Greater Occipital Nerve Stimulation Boosts Associative Memory in Older Individuals: A Randomized Trial

Abstract

Transcutaneous electrical stimulation (tES) is a new approach that aims to stimulate the brain. Recently, we have developed tES approaches to enhance plasticity that modulate cortical activity via the greater occipital nerve (ON) in a “bottom-up” way. Thirty subjects between the ages of 55 and 70 years were enrolled and tested using a double-blind, sham-controlled, and randomized design. Half of the participants received active stimulation, while the other half received sham stimulation. Our results demonstrate that ON-tES can enhance memory in older individuals after one session, with effects persisting up to 28 days after stimulation. The hypothesized mechanism by which ON-tES enhances memory is activation of the locus coeruleus–noradrenaline (LC-NA) pathway. It is likely that this pathway was activated after ON-tES, as supported by observed changes in α-amylase concentrations, a biomarker for noradrenaline. There were no significant or long-lasting side effects observed during stimulation. Clinicaltrial.gov (NCT03467698).

Potential role for peripheral nerve stimulation on learning and long-term memory: A comparison of alternating and direct current stimulations

“…The present study provides a replication of ON-tDCS having no direct effect on learning, but does have an effect on memory being observed on Day 7, further depicting active ON-tDCS' viability for upregulating the LC-NA pathway to modulate memory, and corroborating that the effect transpires offline, during consolidation [16,17]. Despite no overall effect of tES side effects in the current study, we note that participants who received active ON-tDCS reported difficulty concentrating when this variable was taken separately.…”

“…Alternatively, the present study incorporated a highly divergent study design regarding stimulation protocol, electrode location, and task type, to directly compare the behavioral effects generated by tDCS and tACS (an active and control for each: active tDCS, sham tDCS, 40 Hz tACS, 1 Hz tACS) when applied to the greater occipital nerve (ON) targeting the locus coeruleus (LC) while learning an associative memory task e replicating previous laboratory parameters strategic placement of electrodes on the left and right C2 nerve dermatomes [16,17] in an effort to polarize the regions [18]. In a series of experiments, we demonstrated ON-tDCS 0 viability to upregulate the locus coeruleus noradrenaline (LC-NA) pathway to increase LC and hippocampus connectivity and improve associative memory recall in young [17] and older [17] healthy participants.…”

Human-In-The-Loop Optimization of Transcranial Electrical Stimulation Effects: A Computational Perspective Based on Systems Analysis

“…Then, the Pathway 4 transfer function fitted to the post-stroke HbT data (shown in Figure 7C It is postulated that the Pathway 4 effects can be via norepinephrine [13] receptors on the pial arterial smooth muscle cells [14,15] that may be relevant at the onset (<150 sec after tDCS) of tDCS [9], [31]. Also, tES-evoked LC-NE activity can have therapeutic effects, e.g., cerebellar tDCS (ctDCS) electrode [34] may stimulate the ascending fibers of the occipital nerve [77]. Here, tDCS may stimulate the peripheral nerves [33] and the LC-NE system that can also lead to psychosensory pupil response as a dilation of the pupil.…”

Human-in-the-Loop Optimization of Transcranial Electrical Stimulation at the Point of Care: A Computational Perspective

“…Pathway 4 effects can postulated via norepinephrine [ 13 ] receptors on the pial arterial smooth muscle cells [ 14 , 15 ], which may be relevant at the onset (<150 s after tDCS) of tDCS [ 9 ]. Moreover, tES-evoked LC-NE activity via projections innervating the cerebral vasculature can have therapeutic effects, e.g., cerebellar tDCS (ctDCS) electrodes [ 33 ] may stimulate the ascending fibers of the occipital nerve [ 70 ]. Here, tES can be optimized to stimulate the peripheral nerves [ 32 ] and the LC-NE system.…”