Recent meta-analyses published in journals e-life Evidence shows that applying non-invasive magnetic stimulation to specific brain networks selectively enhances a person’s ability to recall past experiences. The findings suggest that targeting this brain circuit improves event-based memory without changing other cognitive skills. This provides a promising basis for developing specialized treatments for memory disorders.
Episodic memory is the brain’s ability to remember specific personal experiences, such as what you had for breakfast or details of a recent conversation. This type of memory relies heavily on a seahorse-shaped structure deep in the brain called the hippocampus. The hippocampus does not function alone. It constantly communicates with surface-level regions of the brain to form an extensively interconnected system known as the hippocampal network.
Many neurological and psychiatric conditions tend to disrupt connections within this network and cause significant memory impairment. Because the hippocampus is located deep within the brain, it is difficult to directly influence it without invasive surgery. To get around this problem, researchers are using a technique called transcranial magnetic stimulation (TMS). This method uses a magnetic coil placed on the scalp to safely deliver short magnetic pulses to the brain.
These magnetic pulses induce small electrical currents that stimulate nerve cells in targeted areas near the surface of the brain. Scientists can indirectly influence deeper memory centers by targeting surface areas that communicate directly with the hippocampus. This particular approach is known as hippocampal indirect target stimulation (HITS).
Joel Voss, a professor of neurology at the University of Chicago, developed the technique in his lab, the Center for Neurocognitive Outcome Improvement Research. “My laboratory developed the Hippocampal Indirect Target Stimulation (HITS) method, first reported in a 2012 publication, and have since used HITS for basic and applied studies of memory function,” Voss said. Over the years, many independent research groups have tested this method of indirect stimulation, but the designs and results of individual experiments have varied widely.
Some studies found significant improvements in memory, while others reported small or negligible effects. “It was natural to ask whether there was a reliable effect on memory across studies and laboratories, and whether that effect was specific to the types of memory that rely most heavily on the hippocampus,” Voss explained. To find the answer, researchers conducted a meta-analysis. Meta-analysis is a statistical method that combines data from many separate studies to identify overall trends.
They evaluated 38 individual studies that exactly met the inclusion criteria. The combined data included 1,009 participants. Participants included healthy young people, healthy older adults, and people experiencing clinical memory impairment, such as mild dementia.
The authors extracted 253 statistical comparisons from these studies. Of these, 140 comparisons measured the effects of stimulation on episodic memory tasks. The remaining 113 comparisons measured effects on cognitive tasks other than memory, such as tests of attention, working memory, and language processing. The researchers then converted all results into a standardized metric known as an effect size in order to accurately compare results across different experimental settings.
Synthetic data showed that indirect hippocampal stimulation reliably improves episodic memory performance. The overall positive effect was highly statistically significant, providing evidence that this intervention was indeed helping the brain remember specific events. The researchers noted that the improvements were highly selective. When they analyzed 113 comparisons of non-memory tasks, the effect size was virtually 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 affect specific cognitive functions,” Voss said. “So many separate studies in humans and animal models have used different methods to show that doing something to the brain can affect certain functions.”
However, these results rarely stand up to widespread scrutiny. “However, these individual instances of specific outcomes from brain intervention experiments have not been proven to be robust and reproducible across many experiments and laboratories in the manner tested by meta-analysis,” Voss explained. “Some of the interventions that people hoped would be specific turn out to be not when tested in meta-analyses. This undermines the conclusion that the intervention is doing something specific to the brain, rather than something very general that temporarily affects arousal.”
“The findings of our meta-analysis are therefore very noteworthy in that they demonstrate strong and reliable evidence that specific brain interventions can influence specific cognitive functions,” Voss added. To understand exactly how stimulation works optimally, researchers classified memory effects based on several experimental design factors. One of the factors they considered was the format of the memory test.
Memory tasks generally fall into two categories: recall and recognition. Reminiscence involves replaying certain details of past events in your head without many clues, such as answering an open-ended essay question. Recognition involves identifying previously learned information when it is presented again, similar to answering multiple-choice questions. Analyzes showed that stimulation led to significantly greater improvements on tests that required recollection compared to tests that relied on basic cognition.
“We were surprised that even within the domain of memory function, HITS specifically affected the reminiscence component,” Voss said. “This is measured, for example, in tests where you are asked to remember the name of someone you just met or the location of a particular object,” he noted, which is important for several reasons.
“First, we show that the effects are specific. HITS affects memory, not general cognitive abilities, but recollection rather than more general aspects of memory, such as being able to recognize that you have seen a picture before,” Voss explained. “This shows that HITS doesn’t just cause excitement or affect brain function in general.”
Because recollection is highly dependent on the hippocampus, these selective effects prove a therapeutic pathway. “Second, reminiscence is the type of memory that relies most heavily on the hippocampus,” Voss said. “The finding that the effect is selective for recollection indicates that the targeted brain regions are affected by HITS.”
Furthermore, this particular type of memory is highly vulnerable to cognitive decline. “Finally, recollection is the type of memory that is most impaired in memory disorders such as dementia,” Voss added. “This suggests that HITS may hold promise for intervention in these disorders. We were surprised that this selectivity came about through the different ways in which the studies we included in our meta-analysis were conducted.”
The timing of stimulation also has a significant impact on its effectiveness. The intervention was more successful when researchers applied magnetic pulses before participants started the memory task. When the stimulus was presented during the delay period between learning new information and testing 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 memory retrieval. The brain appears to need network reinforcement the moment it encounters new information. Interestingly, although the time between the pretask stimulus and the learning phase varied widely across studies, the benefits were nevertheless consistent.
The authors also considered how stimulus targets were selected across different experiments by comparing individual MRI brain scans with generalized brain maps. Although there were some early signs that personalized targeting was more effective, this difference did not remain statistically significant after the researchers performed additional sensitivity tests. Safety is always a major consideration in brain stimulation studies, and no serious adverse events were reported across the reviewed studies. This suggests that indirect hippocampal stimulation is a safe procedure with very low risk of harm.
The findings provide 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 certain types of brain stimulation can (positively) influence memory performance,” Voss said. “This provides scientific motivation to test whether this type of brain stimulation can be applied to address memory impairments that occur in certain neurological and psychiatric diseases, such as Alzheimer’s disease and major depression.”
However, researchers need more data to understand long-term outcomes and clinical viability. “It is important to note that, however promising, this study itself does not provide evidence that this memory-related brain stimulation is safe or effective for any particular disease state or person,” Voss cautioned. “This is basic science research, and the implications are scientific.”
“These findings do not indicate that receiving this type of brain stimulation to treat a particular disease is safe or effective,” he added. “There’s a lot of work to do to establish this.”
The study, “Meta-analysis suggests that TMS targeting hippocampal networks selectively improves episodic memory,” was authored by Elena Badillo Goicoechea, Phillip F Agres, Johanna MH Rau, Arantzazu San Agustín, and Joel L Voss.
