. The model predicts dwell time statistics, sequences of motor commands and individual neuron activation. To develop this model, we extracted loops spanned by neuronal activity in phase space using novel methodology. The model uses only two variables: the identity of the loop and the phase along it. Current values of these macroscopic variables predict future neuronal activity. Remarkably, our model based on macroscopic variables succeeds despite consistent inter-individual differences in neuronal activation. Thus, our analytical framework reconciles consistent individual differences in neuronal activation with macroscopic dynamics that operate universally across individuals.

Coherence of Visual-Evoked Gamma Oscillations Is Disrupted by Propofol but Preserved Under Equipotent Doses of Isoflurane.

Previous research demonstrates that the underlying state of the brain influences how sensory stimuli are processed. Canonically, the state of the brain has been defined by quantifying the spectral characteristics of spontaneous fluctuations in local field potentials (LFP). Here, we utilized isoflurane and propofol anesthesia to parametrically alter the spectral state of the murine brain. With either drug, we produce slow wave activity, with low anesthetic doses, or burst suppression, with higher doses. We find that while spontaneous LFP oscillations were similar, the average visual-evoked potential (VEP) was always smaller in amplitude and shorter in duration under propofol than under comparable doses of isoflurane. This diminished average VEP results from increased trial-to-trial variability in VEPs under propofol. One feature of single trial VEPs that was consistent in all animals was visual-evoked gamma band oscillation (20-60 Hz). This gamma band oscillation was coherent between trials in the early phase (<250 ms) of the visual evoked potential under isoflurane. Inter trial phase coherence (ITPC) of gamma oscillations was dramatically attenuated in the same propofol anesthetized mice despite similar spontaneous oscillations in the LFP. This suggests that while both anesthetics lead to loss of consciousness (LOC), elicit slow oscillations and burst suppression, only the isoflurane permits phase resetting of gamma oscillations by visual stimuli. These results demonstrate that accurate characterization of a brain state must include both spontaneous as well as stimulus-induced perturbations of brain activity.