A Brain Structure Looking for a Function

hub of sentience A Brain Structure Looking for a Function

Could a thin, enigmatic layer of nerve cells be a key component of the networks generating conscious experience?

Point to any one organ in the body, and doctors can tell you something about what it does and what happens if that organ is injured by accident or disease or is removed by surgery—whether it be the pituitary gland, the kidney or the inner ear. Yet like the blank spots on maps of Central Africa from the mid-19th century, there are structures whose functions remain unknown despite whole-brain imaging, electroencephalographic re cordings that monitor the brain’s ca cophony of electrical signals and other advanced tools of the 21st century. Consider the claustrum. It is a thin, irregular sheet of cells, tucked below the neocortex, the gray matter that by white matter—the tracts, or wire reveal that it is a neural Grand Central allows us to see, hear, reason, think and bundles, that interconnect cortical re Station. Almost every region of the cor- remember. It is surrounded on all sides gions with one another and with other tex sends fibers to the claustrum. These brain regions. The claustra—for there connections are reciprocated by other ) are two of them, one on the left side of fibers that extend back from the claus- Koch

By christof koch the brain and one on the right—lie below trum to the originating cortical region. ( the general region of the insular cortex, Neuroanatomical studies in mice and CABE c Christof Koch is chief underneath the temples, just above the rats reveal a unique asymmetry—each scientific officer at the Allen ears. They assume a long, thin wisp of a claustrum receives input from both cor- Institute for Brain Science SEAN M shape that is easily overlooked when tical hemispheres but only projects back ); in Seattle. He serves on Scientific American Mind’s inspecting the topography of a brain to the overlying cortex on the same side. board of advisers. image. Whether or not this is true in people is Advanced brain-imaging techniques not known. Curiouser and curiouser, as illustration

Send suggestions for column topics to that look at the white matter fibers Alice would have said.

[email protected] coursing to and from the claustrum Unlike most other parts of the brain, jon han (

24 scientific american mind November/December 2014 Exploring the riddle of our existence

there are no reliable case studies of pa all agree that one of the defining proper- but a fleeting moment until the next neu- tients with selective destruction of one ties of any subjective experience is that ronal assembly comes into being and a or both claustra from stroke, viral infec- it is unified. No experience can be re new experience supersedes the old one. tion or other calamity. Lesioning the duced to independent components. Looking at the far-flung two-way structure in laboratory animals is chal- Every experience is irreducible. When I connections between the claustrum and lenging given its thin and elongated look at my wife’s face, I do not see two the cortex, Crick and I—for at that time nature. For the same reason, brain imag- eyes in a black-and-white picture with a in 2004, I was working closely with him ing has not been very useful: the small- disembodied layer of blue superimposed and had been for 16 years—hypothe- est spatial features distinguishable on top. No, I perceive her blue eyes as sized that this superhub of neuronal through positron-emission tomography one integral and seamless whole. Nor do activity could be pivotal for conscious- or functional MRI, two of the most I experience my Bernese mountain dog ness. Because every region of cortex pro- widely used imaging techniques, are two doing funny things with her snout while jected to its associated claustral target area, and this neural communications hub reciprocated the connection, the claustrum could serve as an integrator francis Crick and I hypothesized that for crisscrossing electrical signals, pro- vided that all of this information could this superhub of neuronal activity be freely admixed within the structure. could be pivotal for consciousness. We endlessly discussed various neuroanatomical and biophysical means for the claustrum to achieve this integration and wrote a manuscript. to three millimeters across, bigger than a loud noise fills the room; no, I hear her Francis knew that he only had a lim- the claustrum’s width. And because it is bark. The experience of seeing the word ited amount of time left; he had end- embedded within white matter and “honeymoon” is not reducible to the stage colon cancer. He called me on the sandwiched between two very active experience of seeing “honey” on the left way to the hospital, calmly telling me neuronal tissues—below the neocortex and “moon” on the right. not to worry about the manuscript fol- and above the putamen, part of a larger We know that different groups of lowing our last brainstorming session region, the basal ganglia, lodged deep neurons become active in response to because he was going to make correc- within the brain—it is problematic to such commonly encountered features as tions to it (which he did, dictating them unambiguously pinpoint changes in colors and motion, faces and dogs, to his secretary from the clinic). Two blood flow to the claustrum and not to words, sounds, and so on. These cells are days later, on his deathbed, Francis hal- these nearby, large structures. dispersed among the 16 billion neurons lucinated a debate with me about the making up the cerebral cortex. Together role of the claustrum’s connection to Enter the Dragon the active and inactive cells give rise to consciousness, a scientist to the very In biology, a reliable guide to under- a conscious experience. Furthermore, end. The paper was published a year lat- standing function is to study structure. we know from introspection that what er in the world’s oldest scientific journal, Francis Crick and James Watson proved we are conscious of is in constant flux. the Philosophical Transactions of the this idea spectacularly in 1953. They Distracted by the sight of a passing Royal Society. inferred the key function of DNA, the motorboat on the lake outside my house, molecule of heredity—that is to say, stor- I am about to turn back to writing my Enter the Electrodes ing and copying genetic information— article when I suddenly recall that I In the intervening years, a handful of from its double-helical chemical structure. promised to pick up dog food, and then studies further delineated the molecular Half a century later Crick, by then biolo- my attention shifts without warning to neuroanatomy of the claustrum in ro gy’s most respected sage, tried his hand at Richard Wagner’s “Liebestod” playing dents and a crude map of its connections the same game, linking a structure—the on the radio. Each of these sights, in people. One investigation focused on claustrum—to a function—the emergence sounds, memories or thoughts requires the role of the claustrum in integrating of integrated, conscious experience. that the underlying electrical and chem- visual and auditory stimuli. Using micro Whereas scholars of consciousness ical activity of a privileged set of neurons electrodes that recorded the electrical disagree about many aspects of this is rapidly bound to give rise to an inte- activity in awake monkeys, the investiga- most mysterious phenomenon, virtually grated conscious experience that lasts tors confirmed that part of the claustrum

mind.scientificamerican.com scientific american mind 25 consciousness redux

A possible nexus of consciousness, the claustrum reveals itself through high-definition fiber tractography as a locus at which connections arrive from—and extend outward to—distinct regions of the cerebral cortex. tended to respond more to visual stimu- versity, the clinical team made a remark- stimulation started—behaviors such as li, whereas one of its nearby regions was able observation: electrically stimulat- making repetitive tongue or hand move- sensitive to tones. But no individual neu- ing a single site with a fairly large cur- ments or repeating a word. Koubeissi rons responded to both visual and audi- rent abruptly impaired consciousness in was careful to monitor electrical activi- tory events, arguing against a multisen- 10 out of 10 trials—the patient stared ty throughout her brain to confirm that sory role for the claustrum, thereby leav- blankly ahead, became unresponsive to episodes of loss of consciousness did not ing it bereft of any obvious function. commands and stopped reading. As accompany a seizure. This seeming impasse may have soon as the stimulation stopped, con- Two aspects of this patient’s case had changed with a single dramatic case sciousness returned, without the patient never been seen before. First, no abrupt report. A 54-year-old woman who had recalling any events during the period and specific cessation and resumption of uncontrollable epileptic seizures had electrodes implanted deep within her brain to help pinpoint the exact origin of her seizures. During this procedure, electrical Stimulation of a single site University Pittsburgh of electrodes can triangulate the focal area where the seizure originates so that it in the brain impaired consciousness in iranda M can be surgically removed. They can every one of 10 experimental trials. also inject electric current to help map

the brain, identifying areas responsible ernandez- for important functions such as speech . F or movement and thus sparing them dur- when she was out. Note that she did not consciousness have previously been uan C ing the surgery. become unconscious in the usual sense, reported, despite decades of electrically Led by Mohamad Z. Koubeissi, an because she could still continue to car- stimulating the forebrain of awake associate professor in the department of ry out simple behaviors for a few sec- patients in the operating room. Depend- ourtesy of J neurology at George Washington Uni- onds if these were initiated before the ing on the location of the stimulating C

26 scientific american mind November/December 2014 consciousness redux

A switch that toggles consciousness off and on consists of a simple elec-

trode (red circle) near the claustrum (yellow). Stimulation by the electrode at that location—shown from three perspectives—abruptly curtailed all conscious activity until the current flow stopped.

electrode, patients usually do not feel Unfortunately, this tantalizing case role in generating conscious experiences, anything in particular. Less frequently, a report cannot easily be followed up with we will find out and take another small patient may report flashes of light, smells more experiments, because the patient’s step toward the ultimate goal of iden

ugust 2014 or some difficult-to-verbalize body feel- electrodes were subsequently removed. tifying the footprints of consciousness ings, or perhaps even a specific memory We do not have the luxury of waiting in highly excitable matter. Per claustra

ol. A 37; from long ago that the electric current for an analogous finding, perhaps as long ad astra! M V evokes. Or the patient will twitch a finger as a century hence, so it is important to

vior, vior, or a muscle. But this case was different. devise experiments to confirm the exis- h a e Here consciousness as a whole appeared tence and properties of any claustrum on/ Further Reading

y & B & y to be turned off and then on again. Sec- off switch. The most promising idea ■■What Is the Function of the Claustrum? ond, it happened only at a single place, in would take advantage of proteins specif-

il eps Francis C. Crick and Christof Koch in p E the white matter close to the claustrum ically expressed in cells in the claustrum Philosophical Transactions of the Royal and the cortex. Because electrical stimu- but not in other brain structures. Knowl- Society B, Vol. 360, No. 1458, pages 1271– 1279; June 29, 2005. lation of the nearby insula is not known edge of these cells’ molecular zip code can ■■The Claustrum: Structural, Functional, to elicit a loss of consciousness, the then be exploited by tools of molecular and Clinical Neuroscience. Edited by researchers implicated the claustrum. biology to quickly and transiently turn John R. Smythies, Lawrence R. Edelstein It is difficult to be confident of the the electrical activity of neurons in the and Vilayanur S. Ramachandran. Academic . Koubeissi et al., in actual causal mechanisms—the stimula- claustrum off and on with beams of col- Press, 2014. ■■Electrical Stimulation of a Small Brain lectrical stimulation of a small brain area reversibly disrupts consciousness,” tion may have triggered electrical dis- ored light and to observe the effects on E Area Reversibly Disrupts Consciousness. charges from neurons’ wirelike exten- the behavior of lab mice. Mohamad Z. Koubeissi et al. in Epilepsy & Be rom “

F by mohamad Z sions to exert effects at another site. If the claustrum truly plays a critical havior, Vol. 37, pages 32–35; August 2014.

mind.scientificamerican.com scientific american mind 27