Biology subjects

Schultz, S. R.

Publications and source records attributed to Schultz, S. R..

6 recordsLinked to original sources

bioRxiv2018

Distinct cross-frequency coupling signatures for top-down and bottom-up information processing in auditory cortex

Predictive coding is a theoretical framework that provides a functional interpretation of top-down and bottom up interactions in sensory processing. The theory has suggested that specific frequency bands relay bottom-up and top-down information (e.g. \"{gamma} up, {beta} down\"). But it remains unclear whether this notion generalizes to cross-frequency interactions. Furthermore, most of the evidence so far comes from visual pathways. Here we examined cross-frequency coupling across four sectors of the auditory hierarchy in the macaque. We computed two measures of cross-frequency coupling, phase-amplitude coupling (PAC) and amplitude-amplitude coupling (AAC). Our findings revealed distinct patterns for bottom-up and top-down information processing among cross-frequency interactions. Both top-down and bottom-up made prominent use of low frequencies: low-to-low frequency ({theta}, , {beta}) and low frequency-to-high {gamma} couplings were predominant top-down, while low frequency-to-low {gamma} couplings were predominant bottom-up. These patterns were largely preserved across coupling types (PAC and AAC) and across stimulus types (natural and synthetic auditory stimuli), suggesting they are a general feature of information processing in auditory cortex. Moreover, our findings showed that low-frequency PAC alternated between predominantly top-down or bottom-up over time. Altogether, this suggests sensory information need not be propagated along separate frequencies upwards and downwards. Rather, information can be unmixed by having low frequencies couple to distinct frequency ranges in the target region, and by alternating top-down and bottom-up processing over time.\n\n1 SignificanceThe brain consists of highly interconnected cortical areas, yet the patterns in directional cortical communication are not fully understood, in particular with regards to interactions between different signal components across frequencies. We employed a a unified, computationally advantageous Granger-causal framework to examine bi-directional cross-frequency interactions across four sectors of the auditory cortical hierarchy in macaques. Our findings extend the view of cross-frequency interactions in auditory cortex, suggesting they also play a prominent role in top-down processing. Our findings also suggest information need not be propagated along separate channels up and down the cortical hierarchy, with important implications for theories of information processing in the brain such as predictive coding.

neuroscience↗

bioRxiv2018

Visual reconstruction from 2-photon calcium imaging suggests linear readout properties of neurons in mouse primary visual cortex

Deciphering the neural code, that is interpreting the responses of sensory neurons from the perspective of a downstream population, is an important step towards understanding how the brain processes sensory stimulation. While previous work has focused on classification algorithms to identify the most likely stimulus label in a predefined set of categories, fewer studies have approached a full stimulus reconstruction task. Outstanding questions revolve around the type of algorithm that is most suited to decoding (i.e. full reconstruction, in the context of this study), especially in the presence of strong encoding non-linearities, and the possible role of pairwise correlations. We present, here, the first pixel-by-pixel reconstruction of a complex natural stimulus from 2-photon calcium imaging responses of mouse primary visual cortex (V1). We decoded the activity of approximately 100 neurons from layer 2/3 using an optimal linear estimator and an artificial neural network. We also investigated how much accuracy is lost in this decoding operation when ignoring pairwise neural correlations. We found that a simple linear estimator is sufficient to extract relevant stimulus features from the neural responses, and that it was not significantly outperformed by a non-linear decoding algorithm. The importance of pairwise correlations for reconstruction accuracy was also limited. The results of this study suggest that, conditional on the spatial and temporal limits of the recording technique, V1 neurons display linear readout properties, with low information content in the joint distribution of their activity.

neuroscience↗

bioRxiv2017

CosMIC: A Consistent Metric for Spike Inference from Calcium Imaging

In recent years, the development of algorithms to detect neuronal spiking activity from two-photon calcium imaging data has received much attention. Meanwhile, few researchers have examined the metrics used to assess the similarity of detected spike trains with the ground truth. We highlight the limitations of the two most commonly used metrics, the spike train correlation and success rate, and propose an alternative, which we refer to as CosMIC. Rather than operating on the true and estimated spike trains directly, the proposed metric assesses the similarity of the pulse trains obtained from convolution of the spike trains with a smoothing pulse. The pulse width, which is derived from the statistics of the imaging data, reflects the temporal tolerance of the metric. The final metric score is the size of the commonalities of the pulse trains as a fraction of their average size. Viewed through the lens of set theory, CosMIC resembles a continuous Sorensen-Dice coefficient -- an index commonly used to assess the similarity of discrete, presence/absence data. We demonstrate the ability of the proposed metric to discriminate the precision and recall of spike train estimates. Unlike the spike train correlation, which appears to reward overestimation, the proposed metric score is maximised when the correct number of spikes have been detected. Furthermore, we show that CosMIC is more sensitive to the temporal precision of estimates than the success rate.

neuroscience↗

bioRxiv2017

Multiscale simulation of peripheral neural signaling

Bioelectronic Medicines that modulate the activity patterns on peripheral nerves have promise as a new way of treating diverse medical conditions from epilepsy to rheumatism. Progress in the field builds upon time consuming and expensive experiments in living organisms to evaluate spontaneous activity patterns, stimulation efficiency, and organ responses. To reduce experimentation load and allow for a faster, more detailed analysis of both recording from and stimulation of peripheral nerves, adaptable computational models incorporating insights won in experiments will be of great help. We present a peripheral nerve simulator that combines biophysical axon models and numerically solved and idealized extracellular space models in one environment. Two different scales of abstraction were merged. On the one hand we modeled the extracellular space in a finite element solver as a three dimensional resistive continuum governed by the electro-quasistatic approximation of the Maxwell equations. Potential distributions were precomputed for different media (homogeneous, nerve in saline, nerve in cuff). Axons, on the other hand, were modeled at a higher level of abstraction as one dimensional chains of compartments; each consisting of lumped linear elements and, for some, channels with non-linear dynamics. Unmyelinated fibres were based on the Hodgkin-Huxley model; for myelinated fibers, we instead adapted the model proposed by McIntyre et al. in 2002 to smaller diameters. To obtain realistic axon shapes, an iterative algorithm positioned fibers along the nerve with variable tortuosity, with tortuosity values fit to imaged trajectories. We validated our model with data from the stimulated rat vagus nerve. Simulation results predicted that tortuosity leads to differentiation in recorded signal shapes, with unmyelinated axons being the most affected. Tortuosity was further shown to increase the stimulation threshold. The model we developed can easily be adapted to different nerves, and may be of use for Bioelectronic Medicine research in the future.

neuroscience↗

bioRxiv2017

ABLE: an Activity-Based Level Set Segmentation Algorithm for Two-Photon Calcium Imaging Data

We present an algorithm for detecting the location of cells from two-photon calcium imaging data. In our framework, multiple coupled active contours evolve, guided by a model-based cost function, to identify cell boundaries. An active contour seeks to partition a local region into two subregions, a cell interior and ex-terior, in which all pixels have maximally similar time courses. This simple, local model allows contours to be evolved predominantly independently. When contours are sufficiently close, their evolution is coupled, in a manner that permits overlap. We illustrate the ability of the proposed method to demix overlapping cells on real data. The proposed framework is flexible, incorporating no prior information regarding a cells morphology or stereotypical temporal activity, which enables the detection of cells with diverse properties. We demonstrate algorithm performance on a challenging mouse in vitro dataset, containing synchronously spiking cells, and a manually labelled mouse in vivo dataset, on which ABLE achieves a 67.5% success rate.\n\nSignificance statementTwo-photon calcium imaging enables the study of brain activity during learning and behaviour at single-cell resolution. To decode neuronal spiking activity from the data, algorithms are first required to detect the location of cells in the video. It is still common for scientists to perform this task manually, as the heterogeneity in cell shape and frequency of cellular overlap impede automatic segmentation algorithms. We developed a versatile algorithm based on a popular image segmentation approach (the Level Set Method) and demonstrated its capability to overcome these challenges. We include no assumptions on cell shape or stereotypical temporal activity. This lends our framework the flexibility to be applied to new datasets with minimal adjustment.

neuroscience↗

bioRxiv2017

Real-time decoding of bladder pressure from pelvic nerve activity

Real time algorithms for decoding physiological signals from peripheral nerve recordings form an important component of closed loop bioelectronic medicine (electroceutical) systems. As a feasibility demonstration, we considered the problem of decoding bladder pressure from pelvic nerve electroneurograms. We extracted power spectral density of the nerve signal across a band optimised for Shannon Mutual Information, followed by linearization via piece-wise linear regression, and finally decoded signal reconstruction through optimal linear filtering. We demonstrate robust and effective reconstruction of bladder pressure, both prior to and following pharmacological manipulation.

neuroscience↗