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

BACKGROUND: In the past decade, a rising interest in transcranial electrical stimulation has emerged owing to its advantageous capacity to facilitate the extraction of casual links between neuromodulation and the obtained behavioral effects in cognitive performance. However, an insufficient number of direct comparative studies between transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS) effects on associative memory have caused optimal parameters and procedural application to remain undefined. OBJECTIVE: The current study aimed to comparatively investigate the effects of tDCS and tACS applied to the occipital nerve (ON), targeting the locus coeruleus, on associative memory performance. METHODS: We employed a randomized, double-blind, two-visit, active-controlled study design. 85 cognitively normal adults were assigned to receive either active ON-tDCS, 40 Hz ON-tACS, sham ON-tDCS, or 1 Hz ON-tACS during encoding of a 50-word Swahili-English associative memory recall task. To evaluate the effects of electrical stimulation, we measured the cumulative rate of learning on Day 1 and to assess possible long-term effects, we measured the number of words recalled on Day 7. RESULTS: Results presented two notable findings: (1) participants who received 40 Hz ON-tACS learned significantly more words on Day 1 (F3,81 = 4.37, p = .007, η2 = 0.14), and (2) participants who received 40 Hz ON-tACS or active ON-tDCS recalled significantly more words on Day 7 (F3,81 = 11.08, p < .001, η2 = 0.29). CONCLUSIONS: The evidence from this study alludes to 40 Hz ON-tACS and active ON-tDCS inducing distinct behavioral effects, whereby 40 Hz ON-tACS generated an effect during memory encoding via enhanced attention, however, active ON-tDCS elicited an offline effect transpiring during consolidation. Further neuroimaging studies are needed to validate these findings and proposed mechanisms of action.

Polarity-specific high-definition transcranial direct current stimulation of the anterior and posterior default mode network improves remote memory retrieval.

BACKGROUND: Previous studies show that activity in the posterior default mode network (pDMN), including the posterior cingulate cortex and the precuneus, is correlated with the success of long-term episodic memory retrieval. However, the role of the anterior DMN (aDMN) including the medial prefrontal cortex is still unclear. Some studies show that activating the medial prefrontal cortex improves memory retrieval while other studies show deactivation of the medial prefrontal cortex in successful retrieval of episodic memories, suggesting a possible functional dissociation between the aDMN and pDMN. OBJECTIVE: In the current study, we aim to causally explore this probable dissociation using high-definition transcranial direct current stimulation (HD-tDCS). METHODS: We perform a randomised double-blinded two-visit placebo-controlled study with 84 healthy young adults. During Visit 1 they learn 75 Swahili-English word-associations. Seven days later, they randomly receive either anodal, cathodal or sham HD-tDCS targeting the pDMN or aDMN while they recall what they have previously learned. RESULTS: We demonstrate that anodal stimulation of the pDMN and cathodal stimulation of the aDMN, equally improve the percentage of Swahili-English word-associations recalled 7 days after learning. CONCLUSIONS: Modulating the activity in the aDMN and pDMN causally affect memory retrieval performance. HD-tDCS of the aDMN and pDMN shows that anodal stimulation of the pDMN and cathodal stimulation of the aDMN increases memory retrieval performance one week after the learning phase. Given consistent evidence, it is highly likely that we are increasing the activity in the pDMN with anodal pDMN stimulation. However, it is not clear if cathodal HD-tDCS targetting aDMN works via decoupling from the pDMN or via indirectly disinhibit pDMN.

Impaired posterior cingulate cortex-parahippocampus connectivity is associated with episodic memory retrieval problems in amnestic mild cognitive impairment.

Episodic memory retention and retrieval decline are the most common impairments observed in amnestic mild cognitive impairment (aMCI) patients who progress to Alzheimer's disease (AD). Clinical electroencephalography research shows that patients with dementia due to AD exhibit a slowing of neural electrical activity in the parietal cortex. Memory research has further suggested that successful memory performance is associated with changes in a posterior cingulate-parahippocampal cortical network together with increased θ-γ oscillatory coupling, where θ oscillations act as carrier waves for γ oscillations, which contain the actual information. However, the neurophysiological link between the memory research and clinical studies investigating aMCI and AD is lacking. In this study, we look at brain activity in aMCI and how it relates to memory performance. We demonstrate decreased γ power in the posterior cingulate cortex and the left and right parahippocampus in aMCI patients in comparison to control participants. This goes together with reduced θ coherence between the posterior cingulate cortex and parahippocampus associated with altered memory performance aMCI patients in comparison to control participants. In addition, comparing patients with aMCI to control participants reveals an effect for θ-γ coupling for the posterior cingulate cortex, and the left and right parahippocampus. Taken together, our results show that parahippocampus and posterior cingulate cortex interact via θ-γ coupling, which is associated with memory recollection and is altered in aMCI patients, offering a potential candidate mechanism for memory decline in aMCI.

The peripheral effect of direct current stimulation on brain circuits involving memory.

An ongoing debate surrounding transcranial direct current stimulation (tDCS) of the scalp is whether it modulates brain activity both directly and in a regionally constrained manner enough to positively affect symptoms in patients with neurological disorders. One alternative explanation is that direct current stimulation affects neural circuits mainly indirectly, i.e., via peripheral nerves. Here, we report that noninvasive direct current stimulation indirectly affects neural circuits via peripheral nerves. In a series of studies, we show that direct current stimulation can cause activation of the greater occipital nerve (ON-tDCS) and augments memory via the ascending fibers of the occipital nerve to the locus coeruleus, promoting noradrenaline release. This noradrenergic pathway plays a key role in driving hippocampal activity by modifying functional connectivity supporting the consolidation of a memory event.

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

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).