A recent meta-analysis published in the journal eLife provides evidence that applying noninvasive magnetic stimulation to a specific brain network selectively enhances a person’s ability to remember past experiences. The findings suggest that targeting this brain circuit improves event-based memory without altering other cognitive skills. This provides a promising foundation for developing specialized treatments for memory disorders.
Episodic memory is the brain’s ability to recall specific, personal experiences, such as what you ate for breakfast or the details of a recent conversation. This type of memory relies heavily on a seahorse-shaped structure deep inside the brain called the hippocampus. The hippocampus does not work alone. It constantly communicates with surface-level brain regions to form a widespread interconnected system known as the hippocampal network.
Many neurological and psychiatric conditions disrupt the connections within this network, which tends to result in noticeable memory problems. Because the hippocampus sits deep inside the brain, it is difficult to influence directly without invasive surgery. To bypass this problem, researchers use a technique called Transcranial Magnetic Stimulation, or TMS. This method uses a magnetic coil placed against the scalp to safely pass short magnetic pulses into the brain.
These magnetic pulses induce small electrical currents that stimulate nerve cells in targeted areas near the brain’s surface. By targeting surface regions that communicate directly with the hippocampus, scientists can indirectly influence the deeper memory centers. This specific approach is known as Hippocampal Indirectly Targeted Stimulation, or HITS.
Joel Voss, a professor of neurology at the University of Chicago, pioneered this technique in his laboratory, the Center for Neurocognitive Outcomes Improvement Research. “My laboratory developed the Hippocampal Indirectly Targeted Stimulation (HITS) method, as first reported in a 2012 publication, and have been using HITS in basic and applied investigations of memory function ever since,” Voss said. Over the years, many independent research groups have tested this indirect stimulation method, but their individual experiments varied widely in design and outcome.
Some studies found large memory improvements, while others reported smaller or negligible effects. “It was natural for us to ask the question of whether it has reliable effects on memory across investigations/laboratories and whether the effects are specific to the type of memory that depends most heavily on the hippocampus,” Voss explained. To find answers, the researchers conducted a meta-analysis, which is a statistical technique that combines data from many separate studies to identify overall trends.
They evaluated 38 individual studies that met their exact inclusion criteria. The combined data included 1,009 participants. The participant pool included healthy young adults, healthy older adults, and individuals experiencing clinical memory impairments, such as mild dementia.
The authors extracted 253 statistical comparisons from these studies. Of these, 140 comparisons measured the effects of the stimulation on episodic memory tasks. The remaining 113 comparisons measured the effects on non-memory cognitive tasks, such as tests of attention, working memory, and language processing. The researchers then converted all the outcomes into a standardized metric known as an effect size to accurately compare the results across different experimental setups.
The synthesized data indicated that indirect hippocampal stimulation robustly improved episodic memory performance. The overall positive effect was highly statistically significant, providing evidence that the intervention genuinely aids the brain in recalling specific events. The researchers noted that the improvements were highly selective. When they analyzed the 113 comparisons for non-memory tasks, the effect size was essentially zero.
This level of selectivity across multiple studies is highly unusual in neuroscience. “To my knowledge, this is the first meta-analytic evidence that ANY type of ‘neural intervention’ in any organism can influence a specific cognitive function,” Voss said. “That is, many individual studies in humans and in animal models have used many different methods to show that doing something to the brain can impact some specific function.”
However, these results rarely hold up to broader scrutiny. “But these individual instances of specific outcomes from brain intervention experiments have not been demonstrated to be robust and replicable across many experiments and laboratories in the way that is tested via meta-analysis,” Voss explained. “Some interventions that people hope will be specific turn out not to be when tested via meta-analysis, which undermines the conclusion that the intervention is doing something specific to the brain rather than something very general like temporarily influencing arousal.”
“Our meta-analytic findings are thus very remarkable in demonstrating robust and reliable evidence that a specific brain intervention can impact a specific cognitive function,” Voss added. To understand exactly how the stimulation worked best, the researchers categorized the memory effects based on several experimental design factors. One factor they examined was the format of the memory test.
Memory tasks generally fall into two categories: recollection and recognition. Recollection involves mentally recreating the specific details of a past event without many clues, like answering an open-ended essay question. Recognition involves simply identifying previously learned information when it is presented again, similar to answering a multiple-choice question. The analysis found that the stimulation produced significantly greater improvements on tests requiring recollection compared to tests relying on basic recognition.
“We were surprised that, even within the domain of memory function, HITS specifically affected the Recollection component,” Voss said. “This is measured in tests that require you to, for instance, remember the names of people you just met, or where specific objects are located.” He noted that this is important for several reasons.
“First, it shows that the effects are specific: HITS affects memory and not general cognitive abilities, but even within memory, Recollection is affected rather than more general aspects of memory, such as being able to recognize that you’ve seen a picture before,” Voss explained. “This demonstrates that HITS isn’t just causing arousal or generally influencing brain function.”
Because recollection heavily depends on the hippocampus, these selective effects verify the treatment’s pathway. “Second, Recollection is the type of memory most heavily dependent on the hippocampus,” Voss said. “The finding that effects are selective to Recollection indicates that the targeted brain region is being affected by HITS.”
Additionally, this specific type of memory is highly vulnerable to cognitive decline. “Finally, Recollection is the type of memory most heavily impaired in memory disorders such as dementia,” Voss added. “This suggests that HITS might be promising for intervention in these disorders. It was surprising that this selectivity came through across the many different ways the studies we included in our meta-analysis were conducted.”
The timing of the stimulation also played a major role in its effectiveness. The intervention was much more successful when researchers applied the magnetic pulses before the participants began the memory task. When the stimulation was applied during the delay period between learning the new information and being tested on it, the effect on memory was almost zero.
This timing difference provides evidence that the stimulation primarily improves memory formation, also known as encoding, rather than memory retention or retrieval. The brain seems to need the network enhancement right as it encounters new information. Interestingly, the amount of time between the pre-task stimulation and the learning phase varied widely among studies, yet the benefits remained consistent.
The authors also looked at how the stimulation target was selected across the different experiments, comparing individualized MRI brain scans against generalized brain maps. While individualized targeting showed some initial signs of being more effective, this difference did not remain statistically significant after the researchers ran additional sensitivity tests. Safety is always a major consideration in brain stimulation research, and across the reviewed studies, no serious adverse events were reported. This suggests that indirect hippocampal stimulation is a safe procedure with a very low risk of harm.
The findings offer a strong foundation for future clinical trials, but experts urge caution regarding immediate medical applications. “There is strong evidence from many experiments and laboratories that a particular type of brain stimulation can (positively) influence memory ability,” Voss said. “This provides a scientific motivation to test whether this type of brain stimulation can be applied to address the memory problems that occur in specific neurological or psychiatric disorders, such as Alzheimer’s disease or major depression.”
However, researchers need more data to understand long-term outcomes and clinical viability. “However promising, it is important to note that this study does not itself provide the evidence to indicate that this memory-related brain stimulation is safe or effective for any particular medical condition or person,” Voss cautioned. “This is a basic-science investigation and the impact is scientific.”
“These findings are NOT showing that it is safe or effective to get this type of brain stimulation to treat any particular disorder,” he added. “There is much work to be done to establish this.”
The study, “A meta-analysis suggests that TMS targeting the hippocampal network selectively improves episodic memory,” was authored by Elena Badillo Goicoechea, Phillip F Agres, Johanna MH Rau, Arantzazu San Agustín, and Joel L Voss.