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. 2024 Nov 14;15(1):9858.
doi: 10.1038/s41467-024-54244-8.

Lateral prefrontal theta oscillations causally drive a computational mechanism underlying conflict expectation and adaptation

María Paz Martínez-Molina  1 , Gabriela Valdebenito-Oyarzo  1 , Patricia Soto-Icaza  1 , Francisco Zamorano  2   3 , Alejandra Figueroa-Vargas  1   4 , Patricio Carvajal-Paredes  1 , Ximena Stecher  5 , César Salinas  5 , Antoni Valero-Cabré  6   7   8 , Rafael Polania  9 , Pablo Billeke  10
Affiliations

Lateral prefrontal theta oscillations causally drive a computational mechanism underlying conflict expectation and adaptation

María Paz Martínez-Molina et al. Nat Commun. .

Abstract

Adapting our behavior to environmental demands relies on our capacity to perceive and manage potential conflicts within our surroundings. While evidence implicates the involvement of the lateral prefrontal cortex and theta oscillations in detecting conflict stimuli, their causal role in conflict expectation remains elusive. Consequently, the exact computations and neural mechanisms underlying these cognitive processes still need to be determined. We employed an integrative approach involving cognitive computational modeling, fMRI, TMS, and EEG to establish a causal link between oscillatory brain function, its neurocomputational role, and the resulting conflict processing and adaptation behavior. Our results reveal a computational process underlying conflict expectation, which correlates with BOLD-fMRI and theta activity in the superior frontal gyrus (SFG). Modulation of theta activity via rhythmic TMS applied over the SFG induces endogenous theta activity, which in turn enhances computations associated with conflict expectation. These findings provide evidence for the causal involvement of SFG theta activity in learning and allocating cognitive resources to address forthcoming conflict stimuli.

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Conflict of interest statement

Competing interests The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Behavioral analysis of Go-Nogo task.
A Single-trial example of reaction time and model variables. B Go-Nogo Task. C Reaction time comparison between the first Go trials (early) and the last Go trial (late) of a sequence (n = 30 participants, Wilcoxon test, two-sided, p = 8.8e-5). Boxplots display the extreme values, interquartile range, and median, and each point representing the mean for an individual subject. D Models comparison. E Posterior distribution of model parameters (Bayesian hypothesis test using pMCMC, two-sided, p < 0.001). Black dots represent the mean of the distribution, and black lines represent the 95% high-density intervals. The colored areas represent the complete posterior distribution. * indicates p < 0.05, **p < 0.01,***p < 0.001.CE commission error, DIC deviance information criteria, Ex conflict expectation, OE omission error. pCE previous commission error, pOE previous omission error, RT reaction time. See also Supplementary Tables 1 and 2. Source data are provided as a SourceData file.
Fig. 2
Fig. 2. MRI experiment results.
A Example of trial-by-trial variation in the reaction time and model variables. B MSIT Task stimuli. C Comparison of reaction times between trials with predicted lower and higher conflict expectations per sequence (n = 26 participants, Wilcoxon test, two-sided, p = 2.9e-8). Boxplots display the extreme values, interquartile range, and median, and each point representing the mean for an individual subject. D Posterior distribution of model parameters (n = 26 participants, Bayesian hypothesis test using pMCMC, two-sided, p < 0.001). Black dots represent the mean of the distribution, and black lines represent the 95% high-density intervals. The colored areas represent the complete posterior distribution. E Brain activity is associated with conflict expectation in the lateral prefrontal cortex (yellow) and conflict stimulus processing (blue). Lowercase letters a and b indicate the target sites for TMS experiments. The right panel shows the comparative results for the Conflict Expectancy regressor for the discovery sample (red) and the replication sample (green), highlighting the intersection of both results (yellow). The blue lines indicate the site of TMS stimulation in the SFG. * indicates p < 0.05, **p < 0.01,***p < 0.001. CNF conflict trial, Ex conflict expectation, MSIT multiple source interference task, pEr error in the prior trial, p(cnf) predicted probability of conflict, RT reaction time, SFG superior frontal gyrus, TMS transcranial magnetic stimulation. See Supplementary Tables 3 and 4. Source data are provided as a SourceData file.
Fig. 3
Fig. 3. TMS experiment behavioral results.
A Experimental design of the Go-Nogo Task during EEG-TMS sessions. B Reaction time (RT) modulation by the trial position in a sequence (n = 44 sessions, Wilcoxon test, two-sided, p = 0.0001). C The modulation of the effect of trial position by the TMS stimulation (n = 22 participants, Wilcoxon test, two-sided, TMS-SFG p = 0.04, TMS-SFG vs TMS-IFG p = 0.04, uncorrected). B, C Boxplots display the extreme values, interquartile range, and median, and each point representing the mean for an individual subject. D Posterior distribution of model parameters (n = 24 participants, Bayesian hypothesis test using pMCMC, two-sided, Ex pMCMC < 0.001, Ex:TMS:Th:SFG interaction pMCMC = 0.0006). Black dots represent the mean of the distribution, and black lines represent the 95% high-density intervals. The colored areas represent the complete posterior distribution. The grey rectangle indicates interaction regressors with the Ex regressor. * indicates p < 0.05, **p < 0.01,***p < 0.001. RT reaction time, SFG superior frontal gyrus, Th theta rhythm, TMS transcranial magnetic stimulation. see Supplementary Table 5. Source data are provided as a SourceData file.
Fig. 4
Fig. 4. Oscillatory effects post-TMS.
A Power increases after theta TMS stimulation over the SFG compared to sham stimulation. The left panel shows the time-frequency chart for a second after the last TMS pulse and before the first Go stimuli (TMStheta regressor for SFG sessions) over frontal electrodes (F1, F2, F3, F4, Fz, FC1, FC2, FC3, FC4 and FCz). The right panel shows the scalp distribution and source estimation of theta modulation. B Power increases after theta TMS stimulation over the SFG compared to no theta stimulation (TMStheta regressor > TMSno-theta regressor for SFG sessions). No modulation in source space survived multiple comparison corrections. C Power increases after theta TMS stimulation over the SFG compared to theta TMS stimulation over the IFJ (TMStheta regressor for SFG sessions > TMStheta regressor for IFJ sessions). The scalp distribution and source estimation reveal the main modulation of the left lateral frontal cortex. The gray rectangle shows the conjunction analysis for the contrasts shown in (A) and (B). The green line represents the BOLD modulation for the Ex regressor in fMRI experiments (see Fig. 2). The yellow line represents the homologous contralateral area of stimulation (Braintomme atlas area: A9/46d). A–C The highlighted areas represent significant modulation identified by the cluster-based permutation test (two-side test, corrected by multiple comparison). The p-value indicated in each chart represents the highest pcorrected value of the cluster highlighted for that chart. The electrodes highlighted indicate those with significant modulation. IFJ inferior frontal junction, SFG superior frontal gyrus, TMS transcranial magnetic stimulation. Source data are provided as a SourceData file.
Fig. 5
Fig. 5. Oscillatory modulation related to conflict expectation and TMS effects.
A Oscillatory activity associated with the expectation of conflict in sham conditions is depicted (Ex regressor for SFG and IFJ sessions). The left panel illustrates the time-frequency chart over frontal electrodes (F1, F2, F3, F4, Fz, FC1, FC2, FC3, FC4 and FCz), while the right panel displays the topographic and cortical surface distribution of theta modulation. B Phase amplitude coupling during the second following Go stimuli modulated by the expectation of control (Ex regressor for SFG and IFJ sessions). C Oscillatory activity related to the conflict expectation and TMS theta interaction during SFG stimulation (Ex*TMStheta regressor for SFG). D Oscillatory activity related to the conflict expectation and TMS theta interaction for the contrast between the SFG and IFJ stimulation (Ex*TMStheta regressor for SFG > Ex*TMStheta regressor for IFJ). A–D The highlighted areas represent significant modulation identified by the cluster-based permutation test (two-side test, corrected by multiple comparison). The p-value indicated in each chart represents the highest pcorrected value of the cluster highlighted for that chart. The electrodes highlighted indicate those with significant modulation. The vertical dotted lines denote the appearance of Go stimuli, and the horizontal dotted line represents the frequency of theta stimulation. IFJ inferior frontal junction, SFG superior frontal gyrus, TMS transcranial magnetic stimulation. Source data are provided as a SourceData file.
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