Among the great enigmas of human existence, few have proven so intractable as the human brain.
Neuroscientist V.S. Ramachandran says our current understanding of the body's most complex organ approximates what we knew about chemistry in the 19th century: in short, not much. On a scale of 100, estimates Toronto psychiatrist Colin Shapiro, our comprehension of how the brain actually functions ranks at a lowly 2.
Now, two Toronto doctors, a general practitioner and a medical biophysicist, are laying claim to a research innovation that could expand our knowledge exponentially.
Using one of the earliest imaging technologies, the electroencephalograph (EEG), Mark Doidge and Joseph Mocanu have written software that creates dynamic, real-time, three-dimensional colour movies of the brain.
If their research is validated, it could revolutionize neuroscience - and, not incidentally, make them a fortune. But while the software is proven, its application to medical treatment has yet to be clinically tested in traditional, double-blind studies.
"We usually think of cameras as looking out at the world," Dr. Doidge said. "This is a new kind of camera. It gives you a window on your mind."
It's not a camera in the conventional sense. Instead, adapting an algorithm known as eLORETA, the software amplifies EEG signals from 32 electrodes attached to the cerebral cortex, and converts them into colour-coded movies of neuronal activity. In a brain divided in more than 6,200 voxels (3D pixels), the algorithm infers and maps where electrical events are occurring. The movie can then be watched in real time, recorded and played back on computer screens.
One significant advantage of the Doidge/Mocanu invention - dubbed dynamic electrical cortical imaging (DECI) - is speed. Other imaging technologies snap pictures of the brain once every few seconds. DECI takes visual impressions less than 1/1,000 of a second apart - in virtual real-time.
If validated by clinical studies, the technology could have far-reaching implications for diagnosis and treatment of pain, sleep and other behavioural disorders, as well as neurological diseases and dementias. By identifying the location and dynamics that underlie EEG abnormalities, clinical trials might, for example, lead to an early test for evidence of Alzheimer's.
"I'm not claiming this is the be-all and end-all or that it's ready for prime time," insisted Dr. Doidge, 55. "Certainly we need clinical studies. But I do think we have advanced the science. And it's only going to get better."
Among the scientific community, reaction to DECI has varied from cautious endorsement to curious skepticism. After seeing two demonstrations, Dr. Shapiro, who heads Toronto Western Hospital's sleep clinic, said the technology "clearly has a lot of under-realized potential. It's a novel idea. They're on the threshold."
Ze'ev Seltzer, who runs the University of Toronto's Centre for the Study of Pain, called Dr. Doidge "a genius. Look, I don't know him. He's not a friend. I have no equity. But what I saw astonished me. Of course, the questions it gives rise to are, 'How do you correlate these images? How do you make meaning out of it?' And he needs resources, money, to be able to do that."
Elizabeth Munro, business development manager of Ontario's Centres of Excellence, calls the technology "pretty neat … a movie of the brain that is not invasive and not expensive." Ms. Munro, who has a background in neuroscience, says the OCE is waiting for Dr. Doidge to get the invention to the next stage, before evaluating it for investment.
Other neuroscientists are more wary. Aaron Newman, a neurologist at Dalhousie University's Neuroscience Institute, said algorithms used to localize the sources of EEG signals "are often unreliable in their accuracy." In general, said Dr. Newman, localizing EEG signals is a "problem fundamentally ill-posed in the language of mathematics and physics."
Dr. Doidge, whose firm has received about $300,000 in federal funding, acknowledges the debate about the emerging field of source localization. But he notes that pubmed - an online data base of medical journal articles - has published more than 500 peer-reviewed articles on the subject. Peer review means that a panel of objective experts have read the research and validated its science, if not its conclusions.
"Since its inception 20 years ago, many naysayers have attacked source localization," Dr. Doidge allowed, "but there are also many supporters."
The electroencephalograph is medicine's oldest brain-imaging technique - invented by German scientist Joseph Berger in 1924. In the decades since, other modalities - computer tomography (CT scan), positron emission tomography (PET scan), functional magnetic resonance imaging (fMRI) and magneto-encephalography (MEG) - have added significantly to our knowledge. But as Dr. Newman noted, "there is no one 'killer app'- each technology has its strengths and weaknesses."
MEG, for example, is more precise, but costs millions of dollars and is immobile. PET scans, relying on nuclear isotope imaging, expose subjects to potentially significant amounts of radiation. Functional MRIs, which measure blood oxygen changes in relation to neural activity, are safe, but difficult to interpret.
Indeed, all of the brain-mapping technologies require inferential reasoning - the necessary art of medicine to complement the hard science.
What's surprising about Cerebral Diagnostics, the company that has applied for a worldwide patent on its research, is that neither Dr. Doidge nor Dr. Mocanu have conventional backgrounds in neuroscience.
Dr. Doidge, the son of a Holocaust survivor (father) and a psychologist - his brother is writer and psychiatrist Norman Doidge, author of the bestselling The Brain That Changes Itself - maintains a downtown Toronto practice in travel medicine. With a long professional interest in the mysteries of the brain, he says he's spent several years and about half a million dollars developing the DECI project. It's part of an eclectic range of interests that includes a still-unpublished manuscript on the roots of nazism.
Dr. Mocanu, 30, the son of a Romanian nuclear engineer, did his PhD in medical biophysics at the University of Toronto, worked as a video game programmer, spent a few years working with Dr. Doidge, took an MBA from the Ivey School of Business at the University of Western Ontario, and then went to Taiwan to study Chinese.
"A skeptic of our work might ask, 'What additional insights are we bringing that an ordinary EEG doesn't do?' " Dr. Mocanu said. "The algorithm itself has been around for a while. But very few people have thought to apply it in real time, so that you can collect real-time data, analyze it for instant diagnoses and triage."
Its first real test will likely come at Toronto Western Hospital's sleep clinic - a clinical study to help determine what makes sleep restorative. "There's a debate in the medical literature about whether deep sleep - delta waves - consists of one stage or two," explained Dr. Shapiro. "By showing whether those waves originate from the same or different places in the brain, we could potentially make that determination. If there's a difference in location, you're going to think there's a difference in function. And I know of no other technique that could potentially set that apart."
That, conceded Dr. Newman, "is a feasible research question, and certainly there's a place for privately funded R&D. The team at Cerebral Diagnostics may have the skills to do the research they're claiming. But I'd be more optimistic if it were coming from people with a proven track record and whose work had the credentials of scientific peer review. I've seen a lot of people attempt to reliably use EEG source localization clinically, and so far there are no standard-of-care solutions out there. Maybe these guys will beat the odds, but I wouldn't put my money on this racehorse. We are focusing on other technologies."
However, the value of an imaging technology, countered Dr. Doidge, "is not determined solely by the accuracy of localization algorithms." Spatial and time factors also need to be factored in.
Beyond its possible medical utility, Dr. Doidge has also set up a consumer application, called Portrait of Your Mind, offering colour photographs (about $700) and/or a 90-minute movie in colour (about $5,000) of the brain in action.