The entrainment of brain oscillations through transcranial alternating current stimulation (tACS) delivered at off-peak frequencies.

It has been demonstrated that endogenous brain oscillations can become entrained to rhythmic stimulation. Four studies were conducted to investigate the possibility of modulating endogenous frequency peaks, through entrainment, from stimulation delivered at off-peak frequencies. Study 1 utilised EEG recordings to establish whether off-peak stimulation within the alpha frequency range could successfully shift individual alpha peak frequencies in the direction of stimulation. Stimulation was delivered at 2Hz above and below the individual alpha peak frequency of each participant. EEG recordings taken immediately after stimulation found no significant modulation of individual alpha peak frequencies. In light of this, the subsequent studies assessed the effects of off-peak stimulation during the stimulation rather than immediately following it. These studies used a working memory task and were based on the theory that differences in theta and gamma frequency peaks causally effect working memory capacity. Studies 2 and 3 delivered tACS at off-peak theta frequencies (4Hz and 7Hz) and study 4 delivered tACS at off-peak gamma frequencies (40Hz and 70Hz) during a working memory task. This was done to ascertain whether such stimulation could alter working memory capacity, which would indicate that peak frequencies had been shifted. Studies 2 and 3 utilised two different electrode configurations (P4/Cz and P4/right supraorbital respectively). In study 3, working memory capacity was enhanced and impaired in the 4Hz and 7Hz conditions respectively. In studies 2 and 4, no significant changes in working memory capacity were found. The findings from study 3 indicate that off-peak entrainment can be used to shift frequency peaks in the direction of the stimulation frequency and that such shifts can have observable cognitive effects. The contrast between studies 2 and 3 highlights the importance of electrode placement in tACS studies

The speed of parietal theta frequency drives visuospatial working memory capacity

The speed of theta brain oscillatory activity is thought to play a key role in determining working memory (WM) capacity. Individual differences in the length of a theta cycle (ranging between 4 and 7 Hz) might determine how many gamma cycles (>30 Hz) can be nested into a theta wave. Gamma cycles are thought to represent single memory items; therefore, this interplay could determine individual memory capacity. We directly tested this hypothesis by means of parietal transcranial alternating current stimulation (tACS) set at slower (4 Hz) and faster (7 Hz) theta frequencies during a visuospatial WM paradigm. Accordingly, we found that 4-Hz tACS enhanced WM capacity, while 7-Hz tACS reduced WM capacity. Notably, these effects were found only for items presented to the hemifield contralateral to the stimulation site. This provides causal evidence for a frequency-dependent and spatially specific organization of WM storage, supporting the theta–gamma phase coupling theory of WM capacity

The speed of parietal theta frequency drives visuospatial working memory capacity - Fig 1

<p><b>(A) Theta–gamma phase coupling theory</b>. The maximum number of items stored in WM is thought to be a function of the number of gamma cycles nested into a theta wave [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2005348#pbio.2005348.ref001" target="_blank">1</a>,<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2005348#pbio.2005348.ref002" target="_blank">2</a>]. We tested this theory by applying slower (4 Hz) and faster (7 Hz) theta frequency tACS, aiming at modulating the speed of theta cycles (as per the entrainment hypothesis; see [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2005348#pbio.2005348.ref010" target="_blank">10</a>,<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2005348#pbio.2005348.ref012" target="_blank">12</a>,<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2005348#pbio.2005348.ref013" target="_blank">13</a>,<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2005348#pbio.2005348.ref019" target="_blank">19</a>]) to allow higher/lower numbers of gamma cycles nested within a theta phase. Four-hertz tACS (yellow panel) should slow down theta oscillations, allowing more gamma cycles to nest within a theta cycle, relative to sham (green panel), enhancing WM capacity. Seven-hertz tACS (blue panel) should speed up theta oscillations, allowing fewer gamma cycles to nest within a theta cycle, relative to sham (green panel), worsening WM capacity. <b>(B) Visual delayed match to sample task</b>. Two arrays of coloured squares were situated on either side of a white fixation cross in the centre of a black screen. The number of squares in each array (memory load) was 4, 5, or 6, with 20 trials presented for each load. The task started with a fixation cross on the screen. Prior to presentation of the arrays, an arrow appeared on the screen (200 ms) to indicate which of the two upcoming arrays (left or right) needed to be memorised. The two arrays then appeared on the screen (100 ms), followed by a retention interval (900 ms), again followed by two arrays (left and right; 2,000 ms). Participants had to indicate whether the array in the cued hemifield had changed. <b>(C) (Experimental Montage) and (D) (Control Montage): results</b> (underlying data can be found at: <a href="https://osf.io/rm6qp/" target="_blank">https://osf.io/rm6qp/</a>). K-values for each combination of load and hemisphere for each condition per participant were calculated with the formula: (hit rate − false alarms) * set size [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2005348#pbio.2005348.ref020" target="_blank">20</a>] (see Data analysis). Leftmost graphs depict mean and individual K-values obtained for trials presented on the left hemifield for each active stimulation condition after sham correction (Sham-corrected 4 Hz, Sham-corrected 7 Hz). Rightmost graphs depict mean and individual K-values obtained for trials presented on the right hemifield for each active stimulation condition after sham correction (Sham-corrected 4 Hz, Sham-corrected 7 Hz). Significant differences between conditions were observed for the Experimental Montage (C) but not for the Control Montage (D) and only for stimuli presented to the left hemifield (i.e., contralateral to the stimulated parietal site). For non-sham-corrected K and accuracy data, see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2005348#pbio.2005348.s001" target="_blank">S1A and S1B Fig</a> (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2005348#pbio.2005348.s002" target="_blank">S1A and S1B Table</a>), respectively (underlying data can be found at: <a href="https://osf.io/rm6qp/" target="_blank">https://osf.io/rm6qp/</a>). *<i>p</i> < 0.05; ****<i>p</i> <0.0001. Error bars depict standard error of the mean. tACS, transcranial alternating current stimulation; WM, working memory.</p

The speed of parietal theta frequency drives visuospatial working memory capacity - Fig 2

<p><b>(A) Electric field distribution calculation</b> (NIC 2.0 Software: <a href="http://www.neuroelectrics.com/products/software/nic2/" target="_blank">http://www.neuroelectrics.com/products/software/nic2/</a>) for Experimental (left) and Control (right) electrode montages. The Experimental Montage (P4-supraorbital) shows (i) a more right-lateralised field distribution with (ii) maximum current over more posterior parietal areas relative to the control montage (P4-Cz). The Control Montage shows (i) some left-lateralised field distribution with (ii) maximum current over right superior parietal areas, thus more anterior to P4. These differences in electric field distribution might be responsible for the significantly different impact obtained across the two montages and may possibly explain the null effects obtained using the Control Montage. <b>(B) Masked display with highlights of right IPS electric field distribution calculation</b> (NIC 2.0 Software: <a href="http://www.neuroelectrics.com/products/software/nic2/" target="_blank">http://www.neuroelectrics.com/products/software/nic2/</a>), relative to the Experimental (left) and Control Montages (right). Here, it can be more closely appreciated how the Experimental Montage induced a maximum current over IPS, relative to the Control Montage. IPS, intraparietal sulcus; NIC, Neuroelectrics Instrument Controller; rIPS, right intraparietal sulcus.</p