Key takeaways:
- A tiny region in the brain works like a reset button that separates memory of one meaningful event from the next. Without this reset mechanism, moments could blur together and lead to the kinds of memory disruptions seen in PTSD, Alzheimer's disease, anxiety and even healthy aging.
- Data from the study suggests that stress may disrupt processes that organize events in memory.
- The findings not only reveal how the brain builds distinct episodes in memory but also identify a potential target for interventions to restore memory function and improve quality of life.
Life may unfold as a continuous stream, but our memories tell a different story. We do not recall the past as one long, unbroken text. Instead, we remember it as a series of meaningful events, like how sentences are structured with grammar and punctuation. Like any narrative, this organization gives our experiences shape and coherence, helping us make sense of what and when things happen.
The brain must devote a lot of space to this herculean task, right?
Wrong! It turns out that a tiny but mighty region pulls far more than its weight.
In a paper published in the journal Neuron, psychologists at UCLA and Columbia University combined brain imaging and pupil measurements to show that a small collection of neurons in the brainstem, known as the locus coeruleus, acts like a "memory reset button" during meaningful changes.
"Our key question was: as an experience unfolds, how does the brain 'know' when one meaningful memory has ended and the next should begin?" said UCLA psychology professor and first author David Clewett. "Research has shown that remaining in a stable context, such as the same room, binds sequential experiences together in memory. By contrast, experiencing a shift in context, or event boundary, drives memories apart to represent distinct events. In this way, context acts as the grammar of human memory. What we found is that the locus coeruleus is most active at event boundaries when memories become separated. Thus, this small region at the core of the brain's arousal system may serve to punctuate our thoughts and memories."
Clewett and co-authors Ringo Huang at UCLA and Lila Davachi at Columbia recruited 32 volunteers who looked at pictures of neutral objects while inside an MRI scanner. To manipulate whether the surrounding context was stable or changing, simple tones were played in either the right or left ear. Eight pure tones were repeated in the same ear to create a sense of a coherent event, then the tone switched to the other ear and changed in pitch to elicit perception of an event boundary. This repeat-switch pattern continued throughout the remainder of the sequence, creating the perception of four different auditory events.
The researchers then tested how these tone switches influenced memory. They reasoned that time provides a window into how events are formed: when people successfully reconstruct the order of a sequence, it suggests these items are linked within a single memory. In contrast, it is harder to remember the precise sequence of events when they have been stored in separate, distinct memories.
As they predicted, locus coeruleus activation at event boundaries predicted later memory separation, as shown by worse ability to remember the order of item pairs that spanned boundaries. The researchers also cross-checked their measurements of locus coeruleus activation against eye pupil dilation measurements taken at the same time, because pupils are known to dilate slightly both as new events occur and when the locus coeruleus is active. These measurements confirmed that observations during the fMRI were indeed capturing activation in this small brain area. Functional magnetic resonance imaging, or fMRI, measures brain activity by detecting changes in blood flow while a person is inside the scanner.
The consequences of this neural and memory reset signal were far-reaching. Stronger locus coeruleus activation at boundaries between events predicted larger changes in activation patterns within the hippocampus, a brain region that tracks contextual details like place and time and is central to the formation of new memories.
"Part of the job of the hippocampus is to map the structure of our experiences, so it has an index of the beginning, middle and ends of events. We found that the locus coeruleus may provide the critical 'start' signal to the hippocampus, as if saying, 'Hey, we're in a new event now,'" said Davachi. "Prior work had shown that bursts of locus coeruleus activity help reconfigure brain networks to direct attention to new and important experiences. Our findings suggest that this updating signal is even more widespread, also reaching memory-related regions that carry representations of ongoing events."
The researchers also examined how brief bursts of locus coeruleus activation are influenced by background levels of locus coeruleus activity. This matters because locus coeruleus neurons operate in two distinct modes: a burst-like mode that flags significant events and forms new memories, and a background mode that regulates general alertness and stress.
"The locus coeruleus is like the brain's internal alarm system," Clewett said. "But under chronic stress, this system becomes overactive. The result is like living with a fire alarm that never stops ringing, making it difficult to notice when a real fire breaks out."
Although the dynamic interplay between these firing patterns has been studied in the context of decision-making, perception and learning, its relevance for how we perceive and remember events has, thus far, been unclear. So, the authors set out to test whether bursts of locus coeruleus activation at event boundaries, the neural signals that segment memories, might be weakened or lost under conditions of chronic stress. This question posed a challenge, as fMRI alone cannot measure absolute levels of stress or locus coeruleus activation. To address this, they used an imaging method that indirectly measures neuromelanin, a pigmented neurochemical that accumulates in the locus coeruleus with repeated activation over time.
As predicted, participants with a higher neuromelanin-related signal, thought to indicate chronic stress, showed weaker pupil dilation responses to event boundaries. Stronger low-frequency fluctuations in locus coeruleus activation, a proxy for background levels of activity, also predicted weaker spikes in locus coeruleus activation and pupil responses to boundaries during the task. Together, these findings suggest that chronic hyperarousal may blunt one's sensitivity to change, disrupting the cues that anchor and organize new episodes in memory.
Identification of the locus coeruleus as the gateway or conductor for memory formation may lead to better ways to treat PTSD and other memory-related disorders, such as Alzheimer's disease, where the locus coeruleus is unusually hyperactive. There are potential ways to quiet an overactive locus coeruleus, whether pharmacologically or through slow-paced breathing or even hand-squeezed stress balls. But good long-term solutions require further research and will take time to discover and bring to market. Perceiving events in the "right" way is directly linked to better memory, suggesting that improving locus coeruleus function is an effective target for either protecting or recovering memory function.
Clewett said that the sophisticated tools necessary to look into the brain require the kind of funding that only the federal government can provide. Clewett said that several NIH grants that funded this research paid for the scanning and facilities they used to do the experiments, for example.
"Conducting basic science and clinical research is critical for opening new doors for treating debilitating disorders," Clewett said. "Recent legislative actions threaten this future, not only for scientific research but for breakthroughs that can improve the lives of patients and their families. It is perhaps ironic that at a time when legislation promises 'big and beautiful change,' it turns out one of the brain's smallest players may have the biggest impact on how we understand and remember our lives."
