The brain’s ability to rewire itself by forming new connections is seen as a prerequisite for cognitive flexibility, yet a loss of this so-called plasticity as we age can reduce our capacity to adapt or overcome traumatic experiences. According to a new study in the journal Cell Reports, however, it may be possible to restore a more youthful level of plasticity in adult brains using either ketamine or flickering lights – in mice, at least.
When we talk about brain plasticity, we are referring to the rate at which neuronal connections – or synapses – are remodeled, with older synapses being eliminated so that new ones can form. This occurs relatively freely in early childhood but diminishes over the course of our lives as brain connections become more firmly established and connectivity patterns become increasingly rigid.
This loss of plasticity is largely driven by a structure called the perineuronal net, which develops around neurons in order to preserve connections that encode memories relating to important events, thereby preventing them from being erased. While this is extremely useful, it can also cement certain traumatic memories, potentially leading to post-traumatic stress disorder (PTSD).
In recent experiments, however, researchers have noted that the perineuronal net becomes weakened in mice that are anesthetized with ketamine. To understand how this occurs, the authors of the new study used a cellular labeling compound to stain the components of the animals’ perineuronal nets prior to administering the drug.
Their observations revealed that ketamine triggered the brain’s immune cells, known as microglia, to consume the cells within the perineuronal net. According to the researchers, this reinstated a “juvenile-like plasticity” within the rodents’ brains, as synapses that had been protected were now free to be remodeled.
“After just three treatments, we could see a considerable loss in the perineuronal net, which lasted for seven days before being rebuilt," explained study author Sandra Siegert in a statement.
However, because ketamine is a psychoactive drug and may therefore be unsuitable for certain individuals, the team decided to investigate whether this effect could be attained via non-pharmacological means. They, therefore, attempted to manipulate the animals’ brainwaves using flickering lights, in the hope of activating their microglia.
Previous research has shown that microglia can be induced to eliminate plaques in the brain when brainwaves become synchronized with a light that is flickering at 40 times a second – a frequency of 40 hertz. However, in the study authors’ experiments, this frequency did not lead to a loss of perineuronal nets.
Only when the frequency of the flickering light was increased to 60 hertz did microglia begin to consume the rodents’ perineuronal nets, suggesting that this particular brainwave may induce this specific response. As such, the researchers speculate that it may be possible to re-establish a more youthful state of brain plasticity in humans using non-invasive tools such as flashing lights.
"This fine-tuning between distinct brainwaves and the microglia action is the most fascinating and might be a new way of thinking about brainwaves," explained study author Alessandro Venturino.
Should this turn out to be the case, it raises hopes for the development of novel therapies for PTSD and other conditions that are characterized by a loss of cognitive flexibility. However, as Siegert points out, “we are [remaining] very cautious because in this formative window also something traumatic could happen."
"It is probably also not a good idea to blast yourself with flickering light."