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Malach and his research team. Brain at work, even while resting


What's happening in a brain that's disengaged from any focused task? The owner of that brain might be under the impression that when his feet are up and his eyes are closed, most mental activity comes to a standstill; but research at the Weizmann Institute shows that, in truth, the nerve cells in his brain – even those in the visual centers – are still humming with activity.

Previous research conducted by Prof. Rafael Malach and research student Yuval Nir of the Neurobiology Department used functional magnetic resonance imaging (fMRI) to measure brain activity in active and resting states. The results of their study and other similar studies around the world were as surprising as they were controversial: The magnitude of brain activity for the various senses (sight, touch, etc.) in a resting brain is quite similar to that of one exposed to a stimulus. Each sense exhibits a distinctive pattern, spread around different areas of both hemispheres in the brain; the fMRI images show activity in all the areas, whether an outside stimulus is present or not. But fMRI is an indirect measurement of brain activity; it can't catch the nuances of the pulses of electricity that characterize neuron activity.

Together with Prof. Itzhak Fried of the University of California at Los Angeles and a superb team in the EEG unit of the Tel Aviv Sourasky Medical Center, the researchers found a unique source of direct measurement of electrical activity in the brain: data collected from epilepsy patients who underwent extensive testing, including measurement of neuronal pulses in various parts of their brain, in the course of diagnosis and treatment.

An analysis of these data showed conclusively that electrical activity does, indeed, take place even in the absence of stimuli. On the other hand, the nature of the electrical activity differs between the two states. In results that appeared recently in Nature Neuroscience, the scientists showed that the resting activity consists of extremely slow fluctuations, as opposed to the short, quick bursts that typify a response associated with a sensory percept. This difference may explain why, even though our sensory neurons are constantly active, we don't experience non-existent stimuli – hallucinations or voices that aren't there – during rest. Moreover, according to the research, the rest-time oscillations appear to be strongest when we sense nothing at all – during dream-free sleep.

Malach compares the slow fluctuation pattern to a computer screen saver. Though its function is still unclear, the researchers have a number of hypotheses. One possibility is that neurons, like certain philosophers, must "think" in order to be. Survival, therefore, is dependent on a constant state of activity. Another suggestion is that the minimal level of activity enables a quick start when a stimulus eventually presents itself, something like a getaway car with the engine running. Nir: "In the old approach, the senses are 'turned on' by the switch of an outside stimulus. This is giving way to a new paradigm in which the brain is constantly active, and stimuli change and shape that activity."

Malach: "The use of clinical data from a hospital enabled us to solve a riddle of basic science in a way that would have been impossible with conventional methods. These findings could, in the future, become the basis of advanced diagnostic techniques." Such techniques might not necessarily require the cooperation of the patient, allowing them to be used, for instance on people in a coma or on young children.  



In research that appeared in Science, Malach, research student Hagar Gelbard-Sagiv with Dr. Michal Harel of the Institute's Neurobiology Department, and Fried with postdoctoral fellow Dr. Roy Mukamel of UCLA, showed how remembering, at least a few minutes after the original event, is something like a rerun of that event.

Working with epilepsy patients who had thin electrodes implanted in their brains for medical purposes, the scientists were able to measure the electrical activity of individual neurons. The participants were shown a series of film clips of everything from The Simpsons and Seinfeld episodes to historical events and classic movies. As they watched, their brain's electrical activity was being measured, particularly groups of neurons in several brain areas associated with memory. These nerve cells showed preferences for some clips over others by increasing their activity; the researchers were able to connect specific patterns of electrical activity to the clips that elicited them.

A few minutes later, while their brain activity was still being measured, the subjects were invited to think about the clips they had viewed, and to report each time a new clip came to mind. The scientists found that the patterns of brain activity in remembering were so similar to those observed during the original viewing that they were able to tell which clip the subject was recalling – about a second and a half before he or she said it aloud. "It's possible that it takes a second and a half – not a short period by brain activity standards – for the subject to be able to articulate his memory. On the other hand, it might be that part of that time is spent in bringing that memory to the surface, while the conscious brain is still unaware of the event it will recall," says Gelbard-Sagiv.

Prof. Rafael Malach's research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; Vera Benedek, Israel; the Benjamin and Seema Pulier Charitable Foundation, Inc.; and Mary Helen Rowen, New York, NY. Prof. Malach is the incumbent of the Barbara and Morris Levinson Professorial Chair in Brain Research.