Journal: Cell Reports Methods
Article Title: Neural barcoding representing cortical spatiotemporal dynamics based on continuous-time Markov chains
doi: 10.1016/j.crmeth.2025.101294
Figure Lengend Snippet: The Markovian neural barcode and sensory evoked processing (A) A schematic representation of mesoscale cortical imaging during full-field visual flash experiments. Awake head-fixed animals were imaged as a 450-nm LED placed adjacent to the right eye delivered full-field visual flashes. (B) Visual evoked responses from a full-field flash produce a characteristic response in V1 as shown in the montage depicting an average of 100 trials (top) and a single trial (bottom). The montage represents the visual evoked response pre-stimulation (−100 ms), the stimulation denoted by a schematic LED and blue line, and post-stimulation (+100, +300, and +500 ms). Note the considerable variability in the late component (+300 ms) of the visual evoked response as exemplified by the difference seen between the average and the single trial. (C) The heterogeneity in visual evoked response amplitudes is shown on a per trial basis (gray lines) representing the Δ F / F signal within a 10 × 10 pixel region of interest in V1. The average visual evoked response trace is shown in red, revealing the primary and secondary visual evoked responses (the secondary response is highlighted by the blue arrow). (D) A “raster plot” of the Markov state occupancy ( y axis) vs. time ( x axis), with the states color coded according to the Louvain sorted activity modules. The blue vertical lines denote full-field LED flashes. (E) The histogram of the Markov state occupancy across time, organized by modules and separated by green boundaries, for the second preceding and following a full-field LED flash. Brighter colors denote higher occupancy in time. (F) A sample set of 4 Markov elements from different modules that were upregulated by the stimulus flash immediately after the full-field visual flash as compared to pre-stimulus. (G) The Louvain sorted TPMs derived from transitions occurring prior to the full-field visual flash (left) and after the flash onset (right). Note the upregulation of inter-module transition probabilities. Brighter colors denote higher probabilities of transitions. (H) The Markovian neural barcode for the same animals imaged under a control quiet wakefulness condition and with field visual flashes occurring every 3 s with 1-s jitter (as described in A). The red vertical lines denote the boundary between modules as well as the occupancy distribution in the Markovian neural barcode. Darker colors denote higher probabilities/proportions in the neural barcode. (I) The first two PC projections of the neural barcode for the full barcode (left), the TPMs only (middle), and the occupancy distribution only (right) for the control (white circles) and visual stimulation protocol recordings (blue circles). Note the condition clustering and separation. (J) Statistical quantification of the PC distance distributions displayed as violin plots for the controls (white circles) vs. the visual stimulation (blue circles). Recordings in which animals receive a full-field visual flash differ from control recordings for the full neural barcode ([left] Wilcoxon rank-sum test; control: 0.2517, visual: 0.5045, p = 3.1908 e -3), the TPMs only ([middle] Wilcoxon rank-sum test; control: 0.2507, visual: 0.5041, p = 3.2795 e -03), and the occupancy distribution only ([right] Wilcoxon rank-sum test; control: 0.3670, visual: 0.5829, p = 4.9088 e -3). Please see figure for interquartile range. (K) Visual flash trials are dichotomized according to a median split of the secondary response amplitude from n = 8 mice. The projections of the Markovian neural barcode along the first two PCs plotted for (left) the full barcode, (middle) transitions only, and (right) occupancy only in the second preceding the flash. Clustering is evident along the PC projection for the occupancy distribution. (L) Quantification of the PC projections from the first three components reveals that only the Markov element occupancy distribution distinguishes visual evoked response trials with high and low Δ F / F secondary responses (Wilcoxon rank-sum test; [Full] low: 0.3870, high: 0.3004, p = 6.9315 e -01; [TPM] low: 0.3822, high: 0.3024, p = 7.3749 e -01; [OCC] low: 0.3766, high: 0.5639, p = 6.5393 e -05). Please see figure for interquartile range. (OCC, occupancy distribution). (M) The Markov element occupancy bar code is presented for n = 8 animals for trials that elicited high and low Δ F / F secondary responses. This reveals a marked upregulation of Module 2 Markov elements in trials that elicited Δ F / F amplitude secondary responses and an upregulation of Module 1 Markov elements in trials that elicited Δ F / F amplitude secondary responses.
Article Snippet: • We develop a compact, low-dimensional representation of cortical dynamics • We utilize a continuous-time Markov chain modeling framework • We demonstrate model sensitivity to individual animal signatures • We also demonstrate model robustness to experimental manipulations
Techniques: Imaging, Activity Assay, Derivative Assay, Control