The accurate relay of electrical signals within cortical networks is key to perception and cognitive function. Theoretically, it has long been proposed that temporal coordination of neuronal spiking activity controls signal transmission and behavior. However, whether and how temporally precise neuronal coordination in population activity influences perception are unknown. Here, we recorded populations of neurons in early and mid-level visual cortex (areas V1 and V4) simultaneously to discover that the precise temporal coordination between the spiking activity of three or more cells carries information about visual perception in the absence of firing rate modulation. The accuracy of perceptual responses correlated with high-order spiking coordination within V4, but not V1, and with feedforward coordination between V1 and V4. These results indicate that while visual stimuli are encoded in the discharge rates of neurons, perceptual accuracy is related to temporally precise spiking coordination within and between cortical networks.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
The custom-written software supporting the findings of this study is available from the corresponding author upon reasonable request.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
These authors contributed equally: Ariana R. Andrei, Ming Hu.
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Integrated supplementary information
We calculated the coordination rates using conventional cross-correlograms8 between all possible pairs of three participating neurons (neurons 5, 6, and 7) for an example triplet. No significant difference between the peaks of cross-correlograms was observed (p > 0.1, 2-sided unpaired t-test). Shaded regions represent SEM across trials (correct: n = 69, incorrect: n = 31). Across all sessions (V1: n = 22, V4: n = 12), the difference between correct and incorrect CCG peaks was not statistically significant (2-sided Wilcoxon signed rank test with FDR correction; V1: p = 0.27, V4: p = 0.79).
Normalized coordination rates for cell ensembles of size 2 to 5 in areas V1 (22 sessions) and V4 (12 sessions). Error bars represent SEM.
Supplementary Fig. 3 Stimulus classification performance in areas V1 and V4 of a SVM decoder with RBF kernel.
The inputs to the decoder were the coordination rates of pairs, triplets, and quarters in each area. The decoder’s output is the classification of test stimulus identity (stim1 vs. stim2). The analysis window is a 300-ms window of the sustained response to the test stimulus (150–450 ms relative to stimulus onset). The analysis window is the 300-ms period of the sustained response to the test stimulus (150–450 ms relative to stimulus onset; this window provides the most significant results in the analysis of coordination rates in relation to perceptual accuracy, MEP_L_fig3Fig. 3; choosing a window including the onset transient response yields similar results). The parameters of the cross-validation are stated in the original manuscript. The data points represent averages and error bars represent SEM across sessions (n = 22 for V1 and n = 12 for V4; decoder performance was not statistically significant in any session regardless of the cortical area that was tested; p > 0.1, 2-sided Wilcoxon rank-sum test with FDR correction).
a) Performance of stimulus decoder tested for correct and incorrect trials for a 200-ms analysis window (to maximize decoder performance), as in Fig. 3a (asterisks indicate p < 0.01). This figure confirms that (in each animal) stimuli can be decoded above chance level both in correct and incorrect trials in V1, but only in correct trials in V4. The bars show the average across sessions (monkey W: n = 8 in V1, and n = 8 in V4; monkey C: n = 14 in V1, and n = 4 in V4). Error bars represent SEM. b) Normalized coordination rates (correct - incorrect trials) in V4 for 2nd and higher order events during the 300-ms window associated with the target (left) and test (right) stimuli, as well as the delay period (100–400 ms following target onset). As in the original average results across animals, the only significant cases are the occurrence of higher order coordinated events during the test stimulus presentation (asterisks indicate p < 0.01; the actual p-values are reported in the manuscript). The bars show the average across sessions (monkey W: n = 8 for SO and n = 16 for HO; monkey C: n = 4 for SO and n = 8 for HO). Error bars show SEM. c) Peak coordination rate between V1 and V4 for correct and incorrect trials. For all higher order events combined, the p-value is 0.0029 for monkey W (n = 16) and 0.0004 for monkey C (n = 16). The traces represent the average and the error-bars represent SEM. For the high-order cross-correlation analysis (manuscript MEP_L_fig5Fig. 5e), the p-values are 0.0420 for monkey W (n = 4) and 0.0117 for monkey C (n = 4). This figure confirms that (for each animal) there is higher coordination of high-order spiking events in correct trials compared to incorrect.
a) Distribution of firing rates of a sample neuron calculated for 20 ms time bins, separately for a correct and incorrect trial. b) Percentage of neurons (n = 293) for which the distributions of firing rates for correct and incorrect trials were statistically different (2-sided Wilcoxon rank-sum test, p < 0.05 with FDR correction) as a function of bin size (by pooling cells across sessions). The two firing rate distributions were constructed by pooling the firing rates of a neuron across trials for each time bin, separately for correct and incorrect trials. Subsequently, for each time bin we tested whether the two response distributions are significantly different. This analysis was repeated for each cell in the population. c,d) Baseline-removed population-averaged PSTHs of all the neurons in V1 (n = 183) and V4 (n = 110) for correct and incorrect trials separately for the match conditions (c) and non-match condition in each monkey (d). The bin size was 20 ms. (2-sided Wilcoxon rank-sum test with FDR correction; match condition: p = 0.08; monkey W, p = 0.51 for V1 and p = 0.16 for V4. monkey C: p = 0.22 for V1 and p = 0.19 for V4). Shaded regions show SEM.
Supplementary Fig. 6 Performance of the classifier that uses the firing rates of all simultaneously recorded neurons to decode perceptual accuracy (correct vs incorrect).
A 200-ms window sliding in 20-ms incremental steps was used. The classifier was trained using 80% of the trials and performance was measured by classifying the remaining 20% of trials. The performance was cross-validated 1,000 times by randomly dividing trials to training and test sets. In shuffled classifiers, the trial labels (correct vs. incorrect) were shuffled before training; then the cross-validation procedure was repeated. The performance of the classifier was not significantly different from the null hypothesis (p > 0.1) for any analysis window in any cortical area. Shaded regions represent SEM across sessions (n = 22 for V1 and n = 12 for V4).
Supplementary Fig. 7 Three measures of neural activity in V1 and V4 related to attentional modulation.
Mean firing rates (panel a), Fano factor (panel b), and mean noise correlations (panel c), previously demonstrated to be correlated with attentional modulation, do not exhibit statistically significant differences between correct and incorrect trials. The vertical lines in each panel represent the means of each distribution. All tests were 2-sided; V1: n = 183, V4: n = 110.
The difference between coordination rates of correct and incorrect trials are shown separately for second-order and higher-order coordinated. Coordination rates were calculated for a 300 ms window sliding in 10 ms steps over the test stimulus. Each trace represents the averages across trials (correct: n = 46, incorrect: n = 46); shaded areas represent SEM.
As an additional control, we shuffled the spike trains associated with correct and incorrect trial sets (within each set), then recalculated the coordination rates for pairs, triplets, and quartets, and finally subtracted the coordination rates for the incorrect trials from the rates associated with correct trials. No significant difference between coordination rates was observed (p > 0.1) when spike trains were shuffled. Horizontal lines show the average across sessions (V1: n = 22, V4: n = 12).
Supplementary Fig. 11 Coordination rates are significantly different between correct and incorrect trials (p < 0.05) for a range of bin sizes and jitter ranges.
a) Coordination rates as a function of bin size (top) and associated p-values (bottom), 2-sided Wilcoxon signed rank test, calculated across V4 sessions (n = 12). The bin width varied in the range of 1 and 11 ms with steps of 1 ms. For bin sizes of 4 ms and higher, p-values of triplets and quartets are smaller than 0.05. b) Same analysis as in (a) but for jitter range of 3 to 13 ms with steps of 1 ms. For jitter range of 8 ms and higher, the p-value was smaller than 0.05.
Each cross-correlogram was normalized by the geometric mean of the firing rates of participating neurons. No significant peak in the CCG (z-score > 2) was observed within the ± 40 ms time lag range. Shaded area represents SEM across all V1-V4 pairs (n = 734).
Supplementary Fig. 13 Cross-correlogram (CCG) between V1 and V4 to test whether high-order spiking coordination drives spiking activity in a target area.
Left: CCG between convergent feedforward inputs from V1 (high-order spiking events) and V4 individual spikes reveals that high-order coordination in V1 is not associated with elevated spiking in V4. Right: CCG between convergent feedback inputs from V4 (high-order spiking events) and V1 individual spikes reveals that high-order coordination in V4 is not associated with elevated spiking in V1. Each cross-correlogram was normalized by the geometric mean of the firing rates of participating neurons. No significant CCG peak (z-score > 2) was observed within the ± 40 ms time lag range that we explored. Shaded areas represent SEM across sessions (n = 7).
Supplementary Fig. 14 Cross-correlogram between higher-order events in V1 and individual neurons in V4, sorted by the magnitude of their peak.
Each row shows the trial averaged cross-correlogram for one V4 neuron. The peaks were z-scored using the tail of the cross-correlogram, similar to the original analysis in the manuscript; only 3 cross-correlograms showed a significant peak (p < 0.05, t-test).
a) ‘Local’ behavioral performance was calculated as percentage of correct responses in the last 10 trials for a sample session. In the same panel we represent the coordination rate in the trial immediately following the window of trials for which behavioral performance was calculated. The Pearson’s correlation coefficient between local behavioral performance and coordination rate and the associated p-value are shown (2-sided t-test was used to calculate p-value). b) Pearson’s correlation coefficient of coordination rates with behavioral performance in the recent trials. The width of the window for which behavioral performance was measured is 1–30 trials before current trial. The Pearson’s correlation coefficient between the coordination rates and behavioral outcomes in the current trial (0 for incorrect and 1 for correct) is shown as a separate data point. The red traces and dots represent averages across V4 sessions (n = 12); error-bars and shaded regions represent SEM.