Neuroscientists find individual differences in memory response to amygdala stimulation

A new study published in Cognitive, Affective, & Behavioral Neuroscience provides evidence that electrical stimulation of the amygdala during learning can enhance long-term memory for neutral images—but only after a delay and not for everyone. The researchers found that this stimulation can help prioritize memories for later recall, but the effect varies widely across individuals. In fact, some participants experienced memory enhancement, while others saw a decline. The best predictor of whether stimulation helped or hurt was each person’s baseline memory performance.

The study builds on a growing body of work exploring how the amygdala influences memory. While it’s well known that emotional events tend to be remembered better than neutral ones, this isn’t only because of their emotional content. It’s also because the brain, especially the amygdala, plays a role in prioritizing these memories for long-term storage. This prioritization process interacts with the hippocampus and other nearby regions that are responsible for encoding the details of experiences. But the researchers behind this study wanted to know whether it’s possible to stimulate the amygdala to improve memory even when emotional arousal isn’t involved.

In a previous study, the same research team showed that stimulating the basolateral amygdala (BLA) at low electrical levels—levels that didn’t produce any conscious emotional sensation—could enhance memory for neutral images after 24 hours. That finding suggested it might be possible to separate the memory-boosting power of the amygdala from its usual role in processing emotions. The new study set out to test this idea in a larger sample and to examine why some people benefit from stimulation while others do not.

To do this, the researchers recruited 31 adults who were undergoing brain monitoring for treatment-resistant epilepsy. These patients had already undergone a procedure in which depth electrodes were implanted into various brain regions, including the amygdala, to help identify the origin of their seizures. This setup gave the research team a rare opportunity to directly stimulate the amygdala while participants were awake and performing memory tasks.

Each participant was shown a series of neutral images—pictures of objects—and asked to judge whether the object was more often found indoors or outdoors. On half of the trials, while the image was being shown, the researchers delivered a short burst of electrical stimulation to the BLA. On the other half, there was no stimulation. Importantly, the stimulation was below the threshold of awareness, and none of the participants reported feeling anything during the trials.

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After viewing the images, participants were tested twice: once immediately after the session, and again 24 hours later. In line with the researchers’ predictions, there was no significant difference in memory performance at the immediate test. But at the 24-hour mark, the researchers found that participants remembered the stimulated images better than the non-stimulated ones—at least on average.

The average, however, masked a striking degree of individual variation. Some participants showed strong memory enhancement after amygdala stimulation, others showed no change, and a few actually performed worse on stimulated trials. This led the researchers to investigate what personal factors might be driving these differences.

The most consistent predictor was each person’s baseline memory performance, assessed before surgery using standard neuropsychological tests. People who scored lower on these baseline tests were more likely to experience a strong effect—whether positive or negative—from the stimulation. In contrast, individuals with high baseline memory tended to show little or no change. This suggests that stimulation may interact with existing memory function, enhancing weak systems or disrupting already well-functioning ones.

Other factors also played a role. There were hints of sex differences, with males more likely to show strong memory enhancement and females more likely to show no effect or even impairment. However, these sex differences did not reach statistical significance in all analyses. Additionally, participants who showed more frequent abnormal brain activity (known as interictal epileptiform discharges, or IEDs) during the task tended to show greater variability in response to stimulation. This could mean that the brain’s baseline state during learning—its electrical activity and susceptibility to interference—affects how well stimulation works.

The location of the stimulation electrode within the amygdala and its distance from nearby brain structures such as the hippocampus, entorhinal cortex, and perirhinal cortex was also examined. However, the researchers found no consistent relationship between proximity to these regions and memory outcomes. This was somewhat unexpected, given that past research has shown that stimulating certain parts of the medial temporal lobe can either help or harm memory, depending on the precise target.

The study’s findings point to the importance of personalizing neuromodulation strategies. While amygdala stimulation appears to hold promise as a tool for enhancing memory, especially in people with memory impairments, it’s clear that one-size-fits-all approaches are unlikely to be effective. Instead, understanding who is most likely to benefit—and under what conditions—will be key to developing safe and effective therapeutic uses.

As with any study involving neurosurgical patients, there are limitations. All of the participants had epilepsy, and many were taking medications that can affect memory. The sample size, while larger than previous work in this area, was still relatively small. Additionally, the researchers combined data from three slightly different sub-experiments that varied in how and when stimulation was delivered. Although this allowed them to examine a wider range of stimulation conditions, it also added complexity to the analysis.

The researchers also note that while their stimulation protocol did not produce subjective emotional effects, they can’t entirely rule out the possibility that it influenced unconscious emotional processes. Future studies could explore whether adjusting the intensity or timing of stimulation can further optimize memory outcomes, and whether these methods can be safely used in non-epileptic populations, including older adults or individuals with memory disorders such as Alzheimer’s disease.

The study, “Exploring individual differences in amygdala-mediated memory modulation,” was authored by Martina K. Hollearn, Joseph R. Manns, Lou T. Blanpain, Stephan B. Hamann, Kelly Bijanki, Robert E. Gross, Daniel L. Drane, Justin M. Campbell, Krista L. Wahlstrom, Griffin F. Light, Aydin Tasevac, Phillip Demarest, Peter Brunner, Jon T. Willie, and Cory S. Inman.