How to Make a 60 Year Old Brain Work Like a 20 Year Old’s

Theta-gamma nerve coupling between brain regions is key to cognitive functioning

Zapping the brains of people over 60 with a mild electrical current improved a form of memory enough that they performed like people in their 20s, a new study found.

Someday, people might visit clinics to boost that ability, which declines both in normal aging and in dementias like Alzheimer’s disease, said researcher Robert Reinhart of Boston University.

The treatment is aimed at “working memory,” the ability to hold information in mind for a matter of seconds as you perform a task, such as doing math in your head. Sometimes called the workbench or scratchpad of the mind, it’s crucial for things like taking medications, paying bills, buying groceries or planning, Reinhart said.

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Article abstract in Nature

Electrical brain stimulation was used to strengthen the brain wave coupling between the pre-frontal cortex and the temporal lobe of the brain. EEG monitoring was also utilised to improve the brain wave synchrony between the two regions considered to be important in human working memory.

A well-studied mechanism is cross-frequency coupling. As described first in the hippocampus, the phase of theta oscillations biases the amplitude of the gamma waves [phase–amplitude (P–A) coupling or nested oscillations].

Here is more information on the particular type of brain waves [Theta-gamma] that were the focus of the researchers in the study discussed above:

Working memory deficits are common among individuals with Alzheimer’s dementia (AD) or mild cognitive impairment (MCI). Yet, little is known about the mechanisms underlying these deficits. Theta-gamma coupling—the modulation of high-frequency gamma oscillations by low-frequency theta oscillations—is a neurophysiologic process underlying working memory. We assessed the relationship between theta-gamma coupling and working memory deficits in AD and MCI.

We hypothesized that: (1) individuals with AD would display the most significant working memory impairments followed by MCI and finally healthy control (HC) participants; and (2) there would be a significant association between working memory performance and theta-gamma coupling across all participants. Ninety-eight participants completed the N-back working memory task during an electroencephalography (EEG) recording: 33 with AD (mean ± SD age: 76.5 ± 6.2), 34 with MCI (mean ± SD age: 74.8 ± 5.9) and 31 HCs (mean ± SD age: 73.5 ± 5.2).

AD participants performed significantly worse than control and MCI participants on the 1- and 2-back conditions. Regarding theta-gamma coupling, AD participants demonstrated the lowest level of coupling followed by the MCI and finally control participants on the 2-back condition. Finally, a linear regression analysis demonstrated that theta-gamma coupling (β = 0.69, p < 0.001) was the most significant predictor of 2-back performance. Our results provide evidence for a relationship between altered theta-gamma coupling and working memory deficits in individuals with AD and MCI. They also provide insight into a potential mechanism underlying working memory impairments in these individuals. __

One of many places to download the “Dual N-Back” game free of charge to test yourself

For those who want more details on Theta-gamma brain coupling and how this coding system of the brain works, here are some scientific articles with more information:

The Theta-Gamma Neural Code published in 2013 in “Cell (Neuron)”

Hippocampal Theta-Gamma Coupling published in 2013 in Journal of Neurophysiology

Brain Stimulation Using Low Intensity Ultrasound published in 2016 in Basic and Clinical Neuroscience

Comparison of various brain stimulation methods from above article:

Parameter specify Deep brain stimulation (DBS) Transcranial current stimulation (tCS) Transcranial magnetic stimulation (TMS) Low intensity focused ultrasound stimulation (LIFU)
Invasiveness Invasive Noninvasive Noninvasive Noninvasive
Spatial resolution ~1 mm Undetectable ~3–5 cm Depending on the frequency 1–5mm
Depth of stimulation Unlimited Undetectable ~1–1.5 cm unless H-coil is used 10–15 cm or more
Duration of reversible effect ~5 s 24 h ~5 s ~10–40 min
fMRI brain mapping Difficult Difficult Very difficult Easily possible

The Al Fin blogs have discussed electrical and magnetic transcranial brain stimulation methods as well as deep brain implant stimulation. The low intensity focused ultrasound method of brain stimulation is less well studied but from the comparison table above, LIFU appears to offer important advantages in spatial resolution and effective depth of reach inside the brain — for a noninvasive technique.

Neuroscientists try to make brain stimulation technologies noninvasive, inexpensive, user-friendly, direct, and safe. They believe that LIFU, regarding its features, can have a prominent role in brain stimulation and brain mapping in the future (Bystritsky et al., 2011). __


The brain stimulation method used by the Boston University researchers mentioned in the topmost article was a transcranial electrical current stimulator. Using a relatively simple device, the BU researchers were able to temporarily improve working memory performance for 60+ year-olds to the level of 20 something year-olds. The neural-coupling [Theta-gamma] effect was confirmed by EEG and the working memory improvement was confirmed using standard short term memory testing. The improvement for the seniors’ memories lasted at least 50 minutes after the end of electrical stimulation.

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