CONSCIOUSNESS REDUX

“It was literally true: I was going through life asleep. My body had no more feeling than a drowned corpse. My very existence, my life in the world, seemed like a hallucination. A strong wind would make me think my body was about to be blown to the end of the earth, to some land I had never seen or heard of, where my mind and body would separate forever.” —From Sleep, by Haruki Murakami, 1989

PHYSIOLOGY

turn off—your mind remains hypervigi- Sleeping While Awake lant. You toss and turn but can’t find the blessed relief of sleep. The reasons for During microsleep, the entire brain nods off so briefly that we often don’t notice it. sleeplessness may be many, but the con- ) Now research shows that individual neurons in the brain can slumber, too, sequences are always the same: You are fatigued the following day, you feel Koch 

especially when we are sleep-deprived E (  sleepy, you nap. Attention wanders, your B CA We’ve all been there. You go to bed, reaction time slows, you have less cogni- C BY CHRISTOF KOCH close your eyes, blanket your mind and tive-emotional control. Fortunately,

wait for consciousness to fade. A timeless fatigue is reversible and disappears after SEAN ); M

Christof Koch is president interval later, you wake up, refreshed a night or two of solid sleep. and chief scientific officer at and ready to face the challenges of a new We spend about one third of our lives the Allen Institute for Brain day (note how you can never catch your- in a state of repose, defined by relative  illustration Science in Seattle. He serves on Scientific American self in the act of losing consciousness!). behavioral immobility and reduced re- N HAN ( O

Mind’s board of advisers. But sometimes your inner world does not sponsiveness to external stimuli. Cumu- J

20 SCIENTIFIC AMERICAN MIND November/December 2016 Exploring the riddle of our existence

latively, this amounts to several decades’ as fast as four times a second (that is, in pants had 79 microsleep episodes per worth of sleep over the lifetime of an av- the 0.25- to four-hertz frequency range). hour, lasting between 1.1 and 6.3 sec- erage person. Ah, I know you’re think- Tuning into the discharge of individual onds apiece, with an attendant drop in ing, Wouldn’t it be great if we cut down neurons during deep sleep reveals dis- performance. Microsleep shows up in on this “wasted” time to be able to do crete off periods, when nerve cells cease the EEG record by a downward shift more! When I was younger, I, too, lived generating any electrical activity for 300 from activity dominated by the alpha by the motto “You can sleep when you’re to 400 milliseconds. Such recurring si- band (8 to 13 Hz range) to oscillations dead.” But I’ve woken up to the fact that lent periods, synchronized across large in the theta band (4 to 7 Hz). for optimal, long-term physical and mental health, we need sleep. Humans share this need for daily sleep with all multicellular creatures, as MICROSLEEP CAN BE FATAL WHEN DRIVING OR anybody growing up with dogs, cats or oPERATING MACHINERY SUCH AS TRAINS OR other pets knows. AIRPLANES, HOUR AFTER TEDIOUS HOUR. An understanding of sleep’s impor- tance can be observed by contemplat- ing the biological process itself. Sleep is homeostatically regulated with exqui- parts of the cortex, are the cellular hall- Perniciously, subjects typically be- site precision: pressure to go to sleep mark of deep sleep. lieve themselves to be alert all the time builds up during the day until we feel during microsleep without recalling any sleepy in the evening, yawn continuous- Microsleep period of unconsciousness. This misap- ly and nod off. If deprived of sleep, hu- My last column, “To Sleep with Half prehension can be perilous to someone mans experience an ultimately irresist- a Brain,” highlighted the growing real- in the driver’s seat. Microsleep can be fa- ible need to seek repose—they, in fact, ization of sleep researchers that being tal when driving or operating machinery become “sleep drunk.” An older, 19th- awake and asleep are not all-or-none such as trains or airplanes, hour after te- century term, closer to the truth, is “ce- phenomena. Just because you’re asleep dious hour. During a microsleep epi- rebral exhaustion,” the brain demand- doesn’t necessarily imply that your en- sode, the entire brain briefly falls asleep, ing its rest. tire brain is asleep. Conversely, as I will raising the question of whether bits and In my last Consciousness Redux col- describe now, we have also learned that pieces of the brain can go to sleep by umn, I described how clinicians define even when you’re awake, your entire themselves, without the entire organ sleep by recording brain waves from a brain may not be awake. succumbing to slumber. net of electroencephalogram (EEG) sen- A case in point for sleep intruding Indeed, Italian-born neuroscientists sors placed on the scalp of the sleeper into wakefulness involves brief episodes Chiara Cirelli and Giulio Tononi, who [see photograph on next page]. Like the of sleep known as microsleep. These in- study sleep and consciousness at the surface of the sea, the electrical brain is tervals can occur during any monoto- University of Wisconsin–Madison, dis- ceaselessly in commotion, reflecting the nous task, whether driving long distanc- covered “sleepy neurons” in experimen- unseen, tiny tremors in the cerebral cor- es across the country, listening to a tal animals that showed no behavioral tex underneath the skull that are picked speaker droning on or attending yet an- manifestation of sleep. In this research, up by the EEG electrodes. Rapid eye other never-ending departmental meet- 11 adult rats had microwires implanted movement (REM) sleep is characterized ing. You’re drowsy, your eyes get into their frontal motor cortex, which by low-voltage, choppy, swiftly chang- droopy, the eyelids close, your head re- controls movement. Inserted into the ing brain waves (paradoxically, also typ- peatedly nods up and down and then cortical tissue, the sensors picked up ical of relaxed wakefulness), whereas snaps up: your consciousness lapses. both the voltage called the local field po- non-REM sleep is marked by slowly ris- In one experiment attempting to ex- tential (LFP), akin to the EEG, in addi- ing and falling waves of larger ampli- plore this condition, participants had to tion to the spiking activity of nearby tude. Indeed, the deeper and more rest- track a randomly moving target on a nerve cells. As expected, when awake, ful the sleep, the slower and larger the computer monitor with a joystick for 50 the LFP was dominated by low-ampli- waves that reflect the brain’s idling, re- minutes. While straightforward, this vi- tude, fast waves readily distinguishable storative activity. These voltage oscilla- suomotor task demands nonstop atten- from the larger and slower waves char- tions, referred to as delta waves, can be tion that becomes difficult to sustain af- acteristic of non-REM deep sleep [see as slow as once every four seconds and ter a while. Indeed, on average, partici- box on page 23].

MIND.SCIENTIFICAMERICAN.COM SCIENTIFIC AMERICAN MIND 21 CONSCIOUSNESS REDUX

As expected from pre- One question was whether any one vious animal and human neuron fell asleep independent of any studies, by the end of the other neuron. Or was this occurrence sleep deprivation phase, more of a global phenomenon, whereby the LFP began to shift all neurons simultaneously transition to lower frequencies, to an off period? The answer, obtained compatible with the idea by implanting a second array of micro­­ that the pressure for the wires into a second cortical region—the animals to sleep steadily parietal cortex, a quite distinct region built up. Closer inspection from the motor cortex—was “yes” to of the electrical signatures, both questions. however, revealed some- That is, sometimes neurons in both thing unexpected: occa- regions went off together, whereas at sional, spo­­radic, silent other times they did so independently. periods of all or most of Yet as the sleep pressure built up, after the neurons in the record- several hours of being kept awake, neu- ed brain region [see box ronal activity during sleep deprivation on opposite page] without did become more globally synchronized the animals showing ei- (as it does in deep sleep). Likewise, the ther behavioral or EEG longer the animal slept during the recov- manifestations of micro- ery period, the less likely slow waves sleep. These short, off- were simultaneously detected at both The author, his head clad in a dense net of EEG sensors, par- like episodes were often cortical sites. Groups of neurons can be ticipates in a sleep study in the laboratory of Chiara Cirelli associated with slow more easily recruited to produce the and Giulio Tononi at the University of Wisconsin–Madison. waves in the LFP. The op- slow oscillations that constitute deep posite happened during sleep when sleep pressure is high. At the level of individual neurons, recovery sleep, toward the end of this These results paint a more nuanced the awake animals’ cortical cells chat- six-hour period, when the pressure to view of wakefulness and sleep than the ted away in an irregular, staccato man- sleep had presumably abated. At this prevailing one, in which both conditions ner over an extended period. Converse- point, large and slow waves in the LFP were considered to be global, all-or-none ly, during deep sleep, cortical neurons became more infrequent, and neuronal states of consciousness. Instead these experienced pronounced “on” periods activity turned more irregular, as it did data, buttressed by single-neuron re- of neural activity and “off” times dur- during wakefulness. cordings from patients with implanted ing which they are silent. This neuronal It appears that when awake but sleep- microelectrodes, as used occasionally in reticence occurs simultaneously all over deprived, neurons show signs of sleepi- epilepsy treatment, suggest that even the cortex. It alternates with regular on periods, leading to the rising and falling brain waves that are the hallmark of deep sleep. WHEN SLEEP-DEPRIVED, NEURONS CAN BECOME Knowing all this, the researchers de- TIRED AND DISENGAGED, A MICROCOSM OF cided to probe further. Instead of letting WHAT HAPPENS TO THE WHOLE ORGANISM. the rats go to sleep at their usual bedtime, the experimentalists engaged the animals in a rodent version of late-night video CH gaming, continuously exposing them to ness, whereas after hours of solid sleep, in- when the subject is awake, the individu- O F K F toys and other objects to sniff, explore dividual neurons start waking up. Careful al’s neurons can become tired and occa- O and play with. They tapped on the cage statistical analysis confirmed these trends: sionally check out. The heavier the sleep and otherwise prevented them from as- the number of off periods increased dur- pressure, the more likely this will happen CHRIST F suming a sleep posture or becoming ing the four hours the rats were forced to simultaneously at many places in cortex. drowsy. After four hours of such excite- stay awake, and the opposite dynamic oc- Conversely, after many hours of restful URTESY O URTESY O ment, the rats could finally slumber. curred during recovery sleep. sleep, some of these neurons become de- C

22 SCIENTIFIC AMERICAN MIND November/December 2016 CONSCIOUSNESS REDUX

Partially Asleep of nerve cells—show fast, low peaks present activity akin to those registered during deep when an animal is awake (left panel) and slow- sleep (right panel). Brain studies in animals back the notion that a er, wider waves (center) during deep non-REM The tick marks at the bottom show the person could be partially asleep on the job after sleep (also called slow-wave sleep). But when activity of six closely spaced neurons—all of a late night, with no outward signs of weari- an animal is coaxed to stay awake past its bed- which periodically switch off during slow-wave ness. Local field potential measurements— time, parts of its brain can go to sleep (local sleep. The red boxes highlight the similarity summed electrical activity of large populations sleep), with occasional sharp peaks in neural between non-REM and local sleep.

Awake Deep Sleep Sleep Deprivation 1 second

Local Field Potential

Recordings from Six Neurons

1 2 3 4 5 6

coupled from these brain-wide oscilla- ed to the motor cortex and were not seen head nods. The subject enters micro­sleep. tions and begin to wake up. in the parietal cortex, which is not en- Sleep is a fascinating subject, even But with neurons going off-line dur- gaged by the reaching task. As the ani- though we cannot knowingly experience ing sleep deprivation, shouldn’t there be mals became more sleep-deprived, their deep sleep, because our consciousness is some deterioration in performance? Af- overall performance suffered, as is typi- switched off. Sleep is a finely regulated ter all, these neurons must serve some cal for sleep-deprived humans. aspect of our brain’s daily cycle as the purpose, and if they drowse, something sun rises and sets, a state whose function ought to suffer. To investigate this ques- Local Slumber remains controversial.

tion, Cirelli, Tononi and their collabo- What this study discovered is the ex- Over the past century clinicians and rators trained the rats to reach with one istence of local sleep during sleep depri- neuroscientists have discovered different of their front paws through a narrow vation: isolated cortical groups of neu- sleep phases (rapid eye and nonrapid eye

SKIY ET AL., opening to grasp a sugar pellet on a rons that briefly go off-line while the movements) and the distinct regions of

OV shelf. If done clumsily, the pellet falls off animal, to all outward appearances, the midbrain and brain stem involved in

YAZ and cannot be retrieved anymore. continues to move about and do what it controlling them. What is more, these . V V

V Learning this task engages a particu- does. Local shut-eye is more likely to oc- researchers have demystified narcolepsy, lar sector of the motor cortex that under- cur if those neurons are actively en- when patients abruptly and irresistibly goes change as a consequence of train- gaged, as they are when learning to grab fall asleep, microsleep and now local LADYSLA

Y V ing. Trawling for off periods while the a sugar pellet. Neurons, too, become sleep. What will come next? M animal reaches out for the sweets, the in- tired and disengaged, a microcosm of vestigators found these gaps in neuronal what happens to the whole organism. MORE TO EXPLORE firing are more likely to occur in the mo- Extrapolating from these data, it ■■Local Sleep in Awake Rats. Vladyslav V. tor cortex a fraction of a second before a seems plausible that as the pressure for Vyazovskiy et al. in Nature, V ol. 472, pages failed attempt to grab the pellet as com- sleep increases, the frequency of these 443–447; April 28, 2011. pared with when the rat successfully off events and their preponderance in ■■Losing the Struggle to Stay Awake: Diver- L. 472; APRILL. 472; 28, 2011 gent Thalamic and Cortical Activity during

VO picked up a sweet treat. Indeed, the oc- the cortex increase until activity in

CAL SLEEP IN AWAKE RATS,” B Microsleeps. Govinda R. Poudel, Carrie R. H. O currence of a single off period lowered the entire brain becomes suddenly but Innes, Philip J. Bones, Richard Watts and Rich-

M “L the odds of a successful trial by more briefly synchronized and the brain falls

NATURE,  NATURE, ard D. Jones in Human Brain Mapping, V ol. 35, O

FR IN  than a third. These effects were restrict- into deep sleep—the eyes close, and the No. 1, pages 257–269; January 2014.

MIND.SCIENTIFICAMERICAN.COM SCIENTIFIC AMERICAN MIND 23