If you were to ask people how they would most want to “upgrade” about their brain, chances are most will mention something about their memory. Good memory is crucial for life in the modern world, not only in a conscious, day-to-day sense – don’t we all forget things a little bit more often than we’d like? — but also on a more fundamental level. Memory allows us to navigate our world, perform our work, and hold together our concepts of who we are.
In the field of neuroscience, memory is broken down into various subcomponents, supported by different neural mechanisms. These include short-term or working memory, and long-term memory of various types: episodic, declarative, procedural, etc. Now that researchers have achieved a greater understanding of these underlying processes, they have begun to manipulate and enhance memories in interesting ways that may eventually make their way out of the lab.
With the introduction of optogenetics, an advanced research technique that allows the activity of individual neurons to be manipulated, a whole body of research has sprung up that focuses on creating, modulating, and erasing memories.
In one particularly interesting study, entirely new memories were created when researchers stimulated the brains of mice while they were asleep.
It is thought that neurons in the hippocampus establish or consolidate memories by replaying activity that occurred during the daytime while we sleep. Some of these neurons, so-called “place cells” in the CA1 region of the hippocampus, are thought to fire in patterns that map specifically on to locations in environments that the animal has explored.
In this experiment, place cells in the CA1 and the medial forebrain bundle, an area of the brain involved in the reward system, were simultaneously stimulated while mice were asleep. When the mice woke up, they demonstrated a preference for certain locations in their environment that they had not attachment to before. These researchers conclude that by pairing place cells with reward while the mice were “reliving” the events of that day, they were able to artificially create positive memories with certain areas in their environment.
Animal studies that create artificial memories are useful for learning how the brain remembers, but they’re often far removed from technology that can help humans in the real world. Fortunately, there are a number of startups and research projects focused specifically on this task, preventing the deterioration of memory due to aging and maintaining the quality of life. This research has far-reaching implications as cognitive performance is directly connected to productivity.
One particularly exciting area of applied memory enhancing technology comes from professor Theodore W. Berger at the University of Southern California. Doctor Berger has been studying the mechanisms of memory formation and recall in the hippocampus and attempting to develop a memory prosthesis.
Dr. Berger developed a computational model that imitates the flow of neural pulse in hippocampus while rats carry out a delayed non-match-to-sample（DNMS）task. When hippocampus modifies memory, a signal is transmitted from CA3 to CA1. In the experiment, 16 electrodes were stuck to CA3 and CA1 respectively, and they recorded the CA3 spike train and CA1 spike train. Based on that experiment, they structured a precise nonlinear model which imitates the pattern of time and space of recorded CA3 and CA1 spike train.
Then the rats were given an injection of MK801 in their hippocampus and their ability to remember was hindered. MK801 is a glutamatergic NMDA channel blocker and it interferes with the signal flow between CA3 and CA1. As a result, the performance of the rats in the tasks declined (blue line).
Then, while the connection between CA3 and CA1 was lost, artificial stimulation from the model was delivered to the CA1, reproducing the natural flow of information. Interestingly, performance was restored to the level of a normal rat. (red line)
In a follow-up experiment, adding the artificial stimulation recreating natural CA1 -> CA3 information flow in the brain of normal rats enhanced their performance.
Theodore Berger plans to carry out additional experiments with not only rats but also with apes and humans, hoping to eventually produce a chip that can deliver to patients with dementia or Alzheimer’s.
In order to make memory prosthetics a reality, Dr. Berger was collaborating with Bryan Johnson, a serial entrepreneur and founder of Braintree Payments, to create Kernel, a start-up with an initial investment of 100 million dollars and a mission to develop an invasive device for treating patients with neurological diseases.
Working memory is the short-term memory we use for holding concepts in mind when performing tasks. It is said that working memory declines as we get older and that people with ADHD have lower working memory.
One study suggests that carrying out transcranial direct current stimulation (tDCS) in the frontal lobe enhances working memory. Applying tDCS for 25 minutes on right/left dorsolateral prefrontal cortex (F4/F3) while doing the N-back working memory task for seven days strengthened working memory.
On the other hand, another study shows that when aged people (65 to 75) received tDCS on the left dorsolateral prefrontal cortex (F3), their working memory did not improve. Thus, further study is necessary for determining whether tDCS is effective in enhancing working memory or not.
Sleep is thought to be deeply important to memory consolidation.
One interesting study shows that memory is reinforced by listening to a certain sound while sleeping. It is known that slow-wave sleep, in which brain wave oscillates at slower than 1Hz (sleep slow oscillation, SO) is important in consolidating memory. When a SO wave was detected during non-REM sleep from the location of Fpz, a pink noise was played for 50ms when a positive peak of the wave just after a negative peak and the next positive peak arrived. Repeating this for several hours in the sleep lead to a meaningful increase in the recalled number of word pairs which were memorized before going to sleep.
Might we use this result for exams?
Eric Kandel, a winner of the 2000 Nobel Prize in Medicine has revealed that CBEB gene relates to long-term memory. The biggest rival is Timothy Tully at Dart neuroscience.
Timothy Tully has done research as a professor at Cold Spring Harbor Laboratory, which is famous for having produced many Nobel Prize winners. He now works as chief science officer at Dart neuroscience. The company does research and development of drugs which reinforce long-term memory.
He continues to deliver his papers, and Richard Morris at the University of Edinburgh, who is famous for his study of the hippocampus, has participated his research as one of the scientific advisory boards and a coauthor.
Eric Kandel has also founded Memory Pharmaceuticals Corp., a pharmaceutical company which focuses on long-term memory, but it seems to be closed now.
FDA has not yet approved a drug aimed to enhance memory except for those to help people with dementia or Alzheimer’s improve their cognitive ability. This would be a bottleneck at the final phase of the development of the medicine.
Memory or cognition is an important function for human beings and it will surely cause a big problem in an aging society, not to mention patients with dementia or Alzheimer’s disease. To solve this problem, there are many approaches, including cognitive training, electronic stimulation, drugs, neurofeedback, and BMIs. Among all of them, the greater understanding of the neuroscience of memory is highly useful.
There is also a study in which depression was treated by DecNef based on the biomarker from fMRI. If we could change the function of the brain by modulating brain activity, it may also be possible to reinforce memory function in some way.