Wendy Science: Exclusive: Oliver Sacks, Antonio Damasio and Others Debate Christof Koch on the Nature of Consciousness

The structure of the living cell is defined by the difference between what’s inside and what’s not. Biologists have taken great pains over the years to document the minute workings of the openings in cell membranes that allow hydrogen, sodium, calcium and other ions to make their way inside across the barrier that envelops the cell and its contents.

Five scholars of the brain have built upon these observations to suggest that these activities may provide a foundation for a badly needed theory to understand consciousness and some of the cognitive processes that underlie it. They contend that when animal cells open and close themselves to the outside world, these actions can be construed as more than just responses to external stimuli. In fact, they constitute the basis for perception, cognition and movement in the animal kingdom—and may underlie consciousness itself.

Read about what the five have to say and then continue to Koch’s reply. The five authors and NYU neurology professor Oliver Sacks; Antonio Damasio and Gil B. Carvalho from the University of Southern California, Norman D. Cook from the faculty of Kansai University in Osaka, Japan and Harry T. Hunt from Brock University in Ontario. They have framed their ideas in the form of an open letter to Christof Koch, president of the Allen Institute for Brain Science, and a MIND columnist () and member of board of advisers.

Dear Dr. Koch,

That approach entails the search for the properties underlying consciousness down to the level of the protozoan [a single-celled organism] in order to identify the fundamental cell-level mechanisms that, when scaled up in complex nervous systems, give rise to the properties that are typically referred to as “mind”. The unanswered question is: What characteristics of living cells lead ultimately to the various, higher-level psychological phenomena that are apparently unique to certain animal organisms? This question concerns essentially functions—and is distinct from “information processing” approaches that might be implemented in silicon systems.

From a biological perspective, we suggest that the lowest-level candidate mechanism is membrane “excitability:” the unusual capability of certain types of living cells to sense and respond to stimuli within several milliseconds. In light of the fact that all living cells have enveloping membranes and exchange materials with their external worlds, it is unlikely that metabolic activity, biochemical homeostasis [keeping cellular systems in balance], or the mere presence of a boundary between the cellular self and the external world alone is sufficient to explain the origins of mind. Rather, the dynamics of the exchange of materials across biological membranes differ remarkably among cell types. Understanding these differences may be relevant in explaining consciousness.

Importantly, the mechanisms underlying the “irritability” of protozoa are known to be the same as those involved in the hyper-sensitivity of all three main types of excitable cell in metazoan organisms (animals)—that is, sensory receptor cells, neurons, and muscle cells. These mechanisms are essentially the opening and closing of certain pores that allow certain ions to pass freely across the cell membrane. Parsimony suggests that the sudden onslaught of positively-charged ions (cations) into the alkaline cytoplasm—the very definition of membrane excitability—is the key phenomenon involved in a cell’s "awareness" of its environment ("sentience"). In other words, what makes cells with excitable membranes so unusual is their response to electrostatic disturbances of homeostasis (slight acidification of the normally alkaline cellular interior) following external stimulation. In order to produce the higher-level “awareness” of animal organisms, the activity of these numerous excitable cells to achieve a kind of sentience must be synchronized (in ways yet to be determined) for coherent organism-level behavior.

This positively charged electrostatic “shock” signals the detection of potential danger (most critically, rupture of the plasma membrane and the influx of slightly acidic “seawater”) that occurs in milliseconds. In unicellular protozoa, most responses are the simple movements in response to a chemical stimulus in flagella, cilia or pseudopodia, which are determined by concentrations of ions in the cytoplasm. In animals containing many billions of sensory receptor cells, neurons and muscle cells, the responses are coordinated into the goal-directed motor activity of certain musculature.

This membrane excitability has, of course, taken a center-stage in neuroscience since the work of in the 1930s. But the focus on the action potential, in particular, has been primarily with regard to its role in the conduction of signals within the cell that ultimately leads to the release of chemicals called neurotransmitters. This focus ignores the biological significance of cation influx itself. We hypothesize that the “hard problems” of sentience, awareness, and ultimately primate self-consciousness begin with the response of excitable cells to external stimuli that threaten to disturb cellular homeostasis. As plant physiologists have noted, animal cells are unique in responding to environmental stimuli, unique in inducing whole-organism responses, and even unique in generating action potentials. Nevertheless, the hypersensitivity of neurons in the animal nervous system is truly unusual in terms of its rapid recruitment of other similarly excitable cells in driving behavior that can restore biological equanimity. We therefore suggest that the higher-level awareness of animal organisms is, in essence, a consequence of the coordinated “irritability” of billions of excitable cells.

The early evolutionary theorists (George John Romanes, Herbert Spencer Jennings, Alfred Binet, and Charles Darwin himself) were duly impressed by the seemingly goal-directed behavior of even single-cell “animalcules”—despite the complete absence of nervous systems. Their interest was clearly focused on cellular and subcellular phenomena, but a proper understanding of ion flux in producing membrane excitability lay a century ahead. Recent progress in the genetics and physiology of ion channels now indicates both how and why the disruption and restoration of the electrostatic equilibrium of the cellular cytoplasm is so crucial to the unprecedented sentience of both neurons and animalcules.

The qualitative argument for considering cation influx to be the “spark of sentience”, as outlined above, is perhaps already plausible, but the quantitative details require further study. As summarized by the foremost contributor to the science of excitable membranes, Bertil Hille, the perceptual significance of cation influx is unlikely to be strong in, for example, the giant motor axon of the squid. Although the large diameter of the squid axon makes it ideal for experimental study, the huge volume of this motor neuron also means that its action potential results in an atypically change in the voltage gradient (only 1 part in 105). In contrast, sensory potentials and action potentials in the small dendrites and axons of most animal nervous systems (where cation influx results in a 10 percent change in ionic content) are much more likely to be perceptually relevant and therefore motivating stimuli. Could these be the cellular-level phenomena that ignite “awareness” and ultimately drive animal behavior? Is this the relevant membrane biology that underlies “mind” and most clearly distinguishes between the placid existence of flora and the feisty, fidgety behavior of fauna?

Sincerely yours,

Norman D. CookGil B. CarvalhoOliver Sacks

Norman D. Cook from the faculty of Kansai University in Osaka, Japan; Antonio Damasio and Gil B. Carvalho from the Brain and Creativity Institute of the University of Southern California; Harry T. Hunt from the faculty of Brock University in Ontario, Canada; and NYU neurology professor Oliver Sacks.

A Response to Cook and Colleagues from Christof Koch

Esteemed colleagues:

Like you, I am an aficionado of ionic, membrane-bound channels and I frequently refer to Bertil Hille’s magisterial tome on this subject in my own writing and teaching.

I fully concur with your sentiment that the influx of cations is of vital importance in cellular excitability. Without this, we would not be conscious. Of course, we also would not be conscious without a beating heart, adequate oxygenated blood-flow, an appropriate cocktail of neuromodulatory chemicals suffusing various brain regions, such as the cortico-thalamic system, and so on. These are all background conditions that enable consciousness to occur but they are by themselves insufficient. More is needed.

During a grand mal epileptic attack the cortex is engulfed in hyper-synchronized spiking activity; that is to say, massive amounts of cations flow into cells and the patient quickly loses consciousness. Indeed, if left unchecked, seizure activity may lead to and death. So it can’t just be the influx of cations that matters for consciousness, but how this inflow is patterned across time and neurons.

As Antonio Damasio, one of the modern masters of inferring functions from loss of structure in brain-lesioned patients, well knows, the loss of regions such as the basal ganglia or the cerebellum, home to four out of five neurons in the human brain, does not measurably impact the presence or the content of consciousness. These structures don’t appear to contribute much to sentience, even though they contain beautiful, shaped nerve cells firing action potentials at a high rate. So it can’t just be the inflow of cations into any neuron in any brain structure that matters for consciousness, but which neurons in which particular structures are active.