Jerusalem's 16-year-old Bloomfield Science Museum invites children to press buttons, twirl knobs, push and pull objects in its nearly unbreakable exhibits. But for only the second time in its history (the first was an exhibit marking the 100th anniversary of Albert Einstein's major theories), the museum has dedicated an exhibition to adults and well-versed teenagers. The new neurobiology exhibit is a thinking person's show that will be open over the next six months, in cooperation with the Hebrew University of Jerusalem's Interdisciplinary Center for Neural Computation, the Jerusalem Foundation, Teva Pharmaceuticals and the German state of North Rhine-Westphalia. Called "The Brain in Research," it demonstrates difficult concepts involving the function of the brain, certainly the most baffling organ in the body. If every person alive today were to produce 1,000 children, the resulting number of people would be equal to the number of neurons in a single human brain. The exhibit focuses on six different research projects being carried out at HU and the Weizmann Institute in Rehovot (with some collaborators abroad) and integrates the use of computers, models and other props to make the research tangible. There are some buttons and computer mice to manipulate as well. The six themes are:
You look familiar: It is known that people are better at identifying faces than objects. What are the mechanisms behind this ability? How do we learn to classify objects? This deals with the ability to learn principles for classifying unfamiliar objects after being exposed to a series of the same type and of other types.
Categorizing unfamiliar objects by comparing them to others of the same type.
Do all humans see the world in the same way? Watching an identical movie while lying inside a functional magnetic resonance imaging (fMRI) scanner shows how brains react in real time.
The Israeli contribution to the "Blue Brain" project. An international team of researchers is striving to "create a model of the brain and its functioning in minute detail, thus opening the possibility of identifying defects that cause disease and devising ways of dealing with them."
Treating depression. Chronic depression that does not respond to drugs can be relieved by magnetic stimulation deep in the brain.
Coping with Alzheimer's disease. The research is developing an innovative technique for treating Alzheimer's that use a bioengineered protein from goat milk that retards the development of toxic plaques in the brain.
THE PROJECT studying neural mechanisms involved in the identification of human faces was headed by doctoral candidate Elana Zion-Golumbic, whose adviser is Prof. Shlomo Bentin, with collaboration by Dr. David Anaki, Tal Golan and Viki Aizenberg of the HU's psychology and cognitive science departments. Zion-Golumbic notes that humans share the same facial features - two eyes, a nose, a mouth, ears and hair - yet they are very good at distinguishing between people, even strangers.
"Scientists have pinpointed an area of the brain involved in this task. We wanted to examine how it happens," she said. Her team used electroencephalography (EEG) to measure electrical activity in the brain. A response mainly on the right side of the brain (called the N170 component) occurs 100 to 200 milliseconds after a stimulus. Previous research has shown that the N170 is greater for faces than for other objects, indicating that specific brain activity is involved. The team previously discovered that the N170 component for responses to human faces and responses to monkeys' faces is similar.
RUBI HAMMER of the HU's interdisciplinary center was advised by Prof. Shaul Hochstein on the categorization of unfamiliar objects based on familiarity with other objects that are similar. "In nature, for example, we can quickly and efficiently differentiate between predators and animals that can be hunted, even though they may be similar in color, form or size," he explains. While most people are able to categorize objects, little is known about how our brains allow them to do so.
The research team decided to examine whether the ability to categorize sets of unfamiliar objects by comparing them to objects of the same type varies with age. Participants in the experiment were asked to determine if unfamiliar objects appearing together on a computer screen were of the same type or of different types. In the pre-learning stage of the study, all the participants could do was guess. In the second stage, some learned the rule for categorizing objects by comparing objects of the same type, while other participants learned this rule by comparing objects of different types. Later, they were asked again to determine if pairs of objects appearing on the screen were of the same or different types. By comparing their performance levels at this stage, they could estimate the effectiveness of the categorization rule they had learned for both types of comparisons.
They found that the amount of information that can be gained by comparing objects of the same type will in most cases be greater than the amount gained by comparing objects of different types. When the participants were trained by comparing objects of the same type, young children demonstrated generally the same learning ability as older people. However, when participants were trained by comparing objects of different types, younger children demonstrated less learning ability than older children and adults. More efficient learning comes only after the age of 10, when human beings learn by comparing objects of different types.
The famous film The Good, The Bad and The Ugly - a 1966 "spaghetti Western" that starred Clint Eastwood, served as the centerpiece for research by Dr. Uri Hasson and Prof. Rafi Malach of the Weizmann Institute. Instead of merely attaching electrodes to the heads of subjects and showing them pictures to detect the location and pattern of elicited brain activity, this innovative team put each subject into an fMRI scanner and had them watch the whole movie, with its highly complex visual and auditory information. They had some surprises when comparing brain activity in such subjects. The fMRI, Malach said at the opening of the Bloomfield exhibit, demonstrates how active nerve cells make use of energy. One indication is the level of oxygen in the blood. The magnetic characteristics of the blood's hemoglobin (which makes it red and carries the oxygen) change depending on whether oxygen is present. By measuring the corresponding magnetic signals, active areas in the brain can be monitored in real time.
The movie's visual imagery was transmitted in such a way that the computer generating the images and the screen on which they appeared were not affected by the magnetic field of the scanner. A second computer continually recorded brain activity and later analyzed the accumulated data. Researchers were looking for those moments during which the greatest amount of activity was recorded in each brain region. Malach said that amazingly, the brain activity pattern of the subjects was identical in each segment of the movie, as if the film had "taken control" of them and elicited the same response in each. The team also found that different parts of the brain "specialize" in certain tasks, such as recognizing faces shown in closeups, while others "specialize" in processing broad panoramas. Malach said the technique could be used on autistic and mentally ill people to see how their brain activity differs.
THE WORK of Shaul Druckmann, Albert Gidon, Prof. Idan Segev of the HU and Swiss collaborators Felix Schuermann, Henry Markram and colleagues on the Blue Brain project could take a decade to reach its goal. Idan, whose longish hair gives him the air of a hippie, said there is growing experimental evidence that the neocortex is organized in column-like structures arranged in grid-like formation, each consisting of 10 to 100,000 cells. "It has been suggested that each such column has a specific computational function, for instance processing the information from a specific whisker in a rat's moustache." Thus, he said, it is tempting to think of the cortical column as a basic universal computational unit of the cortex.
"In the past few decades, there has been a growing understanding of the processing carried out by single neurons. Indeed, very detailed understanding of the electrical activity within a single neuron has been achieved by mathematical modeling. Yet so far, the activity of neuronal networks has been described in more abstract fashion, partly due to the huge computational resources required," Idan added.
Using $300 million worth of IBM Blue Gene supercomputers - comprised of over 8,000 parallel processors - the international team is doing simulations in one day that would have taken 20 years on a standard desktop. All in all, the network simulates something like 10,000 neurons connected by 10 billion synapses in a rat brain. "Thus we have the computational power to simulate each neuron and synapse in realistic detail," says Segev.
Based on data collected for over a decade in Markram's lab through electrophysiological recordings of single-cell activity in the rat cortex, Idan and colleagues can generate a model of a cortical column, simulate its activity in different scenarios and visualize the result.
As studies have already shown that diseased brains are physically different than normal brains, the researchers believe these differences might cause different behaviors. The supercomputer model they are working on, he predicted, can check the differences one by one and attempt to elucidate the main cause. Then one could decide how good potential treatments are by simulating their effect on the model network. Obviously, Segev said, rats' brains are less complex than human brains, but the basic functions and structures are similar.
THE USE of deep magnetic brain stimulation to treat depression is being researched by Dr. Abraham Zangen of the Weizmann Institute, Dr. Yiftach Roth of Brainsway Ltd. and colleagues.
Severe chronic depression plagues millions of people. Most receive psychological treatment, medication or a combination of the two, but some get no relief. Until recently, the only recourse for these people has been electroconvulsive (electroshock) therapy - a controversial method that requires general anesthesia so the patient doesn't suffer when current is shot through his brain. But in recent years, scientists have been developing instruments for transcranial magnetic stimulation (TMS) that involve placing magnets on the scalp. It is painless, noninvasive and can be done while a patient is conscious.
One problem is that most TMS devices have a range of only about two centimeters below the skull, meaning they have no effect on deeper tissue, including parts connected with emotions, satisfaction, pleasure and reinforcement. Now, the Israeli team is using an experimental device, belonging to the Jerusalem startup company Brainsway, to reach five or six centimeters beyond the skull. Staff are working with animals and in clinical trials on psychiatric patients to perfect its functioning.
So far, the results have been encouraging, with about 50 percent of patients ranking at least 50% lower on the "depression scale" after treatment. Only 8% showed no improvement. Beneficial effects in most were apparent after only seven to 10 days of treatment, and even three months later, the condition of most patients who had responded positively hadn't deteriorated. There were no harmful side effects, and no signs of addiction. However, there is still a long road ahead before this treatment becomes widely used.
FINALLY, Erez Podoly, advised by HU biochemistry and structural biology Profs. Hermona Soreq and Oded Livnah, studied Alzheimer's disease (AD) - a progressive, incurable disorder characterized by a gradual decline in brain activity leading to a progressive loss of memory, reasoning ability and personality and, eventually, to death. It is believed that AD results from the accumulation of microscopic neurotoxic plaques that contain insoluble amyloid proteins. Nerve cells die, causing a decline in the secretion of acetylcholine neurotransmitter, thus disrupting messages transmitted to other nerves, muscles and glands. Potential treatments suppress proteins that break down the neurotransmitter, and are aimed at restoring the normal amount, but this approach treats the symptoms and not the cause. It may slow down a patient's deterioration and slightly improve quality of life, but it fails to halt or cure AD.
The researchers were surprised to find that the plaque in the brains of AD patients already contains a protein that slows down the plaque's production. This protein "may be the brain's way of fighting AD," the researchers suggested. They are now working intensively on cell cultures and laboratory mice, and believe that if these produce results consistent with those of test-tube experiments, the research might move to the clinical stages, in which patients are tested. If so, the work may become the basis for an AD drug.
If these exciting research projects tickle your fancy, a visit to the Bloomfield Science Museum before Rosh Hashana is in order.