Assessing the spatiotemporal evolution of neuronal activation with single-trial event-related potentials and functional MRI

Abstract

The brain acts as an integrated information processing system, which methods in cognitive neuroscience have so far depicted in a fragmented fashion. Here, we propose a simple and robust way to integrate functional MRI (fMRI) with single trial event-related potentials (ERP) to provide a more complete spatiotemporal characterization of evoked responses in the human brain. The idea behind the approach is to find brain regions whose fMRI responses can be predicted by paradigm-induced amplitude modulations of simultaneously acquired single trial ERPs. The method was used to study a variant of a two-stimulus auditory target detection (odd-ball) paradigm that manipulated predictability through alternations of stimulus sequences with random or regular target-to-target intervals. In addition to electrophysiologic and hemodynamic evoked responses to auditory targets per se, single-trial modulations were expressed during the latencies of the P2 (170-ms), N2 (200-ms), and P3 (320-ms) components and predicted spatially separated fMRI activation patterns. These spatiotemporal matches, i.e., the prediction of hemodynamic activation by time-variant information from single trial ERPs, permit inferences about regional responses using fMRI with the temporal resolution provided by electrophysiology.

Fig. 1.

Illustration of how ERP AM can achieve high temporal resolution in fMRI. A suitable paradigm in a simultaneous ERP-fMRI recording can be used to induce slow and localized AM (a, b, and c) at or below the sampling frequency of the MR data acquisition. In this example, the model AM are generated in separate areas sensitive to the manipulation and are detectable in both ERP and fMRI. Consecutive correlation analysis between the fMRI time series and the multiple ERP time series yields complementary information regarding the spatial location and timing of these processes. Neuroelectric source acitivities need not necessarily propagate to the scalp directly but can modulate or be modulated by remote sources (indicated by arrows).

Fig. 2.

Flowchart of the single-trial ERP and fMRI analysis. Data are decomposed with independent components analysis (a), and artifact topographies (cardioballistic, eye movement) are removed. Effects of component removal on the ERPs are shown in a representative subject (Upper Center). Subsequently, wavelet denoising (b) is applied to the single trials. AM vectors are derived separately for each time point and electrode. To ensure specificity, shared variance between target presentation and AM is removed by orthogonalization. The regressors are convolved with canonical hemodynamic response functions (HRF) to account for the neurovascular coupling before voxelwise correlations with the fMRI signal (c).

Fig. 3.

Grand-average ERP at frontocentral sites. Waveforms are shown from -100 to 600 ms around stimulus onset for all targets at the third to sixth position of all random TTI cycles (blue), all targets at the third to sixth position of all regular TTI cycles (orange), and all standards not immediately before or after a target (gray dotted). Effects of target predictability appear most prominently as amplitude reductions of N2 and P3 and, to a lesser degree, P1, N1, and P2 are also affected. Above the waveform, significant differences (P < 0.05) from a pointwise t statistic are plotted as blue rectangles for random target vs. standard comparison and in orange for the regular target vs. standard comparison. Black rectangles below the waveform indicate significant differences between the random and regular target categories.

Fig. 4.

AM-correlated fMRI results. Render views and maximum-intensity projections of the general target related activation and positive (red) and negative (blue) correlations with the respective AM. Each correlation map shows for each voxel the maximum t value from the four electrodes (FZ, FC1, FC2, and Cz). To the left of each rendering of the AM-correlated fMRI, the average AM (empty circles ± SEM) and the fitted sigmoid curves are shown. Top row, target-related activation, P < 0.05 (FWE), cluster size ≥10; second row, P2 (170 ms); third row, N2 (200 ms); and fourth row, P3 (320 ms). All AM-related activations were thresholded at P < 0.001 (uncorrected), cluster extent threshold P < 0.01.