In a recent study published in the journal Nature Neuroscience, researchers evaluate the effectiveness of repetitive neuromodulation in improving the working memory (WM) and long-term memory (LTM) of older adults.
Study: Long-lasting, dissociable improvements in working memory and long-term memory in older adults with repetitive neuromodulation. Image Credit: Robert Kneschke / Shutterstock.com
Advances in neurosciences have helped scientists identify the brain circuits and networks that strengthen memory functions. For example, the rhythmic activity of cognitive circuits helps coordinate information processing.
Nevertheless, it remains challenging to overcome concurrent and selective deficits in the dual-store framework comprised of capacity-limited WM and unlimited LTM. Previous research also suggests varying contributions of the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL) to the corresponding WM and LTM memory stores.
Therefore, it is crucial to identify unique rhythmic mechanisms in spatially distinct brain regions. Advanced techniques, such as high-definition transcranial alternating current stimulation (HD-tACS), could then be used to non-invasively and independently manipulate these brain regions and improve memory function in older adults.
Theta and gamma frequency ranges contribute to WM and LTM function, especially during free recall. However, it is unclear which neuromodulation combinations of location and frequency selectively improve WM and LTM function in older adults.
About the study
In the present study, researchers tested the modulation of which theta rhythms in the IPL would improve auditory-verbal WM function in older adults referred to as the recency effect. Additionally, the modulation of which DLPFC-nested gamma rhythms would improve auditory-verbal LTM function called the primacy effect was determined in what the researchers referred to as ‘Experiment 1.’
HD-tACS was combined with optimal source-sink configurations of nine 12 mm ring electrodes (8 × 1, tACS) to perform these neurorhythm modulation experiments. Furthermore, the researchers assessed whether older adults with lower general cognitive performance would benefit more from neuromodulation.
The goal of Experiment 2 was to confirm the location and frequency specificity of Experiment 1. To this end, the entrainment frequencies were switched in two regions.
Experiment 3, which was similar to Experiment 1, examined the effect of gamma modulation in the DLPFC and theta modulation in the IPL in another distinct sample of participants. Across all three experiments, the researchers were interested in determining dissociable dual-memory stores based on the distinct spatiospectral functional and anatomical features of their substrates.
Study participants aged 65 or older were recruited from the greater Boston metropolitan area in the United States. These participants were fluent in English and had normal or corrected-to-normal vision and hearing. Study participants self-identified as African American, Caucasian, Native American, Asian, or Hispanic.
Taken together, a total of 150 participants were included in the study, with 60, 60, and 30 participants in Experiments 1, 2, and 3, respectively. The participants’ depressive symptoms and general cognitive performance were assessed using the Geriatric Depression Scale (GDS) and Montreal Cognitive Assessment (MoCA), respectively, at baseline.
Experiment 1 results revealed that selective changes to WM and LTM functions were possible through entrainment of theta rhythms in the IPL and gamma rhythms in the DLPFC. However, Experiment 2 demonstrated that switching modulation frequencies between the two regions did not improve memory function. Accordingly, a combination of anatomical location and rhythm frequency primarily determines the functional substrate for memory improvement.
Memory function improvements observed during Experiment 1 were due to entrainment of functionally specific brain circuits, rather than due to non-specific effects like transcutaneous stimulation. Notably, individuals with poorer cognitive function showed greater improvement in memory function.
The speed of memory function improvement during the intervention predicted memory strength one month after the intervention. Thus, the current study provided a metric to measure treatment responsiveness in future studies.
Taken together, the study results indicated that the modulation of specific brain rhythms through a four-day intervention selectively and sustainably improved memory function in older adults for at least one month.
The neuroplastic changes after phase-locking of intrinsic brain rhythms with tACS most likely caused these long-lasting effects. Additionally, functional differentiation, which typically reduces with aging, could also be promoted through neuromodulation.
The current study also opened new avenues to examine the clinical potential of repetitive neuromodulation of specific brain rhythms more comprehensively. Future studies should assess whether the current findings could be generalized to cognitive paradigms spanning memory function across other sensory domains.
Furthermore, future research should evaluate the translational implications for patients with neurodegenerative disorders, selective memory deficits, and dementia risk.
- Grover, S., Wen, W., Viswanathan, V., et al. (2022). Long-lasting, dissociable improvements in working memory and long-term memory in older adults with repetitive neuromodulation. Nature Neuroscience. doi:10.1038/s41593-022-01132-3.