Posted on by Dr. Francis Collins
Note to my blog readers: the whole world is now facing a major threat from the COVID-19 pandemic. We at NIH are doing everything we can to apply the best and most powerful science to the development of diagnostics, therapeutics, and vaccines, while also implementing public health measures to protect our staff and the patients in our hospital. This crisis is expected to span many weeks, and I will occasionally report on COVID-19 in this blog format. Meanwhile, science continues to progress on many other fronts—and so I will continue to try to bring you stories across a wide range of topics. Perhaps everyone can use a little break now and then from the coronavirus news? Today’s blog takes you into the intricacies of memory.
When recalling the name of an acquaintance, you might replay an earlier introduction, trying to remember the correct combination of first and last names. (Was it Scott James? Or James Scott?) Now, neuroscientists have found that in the split second before you come up with the right answer, your brain’s neurons fire in the same order as when you first learned the information .
This new insight into memory retrieval comes from recording the electrical activity of thousands of neurons in the brains of six people during memory tests of random word pairs, such as “jeep” and “crow.” While similar firing patterns had been described before in mice, the new study is the first to confirm that the human brain stores memories in specific sequences of neural activity that can be replayed again and again.
The new study, published in the journal Science, is the latest insight from neurosurgeon and researcher Kareem Zaghloul at NIH’s National Institute of Neurological Disorders and Stroke (NINDS). Zaghloul’s team has for years been involved in an NIH Clinical Center study for patients with drug-resistant epilepsy whose seizures cannot be controlled with drugs.
As part of this work, his surgical team often temporarily places a 4 millimeter-by-4 millimeter array of tiny electrodes on the surface of the brains of the study’s participants. They do this in an effort to pinpoint brain tissues that may be the source of their seizures before performing surgery to remove them. With a patient’s informed consent to take part in additional research, the procedure also has led to a series of insights into what happens in the human brain when we make and later retrieve new memories.
Here’s how it works: The researchers record electrical currents as participants are asked to learn random word pairs presented to them on a computer screen, such as “cake” and “fox,” or “lime” and “camel.” After a period of rest, their brain activity is again recorded as they are given a word and asked to recall the matching word.
Last year, the researchers reported that the split second before a person got the right answer, tiny ripples of electrical activity appeared in two specific areas of the brain . The team also had shown that, when a person correctly recalled a word pair, the brain showed patterns of activity that corresponded to those formed when he or she first learned to make a word association.
The new work takes this a step further. As study participants learned a word pair, the researchers noticed not only the initial rippling wave of electricity, but also that particular neurons in the brain’s cerebral cortex fired repeatedly in a sequential order. In fact, with each new word pair, the researchers observed unique firing patterns among the active neurons.
If the order of neuronal firing was essential for storing new memories, the researchers reasoned that the same would be true for correctly retrieving the information. And, indeed, that’s what they were able to show. For example, when individuals were shown “cake” for a second time, they replayed a very similar firing pattern to the one recorded initially for this word just milliseconds before correctly recalling the paired word “fox.”
The researchers then calculated the average sequence similarity between the firing patterns of learning and retrieval. They found that as a person recalled a word, those patterns gradually became more similar. Just before a correct answer was given, the recorded neurons locked onto the right firing sequence. That didn’t happen when a person gave an incorrect answer.
Further analysis confirmed that the exact order of neural firing was specific to each word pair. The findings show that our memories are encoded as unique sequences that must be replayed for accurate retrieval, though we still don’t understand the molecular mechanisms that undergird this.
Zaghloul reports that there’s still more to learn about how these processes are influenced by other factors such as our attention. It’s not yet known whether the brain replays sequences similarly when retrieving longer-term memories. Along with these intriguing insights into normal learning and memory, the researchers think this line of research will yield important clues as to what changes in people who suffer from memory disorders, with potentially important implications for developing the next generation of treatments.
 Replay of cortical spiking sequences during human memory retrieval. Vaz AP, Wittig JH Jr, Inati SK, Zaghloul KA. Science. 2020 Mar 6;367(6482):1131-1134.
 Coupled ripple oscillations between the medial temporal lobe and neocortex retrieve human memory. Vaz AP, Inati SK, Brunel N, Zaghloul KA. Science. 2019 Mar 1;363(6430):975-978.
Epilepsy Information Page (National Institute of Neurological Disorders and Stroke/NIH)
Brain Basics (NINDS)
Zaghloul Lab (NINDS)
NIH Support: National Institute of Neurological Disorders and Stroke; National Institute of General Medical Sciences
Posted on by Dr. Francis Collins
Hop aboard as we fly up, down, left, and right through the information highways of the human brain! This captivating and eye-catching video was one of the winners of the 2019 “Show us Your Brain!” contest sponsored by the NIH-led Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative.
The video travels through several portions of the brain’s white matter—bundles of fiber that carry nerve signals between the brain and the body, as well as within the brain itself. Fiber colors indicate directionality: left-right fibers (red), front-back fibers (green), and top-bottom fibers (blue).
Looking from the back, we start our journey deep within the brain in the limbic system, the area that helps control emotion, learning, and memory. About three seconds in, visual fibers pop into view extending from the eyes to various brain areas into the occipital lobe (one of four major brain lobes) in the back of the brain.
About two seconds later, flying over top as the brain starts rotating, we see various fiber bundles spray upward throughout the cerebral cortex, communicating information related to language processing, short-term memory, and other functions. About halfway through the video, several green bundles emerge arching across the brain’s midline. These bundles, called the corpus callosum, house the fibers enabling communication between left and right sides of the brain. Finally, the video closes as we see many different fiber bundles lighting up all over, enabling communication between different cortical and subcortical portions of the brain through association and projection pathways.
Dynamic maps like these are created using a 3D imaging technique called diffusion MRI tractography . The technique tracks subtle pathways of water movement in the brain, and allows researchers to model the physical properties (connectional anatomy) that underlie the brain’s electrical properties (neuronal signaling). Postdoctoral researcher Ryan Cabeen and Arthur Toga, director of the University of Southern California Mark and Mary Stevens Neuroimaging and Informatics Institute, Los Angeles, used the method to study how white matter changes in developing and aging brains, as well as in brains affected by neurodegenerative or neurological disorders.
Scientific animator Jim Stanis produced the video with Cabeen and Toga. The team first created a population-averaged brain using high-quality diffusion MRI datasets from the Human Connectome Project ,and then used sophisticated computational tools to delineate each bundle manually .
The tractography technique lets scientists visualize and quantitatively analyze the brain’s wiring patterns, complementing our understanding of how the brain functions. Such methods are especially useful to learn about the organization of deep-brain areas that remain out of reach for scientists using current tools and imaging techniques.
 Kernel regression estimation of fiber orientation mixtures in diffusion MRI. Cabeen RP, Bastin ME, Laidlaw DH. Neuroimage. 2016 Feb 15;127:158-172.
Arthur Toga (USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Los Angeles)
Ryan Cabeen (USC Mark and Mary Stevens Neuroimaging and Informatics Institute)
Human Connectome Project (USC)
Show Us Your Brain Contest! (BRAIN Initiative/NIH)
NIH Support: National Institute of Neurological Disorders and Stroke; National Institute of Mental Health
Posted on by Dr. Francis Collins
How much exercise does it take to boost your memory skills? Possibly a lot less than you’d think, according to the results of a new study that examined the impact of light exercise on memory.
In their study of 36 healthy young adults, researchers found surprisingly immediate improvements in memory after just 10 minutes of low-intensity pedaling on a stationary bike . Further testing by the international research team reported that the quick, light workout—which they liken in intensity to a short yoga or tai chi session—was associated with heightened activity in the brain’s hippocampus. That’s noteworthy because the hippocampus is known for its involvement in remembering facts and events.
Posted on by Dr. Francis Collins
Credit: University of California, San Francisco
Whether it’s hitting a high note, delivering a punch line, or reading a bedtime story, the pitch of our voices is a vital part of human communication. Now, as part of their ongoing quest to produce a dynamic picture of neural function in real time, researchers funded by the NIH’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative have identified the part of the brain that controls vocal pitch .
This improved understanding of how the human brain regulates the pitch of sounds emanating from the voice box, or larynx, is more than cool neuroscience. It could aid in the development of new, more natural-sounding technologies to assist people who have speech disorders or who’ve had their larynxes removed due to injury or disease.