Effect of five consecutive sessions of theta-band oscillatory brain stimulation on verbal working memory and theta power (Hebrew)

Working memory is a central cognitive mechanism in humans that enables the temporary maintenance, updating, and manipulation of information required for complex functions such as decision-making, planning, retrieval, executive control, and response inhibition. Oscillatory brain activity in the theta-frequency range over frontal regions has been associated in the scientific literature with encoding, active retention, and retrieval processes, and is therefore considered a relevant neurophysiological measure for understanding the mechanisms underlying working memory. The present study examined the effect of non-invasive brain stimulation using transcranial alternating current stimulation (tACS) at 6 Hz, within the theta-frequency range, on verbal working memory performance and frontal theta activity among healthy young participants.

The study included 42 healthy participants, who were assigned under double-blind conditions to either an active stimulation group or a sham stimulation group. The intervention consisted of five consecutive sessions of non-invasive oscillatory brain stimulation using bipolar tACS at 6 Hz, delivered over prefrontal electrodes F3 and F4, corresponding to the right and left DLPFC.

Participants completed a verbal 2-back task while EEG was recorded to monitor oscillatory brain activity in the theta-frequency range at three time points: on the first day, before the stimulation series (T1); on the fifth day, immediately after the stimulation series (T2); and at an additional follow-up session 4–6 weeks later (T3). Behavioral measures included reaction time and overall accuracy, which comprised correct keypresses and correct withholding of responses to distractors. In addition, electrophysiological measures were analyzed, including mean theta power across all trials over frontal electrodes during the three task phases: encoding, active retention, and retrieval.

The findings indicated a change in the pattern of frontal theta activity following the stimulation series. In the active stimulation group, a significant decrease in frontal theta power was observed immediately after the stimulation series, whereas no parallel pattern of decrease was observed in the sham group. In addition, across the task phases, a relative dominance of theta activity was found in the right hemisphere compared with the left hemisphere. This finding may reflect the involvement of attentional, executive-control, and response-inhibition mechanisms, such as withholding a response, during performance of the verbal working memory task. At the behavioral level, improvement over time was found in overall accuracy and in correct withholding of responses across the entire sample. This finding may reflect a practice effect following repeated task performance. However, the absence of a significant advantage for the active stimulation group may be related to the participants’ high baseline performance levels, which restricted the possible range for detecting further improvement and between-group differences, among other factors due to the characteristics of the sample, which consisted of healthy young participants whose prefrontal activity is considered to be at its peak with respect to working memory functions. Furthermore, associations were found between changes in theta power over time, from T1 to T3, and changes in performance within the active stimulation group. Specifically, greater decreases in frontal theta power during the encoding, active-retention, and retrieval phases were associated with improved overall accuracy, and in some analyses also with shorter reaction times and improved correct withholding of responses to distractors. This finding supports the possibility that reduced theta power following tACS may reflect increased neurophysiological efficiency of frontal networks involved in the active maintenance of information in working memory. In addition, baseline frontal theta activity was associated with future performance, and in the hierarchical regression analyses, significant coefficients were found for several EEG measures. However, because the full regression models did not reach statistical significance, these findings should be interpreted with caution.

The findings of the present study contribute to the understanding of the relationship between non-invasive brain stimulation, frontal theta activity, and verbal working memory, and highlight the potential of quantitative EEG (qEEG) measures as possible markers for the future personalization of stimulation protocols in adults. Nevertheless, further studies with larger samples and clinical populations are needed to examine the generalizability of the findings to more diverse populations and over longer follow-up periods, thereby beginning to outline applied strategies for improving verbal working memory in healthy populations and in neurodevelopmental populations. Future studies among populations with working memory difficulties may examine whether these findings can be translated into personalized interventions in educational or rehabilitative contexts.