A Brain Rhythm Underlying Detachment from Reality
Post by D. Chloe Chung
What's the science?
Dissociation is an altered mental state in which a person feels disconnected from their body and the physical world. Dissociation can happen not only with the use of dissociative drugs like ketamine, but also with certain neuropsychiatric conditions such as epilepsy and trauma. While the underlying neural mechanisms of this subjective experience have been largely unknown previously, advanced imaging technologies allow for scanning the whole brain for neural activity with high spatial and temporal resolution. This week in Nature, Vesuna, Kauvar, and colleagues utilized such technologies to identify oscillations in the specific locations of the brain that underlie dissociation.
How did they do it?
The authors used a mouse model that is genetically modified so that neuronal activity in the cortex can be visualized under the green light. These mice were injected with a low dosage of ketamine or other drugs (dissociative or non-dissociative), and their whole brains were monitored to identify the location of neuronal activity. The firing patterns of hundreds of neurons were also recorded using probes throughout the brain to investigate oscillations in brain regions that were not accessed by imaging. Since mice cannot report their subjective mental state, the authors indirectly determined whether ketamine-injected mice were experiencing something similar to dissociation by placing them on a moderately hot plate. Paw-flicking indicated that mice can feel the heat from the plate and reflexively react to it, while paw-licking indicated instead that mice were “emotionally” behaving to protect their paws from heat. To test whether rhythm in a specific brain location can cause a dissociation-like state and related behaviors in mice, the authors used an optogenetics approach to rhythmically activate the brain region of interest and observed changes in their behaviors during the hot plate test. For clinical relevance, the authors examined the neural activity of an epilepsy patient who received electrode implantation in the brain after experiencing seizure and dissociation.
What did they find?
After being injected with ketamine, mice showed an oscillation of 1-3 Hz (1-3 cycles per second) localized to the retrosplenial cortex (RSP). This brain rhythm appeared to be specifically induced by dissociative drugs as it was not observed when mice received drugs without dissociative properties. Further examination of the whole brain revealed that, among thalamic nuclei neighboring the RSP, the ones connected to the RSP entered a similar oscillation phase with the RSP while the others went out of phase, defining a brain circuitry responsive to dissociative drugs. Also, ketamine-injected mice on the hot plate were found to be able to detect the stimulus (heat) but fail to have an emotional response to it, as they flicked their paws but did not lick them to cool off. The authors interpreted these behaviors to mean that mice were having dissociation-like experiences under the influence of ketamine. Importantly, optogenetic stimulation of RSP similarly reduced paw-licking responses in mice, suggesting that oscillation in the RSP is responsible for a dissociation-like state. The authors expanded upon this observation in humans by confirming that, when an epilepsy patient experiences seizure-related dissociation, oscillations similar to those that occurred in the mouse RSP-equivalent brain region were present. Electrode stimulation in this brain region also induced a dissociative experience in the patient, which further emphasized the causal link between this brain rhythm and dissociation, mirroring that found in mouse experiments.
What’s the impact?
Our understanding of the biological basis of dissociation has been rather poor, as it is highly challenging to investigate a dissociative state of mind given its subjective and complex nature. This work is the first study to reveal that oscillations in a specific brain region can be responsible for dissociation. From this study, we can now better understand how drugs like ketamine work to exert dissociative effects. Also, findings from this study may help the development of clinical strategies that can effectively modulate neurological conditions accompanied by dissociation.
Vesuna, Kauvar et al. Deep posteromedial cortical rhythm in dissociation. Nature (2020). Access the original scientific publication here.