Laughlin, M. M. | bioRxiv Science

bioRxiv2023

Trigeminal nerve direct current stimulation causes sustained increase in neural activity in the rat hippocampus

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation method that can modulate many brain functions including learning and memory. Recent evidence suggests that tDCS memory effects may be caused by co-stimulation of scalp nerves such as the trigeminal nerve (TN), and not the electric field in the brain. The TN gives input to brainstem nuclei, including the locus coeruleus that controls noradrenaline release across brain regions, including hippocampus. However, the effects of TN direct current stimulation (TN-DCS) are currently not well understood. In this study we hypothesized that TN-DCS manipulates hippocampal activity via an LC-noradrenergic bottom-up pathway. We recorded neural activity in rat hippocampus using multichannel silicon probes. We applied 3 minutes of 0.25 mA or 1 mA TN-DCS, monitored hippocampal activity for up to 1 hour and calculated spikes-rate and spike-field coherence metrics. Subcutaneous injections of xylocaine were used to block TN and intraperitoneal injection of clonidine to block the LC pathway. We found that 1 mA TN-DCS caused a significant increase in hippocampal spike-rate lasting 45 minutes in addition to significant changes in spike-field coherence, while 0.25 mA TN-DCS did not. TN blockage prevented spike-rate increases, confirming effects were not caused by the electric field in the brain. When 1 mA TN-DCS was delivered during clonidine blockage no increase in spike-rate was observed, suggesting an important role for the LC-noradrenergic pathway. These results provide a neural basis to support a tDCS TN co-stimulation mechanism. TN-DCS emerges as an important tool to potentially modulate learning and memory. HighlightsO_LITrigeminal nerve direct current stimulation (TN-DCS) boosts hippocampal spike rates C_LIO_LITN-DCS alters spike-field coherence in theta and gamma bands across the hippocampus. C_LIO_LIBlockade experiments indicate that TN-DCS modulated hippocampal activity via the LC-noradrenergic pathway. C_LIO_LITN-DCS emerges as a potential tool for memory manipulation. C_LI Figure Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/571341v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@d60a69org.highwire.dtl.DTLVardef@4598daorg.highwire.dtl.DTLVardef@1363f89org.highwire.dtl.DTLVardef@856b2e_HPS_FORMAT_FIGEXP M_FIG C_FIG

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bioRxiv2021

Alpha oscillatory activity causally linked to working memory retention: insights from online phase-locking closed-loop transcranial alternating current stimulation (tACS)

Although previous studies have reported correlations between alpha oscillations and the "retention" sub-process of working memory (WM), causal evidence has been limited in human neuroscience due to the lack of delicate modulation of human brain. Conventional tACS is not suitable for demonstrating the causal evidence for parietal alpha oscillations in WM retention because of its inability to modulate brain oscillations within a short period (i.e., the retention sub-process). Here, we developed an online phase-corrected closed-loop transcranial alternating current stimulation (tACS) system capable of precisely correcting for the phase differences between tACS and concurrent endogenous oscillations. This system permits both up- and down-regulation of brain oscillations at the target stimulation frequency within a short stimulation period, and is here applied to empirically demonstrate that parietal alpha oscillations causally relate to WM retention. Our experimental design included both in-phase and anti-phase alpha-tACS applied to 39 participants during the retention sub-processes of a modified Sternberg paradigm. Compared to in-phase alpha-tACS, anti-phase alpha-tACS decreased both WM performance and alpha activity. Moreover, the in-phase tACS-induced changes in WM performance were positively correlated with alpha oscillatory activity. These findings strongly support a causal link between alpha oscillations and WM retention, and illustrate the broad application prospects of phase-corrected tACS.

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