New research raises questions about caffeine’s impact on brain plasticity

A recent study has raised questions about the impact of chronic caffeine consumption on our brain’s ability to adapt and learn. In a new study published in Frontiers in Psychiatry, scientists found that long-term caffeine users may exhibit decreased brain plasticity, a critical factor in the processes of learning and memory, when subjected to a brain stimulation protocol.

Caffeine is a common stimulant found in coffee, tea, soda, and other beverages. It’s known to help with alertness and concentration, but its effects on the brain’s ability to change and adapt over time, a process called plasticity, have been less clear.

Previous studies have shown mixed results when it comes to caffeine’s influence on brain plasticity. Some studies hinted that caffeine might hinder the brain’s ability to learn and adapt, while others suggested potential benefits. The researchers conducted this study to investigate the effects of caffeine on human brain plasticity, specifically focusing on its impact on long-term potentiation (LTP) and its potential interaction with a neuromodulation technique called repetitive transcranial magnetic stimulation (rTMS).

LTP is a fundamental neurophysiological process related to synaptic plasticity. It refers to the long-lasting increase in the strength of synaptic connections between neurons in response to repeated and persistent stimulation. rTMS is a non-invasive neurostimulation technique used in neuropsychiatry and neuroscience. It involves the use of a special device that generates magnetic fields to induce electrical currents in specific regions of the brain.

rTMS is often used in research to investigate and modulate brain plasticity, including LTP-like effects. By applying repetitive magnetic pulses to specific brain regions, rTMS can induce changes in neural activity and potentially mimic the processes associated with LTP.

“While researchers have looked at acute caffeine effects on rTMS-induced plasticity, chronic caffeine use as we see in the real world had not yet been explored,” explained study authors Joshua C. Brown (director of the Brain Stimulation Mechanisms Laboratory at McLean Hospital) and Megan Vigne (a neuromodulation research assistant at Butler Hospital).

“More generally, we are always interested in better understanding treatment moderators in clinical rTMS. Our research has the potential to prompt a new wave of research evaluating chronic caffeine use in patients undergoing rTMS therapy.”

In this study, researchers analyzed data from two previously conducted experiments involving a total of 20 healthy participants. Out of these, 16 were regular caffeine consumers, while 4 were not. All participants underwent rTMS paired with a partial agonist of the NMDA receptor called d-cycloserine (DCS). This protocol is thought to induce a process similar to long-term potentiation, which is crucial for learning and memory.

Before and after this stimulation, the researchers measured the participants’ brain responses using a method called motor evoked potentials (MEPs). These MEPs are like windows into the brain’s plasticity, allowing scientists to observe how the brain changes in response to the stimulation.

The researchers found that participants who regularly consumed caffeine had different brain responses compared to those who didn’t. In the group that didn’t regularly consume caffeine, the brain showed robust facilitation in response to the stimulation protocol involving DCS and rTMS. However, in the group of caffeine users, this facilitation was significantly reduced, resembling the brain’s response in the placebo group.

In simpler terms, it means that chronic caffeine users appeared to have a diminished capacity for the type of brain plasticity linked to learning and memory, even though they were subjected to the same stimulation as non-caffeine users.

“Our data suggest that chronic caffeine use may blunt synaptic plasticity, which is accepted as the cellular basis of learning and memory,” Brown and Vigne told PsyPost. “Since rTMS may exert its long-term effects through synaptic plasticity, chronic caffeine use may also diminish clinical rTMS effectiveness, though this has not been looked at directly. It is very important to remember that our findings came from a small sample and really need to be replicated before reaching conclusions.”

The researchers initially hypothesized that chronic caffeine use might enhance brain plasticity. This expectation was based on previous research suggesting that caffeine could have positive effects on memory and synaptic strengthening.

“Acute caffeine use increases plasticity (as measured by motor evoked potentials) following rTMS,” the researchers explained. “It also seems to be conventional wisdom that caffeine enhances our cognitive abilities, and it does recover plasticity when a deficit exists. So, we were particularly surprised to see that chronic caffeine use blunted plasticity responses in our motor plasticity assay – which is probably the most commonly used plasticity assay in non-invasive brain stimulation.”

“However, once we thought about it more, we see this pattern all the time in the brain. With chronic exogenous excitation or inhibition, the brain will respond in kind to counteract those effects to remain scalable. This process is called homeostatic plasticity.”

While these findings are intriguing, it’s important to note some limitations. The study had a relatively small number of participants who didn’t consume caffeine regularly compared to the caffeine users, which could have skewed the results. Additionally, this research relied on self-reported caffeine consumption and did not consider the actual caffeine levels in the participants’ bloodstreams.

“It is very important to remember that our findings came from a small sample and really need to be replicated before reaching conclusions,” Brown and Vigne said. “We are currently asking patients in our TMS clinic about caffeine use to see if there is a correlation between caffeine use and clinical responsiveness to TMS. Because caffeine use is so pervasive, more research on its relationship with plasticity is warranted.”

The study, “Chronic caffeine consumption curbs rTMS-induced plasticity“, was authored by Megan Vigne, Jamie Kweon, Prayushi Sharma, Benjamin D. Greenberg, Linda L. Carpenter, and Joshua C. Brown.

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