Abstract:
In this study, we used brain state-dependent EEG-triggered transcranial magnetic stimulation (TMS) to target predefined phases of prefrontal theta oscillation with the attempt to modulate working memory performance of healthy human subjects in real time. For the real-time phase detection and estimation, we used an individualized spatial filter based on the MRI and EEG recording of each subject in order to source-project theta oscillations in the prefrontal cortical area. Subjects were enrolled in two sessions of randomized order with different cortical stimulation targets (right posterior-parietal cortex/left dorsomedial prefrontal cortex). Throughout the session, EEG was recorded with a 126-channel EEG cap. Subjects were instructed to perform two different types of working memory tasks on a monitor with a handheld response box (Sternberg, visuospatial). TMS triple pulses (100Hz, 120% RMT, active condition) and electrical pulses (sham condition) were applied to the respective cortical targets during the retention period of the working memory tasks, either at the timepoint of prefrontal theta trough or of any random phase. Responses and response times of the working memory tasks were recorded. In our study, the phase accuracy of TMS pulses was comparable to other brain state-dependent real-time EEG-TMS studies. TMS in the trough of the prefrontal theta oscillation did not affect working memory performance in comparison to the random phase. No significant difference regarding response accuracies and response times between TMS application in the trough and in the random phase of theta oscillations could be achieved in the real-time results. Significant differences were neither found by stimulating the right posterior-parietal cortex, nor the left dorsomedial prefrontal cortex. Post-hoc results did not yield significant phase correlations between response accuracy and different phases of prefrontal theta oscillation and posterior-parietal alpha oscillation. These negative results inevitably lead to the revisit of current understandings of working memory function. Neuronal oscillations in the theta band might reflect attentional processes in the WM processing system. Thus, working memory processing might only be sensitive to oscillatory effects in earlier stages, e.g. the encoding period, whereas in the retention period, dynamic changes in hidden brain states might portray a more efficient and robust method for maintaining working memory content.
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