Background

Noninvasive transcranial electrical stimulation (tES) research has been plagued with inconsistent effects. Recent work has suggested neuroanatomical and neurophysiological variability may alter tES efficacy. However, direct evidence is limited.

Objective

We have previously replicated effects of transcranial alternating current stimulation (tACS) on improving multitasking ability in young adults. Here, we attempt to assess whether these stimulation parameters have comparable effects in older adults (aged 60-80 years), which is a population known to have greater variability in neuroanatomy and neurophysiology. It is hypothesized that this variability in neuroanatomy and neurophysiology will be predictive of tACS efficacy.

Methods

We conducted a pre-registered study where tACS was applied above the prefrontal cortex (between electrodes F3-F4) while participants were engaged in multitasking. Participants were randomized to receive either 6-Hz (theta) tACS for 26.67 min daily for three days (80 min total; Long Exposure Theta group), 6-Hz tACS for 5.33 min daily (16-min total; Short Exposure Theta group), or 1-Hz tACS for 26.67 min (80 min total; Control group). To account for neuroanatomy, magnetic resonance imaging data was used to form individualized models of the tACS-induced electric field (EF) within the brain. To account for neurophysiology, electroencephalography data was used to identify individual peak theta frequency.

Results

Results indicated that only in the Long Theta group, performance change was correlated with modeled EF and peak theta frequency. Together, modeled EF and peak theta frequency accounted for 54%-65% of the variance in tACS-related performance improvements, which sustained for a month.

Conclusion

These results demonstrate the importance of individual differences in neuroanatomy and neurophysiology in tACS research and help account for inconsistent effects across studies.

Individuals with multi-domain amnestic mild cognitive impairment (md-aMCI) have an elevated risk of dementia and need interventions that may retain or remediate cognitive function. In a feasibility pilot study, 30 older adults aged 60-80 years with md-aMCI were randomized to 8 sessions of transcranial alternating current stimulation (tACS) with simultaneous cognitive control training (CCT). The intervention took place within the participant's home without direct researcher assistance. Half of the participants received prefrontal theta tACS during CCT and the other half received control tACS. We observed high tolerability and adherence for at-home tACS + CCT. Within 1-week, only those who received theta tACS exhibited improved attentional abilities. Neuromodulation is feasible for in-home settings, which can be conducted by the patient, thereby enabling treatment in difficult to reach populations. TACS with CCT may facilitate cognitive control abilities in md-aMCI, but research in a larger population is needed to validate efficacy.

Musical instrument training has been linked to improved academic and cognitive abilities in children, but it remains unclear why this occurs. Moreover, access to instrument training is not always feasible, thereby leaving less fortunate children without opportunity to benefit from such training. Although music-based video games may be more accessible to a broader population, research is lacking regarding their benefits on academic and cognitive performance. To address this gap, we assessed a custom-designed, digital rhythm training game as a proxy for instrument training to evaluate its ability to engender benefits in math and reading abilities. Furthermore, we tested for changes in core cognitive functions related to math and reading to inform how rhythm training may facilitate improved academic abilities. Classrooms of 8-9 year old children were randomized to receive either 6 weeks of rhythm training (N = 32) or classroom instruction as usual (control; N = 21). Compared to the control group, results showed that rhythm training improved reading, but not math, fluency. Assessments of cognition showed that rhythm training also led to improved rhythmic timing and language-based executive function (Stroop task), but not sustained attention, inhibitory control, or working memory. Interestingly, only the improvements in rhythmic timing correlated with improvements in reading ability. Together, these results provide novel evidence that a digital platform may serve as a proxy for musical instrument training to facilitate reading fluency in children, and that such reading improvements are related to enhanced rhythmic timing ability and not other cognitive functions associated with reading performance. RESEARCH HIGHLIGHTS: Digital rhythm training in the classroom can improve reading fluency in 8-9 year old children Improvements in reading fluency were positively correlated with enhanced rhythmic timing ability Alterations in reading fluency were not predicted by changes in other executive functions that support reading A digital platform may be a convenient and cost-effective means to provide musical rhythm training, which in turn, can facilitate academic skills.

Amnestic mild cognitive impairment (aMCI) is a predementia stage of Alzheimer's disease associated with dysfunctional episodic memory and limited treatment options. We aimed to characterize feasibility, clinical, and biomarker effects of noninvasive neurostimulation for aMCI. 13 individuals with aMCI received eight 60-minute sessions of 40-Hz (gamma) transcranial alternating current stimulation (tACS) targeting regions related to episodic memory processing. Feasibility, episodic memory, and plasma Alzheimer's disease biomarkers were assessed. Neuroplastic changes were characterized by resting-state functional connectivity (RSFC) and neuronal excitatory/inhibitory balance. Gamma tACS was feasible and aMCI participants demonstrated improvement in multiple metrics of episodic memory, but no changes in biomarkers. Improvements in episodic memory were most pronounced in participants who had the highest modeled tACS-induced electric fields and exhibited the greatest changes in RSFC. Increased RSFC was also associated with greater hippocampal excitability and higher baseline white matter integrity. This study highlights initial feasibility and the potential of gamma tACS to rescue episodic memory in an aMCI population by modulating connectivity and excitability within an episodic memory network.