By prodding a tiny brain region linked to consciousness, scientists caused anaesthetised monkeys to suddenly become awake and alert. This fascinating result is providing new clues about the brain and how it produces conscious awareness – insights that could potentially lead to therapies for patients trapped in a coma.
The brain remains the most mysterious organ in the human body. Over the past several decades, neuroscientists have teased apart the various regions and networks in the brain to better understand how they contribute to normal cognitive function, but huge questions remain about consciousness and which parts of the brain can be described as the neural correlates of consciousness (NCCs) – that is, the specific brain regions that allow us to experience the smell of burnt toast, the redness of a blooming rose, or the richness of our internal thoughts.
New research published yesterday in Neuron takes us a small but important step closer to the answer.
By experimenting on macaque monkeys, researchers from the University of Wisconsin-Madison have uncovered new evidence affirming the central lateral thalamus as an NCC. Stimulating this small brain region, which is located deep in the forebrain, caused anaesthetised monkeys to suddenly wake up and be alert, despite the fact that anaesthetic drugs were still being administered. Neuroscientists had previously pegged the central lateral thalamus as an NCC, but this latest research adds more credence to the claim.
The location of the thalamus in the human brain. (Image: Life Science Databases/LSDB)
“This study is significant,” said Earl Miller, a professor of neuroscience from the Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology, in an email to Gizmodo. “Theories of consciousness have suggested that central lateral thalamus plays a key role in keeping the cortex ‘awake.’ This study provides important evidence supporting that theory.”
Moreover, the paper “gives us new insights into the circuitry and brain dynamics that produce consciousness,” wrote Miller, who wasn’t involved with the new research. “Thousands of people are given general anaesthesia each year. Knowing how it makes people unconscious is an important step in making anaesthesia safer.”
Michelle Redinbaugh, the first author of the new study and a graduate student at the University of Wisconsin-Madison, said the primary goal of the experiment was to locate NCCs in the brain.
“Achieving this goal will allow us to better understand the mechanisms of general anaesthesia and the impacts of brain trauma, [and also] target clinical interventions to improve the lives of patients who suffer from disorders of consciousness, such as coma,” she told Gizmodo.
To that end, Redinbaugh, along with senior author Yuri Saalmann and their colleagues, devised an experiment with the intent of inducing consciousness in anaesthetised subjects. To do so, they designed a stimulation method that mimicked the way brain cells act in the central lateral thalamus during the waking state. Using electrode arrays, the scientists were able to record brain activity from multiple brain areas, allowing them to monitor consciousness in the macaques while they were awake, sleeping, and under anaesthesia.
During the experiment, the scientists attempted to stimulate various parts of the deep brain, but none elicited the same response as the central lateral thalamus, which emerged a kind of consciousness hotspot in the brain. Stimulating this brain region at 50 Hertz while the monkeys were under anaesthesia caused them to wake up. When this happened, the primates behaved just as they would when awake. Once the stimulation was turned off, the macaques returned to an unconscious state.
A critical aspect of the experiment was to correctly evaluate wakefulness in the two monkeys used in the experiment, dubbed Monkey R and Monkey W.
“We modelled our assessment of wakefulness in monkeys on clinical measures that are used to assess coma patients or patients that are undergoing anaesthesia,” Redinbaugh told Gizmodo. “Essentially, we were looking for increases in behaviours that you would normally see in an animal – or human – that was waking up from anaesthesia.”
These measures included such things as the monkeys opening their eyes, making purposeful reaches, moving their faces, and showing responsiveness to touch, explained Redinbaugh. The scientists also monitored their EEG responses to both common and unusual sounds, “which can distinguish consciousness from unconscious subjects,” she added.
In terms of the ethics involved, “University of Wisconsin-Madison Institutional Animal Care and Use Committee approved all procedures, which conformed to the National Institutes of Health Guide for the Care and Use of Laboratory Animals,” the authors wrote in the paper.
During the experiments, for example, a clinical anaesthesiologist was to present to make sure the monkeys “received the same level of care as human patients in the hospital,” said Redinbaugh, and the animals were monitored both during and after the experiments to “ensure their health and wellbeing,” among other measures, she said.
That said, the scientists used a dozen ceramic skull screws and dental acrylic to “affix head implants” on the monkeys, among other severely invasive measures required for the experiment, some of which were designed to immobilise the heads of the monkeys during EEG readings. A strong argument can be made that, despite the measures taken, the animals did suffer during this experiment and that monkeys should never be used for experiments such as this.
What that in mind, the new research could result in effective new therapies to treat disorders of consciousness, improved deep brain stimulation as a surgical technique, and better drugs for anaesthesia. What’s more, the findings could take us closer to understanding consciousness itself.
Jaan Aru, a neuroscientist at Humboldt University in Berlin, said researchers in the 1990s began to think that the thalamus was important for consciousness – a belief predicated on the fact that the thalamus is located in a central position for control and that it can change how other brain regions process information. Since the 2000s, however, neuroscientists have focused primarily on the cortex to find the mechanisms of consciousness, he said.
“This study puts thalamus back to the picture,” Aru, who is not affiliated with the new study, told Gizmodo. “I hope many studies will follow that will try to better understand the role of thalamus not only in the state of consciousness, but also in perceptual processes.”
Looking ahead, Redinbaugh said that, since her team now has a method to finely manipulate consciousness, they can test predictions of the major theories of consciousness, “which differ with respect to the brain areas that are most important for consciousness.” They also plan to stimulate a fuller range of areas in the thalamus and determine which frequencies are most effective in influencing consciousness.
“This would pave the way for a similar stimulation paradigm to be used in the clinic,” said Redinbaugh.
Featured image: NIH