Neuroengineers at Columbia engineering have found the first evidence that individual neuron in the human brain targets specific memories during recall. The researchers identified “memory-trace cells” whose activity was spatially tuned to the location where subjects remembered encountering specific objects.









They studied recordings in neurosurgical patients who had electrodes implanted in their brains and examined how the patients’ brain signals corresponded to their behavior while performing a virtual- reality (VR) object-location memory task. The study is published in Nature Neuroscience.





Let’s understand what specific parts of the brain working with memories

Memories aren’t stored in just one part of the brain. Different types are stored across different, interconnected brain regions. The main parts of the brain involved with memory are the amygdala, the hippocampus, the cerebellum and the prefrontal cortex which is the part of the cerebral cortex.





For explicit memories – which are about events that happened to you (episodic), as well as general facts and information (sematic) – these three important areas of the brain: the hippocampus, the neocortex, and the amygdala. Implicit memories, such as motor memories, rely on the basal ganglia and cerebellum. Short-term working memory relies most heavily on the prefrontal cortex.





Three areas of the brain involved in explicit memory: the hippocampus, the neocortex and the amygdala.





Hippocampus

The hippocampus, located in the brain’s temporal lobe, is where episodic memories are formed and indexed for later access. Episodic memories are autobiographical memories from specific events in our lived, like the coffee we had with a friend last week.





Neocortex (the largest part of the cerebral cortex)

The neocortex is the largest part of the cerebral cortex, the sheet of neural tissue that forms the outside surface of the brain, distinctive in higher mammals for its wrinkly appearance. In humans, the neocortex is involved in higher functions such as sensory perception, generation of motor commands, spatial reasoning, and language.





Over time, information from certain memories that temporarily stored in the hippocampus can be transferred to the neocortex as general knowledge – things like knowing that coffee provides a pick-me-up. Researchers think this transfer from the hippocampus to neocortex happens as we sleep.





Amygdala

The amygdala, an almond-shaped structure in the brain’s temporal lobe, attaches emotional significance to memories. This is particularly important because strong emotional memories (e.g. those associated with shame, joy, love or grief) are difficult to forget. The performance of these memories suggests that interactions between the amygdala, hippocampus and neocortex are crucial in determining the ‘stability’ of memory – that is how effectively it is retained over time.

There's an additional aspect to the amygdala’s involvement in memory. The amygdala doesn't just modify the strength and emotional content of memories; it also plays a key role in

forming new memories specifically related to fear. Fearful memories are able to be formed after only a few repetitions.





This makes ‘fear learning’ a popular way to investigate the mechanisms of memory formation, consolidation and recall. Understanding how the amygdala processes fear is important because of its relevance to post-traumatic stress disorder (PTSD), which affects many of our veterans as well as police, paramedics and others exposed to trauma. Anxiety in learning situations is also likely to involve the amygdala and may lead to avoidance of particularly challenging or stressful tasks.

Two areas of brain involved in implicit memory: the basal ganglia and cerebellum





Basal ganglia

The basal ganglia are structures lying deep within the brain and are involved in a wide range of processes such as emotion, reward processing, habit formation, movement, and learning. They are particularly involved in co-ordinating sequences of motor activity, as would be needed when playing a musical instrument, dancing or playing basketball.





The basal ganglia are the regions most affected by Parkinson’s disease. This is evident in the impaired movements of Parkinson’s patients.





Cerebellum

The cerebellum, a separate structure located at the rear base of the brain, is most important in fine motor control, the type that allows us to use chopsticks or press that piano key a fraction more softly. A well-studied example of cerebellar motor learning is the vestibule-ocular reflex, which lets us maintain our gaze on a location as we rotate our heads .





Prefrontal cortex – Working memory

The prefrontal cortex (PFC) is the part of the neocortex that sits at the very front of the brain. It is the most recent addition to the mammalian brain, and is involved in many complex cognitive functions. Human neuroimaging studies using magnetic resonance imaging (MRI) machines show that when people perform tasks requiring them to hold information in their

short-term memory , such as the location of a flash of light, the PFC becomes active.





There also seems to be a functional separation between left and right sides of the PFC: the left is more involved in verbal working memory while the right is more active in spatial working memory, such as remembering where the flash of light occurred.





How Neuroengineers have found the first evidence that indicial neurons in the human brain target specific memories during recall?





Studies have shown that declarative memory – the kind of memory you can consciously recall like your how address or your mother’s name – relies on healthy medial temporal lobe structure in the brain, including the hippocampus and entorhinal cortex (EC).





These regions are also important for spatial cognition, demonstrated by Nobel-prize-wining discovery of “place cells” and “grid cells”

in these regions -- neurons that activate to represent specific locations in the environment during navigation (akin to a GPS). However, it has not been clear if or how this "spatial map" in the brain relates to a person's memory of events at those locations, and how neuronal activity in these regions enables us to target a particular memory for retrieval among related experiences.





Joshua Jacobs, associate professor of biomedical engineering, who directed the study says – they found these memory-trace neurons primarily in the the entorhinal cortex (EC), which is one of the first regions of the brain affected by the onset of Alzheimer’s disease. Because the activity of these neurons is closely related to what a person is trying to remember, it is possible that their activity is disrupted by diseases like Alzheimer’s leading to memory deficit.





Findings open up new lines of investigation into how neural activity in the entorhinal cortex and medial temporal lobe helps us target past events for recall, and more generally how space and memory overlap in the brain.





Study demonstrates that neurons in the human brain track the experiences we are wilfully recalling, and can change their activity patterns to differentiate between memories. They're just like the pins on your Google map that mark the locations you remember for

important events.









How did they do that?

The team was able to measure the activity of single neurons by taking advantage of a rare opportunity: invasively recording from the brains of 19 neurosurgical patients at several hospitals, including the Columbia University Irving Medical Center. The patients had drug-resistant epilepsy and so had already had recording electrodes implanted in their brains for their clinical treatment.

The researchers designed experiments as engaging and immersive VR computer games and the bedridden patients used laptops and handheld controllers to move through virtual environments. In performing the task, subjects first navigated through the environment to learn the locations of four unique objects. Then the researchers removed the objects and asked patients to move through the environment and mark the location of one specific object on each trial.

The team measured the activity of neurons as the patients moved through the environment and marked their memory targets. Initially, they identified purely spatially tuned neurons similar to "place cells" that always activated when patients moved through specific locations, regardless of the subjects' memory target. "These neurons seemed only to care about the person's spatial location, like a pure GPS ,"

However,

the researchers also noticed that other neurons only activated in locations relevant to the memory the patient was recalling on that trial -- whenever patients were instructed to target a different memory for recall, these neurons changed their activity to match the new target's remembered location.